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Glial Tumor Grading and Outcome Prediction Using Dynamic Spin-Echo MR Susceptibility Mapping Compared with Conventional Contrast-Enhanced MR: Confounding Effect of Elevated rCBV of Oligodendroglimoas

Michael H. Leva, Yelda Ozsunara,d, John W. Hensona,c, Amjad A. Rasheeda, Glenn D. Baresta, Griffith R. Harsh, IVe, Markus M. Fitzekf, E. Antonio Chioccab, James D. Rabinova, Andrew N. Csavoyg, Bruce R. Rosena, Fred H. Hochbergc, Pamela W. Schaefera and R. Gilberto Gonzaleza

a Departments of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston
b Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston
c Neurology, Massachusetts General Hospital and Harvard Medical School, Boston
d Department of Radiology, Adnan Menderes University, School of Medicine, Aydin, Turkey
e Department of Neurosurgery, Stanford University School of Medicine, Palo Alto, CA
f University of Essen, Germany
g Radionics, Inc., Burlington, MA



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FIG 1. Scatterplot of maximum nCBV (mean normalized rCBV region-of-interest) values versus glial tumor grade. The degree of contrast enhancement on conventional T1-weighted MR images is indicated for each data point. Note that seven (41%) of the 17 high-grade tumors had absent or equivocal enhancement, whereas three (23%) of the 13 low-grade tumors had definite enhancement. At an nCBV cutoff value of 1.5 (horizontal line), no high-grade lesions were incorrectly classified as low grade (100% predictive value for excluding malignancy).



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FIG 2. 61-year-old man with grade II astrocytoma.

A and B, Axial T2-weighted (A) and contrast-enhanced T1-weighted (B) images demonstrate a mass (arrow) in the left medial temporal lobe that is hyperintense on the T2-weighted image and hypointense, nonenhancing on the T1-weighted image.

C, Correlative rCBV map shows diminished blood volume relative to both gray and white matter in this biopsy-proved low-grade astrocytoma.



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FIG 3. 39-year-old man with grade IV glioma.

A and B, Axial contrast-enhanced T1-weighted (A) and rCBV (B) images through the level of the lateral ventricles demonstrate an enhancing mass. There is elevated blood volume relative to both normal gray and white matter, consistent with biopsy-proved high-grade glioma (arrow). Note the decreased blood volume in the white matter immediately surrounding the lesion, secondary to the space-occupying effects of vasogenic edema.



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FIG 4. 65-year-old man with biopsy-proved low-grade oligodendroglioma.

A–C, Axial nonenhanced CT image through the frontal lobes (A), as well as axial contrast-enhanced T1-weighted (B) and rCBV (C) MR images through the same region, demonstrate a calcified left frontal mass (arrow in A). There is trace contrast enhancement and increased blood volume compared with the adjacent gray and white matter. The combination of calcification, relatively mild contrast enhancement, and increased rCBV is not uncommon for oligodendrogliomas of any grade.



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FIG 5. 29-year-old man with mixed malignant oligoastrocytoma.

AC, Axial T2-weighted (A), contrast-enhanced T1-weighted (B), and rCBV (C) MR images show a lesion in the anterior left mesial temporal lobe that is hyperintense on the T2-weighted image and minimally enhancing on the T1-weighted image. The lesion demonstrates intensely elevated blood volume relative to both gray and white matter (arrow in C).



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FIG 6. 65-year-old man with biopsy-proved anaplastic astrocytoma.

A and B, rCBV map (A) corresponds to the contrast-enhanced T1-weighted MR image (B). Despite only mild enhancement of this high-grade temporal lobe neoplasm on the T1-weighted image, the lesion demonstrates intensely elevated blood volume on the corresponding rCBV map (arrows).



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FIG 7. ROC curves generated by varying the nCBV cutoff values used to classify the tumor regions of interest (ROIs) shown in Fig 1 as low grade versus high grade. The left curve (diamond-shaped data points) describes the sensitivity and specificity values for low- versus high-grade astrocytomas only. The right curve (square data points) describes the sensitivity and specificity values for low- versus high-grade astrocytomas and oligodendrogliomas grouped together. Of note, the larger area under the left as compared with the right-shifted curve (proportional to accuracy) reflects the superior discriminatory ability of rCBV imaging in distinguishing low- from high-grade astrocytomas than in distinguishing low- from high-grade oligodendrogliomas. At a critical test cutoff value of nCBV = 1.5 for the right-shifted curve (as per Fig 1), sensitivity and specificity for distinguishing low- versus high-grade glial neoplasms are 0.96 and 0.60, respectively. TPF indicates true-positive fraction; FPF, false-positive fraction.



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FIG 8. Kaplan-Meir survival curves for the data shown in the Table. Left-shifted curves reflect poor survival, and right-shifted curves reflect good survival. The far left-shifted curve (blue) is for patients with enhancing, high-nCBV (>1.5) tumors; the adjacent left-shifted curve (red) is for patients with nonenhancing, high-nCBV tumors. The far right-shifted curves are for patients with low-nCBV (<1.5) tumors: the rightmost curve (green) is for patients with enhancing tumors and the adjacent curve (black) is for patients with nonenhancing tumors. Although the number of tumors studied was too low to establish a statistically significant difference between enhancement and nCBV as outcome predictors, these data suggest a strong trend toward nCBV being a stronger predictor of survival than is enhancement. Open circles indicate censored data (ie, patients still alive at the time of most recent follow-up.)



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FIG 9. 60-year-old woman with glioblastoma.

A and B, Contrast-enhanced T1-weighted (A) and rCBV (B) MR images show a heterogeneously enhancing anterior right temporal lobe mass. The entire mass, including regions of both minimal and maximal contrast enhancement, demonstrates homogeneously increased rCBV, consistent with biopsy proved high-grade glioma (arrow in B). The elevated blood volume extends even to tumor foci without significant contrast enhancement.