在体快速同步测量磷代谢物池大小比率和酶反应动力学。
Rapid and simultaneous measurement of phosphorus metabolite pool size ratio and reaction kinetics of enzymes in vivo.
机构信息
McLean Imaging Center, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA.
Psychotic Disorders Division, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA.
出版信息
J Magn Reson Imaging. 2018 Jan;47(1):210-221. doi: 10.1002/jmri.25744. Epub 2017 May 8.
PURPOSE
The metabolites phosphocreatine (PCr), adenosine triphosphate (ATP), and in-organic phosphate (Pi) are biochemically coupled. Their pool sizes, assessed by their magnetization ratios, have been extensively studied and reflect bioenergetics status in vivo. However, most such studies have ignored chemical exchange and T relaxation effects. In this work, we aimed to extend the T1nom method to simultaneously quantify the reaction rate constants as well as phosphorus metabolite pool size ratios under partially relaxed conditions.
MATERIALS AND METHODS
Modified Bloch-McConnell equations were used to simulate the effects of chemical exchanges on T relaxation times and magnetization ratios among PCr, γ-ATP, and Pi. The T1nom method with iteration approach was used to measure both reaction constants and metabolite pool size ratios. To validate our method, in vivo data from rat brains (N = 8) at 9.4 Tesla were acquired under two conditions, i.e., approximately full relaxation (TR = 9 s) and partial relaxation (TR = 3 s). We compared metabolite pool size ratios and reaction constants before and after correcting the chemical exchange and T relaxation effects.
RESULTS
There were significant errors in underestimation of PCr/γATP by 12 % (P = 0.03) and overestimation of ATP/Pi ratios by 14 % (P = 0.04) when not considering chemical exchange effects. These errors were minimized using our iteration approach, resulting in no significant differences (PCr/γATP, P = 0.47; ATP/Pi, P = 0.81) in metabolite pool size ratios and reaction constants between the two measurements (i.e., short versus long TR conditions).
CONCLUSION
Our method can facilitate broad biomedical applications of P magnetization saturation transfer spectroscopy, requiring high temporal and/or spatial resolution for assessment of altered bioenergetics.
LEVEL OF EVIDENCE
2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:210-221.
目的
磷酸肌酸 (PCr)、三磷酸腺苷 (ATP) 和无机磷 (Pi) 的代谢物在生化上是耦合的。它们的磁化率比值的池大小已被广泛研究，反映了体内的生物能量状态。然而，大多数此类研究都忽略了化学交换和 T 弛豫效应。在这项工作中，我们旨在扩展 T1nom 方法，以便在部分弛豫条件下同时定量反应速率常数以及磷代谢物池大小比。
材料和方法
使用改进的 Bloch-McConnell 方程模拟化学交换对 T 弛豫时间和 PCr、γ-ATP 和 Pi 之间的磁化率比的影响。使用具有迭代方法的 T1nom 方法来测量反应常数和代谢物池大小比。为了验证我们的方法，在 9.4 Tesla 下对大鼠脑的体内数据（N=8）在两种条件下进行了采集，即近似完全弛豫（TR=9 s）和部分弛豫（TR=3 s）。我们比较了校正化学交换和 T 弛豫效应前后的代谢物池大小比和反应常数。
结果
如果不考虑化学交换效应，PCr/γATP 的低估率为 12%（P=0.03），ATP/Pi 比值的高估率为 14%（P=0.04），存在显著误差。使用我们的迭代方法可以将这些误差最小化，导致两种测量之间（即短 TR 与长 TR 条件）代谢物池大小比和反应常数没有显著差异（PCr/γATP，P=0.47；ATP/Pi，P=0.81）。
结论
我们的方法可以促进 P 磁化饱和转移光谱学的广泛生物医学应用，这些应用需要高时间和/或空间分辨率来评估生物能量变化。
证据水平
2 技术功效：第 1 阶段 J. Magn. Reson. Imaging 2018；47：210-221。
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