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 and personalize treatment based on individual perfusion targets is essential. The objective of this proposal is to create a swine cardiac arrest model, and to determine the impact of using cerebral autoregulation-based vs standard MAP targets on cerebral perfusion and neurologic injury. In additional to continuous optical monitoring of cerebral perfusion using diffuse correlation spectroscopy and of cerebral oxygenation using frequency domain near infrared spectrometry, we will invasively monitor tissue oxygenation and perfusion and also obtain 6 hours post-arrest CT scans to evaluate structural measures of tissue injury to confirm optically observed perfusion changes using iodine bolus dynamic scan sequences. Neurological outcomes and neural injury serum biomarkers will be assessed 24 hours post-arrest. We hypothesize that the use of real-time noninvasive measures of cerebral autoregulation (using DCS) to identify and target an individualized optimal MAP (MAPOPT) will improve cerebral perfusion and decrease neurologic injury after a resuscitated cardiac arrest.