Advanced Distance-Resolved Evaluation of the Perienhancing Tumor Areas with FLAIR Hyperintensity Indicates Different ADC Profiles byMGMTPromoter Methylation Status in Glioblastoma

Whether differences in the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status of glioblastoma (GBM) are reflected in MRI markers remains largely unknown. In this work, we analyze the ADC in the perienhancing infiltration zone of GBM according to the corresponding MGMT status by using a novel distance-resolved 3D evaluation. One hundred one patients with IDH wild-type GBM were retrospectively analyzed. GBM was segmented in 3D with deep learning. Tissue with FLAIR hyperintensity around the contrast-enhanced tumor was divided into concentric distance-resolved subvolumes. Mean ADC was calculated for the 3D tumor core and for the distance-resolved volumes around the core. Differences in group mean ADC between patients with MGMT promoter methylated (mMGMT, n = 43) and MGMT promoter unmethylated (uMGMT, n = 58) GBM was analyzed with Wilcoxon signed rank test. For both mMGMT and uMGMT GBM, mean ADC values around the tumor core significantly increased as a function of distance from the core toward the periphery of the perienhancing FLAIR hyperintensity (approximately 10% increase within 5 voxels with P < 001). While group mean ADC in the tumor core was not significantly different, the distance-resolved ADC profile around the core was approximately 10% higher in mMGMT than in uMGMT GBM (P < 10-8 at 5 voxel distance from the tumor core). Distance-resolved volumetric ADC analysis around the tumor core reveals tissue signatures of GBM imperceptible to the human eye on conventional MRI. The different ADC profiles around the core suggest epigenetically influenced differences in perienhancing tissue characteristics between mMGMT and uMGMT GBM.