Number of subjects required in common study designs for functional GABA magnetic resonance spectroscopy in the human brain at 3 Tesla

• Published in: The European journal of neuroscience Vol. 51; no. 8; pp. 1784 - 1793
• Main Authors: Sanaei Nezhad, Faezeh, Lea‐Carnall, Caroline A., Anton, Adriana, Jung, JeYoung, Michou, Emilia, Williams, Stephen R., Parkes, Laura M.
• Format: Journal Article
• Language: English
• Published: France Wiley Subscription Services, Inc 01.04.2020; John Wiley and Sons Inc
• Subjects: Brain; Brain - diagnostic imaging; fMRS; GABA; gamma-Aminobutyric Acid; Glutamic Acid; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; MEGA‐PRESS; Metabolites; Neurotransmitters; power calculation; precision; quantification; Research Report; Spectrum analysis; Systems Neuroscience; γ-Aminobutyric acid; GABA; power calculation; MEGA-PRESS; quantification; fMRS; precision
• DOI: 10.1111/ejn.14618
• ISSN: 0953-816X; 1460-9568

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. The impact of acquisition time on variability of GABA data. The figure shows the relative SD of regional GABA estimates across subjects. In general, there is little benefit in collecting data beyond 4 min acquisition duration in terms of improved power to detect group differences.