In vivo detection of GABA and glutamate with MEGA-PRESS: Reproducibility and gender effects

Purpose: To evaluate the reproducibility of γ-amino-butyric acid (GABA) and glutamate concentrations derived using three different spectral fitting methods, and to investigate gender-related differences in neurotransmitter levels. Materials and Methods: Single voxel MEGA-edited PRESS MR spectra were acquired from a 30-mL voxel in the dorso-lateral prefrontal cortex in 14 adult volunteers (7 female) at 3 Tesla (3T). For each participant, four consecutive resting spectra were acquired within the same scanning session. Metabolite concentrations were derived using LCModel, jMRUI, and locally written peak fitting software. The within-session reproducibility for each analysis method was calculated as the average coefficient of variation (CV) of the GABA and Glx (glutamate+glutamine) concentrations. Gender differences in GABA and Glx were evaluated using a two-tailed unpaired t-test. Results: LCModel provided the best reproducibility for both GABA (CV 7%) and Glx (CV 6%). GABA, Glx, and glutamate concentrations were significantly higher in the male participants, (P = 0.02, P = 0.001, and P < 0.001, respectively). Conclusion: GABA and glutamate can be quantified in vivo with high reproducibility (CV 6-7%) using frequency-domain spectral fitting methods like LCModel. However, the GABA and glutamate concentrations vary significantly between men and women, emphasizing the importance of gender-matching for studies investigating differences in neurotransmitter concentrations between mixed-cohort groups.