Rapid, B1‐insensitive, dual‐band quasi‐adiabatic saturation transfer with optimal control for complete quantification of myocardial ATP flux

• Published in: Magnetic resonance in medicine 2021-06, Vol.85 (6), p.2978-2991
• Main Authors: Miller, Jack J., Valkovič, Ladislav, Kerr, Matthew, Timm, Kerstin N., Watson, William D., Lau, Justin Y. C., Tyler, Andrew, Rodgers, Christopher, Bottomley, Paul A., Heather, Lisa C., Tyler, Damian J.
• Format: Article
• Language: English
• Subjects: 31P‐MRS; Adiabatic; Adiabatic flow; ATP; cardiac metabolism; CK‐flux reaction; CMR; Creatine; Creatine kinase; Degradation; Error analysis; Fluctuations; Fluxes; Full Papers—Spectroscopic Methodology; Heart; Kinases; metabolism; Optimal control; PCr; Phosphocreatine; Phosphorus; pulse design; Reduction; RF design; Saturation; saturation transfer; Synthesis; Uncertainty analysis
• ISSN: 0740-3194; 1522-2594
• DOI: 10.1002/mrm.28647

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 (Pi) 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 Pi 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 B1, producing equivalent saturation with a 53% reduction in delivered pulse power and a 33‐fold reduction in spillover at the minimum effective B1. 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.