A technique for in vivo mapping of myocardial creatine kinase metabolism

Mohammad Haris, Anup Singh, Kejia Cai, Feliks Kogan, Jeremy McGarvey, Catherine Debrosse, Gerald A. Zsido, Walter R T Witschey, Kevin Koomalsingh, James J. Pilla, Julio A. Chirinos, Victor A. Ferrari, Joseph H. Gorman, Hari Hariharan, Robert C. Gorman, Ravinder Reddy

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Abstract

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.

Original languageEnglish
Pages (from-to)209-214
Number of pages6
JournalNature Medicine
Volume20
Issue number2
DOIs
Publication statusPublished - Feb 2014
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Haris, M., Singh, A., Cai, K., Kogan, F., McGarvey, J., Debrosse, C., Zsido, G. A., Witschey, W. R. T., Koomalsingh, K., Pilla, J. J., Chirinos, J. A., Ferrari, V. A., Gorman, J. H., Hariharan, H., Gorman, R. C., & Reddy, R. (2014). A technique for in vivo mapping of myocardial creatine kinase metabolism. Nature Medicine, 20(2), 209-214. https://doi.org/10.1038/nm.3436