Purpose: To 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. Methods: An 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. Results: For 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 μT. 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 μT. The current study suggests that the inverse pH dependence in GuanCEST of brain is led by the CrCEST component, not ArgCEST. Conclusion: The current pipeline is expected to have general use for in vivo CEST quantitation and optimization of visible CEST resonances.

Purpose: To extract guanidinium (Guan) and amide CEST on the human brain at 3 T MRI with the high spectral resolution (HSR) CEST combined with the polynomial Lorentzian line-shape fitting (PLOF).Methods: Continuous wave (cw) turbo spin-echo (TSE) CEST was implemented to obtain the optimum saturation parameters. Both Guan and amide CEST peaks were extracted and quantified using the PLOF method. The NMR spectra on the egg white phantoms were acquired to reveal the fitting range and the contributions to the amide and GuanCEST. Two types of CEST approaches, including cw gradient-and spin-echo (cwGRASE) and steady state EPI (ssEPI), were implemented to acquire multi-slice HSR-CEST. Results: GuanCEST can be extracted with the PLOF method at 3 T, and the optimum B 1 = 0.6 μT was determined for GuanCEST in white matter (WM) and 1.0 μT in gray matter (GM). The optimum B 1 = 0.8-1 μT was found for amide-CEST. AmideCEST is lower in both WM and GM collected with ssEPI compared to those by cwGRASE (ssEPI = [1.27-1.63]%; cwGRASE = [2.19-2.25]%). The coefficients of variation (COV) of the amide and Guan CEST in both WM and GM for ssEPI (COV: 28.6-33.4%) are significantly higher than those of cwGRASE (COV: 8.6-18.8%). Completely different WM/GM contrasts for Guan and amide CEST were observed between ssEPI and cwGRASE. The amideCEST was found to have originated from the unstructured amide protons as suggested by the NMR spectrum of the unfolded proteins in egg white. Conclusion:Guan and amide CEST mapping can be achieved by the HSR-CEST at 3 T combing with the PLOF method. K E Y W O R D Schemical exchange saturation transfer (CEST), magnetization transfer contrast (MTC), guanidinium CEST, amide CEST, continuous wave gradient-and spin-echo (cwGRASE), steady state EPI (ssEPI), polynomial Lorentzian line-shape fitting (PLOF)

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