Noninvasive monitoring of cerebrovascular regulation in subarachnoid hemorrhage. - PROJECT SUMMARY/ABSTRACT Aneurysmal subarachnoid hemorrhage (aSAH) is a type of stroke that usually results from rupture of an intracranial aneurysm. Delayed cerebral ischemia (DCI) is a clinical syndrome of a focal neurological deficit, cognitive deficit, or both is the strongest predictor of poor outcomes after aSAH. One of the most feared complications of aSAH, which occurs in approximately 30-50% of patients, mostly between days 4 and 10 after the initial aneurysm rupture. Cerebral vasospasm is considered the key pathophysiology that causes DCI after aSAH. The central hypothesis of this proposal is that bedside monitoring of cerebrovascular physiology can be used to track and predict functional outcomes after aSAH, including the occurrence of DCI, as well as assess the efficacy of medical and endovascular interventions. Various diagnostic tools have been applied to detect patients with cerebral vasospasm after aSAH such as transcranial doppler, angiography or perfusion imaging. However, many of these tools have significant limitations. If better means existed to identify which patients were at highest risk of developing DCI, or those in very early stages of DCI, clinicians may be able to more effectively intervene and manage this debilitating complication of SAH. Here, we propose to use a novel, noninvasive, bedside optical instrument Pathlength Resolved Diffuse Correlation Spectroscopy (PR-DCS) to continuously measure cerebral tissue hemodynamics in patients with aSAH. The PR-DCS instrument will provide an accurate, depth-sensitive measurement of cerebral blood flow (CBF), overcoming systemic errors prevalent in conventional optical instruments. Further, these CBF measurements enable bedside characterization of cerebrovascular autoregulation, which hold the power/potential to predict complications in the recovery from aSAH. Aim 1 deploys PR-DCS technology to measure cerebral physiology of patients hospitalized with aSAH. We will use PR-DCS to monitor CBF and to estimate an index of cerebrovascular autoregulation throughout the duration of acute hospitalization. Aim 2 uses PR-DCS as a clinical tool for real-time monitoring of CBF changes during pharmaceutical and endovascular interventions aimed at treating DCI. These innovations directly overcome the limitations of current clinical monitoring instruments that have prevented continuous beside monitoring of brain ischemia in aSAH. Our project is highly translational because the knowledge gained around the mechanisms of cerebrovascular autoregulation can be applied to individual patient care situations.