PHYSIOLOGIC BASIS OF MUSCLE FUNCTIONAL MRI

Summary

Principal Investigator: RONALD MEYER
Abstract: This project will develop functional magnetic resonance imaging (FMRI) methods for diagnosis and monitoring the progression of neuromuscular diseases and other fatigue syndromes. Aim 1 of the project will develop a non-invasive FMRI method for the quantitative assessment of motor unit loss in the muscles of patients with compensated peripheral muscle denervation. This aim is based on previous results, which indicate that the heterogeneity of the metabolically-linked increase in transverse relaxation time (T2) within exercised muscles depends on the number, size, and spatial distribution of motor unit territories in the muscle. This new idea will be tested by comparing indices of T2 heterogeneity (e.g., T2 variance, T2 spatial autocorrelation coefficient) after exercise in anterior tibialis muscles of well-compensated Amyotrophic Lateral Sclerosis (ALS) patients vs, age and sex matched control subjects (20/group). FMRI results will be correlated with EMG based motor unit number estimates in both groups. In addition, a subset of eight ALS patients will be examined by both MRI and EMG after one year, in order to examine the ability of FMRI to detect loss of motor units in individual patients during disease progression. Finally, a separate study will examine if the same FMRI procedures can be used to measure the age-dependent loss of motor units in otherwise healthy elderly vs. younger subjects (12/group). Aim 2 of the project will examine the physiologic basis of a new variant of muscle FMRI based on transient changes in muscle oxygenation and blood flow after brief contractions. Analogous blood-oxygen-level-dependent (BOLD) effects are commonly exploited in brain FMRI studies, but not in muscle studies, which have been based on the T2 increase during more intense exercise. First, this Aim will examine the physiologic basis of muscle BOLD FMRI by comparing transient BOLD changes with transient changes in vessel blood flow (MRI and Doppler ultrasound) and hemoglobin saturation (near infrared spectroscopy, NIRS) in healthy subjects. The results will be compared to the BOLD responses predicted from models developed by others to explain the analogous BOLD effects in the brain. Second, this Aim will explore the application of BOLD-based muscle FMRI for quantitative imaging of muscle vascular reactivity by comparing MRI and NIRS results in healthy elderly vs. young subjects. This study will utilize the same elderly and young subjects as Aim 1, enabling direct comparison of BOLD vs. conventional T2-based muscle FMRI. Aim 3 will examine the quantitative relationship between muscle recruitment and fatigue vs. the intensity of BOLD FMRI response in motor cortical areas in the brain. This study of healthy young subjects will resolve two questions that are essential for any future application of brain FMRI to study central involvement in various fatigue syndromes: first, is the intensity of the BOLD response in motor cortical areas quantitatively dependent on force development, and second, how is this central response altered by peripheral muscle fatigue?
Funding Period: 1996-07-20 - 2008-02-28
more information: NIH RePORT

Top Publications

  1. pmc Peripheral microvascular response to muscle contraction is unaltered by early diabetes but decreases with age
    Jill M Slade
    Dept of Radiology, East Lansing, MI 48824, USA
    J Appl Physiol (1985) 111:1361-71. 2011
  2. pmc Quantitative analysis of the postcontractile blood-oxygenation-level-dependent (BOLD) effect in skeletal muscle
    Theodore F Towse
    Department of Physiology, Michigan State University, East Lansing, MI 48824, USA
    J Appl Physiol (1985) 111:27-39. 2011
  3. ncbi Comparison of oxidative capacity among leg muscles in humans using gated 31P 2-D chemical shift imaging
    Sean C Forbes
    Department of Physiology, Michigan State University, East Lansing, MI 48824, USA
    NMR Biomed 22:1063-71. 2009
  4. ncbi Short-term high-intensity interval training improves phosphocreatine recovery kinetics following moderate-intensity exercise in humans
    Sean C Forbes
    Department of Physiology, Michigan State University, East Landing, MI 48824, USA
    Appl Physiol Nutr Metab 33:1124-31. 2008
  5. pmc Phosphocreatine recovery kinetics following low- and high-intensity exercise in human triceps surae and rat posterior hindlimb muscles
    Sean C Forbes
    Dept of Physiology 2201 BPS Bldg, Michigan State Univ, East Lansing, MI 48824, USA
    Am J Physiol Regul Integr Comp Physiol 296:R161-70. 2009
  6. ncbi Parallel increases in phosphocreatine and total creatine in human vastus lateralis muscle during creatine supplementation
    Jeffrey J Brault
    Dept of Physiology, Michigan State University, East Lansing, MI 48824, USA
    Int J Sport Nutr Exerc Metab 17:624-34. 2007
  7. ncbi Protecting the cellular energy state during contractions: role of AMP deaminase
    C R Hancock
    Biomedical Sciences, Physiology, Dalton Cardiovascular Center, University of Missouri Columbia, MO 65211, USA
    J Physiol Pharmacol 57:17-29. 2006
  8. ncbi A gated 31P NMR method for the estimation of phosphocreatine recovery time and contractile ATP cost in human muscle
    Jill M Slade
    Department of Osteopathic Manipulative Medicine, Michigan State University, East Lansing, 48824, USA
    NMR Biomed 19:573-80. 2006
  9. ncbi Effect of physical activity on MRI-measured blood oxygen level-dependent transients in skeletal muscle after brief contractions
    Theodore F Towse
    Molecular Imaging Research Center, Department of Physiology, 2201 BPS Bldg, Michigan State University, East Lansing, MI 48824, USA
    J Appl Physiol 99:715-22. 2005
  10. ncbi 31P-NMR observation of free ADP during fatiguing, repetitive contractions of murine skeletal muscle lacking AK1
    Chad R Hancock
    Medical Pharmacology and Physiology, College of Medicine, University of Missouri Columbia, Columbia, MO, USA
    Am J Physiol Cell Physiol 288:C1298-304. 2005

Scientific Experts

  • J M Slade
  • Sean C Forbes
  • Theodore F Towse
  • Ronald A Meyer
  • Jeffrey J Brault
  • C R Hancock
  • Chad R Hancock
  • Jeffrey A Ambrose
  • Mark C DeLano
  • R L Terjung
  • J J Brault
  • Ronald L Terjung
  • Robert W Wiseman
  • R W Wiseman

Detail Information

Publications10

  1. pmc Peripheral microvascular response to muscle contraction is unaltered by early diabetes but decreases with age
    Jill M Slade
    Dept of Radiology, East Lansing, MI 48824, USA
    J Appl Physiol (1985) 111:1361-71. 2011
    ..Although the BOLD microvascular response was not impaired in early diabetes, these results encourage further investigation of muscle BOLD as it relates to peripheral microvascular health...
  2. pmc Quantitative analysis of the postcontractile blood-oxygenation-level-dependent (BOLD) effect in skeletal muscle
    Theodore F Towse
    Department of Physiology, Michigan State University, East Lansing, MI 48824, USA
    J Appl Physiol (1985) 111:27-39. 2011
    ..The results show that muscle postcontractile BOLD SI changes depend critically on the balance between O(2) delivery and O(2) consumption, both of which can be altered by chronic physical activity...
  3. ncbi Comparison of oxidative capacity among leg muscles in humans using gated 31P 2-D chemical shift imaging
    Sean C Forbes
    Department of Physiology, Michigan State University, East Lansing, MI 48824, USA
    NMR Biomed 22:1063-71. 2009
    ..These findings suggest that the oxidative capacity is lower in the anterior compartment than in the triceps surae muscles and is consistent with the notion that fiber-type phenotypes vary among the leg muscles of humans...
  4. ncbi Short-term high-intensity interval training improves phosphocreatine recovery kinetics following moderate-intensity exercise in humans
    Sean C Forbes
    Department of Physiology, Michigan State University, East Landing, MI 48824, USA
    Appl Physiol Nutr Metab 33:1124-31. 2008
    ..43 +/- 12 s, respectively; p > 0.05). These findings demonstrate that short-term high-intensity interval training is an effective means of increasing functional oxidative capacity in skeletal muscle...
  5. pmc Phosphocreatine recovery kinetics following low- and high-intensity exercise in human triceps surae and rat posterior hindlimb muscles
    Sean C Forbes
    Dept of Physiology 2201 BPS Bldg, Michigan State Univ, East Lansing, MI 48824, USA
    Am J Physiol Regul Integr Comp Physiol 296:R161-70. 2009
    ..In addition, the observation of a fast component following high-intensity exercise is consistent with the notion that glycolytic ATP production contributes to PCr resynthesis during the initial stage of recovery...
  6. ncbi Parallel increases in phosphocreatine and total creatine in human vastus lateralis muscle during creatine supplementation
    Jeffrey J Brault
    Dept of Physiology, Michigan State University, East Lansing, MI 48824, USA
    Int J Sport Nutr Exerc Metab 17:624-34. 2007
    ..TCr (14.9% +/- 4.1%) at any time point. The results indicate that creatine supplementation does not alter the PCr:TCr ratio, and hence the cytoplasmic Gibbs free energy of ATP hydrolysis, in human skeletal muscle at rest...
  7. ncbi Protecting the cellular energy state during contractions: role of AMP deaminase
    C R Hancock
    Biomedical Sciences, Physiology, Dalton Cardiovascular Center, University of Missouri Columbia, MO 65211, USA
    J Physiol Pharmacol 57:17-29. 2006
    ..Thus, it is not essential that the AMP deaminase reaction be operating during intense contraction conditions. This helps explain why patients deficient in AMP deaminase do not always exhibit an impaired muscle function...
  8. ncbi A gated 31P NMR method for the estimation of phosphocreatine recovery time and contractile ATP cost in human muscle
    Jill M Slade
    Department of Osteopathic Manipulative Medicine, Michigan State University, East Lansing, 48824, USA
    NMR Biomed 19:573-80. 2006
    ..01 +/- 0.01 to 6.78 +/- 0.04 during recovery after the repetitive protocol. Hence the gated protocol allows the estimation of muscle ATP cost and PCr recovery without intense exercise or muscle acidification...
  9. ncbi Effect of physical activity on MRI-measured blood oxygen level-dependent transients in skeletal muscle after brief contractions
    Theodore F Towse
    Molecular Imaging Research Center, Department of Physiology, 2201 BPS Bldg, Michigan State University, East Lansing, MI 48824, USA
    J Appl Physiol 99:715-22. 2005
    ..The results indicate that transient hyperemia and oxygenation in muscle after single contractions are enhanced by chronic physical activity to a greater extent than peak muscle blood flow...
  10. ncbi 31P-NMR observation of free ADP during fatiguing, repetitive contractions of murine skeletal muscle lacking AK1
    Chad R Hancock
    Medical Pharmacology and Physiology, College of Medicine, University of Missouri Columbia, Columbia, MO, USA
    Am J Physiol Cell Physiol 288:C1298-304. 2005
    ..Remarkably, the AK1(-/-) and WT muscles exhibited similar fatigue profiles. Our findings suggest that skeletal muscle is surprisingly tolerant to a large increase in ADP and by extension, a decline in energy from ATP...