Simultaneous in vivo detection of spectrally resolved glutamate, glutamine, and glutathione at 3 T with NAA-aspartyl editing and echo-time optimization.

Purpose: To achieve spectrally resolved in vivo detection of glutamate, glutamine, and glutathione at 3 T.

Methods: Difference editing of N-acetylaspartate CH₂ protons (NAA-CH₂) combined with a new echo-time (TE) optimization approach is introduced. Difference editing was used to detect NAA-CH₂ independently of NAA-CH₃, thereby eliminating systematic errors arising from constrained fitting of the entire NAA molecule. Numerical optimization of TE and TE₁ minimized interference from highly dominant glutamate in glutamine detection in the ON/OFF sum spectrum. In vivo data were acquired from 6 healthy participants, including 2 who underwent oral administration of [U-¹³C]glucose.

Results: The NAA-aspartyl-edited, cleaned-up in vivo spectrum showed distinct separation of glutamate, glutamine, and glutathione peaks at 3 T, facilitating spectral quantification and clinical applications. The post-¹³C proton MR-spectroscopy spectra clearly demonstrated the dynamic ¹³C-labeling of glutamate C4 following oral [U-¹³C]glucose intake.

Conclusion: This technique enables simultaneous spectral resolution of glutamate, glutamine, and glutathione peaks at 3 T using difference editing of NAA-CH₂ and an optimized TE of 85 ms. Additionally, it demonstrates, for the first time, the feasibility of measuring ¹³C turnovers of spectrally resolved glutamate at 3 T with the high sensitivity and spatial resolution of proton MR spectroscopy.