Hypoxia-targeted BOLD MRI signal heterogeneity as a complementary metric for glioblastoma characterization: a pilot study

PURPOSE: Hypoxia-targeted blood oxygen level-dependent (BOLD) MRI is an emerging non-contrast imaging technique for characterizing tumor biology in isocitrate dehydrogenase-wildtype glioblastoma. Beyond the magnitude of BOLD signal changes, signal heterogeneity may provide valuable information about tumor aggressiveness and microenvironmental complexity. The aim was to assess both the magnitude and heterogeneity of hypoxia-targeted BOLD signal changes across subregions of glioblastomas. METHODS: In this prospective pilot study, hypoxia-targeted BOLD MRI data from 12 patients with histopathologically confirmed glioblastoma were analyzed. Tumor subregions were defined using an automated segmentation framework (Oncohabitats) based on conventional MRI and dynamic susceptibility contrast (DSC) MR perfusion imaging. Voxel-wise BOLD signal changes were calculated within the following volumes of interest: highly angiogenic tumor (HAT), low angiogenic tumor (LAT), peritumoral edema, and mirrored contralateral control tissue (mCET). The magnitude of BOLD signal changes was assessed using median BOLD signal changes, while heterogeneity was quantified using interquartile ranges (IQR), and kernel density estimation-derived entropy. Friedman tests with Dunn post-hoc tests were used to assess parameter differences between the VOIs. RESULTS: HAT demonstrated the largest BOLD signal changes compared with LAT, edema, and mCET (all FDR-adjusted p ≤ 0.017). Heterogeneity metrics revealed significantly increased IQR and entropy in HAT compared with edema and mCET (all FDR-adjusted p < 0.008), with LAT showing intermediate values. CONCLUSION: Hypoxia-targeted BOLD MRI reveals both greater BOLD signal changes and elevated intratumoral heterogeneity in highly angiogenic and likely aggressive glioblastoma subregions. These findings suggest that heterogeneity metrics may provide complementary information to BOLD signal magnitude alone.