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

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 ³¹P_γ(α)ATP ↔ ³¹P_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.