Modeling of Collateral Perfusion in the Ischemic Brain

描述（由申请人提供）：常见的神经系统疾病构成了日益严重的公共卫生负担，需要对潜在机制的研究和以患者为导向的研究（POR）研究者的大量努力。这项中期职业申请的长期指导计划的目标是培养来自不同神经病学POR亚专业的领先年轻转化科学家，弥补神经病学POR中威胁未来进展的指导差距，长期研究项目的目标是增加对卒中侧支灌注的理解。为选定的住院医师，临床研究员和初级教师提供创新的指导基础设施，包括神经病学亚专业的内容导师和整体POR导师。指导目标包括：1)建立部门指导基础设施、一对一指导、学员研究、职业发展和网站资源；2)开设神经病学临床和转化研究以及科学传播方面的新课程；3)不断提高教师的指导技能。加州大学洛杉矶分校的这项指导计划的影响将通过具体的结果测量来跟踪，以确保学员和整个计划的里程碑的实现。这个K24奖将有助于实现部门的长期目标，以加强神经病学亚专业的POR，建立正式的神经病学POR导师，激励学员的独立研究，并营造一个鼓舞人心的智力环境，以增加未来神经病学POR研究者的数量。这种神经学POR培训的综合方法还受益于一项重点研究策略，即为卒中的内容指导开发侧支灌注模型，该项目提供了多种POR技术的指导机会。新的神经成像和血管造影方法将用于开发和验证侧支灌注的区域模型，利用动脉、组织和静脉的压差来预测急性缺血性卒中的组织命运和神经预后。这项临床相关的工作在卒中护理中的一个重要课题将加强对侧支灌注的理解，包括脑循环中动脉和静脉段的独特贡献。除了科学知识的进步和指导机会的提供，一个有形的成果将是一个软件工具，以加强预测组织命运和神经系统的结果在急性中风的各种脑缺血的原因。

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.