Imaging Cerebral and Retinal Microvasculature in Cerebral Small Vessel Disease

脑小血管疾病的脑和视网膜微血管成像

• 批准号: 9356350
• 负责人: Amir H Kashani
• 金额: $ 119.17万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9356350
• 关键词: Adopted; Agreement; Alzheimer' s Disease; Angiography; Arteries; Biochemical; Biological Markers; Blood; Blood - brain barrier anatomy; Blood Vessels; Blood capillaries; Cerebral Amyloid Angiopathy; Cerebral small vessel disease; Cerebrovascular Disorders; Cerebrum; Characteristics; Clinical; Clinical Research; Clinical assessments; Cognitive; Data Analyses; Data Collection; Dementia; Development; Disease; Early Intervention; Enrollment; Eye; FDA approved; Goals; Guidelines; Image; Imaging technology; Impaired cognition; Impairment; Individual; Intervention; Lacunar Infarctions; Latino; Lead; Lesion; Liquid substance; Los Angeles; Magnetic Resonance Imaging; Measurement; Methods; Mexican; Microvascular Dysfunction; Morphology; Neurologic; Neuropsychology; Optical Coherence Tomography; Participant; Perforating Artery; Perfusion; Persons; Phase; Phase III Clinical Trials; Prevention; Process; Protocols documentation; Public Health; Readiness; Reproducibility; Resolution; Rest; Retinal; Risk Factors; Scheme; Site; Spin Labels; Stroke; Structure; Study Subject; Surrogate Markers; Technical Expertise; Techniques; Testing; Time; Travel; Vascular Dementia; Vascular Diseases; Water; Work; arterial stiffness; arteriole; base; capillary; clinical imaging; clinical research site; cohort; density; design; epidemiology study; imaging biomarker; imaging genetics; in vivo; in vivo imaging; non-invasive imaging; optical imaging; prevent; research study; retina blood vessel structure; validation studies; vascular cognitive impairment and dementia; vascular contributions; vascular factor; venule; white matter

Project Summary/Abstract While Alzheimer's disease (AD) is the most common cause of dementia, the contribution of vascular factors to cognitive impairment and dementia is becoming increasingly recognized. Vascular cognitive impairment and dementia (VCID) is most commonly caused by cerebral small vessel disease (SVD). To date, cerebral small vessels including arterioles, capillaries and venules are inaccessible to existing imaging technologies. Characteristic parenchymal lesions on MRI, such as lacunar infarcts, white matter lesions, and microbleeds, have been adopted as markers of SVD. However, these parenchymal lesions are the consequences of SVD rather than the surrogate markers of microvascular changes, and are unsuitable for early interventions to change the course of VCID. During the past few years, our group has spearheaded the development of a suite of cutting edge MRI technologies for in vivo and noninvasive assessment of microvascular structure and function, including (1) high-resolution black blood MRI for direct imaging of perforating arteries; (2) arterial spin labeling (ASL) techniques for mapping microvascular perfusion, arterial stiffness or vascular compliance (VC) of small arteries/arterioles, and water exchange rate across the blood-brain barrier (BBB). Furthermore, we recently developed quantitative metrics for retinal capillary density and morphology using an FDA approved optical coherence tomography angiography (OCTA) platform. This method allows clinically feasible, in vivo and completely noninvasive imaging of retinal arterioles and capillaries with a spatial resolution of ~10 microns. Capitalizing on our extensive technical expertise and longstanding track record of clinical studies on VCID, we propose this UH2/UH3 project to further develop and evaluate a suite of MRI and OCTA markers for assessing the structure and function of cerebral and retinal microvasculature, in a cohort of Latino subjects enrolled in the Los Angeles Latino Eye Study (LALES) and in the study of autosomal dominant AD in persons of Mexican origin (Estudio de Enfermedad de Alzheimer en Jalisciences, or EEAJ). During the UH2 phase, we will further develop and evaluate the proposed MRI and OCTA imaging markers of SVD, establish their test-retest repeatability and clinical utility. We will work with the other participating sites and with the Coordinating Center to establish collaborative parameters and agreements of the consortium. During the UH3 phase, we will contribute to and execute cross-site research studies as designed by the consortium. We will perform unified and comprehensive clinical, cognitive, imaging, genetic and biochemical assessments on the cohort of LALES and EEAJ participants locally and perform data analyses as required by the consortium. At the closing of this project, we expect to develop the suite of microvascular imaging markers to readiness to enter into large-scale multi-site clinical validation studies toward FDA qualification for phase II and phase III clinical trials on small vessel disease to prevent and treat VCID.

项目摘要/摘要 虽然阿尔茨海默病(AD)是痴呆症最常见的原因，但血管因素对 认知障碍和痴呆症正日益被人们所认识。血管性认知障碍和 痴呆症(VCID)最常见的原因是脑部小血管疾病(SVD)。到目前为止，大脑规模很小 现有的成像技术无法接触到包括小动脉、毛细血管和小静脉在内的血管。 MRI上的特征性实质病变，如腔隙梗死、白质病变和微出血， 已被用作SVD的标志物。然而，这些实质损害是SVD的后果。 而不是微血管改变的替代标记物，不适合早期干预 改变VCID的进程。在过去的几年里，我们集团带头开发了一套 先进的磁共振成像技术用于体内和非侵入性微血管结构和 功能，包括(1)高分辨率黑血磁共振成像，直接成像穿支动脉；(2)动脉旋转 微血管灌注、动脉僵硬或血管顺应性(VC)的标记(ASL)技术 小动脉/小动脉和血脑屏障(BBB)的水交换率。此外，我们 最近开发的视网膜毛细血管密度和形态的定量测量方法使用FDA批准的 光学相干断层血管成像(OCTA)平台。这种方法在临床上是可行的，在体内和 完全无创的视网膜小动脉和毛细血管成像，空间分辨率约为10微米。 凭借我们在VCID方面的广泛技术专长和长期临床研究记录，我们 提出UH2/UH3项目，以进一步开发和评估一套MRI和OCTA标记物 脑微血管和视网膜微血管的结构和功能，在一组参加 洛杉矶拉丁裔眼科研究(LALES)和墨西哥人常染色体显性AD研究 起源(EStudio de Enfermedad de阿尔茨海默en Jalisciences，简称EEAJ)。在UH2阶段，我们将进一步 开发和评价所提出的SVD的MRI和OCTA成像标记物，建立其重测 重复性和临床实用性。我们将与其他参与站点和协调中心合作 建立联合体的合作参数和协议。在UH3阶段，我们将 参与并执行由该联盟设计的跨站点研究。我们将执行统一的 并对LALES队列进行全面的临床、认知、成像、遗传和生化评估 和EEAJ参与者在当地，并按照财团的要求进行数据分析。在这个结束的时候 项目，我们希望开发一套微血管成像标记物，准备进入大规模 美国食品和药物管理局对Small进行II期和III期临床试验资格的多点临床验证研究 血管疾病预防和治疗VCID。