Feasibility of Time-Dependent Diffusion MRI-Based Indicators for Identifying MGMT Promoter Methylation in High-Grade Gliomas

Motivation: High-grade gliomas (HGGs) require accurate diagnosis of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, which requires invasive biopsies. Therefore, non-invasive diagnostic alternatives are needed. Goal(s): We aimed to assess the feasibility of using time-dependent diffusion MRI to differentiate between methylated and unmethylated MGMT promoters in HGGs. Approach: We used pulsed and oscillating gradient sequences in diffusion MRI to measure microstructural indicators, such as intracellular volume fraction and cellularity, in patients with HGGs. Results: Time-dependent diffusion MRI revealed significant differences between HGGs with methylated vs unmethylated MGMT, providing a highly accurate diagnostic model based on intracellular volume fraction and cellularity. Impact: Our findings may help enabling non-invasive diagnostics for patients with HGGs by providing reliable prognostic tools and may inspire further research into MRI-based techniques for characterizing tumors as well as help guide clinical decision-making for patients unsuitable for biopsy.