This study has elucidated a nuanced relationship between imaging habitats derived from MR images, clinical characteristics, and molecular data in a cohort of GBM patients. The present study implemented an automated methodology that parallels the traditional practice of a neuroradiologist by considering the totality of 3D imaging data (i.e. across multiple MR sequences) from each patient. This technique represents an advance in imaging-genomics. Whereas previous studies derived associated imaging features and genomic data from 2D imaging datasets [12, 29, 30], this study adopted a 3D approach, which is consistent with the progress of the field towards studying 3D image features [10, 31–34] for imaging-genomic analysis. Our approach utilized a multi-parametric representation of 3D image features derived from different imaging sequences overlaid upon each other to generate an imaging phenotype that predicts OS duration, after adjusting for clinical covariates.