Characterization of creatine guanidinium proton exchange by water- exchange ( WEX) spectroscopy for absolute- pH CEST imaging in vitro
Characterization of creatine guanidinium proton exchange by water- exchange ( WEX) spectroscopy for absolute- pH CEST imaging in vitro
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DOI：
10.1002/nbm.3086
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发表时间：
2014-05-01
影响因子：
2.9
通讯作者：
Bachert, Peter
中科院分区：
文献类型：
--
作者：
Goerke, Steffen;Zaiss, Moritz;Bachert, Peter
化学交换饱和转移（CEST）能够通过MR成像间接检测组织中的小代谢物。为了优化和解释肌酸CEST成像，我们表征了肌酸胍质子在肌酸水溶液中的交换速率常数k（sw）作为pH和温度T的函数在体外的依赖性。在低pH范围（pH=5-6.4）中的模型溶液通过水交换（WEX）过滤的H-1 NMR光谱在3 T全身MR断层扫描仪上测量。扩展的Arrhenius方程与有效的碱催化的Arrhenius参数得到了一般表达式k（sw）（pH，T）。在缓冲液浓度c（buffer）=（1/15）M时，有效碱催化速率常数k（B，eff）（298.15 K）=（3.009 +/- 0.16）× 10（9）Hzl/mol，有效活化能E-A，E-B，E-eff=（32.27 +/- 7.43）kJ/mol。正如预期的那样，观察到k（sw）对温度的强烈依赖性。将交换速率常数外推到体内条件（pH=7.1，T=37 ℃），得到交换速率常数k（sw）= 1499 Hz。利用显式函数k（sw）（pH，T），可以实现绝对pH CEST成像，并在体外进行了实验验证。通过我们的校准方法，可以通过制备具有特定pH和温度的肌酸模型溶液来将胍质子交换速率常数k（sw）调节到任何期望值。版权所有（c）2014约翰威利父子有限公司
Chemical exchange saturation transfer (CEST) enables indirect detection of small metabolites in tissue by MR imaging. To optimize and interpret creatine-CEST imaging we characterized the dependence of the exchange-rate constant k(sw) of creatine guanidinium protons in aqueous creatine solutions as a function of pH and temperature T in vitro. Model solutions in the low pH range (pH=5-6.4) were measured by means of water-exchange (WEX)-filtered H-1 NMR spectroscopy on a 3T whole-body MR tomograph. An extension of the Arrhenius equation with effective base-catalyzed Arrhenius parameters yielded a general expression for k(sw)(pH, T). The defining parameters were identified as the effective base-catalyzed rate constant k(b,eff)(298.15K)=(3.009 +/- 0.16)x10(9)Hzl/mol and the effective activation energy E-A,E-b,E-eff=(32.27 +/- 7.43) kJ/mol at a buffer concentration of c(buffer)=(1/15) M. As expected, a strong dependence of k(sw) on temperature was observed. The extrapolation of the exchange-rate constant to in vivo conditions (pH=7.1, T=37 degrees C) led to the value of the exchange-rate constant k(sw)=1499Hz. With the explicit function k(sw)(pH, T) available, absolute-pH CEST imaging could be realized and experimentally verified in vitro. By means of our calibration method it is possible to adjust the guanidinium proton exchange-rate constant k(sw) to any desired value by preparing creatine model solutions with a specific pH and temperature. Copyright (c) 2014 John Wiley & Sons, Ltd.