Accuracy and precision of quantitative31P-MRS measurements of human skeletal muscle mitochondrial function

Gwenael Layec, Jayson R. Gifford, Joel D. Trinity, Corey R. Hart, Ryan S. Garten, Song Y. Park, Yann Le Fur, Eun Kee Jeong, Russell S. Richardson

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Although theoretically sound, the accuracy and precision of31Pmagnetic resonance spectroscopy (31P-MRS) approaches to quantitatively estimate mitochondrial capacity are not well documented. Therefore, employing four differing models of respiratory control [linear, kinetic, and multipoint adenosine diphosphate (ADP) and phosphorylation potential], this study sought to determine the accuracy and precision of31P-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,31P-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) and phosphorylation potential (47 ± 16 mM/min) models grossly overestimated the calculated in vitro peak ATP synthesis rate (P < 0.05). Of the ADP models, the kinetic model was well correlated with State 3 respiration (r = 0.72, P < 0.05), but moderately overestimated ATP synthesis rate (P < 0.05), while the multipoint model, although being somewhat less well correlated with State 3 respiration (r = 0.55, P < 0.05), 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 < 0.05). Therefore, this study reveals that each of the31P-MRS data analyses, including PCr τ, exhibit precision in terms of mitochondrial capacity. As only the multipoint ADP model did not overstimate the peak skeletal muscle mitochondrial ATP synthesis, the multipoint ADP model is the only quantitative approach to exhibit both accuracy and precision.

Original languageEnglish (US)
Pages (from-to)E358-E366
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume311
Issue number2
DOIs
StatePublished - Aug 1 2016
Externally publishedYes

Keywords

  • Mitochondrial capacity assessment
  • PCr recovery
  • Respirometry
  • State 3 respiration

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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