Mapping tumor habitats in isocitrate dehydrogenase -wild type glioblastoma: Integrating MRI, pathologic, and RNA data from the Ivy Glioblastoma Atlas Project

Abstract

Background. The goal of the study was to spatially validate intratumoral subregions (tumor habitat) using physiologic magnetic resonance imaging (MRI) on the pathology of the isocitrate dehydrogenase (IDH)-wild-type whole-glioblastoma sample. Methods. Data from 20 patients (168 slides) were obtained from the Ivy Glioblastoma Atlas Project. On MRI, tumor habitats were defined using voxel-wise clustering of the apparent diffusion coefficient and cerebral blood volume maps for contrast-enhancing lesions (CEL) and non-enhancing lesions (NEL). On pathology slides, normalized areas of leading-edge, infiltrating tumor (IT), cellular tumor (CT), hypervascular lesion (CThypervascular), and perinecrotic lesion (CTperinecrotic) were obtained. Gross specimen was coregistered on MRI and correlation between pathology-MRI habitats was calculated. RNA sequencing of 67 samples was assessed using 4 Neftel subtypes and further correlated with pathology. Results. Six tumor habitats were identified: hypervascular, hypovascular cellular, and hypovascular hypocellular habitats for CEL and NEL. CT was correlated with hypovascular cellular habitat in CEL (r = 0.238, P = .005). IT was correlated with hypovascular cellular habitat in NEL (r = 0.294, P = .017). CThypervascular was correlated with hypervascular habitat in NEL (r = 0.195, P = .023). CTperinecrotic was correlated with imaging necrosis (r = 0.199, P = .005). Astrocyte-like subtypes were correlated with IT (r = 0.256, P < .001), while mesenchymal-like subtypes were correlated with CTperinecrotic area (r = 0.246, P < .001). Conclusions. Pathologically matched tumor subregions were CT with hypovascular cellular habitat in CEL and infiltrative tumor with hypovascular cellular habitat in NEL. Identification of the most aggressive, as well as infiltrative tumor portion, can be achieved using noninvasive MRI tumor habitats.