Physiological MRI of Microvascular Architecture, Neovascularization Activity, and Oxygen Metabolism Facilitate Early Recurrence Detection in Patients with IDH-mutant WHO Grade 3 Glioma

Purpose This study aimed to determine the diagnostic performance of physiological MRI biomarkers including microvascular perfusion and architecture, neovascularization activity, tissue oxygen metabolism, and tension for recurrence detection of IDH-mutant WHO grade 3 glioma. Methods Sixty patients with IDH-mutant WHO grade 3 glioma who received overall 288 follow-up MRI examinations at 3 Tesla after standard treatment were retrospectively evaluated. A conventional MRI protocol was extended with a physiological MRI approach including vascular architecture mapping and quantitative blood-oxygen-level-dependent imaging which required 7 min extra data acquisition time. Custom-made MATLAB software was used for the calculation of MRI biomarker maps of microvascular perfusion and architecture, neovascularization activity, tissue oxygen metabolism, and tension. Statistical procedures included receiver operating characteristic analysis. Results Overall, 34 patients showed recurrence of the WHO grade 3 glioma; of these, in 15 patients, recurrence was detected one follow-up examination (averaged 160 days) earlier by physiological MRI data than by conventional MRI. During this time period, the tumor volume increased significantly ( P = 0.001) on average 7.4-fold from 1.5 to 11.1 cm 3 . Quantitative analysis of MRI biomarkers demonstrated microvascular but no macrovascular hyperperfusion in early recurrence. Neovascularization activity (AUC = 0.833), microvascular perfusion (0.682), and oxygen metabolism (0.661) showed higher diagnostic performance for early recurrence detection of WHO grade 3 glioma compared to conventional MRI including cerebral blood volume (0.649). Conclusion This study demonstrated that the targeted assessment of microvascular features and tissue oxygen tension as an early sign of neovascularization activity provided valuable information for recurrence diagnostic of WHO grade 3 glioma.