Validation of Imaging and Blood-based Small Vessel VCID Biomarkers in Multiethnic Population

多种族人群中影像学和基于血液的小血管 VCID 生物标志物的验证

• 批准号: 10369505
• 负责人: Amir H Kashani
• 金额: $ 262.38万
• 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 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10369505
• 关键词: African American; American; Angiography; Area; Biological Markers; Blood; Blood capillaries; Blood specimen; California; Categories; Caucasians; Clinical; Clinical Data; Clinical Trials; Cognitive; Community Outreach; Data Analyses; Data Collection; Dementia; Development; Devices; Diffuse; Endothelium; Enrollment; Equipment; Evaluation; Eye; Eye diseases; FDA approved; Follow-Up Studies; Goals; Growth; Image; Impaired cognition; Inflammation; Infrastructure; Intervention; Laboratories; Latino; Latinx; Lead; Light; Liquid substance; Longitudinal Studies; Longitudinal cohort; Los Angeles; Magnetic Resonance Imaging; Minority Groups; National Institute of Neurological Disorders and Stroke; Optical Coherence Tomography; Participant; Phase; Pilot Projects; Plasma; Population; Population Heterogeneity; Protocols documentation; Public Health; Research; Research Personnel; Resolution; Signal Transduction; Site; Skeleton; Universities; Validation; Water; White Matter Hyperintensity; base; blood-based biomarker; candidate marker; candidate validation; cerebrovascular; clinical research site; cohort; density; design; exosome; human subject; in vivo; multi-ethnic; neurofilament; neuroimaging; non-invasive imaging; novel; programs; racial diversity; recruit; research study; retina blood vessel structure; retinal imaging; scale up; validation studies; vascular cognitive impairment and dementia

PROJECT SUMMARY/ABSTRACT The MarkVCID consortium was established in 2016 to pursue the initial stages of multi-site validation of 7 imaging-based and 4 fluid-based candidate biomarkers for small vessel vascular contributions to cognitive impairment and dementia (VCID). As one of the 7 participating sites, our team at the University of Southern California (USC) has analyzed and optimized candidate VCID biomarkers during the UH2 phase (years 1-2) and participated in the consortium-wide program of biomarker scaling-up, multi-site protocol implementation, and initial multi-site validation during the UH3 phase (years 3-5). USC has led the consortium-wide development and implementation of the optical coherence tomography angiography (OCTA) biomarker kit which is based on an FDA-approved device that allows in vivo and completely noninvasive imaging of retinal capillaries with a spatial resolution of ~10 microns. We have also participated in the validation of the other 6 MRI based candidate biomarkers while contributing blood samples for the validation of the 3 plasma-based candidate biomarkers. The primary objective of the next 5 years is to carry out comprehensive multi-site clinical validation of candidate VCID biomarkers in longitudinal studies of diverse populations that are typical in clinical settings in the US. Capitalizing on the high racial diversity in Los Angeles, we plan to enroll a multiethnic longitudinal cohort of at least 200 subjects that are enriched for small vessel VCID, including 100 Latinx subjects from the Los Angeles Latino Eye Study (LALES), 50 African Americans (AAs) enrolled in the African American Eye Disease Study (AFEDS), and 50 Caucasian participants from the Clinical Core of the USC ADRC. We have performed pilot studies in both Latinx and AA subjects (the two largest minority groups in the US) using MarkVCID protocols to show the feasibility of conducting such studies in a multiethnic cohort. We have also built a multiethnic team of investigators, technical staff, research coordinators, and community outreach staff to streamline enrollment, achieve the recruitment milestones, and perform longitudinal follow-up studies. Our team includes established expertise, equipment and infrastructure for OCTA, MRI, fluid biomarker and clinical/cognitive evaluation of VCID, as well as a proven track record in the sharing of de-identified clinical data through the Laboratory of Neuro Imaging (LONI) for the second phase of MarkVCID project.

项目总结/摘要 MarkVCID联盟成立于2016年，旨在对7种基于成像和4种基于液体的候选生物标志物进行多中心验证的初始阶段，以评估小血管血管对认知障碍和痴呆（VCID）的贡献。作为7个参与研究中心之一，我们在南加州大学（USC）的团队在UH 2阶段（第1-2年）分析和优化了候选VCID生物标志物，并在UH 3阶段（第3-5年）参与了生物标志物规模扩大、多中心方案实施和初始多中心验证的联盟范围计划。南加州大学领导了光学相干断层扫描血管造影（OCTA）生物标志物试剂盒的联盟范围内的开发和实施，该试剂盒基于FDA批准的设备，该设备允许以约10微米的空间分辨率对视网膜毛细血管进行体内和完全非侵入性成像。我们还参与了其他6种基于MRI的候选生物标志物的验证，同时为3种基于血浆的候选生物标志物的验证提供血液样本。未来5年的主要目标是在美国临床环境中典型的不同人群的纵向研究中对候选VCID生物标志物进行全面的多中心临床验证。利用洛杉矶的高度种族多样性，我们计划入组一个多种族纵向队列，其中至少有200例受试者富集了小血管VCID，包括来自洛杉矶拉丁裔眼科研究（LALES）的100例拉丁裔受试者、入组非裔美国人眼科疾病研究（AFEDS）的50例非裔美国人（AA）和来自USC ADRC临床核心的50例白人受试者。我们使用MarkVCID方案在拉丁裔和AA受试者（美国最大的两个少数群体）中进行了试点研究，以显示在多种族队列中进行此类研究的可行性。我们还建立了一个由研究人员、技术人员、研究协调员和社区外展人员组成的多种族团队，以简化招募工作，实现招募里程碑，并进行纵向随访研究。我们的团队包括OCTA、MRI、液体生物标志物和VCID临床/认知评估的成熟专业知识、设备和基础设施，以及通过神经成像实验室（LONI）为MarkVCID项目第二阶段共享去识别临床数据的良好记录。