Molecular Neuroimaging of Disease Mechanisms in Cerebral Amyloid Angiopathy

描述（由申请人提供）：Dr. M. Edip Gurol是马萨诸塞州总医院的中风神经学家和早期职业研究者，他的目标是成为一名独立的研究者，在老年人小血管脑疾病的分子和功能成像方面具有专业知识。Gurol博士的职业发展计划充分利用世界一流环境的资源，将来自马萨诸塞州总医院和哈佛医学院的优秀研究人员团队聚集在小血管脑疾病（SVD）领域的最前沿。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，该计划使用分子和功能成像来研究脑淀粉样血管病（CAA）和高血压小动脉硬化症的组织损伤机制。在Steven M博士的指导下，Greenberg和共同导师基思约翰逊博士、布鲁斯罗森博士和丽贝卡·贝滕斯基博士，Gurol博士建议：1）确定血管淀粉样蛋白沉积的严重程度是否与CAA中出血性和缺血性组织损伤的新标志物相关，2）绘制血管生理学的功能测量并分析其与SVD中淀粉样蛋白沉积、缺血性脑损伤和认知缺陷的相关性，以及3）确定SVD相关的微损伤（微出血和微梗死）是否与原位分子变化和认知缺陷相关。本提案的总体目标是阐明CAA中出血性和缺血性脑损伤和小动脉硬化的分子机制，这是脑出血和血管性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专业知识的团队，将促进我们对快速增长的老年人残疾原因的理解，并作为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博士提供在科学前沿发展SVD研究独立职业所必需的技能。利用从拟议项目中获得的疾病严重程度和进展的成像标志物的结果，候选人预计将准备他的第一个独立的RO1应用程序，以确定预防和治疗SVD相关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.