Number of subjects required in common study designs for functional GABA magnetic resonance spectroscopy in the human...

Magnetic resonance spectroscopy (MRS) is a research tool for measuring the concentration of metabolites such as γ-aminobutyric acid (GABA) and glutamate in the brain. MEGA-PRESS has been the preferred pulse sequence for GABA measurements due to low physiological GABA concentrations, hence low signal. To compensate, researchers incorporate long acquisition durations (7-10 min) making functional measurements of this metabolite challenging. Here, the acquisition duration and sample sizes required to detect specific concentration changes in GABA using MEGA-PRESS at 3 T are presented for both between-groups and within-session study designs. 75 spectra were acquired during rest using MEGA-PRESS from 41 healthy volunteers in 6 different brain regions at 3 T with voxel sizes between 13 and 22 cm³ . Between-group and within-session variance was calculated for different acquisition durations and power calculations were performed to determine the number of subjects required to detect a given percentage change in GABA/NAA signal ratio. Within-subject variability was assessed by sampling different segments of a single acquisition. Power calculations suggest that detecting a 15% change in GABA using a 2 min acquisition and a 27 cm³ voxel size, depending on the region, requires between 8 and 93 subjects using a within-session design. A between-group design typically requires more participants to detect the same difference. In brain regions with suboptimal shimming, the subject numbers can be up to 4-fold more. Collecting data for longer than 4 min in brain regions examined in this study is deemed unnecessary, as variance in the signal did not reduce further for longer durations.