University of Southern California

USC Site ImageImaging Cerebral and Retinal Microvasculature in Cerebral Small Vessel Disease

Cerebral small vessel disease (SVD) is the most common vascular cause of dementia, a major contributor to mixed Alzheimer’s disease and vascular dementia, and the cause of about one fifth of all strokes worldwide. This project will develop and evaluate a suite of non-invasive magnetic resonance imaging (MRI) and optical coherence tomography angiography (OCTA) techniques for in vivo imaging of the cerebral and retinal small vessels. There is growing evidence that changes in retinal vessels correlate with vascular changes elsewhere in the central nervous system (CNS), indicative of cerebral small vessel disease (SVD). The objective of this proposal during the UH3 phase is to develop and validate a clinic-ready biomarker of SVD and vascular cognitive impairment and dementia (VCID) using a non-invasive, imaging method called optical coherence tomography angiography (OCTA) to quantify retinal capillary density in vivo. The OCTA based assessment of retinal capillary density is called vessel skeleton density (VSD). OCTA is an FDA approved, noninvasive, minimal risk, high resolution imaging modality that can quantify capillary density in the retina of human subjects in less than 15 minutes per subject and possibly through an undilated pupil. Our site will lead a multisite, prospective, non-interventional study to assess baseline VSD measurements in a cohort of subjects enriched for risk factors for SVD and VCID. We will take advantage of the resources available from the MarkVCID consortium which is supporting extensive and standardized neuroimaging, cognitive and clinical testing of the prospective multisite cohort. The VSD biomarker will be validated in parallel and independent cohorts of subjects at each participating site of the MarkVCID consortium to ensure reliability and reproducibility of the biomarker for clinical trials. At the end of this proposal, we will have a well-annotated dataset of OCTA, neuroimaging markers, neurocognitive markers, and comprehensive clinical data to demonstrate a correlation between VSD and SVD, VCID or both. USC will also participate in the evaluation of 5 MRI based biomarkers of VCID and collect blood samples for the evaluation of fluid-based biomarkers. This proposal is supported by funding from NINDS and BrightFocus Foundation.



Investigators Information

PI: Danny JJ Wang, PhD, MSCE
Professor of Neurology
Director of Imaging Technology Innovation
Stevens Neuroimaging and Informatics Institute
University of Southern California


MPI: John Ringman, MD, MS
Helene and Lou Galen Endowed Professor of Neurology
Keck School of Medicine
University of Southern California


MPI: Amir Kashani, MD, PhD
Associate Professor of Ophthalmology
Director of Ocular Imaging Center
University of Southern California Eye institute

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