Glioblastoma multiforme regional genetic and cellular expression patterns: Influence on anatomic and physiologic MR imaging

Purpose: To determine whether magnetic resonance (MR) imaging is influenced by genetic and cellular features of glioblastoma multiforme (GBM) aggressiveness. Materials and Methods: In this HIPAA-compliant institutional review board-approved study, multiple enhancing and peritumoral nonenhancing stereotactic neurosurgical biopsy samples from treatment-naïve GBMs were collected prospectively, with guidance from cerebral blood volume (CBV) MR imaging measurements. By using monoclonal antibodies, tissue specimens were examined for microvascular expression, hypoxia, tumor and overall cellular density, and histopathologic features of GBM aggressiveness. Genetic expression patterns were investigated with RNA microarrays. Imaging and histopathologic variables were compared with the Welch t test and Pearson correlations. Microarray analysis was performed by using false discovery rate (FDR) statistics. Results: Tumor biopsy of 13 adult patients yielded 16 enhancing and 14 peritumoral nonenhancing specimens. Enhancing regions had elevated relative CBV and reduced relative apparent diffusion coefficient (ADC) measurements compared with peritumoral nonenhancing biopsy regions (P < .01). A positive correlation was found between relative CBV and all histopathologic features of aggressiveness (P < .04). An inverse correlation was found between relative ADC and all histopathologic features of aggressiveness (P < .05). RNA expression patterns between tumor regions were found to be significantly different (FDR < 0.05), with hierarchical clustering by biopsy region only. Conclusion: These findings suggest MR imaging is significantly influenced by GBM genetic and cellular biologic features of aggressiveness and imply physiologic MR imaging may be useful in pinpointing regions of highest malignancy within heterogeneous tissues, thus facilitating histologic grading of primary glial brain tumors.