Magnetic Resonance Imaging of Glutamate

Glutamate (Glu) exhibits a pH and concentration dependent chemical exchange saturation transfer effect (CEST) between its -amine group and bulk water, here termed GluCEST. GluCEST asymmetry is observed at ~3 parts per million downfield from bulk water. Following middle cerebral artery occlusion in the rat brain, an approximately 100% elevation of GluCEST in the ipsilateral side compared to the contralateral side was observed, and is predominantly due to pH changes. In a rat brain tumor model with blood brain barrier disruption, intravenous Glu injection resulted in a clear elevation of GluCEST and a comparable increase in the proton magnetic resonance spectroscopy signal of Glu. GluCEST maps from healthy human brain at 7T were also obtained. These results demonstrate the feasibility and potential of GluCEST for mapping relative changes in Glu concentration as well as pH in vivo. Potential contributions from other brain metabolites to the GluCEST effect are also discussed.