Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Magn Reson Med. 2022 Feb;87(2):837-849. doi: 10.1002/mrm.29030. Epub 2021 Sep 30.
Chemical exchange saturation transfer signals from amines are sensitive to pH, and detection of these signals can serve as an alternative pH imaging method to amide proton transfer (APT). However, conflicting results regarding amine CEST imaging at 2 ppm in ischemic stroke have been reported. Here, we correlated amine CEST with APT in animal stroke models to evaluate its specificity to pH, and investigated the reason for the different results through simulations and sample studies.
A three-point quantification method was used to quantify APT. A polynomial fit method and a multiple-pool Lorentzian fit method were used to quantify amine CEST. Samples of creatine and glutamate were prepared to study the different CEST effects from arginine amine and fast exchanging pools. Samples of tissue homogenates with different pH were prepared to study the variation in CEST signals due only to changes in pH.
The polynomial fit of amine CEST at 2 ppm had a significant correlation with APT, whereas the Lorentzian fit did not. Further studies showed that arginine amine contributed to the polynomial fit, whereas both the arginine amine and the fast exchanging pools contributed to the Lorentzian fit with their CEST effects varying in opposite directions after stroke. The CEST signal from the fast exchanging pool decreased, probably due to the reduced pool concentration but not pH.
The variation in opposite directions led to an insignificant correlation of the Lorentzian fit of amine CEST with APT and the different results in different experimental conditions.
胺的化学交换饱和转移信号对 pH 敏感,检测这些信号可以作为酰胺质子转移 (APT) 的替代 pH 成像方法。然而,在缺血性中风中,关于 2 ppm 处胺 CEST 成像的结果存在矛盾。在这里,我们将胺 CEST 与动物中风模型中的 APT 相关联,以评估其对 pH 的特异性,并通过模拟和样本研究探讨产生不同结果的原因。
采用三点定量法定量 APT。采用多项式拟合法和多池洛伦兹拟合法定量胺 CEST。制备肌酸和谷氨酸样品,研究精氨酸胺和快速交换池的不同 CEST 效应。制备不同 pH 值的组织匀浆样品,研究仅由于 pH 值变化而导致的 CEST 信号变化。
2 ppm 处的多项式拟合胺 CEST 与 APT 具有显著相关性,而洛伦兹拟合则没有。进一步的研究表明,精氨酸胺对多项式拟合有贡献,而洛伦兹拟合则同时由精氨酸胺和快速交换池贡献,两者的 CEST 效应在中风后呈相反方向变化。快速交换池的 CEST 信号降低,可能是由于池浓度降低而不是 pH 值降低所致。
相反的变化导致洛伦兹拟合胺 CEST 与 APT 的相关性不显著,以及在不同实验条件下的结果不同。