Proton magnetic resonance spectroscopy in skeletal muscle: Experts' consensus recommendations

1H‐MR spectroscopy of skeletal muscle provides insight into metabolism that is not available noninvasively by other methods. The recommendations given in this article are intended to guide those who have basic experience in general MRS to the special application of 1H‐MRS in skeletal muscle. The highly organized structure of skeletal muscle leads to effects that change spectral features far beyond simple peak heights, depending on the type and orientation of the muscle. Specific recommendations are given for the acquisition of three particular metabolites (intramyocellular lipids, carnosine and acetylcarnitine) and for preconditioning of experiments and instructions to study volunteers.

[1]  Simon C Watkins,et al.  Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. , 2001, The Journal of clinical endocrinology and metabolism.

[2]  J. A. Wise,et al.  Influence of β-alanine supplementation on skeletal muscle carnosine concentrations and high intensity cycling capacity , 2007, Amino Acids.

[3]  M. Kushmerick,et al.  Mammalian skeletal muscle fibers distinguished by contents of phosphocreatine, ATP, and Pi. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Wolfgang Bogner,et al.  Depth‐resolved surface coil MRS (DRESS)‐localized dynamic 31P‐MRS of the exercising human gastrocnemius muscle at 7 T , 2014, NMR in biomedicine.

[5]  Britton Chance,et al.  An in vivo phosphorus nuclear magnetic resonance study of the variations with age in the phosphodiers' content of human muscle , 1988, Mechanisms of Ageing and Development.

[6]  Gregory J. Crowther,et al.  Control of glycolysis in contracting skeletal muscle. I. Turning it on. , 2002, American journal of physiology. Endocrinology and metabolism.

[7]  E. Ravussin,et al.  Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. , 2012, Cell metabolism.

[8]  D. Befroy,et al.  Assessment of in vivo mitochondrial metabolism by magnetic resonance spectroscopy. , 2009, Methods in enzymology.

[9]  M. Ferrari,et al.  The use of near-infrared spectroscopy in understanding skeletal muscle physiology: recent developments , 2011, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[10]  Eric Achten,et al.  Important role of muscle carnosine in rowing performance. , 2010, Journal of applied physiology.

[11]  M. McKenna,et al.  Effects of carnosine on contractile apparatus Ca²⁺ sensitivity and sarcoplasmic reticulum Ca²⁺ release in human skeletal muscle fibers. , 2012, Journal of applied physiology.

[12]  C Boesch,et al.  Dipolar coupling and ordering effects observed in magnetic resonance spectra of skeletal muscle , 2001, NMR in biomedicine.

[13]  R. Shulman,et al.  Intracellular pH in human skeletal muscle by 1H NMR. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[14]  R. Kreis,et al.  Standardized protocol for a depletion of intramyocellular lipids (IMCL) , 2010, NMR in biomedicine.

[15]  Matthew D Robson,et al.  OXSA: An open-source magnetic resonance spectroscopy analysis toolbox in MATLAB , 2017, PloS one.

[16]  P. Bachert,et al.  Evidence for a dipolar-coupled AM system in carnosine in human calf muscle from in vivo 1H NMR spectroscopy. , 2003, Journal of magnetic resonance.

[17]  G J Kemp,et al.  Quantification of skeletal muscle mitochondrial function by 31P magnetic resonance spectroscopy techniques: a quantitative review , 2015, Acta physiologica.

[18]  J. Haselgrove,et al.  Functional pools of oxidative and glycolytic fibers in human muscle observed by 31P magnetic resonance spectroscopy during exercise. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[19]  P. Carlier,et al.  Practical implementation of single‐voxel double‐quantum editing on a whole‐body NMR spectrometer: Localized monitoring of lactate in the human leg during and after exercise , 1996, Magnetic resonance in medicine.

[20]  L. DiPietro,et al.  Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study , 1999, Diabetologia.

[21]  R. Meyer,et al.  Energy cost of twitch and tetanic contractions of rat muscle estimated in situ by gated 31P NMR , 1993, NMR in biomedicine.

[22]  C. Hilbers,et al.  31P Saturation Transfer Spectroscopy Predicts Differential Intracellular Macromolecular Association of ATP and ADP in Skeletal Muscle* , 2010, The Journal of Biological Chemistry.

[23]  K. Nicolay,et al.  MRS studies of muscle and heart in obesity and diabetes , 2016 .

[24]  Wolfgang Bogner,et al.  Spectral editing in 1H magnetic resonance spectroscopy: Experts' consensus recommendations , 2020, NMR in biomedicine.

[25]  V. Edgerton,et al.  Muscle fibre type populations of human leg muscles , 1975, The Histochemical Journal.

[26]  J. Wildberger,et al.  Carnitine supplementation improves metabolic flexibility and skeletal muscle acetylcarnitine formation in volunteers with impaired glucose tolerance: A randomised controlled trial , 2017, EBioMedicine.

[27]  Stephen A. Foulis,et al.  Age-related changes in oxidative capacity differ between locomotory muscles and are associated with physical activity behavior. , 2012, Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme.

[28]  S. Perrey,et al.  Reproducibility assessment of metabolic variables characterizing muscle energetics in Vivo: A 31P‐MRS study , 2009, Magnetic resonance in medicine.

[29]  T. Richards,et al.  Activation of glycolysis in human muscle in vivo. , 1997, The American journal of physiology.

[30]  Vanhamme,et al.  Improved method for accurate and efficient quantification of MRS data with use of prior knowledge , 1997, Journal of magnetic resonance.

[31]  D. Stegeman,et al.  pH heterogeneity in tibial anterior muscle during isometric activity studied by (31)P-NMR spectroscopy. , 2001, Journal of applied physiology.

[32]  P. Bottomley Measuring Biochemical Reaction Rates In Vivo with Magnetization Transfer , 2016 .

[33]  P. Kuchel,et al.  Skeletal muscle lipid metabolism studied by advanced magnetic resonance spectroscopy. , 2012, Progress in nuclear magnetic resonance spectroscopy.

[34]  T. Takken,et al.  Altered Energetics of Exercise Explain Risk of Rhabdomyolysis in Very Long-Chain Acyl-CoA Dehydrogenase Deficiency , 2016, PloS one.

[35]  S. Provencher Automatic quantitation of localized in vivo 1H spectra with LCModel , 2001, NMR in biomedicine.

[36]  G. Kemp,et al.  Cytosolic pH buffering during exercise and recovery in skeletal muscle of patients with McArdle’s disease , 2009, European Journal of Applied Physiology.

[37]  Ewald Moser,et al.  Dynamic multivoxel‐localized 31P MRS during plantar flexion exercise with variable knee angle , 2018, NMR in biomedicine.

[38]  David S. Wishart,et al.  HMDB: a knowledgebase for the human metabolome , 2008, Nucleic Acids Res..

[39]  Guy B. Williams,et al.  31P magnetization transfer measurements of Pi→ATP flux in exercising human muscle , 2016, Journal of applied physiology.

[40]  G. Kemp,et al.  Interrelations of ATP synthesis and proton handling in ischaemically exercising human forearm muscle studied by 31P magnetic resonance spectroscopy , 2001, The Journal of physiology.

[41]  Theodoros N. Arvanitis,et al.  A constrained least‐squares approach to the automated quantitation of in vivo 1H magnetic resonance spectroscopy data , 2011, Magnetic resonance in medicine.

[42]  F. Schick,et al.  Measurement of intracellular triglyceride stores by H spectroscopy: validation in vivo. , 1999, American journal of physiology. Endocrinology and metabolism.

[43]  J. Le Bas,et al.  Muscular metabolism during oxygen supplementation in patients with chronic hypoxemia. , 1993, The American review of respiratory disease.

[44]  Ian R. Lanza,et al.  In vivo ATP production during free‐flow and ischaemic muscle contractions in humans , 2006, The Journal of physiology.

[45]  Stefan Neubauer,et al.  Human cardiac 31P magnetic resonance spectroscopy at 7 tesla , 2013, Magnetic resonance in medicine.

[46]  D. Arnold,et al.  Insights into muscle diseases gained by phosphorus magnetic resonance spectroscopy , 2000, Muscle & nerve.

[47]  H. Reyngoudt,et al.  1H NMRS of carnosine combined with 31P NMRS to better characterize skeletal muscle pH dysregulation in Duchenne muscular dystrophy , 2018, NMR in biomedicine.

[48]  D. Lüthi,et al.  Mg‐Atp Binding: Its Modification by Spermine, the Relevance to Cytosolic Mg2+ Buffering, Changes in the Intracellular Ionized Mg2+ Concentration and the Estimation of Mg2+ by 31P‐NMR , 1999, Experimental physiology.

[49]  Theodore F. Towse,et al.  Quantitative analysis of the postcontractile blood-oxygenation-level-dependent (BOLD) effect in skeletal muscle. , 2011, Journal of applied physiology.

[50]  R. R. Ernst,et al.  Application of Fourier Transform Spectroscopy to Magnetic Resonance , 1966 .

[51]  Ewald Moser,et al.  Absolute quantification of phosphorus metabolite concentrations in human muscle in vivo by 31P MRS: a quantitative review , 2007, NMR in biomedicine.

[52]  Martin J. Kushmerick,et al.  A Computational Model for Glycogenolysis in Skeletal Muscle , 2002, Annals of Biomedical Engineering.

[53]  R. B. Moon,et al.  Determination of intracellular pH by 31P magnetic resonance. , 1973, The Journal of biological chemistry.

[54]  G. Hunter,et al.  31P MRS measurement of mitochondrial function in skeletal muscle: reliability, force‐level sensitivity and relation to whole body maximal oxygen uptake , 1995, NMR in biomedicine.

[55]  S Nioka,et al.  Control of oxidative metabolism and oxygen delivery in human skeletal muscle: a steady-state analysis of the work/energy cost transfer function. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[56]  D. Allen,et al.  Skeletal muscle fatigue: cellular mechanisms. , 2008, Physiological reviews.

[57]  P. Scifo,et al.  Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents. , 1999, Diabetes.

[58]  R. Haller,et al.  Dynamic monitoring of carnitine and acetylcarnitine in the trimethylamine signal after exercise in human skeletal muscle by 7T 1H‐MRS , 2013, Magnetic resonance in medicine.

[59]  G. Kemp,et al.  What Do Magnetic Resonance–Based Measurements of Pi→ATP Flux Tell Us About Skeletal Muscle Metabolism? , 2012, Diabetes.

[60]  D L Rothman,et al.  The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 2000 by The Endocrine Society Intramuscular Glycogen and Intramyocellular Lipid Utilization during Prolonged Exercise and Recovery in Man: A 13 C and 1 H Nuclear Magnetic Res , 1999 .

[61]  R. Kreis,et al.  Muscle Studies by 1H MRS , 2016 .

[62]  W. Grodd,et al.  Intramyocellular lipid quantification from 1H long echo time spectra at 1.5 and 3 T by means of the LCModel technique , 2006, Journal of magnetic resonance imaging : JMRI.

[63]  Roland Kreis,et al.  The trouble with quality filtering based on relative Cramér‐Rao lower bounds , 2016, Magnetic resonance in medicine.

[64]  Ewald Moser,et al.  Direct noninvasive quantification of lactate and high energy phosphates simultaneously in exercising human skeletal muscle by localized magnetic resonance spectroscopy , 2007, Magnetic resonance in medicine.

[65]  F. Schick,et al.  Effects of intravenous and dietary lipid challenge on intramyocellular lipid content and the relation with insulin sensitivity in humans. , 2001, Diabetes.

[66]  J. Burakiewicz,et al.  Elevated phosphodiester and T2 levels can be measured in the absence of fat infiltration in Duchenne muscular dystrophy patients , 2017, NMR in biomedicine.

[67]  Anita Christie,et al.  Skeletal muscle fatigue. , 2012, Comprehensive Physiology.

[68]  R. Meyer,et al.  Linear dependence of muscle phosphocreatine kinetics on oxidative capacity. , 1997, The American journal of physiology.

[69]  Ewald Moser,et al.  Semi-LASER localized dynamic 31P magnetic resonance spectroscopy in exercising muscle at ultra-high magnetic field , 2011, Magnetic resonance in medicine.

[70]  N. M. van den Broek,et al.  Intersubject differences in the effect of acidosis on phosphocreatine recovery kinetics in muscle after exercise are due to differences in proton efflux rates. , 2007, American journal of physiology. Cell physiology.

[71]  J. Detre,et al.  Metabolic heterogeneity in human calf muscle during maximal exercise. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[72]  H. Roschel,et al.  β-alanine supplementation to improve exercise capacity and performance: a systematic review and meta-analysis , 2016, British Journal of Sports Medicine.

[73]  D. Wilkie,et al.  Muscular fatigue investigated by phosphorus nuclear magnetic resonance , 1978, Nature.

[74]  Serge Akoka,et al.  A new method for absolute quantitation MRS metabolites , 1997, Magnetic resonance in medicine.

[75]  N. V. van Riel,et al.  Combined in vivo and in silico investigations of activation of glycolysis in contracting skeletal muscle. , 2013, American journal of physiology. Cell physiology.

[76]  D. Manners,et al.  Effects of exercise‐induced intracellular acidosis on the phosphocreatine recovery kinetics: a 31P MRS study in three muscle groups in humans , 2013, NMR in biomedicine.

[77]  T. Jue,et al.  Comparative NMR and NIRS analysis of oxygen-dependent metabolism in exercising finger flexor muscles. , 2017, American journal of physiology. Regulatory, integrative and comparative physiology.

[78]  L. Servais,et al.  Quantitative NMRI and NMRS identify augmented disease progression after loss of ambulation in forearms of boys with Duchenne muscular dystrophy , 2015, NMR in biomedicine.

[79]  W. Derave,et al.  Muscle Carnosine Metabolism and β-Alanine Supplementation in Relation to Exercise and Training , 2010, Sports medicine.

[80]  I. Ronen,et al.  Spatially localized phosphorous metabolism of skeletal muscle in Duchenne muscular dystrophy patients: 24–month follow-up , 2017, PloS one.

[81]  A G Webb,et al.  In vivo 31P MRS detection of an alkaline inorganic phosphate pool with short T1 in human resting skeletal muscle , 2010, NMR in biomedicine.

[82]  R. Kreis,et al.  Postexercise repletion of muscle energy stores with fructose or glucose in mixed meals. , 2017, The American journal of clinical nutrition.

[83]  D. Constantin-Teodosiu,et al.  Maximal-intensity exercise does not fully restore muscle pyruvate dehydrogenase complex activation after 3 days of high-fat dietary intake. , 2018, Clinical nutrition.

[84]  R. Bennett,et al.  Increased incidence of a resonance in the phosphodiester region of 31P nuclear magnetic resonance spectra in the skeletal muscle of fibromyalgia patients. , 1994, Arthritis and rheumatism.

[85]  R. Kreis,et al.  Noninvasive Assessment of Exercise-Related Intramyocellular Acetylcarnitine in Euglycemia and Hyperglycemia in Patients With Type 1 Diabetes Using 1H Magnetic Resonance Spectroscopy , 2010, Diabetes Care.

[86]  Kenneth I Marro,et al.  Synthetic signal injection using inductive coupling. , 2008, Journal of magnetic resonance.

[87]  M. Kushmerick,et al.  Double quantum filtered (1)H NMR spectroscopy enables quantification of lactate in muscle. , 2001, Journal of magnetic resonance.

[88]  M. Kushmerick,et al.  Separate measures of ATP utilization and recovery in human skeletal muscle. , 1993, The Journal of physiology.

[89]  Ewald Moser,et al.  Relaxation times of 31P‐metabolites in human calf muscle at 3 T , 2003, Magnetic resonance in medicine.

[90]  G. Kemp Mitochondrial dysfunction in chronic ischemia and peripheral vascular disease. , 2004, Mitochondrion.

[91]  L. Bains,et al.  Oxidative capacity varies along the length of healthy human tibialis anterior , 2018, The Journal of physiology.

[92]  S Trattnig,et al.  Assessment of 31P relaxation times in the human calf muscle: A comparison between 3 T and 7 T in vivo , 2009, Magnetic resonance in medicine.

[93]  H. Tschan,et al.  Detection and Alterations of Acetylcarnitine in Human Skeletal Muscles by 1H MRS at 7 T , 2017, Investigative radiology.

[94]  S. Keevil Spatial localization in nuclear magnetic resonance spectroscopy , 2006, Physics in medicine and biology.

[95]  M. Krššák 13C MRS in Human Tissue , 2016 .

[96]  Martin Krššák,et al.  In-vivo31P-MRS of skeletal muscle and liver: A way for non-invasive assessment of their metabolism , 2017, Analytical biochemistry.

[97]  B. de Courten,et al.  Improved spectral resolution and high reliability of in vivo 1H MRS at 7 T allow the characterization of the effect of acute exercise on carnosine in skeletal muscle , 2015, NMR in biomedicine.

[98]  Dennis W J Klomp,et al.  Short echo time 1H‐MRSI of the human brain at 3T with minimal chemical shift displacement errors using adiabatic refocusing pulses , 2008, Magnetic resonance in medicine.

[99]  K. Sahlin,et al.  Absence of phosphocreatine resynthesis in human calf muscle during ischaemic recovery. , 1993, The Biochemical journal.

[100]  P Vicini,et al.  Cellular energetics analysis by a mathematical model of energy balance: estimation of parameters in human skeletal muscle. , 2000, American journal of physiology. Cell physiology.

[101]  R. Balaban,et al.  Efficiency of human skeletal muscle in vivo: comparison of isometric, concentric, and eccentric muscle action. , 1997, Journal of applied physiology.

[102]  P. Bachert,et al.  Molecular dynamics and information on possible sites of interaction of intramyocellular metabolites in vivo from resolved dipolar couplings in localized 1H NMR spectra. , 2004, Journal of magnetic resonance.

[103]  S. Forbes,et al.  Comparison of oxidative capacity among leg muscles in humans using gated 31P 2‐D chemical shift imaging , 2009, NMR in biomedicine.

[104]  K. Nicolay,et al.  Intramyocellular lipid content is increased after exercise in nonexercising human skeletal muscle. , 2003, Journal of applied physiology.

[105]  Chris Boesch,et al.  Musculoskeletal spectroscopy , 2007, Journal of magnetic resonance imaging : JMRI.

[106]  N. Sailasuta,et al.  Spatial distribution of deoxy myoglobin in human muscle: an index of local tissue oxygenation , 1999, NMR in biomedicine.

[107]  J. Wildberger,et al.  Long-echo time MR spectroscopy for skeletal muscle acetylcarnitine detection. , 2014, The Journal of clinical investigation.

[108]  Ewald Moser,et al.  Simultaneous and interleaved acquisition of NMR signals from different nuclei with a clinical MRI scanner , 2015, Magnetic resonance in medicine.

[109]  E. Moser,et al.  Interleaved 31P MRS/1H ASL for analysis of metabolic and functional heterogeneity along human lower leg muscles at 7T , 2019, Magnetic resonance in medicine.

[110]  J. Leigh,et al.  Relationships between in vivo and in vitro measurements of metabolism in young and old human calf muscles. , 1993, Journal of applied physiology.

[111]  G. Kemp,et al.  Lactate accumulation, proton buffering, and pH change in ischemically exercising muscle. , 2005, American journal of physiology. Regulatory, integrative and comparative physiology.

[112]  F. Schick,et al.  Intramyocellular lipids: anthropometric determinants and relationships with maximal aerobic capacity and insulin sensitivity. , 2003, The Journal of clinical endocrinology and metabolism.

[113]  R. Kreis,et al.  Postexercise fat intake repletes intramyocellular lipids but no faster in trained than in sedentary subjects. , 2001, American journal of physiology. Regulatory, integrative and comparative physiology.

[114]  R. Kreis,et al.  The Flexibility of Ectopic Lipids , 2016, International journal of molecular sciences.

[115]  J. Jeneson,et al.  Experimental design of 31P MRS assessment of human forearm muscle function: Restrictions imposed by functional anatomy , 1993, Magnetic resonance in medicine.

[116]  S. Trattnig,et al.  Feasibility and repeatability of localized 31P‐MRS four‐angle saturation transfer (FAST) of the human gastrocnemius muscle using a surface coil at 7 T , 2015, NMR in biomedicine.

[117]  G. Aldini,et al.  Muscle Carnosine Is Associated with Cardiometabolic Risk Factors in Humans , 2015, PloS one.

[118]  W. Derave,et al.  The influence of sex, age and heritability on human skeletal muscle carnosine content , 2011, Amino Acids.

[119]  C. W. Hilbers,et al.  Letter to the editor: "Interpretation of (31)P NMR saturation transfer experiments: do not forget the spin relaxation properties". , 2012, American journal of physiology. Cell physiology.

[120]  D. Graveron-Demilly,et al.  Java-based graphical user interface for the MRUI quantitation package , 2001, Magnetic Resonance Materials in Physics, Biology and Medicine.

[121]  C. Boesch,et al.  31P magnetic resonance spectroscopy in skeletal muscle: Experts' consensus recommendations , 2020, NMR in biomedicine.

[122]  R. Kreis,et al.  Dipolar resonance frequency shifts in 1H MR spectra of skeletal muscle: Confirmation in rats at 4.7 T in Vivo and observation of changes postmortem , 1997, Magnetic resonance in medicine.

[123]  S. Kuno,et al.  Comparative analysis of NMR and NIRS measurements of intracellular [Formula: see text] in human skeletal muscle. , 1999, American journal of physiology. Regulatory, integrative and comparative physiology.

[124]  J. Hoff,et al.  Oxygen availability and PCr recovery rate in untrained human calf muscle: evidence of metabolic limitation in normoxia. , 2007, American journal of physiology. Regulatory, integrative and comparative physiology.

[125]  H. Westerhoff,et al.  Quasi-linear relationship between Gibbs free energy of ATP hydrolysis and power output in human forearm muscle. , 1995, The American journal of physiology.

[126]  Robin A. de Graaf In vivo NMR spectroscopy , 1998 .

[127]  Siegfried Trattnig,et al.  Dynamic 31P MR spectroscopy of plantar flexion: influence of ergometer design, magnetic field strength (3 and 7 T), and RF-coil design. , 2015, Medical physics.

[128]  Carlo Reggiani,et al.  Fiber types in mammalian skeletal muscles. , 2011, Physiological reviews.

[129]  T. Brown,et al.  Application of 31P-NMR spectroscopy to the study of striated muscle metabolism. , 1982, The American journal of physiology.

[130]  Robin A. de Graaf,et al.  In Vivo NMR Spectroscopy , 2019 .

[131]  Carnosine: from exercise performance to health , 2013, Amino Acids.

[132]  P. Jakeman,et al.  Carnosine and anserine concentrations in the quadriceps femoris muscle of healthy humans , 2004, European Journal of Applied Physiology and Occupational Physiology.

[133]  F. Schick,et al.  Intramyocellular lipids and insulin resistance , 2004, Diabetes, obesity & metabolism.

[134]  Y. Seo,et al.  High-resolution proton magnetic resonance spectra of muscle. , 1981, Biochimica et biophysica acta.

[135]  P. Carlier,et al.  Evidence for bi‐exponential transverse relaxation of lactate in excised rat muscle , 1999, Magnetic resonance in medicine.

[136]  R. Kreis,et al.  Test–retest analysis of multiple 31P magnetization exchange pathways using asymmetric adiabatic inversion , 2017, Magnetic resonance in medicine.

[137]  S. Trattnig,et al.  Two‐dimensional spectroscopic imaging with combined free induction decay and long‐TE acquisition (FID echo spectroscopic imaging, FIDESI) for the detection of intramyocellular lipids in calf muscle at 7 T , 2014, NMR in biomedicine.

[138]  E. Moser,et al.  1H NMR relaxation times of skeletal muscle metabolites at 3 T , 2004, Magnetic Resonance Materials in Physics, Biology and Medicine.

[139]  Arend Heerschap,et al.  Metabolic changes in reflex sympathetic dystrophy: A 31P NMR spectroscopy study , 1993, Muscle & nerve.

[140]  R. Ross,et al.  Skeletal muscle mass and distribution in 468 men and women aged 18-88 yr. , 2000, Journal of applied physiology.

[141]  Jullie W Pan,et al.  A fully localized 1H homonuclear editing sequence to observe lactate in human skeletal muscle after exercise , 1989 .

[142]  S. Stannard,et al.  Fasting for 72 h increases intramyocellular lipid content in nondiabetic, physically fit men. , 2002, American journal of physiology. Endocrinology and metabolism.

[143]  Eric G Shankland,et al.  Acidosis inhibits oxidative phosphorylation in contracting human skeletal muscle in vivo , 2003, The Journal of physiology.

[144]  H. Halvorson,et al.  Assessment of magnesium concentrations by 31P NMR in vivo , 1992, NMR in biomedicine.

[145]  Shoko Nioka,et al.  Skeletal muscle energetics with PNMR: personal views and historic perspectives , 2006, NMR in biomedicine.

[146]  C. Guézennec,et al.  Metabolic and vascular support for the role of myoglobin in humans: a multiparametric NMR study. , 2004, American journal of physiology. Regulatory, integrative and comparative physiology.

[147]  E. Moser,et al.  Comparison of measuring energy metabolism by different 31P‐magnetic resonance spectroscopy techniques in resting, ischemic, and exercising muscle , 2012, Magnetic resonance in medicine.

[148]  H. Reyngoudt,et al.  Free intramuscular Mg2+ concentration calculated using both 31P and 1H NMRS‐based pH in the skeletal muscle of Duchenne muscular dystrophy patients , 2019, NMR in biomedicine.

[149]  T. Stellingwerff,et al.  Carbohydrate ingestion reduces skeletal muscle acetylcarnitine availability but has no effect on substrate phosphorylation at the onset of exercise in man , 2002, The Journal of physiology.

[150]  W. Derave,et al.  Sports Foods and Dietary Supplements for Optimal Function and Performance Enhancement in Track-and-Field Athletes. , 2019, International journal of sport nutrition and exercise metabolism.

[151]  R. T. Thompson,et al.  Coincident thresholds in intracellular phosphorylation potential and pH during progressive exercise. , 1991, Journal of applied physiology.

[152]  W. Saris,et al.  The effects of increasing exercise intensity on muscle fuel utilisation in humans , 2001, The Journal of physiology.

[153]  Wolfgang Bogner,et al.  Dynamic PCr and pH imaging of human calf muscles during exercise and recovery using 31P gradient‐Echo MRI at 7 Tesla , 2016, Magnetic resonance in medicine.

[154]  F. Stephens,et al.  New insights concerning the role of carnitine in the regulation of fuel metabolism in skeletal muscle , 2007, The Journal of physiology.

[155]  S. Provencher Estimation of metabolite concentrations from localized in vivo proton NMR spectra , 1993, Magnetic resonance in medicine.

[156]  P. Carlier,et al.  Multiparametric NMR-based assessment of skeletal muscle perfusion and metabolism during exercise in elderly persons: preliminary findings. , 2009, The journals of gerontology. Series A, Biological sciences and medical sciences.

[157]  J. Leigh,et al.  Noninvasive measurement of phosphocreatine recovery kinetics in single human muscles. , 1997, The American journal of physiology.

[158]  M. Dezortova,et al.  MR compatible ergometers for dynamic 31P MRS. , 2019, Journal of applied biomedicine.

[159]  Fritz Schick,et al.  Role of proton MR for the study of muscle lipid metabolism , 2006, NMR in biomedicine.

[160]  L. Spriet,et al.  Intramuscular triacylglycerol utilization in human skeletal muscle during exercise: is there a controversy? , 2002, Journal of applied physiology.

[161]  F. Schick,et al.  In Vivo Proton NMR Studies in Skeletal Musculature , 2003 .

[162]  C. Caputo,et al.  The excitation–contraction coupling mechanism in skeletal muscle , 2014, Biophysical Reviews.

[163]  P. Carlier,et al.  Muscle blood flow and oxygenation measured by NMR imaging and spectroscopy , 2006, NMR in biomedicine.

[164]  R. Kreis,et al.  Influence of muscle fiber orientation on water and metabolite relaxation times, magnetization transfer, and visibility in human skeletal muscle , 2016, Magnetic resonance in medicine.

[165]  E. Hultman,et al.  Muscle composition in relation to age and sex. , 1991, Clinical science.

[166]  Michelle L Davis,et al.  Estimated contribution of hemoglobin and myoglobin to near infrared spectroscopy , 2013, Respiratory Physiology & Neurobiology.

[167]  A. Sherry,et al.  Amplification of the effects of magnetization exchange by 31P band inversion for measuring adenosine triphosphate synthesis rates in human skeletal muscle , 2015, Magnetic resonance in medicine.

[168]  G. Wary,et al.  Simultaneous determination of muscle perfusion and oxygenation by interleaved NMR plethysmography and deoxymyoglobin spectroscopy , 1997, NMR in biomedicine.

[169]  P Boesiger,et al.  Comparison of methods for the determination of absolute metabolite concentrations in human muscles by 31P MRS , 1993, Magnetic resonance in medicine.

[170]  E. Achten,et al.  beta-Alanine supplementation augments muscle carnosine content and attenuates fatigue during repeated isokinetic contraction bouts in trained sprinters. , 2007, Journal of applied physiology.

[171]  Y. Itai,et al.  Relationships between Fiber Composition and NMR Measurements in Human Skeletal Muscle , 1996, NMR in biomedicine.

[172]  F. Schick,et al.  Utilisation of intramyocellular lipids (IMCLs) during exercise as assessed by proton magnetic resonance spectroscopy (1H-MRS). , 2001, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[173]  Ewald Moser,et al.  Comparing localized and nonlocalized dynamic 31P magnetic resonance spectroscopy in exercising muscle at 7T , 2012, Magnetic resonance in medicine.

[174]  A. Heerschap,et al.  Only fat infiltrated muscles in resting lower leg of FSHD patients show disturbed energy metabolism , 2010, NMR in biomedicine.

[175]  M. Schär,et al.  Quantification of human high‐energy phosphate metabolite concentrations at 3 T with partial volume and sensitivity corrections , 2013, NMR in biomedicine.

[176]  Anke Henning,et al.  Methodological consensus on clinical proton MRS of the brain: Review and recommendations , 2019, Magnetic resonance in medicine.

[177]  R. Kreis,et al.  Comparison of 31P saturation and inversion magnetization transfer in human liver and skeletal muscle using a clinical MR system and surface coils , 2015, NMR in biomedicine.

[178]  W. Saris,et al.  Influence of prolonged endurance cycling and recovery diet on intramuscular triglyceride content in trained males. , 2003, American journal of physiology. Endocrinology and metabolism.

[179]  F. Schick,et al.  Muscle type dependent increase in intramyocellular lipids during prolonged fasting of human subjects: a proton MRS study. , 2004, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[180]  R. H. T. Edwards,et al.  The time course of phosphorylcreatine resynthesis during recovery of the quadriceps muscle in man , 1976, Pflügers Archiv.

[181]  M. Crow,et al.  Chemical energetics of slow- and fast-twitch muscles of the mouse , 1982, The Journal of general physiology.

[182]  R. Kreis,et al.  Quantitative 1H magnetic resonance spectroscopy of myoglobin de‐ and reoxygenation in skeletal muscle: Reproducibility and effects of location and disease , 2001, Magnetic resonance in medicine.

[183]  Theodore F. Towse,et al.  A gated 31P NMR method for the estimation of phosphocreatine recovery time and contractile ATP cost in human muscle , 2006, NMR in biomedicine.

[184]  G. Radda,et al.  Bioenergetics of skeletal muscle in mitochondrial myopathy , 1994, Journal of the Neurological Sciences.

[185]  M. E. Kooi,et al.  Intramyocellular lipid content and molecular adaptations in response to a 1-week high-fat diet. , 2005, Obesity research.

[186]  R S Balaban,et al.  Interpretation of ³¹P NMR saturation transfer experiments: what you can't see might confuse you. Focus on "Standard magnetic resonance-based measurements of the Pi→ATP rate do not index the rate of oxidative phosphorylation in cardiac and skeletal muscles". , 2011, American journal of physiology. Cell physiology.

[187]  A. Webb,et al.  Muscle MRS detects elevated PDE/ATP ratios prior to fatty infiltration in Becker muscular dystrophy , 2014, NMR in biomedicine.

[188]  R. Kreis,et al.  Effect of two β-alanine dosing protocols on muscle carnosine synthesis and washout , 2011, Amino Acids.

[189]  F. Schick,et al.  Intramyocellular lipids and their dynamics assessed by 1H magnetic resonance spectroscopy , 2017, Clinical physiology and functional imaging.

[190]  Longitudinal relaxation time editing for acetylcarnitine detection with 1H‐MRS , 2017, Magnetic resonance in medicine.

[191]  G. Kemp,et al.  Explaining pH change in exercising muscle: lactic acid, proton consumption, and buffering vs. strong ion difference. , 2006, American Journal of Physiology. Regulatory Integrative and Comparative Physiology.

[192]  G. Payne Single-Voxel MR Spectroscopy , 2015 .

[193]  C Boesch,et al.  In vivo determination of intra‐myocellular lipids in human muscle by means of localized 1H‐MR‐spectroscopy , 1997, Magnetic resonance in medicine.

[194]  P. Carlier,et al.  Splitting of Pi and other 31P NMR anomalies of skeletal muscle metabolites in canine muscular dystrophy , 2012, NMR in biomedicine.

[195]  Ewald Moser,et al.  Exercising calf muscle changes correlate with pH, PCr recovery and maximum oxidative phosphorylation , 2014, NMR in biomedicine.

[196]  W. Herzog,et al.  Eccentric exercise: many questions unanswered. , 2014, Journal of applied physiology.

[197]  R B Buxton,et al.  Dynamic imaging of perfusion in human skeletal muscle during exercise with arterial spin labeling , 1999, Magnetic resonance in medicine.

[198]  R. Kreis,et al.  Effect of exercise on the creatine resonances in 1H MR spectra of human skeletal muscle. , 1999, Journal of magnetic resonance.

[199]  M. Weiner,et al.  Central basis of muscle fatigue in chronic fatigue syndrome , 1993, Neurology.

[200]  L. Arsac,et al.  Parameter estimation in modeling phosphocreatine recovery in human skeletal muscle , 2004, European Journal of Applied Physiology.

[201]  S. Frostick,et al.  Cellular energetics of dystrophic muscle , 1993, Journal of the Neurological Sciences.

[202]  R. Nagarajan,et al.  A pilot validation of multi‐echo based echo‐planar correlated spectroscopic imaging in human calf muscles , 2014, NMR in biomedicine.

[203]  Ewald Moser,et al.  Skeletal muscle ATP synthesis and cellular H+ handling measured by localized 31P-MRS during exercise and recovery , 2016, Scientific Reports.

[204]  Jullie W Pan,et al.  Correlation of lactate and pH in human skeletal muscle after exercise by 1H NMR , 1991, Magnetic resonance in medicine.

[205]  J. McGarry,et al.  Bulk magnetic susceptibility effects on the assessment of intra‐ and extramyocellular lipids in vivo , 2002, Magnetic resonance in medicine.

[206]  P. Carlier,et al.  Evidence of muscle BOLD effect revealed by simultaneous interleaved gradient‐echo NMRI and myoglobin NMRS during leg ischemia , 1998, Magnetic resonance in medicine.

[207]  G. Marsh,et al.  Effects of hyperventilation on phosphocreatine kinetics and muscle deoxygenation during moderate-intensity plantar flexion exercise. , 2007, Journal of applied physiology.

[208]  R. Meyer,et al.  A linear model of muscle respiration explains monoexponential phosphocreatine changes. , 1988, The American journal of physiology.

[209]  K. Conley,et al.  Shaking up glycolysis: Sustained, high lactate flux during aerobic rattling. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[210]  C. Hilbers,et al.  Proton MR spectroscopy of wild‐type and creatine kinase deficient mouse skeletal muscle: Dipole–dipole coupling effects and post‐mortem changes , 2000, Magnetic resonance in medicine.

[211]  F. Schick,et al.  Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offspring of type 2 diabetic subjects. , 1999, Diabetes.

[212]  F. Bruggeman,et al.  Robust homeostatic control of quadriceps pH during natural locomotor activity in man , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[213]  F Schick,et al.  Comparison of localized proton NMR signals of skeletal muscle and fat tissue in vivo: Two lipid compartments in muscle tissue , 1993, Magnetic resonance in medicine.

[214]  A. Sherry,et al.  Modular 31P wideband inversion transfer for integrative analysis of adenosine triphosphate metabolism, T1 relaxation and molecular dynamics in skeletal muscle at 7T , 2019, Magnetic resonance in medicine.

[215]  Craig R Malloy,et al.  Noninvasive monitoring of lactate dynamics in human forearm muscle after exhaustive exercise by 1H‐magnetic resonance spectroscopy at 7 tesla , 2013, Magnetic resonance in medicine.

[216]  R. Kreis,et al.  Non‐invasive observation of acetyl‐group buffering by 1H‐MR spectroscopy in exercising human muscle , 1999, NMR in biomedicine.

[217]  S. Salinari,et al.  Unreliable use of standard muscle hydration value in obesity. , 2001, American journal of physiology. Endocrinology and metabolism.

[218]  Sriram Subramaniam,et al.  Mitochondrial reticulum for cellular energy distribution in muscle , 2015, Nature.

[219]  K. Conley,et al.  Mitochondrial NAD(P)H In vivo: Identifying Natural Indicators of Oxidative Phosphorylation in the 31P Magnetic Resonance Spectrum , 2016, Front. Physiol..

[220]  D. Dunger,et al.  Compositional marker in vivo reveals intramyocellular lipid turnover during fasting-induced lipolysis , 2018, Scientific Reports.

[221]  P R Luyten,et al.  Broadband proton decoupling in human 31p NMR spectroscopy , 1989, NMR in biomedicine.

[222]  J A Romijn,et al.  Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration. , 1993, The American journal of physiology.

[223]  A. Sherry,et al.  1H MRS of intramyocellular lipids in soleus muscle at 7 T: Spectral simplification by using long echo times without water suppression , 2010, Magnetic resonance in medicine.

[224]  F. Schick,et al.  Intra‐ and interindividual variability of fatty acid unsaturation in six different human adipose tissue compartments assessed by 1H‐MRS in vivo at 3 T , 2017, NMR in Biomedicine.

[225]  M. Kushmerick,et al.  Creatine Kinase Equilibration Follows Solution Thermodynamics in Skeletal Muscle. , 1995, The Journal of Biological Chemistry.

[226]  T R Brown,et al.  Phosphorus nuclear magnetic resonance of fast- and slow-twitch muscle. , 1985, The American journal of physiology.

[227]  G. Kemp,et al.  Muscle Studies by 31P MRS , 2015 .

[228]  Y. le Fur,et al.  Mitochondrial function and increased convective O2 transport: implications for the assessment of mitochondrial respiration in vivo. , 2013, Journal of applied physiology.

[229]  G. Aldini,et al.  Physiology and pathophysiology of carnosine. , 2013, Physiological reviews.

[230]  T K Borg,et al.  Morphology of connective tissue in skeletal muscle. , 1980, Tissue & cell.

[231]  J. Kent,et al.  In vivo mitochondrial function in aging skeletal muscle: capacity, flux, and patterns of use. , 2016, Journal of applied physiology.

[232]  M. Bredella,et al.  Comparison of 3.0 T proton magnetic resonance spectroscopy short and long echo‐time measures of intramyocellular lipids in obese and normal‐weight women , 2010, Journal of magnetic resonance imaging : JMRI.

[233]  F. Schick,et al.  Morning to evening changes of intramyocellular lipid content in dependence on nutrition and physical activity during one single day: a volume selective 1H-MRS study , 2011, Magnetic Resonance Materials in Physics, Biology and Medicine.