Simultaneous Measurement of GABA, Glutathione, and Glutamate-Glutamine in the Thalamus using Edited MR Spectroscopy: Feasibility and Applications in Traumatic Brain Injury

Background: MR spectroscopy (MRS) is a noninvasive tool for evaluating biochemical alterations, such as glutamate (Glu)/gamma-aminobutyric acid (GABA) imbalance and depletion of antioxidative glutathione (GSH) after traumatic brain injury (TBI). Thalamus, a critical and vulnerable region post-TBI, is challenging for MRS acquisitions, necessitating optimization to simultaneously measure GABA/Glu and GSH. Purpose: To assess the feasibility and optimize acquisition and processing approaches for simultaneously measuring GABA, Glx (Glu + glutamine (Gln)), and GSH in the thalamus, employing Hadamard encoding and reconstruction of MEscher-GArwood (MEGA)-edited spectroscopy (HERMES). Study Type: Prospective. Subjects: 28 control subjects (age: 35.9 +/- 15.1 years), and 17 mild TBI (mTBI) patients (age: 32.4 +/- 11.3 years). Field Strength/Sequence: 3T/T1-weighted magnetization-prepared rapid gradient-echo (MP-RAGE), HERMES. Assessment: We evaluated the impact of acquisition with spatial saturation bands and post-processing with spectral alignment on HERMES performance in the thalamus among controls. Within-subject variability was examined in five controls through repeated scans within a week. The HERMES spectra in the posterior cingulate cortex (PCC) of controls were used as a reference for assessing HERMES performance in a reliable target. Furthermore, we compared metabolite levels and fitting quality in the thalamus between mTBI patients and controls. Statistical Tests: Unpaired t-tests and within-subject coefficient-of-variation (CV). A P-value <0.05 was deemed significant. Results: HERMES spectra, acquired with saturation bands and processed with spectral alignment, yielded reliable metabolite measurements in the thalamus. The mean within-subject CV for GABA, Glx, and GSH levels were 18%, 10%, and 16% in the thalamus (7%, 9%, and 16% in the PCC). GABA (3.20 +/- 0.60 vs 2.51 +/- 0.55, P < 0.01) and Glx (8.69 +/- 1.23 vs 7.72 +/- 1.19, P = 0.03) levels in the thalamus were significantly higher in mTBI patients than in controls, with GSH (1.27 +/- 0.35 vs 1.22 +/- 0.28, P = 0.65) levels showing no significant difference. Data Conclusion: Simultaneous measuring GABA/Glx and GSH using HERMES is feasible in the thalamus, providing valuable insight into TBI.