Endothelial dysfunction, an early marker of atherosclerosis, is a significant cardiovascular risk factor that is implicated for many diseases, including hypertension and diabetes. There is therefore a major effort to develop a noninvasive test for endothelial dysfunction. Flow-mediated dilation of the brachial artery measured by ultrasound imaging offers this possibility, and its use has been demonstrated in various clinical studies. Despite encouraging results, the technique is not recommended for routine clinical use, mainly because of its low sensitivity and large coefficient of variation. This application is designed to overcome these limits . We propose the use of compound imaging to enhance image quality; cross-sectional imaging to improve sensitivity and coefficient of variations, and automated boundary detection for continuous monitoring of vasodilation during ultrasound examination. We tested these concepts is flow phantoms and showed that sensitivity can be improved by as much as 150 times over the conventional method. We also demonstrated the technique could be used to image human subjects. The results were published in a recent article. In this R21 application, we are seeking support for a feasibility study in human subjects. Flow-mediated dilation will be measured in a small number (N = 60) of healthy volunteers . The goal is to demonstrate that ultrasound imaging of brachial artery cross-section using compounding and automated boundary detection have higher sensitivity and reproducibility than the conventional approach using longitudinal imaging. The proposed research will lead to a robust method for measuring FMD, suitable for routine clinical applications. Given the broad involvement of endothelial dysfunction in cardiovascular diseases and that ultrasound imaging is noninvasive and suitable for repeated examinations, the proposed research would have major implication in screening subjects for cardiovascular risks, diagnosing atherosclerosis and monitoring treatment responses.