Wermter Felizitas C, Bock Christian, Dreher Wolfgang
University of Bremen, Department of Chemistry, in-vivo-MR Group, Bremen, Germany.
Alfred-Wegener-Institut Helmholtz-Zentrum für Polar- und Meeresforschung, Department of Integrative Ecophysiology, Bremerhaven, Germany.
NMR Biomed. 2015 Nov;28(11):1507-17. doi: 10.1002/nbm.3416. Epub 2015 Sep 28.
Chemical exchange saturation transfer (CEST) from glutamate to water (GluCEST) is a powerful tool for mapping glutamate concentration and intracellular pH. GluCEST could also be helpful to understand the physiology of lower aquatic vertebrates and invertebrates. Therefore, this study aimed to investigate the GluCEST effect and the exchange rate ksw from amine protons of glutamate to water in a broad range of temperatures (1-37°C) and pH (5.5-8.0). Z-spectra were measured from glutamate solutions at different pH values and temperatures and analysed by numerically solving the Bloch-McConnell equation. As expected, a strong dependence of the GluCEST effect and the determined ksw values on pH and temperature was observed. In addition, a strong dependence of the GluCEST effect on phosphate buffer concentration was confirmed. The in vitro data show that GluCEST is detectable in the whole temperature range, even at 1°C. An interpolation function for the exchange rate ksw was determined for the considered range of temperatures and pH values, showing a bijective relation between the exchange rate and pH at a given temperature. To investigate the specificity of GluCEST imaging at low temperatures, the CEST effect was investigated for several metabolites relevant for CEST imaging of the brain. As an example, the contribution of GluCEST to the total CEST effect at 3 ppm was estimated for zebrafish (Danio rerio). It is shown that also at lower temperatures glutamate is the major contributor to the total CEST effect, particularly if the experimental parameters are optimized.
从谷氨酸到水的化学交换饱和转移（CEST）（GluCEST）是一种用于绘制谷氨酸浓度和细胞内pH值的强大工具。GluCEST对于理解低等水生脊椎动物和无脊椎动物的生理学也可能有所帮助。因此，本研究旨在研究在广泛的温度范围（1-37°C）和pH范围（5.5-8.0）内，GluCEST效应以及谷氨酸胺质子到水的交换速率ksw。在不同pH值和温度下从谷氨酸溶液测量Z谱，并通过数值求解Bloch-McConnell方程进行分析。正如预期的那样，观察到GluCEST效应和所确定的ksw值对pH和温度有强烈依赖性。此外，还证实了GluCEST效应对磷酸盐缓冲液浓度有强烈依赖性。体外数据表明，即使在1°C时，在整个温度范围内都可检测到GluCEST。针对所考虑的温度和pH值范围确定了交换速率ksw的插值函数，显示了在给定温度下交换速率与pH之间的双射关系。为了研究低温下GluCEST成像的特异性，对几种与脑部CEST成像相关的代谢物的CEST效应进行了研究。例如，估计了斑马鱼（Danio rerio）中GluCEST对3 ppm处总CEST效应的贡献。结果表明，即使在较低温度下，谷氨酸也是总CEST效应的主要贡献者，特别是如果实验参数得到优化。
