Microvascular Dysfunction in Cerebral Small Vessel Disease and Stroke

脑小血管疾病和中风中的微血管功能障碍

• 批准号: 10301254
• 负责人: MARK ETHERTON
• 金额: $ 19.76万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10301254
• 关键词: Acute; Address; Biological; Biological Markers; Biology; Blood - brain barrier anatomy; Blood Vessels; Blood capillaries; Brain; Cerebral small vessel disease; Chronic; Clinical; Clinical Research; Clinical Treatment; Clinical Trials; Clinical Trials Design; Complex; Coupling; Data; Databases; Development; Diffuse; Diffusion Magnetic Resonance Imaging; Endothelium; Enrollment; Ensure; Environment; Experimental Designs; Extravasation; Foundations; Functional disorder; Future; General Hospitals; Goals; Growth; Hour; Image; Impairment; Individual; Infarction; Injury; Intervention; Investigation; Ischemic Stroke; K-Series Research Career Programs; Knowledge; Lacunar Infarctions; Lead; Lesion; Longitudinal Studies; Longitudinal prospective study; Magnetic Resonance Imaging; Massachusetts; Measurement; Measures; Mediating; Mentors; Mentorship; Microvascular Dysfunction; Modeling; Neurologic; Neurologist; Outcome; Outcome Assessment; Pathogenesis; Patients; Pilot Projects; Plasma; Population; Predisposition; Process; Program Development; Public Health Schools; Research; Research Activity; Research Training; Resolution; Resources; Risk Factors; Role; Scientist; Severities; Signal Transduction; Skeleton; Statistical Data Interpretation; Stroke; Stroke prevention; Structure; Testing; Tissues; Training; Training Activity; Vasodilation; Visualization; White Matter Hyperintensity; Width; aging population; bioimaging; candidate marker; career; career development; cerebrovascular; clinically relevant; cohort; disability; early detection biomarkers; experimental study; follow-up; functional outcomes; high risk; improved; individualized medicine; insight; meetings; multidisciplinary; negative affect; network dysfunction; neuroimaging; new therapeutic target; novel; patient oriented research; patient population; post stroke; programs; prospective; research study; responsible research conduct; risk stratification; stroke clinical trials; stroke outcome; stroke patient; stroke recovery; translational research program; white matter; white matter injury

Project Summary/Abstract Dr. Mark Etherton is a Vascular Neurologist at Massachusetts General Hospital (MGH) whose goal is to become an independent, clinical research scientist with expertise in neuroimaging of cerebral small vessel disease and ischemic stroke. The research aims of this proposal are three-fold: (1) to elucidate the relationship between white matter microvascular function and ischemic tissue outcomes; (2) to advance knowledge on how chronic microvascular dysfunction contributes to white matter structural injury and ischemic stroke outcomes; and (3) to determine the relationship between early plasma and neuroimaging surrogates of microvascular function in small vessel disease-mediated ischemic stroke. The proposed study capitalizes on the clinical research environment of the MGH Stroke Research Center and two unique acute ischemic stroke databases with Dynamic Susceptibility Contrast MRI. The current proposal will analyze these two prospectively enrolled acute ischemic stroke cohorts in combination with a prospective, longitudinal study coupling functional neuroimaging with plasma biomarker analysis. Successful completion of this research study will advance knowledge on how white matter microvascular dysfunction contributes to infarct growth and poor functional outcomes after stroke. This research will yield important pathophysiological insights regarding the complex interrelations of microvascular dysfunction and cerebral small vessel disease, which may contribute to improved stroke prevention, risk stratification, and individualized therapies to improve post-stroke outcomes in patients with small vessel disease. This application proposes a focused training plan with specific measures of proficiency that extends Dr. Etherton’s prior training and research activities in ischemic stroke and diffusion tensor imaging analysis of global white matter integrity by providing necessary new and formal training in (1) neuroimaging of microvascular function; (2) fundamentals of blood-brain barrier biology; and (3) experimental design/statistical analysis. Training will involve individual and research team meetings with an interdisciplinary network of world-renowned mentors and collaborators; formal didactics in neuroimaging, blood-brain barrier biology, clinical trial design, statistical analysis, and responsible conduct of research; educational seminars; and formal neuroimaging training activities. His training plan leverages the resources of world-class environments at MGH, the Martinos Center for Biomedical Imaging, and the Harvard School of Public Health. The mentorship of primary mentor Dr. Natalia Rost, co-mentors Drs. Ona Wu, Cenk Ayata, and Steven Greenberg, along with collaborators Drs. Bruce Rosen, Hanzhang Lu, and Lori Chibnik will ensure Dr. Etherton achieves his training plan goals and milestones. The integrated research and training plans outlined in this application will significantly advance Dr. Etherton’s research career and provide the skillset necessary to pursue an independent program of patient-oriented research studying the mechanisms of microvascular dysfunction in cerebral small vessel disease and stroke.

项目总结/摘要 博士Mark Etherton是马萨诸塞州总医院（MGH）的血管神经科医生，他的目标是成为 一位独立的临床研究科学家，具有脑小血管疾病神经成像方面的专业知识， 缺血性中风本研究的目的有三：（1）阐明 白色物质微血管功能和缺血性组织的结果;（2）推进关于慢性 微血管功能障碍导致白色结构损伤和缺血性卒中结果;和（3） 确定早期血浆和微血管功能的神经影像学替代物之间的关系， 血管疾病介导的缺血性卒中。拟议的研究利用了临床研究环境 和两个独特的急性缺血性卒中数据库， 磁敏感对比MRI。目前的建议将分析这两个前瞻性招募的急性缺血性 卒中队列与一项前瞻性纵向研究相结合， 血浆生物标志物分析。这项研究的成功完成将推进有关白色如何 物质微血管功能障碍导致卒中后梗死生长和不良功能结局。这 研究将产生重要的病理生理学的见解，关于微血管的复杂的相互关系， 功能障碍和脑小血管疾病，这可能有助于改善中风预防，风险 分层和个体化治疗，以改善小血管疾病患者的卒中后结局。 该应用程序提出了一个有针对性的培训计划，具体措施的熟练程度，延长博士。 Etherton之前在缺血性卒中和弥散张量成像分析方面的培训和研究活动 白色物质的完整性，提供必要的新的和正式的培训，在（1）神经成像的微血管 功能;（2）血脑屏障生物学基础;（3）实验设计/统计分析。 培训将涉及个人和研究团队会议与世界知名的跨学科网络 导师和合作者;神经影像学，血脑屏障生物学，临床试验设计， 统计分析和负责任的研究行为;教育研讨会;和正式的神经成像培训 活动他的培训计划利用了MGH Martinos中心世界一流环境的资源 和哈佛公共卫生学院。初级导师娜塔莉亚博士的指导 罗斯特，共同导师奥纳吴博士，森克阿亚塔，和史蒂芬格林伯格，沿着与合作者博士布鲁斯罗森， 卢汉章和洛里奇布尼克将确保埃瑟顿博士实现他的培训计划目标和里程碑。的 本申请中概述的综合研究和培训计划将大大推进埃瑟顿博士的 研究职业生涯，并提供必要的技能，以追求一个独立的计划，以病人为导向 研究脑小血管病和脑卒中微血管功能障碍的机制。