PROJECT SUMMARY Stroke is the fifth largest cause of death and a leading cause of long-term disability among adults in the United States. More than 300 neuroprotective and thrombolytic drug candidates for ischemic stroke have failed in clinical trials between 1995 and 2015, raising concerns regarding the efficacy of preclinical studies. Our long- term goal is to improve the value of animal models of ischemic stroke and accelerate the path of the most efficacious treatments to clinical trials with reduced failure rates and associated costs. The goal of this SBIR proposal is to demonstrate the utility of a wireless optical imaging instrument for providing an in vivo estimate of brain ischemia. Such knowledge will reduce inconsistency in animal models of ischemic stroke and enable longitudinal assessment of treatments’ efficacy. At Barati Medical, LLC, we have developed a miniaturized, wireless near infrared spectroscopy (NIRS) prototype for noninvasive monitoring of cerebral oxygenation parameters, i.e. deoxyhemoglobin (Hb) and oxyhemoglobin (HbO2), in rats. In a preliminary study, our prototype detected a twofold reduction in cerebral oxygenation during deep anesthesia relative to light anesthesia in a male rat. The product of this proposal will be a cost-effective, miniaturized, wireless NIRS platform for the measurement of cerebral oxygenation in small lab animals, which enables in vivo, longitudinal assessment of brain injury models and treatments’ efficacy. Our innovation centers on the utility of a cost-effective NIRS solution in predicting the infarct volume after procedures of middle cerebral artery occlusion (MCAO) in freely moving animals. No other in vivo measure is readily available that accurately predicts infarct volume or behavioral deficit. Our Specific Aims are to refine the NIRS prototype, demonstrate the feasibility of the NIRS device in predicting behavioral deficits and infarct volume at 48h after ischemic stroke, and show the feasibility of continuous, long- term measurement of cerebral oxygenation during the subacute phase of ischemic stroke in rats.