Prediction of oligodendroglial tumor subtype and grade using perfusion weighted magnetic resonance imaging

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Object

Treatment of patients with oligodendrogliomas relies on histopathological grade and characteristic cytogenetic deletions of 1p and 19q, shown to predict radio- and chemosensitivity and prolonged survival. Perfusion weighted magnetic resonance (MR) imaging allows for noninvasive determination of relative tumor blood volume (rTBV) and has been used to predict the grade of astrocytic neoplasms. The aim of this study was to use perfusion weighted MR imaging to predict tumor grade and cytogenetic profile in oligodendroglial neoplasms.

Methods

Thirty patients with oligodendroglial neoplasms who underwent preoperative perfusion MR imaging were retrospectively identified. Tumors were classified by histopathological grade and stratified into two cytogenetic groups: 1p or 1p and 19q loss of heterozygosity (LOH) (Group 1), and 19q LOH only on intact alleles (Group 2). Tumor blood volume was calculated in relation to contralateral white matter. Multivariate logistic regression analysis was used to develop predictive models of cytogenetic profile and tumor grade.

Results

In World Health Organization Grade II neoplasms, the rTBV was significantly greater (p < 0.05) in Group 1 (mean 2.44, range 0.96–3.28; seven patients) compared with Group 2 (mean 1.69, range 1.27–2.08; seven patients). In Grade III neoplasms, the differences between Group 1 (mean 3.38, range 1.59–6.26; four patients) and Group 2 (mean 2.83, range 1.81–3.76; 12 patients) were not significant. The rTBV was significantly greater (p < 0.05) in Grade III neoplasms (mean 2.97, range 1.59–6.26; 16 patients) compared with Grade II neoplasms (mean 2.07, range 0.96–3.28; 14 patients). The models integrating rTBV with cytogenetic profile and grade showed prediction accuracies of 68 and 73%, respectively.

Conclusions

Oligodendroglial classification models derived from advanced imaging will improve the accuracy of tumor grading, provide prognostic information, and have potential to influence treatment decisions.

Abbreviations used in this paper:ASL = arterial spin labeling; CI = confidence interval; DSC = dynamic susceptibility contrast; dUTP = deoxyuridine triphosphate; FISH = fluorescence in situ hybridization; FLAIR = fluid attenuated inversion recovery; LOH = loss of heterozygosity; MR = magnetic resonance; PCR = polymerase chain reaction; ROI = region of interest; rTBF = relative tumor blood flow; rTBV = relative tumor blood volume; VEGF = vascular endothelial growth factor; WHO = World Health Organization; 18FDG = 18fluorodeoxyglucose.

Article Information

Address reprint requests to: Donald M. O'Rourke, M.D., Department of Neurosurgery, Silverstein 3, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, Pennsylvania 19104. email: donald.orourke@uphs.upenn.edu.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Florescence in situ hybridization and PCR techniques for determining the tumor cytogenetic subtype. A: The FISH signals from four cells evaluated with a Zeiss Axioplan fluorescent microscope demonstrate one normal cell with two 19p (green) and two 19q (red) alleles and three oligodendroglioma tumor cells with 19q deletion. B: A 1.5% agarose gel of PCR products stained with ethidium bromide shows deletion of 1p (white arrows) and 19q (black arrows) micro-satellite markers in oligodendroglial tumor (lane on right of each microsatellite pair) compared with normal brain tissue (lane on left). Due to the infiltrative nature of these tumors, some normal brain tissue contaminates the tumor specimen, causing a low level of PCR amplification and a faint band.

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    Box-and-whisker plots. A: Significant difference in rTBV of all low-grade oligodendroglial neoplasms compared with all high-grade tumors. *p < 0.05. B: There is no significant difference in rTBV between all oligodendroglial neoplasms of Group 1 compared with those of cytogenetic Group 2. The asterisk and open circle indicate outlying rTBV values. C: There is a significant difference in rTBV of Group 1 compared with Group 2 in low-grade oligodendroglial tumors, but no significant difference in high-grade tumors between Groups 1 and 2. *p < 0.05.

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    A–H: Matched perfusion MR and FLAIR images obtained in a patient with 1p/19q LOH low-grade oligodendroglioma in the left frontal lobe. Perfusion-weighted MR images demonstrating increased rTBV within three ROIs of maximum signal intensity (D and F). Care is taken to avoid normal cerebral vasculature. I: Photomicrograph depicting typical low-grade oligodendroglioma characteristics. H & E, original magnification × 10.

  • View in gallery

    A–H: Matched perfusion MR and FLAIR images of patient with 1p/19q-intact low-grade oligodendroglioma in the left frontoparietal lobe. Perfusion-weighted MR images demonstrating minimal increase of rTBV within three ROIs of maximum signal intensity (D and F). Care is taken to avoid normal cerebral vasculature. I: Photomicrograph depicting typical low-grade oligodendroglioma characteristics. H & E, original magnification × 10.

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