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Molecular Imaging
MI001-EB-X
PET-CT beyond 18FDG: A New Telling of an Old Tale
All Day Location: S503AB
Awards
RSNA Country Presents Travel Award
Certificate of Merit
Participants
Cesar N. Cristancho Rojas, MD, Mexico City, Mexico (Abstract Co-Author) Nothing to Disclose
Luis Azpeitia Espinosa, MD, Mexico City, Mexico (Presenter) Nothing to Disclose
Julian Ramirez Arango, MD, Mexico City, Mexico (Abstract Co-Author) Nothing to Disclose
Mary C. Herrera-Zarza, MD, Mexico City, Mexico (Abstract Co-Author) Nothing to Disclose
Gisela Estrada, MD, Mexico City, Mexico (Abstract Co-Author) Nothing to Disclose
Luis A. Ruiz Elizondo, MD, Mexico City, Mexico (Abstract Co-Author) Nothing to Disclose
Jose L. Criales, MD, Huixquilucan, Mexico (Abstract Co-Author) Nothing to Disclose
TEACHING POINTS
PET-CT is a powerful metabolic imaging technique. Although it has proved to play a mayor role in the clinical practice, its full
potential is yet to come.The rapid evolution of nuclear medicine has led to a renewed interest in the use of more sensitive and
specific radiopharmaceuticals, other than 18-FDG.A remarkable progress has been made in the development of several other
radiotracers, however, much work is needed to bring many of these agents into routine clinical use.The aim of this exhibit is to:1.
Review in a simplified and schematic fashion the bio-molecular targets and metabolic pathways in the most commonly used
radionuclides.2. Point out the advantages, disadvantages, indications and contraindications for each tracer in different clinical
scenarios.3. Recognize potential pitfalls and limitations of the methods.4. Promote and improve the implementation of these valuable
tools.
TABLE OF CONTENTS/OUTLINE
1. Introduction.2. Basis in nuclear imaging.3. Radiotracers, pharmacokinetics and clinical usages:a. [18F]-Fluorodopamine.b. [18F]Fluoroestradiol.c. [11C]-Acetate.d. [68Ga]-DOTA.e. [18F]-Sodium Fluoride.f. [18F]-Fluoromisonidazole.g. [18F]-Fluorothymidine.4.
Conclusions.
MI100-ED-X
PET MRI in Intractable Epilepsy
All Day Location: S503AB
Participants
Hemant T. Patel Sr, MD, Ahmedabad, India (Presenter) Nothing to Disclose
Shweta Thakkar, Ahmedabad, India (Abstract Co-Author) Nothing to Disclose
Jigar V. Patel, MBBS, Ahmedabad, India (Abstract Co-Author) Nothing to Disclose
Pareshkumar M. Gupta, MBBS, Ahmedabad, India (Abstract Co-Author) Nothing to Disclose
Pooja C. Manavadaria JR, MBBS, Rajkot, India (Abstract Co-Author) Nothing to Disclose
TEACHING POINTS
To review limitations of CT and MRI in intractable epilepsy and discuss the pitfalls of conventional MRI alone as a decision making
modality PET MRI is excellent tool for imaging work up intractable epilepsy which requires functional metabolic evaluation Proper
technical parameters, coregistration techniques and matching of images are essential for better delineation of disease process To
discuss PET MRI findings in intractable epilepsy and its impact on management
TABLE OF CONTENTS/OUTLINE
Etiopathogenesis of intractable epilepsy Co-relation of PET imaging with structural images of MRI for evaluation of functional
changes Matching of images through digital atlas templates that provide normative values from representative image sample may
enhance quantitative evaluation substantially PET MRI findings in intractable epilepsy Future direction and summary
MI101-ED-X
PET-MRI in Alzheimer Disease
All Day Location: S503AB
Participants
Hemant T. Patel Sr, MD, Ahmedabad, India (Presenter) Nothing to Disclose
Shweta Thakkar, Ahmedabad, India (Abstract Co-Author) Nothing to Disclose
Jigar V. Patel, MBBS, Ahmedabad, India (Abstract Co-Author) Nothing to Disclose
Pareshkumar M. Gupta, MBBS, Ahmedabad, India (Abstract Co-Author) Nothing to Disclose
Pooja C. Manavadaria JR, MBBS, Rajkot, India (Abstract Co-Author) Nothing to Disclose
TEACHING POINTS
PET MRI is an excellent tool for imaging work up of dementia with Alzheimer disease in particular which requires functional metabolic
evaluation This exhibit will help for recognition of Alzheimer disease in its early form which eventually helps for better management
TABLE OF CONTENTS/OUTLINE
Classification of dementia and etiopathogenesis of Alzheimer disease Corelation of PET imaging with structural images of MRI for
evaluation of functional changes in presenile and advanced cases of Alzheimer disease Discuss PET MRI findings in Alzheimer disease
: Sample cases and images Overlapping appearances and limitations of PET-MRI Future directions and summary : Role of PET MRI in
diagnosis of other causes of dementia
MI102-ED-X
FDG-PET/CT of Epstein-Barr Virus-related Lymphoproliferative Disorders: Knowledge for Rapid and
Appropriate Diagnosis
All Day Location: S503AB
Awards
Certificate of Merit
Identified for RadioGraphics
Participants
Akira Toriihara, Bunkyo-Ku, Japan (Presenter) Nothing to Disclose
Reiko Nakajima, Shinjyuku-Ku, Japan (Abstract Co-Author) Nothing to Disclose
Ayako Arai, Bunkyo-Ku, Japan (Abstract Co-Author) Nothing to Disclose
Masashi Nakadate, Bunkyo-Ku, Japan (Abstract Co-Author) Nothing to Disclose
Koichiro Abe, MD, Tokyo, Japan (Abstract Co-Author) Nothing to Disclose
Kazunori Kubota, MD, PhD, Bunkyo-Ku, Japan (Abstract Co-Author) Nothing to Disclose
Ukihide Tateishi, MD, PhD, Setagaya-Ku, Japan (Abstract Co-Author) Nothing to Disclose
TEACHING POINTS
The purpose of this exhibit is: 1. To explain the pathogenesis of Epstein-Barr virus (EBV) infection. 2. To illustrate representative
FDG-PET/CT findings of various type of EBV-related LPDs. 3. To review other EBV-related diseases as pitfalls. The major teaching
points of this exhibit are: 1. While evaluating the FDG-PET/CT images of patients with generalized lymphadenopathy of unknown
cause, the possibility of EBV-related LPDs should be considered in some patients. 2. For rapid and appropriate diagnosis, not only
careful evaluation of obtained PET/CT images but also a review of the background and previous history is necessary. 3. Although
most types of EBV-related LPDs are FDG-avid, there are some pitfalls which can cause misdiagnosis.
TABLE OF CONTENTS/OUTLINE
Outline: Pathogenesis of EBV infection EBV-related LPDs in immunocompetent host EBV-related LPDs in immunocompromised host
Pitfalls
MI103-ED-X
A Glimpse into Genetics of Gliomas: Welcome to the Era of Radiogenomics!
All Day Location: S503AB
Participants
Somesh Singh, MBBS, Mumbai, India (Presenter) Nothing to Disclose
Abhishek Mahajan, MD, Mumbai, India (Abstract Co-Author) Nothing to Disclose
Santhosh K. GeethaVirupakshappa, MD, MBBS, Mumbai, India (Abstract Co-Author) Nothing to Disclose
Sureshkumar G, MBBS, Mumbai, India (Abstract Co-Author) Nothing to Disclose
Nikshita A. Jain, MBBS, Mumbai, India (Abstract Co-Author) Nothing to Disclose
Aliasgar Moiyadi, MChir, Mumbai, India (Abstract Co-Author) Nothing to Disclose
Epari Sridhar, Mumbai, India (Abstract Co-Author) Nothing to Disclose
Rakesh Jalali, Mumbai, India (Abstract Co-Author) Nothing to Disclose
TEACHING POINTS
Gliomas are the most frequent tumors occurring in the CNS and are defined and graded on the basis of histological features.
Pathology is fundamental to predict prognosis and guide the correct patient management. Owing to biological heterogeneity, the
histological diagnosis and expected clinical outcome do not match in a significant number of patients and the histological
examination does not distinguish tumors responding or not responding to the therapy. The combination of imaging and gene
expression, referred to as "radiogenomics," has the potential to give insight into tumor biology and impact prognosis and therapy
that would be difficult to acquire from either technique alone.1. To describe common genetic alterations and the resultant cellular
and tissue changes in GBMs and how they are targeted by each specific therapeutic agent or class of agents.2. To highlight the
various Imaging findings suggestive of a particular genetic mutation.
TABLE OF CONTENTS/OUTLINE
1. Haarlem Classification of Gliomas and their grading.2. Common genetic mutation associated with gliomas and the associated
clinical impact.3. Imaging findings which can help us predict the genetic mutation and hence help in prognostication and therapy.4.
Review of current radiogenomics literature.
MI104-ED-X
Visualization and Quantification Techniques of Atherosclerotic Plaques Using 18F-FDG and 18F-Sodium
Fluoride PET/CT: An Update on the Literature
All Day Location: S503AB
Participants
Sina Houshmand, MD, Philadelphia, PA (Presenter) Nothing to Disclose
Ali Salavati, MD, MPH, Philadelphia, PA (Abstract Co-Author) Nothing to Disclose
Thomas J. Werner, Philadelphia, PA (Abstract Co-Author) Nothing to Disclose
Abass Alavi, MD, Philadelphia, PA (Abstract Co-Author) Nothing to Disclose
TEACHING POINTS
1) To discuss methodological factors in accurate quantification of atherosclerosis and calcification in the vessels. 2) To review the
molecular imaging techniques for assessment of atherosclerosis and inflammation in the vessel walls.
TABLE OF CONTENTS/OUTLINE
Quantification of inflammation and cardiovascular disease prediction has been reproducibly shown by 18-F-FDG PET/CT, which is a
non-invasive imaging modality. Sodium 18-F fluoride PET/CT has been shown able to detect calcification in the wall of the vessels
and predict cardiovascular risk. In this review we will discuss the new techniques which have been developed in the assessment of
the atherosclerotic plaque and inflammation/calcification related to it. In this review we will discuss: Pathophysiology of
atherosclerosisRole of inflammation in plaque biologyVulnerable plaquesFDG-PET/CT in assessment of atherosclerosis and vessel wall
inflammation.Sodium Fluoride- PET/CT in atherosclerosis and vascular wall calcification.Quantitative aspectsPre-scan
variablesInjection DoseGlobal inflammatory burdenOptimal Imaging Time
MI105-ED-X
The Clinical Utility of PET/CT and PET/MRI in the Management of Sarcoidosis
All Day Location: S503AB
Participants
Ali Salavati, MD, MPH, Philadelphia, PA (Presenter) Nothing to Disclose
Sina Houshmand, MD, Philadelphia, PA (Abstract Co-Author) Nothing to Disclose
Thomas J. Werner, Philadelphia, PA (Abstract Co-Author) Nothing to Disclose
Abass Alavi, MD, Philadelphia, PA (Abstract Co-Author) Nothing to Disclose
TEACHING POINTS
1) To review current applications of PET/CT imaging in diagnosis, assessment, and management of sarcoidosis and its
complications.2) To discuss new horizons related to molecular imaging in the management of sarcoidosis and its complications
including use of PET/MRI.
TABLE OF CONTENTS/OUTLINE
Sarcoidosis is a multisystem granulomatous disease of unknown etiology. The diagnosis is based on clinical and radiographic findings
as well as by histopathological findings. In recent years, molecular imaging has made significant progress for assessment of various
inflammatory diseases including sarcoidosis. PET/CT has been shown to provide insight into metabolism of this disease. MRI is the
current modality of choice for detection of cardiac sarcoidosis and neurosarcoidosis but has some limitations that may be
compensated with PET. This presentation provides an overview of the applications of PET for evaluation of patients with sarcoidosis
and following subjects will be reviewed: 1. The clinical utility of FDG-PET/CT in detection and response assessment of pulmonary
and nodal sarcoidosis.2. The clinical utility of FDG-PET/CT in cardiac sarcoidosis.3. The clinical utility of FDG-PET/CT in
neurosarcoidosis.4. PET radiotracers beyond FDG for assessment of sarcoidosis.5. Application of PET/MRI for evaluation of patients
with sarcoidosis.
MI106-ED-X
Multimodality Imaging in Multiple Myeloma: International Myeloma Working Group 2015 Updated Criteria for
the Management of Patients
All Day Location: S503AB
Awards
Molecular Imaging Travel Award
Participants
Ana M. Crespo, PhD, Madrid, Spain (Presenter) Nothing to Disclose
Miguel Pastrana, MD, Majadahonda, Spain (Abstract Co-Author) Nothing to Disclose
Mercedes Ruiz Tolon, MD, Madrid, Spain (Abstract Co-Author) Nothing to Disclose
Inaki Lizarbe Rodriguez, Madrid, Spain (Abstract Co-Author) Nothing to Disclose
Luisa F. Leon-Ramirez, Madrid, Spain (Abstract Co-Author) Nothing to Disclose
Isabel Krsnik, MD, PhD, Madrid, Spain (Abstract Co-Author) Nothing to Disclose
Rafael Martinez, Madrid, Spain (Abstract Co-Author) Nothing to Disclose
Ml Vega Gonzalez, Madrid, Spain (Abstract Co-Author) Nothing to Disclose
TEACHING POINTS
The International Myeloma Working Group (IMWG) consensus updates the disease definition of Multiple Myeloma (MM) to include
validated biomarkers. The IMWG has also developed practical recommendations for the use of PET-CT and whole-body MRI (WBMRI) in patients of MM with special focus on the role of smoldering or asymptomatic MM. MRI is useful in detection of bone marrow
infiltration. Regarding new criteria, all patients with smoldering or asymptomatic MM should undergo WB-MRI.FDG PET/CT is
especially sensitive for the detection of extramedullary disease and can help detect the metabolically active lesions that often
precede evidence of osseous destruction at WB-RX. Response monitoring with the use of 18 FDG PET-CT during treatment is
promising, allowing more precise prediction of prognosis compared with the standard response monitoring. In view of the expanding
treatment options for MM, both WB-MRI and PET-CT may provide important information for treatment decisions in the future.
TABLE OF CONTENTS/OUTLINE
1. Definition of MM2. Staging systems3. Role of imaging modalities: WB-XR, low dose CT, WB-MRI and PET-CT3. a. Diagnosis and
assessment of the extent and severity of the disease at presentation3. b. Prognosis3. c. Detection of complications 3. d.
Assessment of response to therapy 4. Conclusions
MI107-ED-X
PET Tracers for Functional Imaging of Prostate Cancer: A Pictorial Review of Normal Biodistribution,
Scintigraphic Appearances, Imaging Approaches, Patterns and Pitfalls
All Day Location: S503AB
Participants
Venkatesh Rangarajan, MBBS, Mumbai, India (Presenter) Nothing to Disclose
Rasika Kabnurkar, MBBS, Mumbai, India (Abstract Co-Author) Nothing to Disclose
Archi Agrawal, MBBS, Mumbai, India (Abstract Co-Author) Nothing to Disclose
Sneha A. Shah, Mumbai, India (Abstract Co-Author) Nothing to Disclose
Nilendu C. Purandare, DMRD, Mumbai, India (Abstract Co-Author) Nothing to Disclose
TEACHING POINTS
1)18F NaF ,18F Choline PET/CT are currently used in Staging and restaging Prostate Ca.2)PSMA is a cell surface protein with high
expression in prostate cancers. Ga-68 PSMA PET/CT appears promising for local staging and restaging of PCa and provides one stop
shop for detecting primary tumor, nodal and distant metastases with high contrast resolution.3) Ga-68 PSMA PET/CT potentially
has higher accuracy for marrow, lytic and extra skeletal lesions compared to F18 fluoride PET/CT.F18 Fluorocholine, a biological
marker for cell membrane synthesis.
TABLE OF CONTENTS/OUTLINE
Mechanism of localization, normal biodistribution, imaging patterns, utility and limitations of various PET/CT tracers for the imaging
of treatment naïve and castration resistant prostate cancerThe normal biodistribution of Ga-68 Prostate Specific Membrane Antigen
(PSMA)Imaging patterns and utility of Ga-68 PSMA PET/CT in staging and restaging Prostate cancer (PCa).Imaging patterns and
advantages of Ga-68 PSMA PET/CT over F18 Fluoride PET/CT for detection of skeletal metastases in staging and restaging of
PCa.The normal biodistribution of F18 Fluorocholine and its current application in prostate cancer
MI108-ED-X
Imaging Tumor Treatment Response Criteria: Multimodality Case-based Review
All Day Location: S503AB
Awards
Certificate of Merit
Participants
Pouya Ziai, MD, Darby, PA (Presenter) Nothing to Disclose
Mohammadreza Hayeri, MD, San Diego, CA (Abstract Co-Author) Nothing to Disclose
Vivek Gowdra Halappa, MD, Philadelphia, PA (Abstract Co-Author) Nothing to Disclose
Aliaksei Salei, MD, Darby, PA (Abstract Co-Author) Nothing to Disclose
Oleg Teytelboym, MD, Philadelphia, PA (Abstract Co-Author) Nothing to Disclose
TEACHING POINTS
Review imaging tumor treatment response criteria for solid tumors. Review similarities and differences between response criteria:
thresholds of progression, stability and response, number and kind of lesions to be targeted and criteria for progression Practical
tips and cases based review of response
TABLE OF CONTENTS/OUTLINE
Anatomic response criteria RECIST (Response Evaluation Criteria In Solid Tumors) WHO criteria Choi criteria for GIST EASL, mRECIST
(European Association for the Study of the Liver, modified RECIST) criteria for hepatomaFunctional MRI Diffusion weighted and
Dynamic- Contrast enhanced MRI for HCCMetabolic response criteria Quantitative PERCIST (PET Response Criteria in Solid Tumors)
EORTC Qualitative Deauville response criteria for Hodgkin lymphoma Controversies and shortcoming of current guidelines in assessing
treatment responseFuture directions and assessing response of cytostatic therapies.
MI109-ED-X
Multimodality and Molecular Imaging of Adrenal Lesions - Case Reviews with a Proposed Imaging and
Management Pathway Incorporating Radiology and Novel Nuclear and Molecular Imaging Techniques
All Day Location: S503AB
Participants
James Drummond, MBBS, Sydney, Australia (Presenter) Nothing to Disclose
Edward Hsiao, MD, Cleveland, OH (Abstract Co-Author) Nothing to Disclose
Geoff Schembri, MBBS, Sydney, Australia (Abstract Co-Author) Nothing to Disclose
Allison Newey, MBBS, Sydney, Australia (Abstract Co-Author) Nothing to Disclose
Gowri L. Kanthan, MBBS, Sydney, Australia (Abstract Co-Author) Nothing to Disclose
TEACHING POINTS
1.Review current CT & MRI imaging with thorough adrenal lesion case reviews.2.Introduce a radiological audience to nuclear
molecular imaging with functional scintigraphy for adrenal lesions.3.Discuss hybrid imaging for adrenal lesions with an emphasis on
novel PET/CT radioisotopes including Ga-68 Dotatate.4.Proposed pathway for complementary radiologic & nuclear medicine imaging
and management for adrenal lesions.5.Case review of complex adrenal lesions with combined radiological and nuclear medicine
imaging.
TABLE OF CONTENTS/OUTLINE
A. Radiological: (i)Multiphase CT (ii)MRI (iii) Pitfalls in CT/MRI. B. Scintigraphy of Adrenal Lesions: (i) 123/131I-MIBG (ii) 131I
Norcholesterol. C. PET/CT of Adrenal lesions: (i) FDG/PET (ii) Gallium 68-Dotatate PET (iii) Gallium 68-Dotatate normal distribution.
D. Nuclear Medicine Therapies: (i) 131I MIBG therapy (ii) Peptide Receptor Radionuclide Therapy: Lu-177 octreotate. E. Proposed
complementary radiologic and nuclear imaging and management pathway for adrenal lesions. F. Complex adrenal lesion case review
with combined radiological / nuclear medicine imaging.
MI110-ED-X
The Lugano Standardized Criteria for Staging and Response Assessment of Hodgkin and Non-Hodgkin
Lymphoma
All Day Location: S503AB
Awards
Cum Laude
Participants
Sara Sheikhbahaei, MD, MPH, Baltimore, MD (Presenter) Nothing to Disclose
Mehdi Taghipour, MD, Baltimore, MD (Abstract Co-Author) Nothing to Disclose
Esther Mena, MD, Bethesda, MD (Abstract Co-Author) Nothing to Disclose
Rick Wray, MD, Baltimore, MD (Abstract Co-Author) Nothing to Disclose
Se Jin Ahn, MD, Seoul, Korea, Republic Of (Abstract Co-Author) Nothing to Disclose
Jennifer Xiao, Boston, MA (Abstract Co-Author) Nothing to Disclose
Charles Marcus, MD, Baltimore, MD (Abstract Co-Author) Nothing to Disclose
Rathan M. Subramaniam, MD, PhD, Baltimore, MD (Abstract Co-Author) Travel support, Koninklijke Philips NV
TEACHING POINTS
1. Review the history and developments of standardize response criteria for Hodgkin (HL) and Non-Hodgkin lymphoma (NHL), the
International Working Group guideline and the Lugano classification.2. Discuss the substantial changes in the Lugano guideline
including lymphoma staging [incorporation of positron emission tomography, revision of Ann Arbor staging, staging of bulky disease,
indication of bone marrow biopsy] and therapy assessment.3. Case illustration of therapy assessment according to the Lugano
criteria.
TABLE OF CONTENTS/OUTLINE
- Different staging systems in Hodgkin (HL) and Non-Hodgkin lymphoma (NHL)- The history and the development of Lugano guideline
for initial staging and response assessment of HL/NHL- The Lugano practice guideline for staging of HL/NHL and its clinical contextThe Lugano practice guideline for prognosis and planning treatment strategies of HL/NHL and its clinical context- The Lugano
practice guideline in therapy response assessment of HL/NHL and its clinical context- Advantages and limitations of Lugano
classification compared to other classification systems- Recent clinical trials and recommendations on the Lugano guideline
ED015-SU
Molecular Imaging Sunday Case of the Day
Sunday, Nov. 29 8:00AM - 11:59PM Location: Case of Day, Learning Center
MI
AMA PRA Category 1 Credit ™: .50
Participants
Jonathan E. McConathy, MD, PhD, Saint Louis, MO (Presenter) Research Consultant, Eli Lilly and Company; Research Consultant,
Blue Earth Diagnostics Ltd; Research Consultant, Siemens AG; Research support, GlaxoSmithKline plc
Suzanne E. Lapi, PhD, Saint Louis, MO (Presenter) Research Grant, ImaginAB, Inc
Bernadette V. Marquez, PhD, Saint Louis, MO (Abstract Co-Author) Nothing to Disclose
Ephraim E. Parent, MD, PhD, Saint Louis, MO (Abstract Co-Author) Nothing to Disclose
Alexander Drzezga, MD, Cologne, Germany (Abstract Co-Author) Research Grant, Eli Lilly and Company; Speakers Bureau, Siemens
AG; Speakers Bureau, General Electric Company; Speakers Bureau, Piramal Enterprises Limited; Research Consultant, Eli Lilly and
Company; Research Consultant, Piramal Enterprises Limited; ; ; ; ; ;
TEACHING POINTS
1) The case of the day exhibit will highlight molecular imaging techniques currently available in clinical practice and new tracers
expected to become available in the near future. 2) Participants completing this exhibit will recognize the biodistribution of newer
molecular imaging agents, understand their mechanism of action, and be familiar with their clinical utility and potential causes of
diagnostic errors.
SSA12
Molecular Imaging (Neuroimaging)
Sunday, Nov. 29 10:45AM - 12:15PM Location: S504CD
NR
MI
MR
AMA PRA Category 1 Credits ™: 1.50
ARRT Category A+ Credits: 1.50
FDA
Discussions may include off-label uses.
Participants
Alexander Drzezga, MD, Cologne, Germany (Moderator) Research Grant, Eli Lilly and Company; Speakers Bureau, Siemens AG;
Speakers Bureau, General Electric Company; Speakers Bureau, Piramal Enterprises Limited; Research Consultant, Eli Lilly and
Company; Research Consultant, Piramal Enterprises Limited; ; ; ; ; ;
Satoshi Minoshima, MD, PhD, Salt Lake City, UT (Moderator) Royalties, General Electric Company; Consultant, Hamamatsu
Photonics KK; Research Grant, Hitachi, Ltd; Research Grant, Nihon Medi-Physics Co, Ltd; Research Grant, Astellas Group; Research
Grant, Seattle Genetics, Inc;
Sub-Events
SSA12-01
Molecular Imaging Profiling of Treatment Effects in Experimental Multiple Sclerosis
Sunday, Nov. 29 10:45AM - 10:55AM Location: S504CD
Awards
Molecular Imaging Travel Award
Participants
Benjamin Pulli, MD, Boston, MA (Presenter) Nothing to Disclose
Reza Forghani, MD, PhD, Montreal, QC (Abstract Co-Author) Shareholder, Real-Time Medical, Inc; Committee member, Real Time
Medical, Inc
Gregory R. Wojtkiewicz, MSc, Boston, MA (Abstract Co-Author) Nothing to Disclose
Cuihua Wang, PhD, Boston, MA (Abstract Co-Author) Nothing to Disclose
Matthias Zeller, MD, 02114, MA (Abstract Co-Author) Nothing to Disclose
Neng Dai, MD, Boston, MA (Abstract Co-Author) Nothing to Disclose
John W. Chen, MD, PhD, Boston, MA (Abstract Co-Author) Research Grant, Pfizer Inc
PURPOSE
Treatment effects of interferon beta (IFN) and glatiramer acetate (GA), two first-line agents used in multiple sclerosis (MS), are
similar as evaluated by conventional MRI. We imaged these two drugs with MPO-Gd, an activatable molecular MR probe specific to
myeloperoxidase (MPO), an enzyme secreted by pro-inflammatory myeloid cells, to better profile and study their effects on the
innate immune response in vivo.
METHOD AND MATERIALS
Thirty-five female SJL mice were injected with proteolipid protein to induce experimental autoimmune encephalomyelitis, a mouse
model of MS, and treated with IFN (1 μg/day), GA (150 μg/day), MPO inhibitor ABAH (0.8 mg/day), or saline. Mice underwent MRI
at 4.7T with MPO-Gd at disease peak (day 12). Lesion volume, number, contrast-to-noise ratio (CNR), and total MPO-Gd
enhancement were quantified on delayed images. Mechanistic in vitro experiments were performed.
RESULTS
CNR (MPO activity in vivo) was decreased with ABAH and IFN, but not with GA. Lesion volume, lesion number, and total MPO-Gd
enhancement was decreased with all three agents (Fig., A-B). These findings suggest that IFN may have the imaging signature of
an MPO inhibitor. However, direct enzymatic inhibition was only found with ABAH, and not with IFN or GA (C). When primary
neutrophils were stimulated to secrete MPO, IFN decreased activity of the MPO enzyme, similar to ABAH (D), while GA did not have
a similar effect (D). When neutrophils were incubated with IFN, increased superoxide anion production (as measured by
dihydroethidium [DHE] fluorescence) was detected (E). Inhibition of superoxide anion production by apocynin resulted in the
restoration of MPO activity from stimulated neutrophils (F). Spectrophotometry revealed that IFN-mediated superoxide anion
production abolished absorbance of MPO at 430 nm, consistent with irreversible destruction of the iron-containing prosthetic group
(G).
CONCLUSION
Molecular imaging profiling with MPO-Gd reveals differential treatment effects of the two first-line drugs used in the treatment of
MS (H), and led to the discovery of a novel mechanism of action of IFN: IFN triggers superoxide anion production in myeloid cells to
irreversibly inactivate MPO.
CLINICAL RELEVANCE/APPLICATION
Molecular imaging profiling with imaging agents that probe the immune response could open up a new avenue to study the effects
of current and future novel therapeutic drugs for MS.
SSA12-02
Microtubule Stabilization Therapeutic Improves Cognition and Acutely Increases Axonal Transport on
Manganese-enhanced MRI in Aged Mice with AD Pathology
Sunday, Nov. 29 10:55AM - 11:05AM Location: S504CD
Participants
Chloe G. Cross, BSC, Seattle, WA (Presenter) Nothing to Disclose
Marcella Cline, BS, Seattle, WA (Abstract Co-Author) Nothing to Disclose
Greg Garwin, Seattle, WA (Abstract Co-Author) Nothing to Disclose
Satoshi Minoshima, MD, PhD, Salt Lake City, UT (Abstract Co-Author) Royalties, General Electric Company; Consultant, Hamamatsu
Photonics KK; Research Grant, Hitachi, Ltd; Research Grant, Nihon Medi-Physics Co, Ltd; Research Grant, Astellas Group; Research
Grant, Seattle Genetics, Inc;
Donna J. Cross, PhD, Seattle, WA (Abstract Co-Author) Nothing to Disclose
PURPOSE
Previously we reported increased axonal transport in young mice transgenic (Tg) for Alzheimer's disease (AD) after intranasal
administration of a microtubule-stabilizing therapeutic, paclitaxel using MRI with manganese (MEMRI). In this study we administered
paclitaxel to AGED 3xTg-AD mice with established pathology from 10-18 mos and hypothesized that cognition would improve and be
associated with increased axonal transport.
METHOD AND MATERIALS
Mice, (3xTg-AD n=10, age=44wks) were treated by intranasal lavage with paclitaxel (TAX: 0.6 mg/kg) or 0.9% saline (SAL) in 5 µl
per nostril at intervals of 2wks. MEMRI was obtained after first treatment to assess acute effect on transport. Scanning (14T
Bruker MR: MDEFT, TR/TE: 5000ms/1.9ms, 0.140x0.140x0.25mm3) pre and immediately after treatment occurred at 100 min. and
from 370-400 min after delivery of 5 µL of 1M MnCl2 intranasally. Images were coregistered stereotactically aligned and normalized
to a mouse atlas. Tracer kinetic analysis based on dispersion model was used to estimate transport. At 56 wks after 5 treatments,
mice were tested in radial water tread maze for memory deficits and compared to age-matched WT (n=5) and at 75 wks after 11
treatments, anxiety was assessed by elevated plus maze.
RESULTS
At 10 mos, 3xTg-AD have amyloid and neurofibrillary tangles. There was a significant acute effect of TAX on transport in the
olfactory tract. Transport rates decreased slightly in SAL (-13%) in the 3wk interval between MEMRI scans however TAX increased
(>100%) transport at 24hrs after administration (p=0.05). Cognition was tested in the water tread maze (memory) and elevated
plus maze (anxiety). TAX had improved memory as compared to SAL and not significantly different from WT (Day 5, 36% dec,
143.8±43 vs 91.5±77s and Day 12, 22% dec, 138.3±52 vs 107.7±75s for SAL vs. TAX, p<0.05). 3xTg-AD mice exhibit anxiety. TAX
spent more time exploring open arms than SAL (Open arm 84% inc, 129.1±80 vs 20.9±31s for TAX vs SAL, p≤0.05). There were no
differences in Mn2+ uptake indicating delivery thru activity-dependent Ca2+ channels was not affected by treatment.
CONCLUSION
MEMRI indicated that paclitaxel has an acute effect on axonal transport processes in AD mice. Paclitaxel also improved cognition
and anxiety in AD mice when administered after pathology was well-established.
CLINICAL RELEVANCE/APPLICATION
Microtubule-stabilizing drugs present an exciting new therapeutic option for Alzheimer's disease.
SSA12-03
Whole-Brain, Volumetric MR Spectroscopic Profiles Identify Infiltrating Glioblastoma Margin for
Fluorescence-Guided Surgery
Sunday, Nov. 29 11:05AM - 11:15AM Location: S504CD
Participants
James S. Cordova, BS, Atlanta, GA (Presenter) Nothing to Disclose
Constantinos G. Hadjipanayis, MD, PhD, Atlanta, GA (Abstract Co-Author) Nothing to Disclose
Zhongxing Liang, PhD, Atlanta, GA (Abstract Co-Author) Nothing to Disclose
Lee Cooper, Atlanta, GA (Abstract Co-Author) Nothing to Disclose
Saumya Gurbani, MS, Atlanta, GA (Abstract Co-Author) Nothing to Disclose
Stewart Neill, MD, Atlanta, GA (Abstract Co-Author) Nothing to Disclose
Eduard Schreibmann, PhD, Atlanta, GA (Abstract Co-Author) Nothing to Disclose
Hui-Kuo G. Shu, MD, PhD, Atlanta, GA (Abstract Co-Author) Speakers Bureau, Varian Medical Systems, Inc; Stockholder, General
ELectric Company; Stockholder, Medtronics, Inc; Stockholder, Mylan NV; Stockholder, Apple Inc
Jeffrey Olson, PHD, Atlanta, GA (Abstract Co-Author) Nothing to Disclose
Chad A. Holder, MD, Atlanta, GA (Abstract Co-Author) Nothing to Disclose
Hyunsuk Shim, PhD, Atlanta, GA (Abstract Co-Author) Nothing to Disclose
PURPOSE
Glioblastoma (GBM) resection based on T1W-contrast enhanced MRI (T1W-CE) results in high rates of local recurrence due to
tumor infiltration beyond contrast enhancing margins. MR spectroscopic imaging (MRSI) maps are thought to identify tumor
infiltration outside of T1W-CE regions more specifically than T2-FLAIR. Thus, coupling preoperative MRSI with real-time
fluorescence-guided surgery (FGS) using 5-aminolevulinic acid (5-ALA) may allow the maximal removal of tumor beyond the
enhancing margin.
METHOD AND MATERIALS
In a trial for new and recurrent GBM (n=20 patients), 3D whole-brain MRSI volumes, including choline (Cho), creatine (Cr), and Nacetylaspartate (NAA) maps, were acquired and used for surgical planning in patients receiving FGS. Biopsies were collected from
regions with elevated Cho/NAA before bulk resection using 5-ALA fluorescence. Fluorescence of resected tissue was quantified ex
vivo with a hand-held spectrometer, and metabolic data was sampled from MRSI volumes using an 8 mm³ region-of-interest
centered at the point of tissue extraction. Samples were stained for SOX2, a tumor-specific marker, and analyzed to quantify tumor
infiltration using an automated histology image analysis tool. Semi-automated tumor segmentation was used to evaluate extent-oftumor resection (EOR) ( Cordova et al. 2014 ).
RESULTS
One-hundred percent of tissue samples from metabolically abnormal regions, even those devoid of T2 abnormality, contained SOX2
positive cells (range: 3 - 96% of cells). Cho/NAA, Cho/Cr, and Cho showed strong, statistically significant correlations with the
proportion of SOX2-positive cells ( ρ = 0.70, 0.66, and 0.60, respectively; p < 0.05). Ex vivo tissue fluorescence showed a weaker
yet significant correlation with Cho/NAA and Cho ( ρ = 0.365 and 0.404; p<0.05). Median EOR in MRSI/5-ALA cases was 97.5%
whereas that in a concurrent study using FGS alone was 94.2%.
CONCLUSION
This is the first time that 5-ALA-induced fluorescence has been shown to correlate with MRSI-derived metabolic markers in brain
tumors. The correlation of MRSI abnormality with histopathology and quantitative intraoperative fluorescence supports the use of
MRSI for identifying regions of tumor infiltration outside of T1W-CE.
CLINICAL RELEVANCE/APPLICATION
As MRSI is independent of contrast diffusion, it defines tumor infiltration more precisely than T1W-CE; and when combined with
FGS, results in more complete resections that may extend patient survival.
SSA12-04
Motexafin Gadolinium (MGd) - Enhanced MR and Optical Imaging of Rat Gliomas for Potential
Intraoperative Determination of Tumor Margins
Sunday, Nov. 29 11:15AM - 11:25AM Location: S504CD
Participants
Longhua Qiu, Seattle, WA (Presenter) Nothing to Disclose
Feng Zhang, MD, Seattle, WA (Abstract Co-Author) Nothing to Disclose
Yaoping Shi, MD, Seattle, WA (Abstract Co-Author) Nothing to Disclose
Zhibin Bai, Seattle, WA (Abstract Co-Author) Nothing to Disclose
Jianfeng Wang, MD, Seattle, WA (Abstract Co-Author) Nothing to Disclose
Donghoon Lee, PhD, Seattle, WA (Abstract Co-Author) Nothing to Disclose
Xiaoyuan Feng, MD, Shanghai, China (Abstract Co-Author) Nothing to Disclose
Xiaoming Yang, MD, PhD, Seattle, WA (Abstract Co-Author) Nothing to Disclose
PURPOSE
To investigate the possibility of using motexafin gadolinium (MGd)-enhanced molecular MR imaging and optical imaging to identify
the genuine margins of rat gliomas.To investigate the possibility of using motexafin gadolinium (MGd)-enhanced molecular MR
imaging and optical imaging to identify the genuine margins of rat gliomas.
METHOD AND MATERIALS
Rat glioma model was created by inoculating C6 glioma cells in right caudate nucleuses of male Sprague-Dawley rats (160g ± 20g).
Thirty six rats with tumors were randomized into six groups (n=6/group). Five groups were euthanized at different time points of 15,
30, 60, 120 and 240 minutes after intravenous administration of 6-mg/kg MGd respectively, while one group received saline as a
control. After a craniotomy, ex vivo optical imaging was performed to identify the tumors featuring as MGd-emitting red
fluorescence. Then, the whole brains were harvested for ex-vivo T1-weighted MRI (T1WI). Optical photon intensities and MRI
signal-to-noise ratio (SNR) were quantified for plotting the times to photon/SNR curves. Tumor extent was demarcated on both
optical and MR imaging. Subsequently, confocal microscopy of brain tissues was performed to confirm the intracellular uptake of
MGd by tumor cells and correlate the tumor margins determined on both optical and MR images.
RESULTS
Fluorescent optical imaging could sensitively detect the deep-seated tumors with red fluorescence in rat brains and clearly outlined
the tumor margins. T1WI showed the tumors heterogeneous enhancement. Both the photon intensity and the maximal enhancement
on T1WI reached the peak at 15 minutes after MGd administration, with a continuing tumor visibility lasting for 2-4 hours. Confocal
microscopy confirmed the exclusive accumulation of MGd in tumor cells which was well correlated with imaging findings.
CONCLUSION
Both MGd-enhanced optical imaging and molecular MR imaging can sensitively determine rat glioma tumor margin within the optimal
time window of 15~30 minutes post-MGd administration, which pose the potential clinical application for aiding the complete
removal of gliomas at a hybrid surgical setting with intraoperative optical and MR imaging capabilities.
CLINICAL RELEVANCE/APPLICATION
MGd-enhanced imaging poses a potential clinical application for aiding the complete removal of gliomas at a hybrid surgical setting
with intraoperative optical and MR imaging capabilities.
SSA12-05
Generation of a Bispecific Antibody for Combined EGFR/CD105 Targeting of High-Grade Gliomas
Sunday, Nov. 29 11:25AM - 11:35AM Location: S504CD
Awards
Molecular Imaging Travel Award
Participants
Reinier Hernandez, MSc, Madison, WI (Presenter) Nothing to Disclose
Haiming Luo, PhD, Madison, WI (Abstract Co-Author) Nothing to Disclose
Hao Hong, PhD, Madison, WI (Abstract Co-Author) Nothing to Disclose
Stephen Graves, Madison, WI (Abstract Co-Author) Nothing to Disclose
Robert J. Nickles, PhD, Madison, WI (Abstract Co-Author) Nothing to Disclose
Weibo Cai, PhD, Palo Alto, CA (Abstract Co-Author) Nothing to Disclose
PURPOSE
Our aim was to design and generate a heterodimer [Bs-F(ab')2] using two mAb Fab fragments for dual-targeting of epidermal
growth factor receptor (EGFR) and CD105. The synergistic targeting properties of Bs-F(ab')2 were investigated in vitro/in vivo.
METHOD AND MATERIALS
Bs-Fab'2 was synthesized by reacting two mAb fragments (Cetuximab Fab and TRC105 Fab) derivatized with the "Click' chemistry
pair tetrazine/trans-cyclooctene. Bs-Fab'2 was purified by size exclusion chromatography, conjugated to NOTA, and labeled with
64Cu for positron emission tomography (PET). In vitro and in vivo dual-receptor binding studies were performed in a U87MG human
glioblastoma cancer model (EGFR/ CD105 +/+). Blocking, biodistribution, and ex vivo histological examination were performed to
validate the in vivo data.
RESULTS
Purified Bs-F(ab')2 was confirmed by SDS-PAGE (~100 kDa, >90% pure), whereas the two Fab fragments were each at ~50 kDa.
Flow cytometry showed an enhanced fluorescence signal for the heterodimer compared with either Fab. PET of U87MG tumor
bearing mice with 64Cu-NOTA-Bs-F(ab')2 revealed a strikingly higher tumor uptake (32.0±6.9, 47.5±6.7, 46.0±3.3 and 44.1±9.4
%ID/g at 3, 15, 24, and 36 h postinjection, respectively; n=3) compared to those observed with 64Cu-NOTA-Cet-Fab and 64CuNOTA-TRC105-Fab (both <15%ID/g). Injection of a blocking dose (100mg/kg) of Cetuximab or TRC105 prior to the administration of
the tracer resulted in a significantly reduced tumor uptake of 64Cu-NOTA-Bs-F(ab')2, which confirmed that Bs-F(ab')2 tumoruptake was mediated by both EGFR and CD105 expression. Owing to the low tracer uptake in non-target organs (e.g. liver and
kidney), we attained excellent tumor-to-normal tissue contrasts.
CONCLUSION
We report the first successful dual-targeting of EGFR and CD105, with a "click" heterodimer featuring two mAb Fab fragments,
which led to synergistic enhancement of tumor uptake over either Fab alone. These results may improve future cancer diagnosis
and therapeutic efficacy.
CLINICAL RELEVANCE/APPLICATION
Combined EGFR/CD105-targeting provides increased tumor-targeting efficacy and specificity, which may ultimately lead to better
diagnostic sensitivity and increased tumor cytotoxicity.
SSA12-07
MRI Contrasts Induced by Direct Saturation: Demonstration in the Central Nerve System
Sunday, Nov. 29 11:45AM - 11:55AM Location: S504CD
Participants
Rongwen Tain, PhD, Chicago, IL (Presenter) Nothing to Disclose
Feliks Kogan, PhD, Stanford, CA (Abstract Co-Author) Nothing to Disclose
Xiaohong J. Zhou, PhD, Houston, TX (Abstract Co-Author) Nothing to Disclose
Kejia Cai, PhD, Chicago, IL (Abstract Co-Author) Nothing to Disclose
PURPOSE
A frequency selective saturation RF pulse across a broad frequency range produces a Z-spectrum. This Z-sprectrum receives
contributions from components mainly including direct saturation (DS) of bulk water, magnetization transfer, chemical exchange
saturation transfer, and Nuclear Overhauser Enhancement. When a weak saturation regime is applied, such as B1rms< 50 Hz and
duration < 500 ms, the Z-spectrum is mainly attributed to the DS spectrum, characterized by a Lorentzian-shape. The DS
magnitude at a given frequency offset has been used to measure iron content in brain. Additionally, the position of maximum DS has
been exploited to map B0 field variations (ΔB0). In this study, we investigate additional contrasts revealed by analyzing DS
spectrum.
METHOD AND MATERIALS
This study was performed under an approved IRB protocol. DS spectra within ±1 ppm were acquired from the brain and cervical
spinal cord of healthy subjects at 3T scanner with a 32 channel head-coil and a 16 channel head and neck spine coil, respectively.
The pulse sequence consists of a pre-saturation pulse (B1rms = 12.2 Hz for brain, 24.4 Hz for spinal cord, 200 ms) followed by a 2D
single-shot SPGR readout. The DS data was fitted pixel by pixel with a Lorentzian function to produce B0 field, DS line-width, and
DS magnitude maps. In addition, simulations with Bloch equations were performed to correlate with experimental data.
RESULTS
Beside the ΔB0 map, the Lorentzian fitting of data obtained from both brain and spinal cord was used to produce new maps based
on the DS line-width and magnitude. In the brain and spinal cord respectively, the DS line-width of gray matter is slightly narrower
than that of the white matter. As expected, CSF gave the narrowest line-widths. DS amplitude was reversed. Simulation further
showed that DS line-width is positively proportional to 1/T2 and inversely proportional to 1/T1. DS magnitude was found to be
proportional to proton density.
CONCLUSION
Two quantitative contrasts (DS line-width and magnitude) that reflect tissue relaxation rates and proton density have been
demonstrated in the human CNS tissues.
CLINICAL RELEVANCE/APPLICATION
The discovered contrasts induced by DS MRI have the clinically potential for characterization of normal and pathological tissues.
SSA12-08
CD146-based Noninvasive ImmunoPET Imaging of High-grade Gliomas
Sunday, Nov. 29 11:55AM - 12:05PM Location: S504CD
Participants
Reinier Hernandez, MSc, Madison, WI (Presenter) Nothing to Disclose
Yunan Yang, Madison, WI (Abstract Co-Author) Nothing to Disclose
Stephen Graves, Madison, WI (Abstract Co-Author) Nothing to Disclose
Robert J. Nickles, PhD, Madison, WI (Abstract Co-Author) Nothing to Disclose
Weibo Cai, PhD, Palo Alto, CA (Abstract Co-Author) Nothing to Disclose
PURPOSE
The goal of this study is to establish CD146 as a novel target for in vivo immunoPET imaging of mice bearing orthotopic high-grade
gliomas (HGG).
METHOD AND MATERIALS
An improved immunization approach was used to generate YY146, a murine anti-CD146 monoclonal antibody. RT-PCR, western blot,
flow cytometry, and immunofluorescence staining studies were conducted to determine in vitro CD146 expression. Subcutaneous
(s.c.) U87MG human glioblastoma (CD146+) and PC3 human prostate cancer (CD146-) tumors were induced in athymic nude mice.
Additionally, orthotopic U87MG tumors were generated in nude mice and its progression monitored by T2-weighted MRI. YY146 was
conjugated to p-SCN-Bn-NOTA and radiolabeled with 64Cu. Sequential PET scans, blocking, histological, and biodistribution studies
were carried out to determine in vivo CD146 specificity of 64Cu-NOTA-YY146.
RESULTS
Flow cytometry demonstrated that chelator conjugation to YY146 did not compromise its CD146-binding affinity/specificity. 64CuNOTA-YY146 was obtained with high radiochemical purity (>95%) and specific activity, in yields surpassing 90%. MicroPET imaging
studies revealed an elevated and persistent uptake of 64Cu-NOTA-YY146 in U87MG (CD146+) s.c. xenografts which peaked at
13.7±0.7 %ID/g, 48h post-injection (n=3). In contrast, significantly lower accumulation was observed in PC3 (CD146-) tumors (<5
%ID/g). Excellent tumor homing was observed from PET/CT imaging of orthotopic U87MG tumors, where 64Cu-NOTA-YY146 was
able to infiltrate the brain and accumulate in tumorous tissue (21.5±3.5 %ID/g at 48h post-injection; n=5). The attained exquisite
tumor-to-normal brain contrast allowed for the sensitive detection of small malignancies (~2 mm). Biodistribution, blocking
experiments, as well as histological examination validated PET data, and confirmed the CD146 specificity of 64Cu-NOTA-YY146.
CONCLUSION
We successfully implemented noninvasive immunoPET imaging of in vivo CD146 expression in an orthotopic human glioblastoma
cancer model. The high affinity and specificity of 64Cu-NOTA-YY146 envisages the potential of this novel mAb for targeted HGG
diagnosis and therapy.
CLINICAL RELEVANCE/APPLICATION
Herein, we show for the first time that CD146 is a promising tumor-specific target for noninvasive in vivo imaging and targeted
therapy of high-grade gliomas.
SSA12-09
The Expression of P2X7 Receptors in EPCs and Their Potential Role in the Targeting of EPCs to Brain
Gliomas
Sunday, Nov. 29 12:05PM - 12:15PM Location: S504CD
Participants
Xiao Chen, Chongqing, China (Presenter) Nothing to Disclose
Weiguo Zhang, Chongqing, China (Abstract Co-Author) Nothing to Disclose
Jingqin Fang, Chongqing, China (Abstract Co-Author) Nothing to Disclose
PURPOSE
To investigate the functional expression of P2X7 receptors in EPCs, role of P2X7 receptors in proliferation and homing to glioma of
EPCs.
RESULTS
We confirmed, for the first time, the expression of P2X7 receptors in rat spleen-derived EPCs. Activation of P2X7 receptors in EPCs
by BzATP promoted cells proliferation and migration, rather than apoptosis. Compared to the group without BBG treatment, less
transplanted EPCs homed to gliomas in the group with BBG treatment, especially integrated into the vessels containing tumorderived endothelial cells in gliomas. Moreover, western blot showed that CXCL1 expression was downregulated in gliomas with BBG
treatment, which meant P2X7 receptors suppression inhibited the homing of EPCs to gliomas through down-regulation of CXCLl
expression. Additionally, MTT assay and MRI revealed that P2X7 receptors exerted no significant promoting effect on C6 glioma cells
proliferation, glioma growth and angiogenesis.
CONCLUSION
Taken together, our findings imply the possibility of promoting proliferation and targeting ability of transplanted EPCs to brain
gliomas in vivo through P2X7 receptors, which may provide new perspectives on application of EPCs as a therapeutic and imaging
probe to overcome antiangiogenic resistance for gliomas.
CLINICAL RELEVANCE/APPLICATION
Apply EPCs as a therapeutic and imaging probe to overcome antiangiogenic resistance for gliomas.
MIS-SUA
Molecular Imaging Sunday Poster Discussions
Sunday, Nov. 29 12:30PM - 1:00PM Location: S503AB
MI
AMA PRA Category 1 Credit ™: .50
FDA
Discussions may include off-label uses.
Participants
Carsten Kobe, Cologne, Germany (Moderator) Nothing to Disclose
Sub-Events
MI200-SDSUA1
Detection of Calcified Aortic Plaques in ApoE Knockout Mice on a Human 3rd Generation Dual Source
CT System for Ultra-high Resolution Imaging: A Feasibility Study
Station #1
Awards
Molecular Imaging Travel Award
Participants
Melissa Ong, MD, Mannheim, Germany (Presenter) Nothing to Disclose
Calin-Petru Manta, Mannheim, Germany (Abstract Co-Author) Nothing to Disclose
Mathias Meyer, Mannheim, Germany (Abstract Co-Author) Speaker, Siemens AG; Speaker, Bracco Group
Mareike Roscher, Mannheim, Germany (Abstract Co-Author) Nothing to Disclose
Cyrill Geraud, Mannheim, Germany (Abstract Co-Author) Nothing to Disclose
Sergij Goerdt, Mannheim, Germany (Abstract Co-Author) Nothing to Disclose
Stefan O. Schoenberg, MD, PhD, Mannheim , Germany (Abstract Co-Author) Institutional research agreement, Siemens AG
Thomas Henzler, MD, Mannheim, Germany (Abstract Co-Author) Nothing to Disclose
PURPOSE
To prospectively evaluate the feasibility of detecting calcified aortic plaques in ApoE knockout (KO) mice using a human third
generation 2x192 slices dual source CT (DSCT).
METHOD AND MATERIALS
11 ApoE knockout and 4 B6 wild type mice, all male, were examined in this study. After injection of 6.6% ketamine i.p. all mice
underwent an ultra-high-resolution CT protocol on a 3rd generation DSCT system at 120 kVp and 130 kVp with 1300 reference mAs.
0.4mm images with an increment of 0.2 mm were reconstructed using a third generation iterative reconstruction algorithm. All
images were binary evaluated with regard to detection of calcified plaques on a dedicated off-line workstation by two experienced
radiologists in consensus. After the CT examination histological evaluations of the aorta were performed to quantify the plaque
amount and calcium core position. A calcium quantification assay was performed in order to determine the total calcium amount of
each mouse. A ROC analysis was performed to evaluate the total calcium amount necessary for detection of macroscopic calcified
plaques in CT.
RESULTS
The CT scan time ranged between 40-48 seconds. Calcified plaques could be detected in 8 of the ApoE KO mice (72.5%), whereas
no calcified plaques could be detected in the wild type mice. The ROC analysis revealed a cut-off for the total value of 0.7 µg
Ca2+/mg. Use of this cut-off lead to an overall detection rate of aortic calcifications of 100%.
CONCLUSION
3rd generation clinical DSCT high resolution imaging allows for the detection of calcified aortic plaques in ApoE mice. Our promising
findings facilitate the integration of a human 3rd generation DSCT into preclinical imaging for translational research studies.
CLINICAL RELEVANCE/APPLICATION
Using a 3rd generation DSCT with ultra-high resolution 0.4 mm images allows for the detection of calcified aortic plaques down to
0.7 µg Ca2+/mg in ApoE KO mice. This may have the potential to detect spotty micro-calcifications in atherosclerotic plaques.
MI201-SDSUA2
Imaging of Thromboembolism Using Polymer based Targeted Theranostic Delivery System
Station #2
Participants
Kye S. Kim, MD, Boston, MA (Presenter) Nothing to Disclose
Peter Kang, MD, Boston, MA (Abstract Co-Author) Nothing to Disclose
PURPOSE
Diagnosis and treatment of thromboembolism can be limited by nonspecific nature of thrombus and bleeding complications. Targeted
approach by an adjunctive means would be an addition to the current methods. In this study, we have developed a novel
theranostic delivery system to effectively image and treat actively forming thrombus.
METHOD AND MATERIALS
The polymer-based micelles were generated through hydrophilic-hydrophobic interactions and consisted of mPEG-PCL (methoxy poly
(ethylene glycol)-poly (caprolactone)) and pluronic F-127. A pentapeptide, CREKA (H-Cys-Arg-Glu-Lys-Ala-OH), which showed a
high affinity to fibrinogen-fibrin complex, was covalently bonded to the micelle. For thrombus specific therapy, tirofiban, a
glycoprotein IIb-IIIa inhibitor, was also loaded into the micelles. For animal model of thrombus, we used the rat inferior vena cava
(IVC) stenosis model that induced subacute thrombus formation within 24-48 hours.
RESULTS
We found that the ratio of 80% mPEG-PCL and 20% pluronic F-127 generated most uniform sized micelles with the mean size of 29
nm. The half-life of micelle complex was about 15 hours. For imaging, we loaded the micelles with indocyanine green (ICG), a nearinfrared fluorophore with peak absorption at ~800nm. The imaging using thrombus targeted micelles with CREKA was highly sensitive
and specific at the actively thrombogenic area at both 6 (no visible thrombus) and 24 hours (maximal amount of visible thrombus)
after IVC stenosis. In animals with IVC stenosis, treatment with micelle containing CREKA loaded with 10% of therapeutic dose of
tirofiban (T10/CREKA) showed 65% reduction in thrombus weight compared to 10% of therapeutic tirofiban dose without micelle
complex (p<0.05). T10/CREKA micelles, in fact, demonstrated a similar effectiveness as 100% of therapeutic tirofiban dose without
micelle, suggesting that equivalent therapeutic effect is achievable with 10% amount of tirofiban.
CONCLUSION
We conclude that our novel polymer based theranostic delivery system using micelle complex and CREKA may be used for more
effective imaging and safer treatment of thromboembolic diseases.
CLINICAL RELEVANCE/APPLICATION
Our polymer based targeted theranostic delivery system may be used for more effective imaging and safer treatment of
thromboembolic diseases.
MI202-SDSUA3
Velocity Determination by Magnetic Particle Imaging: Phantom Validation and in Vivo Measurements
in a Mouse Model
Station #3
Participants
Michael G. Kaul, Hamburg, Germany (Presenter) Nothing to Disclose
Caroline Jung, Hamburg, Germany (Abstract Co-Author) Nothing to Disclose
Johannes M. Salamon, MD, Hamburg, Germany (Abstract Co-Author) Nothing to Disclose
Tobias Mummert, Hamburg, Germany (Abstract Co-Author) Nothing to Disclose
Martin Hofmann, Dipl Phys, Hamburg, Germany (Abstract Co-Author) Nothing to Disclose
Kolja Them, Hamburg, Germany (Abstract Co-Author) Nothing to Disclose
Gerhard B. Adam, MD, Hamburg, Germany (Abstract Co-Author) Nothing to Disclose
Harald Ittrich, MD, Hamburg, Germany (Abstract Co-Author) Nothing to Disclose
Tobias Knopp, DIPLENG, Hamburg, Germany (Abstract Co-Author) Nothing to Disclose
PURPOSE
Magnetic particle imaging (MPI) is a new radiologic imaging modality. The goal of this study was to perform velocity measurements
by MPI using bolus tracking in a phantom and in the caval vein of a mouse.
METHOD AND MATERIALS
A tube (Øinner=1.3mm, Øouter=1.9mm) was wrapped spirally around a cylinder (Ø=21.3mm) to build a flow phantom. The inner
diameter is similar to the mean diameter of mices' caval vein. A drop of ferucarbotran was placed inside the tube surrounded by oil.
The drop was pushed by an injection pump with different flow rates to emulate velocities of 2, 5, 10, 14, 17, and 19 cm/s. The
movement was scanned dynamically with a preclinical MPI scanner (Philips/Bruker) sampling a 3D volume within 21.5ms.
Measurements were repeated five times for each flow rate to calculate measurement errors. Measurements parameters were 2.5
T/m gradient strength, 14 mT drive-field amplitude covering a volume of 22.4x22.4x11.2 mm³. In-vivo measurements were carried
out in a healthy mouse with 1 T/m and 10 mT covering 40x40x20 mm³. A bolus of 50 µL ferucarbotran was applied during the
dynamic scan within 3 seconds by tail vein injection.Maximum intensity projections along the symmetriy axis of the spiral were
calculated. A region of interest was placed where the bolus periodically was occuring. Time between first and last temporal arrival
was measured. Analogous the signal in the distal part of the vena caval inferior and the heart were measured and arrival times were
calculated. The propagated distance was derived from MPI and co-registered with MRI.
RESULTS
Estimated velocities were 1.8, 4.7, 9.8, 13.9, 17.0, 19.1 cm/s. Relative errors were less than 0.2%. In vivo analysis revealed a
velocity of approximately 3.5 cm/s. This is in good accordance to MRI velocity measurements, which show mean velocities between
2.5 and 5 cm/s depending on the vessel diameter.
CONCLUSION
Bolus tracking in the vena cava can be performed. Phantom measurements approve that MPI is fast enough to detect velocities
surely up to 19 cm/s. Extrapolation of in vitro results predict a theoretical limit of around 150 cm/s, which would cover arterial
velocities in mice.
CLINICAL RELEVANCE/APPLICATION
Bolus tracking and velocity estimation are elementary techniques to investigate and validate the status vessels and perfusion of
healthy and unhealthy tissue. A clinical MPI scanner would offer the radiologist and the patient a radiation free diagnostic.
MIS-SUB
Molecular Imaging Sunday Poster Discussions
Sunday, Nov. 29 1:00PM - 1:30PM Location: S503AB
MI
AMA PRA Category 1 Credit ™: .50
FDA
Discussions may include off-label uses.
Participants
Carsten Kobe, Cologne, Germany (Moderator) Nothing to Disclose
Sub-Events
MI204-SDSUB1
Assessment of Iron Labeled Mesenchymal Stem Cells for Endoscopic Injection into the Porcine
Urethral Sphincter using MRI
Station #1
Participants
Susanne Will, Tuebingen, Germany (Abstract Co-Author) Nothing to Disclose
Petros Martirosian, PhD, Tuebingen, Germany (Abstract Co-Author) Nothing to Disclose
Frank Eibofner, Tubingen, Germany (Abstract Co-Author) Nothing to Disclose
Joerg Schmehl, Tuebingen, Germany (Abstract Co-Author) Nothing to Disclose
Konstantin Nikolaou, MD, Tuebingen, Germany (Abstract Co-Author) Speakers Bureau, Siemens AG Speakers Bureau, Bracco Group
Speakers Bureau, Bayer AG
Ulrich Kramer, MD, Tuebingen, Germany (Presenter) Nothing to Disclose
Fritz Schick, MD, PhD, Tuebingen, Germany (Abstract Co-Author) Nothing to Disclose
Martin Vaegler, Tuebingen, Germany (Abstract Co-Author) Nothing to Disclose
Karl-Dietrich Sievert, Tuebingen, Germany (Abstract Co-Author) Nothing to Disclose
PURPOSE
To restore damaged urethral sphincter function, different aspects of cell-based treatments should be investigated. Local injection
of therapeutic mesenchymal stem cells (MSC) has been proved as a promising approach for tissue regeneration. The aim of this
study was to evaluate the effects of superparamagnetic iron oxide (SPIO) cell labeling on the visualization of therapeutic MSC and
validate in vitro and in vivo using a mini-pig animal model. After injection into the porcine urethral sphincter, the labeled cells were
monitored up to six months using magnetic resonance imaging (MRI).
METHOD AND MATERIALS
Iron labeled MSC were injected transurethral under cystoscopic guidance into the urethral sphincter of a mini-pig model (n=14). In
all animals a total amount of approx. 2.000.000 cells/mL were circularly injected into the rhabdosphincter distributed over four
depots and monitored on a 3T MRI scanner. The animals were examined three weeks, three months as well as six months after MSC
injection. High resolution anatomical images of the porcine urethral sphincter were measured to detect SPIO particles using a fastspin-echo sequence (voxel size 0.4×0.4×2mm³). A gradient echo sequence with multiple echo times (5.29, 13.62, and 22.01 ms)
was utilized to visually identify and verify locations of iron particles. The distribution of injected cells was then correlated with
histological findings.
RESULTS
Measurements of the sphincter muscle in the mini-pig clearly demonstrated visible iron deposits inside the sphincter muscle.
Additionally, iron depositions could be verified in vivo six months after stem cell injection. The comparison of MRI and tissue
sections illustrated preeminent correlation of location and dilatation of iron depots (see figure 1).
CONCLUSION
SPIO-labeled MSC injection into the porcine urethral sphincter and subsequent evaluation with highly resolved MR data acquisition
allows sensitive tracking of MSC for several months without any biological effects.
CLINICAL RELEVANCE/APPLICATION
Against the standard of knowledge iron deposits within the MSC have been detectable even six months after injection; furthermore,
there was a very good correlation to histological findings. As a consequence, MRI can serve as a valuable tool to identify MSC
immediately after sucsessfull application as well as verification of local persistence.
MI207-SDSUB4
MRI Contrasts Induced by Direct Saturation: Demonstration in the Central Nerve System
Station #4
Participants
Rongwen Tain, PhD, Chicago, IL (Presenter) Nothing to Disclose
Feliks Kogan, PhD, Stanford, CA (Abstract Co-Author) Nothing to Disclose
Xiaohong J. Zhou, PhD, Houston, TX (Abstract Co-Author) Nothing to Disclose
Kejia Cai, PhD, Chicago, IL (Abstract Co-Author) Nothing to Disclose
PURPOSE
A frequency selective saturation RF pulse across a broad frequency range produces a Z-spectrum. This Z-sprectrum receives
contributions from components mainly including direct saturation (DS) of bulk water, magnetization transfer, chemical exchange
saturation transfer, and Nuclear Overhauser Enhancement. When a weak saturation regime is applied, such as B1rms< 50 Hz and
duration < 500 ms, the Z-spectrum is mainly attributed to the DS spectrum, characterized by a Lorentzian-shape. The DS
magnitude at a given frequency offset has been used to measure iron content in brain. Additionally, the position of maximum DS has
been exploited to map B0 field variations (ΔB0). In this study, we investigate additional contrasts revealed by analyzing DS
spectrum.
METHOD AND MATERIALS
This study was performed under an approved IRB protocol. DS spectra within ±1 ppm were acquired from the brain and cervical
spinal cord of healthy subjects at 3T scanner with a 32 channel head-coil and a 16 channel head and neck spine coil, respectively.
The pulse sequence consists of a pre-saturation pulse (B1rms = 12.2 Hz for brain, 24.4 Hz for spinal cord, 200 ms) followed by a 2D
single-shot SPGR readout. The DS data was fitted pixel by pixel with a Lorentzian function to produce B0 field, DS line-width, and
DS magnitude maps. In addition, simulations with Bloch equations were performed to correlate with experimental data.
RESULTS
Beside the ΔB0 map, the Lorentzian fitting of data obtained from both brain and spinal cord was used to produce new maps based
on the DS line-width and magnitude. In the brain and spinal cord respectively, the DS line-width of gray matter is slightly narrower
than that of the white matter. As expected, CSF gave the narrowest line-widths. DS amplitude was reversed. Simulation further
showed that DS line-width is positively proportional to 1/T2 and inversely proportional to 1/T1. DS magnitude was found to be
proportional to proton density.
CONCLUSION
Two quantitative contrasts (DS line-width and magnitude) that reflect tissue relaxation rates and proton density have been
demonstrated in the human CNS tissues.
CLINICAL RELEVANCE/APPLICATION
The discovered contrasts induced by DS MRI have the clinically potential for characterization of normal and pathological tissues.
RC123
Molecular Imaging Mini-Course: Basics of Molecular Imaging
Sunday, Nov. 29 2:00PM - 3:30PM Location: E451A
CT
MI
NM
PH
AMA PRA Category 1 Credits ™: 1.50
ARRT Category A+ Credits: 1.50
FDA
Discussions may include off-label uses.
Participants
Sub-Events
RC123A
Developing Molecular Imaging Agents
Participants
Julie L. Sutcliffe, PhD, Sacramento, CA, ([email protected]) (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
1) Describe the ideal properties of a molecular imaging agent. 2) Describe the in vitro validation of the molecular imaging agent. 3)
Describe specific examples of successful molecular imaging agents.
RC123B
Instrumentation (PET and CT) and Image Reconstruction
Participants
John Sunderland, PhD, Iowa City, IA, ([email protected]) (Presenter) Research Grant, Siemens AG
LEARNING OBJECTIVES
1) Identify the primary design components of a modern PET/CT system. 2)Design and implement a PET/CT quality control program
to assure high quality and quantitatively accurate clinical imaging. 3) Describe commonly used PET reconstruction algorithms and
the practical impact of reconstruction parameters upon image quality and quantitation.
ABSTRACT
Handout:John Sunderland
http://abstract.rsna.org/uploads/2015/15002826/RSNA Physics Recon Talk.pdf
RC123C
Basic Clinical Applications
Participants
Hubert J. Vesselle, MD, PhD, Seattle, WA (Presenter) Consultant, MIM Software Inc
ABSTRACT
ED015-MO
Molecular Imaging Monday Case of the Day
Monday, Nov. 30 7:00AM - 11:59PM Location: Case of Day, Learning Center
MI
AMA PRA Category 1 Credit ™: .50
Participants
Jonathan E. McConathy, MD, PhD, Saint Louis, MO (Presenter) Research Consultant, Eli Lilly and Company; Research Consultant,
Blue Earth Diagnostics Ltd; Research Consultant, Siemens AG; Research support, GlaxoSmithKline plc
Suzanne E. Lapi, PhD, Saint Louis, MO (Presenter) Research Grant, ImaginAB, Inc
Bernadette V. Marquez, PhD, Saint Louis, MO (Abstract Co-Author) Nothing to Disclose
Ephraim E. Parent, MD, PhD, Saint Louis, MO (Abstract Co-Author) Nothing to Disclose
Alexander Drzezga, MD, Cologne, Germany (Abstract Co-Author) Research Grant, Eli Lilly and Company; Speakers Bureau, Siemens
AG; Speakers Bureau, General Electric Company; Speakers Bureau, Piramal Enterprises Limited; Research Consultant, Eli Lilly and
Company; Research Consultant, Piramal Enterprises Limited; ; ; ; ; ;
Jason M. Warram, BS, Birmingham, AL (Abstract Co-Author) Nothing to Disclose
Kurt R. Zinn, DVM, PhD, Birmingham, AL (Abstract Co-Author) Nothing to Disclose
Eben Rosenthal, MD, Birmingham, AL (Abstract Co-Author) Research Grant, Novadaq Technologies Inc; Equipment support, Novadaq
Technologies Inc; Equipment support, Li-Cor Biosciences
TEACHING POINTS
1) The case of the day exhibit will highlight molecular imaging techniques currently available in clinical practice and new tracers
expected to become available in the near future. 2) Participants completing this exhibit will recognize the biodistribution of newer
molecular imaging agents, understand their mechanism of action, and be familiar with their clinical utility and potential causes of
diagnostic errors.
MSMI21
Molecular Imaging Symposium: Basics of Molecular Imaging
Monday, Nov. 30 8:30AM - 10:00AM Location: S405AB
BQ
MI
MR
US
AMA PRA Category 1 Credits ™: 1.50
ARRT Category A+ Credits: 1.50
FDA
Discussions may include off-label uses.
Participants
Jan Grimm, MD, PhD, New York, NY (Moderator) Nothing to Disclose
Zaver M. Bhujwalla, PhD, Baltimore, MD (Moderator) Nothing to Disclose
Sub-Events
MSMI21A
MI Using Radioactive Tracers
Participants
Jan Grimm, MD, PhD, New York, NY (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
1) In this course, we will discuss the various radio tracers and their applications in Molecular Imaging studies. Participants will
understand in which situations to use which radio tracers, what to consider when developing the imaging construct and what
controls to obtain for nuclear imaging studies. Examples will contain imaging with small molecules, with antibodies and nanoparticles
as well as with cells in order to provide the participants with examples how o correctly perform their imaging studies. Most of the
examples will be from the oncology field but their underlying principles are universally applicable to other areas as well.
ABSTRACT
Nuclear Imaging is currently the only true "molecular" imaging method utilized in clinic. It offers quantitative imaging of biological
processes in vivo. Therefore, it is not surprising that it is also highly frequented in preclinical imaging applications since it is
currently the only true quantitative imaging method. Multiple agents have been developed, predominantly for PET imaging but also
for SPECT imaging.In this talk, we will discuss the application of radio tracers to molecular imaging and what to consider. Common
pitfalls and mistakes as well as required measures to avoid these will be discussed. We will discuss various examples of imaging
constructs, ranging from small molecules to antibodies, nanoparticles and even cells. In addition, the imaging modalities will also
briefly discussed, including PET, SPECT and Cherenkov imaging.
MSMI21B
Molecular MRI and MRS
Participants
Zaver M. Bhujwalla, PhD, Baltimore, MD, ([email protected]) (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
To define the role of MRI and MRS in molecular and functional imaging and cover specific applications in disease processes. The
primary focus will be advances in novel theranostic approaches for precision medicine.
ABSTRACT
With an array of functional imaging capabilities, magnetic resonance imaging (MRI) and spectroscopy (MRS) techniques are valuable
in obtaining functional information, but the sensitivity of detection is limited to the 0.1-1 mM range for contrast agents and
metabolites, respectively. Nevertheless, MRI and MRS are finding important applications in providing wide-ranging capabilities to
tackle key questions in cancer and other diseases with a 'molecular-functional' approach. An overview of these capabilities and
examples of MR molecular and functional imaging applications will be presented with a focus on theranostic imaging for precision
medicine.
MSMI21C
Nanoparticles
Participants
Heike E. Daldrup-Link, MD, Palo Alto, CA (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
1) To understand important safety aspects of USPIO. 2) To recognize the value of immediately clinically applicable iron oxide
nanoparticles for tumor MR imaging applications. 3) To learn about clinically relevant new developments of theranostic USPIO.
ABSTRACT
Nanoparticles Nanoscale materials can be employed to develop novel platforms for understanding, diagnosing, and treating diseases.
Integrating nanomedicine with novel multi-modality imaging technologies spurs the development of new personalized diagnostic
tests and theranostic (combined diagnostic and therapeutic) procedures. This presentation will provide an overview over the
safety, diagnostic applications and theranostic developments of clinically applicable ultrasmall superparamagnetic iron oxide
nanoparticles (USPIO). USPIO which are currently used for clinical applications include ferumoxytol (Feraheme), an FDA-approved
iron supplement, and ferumoxtran-10 (Combidex/Sinerem), which is currently undergoing renewed clinical trials in Europe. Safety
considerations for these agents will be discussed. Both compounds provide long lasting blood pool enhancement, which can be used
for MR angiographies and tissue perfusion studies. Subsequently, USPIO are slowly phagocytosed by macrophages in the
reticuloendothelial system (RES), which can be used to improve MRI detection of tumors in liver, spleen, lymph nodes and bone
marrow. A slow phagocytosis by macrophages in inflammations and high grade tumors can be used to grade the severity of the
disease process and monitor new immune-modulating therapies. Novel developments include synthesis of multi-functional
nanoparticles, which can be detected with two or more imaging modalities, as well as clinically applicable approaches for in vivo
tracking of stem cell therapies. Since USPIO are not associated with any risk of nephrogenic sclerosis, they can be used as
alternative contrast agents to gadolinium chelates in patients with renal insufficiency or in patients in whom creatinine lab values
are not available. Ongoing pre-clinical developments include the development of improved, targeted and activatable nanoparticle
formulations, which can further improve sensitivity, specificity and theranostic imaging capabilities.
MSMI21D
Contrast Ultrasound
Participants
Steven B. Feinstein, MD, Chicago, IL (Presenter) Research support, General Electric Company; Consultant, General Electric
Company; Investor, SonoGene LLC;
LEARNING OBJECTIVES
1) Inform: Clinical utility and safety of contrast enhanced ultrasound (CEUS) imaging. 2) Educate: Current diagnostic and
therapeutic approaches. 3) Introduce: Newer concepts for combined diagnostic and therapeutic applications.
MSMI21E
Quantitative Imaging Biomarkers
Participants
Richard L. Wahl, MD, Saint Louis, MO (Presenter) Research Consultant, Nihon Medi-Physics Co, Ltd;
LEARNING OBJECTIVES
1) Identify at least one method of assessing anatomic tumor response quantitatively. 2) Identify at least one method of assessing
metabolic tumor response using FDG PET quantitative. 3) Identify an MRI quantitative metric which is associated with cellularity of
biological processes.
ABSTRACT
Radiology initially developed as an analog imaging method in which non quantitative data were interpreted in a 'qualitative and
subjective' manner. This approach has worked well, but modern imaging also is digital, quantitative and has the opportunity for
more quantitative and objective interpretations. This lecture will focus on a few areas in which quantitative imaging is augmenting
qualitative image assessments to lead to more precise interpretation of images. Examples of such an approach can include
measuremental of tumor 'metabolic' activity using formalisms such as PERCIST 1.0; methods of assessment of tumor size and
volumes using the RECIST 1.1 and emerging formalisms and metrics of tumor heterogeneity, density, receptor density, diffusion,
vascular permeability and elasticity using techniques incuding PET/SPECT, MRI, CT and ultrasound. With quantitative imaging, the
opportunity to move from qualitative methods to precise in vivo quantitative pheontyping is a real one, with a quantitative
'phenome' complementing other 'omics' such as genomics. However, the quality of quantitation may vary and close attention to
technical methodologies and process are required to have reliable and accurate quantitation. The RSNA QIBA effort will be briefly
reviewed as one approach to achieve precise quantiative phenotyping. Examples of the use of quantitative phenotyping to inform
patient management will be discussed.
Honored Educators
Presenters or authors on this event have been recognized as RSNA Honored Educators for participating in multiple qualifying
educational activities. Honored Educators are invested in furthering the profession of radiology by delivering high-quality
educational content in their field of study. Learn how you can become an honored educator by visiting the website at:
https://www.rsna.org/Honored-Educator-Award/
Richard L. Wahl, MD - 2013 Honored Educator
RC223
Molecular Imaging Mini-Course: Advanced Molecular Imaging
Monday, Nov. 30 8:30AM - 10:00AM Location: E350
MI
MR
NM
PH
AMA PRA Category 1 Credits ™: 1.50
ARRT Category A+ Credits: 1.50
FDA
Discussions may include off-label uses.
Participants
Sub-Events
RC223A
Novel Tracers
Participants
Timothy R. DeGrado, PhD, Rochester, MN (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
1) Identify the major considerations when developing a novel molecular imaging probe. 2) Compare the strengths and weaknesses
of the various imaging modalities with regard to probe development and implementation. 3) Define appropriate experiments for probe
validation. 4) Gain an understanding of the process of translation of a probe to clinical practice.
ABSTRACT
Molecular imaging is rapidly advancing as new imaging biomarkers are invented to allow noninvasive assessment of biochemical
function. Those who embark on the process of developing novel probes come to know the excitement of imaging biological
processes for the first time, but are also well aware of the great effort and many pitfalls that can impede progress. This
introductory lecture will provide an overview of the process of molecular imaging probe conception, development, preclinical
validation, and translation. Specific examples will be used to illustrate the presenter's experience with meeting these challenges.
RC223B
Novel Instrumentation (PET/MR)
Participants
Ciprian Catana, MD, PhD, Charlestown, MA (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
1) Distinguish the technical approaches that have been proposed for integrating PET and MRI for the purpose of simultaneous data
acquisition. 2) Evaluate the latest methodological developments in PET/MRI for improving PET data quantification. 3) Incorporate
simultaneous PET/MRI techniques into research and clinical projects.
ABSTRACT
RC223C
Molecular Imaging with MR
Participants
Bruce R. Rosen, MD, PhD, Charlestown, MA, ([email protected]) (Presenter) Research Consultant, Siemens AG
MSMI22
Molecular Imaging Symposium: Neurologic MI Applications
Monday, Nov. 30 10:30AM - 12:00PM Location: S405AB
NR
MI
AMA PRA Category 1 Credits ™: 1.50
ARRT Category A+ Credits: 1.50
FDA
Discussions may include off-label uses.
Participants
Satoshi Minoshima, MD, PhD, Salt Lake City, UT, ([email protected]​ ) (Moderator) Royalties, General Electric Company;
Consultant, Hamamatsu Photonics KK; Research Grant, Hitachi, Ltd; Research Grant, Nihon Medi-Physics Co, Ltd; Research Grant,
Astellas Group; Research Grant, Seattle Genetics, Inc;
Peter Herscovitch, MD, Bethesda, MD (Moderator) Nothing to Disclose
Sub-Events
MSMI22A
Overview of MI in Neurology
Participants
Satoshi Minoshima, MD, PhD, Salt Lake City, UT (Presenter) Royalties, General Electric Company; Consultant, Hamamatsu Photonics
KK; Research Grant, Hitachi, Ltd; Research Grant, Nihon Medi-Physics Co, Ltd; Research Grant, Astellas Group; Research Grant,
Seattle Genetics, Inc;
LEARNING OBJECTIVES
1) Learn recent development of molecular imaging in the field of neurosciences. 2) Understand technologies used in molecular brain
imaging. 3) Discuss opportunities and challenges in molecular brain imaging.
MSMI22B
MI in Dementia
Participants
Alexander Drzezga, MD, Cologne, Germany (Presenter) Research Grant, Eli Lilly and Company; Speakers Bureau, Siemens AG;
Speakers Bureau, General Electric Company; Speakers Bureau, Piramal Enterprises Limited; Research Consultant, Eli Lilly and
Company; Research Consultant, Piramal Enterprises Limited; ; ; ; ; ;
LEARNING OBJECTIVES
1) Gain overview on types of molecular neuropathology involved in the development of different forms of dementia and understand
currently discussed disease concepts. 2) Learn about the currently available methods for imaging molecular pathology such as
amyloid-deposition and tau-aggregation in dementia and their current status of validation. 3) Gain insights on the clinical value of
the individual available methods and their combination with regard to earlier detection, more reliable diagnosis and therapy
monitoring of disease.
MSMI22C
MI in Movement Disorders
Participants
Kirk A. Frey, MD, PhD, Ann Arbor, MI (Presenter) Consultant, MIM Software Inc; Consultant, Siemens AG; Consultant, Eli Lilly and
Company; Stockholder, General Electric Company; Stockholder, Novo Nordisk AS; Stockholder, Bristol-Myers Squibb Company;
Stockholder, Merck & Co, Inc; Stockholder, Medtronic, Inc
MSMI22D
Clinical Translation and Approval
Participants
Peter Herscovitch, MD, Bethesda, MD (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
1) Discuss the FDA approval process for diagnostic radiopharmaceuticals Describe the current status of CMS coverage for
diagnostic radiopharmaceuticals. 2) Describe the current status of CMS coverage for amyloid PET radiopharmaceuticals and
coverage with evidence development (CED).
ABSTRACT
The final steps in clinical translation of molecular imaging radiopharmaceuticals for neurological studies are approval by the U.S.
Food and Drug Administration (FDA) for marketing and by insurance carriers for reimbursement. Given the age of patients most likely
to require brain imaging studies for neurodegenerative disorders, coverage approval by the U.S. Centers for Medicare and Medicaid
("Medicare") is crucial. This talk will discuss the steps required that lead to FDA approval of a radiopharmaceutical, including the IND
process and Phase 1, 2, and 3 clinical trials. It should be noted that FDA approval does not necessarily lead to Medicare approval,
especially for PET agents. The CMS approval process will be outlined, including the increasing need to demonstrate the ability of
PET imaging to provide improved health outcomes. CMS coverage with evidence development (CED) of PET amyloid imaging agents
will be described.
MSMI22E
Emerging Molecular Brain Imaging
Participants
Jonathan E. McConathy, MD, PhD, Saint Louis, MO, ([email protected]) (Presenter) Research Consultant, Eli Lilly and
Company; Research Consultant, Blue Earth Diagnostics Ltd; Research Consultant, Siemens AG; Research support, GlaxoSmithKline
plc
LEARNING OBJECTIVES
1) Participants will be familiar with newer molecular imaging approaches to dementia including tracers targeting tau, alphasynuclein, and neuroinflammation as well as simultaneous PET/MRI which is particularly well-suited to neuroimaging.
ABSTRACT
Imaging biomarkers for Alzheimer's disease (AD) and other neurodegenerative diseases are playing increasingly important roles in
both research and patient care. Many neurodegenerative diseases involve the deposition of characteristic proteins including
amyloid, tau, and alpha-synuclein which are target for molecular neuroimaging and potentially for therapy. Additionally, processes
such as neuroinflammation appear to contribute to the pathophysiology of many neurodegenerative diseases including AD. In this
talk, these newer approaches to molecular neuroimaging in dementia will be discussed including their potential clinical applications in
patients with cognitive impairment and dementia.
MIS-MOA
Molecular Imaging Monday Poster Discussions
Monday, Nov. 30 12:15PM - 12:45PM Location: S503AB
MI
AMA PRA Category 1 Credit ™: .50
Participants
Homer A. Macapinlac, MD, Houston, TX (Moderator) Nothing to Disclose
Sub-Events
MI208-SDMOA1
Relationship between Calorie Consumption and Brain Glucose Metabolism in the Patients with Chronic
Severe Brain Injury - A Study using Brain 18F-FDGPET
Station #1
Participants
Yoshio Uchino, MD, PhD, Chiba-City, Japan (Presenter) Nothing to Disclose
PURPOSE
In the chronic severe brain injury (cs-TBI) patients, it is known that requirement level of intake calorie is lower as compared to
healthy subjects. Low physical activity and reduction of muscle mass have been mentioned as reasons of low calorie consumption,
but a decrease in brain glucose metabolisn can be considered as another important factor. In the cs-TBI patients, we compared
the actual calorie intake and semi-quantitative values obtained from brain FDGPET, and examined the relationship between brain
glucose metabolism and calorie consumption.
METHOD AND MATERIALS
This study included 39 cases with cs-TBI patients, age ranging 20 to 75 years (41±16yrs, mean±SD). For the measurement method
of brain glucose metabolism with FDGPET, we placed the volume of interest (VOI) including the whole brain automatically, and the
average standardized uptake value (SUVavg) was obtained. The whole brain uptake value (WBu) was defined as the value of
multiplying SUVavg by the brain volume. Basal Energy Expenditure (BEE), considering the active factor, was obtained by the Harris
Benedict Equation. Activitiy of the patients was evaluated by using level determination score (CHIBA score). We classified the
patients into two groups (low WBu (WBu<50): A group, 27 cases, moderate WBu (WBu>=50): B group, 12 patients), and examined
the relationship among WBu, calorie intake, activity.
RESULTS
In 38 cases out of 39, calorie intake of the patients was below the BEE, but there was no problem in their nutritional condition.
Calorie intake and activity of each group was significantly higher in the group B (calorie, A: 1093±200Kcal, B: 1390±266Kcal,
p<0.01), (activity, A: 20±17, B: 53±20, p<0.01). Regard to calorie intake and activity level, a positive correlation was observed
(R^2=0.51), and correlation was also observed between calorie intake and WBu (R^2=0.53).
CONCLUSION
In the chronic severe brain injury patients, there is a relationship between the caloric needs and the degree of brain glucose
metabolism. Physical activity of the patients is generally low, so the proportion of calorie consumption of the brain is high degree
against that of the whole body.
CLINICAL RELEVANCE/APPLICATION
In the chronic severe brain injury patients, there is a relationship between the daily caloric needs and the degree of brain glucose
metabolism. When estimating their intake calorie, we need to take into account the degree of glucose metabolism of the brain.
MI209-SDMOA2
Phase Information Enables Amyloid Plaque Imaging of the Human Brain on Clinical MRI
Station #2
Participants
Nan Kurehana, MMedSc, Kumamoto, Japan (Presenter) Nothing to Disclose
Tetsuya Yoneda, PhD, Kumamoto, Japan (Abstract Co-Author) Nothing to Disclose
Koji Hashimoto, Kumamoto, Japan (Abstract Co-Author) Nothing to Disclose
Machiko Tateishi, Kumamoto, Japan (Abstract Co-Author) Nothing to Disclose
Minako Azuma, Kumamoto, Japan (Abstract Co-Author) Nothing to Disclose
Mika Kitajima, MD, Kumamoto, Japan (Abstract Co-Author) Nothing to Disclose
Mamoru Hashimoto, Kumamoto, Japan (Abstract Co-Author) Nothing to Disclose
Sosuke Yoshinaga, Kumamoto, Japan (Abstract Co-Author) Nothing to Disclose
Akihiko Kuniyasu, Kumamoto, Japan (Abstract Co-Author) Nothing to Disclose
Hiroaki Terasawa, Kumamoto, Japan (Abstract Co-Author) Nothing to Disclose
Toshinori Hirai, MD, PhD, Miyazaki, Japan (Abstract Co-Author) Nothing to Disclose
Manabu Ikeda, Kumamoto, Japan (Abstract Co-Author) Nothing to Disclose
Yasuyuki Yamashita, MD, Kumamoto, Japan (Abstract Co-Author) Consultant, DAIICHI SANKYO Group
PURPOSE
The purpose of this study was to show that phase imaging (PhAse DiffeRence Enhanced imaging: PADRE) could correctly delineate
density of AP in the brain cortex on the MRI image via animal study. This animal study was applied to human cases using clinical
cases and leaded to reasonable signal appearances which might be corresponding to AP staining in human brain.
METHOD AND MATERIALS
For animal study, we have used APP23 mouse which showed AP loading in the brain with different age of months (from 9 to 16 m/o,
in-vivo/ex-vivo). Animal scans were performed on 7T-MRI (BioSpec 70/20, Bruker) and PADRE images were obtained from magnitude
and phase images. PADRE equipped phase band selection in order to enhance AP location correctly. We suggested, in this study,
double Gaussian model of phase distribution for cortex region so as to have correct phase bands corresponding to AP loading. AP
signal was evaluated as signal density (will be defined in the presentation) in order to fit our study to clinical MRI images because
of regulation of spatial resolution in clinical cases. Clinical images were obtained 3T-MRI (Achieva 3.0T, Philips, scan duration < 4
min.) and reconstructed by PADRE with suggested Gaussian model.
RESULTS
We confirmed that signal locations of PADRE images in APP23 mouse brain were coincident to one of immunostaining images. In
contrast, control mouse brain did not show any signals in both of PADRE and immunostaining images. Signal density of PADRE and
immunosgaining images were changed from 0 to less than 10%. We found signal density of PADRE images showed high linear
correlation (> 0.85, p < 0.01) by increasing age. Grading examination by radiologists showed clinical PADRE AD images represented
locational dependence of signal; high signal at parietal gyrus (cuneus, precuneus) and superior temporal gyrus (p < 0.01), but low
signal at superior frontal gyrus by comparison with control cases.
CONCLUSION
PADRE images with Gaussian model could show true AP density even for the lower signal density (< 3%). Therefore, PADRE has high
potential for clinical screening for AP detection, which may be applicable for preclinical examination for AD using clinical MRI.
CLINICAL RELEVANCE/APPLICATION
This study enables us to quantify amyloid plaque (AP) accumulation in the cerebral cortex regions of human brain on the MRI image,
which makes us precisely diagnose Alzheimer's disease (AD).
MI210-SDMOA3
SPECT/CT with 99mTc-sestamibi in the Differentiation between Recurrent Gliomas and Radionecrosis
Station #3
Participants
Rafael F. Nunes, MD, Sao Paulo, Brazil (Presenter) Nothing to Disclose
Artur Coutinho, MD, Sao Paulo, Brazil (Abstract Co-Author) Nothing to Disclose
Aline Sgnolf, MD, Sao Jose do Rio Preto, Brazil (Abstract Co-Author) Nothing to Disclose
Marcelo A. Queiroz, MD, Sao Paulo, Brazil (Abstract Co-Author) Nothing to Disclose
Luiz G. Lima, MD, Sao Paulo, Brazil (Abstract Co-Author) Nothing to Disclose
Romulo H. do Vale, MD, Sao Paulo, Brazil (Abstract Co-Author) Nothing to Disclose
Rodolfo F. Nunes, MD, Sao Paulo, Brazil (Abstract Co-Author) Nothing to Disclose
Carla R. Ono, MD,PhD, Sao Paulo, Brazil (Abstract Co-Author) Nothing to Disclose
Fabiana D. Hirata, MD, Sao Paulo, Brazil (Abstract Co-Author) Nothing to Disclose
Olavo Feher, MD, Sao Paulo, Brazil (Abstract Co-Author) Nothing to Disclose
Helder Picarelli, MD,PhD, Sao Paulo, Brazil (Abstract Co-Author) Nothing to Disclose
Carlos A. Buchpiguel, MD, Sao Paulo, Brazil (Abstract Co-Author) Nothing to Disclose
PURPOSE
It is still a challenge to differentiate radionecrosis from recurrence after radiotherapy of brain tumors. 99mTc-sestamibi has been
tested to differentiate tumor from necrosis in high-grade gliomas (HGG). Low spatial resolution represents a major limitation for
SPECT, which could be partially overcome by hybrid imaging such as the SPECT/CT. This study investigated the role of SPECT/CT
with 99mTc-sestamibi and compared its accuracy with multiparametric magnetic resonance imaging (MRI) in differentiating tumor
from necrosis in HGG.
METHOD AND MATERIALS
Fourteen consecutive patients clinically suspected of HGG recurrence underwent preoperative SPECT/CT and MRI. SPECT/CT was
assessed by visual and semiquantitative analysis. Images were blindly evaluated and then assigned as positive, negative or
indeterminate (not included for sensitivity - Se, or specificity - Sp evaluation). The ratio between a region-of-interest (ROI) drawn
in the tumor and a contralateral mirror area in the opposite hemisphere was obtained 15 (early) and 120 (late) min post-injection
(T/C ratio). Histologic confirmation after surgery was performed in all cases as the reference method for confirming recurrence.
RESULTS
Histopathological data showed recurrence of HGG in 12/14 patients, and radionecrosis in 2/14. SPECT/CT studies were: 11 positive
(11 true positive), 2 negative (1 true negative), 1 indeterminate (negative at biopsy). MRI studies were: 7 positive (7 true
positive), 3 negative (2 true negative), 4 indeterminate (3 positive in biopsy). SPECT/CT showed Se = 91.7% and Sp = 100%. MRI
showed Se = 87.5% and Sp = 100%. When using both methods, no patient was classified as indeterminate. One false negative
SPECT/CT study was due to one infratentorial lesion. Two out of 4 indeterminate lesions on MRI were clearly positive on SPECT/CT,
and biopsy proved them as gliomas. Mean (SD) T/C ratio was 15.3 (±7.8) in the early images and 24.9 (±9.9) in the late images. All
positive cases showed a T/C ratio higher than 7.5 in early images.
CONCLUSION
SPECT/CT may be a useful complementary tool in HGG, helping distinguishing viable tumor from radionecrosis, reducing falsenegative results from MRI.
CLINICAL RELEVANCE/APPLICATION
SPECT/CT with 99mTc-sestamibi, a less expensive technology than PET/CT, added valuable complementary information to MRI in
selected clinical patients with suspected recurrent HGG.
MIS-MOB
Molecular Imaging Monday Poster Discussions
Monday, Nov. 30 12:45PM - 1:15PM Location: S503AB
MI
AMA PRA Category 1 Credit ™: .50
Participants
Homer A. Macapinlac, MD, Houston, TX (Moderator) Nothing to Disclose
Sub-Events
MI239-SDMOB1
Correlating Advanced MR Techniques with MIB Index to Grade and Prognosticate Gliomas: Can
Perfusion and Diffusion MR Solve the Riddle?
Station #1
Participants
Sureshkumar G, MBBS, Mumbai, India (Presenter) Nothing to Disclose
Abhishek Mahajan, MD, Mumbai, India (Abstract Co-Author) Nothing to Disclose
Ashita Rastogi, MBBS, MD, Mumbai, India (Abstract Co-Author) Nothing to Disclose
Nikshita A. Jain, MBBS, Mumbai, India (Abstract Co-Author) Nothing to Disclose
Somesh Singh, MBBS, Mumbai, India (Abstract Co-Author) Nothing to Disclose
Santhosh K. GeethaVirupakshappa, MD, MBBS, Mumbai, India (Abstract Co-Author) Nothing to Disclose
Aliasgar Moiyadi, MChir, Mumbai, India (Abstract Co-Author) Nothing to Disclose
Epari Sridhar, Mumbai, India (Abstract Co-Author) Nothing to Disclose
Rakesh Jalali, Mumbai, India (Abstract Co-Author) Nothing to Disclose
PURPOSE
To analyze the MIB index and grade of gliomas by assessment of MR tumor perfusion (rCBV values) and MR diffusion (ADC values)
imaging and to determine the correlation between MR findings and MIB index.
METHOD AND MATERIALS
Available data set at our institute, containing no linkage to patient identifiers was used to retrospectively evaluate presurgical MR
of a total of 68 patients with gliomas. In 22 patients the MRI scanning was not adequate hence these were excluded from the
study. Of the 46 patients with satisfactory imaging as reviewed by two radiologists, MR perfusion (rCBV values)was available for 32
patients and MR diffusion (ADC values) for 35 patients. Correlationwas done between grade of gliomas and MIB1 (Ki 67) index as
reported by pathologists post operatively.
RESULTS
rCBV was shown to correlate with MIB1(Ki 67) index, with low values suggestive of low grade lesions and hence favorable
prognosis. rCBV threshold value of 1.75 revealed a sensitivity of 88%, specificity of 33%, positive predictive value of 60 % and
negative predictive value of 71%.Similarly high ADC values were found to be associated with low MIB1(Ki 67) index. The cut-off
value of 1.185 × 10-3 mm2/s for the minimum ADC showed sensitivity of 83.3 % and specificity of 53 % in the discrimination of
high- and low-grade gliomas withpositive predictive value of 65.2% and negative predictive value of 75%.
CONCLUSION
Our results demonstrate that rCBV and ADC analysis is sensitive for preoperatively assessing the MIB index in gliomas and is a
promising adjunct to conventional imaging features to provide deeper insight to the underlying biology of gliomas that may help in
grading and prognostication. The findings of our study is in keeping with the current literature.alues were found to be associated
with low MIB1(Ki 67) index. The cut-off value of 1.185 × 10-3 mm2/s for the minimum ADC showed sensitivity of 83.3 % and
specificity of 53 % in the discrimination of high- and low-grade gliomas withpositive predictive value of 65.2% and negative
predictive value of 75%.
CLINICAL RELEVANCE/APPLICATION
Can be used to prognosticate patients, guide treatment and follow up to detect early recurrence.
MI241-SDMOB3
An Open-Science Toolkit for Image Texture Analysis of PET Oncology Images
Station #3
Participants
Paul E. Kinahan, PhD, Seattle, WA (Presenter) Research Grant, General Electric Company; Co-founder, PET/X LLC
Larry A. Pierce II, PhD, Seattle, WA (Abstract Co-Author) Nothing to Disclose
Matthew J. Nyflot, PhD, Seattle, WA (Abstract Co-Author) Nothing to Disclose
David R. Haynor, MD, PhD, Seattle, WA (Abstract Co-Author) Nothing to Disclose
Art Chaovalitwongse, PhD, Seattle, WA (Abstract Co-Author) Nothing to Disclose
Hannah M. Linden, MD, Seattle, WA (Abstract Co-Author) Nothing to Disclose
Tobias R. Chapman, MD, MS, Seattle, WA (Abstract Co-Author) Nothing to Disclose
Stephen R. Bowen, PhD, Seattle, WA (Abstract Co-Author) Nothing to Disclose
PURPOSE
The analysis of PET image textural feature metrics to determine correlations with clinical outcomes is a rapidly expanding field.
However, there is a currently a lack of understanding of the stability of these metrics, as well as a lack of standards to assess
repeatability and error bounds. Our goal is to analyze these variations and provide tools to both assess and reduce variance.
METHOD AND MATERIALS
We developed a prototype open-science texture analysis framework for PET oncology imaging. This includes: (1) A database of deidentified (i.e. shareable) test-retest FDG-PET/CT oncology images. (2) A computationally-efficient prototype open-source texture
analysis software package that has been extensively tested. (3) A reference synthetic test object for evaluating texture analysis
software packages. (4) A parametric texture-analysis approach that is independent of ROI definition for texture (not shape)
analyses. We then applied this approach to a subset of commonly used image texture metrics and evaluated their correlations
within-study and test-retest variation.
RESULTS
The prototype optimized open-source texture analysis package was tested with the reference synthetic test object and compared
with results from available texture analysis packages. Several discrepancies resulted, which were resolved by root-cause analysis.
Remaining discrepancies were identified as specific errors in the available texture analysis packages and/or errors in the underlying
formulae. Initial variability and stability estimates of image texture metrics were also provided. Applying the validated texture
analysis methods to the test-retest patent data demonstrated the potential for identifying which texture metrics are unstable, and
which have lower variability but are still sensitive to oncologic signals in the FDG-PET images.
CONCLUSION
The test-retest correlation analysis of commonly used image texture metrics demonstrated that the quantitative accuracy and
sensitivity of PET textural features is parameter and feature-dependent. Standards are needed to ensure that prospective studies
that incorporate textural features are properly designed to measure true effects that may impact clinical outcomes.
CLINICAL RELEVANCE/APPLICATION
Textural features have been correlated to clinical data such as survival, clinical response, and prognosis in cervical, head and neck,
lung, esophageal, rectal, and breast cancers.
MSMI23
Molecular Imaging Symposium: Oncologic MI Applications
Monday, Nov. 30 1:30PM - 3:00PM Location: S405AB
GU
MI
MR
OI
RO
AMA PRA Category 1 Credits ™: 1.50
ARRT Category A+ Credits: 1.50
FDA
Discussions may include off-label uses.
Participants
Peter L. Choyke, MD, Rockville, MD, ([email protected]) (Moderator) Researcher, Koninklijke Philips NV Researcher, General Electric
Company Researcher, Siemens AG Researcher, iCAD, Inc Researcher, Aspyrian Therapeutics, Inc Researcher, ImaginAb, Inc
Researcher, Aura Biosciences, Inc
Umar Mahmood, MD, PhD, Charlestown, MA (Moderator) Research Grant, Sabik Medical Inc; Advisory Board, Blue Earth Diagnostics
Limited;
LEARNING OBJECTIVES
1) To understand the role of molecular imaging in cancer therapy. 2) To understand the impact that new molecular imaging agents
could have on drug development. 3) To understand the barriers facing the development of new molecular imaging agents.
ABSTRACT
Molecular Imaging is expanding in many new directions. Most research is being performed for PET and SPECT agents. However,
optical and MRI agents are also being developed. Molecular Imaging can play a role in accelerating the development and approval of
new cancer therapeutics by quantifying the impact drugs have in early Phase studies and by selecting the most appropriate
patients for trials. Molecular Imaging agents can be useful in determining the utility and mechanism of actions of drugs that are
already approved and may provide insights to oncologists regarding the best treatment combinations for individual patients.
Molecular Imaging methods have already expanded our knowledge of cancer behavior and this will ultimately lead to new forms of
the therapy that will one day cure this dreaded disease.
Sub-Events
MSMI23A
Overview of MI in Oncology
Participants
Peter L. Choyke, MD, Rockville, MD, ([email protected]) (Presenter) Researcher, Koninklijke Philips NV Researcher, General Electric
Company Researcher, Siemens AG Researcher, iCAD, Inc Researcher, Aspyrian Therapeutics, Inc Researcher, ImaginAb, Inc
Researcher, Aura Biosciences, Inc
LEARNING OBJECTIVES
1) To understand the broad spectrum of activities in molecular imaging including PET, SPECT, optical and MRI. 2) To understand the
potential impact of Molecular Imaging on cancer treatment.
ABSTRACT
Molecular Imaging is expanding at a rapid rate. This overview will provide a panoramic view of the field of Molecular Imaging and
major trends that are emerging among the different modalities, PET, SPECT, optical, ultrasound and MRI that constitute molecular
imaging.
MSMI23B
Hyperpolarized MRI of Prostate Cancer
Participants
Daniel B. Vigneron, PhD, San Francisco, CA (Presenter) Research Grant, General Electric Company
LEARNING OBJECTIVES
View learning objectives under main course title.
MSMI23C
Radiogenomics
Participants
Michael D. Kuo, MD, Los Angeles, CA (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
1) To discuss the principles behind radgiogenomics and to highlight areas of clinical application and future development.
ABSTRACT
MSMI23D
Somatastatin Receptor Imaging
Participants
Ronald C. Walker, MD, Nashville, TN, ([email protected]) (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
1) Describe the advantages of 68Ga-somatostatin PET/CT over 111In-DTPA-octreotide ]imaging. 2) Detect patients likely to benefit
1) Describe the advantages of 68Ga-somatostatin PET/CT over 111In-DTPA-octreotide ]imaging. 2) Detect patients likely to benefit
from peptide receptor radiotherapy (PRRT).
ABSTRACT
68Ga-labeled somatostatin analogs (DOTATATE, DOTATOC and DOTANOC) PET/CT imaging provides higher resolution scans than
111In-DTPA-octreotide with less radiation, comparable cost, and imaging completion within 2 hours vs. 2-3 days. 68Gasomatostatin analogs have a higher impact on care than 111In-DTPA-octreotide, including superior ability to identify patients likely
to benefit from PRRT. This activity will provide results from the literature and the author's experience to illustrate the advantages of
68Ga-based PET/CT imaging of neuroendocrine tumors.
Active Handout:Ronald Clark Walker
http://abstract.rsna.org/uploads/2015/15003715/MSMI23D.pdf
MSMI23E
Multimodal MI in Oncology
Participants
Umar Mahmood, MD, PhD, Charlestown, MA (Presenter) Research Grant, Sabik Medical Inc; Advisory Board, Blue Earth Diagnostics
Limited;
LEARNING OBJECTIVES
1) To understand strengths of various imaging modalities for specific target/disease assessment.
ABSTRACT
Each imaging modality has a set of characteristics that helps define optimal use. These constraints include sensitivity, depth of
imaging, integration time for signal, and radiation dose, among other factors. Understanding when each modality can be used and
when combining the relative strengths of differerent modalities can be synergistic allows greater molecular information to be
acquired.
MSMI24
Molecular Imaging Symposium: Case-based MI
Monday, Nov. 30 3:30PM - 5:00PM Location: S405AB
CA
NR
VA
MI
RO
AMA PRA Category 1 Credits ™: 1.50
ARRT Category A+ Credits: 1.50
FDA
Discussions may include off-label uses.
Participants
Vikas Kundra, MD, PhD, Houston, TX (Moderator) License agreement, Introgen Therapeutics, Inc
Jeffrey T. Yap, PhD, Salt Lake City, UT (Moderator) Nothing to Disclose
LEARNING OBJECTIVES
1) ldentify molecular imaging. 2) Comprehend the basis of aspects of molecular imaging. 3) Describe molecular imaging performed in
a radiology setting.
ABSTRACT
This course will describe molecular imaging, identify the mechanisms of some aspects of molecular imaging, and give examples of
molecular imaging in oncology. Cases will include those from current practice. Mechanisms and scientific basis of examples will be
discussed. Sample applications will be discussed and illustrated. Translational examples, including those that have good potential for
clinical application, will be used to illustrate interesting aspects of molecular imaging in oncology.
Sub-Events
MSMI24A
Oncology
Participants
Vikas Kundra, MD, PhD, Houston, TX (Presenter) License agreement, Introgen Therapeutics, Inc
LEARNING OBJECTIVES
View learning objectives under main course title.
MSMI24B
Neurology
Participants
Rathan M. Subramaniam, MD, PhD, Baltimore, MD, ([email protected]) (Presenter) Travel support, Koninklijke Philips NV
LEARNING OBJECTIVES
View learning objectives under main course title.
MSMI24C
Cardiology
Participants
Robert J. Gropler, MD, Saint Louis, MO (Presenter) Advisory Board, Bracco Group Advisory Board, GlaxoSmithKline plc Advisory
Board, Pfizer Inc Advisory Board, Bayer AG Research Grant, GlaxoSmithKline plc Research Grant, Pfizer Inc Research Grant, Clinical
Data, Inc Research Grant, Lantheus Medical Imaging, Inc
LEARNING OBJECTIVES
View learning objectives under main course title.
MSMI24D
Vascular Inflammation
Participants
Chun Yuan, PhD, Seattle, WA (Presenter) Research Grant, Koninklijke Philips NV; Consultant, Koninklijke Philips NV; ;
LEARNING OBJECTIVES
View learning objectives under main course title.
MSMI24E
Instrumentation
Participants
Jeffrey T. Yap, PhD, Salt Lake City, UT (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
View learning objectives under main course title.
ED015-TU
Molecular Imaging Tuesday Case of the Day
Tuesday, Dec. 1 7:00AM - 11:59PM Location: Case of Day, Learning Center
MI
AMA PRA Category 1 Credit ™: .50
Participants
Jonathan E. McConathy, MD, PhD, Saint Louis, MO (Presenter) Research Consultant, Eli Lilly and Company; Research Consultant,
Blue Earth Diagnostics Ltd; Research Consultant, Siemens AG; Research support, GlaxoSmithKline plc
Suzanne E. Lapi, PhD, Saint Louis, MO (Presenter) Research Grant, ImaginAB, Inc
Bernadette V. Marquez, PhD, Saint Louis, MO (Abstract Co-Author) Nothing to Disclose
Ephraim E. Parent, MD, PhD, Saint Louis, MO (Abstract Co-Author) Nothing to Disclose
Alexander Drzezga, MD, Cologne, Germany (Abstract Co-Author) Research Grant, Eli Lilly and Company; Speakers Bureau, Siemens
AG; Speakers Bureau, General Electric Company; Speakers Bureau, Piramal Enterprises Limited; Research Consultant, Eli Lilly and
Company; Research Consultant, Piramal Enterprises Limited; ; ; ; ; ;
Farrokh Dehdashti, MD, Saint Louis, MO (Abstract Co-Author) Nothing to Disclose
Ron Bose, MD, PhD, Saint Louis, MO (Abstract Co-Author) Speaker, Novartis AG; Speaker, F. Hoffmann-La Roche Ltd; Consultant,
F. Hoffmann-La Roche Ltd
TEACHING POINTS
1) The case of the day exhibit will highlight molecular imaging techniques currently available in clinical practice and new tracers
expected to become available in the near future. 2) Participants completing this exhibit will recognize the biodistribution of newer
molecular imaging agents, understand their mechanism of action, and be familiar with their clinical utility and potential causes of
diagnostic errors.
RC323
Molecular Imaging Mini-Course: Clinical Applications of Molecular Imaging - Neuro
Tuesday, Dec. 1 8:30AM - 10:00AM Location: N226
NR
MI
RO
PH
AMA PRA Category 1 Credits ™: 1.50
ARRT Category A+ Credits: 1.50
Participants
Sub-Events
RC323A
Oncology Applications
Participants
Hyunsuk Shim, PhD, Atlanta, GA, ([email protected]) (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
1) To learn about the potential of combining an advanced MR spectroscopic imaging with standard MR images to reduce the
recurence rate in glioblatomas.
ABSTRACT
Radiation therapy (RT) is as good as the images that guide RT planning. RT based on conventional MRIs may not fully target tumor
extent in glioblastomas (GBM), which may, in part, account for high recurrence rates (60-70 percent at 6 months). Magnetic
resonance spectroscopic imaging (MRSI), a molecular imaging modality that quantifies endogenous metabolite levels without relying
on perfusion, leakage and diffusion of injected material, may better define extent of actively proliferating tumor. In addition,
advances in this technology now permit acquisition of full-brain high-resolution 3D MRSIs in 12-14 minutes. We correlated state-ofthe-art MRSI metabolite maps with tissue histopathology to validate further its use for identifying tumor that may not be fully
imaged by conventional MRI sequences and provide support for its adjunctive use in tumor contouring for RT planning. Integration
of histologically-verified, whole brain 3D MRSI into RT planning is feasible and may considerably modify target volumes. Thus, RT
planning for GBMs may be augmented by MRSI potentially leading to reduced recurrence rates.
RC323B
Functional Applications
Participants
Satoshi Minoshima, MD, PhD, Salt Lake City, UT (Presenter) Royalties, General Electric Company; Consultant, Hamamatsu Photonics
KK; Research Grant, Hitachi, Ltd; Research Grant, Nihon Medi-Physics Co, Ltd; Research Grant, Astellas Group; Research Grant,
Seattle Genetics, Inc;
SSG09
Molecular Imaging (Gynecologic Oncology)
Tuesday, Dec. 1 10:30AM - 12:00PM Location: S504CD
BR
GU
MI
MR
RO
AMA PRA Category 1 Credits ™: 1.50
ARRT Category A+ Credits: 1.50
FDA
Discussions may include off-label uses.
Participants
Kathryn A. Morton, MD, Salt Lake City, UT (Moderator) Nothing to Disclose
Zaver M. Bhujwalla, PhD, Baltimore, MD (Moderator) Nothing to Disclose
Sub-Events
SSG09-01
First Clinical Trial on Ultrasound Molecular Imaging Using KDR-Targeted Microbubbles in Patients with
Breast and Ovarian Lesions
Tuesday, Dec. 1 10:30AM - 10:40AM Location: S504CD
Participants
Juergen K. Willmann, MD, Stanford, CA (Presenter) Research Consultant, Bracco Group; Research Consultant, Triple Ring
Technologies, Inc; Research Grant, Siemens AG; Research Grant, Bracco Group; Research Grant, Koninklijke Philips NV; Research
Grant, General Electric Company
Lorenzo Bonomo, MD, Rome, Italy (Abstract Co-Author) Nothing to Disclose
Antonia Testa, Rome, Italy (Abstract Co-Author) Nothing to Disclose
Pierluigi Rinaldi, MD, Rome, Italy (Abstract Co-Author) Nothing to Disclose
Guido Rindi, Rome, Italy (Abstract Co-Author) Nothing to Disclose
Sanjiv S. Gambhir, MD, PhD, Stanford, CA (Abstract Co-Author) Board Member, Enlight Biosciences; Board Member, ImaginAb, Inc;
Board Member, FUJIFILM Holdings Corporation; Board Member, ClickDiagnostics, Inc; Consultant, FUJIFILM Holdings Corporation;
Consultant, Gamma Medica, Inc; Speaker, ImaginAb, Inc; Stock, Enlight Biosciences; Stock options, Enlight Biosciences; Travel
support, Gamma Medica, Inc
PURPOSE
To assess if clinical ultrasound molecular imaging (USMI) using a novel clinical grade human kinase domain receptor (KDR)-targeted
microbubble (BR55, Bracco) is safe and allows assessment of KDR expression in patients with breast and ovarian lesions, using
immunohistochemistry (IHC) as gold standard.
METHOD AND MATERIALS
21 women (34-66 yrs) with focal breast lesions and 24 women (48-79 yrs) with focal ovarian lesions were injected IV with BR55
(0.03-0.08 mL/kg bw) and 2D USMI of the target lesions was performed dynamically every 2 min starting 5 min after injection up to
29 min, using the linear 15L8 probe (Siemens) or the endocavitary 1123 probe (Esaote). Normal breast tissues surrounding the
lesion or the contralateral presumed normal ovary served as intra-patient controls. Blood pressure, EKG, oxygen levels, heart rate,
CBC, and metabolic panel were obtained before, and 30 min, 1h, 24h after BR55 administration. Persistent focal BR55 binding on
USMI was visually assessed in consensus by 2 blinded offsite radiologists as none, possibly or definitely. Patients underwent surgical
resection of the target lesions and tissues were stained for CD31 and KDR. A pathologist assessed vascular KDR expression using a
4-point scale (none, weak, intermediate, high). Adjudication was performed in consensus (offsite radiologists and pathologist) to
match clinically.
RESULTS
USMI with BR55 was well tolerated by all patients at all doses, without safety concerns. Among the 40 patients included in the
analysis, KDR expression was higher in malignant breast and ovarian lesions (score 2.40±0.63 and 2.08±0.64, respectively)
compared to benign breast and ovarian lesions (2.08±0.64 and 1.33±0.50). KDR expression matched well with presence of focal
BR55 binding on USMI in malignant breast (13/15; 86.7%) and ovarian (11/13; 84.6%) lesions, as well as benign breast (2/3;
66.7%) and ovarian (8/9; 88.9%) lesions. Focal USMI signal could be detected up to 29 min after injection.
CONCLUSION
Use of BR55 in USMI of breast and ovarian lesions is safe and effective and preliminary data indicate that KDR-targeted USMI signal
matches well with vascular KDR expression on IHC.
CLINICAL RELEVANCE/APPLICATION
This study provides proof of principle on feasibility and safety of KDR-targeted USMI in patients with breast and ovarian lesions and
lays the foundation for further clinical trials.
SSG09-02
Imaged EGFR Expression Level Reflects Inhibited Growth-Pathway Node in Model of Triple-Negative
Breast Cancer
Tuesday, Dec. 1 10:40AM - 10:50AM Location: S504CD
Participants
Eric Wehrenberg-Klee, MD, Boston, MA (Presenter) Nothing to Disclose
Nafize S. Turker, PhD, Boston, MA (Abstract Co-Author) Nothing to Disclose
Pedram Heidari, MD, Boston, MA (Abstract Co-Author) Nothing to Disclose
Mauri Scaltriti, PhD, New York, NY (Abstract Co-Author) Nothing to Disclose
Umar Mahmood, MD, PhD, Charlestown, MA (Abstract Co-Author) Research Grant, Sabik Medical Inc; Advisory Board, Blue Earth
Diagnostics Limited;
PURPOSE
Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype for which targeted inhibitors of the
RTK/PI3K/AKT/mTOR growth pathway have demonstrated early treatment success. The surface receptor EGFR is one of the
dominant RTKs mediating downstream growth signals along this pathway and changes in EGFR expression may be predictive of
therapeutic inhibition. We sought to demonstrate that the changes in EGFR expression predictive of treatment response could be
non-invasively assessed.
METHOD AND MATERIALS
64Cu-DOTA-cetuximab F(ab´)2 was prepared from cetuximab monoclonal antibody and probe affinity for EGFR assessed. A panel of
TNBC cell lines (MDMBA468, MDMBA231, HCC70) was treated with the AKT inhibitor GDC-0068 or the PI3K inhibitor GDC-0941 for
one day at a range of concentrations. Following treatment, we assessed in vitro EGFR probe uptake. In vitro uptake study results
were compared to protein quantification as assessed by Western blot. After treatment of HCC70 mouse xenografts with control,
GDC-0068, or GDC-0941 for two days, PET-CT imaging of HCC-70 tumors with 64Cu-DOTA-EGFR F(ab´)2 was performed.
RESULTS
In vitro treatment with GDC-0068 resulted in increased EGFR Probe uptake of 25%, 139%, and 16% for MDAMB468, MDMBA231, and
HCC70, respectively. In vitro treatment with GDC-0941 resulted in increased EGFR uptake of 6%, 87%, and 88%, for the same
panel of cell lines. In vitro uptake studies demonstrate close correlation with changes in EGFR expression as assessed by Western
blot. In vivo imaging of HCC70 mouse xenografts with EGFR PET Probe after treatment with control, GDC-0068, or GDC-0941
demonstrate SUVmean of 0.32 (±0.03), 0.50 (±0.01), 0.62 (±0.01), with all comparisons significant (p<0.01).
CONCLUSION
We demonstrate in a murine model of triple-negative breast cancer that changes in EGFR expression induced by targeted
therapeutics can be non-invasively assessed using a 64Cu-DOTA-EGFR F(ab´)2 PET imaging probe. We demonstrate that changes
in the level of EGFR expression, potentially indicative of therapeutic response, differ depending on the growth-pathway inhibited.
CLINICAL RELEVANCE/APPLICATION
Noninvasive assessment of changes in EGFR expression could be a valuable clinical tool for rapid assessment of therapeutic efficacy
of targeted growth pathway inhibitors in TNBC, allowing for dynamic clinical decision making in response to imaged resistance
profiles.
SSG09-03
FACBC PET/CT Before and After Neoadjuvant Therapy in Locally Advanced Breast Cancer: A
Prospective Pilot Clinical Trial
Tuesday, Dec. 1 10:50AM - 11:00AM Location: S504CD
Participants
Gary A. Ulaner, MD, PhD, New York, NY (Presenter) Research support, General Electric Company; Research support, F. Hoffmann-La
Roche Ltd
Serge Lyashchenko, New York, NY (Abstract Co-Author) Nothing to Disclose
Hanh Pham, New York, NY (Abstract Co-Author) Nothing to Disclose
Jason S. Lewis, PhD, New York, NY (Abstract Co-Author) Nothing to Disclose
PURPOSE
Genes for amino acid transport proteins are highly upregulated in both invasive ductal carcinoma (IDC) and ILC, as compared to
normal breast epithelium. This molecular phenotype may allow for the development of imaging agents based on amino acid
metabolism. We evaluated whether Fluorine-18 labeled 1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC), an amino acid
analog labelled with fluorine-18, could be used as an imaging agent for local staging of locally advanced breast cancer before and
after neoadjuvant therapy.
METHOD AND MATERIALS
This prospective clinical trial is being performed under IRB approval. In this trial, newly diagnosed breast cancer patients that are
planned for neoadjuvant systemic therapy followed by surgical resection undergo FACBC PET/CT prior to systemic therapy and then
again following completion of systemic therapy. Maximum Standardized Uptake Values (SUVmax) and other quantitative measures of
FACBC-avidity are measured for the primary breast tumor and nodal metastases before and after systemic therapy. Following
surgery, FACBC results are correlated with postoperative histopathologic results.
RESULTS
Of 28 planned patients, we have currently accrued 23. All 23 accrued patients have undergone the pre-neoadjuvant therapy FACBC
PET/CT. All 23 primary breast lesions were FACBC avid with SUVmax values of 2.3 to 17.5. 18 of 23 patients (78%) had FACBC avid
axillary nodes with SUVmax values of 1.2 to 14.6. In 2 of 23 patients (9%), an unsuspected extra-axillary local nodal metastasis
was detected on the pre neoadjuvant therapy FACBC PET/CT. SUVmax of these nodes was 2.1 and 2.2, and both were
pathologically proven to be metastases. 15 of 23 patients (65%) have completed both pre- and post-neoadjuvant PET/CT scans
and histological analysis following surgical resection. In 13 of these 15 patients (87%), a reduction of SUVmax in the primary breast
cancer of greater than 90% could accurately identify the presence or absence of complete response/near complete response as
defined by post surgical histologic analysis.
CONCLUSION
This pilot trial of FACBC PET/CT in locally advanced breast cancer demonstrates potential uses of FACBC PET/CT before and after
neoadjuvant therapy.
CLINICAL RELEVANCE/APPLICATION
Further work on FACBC as a radiotracer in locally advanced breast cancer is warranted.
SSG09-04
Operation-naive Invasive Ductal Carcinoma of the Breast. Comparison of Staging Performed with
Whole Body DWI, PET, PET-CT, and PET-MR
Tuesday, Dec. 1 11:00AM - 11:10AM Location: S504CD
Participants
Onofrio A. Catalano, MD, Napoli, Italy (Presenter) Nothing to Disclose
Bruce R. Rosen, MD, PhD, Charlestown, MA (Abstract Co-Author) Research Consultant, Siemens AG
Angelo Luongo, Napoli, Italy (Abstract Co-Author) Nothing to Disclose
Mark Vangel, PhD, Charlestown, MA (Abstract Co-Author) Nothing to Disclose
Marco Catalano, Napoli, Italy (Abstract Co-Author) Nothing to Disclose
Umar Mahmood, MD, PhD, Charlestown, MA (Abstract Co-Author) Research Grant, Sabik Medical Inc; Advisory Board, Blue Earth
Diagnostics Limited;
Emanuele Nicolai, Napoli, Italy (Abstract Co-Author) Nothing to Disclose
Andrea Soricelli, MD, Napoli, Italy (Abstract Co-Author) Nothing to Disclose
Marco Salvatore, MD, Napoli, Italy (Abstract Co-Author) Nothing to Disclose
PURPOSE
To compare the performance of whole body (WB) DW, WB-PET, WB-PETCT, and WB-PETMR in patients with newly diagnosed
invasive ductal breast cancer, before undergoing treatment.
METHOD AND MATERIALS
49 consecutive women with newly diagnosed invasive ductal carcinoma of the breast underwent WB-DWI, WB-PET, WB-contrast
enhanced (CE) PETCT and WB-CE-PETMR before treatment. A radiologist and a nuclear medicine physician evaluated in consensus
the studies and searched for occurrence, number, and location of metastases. Final staging and number of lesions, according to
each technique, were compared. Pathology and imaging follow up were used as the ground truth reference.
RESULTS
All the techniques correctly staged 32/49 patients: stage2b in 8, 2c in 7, 3c in 4, 4 in 13. They provided discordant stages in 17/49
patients: 1 (stage 2a): staged-4 by WB-PET; 4 (stage 2b): 3/4 staged-2a by WB-PET and WB-PETCT, 1/4 staged-4 by WB-DWI;3
(stage 3a): 2/3 staged-2b by WB-PET and WB-PETCT, 1/3 staged-4 by WB-DWI;3(stage 3c): 2/3 staged-2a by WB-PET and WBPETCT, 1/3 staged-4 by WB-PET and WB-PETCT;6 (stage 4): 1/6 staged-3a by WB-PET, WB-DWI, and WB-PETCT, 1/6 staged-2b
by WB-PET and WB-PETCT, 1/6 staged-2b by WB-PET, WB-DWI, and WB-PETCT, 1/6 staged-3a by WB-DWI, 1/6 staged-3c by
WB-DWI, and 1/6 staged-3a by WB-PET, WB-PETCT and 3c by WB-DWI. Staging performance of WB-PETMR (49 correctly staged)
was significantly better than WB-PETCT (38 correctly staged) (P=0.001, chi square-test).The best performing modality for
malignant lymph-node detection was WB-PETMR (47 of 49 patients), followed by WB-DWI (37/49), followed by WB-PET and WBPETCT (15 patients each). Significantly more malignant nodes were detected by WB-PETMR (P<0.0001, paired t-tests). At least as
many true-positive lesions were detected by WB-PETMR than by any of the other three modalities for 46 patients. The
corresponding number of patients for WB-PET, WB-PETCT, and WB-DWI were 40, 39 and 34, respectively.
CONCLUSION
PETMR allows a better accuracy in initial staging of surgical-naive ductal invasive breast cancer. The higher performance is likely
related to the additive information of PET, DWI, as well as of the other sequences (STIR, T1-weighted Dixon, HASTE, ADC maps,
and CE-T1-weighed images) of WB-PETMR
CLINICAL RELEVANCE/APPLICATION
When available WB-PETMR should be considered for proper staging of naive ductal invasive breast cancer.
SSG09-05
Multiparametric 18F-FMISO PET/MRI for Assessment of Treatment Response to Chemo-radiation and
Hypoxia Monitoring in Cervix Cancer Patients: A Feasibility Study
Tuesday, Dec. 1 11:10AM - 11:20AM Location: S504CD
Participants
Petra Georg, MD,PhD, Wiener Neustadt, Austria (Abstract Co-Author) Nothing to Disclose
Piotr Andrzejewski, MA, Vienna, Austria (Abstract Co-Author) Nothing to Disclose
Pascal A. Baltzer, MD, Vienna, Austria (Abstract Co-Author) Nothing to Disclose
Stephan H. Polanec, MD, Vienna, Austria (Abstract Co-Author) Nothing to Disclose
Wolfgang Wadsak, Vienna, Austria (Abstract Co-Author) Speaker, General Electric Company; Consultant, THP Medical; Research
Grant, ABX GmbH; Research Grant, Rotem GmbH
Alina Sturdza, MD, Vienna, Austria (Abstract Co-Author) Nothing to Disclose
Georgios Karanikas, MD, Vienna, Austria (Abstract Co-Author) Nothing to Disclose
Stephan Polterauer, MD, Vienna, Austria (Abstract Co-Author) Nothing to Disclose
Richard Poetter, MD, Vienna, Austria (Abstract Co-Author) Nothing to Disclose
Thomas H. Helbich, MD, Vienna, Austria (Abstract Co-Author) Research Grant, Medicor, Inc; Research Grant, Siemens AG; Research
Grant, C. R. Bard, Inc
Dietmar Georg, PhD, Vienna, Austria (Abstract Co-Author) Nothing to Disclose
Katja Pinker, MD, New York, NY (Presenter) Nothing to Disclose
PURPOSE
To demonstrate feasibility of combined multiparametric positron emission tomography/magnetic resonance imaging at 3T (3T MP
PET/MRI) and to assess treatment response and hypoxia monitoring in cervix cancer patients undergoing chemo-radiation therapy.
METHOD AND MATERIALS
In this IRB-approved prospective study 7 patients underwent sequential 3T MP 18F-FMISO PET/MRI at baseline; 2 and 5 weeks (w)
after start and 3 months (FU) after treatment. MRI protocol consisted of a high-resolution isotropic T2-w SPACE, a DWI EPI
(b=50/850 sec/mm²) and a high-resolution contrast-enhanced (CE) T1-w VIBE sequence. Patients were injected with 330 MBq
18F-FMISO and scanning was started 240 min after injection. CT data was used for attenuation correction. PET and MR image
registrations were performed using Mirada RTx (Mirada Medical, Oxford, UK , ver. 1.4.0.23) software. Gross tumour volume (GTV)
was contoured by an experienced radiation oncologist on PET/MRI data sets. The volume of GTV was assessed for tumor size, CEkinetics, restricted diffusivity and 18F-FMISO-avidity using SUVmax and SUV (SUVnorm ) normalized to gluteal muscle uptake. At
follow up, cervix was contoured, since all patients showed clinically complete remission.
RESULTS
3T MP 18F-FMISO PET/MRI was successfully performed in all patients at every time-point. Median GTV volume was 43.9cc at
baseline, 22.4cc after 2w (20-25Gy) and 7.7cc after 5w (40-45Gy). Mean ADC values were 1.02x10-3mm2/sec increasing to
1.18x10-3mm2/sec after 2w and to 1.27x10-3mm2/sec after 5w and to 1.37x10-3mm2/sec at FU. All GTVs showed mean initialenhancement (IE) followed by a plateau with an increasing IE at 2w and 5w and wash-out at 5w. At FU, there was a persistent
enhancement. The mean 18F-FMISO SUVnorm was 3.1 at baseline and decreased to 2.3 at 2w and 2.0 at 5w and follow-up. In all
patients there was never the whole tumor 18F-FMISO-avid, but 18F-FMISO-avid spots within the tumor indicative of hypoxia could
be identified before and during the course of therapy.
CONCLUSION
MP 18F-FMISO PET/MRI in cervix cancer patients at 3T is feasible and enables non-invasive monitoring of morphological and
functional changes during treatment.
CLINICAL RELEVANCE/APPLICATION
3T MP 18F-FMISO PET/MRI can depict areas of tumor hypoxia during therapy and thus identify patients at risk who need an
aggressive treatment approach.
SSG09-06
Correlation of PET-MR Biomarkers with Breast Cancer Molecular Subtypes, Grading and Presence of
Distant Metastases at Time of Presentation
Tuesday, Dec. 1 11:20AM - 11:30AM Location: S504CD
Participants
Onofrio A. Catalano, MD, Napoli, Italy (Presenter) Nothing to Disclose
Bruce R. Rosen, MD, PhD, Charlestown, MA (Abstract Co-Author) Research Consultant, Siemens AG
Carlo Iannace, MD, San Leucio del Sannio, Italy (Abstract Co-Author) Nothing to Disclose
Angelo Luongo, Napoli, Italy (Abstract Co-Author) Nothing to Disclose
Marco Catalano, Napoli, Italy (Abstract Co-Author) Nothing to Disclose
Mark Vangel, PhD, Charlestown, MA (Abstract Co-Author) Nothing to Disclose
Umar Mahmood, MD, PhD, Charlestown, MA (Abstract Co-Author) Research Grant, Sabik Medical Inc; Advisory Board, Blue Earth
Diagnostics Limited;
Maria Lepore, MD, Avellino, Italy (Abstract Co-Author) Nothing to Disclose
Bethany L. Niell, MD, Boston, MA (Abstract Co-Author) Nothing to Disclose
Emanuele Nicolai, Napoli, Italy (Abstract Co-Author) Nothing to Disclose
Andrea Soricelli, MD, Napoli, Italy (Abstract Co-Author) Nothing to Disclose
PURPOSE
To evaluate if PET-MR biomarkers correlate with molecular genetic subtypes, grading, and presence of distant metastases at time
of presentation in naïve ductal invasive breast cancers.
METHOD AND MATERIALS
21 consecutive patients with naïve ductal invasive breast cancer and genetic molecular subtype profiling underwent whole-body
contrast enhanced FDG-PET-MR (Biograph mMR, Siemens). Two readers, using commercially available software, measured the
following PET-MR biomarkers: ADC, Ktrans, Ve, Kep, IAUC, SUVmax, SUVmean, and MTV. They were correlated with genetic
molecular subtypes, grading and occurrence of distant metastases.
RESULTS
Genetic molecular subtypes were as follows: ER-7, ER+14; PR-8, PR+13; HER2-11, HER2+10; Ki67-low (<=35%), Ki67 medium/high
(>35%). Grading was G2 in 14 and G3 in 7. Six patients had distant metastases. The following biomarkers were higher in the ERand PR- compared to ER+ and PR+ patients: Kep (9234±1320 versus 6492 ±2358, p0.01), SUVmax (14.19±7.17 versus 6.17±4.24,
p0.004), and SUVmean (8.44±4.01, p0.004). ADC directly correlated with the degree of Ki67 expression (1019±256 for Ki67<=35%,
1338±105 forKi67>35%, p0.002). The following biomarkers were lower in HER2- patients compared to HER2+ cases: ADC (1050±280
versus 1306±122, p0.009), Kep (6726±2240 versus 8599±2122, p0.028), SUVmax (6.29±4 versus 11.8±7.65, p0.046), and
SUVmean (3.72±2.28 versus 7.03±4.43, p0.04).G2 patients experienced lower Kep (6638±2391 versus 8944±1764, p0.04) and lower
SUVmax (6.83±4.73 versus 12.89±8.07, p 0.04) than G3 patients.No biomarkers correlated with presence of distant metastases.
CONCLUSION
In naïve ductal invasive breast cancers, PET-MR biomarkers correlate with molecular genetic subtypes and with grading, but not
with the presence of distant metastases.
CLINICAL RELEVANCE/APPLICATION
PET-MR biomarkers might have prognostic and therapeutic implications on patients' management.
SSG09-07
Impact of Estrogen Receptor Gene Mutations on [18F]-Fluoroestradiol Uptake in Breast Cancer
Tuesday, Dec. 1 11:30AM - 11:40AM Location: S504CD
Participants
Manoj Kumar, MS, Madison, WI (Abstract Co-Author) Nothing to Disclose
Ginny L. Powers, PhD, Madison, WI (Abstract Co-Author) Nothing to Disclose
Justin Jeffery, Madison, WI (Abstract Co-Author) Nothing to Disclose
Yongjun Yan, PhD, Madison, WI (Abstract Co-Author) Nothing to Disclose
Amy M. Fowler, MD, PhD, Saint Louis, MO (Presenter) Nothing to Disclose
PURPOSE
Accurately predicting therapeutic responsiveness in women with breast cancer remains challenging. Positron emission tomography
(PET) imaging using [18F]-16alpha-17beta-fluoroestradiol (FES) provides a way to non-invasively and longitudinally examine the
subset of tumors expressing estrogen receptor alpha (ERα) which comprise approximately 70% of all breast cancers. However, the
effect of mutations in the gene encoding ERα, recently identified in patients with endocrine-resistant, metastatic breast cancer, on
FES uptake is unknown. We developed a model system to test how mutations in ERα influence the uptake of FES.
METHOD AND MATERIALS
Stable cell lines expressing either wild-type ERα (231-ER) or a point mutation in the ligand-binding pocket, G521R (231-G521R),
were created in the ERα-negative human breast cancer cell line MDA-MB-231. ERα-positive MCF7 human breast cancer cells were
used as a positive control and parental MDA-MB-231 cells were used as a negative control. Cell uptake of FES was measured in
vitro with microPET/CT imaging and gamma counting. In addition, in vivo FES uptake was measured in MCF7 and 231-ER tumors
grown as xenografts in athymic nude mice.
RESULTS
FES uptake was observed both in vitro and in vivo in the MCF7 and 231-ER cells/tumors. However, there was no significant FES
uptake in the 231-G521R cells or parental MDA-MB-231 cells. The 231-ER cells had a similar dose response curve to MCF7 in
competition assays using increasing doses of cold estradiol, and as consistent with the uptake data, 231-G521R binding was not
altered by cold competition.
CONCLUSION
These data support the use of stable cell lines expressing variant forms of ERα as models for demonstrating the effects of ERα gene
mutations on FES uptake. Ongoing studies are focusing on the effects of recently identified clinically-relevant ERα mutations on FES
uptake and on the prediction of response to ER-targeted therapies.
CLINICAL RELEVANCE/APPLICATION
FES-PET imaging provides a non-invasive way to probe ERα function and may prove useful in identifying the development of ERα
gene mutations and thus predicting endocrine resistance in ERα-positive breast cancer patients.
SSG09-08
Imaging Patients with Breast and Prostate Cancers Using Combined 18F NaF/18F FDG and TOF
simultaneous PET/ MRI
Tuesday, Dec. 1 11:40AM - 11:50AM Location: S504CD
Participants
Ryogo Minamimoto, MD, PhD, Stanford, CA (Presenter) Nothing to Disclose
Andreas M. Loening, MD, PhD, San Francisco, CA (Abstract Co-Author) Nothing to Disclose
Valentina Taviani, PhD, Stanford, CA (Abstract Co-Author) Nothing to Disclose
Sanjiv S. Gambhir, MD, PhD, Stanford, CA (Abstract Co-Author) Board Member, Enlight Biosciences; Board Member, ImaginAb, Inc;
Board Member, FUJIFILM Holdings Corporation; Board Member, ClickDiagnostics, Inc; Consultant, FUJIFILM Holdings Corporation;
Consultant, Gamma Medica, Inc; Speaker, ImaginAb, Inc; Stock, Enlight Biosciences; Stock options, Enlight Biosciences; Travel
support, Gamma Medica, Inc
Shreyas S. Vasanawala, MD, PhD, Palo Alto, CA (Abstract Co-Author) Research collaboration, General Electric Company;
Consultant, Arterys; Research Grant, Bayer AG;
Andrei Iagaru, MD, Stanford, CA (Abstract Co-Author) Research Grant, General Electric Company; Research Grant, Bayer AG
PURPOSE
We previously reported the pilot evaluation of a simultaneous PET/MRI scanner with TOF capability, as well as the use of combined
18F NaF/18F FDG PET/CT in cancer patients. Here we prospectively compared the combined 18F NaF/18F FDG PET/ MRI against
99mTc-MDP in patients with breast and prostate cancers for the detection of metastatic disease.
METHOD AND MATERIALS
Fifteen patients referred for 99mTc-MDP bone scans were prospectively enrolled from Oct 14 - Mar 15. The cohort included 7 men
with prostate cancer and 8 women with breast cancer, 41 - 85 year-old (average 61 ± 13). 18F NaF (0.7-2.2 mCi, mean: 1.2 mCi)
and 18F FDG (3.8-5.2 mCi, mean: 4.2 mCi) were subsequently injected from separate syringes. The PET/MRI was done 6-30 days
(average 9.3 ± 3.2) after bone scan. The whole body MRI protocol consisted of T2-weighted, DWI, and contrast-enhanced T1weighted imaging. Lesions detected with each test were tabulated and the results were compared.
RESULTS
All patients tolerated the PET/MRI exam, and PET image quality was diagnostic despite the marked reduction in the administered
dosage of radiopharmaceuticals (80% less for 18F NaF and 67% less for 18F FDG compared to standard protocols). Five patients
had no bone metastases identified on either scans. Bone scintigraphy and PET/MRI showed osseous metastases in 9 patients, but
more numerous bone findings were noted on PET/MRI than on bone scintigraphy in 3 patients. One patient had negative bone scan,
but bone metastases were seen on PET/MRI. Lesions outside the skeleton were identified by PET/MRI in 3 patients.
CONCLUSION
The combined 18F NaF/18F FDG PET/MRI is superior to 99mTc-MDP scintigraphy for evaluation of skeletal disease extent. Further, it
detected extra-skeletal disease that may change the management of these patients, while allowing a significant reduction in
radiation exposure from lower dosages of PET radiopharmaceuticals administered. A combination of 18F NaF/18F FDG PET/MRI may
provide the most accurate staging of patients with breast and prostate cancers prior to the start of treatment.
CLINICAL RELEVANCE/APPLICATION
The combined 18F NaF/18F FDG PET/MRI is superior to 99mTc-MDP scintigraphy for evaluation of skeletal disease extent.
SSG09-09
In Vivo Assessment of Ovarian Tumor Response to Tyrosine Kinase Inhibitor Pazopanib using
Hyperpolarized 13C-Pyruvate MRS and 18F-FDG PET/CT Imaging in a Mouse Model
Tuesday, Dec. 1 11:50AM - 12:00PM Location: S504CD
Participants
Murali Ravoori, Houston, TX (Abstract Co-Author) Nothing to Disclose
Sheela Singh, Houston, TX (Abstract Co-Author) Nothing to Disclose
Jaehyuk Lee, Houston, TX (Abstract Co-Author) Nothing to Disclose
James Bankson, PhD, Houston, TX (Abstract Co-Author) Nothing to Disclose
Vikas Kundra, MD, PhD, Houston, TX (Presenter) License agreement, Introgen Therapeutics, Inc
PURPOSE
Early response measures for ovarian cancer are needed to common targets such as tyrosine kinases. Via effects on signaling within
tumor cells or via effects on angiogenesis, such inhibitory drugs have the potential to alter tumor metabolism. 18Fluorodeoxyglucose
(18F-FDG) mimics glucose and can be used to evaluate early glycolysis. Hyperpolarization magnetic resonance spectroscopy (MRS)
imaging can be used to study pyruvate, which can be produced by glycolysis and other pathways and sits at a decision point for
aerobic versus anaerobic metabolism. Our purpose was to assess whether either early or late components of metabolism can serve
as indicators of response of ovarian cancer to tyrosine kinase inhibitor (including angiogenesis inhibitor via VEGF receptor inhibition)
Pazopanib.
METHOD AND MATERIALS
Seventeen days after injection of 2 x 106 human ovarian SKOV3 tumors cells into female nude mice, treatment with vehicle or
Pazopanib (2.5 mg/mouse po) was initiated. Longitudinal T2-weighted MR, hyperpolarized pyruvate MRS, and 18F-FDG PET/CT
imaging were performed pre-treatment as well as 2 days and 2 weeks after treatment.
RESULTS
Pazopanib was effective in inhibiting ovarian tumor growth compared to control (p<0.05). Significantly higher pyruvate to lactate
conversion (lactate/pyruvate+lactate ratio) was found 2 days after treatment with pazopanib compared to pre-therapy (p<0.005,
n=8). This was not seen with control or with 18F-FDG PET/CT imaging.
CONCLUSION
Findings suggest that later metabolic events (pyruvate to lactate conversion) may serve as as an early indicator of response of
ovarian cancer to tyrosine kinase (angiogenesis) inhibitor pazopanib in mouse models, even when early glycolytic events do not.
CLINICAL RELEVANCE/APPLICATION
Hyperpolarized 13C-Pyruvate MRS may serve as an early indicator of response to tyrosine kinase (angiogenesis) inhibitors such as
pazopanib in ovarian cancer even when 18F-FDG PET/CT does not.
MIS-TUA
Molecular Imaging Tuesday Poster Discussions
Tuesday, Dec. 1 12:15PM - 12:45PM Location: S503AB
MI
AMA PRA Category 1 Credit ™: .50
FDA
Discussions may include off-label uses.
Participants
Donna J. Cross, PhD, Seattle, WA (Moderator) Nothing to Disclose
Sub-Events
MI211-SDTUA1
Effect of Point Spread Function Correction and Gaussian Filtering on Quantification in Oncologic PET:
An Impact Assessment Using Initial Clinical Studies Using a Solid-State Digital Detector PET/CT
Station #1
Participants
Katherine Binzel, PhD, Columbus, OH (Presenter) Nothing to Disclose
Jun Zhang, PhD, Columbus, OH (Abstract Co-Author) Nothing to Disclose
Michael V. Knopp, MD, PhD, Columbus, OH (Abstract Co-Author) Nothing to Disclose
PURPOSE
To assess the impact of advanced reconstruction techniques, point spread function (PSF) correction and Gaussian filtering, on the
quantification of clinical data acquired on a next-generation digital PET/CT system. Previous phantom validation has shown that
PSF correction leads to more accurate quantification, with evaluation of the impact on quantification of clinical data sets being the
aim of this work.
METHOD AND MATERIALS
PET/CT images were acquired on the Philips Vereos TF 64 (Cleveland, OH), following injection of a target dose of 13 mCi of 18Ffluorodeoxyglucose (FDG). Patients were imaged for 90 seconds per bed position from the skull to the mid-thigh. 4mm PET images
were reconstructed with 3 iterations each with 29 subsets (default) based on an ultra-low dose iteratively reconstructed CT. PET
listmode data were subsequently used for secondary image reconstruction using the Gaussian filter and/or PSF correction. The
resulting image sets were quantitatively evaluated, measuring SUVmax of the target lesions as well as physiologic uptake in
background tissues. The percent differences from the SUVmax of the default reconstruction were calculated for the Gaussian filter
and PSF reconstructed images.
RESULTS
Adding the Gaussian filter lowered the SUVmax in all measured tissues, including target lesions. The average decrease in SUVmax
ranged between 3% and 12% for the different tissue types. For target lesions, the Gaussian filter decreased the SUVmax between
6% and 22% from default readouts. PSF correction lead to a wider range of changes in SUVmax. The average change in SUVmax
among all tissue types was between a 5% and 25% increase from default. For target lesions the PSF increased SUVmax between
12% and 33% from default reconstruction measurements.
CONCLUSION
Gaussian filtering and PSF have significant and diverging impact on quantification with notable differences depending upon tissue
characteristics. The observed changes in in-vivo SUVs accompanying these refinements to PET reconstruction are in line with
previous phantom experiments. Further rigorous optimization and validation in clinical data sets will enable a more robust
quantitative accuracy in clinical PET/CT.
CLINICAL RELEVANCE/APPLICATION
Application of advanced reconstruction techniques for next-generation PET/CT imaging improves quantitative accuracy, enabling
increasingly robust clinical utility.
MI212-SDTUA2
The Bioeffects of 3T High Magnetic Field on Endothelial Cells in Vitro
Station #2
Participants
Po-Hsiang Hsu, Hualien, Taiwan (Abstract Co-Author) Nothing to Disclose
Li-Chuan Huang, Hualien, Taiwan (Presenter) Nothing to Disclose
PURPOSE
Magnetic resonance imaging (MRI) is a technology using high magnetic fields and radio frequency resonance. It provides highresolution medical imaging in clinical practice without the involvement of radiation. The magnetic field strength of mainstream MRI
instrument is 3 Tesla which is sixty thousand times higher than that of geomagnetic environment. The biologic effect associated
with the exposure of high magnetic field therefore becomes and important issue for medical device. The endothelial cells are the
inner layer of blood vessels which play an important role in nutrient and metabolite exchanged. High magnetic effects of endothelial
cells were investigated in this study.
METHOD AND MATERIALS
The human umbilical cord vein endothelial cell (HUVEC) is cultured for 3T high magnetic field. Flourescent nanoparticles (40 nm,
FluoSpheres carboxylate modifid-micro spheres) are administrated before experiment. The excitation and emission wavelenght of
these nanoparticles are 488/605 nm. We use immunohistochemisty, MTT cell proliferation assay. Cell was placed in Tzu Chi
hospital's GE 3T MRI. The distribution of the nanoparticles uptake inside the cell were quantitatively measured by confocal
flourescent microscope method.
RESULTS
The results of cell morphology observation, MTT cell viability and wound-healing assay show that no significant difference was
observed between controls and cells under 3 Tesla magnetic fields exposure. Uptake of fluorescent nanoparticles by vascular
endothelial cells was also investigated. Cell viability was reduced in the presence of 250 μg/ml nanoparticle, but no significant
change was observed in 25 μg/ml nanoparticle.
CONCLUSION
The cell morphology showed that no significant difference between 3 Tesla and control, but high magnetic field leads to the
increase of nanoparticles uptake by vascular endothelial cells.
CLINICAL RELEVANCE/APPLICATION
The endothelial cells are the inner layer of blood vessels which play an important role in nutrient and metabolite exchanged. The
magnetic field strength of mainstream MRI instrument is 3 Tesla which is sixty thousand times higher than that of geomagnetic
environment. The biologic effect associated with the exposure of high magnetic field therefore becomes and important issue for
medical device. The results presented in this study might refer to the practical applications of high magnetic field safety.
MI214-SDTUA4
Detection of Bone-marrow Lipid Profiles of Femoral Neck and Calcaneus in Postmenopausal Women
by 3T MR Spectroscopy: New Perspective in Osteoporosis Diagnosis
Station #4
Participants
Guglielmo Manenti, MD, Rome, Italy (Abstract Co-Author) Nothing to Disclose
Armando Fusco, Roma, Italy (Presenter) Nothing to Disclose
Giulia Di Pietro, Rome, Italy (Abstract Co-Author) Nothing to Disclose
Marco Nezzo, MD, Rome, Italy (Abstract Co-Author) Nothing to Disclose
Giovanni Simonetti, MD, Rome, Italy (Abstract Co-Author) Nothing to Disclose
Silvia Capuani, Rome, Italy (Abstract Co-Author) Nothing to Disclose
PURPOSE
The aim of the study was to identify specific metabolites of bone-marrow in the calcaneus and femoral-neck of with the potential
ability to discriminate between healthy, osteopenic and osteoporotic subjects by using Magnetic Resonance Spectroscopy (MRS) at
3T.
METHOD AND MATERIALS
MRS spectra of the calcaneus and femoral neck were obtained in Sixty-two and thirty-three women, respectively; they underwent
to bone mineral density (BMD) measurements to be classified as healthy subjects (n=22), osteopenic (n=45) or osteoporotic (n=28)
patients. Optimized LCmodel software was used to quantify and compare bone-marrow fat resonances between the three BMD
groups. Between-group differences were tested using a Welch ANOVA. Multiple comparisons were made with the Games-Howell
correction. Reproducibility analysis was performed for all the lipid resonances in both sites, by using coefficient of variation (CV).
RESULTS
LcModel allows to quantify with an error less than 5% fatty acids related to partially overlapping resonances,such as those which
lie between 4 and 5.4 ppm (i.e. glycerol, unsaturated lipids). In femoral neck, methylene, glycerol and total lipid resonances were
significantly lower in healthy as compared to osteoporotic subjects.In calcaneus, methylene/glycerol significantly discriminated
between osteopenic and osteoporotic subjects while methylene/(unsaturated lipid) discriminated between healthy and osteopenic
group. The reproducibility is acceptable because the percent differences in discriminating lipid resonances between BMD groups are
much higher than their CVs.
CONCLUSION
MRS of bone-marrow lipid profiles from peripheral skeletal sites is a promising tool for screening of large population to identify
individuals with or at risk for developing osteoporosis. Moreover, it provides information about the metabolic changes occurring in
bone-marrow with the development of osteoporosis, which are skeletal site dependent.
CLINICAL RELEVANCE/APPLICATION
MRS-spectra evaluated with LcModel allow to monitor bone-marrow fatty-acids changing due to osteoporosis development . This
method could be useful to test the effectiveness of osteoporosis drugs and diet.
MI215-SDTUA5
Evaluation of Fast Non-enhanced PET/MR Examination Protocols in a Fully Integrated PET/MR
System for Patients with Neuroendocrine Tumours: Direct Comparison to Multiphase Contrastenhanced PET/CT
Station #5
Participants
Ferdinand F. Seith, BSC, Tuebingen, Germany (Presenter) Nothing to Disclose
Christian la Fougere, Munich, Germany (Abstract Co-Author) Nothing to Disclose
Christina Pfannenberg, MD, Tuebingen, Germany (Abstract Co-Author) Nothing to Disclose
Konstantin Nikolaou, MD, Tuebingen, Germany (Abstract Co-Author) Speakers Bureau, Siemens AG Speakers Bureau, Bracco Group
Speakers Bureau, Bayer AG
Nina Schwenzer, MD, Tuebingen, Germany (Abstract Co-Author) Nothing to Disclose
Cornelia Brendle, MD, Tubingen, Germany (Abstract Co-Author) Nothing to Disclose
Christina Schraml, MD, Tuebingen, Germany (Abstract Co-Author) Nothing to Disclose
PURPOSE
In patients with neuroendocrine tumours (NET), kidney failure is a common complication of radionuclide therapy. It is known that
multiphase contrast-enhanced PET/CT is superior to non-enhanced PET/CT in diagnosing metastases with low or no tracer uptake
as well as small lesions especially in the liver. However, due to the superior soft tissue contrast of MRI it is possible that nonenhanced PET/MR offers the same information as contrast-enhanced PET/CT. The aim of the study was therefore to evaluate a
fast protocol in PET/MR without contrast agent in direct comparison to multiphase contrast-enhanced PET/CT as gold standard.
METHOD AND MATERIALS
39 Patients (22 female, 58±13 years) were examined in multiphase contrast-enhanced 68Ga-DOMITATE-PET/CT in a clinical setup
and in PET/MR subsequently. 2 blinded readers investigated PET/MR examinations of the abdomen with 3 different setups:
T2HASTE+PET (30min), T2HASTE+TSET2+PET (35min) and T2HASTE+TSET2+DWI+PET (35min). The T2HASTE was acquired under
free breathing with continuous table move. DWI was acquired with two b-values (0, 800 s/mm2). Metastatic lesions were defined
as functional and/or morphological suspicious lesions or lymph nodes. The results were compared with the contrast-enhanced
PET/CT, follow-up examinations and histopathology, if available.
RESULTS
T2HASTE sequences were of diagnostic quality in all patients. DWI suffered from artefacts especially in the upper regions of the
liver. Compared with contrast-enhanced PET/CT high agreement was found with T2HASTE+TSET2+DWI+PET.
CONCLUSION
A protocol for PET/MR including T2HASTE, TSET2, DWI and PET seems to provide comparable results compared with multiphase
contrast-enhanced PET/CT. With an estimated time of 35 min for a whole body examination, this might serve as a legitimate
alternative to contrast-enhanced PET/CT for patients with kidney failure in the future.
CLINICAL RELEVANCE/APPLICATION
In patients with neuroendocrine tumours (NET) and kidney failure, fast non-enhanced PET/MR protocols can serve as a legitimate
alternative to multiphase contrast-enhanced PET/CT examinations.
MIS-TUB
Molecular Imaging Tuesday Poster Discussions
Tuesday, Dec. 1 12:45PM - 1:15PM Location: S503AB
MI
AMA PRA Category 1 Credit ™: .50
FDA
Discussions may include off-label uses.
Participants
Donna J. Cross, PhD, Seattle, WA (Moderator) Nothing to Disclose
Sub-Events
MI216-SDTUB1
Synthesis and Biological Evaluation of (S)-2-amino-5-azido-4-[F-18]fluoro Pentanoic Acid as a Novel
PET Brain Glioa Imaging Agent
Station #1
Participants
Ephraim E. Parent, MD, PhD, Saint Louis, MO (Presenter) Nothing to Disclose
Ahlem Bouhlel, Saint Louis, MO (Abstract Co-Author) Nothing to Disclose
Liya Yuan, MD, Saint Louis, MO (Abstract Co-Author) Nothing to Disclose
Keith M. Rich, MD, Saint Louis, MO (Abstract Co-Author) Nothing to Disclose
Jonathan E. McConathy, MD, PhD, Saint Louis, MO (Abstract Co-Author) Research Consultant, Eli Lilly and Company; Research
Consultant, Blue Earth Diagnostics Ltd; Research Consultant, Siemens AG; Research support, GlaxoSmithKline plc
PURPOSE
To evaluate (S)-2-amino-5-azido-4-[F-18]fluoro pentanoic acid, a novel F-18 labeled amino acid radiopharmaceutical, as a brain
glioma imaging agent and potential vivo 'click' chemistry substrate.
METHOD AND MATERIALS
(S)-2-amino-5-azido-4-[F-18]fluoropentanoic acid (AzFPe) is a novel F-18 labeled amino acid containing a terminal azido
substituent. AzFPe was synthesized in 7 steps starting with commercially available 2-amino-4-penenoic acid. Labeling of AzFPe was
achieved through nucleophilic SN2 displacement of the methanesulfonyl precursor in a radiochemical yield of 48%. In vivo biological
evaluation was performed in male BALB/c mice with intracranial implanted delayed brain tumor (DBT) gliomas. Biodistribution and
dynamic small-animal PET imaging for 60 minutes were performed in 2 mice after intravenous injection of AzFPe.
RESULTS
AzFPe demonstrated good brain availability and uptake in normal brain tissue comparable to other known system L amino acid
transporter substrates such as FDOPA and FET. AzFPe demonstrated rapid and high uptake in intracranial DBT tumors with average
tumor to brain ratios of 2.0 at 60 min after injection. These finding demonstrate the potential of AzFPe and structurally related
compounds as an in vivo brain tumor imaging agent. The terminal azide of AzFPe has the potential to be used for in vivo
biorthogonal 'click chemistry' bioconjugation.
CONCLUSION
AzFPe is a novel azido-substituted PET amino acid which demonstrates good brain availability and promising imaging properties in a
mouse model of high grade glioma.
CLINICAL RELEVANCE/APPLICATION
[F-18]AzFPe is a novel radiolabeled amino acid with good preclinical imaging properties and the potential for use as an in vivo 'click
chemistry' substrate.
MI218-SDTUB3
Tumor-avid 3Gd-HPPH Defines Metstases as Small as 1.5 mm in Adult Rabbits at 1.5 Tesla
Station #3
Participants
Zachary D. Grossman, MD, Buffalo, NY (Presenter) Nothing to Disclose
Ravindra K. Pandey, PhD, Buffalo, NY (Abstract Co-Author) Nothing to Disclose
Ronald A. Alberico, MD, East Amherst, NY (Abstract Co-Author) Nothing to Disclose
Craig M. Hendler, MD, Stony Brook, NY (Abstract Co-Author) Nothing to Disclose
Nicholas Perry, MD, Buffalo, NY (Abstract Co-Author) Nothing to Disclose
Sandra Sexton, DVM, Buffalo, NY (Abstract Co-Author) Nothing to Disclose
Leslie Curtin, DVM, Buffalo, NY (Abstract Co-Author) Nothing to Disclose
Patrick Manzella, RT, Buffalo, NY (Abstract Co-Author) Nothing to Disclose
John C. Warner, RT, Buffalo, NY (Abstract Co-Author) Nothing to Disclose
PURPOSE
Purpose: To demonstrate the tumor-imaging potential of 3Gd-HPPH, a chlorophyll-a derivative (HPPH) linked with 3Gd(DTPA), for
widespread metastatic lesions, 1-2 mm in diameter, whose location is not known before imaging, at 1.5 Tesla.
METHOD AND MATERIALS
Methods and Materials: Suspended VX2 anaplastic rabbit carcinoma cells were forcefully hand-injected, retrograde, into the central
auricular artery of 8 rabbits. Radiographic contrast medium injected by the same method, at the same sitting, revealed that the
injected material reached the aorta, and cells were disseminated systemically. After 2-3 weeks, the animals were injected with F18-FDG for PET/CT, scanned 30 min later, and subsequently injected with 3Gd-HPPH, 10 umol/kg (30 umol of Gd/kg) and imaged at
1.5 T, in the immediate vascular phase, 24 h, and 48 h.
RESULTS
Results: In all rabbits tumor signal increased at 24 and 48 hours after 3Gd-HPPH injection. More lesions were defined on MRI than on
PET/CT; histologic examination confirmed that these corresponded to VX2 metastases, many 1-2 mm.
CONCLUSION
Conclusions: Although 3Gd-HPPH was reported previously as a new tumor-avid contrast medium, it was studied at 4.7 T, in rats
with subcutaneously-implanted human Ward carcinoma cells. This work was not fully convincing to clinical imagers, because: (1)
the abdominal wall tumor implants were large, analogous to a subcutaneous 25 cm mass in a human, (2) the lesions were identified
by scanning, but the investigators knew their location before imaging, (3) foreign tumor cells were implanted, so that immunologic
factors might have been involved in enhanced tumor signal, and (4) signal enhancement at 4.7 T did not really prove that sufficient
signal for diagnosis would be present at clinical magnet strength. This study successfully addressed all of these concerns and
confirms that 3Gd-HPPH is progressively tumor-avid for 48 h, unlike all currently available clinical MRI contrast agents, and at 1.5 T
effectively defines minute, scattered lesions whose location is unknown before scanning. Persistent tumor signal would enable
tumor definition during a lengthy total-body MRI and would permit MRI-guided biopsy without concern for signal wash-out.
CLINICAL RELEVANCE/APPLICATION
Metastases no more than 2 mm are easily defined by 3Gd-HPPH, which is tumor-avid for 48 h; this compound may represent an
"FDG for total body MRI", changing the paradigm of tumor staging/imaging.
MI219-SDTUB4
18F-FDG-PET/CT in Breast Carcinoma, A Role of Time-of-flight and Point Spread Function in
Improvement of Diagnostic Performance
Station #4
Participants
Jiri Ferda, MD, PhD, Plzen, Czech Republic (Presenter) Nothing to Disclose
Eva Ferdova, MD, Plzen, Czech Republic (Abstract Co-Author) Nothing to Disclose
Ondrej Hes, MD, PhD, Plzen, Czech Republic (Abstract Co-Author) Nothing to Disclose
Boris Kreuzberg, Plzen, Czech Republic (Abstract Co-Author) Nothing to Disclose
PURPOSE
To evaluate the possibilities of the breast carcinoma detection and and N-staging assesment of the breast carcinoma using 18FFDG-PET/CT and to compare the performance of the equipment with diferent reconstruction and acquisition systems.
METHOD AND MATERIALS
In 35 women with breast carcinoma (mean age 45.6, range 29- 73) were examined before surgery using 18F-FDG-PET/CT. The
diagnositc performance was compared when the three-ring PET subsystem with 16 slice CT configuration was used (15 women) and
four-ring PET subsystem with 128-slice CT configuration (20 women). Both systems were equiped with lutetium ortosilicate
detector material. The thre-ring system enables reconstruction ordered subset expectation maximization (OSEM) iterative
reconstruction and matrix 256 x 256 points. Four-ring system used image reconstruction using time-of-flight and point spread
function. The dose of 4 MBq/kg of FDG and 3 min acquisition per bed position was used in three-ring system, 2.5 MBq/kg of FDG
and 1.5 min acquisition per bed position was used in four-ring system, the matrix was used 400 x 400 points.
RESULTS
The FDG avid carcinoma was identified in the whole sample in all of 35 cases. The sensitivity to detect axillary lymph nodes
metastases reached 71% (5/7), specificity of 65% (5/8) using three ring system with OSEM reconstruction, in patients examined by
the system enabling the reconstruction time-of-flight and point spread function, the sensitivity was improved significantly to 100%
(9/9) with specificity of 82 (9/11)%.
CONCLUSION
The novel imaging system with reconstructions of the PET images with time-of-flight and point spread function were enabling the
improvement of the diagnostic performance in N-staging of breast carcinoma even the dose of radiopharmaceutical was descreased
from 4 to 2,5 MBq/kg and the acquisition time dropped from 3 to 1.5 min.
CLINICAL RELEVANCE/APPLICATION
Time-of-flight and point spread function reconstructions impoved the imaging of axillary lymph nodes affected by the metastases of
the breast carcinoma even if the dose of FDG and acquisition time were significantly reduced.
SSJ02
Breast Imaging (Nuclear Medicine/Molecular Imaging)
Tuesday, Dec. 1 3:00PM - 4:00PM Location: E450A
BR
MI
MR
NM
AMA PRA Category 1 Credit ™: 1.00
ARRT Category A+ Credit: 1.00
Participants
Priscilla J. Slanetz, MD, MPH, Belmont, MA (Moderator) Nothing to Disclose
Donna M. Plecha, MD, Strongsville, OH (Moderator) Advisory Board, Hologic, Inc;
Sub-Events
SSJ02-01
Multiparametic Evaluation of Breast Lesions with 18-Fluorodeoxyglucose Positron Emission
Tomography Magnetic Resonance Imaging
Tuesday, Dec. 1 3:00PM - 3:10PM Location: E450A
Participants
Courtney A. Garlick, MD, Cleveland, OH (Presenter) Nothing to Disclose
Jenny Wang-Peterman, MD, Cleveland, OH (Abstract Co-Author) Nothing to Disclose
Peter F. Faulhaber, MD, Cleveland, OH (Abstract Co-Author) Speaker, Koninklijke Philips NV; Grant, Koninklijke Philips NV; Medical
Advisor, MIM Software Inc
Kuan-Hao Su, Shaker Heights, OH (Abstract Co-Author) Research Grant, Koninklijke Philips NV
Raymond Muzic, PhD, Cleveland, OH (Abstract Co-Author) Research Grant, Koninklijke Philips NV
Maryam Etesami, MD, Cleveland, OH (Abstract Co-Author) Nothing to Disclose
Nelly Salem, MD, Cleveland, AL (Abstract Co-Author) Nothing to Disclose
Donna M. Plecha, MD, Strongsville, OH (Abstract Co-Author) Advisory Board, Hologic, Inc;
PURPOSE
To assess the performance of multiparametric 18-Fluorodeoxyglucose positron emission tomography magnetic resonance imaging
(MP PET-MRI) using dynamic contrast-enhanced MRI (DCE-MRI), diffusion weighted imaging (DWI) and FDG-PET in differentiating
between benign and malignant abnormalities identified on DCE-MRI.
METHOD AND MATERIALS
28 newly diagnosed breast cancer patients were prospectively enrolled in this Institutional Review Board (IRB) approved study. 25
patients underwent FDG PET-MRI imaging. Breast abnormalities identified in these patients on DCE-MRI were assessed for their
likelihood of malignancy for each individual parameter (DCE-MRI, DWI and PET) as well as for combinations of the parameters.
Malignancy vs. benignity of each lesion was then determined by histopathology or, in some cases where final pathologic diagnosis
was not available, by pre- and post-chemotherapy imaging. If an abnormality showed a response to chemotherapy, it was
presumed malignant. Sensitivity, Specificity, PPV and NPV were then measured.
RESULTS
60 lesions were identified, of which 6 had no pathology or imaging follow-up, 11 were deemed benign and 43 malignant (6 presumed
malignant). MP PET-MRI significantly improved specificity over DCE-MRI (100% vs 45%, p=0.012) and DCE-MRI combined with PET
(100% vs 36%, p=0.004) or DWI (100% vs 44%, p=0.011). There was a trend toward increased PPV with MP PET-MRI vs DCE-MRI
(100% vs 88%), but was not statistically significant. Further, there was no statistically significant differences in sensitivity or NPV
(p>0.05).
CONCLUSION
Multiparameter 18FDG PET-MRI increases specificity and decreases false positives of DCE-MRI without significant loss of sensitivity.
CLINICAL RELEVANCE/APPLICATION
MP PET-MRI improves specificity of DCE-MRI which may lead to more accurate staging, decreasing false positives and unnecessary
biopsies.
SSJ02-02
Visualization of Primary Breast Cancer Lesions with a Dedicated PET for Hanging Breast Imaging in
Comparison to PET/CT
Tuesday, Dec. 1 3:10PM - 3:20PM Location: E450A
Participants
Suzana Teixeira, MD, Amsterdam, Netherlands (Presenter) Nothing to Disclose
Jose Ferrer Rebolleda, MD, Valencia, Spain (Abstract Co-Author) Nothing to Disclose
Bastiaan Koolen, MD, Amsterdam, Netherlands (Abstract Co-Author) Nothing to Disclose
Jelle Wesseling, Amsterdam, Netherlands (Abstract Co-Author) Nothing to Disclose
Raul Sanchez Jurado, Valencia, Spain (Abstract Co-Author) Nothing to Disclose
M P. Stokkel, MD,PHD, Leiden, Netherlands (Abstract Co-Author) Nothing to Disclose
Maria Del Puig Cozar Santiago, MD, Valencia, Spain (Abstract Co-Author) Nothing to Disclose
Vincent van der Noort, PhD, Amsterdam, Netherlands (Abstract Co-Author) Nothing to Disclose
Emiel Rutgers, Amsterdam, Netherlands (Abstract Co-Author) Nothing to Disclose
Renato Valdes Olmos, Amsterdam, Netherlands (Abstract Co-Author) Nothing to Disclose
PURPOSE
Evaluate the performance of a dedicated PET for hanging breast imaging (MAMMI-PET) for the visualization of breast cancer lesions
in two European hospitals while comparing the results obtained with whole body PET/CT.
METHOD AND MATERIALS
After institutional review board approval we prospectively included 230 female patients (age: mean 52 y, range 24-82y) with >= 1
histologically confirmed primary breast cancer lesion (=index lesion) between March 2011 and March 2014. All patients that gave
written informed consent were scanned with the MAMMI-PET (Oncovision, Valencia, Spain) after injection of 180-240 MBq and
following standard whole body PET/CT. All index lesions on the MAMMI-PET scored 0, 1 or 2 for quantity of FDG uptake, which was
tested in relation to histological (ductal, lobular) and molecular (ER/PR/Her2) breast cancer subtype, tumor grade, breast length,
maximal tumor diameter and affected breast quadrants. We also compared the visibility score of the primary tumor between
MAMMI-PET with standard PET/CT.
RESULTS
Totally 234 affected breasts were scanned with proven primary breast cancer lesions (diameter 5-170 mm). The MAMMI-PET
sensitivity was 98.6% for lesions located within the device scanning range. Twenty-three lesions (9.8%) near the pectoral muscle
did not reach the scanning range and where therefore not visualised by MAMMI-PET. Of 11 index lesions smaller than 1 cm 9 where
visualised by MAMMI-PET. Lesion visibility was not influenced by tumor grade (p=0.21) or cancer subtype (p=0.8345). In
comparison to PET/CT MAMMI missed 19 lesions of which 18 were outside its scanning range. However PET/CT was not able to
detect 15 index lesions visualized by MAMMI (p=0.61). MAMMI-PET detected 41 additional lesions of which 16 where proven
malignant (39%), 15 (36.6%) seen on other modalities, and 14 (34,2%) only visible on MAMMI-PET.
CONCLUSION
Without limitations due to tumor size, grade or histological subtype the MAMMI-PET is able to detect almost all breast cancer index
lesions located within its scanning range and is for this lesion category more sensitive than PET/CT.
CLINICAL RELEVANCE/APPLICATION
With the dedicated MAMMI-PET it is possible to visualise primary breast cancer lesions in prone position without compression
without the limitation known for PET/CT of tumor size and histological subtype.
SSJ02-03
Pretreatment Prediction of Response to Preoperative Chemotherapy by Multiparametric F-18
Fluorodeoxyglucose Positron Emission Tomography - Magnetic Resonance Imaging in Breast Cancer
Patients
Tuesday, Dec. 1 3:20PM - 3:30PM Location: E450A
Participants
Maryam Etesami, MD, Cleveland, OH (Presenter) Nothing to Disclose
Peter F. Faulhaber, MD, Cleveland, OH (Abstract Co-Author) Speaker, Koninklijke Philips NV; Grant, Koninklijke Philips NV; Medical
Advisor, MIM Software Inc
Courtney A. Garlick, MD, Cleveland, OH (Abstract Co-Author) Nothing to Disclose
Jenny Wang-Peterman, MD, Cleveland, OH (Abstract Co-Author) Nothing to Disclose
Raymond Muzic, PhD, Cleveland, OH (Abstract Co-Author) Research Grant, Koninklijke Philips NV
Kuan-Hao Su, Shaker Heights, OH (Abstract Co-Author) Research Grant, Koninklijke Philips NV
Nelly Salem, MD, Cleveland, AL (Abstract Co-Author) Nothing to Disclose
Donna M. Plecha, MD, Strongsville, OH (Abstract Co-Author) Advisory Board, Hologic, Inc;
PURPOSE
To assess whether multiparametric [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET) - magnetic resonance
imaging (FDG-PET/MR) using dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted imaging (DWI), and FDG-PET is able to
predict response to preoperative chemotherapy in breast cancer patients. A pilot study.
METHOD AND MATERIALS
A prospective, IRB approved study including twenty seven female patients with biopsy proven primary breast cancer underwent
breast-specific PET/MR using Philips Ingenuity TF, 3T system. Patients treated with preoperative chemotherapy followed by surgery
or post chemotherapy imaging were enrolled. Patients who had evidence of systemic metastases were excluded. DCE-MRI, DWI,
and FDG-PET were qualitatively and semiquantitatively analyzed. The response to chemotherapy was assessed by the pathologic
analysis of surgical specimen, or post chemotherapy imaging in two patients awaiting definitive surgery, and then correlated with
PET/MR data.
RESULTS
Eighteen patients met the criteria to be enrolled in the study. Response to chemotherapy was complete in 4 (22%), partial in 8
(44%), and no response in 6 (33%) patients. On MRI, the apparent diffusion coefficient (ADC) value for responders to
chemotherapy (partial or complete) (mean=0.78 x 10¯³ mm²/s) was significantly higher than for non-responders (mean=0.56 x 10¯³
mm²/s) (p=0.45). All the responders had ADC value of greater than 0.65 x 10¯³ mm²/s. With FDG-PET, there was no significant
difference in maximum standardized uptake value (SUVmax) in responders (mean=7.38) versus non-responders (mean= 6.87)
(p=0.85). The DCE-MRI kinetic curves and morphology showed no significant difference between responders and non-responders.
CONCLUSION
In our pilot study, DCE-MRI with DWI was found to be valuable for pretreatment prediction of response to chemotherapy in breast
cancer. Higher ADC values were associated with response. With limited number of patients, there was no proven benefit of PET/MR
over DCE-MRI in the prediction of response to chemotherapy. Further studies with larger cohorts and evaluating imaging
characteristic changes after an early dose of chemotherapy would be helpful.
CLINICAL RELEVANCE/APPLICATION
DCE-MRI with DWI may improve the ability to predict response to preoperative chemotherapy in patients with breast cancer.
SSJ02-04
Insights in Physiology of Breast Parenchyma: Is There a Correlation of Breast Parenchymal Uptake of
18FDG, Breast Parenchymal Enhancement on DCE-MRI, Amount of Fibroglandular Tissue and Age?
Tuesday, Dec. 1 3:30PM - 3:40PM Location: E450A
Participants
Doris Leithner, Frankfurt am Main, Germany (Presenter) Nothing to Disclose
Pascal A. Baltzer, MD, Vienna, Austria (Abstract Co-Author) Nothing to Disclose
Heinrich Magometschnigg, Vienna, Austria (Abstract Co-Author) Nothing to Disclose
Georg J. Wengert, MD, Vienna, Austria (Abstract Co-Author) Nothing to Disclose
Thomas H. Helbich, MD, Vienna, Austria (Abstract Co-Author) Research Grant, Medicor, Inc; Research Grant, Siemens AG; Research
Grant, C. R. Bard, Inc
Katja Pinker-Domenig, MD, Vienna, Austria (Abstract Co-Author) Nothing to Disclose
PURPOSE
To assess and correlate breast parenchymal uptake (BPU) in 18FDG PET-CT with breast parenchymal enhancement (BPE) and
amount of fibroglandular tissue (FGT) with 3T DCE-MRI and to determine the influence of patient age on BPU, BPE and FGT.
METHOD AND MATERIALS
In this IRB-approved prospective study 129 patients with a BIRADS 4/5 lesion underwent 18FDG PET-CT and 3T DCE-MRI.
Examinations were no longer than six days apart. Patients were injected with approximately 300 MBq 18FDG. After 60 min a prone
PET-CT dataset over the breasts was acquired and CT data was solely used for attenuation correction. For DCE-MRI a contrastenhanced high resolution 3D-T1-weighted sequence before and after application of a standard dose of 0.1 mmol/kg Gd-DOTA
(Dotarem®) was employed. BPU and BPE were assessed in the healthy contralateral breast. BPU was calculated quantitatively using
SUVmax. FGT and BPE were qualitatively assessed by two independent readers using the revised ACR BI-RADS® classification. To
assess reproducibility all measurements were repeated by reader 1. Appropriate statistical tests were used to assess correlation of
FGT, BPE, BPU, inter- and intra-reader agreement.
RESULTS
There was no BPE in 58, mild in 54, moderate in 14 and marked in 3 patients. SUVmax for patients with no BPE was 1.57 (SD 0.6),
for mild BPE 1.93 (SD 0.6), for moderate BPE 2.42 (SD 0.5), and for marked BPE 1.45 (SD 0.3). There were highly significant
correlations between age, BPU, BPE and FGT.Correlation coefficients ranged between moderate and strong. While BPE, BPU and FGT
were positively correlated with each other, all of these parameters were negatively correlated with age (Figure 1). The intraclass
correlation coefficient for BPU measurements was excellent with 0.973. Inter-reader and intra-reader agreement for BPE was very
good with a Kappa-value of 0.860 and 0.822 respectively.
CONCLUSION
BPU of normal breast parenchyma can be reproducibly assessed using SUV metrics and is positively correlated with BPE and FGT in
DCE-MRI. There is a negative correlation of BPU, BPE and FGT with age.
CLINICAL RELEVANCE/APPLICATION
BPU, BPE and FGT provide insights in tumor physiology and decrease with age. In patients with dense breasts a possible masking
effect of lesions by BPU/BPE must be considered.
SSJ02-05
Clinical Comparison of MBI and BSGI for Low Dose Breast Imaging
Tuesday, Dec. 1 3:40PM - 3:50PM Location: E450A
Participants
Zaiyang Long, PhD, Rochester, MN (Presenter) Nothing to Disclose
Carrie B. Hruska, PhD, Rochester, MN (Abstract Co-Author) Institutional license agreement, Gamma Medica, Inc
Michael K. O'Connor, PhD, Rochester, MN (Abstract Co-Author) Royalties, Gamma Medica, Inc
PURPOSE
Breast specific gamma imaging (BSGI) and molecular breast imaging (MBI) are promising techniques for supplemental imaging in
women with dense breast tissue. This study compares the performance of such systems at administered doses of Tc-99m sestamibi
that are acceptable for low dose imaging.
METHOD AND MATERIALS
The BSGI system comprised a single-head multi-crystal NaI system (pixel size 3.2×3.2 mm) equipped with a hexagonal-hole lead
collimator. The MBI system comprised a dual-head cadmium zinc telluride detector system (pixel size 1.6×1.6 mm) equipped with
registered tungsten collimators. System sensitivity, uniformity, energy and spatial resolution were measured using NEMA methods. A
6-cm thick contrast detail (CD) phantom with 48 hot spots (3-10 mm diameter) was used to assess contrast-noise-ratio (CNR)
using average background count densities observed in clinical studies at 4mCi dose. 25 patients receiving 4-8mCi doses were
imaged on both systems under IRB approval.
RESULTS
The BSGI and MBI systems had integral uniformities of 6.1% and 3.8%, and energy resolution (at 140 keV) of 13.1% and 4.3%,
respectively. System sensitivity was 403 cpm/uCi (BSGI) and 790 cpm/uCi (MBI) using a standard +/-10% energy window. In
clinical use, MBI employs an energy window of 110-154 keV, yielding a sensitivity of 1042 cpm/uCi. At distances of 1, 3 and 5 cm
from the collimator, spatial resolution was 4.1, 5.1 and 6.2 mm on BSGI, and 2.0, 4.7 and 7.3 mm on MBI, respectively. However,
with the dual head configuration of MBI, spatial resolution at 5 cm distance from one detector is equivalent to 1cm from the
opposing detector for the most frequently observed compressed breast thickness of 6cm. Application of the Rose criterion for lesion
detection (CNR>3) to images of the CD phantom showed that for BSGI, 9 hot spots at 4mCi were undetectable. For MBI, 5 hot
spots at 4mCi were undetectable. In the 25 patient studies, 5 lesions (CNR>3) were identified on MBI whereas 3 were identified on
BSGI.
CONCLUSION
Over the clinical range 0-6 cm, the MBI system demonstrated better spatial resolution than the BSGI system while yielding a 2.6-
fold greater sensitivity. This resulted in improved lesion detection and allows MBI to be utilized at lower doses than BSGI.
CLINICAL RELEVANCE/APPLICATION
Molecular breast imaging (MBI) system demonstrated better performance characteristics than BSGI system. MBI is more suitable for
low dose breast imaging.
SSJ02-06
Correlation of Semi-Quantitative Breast-Specific Gamma Imaging Findings with Dynamic ContrastEnhanced MRI Parameters assessed by a Computer-Aided Evaluation Program and Prognostic
Factors of Breast Cancers
Tuesday, Dec. 1 3:50PM - 4:00PM Location: E450A
Participants
Saemee Ahn, MD, PhD, Seoul, Korea, Republic Of (Presenter) Nothing to Disclose
Hye Ryoung Koo, MD, Seoul, Korea, Republic Of (Abstract Co-Author) Nothing to Disclose
Jeong Seon Park, MD, Seoul, Korea, Republic Of (Abstract Co-Author) Nothing to Disclose
Soo-Yeon Kim, MD, Guri, Korea, Republic Of (Abstract Co-Author) Nothing to Disclose
PURPOSE
To investigate whether a correlation exists between the semi-quantitative breast-specific gamma imaging (BSGI) findings and
dynamic contrast-enhanced (DCE) MRI parameters assessed by a computer-aided evaluation program or prognostic factors of
breast cancers
METHOD AND MATERIALS
Semi-quantitative index of lesion to non-lesion ratio (L/N) in BSGI and DCE-MRI parameters assessed by a computer-aided
evaluation program and histopathologic prognostic factors of 47 invasive breast cancers were obtained. Correlation between L/N
ratio and DCE-MRI parameters assessed by a computer-aided evaluation program, including tumor size (cm), angio-volume (cc),
degree of initial peak enhancement (%), persistent enhancement proportion (%), washout enhancement proportion (%), or
prognostic factors, including axillary nodal status, histologic grade, expression of estrogen receptor (ER), progesterone receptor
(PR), human epidermal growth factor receptor 2 (HER2) and Ki-67 were analyzed.
RESULTS
The mean L/N ratio of 47 tumors was 3.63 ± 2.19 (range: 1-13.1). The L/N ratio was higher in tumors with larger tumor size
(P<0.001), increased angio-volume (P<0.001), higher degree of initial peak enhancement (P<0.001), increased washout
enhancement proportion (P=0.003), high histologic grade (P=0.013), and higher Ki-67 (P=0.002). The calculated multiple correlation
coefficient was 0.80 (P<0.001).
CONCLUSION
There was a strong multiple correlation between the semi-quantitative L/N ratio in BSGI with DCE-MRI parameters assessed by a
computer-aided evaluation program and prognostic factors of breast cancers.
CLINICAL RELEVANCE/APPLICATION
The relationship between the radiotracer uptake in molecular imaging and DCE-MRI parameters may offer an in-depth understanding
into the characterization of breast cancer.
SSJ14
Molecular Imaging (Prostate/Neuroendocrine Tumors)
Tuesday, Dec. 1 3:00PM - 4:00PM Location: S504CD
GU
BQ
MI
MR
AMA PRA Category 1 Credit ™: 1.00
ARRT Category A+ Credit: 1.00
FDA
Discussions may include off-label uses.
Participants
Peter L. Choyke, MD, Rockville, MD (Moderator) Researcher, Koninklijke Philips NV Researcher, General Electric Company Researcher,
Siemens AG Researcher, iCAD, Inc Researcher, Aspyrian Therapeutics, Inc Researcher, ImaginAb, Inc Researcher, Aura Biosciences,
Inc
Vikas Kundra, MD, PhD, Houston, TX (Moderator) License agreement, Introgen Therapeutics, Inc
Sub-Events
SSJ14-01
Promising Role of Ga-68 PSMA PET/CT over Conventional Imaging in Staging and Restaging of
Carcinoma Prostate
Tuesday, Dec. 1 3:00PM - 3:10PM Location: S504CD
Participants
Venkatesh Rangarajan, MBBS, Mumbai, India (Presenter) Nothing to Disclose
Archi Agrawal, MBBS, Mumbai, India (Abstract Co-Author) Nothing to Disclose
Rasika Kabnurkar, MBBS, Mumbai, India (Abstract Co-Author) Nothing to Disclose
Nilendu C. Purandare, DMRD, Mumbai, India (Abstract Co-Author) Nothing to Disclose
Sneha A. Shah, Mumbai, India (Abstract Co-Author) Nothing to Disclose
PURPOSE
1) To study the utility of Ga-68 Prostate Specific Membrane Antigen (PSMA) Positron Emission Tomography/Computed Tomography
(PET/CT) for staging and restaging of Carcinoma Prostate (CaP).2) To compare the efficacy of Ga-68 PSMA PET/CT with Contrast
Enhanced Computed Tomography (CECT) and F18 Sodium Fluoride (NaF) PET/CT for lesion detection
METHOD AND MATERIALS
Retrospective audit of prospectively maintained data of 25 patients of CaP (3 for staging and 22 with biochemical failure for
restaging) who underwent Ga-68 PSMA PET/CT, CECT and F18 NaF PET/CT scan. The imaging findings were analyzed on lesionlesion and patient-patient basis for concordance and discordance.
RESULTS
All the 3 cases imaged for staging evaluation demonstrated Ga-68 PSMA uptake at the site of primary while CECT demonstrated
lesion in only 1 patient. In cases with suspected biochemical failure, local recurrence was detected in 59% (13/22) patients on Ga68 PSMA PET/CT as against 9 % (2/22) detected on CECT. In 25 patients studied, Ga-68 PSMA PET/CT detected 43 metastatic
nodes compared to 29 detected on CECT. Ga-68 PSMA detected additional metastases in sub cm sized nodes in 24% (6/25)
patients. Ga-68 PSMA had incremental value in detecting occult extranodal metastases involving urinary bladder, pararectal nodule
and peritoneal deposit in 8% (2/25) patients .In 25 patients, 109 skeletal lesions were detected on Ga-68 PSMA while F18 NaF
PET/CT demonsrated147 lesions. Concordance in imaging findings of Ga-68 PSMA PET/CT and F 18 Fluoride PET/CT was noted in
68% (17/25) patients. Ga-68 PSMA PET/CT had an incremental value in staging of 1 patient where it detected lytic and marrow
metastases. In restaging group, 7 patients showed additional lesions on F18 NaF PET/CT.
CONCLUSION
Ga-68 PSMA PET/CT is superior in detection of primary, nodal and soft tissue metastases as compared to conventional imaging
techniques. However, F18 NaF PET/CT appears to detect more skeletal lesions in patients with biochemical failure in our study and
further prospective trials are warranted to confirm these findings.
CLINICAL RELEVANCE/APPLICATION
Ga-68 PSMA PET/CT has an incremental value as a one stop shop in staging and restaging of carcinoma prostate
SSJ14-02
18F-fluoro-4-thia-palmitate (18F-FTP) PET Imaging for Evaluation of Exogenous Fatty Acid
Metabolism in Prostate Cancer: Implications for Treatment Optimization
Tuesday, Dec. 1 3:10PM - 3:20PM Location: S504CD
Participants
Pedram Heidari, MD, Boston, MA (Presenter) Nothing to Disclose
Shadi A. Esfahani, MD, MPH, Boston, MA (Abstract Co-Author) Nothing to Disclose
Giorgia Zadra, PhD, Boston, MA (Abstract Co-Author) Nothing to Disclose
Michael S. Placzek, PhD, Charlestown, MA (Abstract Co-Author) Nothing to Disclose
Benjamin Larimer, PhD, Charlestown, MA (Abstract Co-Author) Nothing to Disclose
Jacob M. Hooker, PhD, Charlestown, MA (Abstract Co-Author) Nothing to Disclose
Massimo Loda, MD, Boston, MA (Abstract Co-Author) Nothing to Disclose
Umar Mahmood, MD, PhD, Charlestown, MA (Abstract Co-Author) Research Grant, Sabik Medical Inc; Advisory Board, Blue Earth
Diagnostics Limited;
PURPOSE
Upregulation of de novo lipogenesis is a major metabolic change in PCa development, and correlates with tumor progression and
Upregulation of de novo lipogenesis is a major metabolic change in PCa development, and correlates with tumor progression and
poor prognosis. Differentiation of diet-derived versus de novo fatty acid (FA) utilization in PCa is essential in designing anti-lipogenic
therapeutics. We aim to evaluate the use of 18F-fluoro-4-thia-palmitate (18F-FTP) PET for assessment of exogenous FA utilization
by PCa.
METHOD AND MATERIALS
14C incorporation into lipids of LNCaP cells by a glucose donor (marker of de novo lipogenesis) was measured by a beta-counter
after treatment with vehicle, IPI-9119, or C75. Growth inhibition rescue of LNCaP cells was performed using Cell Titer Glo assay
after incubation with IPI-9119 alone or in the presence of BSA or of BSA-conjugated palmitate. For in-vitro 18F-FTP uptake study
LNCaP cells were incubated with IPI-9119, C75, Etomoxir, SSO, DMSO, and combination of IPI-9119 with Etomoxir or C75 for 24
hours. The cells were then incubated with 18F-FTP and harvested to measure retained activity corrected for cell count. IACUC
approval was obtained. Mice with subcutaneous LNCaP xenografts were fasted. PET data was acquired in list mode after injection
of 18F-FTP. The SUVmean and tracer influx constant were measured.
RESULTS
14C incorporation in lipids decreased to approximately 25% of control using both IPI-9119 and C75 indicating FASN inhibition. LNCaP
growth inhibition was aborted by BSA-conjugated palmitate. 18F-FTP uptake significantly increased with IPI-9119 treatment, while
C75, etomoxir, SSO treatment reduced 18F-FTP uptake. 18F-FTP PET demonstrated significantly decreased uptake in LNCaP tumors
following treatment with C75 and etomoxir compared to control (SUVmean=0.20±0.01, 0.25±0.2, and 0.40±0.02, respectively).
CONCLUSION
We demonstrated that metabolic imaging using 18F-FTP can be used to assess the exogenous FA utilization by PCa. As expected,
IPI-9119 (selective FASN inhibitor) increased the exogenous FA (18F-FTP) uptake while C75, which induces a host of metabolic
modulations other than FASN inhibition paradoxically reduces 18F-FTP uptake. Etomoxir (FAO inhibitor) and SSO (FA transporter
inhibitor) reduce 18F-FTP uptake as expected.
CLINICAL RELEVANCE/APPLICATION
Understanding the effect of exogenous lipid availability on therapeutic potential of targeting de novo lipogenesis is critical in
prostate cancer treatment. This could lead to treatment strategies that result in maximal efficacy.
SSJ14-03
Feasibility of Hyperpolarized 13C-Pyruvate Magnetic Resonance Spectroscopy for Pancreatic Cancer
Diagnostic Imaging
Tuesday, Dec. 1 3:20PM - 3:30PM Location: S504CD
Participants
Stephanie K. Carlson, MD, Rochester, MN (Presenter) Royalties, Medspira, LLC
Alan Penheiter, PhD, Rochester, MN (Abstract Co-Author) Nothing to Disclose
Prasanna K. Mishra, PhD, Rochester, MN (Abstract Co-Author) Nothing to Disclose
Fergus J. Couch, PhD, Rochester, MN (Abstract Co-Author) Nothing to Disclose
Slobodan I. Macura, PhD, Rochester, MN (Abstract Co-Author) Nothing to Disclose
John D. Port, MD, PhD, Rochester, MN (Abstract Co-Author) Nothing to Disclose
Malgorzata Marjanska, PhD, Minneapolis, MN (Abstract Co-Author) Nothing to Disclose
Claire E. Bender, MD, Rochester, MN (Abstract Co-Author) Nothing to Disclose
PURPOSE
Hyperpolarized (HP) 13C magnetic resonance spectroscopic imaging (MRSI) is a recently developed technique that allows the
detection of injected 13C-labeled agents and their metabolites in real-time. The purpose of this study was to identify and explore
potential metabolic pathways in pancreatic ductal adenocarcinoma (PDAC) that could be targeted with HP-13C MRSI to increase
the diagnostic accuracy of pancreatic cancer imaging.
METHOD AND MATERIALS
We performed gene expression profiling using laser capture microdissection and RNAseq on histologically-confirmed primary PDAC
tumors and normal pancreas tissue from 21 patients. A promising, highly upregulated and imageable metabolic pathway (the
conversion of pyruvate to lactate) was identified. To further explore this pathway in vivo, mice bearing genetically-engineered
PDAC tumors were injected with 200 microliters of 80 mM [1-13C]-pyruvate. Tumors were quench-frozen and excised 30 s postinjection. Spectroscopic data on tumor lysates was obtained using 1H and 13C nuclear magnetic resonance. Studies were approved
by our IRB and IACUC.
RESULTS
Gene expression studies showed that transcripts encoding transporters and enzymes responsible for cellular import of pyruvate,
export of lactate, and conversion of pyruvate to lactate are almost universally upregulated in PDAC compared to normal pancreas,
while competing pathways of mitochondrial pyruvate metabolism and cytoplasmic pyruvate to alanine conversion are consistently
low. NMR analysis of PDAC tumors showed a tumor metabolic signature consistent with a very high lactate concentration and high
lactate-to-alanine ratio. Quantitative analysis after injection of [1-13C]-pyruvate showed a 4.8-fold enrichment of intratumoral [113C]-lactate over natural abundance, indicating that ~5% of the total lactate in the tumor at 30 s post-injection was derived from
the injected [1-13C]-pyruvate.
CONCLUSION
PDAC tumors have a pyruvate-lactate metabolic signature that can be quantitated with 13C-pyruvate NMR. Further exploration of
HP-13C-pyruvate MRSI for PDAC is warranted.
CLINICAL RELEVANCE/APPLICATION
A new molecular imaging strategy for PDAC used in conjunction with existing morphological imaging could transform patient
management in clinically-challenging scenarios.
SSJ14-04
Evaluation of Fast Non-enhanced PET/MR Examination Protocols in a Fully Integrated PET/MR
System for Patients with Neuroendocrine Tumours: Direct Comparison to Multiphase Contrastenhanced PET/CT
Tuesday, Dec. 1 3:30PM - 3:40PM Location: S504CD
Participants
Ferdinand F. Seith, BSC, Tuebingen, Germany (Presenter) Nothing to Disclose
Christian la Fougere, Munich, Germany (Abstract Co-Author) Nothing to Disclose
Christina Pfannenberg, MD, Tuebingen, Germany (Abstract Co-Author) Nothing to Disclose
Konstantin Nikolaou, MD, Tuebingen, Germany (Abstract Co-Author) Speakers Bureau, Siemens AG Speakers Bureau, Bracco Group
Speakers Bureau, Bayer AG
Nina Schwenzer, MD, Tuebingen, Germany (Abstract Co-Author) Nothing to Disclose
Cornelia Brendle, MD, Tubingen, Germany (Abstract Co-Author) Nothing to Disclose
Christina Schraml, MD, Tuebingen, Germany (Abstract Co-Author) Nothing to Disclose
PURPOSE
In patients with neuroendocrine tumours (NET), kidney failure is a common complication of radionuclide therapy. It is known that
multiphase contrast-enhanced PET/CT is superior to non-enhanced PET/CT in diagnosing metastases with low or no tracer uptake
as well as small lesions especially in the liver. However, due to the superior soft tissue contrast of MRI it is possible that nonenhanced PET/MR offers the same information as contrast-enhanced PET/CT. The aim of the study was therefore to evaluate a
fast protocol in PET/MR without contrast agent in direct comparison to multiphase contrast-enhanced PET/CT as gold standard.
METHOD AND MATERIALS
39 Patients (22 female, 58±13 years) were examined in multiphase contrast-enhanced 68Ga-DOMITATE-PET/CT in a clinical setup
and in PET/MR subsequently. 2 blinded readers investigated PET/MR examinations of the abdomen with 3 different setups:
T2HASTE+PET (30min), T2HASTE+TSET2+PET (35min) and T2HASTE+TSET2+DWI+PET (35min). The T2HASTE was acquired under
free breathing with continuous table move. DWI was acquired with two b-values (0, 800 s/mm2). Metastatic lesions were defined
as functional and/or morphological suspicious lesions or lymph nodes. The results were compared with the contrast-enhanced
PET/CT, follow-up examinations and histopathology, if available.
RESULTS
T2HASTE sequences were of diagnostic quality in all patients. DWI suffered from artefacts especially in the upper regions of the
liver. Compared with contrast-enhanced PET/CT high agreement was found with T2HASTE+TSET2+DWI+PET.
CONCLUSION
A protocol for PET/MR including T2HASTE, TSET2, DWI and PET seems to provide comparable results compared with multiphase
contrast-enhanced PET/CT. With an estimated time of 35 min for a whole body examination, this might serve as a legitimate
alternative to contrast-enhanced PET/CT for patients with kidney failure in the future.
CLINICAL RELEVANCE/APPLICATION
In patients with neuroendocrine tumours (NET) and kidney failure, fast non-enhanced PET/MR protocols can serve as a legitimate
alternative to multiphase contrast-enhanced PET/CT examinations.
SSJ14-05
Qualitative and Quantitative Comparison of 68Ga-DOTATATE PET/CT and PET/ MRI in
Neuroendocrine Tumours
Tuesday, Dec. 1 3:40PM - 3:50PM Location: S504CD
Participants
Francesco Fraioli, MD, London, United Kingdom (Presenter) Nothing to Disclose
Alshaima Alshammari, London, United Kingdom (Abstract Co-Author) Nothing to Disclose
Evangelia Skoura, Athens, Greece (Abstract Co-Author) Nothing to Disclose
Rizwan Syed, MBBS, FRCR, London, United Kingdom (Abstract Co-Author) Nothing to Disclose
Sofia Michopoulou, London, United Kingdom (Abstract Co-Author) Nothing to Disclose
Jamshed Bomanji, London, United Kingdom (Abstract Co-Author) Nothing to Disclose
Ashley M. Groves, MBBS, Hitchin, United Kingdom (Abstract Co-Author) Investigator, GlaxoSmithKline plc; Investigator, General
Electric Company; Investigator, Siemens AG; ; ;
PURPOSE
Many Neuroendocrine tumours (NET) show high somatostatin receptor avidity. The aim of this study is to compare 68Ga-DOTATATE
PET/CT with 68Ga-DOTATATE PET/MRI imaging in patients with known NET, and assess the confidence in anatomic lesion detection
and localization. Furthermore, the value of each sequence of MRI was separately evaluated.
METHOD AND MATERIALS
We analysed the data of 38 NET patients. Cross over of both 68Ga-DOTATE PET/CT and PET/MRI scans were performed. MR
protocol was as follow: T1 MPR, pre and post gadolinium injection, T2 haste, DW1 (b0, 500, 1000). Two observers for 68GaDOTATATE PET/MRI and one observer for 68Ga-DOTATATE PET/CT, independently, reviewed the images and inter observer and
inter modality correlation was assessed by using interclass correlation.
RESULTS
Our initial data showed good inter modality correlation between 68Ga-PET/CT and PET/MRI. All lesions considered as malignant in
PET/CT were equally depicted in PET/MRI in the compared regions. Both modalities, revealed liver metastases in the same number
of patients (18 patients), and bone metastases in 7 patients. However, counting the number of liver lesions in each patient, 68GaDOTATATE PET/MRI was able to recognize more lesions in 3 patients. On the other hand, more lung lesions were detected in the
lung in the CT component compared to MRI component (7 lesions versus 4). The contrast and DWI sequence of PET/MRI did not
have a significant effect on final outcome, but in a selected number of cases these images confirmed and helped to further
characterize and detect more lesions. Inter observer reliability was equally very good in both modalities.
CONCLUSION
This study demonstrates the potential of 68Ga-DOTATOC PET/MRI in patients with NET, with special advantages in the
characterization of liver lesions.
CLINICAL RELEVANCE/APPLICATION
68Ga-DOTATOC PET/MRI can help in diagnosis and staging of patients with NET, with special advantages in the characterization of
liver lesions.
SSJ14-06
68Ga-DOTATOC Uptake in Somatostatin Expressing Tumors is Directly Related to Specific Activity:
Implications for Receptor Quantitation Imaging
Tuesday, Dec. 1 3:50PM - 4:00PM Location: S504CD
Participants
Pedram Heidari, MD, Boston, MA (Presenter) Nothing to Disclose
Dominik Berzaczy, MD, Vienna, Austria (Abstract Co-Author) Nothing to Disclose
Alicia Leece, Boston, MA (Abstract Co-Author) Nothing to Disclose
Shadi A. Esfahani, MD, MPH, Boston, MA (Abstract Co-Author) Nothing to Disclose
Umar Mahmood, MD, PhD, Charlestown, MA (Abstract Co-Author) Research Grant, Sabik Medical Inc; Advisory Board, Blue Earth
Diagnostics Limited;
PURPOSE
The importance of specific activity (SA) has been previously shown in functional PET imaging studies. We hypothesized that tracer
uptake, measured using semiquantitative (SUV) or quantitative (Patlak plot) parameters, would vary considerably according to SA in
cancer receptor imaging. This study aims to evaluate the effect of SA on PET parameters used for quantitation of 68Ga-DOTATOC
uptake in somatostatin receptor (SSTR) tumor models.
METHOD AND MATERIALS
In-vitro, SSTR2 expression level was assessed using Western blot across multiple cancer lines including IMR32, Capan1, A549 and
AR42J, and was normalized for Β-actin expression. The SSTR2/Β-actin ratio was correlated to in-vitro 68Ga-DOTATOC uptake
normalized for cell counts. AR42J and IMR32 normalized 68Ga-DOTATOC uptake was plotted against 68Ga-DOTATOC SA ranging
from 0.2 to 20 Ci/g and correlation was assessed. The in-vitro studies were performed in triplicate. For in-vivo studies Institutional
Animal Care and Use Committees approval was obtained. Subcutaneous AR42J xenografts were implanted in Nu/Nu mice. Dynamic
PET scans in list mode were acquired following injection of 68Ga-DOTATOC with a wide range of SAs (0.3 - 50 Ci/g). Net tracer
influx (Ki), SUVmax and SUVmean were plotted against the SA to establish the correlation between quantitative parameters and SA.
Patlak-plot was used to calculate the tracer influx constant for the tumor ((Ki= (k1 × k3 / k2 + k3)).
RESULTS
We observed a consistent ratio between 68Ga-DOTATOC uptake per cell and SSTR2/Β-actin level across the cell lines (R2=0.95,
p<0.024). In-vitro we demonstrated a linear correlation between SA and 68Ga-DOTATOC uptake per cell in IMR32 (R2=0.98,
P<0.015) and AR42J (R2=0.99, P<0.005). We found that Ki, SUVmax, and SUVmean decreased in a linear fashion with reduction in
SA. Quantitative 68Ga-DOTATOC PET parameters had a direct linear correlation with SA (R2=0.89, p<0001 for Ki, R2=0.66,
p<0.0001 for SUVmax and R2=0.82 and p<0.0001 for SUVmean).
CONCLUSION
68Ga-DOTATOC uptake is strongly correlated to SSTR2 expression for each given SA. However, 68Ga-DOTATOC uptake in SSTRexpressing tumors increases in a linear fashion with increase in SA, over the range studied.
CLINICAL RELEVANCE/APPLICATION
68Ga-DOTATOC uptake by tumors can vary widely with change in specific activity. Quantitation for radiotherapy dosimetry and
response assessment is improved with correction for specific activity.
RC423
Molecular Imaging Mini-Course: Clinical Applications of Molecular Imaging - Oncology
Tuesday, Dec. 1 4:30PM - 6:00PM Location: E352
MI
OI
RO
PH
AMA PRA Category 1 Credits ™: 1.50
ARRT Category A+ Credits: 1.50
FDA
Discussions may include off-label uses.
Participants
Sub-Events
RC423A
Diagnosis
Participants
Terence Z. Wong, MD, PhD, Chapel Hill, NC (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
1) Discuss the potential roles and limitations of PET imaging for amyloid and tau protein in evaluating patients with dementia. 2)
Describe anatomic and functional MRI techniques for evaluating Alzheimer's disease. 3) Understand the clinical challenges of
diagnosing and managing patients with dementia.
RC423B
Staging
Participants
Dominique Delbeke, MD, PhD, Nashville, TN (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
1) The potential clinical indications of PET and PET/CT in the evaluation of patients with malignancies. 2) The impact on patient
care. 3) Recommendations for PET/CT in the NCCN guidelines.
RC423C
Evaluation of Treatment
Participants
David A. Mankoff, MD, PhD, Philadelphia, PA, ([email protected]) (Presenter) Speaker, Koninklijke Philips NV;
Consultant, General Electric Company
LEARNING OBJECTIVES
1) List applications of quantitative imaigng for clinical trials. 2) Describe the approach to the design of cancer imaging trials. 3)
Discuss biomarkers applicationf forf cancer imaging.
Honored Educators
Presenters or authors on this event have been recognized as RSNA Honored Educators for participating in multiple qualifying
educational activities. Honored Educators are invested in furthering the profession of radiology by delivering high-quality
educational content in their field of study. Learn how you can become an honored educator by visiting the website at:
https://www.rsna.org/Honored-Educator-Award/
David A. Mankoff, MD, PhD - 2013 Honored Educator
ED015-W E
Molecular Imaging Wednesday Case of the Day
W ednesday, Dec. 2 7:00AM - 11:59PM Location: Case of Day, Learning Center
MI
AMA PRA Category 1 Credit ™: .50
Participants
Jonathan E. McConathy, MD, PhD, Saint Louis, MO (Presenter) Research Consultant, Eli Lilly and Company; Research Consultant,
Blue Earth Diagnostics Ltd; Research Consultant, Siemens AG; Research support, GlaxoSmithKline plc
Suzanne E. Lapi, PhD, Saint Louis, MO (Presenter) Research Grant, ImaginAB, Inc
Bernadette V. Marquez, PhD, Saint Louis, MO (Abstract Co-Author) Nothing to Disclose
Ephraim E. Parent, MD, PhD, Saint Louis, MO (Abstract Co-Author) Nothing to Disclose
Alexander Drzezga, MD, Cologne, Germany (Abstract Co-Author) Research Grant, Eli Lilly and Company; Speakers Bureau, Siemens
AG; Speakers Bureau, General Electric Company; Speakers Bureau, Piramal Enterprises Limited; Research Consultant, Eli Lilly and
Company; Research Consultant, Piramal Enterprises Limited; ; ; ; ; ;
Keith M. Rich, MD, Saint Louis, MO (Abstract Co-Author) Nothing to Disclose
TEACHING POINTS
1) The case of the day exhibit will highlight molecular imaging techniques currently available in clinical practice and new tracers
expected to become available in the near future. 2) Participants completing this exhibit will recognize the biodistribution of newer
molecular imaging agents, understand their mechanism of action, and be familiar with their clinical utility and potential causes of
diagnostic errors.
SPSH40
Hot Topic Session: Molecular Imaging and Radionuclide Therapy for Prostate Cancer
W ednesday, Dec. 2 7:15AM - 8:15AM Location: E451A
GU
MI
OI
RO
AMA PRA Category 1 Credit ™: 1.00
ARRT Category A+ Credit: 1.00
FDA
Discussions may include off-label uses.
Participants
Uwe Haberkorn, MD, Heidelberg, Germany, ([email protected]) (Moderator) Nothing to Disclose
Eric M. Rohren, MD, PhD, Houston, TX (Moderator) Nothing to Disclose
Alexander Drzezga, MD, Cologne, Germany (Moderator) Research Grant, Eli Lilly and Company; Speakers Bureau, Siemens AG;
Speakers Bureau, General Electric Company; Speakers Bureau, Piramal Enterprises Limited; Research Consultant, Eli Lilly and
Company; Research Consultant, Piramal Enterprises Limited; ; ; ; ; ;
ABSTRACT
Radium-223 is a recently approved therapy for treatment of bone metastases in patients with metastatic prostate carcinoma. As an
alpha-emitting radioisotope, radium has the potential to be a powerful therapy for treatment of a variety of skeletal malignancies.
In this presentation, the use of radium-223 in the treatment of prostate cancer will be reviewed through a case-based format.
Future directions in radium-223 therapy will be discussed.
URL
Sub-Events
SPSH40A
Ra-223 Therapy for Skeletal Metastases from Prostate Cancer
Participants
Eric M. Rohren, MD, PhD, Houston, TX (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
1) Review the chemical and physical features of radium-223 dichloride. 2) Discuss the clinical utility of radium-223 therapy. 3)
Understand the technique for radium-223 administration. 4) Review the anticipated outcomes of radium-223 therapy through casebased review.
ABSTRACT
Radium-223 is a recently approved therapy for treatment of bone metastases in patients with metastatic prostate carcinoma. As an
alpha-emitting radioisotope, radium has the potential to be a powerful therapy for treatment of a variety of skeletal malignancies.
URL
Honored Educators
Presenters or authors on this event have been recognized as RSNA Honored Educators for participating in multiple qualifying
educational activities. Honored Educators are invested in furthering the profession of radiology by delivering high-quality
educational content in their field of study. Learn how you can become an honored educator by visiting the website at:
https://www.rsna.org/Honored-Educator-Award/
Eric M. Rohren, MD, PhD - 2015 Honored Educator
SPSH40B
Comparison of Ga-68 and F-18 Labeled Small Molecule PSMA Tracers for Prostate Cancer Imaging
Participants
Carsten Kobe, Cologne, Germany (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
1) Understand the concept of PSMA PET-imaging in the diagnosis of prostate cancer in general and in comparison to conventional
methods. 2) Learn about the currently available alternatives for radiolableling of PSMA-tracers, e.g. 68-Gallium and 18F-Fluoride and
their characteristics. 3) Gain insights from first comparative studies about the clinical value of the availble tracers with regard to
their sensitivity, specificity and practicability.
SPSH40C
PSMA Ligands for Imaging and Therapy of Prostate Cancer
Participants
Uwe Haberkorn, MD, Heidelberg, Germany (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
1) Understand the background and pharmacokinetics of PSMA ligands for PET/CT. 2) Estimate the value of PSMA-based imaging in
comparison to choline-based imaging. 3) Assess the value of PSMA-targeting for diagnosis and therapy. 4) Estimate the effects and
side effects of endoradiotherapy with PSMA ligands
ABSTRACT
The prostate-specific membrane antigen (PSMA) is frequently over-expressed in prostate cancer (PCa) which led to the
The prostate-specific membrane antigen (PSMA) is frequently over-expressed in prostate cancer (PCa) which led to the
development of several PSMA-targeting molecules are for the detection and therapy of metastatic castration resistant prostate
cancer (mCRPC).In a first diagnostic study 82.8% of 319 patients investigated with 68Ga-PSMAHBED-PET/CT at least one lesion
indicative for PCa was detected. Amongst lesions investigated by histology, 30 were false-negative in 68Ga-PSMAHBED-PET/CT, all
other lesions (n=416) were diagnosed true-positive or -negative. Fifty of 116 patients available for follow-up received a local
treatment after 68Ga-PSMAHBED-PET/CT. A comparison of the 68Ga-PSMA-ligand with 18F-fluoromethylcholine PET/CT revealed 78
PC-suspicious lesions in 32 patients using 68Ga-PSMA-PET/CT and 56 lesions in 26 patients using Choline-PET/CT (significant with
p=0.04). All lesions detected by 18F-fluoromethylcholine-PET/CT were also seen by 68Ga-PSMA-PET/CT. Since the ligand bound to
PSMA is internalized, the target may also be used for endoradiotherapy. We used a small molecule inhibitor of PSMA MIP-1095 for
therapy in 25 men with final stage mCRPC. PSA values decreased by >50% in 60.7% of the men treated. 84.6 % of men with bone
pain showed complete or moderate reduction in pain. Hematological toxicities were mild. 25% of men treated had a transient slight
to moderate dry mouth. No adverse effects on renal function were observed.In order to increase the therapeutic flexibilty a
theranostic PSMA ligand coupled to DOTA was synthesized which allows coupling to Ga-68 for diagnostic use or to Lu-177 or Ac225 for therapy. Initial experience in 30 patients shows promising results concerning antitumor activity with mild side effects.
URL
RC520
Molecular and Functional Imaging/Surrogate Markers in Radiation Oncology
W ednesday, Dec. 2 8:30AM - 10:00AM Location: S102C
BQ
MI
RO
AMA PRA Category 1 Credits ™: 1.50
ARRT Category A+ Credits: 1.50
Participants
Anca L. Grosu, MD, Freiburg, Germany (Moderator) Nothing to Disclose
LEARNING OBJECTIVES
1) To understand challenges of morphological radiological investigations for the detection and characterization of tumor biology and
the timely assessment of tumor response in clinical cancer therapy and in clinical trials testing new therapy regimens. 2) To
understand the role and the potential of functional and molecular imaging modalities and techniques used a. prior to therapy for
tumor delineation and targeting, b. during cytotoxic therapy, such as radiation and chemotherapy for intra-treatment tumor
response monitoring, and .) after cytotoxic therapy for response assessment. 3) To apply and integrate imaging modalities into the
therapeutic management of cancer. 4) To review the role of imaging as predictors of tumor control and survival and their emerging
role as short-term surrogate markers for long-term therapeutic outcome of cancer treatment regimens and its potential for adaptive
therapy.
Sub-Events
RC520A
Imaging Surrogate Markers in CNS Tumors
Participants
Anca L. Grosu, MD, Freiburg, Germany (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
1) Clinical problem: Limitations of the morphological/radiological investigations (CT and MRI) for the detection of the gross tumor
mass and visualization of tumor biology. 2) Gross Tumor Volume (GTV) Delineation: Amino- Acids PET (AA-PET) and SPECT: a.
Sensitivity and specificity of MET-PET, FET-PET and IMT-SPECT b. Comparison MET-PET, FET-PET and IMT-SPECT c. AA-PET for
GTV delineation in gliomas d. Future trials. 3) Tumor Biologys: a. Glucose metabolism: FDG-PET b. Tumor proliferation: FLT-PET c.
Tumor hypoxia: F-MISO-PET d. Tumor angiogenesis: RGD-PET, MRI e. Visualization of tumor stemm cells in vivo: animal-PET f.
Tumor heterogeneity: MRI.
ABSTRACT
1) Clinical problem: Limitations of the morphological/radiological investigations (CT and MRI) for the detection of the gross tumor
mass and visualization of tumor biology. 2) Gross Tumor Volume (GTV) Delineation: Amino- Acids PET (AA-PET) and SPECT: a.
Sensitivity and specificity of MET-PET, FET-PET and IMT-SPECT b. Comparison MET-PET, FET-PET and IMT-SPECT c. AA-PET for
GTV delineation in gliomas d. Future trials. 3) Tumor Biologys: a. Glucose metabolism: FDG-PET b. Tumor proliferation: FLT-PET c.
Tumor hypoxia: F-MISO-PET d. Tumor angiogenesis: RGD-PET, MRI e. Visualization of tumor stemm cells in vivo: animal-PET f.
Tumor heterogeneity: MRI.
RC520B
Imaging Surrogate Markers in Pelvic Tumors
Participants
Nina A. Mayr, MD, Seattle, WA (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
View learning objectives under main course title.
RC520C
Imaging Surrogate Markers in Lung Tumors
Participants
Meng X. Welliver, MD, Columbus, OH (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
View learning objectives under main course title.
RC520D
Imaging Surrogate Markers in Head and Neck Cancer
Participants
Min Yao, MD, PhD, Cleveland, OH (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
1) Prognostic indications of FDG PET in head and neck cancer. 2) How to use FDG PET in radiation treatment planning in head and
neck cancer. 3) Further treatment decision based on PET. 4) Future prospectives including potential new tracers.
SSK11
Molecular Imaging (Staging and Therapy Control)
W ednesday, Dec. 2 10:30AM - 12:00PM Location: S504CD
MI
NM
OI
AMA PRA Category 1 Credits ™: 1.50
ARRT Category A+ Credits: 1.50
FDA
Discussions may include off-label uses.
Participants
Umar Mahmood, MD, PhD, Charlestown, MA (Moderator) Research Grant, Sabik Medical Inc; Advisory Board, Blue Earth Diagnostics
Limited;
Suzanne E. Lapi, PhD, Saint Louis, MO (Moderator) Research Grant, ImaginAB, Inc
Sub-Events
SSK11-01
Noninvasive Monitoring of Early Antiangiogenic Therapy Response using RGD-conjugated Ultrasmall
Superparamagnetic Iron Oxide Nanoparticles in an Orthotopic Human Nasopharyngeal Carcinoma
Model
W ednesday, Dec. 2 10:30AM - 10:40AM Location: S504CD
Participants
Yanfen Cui, Shanghai, China (Presenter) Nothing to Disclose
Caiyuan Zhang, MD, Shanghai, China (Abstract Co-Author) Nothing to Disclose
Huanhuan Liu, Shanghai, China (Abstract Co-Author) Nothing to Disclose
Dengbin Wang, Shanghai, China (Abstract Co-Author) Nothing to Disclose
PURPOSE
Molecular imaging is merging as a powerful tool for the noninvasive imaging of the biological processes. The purpose of this study
was to validate a novel integrin αvβ3-targeted ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, Fe3O4@PAA-RGD, for
its ability to detect tumor angiogenesis and assess the early response of an antiangiogenesis agent Avastin® in an orthotopic
human nasopharyngeal carcinoma (NPC) model.
METHOD AND MATERIALS
The specific uptake of Fe3O4@PAA-RGD in HUVECs and CNE-2 Cells was evaluated using Prussian blue staining, transmission
electron microscopy (TEM).The ability of Fe3O4@PAA-RGD to noninvasively assess αvβ3 integrin positive vessels in NPC tumor
xenografts was evaluated with a 3.0T MR scanner. For the assessment of antiangiogenesis therapy, the mice bearing human NPC
tumor xenografts were intraperitoneally injected with Avastin® (n=12) or normal saline (n=12) three times in a week at a dose of
200 µg/mouse .T2* mapping was performed baseline and after 2 and 7 days of treatment.
RESULTS
The specific uptake of the particles was mainly dependent on the interaction between RGD and integrin αvβ3 of HUVEC, which could
be competitively inhibited by addition of unbound RGD. The tumor targeting of Fe3O4@PAA-RGD was observed in the orthotopic NPC
model, which demonstrates accumulation of nanoparticles exclusively at the neovasculature but not within tumor cells. The
vascular accumulation of Fe3O4@PAA-RGD caused significantly higher changes of the R2* value of tumors than observed for
unlabelled USPIO. Bevacizumab treatment resulted in a significant reduction of the R2* values compared with the control group
both at day2 and day7, confirmed by the immunohistochemistry of MVD after treatment.
CONCLUSION
This study demonstrates that RGD-coupled, PAA-coated USPIOs efficiently label integrin αvβ3expressed on endothelial cells.
Furthermore, these molecular MR imaging probes are capable of noninvasive monitoring of the tumor response to bevacizumab
therapy at early stages of treatment.
CLINICAL RELEVANCE/APPLICATION
RGD-coupled, PAA-coated USPIOs efficiently label integrin αvβ3expressed on endothelial cells. Furthermore, these molecular MR
imaging probes are capable of noninvasive monitoring of the tumor response to bevacizumab therapy at early stages of treatment.
SSK11-02
Point of Care Assessment of Melanoma Tumor Signaling and Metastatic Burden from μNMR Analysis
of Tumor Fine Needle Aspirates and Peripheral Blood
W ednesday, Dec. 2 10:40AM - 10:50AM Location: S504CD
Participants
Michael S. Gee, MD, PhD, Jamaica Plain, MA (Presenter) Nothing to Disclose
Arezou Ghazani, PhD, Boston, MA (Abstract Co-Author) Nothing to Disclose
Hakho Lee, PhD, Boston, MA (Abstract Co-Author) Nothing to Disclose
Ralph Weissleder, MD, PhD, Boston, MA (Abstract Co-Author) Investor, T2 Biosystems, Inc
PURPOSE
To use μNMR technology for molecular profiling of tumor fine needle aspirates and peripheral blood of melanoma patients, in order to
assess BRAF signaling compared with genetic reference and metastatic burden compared with imaging reference.
METHOD AND MATERIALS
μNMR in vitro assessment of expression of melanocyte (MelanA, HMB45) and MAP kinase signaling (pERK, pS6K) molecules was
μNMR in vitro assessment of expression of melanocyte (MelanA, HMB45) and MAP kinase signaling (pERK, pS6K) molecules was
performed in human cell lines on a miniaturized μNMR device as described (JB Haun, Sci Transl Med 2011) using nanoparticleconjugated antibodies. Clinical μNMR validation was performed in an IRB-approved study of melanoma patients scheduled for biopsy
of suspected metastasis, who also underwent tumor FNA and peripheral blood sampling for μNMR. Tumor FNA specimens were
assessed for pERK and pS6K, while peripheral blood was evaluated for circulating tumor cells (CTC) as described (AA Ghazani,
Neoplasia 2012). Reference standards for μNMR results included Western blot, BRAF genetic analysis, and metastatic burden on
clinical imaging obtained near the time of biopsy. Student's t-test was used to assess for statistical significance.
RESULTS
μNMR in vitro analysis showed increased expression of melanocyte markers MART1 and HMB45 in human melanoma cell lines
compared with nonmelanoma cells (P<0.0001). Expression of MAP kinase targets pERK and pS6K was significantly increased in BRAF
mutant compared with BRAF WT melanoma cells (P < 0.01), with levels confirmed by Western blot. Ten patients in the clinical study
included 5 BRAF wild-type and 5 BRAF V600E mutant melanoma patients. μNMR analysis of tumor FNA samples showed increased
pERK (41.0 +/- 8.6) and pS6K (34.4 +/- 15.5) levels in BRAF mutant compared with BRAF WT (24.8 +/- 15.0 and 23.5 +/- 9.0; P=
0.009 and 0.13 respectively) melanomas. μNMR blood CTC level was significantly increased in patients with multiple metastases on
imaging (90.3 +/- 57.9) compared with those with 0-1 lesions (39.3 +/- 31.5; P = 0.045). CTC threshold >60 was associated with
significantly higher RECIST metastatic score on imaging and had 80% acc/83% sens/75% spec for multiple metastases.
CONCLUSION
μNMR technology provides point of care evaluation of tumor signaling in patients with cancer in a minimally invasive manner. μNMRbased blood CTC level is significantly associated with metastatic burden on imaging.
CLINICAL RELEVANCE/APPLICATION
Molecular tracking of metastatic disease is possible by serial sampling of tumor cells and peripheral blood.
SSK11-03
Optical Molecular Imaging of Mesenchymal-Epithelial Transition Factor (c-Met) for Enhanced
Detection and Characterization of Primary and Metastatic Hepatic Tumors
W ednesday, Dec. 2 10:50AM - 11:00AM Location: S504CD
Awards
Trainee Research Prize - Resident
Participants
Shadi A. Esfahani, MD, MPH, Boston, MA (Presenter) Nothing to Disclose
Pedram Heidari, MD, Boston, MA (Abstract Co-Author) Nothing to Disclose
Umar Mahmood, MD, PhD, Charlestown, MA (Abstract Co-Author) Research Grant, Sabik Medical Inc; Advisory Board, Blue Earth
Diagnostics Limited;
PURPOSE
Primary liver cancer as well as metastatic liver disease, predominantly from colorectal cancer (CRC) are major causes of cancer
death. The success of liver cancer therapy depends on accurate diagnosis at the time of biopsy and efficiency of cytoreductive
surgery. c-Met is a proto-oncogene overexpressed in 74-90 % of hepatocellular carcinoma (HCC) and CRC. We assessed whether
optical imaging of c-Met using a targeted fluorescence probe, can be used to delineate and characterize the liver tumors and be
effectively employed for intraoperative interventions and personalized therapy.
METHOD AND MATERIALS
A modified cyanine 5-tagged peptide with high affinity to c-Met was used. Cell binding assay was performed by incubation of human
HCC cells (HepG2,Huh-7), CRC cells (HT-29), and cMET-negative cells (LNCaP) with probe ± HGF. Fluorescence signal was
correlated to c-Met expression level. Focal models of primary and metastatic liver cancer were generated by injection of HepG2,
Huh-7, and HT-29 in hepatic subcapsular space of nude mice (n=24). Near infrared fluorescence (NIRF) imaging was performed over
8 h after probe injection. Uptake in liver and tumor, and tumor to background ratio (TBR) were calculated. Probe biodistribution was
assessed by measuring NIRF signal in multiple organs. IHC evaluation of c-Met expression in human CRCs and HCCs was performed
using tissue arrays.
RESULTS
Incubation of cells with probe showed enhanced fluorescence signal in c-Met expressing cells compared to LNCaP, and strong
correlation between signal and c-MET expression level (R2=0.99,p<0.0001). NIRF imaging showed high uptake in subcapsularly
grown tumors and greater signal compared to the liver over 8 h; TBR reached a peak of 5.46±0.46 in Huh-7, 3.55±0.38 in HepG2
and 15.93±0.61 in HT-29, 4 h post-injection. IHC of tissue arrays confirmed c-Met overexpression in 86% of CRC and 84.9% of HCC
cores.
CONCLUSION
High TBR achieved in our tumor models and overexpression of c-Met in a majority of human HCC and metastatic CRC tumors suggest
that optical imaging of c-Met is a promising approach for accurate delineation and characterization of liver tumors. This is a
translatable advancement for intraoperative image-guided interventions and personalized treatment.
CLINICAL RELEVANCE/APPLICATION
c-MET receptor imaging helps in precise delineation and in-situ characterization of primary hepatic tumors and metastases of other
cancers to the liver.
SSK11-04
Volumetric Molecular Ultrasound Imaging of Tumor Angiogenesis: Intra-Animal Comparison with
Volumetric Dynamic Contrast-Enhanced Imaging
W ednesday, Dec. 2 11:00AM - 11:10AM Location: S504CD
Participants
Huaijun Wang, MD, PhD, Stanford, CA (Presenter) Nothing to Disclose
Dimitre Hristov, PhD, Stanford, CA (Abstract Co-Author) Research Grant, Koninklijke Philips NV; Partner, SoniTrack Systems, Inc
Lu Tian, Stanford, CA (Abstract Co-Author) Nothing to Disclose
Juergen K. Willmann, MD, Stanford, CA (Abstract Co-Author) Research Consultant, Bracco Group; Research Consultant, Triple Ring
Technologies, Inc; Research Grant, Siemens AG; Research Grant, Bracco Group; Research Grant, Koninklijke Philips NV; Research
Grant, General Electric Company
PURPOSE
To perform an intra-animal comparison between 3D ultrasound molecular imaging (USMI) using clinical grade vascular endothelial
growth factor receptor 2 (VEGFR2)-targeted contrast microbubble (MBVEGFR2) and 3D dynamic contrast-enhanced (DCE)-US for
assessing tumor angiogenesis and anti-angiogenic treatment effects in a murine model of human colon cancer.
METHOD AND MATERIALS
Subcutaneous human colon cancers were induced in 19 mice and randomized to either anti-angiogenic treatment (n=11; i.v. single
dose of anti-angiogenic agent, bevacizumab at 10mg/kg) or vehicle treatment (n=8; saline). 3D US imaging was performed with a
clinical system (IU22 xMATRIX; Philips) and a matrix array transducer (X6-1; 3.2MHz) using 2 techniques: 1) USMI was performed
4min after i.v. injection of 5×107 MBVEGFR2; and 2) DCE-US was performed with destruction-replenishment approach by constantly
infusing non-targeted microbubbles at 40µL/min. VEGFR2-targeted signal intensity (SI) was quantified from USMI and 2 perfusion
parameters, relative blood volume (rBV) and flow (rBF) were calculated from DCE-US. VEGFR2 expression levels and the percent
area of blood vessels (PABV) were assessed ex vivo using immunofluorescence (IF) and correlated with correponding in vivo US
parameters.
RESULTS
Both 3D US imaging techniques showed strong anti-angiogenic treatment effects. All 3 parameters including VEGFR2-targeted SI
(58%, P=0.002), rBV (52%, P=0.002) and rBF (38%, P=0.02) significantly decreased following anti-angiogenic treatment compared
to controls. IF showed significantly diminished VEGFR2 expression (P=0.03) and PABV (P=0.03) in treated tumors, while no
significant change was observed in control tumors. SI was highly correlated with VEGFR2 expression (r=0.95, P=0.001), and rBV
(r=0.71, P=0.08) and rBF (r=0.82, P=0.02) showed good correlation with PABV.
CONCLUSION
Both 3D USMI and 3D DCE-US provide complementary in vivo information on anti-angiogenic treatment effects and allow accurate
quantification of tumor angiogenesis in human colon cancer xenografts compared to ex vivo reference gold standard techniques.
CLINICAL RELEVANCE/APPLICATION
3D imaging capabilities may further expand the future clinical role of both USMI and DCE-US in cancer imaging.
SSK11-05
Accurate Prediction of Nodal Status in Preoperative Patients with Thyroid Carcinoma Using Next-Gen
Nanoparticle
W ednesday, Dec. 2 11:10AM - 11:20AM Location: S504CD
Participants
Aoife Kilcoyne, MBBCh, Boston, MA (Presenter) Nothing to Disclose
Roy Phitayakorn, Boston, MA (Abstract Co-Author) Nothing to Disclose
Gilbert H. Daniels, MD, Boston, MA (Abstract Co-Author) Nothing to Disclose
Sareh Parangi, Boston, MA (Abstract Co-Author) Nothing to Disclose
Gregory Randolph, Bosotn, MA (Abstract Co-Author) Nothing to Disclose
Mukesh G. Harisinghani, MD, Boston, MA (Abstract Co-Author) Nothing to Disclose
PURPOSE
The goal of the study is to test the ability to image lymph node metastases in thyroid cancer by a novel MRI imaging agent the
ferromagnetic nanoparticle Ferumoxytol (Feraheme; AMAG Pharmaceuticals, Lexington, MA), which has residual magnetic properties
that are detectable by MRI. These carboxymethyl dextran-coated iron oxide ((FeO)1 - n(Fe2O3)n) nanoparticles slowly extravasate
and travel through the lymphatic system to lymph nodes. The particles are subsequently internalized into macrophages, presumably
through macropinocytosis. Prior studies using this approach with other malignancies (such as prostate cancer) demonstrated
abnormal nanoparticle accumulation patterns which are detectable by MRI. We prospectively enrolled 12 patients with confirmed
metastatic thryoid carcinoma (3 medullary, 9 papillary) undergoing surgery and compared preoperative MRI appearance of lymph
nodes to post-operative histopathologic analysis. The study group consisted of 5 male and 7 female patients, with an mean of 34
nodes resected (range from 1 - 135).
METHOD AND MATERIALS
This exploratory study was performed as a prospective, single-dose pilot study and was approved by the Institutional Review
Board. All patients with known thyroid cancer who were scheduled for surgical resection were eligible for enrollment in this study.
Exclusion criteria included: age < 18, history of iron overload or known allergy to parenteral iron.
RESULTS
)We demonstrated 76.92% sensitivity and 95.74% specificity, 90.91% PPV (CI 70.84% to 98.88%) NPV 88.24% (76.13% to
95.56%) for the detection of central nodes. There was 82.76% sensitivity and 91.78% specificity, PPV 61.54% (CI 49.83% to
72.34%) NPV 97.1% (CI 94.73% to 98.6%) for the detection of peripheral nodes.
CONCLUSION
Lymph node metastases correlate with recurrent disease in patients with thyroid carcinoma. We currently have limited ability to
image central lymph nodes prior to thyroidectomy in patients with thyroid carcinoma. This preliminary study suggests that MRI
imaging following nanoparticle injection is a potentially worthwhile imaging modality. Additional studies are necessary comparing this
with other established methods.
CLINICAL RELEVANCE/APPLICATION
Our study has demonstrated that nanoparticle-enhanced MRI is an accurate and safe method for pre-operatively detecting nodal
metastases in patients with thyroid carcinoma.
SSK11-06
Chemical Exchange Saturation Transfer (CEST) Imaging: Comparison of Capability for Differentiation
of Malignant from Benign Pulmonary Nodules and/ or Masses with FDG-PET/CT
W ednesday, Dec. 2 11:20AM - 11:30AM Location: S504CD
Participants
Yoshiharu Ohno, MD, PhD, Kobe, Japan (Presenter) Research Grant, Toshiba Corporation; Research Grant, Koninklijke Philips NV;
Research Grant, Bayer AG; Research Grant, DAIICHI SANKYO Group; Research Grant, Eisai Co, Ltd; Research Grant, Terumo
Corporation; Research Grant, Fuji Yakuhin Co, Ltd; Research Grant, FUJIFILM Holdings Corporation; Research Grant, Guerbet SA;
Masao Yui, Otawara, Japan (Abstract Co-Author) Employee, Toshiba Corporation
Cheng Ouyang, Vernon Hills, IL (Abstract Co-Author) Employee, Toshiba Corporation
Mitsue Miyazaki, PhD, Vernon Hills, IL (Abstract Co-Author) Employee, Toshiba Corporation
Shinichiro Seki, Kobe, Japan (Abstract Co-Author) Nothing to Disclose
Hisanobu Koyama, MD, PhD, Kobe, Japan (Abstract Co-Author) Nothing to Disclose
Takeshi Yoshikawa, MD, Kobe, Japan (Abstract Co-Author) Research Grant, Toshiba Corporation
Sumiaki Matsumoto, MD, PhD, Kobe, Japan (Abstract Co-Author) Research Grant, Toshiba Corporation;
Katsusuke Kyotani, RT, Kobe, Japan (Abstract Co-Author) Nothing to Disclose
Kazuro Sugimura, MD, PhD, Kobe, Japan (Abstract Co-Author) Research Grant, Toshiba Corporation Research Grant, Koninklijke
Philips NV Research Grant, Bayer AG Research Grant, Eisai Co, Ltd Research Grant, DAIICHI SANKYO Group
PURPOSE
To directly and prospectively compare the capability of chemical exchange saturation transfer (CEST) imaging targeted to amide
groups (-NH) for differentiation of malignant from benign pulmonary nodules and/ or masses with FDG-PET/CT.
METHOD AND MATERIALS
Thirty-six consecutive patients (26 men and 10 women; mean age 67 years) with pulmonary nodules and/ or masses underwent
CEST imaging, FDG-PET/CT and pathological and/or follow-up examinations. According to final diagnoses, all lesions were divided
into malignant (n=26) and benign (n=10) groups. To obtain CEST imaging data in each subject, respiratory-synchronized fast
advanced spin-echo images were conducted following a series of magnetization transfer (MT) pulses. Then, magnetization transfer
ratio asymmetry (MTRasym) was calculated from z-spectra at 3.5ppm in each pixel, and MTRasym map was computationally
generated. To evaluate the capability for differentiation between two groups at each lesion, MTRasym and SUVmax were assessed
by ROI measurements. Then, MTRasym was statistically correlated with SUVmax. To compare each index between two groups,
Student's t-test was performed. Then, ROC-based positive test was performed to determine each feasible threshold value for
differentiation of two groups. Finally, sensitivity, specificity and accuracy were compared each other by McNemar's test.
RESULTS
MTRasym had no significant correlation with SUVmax (p=0.10). Mean MTRasym (0.1±5.5%) and SUVmax (3.0±0.8) of malignant
group were significantly higher than those of benign group (MTRasym: -4.2±4.4%, p=0.03; SUVmax: 2.5±0.5, p=0.04). When
applied each feasible threshold value, sensitivity (SE: 80.8 [21/26] %), specificity (SP: 70.0 [7/10] %) and accuracy (77.8 [28/36]
%) of MTRasym had no significant difference with those of SUVmax (SE: 69.2 [18/26] %, p=0.25; SP: 60.0 [6/10] %, p=1.0; AC:
66.7 [24/36] %, p=0.13).
CONCLUSION
CEST imaging is considered at least as valuable as FDG-PET/CT for differentiation of malignant from benign pulmonary nodules and/
or masses.
CLINICAL RELEVANCE/APPLICATION
CEST imaging is considered at least as valuable as FDG-PET/CT for differentiation of malignant from benign pulmonary nodules and/
or masses.
SSK11-07
Radiofrequency Hyperthermia (RFH)-Enhanced Herpes Simplex Virus-Thymidine Kinase/Ganciclovir
(HSV-TK/GCV) Gene Therapy of Hepatocellular Carcinoma: Monitored by Ultrasound and Optical
Imaging
W ednesday, Dec. 2 11:30AM - 11:40AM Location: S504CD
Awards
Molecular Imaging Travel Award
Participants
Jianfeng Wang, MD, Seattle, WA (Presenter) Nothing to Disclose
Feng Zhang, MD, Seattle, WA (Abstract Co-Author) Nothing to Disclose
Yaoping Shi, MD, Seattle, WA (Abstract Co-Author) Nothing to Disclose
Zhibin Bai, Seattle, WA (Abstract Co-Author) Nothing to Disclose
Long-Hua Qiu, Shanghai, China (Abstract Co-Author) Nothing to Disclose
Renyou Zhai, MD, Beijing, China (Abstract Co-Author) Nothing to Disclose
Xiaoming Yang, MD, PhD, Seattle, WA (Abstract Co-Author) Nothing to Disclose
PURPOSE
To determine the possibility of using radiofrequency hyperthermia (RFH) to enhance therapeutic effect of herpes simplex virus
thymidine kinase/ganciclovir (HSV-TK/GCV) on hepatocellular carcinoma (HCC).
METHOD AND MATERIALS
Human HCC cells (HepG2) were first transfected with lentivirus/luciferase. For both in-vitro confirmation and in-vivo validation,
Luciferase-labeled HCC cells and HCC tumor xenografts on mice received different treatments: (i) combination therapy of
intratumoral HSV-TK/GCV-mediated gene therapy plus MR imaging-heating-guidewire (MRIHG)-mediated RFH; (ii) gene therapy only;
(iii) RFH only; and (iv) phosphate-buffered saline (PBS) as control. Cell proliferation was quantified by MTS assay. Tumor size and
signal changes were monitored by ultrasound imaging and optical imaging before and at days 7 and 14 after treatments, which were
correlated with subsequent histology.
RESULTS
Of in vitro experiments, MTS assay demonstrated the lowest cell proliferation in combination therapy group compared with those in
three control groups (29±6% VS 56±9%, 93±4%, and 100±5%, ρ<0.05). Of in vivo experiments, ultrasound imaging showed smaller
relative tumor volume in combination therapy group than those in three control groups (0.74±0.19 VS 1.79±0.24, 3.14±0.49 and
3.22±0.52, ρ<0.05). Optical imaging demonstrated significant decrease of bioluminescence signals of tumors in the combination
therapy group, compared to those in three control groups (1.2±0.1 VS 1.9±0.2% VS 3.3±0.6% VS 3.5±0.4%, ρ<0.05)(Figure).
These imaging findings were correlated well with histologic confirmation.
CONCLUSION
RF-hyperthermia can enhance HSV-TK/GCV-mediated gene therapy of hepatocellular cancer, which may open new avenues for
efficient management of hepatocellular carcinoma using MR/RF hyperthermia-integrated interventional gene therapy.
CLINICAL RELEVANCE/APPLICATION
RF-hyperthermia can enhance HSV-TK/GCV-mediated gene therapy of hepatocellular cancer.
SSK11-08
Identification of a Prognostic PET-miRNA Radiogenomic Signature Associated with the mir-200 Family
W ednesday, Dec. 2 11:40AM - 11:50AM Location: S504CD
Awards
Molecular Imaging Travel Award
Participants
Shota Yamamoto, MD, Los Angeles, CA (Presenter) Nothing to Disclose
Christopher W. Migdal, Petaluma, CA (Abstract Co-Author) Nothing to Disclose
Ronald L. Korn, MD, PhD, Scottsdale, AZ (Abstract Co-Author) Chief Medical Officer, Imaging Endpoints; Founder, Imaging
Endpoints; Shareholder, Imaging Endpoints
Michael B. Gotway, MD, Scottsdale, AZ (Abstract Co-Author) Nothing to Disclose
Neema Jamshidi, MD, PhD, Los Angeles, CA (Abstract Co-Author) Nothing to Disclose
Michael D. Kuo, MD, Los Angeles, CA (Abstract Co-Author) Nothing to Disclose
PURPOSE
To use radiogenomic analysis to define and contextualize a prognostic microRNA signature in non-small-cell lung carcinoma (NSCLC).
METHOD AND MATERIALS
Using a known prognostic PET signature, differential expression analysis using linear models of microarray data (limma) was
performed on 10 NSCLC (adenocarcinoma ad squamous cell carcinoma) patients with Positron Emission Tomography (PET) and
microRNA (miRNA) expression data to identify potential prognostic PET associated radiogenomic signatures. The same signature
candidate was selected and analyzed on a public dataset of 105 patients with clinical outcome and miRNA expression data to
confirm its prognostic value. Furthermore, the PET phenotype was validated in an independent dataset with PET and outcomes
data in 21 patients.
RESULTS
Significant correlations between high SUV max lesion normalized to the SUV mean liver and the downregulation of hsa-mir-200b and
hsa-miR-149 were identified (p<0.05). Low expression of the mir-200 family is a well known marker for aggressive lung cancer
behavior and chemoresistance.Testing of the miRNA surrogate for SUV signature in the PET-miRNA validation was validated in the
public dataset as a predictor of survival (P=0.04). The PET trait also stratified patient outcome in an independent dataset
(p=0.048).
CONCLUSION
Radiogenomic analysis allows integration of multiple independent datasets thereby providing not only molecular biological context
behind a given biomarker, but also enabling robust validation of biomarkers that is often not feasible with existing approaches.
CLINICAL RELEVANCE/APPLICATION
This approach allows integration of independent datasets thereby providing biological context behind a given biomarker in a cost
effective way.
SSK11-09
Differential Receptor Tyrosine Kinase PET Imaging in Response to Targeted Inhibition
W ednesday, Dec. 2 11:50AM - 12:00PM Location: S504CD
Awards
Trainee Research Prize - Resident
Participants
Eric Wehrenberg-Klee, MD, Boston, MA (Presenter) Nothing to Disclose
Nafize S. Turker, PhD, Boston, MA (Abstract Co-Author) Nothing to Disclose
Pedram Heidari, MD, Boston, MA (Abstract Co-Author) Nothing to Disclose
Mauri Scaltriti, PhD, New York, NY (Abstract Co-Author) Nothing to Disclose
Umar Mahmood, MD, PhD, Charlestown, MA (Abstract Co-Author) Research Grant, Sabik Medical Inc; Advisory Board, Blue Earth
Diagnostics Limited;
PURPOSE
The targeted AKT inhibitor GDC-0068 shows promise for the treatment of triple-negative breast cancer (TNBC). Resistance to AKT
inhibition is mediated through upregulation of the receptor tyrosine kinases (RTK) EGFR and HER3, however the profile of
upregulation differs across cell lines, and may be predictive of treatment response. We sought to noninvasively image these
expression changes for the purpose of therapeutic guidance.
METHOD AND MATERIALS
64Cu-DOTA-cetuximab F(ab´)2 and 64Cu-DOTA-HER3 F(ab´)2 were prepared and probe affinity for their targets assessed. The
TNBC cell lines MDMBA468 and HCC70 were treated with the AKT inhibitor GDC-0068 for one day at a range of concentrations.
Following treatment, uptake of EGFR probe or HER3 probe was assessed, and results compared to protein expression changes of
EGFR or HER3, respectively, as assessed by Western blot. MDAMB468 mice were then treated with GDC-0068 or control for 2 days.
After treatment, mice were imaged with either 64Cu-DOTA-EGFR F(ab´)2 or 64Cu-DOTA-HER3 F(ab´)2 to assess changes in EGFR
or HER3 expression, respectively.
RESULTS
Treatment of the TNBC cell lines MDAMB468 and HCC70 with GDC-0068 resulted in increased EGFR Probe uptake of 6% and 88%
respectively. Interrogation of the same cell lines with HER3 Probe demonstrated uptake changes of 74% and 102%. These findings
correlate closely to changes in protein expression as assessed by Western blot. MDAMB468 mouse xenografts treated with control
or AKT inhibitor for two days and then imaged demonstrate no significant change in SUVmean of EGFR PET Probe (0.48 vs. 0.53,
p=0.11), however demonstrate a significant change in SUVmean of HER3 PET Probe (0.35 vs 0.73, p<0.01).
CONCLUSION
TNBC resistance to AKT inhibition can be mediated through increased RTK expression in a pattern that differs across cell lines and
patient tumors. We demonstrate that the differential change in RTK expression can be noninvasively assessed, demonstrating in a
model of TNBC that while imaged EGFR expression does not change, imaged HER3 expression increases by 108%. These
noninvasively assessed differential changes in RTK expression may inform subsequent therapeutic choices.
CLINICAL RELEVANCE/APPLICATION
The pattern of RTK expression change induced by AKT inhibition is not known prior to treatment. RTK PET imaging may allow for
noninvasive assessment of these changes to optimize therapeutic regimens.
MIS-W EA
Molecular Imaging Wednesday Poster Discussions
W ednesday, Dec. 2 12:15PM - 12:45PM Location: S503AB
MI
AMA PRA Category 1 Credit ™: .50
Participants
Rathan M. Subramaniam, MD, PhD, Baltimore, MD (Moderator) Travel support, Koninklijke Philips NV
Sub-Events
MI221-SDWEA1
Radionuclide Gene Therapy Combined with Dendritic Cell-based Immunotherapy Enhance Antitumor
Effects in Lewis Lung Cancer Model
Station #1
Participants
Hong Je Lee, MD, Busan, Korea, Republic Of (Presenter) Nothing to Disclose
You La Lee, PhD, Busan, Korea, Republic Of (Abstract Co-Author) Nothing to Disclose
Byeong Chul Ahn, MD, Daegu, Korea, Republic Of (Abstract Co-Author) Nothing to Disclose
PURPOSE
We investigated the combined-therapeutic effects using radioiodine gene therapy and dendritic cell (DC)-based immunotherapy in
lung cancer model.
METHOD AND MATERIALS
Recombinant retrovirus that expresses human sodium iodide symporter (hNIS), luciferase (Luc2) and wasabi gene under the control
of a cytomegalovirus (CMV) promoter was transduced to Lewis lung cancer cell (LLC/NLW). Bone marrow cells were isolated from
femurs and tibias of C57BL/6 mice. GM-CSF and IL-4 induced dendritic cell differentiation. Nonadherent cells were harvested by a
gentle pipetting and the surface molecules of these cells were analyzed with flow cytometry. For in vivo therapy, 5x10e6 LLC/NLW
were transplanted into both thighs of C57BL/6 mice. In I-131 therapy group, the mice were treated with intraperitoneal injection of
1mCi of I-131. In DC-based immunotherapy group, 5x10e6 primary dendritic cells (pDCs) were injected intratumorally every 1 week.
In dual therapy group, the mice were treated with intraperitoneal injection of 1mCi of I-131 and intratumoral injection of 5x10e6 of
pDCs. Therapeutic effect of each group was serially monitored using in vivo PET/SPECT/CT and bioluminescence imaging systems.
RESULTS
The hNIS, Luc2 and wasabi mRNA were identified in infected Lewis lung cancer cell (LLC) by RT-PCR. In fluorescence microscopy,
wasabi protein was well expressed. The hNIS and luc2 transcription activity that were assessed using I-125 uptake and luciferase
assay in LLC/NLW increased up to 50 and 100-fold than that in LLC, respectively. Potassium perchlorate blocked the iodine uptake
completely in LLC/NLW. The survival rate of the LLC/NLW treated with I-131 decreased up to 50%. The surface molecules of MHCI,
MHCII, CD86, ICAM-I and CCR7 that is phenotypic markers of pDCs were well expressed in pDCs. In small animal imaging study,
LLC/NLW tumors showed higher I-124 uptake than LLC tumors. Bioluminescence imaging also demonstrated higher activity in
LLC/NLW tumors than in LLC tumors. LLC/NLW tumor size was significantly decreased in dual therapy group.
CONCLUSION
This study supports combined-therapeutic effects using radioiodine gene therapy and dendritic cell (DC)-based immunotherapy in
lung cancer model.
CLINICAL RELEVANCE/APPLICATION
Combined-therapeutic effects using radioiodine gene therapy and dendritic cell (DC)-based immunotherapy is recommended in the
treatment of incurable cancers, such as lung cancer with multiple metastasis.
MI222-SDWEA2
Development of a Dedicated Breast SPECT/ Spectral-CT System Sharing a Photon Counting CZT
Detector
Station #2
Participants
Su-Jin Park, Wonju, Korea, Republic Of (Presenter) Nothing to Disclose
Hyemi Kim, Wonjusi, Korea, Republic Of (Abstract Co-Author) Nothing to Disclose
Byungdu Jo, Wonju-Si, Korea, Republic Of (Abstract Co-Author) Nothing to Disclose
Dohyeon Kim, Wonju, Korea, Republic Of (Abstract Co-Author) Nothing to Disclose
Hee-Joung Kim, PhD, Seoul, Korea, Republic Of (Abstract Co-Author) Nothing to Disclose
PURPOSE
Dual-modality systems offer great promise in improving detection and evaluation of cancer through improvement of the visual
quality and quantitative accuracy. A prototype SPECT/Spectral-CT system using a photon counting CZT detector has been in
development for a dedicated uncompressed 3D breast imaging. The photon counting CZT detector can be available on both gammaray and x-ray systems with energy-resolved information. In this work, we described the configuration of the SPECT/Spectral-CT
design and test results of simultaneous uncompressed breast imaging.
METHOD AND MATERIALS
The SPECT/Spectral-CT system sharing a photon counting CZT detector was designed to have a single gantry for both systems. An
eValuator-2500 (eV-Products, USA) linear array sensor based on CZT was simulated. The detector has a pixel pitch of 0.8 mm, and
a thickness of 3 mm. The SPECT subsystem has a parallel-hole collimator with hexagonal holes (1.2 mm hole size flat-to-flat, 0.2
mm septa, and 25 mm height). The CT subsystem consists of a tungsten x-ray target with Al filter. Both systems are coupled to a
common rotation stage and FOV of 20 x 20 cm2. The uncompressed XCAT breast phantom contained 6 mm-diameter lesion was
used, and the lesion-to-background breast activity concentration ratio was 6.1:1. In addition, the low- and high-energy images
were obtained from 20-33 and 34-45keV, respectively.
RESULTS
A functional-anatomical uncompressed breast image was obtained as shown in Figure 1. The breast SPECT with high- and that with
low-energy x-ray images were acquired using single CZT detector with one exposure. The lesion in breast SPECT image was clearly
observed while the glandular tissue was more visible with low-energy rather than high-energy X-ray image.
CONCLUSION
We have designed and tested a prototype SPECT/Spectral-CT sharing the single CZT detector. Our results demonstrated a
simultaneous dedicated breast imaging in SPECT/Spectral-CT was feasible, and could help improve the identification and localization
of lesion.
CLINICAL RELEVANCE/APPLICATION
This SPECT/Spectral-CT breast imaging could be used for various breast cancer and diagnosis without painful compression.
MI223-SDWEA3
A Comparison between 18F-FDG-PET/CT and 18F-FDG-PET/MRI for Detection of Recurrent Handand-neck Cancer
Station #3
Participants
Patrick Stumpp, MD, Leipzig, Germany (Presenter) Nothing to Disclose
Rakel Diogo, Leipzig, Germany (Abstract Co-Author) Nothing to Disclose
Matthias Gawlitza, MD, Leipzig, Germany (Abstract Co-Author) Nothing to Disclose
Sandra Purz, MD, Leipzig, Germany (Abstract Co-Author) Nothing to Disclose
Osama Sabri, MD, Leipzig, Germany (Abstract Co-Author) Research Consultant, The Piramal Group; Research Consultant, Siemens
AG;
Thomas K. Kahn, MD, Leipzig, Germany (Abstract Co-Author) Nothing to Disclose
PURPOSE
This study compares the diagnostic performance of simultaneous 18F-FDG PET/MRI to conventional 18F-FDG PET/CT in patients
with suspected recurrent or residual head and neck cancer.
METHOD AND MATERIALS
The study population consisted of 22 consecutive patients (3 female, 19 male, mean age 56 years) with suspected recurrent or
residual head and neck cancer who underwent 18F-FDG PET/CT immediately followed by simultaneous 18F-FDG PET/MRI.
Subsequently all PET/MRI and PET/CT scans were assigned to an expert panel for independent, blinded evaluation. Their findings
were compared to the gold standard, derived from histopathology (n=17) or follow-up (n=5). Standard statistic indicators were
calculated.
RESULTS
Gold standard defined 125 lesions, whereof 19 were recurrent malignant tumors and 31 were metastatic cervical lymph nodes.
PET/MRI showed a sensitivity of 72 %, a specificity of 67.2 %, a PPV of 62.1 %, a NPV of 76.3 %. Respective values for PET/CT
were 50 %, 97.1 %, 92.6 %, 72.5 %. The differences were statistically significant, as shown by the McNemar test (p<0.001).
CONCLUSION
18F-FDG-PET/MRI shows a significantly higher sensitivity in detection of recurrent or residual head and neck cancer as compared to
PET/CT, while specificity is reduced.
CLINICAL RELEVANCE/APPLICATION
A high sensitivity in detection of tumour sites is important for correct treatment decisions in patients with recurrent head and neck
cancer, so 18F-FDG-PET/MRI should be the preferred imaging modality for the evaluation of these patients.
MI224-SDWEA4
Prognostic Value of Tumor Burden in Metastatic Cancers at Anti-PD1 Initiation: Toward a CT-scan
Based M-staging System?
Station #4
Awards
Molecular Imaging Travel Award
Participants
Laurent Dercle, MD, Villejuif, France (Presenter) Nothing to Disclose
Aurelien Marabelle, Villejuif, France (Abstract Co-Author) Nothing to Disclose
Matthieu Texier, Villejuif, France (Abstract Co-Author) Nothing to Disclose
Emilie Lanoy, Villejuif, France (Abstract Co-Author) Nothing to Disclose
Stephane Champiat, Villejuif, France (Abstract Co-Author) Nothing to Disclose
Clarisse Dromain, MD, Villejuif, France (Abstract Co-Author) Nothing to Disclose
Martin Schlumberger, Villejuif, France (Abstract Co-Author) Nothing to Disclose
Jean-Charles Soria, Villejuif, France (Abstract Co-Author) Nothing to Disclose
Samy Ammari, Villejuif, France (Abstract Co-Author) Nothing to Disclose
PURPOSE
Therapies that target the programmed death-1 (PD1) receptor have revolutionized the outcome of metastatic patients and led to
durable clinical responses. However, its evaluation in oncology raised new methodologic questions. We aimed to investigate the
prognostic role of different tumor burden (TB) biomarkers measured by CT-scan at anti-PD1 treatment initiation.
METHOD AND MATERIALS
Patients with metastatic disease prospectively included in phase I trials were eligible. An analysis of all the lesions was performed
and we calculated and recorded 3 parameters of anatomic TB: TB1D "RECIST LIKE", TB2D "WHO OR IRRC LIKE", and an exhaustive
TB3D. In patients with malignant melanoma, a CT-scan based staging system was defined by replacing serum LDH (current
reference standard: "biologic TB"; cut off: 250) by TB3D and by using the traditional staging of site of distant metastases (M1a:
non-visceral vs M1b lung vs M1c all other visceral metastatic sites). Effect on overall survival (OS) and progression-free survival
(PFS) was evaluated.
RESULTS
TB was a predictor of outcome in the 122 included patients with a median follow-up of 13.2 months: the hazard ratio of death for 1
SD increase [95% Confidence Interval] were 1.29 [0.95; 1.75] for TB1D, 1.48 [1.10;1.97] for TB2D and 1.50 [1.22; 1.85] for TB3D.
Model with TB3D had the smallest Akaike Information Criterion for OS and PFS. TB3D was inaccurately evaluated by TB1D (r=.71)
and LDH (r=.49).In the subgroup of 79 patients with malignant melanoma, the current staging system based on LDH was not
significantly associated with OS whereas the CT-scan based staging system identified two groups of patients with different OS (HR
4.7 [1.1;20]; p.04): 1/ LOW RISK (M1a or M1b): Non visceral or lung metastases AND TB3D<202cm3; 2/ HIGH RISK (M1c):
TB3D>202cm3 OR Visceral metastases excluding lung metastases.In a subroup of 28 patients with malignant melanoma, metabolic
TB from FDG-PET did not provide a significant additional information.
CONCLUSION
TB3D at anti-PD1 treatment initiation is a strong predictor of outcome. TB1D is a less accurate but correct approximation of TB3D
excepted in patients with multiple and small metastases. In patients with metastatic melanoma (n=79), a CT-scan based M-staging
system was created and defined with the two dominants components of the AJCC classification.
CLINICAL RELEVANCE/APPLICATION
New CT-scan derived M-staging system designed for Immune-checkpoint inhibitor.
MI225-SDWEA5
Glycosaminoglycan Chemical Exchange Saturation Transfer of Lumbar Intervertebral Discs in Healthy
Volunteers
Station #5
Participants
Christoph Schleich, Dusseldorf, Germany (Presenter) Nothing to Disclose
Falk R. Miese, MD, Dusseldorf, Germany (Abstract Co-Author) Nothing to Disclose
Johannes Boos, MD, Boston, MA (Abstract Co-Author) Nothing to Disclose
Christian Buchbender, Duesseldorf, Germany (Abstract Co-Author) Nothing to Disclose
Bernd Bittersohl, MD, Bern, Switzerland (Abstract Co-Author) Nothing to Disclose
Benjamin Schmitt, Vienna, Austria (Abstract Co-Author) Nothing to Disclose
Hans-Joerg Wittsack, PhD, Duesseldorf, Germany (Abstract Co-Author) Nothing to Disclose
Gerald Antoch, MD, Duesseldorf, Germany (Abstract Co-Author) Nothing to Disclose
Anja Lutz, Dusseldorf, Germany (Abstract Co-Author) Nothing to Disclose
PURPOSE
Glycosaminoglycans (GAG) play a central role in degenerativedisc changes.Our purpose was to assess GAG content of lumbar
intervertebral discs (IVD) in healthy volunteers with chemical exchange saturation transfer (CEST).
METHOD AND MATERIALS
Lumbar intervertebral discs of healthy controls (26 females, 22 males; mean age 31 ± 8 years; range: 21 - 49 years) without
lumbar back pain were examined at a 3 Tesla MRI scanner in this prospective study. None of the participants were overweight or
had previous surgery of the lumbar spine. The MRI protocol included standard morphological, sagittal and transversal T2 weighted
(T2w) images to assess Pfirrmann score and to detect disc pathologies according to the Combined Task Force (CTF) classification
of the five lumbar IVDs (L1 to S1). A prototype gagCEST sequence was applied to measure GAG content of the nucleus pulposus
(NP) and annulus fibrosus (AF) by identifying the magnetization transfer asymmetry ratio (MTRasym) in a region-of-interest
analysis. Morphological and biochemical imaging analysis were statistically tested for quantitative differences between different
grades of IVD degeneration and disc pathologies.
RESULTS
GagCEST values of NP demonstrated a significant, negative correlation with morphological Pfirrmann scoring (r = -0.562; p <
0.0001). The MTRasym values were higher in morphological non-degenerative lumbar IVDs (Pfirrmann 1 - 2) compared with
degenerative lumbar discs (Pfirrmann 3 - 5; 2.92 % ± 1.42 % vs. 0.78 % ± 1.38 %; p < 0.0001). The MTRasym values of NP were
significantly higher in normal appearing discs compared with herniated IVDs (2.83 % ± 1.52 % vs. 1.55 % ± 1.61 %; p < 0.0001).
We found a significant negative correlation between gagCEST values and the graduation of disc herniation (r = -0.372; p <
0.0001).
CONCLUSION
Biochemical imaging with gagCEST facilitated to distinguish morphologically degenerative from non-degenerative lumbar IVDs in NP
and AF of healthy volunteers at a clinical 3T-MRI system. The depletion of GAG content in degenerative lumbar discs correlated
significantly with the morphological disc classification. We could demonstrate that disc pathologies, such as protrusion and
extrusion, were accompanied by lower GAG content.
CLINICAL RELEVANCE/APPLICATION
GagCEST may have the ability to visualize GAG content of the lumbar IVDs and may show degenerative disc changes before the
appearance of morphological alterations.
MIS-W EB
Molecular Imaging Wednesday Poster Discussions
W ednesday, Dec. 2 12:45PM - 1:15PM Location: S503AB
MI
AMA PRA Category 1 Credit ™: .50
FDA
Discussions may include off-label uses.
Participants
Rathan M. Subramaniam, MD, PhD, Baltimore, MD (Moderator) Travel support, Koninklijke Philips NV
Sub-Events
MI226-SDWEB1
Quantitative CT Imaging of Nanoparticle Uptake and Distribution within Solid Tumors
Station #1
Participants
Ketan B. Ghaghada, PhD, Houston, TX (Presenter) Nothing to Disclose
Zbigniew Starosolski, PhD, Houston, TX (Abstract Co-Author) Stockholder, Alzeca Biosciences, LLC
Siddharth Ray, Houston, TX (Abstract Co-Author) Nothing to Disclose
Jason M. Shohet, MD,PhD, Houston, TX (Abstract Co-Author) Nothing to Disclose
Ananth Annapragada, PhD, Houston, TX (Abstract Co-Author) Stockholder, Marval Pharma Ltd Stockholder, Alzeca Biosciences LLC
Stockholder, Sensulin LLC Stockholder, Abbott Laboratories Stockholder, Johnson & Johnson
PURPOSE
Non-invasive imaging techniques that could predict the uptake and distribution of nanoparticles in tumors are of interest for
personalized nano-medicine. In this work, we investigate a liposomal iodinated contrast agent for CT imaging of nanoparticle uptake
and distribution in solid tumors. We also investigated the relationship between the distribution of nanoparticles and cancer stems
cells in tumors.
METHOD AND MATERIALS
In vivo studies were performed in two orthotopic mouse models of neuroblastoma. MYCN-amplified NGP cells and MYCN nonamplified SY5Y cells were implanted in the renal capsule of nude mice (n=60). A liposomal-iodinated contrast agent was used to
study tumor uptake of nanoparticles. The uptake and distribution was studied as a function of tumor age and size. Longitudinal
high-resolution CT scans were acquired pre-contrast, immediately post-contrast and at 5 days post-contrast. Tumor uptake of
nanoparticle contrast agent was determined based on CT signal enhancement. 3D distribution of nanoparticles was studied using a
shell-based approach with the tumor mass sub-divided into a core, an intermediate and a periphery region. Following imaging, the
tumors were extracted, sectioned and analyzed using flow cytometry for the presence of cancer stem cells.
RESULTS
CT imaging demonstrated intra- and inter-tumor heterogeneity in nanoparticle uptake and distribution (Fig 1A). The enhanced tumor
fraction, an indicator of tumor accessibility to nanoparticles, increased with tumor age and size. 3D distribution analysis
demonstrated a peripheral pattern of signal enhancement in the majority of tumors; albeit with a high level of variability.
Additionally, some of the tumors also showed enhancement in the intermediate, and in some cases core regions, of the tumor (Fig
1B). Flow cytometry analysis indicated that the nanoparticle agent preferentially accumulated (p =0.05) in tumor regions with a
high density of cancer stem cells.
CONCLUSION
The current work demonstrates the feasibility of CT imaging with liposomal-iodinated contrast agent to quantify the uptake and
distribution of nanoparticles within tumors. Additionally, the nanoparticle agent preferentially accumulated in tumor regions with a
high density of cancer stem cells.
CLINICAL RELEVANCE/APPLICATION
CT imaging using a nanoparticle contrast agent could help in treatment prognostication, monitoring of cancer nanomedicines, and
predicting the locations of cancer stem cells.
MI227-SDWEB2
Prognostic Value of Dynamic Contrast-enhanced CT with Perfusion Imaging in the Quantitative
Assessment of Response to Anti-angiogenic Therapy in Patients with Advanced Hepatocellular
Carcinoma: A Feasibility Study
Station #2
Participants
Giulia Querques, MD, Monza, Italy (Abstract Co-Author) Nothing to Disclose
Davide Ippolito, MD, Monza, Italy (Presenter) Nothing to Disclose
Pietro A. Bonaffini, MD, Monza, Italy (Abstract Co-Author) Nothing to Disclose
Cammillo R. Talei Franzesi, Milan, Italy (Abstract Co-Author) Nothing to Disclose
Silvia Girolama Drago, Monza, Italy (Abstract Co-Author) Nothing to Disclose
Sandro Sironi, MD, Monza, Italy (Abstract Co-Author) Nothing to Disclose
PURPOSE
To investigate the feasibility of quantitative perfusion-CT (pCT) values, as surrogate biomarkers of angiogenesis, in evaluating the
response to Sorafenib in patients with advanced hepatocellular carcinoma (HCC).
METHOD AND MATERIALS
A total of 40 pCT study were performed in 20 cirrhotic patients with biopsy proven HCC before and 2 months after Sorafenib
administration. Dynamic scans were performed on a 256-slice MDCT scanner (Brilliance iCT, Philips) by acquiring 16 dynamic
slices/scan per 40 scans after iv bolus injection of 50 ml of iodinated contrast agent (350 mgI/ml). The following pCT parameters
were calculated: hepatic perfusion (HP,ml/min/100g), blood volume (BV,ml/100g), arterial perfusion (AP,ml/min), hepatic perfusion
index (HPI,%), and time-to-peak (TTP,s). Patient response was defined as complete (CR), partial response (PR), stable (SD) or
progressive disease (PD), according to mRECIST. pCT values at baseline and follow-up were statistically analyzed and compared in
HCC lesions between groups.
RESULTS
In patients with CR and PR (n=11) mean pCT values, except for TTP, were significantly higher at baseline compared to follow-up
(HP 54.6±19.2 vs 25.0±23.3; BV 18.3±10.5 vs 9.3±7.5; AP 54.0±20.4 vs 25.5±26.0; HPI 84.8±23.4 vs 46.1±35.3; TTP 15.8±1.7 vs
23.2±8.2; p<0.05). In patients with SD (n=6) no significant differences in pCT values were observed before and after treatment
(HP 46.9±11.2 vs 37.6±24.1; BV 15.9±7.3 vs 15.8±13.5; AP 49.0±13.3 vs 37.8±24.6; HPI 73.7±31.7 vs 57.5±34.9; TTP 19.2±2.7
vs 19.2±6.9), while in patients with PD (n=3) an increase of mean pCT values, except for TTP, was recorded (HP 38.5±11.8 vs
52.5±28.3; BV 15.7±4.1 vs 9.7±6.4; AP 35.9±11.2 vs 47.5±22.6; HPI 100.0±0.0 vs 100.0±0.0; TTP 18.8±1.8 vs 15.7±2.4).
Moreover, higher values of HP and AP at baseline in patients with CR and PR have been demonstrated to be optimal predictors of
response to treatment, compared to other groups.
CONCLUSION
pCT might represent a complementary tool for non-invasive assessment of hemodynamic changes related to Sorafenib in patients
with advanced HCC, allowing for early outcome prediction and patient stratification according to prognosis.
CLINICAL RELEVANCE/APPLICATION
Higher pCT values at baseline might be considered as an important prognostic indicator of response to antiangiogenic therapy, thus
permitting the selection of patients who will benefit from treatment.
MI228-SDWEB3
Multiparametric Contrast Enhanced Ultrasound with VEGFR-2 Targeted Microbubbles and DCE-MRI
for Monitoring the Effects of Regorafenib on Colorectal Adenocarcinoma Xenografts in Rats with
Immunohistochemical Validation
Station #3
Participants
Ralf Eschbach, Munich, Germany (Abstract Co-Author) Research Grant, Bracco Group; Research Grant, Bayer AG
Dirk-Andre Clevert, MD, Munich, Germany (Abstract Co-Author) Speaker, Siemens AG; Speaker, Koninklijke Philips NV; Speaker,
Bracco Group;
Philipp M. Kazmierczak, MD, Munich, Germany (Abstract Co-Author) Nothing to Disclose
Heidrun Hirner, PhD, Munich, Germany (Abstract Co-Author) Nothing to Disclose
Jessica Schuster, Munich, Germany (Abstract Co-Author) Nothing to Disclose
Matthias Moser, Munich, Germany (Abstract Co-Author) Nothing to Disclose
Dina Tadros, Munich, Germany (Abstract Co-Author) Nothing to Disclose
Lukas Havla, Munich, Germany (Abstract Co-Author) Nothing to Disclose
Moritz Schneider, Munich, Germany (Abstract Co-Author) Nothing to Disclose
Clemens C. Cyran, MD, Munich, Germany (Presenter) Research Grant, Bayer AG Research Grant, Novartis AG Speakers Bureau,
Bayer AG
PURPOSE
To investigate contrast enhanced ultrasound with VEGFR-2 targeted microbubbles for monitoring the effects of regorafenib on
experimental colon carcinomas in rats with correlation to DCE-MRI and immunohstochemical validation.
METHOD AND MATERIALS
Human colorectal adenocarcinoma xenografts were implanted in n=20 female athymic nude rats. The animals were imaged at
baseline and after a one-week treatment with regorafenib or a placebo, using contrast enhanced ultrasound (CEUS) with VEGFR-2
targeted microbubbles (BR55) and DCE-MRI. In CEUS with BR55, functional and molecular parameters were quantified: Tumor
perfusion (e.g. peak enhancement, wash-in-rate, mean transit time) during an early vascular phase and VEGFR-2 specific binding of
the microbubbles during a late phase. In DCE-MRI, functional parameters of plasma flow (PF,mL/100 mL/min) and plasma volume
(PV,%) were quantified. For validation purposes, CEUS parameters were correlated with DCE-MRI parameters and
immunohistochemical CD-31 (microvascular densisty), TUNEL (apoptosis) and VEGFR-2 stainings.
RESULTS
In CEUS parameters of tumor perfusion and the number of VEGFR-2 bound microbubbles decreased significantly (p<0.05) under
therapy from day 0 to day 7 and were significantly (p<0.05) lower in therapy than in control group on day 7, while there were no
significant changes in control group. In DCE-MRI PF and PV declined significantly (p<0.05) between day 0 and day 7 in therapy
group with no significant changes in control group. PF and PV were significantly lower (p<0.05) in therapy than in control group on
day 7. Immunohistochemistry revealed significantly (p<0.05) fewer CD-31, TUNEL and VEGFR-2 positive cells in therapy than in
control group. CEUS parameters showed significant (p<0.05) correlations to PF and PV as well as to CD-31, TUNEL and VEGFR-2
stainings.
CONCLUSION
Regorafenib therapy significantly suppressed tumor perfusion assessed by CEUS and DCE-MRI. Additionally significant fewer VEGFR2 specific bound microbubbles were detected in therapy group, consistent with a significantly reduced expression of VEGFR-2 in
immunohistochemistry. Therefore CEUS with VEGFR-2 targeted microbubbles allowed for monitoring regorafenib therapy effects on
experimental colorectal adenocarcinomas with significant correlations to DCE-MRI and immunohistochemistry.
CLINICAL RELEVANCE/APPLICATION
Need for reliable imaging biomarkers for an in vivo monitoring of anti-angiogenic therapy effects.
MI229-SDWEB4
Preliminary Experiences with CEST Imaging in Head and Neck Cancer Patients
Station #4
Participants
Jihong Wang, PhD, Houston, TX (Presenter) Nothing to Disclose
Ken-Pin Hwang, MS, PhD, Cleveland, OH (Abstract Co-Author) Nothing to Disclose
Clifton D. Fuller, MD, PhD, Houston, TX (Abstract Co-Author) In-kind support, General Electric Company; Research Grant, Elekta AB;
;;
Yao Ding, MS, Dallas, TX (Abstract Co-Author) Nothing to Disclose
Abdallah S. Mohamed, MD, MSc, Houston, TX (Abstract Co-Author) Nothing to Disclose
S J. Frank, MD, Houston, TX (Abstract Co-Author) Board Member, C4 Imaging LLC; Stockholder, C4 Imaging LLC; Advisory Board,
Elekta AB
Jinyuan Zhou, PhD, Baltimore, MD (Abstract Co-Author) Nothing to Disclose
PURPOSE
Chemical Exchange Saturation Transfer (CEST) imaging is an MRI technique enables the detection and imaging of metabolically
active compounds in vivo. It has been used to differentiate tumor types and metabolic characteristics. Unlike PET/CT,CEST imaging
does not use isotopes so it can be used on patient repeatedly. This study is to report the preliminary results of CEST imaging in
Head and Neck cancer (HNC) patients.
METHOD AND MATERIALS
A CEST imaging sequence and the post-processing software was developed on a 3T clinical MRI scanner. Ten patients with Human
papilloma virus positive oropharyngeal cancer were imaged in their immobilized treatment position. A 5 mm slice CEST image was
acquired (128x128, FOV=20~24cm) to encompass the maximum dimension of tumor. Twenty-nine off-set frequencies (from -7.8ppm
to +7.8 ppm) were acquired to obtain the Z-spectrum. Asymmetry analysis was used to extract the CEST contrasts. ROI at the
tumor, node and surrounding tissues were measured.
RESULTS
CEST images were successfully acquired and Z-spectrum asymmetry analysis demonstrated clear CEST contrasts in tumor as well
as the surrounding tissues. 3~5% CEST contrast in the range of 1 to 4 ppm was noted in tumor as well as grossly involved nodes.
Injection of glucose produced a marked increase of CEST contrast in tumor region (~10%). Motion and pulsation artifacts tend to
smear the CEST contrast, making the interpretation of the image contrast difficult. Field non-uniformity, pulsation in blood vesicle
and susceptibility artifacts caused by air cavities were also problematic for CEST imaging.
CONCLUSION
We have demonstrated successful CEST acquisition and Z-spectrum reconstruction on HNC patients with a clinical scanner. MRI
acquisition in immobilized treatment position is critical for image quality as well as the success of CEST image acquisition. CEST
images provide novel contrast of metabolites in HNC and present great potential in the pre- and post-treatment assessment of
patients undergoing radiation therapy.
CLINICAL RELEVANCE/APPLICATION
Successful implementation of an in vivo metabolic imaging technique such as CEST will be very helpful in assessing tumor response
to therapy
SSM09
Gastrointestinal (Esophagus Imaging)
W ednesday, Dec. 2 3:00PM - 4:00PM Location: E353B
GI
CT
MI
MR
NM
OI
AMA PRA Category 1 Credit ™: 1.00
ARRT Category A+ Credit: 1.00
Participants
David J. Lomas, MD, Cambridge, United Kingdom (Moderator) Nothing to Disclose
Lisa M. Ho, MD, Durham, NC (Moderator) Nothing to Disclose
Sub-Events
SSM09-01
Changes in Esophageal Dimensions during Continuous Swallowing in Healthy Adults as Detected by
Magnetic Resonance Imaging
W ednesday, Dec. 2 3:00PM - 3:10PM Location: E353B
Participants
Sabarish Narayanasamy, MBBS,MD, Aligarh, India (Presenter) Nothing to Disclose
Mehtab Ahmad, MBBS, Aligarh, India (Abstract Co-Author) Nothing to Disclose
Mudit Arora, DMRD, Aligarh Ho, India (Abstract Co-Author) Nothing to Disclose
Faisal Janal, MBBS, Aligarh, India (Abstract Co-Author) Nothing to Disclose
Breethaa J. Selvamani, Aligarh, India (Abstract Co-Author) Nothing to Disclose
Anusha Sundararajan, Loma Linda, CA (Abstract Co-Author) Nothing to Disclose
PURPOSE
This study was designed to quantify the degree of fluctuation in esophageal dimensions during continuous swallowing on Magnetic
Resonance (MR) Imaging.
METHOD AND MATERIALS
30 healthy volunteers (25 males and 5 females, age range: 15-45 years) were chosen for the study. MR examination was done
using a 1.5 tesla magnet. Initially, the esophagus was imaged in the resting state (Resting MR). Then, the volunteer was asked
drink water continuously and another set of MR images were obtained (Swallowing MR). The thoracic esophagus was divided into
three segments (upper, middle and lower) based on anatomical landmarks. Diameter and the wall thickness of the esophagus were
measured in each segment and the cross sectional area (CSA) was calculated.
RESULTS
The esophageal CSA increased by twofold on swallowing MR scans as compared to the resting scans [Median(interquartile range)
increase in CSA in upper segment - 117.3%(61-162.2), in middle segment - 87.7%(54.3-162.9) and in the lower segment - 122.1%
(78.9 - 188.1)]. The anteroposterior and transverse diameters of the thoracic esophagus increased by about 60% as compared to
the resting MR scans. The mean wall thickness of the thoracic esophagus was reduced by about 25% on swallowing MR as
compared to resting scan.
CONCLUSION
Our study helps to define normal changes in esophageal dimensions during continuous swallowing. The lower third of the thoracic
esophagus appears to be the most distensible segment.
CLINICAL RELEVANCE/APPLICATION
Swallowing MRI has been proposed as an experimental investigative modality for motility disorders of the esophagus and knowledge
of the fluctuation in esophageal dimensions during swallowing might be of clinical utility.
SSM09-02
Differentiate Esophageal Cancer Stages with Spectral CT Imaging
W ednesday, Dec. 2 3:10PM - 3:20PM Location: E353B
Participants
Yang Chuangbo, MMed, Xianyang City, China (Presenter) Nothing to Disclose
Yongjun Jia, MMed, Xianyang City, China (Abstract Co-Author) Nothing to Disclose
Xirong Zhang, Xianyang, China (Abstract Co-Author) Nothing to Disclose
Chenglong Ren, Shanxi, China (Abstract Co-Author) Nothing to Disclose
Haifeng Duan, Xianyang City, China (Abstract Co-Author) Nothing to Disclose
Taiping He, Xianyang, China (Abstract Co-Author) Nothing to Disclose
Xiaoxia Chen, MMed, Xianyang City, China (Abstract Co-Author) Nothing to Disclose
PURPOSE
To explore the value of spectral CT imaging to differentiate esophageal cancer stages.
METHOD AND MATERIALS
67 patients with esophageal cancer diagnosed by esophagoscopy underwent plain and double-phase enhanced CT scan with
spectral CT mode. Patients were divided into well-to-moderately differentiated and poorly differentiated squamous carcinoma
groups. The iodine-based material decomposition (MD) images were generated and analyzed with GSI Viewer software to measure
the iodine concentration (IC) in tumors. Normalized iodine concentration (NIC) was obtained by dividing tumor IC to that of aorta.
Data from the two cancer groups were analyzed statistically by independent-samples t test and were correlated with pathological
findings.
RESULTS
There were 32 well-to-moderately differentiated(Picture 1) and 35 poorly differentiated(Picture 2) squamous carcinoma verified by
pathology. IC values of the well-to-moderately differentiated squamous carcinoma in both the arterial phase (AP) (2.66±1.07mg/ml)
and venous phase (VP) (2.12±0.94mg/ml) were lower than that of the poorly differentiated squamous carcinoma (2.85±1.25mg/ml
and 2.57±1.06mg/ml, respectively). The NIC value of the well-to-moderately differentiated squamous carcinoma was also lower
than that of the poorly differentiated squamous carcinoma: 0.12±0.05 vs. 0.13±0.06 in AP and 0.42±0.13 vs. 0.61±0.18 in VP,
respectively. Statistical differences of IC and NIC were found between the two groups in VP (both p<0.05) but not in AP (p>0.05).
CONCLUSION
There are correlation between the iodine concentration and normalized iodine concentration of esophageal cancers and their
histological differentiation stages. IC and NIC parameters obtained in spectral CT for the esophageal cancer in the venous phase
can be used as new indexes to differentiate esophageal cancer stages.
CLINICAL RELEVANCE/APPLICATION
Parameters such as normalized iodine concentration in esophageal cancer determined in spectral CT may be used to differentiate
esophageal cancer stages.
SSM09-03
Diffusion-Weighted MRI in the Staging of Esophageal Cancer: Ready for Clinical Use? Prospective
Comparison with EUS and MDCT
W ednesday, Dec. 2 3:20PM - 3:30PM Location: E353B
Participants
Francesco Giganti, MD, Milan, Italy (Presenter) Nothing to Disclose
Paolo G. Arcidiacono, Milan, Italy (Abstract Co-Author) Nothing to Disclose
Roberto Nicoletti, MD, Milan, Italy (Abstract Co-Author) Nothing to Disclose
Elena Orsenigo, Milan, Italy (Abstract Co-Author) Nothing to Disclose
Alessandro Del Maschio, MD, Milan, Italy (Abstract Co-Author) Nothing to Disclose
Francesco A. De Cobelli, MD, Milan, Italy (Abstract Co-Author) Nothing to Disclose
PURPOSE
This pilot study was intended to prospectively compare the diagnostic performance of Diffusion-Weighted Magnetic Resonance
Imaging (DW-MRI), Multidetector Computed Tomography (MDCT) and Endoscopic Ultrasonography (EUS) in the preoperative locoregional staging of esophageal cancer.
METHOD AND MATERIALS
This study was institutional review board-approved. Eighteen patients with biopsy proved esophageal or gastro-esophageal
(Siewert I) tumor (9 directly treated with surgery and 9 addressed to chemo/radiotherapy before) underwent 1.5 T DW-MRI, 64channels MDCT and EUS before and after neoadjuvant treatment. All images were analyzed and staged blindly by dedicated
operators according to the 7th TNM edition and two radiologists calculated indipendently the Apparent Diffusion Coefficient (ADC)
from the initial scan. The results were then compared with histopathological findings. Statistical analysis included Spearman and
intraclass correlation coefficients, Mann-Whitney U test and receiver operator characteristic curve analysis. After the population
had been divided according to local invasion (T1-2 vs T3-4) and nodal involvement (N0 vs N+), sensitivity, specificity, accuracy,
positive and negative predictive value were calculated and compared for each technique. Quantitative measurements from DWI
were also analyzed.
RESULTS
For T staging, EUS showed the best sensitivity (100%) while MR showed the highest specificity (92%) and accuracy (83%). For N
staging, MR and EUS showed the highest sensitivity (100%) but none of the three techniques showed adequate results for
specificity. Overall, MR showed the highest accuracy (66%) for N stage. Mean pathological ADC was different between surgery-only
and chemo/radiotherapy groups (1.90 vs 1.30 x 10-3 mm2/s, respectively; p= 0.005), with an optimal cut off for local invasion of
1.33 x 10-3 mm2/s (p=0.05).
CONCLUSION
DW-MRI could improve the current preoperative staging workup for esophageal cancer, showing characteristic advantages for both
staging and initial treatment decision-making.
CLINICAL RELEVANCE/APPLICATION
DW-MRI can be useful in the preoperative workup for esophageal cancer and could help to select appropriate treatments after
initial staging.
SSM09-04
The Use of 3T Multiparametric MRI in the Staging of Esophageal Cancer (EC)
W ednesday, Dec. 2 3:30PM - 3:40PM Location: E353B
Participants
Daniela A. Cenzi, MD, Verona, Italy (Presenter) Nothing to Disclose
Lisa Zantedeschi, MD, Verona, Italy (Abstract Co-Author) Nothing to Disclose
Lucia Camera, Verona, Italy (Abstract Co-Author) Nothing to Disclose
Giacomo Schenal, Verona, Italy (Abstract Co-Author) Nothing to Disclose
Massimiliano Motton, MD, Verona, Italy (Abstract Co-Author) Nothing to Disclose
Stefania Montemezzi, MD, Verona, Italy (Abstract Co-Author) Nothing to Disclose
PURPOSE
To evaluate diagnostic feasability of MP-MRI for the preoperative staging of EC and to assess its efficacy in discrimination between
responders and non-responders in those who underwent neoadjuvant treatment (NT).
METHOD AND MATERIALS
Between 2011 and January 2015, 36 patients with biopsy-proven EC underwent 3T MRI with the same approach: T2 weighted
images, DWI and DCE sequences, with cardiac and respiratory gating. According to local invasion (T1-2 vs T3-4) and nodal
involvement (N- vs N+), we identified 11 patients with organ confined lesion who underwent surgery: MR-staging results were
compared with histopathological findings directly. 25 patients were addressed to NT and restaging MRI after treatment was
compared to histological findings after surgery. Sensitivity (SE), specificity (SP), positive (PPV) and negative (NPV) predictive value
and accuracy were calculated for the both groups. For NT group, changes in ACD and changes in DCE time intensity curve at MRI
before and after treatment were calculated. 2 readers indipendently determined: pre-NT and post-NT ADC, percentage changes in
ADC (ΔADC), DCE time intensity curves and interobserver variability.
RESULTS
Surgery group: for T staging, SE was 98 %, SP 78 %, accuracy 90%; for N staging SE was 67 %, SP 60 %, accuracy 64%. NT
group after NT: for T staging SE was 80 %, SP 85 %, PPV 67%, NPV 92%, accuracy 89% and 76%, 78%, 50%, 91% and 91%
respectively for N staging.Responders showed lower pre-NT ADC (1.30 vs 1.80Å~10-3mm2/s; P=0.002) and higher post-NT ADC
(2.50 vs 1.64Å~10-3mm2/s; P=0.001) than non-responders and ADC increased in responders (ΔADC, 90.28 versus 11 %,
respectively). A slight difference was observed in DCE curves but without a significant difference (p>0.05).Interobserver
reproducibility was good both for surgery (k 0.68) and post-NT (k 0.86).
CONCLUSION
MR can correctly stage organ-confined lesions according to the high specificity (for the T stage) and to rightly assess pathological
nodal involvement (for the N stage) thanks to the good SE. The ADC can be used to assess esophageal tumour response to NT
treatment as a reliable expression of tumour regression.
CLINICAL RELEVANCE/APPLICATION
Preoperative staging in esophageal cancer is critical in order to prompt a surgical (T1-T2 stages without nodal involvement) or neoadjuvant therapy (T3-T4 stages with nodal involvement).
SSM09-05
Textural Analysis of Baseline 18F-FDG PET for Predicting Treatment Response and Prognosis in
Patients with Locally Advanced Esophageal Cancer
W ednesday, Dec. 2 3:40PM - 3:50PM Location: E353B
Participants
Xiaorong Sun, Jinan, China (Presenter) Nothing to Disclose
Lu Sun, Jinan, China (Abstract Co-Author) Nothing to Disclose
Ligang Xing, Jinan, China (Abstract Co-Author) Nothing to Disclose
PURPOSE
Textural features on baseline 18F-FDG PET have shown the potential role in predicting treatment response in mixed stage
esophageal cancer. This study is aim to investigate the value of this new technique for locally advanced esophageal squamous cell
cancer (ESCC) receiving chemoradiotherapy.
METHOD AND MATERIALS
Under a waiver from IRB, 48 patients with newly diagnosed locally advanced ESCC who treated with concurrent chemoradiotherapy
were retrospectively reviewed. Thirty-nine patients with early stage ESCC were included as control. All patients underwent
pretreatment whole-body 18F-FDG PET/CT. Fifty-four texture indices describing global, local, and regional features were measured
in addition to 5 conventional indices as standardized uptake values (SUVs, including maximum, peak, and mean SUV), metabolic
volume (MV), and total lesion glycolysis (TLG). Patients were classified as responders (R, complete or partial response) and nonresponders (NR, stable or progressive disease) according to RECIST1.1. Progression-free survival (PFS) and overall survival (OS)
were recorded. The prognostic significance of parameters was examined using receiver-operating-characteristic curves, KaplanMeier analysis, and Cox regression analysis.
RESULTS
Both intratumor heterogeneity and mean/peak intensity of FDG uptake were significantly higher in locally advanced ESCC than those
in early stage. Thirty-four texture indices, MV, and TLG showed the ability to differentiate R from NR. Nine texture indices showed
higher sensitivity (76.7%~86.7%) and specificity (77.8%~94.4%) than MV (76.7% and 83.3%) and TLG (73.3% and 83.3%). Ten
texture indices and MV were hazard factors of PFS and OS. Large-zone emphasis, one of the regional texture indices, was the only
independent predictor of survival, with hazard ratio of 4.22 (95%CI:1.83~9.72) for PFS and 3.90 (1.74~8.79) for OS. None of the
SUVs could predict treatment response and survival.
CONCLUSION
FDG PET texture indices provide better predictive information than conventional parameters for locally advanced ESCC.
CLINICAL RELEVANCE/APPLICATION
The clinical application of FDG PET texture analysis could be an important step in personalized treatment of esophageal cancer.
SSM09-06
CT Signs Can Predict Treatment Response and Long-Term Survival: A Study in Locally Advanced
Esophageal Cancer with Preoperative Chemotherapy
W ednesday, Dec. 2 3:50PM - 4:00PM Location: E353B
Participants
Xiao-Yan Zhang, Beijing, China (Presenter) Nothing to Disclose
Xiaoting Li, Beijing, China (Abstract Co-Author) Nothing to Disclose
Zhilong Wang, MD, Beijing, China (Abstract Co-Author) Nothing to Disclose
Ying-Shi Sun, MD, PhD, Beijing, China (Abstract Co-Author) Nothing to Disclose
PURPOSE
Accurate prediction of treatment response and prognosis before surgery will allow prompt therapy adjustment. This study proposed
to evaluate the efficacy of CT signs on treatment response and survival for advanced esophageal squamous cell carcinoma patients
with preoperative chemotherapy.
METHOD AND MATERIALS
This study retrospectively enrolled 135 consecutive patients with preoperative chemotherapy from September 2005 to December
2011. Logistic regression model was conducted to evaluate the association between pathological response and CT signs. Overall
survival(OS) and disease-free survival (DFS) were estimated using Kaplan-Meier method and Cox proportional hazards model was
constructed to determine associations between CT signs after neoadjuvant chemotherapy and survival outcomes.
RESULTS
The logistic regression showed the total LN number(> 6) at baseline and the CT value change rate (≤ 17%) were significant for
poor response; OR were 5.07 (95% CI, 1.86 to 13.81, P = 0.002) and 2.35 (95% CI, 1.05 to 5.23, P = 0.037), respectively. In Cox
analyses, preoperative tumor thickness (> 10 mm), total LN number (>6), and short diameter of the largest LN (> 10 mm) were
significant for OS, HR were 2.33(95% CI, 1.36 to 4, P = 0.002), 1.88(95% CI, 1.12 to 3.17, P = 0.017) and 1.87(95% CI, 1.07 to
3.28, P = 0.028), respectively; whereas only the short diameter of the largest LN was significant for DFS, HR was 2.36(95% CI,
1.23 to 4.54, P = 0.01).
CONCLUSION
CT signs can predict therapeutic efficacy and survival outcomes and provide an opportunity to offer additional treatment options
before surgery.
CLINICAL RELEVANCE/APPLICATION
This study provided the first evidence that CT signs can predict survival outcomes and therapeutic efficacy of patients with
esophageal cancer who received preoperative chemotherapy. Therefore, it is of great clinical significance to perform CT
examinations before and after neo-adjuvant therapies in esophageal cancer patients. The CT images interpreted before surgery
could provide important information about survival and response, which would improve individualized treatment programs.
SSM14
Molecular Imaging (Inflammation/Immunology)
W ednesday, Dec. 2 3:00PM - 4:00PM Location: S504CD
MI
MR
NM
AMA PRA Category 1 Credit ™: 1.00
ARRT Category A+ Credit: 1.00
FDA
Discussions may include off-label uses.
Participants
Michael S. Gee, MD, PhD, Jamaica Plain, MA (Moderator) Nothing to Disclose
Tomio Inoue, MD, PhD, Yokohama, Japan (Moderator) Nothing to Disclose
Sub-Events
SSM14-01
Assessment of Renal Allograft Pathology by Arterial Spin Labelling and Diffusion Weighted Imaging
W ednesday, Dec. 2 3:00PM - 3:10PM Location: S504CD
Awards
RSNA Country Presents Travel Award
Participants
Katja Hueper, Hannover, Germany (Presenter) Nothing to Disclose
Marcel Gutberlet, Dipl Phys, Hannover, Germany (Abstract Co-Author) Nothing to Disclose
Dagmar Hartung, MD, Hannover, Germany (Abstract Co-Author) Nothing to Disclose
Song Rong, MD, Hannover, Germany (Abstract Co-Author) Nothing to Disclose
Frank K. Wacker, MD, Hannover, Germany (Abstract Co-Author) Research Grant, Siemens AG Research Grant, Pro Medicus Limited
Faikah Gueler, MD, Hannover, Germany (Abstract Co-Author) Nothing to Disclose
Jan Hinrich Braesen, Hannover, Germany (Abstract Co-Author) Nothing to Disclose
Bennet J. Hensen, Hanover, Germany (Abstract Co-Author) Nothing to Disclose
Martin Meier, PhD, Hannover, Germany (Abstract Co-Author) Nothing to Disclose
Rongjun Chen, Hannover, Germany (Abstract Co-Author) Nothing to Disclose
Michael Mengel, Edmonton, AB (Abstract Co-Author) Nothing to Disclose
PURPOSE
Renal allograft dysfunction early after kidney transplantation (ktx) is frequent, and may be caused by ischemia reperfusion injury or
acute rejection. The purpose was to investigate renal allograft pathology in a mouse model of allogenic and isogenic ktx by
perfusion imaging with arterial spin labelling (ASL) and diffusion weighted imaging (DWI) in correlation to histology.
METHOD AND MATERIALS
Allograft rejection was induced by allogenic ktx of C57Bl/6 (B6)-kidneys to Balb/c-mice in n=14 animals, isogenic ktx (B6-kindeys to
B6-mice) was performed in n=18 mice. Cold and warm ischemia times were 60 and 30 min, respectively, in both groups. Healthy B6mice served as controls. MRI was performed 1 and 6 days after ktx using a 7T-scanner. Flow alternating inversion recovery (FAIR)
ASL and DWI sequences (7 b-values) were acquired, and maps of renal perfusion and apparent diffusion coefficient (ADC) were
calculated. Renal histology was assessed for rejection and the severity of tubular injury and cell infiltration.
RESULTS
Following allogenic ktx animals developed a T-cell-mediated rejection, whereas isogenic mice had mild tubular injury but no
rejection. Renal perfusion at d1 was reduced after allogenic (262±43 ml/(min*100g)) and isogenic ktx (335±41 ml/(min*100g))
compared to normal B6-mice (483±23 ml/(min*100g), p<0.001). After allogenic ktx, renal perfusion further decreased until d6 and
was lower than in the isogenic group (80±13 vs 260±33 ml/(min*100ml), p<0.001). In contrast, ADC was unchanged after isogenic
ktx compared to normal B6-mice. In the allogenic group with acute rejection ADC was reduced compared to the isogenic group at
d1 (1.24±0.11 vs 1.61±0.03*10¯³mm²/s, p<0.001) and d6 (1.09±0.04 vs 1.55±0.07*10¯³mm²/s, p<0.001). Higher tubular injury
and inflammation scores and higher percentage of infiltrating T-cells significantly correlated with ADC reduction at d1and6 and
perfusion impairment at d6.
CONCLUSION
Renal allograft rejection is associated with progressive perfusion impairment and ADC reduction representing inflammation and cell
infiltration. Isogenic ktx with prolonged cold ischemia time leads to moderate perfusion impairment without ADC reduction. MRI
parameters correlate with histology.
CLINICAL RELEVANCE/APPLICATION
Functional MRI with ASL and DWI allows differentiation of renal graft pathology after transplantation. Parameters correlate with
histology and may improve non-invasive diagnosis in ktx patients.
SSM14-02
The Value of Whole Body Fully Integrated 18F-FDG-PET/MR in Idiopathic Retroperitoneal Fibrosis
W ednesday, Dec. 2 3:10PM - 3:20PM Location: S504CD
Awards
Molecular Imaging Travel Award
Participants
Ingo Einspieler, Munich, Germany (Presenter) Nothing to Disclose
Klaus Thurmel, Munich, Germany (Abstract Co-Author) Nothing to Disclose
Sabine Wolfram, Munich, Germany (Abstract Co-Author) Nothing to Disclose
Martin Henninger, Munich, Germany (Abstract Co-Author) Nothing to Disclose
Matthias J. Eiber, MD, Muenchen, Germany (Abstract Co-Author) Speakers Bureau, Johnson & Johnson
Markus Schwaiger, MD, Munich, Germany (Abstract Co-Author) Nothing to Disclose
Markus Essler, MD, Muenchen, Germany (Abstract Co-Author) Nothing to Disclose
PURPOSE
Idiopathic retroperitoneal fibrosis (IRF) is a rare inflammatory condition potentially leading to severe complications such as renal
failure. Besides, there is evidence of associated large vessel vasculitis (LVV), potentially causing life-threatening consequences
such as vessel stenosis and aneurysms. Therefore, early and precise assessment of both disease extent and activity is essential to
guide therapy decision. Due to the lack of reliable parameters to objectively assess the degree of inflammation, imaging by whole
body 18F-FDG PET/MR might help as a new approach.
METHOD AND MATERIALS
14 whole body 18F-FDG-PET/MR examinations were performed in 12 patients with IRF. T1 and T2 sequences were used for
anatomical localization of FDG uptake and identification of morphological changes associated with IRF. Contrast enhanced-MRA was
performed to judge changes of the vessel lumen. IRF tissue volume was calculated on MRI in cm3. FDG-uptake was assessed
visually (using a 4-point scale) and quantitatively (maximal standardized uptake value [SUV max], target to background ratio
[TBR]). Correlations between PET/MR findings (SUV max, TBR, visual score, IRF volume) and DAS (disease activity score),
combining typical clinical symptoms for IRF, CRP/ESR/IL-6 levels and results of previous examinations by ultrasound, CT and MRI,
were analyzed. Intended therapeutic management was documented before and after availability of PET/MR findings.
RESULTS
DAS classified 7 cases as having active disease and 7 as inactive. In contrast, PET/MR revealed active IRF in 10/14 cases and
changed disease status according to DAS in 5 cases (36%), more specifically in 4 cases from inactive to active disease and active
to inactive disease in 1 case. There was no association between DAS and the various PET/MR findings (p > 0.05). PET/MR showed
vessel changes suggestive for active LVV in 3 cases. In addition, PET/MR imaging results had impact on therapeutic management in
6/14 cases (43%), in particular by starting or avoiding immunosuppressive therapy.
CONCLUSION
Whole body 18F-FDG-PET/MR may be considered as a useful approach for aiding in the management of patients with IRF.
CLINICAL RELEVANCE/APPLICATION
In IRF there is still a lack of reliable parameters to objectively assess the degree of inflammation and to guide therapy decisions.
Imaging by whole body 18F-FDG PET/MR might help as a new approach.
SSM14-03
Glycosaminoglycan Chemical Exchange Saturation Transfer of Lumbar Intervertebral Discs in Patients
with Spondyloarthritis
W ednesday, Dec. 2 3:20PM - 3:30PM Location: S504CD
Awards
Molecular Imaging Travel Award
Participants
Christoph Schleich, Dusseldorf, Germany (Presenter) Nothing to Disclose
Anja Lutz, Dusseldorf, Germany (Abstract Co-Author) Nothing to Disclose
Joel Aissa, Duesseldorf, Germany (Abstract Co-Author) Nothing to Disclose
Philipp Sewerin, Dusseldorf, Germany (Abstract Co-Author) Nothing to Disclose
Ruben Sengewein, Duesseldorf, Germany (Abstract Co-Author) Nothing to Disclose
Benedikt Ostendorf, Dusseldorf, Germany (Abstract Co-Author) Nothing to Disclose
Benjamin Schmitt, Vienna, Austria (Abstract Co-Author) Nothing to Disclose
Gerald Antoch, MD, Duesseldorf, Germany (Abstract Co-Author) Nothing to Disclose
Falk R. Miese, MD, Dusseldorf, Germany (Abstract Co-Author) Nothing to Disclose
PURPOSE
To assess glycosaminoglycan (GAG) content of lumbar intervertebral discs (IVD) in patients with spondyloarthritis (SpA) using
glycosaminoglycan chemical exchange saturation transfer (gagCEST).
METHOD AND MATERIALS
Ninety lumbar intervertebral discs of nine patients with SpA and nine age-matched healthy controls (eight patients with ankylosing
spondylitis; one patient with spondylitis related to inflammatory bowel disease; mean age: 44.1 ± 14.0 years; range: 27 - 72 years)
were examined at a 3T MRI scanner in this prospective study. The MRI protocol included standard morphological, sagittal T2
weighted (T2w) images to assess Pfirrmann score of the five lumbar IVDs (L1 to S1) and biochemical imaging with gagCEST to
calculate a region-of-interest analysis of nucleus pulposus (NP) and annulus fibrosus (AF). Prior to statistical testing of gagCEST
effects (MTRasym values in %) in patients and controls, IVDs were classified according to the Pfirrmann score.
RESULTS
Significantly lower gagCEST values of NP and AF were found in SpA patients compared with healthy volunteers (NP: 1.41 % ± 0.41
%, p = 0.001; 95%-confidence interval, CI [0.600% - 2.226 %]; AF: 1.19 % ± 0.32 %, p < 0.001; CI [0.560 % - 1.822 %]) by
comparing the differences of the means. Pooled non-degenerative IVDs (Pfirrmann 1 and 2) had significantly lower gagCEST effects
in patients suffering from SpA compared with healthy controls in NP (p < 0.001; CI [1.176 % - 2.337 %]) and AF (p < 0.001; CI
[0.858 % - 1.779 %]). No significant difference of MTRasym values was found in degenerative IVDs between patients and controls
in NP (p = 0.204; CI [-0.504 % - 2.170 %]).
CONCLUSION
GagCEST analysis of morphologically non-degenerative IVDs (Pfirrmann score 1 and 2) in T2w images demonstrated significantly
lower GAG values in patients with spondyloarthritis in NP and AF possibly representing a depletion of GAG in spondyloarthritis in the
absence of morphologic degeneration.
CLINICAL RELEVANCE/APPLICATION
GagCEST may be a powerful tool to access IVD composition in spondyloarthritis and to investigate therapy effects on GAG content
in advanced studies.
SSM14-04
Preliminary Experience with 3T Time of Flight Simultaneous Cardiac PET/MRI in the Evaluation of
Cardiac Sarcoidosis
W ednesday, Dec. 2 3:30PM - 3:40PM Location: S504CD
Awards
Trainee Research Prize - Fellow
Participants
Kate Hanneman, MD, Toronto, ON (Presenter) Nothing to Disclose
Andrei Iagaru, MD, Stanford, CA (Abstract Co-Author) Research Grant, General Electric Company; Research Grant, Bayer AG
Henry Guo, Stanford, CA (Abstract Co-Author) Nothing to Disclose
Amir Barkhodari, Stanford, CA (Abstract Co-Author) Nothing to Disclose
Mehran Jamali, Stanford, CA (Abstract Co-Author) Nothing to Disclose
Dawn Holley, Stanford, CA (Abstract Co-Author) Nothing to Disclose
Robert J. Herfkens, MD, Stanford, CA (Abstract Co-Author) Nothing to Disclose
PURPOSE
The aim of this study is to investigate the utility of simultaneous time of flight (TOF) cardiac PET/MRI in the evaluation of cardiac
sarcoidosis.
METHOD AND MATERIALS
Six consecutive patients (50% male, 53.3±12.3 years) were prospectively recruited over a 3-month period for parallel assessment
of suspected cardiac sarcoidosis by standard clinical evaluation and simultaneous PET/MRI. Five healthy volunteers were initially
scanned for protocol optimization. Patients first underwent standard cardiac PET/CT (Discovery 600 or 690, GE Healthcare) after
administration of 9.7±0.4 mCi of 18F FDG. This was followed by a cardiac PET/MRI using a simultaneous scanner with TOF and 3T
(Signa, GE Healthcare). Participants were prepared with 8-hour dietary instructions in order to suppress physiologic myocardial
glucose uptake. Cardiac MRI sequences included breath-hold, ECG-triggered cine SSFP, T2-weighted, T1-mapping (pre- and postcontrast), and delayed myocardial enhanced (DME). Three experienced readers performed image analysis using an independent
workstation with dedicated post-processing software.
RESULTS
PET/CT was acquired with a delay of 95.8±26.6 min, while PET/MRI had a delay of 195.5±35.6 min from 18F FDG injection. Total
scan time for PET/MRI was significantly longer than for PET/CT (75.8±17.7 vs. 36.6±6.3 min, p=0.016). PET from PET/CT was
positive for cardiac sarcoidosis in 50% of patients, while PET from PET/MRI was positive for cardiac sarcoidosis in 100% of patients.
LV measurements by MRI were: EDV (159.3±33.5mL), ESV (87.6±50.0mL), LVEF (47.3±19.7%), pre-contrast T1 (1455.9±25.6ms),
post-contrast T1 (307.0±63.6ms) and extra-cellular volume (ECV) (38.5%). DME and T2 hyper-intensity were identified in 67% and
33% of patients, respectively. There was a significant difference in effective radiation dose (ED) between PET/CT and PET/MRI
(p=0.007). ED from the CT component of the PET/CT exam alone was 4.6±1.4mSv.
CONCLUSION
Simultaneous cardiac PET/MRI is feasible achieving diagnostic image quality with the added benefit of radiation dose reduction in
comparison to PET/CT.
CLINICAL RELEVANCE/APPLICATION
Simultaneous cardiac PET/MRI is feasible, and provides additional information over PET/CT, potentially reducing the number of
exams for patients.
SSM14-05
Role of FDG PET/CT for the Detection of Renal Infections in Cases of Pyrexia of Unknown Origin
W ednesday, Dec. 2 3:40PM - 3:50PM Location: S504CD
Participants
Sikandar M. Shaikh, DMRD, Hyderabad, India (Presenter) Nothing to Disclose
Hrushikesh Aurangabadkar, Hyderabad, India (Abstract Co-Author) Nothing to Disclose
Madhur K. Srivastava SR, MBBS, Chennai, India (Abstract Co-Author) Nothing to Disclose
PURPOSE
Patients with pyrexia of unknown origin were evaluated by FDG PET/CT for the detection of renal infections
METHOD AND MATERIALS
26 patients underwent FDG PET/CT for the detection of infection foci involving the kidneys. Positive FDG PET/CT findings and
pathological correlation served as the main outcome measures.
RESULTS
Of the 26 study patients, 18 (70.2%) had positive FDG PET/CT findings and a total of 24 major infection foci were identified. Five
patients (24.6%) had at least two infection foci on FDG PET/CT scans. Two (53.8%) of the 3 patients with primary renal infections
had concurrent multiple foci. seven patients (26.9%) had their treatments modified by FDG PET/CT results. Multivariate logistic
regression analysis demonstrated that leucocyte count at diagnosis along with correlation with positive FDG PET/CT results. seven
patients (26.0%) landed in hemodialysis during their hospital stay, and 6 of them had positive FDG PET/CT findings (P = 0.014).
Positive FDG PET/CT results were an independent predictor of mortality (hazard ratio [HR]=3.896, 95% CI=1.039-14.613, P =
0.044).
CONCLUSION
Our results suggest that FDG PET/CT is clinically useful for detecting occult infection foci in renal infections. In this population,
positive FDG PET/CT findings may lead to a significant change in clinical management and independently predict mortality.
CLINICAL RELEVANCE/APPLICATION
PET-CT IS HIGHLY SENSITIVE IN EVALUATING THE RENAL INFECTION IN CONTEXT OF PYREXIA OF UNKNOWN ORIGIN.
SSM14-06
Image Monitoring of Impaired Phagocytic Activity of Kupffer Cells and Liver Oxygen Saturation in a
Mouse Cholangitis Model Using Sonazoid-Enhanced US and Photoacoustic Image
W ednesday, Dec. 2 3:50PM - 4:00PM Location: S504CD
Participants
Jung Hoon Kim, MD, Seoul, Korea, Republic Of (Presenter) Nothing to Disclose
Seo-Youn Choi, MD, Bucheon, Korea, Republic Of (Abstract Co-Author) Nothing to Disclose
Hyo Won Eun, MD, PhD, Seoul, Korea, Republic Of (Abstract Co-Author) Nothing to Disclose
Seunghyun Lee, Seoul, Korea, Republic Of (Abstract Co-Author) Nothing to Disclose
Joon Koo Han, MD, Seoul, Korea, Republic Of (Abstract Co-Author) Nothing to Disclose
PURPOSE
To investigate serial change of impaired phagocytic activity of Kupffer cells and liver Oxygen Saturation (sO2) in a mouse
cholangitis model using sonazoid enhanced US (SEUS) and photoacoustic image (PI)
METHOD AND MATERIALS
Mouse cholangitis models were created by ligation of common bile duct (n=20, G1), left intrahepatic bile duct (n=19, G2-left and
G2-right) and compared with control (n=14, G3). SEUS and PI were performed at 1, 2, and 4 weeks. PA images were collected at
750 and 850 nm and parametric maps of sO2 were generated. Serial change of echogenicity on the Kupffer phase and liver sO2were
measured in each groups. Serial changes in each group were analyzed using one way ANOVA with Bonferroni's method. Kupffer cell
fraction using CD68 immunohistochemistry stain was also compared with SEUS.
RESULTS
Serial change of sonazoid enhacement enhancement showed decreased in G1 (15.1 + 8.6 x 10-5) and G2-left (9.3+7.9 x 10-5) than
G2-right (248.8+253.3 x 10-5) and control (153.7+34.7 x 10-5). However, Kupffer cell fraction showed increased in G1 (36.1+7.1%)
and G2-left (26.8+5.1%) than G2-right (16.6+5.6%) and control (12.3+3.3%), suggesting impaired phagocytic activity of Kupffer
cells. Liver sO2 showed decreased in G1 (24.0+8.0%) and G2-left (22.7+8.4%) than G2-right (39.1+12.0%) and control
(41.7+8.1%).
CONCLUSION
SEUS and PI are useful for monitoring of serial change of impaired phagocytic activity of Kupffer cells and liver sO2 in a mouse
cholangitis model.
CLINICAL RELEVANCE/APPLICATION
SEUS and PI are feasible to assess the serial change of phagocytic activity of Kupffer cells and liver sO2 in a mouse cholangitis
model.
ED015-TH
Molecular Imaging Thursday Case of the Day
Thursday, Dec. 3 7:00AM - 11:59PM Location: Case of Day, Learning Center
MI
AMA PRA Category 1 Credit ™: .50
Participants
Jonathan E. McConathy, MD, PhD, Saint Louis, MO (Presenter) Research Consultant, Eli Lilly and Company; Research Consultant,
Blue Earth Diagnostics Ltd; Research Consultant, Siemens AG; Research support, GlaxoSmithKline plc
Suzanne E. Lapi, PhD, Saint Louis, MO (Presenter) Research Grant, ImaginAB, Inc
Bernadette V. Marquez, PhD, Saint Louis, MO (Abstract Co-Author) Nothing to Disclose
Ephraim E. Parent, MD, PhD, Saint Louis, MO (Abstract Co-Author) Nothing to Disclose
Alexander Drzezga, MD, Cologne, Germany (Abstract Co-Author) Research Grant, Eli Lilly and Company; Speakers Bureau, Siemens
AG; Speakers Bureau, General Electric Company; Speakers Bureau, Piramal Enterprises Limited; Research Consultant, Eli Lilly and
Company; Research Consultant, Piramal Enterprises Limited; ; ; ; ; ;
TEACHING POINTS
1) The case of the day exhibit will highlight molecular imaging techniques currently available in clinical practice and new tracers
expected to become available in the near future. 2) Participants completing this exhibit will recognize the biodistribution of newer
molecular imaging agents, understand their mechanism of action, and be familiar with their clinical utility and potential causes of
diagnostic errors.
RC601
Contemporary Imaging of Lung Cancer
Thursday, Dec. 3 8:30AM - 10:00AM Location: N227
CH
CT
MI
MR
OI
AMA PRA Category 1 Credits ™: 1.50
ARRT Category A+ Credits: 1.50
Participants
Jeremy J. Erasmus, MD, Houston, TX (Moderator) Nothing to Disclose
Sub-Events
RC601A
Non-small Cell Lung Cancer Staging: Concepts and Controversies
Participants
Ioannis Vlahos, MRCP, FRCR, London, United Kingdom (Presenter) Research Consultant, Siemens AG Research Consultant, General
Electric Company
LEARNING OBJECTIVES
1) Summarize the origins, basis and rationale of the current TNM classification of lung cancer. 2) Discuss the strengths and
limitations of the current system and how to practically address these 3) Highlight areas where current radiology, oncological,
surgical and pathological best practice and evolving knowledge in these area are progressing beyond the current staging system.
Honored Educators
Presenters or authors on this event have been recognized as RSNA Honored Educators for participating in multiple qualifying
educational activities. Honored Educators are invested in furthering the profession of radiology by delivering high-quality
educational content in their field of study. Learn how you can become an honored educator by visiting the website at:
https://www.rsna.org/Honored-Educator-Award/
Ioannis Vlahos, MRCP, FRCR - 2015 Honored Educator
RC601B
Contemporary Concepts in Small Cell Lung Cancer
Participants
Fergus V. Gleeson, MBBS, Oxford, United Kingdom (Presenter) Consultant, Alliance Medical Limited; Consultant, Blue Earth
Diagnostics Limited; Consultant, Polarean, Inc;
LEARNING OBJECTIVES
1) To learn the clinical manifestations, staging and prognostic factors of small cell lung cancer. 2) To become familiar with the role
of PET-CT in the investigation and management of small cell lung cancer. 3) To review unusual presentations of small cell lung
cancer and their investigation and treatment.
ABSTRACT
Small cell lung cancer, SCLC, accounts for approximately 15% of all lung cancers, with its overall incidence decreasing, although it
is increasing in women, with the male to female incidence ratio now 1:1. Small cell lung cancer has a more rapid doubling time than
non-small cell lung cancer, with most patients presenting with hematogenous metastases, and only approximately one-third
presenting with limited-stage disease confined to the chest.Small cell lung cancer uncommonly presents with a solitary pulmonary
nodule, and the disease does not appear to have benefited from Lung Cancer Screening. There are multiple neurologic and
endocrine paraneoplastic syndromes associated with small cell lung cancer, with marked improvement on treatment of the
underlying tumour.Historically SCLC was staged according to the Veteran's Administration Lung Group's 2 stage classification of 1)
extensive-stage disease or 2) limited-stage disease, and this classification used to guide therapy. More recently it has been
recommended that SCLC is staged according to the International Association of the Study of Lung Cancer (IASLC) and the AJCC
Cancer Staging Manual 7th edition, using the same staging system for NSCLC and SCLC.Whilst contrast enhanced CT scan of the
chest and abdomen remain routine as the initial method for staging SCLC, FDG PET-CT now plays a more important role in staging
and management. SCLC is a highly metabolic disease, and PET-CT both upstages and downstages disease, potentially altering
management
RC601C
PET Imaging of Lung Cancer: Beyond Standard Metabolic Assessment
Participants
Eric M. Rohren, MD, PhD, Houston, TX (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
1) Review advanced image processing and metabolic parameters in FDG-PET/CT. 2) Discuss non-FDG radiotracers and their
potential applications in non-small cell lung cancer. 3) Illustrate the application and clinical use of advanced metabolic imaging
biomarkers derived from FDG-PET/CT using case examples.
ABSTRACT
Assessment of non-small cell lung cancer with PET is typically performed using F-18 fluorodeoxyglucose (FDG). The uptake and
retention of FDG by the tumor is taken to be a measure of metabolism, which in turn can provide useful information on staging,
grading, and prognosis. Advances in the field of PET/CT imaging may provide additional information for the evaluation and care of
patients with lung cancer. Advanced semi-quantitative analyses including total lesion glycolysis (TLG) and metabolic tumor volume
(MTV) have been employed to capture additional information from FDG-PET/CT studies, which in some cases is additive to standard
metabolic parameters such as SUVmax. New tracers are under development, with some nearing approval in the U.S. and elsewhere.
These include tracers targeting proliferation, receptor expression, and protein catabolism, investigating molecular events and
processes beyond glucose metabolism.
Honored Educators
Presenters or authors on this event have been recognized as RSNA Honored Educators for participating in multiple qualifying
educational activities. Honored Educators are invested in furthering the profession of radiology by delivering high-quality
educational content in their field of study. Learn how you can become an honored educator by visiting the website at:
https://www.rsna.org/Honored-Educator-Award/
Eric M. Rohren, MD, PhD - 2015 Honored Educator
RC601D
MRI: Advances in Nodule Characterization and Lung Cancer Staging
Participants
Kyung S. Lee, MD, PhD, Seoul, Korea, Republic Of, ([email protected]) (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
1) To review most popular MRI techniques that are used in thoracic MR imaging. 2) To demonstrate how effective MR imaging is in
nodule characterization and lung cancer staging, particularly focused on diffusion-weighted imaging (DWI) and diffusion-weighted
whole-body imaging with background body signal suppression (DWIBS).
ABSTRACT
Diffusion-weighted MR imaging helps characterize lung nodule, and enables staging and prognosis prediction in lung cancer.
Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) is known to be specific in nodal staging
and effective in whole body MR imaging. Both whole body MRI and PET-CT may be used in extra-thoracic lung cancer staging, but
each modality has its own and different merits in lung cancer staging. Whole body MRI-PET may be the future oncologic imaging
modality.
URL
RC601E
CT Perfusion Imaging in Lung Cancer
Participants
Friedrich D. Knollmann, MD, PhD, Sacramento, CA, ([email protected]) (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
1) To identify suitable indications for the use of CT perfusion imaging in lung cancer. 2) To apply CT perfusion imaging to lung
tumors. 3) To recognize important features of a valid CT perfusion imaging protocol. 4) To interpret the results of a CT perfusion
study in lung tumors.
ABSTRACT
CT perfusion (CTP) imaging has become a tenable proposition with the advent of multislice CT. Preliminary data have indicated a
potential role in the assessment of treatment response in lung cancer, but the method is not widely used. In this course, the
rationale for using CT perfusion imaging as a quantitative imaging biomarker in lung cancer is discussed. A review of CT protocols
includes factors that have impeded a wider adoption of the method in the clinical sphere, such as the reproducibility of
measurements, and validation efforts. Solutions to these problems, such as improved anatomic coverage with wider detectors and
table motion, reduced radiation exposure with iterative reconstruction, advanced postprocessing with dual blood supply algorithms,
motion registration and correction, and volumetric perfusion analysis are addressed. With these methods, tumor classification,
assessment of tumor response, and prognostic testing are promising applications of CTP imaging.
RC601F
Thoracic Oncologic Imaging: Treatment Effects and Complications
Participants
Brett W. Carter, MD, Houston, TX (Presenter) Author, Reed Elsevier; Consultant, St. Jude Medical, Inc; ;
LEARNING OBJECTIVES
1) Understand the role of imaging in the evaluation of patients who have been treated for thoracic malignancies. 2) Recognize the
manifestations of radiation therapy in the chest and be able to differentiate expected changes from residual or recurrent disease.
3) Identify intrathoracic complications from radiation therapy, chemotherapy, and surgery.
ABSTRACT
Imaging plays an important role in the evaluation of patients who have been treated with radiation therapy, chemotherapy, and/or
surgery for intrathoracic malignancies such as lung cancer, esophageal cancer, malignant pleural mesothelioma, and thymoma.
Following thoracic radiation therapy, radiation pneumonitis (1-6 months following therapy) and radiation fibrosis (6-12 months
following therapy) are typically identified in the lungs. However, complications such as esophagitis, esophageal ulceration, and
radiation-induced cardiovascular disease may develop. Patients treated with chemotherapy may develop pulmonary and
cardiovascular complications such as drug toxicity, organizing pneumonia, thromboembolic disease, vasculitis, and cardiomyopathy.
Knowledge of the spectrum of expected treatment-related changes, potential treatment complications and the appearance of
tumor recurrence is critical in order to properly monitor patients, identify iatrogenic complications, and avoid misinterpretation.
Honored Educators
Presenters or authors on this event have been recognized as RSNA Honored Educators for participating in multiple qualifying
educational activities. Honored Educators are invested in furthering the profession of radiology by delivering high-quality
educational content in their field of study. Learn how you can become an honored educator by visiting the website at:
https://www.rsna.org/Honored-Educator-Award/
Brett W. Carter, MD - 2015 Honored Educator
SSQ06
Gastrointestinal (Quantitative Imaging)
Thursday, Dec. 3 10:30AM - 12:00PM Location: E350
GI
BQ
CT
MI
MR
AMA PRA Category 1 Credits ™: 1.50
ARRT Category A+ Credits: 1.50
FDA
Discussions may include off-label uses.
Participants
Claude B. Sirlin, MD, San Diego, CA (Moderator) Research Grant, General Electric Company; Speakers Bureau, Bayer AG; Consultant,
Bayer AG ; ;
Alexander R. Guimaraes, MD, PhD, Portland, OR (Moderator) Speakers Bureau, Siemens AG; Expert Witness, Rice, Dolan, Kershaw
Andrew D. Smith, MD, PhD, Jackson, MS (Moderator) Research Grant, Pfizer Inc; President, Radiostics LLC; President, Liver
Nodularity LLC; President, Color Enhanced Detection LLC; Pending patent, Liver Nodularity LLC; Pending patent, Color Enhanced
Detection LLC;
Sub-Events
SSQ06-01
3D Vibe-Dixon MR Sequence in Hepatic Fat Quantification: Inter-reader Reproducibility and
Correlation to MRS Results in a Liver Donor Cohort
Thursday, Dec. 3 10:30AM - 10:40AM Location: E350
Participants
Chiara Pozzessere, MD, Siena, Italy (Presenter) Nothing to Disclose
Xiangyu Zhu, Baltimore, MD (Abstract Co-Author) Nothing to Disclose
Celia P. Corona-Villalobos, MD, Baltimore, MD (Abstract Co-Author) Nothing to Disclose
Lorenzo Righi, Siena, Italy (Abstract Co-Author) Nothing to Disclose
Sandra L. Castanos Gutierrez, MD, Baltimore, MD (Abstract Co-Author) Nothing to Disclose
Fatemeh Sobhani, Baltimore, MD (Abstract Co-Author) Nothing to Disclose
Neda Rastegar, MD, Baltimore, MD (Abstract Co-Author) Nothing to Disclose
Li Pan, Baltimore, MD (Abstract Co-Author) Employee, Siemens AG
Ihab R. Kamel, MD, PhD, Baltimore, MD (Abstract Co-Author) Nothing to Disclose
PURPOSE
Liver steatosis is the most common liver disease in Western Countries and it may progress to steatohepatis and cirrhosis. Magnetic
Resonance Spectroscopy (MRS) has been shown to strongly correlate with histology in fat quantification. However, MRS has some
limitations such as breathing artifact and difficulties in avoiding vessels or bile ducts within the voxel. 3D VIBE-Dixon is a MR
sequence which can quantify fat content. The aim of this study was to compare fat quantification of liver using 3D VIBE-DIXON to
that using MRS.
METHOD AND MATERIALS
IRB approved this prospective, HIPAA compliant study. Thirty potential liver donors (14 males, 12 females; mean age 38 yo)
underwent liver MR, including single voxel MRS, within the right (RL) and left lobe (LL) and axial 3D VIBE-Dixon. Liver biopsy was
performed in 8 patients. Fat percentage (FP) was generated by MRS. Two readers blinded to MRS results independently quantified
the FP on 3D VIBE-Dixon by drawing a ROI in both lobes in the same locations of the MRS voxels.Lin's concordance correlation was
used to assess concordance between MRS and 3D VIBE-Dixon, for the two readers. Intraclass correlation coefficient was used to
compare 3D VIBE-Dixon to histology. Inter-observer agreement was calculated. A p ≤0.05 was considered statistically significant.
RESULTS
In the RL, mean FP was 5.8% by MRS, and 4.8% and 4.8% by 3D VIBE-Dixon for readers 1 and 2, respectively, with a strong
concordance between the two technique (rho= 0.78 and 0.76 for reader 1 and 2, respectively, p<0.001). In the LL, mean FP was
5.2% by MRS, and 4.2% and 4% by 3D VIBE DIXON for readers 1 and 2, respectively, with medium concordance between the two
sequences (rho=0.44 and 0.38 for readers 1 and 2, respectively). Inter-observer agreement was excellent in both RL and LL
(rho=0.96 and 0.92, respectively, p<0.001). In the 8 patients who underwent biopsy FP by 3D VIBE-DIXON highly correlated to
histological results (ICC=0.85).
CONCLUSION
In this prospective study, fat quantification using 3D VIBE-DIXON was highly reproducible, with strong correlation to MRS in the RL.
Correlation was moderate in the LL, probably due to artifacts on MRS.
CLINICAL RELEVANCE/APPLICATION
3D VIBE-DIXON is a highly reproducible MR sequence, which may allow non-invasive fat quantification in the liver. Further studies
with larger cohort and pathology comparison are required.
Honored Educators
Presenters or authors on this event have been recognized as RSNA Honored Educators for participating in multiple qualifying
educational activities. Honored Educators are invested in furthering the profession of radiology by delivering high-quality
educational content in their field of study. Learn how you can become an honored educator by visiting the website at:
https://www.rsna.org/Honored-Educator-Award/
Ihab R. Kamel, MD, PhD - 2015 Honored Educator
SSQ06-02
Inter-site Reproducibility of 2D MR Elastography Analysis for Hepatic Stiffness in a Cohort of Obese
Adults
Thursday, Dec. 3 10:40AM - 10:50AM Location: E350
Participants
William Haufe, San Diego, CA (Presenter) Nothing to Disclose
Curtis N. Wiens, PhD, Madison, WI (Abstract Co-Author) Nothing to Disclose
Catherine A. Hooker, BS, San Diego, CA (Abstract Co-Author) Nothing to Disclose
Tanya Wolfson, MS, San Diego, CA (Abstract Co-Author) Nothing to Disclose
Alan B. McMillan, Madison, WI (Abstract Co-Author) Nothing to Disclose
Paul Manning, MSc, La Jolla, CA (Abstract Co-Author) Nothing to Disclose
Kang Wang, PhD, San Diego, CA (Abstract Co-Author) Nothing to Disclose
Scott B. Reeder, MD, PhD, Madison, WI (Abstract Co-Author) Institutional research support, General Electric Company Institutional
research support, Bracco Group
Michael S. Middleton, MD, PhD, San Diego, CA (Abstract Co-Author) Consultant, Allergan, Inc Institutional research contract, Bayer
AG Institutional research contract, sanofi-aventis Group Institutional research contract, Isis Pharmaceuticals, Inc Institutional
research contract, Johnson & Johnson Institutional research contract, Synageva BioPharma Corporation Institutional research
contract, Takeda Pharmaceutical Company Limited Stockholder, General Electric Company Stockholder, Pfizer Inc Institutional
research contract, Pfizer Inc
Claude B. Sirlin, MD, San Diego, CA (Abstract Co-Author) Research Grant, General Electric Company; Speakers Bureau, Bayer AG;
Consultant, Bayer AG ; ;
PURPOSE
To assess the inter-site reproducibility of 2D magnetic resonance elastography (MRE) analysis for hepatic stiffness in obese adults
METHOD AND MATERIALS
In this HIPAA compliant, IRB approved study, obese (BMI ≥ 30 kg/m²) adults underwent 2D MRE on a 1.5T or 3.0T GE scanner at
one of two sites. A passive driver produced 60 Hz acoustic shear waves through the liver, and MRE-generated wave images,
magnitude images, and stiffness maps (elastograms) were transferred offline for manual analysis. Analysts at each of the two
separate sites evaluated all exams from both sites. Analysts drew regions of interest (ROIs) on the elastograms in areas of the liver
where parallel wave propagation was observed on the corresponding wave image. From these ROIs, stiffness values were recorded.
Weighted average was applied to obtain a single per-liver stiffness value. Bland-Altman plot and intraclass correlation coefficient
(ICC) were used to assess inter-site reproducibility. Paired t-test was used to examine systematic shifts.
RESULTS
87 adults (74 female, 13 male) underwent MRE. The mean (± standard deviation) age and BMI were 48.3 (± 12.5) years and 42.6
(± 5.8) kg/m2 respectively. Fourteen scans were considered unanalyzable by at least one of the two sites due to low signal-tonoise or poor wave propagation. Hence, data from 73 subjects were used in reproducibility analyses. ICC for the two sites was .833
[0.724, 0.898]. Mean (± standard deviation) stiffness values for site A and site B were 2.90 (± 1.06 kPa) and 3.13 (±1.15 kPa)
respectively. A small, clinically non-meaningful, but statistically significant bias was observed (mean difference .23 kPa, paired ttest p=0.0016).
CONCLUSION
MRE analysis for hepatic stiffness from independent analysts at two separate sites had high reproducibility. There was a small
systematic bias observed between the two participating study sites, which was not clinically meaningful in the context of staging
liver fibrosis.
CLINICAL RELEVANCE/APPLICATION
In order for 2D MRE to be clinically useful in the staging of hepatic fibrosis, liver stiffness results must be analyst and site
independent. Studies such as this will help demonstrate the reproducibility of MRE stiffness values.
SSQ06-03
¹H-Magnetic Resonance Spectroscopy is Superior to Controlled Attenuation Parameter (CAP) in
Assessing Liver Fat Content in Human Non-alcoholic Fatty Liver Disease (NAFLD)
Thursday, Dec. 3 10:50AM - 11:00AM Location: E350
Awards
Trainee Research Prize - Resident
Participants
Jurgen H. Runge, MD,PhD, Amsterdam, Netherlands (Presenter) Nothing to Disclose
Loek P. Smits, MD,MSc, Amsterdam, Netherlands (Abstract Co-Author) Nothing to Disclose
Joanne Verheij, Rotterdam, Netherlands (Abstract Co-Author) Nothing to Disclose
Aart N. Nederveen, PhD, Amsterdam, Netherlands (Abstract Co-Author) Nothing to Disclose
U Beuers, Amsterdam, Netherlands (Abstract Co-Author) Nothing to Disclose
Jaap Stoker, MD, PhD, Amsterdam, Netherlands (Abstract Co-Author) Research Consultant, Robarts Clinical Trials
PURPOSE
Non-alcoholic fatty liver disease (NAFLD) is an increasingly recognized health problem worldwide. Liver biopsy is the diagnostic
standard, but liver fat content is preferably assessed noninvasively and quantitatively. Recently, the Controlled Attenuation
Parameter (CAP) technique was introduced on the FibroScan®, a transient elastography device with FDA approval since 2013. Only
limited data are available regarding CAP's accuracy compared to established quantitative measures. Therefore, we prospectively
compared CAP and ¹H-Magnetic Resonance Spectroscopy (¹H-MRS) derived fat fractions (FF) against liver biopsy in a cohort of
patients with NAFLD.
METHOD AND MATERIALS
Forty NAFLD patients (M/F: 29/11) with median (IQR) age of 52.6 (48.5-57.3) and BMI of 27.1 (25.4-33.1) were included in this
IRB-approved study. Same-day 3T MRI and CAP measurement were performed by a single examiner within 27 (17-50) days of liver
biopsy, assessed by a single pathologist. ¹H-MRS derived FF and CAP values were compared between Brunt steatosis grades S0-S3
using Kruskall-Wallis and Mann-Whitney-U tests. Correlations were assessed with Spearman's. Diagnostic accuracies of CAP and FF
to identify ≥S1 on biopsy were compared with ROC analyses.
RESULTS
Median FF differed (p<0.0001) between all histological steatosis grades at 1.0%(0.7-1.4), 6.1%(3.9-8.8), 17.4%(11.3-21.1) and
26.3%(25.0-30.1). Median CAP only differed between grades S0 and S2 (p=0.025) and S1 and S2 (p=0.006) at 260 dB/m (221320), 281 dB/m (249-331), 330 dB/m (305-378) and 348 dB/m (321-353). FF (rs 0.90;95%-CI:0.81-0.95) correlated better
(P=0.0002) with steatosis grades than CAP (rs 0.53;95%-CI:0.25-0.73). The area under the ROC curve (AUROC) to identify ≥S1
was higher (P=0.04) for ¹H-MRS at 0.98 (95%-CI:0.93-1.0) than for CAP at 0.76 (95%-CI:0.56-0.95). Optimal cut-off values of
4.1% and 261 dB/m resulted in sensitivity/ specificity/positive/negative predictive values of 89%/100%/100%/56% for ¹H-MRS and
89%/60%/ 94%/43% for CAP.
CONCLUSION
¹H-MRS derived FF differed between all four steatosis grades on biopsy, while CAP did not. Better correlation with histological
features and superior AUROC to identify steatosis stage ≥S1 reaffirm ¹H-MRS as preferred method for noninvasive liver fat content
assessment.
CLINICAL RELEVANCE/APPLICATION
¹H-MRS derived liver fat fractions show better diagnostic accuracy than CAP values for accurate noninvasive liver fat content
assessment.
SSQ06-04
Assessment of Liver and Pancreas Iron Overload with a 3T MRI Multiecho GRE Sequence in Diffuse
Liver Disorders: Rorrelation with Serum Ferritin and Liver Biopsy
Thursday, Dec. 3 11:00AM - 11:10AM Location: E350
Participants
Manuela Franca, MD, Porto, Portugal (Presenter) Nothing to Disclose
Angel Alberich-Bayarri, MD, Valencia, Spain (Abstract Co-Author) Nothing to Disclose
Luis Marti-Bonmati, MD, PhD, Godella, Spain (Abstract Co-Author) Nothing to Disclose
Graca Porto, Porto, Portugal (Abstract Co-Author) Nothing to Disclose
Helena Pessegueiro Miranda, Porto, Portugal (Abstract Co-Author) Nothing to Disclose
Joao A. Oliveira, Porto, Portugal (Abstract Co-Author) Nothing to Disclose
Francisca E. Costa, MD, Porto, Portugal (Abstract Co-Author) Nothing to Disclose
Jose Ramon Vizcaino Vazquez, Porto, Portugal (Abstract Co-Author) Nothing to Disclose
PURPOSE
Iron overload is associated with hereditary hemochromatosis, chronic transfusions, hemolytic conditions and diffuse liver diseases
such as chronic hepatitis C, alcoholic liver disease and NAFLD. Pancreatic iron can be also found in some of these conditions. Our
objective was to assess R2* values of the liver and pancreas in patients with chronic diffuse liver diseases, comparing the R2*
values with serum ferritin levels and liver biopsy.
METHOD AND MATERIALS
A total of 99 consecutive patients with chronic diffuse liver disorders who underwent liver biopsy and abdominal MR examination
were included. The 3T MR examination included a single breath-hold multiecho GRE sequence with 12 echoes. Iron related-R2*
quantification was performed with a dedicated software selecting a ROI within the biopsied liver segment and also in the pancreas
(head, body and tail). Liver biopsy was used as gold standard for liver iron deposits grading (0-4).
CONCLUSION
There is an excellent relationship between liver R2*-iron quantification against liver biopsy and serum ferritin, in different chronic
liver disorders. Pancreas R2* is significantly correlated with serum ferritin, liver R2* and histologic iron grading.
CLINICAL RELEVANCE/APPLICATION
In patients with diffuse chronic liver disorders, pancreas R2* correlate with liver R2* and biopsy-proved liver iron overload.
SSQ06-05
Liver Volume-assisted Estimation of Liver Function Based on Gd-EOB-DTPA- enhanced MRRelaxometry
Thursday, Dec. 3 11:10AM - 11:20AM Location: E350
Awards
RSNA Country Presents Travel Award
Participants
Michael Haimerl, Regensburg, Germany (Presenter) Nothing to Disclose
Niklas Verloh, Regensburg, Germany (Abstract Co-Author) Nothing to Disclose
Claudia Fellner, MD, PhD, Regensburg, Germany (Abstract Co-Author) Nothing to Disclose
Marcel D. Nickel, Erlangen, Germany (Abstract Co-Author) Employee, Siemens AG
Christian R. Stroszczynski, MD, Regensburg, Germany (Abstract Co-Author) Nothing to Disclose
Philipp Wiggermann, Regensburg, Germany (Abstract Co-Author) Nothing to Disclose
PURPOSE
To determine whether liver function as determined by indocyanine green (ICG) clearance can be estimated quantitatively from
gadoxetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance (MR)- Relaxometry and to estimate the impact of liver liver volumes.
METHOD AND MATERIALS
132 patients underwent an ICG clearance test and Gd-EOB-DTPA-enhanced MRI, including MR-Relaxometry at 3 Tesla. A transverse
3D VIBE sequence with an inline T1 calculation was acquired prior to and 20 minutes post-Gd-EOB-DTPA administration. Volumetric
analysis of respective livers was performed on Aquarius iNtuition Viewer (TeraRecon Inc.). The reduction rate of T1 relaxation time
(rrT1) between pre- and post-contrast images and the liver volume-assisted index of T1 reduction rate (LVrrT1) were evaluated.
The plasma disappearance rate of ICG (ICG-PDR) was correlated with the liver volume (LV), rrT1 and LVrrT1, providing an MRIbased estimated ICG-PDR value (ICG-PDRest).
RESULTS
Regression model showed a significant log-linear correlation of ICG-PDR with LV (r = 0.31; p = 0.001), T1post (r = 0.62; p < 0.001)
and rrT1 (r = 0.85; p < 0.001). Assessment of LV and consecutive evaluation of multiple linear regression model revealed a stronger
log-linear correlation of ICG-PDR with LVrrT1 (r = 0.91; p < 0.001), allowing for the calculation of ICG-PDRest.
CONCLUSION
Liver function as determined using ICG-PDR can be estimated quantitatively from Gd-EOB-DTPA-enhanced MR-Relaxometry. Volumeassisted MR-Relaxometry has a stronger correlation with liver function than does MR-Relaxometry.
CLINICAL RELEVANCE/APPLICATION
Global and regional liver function may be visualized by Gd-EOB-DTPA-enhanced MRI, which might be of importance for planning liver
resections.
SSQ06-06
Liver Volume Predicts the Clinical Outcome of Patients with Decompensated Alcoholic Steatohepatitis
Thursday, Dec. 3 11:20AM - 11:30AM Location: E350
Participants
Maxime Ronot, MD, Clichy, France (Abstract Co-Author) Nothing to Disclose
Romain Breguet, MD, Geneva, Switzerland (Abstract Co-Author) Nothing to Disclose
Catrina Hansen, Geneve, Switzerland (Abstract Co-Author) Nothing to Disclose
Christoph D. Becker, MD, Thonex, Switzerland (Abstract Co-Author) Nothing to Disclose
Laurent Spahr, Geneve, Switzerland (Abstract Co-Author) Nothing to Disclose
Sylvain Terraz, MD, Geneva, Switzerland (Abstract Co-Author) Nothing to Disclose
Matthieu Lagadec, MD, Clichy, France (Presenter) Nothing to Disclose
PURPOSE
To evaluate the prognostic value of abdominal multidetector computed tomography (MDCT) in patients with decompensated
alcoholic steatohepatitis (ASH).
METHOD AND MATERIALS
This ancillary study was based on the analysis of data collected during a randomized trial on ASH treatment. Response to treatment
was defined as the improvement of the baseline MELD score ≥3 points at 3 months. All patients underwent contrast-enhanced
MDCT of the abdomen. The following parameters were measured: 1/ liver (DL) and spleen (DS) density on unenhanced images, and
DL/DS ratio, 2/ liver volume-to-body weight ratio (VLBW), 3/ subcutaneous fat (FSC), visceral fat (FV) and muscular (M) surfaces
at the level of L3-L4. Responders and non-responders were compared with uni-, multivariate and ROC analyses. Results were
compared with a validation cohort of patients, clinically and biologically similar to the study cohort.
RESULTS
Fifty-eight patients (34 males; mean age, 56 years) were analyzed, including 34 (59%) responders. Baseline mean MELD and ABIC
scores were 19 (13-28) and 8.3 (6.5-10.3). On multivariate analysis, VLBW (OR=3.73; 95%CI, 1.64-8.46; p=0.002) and FSC
(OR=1.01; 95%CI, 1.00-1.02; p=0.022) were associated with response to treatment, with AUROC curves of 0.78±0.06 (p<0.001)
and 0.66±0.07 (p=0.043), respectively. BMI, baseline MELD and ABIC scores, gender, DL/DS, FV and M were not different between
the two groups. VLBW ≥ 2.4% predicted response with 88% and 63% sensitivity and specificity. In the validation cohort (n=24,
75% responders), the same cut-off value predicted response with 83% and 67% sensitivity and specificity.
CONCLUSION
In patients suffering from decompensated ASH, the liver volume appears to be a major positive prognostic factor. This simple
morphometric parameter may be added to the initial evaluation of the liver disease to improve patient management.
CLINICAL RELEVANCE/APPLICATION
The liver volume-to-body weight ratio appears to be a major prognostic factor in patients with ASH. This morphometric parameter
could be added to the initial workup of patients, to better predict the response to treatment and improve the management.
SSQ06-07
MRI Based Quantification of Hepatic Uptake and Excretion of Gadoxetic Acid: Preliminary Results
Thursday, Dec. 3 11:30AM - 11:40AM Location: E350
Participants
Daniel Truhn, MD, Cologne, Germany (Presenter) Nothing to Disclose
Alexander Ciritsis, Aachen, Germany (Abstract Co-Author) Nothing to Disclose
Nienke L. Hansen, MD, Aachen, Germany (Abstract Co-Author) Nothing to Disclose
Alexandra Barabasch, MD, Aachen, Germany (Abstract Co-Author) Nothing to Disclose
Burkhard Maedler, Bonn, Germany (Abstract Co-Author) Researcher, Koninklijke Philips NV
Christiane K. Kuhl, MD, Bonn, Germany (Abstract Co-Author) Nothing to Disclose
Nils A. Kraemer, Aachen, Germany (Abstract Co-Author) Nothing to Disclose
PURPOSE
Recent research in liver MRI has shown that quantification of hepatic uptake of gadoxetic acid is a promising method for
determination of local liver function and correlates well with established clinical measures of liver function. The aim of this study
was to evaluate a method for combined measurement of hepatic uptake and excretion.
METHOD AND MATERIALS
After intravenous administration of gadoxetic acid, signal enhancement of liver tissue in 14 healthy patients was measured over the
time course of 30 minutes. First, the data was assessed using previously published methods that do not consider excretion. Then, a
dual inlet two compartment model was appended by a parameter describing the excretion of contrast medium into the bile. A least
squares fit was performed to extract the following parameters: extra- and intracellular volume fraction, uptake and excretion rates,
arterial and portal venous flow fractions. Results for the models without and with consideration of excretion were subsequently
compared.
RESULTS
The dual inlet two compartment model provided the best agreement between modeled and measured signal values when compared
to previously published methods that do not consider excretion of contrast agent. The mean value for the uptake rate in healthy
liver tissue was 4.76+-0.54 /100/min. Excretion half-time was 21.9+-2.4 min.Inter-patient variance was significantly greater when
conventional models (uptake only) models were applied. We found a significant deviation between modeled and measured signal
values with an uptake rate of 3.56+-1.34 /100/min. Excretion rates could only be obtained with the dual inlet two compartment
model.
CONCLUSION
The model not considering the excretion was only valid in the first 5 minutes of hepatic signal enhancement and failed over the
course of 30 minutes. Accurate modeling of gadoxetic acid induced hepatic enhancement over a longer time course requires a dual
inlet two compartment model. Including this parameter into models of liver tissue might lead to a more precise correlation between
hepatic function and MRI.
CLINICAL RELEVANCE/APPLICATION
When aiming to measure hepatic function using MRI not only the hepatic uptake, but also the excretion should be taken into
account to get better correlations between MRI and liver function.
SSQ06-08
The Attenuation Distribution Across the Long Axis (ADLA): Evaluation of Predictive Performance in a
Large Clinical Trial
Thursday, Dec. 3 11:40AM - 11:50AM Location: E350
Awards
Trainee Research Prize - Medical Student
Participants
Nikita Lakomkin, Nashville, TN (Presenter) Nothing to Disclose
Allison Hainline, Nashville, TN (Abstract Co-Author) Nothing to Disclose
Hakmook Kang, Nashville, TN (Abstract Co-Author) Nothing to Disclose
M. S. Hutson, Nashville, TN (Abstract Co-Author) Nothing to Disclose
Carlos L. Arteaga, Nashville, TN (Abstract Co-Author) Nothing to Disclose
Richard G. Abramson, MD, Nashville, TN (Abstract Co-Author) Consultant, ICON plc;
PURPOSE
Novel methods of image feature analysis may be a useful adjunct to standard methods of cancer treatment response assessment.
The attenuation distribution across the long axis (ADLA) is a simple, easily extractable measure of lesion heterogeneity; in a recent
preliminary study, ADLA measurements predicted overall survival (OS) better than RECIST 1.1. The purpose of this study was to
evaluate the ability of the ADLA method to predict OS in a larger clinical trial.
METHOD AND MATERIALS
Under a data sharing agreement from Genentech (San Francisco, CA) and an IRB waiver from our institution, we obtained deidentified imaging and clinical data from RIBBON-1, a multi-site phase 3 trial of bevacizumab (Avastin) in metastatic breast cancer.
We analyzed all RIBBON-1 patients treated with Avastin who had at least 1 liver metastasis measuring ≥ 15 mm on baseline
contrast-enhanced CT. For each patient at every time point, up to 2 target liver lesions were evaluated using both RECIST 1.1
criteria and ADLA. The ADLA was obtained as the standard deviation of the post-contrast CT attenuation values in the portal
venous phase across a long-axis diameter function. To define a treatment response using ADLA, Brier scores were computed to
establish the optimal percent decrease for separating patients with longer OS. Using Kaplan-Meier survival analysis, the log-rank
test was then used to evaluate the ability of a treatment response by ADLA measurements to predict OS. The ADLA method was
then compared to RECIST 1.1 using a bootstrapping technique that generated 95% confidence intervals on the Brier scores for both
approaches.
RESULTS
165 patients met inclusion criteria. Median OS was 461 days (range 60-916). The ADLA method discriminated patients with longer
OS at an optimal threshold of a 21.5% decrease from baseline. At this threshold, a treatment response by the ADLA method
successfully separated patients with longer OS (p<0.001). Furthermore, a treatment response by ADLA was superior to a response
by RECIST 1.1 for discriminating patients with longer OS (95% confidence interval for the Brier score difference: [0.070-0.52]).
Kaplan-Meier survival curves are shown below.
CONCLUSION
In retrospective data analysis from a large clinical trial, the ADLA method was superior to RECIST 1.1 for predicting overall survival.
CLINICAL RELEVANCE/APPLICATION
The ADLA measurement is an easily extractable parameter that may be useful for assessing cancer treatment response.
SSQ06-09
Differences of Target Lesion Selection Drives Variability of Response Assessment According to
RECIST 1.1
Thursday, Dec. 3 11:50AM - 12:00PM Location: E350
Awards
RSNA Country Presents Travel Award
Participants
Yunus Alparslan, Aachen, Germany (Presenter) Nothing to Disclose
Jonas Schmoe, Aachen, Germany (Abstract Co-Author) Nothing to Disclose
Hanna Witte, Aachen, Germany (Abstract Co-Author) Nothing to Disclose
Annika Keulers, MD, Aachen, Germany (Abstract Co-Author) Nothing to Disclose
Christiane K. Kuhl, MD, Bonn, Germany (Abstract Co-Author) Nothing to Disclose
Sebastian Keil, MD, Aachen, Germany (Abstract Co-Author) Nothing to Disclose
PURPOSE
To conduct a prospective systematic analysis of factors contributing to variability of response classification in RECIST1.1 beyond
factors related to disease measurement, i.e. variability that persists even if dedicated software for response assessment is used.
METHOD AND MATERIALS
63 patients (60 ± 9 years) underwent a total 132 contrast-enhanced CT studies for initial staging or follow-up after systemic
chemotherapy. A target or non-target lesion satisfying RECIST1.1 criteria could be identified in 52/63 patients (82.5%) and 113/132
(85.6%) of (re-)staging CT studies. Data were independently interpreted by three radiologists with > 4 years of experience who
used specialized software (MintMedical) for standardized response assessment. Response was classified in complete or partial
response (CR, PR), or stable or progressive disease (SD, PD), and stratified as progressive (PD) vs. non-progressive (CR, PR, SD).
RESULTS
Overall, readers agreed in terms of response classification in 58.4% of studies (66/113) and disagreed in 41.6% (47/113). In 50/113
studies, readers had chosen the same, and in 63/113 studies, readers had chosen different target lesions. Selection of the same
target lesions was associated with an 88% rate (44/50) of agreement; selection of different target lesions was associated with a
74.6% rate (47/63) of disagreement. After dichotomizing response classes according to their therapeutic implication in PD vs. nonPD RECIST1.1 response classes, disagreement was observed in 17/113 staging examinations (15%). In 13 of these 17 patients
(76.5%), readers had chosen different target lesions.
CONCLUSION
The basic assumption of standardized response assessment is that different readers should yield the same response classification
for a given patient. In fact, however, different readers disagree in almost half of patient cases, and in 15%, they disagree even
with regards to the basic distinction between PD vs. non-PD. Major source of variability appears to be the fact that different
readers may choose different target lesions. The resulting variability between readers will not be compensated for by software tools
for automated response assessment.
CLINICAL RELEVANCE/APPLICATION
Even with standardized RECIST readings and use of dedicated automated software, different radiologists will yield different results
with regards to response classification, even with regards to broadly different categories (PD vs. non-PD).
SSQ12
Molecular Imaging (New Tracers/Methods)
Thursday, Dec. 3 10:30AM - 12:00PM Location: S504AB
CT
MI
MR
NM
AMA PRA Category 1 Credits ™: 1.50
ARRT Category A+ Credits: 1.50
FDA
Discussions may include off-label uses.
Participants
Brian M. Rodgers, MD, Rockville, MD (Moderator) Nothing to Disclose
Bernadette V. Marquez, PhD, Saint Louis, MO (Moderator) Nothing to Disclose
Sub-Events
SSQ12-01
Hyperpolarized 13C MRI for Non-Invasive Assessment of Liver Injury in a Mouse Model
Thursday, Dec. 3 10:30AM - 10:40AM Location: S504AB
Participants
Michael A. Ohliger, MD, PhD, San Francisco, CA (Presenter) Nothing to Disclose
Irene Marco-Rius, PhD, San Francisco, CA (Abstract Co-Author) Nothing to Disclose
Robert A. Bok, MD, PhD, San Francisco, CA (Abstract Co-Author) Nothing to Disclose
Jacquelyn J. Maher, MD, San Francisco, CA (Abstract Co-Author) Nothing to Disclose
Cornelius Von Morze, San Francisco, CA (Abstract Co-Author) Nothing to Disclose
Subramaniam Sukumar, PhD, San Francisco, CA (Abstract Co-Author) Nothing to Disclose
Zihan Zhu, San Francisco, CA (Abstract Co-Author) Nothing to Disclose
Zhen J. Wang, MD, Hillsborough, CA (Abstract Co-Author) Nothing to Disclose
Benjamin M. Yeh, MD, San Francisco, CA (Abstract Co-Author) Research Grant, General Electric Company; Author with royalties,
Oxford University Press; Shareholder, Nextrast, Inc;
Daniel B. Vigneron, PhD, San Francisco, CA (Abstract Co-Author) Research Grant, General Electric Company
John Kurhanewicz, PhD, San Francisco, CA (Abstract Co-Author) Nothing to Disclose
PURPOSE
Liver injury and inflammation may lead to liver fibrosis, portal hypertension and cirrhosis. There is currently no method to image liver
inflammation. Hyperpolarized 13C MRI is an emerging tool for imaging metabolism. Increased conversion of [13C]pyruvate to
[13C]lactate has been observed in a mouse model of arthritis. We hypothesize that lactate production may be a marker of acute
liver injury.
METHOD AND MATERIALS
11 male CD1 mice were treated via IP injection with either 1 ul/g of the hepatotoxin CCl4 (n=6) to induce liver injury, or with
vehicle alone (n=5, control group). Mice were imaged with a 14 T preclinical MRI scanner prior to and 48 hours after treatment. 350
ul of 80mM [1-13C]pyruvic acid was polarized in a Hypersense DNP polarizer (Oxford Instruments) and injected via tail vein.
Metabolite images were obtained for pyruvate, alanine and lactate at 29 s using a fast spectrally-selective 3D imaging sequence
(resolution 2x2x3.3 mm). Metabolite images were overlayed onto T2 images. An ROI was drawn on the center liver slice avoiding
large vessels. Ratios of lactate and alanine to pyruvate were measured. Mice were sacrificed and livers stained for histology. Liver
damage graded by an experienced hepatologist blinded to the imaging.
RESULTS
Imaging was successful in all 11 mice before and after treatment. Histologic liver damage was seen in 5/6 CCl4-treated mice. Mean
lactate/pyruvate ratio was significantly higher after CCl4 treatment (2.8, SD 0.9) than for untreated mice (1.8, SD 0.6, p<0.05) or
the control group (1.7, SD 0.5, p<0.05). Mean alanine/pyruvate ratio was also significantly higher after CCl4 treatment (2.2, SD
0.6) than for untreated mice (1.3, SD 0.6, p<0.05) or the control group (1.4, SD 0.4, p<0.05). There was no significant difference
in either ratio between the pre-treatment and the control group.
CONCLUSION
Treatment of mice with a single dose of the hepatotoxin CCl4 leads to a significant and rapid rise in hepatic lactate and alanine
production measured by hyperpolarized 13C MRI. Future experiments will determine whether the observed lactate and alanine
production results from activated inflammatory cells within the liver or metabolic alterations within hepatocytes themselves.
CLINICAL RELEVANCE/APPLICATION
Hyperpolarized 13C MRI is a promising tool for non-invasively imaging evaluating liver injury and inflammation.
SSQ12-02
Synthesis and Characterization of Novel Hydrophilic Molecules for 19F-MR Contrast Imaging
Thursday, Dec. 3 10:40AM - 10:50AM Location: S504AB
Participants
Eric Tanifum, PhD, Houston, TX (Presenter) Nothing to Disclose
Matthew Liaw, Houston, TX (Abstract Co-Author) Nothing to Disclose
Robia Pautler, PhD, Houston, TX (Abstract Co-Author) Nothing to Disclose
Ananth Annapragada, PhD, Houston, TX (Abstract Co-Author) Stockholder, Marval Pharma Ltd Stockholder, Alzeca Biosciences LLC
Stockholder, Sensulin LLC Stockholder, Abbott Laboratories Stockholder, Johnson & Johnson
PURPOSE
Conventional MRI contrast agents employ paramagnetic metal ions to generate contrast in 1H MRI scans. While this approach is
Conventional MRI contrast agents employ paramagnetic metal ions to generate contrast in 1H MRI scans. While this approach is
highly sensitive, specificity and unambiguous quantification of signal is challenging and metal ion toxicity is a concern so other
alternatives are sought. 19F presents a great potential for reasons including: spectroscopic properties of 19F are similar to 1H
therefore existing 1H MRI hardware can be used for 19F MRI with minimal modifications; no endogenous 19F in soft tissue so the
potential to generate a directly quantifiable signal with high contrast-to-noise ratio. However, almost all 19F-based agents utilize
perfluorocarbons (PFCs), with several drawbacks: highly hydrophobic (limiting formulation to water emulsions) and magnetically
diverse 19Fs (result in diffuse 19F MR images). We report novel hydrophilic fluorinated molecules with magnetically equivalent 19Fs,
amenable to aqueous formulations for molecular imaging.
METHOD AND MATERIALS
Hydrophilic moieties were linked to fluorinated moieties with equivalent 19Fs, to generate water-soluble monomer units and then
condensed to dimers and oligomers with high 19F content. Structures were confirmed by NMR and MS. Liposome formulation was
achieved using standard protocols and size distribution determined by DLS. 19F content was assessed by UV-VIS and 19F NMR, and
19F MRI scans performed using a TurboRARE 3D scan in a 9.4 T Bruker instrument equipped with a 1H/19F dual-tunable volume RF
coil.
RESULTS
Molecular synthesis was achieved in excellent yields, and 1H and 19F NMR indicated purity of the final products at >97%. All
compounds dissolved readily in saline to give 500 mM to 1 M solutions used to prepare stable liposome formulations. 19F MR scans
showed that formulations are detectable at 2-5 mM concentrations of the molecules, comparable to the high micromolar to milimolar
intravoxel concentrations required for Gd contrast detection.
CONCLUSION
This is a new and facile paradigm to formulate 19F MRI contrast agents in aqueous media and their use to prepare stable liposome
formulations, a proven nanoparticle platform for both passive and active delivery of contrast for molecular imaging, highlights the
potential of this approach.
CLINICAL RELEVANCE/APPLICATION
We believe this approach will have significant impact on molecular imaging.
SSQ12-03
[¹¹C]Me@HAPTHI - A Novel PET-ligand for the Norepinephrine Transporter - Part 1: Target Affinity
and Radiosynthesis
Thursday, Dec. 3 10:50AM - 11:00AM Location: S504AB
Participants
Christina Rami-Mark, MSc, Vienna, Austria (Presenter) Nothing to Disclose
Neydher Berroteran-Infante, MSc, Vienna, Austria (Abstract Co-Author) Nothing to Disclose
Alexander Hoepping, Radeberg, Germany (Abstract Co-Author) Employee, ABX GmbH
Marcus Hacker, Vienna, Austria (Abstract Co-Author) Nothing to Disclose
Markus Mitterhauser, Vienna, Austria (Abstract Co-Author) Speaker, General Electric Company
Wolfgang Wadsak, Vienna, Austria (Abstract Co-Author) Speaker, General Electric Company; Consultant, THP Medical; Research
Grant, ABX GmbH; Research Grant, Rotem GmbH
PURPOSE
The norepinephrine transporter (NET) has been demonstrated to be relevant to a multitude of neuro-psychiatric and cardiovascular
pathologies. Due to the wide range of possible applications for PET imaging of the NET together with the limitations of currently
available radioligands, novel NET-PET tracers are seriously needed.
METHOD AND MATERIALS
Precursor, HAPTHI ((S)-1-(4-amino-3-hydroxybutyl)-3-phenyl-1,3-dihydrobenzo[c] [1,2,5]thiadiazole 2,2-dioxide), and reference
compound, Me@HAPTHI ((S)-1-(3-hydroxy-4-(methylamino)butyl)-3-phenyl-1,3-dihydrobenzo[c][1,2,5]thiadiazole 2,2-dioxide),
were custom-synthesized by ABX.For optimization of radiosynthesis conditions, small-scale reactions (< 2GBq) were performed. The
influence of various reaction conditions, i.e. reaction temperature, solvent and base, precursor concentration and radiomethylation
agent, was investigated. The automation of the N-¹¹C-methylation reaction was done on a TRACERlab FX C Pro synthesizer (GE
Healthcare).The affinity of new radiolabeled ligand was determined in a NET-expressing membrane binding protocol.
RESULTS
In the radiochemical evaluation, best results were obtained with sodium hydroxide catalysis in 2-butanone (MEK) as solvent for
2min at 75°C using 2mg/mL precursor HAPTHI. Thereby, 54.0 ± 8.3% radiochemical incorporation yield was achieved. These
optimum reaction parameters were subsequently used in the fully automated radiosynthesizer. So far, 7 large-scale radiosyntheses
were performed, yielding 2.2 ± 2.0GBq (18.9 ± 13.3%, corrected for decay) of sterile, formulated [¹¹C]Me@HAPTHI within 36min. A
mean specific activity of 46.8±28.5 GBq/µmol was found in the large-scale syntheses. Full radiopharmaceutical quality control took
5min and showed that radiochemical purity always exceeded 98%.Affinity of reference compounds, Me@HAPTHI, using human NET
membranes evinced a Kd of 0.21 ± 0.07nM (n≥9). For determination of selectivity, additionally the affinity towards human DAT and
SERT membranes were measured and revealed >10µM for DAT and 409 ± 43nM for SERT, respectively, (n≥5). Hence, selectivity of
Me@HAPTHI towards NET was determined as DAT/NET>1947.6 and SERT/NET=9757.
CONCLUSION
This study confirms an outstanding affinity and selectivity of the title compound towards human NET as well as its feasible
radiochemical preparation for further preclincal evaluations ans future in-vivo applications.
CLINICAL RELEVANCE/APPLICATION
N/A
SSQ12-04
[¹¹C]Me@HAPTHI - A Novel PET-ligand for the Norepinephrine Transporter - Part 2: Preclinical
Evaluation
Thursday, Dec. 3 11:00AM - 11:10AM Location: S504AB
Participants
Christina Rami-Mark, MSc, Vienna, Austria (Presenter) Nothing to Disclose
Wolfgang Wadsak, Vienna, Austria (Abstract Co-Author) Speaker, General Electric Company; Consultant, THP Medical; Research
Grant, ABX GmbH; Research Grant, Rotem GmbH
Cecile Philippe, PhD, Vienna, Austria (Abstract Co-Author) Nothing to Disclose
Chrysoula Vraka, MSc, Vienna, Austria (Abstract Co-Author) Nothing to Disclose
Marcus Hacker, Vienna, Austria (Abstract Co-Author) Nothing to Disclose
Markus Mitterhauser, Vienna, Austria (Abstract Co-Author) Speaker, General Electric Company
PURPOSE
The norepinephrine transporter (NET) has been demonstrated to be pivotal in many neuro-psychiatric and cardiovascular
pathologies. [¹¹C]Me@HAPTHI, a novel potential NET-PET tracer, was shown to have a high target affinity and selectivity. Hence,
further in vitro evaluation regarding blood-brain-barrier (BBB) penetration, stability and binding properties in autoradiography on
different tissues is required.
METHOD AND MATERIALS
LogD was assessed using HPLC (Donovan and Pescatore J Chrom A, 2002). Immobilized artificial membrane (IAM) chromatography
was performed using a standard method (Vraka C et al. EJNMMI, 2014) to achieve Pm (permeability) values.For evaluation of
stability, incubation with human liver microsomes was performed. Plasma protein binding was determined quantifying the free
fraction (ff) in human pooled plasma (Huang Y et al. J Cereb Blood Flow Metab, 2002). In vitro autoradiography was performed on
human brain tissue (cortex, thalamus, hippocampus, cerebellum, and hypothalamus) as well as rat heart. Non-specific binding was
determined with excess Nisoxetine (10µM). For competition, non-radioactive FMeNER-D2 and Me@HAPTHI were added. After 1h at
room temperature, incubation was stopped and slices were processed on phosphor imaging films.Post-autoradiographic processing
of the slices was done by Nissl staining in order to facilitate morphological mapping. Immunohistochemical (IHC) staining experiments
were performed on rat and human tissue cryo-slices, vicinal to the slices used for autoradiography.
RESULTS
Excellent affinity (Kd of 0.21±0.07nM) and selectivity (DAT/NET>1940; SERT/NET=9700) were already shown for [¹¹C]Me@HAPTHI.
Now, both logD (2.27±0.01) and Pm (1.15±0.25) were found to be in a range for expectable BBB penetration. After 60min
incubation with human liver microsomes, 99.6±0.3% of the tracer were still intact. ff was found to be 8.2±0.3%.In the
autoradiographic experiments, highest uptake of [¹¹C]Me@HAPTHI was observed in NET-rich regions identified with IHC and a
concentration dependent binding displacement was seen for both competitors.(see figure)
CONCLUSION
Side from its high affinity and selectivity, we now demonstrated [¹¹C]Me@HAPTHI's stability, expectable BBB penetration and
specific binding in autoradiography. This encourages us for in vivo application in small animal PET experiments and future clinical
trials.
CLINICAL RELEVANCE/APPLICATION
N/A
SSQ12-05
Multimodal Imaging of Insulin-dependent Triglyceride-rich lipoprotein Uptake into Brown Adipose
Tissue at 7T MRI and Intravital Microscopy
Thursday, Dec. 3 11:10AM - 11:20AM Location: S504AB
Participants
Caroline Jung, Hamburg, Germany (Presenter) Nothing to Disclose
Markus Heine, Hamburg, Germany (Abstract Co-Author) Nothing to Disclose
Gerhard B. Adam, MD, Hamburg, Germany (Abstract Co-Author) Nothing to Disclose
Harald Ittrich, MD, Hamburg, Germany (Abstract Co-Author) Nothing to Disclose
Jorg Heeren, Hamburg, Germany (Abstract Co-Author) Nothing to Disclose
Nils Mangels, Hamburg, Germany (Abstract Co-Author) Nothing to Disclose
PURPOSE
The aim was to determine the metabolic activity of brown adipose tissue (BAT) and its dependence on signalling pathway mediated
by the anabolic hormone insulin using superparamagnetic iron oxide nanoparticles (SPIO - for MRI) or quantum dots (QD - for
intravital microscopy (IVM)) embedded into triglyceride-rich lipoproteins (TRL).
METHOD AND MATERIALS
BAT activity of C57BL/6J wild-type was stimulated by treatment with the β3 receptor agonist CL316,243. Inhibition of insulin
secretion during the course of BAT activation was performed using the potassium channel agonist diazoxide. All mice were starved
for 4 hours before imaging. MRI at 7T ClinScan (Bruker) was performed before and 20 minutes after iv injection of TRL-SPIOs using
a T2*w Multiecho-GRE sequence (TR/TEfirst 400/2ms, ETL 12, ES 1ms, FA 25°). ΔR2* in BAT was estimated. In addition to the MRI
set up, IVM analysis was performed for real time imaging of TRL-QD uptake into BAT. In order to quantify TRL clearance, the fate of
radioactively labelled TRLs were analysed under the same experimental conditions.
RESULTS
While no signal difference in BAT before and after the injection of TRL-SPIO was detectable for control mice, a significant signal
drop and increase of ΔR2* (82.9s-1; p<0.001) was estimated for CL treated, BAT activated mice. Inhibition of insulin signalling
resulted in a significant lower uptake of TRL-SPIO into BAT (ΔR2* = 21.1s-1; p<0.001). MRI results were confirmed by IVM analyses
and by quantitative metabolic studies using radioactive lipid tracers. In both setups inhibition of insulin secretion using diazoxide
abolished TRL uptake into BAT.
CONCLUSION
β3-receptor activation via CL with following acute insulin release lead to BAT activation, which can be visualised in vivo by MRI
β3-receptor activation via CL with following acute insulin release lead to BAT activation, which can be visualised in vivo by MRI
using TRL-SPIO and estimating ΔR2*. Accordingly, the inhibition of insulin signalling blocks TRL uptake into BAT. Thus, MRI can
visualize physiological lipid processing in the vascular endothelium of activated BAT.
CLINICAL RELEVANCE/APPLICATION
MRI in combination with nanoparticle-labelled lipoproteins can be used to noninvasively monitor the molecular pathway of insulindependent lipoprotein metabolism.
SSQ12-06
Using MPI as High Temporal Resolution Imaging Technique for in Vivo Bolus Tracking of
Ferucarbotran in Mouse Model
Thursday, Dec. 3 11:20AM - 11:30AM Location: S504AB
Participants
Caroline Jung, Hamburg, Germany (Presenter) Nothing to Disclose
Johannes M. Salamon, MD, Hamburg, Germany (Abstract Co-Author) Nothing to Disclose
Martin Hofmann, Dipl Phys, Hamburg, Germany (Abstract Co-Author) Nothing to Disclose
Michael G. Kaul, Hamburg, Germany (Abstract Co-Author) Nothing to Disclose
Gerhard B. Adam, MD, Hamburg, Germany (Abstract Co-Author) Nothing to Disclose
Tobias Knopp, DIPLENG, Hamburg, Germany (Abstract Co-Author) Nothing to Disclose
Harald Ittrich, MD, Hamburg, Germany (Abstract Co-Author) Nothing to Disclose
Kolja Them, Hamburg, Germany (Abstract Co-Author) Nothing to Disclose
PURPOSE
Magnetic particle imaging (MPI) is a new radiologic imaging method, potentially capable of rapid 3D dynamic imaging of magnetic
tracer. The goal of this study was to follow and visualize the intravenous injected nanoparticles in real time through cardiovascular
system at MPI.
METHOD AND MATERIALS
MPI scans of FVB mice (n=4) were carried out using a 3D imaging sequence (1 T/m gradient strength, 10 mT drive-field strength,
FOV 40x40x20 mm3). After a first baseline control measurement a dynamic scan consisting of 100 000 repetitions (duration of about
35min and temporal resolution of 21.5ms per 3D volume) was performed. After the 13953th repetition 50µl ferucarbotran (Resovist,
Bayer Schering Pharma AG) was injected into the tailvein via pump (53.7ml/h). As MPI delivers no anatomic information, MRI scans
at 7T ClinScan (Bruker) were performed before and after MPI examination using a T2-weighted 2D turbo spin echo sequence (FOV
32mm, matrix 256x256, TR 1100ms, TE 28ms). The reconstruction was performed on the MPI console (ParaVision 6.0/MPI, Bruker).
Image fusion was done using additional image processing software (Imalytics, Philips). The dynamic information was extracted using
self-written software using the Julia programming environment.
RESULTS
The combined MR-MPI measurements were carried out successfully. No dislocation of the mouse was observed. In the sagittal
views it is clearly visible how the tracer enters the vena cava inferior before it moves to the heart and then into the liver. (Fig. 1
shows different time points over a range of 1.5 s). By co-registration with MRI the anatomical regions were identified. Due to the
frame rate of about 46 volumes per second a signal modulation with the frequency of the heart beat is detectable and a heart beat
of 520bpm can be appreciated. Moreover the bloodflow velocity of approximately 5cm/s in the vena cava can be estimated.
CONCLUSION
The high temporal resolution of MPI allows real-time imaging and bolus tracking of intravenous injected nanoparticles and offers a
tool to estimate blood flow velocity. MRI was successful used for anatomical informations.
CLINICAL RELEVANCE/APPLICATION
Blood flow velocity measurements by MPI may allow the estimation of luminal narrowing in atherosclerotic disease.
SSQ12-07
In Vivo Noninvasive Characterization of Brown Adipose Tissue in Rat by Spectral CT
Thursday, Dec. 3 11:30AM - 11:40AM Location: S504AB
Awards
Molecular Imaging Travel Award
Participants
Xin-Gui Peng, MD,PhD, Nanjing, China (Presenter) Nothing to Disclose
Zhen Zhao, Nanjing, China (Abstract Co-Author) Nothing to Disclose
Di Chang, Nanjing, China (Abstract Co-Author) Nothing to Disclose
Shenghong Ju, MD, PhD, Nanjing, China (Abstract Co-Author) Nothing to Disclose
PURPOSE
Brown adipose tissue (BAT) has lower lipid content, more abundant iron content and mitochondrion campared to white adipose
tissue (WAT). Our study is to evaluate the lipid/water and iron/water content in both types of adipose tissure using material
decomposition and effective atomic number of spectral CT.
METHOD AND MATERIALS
The animal study was approved by the institutional Committee on Animal Research. Six Wistar rats (14 weeks, 304g ±12g)
underwent Spectral CT scan (GE, Discovery CT750 HD). Data were transmitted to AW4.6 workstation to obtain base material
mappings, including fat (water) based imaging and iron (water) based imaging. The fat/water and iron/water concertraction of
brown adipose tissue (interscapular) and white adipose tissue (visceral) were measured on base material mapping. In addition, we
also calculate the effective atomic number of both types of adiopse tissue. Statistical analysis was performed with independent
sample t test.
RESULTS
The base fat (water) material concentration of BAT was significantly lower than that of WAT (587.29 ± 187.61mg/cm3 and 1587.43
± 70.11mg/cm3, respectively; P< 0.001). However, the water (fat) concentration of BAT was significantly higher than that of WAT
(395.81±189.53mg/cm3, and -655.1 ± -69.141mg/cm3, respectively; P<0.001). The based iron (water) material concentration of
BAT was significantly higher compared to WAT (-4.92±1.80mg/cm3 and -13.80 ± 0.36mg/cm3, respectively; P<0.001). Water (iron)
concentration of BAT was also higher than that of WAT (989.33±7.29mg/cm3 and 951.63±-5.49mg/cm3, respectively; P<0.001).
The effective atomic number of BAT was significant higher than that of WAT (6.95±0.28 and 4.7±0.11, respectively; P< 0.001).
CONCLUSION
The quantification of base material concentration and effective atomic number analysis of spectral CT revealed different
characterization of both types of adipose tissue.
CLINICAL RELEVANCE/APPLICATION
It is anticipated that spectral CT provided a new noninvasive method to be translated to a clinical setting for evaluating the
difference of adipose tissue and monitoring the responses to specific therapeutic strategies.
SSQ12-08
Does Iterative CT Reconstruction for Attenuation Correction Impact PET Images? A Qualitative and
Quantitative Assessment for Next-Generation Digital Detector PET/CT
Thursday, Dec. 3 11:40AM - 11:50AM Location: S504AB
Awards
Molecular Imaging Travel Award
Participants
Katherine Binzel, PhD, Columbus, OH (Presenter) Nothing to Disclose
Jun Zhang, PhD, Columbus, OH (Abstract Co-Author) Nothing to Disclose
Philip Bardos, Columbus, OH (Abstract Co-Author) Nothing to Disclose
Veena A. Nagar, MD, Dublin, OH (Abstract Co-Author) Nothing to Disclose
Michael V. Knopp, MD, PhD, Columbus, OH (Abstract Co-Author) Nothing to Disclose
PURPOSE
Implementation of iterative CT reconstruction (ICR) allows for significant dose reduction while generating equivalent visual quality
to conventional CT doses. In this study we determine if there is any quantitative impact of using ultra-low dose ICR for attenuation
correction of PET data, compared to filtered back projection (FBP).
METHOD AND MATERIALS
Clinical patients received 13 mCi FDG prior to imaging on the Vereos TF 64 PET/CT (Philips). Attenuation CTs were performed using
120 kV and 50 mAs for the PET imaging volume, skull to mid-thighs. PET images were reconstructed in two different modes,
standard CT FBP and iDose4 ICR. The PET images were visually and quantitatively evaluated in a blinded fashion. The quantitative
assessment focused on ROI assessment in target lesions in patients and background tissues.
RESULTS
A total of 30 datasets from 15 patients were evaluated. On visual assessment of the PET images benefits from the use of ICR for
attenuation correction were apparent with markedly reduced impact from streaking artifacts. The quantitative analysis revealed
that the overall SUVmax of PET images with iteratively reconstructed attenuation CTs was 0.5% higher for all tissue types [nonsignificant difference]. In target lesions the percent difference ranged from 0.5% to 1.4% increased SUVmax's over SUVmax's
determined from PET images with FBP CT, none having any lower values.
CONCLUSION
Iterative CT reconstruction enables significant reduction of the x-ray dose required to obtain attenuation correction images for
PET. This study validates that there is no impact on the quantitative readout compared to FBP reconstructed attenuation CTs. The
visual appearance of the PET images appeared to be improved at locations where streaking artifacts were visible on FBP
reconstructed CTs. Iterative reconstructed CTs can and should be used on next-generation PET/CT systems.
CLINICAL RELEVANCE/APPLICATION
Iterative CT reconstruction enables significant reduction of the x-ray dose required to obtain attenuation correction images for
PET, while simultaneously improving the appearance of image artifacts.
SSQ12-09
Generalized Syntheses of Tumor Targeted Yolk/Shell Structured Multifunctional Nanosystems
Thursday, Dec. 3 11:50AM - 12:00PM Location: S504AB
Awards
Molecular Imaging Travel Award
Participants
Christopher England, PhD, Madison, WI (Presenter) Nothing to Disclose
Feng Chen, PhD, Madison, WI (Abstract Co-Author) Nothing to Disclose
Hao Hong, PhD, Madison, WI (Abstract Co-Author) Nothing to Disclose
Shreya Goel, Madison, WI (Abstract Co-Author) Nothing to Disclose
Stephen Graves, Madison, WI (Abstract Co-Author) Nothing to Disclose
Todd Barnhart, Madison, WI (Abstract Co-Author) Nothing to Disclose
Weibo Cai, PhD, Palo Alto, CA (Abstract Co-Author) Nothing to Disclose
PURPOSE
The purpose of this work is to develop a generally applicable protocol for synthesizing yolk/shell structured multifunctional
nanosystems to be used for tumor targeted PET image-guided drug delivery.
METHOD AND MATERIALS
Upconversion nanoparticle (UCNP, with NIR-in-NIR-out upconversion luminescence) was used as the initial example. UCNP was first
coated with a dense silica (dSiO2) shell, forming UCNP@dSiO2, followed by re-growth of a shell-thickness controllable mesoporous
silica nanoshell (MSN) to form UCNP@dSiO2@MSN. A Na2CO3 etching protocol was used to selectively etch away dSiO2, leaving
behind yolk/shell structured nanoparticles denoted as UCNP@HMSN. A step-by-step surface engineering process was then adopted
to conjugate (or label) NOTA, polyethylene glycol (PEG) linkers, TRC105 (an anti-CD105 antibody), and 64Cu to form 64CuUCNP@HMSN-PEG- TRC105. Both hydrophobic (i.e. Sunitinib) and hydrophilic (i.e. Doxorubicin) drugs could be loaded inside
UCNP@HMSN. Systematic in vivo PET imaging and biodistribution studies were performed in 4T1 tumor-bearing mice to evaluate and
confirm tumor targeting capability, validated by in vitro/ex vivo studies.
RESULTS
TEM confirmed successful synthesis of UCNP@HMSN. By changing the 'yolk' to superparamagnetic iron oxide nanoparticle (SPION) or
quantum dot (QD), we confirmed the general applicability of this protocol. In vitro CD105 targeting in HUVEC (CD105+) and MCF-7
(CD105-) cells showed strong/specific binding of FITC-conjugated UCNP@HMSN-PEG-TRC105 to CD105+ cells with negligible nonspecific binding. In vivo tumor targeting and PET imaging demonstrated CD105-specific targeting of 64Cu-UCNP@HMSN-PEG-TRC105
in 4T1 tumor-bearing mice, with peak tumor uptake of ~6.5 %ID/g at 6 h post-injection. CD105 specificity was confirmed by
blocking and ex vivo histology studies.
CONCLUSION
This work demonstrates the feasibility of developing targeted yolk/shell structured nanosystems for in vivo imaging. With UCNP, QD,
SPION, or other nanocrystals inside each yolk/shell structure, this nanoplatform is highly versatile for future tumor targeted
multimodality image-guided drug delivery.
CLINICAL RELEVANCE/APPLICATION
We report the generalized syntheses of yolk/shell structured nanosystems for tumor targeted PET imaging and drug delivery, with
potential future applications as theranostic agents for the concurrent imaging and treatment of cancer.
MIS-THA
Molecular Imaging Thursday Poster Discussions
Thursday, Dec. 3 12:15PM - 12:45PM Location: S503AB
MI
AMA PRA Category 1 Credit ™: .50
FDA
Discussions may include off-label uses.
Participants
Umar Mahmood, MD, PhD, Charlestown, MA (Moderator) Research Grant, Sabik Medical Inc; Advisory Board, Blue Earth Diagnostics
Limited;
Sub-Events
MI231-SDTHA1
Imaging Epigenetic Changes in Cancer - Preliminary Experience with [18F]-FAHA for Tumor Histone
Deacetylase Activity
Station #1
Participants
Fiona Li, BSC, London, ON (Presenter) Nothing to Disclose
James Koropatnick, London, ON (Abstract Co-Author) Nothing to Disclose
Robert Hudson, London, ON (Abstract Co-Author) Nothing to Disclose
Sung Ju Cho, London, ON (Abstract Co-Author) Nothing to Disclose
Lihai Yu, London, ON (Abstract Co-Author) Nothing to Disclose
Ting-Yim Lee, MSc, PhD, London, ON (Abstract Co-Author) Research Grant, General Electric Company Royalties, General Electric
Company
Leonard Luyt, London, ON (Abstract Co-Author) Nothing to Disclose
Christopher Pin, London, ON (Abstract Co-Author) Nothing to Disclose
Michael Kovacs, London, ON (Abstract Co-Author) Nothing to Disclose
Adam R. Blais, MSc, London, ON (Abstract Co-Author) Nothing to Disclose
Errol E. Stewart, PhD, London, ON (Abstract Co-Author) Nothing to Disclose
Jennifer Hadway, London, ON (Abstract Co-Author) Nothing to Disclose
Laura Morrison, London, ON (Abstract Co-Author) Nothing to Disclose
PURPOSE
Alteration in genetic expression is as important as gene mutations in cancer development and proliferation. Epigenetic changes
comprise modifications in genetic expression without changes in DNA sequences. Histone deacetylase (HDAC) a key facilitator of
epigenetic changes, has been shown to silence tumor suppressor genes. As such, HDAC is a current therapeutic target in cancer
treatment. We have synthesized a novel PET tracer, 18F- fluoroacetamido-1-hexanoicanilide (18F-FAHA), an HDAC substrate for
the imaging of HDAC activity in animal cancer model.
METHOD AND MATERIALS
7 nude mice bearing MDA-MB-468 tumor xenografts, known to overexpress HDAC, on both side of the chest or flanks of the body
were studied. When the size of the xenografts was palpable (~ 5-10 mm), 9-14 MBq of 18F-FAHA was injected via a tail vein and
dynamic PET scanning with image intervals ranging from 10 s to 5 min was done for 1 hour with a small animal PET scanner (GE
Healthcare/Sedecal). Time-activity curves from the left ventricle and the tumor were analyzed with a 3- compartment kinetics
model to estimate the tumor blood volume (BV) and the 18F-FAHA binding rate constant (k3), a surrogate for HDAC activity.
RESULTS
18F-FAHA was avidly taken up by the tumors with peak uptake at ~ 30 min post injection. The mean BV and k3 estimated using 3compartment analysis were BV= 5.37 mL/100g and 4.5 mL/100g and k3 = 0.035 min-1 and 0.047 min-1 for the left and right tumor
respectively. The k3 values showed wide range of values from 0.0042 min-1 to 0.16 min-1. K1 (influx rate), k2 (efflux rate), and k4
(dissociation rate constant from HDAC) also showed great variability both between and within mice. Averaging over left and right
tumors in all mice, K1, k2 and k4 were 0.19 mL/min/g, 0.32 min-1 and 0.03 min-1 respectively.
CONCLUSION
This study showed that PET imaging can be used to image HDAC activity with the synthesized 18F-FAHA tracer. Quantitative
analysis with a 3-compartment kinetics model allows HDAC activity to be assessed as the binding rate constant of the probe. This
quantitative assessment showed high inter- and intra-subject variability in k3 values (see Figure) or HDAC activity in a uniform
tumor model.
CLINICAL RELEVANCE/APPLICATION
With the ability to determine the intra- and inter-subject variability in HDAC activity using PET imaging, treatment protocols
targeting HDAC can be individualized without the need of biopsies.
MI232-SDTHA2
Magnetic Particle Imaging with Labeled Tumor Cells: Proof of Principal Study in a Murine Small Cell
Lung Cancer Model
Station #2
Participants
Stefan M. Herz, MD, Wuerzburg, Germany (Presenter) Nothing to Disclose
Patrick Vogel, Wurzburg, Germany (Abstract Co-Author) Nothing to Disclose
Christian Brede, Wuerzburg, Germany (Abstract Co-Author) Nothing to Disclose
Martin A. Ruckert, Wurzburg, Germany (Abstract Co-Author) Nothing to Disclose
Thomas Kampf, Wurzburg, Germany (Abstract Co-Author) Nothing to Disclose
Simon Veldhoen, MD, Wurzburg, Germany (Abstract Co-Author) Nothing to Disclose
Peter M. Jakob, PhD, Wuerzburg, Germany (Abstract Co-Author) Nothing to Disclose
Volker C. Behr, Wurzburg, Germany (Abstract Co-Author) Nothing to Disclose
Andreas Beilhack, Wuerzburg, Germany (Abstract Co-Author) Nothing to Disclose
Thorsten A. Bley, MD, Hamburg, Germany (Abstract Co-Author) Nothing to Disclose
Andreas Brandl, Wurzburg, Germany (Abstract Co-Author) Nothing to Disclose
PURPOSE
To investigate the feasibility of visualizing labeled tumor cells with whole-body magnetic particle imaging (MPI) in a clinically
relevant murine lung cancer model. MPI, a new functional imaging tool, was used to detect small cell carcinoma cells labeled with
superparamagnetic iron oxide nanoparticles (SPIOs).
METHOD AND MATERIALS
Small cell lung cancer was induced by transplanting luciferase-expressing human DMS 273 FUGLW cells into immunodeficient NOD
SCID mice. DMS 273 FUGLW cells were plated for 24h (1 x 10^6/well) and subsequently incubated for 24h with SPIOs (40μl:100μg
Fe). Cells were then injected via the tail vein and MPI/MRI were performed 24h after the injection. In-vivo bioluminescence imaging
(BLI) served as reference standard. Using the same holder for both devices ensured identical positioning of mice in MPI and MRI.
MPI was performed with a homemade traveling wave MPI scanner (gradient: 4T/m, bore: 29 mm). MR images were acquired with a
7T scanner (60 mm horizontal bore). A 3D T2-weighted rapid acquisition with refocused echoes (RARE) sequence provided
anatomical background. MPI and MRI data were reconstructed and fused manually. Prussian blue staining was used for histological
analysis of the SPIO distribution.
RESULTS
MPI proofed sensitive to visualize in-vitro labeled tumor cells in a murine small cell lung cancer model. BLI and MPI detected high
signal in the lungs indicating the presence of DMS 273 FUGLW cells. Other organs displayed baseline signal only. Histologic analysis
of the distribution of SPIOs showed that labeled cells were located in the lung parenchyma. Control organs such as liver and heart
did not accumulate any SPIOs.
CONCLUSION
These initial results indicate that MPI is a feasible tool to assess the distribution of labeled tumor cells in clinically relevant murine
models such as small cell lung cancer. Further technical advances concerning MPI scanner resolution and SPIO biocompatibility are
necessary to transfer this technique from preclinical animal models to human imaging.
CLINICAL RELEVANCE/APPLICATION
Magnetic particle imaging is a promising biotechnical approach with the potential to provide radiation-free molecular imaging in
humans.
MI233-SDTHA3
Tumor Heterogeneity Measured on Pre-treatment PET/CT Predicts Overall Survival in Patients with
Anal Squamous Cell Carcinoma
Station #3
Participants
Asim Afaq, FRCR, London, United Kingdom (Abstract Co-Author) Nothing to Disclose
Balaji Ganeshan, PhD, London, United Kingdom (Presenter) Scientific Director, TexRAD Limited
Tal Grenader, London, United Kingdom (Abstract Co-Author) Nothing to Disclose
Gabrielle Azzopardi, London, United Kingdom (Abstract Co-Author) Nothing to Disclose
Raymondo Endozo, London, United Kingdom (Abstract Co-Author) Nothing to Disclose
John Bridgewater, London, United Kingdom (Abstract Co-Author) Nothing to Disclose
Ashley M. Groves, MBBS, Hitchin, United Kingdom (Abstract Co-Author) Investigator, GlaxoSmithKline plc; Investigator, General
Electric Company; Investigator, Siemens AG; ; ;
PURPOSE
There is a lack of established prognostic factors in anal cancer, with nodal stage and male sex being the most consistently
reported. The NCCN guidelines now indicate PET/CT should be considered for the work up of newly diagnosed anal squamous cell
carcinoma (SCC). We proposed imaging biomarkers from PET/CT, including FDG uptake on PET (glucose metabolism) and CT texture
analysis (CTTA which assesses intratumoral heterogeneity) may provide prognostic information in patients treated with
chemoradiotherapy (CRT) for anal SCC.
METHOD AND MATERIALS
46 patients (median age 60.7 years, range 36.8-80.2; 22 males; with anal SCC, who received CRT for anal SCC at our centre
between 2007-2013 and had pre-treatment PET/CT were identified retrospectively from our institutional database. On PET/CT, the
unenhanced low-dose CT image slice with largest tumor diameter was selected for CTTA using proprietary commercial research
software called TexRAD (TexRAD Ltd, part of Feedback Plc - www.texrad.com). CTTA used a filtration-histogram technique where
initial filtration extracted fine, medium and coarse texture features (spatial scale filters - SSF = 2mm, 3-5mm, and 6mm radius,
respectively) and was followed by quantification of standard-deviation (SD, quantifies degree of heterogeneity). Tumor
standardized uptake value (SUVmax) was measured on OSIRIX to indicate glucose metabolism. Mean follow-up period was 44.3
months. Kaplan-Meier analysis assessed the relationships between CTTA and clinical parameters against overall survival (OS)
RESULTS
Mean OS was 110.6 (95% CI: 97.2-124.0) months. Clinical parameters associated with a worse OS included positive nodes on
staging (p=0.002) and male sex (p=0.040). Higher PET SUVmax of the tumor showed a trend towards worse OS but did not reach
significance (p=0.170). Higher pre-treatment CTTA SD value was consistently a significant predictor of OS across fine to coarse
texture features (best at medium-scale for SSF=4mm, p=0.005).
CONCLUSION
This study identified SD, as a marker of tumor heterogeneity on pre-treatment CTTA (part of PET/CT), was associated with poorer
OS. A greater SD indicated greater intratumoral heterogeneity, which in turn was consistently associated with poorer survival.
CLINICAL RELEVANCE/APPLICATION
CTTA has the potential to be a prognostic imaging biomarker in patients with anal cancer undergoing treatment with CRT.
MI234-SDTHA4
Chelator-Free 89Zr-Labeling of Mesoporous Silica Nanoparticles with Superb in Vivo Radiostability
Station #4
Participants
Christopher England, PhD, Madison, WI (Presenter) Nothing to Disclose
Feng Chen, PhD, Madison, WI (Abstract Co-Author) Nothing to Disclose
Shreya Goel, Madison, WI (Abstract Co-Author) Nothing to Disclose
Hector Valdovinos, MS, Madison, WI (Abstract Co-Author) Nothing to Disclose
Sixiang Shi, MS, Madison, WI (Abstract Co-Author) Nothing to Disclose
Todd Barnhart, Madison, WI (Abstract Co-Author) Nothing to Disclose
Weibo Cai, PhD, Palo Alto, CA (Abstract Co-Author) Nothing to Disclose
PURPOSE
The purpose of this study is to demonstrate that 89Zr (t1/2=78.4 h) can be labeled to mesoporous silica nanoparticles (MSN) with
superb in vivo stability in a chelator-free manner.
CONCLUSION
We report the first example of chelator-free 89Zr-labeled MSN, with superb radiostability in vivo. With the long half life of 89Zr and
high potential of MSN for molecular imaging and drug delivery, this method offers a novel, simple, and accurate way for future PET
image-guided drug delivery.
CLINICAL RELEVANCE/APPLICATION
Chelator-free labeling of imaging agents offers a simplified conjugation approach for the development of novel molecular imaging and
drug delivery agents for future clinical applications.
MIS-THB
Molecular Imaging Thursday Poster Discussions
Thursday, Dec. 3 12:45PM - 1:15PM Location: S503AB
MI
AMA PRA Category 1 Credit ™: .50
Participants
Umar Mahmood, MD, PhD, Charlestown, MA (Moderator) Research Grant, Sabik Medical Inc; Advisory Board, Blue Earth Diagnostics
Limited;
Sub-Events
MI235-SDTHB1
Reliablity of PET-CT SUVmax Ratios in the Differentiation of Benign versus Malignant Neurogenic
Tumors in NF1 Patients
Station #1
Participants
Andrew T. Muskara, Cleveland, OH (Presenter) Nothing to Disclose
Murali Sundaram, MD, Cleveland, OH (Abstract Co-Author) Nothing to Disclose
Shetal N. Shah, MD, Broadview Heights, OH (Abstract Co-Author) Nothing to Disclose
Hakan Ilaslan, MD, Pepper Pike, OH (Abstract Co-Author) Nothing to Disclose
PURPOSE
PET-CT has been shown to be a sensitive imaging modality in the diagnosis of malignant peripheral nerve sheath tumors(MPNSTs),
although an overlap of standard uptake values(SUV) exist between neurofibromas and MPNSTs. We demonstrate the value of SUV
max ratios over absolute SUV max values in distinguishing neurofibromas and malignant peripheral nerve sheath tumors(MPNST) in
NF1 patients with PET-CT examinations.
METHOD AND MATERIALS
After obtaining IRB approval a retrospective database search was performed for patients with known NF1 who had PET-CT
examinations in our institution between 5/2007-12/2013. Patients who had neurogenic tumors without the known diagnosis of NF1
were excluded. Patients were divided into 2 groups: NF1 patients with biopsy proven MPNST and NF1 patients without known
MPNST(control group). SUV max values were measured on a dedicated PACS workstation. Two lesions with highest SUV max were
recorded in each patient. Percentage difference between the highest max SUV lesions were calculated(MPNST vs neurofibroma ).
For control group, differences between 2 highest SUV max neurofibromas were calculated.
RESULTS
Sixteen patients formed the study group; seven males and nine females. The patient ages ranged from 7 to 64 years old( average
of 30). There were 7 patients with a diagnosis of malignant peripheral nerve sheath tumors(MPNSTs), and 9 had neurofibromas only.
MPNST SUV max were found to be the highest in all of our patients(100%). MPNST SUV max were variable ranging from 3.9 to
12.7(average 6.2) whereas neurofibromas measured lower ranging from 1.7 to 6.6(average 3.1). The SUV max differences between
MPNSTs and the highest SUV neurofibromas ranged from 52% to 350% (average 163%). In control group(neurofibroma), ratio
difference was smaller ranging from 7 to 31%(average 17%).
CONCLUSION
Differential SUV max ratios between two of the highest SUV max lesions appears to be more reliable than SUV max alone in
diagnosing MPNSTs in patients with known NF1 and multiple neurogenic lesions.
CLINICAL RELEVANCE/APPLICATION
When evaluating an NF1 patient with PET-CT examination for possible MPNST diagnosis, differential SUV max between lesion in
question and second highest SUV max lesion should be made. Ratio of more than 50% is highly suggestive of an MPNST.
MI236-SDTHB2
Assessment of Bevacizumab Resistance Related with Expression of Branched-chain Amino Acid
Transaminase-1 in Isocitrate Dehydrogenase-1 Wild-type Glioblastoma: Application of DSC MR
Imaging
Station #2
Participants
Seung Hong Choi, MD, PhD, Seoul, Korea, Republic Of (Presenter) Nothing to Disclose
Hye Rim Cho, Seoul, Korea, Republic Of (Abstract Co-Author) Nothing to Disclose
PURPOSE
To investigate the bevacizumab resistance related with expression of branched-chain amino acid transaminase 1(BCAT1) in
isocitrate dehydrogenase-1 (IDH1) wild-type (wt) glioblastoma (GBM) in a rat model, which was evaluated by using DSC MR
perfusion, and to correlate the expression level of BCAT1 with cerebral blood volume (CBV) in GBM patients.
METHOD AND MATERIALS
This study was approved by the animal care committee for animal study and the institutional review board for human study at our
institute. We established IDH1 wt expressing U87 human GBM cell line with or without BCAT1 knockdown (IDH1 wt + BCAT1 shRNA,
and IDH1 wt, respectively), and confirmed the BCAT1 knockdown by western blot. For in vivo animal study, U87 cells were
implanted intracerebrally in athymic nude rats; IDH1 wt (n = 6) and IDH1 wt + BCAT1 shRNA (n = 6). All 12 rats underwent pretreatment DSC-MRI 14 days after tumor implantation using 9.4T MRI, and then received bevacizumab (20 mg/kg) twice for a week.
Then, the brain was isolated for histological analysis after post-treatment DSC-MRI. In terms of GBM patients (n = 26), the
expression level of BCAT1 was correlated with CBV from pre-operative DSC MRI.
RESULTS
BCAT1 suppression inhibits cell proliferation and limits cell migration potential in vitro. In vivo MR study, tumor size of the IDH1 wt
tumors (82.52 ± 36.91 mm3) were significantly increased than those with BCAT1 knockdown (6.47 ± 82.52 mm3) (P ≤ 0.05). The
CBV ratio between before and after bevacizumab treatment shows IDH1 wt tumors were significantly higher compare with those
with BCAT1 knockdown (210.29 ± 181.05 % vs 70.15 ± 32.30 %, P ≤ 0.05). In histological analysis, micro vessels reformation by
bevacizumab resistance were observed more in IDH1 wt tumors than those with BCAT1 knockdown. The expression level of BCAT1
was correlated with CBV in GBM patients (r = 0.7025, P = 0.0001).
CONCLUSION
BCAT1 expression in IDH1 wt GBM is related with the bevacizumab resistance, which could be assessed by DSC MRI. This study
shows that CBV can be a surrogate imaging biomarker for the prediction of antiangiogenic treatment in GBM.
CLINICAL RELEVANCE/APPLICATION
DSC MRI can be used for the treatment response prediction in GBM patients, especially for the resistance related with BCAT1
expression level.
MI237-SDTHB3
MR Imaging Genomics of Cholangiocarcinoma: Comparison of Imaging Characteristics of IDH1mutant versus Wild-type Tumors
Station #3
Participants
Cinthia Cruz, MD, Boston, MA (Presenter) Nothing to Disclose
Dushyant V. Sahani, MD, Boston, MA (Abstract Co-Author) Research Grant, General Electric Company; Research Consultant, Allena
Pharmaceuticals, Inc
Lipika Goyal, MD, Boston, MA (Abstract Co-Author) Nothing to Disclose
Sheela Agarwal, MD, MS, Boston, MA (Abstract Co-Author) Subsequent to the conduct of this research, speaker has become an
employee of Bayer HC.
PURPOSE
IDH1 is a recent described common mutation found among cholangiocarcinoma, and is associated with increased risk of metastases.
Specific imaging characteristics have been found in IDH1-mutant glioblastoma; the purpose of this study is to evaluate for MR
imaging characteristics that may differentiate tumors based on mutational status.
METHOD AND MATERIALS
Retrospective study of 16 patients diagnosed with cholangiocaricnoma between 2012 and 2015, who had a baseline liver MRI
performed with and without gadolinium contrast and SNPshot genetic testing. MR imaging was obtained during arterial and portalvenous phase, and delay of 4 minutes for gadopentetic acid-enhanced MRI and delay of 20 minutes for gadoxetic-enhanced MRI.
During each phase, signal intensities were measured for the lesion and liver, and were normalized by paraspinal musculature. Arterial
enhancement was measured in the region of the lesion with the highest signal intensity, excluding central areas of necrosis. Signal
intensity on T2 FSE images and pattern of enhancement were qualitatively evaluated by one blinded reader.
RESULTS
9 patients were found to have tumors demonstrating IDH1-wildtype and 7 demonstrating IDH1-mutant. 10 had MRI examinations
with gadoxetic-acid as well as gadopentatic-acid; six only had MRI exams with one agent or the other. Wild-type tumors were
found to have greater arterial enhancement compared to mutant tumors, although statistical significance was not met (p=0.08).
Mutant tumors had a statistically significant higher lesion-to-liver contrast ratio on hepatobiliary phase (p=0.03).
CONCLUSION
IDH1 wild-type tumors demonstrated increased relatively higher arterial enhancement, and relative hypointensity on hepatobiliary
phase imaging, compared to IDH1 mutant cholangiocarcinoma.
CLINICAL RELEVANCE/APPLICATION
Clinical Relevance: MRI, particularly hepatobiliary phase imaging, may serve as a potential imaging biomarker for genetic profiling and
guided therapies of cholangiocarcinoma.
Honored Educators
Presenters or authors on this event have been recognized as RSNA Honored Educators for participating in multiple qualifying
educational activities. Honored Educators are invested in furthering the profession of radiology by delivering high-quality
educational content in their field of study. Learn how you can become an honored educator by visiting the website at:
https://www.rsna.org/Honored-Educator-Award/
Dushyant V. Sahani, MD - 2012 Honored Educator
Dushyant V. Sahani, MD - 2015 Honored Educator
SPSH52
Hot Topic Session: Molecular Neuroimaging in Dementia: State-of-the-Art and Emerging Techniques
Thursday, Dec. 3 3:00PM - 4:00PM Location: E350
NR
BQ
MI
MR
AMA PRA Category 1 Credit ™: 1.00
ARRT Category A+ Credit: 1.00
FDA
Discussions may include off-label uses.
Participants
Satoshi Minoshima, MD, PhD, Salt Lake City, UT (Moderator) Royalties, General Electric Company; Consultant, Hamamatsu
Photonics KK; Research Grant, Hitachi, Ltd; Research Grant, Nihon Medi-Physics Co, Ltd; Research Grant, Astellas Group; Research
Grant, Seattle Genetics, Inc;
Alexander Drzezga, MD, Cologne, Germany (Moderator) Research Grant, Eli Lilly and Company; Speakers Bureau, Siemens AG;
Speakers Bureau, General Electric Company; Speakers Bureau, Piramal Enterprises Limited; Research Consultant, Eli Lilly and
Company; Research Consultant, Piramal Enterprises Limited; ; ; ; ; ;
Sub-Events
SPSH52A
Potential of Amyloid Imaging versus MRI in the Diagnostic Workup of Dementia
Participants
Clifford R. Jack JR, MD, Rochester, MN (Presenter) Stockholder, Johnson & Johnson; Research Consultant, Eli Lilly and Company; ;
LEARNING OBJECTIVES
1) Explain the utility of structural MRI and amyloid PET in characterizing the pattern of neurodegeneration and pathologic
involvement in dementia syndromes. 2) Identify the advanced MRI techniques that provide information on disease pathophysiology
in dementia. 3) Discuss cases for which MRI and amyloid PET would provide critical information for clinical assessment.
ABSTRACT
Development of molecular imaging agents for fibrillar β-amyloid (Aβ) positron emission tomography (PET), brought molecular imaging
of Alzheimer's disease (AD) pathology into the spotlight. Large cohort studies with longitudinal follow-up in cognitively normal, mild
cognitive impairment and AD patients indicate that Aβ deposition can be detected many years, even decades before the onset of
symptoms with molecular imaging and its progression can be followed longitudinally. The role of molecular imaging in AD clinical trials
is growing rapidly especially in an era when preventive interventions are designed towards eradicating the pathology targeted by
molecular imaging agents. The utility of Aβ PET in differential diagnosis of AD is greatest when there is no pathologic overlap
between the two dementia syndromes such as in frontotemporal lobar degeneration and AD. However Aβ PET alone may be
insufficient in distinguishing dementia syndromes that commonly have overlapping Aβ pathology, such as dementia with Lewy bodies
and vascular dementia, which represent the two most common dementia pathologies after AD. MRI is recommended during the initial
evaluation of dementia, in order to determine potentially treatable causes such as tumors, subdural hematoma or normal pressure
hydrocephalus. In addition, presence and extent of cerebrovascular disease, which may contribute to cognitive impairment and
dementia, can be determined during this initial MRI evaluation. Pattern of structural MRI changes reflect neurodegenerative
pathology and are closely associated with the clinical disease severity in AD. Although Aβ deposition is the most common pathologic
process observed in dementia patients, other pathologic processes such as loss of neuronal integrity and connectivity can be
measured with the advanced MRI techniques and complement Aβ PET.
URL
SPSH52B
Imaging Inflammation and Molecular Pathology in Dementia
Participants
Ana M. Catafau, MD, PhD, Barcelona, Spain, ([email protected]) (Presenter) Employee, Piramal Imaging GmbH
LEARNING OBJECTIVES
1) Explain potential clinical applications of different molecular pathology PET tracers. 2) List different targets for neuroinflammation
PET imaging. 3) Describe advantages and disadvantages of different PET targets for neuroinflammation imaging. 4) Identify
challenges for the development of molecular pathology tracers for neurodegenerative disorders.
ABSTRACT
Clinical classifications of neurodegenerative disorders are often based on neuropathology. The term „proteinopathies" includes
disorders that have in common abnormal proteins as a hallmark, e.g. amyloidoses, tauopathies, synucleopathies, ubiquitinopathies.
Different proteins can also co-exist in the same disease. To further complicate the pathophysiology scenario, not only different
proteins, but also cells are believed to play an active role in neurodegeneration, in particular those participating in
neuroinflammatory processes in the brain, such as activated microglia and astrocytes. In clinical practice, differentiating
pathophysiology from clinical symptoms to allow accurate clinical classification of these disorders during life, becomes difficult in
absence of biomarkers for these pathology hallmarks. PET imaging can be a useful tool in this context. Using PET tracers targeting
misfolded proteins it will be possible to identify the presence or absence of the target, to depict the cerebral distribution and to
quantify the protein load in different cerebral regions, as well as to monitor changes over time. Beta-amyloid is one of the proteins
involved in neurodegenerative disorders, which is currently suitable to be imaged by means of PET. Research efforts are currently
ongoing in order to identify new PET tracers targeting non-amyloid PET tracers for neurodegeneration. This presentation will focus
on the investigational PET tracers targeting tau and alpha-synuclein as misfolded proteins, and activated microglia and astrocytes
as cellular targets for neuroinflammation.
URL
SPSH52C
Tau Imaging. Scientific Tool or Diagnostic Biomarker?
Participants
Jonathan E. McConathy, MD, PhD, Saint Louis, MO (Presenter) Research Consultant, Eli Lilly and Company; Research Consultant,
Blue Earth Diagnostics Ltd; Research Consultant, Siemens AG; Research support, GlaxoSmithKline plc
LEARNING OBJECTIVES
1) Participants will be familiar with the current status of PET tracers targeting tau that are being used in human research studies
and understand their potential roles in therapeutic trials and clinical neuroimaging.
ABSTRACT
Imaging biomarkers for Alzheimer's disease (AD) and other neurodegenerative diseases are playing an increasingly important role in
both research and patient care. Abnormal deposition of the tau and beta-amyloid proteins are pathologic hallmarks of AD, and
several PET tracers targeting tau are now available for human research studies. The optimal use and sequencing of imaging
biomarkers in the evaluation of cognitive impairment and dementia are active areas of investigation. In this presentation, current
and potential future applictions of tau-PET will be discussed in the context of both research studies and possible clinical
applications.
RC817
Molecular Imaging Beyond PET: MRI and Ultrasound/Photoacoustic Molecular Imaging
Friday, Dec. 4 8:30AM - 10:00AM Location: S504CD
MI
MR
OI
US
AMA PRA Category 1 Credits ™: 1.50
ARRT Category A+ Credits: 1.50
FDA
Discussions may include off-label uses.
Participants
Fabian Kiessling, MD, Aachen, Germany, ([email protected]) (Moderator) Advisor, invivoContrast GmbH; Co-owner,
invivoContrast GmbH; Advisor, Molecular Targeting Technologies, Inc; Cooperation, Bayer AG; Cooperation, Bracco Group;
Cooperation, Merck KgaA; Cooperation, AstraZeneca PLC; Cooperation, Koninklijke Philips NV; Cooperation, FUJIFILM Holdings
Corporation
LEARNING OBJECTIVES
1) Attendees will learn the principles and applications of molecular imaging using ultrasound and photoacoustic imaging techniques.
2) Principles and applications of ultrasound molecular imaging will be reviewed. 3) Principles and applications of molecular imaging
using photoacoustic imaging techniques will be presented. 4) Ultrasound guided drug delivery approaches will be reviewed. 5) At the
end of this course, the attendees will understand the principles and potential clinical applications of ultrasound and optoacoustic
molecular imaging as well as of ultrasound guided drug delivery.
Sub-Events
RC817A
Photoacoustic Imaging
Participants
Stanislav Emelianov, PhD, Atlanta, GA (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
1) Understand the fundamental principles of photoacoustic imaging and major components of photoacoustic imaging system. 2)
Knowing how photoacoustic images are formed and how to interpret photoacoustic images. 3) Understand how imaging contrast
agents or imaging probes affect contrast, penetration depth and specificity in photoacoustic imaging. 4) Understand the ability of
photoacoustic imaging system to visualize anatomical, functional and molecular properties of imaged tissue. 5) Identify the role of
photoacoustic imaging in pre-clinical and clinical applications.
ABSTRACT
Photoacoustic imaging or tomography - a non-ionizing, non-invasive, real-time imaging technique capable of visualizing optical
absorption properties of tissue at reasonable depth and high spatial resolution, is a rapidly emerging biomedical and clinical imaging
modality. Photoacoustic imaging is regarded for its ability to provide in-vivo morphological and functional information about the
tissue. With the recent advent of targeted contrast agents, photoacoustics is capable of in-vivo molecular imaging, thus facilitating
further molecular and cellular characterization of tissue. This presentation is designed to provide both a broad overview and a
comprehensive understanding of photoacoustic imaging. With a brief historical introduction, we will examine the foundations of
photoacoustics, including relevant governing equations, optical/acoustic properties of the tissues, laser-tissue interaction, system
hardware and signal/image processing algorithms. Specifically, penetration depth and spatial/temporal resolution of photoacoustic
imaging will be anlyzed. Integration of photoacoustic and ultrasound imaging systems will be discussed. Techniques to increase
contrast and to differentiate various tissues in photoacoustic imaging will be presented. Furthermore, design, synthesis and
optimization of imaging probes (typically, nanoconstructs or dyes) to enable molecular/cellular photoacoustic imaging will be
presented. Special emphasis will be placed on contrast agents capable of multiplexed imaging, multi-modal imaging and imageguided therapy including drug delivery and release. The presentation will continue with an overview of several commercially
available and clinically-relevant systems capable of photoacoustic imaging. Regulatory aspects of photoacoustic imaging systems
and imaging contrast agents will be presented. Finally, current and potential biomedical and clinical applications of photoacoustics
will be discussed.
RC817B
Ultrasound Molecular Imaging
Participants
Juergen K. Willmann, MD, Stanford, CA (Presenter) Research Consultant, Bracco Group; Research Consultant, Triple Ring
Technologies, Inc; Research Grant, Siemens AG; Research Grant, Bracco Group; Research Grant, Koninklijke Philips NV; Research
Grant, General Electric Company
LEARNING OBJECTIVES
1) To understand the acquisition and quantification principles of ultrasound molecular imaging. 2) To understand the characteristics
and biodistribution of molecularly targeted ultrasound contrast agents. 3) To understand the role of ultrasound molecular imaging in
preclinical and clinical applications.
ABSTRACT
Ultrasound imaging is a widely available, relatively inexpensive, and real-time imaging modality that does not expose patients to
radiation and which is the first-line imaging modality for assessment of many organs. Through the introduction of ultrasound
contrast agents, the sensitivity and specificity of ultrasound for detection and characterization of focal lesions has been
substantially improved. Recently, targeted contrast-enhanced ultrasound imaging (ultrasound molecular imaging) has gained great
momentum in preclinical research by the introduction of ultrasound contrast agents that are targeted at molecular markers overexpressed on the vasculature of certain diseases. By combining the advantages of ultrasound with the ability to image molecular
signatures of diseases, ultrasound molecular imaging has great potential as a highly sensitive and quantitative method that could be
used for various clinical applications, including screening for early stage disease (such as cancer); characterization of focal lesions;
quantitative monitoring of disease processes at the molecular level; assisting in image-guided procedures; and, confirming target
expression for treatment planning and monitoring. In this refresher course the concepts of ultrasound molecular imaging are
reviewed along with a discussion on current applications in preclinical and clinical research.
RC817C
Sonographically-guided Drug Therapy
Participants
Alexander L. Klibanov, PhD, Charlottesville, VA, ([email protected]) (Presenter) Co-founder, Targeson, Inc; Stockholder,
Targeson, Inc; Institutional research collaboration, AstraZeneca PLC;
LEARNING OBJECTIVES
1) To identify the basic principles of ultrasound energy deposition as applied to molecular imaging and image-guided therapeutic
interventions. 2) To combine the general physical principles of ultrasound-microbubble interaction, drug-carrier systems
pharmacokinetics and ultrasound contrast imaging, apply this knowledge for the development of triggered delivery approaches in
the setting of personalized medicine. 3) To understand advantages and disadvantages of ultrasound application in the potential
image-guided intervention designs. 4) To identify and compare potential clinical applications of ultrasound-guided drug delivery.
ABSTRACT
The reason of ultrasound use in drug delivery is to enhance drug action specifically in the area of disease. The design of such
therapeutic intervention should assure that drug deposition or action enhancement take place only in the disease site, with the
general goal to improve the therapeutic index. There are several approaches to ultrasound-assisted drug delivery. The first
approach, closest to clinical practice, takes advantage of existing ultrasound contrast agents (intravenous gas microbubbles
approved in US for cardiac imaging). When these bubbles are co-injected intravenously with the drugs, and ultrasound energy
applied to the areas of disease, localized energy deposition leads to endothelium activation or transient "softening" of blood brain
barrier (BBB). Drugs (including antibodies or liposomes) can thus transit BBB and achieve therapeutic action. Ultrasound imaging can
be used for targeted focusing of ultrasound energy in the areas of disease. Second approach suggests attaching microbubbles to
the drug or a drug carrier (including nucleic acid drugs). Microbubbles can be complexed with drug or gene carrier nanoparticles, so
that local action of ultrasound would result in triggered drug release/deposit or transfection in the ultrasound-treated area. Third
approach involves targeted microbubble design, as in ultrasound molecular imaging. Combination of targeted microbubbles with drug
carrier makes possible unfocused ultrasound use, to act only in the areas of the target receptor expression, where microbubbles
adhere and ultrasound energy is then deposited. Lately, formulation moved from microbubbles to smaller nanodroplet drug carriers,
to reach interstitium, where drug release could take place upon ultrasound treatment. Overall, combination of ultrasound imaging,
including contrast (molecular) imaging, focused ultrasound, and drug carrier systems will lead to novel image-guided therapies,
especially applicable in the era of personalized medicine.
RC817D
Magnetic Resonance Molecular Imaging
Participants
Moritz F. Kircher, MD, PhD, New York, NY (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
1) To receive a structured overview of the fundamental principles of generating molecular information with MRI. 2) To understand
how each of these principles functions and what unique information it can provide. 3) To understand the current role of molecular
MRI in preclinical and clinical applications. 4) To understand what the challenges of new molecular MRI approaches towards
translation into humans will be.
ABSTRACT
The field of molecular MRI has exploded in the last decade, with hundreds of different concepts and probe designs developed and
tested in vitro and in vivo. This talk will attempt at giving a structured overview over this vast arsenal of potentially useful
approaches by focusing on those that have the highest potential for clinical translation. The approaches will be grouped into 6
major categories and their principles explained and illustrated with key examples: 1) Multimodal nanoparticles; 2) Activatable MRI
probes; 3) Targeted superparamagnetic iron oxide nanoparticles; 4) non-targeted superparamagnetic iron oxide nanoparticles; 5)
MRI-based Radiogenomics; and 6) Hyperpolarized magnetic resonance spectroscopic imaging.
RC818
Global Cancer Imaging-Insights from Overseas
Friday, Dec. 4 8:30AM - 10:00AM Location: E261
GU
MI
MR
OI
AMA PRA Category 1 Credits ™: 1.50
ARRT Category A+ Credits: 1.50
FDA
Discussions may include off-label uses.
Participants
Sub-Events
RC818A
Functional and Molecular Imaging at Oxford University
Participants
Fergus V. Gleeson, MBBS, Oxford, United Kingdom (Presenter) Consultant, Alliance Medical Limited; Consultant, Blue Earth
Diagnostics Limited; Consultant, Polarean, Inc;
LEARNING OBJECTIVES
1) To learn about the functional and molecular imaging research being conducted within the Radiology Department of Oxford
University Hospitals NHS Trust.
ABSTRACT
There is increasing functional and molecular imaging being performed in medicine. The Radiology department at the Churchill Hospital
in Oxford is conducting a number of trials in these areas, and has designed these trials around interventions to measure the effect
of these new techniques. It has also taken the opportunity to raise the profile of Radiology within the University, to promote
greater collaboration with basic scientists, attracting increased funding, and opportunities for scientists and physicians.
RC818B
Lessons Learned from the National Irish Breast Screening Program: The First 12 years-One Million
Mammograms On
Participants
Michelle M. McNicholas, MD, Dublin, Ireland (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
1) To review the results of the Irish National Breast Screening Program following 12 years of screening with over 1,000,000
mammograms performed. 2) To understand the essential components of setting up and maintaining a national breast screening
program in Ireland. This includes the rationale for the decisions made at the outset, such as age range, frequency of screens,
centralisation of service and responsibility of the screening process to the end of primary surgery. 3) To understand the need for
and the mechanism of developing a national registry of eligible women in the absence of a national unique identifier. 4) To
understand the need for a client charter which sets out client guarantees, objectives and goals around issues of consent,
timeliness of screening results and recall to assessment, biopsy results and admission for surgery and further treatment where
indicated. 5) To understand the necessity of national guidelines, annual reports and external accreditation. 6) To demonstrate the
essential need for ongoing review of key performance indicators (recall rate, biopsy rate, cancer detection rate, DCIS rate, open
biopsy rate, false negative rate, interval cancer rate) as surrogates of program success. 7) To understand the importance of
communication and feedback to clients, units, practitioners and media in maintaining uptake. 8) To understand the reporting
structure and the composition of various roles within the multidisciplinary medical and surgical teams. 9) To understand the
requirements for ongoing training and education of all staff - physicians, technologists, nurses, physicists, administrative staff. 10)
To understand the factors affecting radiation dose to the screened population and the over-riding responsibility of the ALARA
principle, such as: role of physics team, mammographic technique, equipment choice, technologist expertise and training, quality
assessment. 11) To understand the operational issues of different screening units, double reading, discrepancy cases, dealing with
interval cancers, dealing with outliers in key performance parameters. 12) To understand the positive spinoff s from the program
including increased awareness, improving national standards in the screening and the symptomatic population and the contribution
to improved diagnostic and treatment options. 13) To understand how the program achieved, maintained, and monitored
performance and how it adapted to changes in practice as issues or controversies arose. 14) To discuss whether this population
screening program has been a successful and cost effective health care initiative for Ireland. 15) Ultimately, to understand whether
the Irish National Breast Screening Program has led to improved survival in women with breast cancer in Ireland.
RC818C
MRI of Pelvic Malignancy-The View from Down Under
Participants
Nicholas J. Ferris, MBBS, Clayton, Australia, ([email protected]) (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
1) To learn about the local availability and funding of MRI in investigating pelvic malignancy that is unique to Australia.2) To
understand the current usage of Pelvic MRI in investigating pelvic malignancy in the Australian population.3) To review some typical
examples of Pelvic MRI in Oncology that illustrate the advantages of MRI in the assessment of pelvic malignancies and impact MRI
has on patient management in the multidisciplinary setting.
ABSTRACT
Most medical imaging tests in Australia are heavily subsidized by the Federal government as part of the 'Medicare' national health
insurance system.Prostate cancer is a common problem in Australian men, and MRI appears to be a very useful tool in its
assessment and management, however it remains unfunded in the Medicare system. To remedy this, a group of clinicians has made
application to the Medicare Services Advisory Committee (MSAC) for inclusion of the test on the Medicare Benefits Schedule. Steps
in the recently revised MSAC procedure will be reviewed, with reference to the current application for prostate MRI.The impact of
its current unfunded status on the uptake of prostate MRI will be briefly reviewed.Despite the lack of government support, there
has been considerable experience with the technique 'Down Under', leading to some important publications in the international
literature about the role of MRI in selection of patients for biopsy, and the choice of biopsy target.
RC818D
Imaging of HCC-A Korean Perspective
Participants
Byung Ihn Choi, MD, PhD, Seoul, Korea, Republic Of (Presenter) Nothing to Disclose
LEARNING OBJECTIVES
1) To learn recent imaging techniques for the qualitative and quantitative diagnosis, selection of treatment methods, and
evaluation of monitoring after treatment for HCC. 2) To understand the imaging findings of hepatocarcinogenesis from regenerate
nodule going through low and high grade dysplastic nodule, early HCC and finally to advanced HCC. 3) To review current clinical
practice guidelines including role of imaging for the diagnosis and treatment for HCC with focus on recent change of guidelines by
rapid progression of imaging biomarkers.
ABSTRACT
SST02
Cardiac (Molecular Imaging/Other)
Friday, Dec. 4 10:30AM - 12:00PM Location: S501ABC
CA
MI
MR
AMA PRA Category 1 Credits ™: 1.50
ARRT Category A+ Credits: 1.50
Participants
Balazs Ruzsics, MD, PhD, Charleston, SC (Moderator) Nothing to Disclose
Pal Maurovich-Horvat, MD,PhD, Budapest, Hungary (Moderator) Nothing to Disclose
Sub-Events
SST02-01
Age Dependency of Myocardial Triglyceride Content: A 3T 1H-Magnetic Resonance Spectroscopy
Study
Friday, Dec. 4 10:30AM - 10:40AM Location: S501ABC
Participants
Bernhard Petritsch, Wurzburg, Germany (Presenter) Nothing to Disclose
Tobias Gassenmaier, MD, Wurzburg, Germany (Abstract Co-Author) Speaker, Siemens AG
Julian Donhauser, MD, Wurzburg, Germany (Abstract Co-Author) Nothing to Disclose
Andreas Kunz, Wurzburg, Germany (Abstract Co-Author) Nothing to Disclose
Thorsten A. Bley, MD, Hamburg, Germany (Abstract Co-Author) Nothing to Disclose
Michael Horn, PhD, Wurzburg, Germany (Abstract Co-Author) Nothing to Disclose
PURPOSE
The role of myocardial triglyceride (mTG) content in the aging human heart is not entirely understood. The aim of this study was to
measure concentrations of mTG content from healthy volunteers using 1H-magnetic resonance spectroscopy (1H-MRS) and to
determine the association between age, mTG content and systolic heart function (expressed as ejection fraction). Furthermore, the
technical reliability of 1H-MRS at 3 T was evaluated.
METHOD AND MATERIALS
The total study population of 47 healthy volunteers was divided into 4 age classes, according to the age of the subjects (1st
cohort 20 - 29 years (yrs.), n=20; 2nd cohort 30 - 39 yrs., n=10; 3rd cohort 40 - 49 yrs., n=9; 4th cohort 50 - 60 yrs., n=8).
Cardiac MRI and dual triggered 1H-MRS of the myocardium were consecutively performed using a 3 T scanner (MAGNETOM Trio,
Siemens). The mTG content was calculated as quotient of the mTG resonance areas (at 0.9 ppm [CH3 groups] and 1.3 ppm [CH2
groups]) and the tissue water resonance area (at 4.7 ppm), expressed as triglyceride / water resonance ratio in %. Each
participant underwent spectroscopic measurements twice.
RESULTS
mTG content significantly correlates with age (r=0.48; p<0.001). Following age-averaged values for mTG content were determined:
1st cohort 0.25% (± 0.17); 2nd cohort 0.48% (± 0.30); 3rd cohort 0.48% (± 0.18); 4th cohort 0.77% (± 0.70). While we found a
slight correlation between BMI and mTG content (r=0.27; p=0.008), age proved to be the dominant variable accounting for higher
mTG content in healthy humans. There was no significant correlation (r=0.04; p=n.s.) between LV mass and mTG content in
healthy volunteers. No effects of mTG content was seen on systolic heart function (r=-0.01; p=n.s.). Intraclass correlation
coefficient of repeated spectroscopic measurements was high (r=0.965; p<0.001).
CONCLUSION
1H-MRS proved to be a highly reproducible, sensitive tool for myocardial lipid determination. Myocardial TG content is age
dependent and increases with age. Myocardial TG content was independent from LV mass and systolic heart function. Furthermore
a higher scattering of mTG levels was observed with rising age.
CLINICAL RELEVANCE/APPLICATION
Myocardial TG content rises with advancing age. The age-dependent concentration ranges of myocardial lipid metabolites reported
in this study may be helpful for the correction of acquired 1H-MRS data in patients when evaluating metabolic and cardiovascular
diseases infuture studies.
SST02-02
Transplantation of Mesenchymal Stem Cells Overexpressing Integrin-linked Kinase Improves the
Myocardial Repairing Following Acute Myocardial Infarction
Friday, Dec. 4 10:40AM - 10:50AM Location: S501ABC
Participants
Dan Mu, Nanjing, China (Presenter) Nothing to Disclose
Hongming Yu, Nanjing, China (Abstract Co-Author) Nothing to Disclose
Chuan Shuai Tian, Nanjing, China (Abstract Co-Author) Nothing to Disclose
Weibo Chen, PhD, Shanghai, China (Abstract Co-Author) Nothing to Disclose
Biao Xu, Nanjing, China (Abstract Co-Author) Research Grant, General Electric Company
Bin Zhu, Nanjing, China (Abstract Co-Author) Nothing to Disclose
PURPOSE
To investigated the effects of transplanted autologous mesenchymal stem cells overexpressing integrin- linked kinase (ILK) on
myocardial perfusion, myocardial fibrosis and cardiac function in the swine AMI model by MR imaging in vivo.
METHOD AND MATERIALS
MSCs or ILK-MSCs (5×107 cells) were randomly transplanted into the ischemic myocardium via coronary artery 1 week after
establishing the swine acute myocardial infarction model (6 swine per group) by ballon occlusion. The myocardial blood perfusion,
the infarction area and the cardiac function were assessed by MR first pass perfusion, delayed enhanced examination and cine MR
respectively before and 2 weeks after transplantation using MR imaging.The cardiac fibrosis and capillary density were assessed
using immunohistochemistry two weeks later. The data was statistically analyzed with Independent Sample t test using SPSS17.0
software.
RESULTS
Myocardial perfusion was significantly greater in the ILK-MSCs group than in the MSCs group (area under the perfusion
curve:44840±4807mm2 vs. 35681±5548mm2, p<0.05) and was associated with greater neovessel formation (CD31 positive
cells:273.0±28.3cells/field vs. 194.2±30.7cells/field, p<0.05). The variation of infarction areas were larger in the ILK-MSCs group
than in the MSCs group(the infarct size ratio:0.96±0.11 vs. 0.76±0.09, p<0.05) and was associated with less myocardial fibrosis in
Masson staining(the fibrosis area: 46.7±9.0% vs. 62.0±4.9%, p<0.05). Transplantation of ILK-MSCs improved reginal cardiac
function compared with transplantation of MSCs(wall thickness ratio:60.70±6.8% vs. 52.08±5.6% , p<0.05).
CONCLUSION
Transplantation of mesenchymal stem cells modified with ILK enhance the myocardial repairing after AMI.
CLINICAL RELEVANCE/APPLICATION
MR imaging is a reliable method to evaluate the effect of transplantation of MSCs overexpressing ILK on cardiac repairing.
SST02-03
MR Molecular Imaging of Homing of Mesenchymal Stem Cells Overexpressing Intergrin-linked Kinase
after Transplantation via Coronary in Swine Acute Myocardial Infarction
Friday, Dec. 4 10:50AM - 11:00AM Location: S501ABC
Participants
Dan Mu, Nanjing, China (Presenter) Nothing to Disclose
Hongming Yu, Nanjing, China (Abstract Co-Author) Nothing to Disclose
Chuan Shuai Tian, Nanjing, China (Abstract Co-Author) Nothing to Disclose
Weibo Chen, PhD, Shanghai, China (Abstract Co-Author) Nothing to Disclose
Biao Xu, Nanjing, China (Abstract Co-Author) Research Grant, General Electric Company
Bin Zhu, Nanjing, China (Abstract Co-Author) Nothing to Disclose
PURPOSE
To in vivo detect the homing ability of MSCs overexpressing integrin- linked kinase (ILK) after transplantation via coronary in swine
model of AMI using MR molecular imaging technique.
METHOD AND MATERIALS
MSCs or ILK-MSCs(5×107 cells)genetically modified with adenovirus containing GFP or GFP/ILK and labeled with ultrasmall
superparamagnetic iron oxide(USPIO) were transplanted into the ischemic myocardium via coronary artery 1 week after establishing
the swine myocardial infarction model by ballon occlusion.The cell cardiac homing and migration were tracked in vivo at 24h, 1w and
2w after transplantation using MR molecular imaging on clinical 1.5T MR scanner.The GFP expression was calculated from frozen
section and the iron particles in transplanted cells was detected by prussian blue staining 2 weeks later. The data was statistically
analyzed with Independent Sample t test for two group comparison using SPSS17.0 software.
RESULTS
In vivo MR molecular imaging manifested in both Groups that the hypointense area (MSCs:97.60±4.05mm2;ILKMSCs:109.8±6.96mm2) at 1 week was larger (p<0.05) than those at 24 hours(MSCs:80.06±5.47mm2;ILK-MSCs:89.98±6.15mm2)
and the signal intensity variation (MSCs:359.8±44.94; ILK-MSCs:473.6±44.85) was smaller(p<0.05) than those at 24 hours (MSCs:
457.2±43.80; ILK-MSCs:662.4±40.98 ). The hypointense area (MSCs:32.52±7.65mm2; ILK-MSCs:19.00±3.10mm2) and intensity
variation (MSCs:218.6±71.86; ILK-MSCs:108.6±77.87) were all decreased 2 weeks later compared to those at 1week ( p<0.05).
The area and intensity variation of ILK-MSCs group was larger/higher in former 2 time points compared with those of MSCs group(
p<0.05), but smaller/lower in 2 weeks( p<0.05) because of dilution of iron particles in each cells attribute to the promoted cell
proliferation caused by ILK modification, which was explained by more GFP positive(420.0±8.8/field vs.106.5±8.3/field,p<0.001) and
prussian blue staining positive cells (275±54/field vs. 144±54/field, p<0.001) in ILK-MSCs group in two weeks.
CONCLUSION
USPIO labeled MSCs can be reliably detected and tracked in vivo using serial MR molecular imaging. Transplantation of ILK-MSCs
after myocardial infarction can increase the homing rate of MSCs.
CLINICAL RELEVANCE/APPLICATION
MR molecular imaging can identify and dynamically monitor transplanted cells in vivo for verification of effect of ILK on MSCs
homing.
SST02-04
Ferumoxytol-poly-l-lysine Labeling and Non-invasive MR Imaging of Mesenchynal Stem Cells
Friday, Dec. 4 11:00AM - 11:10AM Location: S501ABC
Participants
Dan Mu, Nanjing, China (Presenter) Nothing to Disclose
Hongming Yu, Nanjing, China (Abstract Co-Author) Nothing to Disclose
Chuan Shuai Tian, Nanjing, China (Abstract Co-Author) Nothing to Disclose
Weibo Chen, PhD, Shanghai, China (Abstract Co-Author) Nothing to Disclose
Biao Xu, Nanjing, China (Abstract Co-Author) Research Grant, General Electric Company
Bin Zhu, Nanjing, China (Abstract Co-Author) Nothing to Disclose
PURPOSE
To evaluate the efficiency and the safety of labeling mesenchymal stem cells(MSCs) in vitro with ferumoxytol- poly-l-lysine (PLL) ,
a new negative agent for cell lebeling and to detect the imaging characteristics.
METHOD AND MATERIALS
MSCs were incubated with ferumoxytol-PLL. Labeling efficiency was examined by Prussian blue staining, transmission electron
microscopy and Colorimetric ferrozine assay. MTT growth curves were obtained at a range of iron concentrations from 5 to 200
ug/ml to assess the effects of the labeling on cell viability and to confirm the safe iron concentration for cell labeling. The effect of
ferumoxytol- PLL at iron concentration of 50ug/ml on cell migration,proliferation and cell cycle were determined by transwell
migration assay, EdU staining assay and flow cytometry anlaysis after Propidium iodide staining respectively. Different number MSCs
labeled with ferumoxytol-PLL at different iron concentrations were imaged using a 3.0T MR system with T2WI and T2*WI
sequences. The signal intensity was measured and statistically compared.
RESULTS
The labeling efficiency was 100%. Transmission electron microscopy showed the iron particles in the cytoplasm. The iron content of
each cells was liner correlated with the iron concentration of the labeling media. Higher labeling concentration (more than 100
μg/ml) can affect cell viability detected by MTT assay. There were not significant impairments were documented in cell
proliferation, migration and cell cycles at 50 μg/ml dose when comparing iron-labeled MSCs to unlabeled controls.The ferumoxytolPLL labeling caused a stronger low signal attenuation effect on T2WI and T2*WI. The signal intensity was negatively correlated
with cell numbers and iron concentration of the labeling media.
CONCLUSION
MSCs can be easily and efficiently labeled by ferumoxytol-PLL without interference on the cell viability, migration, proliferation and
cell cycle. MRI visualization of SPIO- labeled MSCs is feasible in bothT2WI and T2*WI.
CLINICAL RELEVANCE/APPLICATION
Ferumoxytol- poly-l-lysine (PLL) can efficiently label MSCs for MR molecular imaging.
SST02-05
Free-Breathing 3D T1-weighted Fat-saturated Contrast-enhanced Gradient-echo Sequence with
Radial Data Sampling in Thoracic and Cardiovascular MRI
Friday, Dec. 4 11:10AM - 11:20AM Location: S501ABC
Participants
Christer Ruff, MD, Tuebingen, Germany (Presenter) Nothing to Disclose
Robert Grimm, Erlangen, Germany (Abstract Co-Author) Employee, Siemens AG
Fabian Bamberg, MD, MPH, Munich, Germany (Abstract Co-Author) Speakers Bureau, Bayer AG; Speakers Bureau, Siemens AG;
Research Grant, Bayer AG; Research Grant, Siemens AG;
Ulrich Kramer, MD, Tuebingen, Germany (Abstract Co-Author) Nothing to Disclose
Konstantin Nikolaou, MD, Tuebingen, Germany (Abstract Co-Author) Speakers Bureau, Siemens AG Speakers Bureau, Bracco Group
Speakers Bureau, Bayer AG
Mike Notohamiprodjo, Munich, Germany (Abstract Co-Author) Nothing to Disclose
PURPOSE
To evaluate free-breathing radially sampled fat-saturated T1-weighted gradient-echo acquisitions (radial volumetric interpolated
breath-hold examination (VIBE)) with self-gated radially sampled, breath-hold (BH) and free-breathing (FB) cartesian sampled VIBE
acquisitions for post-contrast imaging of the thorax and cardiovascular system.
METHOD AND MATERIALS
This IRB approved prospective study was performed according to the declaration of Helsinki. 20 patients referred for myocardial
infarction, myocarditis and cardiomyopathy were imaged at 1,5T (Aera, Siemens Healthcare). Gadobutrol (Bayer Healthcare)enhanced cartesian sampled isotropic (voxel-size 1.4x1.4x1.4mm3) VIBE sequences acquired during BH (18s) were compared to FB
radially sampled sequences (approx. 4min) featuring respiratory self-gating. Multiplanar reformations were performed with SyngoVia
(Siemens). All image data sets (Cartesian, Radial and Radial VIBE with self-gating) were evaluated by two independent readers (5poinz-Likert-scale): overall image quality, large vessel depiction, small vessel depiction, heart depiction, thoracic wall/diaphragm
sharpness and streaking artifacts. Statistical analysis was performed with paired t-tests.
RESULTS
Respiratory self-gating of the radially sampled VIBE led to significantly improved depiction of large (4.4 +/- 0.5 vs 3.9 +/- 0.7,
p<0.05) and small vessels (4.7 +/- 0.5 vs 3.4 +/-0.8, p<0.05) as well as thoracic wall/diaphragm sharpness (4.9 +/- 0.4 vs 3.6 +/0.5, p<0.05), whereas overall image quality was not impaired by the significantly increasing streaking artifacts (3.6 +/- 0.5 vs 4.7
+/- 0.5, p<0.05).Compared to standard BH cartesian VIBE, radially sampled VIBE with self-gating showed improved large and small
vessels (4.4 +/- 0.5 vs 3.3 +/-0.6, p=0.05; 4.7 +/- 0.5 vs 3.3 +/- 0,6, p<0.05), thoracic wall/diaphragm (4.9 +/- 0.4 vs 3.3 +/0.6, p<0.05) and overall image quality (4 +/- 0.6 vs. 3.3 +/- 0.6, p=0.17).
CONCLUSION
Respiratory self-gated radially sampled VIBE acquired during free-breathing is feasible for thoracic and vascular imaging, particularly
of the thoracic wall and large and small vessels compared to radially sampled VIBE without self-gating and breath-hold Cartesian
sampled VIBE.
CLINICAL RELEVANCE/APPLICATION
Respiratory self-gated radially sampled VIBE acquired during free-breathing is feasible for thoracic and vascular imaging, particularly
of the thoracic wall and large and small vessels.
SST02-06
Could Cardiac Magnetic Resonance Imaging be an Effective Alternative to Transthoracic
Echocardiography for Routine Evaluation of the Heart?
Friday, Dec. 4 11:20AM - 11:30AM Location: S501ABC
Participants
Erkan Yilmaz, MD, Izmir, Turkey (Abstract Co-Author) Nothing to Disclose
Uygar Teomete, MD, Miami Beach, FL (Presenter) Nothing to Disclose
Bahri Akdeniz, Izmir, Turkey (Abstract Co-Author) Nothing to Disclose
PURPOSE
This study is designed to investigate the effectiveness of cardiac magnetic resonance imaging (CMR) in routine evaluation of heart
as an alternative method to transthoracic echocardiography.
METHOD AND MATERIALS
The study included 48 randomised patients underwent both echocardiography and CMR. On CMR examination, cine steady-state
free precession (SSFP) sequence was used to calculate ejection fraction (EF), ventricular and atrial measurements and wall
thickness of left ventricle (LV). Velocity and flow information in the aortic, mitral and tricuspid valves were obtained by using
velocity-encoded sequence. CMR and echocardiography outcomes were compared using by paired samples t-, Pearson's correlation,
McNemar's and Kappa statistical tests.
RESULTS
Measurements of LV inner diameter in end-diastole, septal wall and posterior wall thickness in end-systole showed a good
correlation with CMR and echo (r=0,795, r= 0,798, r=0,536). EF estimated with CMR showed perfect correlation with EF estimated
by using echo (r= 0,80, p<0,01). Our results had a good correlation between two methods in terms of diastolic disfunction. When
compared with echocardiography, CMR revealed good (κ=0,660), poor (κ=0,370), moderate (κ=0,504), very good (κ=1,0) and poor
(κ=0,270) correlations for mitral regurgitation, mitral stenosis, aortic regurgitation, aortic stenosis and tricuspid regurgitation,
respectively. Peak E and peak A velocities in the mitral inflow measured by both two methods showed moderate correlation with κ
values of 0,435 and 0,493. A highly good accordance between the two methods in terms of the measurements of peak velocity in
aortic valve (κ=0,778).
CONCLUSION
We found that volume, flow and thickness measurements of the heart on transthoracic echocardiography examination have a
statistically good correlation with CMR measurements. Also, there is a satisfying diagnostic concordance between two modalities in
evaluating the heart.
CLINICAL RELEVANCE/APPLICATION
CMR can be used an alternative method to transthoracic echocardiography, especially for acoustically poor patients.
SST02-07
Improved Ex-vivo Human Cardiac DTI using Optimal b-values on a Clinical 3T MRI System
Friday, Dec. 4 11:30AM - 11:40AM Location: S501ABC
Participants
Jian Cao, MD, Peking, China (Presenter) Nothing to Disclose
Feng Yang, Beijing, China (Abstract Co-Author) Nothing to Disclose
Yining Wang, MD, Beijing, China (Abstract Co-Author) Nothing to Disclose
Chao Ma, Beijing, China (Abstract Co-Author) Nothing to Disclose
Lingyan Kong, MD, Beijing, China (Abstract Co-Author) Nothing to Disclose
Lu Lin, MD, Peking, China (Abstract Co-Author) Nothing to Disclose
Yan Yi, Beijing, China (Abstract Co-Author) Nothing to Disclose
Jing An, Beijing, China (Abstract Co-Author) Research collaboration, Siemens AG
Tianjing Zhang, Beijing, China (Abstract Co-Author) Employee, Siemens AG
PURPOSE
This study aims to investigate the effect of b-value of cardiac DTI in revealing myocardial microstructural remodeling on a 3T MRI
system.
METHOD AND MATERIALS
Seven formalin-fixed healthy human heart samples were acquired at room temperature on a Siemens 3.0T MAGNETOM Skyra MR
scanner for fiber structural analysis using a 20-channel head coil with a DW sequence with multi-shot EPI readout. Each heart
sample was suspended in plastic cylinder filled with liquid paraffin to avoid tissue-air susceptibility artifacts during the acquirement.
DTI acquisitions were the following parameters: TE=67 ms, TR=6500 ms, FOV=200× 200 mm, slice thickness= 2.0 mm, number of
slices=40~45, 100× 100 pixels for each slice, diffusion sensitivity b=600/800/1000 s/mm2, accel factor=2, gradient directions=20,
slice gap=0 mm. Total image acquisition time was about 20 min per sample. Data was post-processed by Matlab based programs.
Diffusion tensor indices, such as FA (Fractional Anisotropy), ADC (Apparent Diffusion Coefficient), fiber length and fiber numbers
with each b-value in the left ventricle were calculated and compared.
RESULTS
In Table 1 is shown variations of DTI indices with different b-values. Gradual decrease on FA value and gradual increase on ADC
value are observed when b value rises from 600 to 1000 s/mm2. Variations of fiber numbers and fiber lengths at different b values
are neither regular nor significant.
CONCLUSION
A b value of 600 s/mm2 would be suggested acquire human cardiac diffusion tensor imaging in order to avoid confusion when using
FA values as an absolute reference for assessing the difference between normal and abnormal zones.
CLINICAL RELEVANCE/APPLICATION
An appropriate b-value would benefit DTI to better reveal the myocardium structural of human hearts. Since no significant
differences occurs in fiber numbers and fiber lengths, a b value of 600 s/mm2 would be suggested acquire human cardiac diffusion
tensor imaging in order to avoid confusion when using FA values as an absolute reference for assessing the difference between
normal and abnormal zones.
SST02-08
CT Coronary Angiography: Effect of Iodine CONcentration on Vascular Attenuation: The CT-CON
Multicentric Study FINAL RESULTS
Friday, Dec. 4 11:40AM - 11:50AM Location: S501ABC
Participants
Marco Rengo, MD, Rome, Italy (Presenter) Nothing to Disclose
Anoeshka S. Dharampal, MD, Rotterdam, Netherlands (Abstract Co-Author) Nothing to Disclose
Damiano Caruso, MD, Rome, Italy (Abstract Co-Author) Nothing to Disclose
Marco Das, MD, Maastricht, Netherlands (Abstract Co-Author) Research Consultant, Bayer AG; Research Grant, Siemens AG;
Speakers Bureau, Siemens AG; Research Grant, Koninklijke Philips NV
Marc C. Kock, MD, Rotterdam, Netherlands (Abstract Co-Author) Nothing to Disclose
Andre Niezen, Rotterdam, Netherlands (Abstract Co-Author) Nothing to Disclose
Fiek Van Tilborg, Bron, Netherlands (Abstract Co-Author) Nothing to Disclose
Koen Nieman, MD, PhD, Rotterdam, Netherlands (Abstract Co-Author) Speakers Bureau, Siemens AG Speakers Bureau, Toshiba
Corporation Research Grant, Bayer AG Research Grant, General Electric Company
Gabriel P. Krestin, MD, PhD, Rotterdam, Netherlands (Abstract Co-Author) Consultant, General Electric Company; Research Grant,
General Electric Company; Research Grant, Bayer AG; Research Grant, Siemens AG; Speakers Bureau, Siemens AG
PURPOSE
To explore the relative impacts of iodine concentration versus iodine delivery rate on intra-coronary attenuation. To describe the
effect of iodine concentration on contrast bolus characteristics
METHOD AND MATERIALS
971 patients were prospectively randomized in 4 groups and underwent CT Coronary Angiography (CTCA). Four CM with different
iodine concentrations (300, 350, 370, 400 mgI/ml) were delivered at a fix iodine delivery rate (2.0 mgI/s). Intracoronary attenuation
values were measured and grouped on a per-vessel and per-segment bases. Time-to-peak, and pressure curves during CM injection
were evaluated and compared
RESULTS
Injection fluxes were 6.7 ml/sec, 5.7 ml/sec, 5.4 ml/sec and 5 ml/sec for group A, B, C and D respectively. No significant
differences were observed among four groups in terms of intravascular density on a per-segment and per-vessels analysis. Timeto-peak was significantly earlier in group A (15.3 sec) than in the other three groups. The injection peak pressure was significantly
lower in group A (185.16 psi) and C (189.05 psi) than in group B (215.89 psi) and D (243.33 psi). No extravasations were noted in
all groups
CONCLUSION
Contrast media with different iodine concentrations, if injected at the same IDR, provide similar intravascular attenuation values.
The lower concentration contrast medium provided significantly lower injection pressure values and a significantly shorter time to
peak enhancement
CLINICAL RELEVANCE/APPLICATION
Intravascular attenuation in CT coronary angiography is mainly influenced by iodine delivery rate and is independent by iodine
concentration
SST02-09
Study of the CT Anatomical Configuration of the Aortic Valve: An Automatic 3D-Shape-based
Comprehensive Analysis
Friday, Dec. 4 11:50AM - 12:00PM Location: S501ABC
Participants
Julien Ognard, MD, MSc, Brest, France (Presenter) Nothing to Disclose
Thomas Hebert, Brest, France (Abstract Co-Author) Nothing to Disclose
Nan Kang, MSc, Brest, France (Abstract Co-Author) Nothing to Disclose
Martine Gilard, MD,PhD, Brest, France (Abstract Co-Author) Nothing to Disclose
Michel Nonent, MD, Brest, France (Abstract Co-Author) Nothing to Disclose
Valerie Burdin, PhD, Plouzane, France (Abstract Co-Author) Nothing to Disclose
PURPOSE
In Transcatheter aortic valve implantation (TAVI) procedures, the determination of AVA (Aortic Valve Annulus) geometric features
is crucial to deciding the size and type of the prosthesis valve to be used. The purpose of this study is to asses quantitatively the
variation of aortic valve shape along its principle axis in order to find the center and diameter of AVA, and to determine at each
levels the measurement that could be done during preoperative plannings, according to the shape.
METHOD AND MATERIALS
A number of 25 ECG-gated cardiac CT (64 channels multidetector CT scanner) were analysed. 2 Experts radiologists manually
defined the centerline and the limits of the aortic valve. Threshold techniques and growing regions were used to mask the left
ventricle and the aorta. Principle Component Analysis were used to extract an approximate aortic centerline, with an iterative
procedure. Then we cut through data to get slices which are perpendicular to the centerline. Each cross section is then unfolded
into polar coordinates. The function of distance which describes the contour of tri-leaflet has three pairs of extrema (minima and
maxima) and smallest min distance. for each cross section, we find 3 points on the contour of the aorta with minimum distance to
the barycenter and calculate ellipse fitting.
RESULTS
The method is based on a quantitative study of shape to find an optimal fit to mimic AVA in the aortic root. Analyses of such
The method is based on a quantitative study of shape to find an optimal fit to mimic AVA in the aortic root. Analyses of such
models have shown the aortic root to have variable distensibility along its length. Our contribution includes extracting a robust
centerline of aortic valve automatically, analyzing the shape changes of cross section along the centerline by the help of polar
representation, providing a flexible circle and ellipse fitting for aortic valve part with the coordinates for the center and
corresponding change intervals for radius.
CONCLUSION
We introduced measurements for aortic valve by a quantitative study compared with previous qualitative research.
CLINICAL RELEVANCE/APPLICATION
Understanding the 3D shape characteristics of the aortic valve will help radiologist and cardiologist in the preoperative plannings of
TAVIs. And could even assist engineer-physicians to design and manufacture customized valve that works in the optimum condition