Accuracy and precision of quantitative 31P-MRS measurements of human skeletal muscle mitochondrial function.
Although 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 multipoint 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) 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 the (31)P-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.
Department of Medicine, Division of Geriatrics, University of Utah, Salt Lake City, Utah; Geriatric Research, Education, and Clinical Center, George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah; gwenael.layec@utah.edu.
Gwenael
G
Layec
Geriatric Research, Education, and Clinical Center, George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah; Department of Exercise and Sport Science, University of Utah, Salt Lake City, Utah;
Jayson R
JR
Gifford
Department of Medicine, Division of Geriatrics, University of Utah, Salt Lake City, Utah; Geriatric Research, Education, and Clinical Center, George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah;
Joel D
JD
Trinity
Geriatric Research, Education, and Clinical Center, George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah; Department of Exercise and Sport Science, University of Utah, Salt Lake City, Utah;
Corey R
CR
Hart
Department of Medicine, Division of Geriatrics, University of Utah, Salt Lake City, Utah; Geriatric Research, Education, and Clinical Center, George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah;
Ryan S
RS
Garten
Geriatric Research, Education, and Clinical Center, George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah; Department of Exercise and Sport Science, University of Utah, Salt Lake City, Utah;
Song Y
SY
Park
Aix-Marseille Université, Centre national de la recherche scientifique, Center for Magnetic Resonance in Biology and Medicine, Unité Mixte de Recherche 7339, Marseille, France.
Yann
Y
Le Fur
Department of Radiology and Utah Center for Advanced Imaging Research, University of Utah, Salt Lake City, Utah; and.
Eun-Kee
EK
Jeong
Department of Medicine, Division of Geriatrics, University of Utah, Salt Lake City, Utah; Geriatric Research, Education, and Clinical Center, George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah; Department of Exercise and Sport Science, University of Utah, Salt Lake City, Utah;
Russell S
RS
Richardson
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000328:Adult; D015444:Exercise; D005260:Female; D006801:Humans; D007537:Isometric Contraction; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D010759:Phosphorus Isotopes; D052097:Quadriceps Muscle / Q000378:metabolism*; D055815:Young Adult
D010759:Phosphorus Isotopes; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate
PCr recovery; State 3 respiration; mitochondrial capacity assessment; respirometry