A short echo time (T_E ) is commonly used for brain glutamate measurement by ¹ H MRS to minimize drawbacks of long T_E such as signal modulation due to J evolution and T₂ relaxation. However, J coupling causes the spectral patterns of glutamate to change with T_E , and the shortest achievable T_E may not produce the optimal glutamate measurement. The purpose of this study was to determine the optimal T_E for glutamate measurement at 7 T using semi-LASER (localization by adiabatic selective refocusing). Time-domain simulations were performed to model the T_E dependence of glutamate signal energy, a measure of glutamate signal strength, and were verified against measurements made in the human sensorimotor cortex (five subjects, 2 × 2 × 2 cm³ voxel, 16 averages) on a 7 T MRI scanner. Simulations showed a local maximum of glutamate signal energy at T_E = 107 ms. In vivo, T_E = 105 ms produced a low Cramér-Rao lower bound of 6.5 ± 2.0% across subjects, indicating high-quality fits of the prior knowledge model to in vivo data. T_E = 105 ms also produced the greatest glutamate signal energy with the smallest inter-subject glutamate-to-creatine ratio (Glu/Cr) coefficient of variation (CV), 4.6%. Using these CVs, we performed sample size calculations to estimate the number of participants per group required to detect a 10% change in Glu/Cr between two groups with 95% confidence. 13 were required at T_E = 45 ms, the shortest achievable echo time on our 7 T MRI scanner, while only 5 were required at T_E = 105 ms, indicating greater statistical power. These results indicate that T_E = 105 ms is optimum for in vivo glutamate measurement at 7 T with semi-LASER. Using long T_E decreases power deposition by allowing lower maximum RF pulse amplitudes in conjunction with longer RF pulses. Importantly, long T_E minimizes macromolecule contributions, eliminating the requirement for acquisition of separate macromolecule spectra or macromolecule fitting techniques, which add additional scan time or bias the estimated glutamate fit.

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