Voxel-Wise Map of Intracerebral Hemorrhage Locations Associated With Worse Outcomes

Prior studies on the clinical impact of intracerebral hemorrhage (ICH) location have used visual localization of hematomas to neuroanatomical structures. However, hematomas often cross neuroanatomical structure boundaries with inter-reviewer variability in visual localization. To address these limitations, we applied voxel-wise analysis to identify brain regions where ICH presence is independently predictive of worse outcomes. We included consecutive patients with acute spontaneous ICH from a comprehensive stroke center in a derivation cohort and validated the results in patients from the control arm of a multicenter clinical trial. Using general linear models, we created and publicly shared a voxel-wise map of brain regions where ICH presence was associated with higher 3-month modified Rankin Scale scores, independent of hematoma volume and clinical risk factors. We also determined the optimal overlap threshold between baseline hematoma and voxel-wise map to categorize ICH location into high versus low risk. Excluding those with missing variables, head computed tomography processing pipeline failure and poor scan quality, 559 of 780 patients were included in derivation (mean age, 69.3±14.5 years; 311 [55.6%] males) and 345 of 500 (mean age, 62.5±12.9 years; 206 [59.7%] males) in validation cohorts. In a voxel-wise analysis, ICH presence in deep white matter, thalami, caudate, midbrain, and pons was associated with worse outcomes. At the patient level, >22% overlap of baseline hematoma with voxel-wise map optimally binarized ICH location to high- versus low-risk categories. In both the derivation and validation cohorts, a high-risk ICH location was independently associated with worse outcomes (higher 3-month modified Rankin Scale score), after adjusting for patients' age, symptom severity at admission, baseline hematoma volume, and the presence of intraventricular hemorrhage, with adjusted odds ratios of 2 ([95% CI, 1.3-3.0] P=0.001) and 1.7 ([95% CI, 1.1-2.9] P=0.027), respectively. We created and publicly shared a voxel-wise map of brain regions where hematoma presence predicts worse outcomes, independent of volume and clinical risk factors.