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. Level of Evidence 2 Technical Efficacy Stage 2