White Matter Hyperintensity Spatial Patterns Provide Clues About Underlying Disease

White matter hyperintensities (WMH) of presumed vascular origin are the most widely studied manifestations of cerebral small vessel disease on brain MRI.1 Despite the growing body of literature on the imaging characteristics, spatial and temporal trajectories, and clinical correlates of WMH, there remain considerable unknowns regarding their underlying pathophysiology.2 Indeed, insights from radiological-histological correlation studies have underscored the heterogeneous nature of WMH pathology, which seems to differ by the brain region studied.3 Multiple approaches have been proposed to further investigate the spatial patterns in which WMH present and determine their association with disease and risk factors. These are often either hypothesis-driven, for example, by differentiating WMH based on their underlying vascular territory,4 or data-driven using more localized, voxel-wise approaches.5 As such, there has been an unmet need for established data-driven approaches to assess global topological patterns of WMH on brain MRI.