The following K23 proposal is for Dr. Nils Petersen, a Neurocritical Care and Stroke Neurologist at Yale-New Haven Hospital, and Assistant Professor at Yale University School of Medicine. Dr. Petersen is a physician- scientist with specialized knowledge of human cerebral hemodynamics who is investigating personalized, autoregulation-guided blood pressure management after ischemic stroke. About 40% of patients with ischemic stroke due to intracranial large-vessel occlusion (LVO) are rendered non-ambulatory, bedridden or deceased despite treatment with endovascular thrombectomy. Abnormalities in cerebrovascular autoregulation in the acute phase of LVO stroke increase the risk of secondary brain injury from relative cerebral hypo- or hyperperfusion. Thus, autoregulation-guided, personalized blood pressure management presents a promising alternative to the current practice of targeting fixed thresholds. By providing a more favorable physiologic environment for the injured brain, the autoregulation-guided approach may reduce secondary brain injury and improve outcomes. Preliminary data obtained by Dr. Petersen have demonstrated the feasibility of a research plan that uses near- infrared spectroscopy and real-time data processing to identify a patient-specific blood pressure range that yields optimal brain blood flow. This research proposal will evaluate if blood pressure management outside personalized limits of autoregulation increases the risk for neurologic worsening from infarct progression or hemorrhagic transformation, leading to increased rates of unfavorable outcome (Aim 1). Next, Dr. Petersen will evaluate the effectiveness of therapeutic blood pressure interventions and explore the feasibility of an intervention protocol targeting a personalized blood pressure range (Aim 2). Under the expert mentorship of Dr. Kevin Sheth, Chief of Neurocritical Care, Dr. Randolph Marshall, Director of Stroke Division at Columbia University, and Dr. Cynthia Brandt, Director of Medical Informatics, this K23 award will allow Dr. Petersen 1) to acquire skills in informatics, advanced signal processing and machine learning in order to enhance current methods of quantifying cerebral autoregulation, 2) to develop expertise in clinical trial design, 3) to build a research group dedicated to discovery and clinical evaluation of physiology-based individualized treatment strategies after stroke, and 4) to foster inter-institutional collaboration and data-sharing. This proposal will leverage Yale?s cutting-edge neuro-monitoring technologies along with extensive informatics and research resources from the Yale Center for Clinical Investigation to generate new insights into cerebral hemodynamics and identify treatment opportunities. At the conclusion of this award period, Dr. Petersen will be well-positioned to become an independently-funded investigator conducting high-quality research in the area of cerebral hemodynamics. His long-term goal is to use neuro-monitoring to develop physiology-based, personalized, early interventions to reduce the disability and morbidity associated with stroke.
/Public Health Relevance: Stroke is the leading cause of disability in the United States, and this research proposal addresses the NIH mission to reduce the burden of neurological disorders and enhance the quality of life of people with disability. Current stroke treatments are primarily aimed at treating blockage of blood vessels but are only partially effective, leaving a great need for additional adjunctive therapies. Effective blood pressure management tailored to individual patients, with the aim of maintaining optimal brain blood flow, may prevent additional brain injury, and is an important first-step towards personalized medicine in stroke.
