title: A technique for in vivo mapping of myocardial creatine kinase metabolism.
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.
authors.affiliation: 1] Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. [2].
authors.forename: Mohammad
authors.initials: M
authors.lastname: Haris
authors.affiliation: 1] Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. [2].
authors.forename: Anup
authors.initials: A
authors.lastname: Singh
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Kejia
authors.initials: K
authors.lastname: Cai
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Feliks
authors.initials: F
authors.lastname: Kogan
authors.affiliation: Gorman Cardiovascular Research Group, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: McGarvey
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Debrosse
authors.affiliation: Gorman Cardiovascular Research Group, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Zsido
authors.affiliation: 1] Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. [2] Gorman Cardiovascular Research Group, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Walter R T
authors.initials: WR
authors.lastname: Witschey
authors.affiliation: Gorman Cardiovascular Research Group, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Koomalsingh
authors.affiliation: Gorman Cardiovascular Research Group, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Pilla
authors.affiliation: 1] Department of Medicine, Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA. [2] Department of Medicine, Cardiovascular Division, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Julio A
authors.initials: JA
authors.lastname: Chirinos
authors.affiliation: Department of Medicine, Cardiovascular Division, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Victor A
authors.initials: VA
authors.lastname: Ferrari
authors.affiliation: Gorman Cardiovascular Research Group, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Gorman
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Hari
authors.initials: H
authors.lastname: Hariharan
authors.affiliation: Gorman Cardiovascular Research Group, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Gorman
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Ravinder
authors.initials: R
authors.lastname: Reddy
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D003401:Creatine / Q000378:metabolism*; D003402:Creatine Kinase / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D057054:Molecular Imaging / Q000379:methods*; D018482:Muscle, Skeletal / Q000378:metabolism; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000201:enzymology*; D011522:Protons; D014867:Water / Q000737:chemistry
chemical_list: D011522:Protons; D014867:Water; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D003401:Creatine