Noninvasive monitoring of cerebrovascular autoregulation during and after endovascular therapy for acute ischemic stroke

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PROJECT SUMMARY/ABSTRACT Ischemic stroke is a debilitating disease that is the leading cause of long-term disability in the US despite the prevalent use of clinical imaging technologies to identify, diagnose and classify brain injuries. Care and management of acute ischemic strokes (AIS) due to large vessel occlusion (LVO) (~200,000 cases/year) is based on endovascular thrombectomy (ET), which improves cerebral blood flow by removing blockage in distal cerebral arteries. Despite the promise and widespread use of ET, about a third of patients with technically successful ET procedures develop reperfusion injuries with high degrees of morbidity and mortality, often identified only after-the-fact by standard of care imaging. Indeed, real-time optimization/personalization of treatment is currently not feasible, because we lack robust technologies that can directly measure CBF or characterize changes in cerebrovascular function at the bedside. The primary goal of this proposal is to address this informational gap in bedside monitoring, through a robust noninvasive optical instrument and data processing scheme. This research will deploy a new noninvasive Diffuse Correlation Spectroscopy (DCS) instrument for fast, depth-sensitive measurement of cerebral blood flow in patients with AIS from LVO. The new instrument will be used to derive high-fidelity, quantitative measurements of pulsatile cerebral blood flow from deep cortical microvasculature, during ET therapy. Quantitative measurements of CBF with DCS will be used to grade/quantify cerebral tissue reperfusion during acute therapy for AIS from LVO. Leveraging the enhanced capabilities of the new instrument, this proposal will utilize measurements of steady-state fluctuations in cortical cerebral blood flow and arterial blood pressure to quantify cerebrovascular autoregulation (CVAR). CVAR is a functional biomarker of cerebrovascular tissue health and is predictive of injury severity and stroke recovery. In the same cohort of patients with AIS with LVO, the new DCS instrument will be used to estimate and track changes in CVAR at the patient’s bedside over the first 24 hours after ET, when reperfusion injuries are thought to occur. Longitudinal measurements of CVAR will be correlated with radiographical assessments of the brain at 24 hours post-ET, to evaluate if CVAR changes are predictive of reperfusion injuries. Clinical application of the innovative strategies proposed here will lead to transformative breakthroughs in bedside monitoring of ischemic stroke by providing neurologists with vital real-time physiological information about cerebrovascular function, paving the way for personalized treatments, precision medicine and improved patient outcomes.