? Coronary artery disease (CAD) is the leading cause of death in industrialized nations. Under normal physiological conditions, myocardial blood flow, oxygen consumption (MVO2), myocardial blood volume, and myocardial mechanical function are intimately related. CAD manifests as imbalances between myocardial oxygen supply and demand. Myocardial oxygen extraction fraction (OEF) and MVO2 directly reflects the balance of oxygen supply and demand of myocardium. Accurate assessment of myocardial ischemic status, particularly myocardial viability, is of paramount importance for selection of patients likely to benefit from coronary revascularization. However, detection of this status in myocardium remains an important clinical problem, partially owning to the inherent difficulty of direct measurement of OEF and MVO2 in vivo, particularly on a non-invasive and regional basis. In this proposal, it is hypothesized that myocardial OEF and MVO2 can be quantified using non-invasive magnetic resonance imaging (MRI) techniques and the BOLD (Blood Oxygen Level Dependent) effect. The later can be characterized by transverse relaxation time T2 contrast in MRI. Therefore, our overall objective is to optimize and validate a series of clinically viable MRI techniques to measure myocardial OEF and MVO2 reliably and consistently. Measurement of MVO2 is based on Pick's law: MVO2 is proportional to the product of myocardial OEF and blood flow. To validate the proposed techniques by invasive methods, we propose to use a closed-chest canine model. The goal of the application will be accomplished by pursuing the following three specific aims.
In Aim 1, a first-pass perfusion method will be further optimized with an established mathematical modeling. This MRI method will be used to measure myocardial blood flow and volume at rest and during pharmacologically induced stress. Accuracy will be determined by comparing with gold standards such as microsphere for blood flow measurements and 99mTc-labeled red blood cells for blood volume measurement.
In Aim 2, established techniques for measuring myocardial OEF will be further optimized and validated in vivo. The gold standard will be simultaneous blood sampling from artery and coronary sinus. These optimized techniques will be integrated in Aim 3 to calculate myocardial OEF and MVO2 in dogs with and without coronary artery stenosis, at rest and during pharmacological stress. Validation will be performed by comparison to PET imaging. This MRI research will provide an important tool for better understanding the physiology and pathophysiology underlying the myocardial ischemia and viability. In addition, this direct measurement may offer an objective and convenient means to assess the efficacy of cardiac therapies. Ultimately, the proposed methods may facilitate more comprehensive MRI assessments of CAD and other cardiac diseases. ? ?
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