Download EE-40: Prediction of Glioma Grade Based on

EE-40: Prediction of Glioma Grade Based on
Preoperative Imaging, Intraoperative ContrastEnhanced Ultrasound Compared to Perfusion
Magnetic Resonance Imaging
Noah Brauner, Mittul Gulati, Mark S. Shiroishi, Edward G. Grant, Ki-Eun Chang,
Joshua Bakhsheshian, Eisha Christian, Gabriel Zada and Ilya Lekht
Keck School of Medicine of the University of Southern California
Los Angeles, CA
Disclosures
- Off-Label Use:
-
This presentation describes the off-label use of an FDA-approved
microbubble ultrasound contrast agent (UCA) for the evaluation of
gliomatous brain tumors.
- Grant Support:
-
M.S.S. is supported in part by SC CTSI (NIH/NCRR/NCATS) Grant #
KL2TR000131 and Toshiba American Medical Systems.
Purpose
- Histopathologic grading of gliomas has important implications on patient
prognosis1.
- Currently, preoperative imaging with contrast-enhanced MRI and perfusion
MRI can be helpful to determine glioma grade prior to resection.
- Intraoperative contrast enhanced ultrasound (iCEUS) offers an adjunct to MRI
and may be more accurate at assessing glioma grade allowing for more
precise tumor sampling and accurate patient prognosis2,3.
Case Report
- BE, a 71 year old female with history of prior resection of a right frontal
atypical meningioma presents for a routine follow up MRI.
Imaging Findings: Initial Follow-up MRI
Axial T2-weighted (A) and
FLAIR (B) images at the level
of the third ventricle show
enlargement of the right medial
temporo-occipital gyrus with
corresponding increased
T2/FLAIR signal (arrows) and
mild mass effect on the right
lateral ventricle. No significant
enhancement was noted on
post contrast images (not
pictured).
A
B
Imaging Findings: Perfusion MRI
Relative cerebral blood flow
(rCBV) color map (A) with region
of interest (ROI) signal intesnitytime curves (B) show increased
rCBV in the anterior portion of the
right temporo-occipital mass with
1.6x rCBV compared to the
contralateral normal white matter,
suggestive of low grade glioma4.
B
A
Imaging Findings: iCEUS -How We Do It
Schematic of Intraoperative Contrast Enhanced Ultrasound (iCEUS)
UCA structure: Lipid shell with
internal gas
Ultrasound Contrast Agent (UCA):
-45 sec agitation
-0.3 ml IV bolus
-followed by 10 ml NS flush
Lungs
Venous system
Heart
Pulmonary artery
UCA lipid shell breaks
-Shell metabolized
-Inner gas released into
bloodstream and exhaled
Lungs
Venous system
Ultrasound Machine
Brain:
Lesion of Interest
Pulmonary vein
UCA particle size: 1-5 um
t1/2 = ~1.3 min
Pulmonary capillary size:
~5.5 um
Pulse Inversion Imaging
Mechanical index < 0.8
Cine images obtained
Arterial system
Heart
Imaging Findings: Intraoperative Contrast Enhanced
Ultrasound (iCEUS)
- Based on prior work by Prada et al, different histopathologic grades of
gliomas demonstrate distinct contrast enhancement patterns2.
Arterial Phase *
Time to CEUS
Peak (TTP)*
Venous Phase*
Contrast
Enhancement
Low Grade Glioma
15 sec
20 sec
30 sec
Mild
Anaplastic Glioma
10 sec
15 sec
20-25 sec
Mild-High
Glioblastoma Multiforme
2-3 sec
5 sec
10 sec
High
*time measured from ultrasound contrast seen in the main adjacent parenchymal arteries.
Imaging Findings: iCEUS
iCEUS cine clip and corresponding Time-Intensity Curve (TIC) of the tumor (blue square/curve) compared to
normal brain parenchyma (orange square/curve) show fast time-to-peak (TTP) of 12 sec, steep wash-in slope
(WIS) and venous phase wash-out of the tumor, suggestive of high grade anaplastic glioma2 and discordant with
perfusion MRI.
Final Pathologic Diagnosis
Anaplastic Astrocytoma (WHO grade III)
Imaging findings: Companion Case - MRI
52 year old male with history of
prior GBM status post resection
and radiation therapy. Axial
FLAIR (A) and T1-weighted post
contrast (B) sequences show an
enhancing mass in the right
fronto-temporal lobe with
surrounding edema-like signal.
MRI perfusion scan with rCBV
color map (C) and ROI perfusion
curves (D) show a rCBV 2.5x
higher than the contralateral
normal parenchyma. Differential
considerations include recurrent
tumor versus radiation necrosis5.
A
C
B
D
Imaging Findings: iCEUS - Recurrence vs. Radiation
Necrosis
- Evaluation of radiation necrosis with iCEUS by Mattei and Prada et al 3,6
showed no significant contrast enhancement on iCEUS versus gliomas
which had characteristic enhancement patterns.
Arterial Phase *
Time to CEUS
Peak (TTP)*
Venous Phase*
Contrast
Enhancement
Low Grade Glioma
15 sec
20 sec
30 sec
Mild
Anaplastic Glioma
10 sec
15 sec
20-25 sec
Mild-High
Glioblastoma Multiforme
2-3 sec
5 sec
10 sec
High
Radiation Necrosis
none
none
none
none
*time measured from ultrasound contrast seen in the main adjacent parenchymal arteries.
Imaging Findings: Companion case - iCEUS
Side-by-side gray scale and iCEUS in the same patient
shows contrast first entering the feeding artery (arrow-A)
five seconds after injection (A). Peak enhancement occurs
in the tumor at ten seconds (B). A representative image
taken in the middle of the venous phase at 27 seconds (C)
shows draining veins (arrow-C). Contrast enhancement
pattern is compatible with recurrent GBM which was
confirmed on pathology. Radiation necrosis would be
expected to lack any significant enhancement.
A
B
C
Discussion
Advantages of iCEUS
- Visualization of dynamic tumor enhancement patterns.
- More accurate evaluation of vascular perfusion (UCAs are purely
intravascular agents and do not diffuse into interstitium).
- Differentiation of radiation necrosis from recurrent tumor
- UCAs are safe in renal failure and have extremely low adverse event rates7.
Discussion
Disadvantages of iCEUS
- Sonographic window limited by size/shape of cranial defect.
- Operator dependent.
- No current fusion imaging between iCEUS and CT/MRI
- Limited but growing amount of high quality evidence on the efficacy and utility
of this emerging modality
Discussion
Future Directions
- Differentiation of normal brain parenchyma from infiltrating gliomatous tissue
during and after resection to improve patient outcomes.
- Improved extent of resection = improved patient survival8
- Decreased normal parenchyma excision = decreased neurologic morbidity
- Guidance of tumor tissue sampling to highest grade areas (prevention of
inappropriate downgrading.)
- iCEUS guided ablative therapy for small intracranial lesions.
Summary
- Gliomatous tumors represent a wide spectrum of neoplasms and delineation
of these tumor’s histopathologic grade has important prognostic implications.
- MRI, and particularly MRI perfusion, is a useful tool in evaluation of glioma
grade pre-operatively but has its limitations.
- The development of iCEUS as a modality may offer an additional and
potentially more accurate way to evaluate glioma grade prior to resection.
- iCEUS has many other potential advantages which may further help in the
diagnosis and treatment of these devastating tumors.
- Future prospective studies are needed to determine iCEUS utility in predicting
tumor grade and how its predictive value compares to that of MRI perfusion
examinations.
References
1. Ostrom QT, Gittleman H, Liao P, Rouse C, Chen Y, Dowling J, et al: CBTRUS statistical report: primary brain and central nervous
system tumors diagnosed in the United States in 2007–2011. Neuro Oncol 16 (Suppl 4):iv1–iv63, 2014
2.Prada F, Mattei L, Del Bene M, Aiani L, Saini M, Casali C, et al: Intraoperative cerebral glioma characterization with contrast
enhanced ultrasound. BioMed Res Int 2014:484261, 2014
3. Prada F, Perin A, Martegani A, Aiani L, Solbiati L, Lamperti M, et al: Intraoperative contrast-enhanced ultrasound for brain tumor
surgery. Neurosurgery 74:542–552, 2014
4. Law M, Yang S, Wang H, et al. Glioma grading: sensitivity, specificity, and predictive values of perfusion MR imaging and proton MR
spectroscopic imaging compared with conventional MR imaging. AJNR Am J Neuroradiol 2003;24:1989–98.
5. Shah R, Vattoth S, Jacob R, et al. Radiation Necrosis in the Brain: Imaging Features and Differentiation from Tumor Recurrence.
Radiographics 32: 1343-1359, 2012
6. Mattei L, Prada F, Legnani F, et al. Differentiating brain radionecrosis from tumor recurrence: A role for contrast enhanced
ultrasound (CEUS)? Case report. Neuro Oncol. 16 (Suppl 2): ii84. 2014 (Abstract)
7. Piscaglia F, Bolondi L: The safety of Sonovue in abdominal applications: retrospective analysis of 23188 investigations. Ultrasound
Med Biol 32:1369–1375, 2006
8. Sanai N, Berger MS: Glioma extent of resection and its impact on patient outcome. Neurosurgery 62:753–764, 264–266, 2008