Project Summary/Abstract Vascular contributions to cognitive impairment and dementia (VCID) is becoming increasingly recognized as an important cause of dementia. Cerebral small vessel disease (cSVD) is the most common vascular cause of dementia, a major contributor to mixed dementia, and the cause of about one fifth of all strokes worldwide. However, the underlying mechanisms of cSVD remain poorly understood. The large knowledge gap in cSVD is partly because cerebral small vessels, including arterioles, capillaries and venules, are inaccessible to existing in vivo imaging technologies. During the past few years, our group has spearheaded the development of a new high-resolution black-blood MRI technique for the visualization, segmentation and quantification of cerebral small vessels including lenticulostriate and superficial perforating arteries and venules. This technique offers an isotropic ~0.5mm spatial resolution, adequate flow suppression for small vessels due to the long echo train, and near whole-brain coverage in ~10min at clinical field strength of 3T. We further developed a comprehensive 3D analysis pipeline for quantifying the morphology and density of cerebral small vessels with sizes on the order of a few hundred microns. In addition, we have a longstanding track record in developing and applying arterial spin labeling (ASL) techniques for quantifying microvascular perfusion – a key physiological parameter and potential biomarker for cSVD. Our preliminary data demonstrated expected changes in small vessel morphology and density as well as microvascular perfusion with aging, vascular risks and mild cognitive impairment (MCI), supporting the use of metrics of small vessel morphology/density and microvascular perfusion as imaging markers of cSVD and VCID. The primary goals of this project are to further optimize the acquisition protocol and analysis pipeline for mapping and quantifying cerebral small vessels using black-blood and ASL MRI at 3T, and to systematically evaluate metrics of small vessel morphology/density and perfusion as imaging biomarkers of VCID in a multiethnic longitudinal cohort of 200 subjects that are enriched for small vessel VCID. In particular, our study will enroll a cohort of 50 Asian Americans who are among the fastest growing populations in the US but are highly underrepresented in ADRD research. This project is expected to result in a powerful suite of imaging tools for comprehensive characterization of the morphology and function of cerebral small vessels, as well as to fill in the important gap in health disparities of Asian Americans in ADRD research.