Modeling of Collateral Perfusion in the Ischemic Brain

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DESCRIPTION (provided by applicant): Common neurological disorders pose an increasingly formidable public health burden that requires studies of underlying mechanisms and ample effort of patient-oriented research (POR) investigators. This midcareer application's long-term mentoring program goal is to train leading young translational scientists from diverse neurologic subspecialties in POR, redressing the mentoring gap in neurology POR that threatens future progress, and the long-term research project goal is to increase understanding of collateral perfusion in stroke. An innovative mentoring infrastructure for selected residents, clinical fellows and junior faculty is proposed with content mentors in neurologic subspecialties and an overall POR mentor. Mentoring aims include 1) establishing departmental mentoring infrastructure, one-on-one mentoring, trainee research, career development and website resources; 2) creating new courses on neurology clinical and translational research and scientific communications; and 3) continually enhancing faculty mentorship skills. The impact of this mentoring program at UCLA will be tracked with specific outcome measures to ensure achievement of trainee and overall program milestones. This K24 award will help achieve departmental long-term goals to enhance POR across neurologic sub-specialties, establish formal neurology POR mentorship, stimulate independent research of trainees and foster an inspiring intellectual environment to increase the number of future neurology POR investigators. This integrated approach to neurology POR training also benefits from a focused research strategy to develop a model of collateral perfusion for content mentoring in stroke, a project that provides mentoring opportunities over a diverse spectrum of POR techniques. Novel neuroimaging and angiography approaches will be used to develop and validate a regional model of collateral perfusion using pressure differentials in arteries, tissue, and veins to predict tissue fate and neurological outcomes in acute ischemic stroke. This clinically relevant work on an important topic in stroke care will enhance understanding of collateral perfusion, including the distinct contributions of arterial and venous segments of the cerebral circulation. In addition to the advancement of scientific knowledge and provision of mentoring opportunities, a tangible resulting product will be a software tool to enhance prediction of tissue fate and neurological outcomes in acute stroke across diverse causes of brain ischemia. PUBLIC HEALTH RELEVANCE: Understanding mechanisms of neurological disorders such as stroke and mentoring trainees in patient-oriented research are key priorities for improving public health. The mentoring program outlined in this proposal will train a new generation of researchers in translational and clinical neuroscience. An exemplar study will investigate collateral perfusion (blood flow around blockages in the brain), developing a realistic model of collateral perfusion in stroke using magnetic resonance, computed tomography, and catheter angiogram imaging technologies. This model may be used to guide and enhance future treatment strategies.