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 Pγ(α)ATP ↔ 31 PßATP . 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→γATP = 0.31 ± 0.05 s-1 and kPi→γATP = 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) ↔ ßATP 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 ß-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.