Linewidth and lineshape bias in modelled outcomes from GABA-edited 1H MRS

Motivation: The study addresses a gap in literature concerning the impact of spectral linewidth and lineshape differences on GABA+ estimates. Goal(s): To assess the degree to which differences in linewidth/lineshape may confound GABA+ estimates. Approach: In-vivo GABA+-edited spectra (N=222) were quantified with six modelling algorithms after applying varying degrees of Lorentzian and Gaussian linebroadening. Results: Most algorithms showed strong negative associations between amount of Lorentzian linebroadening and GABA+ estimate (2-5% per Hz LB), consistently across datasets. Gaussian linebroadening showed contrasting, substantially weaker associations. In functional applications and cases of differing T2 relaxation between regions or subject groups, these results indicate a potentially significant confound. Impact: Comparing metabolite concentration estimates across different anatomical regions, subject groups or experimental conditions requires appropriate handling of differences in linewidth and linebroadening mechanisms. We demonstrate that several modelling algorithms have linebroadening biases, differing by lineshape, that may confound findings.