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

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 P_i is involved in a single reaction, P_i → γ-ATP. By considering the reactions involving γ-ATP only as a lumped constant, the rate constant for the reaction of physiological interest, k_Pi→γATP, can be determined. Here, we present a new IT data analysis method to evaluate k_Pi→γATP using data collected from resting human skeletal muscle at 7 T. The method is based on the basic Bloch–McConnell equation, which relates k_Pi→γATP to (Formula presented.), the rate of P_i magnetization change. The k_Pi→γATP value is accessed from (Formula presented.) data by more familiar linear correlation approaches. For a group of human subjects (n = 15), the k_Pi→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 k_Pi→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 k_Pi→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.