Distinct Spatiotemporal Patterns of White Matter Hyperintensity Progression

White matter hyperintensity (WMH), a key imaging biomarker for brain health, is common in the general population and has prognostic implications for stroke. Using a multicenter MRI dataset of 9,719 stroke patients plus the UK Biobank (n = 36,210 low- and high-risk controls), we employed Subtype and Stage Inference (SuStaIn) modeling and identified three distinct WMH progression subtypes: fronto-parietal (T1), radial (T2), and temporo-occipital (T3). Longitudinal validation confirmed that this classification was stable in the majority of cases. There were three distinct profiles: i) T1 showed delayed WMH onset and more hypertension, while T3 had more atrial fibrillation and coronary heart disease; ii) T1 and T2 were linked to small vessel occlusion, while T3 was linked to cardioembolism; iii) T1 had higher 1-year ischemic recurrence, while T3 showed a higher incidence of early (< 3 weeks) neurological deterioration by symptomatic hemorrhagic transformation and poorer 3-month outcomes. These results were consistent with and complement total or regional Fazekas scale-related findings. We also observed that i) the spatiotemporal patterns of WMH progression in high-risk controls closely paralleled those observed in stroke patients, and ii) distinct stage distributions between the groups enabled greater discriminatory power, compared to crude WMH volume measures, for distinguishing stroke patients from high-risk controls. In conclusion, this new WMH subtyping-staging model can reliably capture WMH progression, demographic profiles, and vascular risk factors, offering improved predictive power for post-stroke outcomes while showing a potential to predict stroke occurrence.