A.P. Sokovikova1, M.V. Gulyaev2, Yu.A. Pirogov3
1–3 M.V. Lomonosov Moscow State University (Moscow, Russia)
An analytical review of publications devoted to the study of metabolic processes in muscle tissues using nuclear magnetic resonance (NMR) spectroscopy is presented. Objective this work was to consider and evaluate the methods of proton and phosphorus NMR spectroscopy as a non-invasive analogue of biopsy in the study of muscle tissue pathologies. As the work results, an analytical review of articles has been made that discusses the use of NMR spectroscopy in the diagnosis of such pathologies of muscle tissue as Duchenne myopathy, myotonic dystrophy, diabetes mellitus and heart failure. Particular attention is paid to the consideration of molecular processes occurring in various muscle tissues with the participation of metabolic transformations of carnosine, creatine, lipids and phosphorus-containing metabolites. Also described are diagnostic methods of proton and phosphorus NMR spectroscopy in the analysis of the state of health of people during physical exertion. Metabolites play an important role in maintaining human life, and changes in their normal content can be used to judge violations in the functioning of muscle tissues. To determine the concentration of metabolites in muscle tissues, a biopsy method is usually used. Although obtaining muscle tissue samples by a biopsy is a relatively simple and safe procedure, the invasive nature of the technique limits its application. Therefore, the development of non-invasive methods for determining the concentration of metabolites is relevant. NMR spectroscopy has long been (since 1980) used in clinical practice to study the brain and other parts of the body. NMR methods can also be used to quantify the content of metabolites in muscle tissue. Their advantage is the possibility of multiple non-invasive measurements, allowing tracking the change in the concentration of the main metabolites over time. Data of this review are useful for clinic practice and can be applied in laboratory and clinical studies of muscle pathologies, as well as in the course of monitoring the health of athletes under normal and critically limiting physical activity of the body.
Sokovikova A.P., Gulyaev M.V., Pirogov Yu.A. Study of metabolic processes in muscle tissues by nuclear magnetic resonance spectroscopy. Biomedicine Radioengineering. 2022. V. 25. № 2–3. Р. 58-65. DOI: https://doi.org/10.18127/j15604136-202202-06 (In Russian)
- Reyngoudt H., Turk S., Carlier P.G. 1H NMRS of carnosine combined with 31P NMRS to better characterize skeletal muscle pH dysregulation in Duchenne muscular dystrophy. NMR in Biomedicine. 2017. V. 31(1). P. e3839.
- Just Kukurová I., Valkovič L., Ukropec J., de Courten B., Chmelík M., Ukropcová B., Krššák M. 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. NMR in Biomedicine. 2015. V. 29(1). P. 24–32.
- Hwang J.-H., Choi C.S. Use of in vivo magnetic resonance spectroscopy for studying metabolic diseases. Experimental & Molecular Medicine. 2015. V. 47(2). P. e139.
- Barnes P. Skeletal muscle metabolism in myotonic dystrophy. A 31P magnetic resonance spectroscopy study. Brain. 1997. V. 120(10). P. 1699–1711.
- Bonati U., Hafner P., Schädelin S., et al. Quantitative muscle MRI: a powerful surrogate outcome measure in Duchenne muscular dystrophy. Neuromuscular Disorders. 2015. V. 25(9). P. 679–685.
- Da Eira Silva V., Painelli V. de S., Shinjo S.K., Ribeiro Pereira W., Cilli E.M., Sale C., Artioli G.G. Magnetic Resonance Spectroscopy as a Non-invasive Method to Quantify Muscle Carnosine in Humans: a Comprehensive Validity Assessment. Scientific Reports. 2020. V. 10(1). P. e4908.
- Chance B., Eleff S., Leigh J.S., Sokolow D., Sapega A. Mitochondrial regulation of phosphocreatine/inorganic phosphate ratios in exercising human muscle: a gated 31P NMR study. Proceedings of the National Academy of Sciences. 1981. V. 78(11). P. 6714–6718.
- Menon R.G., Xia D., Katz S.D. et al. Dynamic 31P-MRI and 31P-MRS of lower leg muscles in heart failure patients. Scientific Reports. 2021. V. 11(1). P. e7412.
- Krššák M., Lindeboom L., Schrauwen‐Hinderling V., Szczepaniak L.S., Derave W., Lundbom J., Boesch C. Proton magnetic resonance spectroscopy in skeletal muscle: Experts’ consensus recommendations. NMR in Biomedicine. 2020. V. 34(5). P. e4266.
- Van der Graaf M. In vivo magnetic resonance spectroscopy: basic methodology and clinical applications. European Biophysics Journal. 2009. V. 39(4). P. 527–540.
- Tkáč I., Gruetter R. Methodology of 1H NMR Spectroscopy of the Human Brain at Very High Magnetic Fields. Applied Magnetic Resonance. 2005. V. 29(1). P. 139–157.
- Ozdemir M.S., Reyngoudt H., De Deene Y., et al. Absolute quantification of carnosine in human calf muscle by proton magnetic resonance spectroscopy. Physics in Medicine and Biology. 2007. V. 52(23). P. 6781–6794.
- Chung W., Baguet A., Bex T., Bishop D.J., Derave W. Doubling of muscle carnosine concentration does not improve laboratory 1-hr cycling time-trial performance. International Journal of Sport Nutrition and Exercise Metabolism 2014. V. 24. P. 315–324.
- Derave W., Oezdemir M.S., Harris R.C., Pottier A., Reyngoudt H., Koppo K., Wise J.A., Achten E. Beta-alanine supplementation augments muscle carnosine content and attenuates fatigue during repeated isokinetic contraction bouts in trained sprinter. Journal of Applied Physiology. 2007. V. 103(5). P. 1736–1743.
- Derave W., Everaert I., Beeckman S., Baguet A. Muscle carnosine metabolism and beta-alanine supplementation in relation to exercise and training. Sports medicine. 2010. V. 40(3). P. 247–263.
- Baguet A., Reyngoudt H., Pottier A., Everaert I., Callens S., Achten E., Derave W. Carnosine loading and washout in human skeletal muscles. Journal of applied physiology. 2009. V. 106(3). P. 837–842.
- Yki-Järvinen H. Liver fat in the pathogenesis of insulin resistance and type 2 diabetes. Digestive diseases. 2010. V. 28. P. 203–209.
- De Bock K., Dresselaers T., Kiens B., Richter E.A., Van Hecke P., Hespel P. Evaluation of intramyocellular lipid breakdown during exercise by biochemical assay, NMR spectroscopy, and Oil Red O staining. American journal of physiology. Endocrinology and metabolism. 2007. V. 293(1). E428–E434.
- Nakagawa Y., Hattori M. Intramyocellular lipids of muscle type in athletes of different sport disciplines. Open Access Journal of Sports Medicine. 2017. V. 8. P. 161–166.
- Meyerspeer M., Boesch C., Cameron D., Dezortová M., Forbes S.C. 31P magnetic resonance spectroscopy in skeletal muscle: Experts’ consensus recommendations. NMR in Biomedicine. 2020. V. 34(7). P. e4246.
- Meyerspeer M., Krššák M., Moser E. Relaxation times of 31P-metabolites in human calf muscle at 3 T. Magnetic Resonance in Medicine. 2003. V. 49(4). P. 620–625.
- Bogner W., Chmelík M., Schmid A.I., Moser E., Trattnig S., Gruber S. Assessment of 31P relaxation times in the human calf muscle: a comparison between 3 T and 7 T in vivo. Magnetic Resonance in Medicine. 2009. V. 62(3). P. 574–582.
- Valkovič L., Chmelík M., Krššák M. In-vivo 31P-MRS of skeletal muscle and liver: A way for non-invasive assessment of their metabolism. Analytical biochemistry. 2017. V. 529. P. 193–215.
- Van der Kemp W.J.M., Stehouwer B.L., Runge J.H., Wijnen J.P., Nederveen A.J., Luijten P.R., Klomp D.W.J. Glycerophosphocholine and Glycerophosphoethanolamine Are Not the Main Sources of the In Vivo 31P MRS Phosphodiester Signals from Healthy Fibroglandular Breast Tissue at 7 T. Frontiers in Oncology. 2016. V. 30(1). P. 145–152.
- Ikehira H., Nishikawa S., Matsumura K., Hasegawa T., Arimizu N., Tateno Y. The functional staging of Duchenne muscular dystrophy using in vivo 31P MR spectroscopy. Radiation medicine. 1995. V. 13(2). P. 63–65.
- Srivastava N.K., Mukherjee S., Sinha N. Alteration of phospholipids in the blood of patients with Duchenne muscular dystrophy (DMD): in vitro, high resolution 31P NMR-based study. Acta Neurologica Belgica. 2016. V. 116(4). P. 573–581.
- Hooijmans M.T., Doorenweerd N., Baligand C., Verschuuren J.J.G.M., Ronen I., et al. Spatially localized phosphorous metabolism of skeletal muscle in Duchenne muscular dystrophy patients: 24–month follow-up. Plos One. 2017. V. 12(8). P. e0182086.
- Ripley E.M., Clarke G.D., Hamidi V., et al. Reduced skeletal muscle phosphocreatine concentration in type 2 diabetic patients: a quantitative image-based phosphorus-31 MR spectroscopy study. American journal of physiology. Endocrinology and metabolism. 2018.
V. 315(2). P. E229–E239. - Trenell M.I., Thompson C.H., Sue C.M. Exercise and myotonic dystrophy: a 31P magnetic resonance spectroscopy and magnetic resonance imaging case study. Annals of neurology. 2006. V. 59(5). P. 871–872.
- Molina A.J., Bharadwaj M.S., Van Horn C., et al. Skeletal muscle mitochondrial content, oxidative capacity, and Mfn2 expression are reduced in older patients with heart failure and preserved ejection fraction and are related to exercise intolerance. JACC Heart Failure. 2016. V. 4(8). P. 636–645.
- Nakae I., Mitsunami K., Matsuo S., et al. Detection of calf muscle alterations in patients with chronic heart failure by P magnetic resonance spectroscopy: Impaired adaptation to continuous exercise. Experimental and clinical cardiology. 2005. V. 10(1). P. 4–8.
- Haykowsky M.J., Kouba E.J., Brubaker P.H., Nicklas B.J., Eggebeen J., Kitzman D.W. Skeletal muscle composition and its relation to exercise intolerance in older patients with heart failure and preserved ejection fraction. The American journal of cardiology. 2014.
V. 113(7). P. 1211–1216. - Jung W.I., Sieverding L., Breuer J., et al. 31P NMR spectroscopy detects metabolic abnormalities in asymptomatic patients with hypertrophic cardiomyopathy. Circulation. 1998. V. 97(25). P. 2536–2542.