Purpose To determine the exchange parameters for the CEST of phosphocreatine (PCrCEST) in phantoms and to characterize PCrCEST in vivo in the muscle at different saturation powers and magnetic fields. Methods Exchange parameters were measured in PCr solutions using varying saturation power at 15.2 T. Z‐spectra were analyzed using multipool Lorentzian fitting in the hindlimb using various powers at 2 different fields: 9.4 T and 15.2 T. Modulation of PCr signal in PCrCEST and phosphorus MRS was observed in the mouse hindlimb before and after euthanasia. Results The exchange rate of PCr at physiological pH in phantoms was confirmed to be in a much slower exchange regime compared with Cr: kex at pH 7.3 and below was less than 400 s–1. There was insufficient signal for detection of PCrCEST in the brain, but PCrCEST in the hindlimb was measured to be 2.98% ± 0.43 at a B1 of 0.47 μT at 15.2 T, which is 29% higher than 9.4T values. The value of PCrCEST at a B1 of 0.71 μT was not significantly different than that measured at a B1 of 0.47 μT. After euthanasia, PCrCEST signal dropped by 82.3% compared with an 85% decrease in PCr in phosphorus MRS, whereas CrCEST signal increased by 90.6%. Conclusion The PCrCEST technique has viable sensitivity in the muscle at high fields and shows promise for the study of metabolic dysfunction and cardiac systems.

Chemical exchange saturation transfer (CEST) MRI has become a promising technique to assay target proteins and metabolites through their exchangeable protons, noninvasively. The ubiquity of creatine (Cr) and phosphocreatine (PCr) due to their pivotal roles in energy homeostasis through the creatine phosphate pathway has made them prime targets for CEST in the diagnosis and monitoring of disease pathologies, particularly in tissues heavily dependent on the maintenance of rich energy reserves. Guanidinium CEST from protein arginine residues (i.e. arginine CEST) can also provide information about the protein profile in tissue. However, numerous obfuscating factors stand as obstacles to the specificity of arginine, Cr, and PCr imaging through CEST, such as semisolid magnetization transfer, fast chemical exchanges such as primary amines, and the effects of nuclear Overhauser enhancement from aromatic and amide protons. In this review, the specific exchange properties of protein arginine residues, Cr, and PCr, along with their validation, are discussed, including the considerations necessary to target and tune their signal effects through CEST imaging. Additionally, strategies that have been employed to enhance the specificity of these exchanges in CEST imaging are described, along with how they have opened up possible applications of protein arginine residues, Cr and PCr CEST imaging in the study and diagnosis of pathology. A clear understanding of the capabilities and caveats of using CEST to image these vital metabolites and mitigation strategies is crucial to expanding the possibilities of this promising technology.

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