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Noninvasive Localized MR Quantification of Creatine Kinase Metabolites in Normal and Infarcted Canine Myocardium¹

¹ From the Department of Radiology, Division of MR Research (P.A.B.), and the Department of Medicine, Division of Cardiology (R.G.W.), Johns Hopkins University, JHOC-4221, 601 N Caroline St, Baltimore, MD 21287-0843. Received June 22, 2000; revision requested August 8; revision received September 6; accepted September 11. Supported by National Institutes of Health grants RO1 HL56882-01, HL52315-05, and HL61912-01. Address correspondence to P.A.B. (e-mail: bottoml@mri.jhu.edu).

PURPOSE: To develop image-guided spatially localized magnetic resonance (MR) spectroscopy to provide a noninvasive quantitative probe of myocardial creatine kinase (CK) metabolism, and to use it to determine the extent of changes in CK energy metabolism in nonviable infarcted canine myocardium.

MATERIALS AND METHODS: Water-referenced localized phosphorus and proton MR spectroscopy were combined in a single protocol to noninvasively measure phosphocreatine (PCr), adenosine triphosphate (ATP), and total of phosphorylated and unphosphorylated creatine (CR) concentrations and pH in the myocardium in six normal dogs and six dogs with surgically induced myocardial infarction. Unphosphorylated creatine and adenosine diphosphate (ADP) levels were calculated. The results were compared with biochemical measurements at postmortem biopsy.

RESULTS: Significant reductions in PCr-to-ATP ratios (1.7 ± 0.3 [SD] vs 1 ± 0.4; P < .001), PCr (10.3 ± 2.1 vs 4.3 ± 2.0 µmol/g wet weight; P < .0001), ATP (6.4 ± 1.4 vs 3.7 ± 1.4 µmol/g wet weight; P < .001), and CR (24.7 ± 6.1 vs 6.3 ± 3.7; P < .0001) were measured noninvasively in infarcted, as compared with normal, tissue. Biopsy measurements confirmed infarct-related reductions observed at MR spectroscopy, although high-energy phosphate concentrations were lower at biopsy. ADP calculated from noninvasive MR spectroscopic measurements was 0.11 ± 0.07 µmol/g wet weight in normal myocardium.

CONCLUSION: This combined phosphorus and proton MR spectroscopic approach provides a near-complete picture of in vivo myocardial CK metabolism in normal and diseased heart and a tool for noninvasively measuring metabolite reductions associated with the loss of viability.

Index terms: Animals • Heart, MR, 511.121411, 511.121415 • Heart, MR spectroscopy, 511.12145 • Magnetic resonance (MR), phosphorus studies, 511.121411, 511.121415, 511.12147 • Magnetic resonance (MR), spectroscopy, 511.12145 • Metabolism, 511.91 • Myocardium, infarction, 511.814

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