Image-based Stroke Assessment for Multi-site Preclinical Evaluation of Cerebroprotectants

Ischemic stroke is a leading cause of death worldwide, but there has been little success translating putative cerebroprotectants from preclinical trials to patients. We investigated computational image-based assessment tools for practical improvement of the quality, scalability, and outlook for large scale preclinical screening for potential therapeutic interventions. We developed, evaluated, and deployed a pipeline for image-based stroke outcome quantification for the Stroke Prelinical Assessment Network (SPAN), which is a multi-site, multi-arm, multi-stage study evaluating a suite of cerebroprotectant interventions. Our fully automated pipeline combines state-of-the-art algorithmic and data analytic approaches to assess stroke outcomes from multi-parameter MRI data collected longitudinally from a rodent model of middle cerebral artery occlusion (MCAO), including measures of infarct volume, brain atrophy, midline shift, and data quality. We tested our approach with 1,368 scans and report population level results of lesion extent and longitudinal changes from injury. We validated our system by comparison with manual annotations of coronal MRI slices and tissue sections from the same brain, using crowdsourcing from blinded stroke experts from the network. Our results demonstrate the efficacy and robustness of our image-based stroke assessments. The pipeline may provide a promising resource for ongoing preclinical studies conducted by SPAN and other networks in the future.