Multi-Site Retrospective Analysis of Diffusion and Perfusion MRI Correlates to Glioma Characteristics Derived from Radio-Pathomic Maps

Abstract Introduction This study determines the relationship between diffusion and perfusion-based MRI signatures and radio-pathomic maps of tumor pathology in a large, multi-site cohort. Methods This study included perfusion imaging from pre-surgical relative cerebral blood volume (rCBV) images from the UPenn-GBM dataset and pre-surgical arterial spin labeling (ASL) imaging from the UCSF-PDGM dataset. Diffusion imaging included fractional anisotropy (FA) estimates derived from diffusion tensor imaging (DTI) for each subject from each institution. A previously validated autopsy-based model was applied to the structural images from each patient to generate quantitative radio-pathomic maps of cell density and extracellular fluid (ECF). Mean cell density, ECF density, FA, rCBV calculated from DSC imaging, and rCBF calculated from ASL were computed for each patient and statistically compared within contrast-enhancement (CE) and the non-enhancing peritumor FLAIR hyperintensity (FH). Results Both rCBV and ASL showed positive correlation with cell density within CE (rCBV: R=0.280, p<0.001; ASL: R=0.117, p=0.023). However, both perfusion metrics also showed no association with cell density within the FH region at the group level (rCBV: R=0.0162, p=0.731; ASL: R=-0.020, p=0.652). Negative correlations were observed between FA and ECF density across both CE and FH in both the UPenn-GBM (CE: r = -0.204, p<0.001, FH: r=-0.332, p<0.001) and the UCSF-PDGM (CE:r=-0.179, p<0.001, FH:-0.355, p<0.001). Additionally, a positive ASL-cell density association per subject within FH was associated with worse survival prognosis (HR=5.58, p=0.022). Discussion These results suggest that radio-pathomic maps of tumor pathology provide complementary information to other MR signatures that reveal prognostically valuable signatures of the non-enhancing tumor margin.