Purpose: The most common g-aminobutyric-acid (GABA) editing approach, MEGA-PRESS, uses J-editing to measure GABA distinct from larger overlapping metabolites, but suffers contamination from coedited macromolecules (MMs) comprising 40 to 60% of the observed signal. MEGA-SPECIAL is an alternative method with better MM suppression, but is not widely used primarily because of its relatively poor spatial localization. Our goal was to develop an improved MM-suppressed GABA editing sequence at 3 Tesla. Methods: We modified a single-voxel MEGA-SPECIAL sequence with an oscillating readout gradient for improved spatial localization, and used very selective 30-ms editing pulses for improved suppression of coedited MMs. Results: Simulation and in vivo experiments confirmed excellent MM suppression, insensitive to the range of B 0 frequency drifts typically encountered in vivo. Both intersubject and intrasubject studies showed that MMs, when suppressed by the improved MEGA-SPECIAL method, contributed approximately 40% to the corresponding MEGA-PRESS measurements. From the intersubject study, the coefficient of variation for GABAþ/Cre (MEGA-PRESS) was 11.2% versus 7% for GABA/Cre (improved MEGA-SPECIAL), demonstrating significantly reduced variance (P ¼ 0.005), likely coming from coedited MMs. Conclusions: This improved MEGA-SPECIAL sequence provides unbiased GABA measurements with reduced variance as compared with conventional MEGA-PRESS. This approach is also relatively insensitive to the range of B 0 drifts typically observed in in vivo human studies. Magn Reson Med 79:41-47,
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