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Background Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by a heterogeneous and abnormal vascularity. Subtypes of vascular habitats within the tumor and edema can be distinguished: high angiogenic tumor (HAT), low angiogenic tumor (LAT), infiltrated peripheral edema (IPE), and vasogenic peripheral edema (VPE). Purpose To validate the association between hemodynamic markers from vascular habitats and overall survival (OS) in glioblastoma patients, considering the intercenter variability of acquisition protocols. Study Type Multicenter retrospective study. Population In all, 184 glioblastoma patients from seven European centers participating in the NCT03439332 clinical study. Field Strength/Sequence 1.5T (for 54 patients) or 3.0T (for 130 patients). Pregadolinium and postgadolinium‐based contrast agent‐enhanced T1‐weighted MRI, T2‐ and FLAIR T2‐weighted, and dynamic susceptibility contrast (DSC) T2* perfusion. Assessment We analyzed preoperative MRIs to establish the association between the maximum relative cerebral blood volume (rCBVmax) at each habitat with OS. Moreover, the stratification capabilities of the markers to divide patients into "vascular" groups were tested. The variability in the markers between individual centers was also assessed. Statistical Tests Uniparametric Cox regression; Kaplan–Meier test; Mann–Whitney test. Results The rCBVmax derived from the HAT, LAT, and IPE habitats were significantly associated with patient OS (P < 0.05; hazard ratio [HR]: 1.05, 1.11, 1.28, respectively). Moreover, these markers can stratify patients into "moderate‐" and "high‐vascular" groups (P < 0.05). The Mann–Whitney test did not find significant differences among most of the centers in markers (HAT: P = 0.02–0.685; LAT: P = 0.010–0.769; IPE: P = 0.093–0.939; VPE: P = 0.016–1.000). Data Conclusion The rCBVmax calculated in HAT, LAT, and IPE habitats have been validated as clinically relevant prognostic biomarkers for glioblastoma patients in the pretreatment stage. This study demonstrates the robustness of the hemodynamic tissue signature (HTS) habitats to assess the GBM vascular heterogeneity and their association with patient prognosis independently of intercenter variability. Level of Evidence: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1478–1486.

Advanced MRI and molecular markers have been raised as crucial to improve prognostic models for patients having glioblastoma (GBM) lesions. In particular, different MR perfusion based markers describing vascular intrapatient heterogeneity have been correlated with tumor aggressiveness, and represent key information to understand tumor resistance against effective therapies of these neoplasms. Recently, hemodynamic tissue signature (HTS) markers based on MR perfusion images have been demonstrated to be useful for describing the heterogeneity of GBM at the voxel level, as well as demonstrating significant correlations with the patient's overall survival. In this work, we analyze the abilities of these markers to improve the conventional prognostic models based on clinical, morphological, and demographic features. Our results, in both the regression and classification tests, show that inclusion of the HTS markers improves the reliability of prognostic models. The HTS method is fully automatic and it is available for research use at http://www.oncohabitats.upv.es.

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