Modular 31 P wideband inversion transfer for integrative analysis of adenosine triphosphate metabolism, T1 relaxation and molecular dynamics in skeletal muscle at 7T

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 P_γ(α)ATP ↔ ³¹ P_βATP . 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, k_PCr→γATP = 0.31 ± 0.05 s^-1 and k_Pi→γATP = 0.064 ± 0.012 s^-1 , and the reverse exchange rate constants, k_γATP→Pi = 0.034 ± 0.006 s^-1 and k_γATP→PCr = 1.37 ± 0.22 s^-1 , respectively. The cross-relaxation rate constant, σ_{γ(α) ↔ βATP} was -0.20 ± 0.03 s^-1 , corresponding to ATP rotational correlation time τ_c 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.