Development of MR-derived parameters of LV diastolic function: Validation and Comparison to LV and LA fibrosis

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Project Summary The clinical impact of this proposal is the development of cardiac MR methods for evaluating diastolic function and determining how it relates to left ventricular and left atrial fibrosis. We will test the hypothesis is that pre- existing ventricular and atrial fibrosis (diffuse fibrosis) may be reflected in increased atrial pressures, or in other diastolic parameters of chamber compliance, which can be evaluated using these new methods. We also hypothesize that diastolic parameters and LV and LA diffuse fibrosis will be independent important predictors of new onset AF. There is a wealth of evidence that atrial fibrosis, heart-failure with preserved EF, and new onset AF are a constellation all strongly associated with each other, and with diastolic dysfunction. The development of tools for measuring diastolic function will have enormous impact in patient care. The goals of this proposal are to develop a method for easily processing cine images to yield e', the early diastolic velocity of the mitral valvular tissue region, using feature tracking methods. Further, the goals are to develop and test methods for simple and robust E and A measurements of blood flow through the mitral valve, and to develop methods for measuring pulmonary vein inflow. The validations will proceed in healthy subjects and then 110 patients. The reproducibility will be included. The innovation of this grant is the recognition that diastolic function is critical-- in conjunction with the recently developed capabilities of measuring left ventricular diffuse fibrosis with and MRI, and left atrial volumes, strain, and fibrosis-- in understanding the relationship between atrial pressure during diastole and left atrial remodeling. We further propose innovative MR methods, including a black blood cine method, which will generate cine images to visualize the valves more clearly, and might have further applications. We propose the use of slice-following with phase-contrast, which is already established, but will combine it with feature- tracking to vastly improve its clinical feasibility. We have assembled a team including an MRI Physicists with expertise in novel acquisition and reconstruction, non-invasive cardiologists and a radiologist who will guide the translational studies, and a multi- modality cardiologist who is expert in animal models of disease, for correlating MR measurements of diastolic function with invasive pressure measurements. The PI is a pioneer in the area of left atrial evaluation, for which diastolic function is a major influence. Together, working on these Aims, we will develop a new approaches for evaluating diastolic functional parameters, E, A, e' and more, and define their role in development of atrial fibrillation.