MRI-based habitats to quantify tumor microenvironment normalization in glioblastoma: validation with histology and transcriptomics

Motivation: The lack of in vivo and noninvasive biomarkers to quantify tumor microenvironment (TME) normalization hinders the evaluation of bevacizumab (BEV) therapy response in glioblastoma (GBM). Goal(s): To quantify TME normalization during BEV therapy in GBM by conventional and multiparametric MRI (mpMRI). Approach: The MRI-based habitats were generated by Gaussian mixture model in patient-derived GBM models. Spatial-paired analyses of MRI, histology, and single-cell RNA sequencing were performed to validate the effetiveness of habitats. Results: A total of eight habitats were generated to quantify TME normalization spatiotemporally. Habitat7 was strongly correlated with TME normalization-associated phenotypes including pericyte coverage, hypoxia and immune cell infiltration. Impact: We developed and validated a quantitative mpMRI-based biomarker to characterize TME normalization in GBM. This may provide a new in vivo approach for precise evaluation of BEV therapy response in GBM noninvasively.