A simple approach to evaluate the kinetic rate constant for ATP synthesis in resting human skeletal muscle at 7 T

• Published in: NMR in biomedicine Vol. 29; no. 9; pp. 1240 - 1248
• Main Authors: Ren, Jimin, Sherry, A. Dean, Malloy, Craig R.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.09.2016; Wiley Subscription Services, Inc
• Subjects: 7 T; Adenosine Triphosphate - biosynthesis; Adult; Algorithms; ATP; chemical exchange; Computer Simulation; energy metabolism; Female; Humans; inversion transfer; Kinetics; Magnetic Resonance Spectroscopy - methods; magnetization transfer; Male; Metabolic Clearance Rate; Models, Biological; Muscle, Skeletal - metabolism; Phosphorus Isotopes - pharmacokinetics; Radiopharmaceuticals - pharmacokinetics; Reproducibility of Results; Rest - physiology; Sensitivity and Specificity; skeletal muscle; T1 relaxation time; inversion transfer; T1 relaxation time; magnetization transfer; 7 T; skeletal muscle; ATP; energy metabolism; chemical exchange
• ISSN: 0952-3480; 1099-1492; 1099-1492
• DOI: 10.1002/nbm.3310

Inversion transfer (IT) is a well‐established technique with multiple attractive features for analysis of kinetics. However, its application in measurement of ATP synthesis rate in vivo has lagged behind the more common saturation transfer (ST) techniques. One well‐recognized issue with IT is the complexity of data analysis in comparison with much simpler analysis by ST. This complexity arises, in part, because the γ‐ATP spin is involved in multiple chemical reactions and magnetization exchanges, whereas Pi is involved in a single reaction, Pi → γ‐ATP. By considering the reactions involving γ‐ATP only as a lumped constant, the rate constant for the reaction of physiological interest, kPi→γATP, can be determined. Here, we present a new IT data analysis method to evaluate kPi→γATP using data collected from resting human skeletal muscle at 7 T. The method is based on the basic Bloch–McConnell equation, which relates kPi→γATP to m˙Pi, the rate of Pi magnetization change. The kPi→γATP value is accessed from m˙Pi data by more familiar linear correlation approaches. For a group of human subjects (n = 15), the kPi→γATP value derived for resting calf muscle was 0.066 ± 0.017 s−1, in agreement with literature‐reported values. In this study we also explored possible time‐saving strategies to speed up data acquisition for kPi→γATP evaluation using simulations. The analysis indicates that it is feasible to carry out a 31P IT experiment in about 10 min or less at 7 T with reasonable outcome in kPi→γATP variance for measurement of ATP synthesis in resting human skeletal muscle. We believe that this new IT data analysis approach will facilitate the wide acceptance of IT to evaluate ATP synthesis rate in vivo. Copyright © 2015 John Wiley & Sons, Ltd. Extracting the ATP synthesis rate constant (kPi→γATP) from 31P inversion transfer measurements is generally complicated by the tangle of multiple spin relaxation and exchange parameters in the magnetization equations describing the exchange system. This problem can be avoided by using a simple alternative approach based on the Bloch–McConnell equation for inorganic phosphate Pi, which allows the evaluation of kPi→γATP by a linear plot of Pi magnetization rate (m˙Pi) against the magnetization difference between Pi and γ‐ATP (mPi − mγATP) .