Abstract: Numerous investigations over the past decades have yielded substantial innovations in MR methods for the characterization of extracranial carotid atherosclerosis. Images obtained with these innovations under ideal conditions have given clinicians rich information about disease in the arterial wall and the hope for tools critically needed for adequate management of this insidious disease. Despite this, the great potential power of this technology has not made it into the routine clinical armamentarium. Indeed, because of the need for gadolinium-based contrast agents (GBCA), the long exam time (typically about 45 minutes to obtain the multiple contrasts in the 5 or 6 necessary sequences), and the steep learning curve required to interpret multi- contrast MRI most practitioners still revert to the simplified metric of diameter stenosis in assessing risk. After many collective years of investigations, the consortium of investigators collaborating on this proposal believes that the time is right to address these remaining limitations and ultimately shift the clinical paradigm. Overarching hypothesis: To achieve the great potential in the management of cervical carotid disease, a highly efficient and easily used MRI technique is required. Our hypothesis is that this can be accomplished using multi-parametric non-contrast MRI sequences coupled with the latest high signal to noise ratio (SNR) neck-shape-specific (NSS) RF coils and innovative machine learning (deep neural network) analysis methods. Aim 1: We will install identical RF coils, MRI sequences, and protocols at each of our 5 participating centers as well as rigorously test the accuracy of measurements and reproducibility of image quality from all centers. Aim 2: We will develop, train, and validate a user friendly, deep learning neural network system for the quantitative analysis of several key components considered to be present in the vulnerable atherosclerotic plaque. Aim 3: We will apply the analysis to a cohort of carotid disease subjects to establish the repeatability of the quantitative measures, as well as the accuracy of characterization in comparison to histopathology. Although we will develop and test the image quality, reproducibility and reliability in a network of highly skilled academic centers, we will design these methods to be applicable in the community hospital setting. At the conclusion of this project, we propose to have an integrated solution that can be used in subsequent investigations such as: the effect of pharmacologic intervention in modifying the composition of the plaque; studying the evolution of features of the untreated atheromatous disease over time; and, eventually, investigating the metrics that are predictive of deleterious outcomes, and that can be used in improving intervention strategies in this population. On successful completion, the RF coils and MRI sequences and analysis methods will be made available to other imaging centers in a manner t...