Quantitative image-based phosphorus-31 MR spectroscopy for evaluating age-based differences in skeletal muscle metabolites

Purpose: To develop and validate a novel in-vivo phosphorus-31 magnetic resonance spectroscopy (31P-MRS) method to determine the absolute concentrations of phosphocreatine [PCr], inorganic phosphate [Pi], and adenosine triphosphate [ATP] in the vastus lateralis muscle. Materials and Methods: An external 6 mL plastic vial with 850 mM of methylenediphosphonic acid (MDP), fixed to the center of a commercial dual-tuned transmit/receive surface coil, was used to calibrate metabolite concentrations from spectral areas. A 15cm diameter, 4 L cylindrical phantom (35 mM H3PO4) was scanned on a custom coil holder using the same parameters. Reproducibility of the 31P-MRS measurements was determined in volunteers (2M/3F, age = 39.2±21.9 years) while accuracy was determined using phantoms of known concentrations. Eight young subjects (24.5+4.2 years; 4M/4F) and eight older subjects (59.6+4.5 years; 4M/4F) were scanned. Student’s t-test was used to compare older versus younger subjects. Results: The percent error between the calculated and known molarity of phantoms was 3.3±1.9%. The mean coefficient of variation for the measurements of [PCr] was 5.2±3.7 %. Phosphorus metabolite concentrations, including [PCr] (25.2±3.4 mM vs. 28.5±3.4 mM, p < 0.005), [ATP] (6.68±0.84 mM vs. 7.71±0.61 mM, p<0.05) and [Pi] (3.18±0.46 mM vs. 2.56±0.55 mM, p<0.05) were significantly lower in older versus younger subjects. A significant, negative correlation was found between [PCr] and BMI (r = -0.50, p < 0.05). Conclusion: Quantitative 31P-MRS measurements reveal previously unappreciated differences in skeletal muscle phosphorus metabolite concentrations between young and older subjects and may provide unique insights when combined with other metabolic tests.

[1]  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.

[2]  K. Conley,et al.  Skeletal muscle mitochondrial capacity and insulin resistance in type 2 diabetes. , 2011, The Journal of clinical endocrinology and metabolism.

[3]  David Bendahan,et al.  Muscle energetics changes throughout maturation: a quantitative 31P-MRS analysis. , 2010, Journal of applied physiology.

[4]  R. DeFronzo,et al.  Pathogenesis of Insulin Resistance in Skeletal Muscle , 2010, Journal of biomedicine & biotechnology.

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

[6]  Muhammad A. Abdul-Ghani,et al.  Mitochondrial dysfunction, insulin resistance, and type 2 diabetes mellitus , 2008, Current diabetes reports.

[7]  N. M. van den Broek,et al.  Early or advanced stage type 2 diabetes is not accompanied by in vivo skeletal muscle mitochondrial dysfunction. , 2008, European journal of endocrinology.

[8]  M. Roden,et al.  Muscular mitochondrial dysfunction and type 2 diabetes mellitus , 2007, Current opinion in clinical nutrition and metabolic care.

[9]  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.

[10]  K. Sahlin,et al.  Mitochondrial Respiration Is Decreased in Skeletal Muscle of Patients With Type 2 Diabetes , 2007, Diabetes.

[11]  Brian C Clark,et al.  Reliability of techniques to assess human neuromuscular function in vivo. , 2007, Journal of electromyography and kinesiology : official journal of the International Society of Electrophysiological Kinesiology.

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

[13]  H. Kuipers,et al.  31P MR spectroscopy and in vitro markers of oxidative capacity in type 2 diabetes patients , 2007, Magnetic Resonance Materials in Physics, Biology and Medicine.

[14]  Ian R. Lanza,et al.  Age-related changes in ATP-producing pathways in human skeletal muscle in vivo. , 2005, Journal of applied physiology.

[15]  B. Lowell,et al.  Mitochondrial Dysfunction and Type 2 Diabetes , 2005, Science.

[16]  G. Radda Ions, transport, and energetics in normal and diseased skeletal muscle , 1994, Magnetic Resonance Materials in Physics, Biology and Medicine.

[17]  Simon C Watkins,et al.  Skeletal muscle lipid content and oxidative enzyme activity in relation to muscle fiber type in type 2 diabetes and obesity. , 2001, Diabetes.

[18]  P. Esselman,et al.  Oxidative capacity and ageing in human muscle , 2000, The Journal of physiology.

[19]  G Atkinson,et al.  Statistical Methods For Assessing Measurement Error (Reliability) in Variables Relevant to Sports Medicine , 1998, Sports medicine.

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

[21]  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.

[22]  C Arús,et al.  31P-MRS of quadriceps reveals quantitative differences between sprinters and long-distance runners. , 1993, Medicine and science in sports and exercise.

[23]  M. Weiner,et al.  Noninvasive quantitation of phosphorus metabolites in human tissue by NMR spectroscopy , 1989 .

[24]  M. Bárány,et al.  Quantitation of phosphate metabolites in human leg in vivo , 1988, Magnetic resonance in medicine.

[25]  D. Altman,et al.  STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT , 1986, The Lancet.

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

[27]  P. Matthews,et al.  metabolic recovery after exercise and the assessment of mitochondrial function in Vivo in human skeletal muscle by means of 31P NMR , 1984, Magnetic resonance in medicine.

[28]  D. Gadian,et al.  Bioenergetics of intact human muscle. A 31P nuclear magnetic resonance study. , 1983, Molecular biology & medicine.

[29]  R. Veech,et al.  Effects of pH and free Mg2+ on the Keq of the creatine kinase reaction and other phosphate hydrolyses and phosphate transfer reactions. , 1979, The Journal of biological chemistry.

[30]  E. Hultman,et al.  Glycogen, glycolytic intermediates and high-energy phosphates determined in biopsy samples of musculus quadriceps femoris of man at rest. Methods and variance of values. , 1974, Scandinavian journal of clinical and laboratory investigation.

[31]  R. Denton,et al.  Measurement of concentrations of metabolites in adipose tissue and effects of insulin, alloxan-diabetes and adrenaline. , 1966, The Biochemical journal.