Glioblastoma is highly heterogeneous in microstructure and vasculature, creating various tumor microenvironments among patients, which may lead to different phenotypes. The purpose was to interrogate the interdependence of microstructure and vasculature using perfusion and diffusion imaging and to investigate the utility of this approach in tumor invasiveness assessment. A total of 115 primary glioblastoma patients were prospectively recruited for preoperative magnetic resonance imaging (MRI) and surgery. Apparent diffusion coefficient (ADC) was calculated from diffusion imaging, and relative cerebral blood volume (rCBV) was calculated from perfusion imaging. The empirical copula transform was applied to ADC and rCBV voxels in the contrast-enhancing tumor region to obtain their joint distribution, which was discretized to extract second-order features for an unsupervised hierarchical clustering. The lactate levels of patient subgroups, measured by MR spectroscopy, were compared. Survivals were analyzed using Kaplan-Meier and multivariate Cox regression analyses. The results showed that three patient subgroups were identified by the unsupervised clustering. These subtypes showed no significant differences in clinical characteristics but were significantly different in lactate level and patient survivals. Specifically, the subtype demonstrating high interdependence of ADC and rCBV displayed a higher lactate level than the other two subtypes (P = .016 and P = .044, respectively). Both subtypes of low and high interdependence showed worse progression-free survival than the intermediate (P = .046 and P = .009 respectively). Our results suggest that the interdependence between perfusion and diffusion imaging may be useful in stratifying patients and evaluating tumor invasiveness, providing overall measure of tumor microenvironment using multiparametric MRI
