A technique for in vivo mapping of myocardial creatine kinase metabolism

The measurement of metabolites such as creatine, which are involved in the tissue creatine kinase reaction, enable the study of the effects of energy deprivation on the heart. Haris and colleagues introduce a new magnetic resonance imaging technique that maps the distribution of creatine in the heart that does not use radiation or exogenous contrast agents and offers higher sensitivity compared to proton ( 1 H) magnetic resonance spectroscopy methods. Feasibility is demonstrated in vivo in infarcted swine myocardium using a standard clinical MRI scanner. ATP derived from the conversion of phosphocreatine to creatine by creatine kinase provides an essential chemical energy source that governs myocardial contraction. Here, we demonstrate that the exchange of amine protons from creatine with protons in bulk water can be exploited to image creatine through chemical exchange saturation transfer (CrEST) in myocardial tissue. We show that CrEST provides about two orders of magnitude higher sensitivity compared to 1 H magnetic resonance spectroscopy. Results of CrEST studies from ex vivo myocardial tissue strongly correlate with results from 1 H and 31 P magnetic resonance spectroscopy and biochemical analysis. We demonstrate the feasibility of CrEST measurement in healthy and infarcted myocardium in animal models in vivo on a 3-T clinical scanner. As proof of principle, we show the conversion of phosphocreatine to creatine by spatiotemporal mapping of creatine changes in the exercised human calf muscle. We also discuss the potential utility of CrEST in studying myocardial disorders.