Modular 31 P wideband inversion transfer for integrative analysis of adenosine triphosphate metabolism, T 1 relaxation and molecular dynamics in skeletal muscle at 7T

Magn Reson Med. 2019 Jun;81(6):3440-3452. doi: 10.1002/mrm.27686. Epub 2019 Feb 22.

Abstract

Purpose: For efficient and integrative analysis of de novo adenosine triphosphate (ATP) synthesis, creatine-kinase-mediated ATP synthesis, T1 relaxation time, and ATP molecular motion dynamics in human skeletal muscle at rest.

Methods: Four inversion-transfer modules differing in center inversion frequency were combined to generate amplified magnetization transfer (MT) effects in targeted MT pathways, including Pi ↔ γ-ATP, PCr ↔ γ-ATP, and 31 Pγ(α)ATP31 PβATP . MT effects from both forward and reverse exchange kinetic pathways were acquired to reduce potential bias and confounding factors in integrated data analysis.

Results: Kinetic data collected using 4 wideband inversion modules (8 minutes each) yielded the forward exchange rate constants, kPCr →γ ATP = 0.31 ± 0.05 s-1 and kPi →γ ATP = 0.064 ± 0.012 s-1 , and the reverse exchange rate constants, kγATP→Pi = 0.034 ± 0.006 s-1 and kγATP→PCr = 1.37 ± 0.22 s-1 , respectively. The cross-relaxation rate constant, σγ(α) ↔ βATP was -0.20 ± 0.03 s-1 , corresponding to ATP rotational correlation time τc of 0.8 ± 0.1 × 10-7 seconds. The intrinsic T1 relaxation times were Pi (9.2 ± 1.4 seconds), PCr (6.2 ± 0.4 seconds), γ-ATP (1.8 ± 0.1 seconds), α-ATP (1.4 ± 0.1 seconds), and β-ATP (1.1 ± 0.1 seconds). Muscle ATP T1 values were found to be significantly longer than those previously measured in the brain using a similar method.

Conclusion: A combination of multiple inversion transfer modules provides a comprehensive and integrated analysis of ATP metabolism and molecular motion dynamics. This relatively fast technique could be potentially useful for studying metabolic disorders in skeletal muscle.

Keywords: 31P MRS; ATP; brain; magnetization transfer; relaxation time; skeletal muscle.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Triphosphate* / chemistry
  • Adenosine Triphosphate* / metabolism
  • Adult
  • Brain* / diagnostic imaging
  • Brain* / metabolism
  • Female
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Male
  • Muscle, Skeletal* / diagnostic imaging
  • Muscle, Skeletal* / metabolism
  • Phosphorus Isotopes / pharmacokinetics*
  • Signal-To-Noise Ratio
  • Young Adult

Substances

  • Phosphorus Isotopes
  • Adenosine Triphosphate