Quantification of GABA in 1H MRS Volumes Composed Heterogeneously of Grey and White Matter

Quantification of -aminobutyric acid (GABA) concentration using localized MRS suffers from partial volume effects related to differences in the intrinsic concentration of GABA in grey matter (GM) and white matter (WM). These differences can be represented as a ratio between intrinsic GABA in GM and WM, rM. Individual differences in GM tissue volume can therefore potentially drive apparent concentration differences. Here, a quantification method that corrects for these effects is formulated and empirically validated. Quantification using tissue water as an internal concentration reference has previously been described. Partial volume effects attributed to rM can be accounted for by incorporating into this established method an additional multiplicative correction factor based on measured or literature values of rM weighted by the proportion of GM and WM within tissue-segmented MRS volumes. Simulations were performed to test the sensitivity of this correction using different assumptions of rM taken from previous studies. The tissue correction method was then validated by applying it to an independent dataset of in vivo GABA measurements using an empirically measured value of rM. It is shown that incorrect assumptions of rM can lead to overcorrection and inflation of GABA concentration measurements quantified in volumes composed predominantly of WM. For the independent dataset, GABA concentration was linearly related to GM tissue volume when only the water signal was corrected for partial volume effects. Performing a full correction that additionally accounts for partial volume effects ascribed to rM successfully removed this dependency. With appropriate assumption of the ratio of intrinsic GABA concentration in GM and WM, GABA measurements can be corrected for partial volume effects, potentially leading to a reduction in between-participant variance, increased power in statistical tests and better discriminability of true effects.