Does it matter which subspectra are modelled in GABA-edited MRS?

Motivation: Modeling of GABA-edited data is commonly performed on the difference spectrum. However, linear-combination modeling can also be performed on each subspectrum, and simultaneous modeling of DIFF and SUM spectra (or the ON and the OFF) has been suggested to improve accuracy. Goal(s): To compare the accuracy of simultaneous against single-spectrum modeling, and to compare ON&OFF to DIFF& SUM modeling. Approach: 100 time-domain spectra containing GABA and Cr were synthesized and modeled with six approaches. Results: Simultaneous modeling (ON&OFF or DIFF&SUM) out-performed DIFF-only, even where the SUM spectrum could not be modeled in isolation. The ON&OFF model gave equivalent outcomes to DIFF&SUM. Impact: New, more flexible MRS modeling software allows modeling of multiple sub-spectra of edited experiments, and it is important to appreciate the implications of choices of modeling approach.