Quantifying the excitatory-inhibitory balance: A comparison of SemiLASER and MEGA-SemiLASER for simultaneously measuring GABA and glutamate at 7T.

The importance of the excitatory-inhibitory (E/I) balance in a wide range of cognitive and behavioral processes has prompted a commensurate interest in methods for reliably quantifying it. Proton Magnetic Resonance Spectroscopy (1H-MRS) remains the only method capable of safely and non-invasively measuring the concentrations of the brain's major excitatory (glutamate) and inhibitory (γ-aminobutyric-acid, GABA) neurotransmitters in-vivo. MRS relies on spectral Mescher-Garwood (MEGA) editing techniques at 3T to distinguish GABA from its overlapping resonances. However, with the increased spectral resolution at ultrahigh field strengths of 7T and above, non-edited spectroscopic techniques become potential viable alternatives to MEGA based approaches, and also address some of their shortcomings, such as signal loss, sensitivity to transmitter inhomogeneities and temporal resolution. We present a comprehensive comparison of both edited and non-edited strategies at 7T for simultaneously quantifying glutamate and GABA from the dorsal anterior cingulate cortex (dACC), and evaluate their reproducibility and relative bias. The combined root-mean-square test-retest reproducibility of Glu and GABA (CVE/I) was as low as 13.3% for unedited MRS at TE=80 ms using SemiLASER localization, while edited MRS at TE=80 ms yielded CVE/I=20% and 21% for asymmetric and symmetric MEGA editing, respectively. An unedited SemiLASER acquisition using a shorter echo time of TE=42 ms yielded CVE/I as low as 24.9%. Our results show that non-edited sequences at an echo time of 80 ms provide better reproducibility than either edited sequences at the same TE, or non-edited sequences at a shorter TE of 42 ms. This is supported by numerical simulations and is driven in part by a pseudo-singlet appearance of the GABA multiplets at TE=80 ms, and the excellent spectral resolution at 7T. Our results uphold a transition to non-edited MRS for monitoring the E/I balance at ultrahigh fields, and stress the importance of using a properly-optimized echo time.