Noninvasive assessment of coronary endothelial function by multi-slice MRI

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Coronary artery disease (CAD) remains a leading and important cause of disability and premature death in the United States. Conventional clinical imaging characterizes coronary artery anatomy, but because most acute coronary events result from plaque rupture in regions previously exhibiting less than 50% luminal stenosis, current state-of-the-art anatomic imaging cannot predict where plaque progression and events will occur. A new approach is needed and evidence suggests that coronary endothelial function (CEF) imaging can fill this gap. CEF is considered a “barometer” of vascular health because endothelial release of nitric oxide in response to certain stressors is a defining characteristic of healthy vascular tissue that results in arterial dilatation and increased blood flow. Impaired endothelial nitric oxide release, or endothelial dysfunction, is a marker for sub-clinical disease, an independent predictor of future CAD progression and cardiac events, and responds favorably to beneficial medical interventions. Despite the well-established diagnostic and prognostic importance of CEF, it is rarely measured in clinical practice because it was mostly measured with invasive cardiac catheterization. We recently developed a noninvasive magnetic resonance imaging (MRI) means to quantify local CEF that combines 2-dimensional (2D) cine MRI with isometric handgrip exercise (IHE). The main limitation is that the 2D approach only allows CEF measurements at just two to four locations and therefore cannot characterize CEF in multiple arteries or regional heterogeneity present throughout a diseased coronary artery. The aims of our proposal are 1) to develop a new multi-slice MRI method that to assess CEF area changes along proximal to mid segments in all major coronary arteries; 2) to optimize and validate the proposed method’s ability to measure cross sectional areas by assessing both accuracy and precision; and 3) to validate the CEF measures from the proposed method against the noninvasive gold-standard including reproducibility testing in both healthy subjects and stable CAD patients. This work will provide a robust, noninvasive means to better and more comprehensively assess CEF, an independent predictor of future atherosclerotic progression and events, and barometer of response to therapy. Knowledge of accuracy, precision, and reproducibility values will enable us to design future studies investigating novel interventions and monitoring disease progression.