Magnetic resonance imaging of glutamate

Abstract

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.