title: ATP production rate via creatine kinase or ATP synthase in vivo: a novel superfast magnetization saturation transfer method.
abstract: BACKGROUND
  ³¹P magnetization saturation transfer (MST) experiment is the most widely used method to study ATP metabolism kinetics. However, its lengthy data acquisition time greatly limits the wide biomedical applications in vivo, especially for studies requiring high spatial and temporal resolutions.
  
  
  OBJECTIVE
  We aimed to develop a novel superfast MST method that can accurately quantify ATP production rate constants (k(f)) through creatine kinase (CK) or ATP synthase (ATPase) with 2 spectra.
  
  
  RESULTS
  The T₁(nom) (T₁ nominal) method uses a correction factor to compensate the partially relaxed MST experiments, thus allowing measurement of enzyme kinetics with an arbitrary repetition time and flip angle, which consequently reduces the data acquisition time of a transmurally differentiated CK k(f) measurement by 91% as compared with the conventional method with spatial localization. The novel T₁(nom) method is validated theoretically with numeric simulation, and further verified with in vivo swine hearts, as well as CK and ATPase activities in rat brain at 9.4 Tesla. Importantly, the in vivo data from swine hearts demonstrate, for the first time, that within an observation window of 30 minutes, the inhibition of CK activity by iodoacetamide does not limit left ventricular chamber contractile function.
  
  
  CONCLUSIONS
  A novel MST method for superfast examination of enzyme kinetics in vivo has been developed and verified theoretically and experimentally. In the in vivo normal heart, redundant multiple supporting systems of myocardial ATP production, transportation, and utilization exist, such that inhibition of one mechanism does not impair the normal left ventricular contractile performance.
authors.affiliation: Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xiong
authors.forename: Fei
authors.initials: F
authors.lastname: Du
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zhu
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Zhang
authors.forename: Piradeep
authors.initials: P
authors.lastname: Suntharalingam
authors.forename: Joseph
authors.initials: J
authors.lastname: Ippolito
authors.forename: Forum D
authors.initials: FD
authors.lastname: Kamdar
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Jianyi
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D003402:Creatine Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004734:Energy Metabolism; D005260:Female; D006439:Hemodynamics; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism; D010759:Phosphorus Isotopes; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine; D013997:Time Factors
chemical_list: D010759:Phosphorus Isotopes; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D006180:Proton-Translocating ATPases