Multi-contrast MRI sequences before and after gadolinium enhancement of the carotid plaque can significantly improve determination of stroke risk compared with simple carotid stenosis measurements. While the improved depiction of plaque features with MRI can be used to better individualize therapy for veterans with carotid disease, its use has been limited because it requires gadolinium-based contrast agents, extended exam times, and extensive interpretive training. To address these remaining limitations and move our field forward into clinical application, our multicenter team of investigators will combine our extensive collective experience in carotid MRI to develop a novel rapid non- contrast quantitative carotid imaging method to automatically and accurately identify vulnerable plaque components. Our goal is to establish a method for accurate carotid plaque mapping that can be obtained with 1 to 3 MRI sequences taking ≤10 minutes for the total plaque exam. To accomplish this goal, we will consolidate our different quantitative carotid MRI sequences into two different methods of measuring these quantitative parameters (NEW1 and NEW2). We will then compare these two methods against each other and against the conventional multi-sequence contrast enhanced carotid MRI method (CONV) in a study of 100 veterans with carotid disease at our 5 VAMC’s. Scans from repeat visits will be used to test repeatability of the parametric measurements and will be performed with high-performance neck-shape-specific (NSS) carotid coils. Our hypothesis is that vulnerable carotid plaque components (intraplaque hemorrhage, lipid rich necrotic core, calcification, total plaque volume, and thin or ruptured fibrous cap) can be accurately identified using rapidly acquired quantitative MRI parameters (relaxation times, diffusion coefficient, and proton density signal intensity). Specifically, that NEW1 or NEW2 or both are non-inferior to CONV in measuring plaque components and equivalent or more accurate than CONV relative to histology. Aim 1 will determine whether NEW1 or NEW2 is more repeatable, Aim 2 will determine whether either or both are non-inferior to CONV in plaque component determination, and Aim 3 will determine the relative accuracy of the three methods, NEW1, NEW2, and CONV compared with histology. This research will provide a rapid and reliable quantitative approach for a comprehensive carotid artery exam. This will benefit veterans at risk for stroke but presently under-treated because the diameter narrowing does not meet criteria for intervention. It will spare others with stenotic but stable plaque the risk of surgery. After demonstrating this method can automatically identify plaque features without expert oversight at the 5 academic VAMCs, this technique will be directly applicable in the community hospital setting. Although the technology has been developed on a single vendor’s MRI platform, the NSS coils and related pulse sequences developed will be transferrable to any MRI scanner hardware and applicable to imaging other vascular territories and nonvascular tissue. This rapid non-contrast MRI protocol will fundamentally change the clinical management of cerebrovascular disease.