Molecular Neuroimaging of Disease Mechanisms in Cerebral Amyloid Angiopathy

描述(申请人提供)：M.Edip Gurol博士是马萨诸塞州总医院的中风神经学家和职业生涯早期的研究员，他的目标是成为一名独立研究员，在老年人小血管脑部疾病的分子和功能成像方面拥有专业知识。Gurol博士的职业发展计划利用世界级环境的资源，汇集了来自马萨诸塞州综合医院和哈佛医学院的一支杰出的研究团队，他们处于小血管脑病(SVD)领域的前沿。Gurol博士已经获得了强有力的初步结果，证明了一项研究计划的可行性，该计划利用分子和功能成像来研究脑淀粉样血管病(CAA)和高血压动脉硬化的组织损伤机制。在Steven M.Greenberg博士以及Keith Johnson博士、Bruce Rosen博士和Rebecca Betensky博士的指导下，Gurol博士建议：1)确定血管淀粉样沉积的严重程度是否与CAA中出血和缺血性组织损伤的新标记物有关；2)绘制血管生理学的功能指标图并分析其与SVD中的淀粉样沉积、缺血性脑损害和认知障碍的关系；以及3)确定SVD相关的微损害(微出血和微梗塞)是否与原位分子变化和认知缺陷有关。这项建议的总体目标是阐明导致CAA和动脉硬化出血和缺血性脑损伤的分子机制，这两种疾病是脑出血和血管认知障碍的主要原因。该项目汇集了尖端技术和具有国际公认的专业知识的团队，既将增进我们对快速增长的老年人残疾原因的了解，也将成为Gurol博士发展为独立调查员的强大培训工具。成功完成拟议的研究，配合结构化的教学课程，将为Gurol博士提供必要的技能，使他能够在科学前沿的SVD研究中发展独立的职业生涯。利用从拟议项目中获得的疾病严重程度和进展的成像标记物的结果，候选人预计将准备他的第一个独立RO1应用程序，以确定预防和治疗与SVD相关的脑损伤和认知障碍的创新方法。

DESCRIPTION (provided by applicant): Dr. M. Edip Gurol is a Stroke Neurologist and early-career investigator at Massachusetts General Hospital, whose goal is to become an independent investigator with expertise in molecular and functional imaging of small vessel brain diseases in the elderly. Dr. Gurol's career development plan leverages the resources of a world-class environment by bringing together an outstanding team of investigators from Massachusetts General Hospital and Harvard Medical School at the forefront of the field of small vessel brain disease (SVD). Dr. Gurol has already obtained strong preliminary results demonstrating the feasibility of a research plan that uses molecular and functional imaging to study mechanisms of tissue injury in cerebral amyloid angiopathy (CAA) and hypertensive arteriolosclerosis. Under the mentorship of Dr. Steven M. Greenberg, and co-Mentors Dr. Keith Johnson, Dr. Bruce Rosen and Dr. Rebecca Betensky, Dr. Gurol proposes: 1) to determine whether the severity of vascular amyloid deposition is associated with novel markers of hemorrhagic and ischemic tissue injury in CAA, 2) to map functional measures of vascular physiology and analyze its association of with amyloid deposits, ischemic brain lesions and cognitive deficits in SVD, and 3) to determine whether SVD- related microlesions (microbleeds and microinfarcts) are associated with in situ molecular changes and cognitive deficits. The overall goal of this proposal is to elucidate molecular mechanisms that result in hemorrhagic and ischemic brain injury in CAA and arteriolosclerosis, major causes of intracerebral hemorrhage and vascular cognitive impairment. Bringing together cutting-edge technology and a team with internationally recognized expertise, this project will both advance our understanding of a rapidly growing cause of disability in the elderly and serve as a strong training vehicle for Dr. Gurol's development as an independent investigator. Successful completion of the proposed studies, in concert with a structured didactic curriculum, will provide Dr. Gurol with the skills that are essential for him to develop an independent career in SVD research at the cutting edge of science. Using results on imaging markers of disease severity and progression obtained from the proposed projects, the candidate anticipates preparing his first independent RO1 application to identify innovative methods for prevention and treatment of SVD-related brain damage and cognitive impairment.