Project Summary/Abstract Left ventricular thrombus (LVT) provides a substrate for embolic events and a rationale for anticoagulation. De- spite advances in coronary reperfusion, LVT remains common after ST elevation myocardial infarction (MI)– occurring in up to 1 in 5 patients with MI involving the LV apex. Predictors of LVT are limited, as evidenced by data that over half of cases occur without marked global LV dysfunction or aneurysm. Uncertainty as to who will develop LVT may explain clinical data that have shown anticoagulation to increase bleeding without decreasing stroke in seemingly at risk post-MI groups. Given the seriousness of stroke and bleeding conferred by LVT and its treatment, improved understanding of LVT is of major importance for the over quarter million people in the U.S. who sustain ST elevation MI each year. Cardiac magnetic resonance (CMR) imaging provides a highly accurate means to identify LVT, but current approaches are limited to predict in whom LVT will occur. This study is predicated on the hypothesis that LVT formation stems from altered LV blood flow and its determinants. To test this, LV blood flow will be quantified via volumetric time resolved “4D flow MRI” - a new method that can measure time-resolved, volumetric velocity vectors in vivo. We will develop a novel imaging approach for accurate assessment of LV flow impairment in in the context of MI. Aim 1 will develop new MRI methods that can be widely applied to quantify left ventricular stasis (low velocities). Specifically, a targeted 4D flow MRI pulse sequence (via radial stack-of-stars acquisition and dual velocity encoding) will be developed to achieve directed flow assessment of the LV with sensitivity to low velocities. Aim 2 will validate the new method: the new targeted acquisition will be compared with conventional full-chest acquisition for similarity to a reference standard (via optical imaging in vitro) or for repeatability in vivo. Aim 3 will test LV flow indices in a pilot cohort of MI patients to evaluate whether apical stasis (regional flow velocity, kinetic energy, residual blood volumes) post-MI is associated with LVT. The project sponsors and collaborators have a track record in successful translational CMR research and MRI physics, uniquely qualifying them to mentor on the proposed work. The novel information to be gained from this research has potential to impact clinical care by more precisely identifying post-MI flow patterns associated with LVT, thereby setting up future trials to test these parameters as predictors of LVT. The skills gained by the PI during this project will position him strongly for a successful independent research career in cardiovascular MRI.