Kejia Cai et al. describe a method to non-invasively detect glutamate (Glu) concentrations in the brain with MRI at high resolution. The approach is based on the pH-dependent chemical exchange saturation transfer (CEST) effect between the amino group of Glu and bulk water and offers advantages over proton magnetic resonance spectroscopy. Feasibility of GluCEST was demonstrated in rat brain after middle cerebral artery occlusion stroke and in a rat brain tumor model, as well as in healthy human brain at 7 Tesla. Glutamate, a major neurotransmitter in the brain, shows a pH- and concentration-dependent chemical exchange saturation transfer effect (GluCEST) between its amine group and bulk water, with potential for in vivo imaging by nuclear magnetic resonance. GluCEST asymmetry is observed ∼3 p.p.m. downfield from bulk water. Middle cerebral artery occlusion in the rat brain resulted in an ∼100% elevation of GluCEST in the ipsilateral side compared with the contralateral side, predominantly owing to pH changes. In a rat brain tumor model with blood-brain barrier disruption, intravenous glutamate injection resulted in a clear elevation of GluCEST and a similar increase in the proton magnetic resonance spectroscopy signal of glutamate. GluCEST maps from healthy human brain were also obtained. These results demonstrate the feasibility of using GluCEST for mapping relative changes in glutamate concentration, as well as pH, in vivo. Contributions from other brain metabolites to the GluCEST effect are also discussed.

Purpose: To develop a chemical exchange saturation transfer (CEST)‐based technique to measure free creatine (Cr) and to validate the technique by measuring the distribution of Cr in muscle with high spatial resolution before and after exercise.Methods: Phantom studies were performed to determine contributions from other Cr kinase metabolites to the CEST effect from Cr (CrCEST). CEST, T₂, magnetization transfer ratio and ³¹P magnetic resonance spectroscopy acquisitions of the lower leg were performed before and after plantar flexion exercise on a 7T whole‐body magnetic resonance scanner on healthy volunteers.Results: Phantom studies demonstrated that while Cr exhibited significant CEST effect there were no appreciable contributions from other metabolites. In healthy human subjects, following mild plantar flexion exercise, increases in the CEST effect from Cr were observed, which recovered exponentially back to baseline. This technique exhibited good spatial resolution and was able to differentiate differences in muscle utilization among subjects. The CEST effect from Cr results were compared with ³¹P magnetic resonance spectroscopy results showing good agreement in the Cr and phosphocreatine recovery kinetics.Conclusion: Demonstrated a CEST‐based technique to measure free Cr changes in in vivo muscle. The CEST effect from Cr imaging can spatially map changes in Cr concentration in muscle following mild exercise. This may serve as a tool for the diagnosis and treatment of various disorders affecting muscle. Magn Reson Med 71:164–172, 2014.