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

项目摘要/摘要 MarkVCID财团成立于2016年，旨在对7个基于成像和4个基于液体的候选生物标记物进行多点验证，以确定小血管血管对认知障碍和痴呆(VCID)的贡献。作为7个参与站点之一，我们在南加州大学(USC)的团队在UH2阶段(1-2年)分析和优化了候选VCID生物标记物，并在UH3阶段(3-5年)参与了生物标记物扩大、多站点协议实施和初始多站点验证的联盟范围计划。南加州大学领导了整个联盟范围内光学相干断层扫描血管成像(OCTA)生物标记试剂盒的开发和实施，该试剂盒基于FDA批准的设备，允许以~10微米的空间分辨率进行视网膜毛细血管的活体和完全非侵入性成像。我们还参与了其他6个基于MRI的候选生物标记物的验证，同时为验证3个基于血浆的候选生物标记物提供了血液样本。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生物标记物进行全面的多点临床验证。利用洛杉矶高度的种族多样性，我们计划招募至少200名为小血管VCID而丰富的多民族纵向队列，包括来自洛杉矶拉丁裔眼科研究(LALES)的100名拉丁裔受试者，参加非裔美国人眼病研究(AFEDS)的50名非裔美国人(AAs)，以及来自南加州大学ADRC临床核心的50名高加索受试者。我们已经使用MarkVCID协议在Latinx和AA受试者(美国两个最大的少数群体)中进行了试点研究，以表明在多种族队列中进行此类研究的可行性。我们还建立了一支由调查人员、技术人员、研究协调员和社区外展人员组成的多民族团队，以简化招生程序，实现招募里程碑，并进行纵向跟踪研究。我们的团队在OCTA、MRI、流体生物标记物和VCID的临床/认知评估方面拥有成熟的专业知识、设备和基础设施，并在通过MarkVCID项目第二阶段的神经成像实验室(LONI)共享未识别的临床数据方面拥有成熟的跟踪记录。

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.