Project Summary/Abstract This is a pilot study to confirm localized lesions in acute pediatric anoxic brain injury (ABI) secondary to nonfatal drowning using magnetic resonance imaging (MRI). Drowning is the third leading cause of death due to unintentional injury worldwide, with the highest incidence in young children (ages 1-4 years). Although drowning (i.e. submersion/immersion in liquid) results in multi-organ damage, the most devastating disability results from brain injury. Current diagnostic neuroimaging findings (largely via qualitative visual inspection) are nonspecific and offer little value for prognosis or for directing therapeutic interventions in the acute injury phase of pediatric ABI post- drowning. Our preliminary MRI studies show that chronic ABI displays lesions limited to the lenticulostriate distribution, which is an end-arterial watershed zone, similar to focal ischemia seen in stroke. We found that this localized pattern of injury exhibits gray matter atrophy and also white matter microstructural abnormalities on diffusion-tensor images (DTI), by using fully automated quantitative imaging analysis. Interestingly, lesion burden limited to the lenticulostriate distribution has not been reported in adults with nonfatal drowning and may be observed only in children. Acute ABI due to different ischemic neuropathologies can be detected sooner on diffusion-weighted images as compared to other structural MRI modalities (i.e. T1 and T2-weighted images) according to evidence provided in the literature. For example, detection of lesions occurs by 30 minutes after occlusion of vasculature in animal stroke models on diffusion-weighted images. Further, focal microstructural compromise can be detected by 16 hours in perinatal asphyxia on diffusion-weighted images—which demonstrates a similar injury pattern in the lenticulostriate distribution. The overall goal of the proposal is to identify and validate acute-imaging markers for ABI in nonfatal drowning. To this end, we seek to test 3 aims using structural MRI. Based on current literature and results from our preliminary work, we expect an injury pattern that is localized to the lenticulostriate vascular distribution affecting both gray and white matter. In the acute phase of injury, we will seek to demonstrate focal abnormalities on DTI (Aim 1) and T2-weighted images (Aim 2). Additionally, we will correlate abnormalities on DTI with duration of hospital stay (Aim 3), which promises to validate diagnostic and prognostic imaging markers. Future testing of neuroprotective agents in the acute injury phase would leverage conclusions from this feasibility study.