Distinction of the GABA 2.29 ppm resonance using triple refocusing at 3 T in vivo

Purpose: To develop ¹H MR spectroscopy that provides distinction of γ-aminobutyric acid (GABA) signal at 3 T in vivo. Methods: Triple-refocusing was tailored at 3 T, with numerical simulations and phantom validation, for distinction of the GABA 2.29-ppm resonance from the neighboring glutamate resonance. The optimization was performed on the inter-RF pulse time delays and the duration and carrier frequency of a non-slice-selective RF pulse. The optimized triple refocusing was tested in multiple regions in 6 healthy subjects, including hippocampus. The in vivo spectra were analyzed with the LCModel using in-house basis spectra. After normalization of the metabolite signal estimates to water, the metabolite concentrations were quantified with reference to medial-occipital creatine at 8 mM. Results: A triple-refocusing scheme with optimized inter-RF pulse time delays (TE = 74 ms) was obtained for GABA detection. With optimized duration (14 ms) and carrier frequency (4.5 ppm) of the non-slice-selective RF pulse, the triple refocusing gave rise to distinction between the GABA 2.29-ppm and glutamate 2.35-ppm signals. The GABA 2.29-ppm signal was clearly discernible in spectra in vivo (voxel size 4 to 12 mL; scan times 4.3 to 17 minutes). With a total of 24 spectra from 6 gray or white matter–dominant regions, the GABA concentration was measured to be 0.62 to 1.15 mM (Cramer-Rao lower bound of 8 to 14%), and the glutamate level 5.8 to 11.2 mM (Cramer-Rao lower bound of 3 to 6%). Conclusion: The optimized triple refocusing provided distinction between GABA and glutamate signals and permitted direct codetection of these metabolites in the human brain at 3 T in vivo.