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Quantitative Intracerebral Hemorrhage Localization. BACKGROUND AND PURPOSE: The location of intracerebral hemorrhage (ICH) is currently described in a qualitative way; we provide a quantitative framework for estimating ICH engagement and its relevance to stroke outcomes. METHODS: We analyzed 111 patients with ICH from the Minimally Invasive Surgery Plus Recombinant-Tissue Plasminogen Activator for Intracerebral Evacuation (MISTIE) II clinical trial. We estimated ICH engagement at a population level using image registration of computed tomographic scans to a template and a previously labeled atlas. Predictive regions of National Institutes of Health Stroke Scale and Glasgow Coma Scale stroke severity scores, collected at enrollment, were estimated. RESULTS: The percent coverage of the ICH by these regions strongly outperformed the reader-labeled locations. The adjusted R(2) almost doubled from 0.129 (reader-labeled model) to 0.254 (quantitative location model) for National Institutes of Health Stroke Scale and more than tripled from 0.069 (reader-labeled model) to 0.214 (quantitative location model). A permutation test confirmed that the new predictive regions are more predictive than chance: P<0.001 for National Institutes of Health Stroke Scale and P<0.01 for Glasgow Coma Scale. CONCLUSIONS: Objective measures of ICH location and engagement using advanced computed tomographic imaging processing provide finer, objective, and more quantitative anatomic information than that provided by human readers. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00224770.