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bioRxiv · 10.1101/2022.02.14.480399

The exchange rates of amide and arginine guanidinium CEST in the mouse brain

Wang, K.·Sui, R.·Chen, L.·Li, Y.·Xu, J.
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Abstract

PurposeTo develop a pipeline for measuring the exchange rates and concentrations of in vivo excgangeable protons, and to demonstrate this for the amide and arginine (Arg) guanidinium (Guan) protons in mobile proteins in the mouse brain. MethodsAn ultra-short echo (UTE) CEST sequence with a continuous wave presaturation (preRadCEST) was applied to acquire Z-spectra with robustness to motion and physiological fluctuations. AmideCEST and Arginine guanCEST (ArgCEST) were extracted and their proton concentrations and exchange rates obtained using a two-step multi-B1 Bloch fitting approach that included the semisolid macromolecular background. To minimize contamination from the amine protons from creatine and phosphocreatine, ArgCEST measurements were performed on the Guanidinoacetate N-methyltransferase deficiency (GAMT-/-) mouse characterized by low creatine and phosphocreatine concentrations in the brain. ResultsFor the amideCEST proton pool, the exchange rate and concentrations were found to be 59.6 {+/-} 9.0 s-1 and 41.7 {+/-} 7.0 mM, respectively, with the maximum signal observed at B1 = 0.8 T. For the ArgCEST proton, the guanidinium exchange these were 70.1 {+/-} 5.5 s-1 and 10.1 {+/-} 1.3 mM, respectively, with the maximum effect observed at B1 = 0.9 T. The current study suggests that the inverse pH dependence in GuanCEST of brain is led by the CrCEST component, not ArgCEST. ConclusionThe current pipeline is expected to have general use for in vivo CEST quantitation and optimization of visible CEST resonances.

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Wang, K., Sui, R., Chen, L., Li, Y., Xu, J.. 2022-02-16. The exchange rates of amide and arginine guanidinium CEST in the mouse brain. https://doi.org/10.1101/2022.02.14.480399

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