Recurrence of glioblastoma is associated with elevated microvascular transit time heterogeneity and increased hypoxia

Abstract

Dynamic susceptibility contrast (DSC) perfusion MRI provide information about differences in macro- and microvasculature when executed with gradient-echo (GE; sensitive to macrovasculature) and spin-echo (SE; sensitive to microvasculature) contrast. This study investigated whether there are differences between macro- and microvascular transit time heterogeneity (MVTH and µVTH) and tissue oxygen tension (PO2 mit ) in newly-diagnosed and recurrent glioblastoma. Fifty-seven patients with glioblastoma (25 newly-diagnosed/32 recurrent) were examined with GE- and SE-DSC perfusion sequences, and a quantitative blood-oxygen-level-dependent (qBOLD) approach. Maps of MVTH, µVTH and coefficient of variation (MCOV and µCOV) were calculated from GE- and SE-DSC data, respectively, using an extended flow-diffusion equation. PO2 mit maps were calculated from qBOLD data. Newly-diagnosed and recurrent glioblastoma showed significantly lower (P ≤ 0.001) µCOV values compared to both normal brain and macrovasculature (MCOV) of the lesions. Recurrent glioblastoma had significantly higher µVTH (P = 0.014) and µCOV (P = 0.039) as well as significantly lower PO2 mit values (P = 0.008) compared to newly-diagnosed glioblastoma. The macrovasculature, however, showed no significant differences. Our findings provide evidence of microvascular adaption in the disorganized tumor vasculature for retaining the metabolic demands in stress response of therapeutically-uncontrolled glioblastomas. Thus, µVTH and PO2 mit mapping gives insight into the tumor microenvironment (vascular and hypoxic niches) responsible for therapy resistance.