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超快 CEST 线扫描定量研究变旋动力学

Ultrafast CEST line scanning as a method to quantify mutarotation kinetics.

机构信息

Translational Research Imaging Center, Clinic of Radiology, University of Münster, Münster, Germany.

NeuroSpin, CEA, University Paris-Saclay, Gif-sur-Yvette, France.

出版信息

J Magn Reson. 2022 Sep;342:107270. doi: 10.1016/j.jmr.2022.107270. Epub 2022 Jul 16.

DOI:10.1016/j.jmr.2022.107270
PMID:35905529
Abstract

The process of mutarotation of sugars caused by a balanced reaction between their corresponding α and β isomers, has been known for almost 200 years. Still, it remains essential in modern biochemical research, as enzymatic reactions catalyzed by mutarotases are crucial for various pathways in the energy metabolism. In our study a fast magnetic resonance technique based on chemical exchange saturation transfer (CEST) line scanning (LS) was implemented as a method to measure mutarotation kinetics on a 9.4 T small animal MRI scanner. As proof of concept, the isomeric conversion of two hexoses (glucose and galactose) and pentoses (xylose and arabinose) was investigated in an aqueous solution over time. The technique allowed for ultrafast data acquisition without the implementation of complicated encoding schemes and acceleration procedures. Thus, CEST LS provided complete CEST spectra with a frequency step size of 19.6 Hz in less than one minute. For the mutarotation analysis, CEST spectra were acquired over a time duration of four hours and analyzed with four established CEST quantification approaches - based on either asymmetry of CEST spectra or a multi-pool Lorentzian fit. The isomer ratios of the different sugars at equilibrium were determined with an overall accuracy of 94 %, using an adapted 2-side chemical exchange (CE) model. The estimated mutarotation rate constants at 22 °C were in good agreement with conventionally measured reference values, derived from optical and spectroscopic techniques.

摘要

糖的互变异构过程是由其相应的α和β异构体之间的平衡反应引起的,这一过程已经为人所知近 200 年。尽管如此,它在现代生化研究中仍然是必不可少的,因为变旋酶催化的酶反应对于能量代谢中的各种途径至关重要。在我们的研究中,一种基于化学交换饱和传递(CEST)线扫描(LS)的快速磁共振技术被用作在 9.4T 小动物 MRI 扫描仪上测量互变异构动力学的方法。作为概念验证,我们在水溶液中随时间研究了两种己糖(葡萄糖和半乳糖)和戊糖(木糖和阿拉伯糖)的异构转化。该技术允许在不实施复杂编码方案和加速程序的情况下进行超快数据采集。因此,CEST LS 在不到一分钟的时间内以 19.6 Hz 的频率步长提供了完整的 CEST 光谱。为了进行互变异构分析,在四个小时的时间内采集 CEST 光谱,并使用四种已建立的 CEST 定量方法进行分析 - 基于 CEST 光谱的不对称性或多池洛伦兹拟合。使用经过改编的 2 侧化学交换(CE)模型,以 94%的总体精度确定了不同糖在平衡时的互变异构体比。在 22°C 下估计的互变异构速率常数与传统光学和光谱技术得出的参考值非常吻合。

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