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Volume 8, Issue 2
2011 . 2
pet center of excellence
newsletter
Potential Clinical Applications of PET/MRI:
On the Frontier of Structural-FunctionalMolecular Imaging
President’s
Report
By Drew A. Torigian, MD, MA, University of Pennsylvania School of Medicine, Philadelphia, Pa.
George M. Segall, MD
Nuclear Medicine and
Molecular Imaging in 2020
The importance of hybrid imaging and the
emergence of molecular imaging have brought
the specialty of nuclear medicine to a crossroads. It is time to reinvent ourselves. By 2020,
we will need a cadre of physicians with robust
training in anatomic and molecular imaging to
do the research that will advance the field as
well as teach future professionals.
In the beginning, these future physicians
will be dual-trained and dual-certified in
nuclear medicine and radiology following
traditional (separate) pathways. The 2011
report of the ACR-SNM Task Force on
Nuclear Medicine Training recommended fully
integrated training programs for future physicians. One pathway would consist of a clinical
year followed by three years of radiology and
two years of nuclear medicine. This is the
pathway envisioned for physicians interested
in research and academic careers. A second
integrated pathway would include 16 months
of nuclear medicine training within a four year
radiology residency. This is the pathway envisioned for clinicians in large practices who will
practice the full scope of molecular imaging,
including using new radiotracers expected to
be approved, hybrid imaging and non-nuclear
technologies. Graduates of these integrated
pathways will be eligible for certification by
ABNM as well as ABR. Details of how these
integrated training programs will work are the
focus of a second ACR-SNM task force.
It remains to be seen if these future professionals will identify themselves primarily as
radiologists or nuclear medicine physicians, or
will recognize themselves as molecular imag(Continued on page 6. See President.)
PET/MRI instruments have recently been
assembled for human use and may have
diagnostic performance superior to that of
PET/CT for particular clinical and research
applications.1-8 This stems from the major
strengths of MRI relative to CT, including
superior soft tissue contrast resolution, multiplanar imaging, and functional imaging capability through specialized techniques such as
diffusion weighted imaging (DWI), diffusion
tensor imaging (DTI), perfusion weighted
imaging (PWI), MR elastography, and MR
spectroscopy (MRS).9
In addition, the lack of ionizing radiation
from MRI is highly appealing, particularly
when pediatric or young adult patients are to
be imaged. When combined with PET, MRI
can also provide the means for partial volume correction of standardized uptake values
for accurate disease quantification, improve
anatomical localization of sites of radiotracer
uptake, improve diagnostic performance,
and provide for comprehensive regional
and global structural-functional-molecular
assessment of various clinical disorders.1, 10
Oncological Disease
In the oncological disease setting, MRI
provides useful structural and functional
information about malignancy that is complementary to the molecular information
provided by PET.1, 6, 11-15 In particular, MRI
provides high resolution structural definition
of tumor volume and extent of local disease
In this Issue
By George M. Segall, MD
June 2009-June 2011
PCOE President
(i.e., T staging). This is particularly useful in
the evaluation of primary tumors that originate
from anatomical sites that are suboptimally
evaluated on CT (e.g., brain, head and neck,
spinal cord, pelvic organs, breasts, musculoskeletal system), as PET provides improved
molecular detection and characterization of
lymph nodes as benign or malignant (i.e., N
staging).12, 16-17 For example, PET/MRI has
recently been shown to be feasible for use
in patients with head and neck cancers and
provided greater spatial resolution and image
contrast compared to PET/CT.18 With regard to
detection of distant metastases (i.e., M staging)
in organs such as liver and bone marrow, PET
and MRI are also complementary to varying
degrees depending on the underlying tumor
biology, the size of metastases, and the specific
anatomical sites involved.19-21
Furthermore, the high spatial resolution data
available from MRI allow for partial volume
correction of PET data, which is essential for
accurate disease quantification and has implications for accurate lesion characterization and
response assessment.22-23 Advanced functional
MRI techniques such as DWI and dynamic
contrast enhanced (DCE) MRI used with PET
can further enhance the detection and characterization of malignant lesions for prognosis
assessment, biopsy and pretreatment planning,
patient selection for certain therapeutic agents,
and response prediction and assessment.1, 21, 24-25
(Continued on page 2. See PET/MRI.)
View You Can Use
3
PET in the News
4
SNM Speaks Out on PET
5
New PCOE President5
(PET/MRI. Continued from page 1.)
For example, addition of DWI to standard MRI technique provided
detection of an additional 20 percent of metastatic melanoma lesions,
with most lesions involving the bone marrow, liver, subcutaneous
tissues, and peritoneum.26 PET/MRI mammography can potentially
lead to an improvement in diagnostic performance for the detection,
characterization and treatment response assessment of breast cancer.11
Hepatobiliary MRI contrast agents can be used to improve detection
of metastatic disease to the liver, and may be useful in the pretransplant evaluation of patients with hepatocellular carcinoma.19, 27 As
such, PET/MRI can potentially be useful to optimize the management
of patients with various types of cancer before, during and after therapeutic intervention.
Neurological Disease
PET/MRI has the potential to provide integrated multidimensional
and multiparametric structural and functional assessment of the
brain in the setting of various neurodegenerative, ischemic/vascular,
neuro-oncological, traumatic, psychiatric, behavioral, seizure-related,
and age-related conditions.15, 28-29 This is, in part, related to the wide
variety of available PET radiotracers that can be used to probe different biological properties of brain tissue in conjunction with the
variety of available functional MRI techniques such as DWI, DTI,
PWI, blood oxygenation level dependent (BOLD) functional MRI
(fMRI), and MRS that provide complementary information.1, 5, 30 In
addition, high degrees of spatial and temporal coregistration of PET
and MRI datasets are feasible, allowing for evaluation of biologically
relevant processes of interest such as metabolism, perfusion, oxygen
consumption, receptor expression, and function in even the smallest
of neuro-anatomical structures.31-32
This is particularly relevant in neuro-oncology, where accurate
alignment of structural and functional information is essential for purposes of biopsy and treatment planning. Again, MRI data allow for
partial volume correction of PET emission data, which is essential for
accurate PET-based quantification of disease.10, 33 Coregistered PET
and MRI are useful for the detection of seizure foci prior to surgery,
and also for the identification of metabolic activity, neurotransmitter concentration, and enzyme expression in small structures of the
brain.34-35 DWI with PET measurements of oxygen consumption
and perfusion can be used for differentiation of intravascular perfusion, tissue blood flow, penumbra and irreversible tissue damage in
ischemic/vascular disease.5 DWI can also be applied with PET to
detect, characterize and monitor changes in brain tumors following
therapeutic intervention.15 DTI, which provides exquisite detail of
the white matter bundles, can be particularly useful for pretreatment
planning of brain tumors by separation of peritumoral edema from
infiltrative tumor, pretreatment assessment of white matter tract
involvement by tumor, and intraoperative visualization and localization of major white matter tracts to decrease the chance of injury to
normal tissues.36-37 PWI with PET may be useful to assess ischemic/
vascular and neoplastic brain disorders. BOLD fMRI can be used to
preoperatively map functional cerebral cortex and to identify eloquent
areas of the cerebral cortex in relation to brain neoplasms, potentially
reducing the time of surgery and minimizing intraoperative cortical
stimulation methods used during surgical resection.38-39 It can also be
used with PET for comparative activation studies, for assessment of
2 PET Center of Excellence Newsletter/2011.2
activation effects upon transmitter release or receptor binding, and
for studying the effects of drugs and withdrawal.5 MRS can quantify
the type, amount, and location of various metabolites within brain tissue, providing complementary information to PET for evaluation of a
variety of disease conditions affecting the brain.1
Cardiovascular Disease
PET/MRI has much potential for the clinical assessment of myocardial viability and infarction, ventricular function, cardiomyopathy,
myocarditis, cardiac masses, atherosclerosis, and vasculitis. This is in
part due to the wide array of available MRI pulse sequences for spin
echo (black blood), gradient echo (bright blood), time-of-flight, phase
contrast, contrast-enhanced, and time-resolved imaging of structure
and function, in conjunction with the wide variety of PET radiotracers
that are available to probe molecular processes of interest. For example, myocardial perfusion imaging [11C]-hydroxyephedrine PET can
image cardiac innervation in combination with high-resolution structural and wall motion imaging by MRI, which can be useful to delineate cardiac regional innervation and control mechanisms in the setting of dilated cardiomyopathy or following cardiac transplantation.40
In addition, respiratory-gated and ECG-gated MRI can also be
used to improve cardiac PET quantification by correcting for errors
due to the misregistration, the partial volume effect and bulk motion.
MRI provides unique insight into the complex anatomy of the heart
and surrounding structures such as the pericardium, coronary arteries,
and great vessels; allows for accurate measurement of cardiac chambers, wall thickness, wall motion, and vessel diameters; provides
quantitative measures of flow in cardiac chambers and vessels; and
is useful to assess myocardial perfusion via dynamic perfusion MRI
with pharmacological stress testing and to detect and quantify the
presence of myocardial fibrosis using delayed post-contrast imaging.41-42 MRI is also useful to show the precise anatomic extent and
location of cardiac and pericardiac tumors, and to characterize their
gross composition, whereas FDG PET can be used for response
assessment purposes.43
Lastly, PET/MRI of the vascular system may be useful for regional
and global detection, characterization and quantification of atherosclerotic disease for purposes of risk assessment and drug response
assessment, as it can simultaneously provide information about
vascular wall thickness, wall inflammation, plaque vulnerability and
degree of luminal narrowing.41, 44-45
Musculoskeletal Disease
PET/MRI may also play a role in the assessment of non-neoplastic
musculoskeletal disorders including infection, diabetic foot, metabolic bone marrow/bone disease, back pain, bone marrow disorders
and arthritis, as MRI provides excellent soft tissue contrast for the
structural assessment of the bone marrow, muscles, tendons, ligaments, cartilaginous structures and fat.14 For example, FDG PET and
MRI have been shown to be synergistic for the detection and characterization of complications of the diabetic foot such as Charcot neuroarthropathy, osteomyelitis, and soft tissue infection.46-47 They are
also complementary for the evaluation of various arthritides and for
treatment monitoring.14, 48 FDG PET/MRI may also be useful to depict
meniscal tears with associated synovitis and can provide for accurate
(Continued on page 6. See PET/MRI.)
Views You Can Use
This 56-year-old man with a history of a reversed gastric bypass
had an abdominal CT scan for evaluation of chronic nausea. The scan
showed a 6 x 7 cm solid anterior splenic mass. A follow-up MRI
confirmed the mass, which did not have clear-cut benign features. A
PET/CT scan was performed for further evaluation of the mass and to
assess for other lesions. The PET/CT scan showed that FDG uptake
in the mass was identical to that in the remainder of the spleen, and
no other lesions were identified. Based on this result, it was decided
that the mass was likely benign and could be followed. A subsequent
CT scan seven months later showed no change in the appearance of
the mass.
How did the PET/CT help?:
Isolated splenic masses are uncommon, but have a high (~80 percent) incidence of malignancy—mostly lymphomas but also metastases and sarcomas. Benign lesions include hemangiomas, hamartomas
and granulomas. PET/CT scans have been shown to have a high negative predictive value for evaluating splenic masses. Positive predictive
value is lower due to false positive scans that may occur in cases of
granulomatous disease1-3.
References:
(1) Surg Endosc. 2008;22:2009-2012
(2) Surg Endosc. 2008;22:2062-2066
About “Views You Can Use”
Advanced Radiology at Medical Arts PET/CT, 410-918-3520, Gabriel Soudry, M.D., Medical Director, 443-777-7492
This case and previous cases can be seen at www.petcases.com
www.snm.org/PET 3
PET in the News
The international literature on PET and PET/CT continues to grow at a pace that challenges both
researchers and clinicians. The media has recognized the value of PET and PET/CT and regularly
features advances in research and technology in the news. In each issue, the PET COE Newsletter
presents a tomographic slice of the breadth of PET media coverage that appears in publications
around the world. Additional news articles can be found online at www.snm.org under
“MI: Making a Difference.”
Abnormal Metabolic Brain Networks in Tourette Syndrome
YahooNews.com
http://news.yahoo.com/s/prweb/20110327/bs_prweb/
prweb8235763_1
FDA Asks for Training Program on Lilly’s Amyvid
BusinessWeek.com
http://www.businessweek.com/ap/financialnews/D9M1MMKG0.
htm
PET Imaging in Adults With Down Syndrome Feasible, Revealing
Medscape.com
http://www.medscape.com/viewarticle/739457
NCCN and SNM Pool Expertise to Advance Oncology Imaging
Research
ImagingEconomics.com
http://www.imagingeconomics.com/techedge/2011-03-16_01.asp
Preclinical To Clinical: 18F-FLT PET Imaging Moving From
Mice To Men
MolecularImaging.net
http://www.mydigitalpublication.com/article/
Preclinical+To+Clinical%3A+18F-FLT+PET+Imaging+Moving+
From+Mice+To+Men/660914/0/article.html
PEM tops whole-body PET for assessing extent of cancer
AuntMinnie.com
http://www.auntminnie.com/index.aspx?d=1&sec=sup&sub=wom
&pag=dis&ItemID=94432
Lung Cancer Imaging in the Era of Molecular Medicine
HealthImaging.com
http://www.healthimaging.com/index.php?option=com_articles&
view=article&id=26653&division=hiit
The Mere Sight, Smell of Food Hikes Dopamine Levels in Binge
Eaters
YahooNews.com
http://in.news.yahoo.com/mere-sight-smell-food-hikes-dopaminelevels-binge-20110301-025900-378.html
PET/MRI Works for Detecting Head and Neck Tumors
AuntMinnie.com
http://www.auntminnie.com/index.aspx?d=1&d=1&sec=sup&sub
=mol&pag=dis&ItemID=94341&wf=4226
Cellphone Use Tied to Changes in Brain Activity
NYTimes.com
http://well.blogs.nytimes.com/2011/02/22/cellphone-use-tied-tochanges-in-brain-activity/?smid=tw-nytimeshealth&seid=auto
FDG-PET Elucidates Link between Periodontal Disease and
Carotid Plaque
HealthImaging.com
http://www.healthimaging.com/index.php?option=com_articles&a
rticle=26368&publication=10&view=portals
Why Women Get Anxious at that ‘Time of the Month’
NewScientist.com
http://www.newscientist.com/article/dn20122-why-women-getanxious-at-that-time-of-the-month.html
4 PET Center of Excellence Newsletter/2011.2
FDA Clears Nanoparticle for Human Cancer Imaging
MolecularImaging.com
http://www.molecularimaging.net/index.php?option=com_articles
&article=26092&publication=131&view=portals
JNM: Preclinical Imaging of Atherosclerosis, Vulnerable Plaque
Shows Promise
HealthImaging.com
http://www.healthimaging.com/index.php?option=com_articles&
view=article&id=26872:jnm-preclinical-imaging-of-atherosclerosis-vulnerable-plaque-shows-promise&division=hiit
Men with type 2 diabetes are more likely to suffer cardiovascular
complications than women
EndocrineWeb.com
http://www.endocrineweb.com/news/type-2-diabetes/5749-mentype-2-diabetes-are-more-likely-suffer-cardiovascular-complications-wo
PET-CT Scan Preferred in the Diagnosis of Mesothelioma
Asbestos.com
http://www.asbestos.com/news/2011/05/13/pet-ct-scan-preferredin-the-diagnosis-of-mesothelioma/
FEC-PET/CT helps direct radiation to prostate tumors
AuntMinnie.com
http://www.auntminnie.com/index.aspx?sec=sup&sub=mol&pag=
dis&ItemID=95227
C Dots Give Doctors Eyes for Cancer
The Cornell Daily Sun
http://www.cornellsun.com/section/science/content/2011/05/04/cdots-give-doctors-eyes-cancer
Speaks Out
on PET
Improved Lesion Detection with Time-of-Flight PET Scans Affirmed
Greatest Gains Seen in Largest Patients and Shortest Studies
For the first time, quantitative—not qualitative—data analysis
has demonstrated that time-of-flight (TOF) positron emission
tomography (PET) scans can improve cancer detection. Research
published in the March issue of The Journal of Nuclear Medicine
shows that oncologic TOF fluorodeoxyglucose (FDG) PET scans
yielded significant improvements in lesion detection of lung and
liver cancers over all contrasts and body mass indexes.
Conventional PET scans create images by detecting gamma
rays produced by radioisotopes that are injected into the body.
Although these conventional scans track where the gamma rays go,
they don’t consider the time it takes for each gamma ray to reach
the detector. TOF PET scans do take into account the travel time,
which results in improved image signal-to-noise.
“We aimed to objectively quantify the improvement in lesion
detection that can be achieved with whole-body TOF FDG PET,”
said Joel S. Karp, one of the authors of the study “Improvement
in Lesion Detection with Whole-Body Oncologic Time-of-Flight
PET.” “In contrast with previously published studies that reported
comparison of TOF and non-TOF PET using simulated data or
measured data with physical phantoms, this study used wholebody patient data in order to encompass a large range of realistic
activity distributions and patient body types.”
To create a lesion-present clinical study while ensuring perfect
knowledge of the presence and location of each lesion, 10-mm
spheric lesions were added to disease-free bed positions, yielding
fused lesion-present studies. These studies appropriately corrected
for the body’s attenuation so that the presence or absence of the
lesions was similar to that of actual patient studies.
TOF PET scans were conducted, and researchers used a numeric
observer—as opposed to a human observer—to rapidly detect a
large number of conditions. The TOF PET images were compared
to conventional PET images (the same data reconstructed without
TOF information) to determine improvement in lesion detection
as a function of lesion location, scan time, contrast and body mass
index.
Improved lesion detection was observed in the TOF PET scans,
with the greatest gains achieved in the shortest-acquisition studies
and in the subjects with a BMI of 30 or more. Also of note—the
greatest gain in performance was achieved at the lowest lesion
contrast and the smallest gain in performance at the highest lesion
contrast.
Nuclear medicine technologists and physicians may be able to
take advantage of the gain achieved with TOF PET to reduce scanning time, therefore increasing patient comfort and minimizing
patient motion. They may also be able to reduce the injected radiopharmaceutical dose, thereby reducing the exposure of patients and
health professionals to radiation.
Authors of the scientific article, “Improvement in Lesion Detection with Whole-Body Oncologic Time-of-Flight PET” include:
Georges El Fakhri and Cathryn M. Trott, Department of Radiology, Division of Nuclear Medicine and Molecular Imaging,
Harvard Medical School and Massachusetts General Hospital,
Boston, Mass.; and Suleman Surti, Joshua Scheuermann and Joel
S. Karp, Department of Radiology, University of Pennsylvania,
Philadelphia, Pa.
Welcome to the New PCOE President
The PCOE is pleased to welcome Eric M. Rohren MD, PhD,
as its 2011-12 president. Having served most recently as vicepresident and as a longtime member of the center, Rohren brings a
great deal of experience to his post.
Rohren is section chief of PET/CT and section chief ad interim
of Clinical Nuclear Medicine at The University of Texas M. D.
Anderson Cancer Center in Houston, Texas. Rohren received his
medical degree from Mayo Medical School, and his doctorate
degree in Immunology from Mayo Graduate School in Rochester,
Minn. He completed residency training in diagnostic radiology
and fellowship training in nuclear medicine and PET at Duke
University.
Rohren is co-chair of the Outreach Committee for SNM and
chair of the Nuclear Medicine and Radiologist Working group of
the SNM PET Utilization Task Force. He is a director and the secretary treasurer of the American Board of Nuclear Medicine, and is
chair of the Education Committee for the ACR’s Nuclear Medicine
Commission. He speaks nationally and internationally on clinical
applications of PET/CT, and is a frequent instructor on CT and
PET/CT interpretation at SNM workshops.
Rohren has been reading nuclear medicine, PET, and PET/CT
studies since 1997 and has a special interest in the complementary
roles of functional and anatomic imaging in the assessment of
malignancy. He has worked extensively on the issue of PET/CT
reporting, and has developed guidelines for report structure and
content through his work with the PET Utilization Task Force. His
research activities include non-FDG imaging of cancer, such as the
use of 18F-fluorothymidine to assess early treatment response.
www.snm.org/PET 5
(President. Continued from page 1.)
ers. Will they attend the annual meetings of SNM for continuing education and
other professional activities? The answer is yes if SNM grows with the field
and meets their needs. As a result of the Bench to Bedside molecular imaging
campaign, SNM has been very successful in incorporating molecular imaging
throughout the activities of the society. SNM members are now being asked to
consider changing the name of the society to the Society of Nuclear Medicine
and Molecular Imaging. The proposed name acknowledges the importance of
nuclear medicine—including therapy—and indicates who we are and where
we are headed.
SNM has formed a 2020 Task Force to look at the challenges and opportunities that lie ahead. The task force members include nuclear medicine physicians and radiologists, as well as scientists, pharmacists, technologists and
industry representatives. The task force will identify scenarios for 2020, define
the actions and identity the uncontrollable external events that would increase
the likelihood of each scenario, and develop a plan for SNM that would maximize the likelihood of the best scenario.
Looking forward to the future in terms of the PET Center of Excellence,
new tracers in development will expand clinical practice beyond FDG and
myocardial perfusion imaging. The PET Center of Excellence has focused
on PET/CT, but will need to broaden its goals to include PET/MR. The lead
article in this newsletter by Drew A. Torigian, MD, MA, on PET/MR is a look
to future. We have a lot of work to do to meet the challenges and opportunities
that lie ahead.
pet center of excellence newsletter
The PET Center of Excellence Newsletter is a quarterly
member information service published under the
direction of the PET COE leadership and SNM.
PCOE Newsletter Editorial Board
François Bénard, MD
[email protected]
Hossein Jadvar, MD, PhD, MPH, MBA, Editor
[email protected]
Gabriel Soudry, MD
[email protected]
Jian (Michael) Yu, MD
[email protected]
PCOE Board of Directors
Eric M. Rohren, MD, PhD
President
Hossein Jadvar, MD, PhD, MPH, MBA
Vice President
Heiko Schoder, MD
Secretary/Treasurer
George M. Segall, MD
Immediate Past President
Ryan Niederkohr, MD
Lalitha Ramanna, MD
(PET/MRI. Continued from page 2.)
quantitative assessment of the bone marrow in normal and abnormal states.49, 50
Summary
PET/MRI offers the potential for a powerful “one-stop shop” combination of
structural, functional and molecular imaging technologies that may be superior
to PET/CT, PET alone or MRI alone for certain clinical applications. Future
research to evaluate the most appropriate clinical applications of PET/MRI
based on diagnostic performance, technical feasibility, practicality, and cost
relative to existing diagnostic techniques will therefore be required before
standard clinical PET/MRI becomes a reality.
For a complete listing of references, please visit http://interactive.snm.org/
index.cfm?PageID=10706.
Bennett Greenspan, MD
John O. Prior, PhD MD
Ruth Tesar, CNMT, RT(N)
Frederic H. Fahey, DSc
Gary Dillehay, MD
SNM Chief Executive Officer
Virginia Pappas, CAE
Managing Editor
Susan Martonik
Graphic Designer
Laura Mahoney
6 PET Center of Excellence Newsletter/2011.2