Modular P wideband inversion transfer for integrative analysis of adenosine triphosphate metabolism, T 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, T 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 P ↔ P . 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 = 0.31 ± 0.05 s and k = 0.064 ± 0.012 s , and the reverse exchange rate constants, k = 0.034 ± 0.006 s and k = 1.37 ± 0.22 s , respectively. The cross-relaxation rate constant, σ was -0.20 ± 0.03 s , corresponding to ATP rotational correlation time τ of 0.8 ± 0.1 × 10 seconds. The intrinsic T 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 T 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.