Purpose: Phosphorus saturation-transfer experiments can quantify metabolic fluxes noninvasively. Typically, the forward flux through the creatine kinase reaction is investigated by observing the decrease in phosphocreatine (PCr) after saturation of γ-ATP. The quantification of total ATP utilization is currently underexplored, as it requires simultaneous saturation of inorganic phosphate ( ) and PCr. This is challenging, as currently available saturation pulses reduce the already-low γ-ATP signal present.
Methods: Using a hybrid optimal-control and Shinnar-Le Roux method, a quasi-adiabatic RF pulse was designed for the dual saturation of PCr and to enable determination of total ATP utilization. The pulses were evaluated in Bloch equation simulations, compared with a conventional hard-cosine DANTE saturation sequence, before being applied to perfused rat hearts at 11.7 T.
Results: The quasi-adiabatic pulse was insensitive to a >2.5-fold variation in , producing equivalent saturation with a 53% reduction in delivered pulse power and a 33-fold reduction in spillover at the minimum effective . This enabled the complete quantification of the synthesis and degradation fluxes for ATP in 30-45 minutes in the perfused rat heart. While the net synthesis flux (4.24 ± 0.8 mM/s, SEM) was not significantly different from degradation flux (6.88 ± 2 mM/s, P = .06) and both measures are consistent with prior work, nonlinear error analysis highlights uncertainties in the Pi -to-ATP measurement that may explain a trend suggesting a possible imbalance.
Conclusions: This work demonstrates a novel quasi-adiabatic dual-saturation RF pulse with significantly improved performance that can be used to measure ATP turnover in the heart in vivo.
Keywords: 31P-MRS; ATP; CK-flux reaction; CMR; PCr; RF design; cardiac metabolism; heart; metabolism; pulse design; saturation transfer.
© 2021 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.