Predictive modeling of hematoma expansion from non-contrast computed tomography in spontaneous intracerebral hemorrhage patients

Hematoma expansion is a consistent predictor of poor neurological outcome and mortality after spontaneous intracerebral hemorrhage (ICH). An incomplete understanding of its biophysiology has limited early preventative intervention. Transport-based morphometry (TBM) is a mathematical modeling technique that uses a physically meaningful metric to quantify and visualize discriminating image features that are not readily perceptible to the human eye. We hypothesized that TBM could discover relationships between hematoma morphology on initial Non-Contrast Computed Tomography (NCCT) and hematoma expansion. 170 spontaneous ICH patients enrolled in the multi-center international Virtual International Trials of Stroke Archive (VISTA-ICH) with time-series NCCT data were used for model derivation. Its performance was assessed on a test dataset of 170 patients from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study. A unique transport-based representation was produced from each presentation NCCT hematoma image to identify morphological features of expansion. The principal hematoma features identified by TBM were larger size, density heterogeneity, shape irregularity, and peripheral density distribution. These were consistent with clinician-identified features of hematoma expansion, corroborating the hypothesis that morphological characteristics of the hematoma promote future growth. Incorporating these traits into a multivariable model comprising morphological, spatial, and clinical information achieved an AUROC of 0.71 for quantifying 24 hr hematoma expansion risk in the test dataset. This outperformed existing clinician protocols and alternate machine learning methods, suggesting that TBM detected features with improved precision than by visual inspection alone. This pre-clinical study presents a quantitative and interpretable method for discovery and visualization of NCCT biomarkers of hematoma expansion in ICH patients. Because TBM has a direct physical meaning, its modeling of NCCT hematoma features can inform hypotheses for hematoma expansion mechanisms. It has potential future application as a clinical risk stratification tool.