Oxidative energy metabolism is essential for normal cardiac contractile function. Phosphorus (31P) magnetic resonance spectroscopy (MRS) is unique in its ability to provide noninvasive access to key metabolites such as adenosine triphosphate (ATP) and phosphocreatine (PCr) in the heart. Patient MRS studies show reduced levels of PCr and ATP in myocardial infarction, and altered PCr/ATP ratios in heart failure that correlate with clinical severity. Biopsy and autopsy date demonstrate that total myocardial creatine (CR, however, have been limited by the invasive nature of existing techniques. But CR can be observed in vivo by proton MRS. Moreover, due to the higher 1H MRS sensitivity and the extraordinarily greater proton concentration of the CR N-CH3 moiety, CR MRS can potentially provide a more than 20 fold gain in signal-to-noise relative to 31P studies of PCr. Thus 1H MRS of CR MRS offers a new, sensitive, window for quantifying, mapping, and even imaging, an important myocardial energy metabolite. We have demonstrated CR detection and mapping in normal human heart and CR reductions in human myocardial infarction in our preliminary 1H MRS work. Here, the development and validation of 1H MRS as a tool for quantifying regional myocardial CR in the human heart is proposed using phantom, MRS, and biopsy studies of canine myocardium, as well as noninvasive human MRS studies. The use of CR MRS for differentiating infarcted myocardium from noninfarcted myocardium will be assessed via quantitative MRS and tissue assays in a well-defined canine model of infarction, and by MRS studies of patients with myocardial infarction. The hypothesis that myocardial CR and PCr levels in the CK reaction are reduced in the failing human heart in proportion to the severity of heart failure will be tested with noninvasive1H and 31P MRS studies of patients with heart failure. The development of a new, sensitive, noninvasive method for quantifying myocardial energy metabolism would significantly advance our understanding of the role of energy deprivation in heart disease, and potentially provide us with a new probe for assessing cardiac tissue viability.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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Diagnostic Radiology Study Section (RNM)
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Johns Hopkins University
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