Study design and histopathologic review of the imaging-based high-grade serous ovarian cancer areas. (A) Phenotypically distinct areas of a high-grade serous ovarian cancer (HGSOC) were identified by k-means clustering of imaging features derived from magnetic resonance imaging (MRI) and positron emission tomography (PET)/computed tomography. The distinct imaging habitats (labeled blue, yellow, and green) were sampled from the surgically removed primary HGSOC and metastatic implant using a three-dimensional (3D) mold. Half of each imaging-based tissue area was formalin-fixed paraffin-embedded for histopathologic review and immunohistochemical analysis, and the other half was flash-frozen for whole-exome sequencing analysis. (B) Micrographs of representative hematoxylin and eosin (H and E)–stained sections of the imaging-based HGSOC areas (top row), and immunohistochemical analysis of CD31, Ki-67, CA-IX, and HIF-1α. (C) Imaging features associated with the distinct color areas as defined by k-means clustering of standardized uptake values (SUV), diffusion coefficient (D), dynamic contrast-enhanced DCE parameter (Ktrans), and water volume fraction flowing through microvessels (f) are plotted on top, and the histopathologic features of the distinct imaging-based tumor areas are shown at the bottom. Color-coding according to the legend. DW, diffusion-weighted; FDG, 18F-fluorodeoxyglucose; TIL, tumor-infiltrating lymphocyte.