Rapid, $B_1$-insensitive, dual-band quasi-adiabatic saturation transfer with optimal control for complete quantification of myocardial ATP flux
Miller JJ., Valkovič L., Kerr M., Timm KN., Watson W., Lau JYC., Tyler A., Rodgers C., Bottomley PA., Heather LC., Tyler DJ.
Purpose: Phosphorus saturation-transfer experiments can quantify metabolic fluxes non-invasively. Typically, the forward flux through the creatine-kinase reaction is investigated by observing the decrease in phosphocreatine (PCr) after saturation of $\gamma$-ATP. The quantification of total ATP utilisation is currently under-explored, as it requires simultaneous saturation of inorganic phosphate (Pi) and PCr. This is challenging, as currently available saturation pulses reduce the already-low $\gamma$-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 Pi to enable determination of total ATP utilisation. The pulses were evaluated in Bloch equation simulations, compared with a conventional hard-cosine DANTE saturation sequence, before application to perfused rat hearts at 11.7 Tesla. Results: The quasi-adiabatic pulse was insensitive to a $>2.5$-fold variation in $B_1$, producing equivalent saturation with a 53% reduction in delivered pulse power and a 33-fold reduction in spillover at the minimum effective $B_1$. 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 ($4.24\pm0.8$ mM/s, SEM) was not significantly different from degradation flux ($6.88\pm2$ mM/s, $p=0.06$) 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. Conclusion: 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.