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
Department of Physics, University of Oxford, Oxford, UK.
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Magn Reson Med. 2021 Jun;85(6):2978-2991. doi: 10.1002/mrm.28647. Epub 2021 Feb 3.
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.
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.
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 P -to-ATP measurement that may explain a trend suggesting a possible imbalance.
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.
磷饱和转移实验可无创地量化代谢通量。通常,通过观察γ-ATP饱和后磷酸肌酸(PCr)的减少来研究肌酸激酶反应的正向通量。目前,总ATP利用率的量化研究不足,因为这需要同时使无机磷酸( )和PCr饱和。这具有挑战性,因为现有的饱和脉冲会降低已存在的低γ-ATP信号。
使用混合最优控制和Shinnar-Le Roux方法,设计了一种准绝热射频脉冲用于PCr和 的双重饱和,以确定总ATP利用率。在Bloch方程模拟中对这些脉冲进行评估,并与传统的硬余弦DANTE饱和序列进行比较,然后应用于11.7 T的灌注大鼠心脏。
准绝热脉冲对 的>2.5倍变化不敏感,在最小有效 时,产生等效饱和,输送脉冲功率降低53%,溢出降低33倍。这使得在灌注大鼠心脏中30 - 45分钟内能够完整地量化ATP的合成和降解通量。虽然净合成通量(4.24±0.8 mM/s,标准误)与降解通量(6.88±2 mM/s,P = 0.06)无显著差异,且这两种测量结果与先前的工作一致,但非线性误差分析突出了P与ATP测量中的不确定性,这可能解释了一个表明可能存在失衡的趋势。
这项工作展示了一种性能显著改善的新型准绝热双饱和射频脉冲,可用于在体测量心脏中的ATP周转。