Impact of acquisition and modeling parameters on test-retest reproducibility of edited GABA+

Literature values for within-subject test-retest reproducibility of gamma-aminobutyric acid (GABA), measured with edited magnetic resonance spectroscopy (MRS), vary widely. Reasons for this variation remain unclear. Here we tested whether sequence complexity (two-experiment MEGA-PRESS versus four-experiment HERMES), editing pulse duration (14 versus 20 ms), scanner frequency drift (interleaved water referencing (IWR) turned ON versus OFF), and linear combination modeling variations (three different co-edited macromolecule models and 0.55 versus 0.4 ppm spline baseline knot spacing) affected the within-subject coefficient of variation of GABA + macromolecules (GABA+). We collected edited MRS data from the dorsal anterior cingulate cortex from 20 participants (30.8 {+/-} 9.5 years; 10 males). Test and retest scans were separated by removing the participant from the scanner for 5-10 minutes. Each acquisition consisted of two MEGA-PRESS and two HERMES sequences with editing pulse durations of 14 and 20 ms (referred to here as: MEGA-14, MEGA-20, HERMES-14, and HERMES-20; all TE = 80 ms, 224 averages). Reproducibility did not consistently differ for MEGA-PRESS compared with HERMES or for 14 compared with 20 ms editing pulses. A composite model of the 0.9 and 3 ppm macromolecules (particularly for HERMES) and sparser (0.55 compared with 0.4 ppm) spline baseline knot spacing yielded generally better test-retest reproducibility for GABA+. Replicating our prior results, linear combination modeling in Osprey compared with simple peak fitting in Gannet resulted in substantially better test-retest reproducibility. These results highlight the importance of model selection for edited MRS studies of GABA+, particularly for clinical studies which focus on individual patient differences in GABA+ or changes following an intervention.