小鼠脑内肌酸 CEST 的交换率。
The exchange rate of creatine CEST in mouse brain.
机构信息
F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, Maryland, USA.
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
出版信息
Magn Reson Med. 2023 Aug;90(2):373-384. doi: 10.1002/mrm.29662. Epub 2023 Apr 10.
PURPOSE
To estimate the exchange rate of creatine (Cr) CEST and to evaluate the pH sensitivity of guanidinium (Guan) CEST in the mouse brain.
METHODS
Polynomial and Lorentzian line-shape fitting (PLOF) were implemented to extract the amine, amide, and Guan CEST signals from the brain Z-spectrum at 11.7T. Wild-type (WT) and knockout mice with the guanidinoacetate N-methyltransferase deficiency (GAMT ) that have low Cr and phosphocreatine (PCr) concentrations in the brain were used to extract the CrCEST signal. To quantify the CrCEST exchange rate, a two-step Bloch-McConnell (BM) fitting was used to fit the CrCEST line-shape, B -dependent CrCEST, and the pH response with different B values. The pH in the brain cells was altered by hypercapnia to measure the pH sensitivity of GuanCEST.
RESULTS
Comparison between the Z-spectra of WT and GAMT mice suggest that the CrCEST is between 20% and 25% of the GuanCEST in the Z-spectrum at 1.95 ppm between B = 0.8 and 2 μT. The CrCEST exchange rate was found to be around 240-480 s in the mouse brain, which is significantly lower than that in solutions (∼1000 s ). The hypercapnia study on the mouse brain revealed that CrCEST at B = 2 μT and amineCEST at B = 0.8 μT are highly sensitive to pH change in the WT mouse brain.
CONCLUSIONS
The in vivo CrCEST exchange rate is slow, and the acquisition parameters for the CrCEST should be adjusted accordingly. CrCEST is the major contribution to the opposite pH-dependence of GuanCEST signal under different conditions of B in the brain.
目的
估计肌酸（Cr）CEST 的交换率，并评估小鼠脑内胍基（Guan）CEST 的 pH 敏感性。
方法
在 11.7T 下，通过多项式和洛伦兹线形拟合（PLOF）从脑 Z 谱中提取胺、酰胺和 Guan CEST 信号。使用野生型（WT）和缺乏胍基乙酸 N-甲基转移酶（GAMT）的基因敲除（GAMT）小鼠来提取 CrCEST 信号，因为这些小鼠脑内 Cr 和磷酸肌酸（PCr）浓度较低。为了量化 CrCEST 交换率，采用两步 Bloch-McConnell（BM）拟合来拟合 CrCEST 线形状、B 依赖性 CrCEST 和不同 B 值下的 pH 响应。通过高碳酸血症改变脑细胞内的 pH 值，以测量 GuanCEST 的 pH 敏感性。
结果
WT 和 GAMT 小鼠的 Z 谱比较表明，在 1.95ppm 处，B 值在 0.8 至 2μT 之间，CrCEST 在 Z 谱中的幅度约为 GuanCEST 的 20%至 25%。在小鼠脑中发现 CrCEST 交换率约为 240-480s，明显低于溶液中的交换率（约 1000s）。对小鼠脑的高碳酸血症研究表明，B 值为 2μT 时的 CrCEST 和 B 值为 0.8μT 时的胺CEST 在 WT 小鼠脑内对 pH 变化非常敏感。
结论
体内 CrCEST 交换率较慢，因此应相应调整 CrCEST 的采集参数。在不同的脑内 B 条件下，CrCEST 是 GuanCEST 信号相反 pH 依赖性的主要贡献者。
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