PROJECT SUMMARY More than 500,000 people in the United States suffer a sudden cardiac arrest (CA) each year, and most successfully resuscitated patients ultimately die from hypoxic ischemic brain injury. Given the substantial neurologic morbidity and mortality in patients who remain comatose following resuscitated cardiac arrest, there is a critical need to identify therapies and treatment strategies to reduce neurologic injury in these patients. Cerebral perfusion is an important contributor to neurologic outcomes in resuscitated CA patients who remain comatose following return of spontaneous circulation (ROSC). Therefore, the ability to continuously monitor cerebral perfusion is essential. The overall objective of this proposal is to evaluate the association between noninvasive measures of cerebral perfusion and neurologic injury in resuscitated CA patients who remain comatose, using innovative technology that directly monitors both cerebral blood flow [rCBF] and regional cerebral oxygen saturation [rSO2]. Our central hypothesis is that real-time noninvasive measurements of cerebral perfusion (rSO2 and rCBF) and measures of autoregulation are associated with neurologic injury, and can help identify optimal and personalized perfusion targets in patients who remain comatose following resuscitated CA. We propose to determine the association between cerebral perfusion rBCF and rSO2 measures and neurologic injury, the association between cerebral autoregulation and neurologic injury and the effect of body temperature on cerebral perfusion and autoregulation. The ultimate goal is provide the foundation for developing personalized cerebral perfusion targets to guide hemodynamic strategies in lieu of current guideline recommendations that provide a ‘one-size-fits-all’ approach.