Accuracy and precision of quantitative 31P-MRS measurements of human skeletal muscle mitochondrial function
Résumé
While theoretically sound, the accuracy and precision of (31)P-magnetic resonance spectroscopy ((31)P-MRS) approaches to quantitatively estimate mitochondrial capacity are not well documented. Therefore, employing four differing models of respiratory control (linear, kinetic and multi-point adenosine diphosphate (ADP), and phosphorylation potential), this study sought to determine the accuracy and precision of (31)P-MRS assessments of peak mitochondrial adenosine-triphosphate (ATP) synthesis rate utilizing directly measured peak respiration (State 3) in permeabilized skeletal muscle fibers. In 23 subjects, of different fitness levels, (31)P-MRS during a 24-s maximal isometric knee-extension and high-resolution respirometry in muscle fibers from the vastus lateralis was performed. Although significantly correlated with State 3 respiration (r=0.72), both the linear (45±13 mM.min(-1)) and phosphorylation potential (47±16mM.min(-1)) models grossly overestimated the calculated in vitro peak ATP synthesis rate (P\textless0.05). Of the ADP models, the kinetic model was well correlated with State 3 respiration (r=0.72; P\textless0.05), but moderately overestimated ATP synthesis rate (P\textless0.05), while the multi-point model, although being somewhat less well correlated with State 3 respiration (r=0.55; P\textless0.05), most accurately reflected peak ATP synthesis rate. Of note, the PCr recovery time constant (τ), a qualitative index of mitochondrial capacity, exhibited the strongest correlation with State 3 respiration (r=0.80; P\textless0.05). Therefore, this study reveals that each of the (31)P-MRS data analyses, including PCr τ, exhibit precision in terms of mitochondrial capacity. As only the multi-point ADP model did not overstimate the peak skeletal muscle mitochondrial ATP synthesis, the multi-point ADP model is the only quantitative approach to exhibit both accuracy and precision.