Type 2 diabetes mellitus (T2DM) and its co-existing target-organ involvement, such as diabetic nephropathy (DN), significantly contribute to the risk of coronary artery disease (CAD). Generally, CAD has a long latency until coronary events (a group of symptoms attributed to myocardial ischemia) affect T2DM patients. During this clinically "silent" period, the coronary structure changes, and the coronary wall continues to be remodeled in response to the progression of atherosclerotic plaques. However, the morphological and functional features in the remodeled coronary artery, which may convey the near-term risk of subclinical CAD, have not been comprehensively investigated in asymptomatic T2DM patients who do not have documented or suspected structural cardiovascular diseases. This knowledge gap exists mainly because clinical examinations for detecting the coronary wall are either invasive or require X-ray exposure and nephrotoxic contrast media. Previous studies by our group and others have shown that MRI can detect morphological and functional changes caused by coronary wall remodeling. Additionally, recent studies have provided evidence that MRI can evaluate changes in myocardial tissue structure (fibrosis and edema) and ventricular motion/function, which may accompany the development of CAD. Therefore, we hypothesize that MRI measures may serve as imaging biomarkers to reveal subclinical CAD burden as well as related myocardial abnormalities in T2DM patients. However, application of coronary MRI in clinical practice remains limited by adverse physiological conditions. In this proposal, we are planning to develop and optimize a three-dimensional (3D) steady-state free precession (SSFP) coronary wall MRI sequence for the detection of coronary plaques with larger coverage and better image quality. A comprehensive MRI protocol will then be built to characterize the subclinical CAD burden, as well as related myocardial changes, in T2DM patients with and without DN. Finally, we will assess whether the relationship between subclinical CAD burden and DN is independent of the conventional T2DM/cardiovascular risk conditions. The research plan is designed to develop and optimize a novel coronary wall MRI methodology, and to conduct a preliminary study to generate pilot data for a consequent longitudinal research project that evaluates the cardiovascular benefits of comprehensive T2DM management. Incorporated with continued mentorship from experts in this field, this mentored research project will serve as a unique vehicle to provide me with broad training in acquiring and interpreting quantitative imaging biomarkers and the necessary skills to achieve my career goal of becoming an independent investigator in cardiovascular medicine.
|Effective start/end date||9/1/15 → 6/30/21|
- National Heart, Lung, and Blood Institute (5K01HL121162-05)
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