Two-Dimensional Proton Magnetic Resonance Spectroscopy versus J-Editing for GABA Quantification in Human Brain: Insights from a GABA-Aminotransferase Inhibitor Study

Metabolite-specific, scalar spin-spin coupling constant (J)-editing (1)H MRS methods have become gold-standard for measuring brain γ-amino butyric acid (GABA) levels in human brain. Localized, two-dimensional (2D) (1)H MRS technology offers an attractive alternative as it significantly alleviates the problem of severe metabolite signal overlap associated with standard 1D MRS and retains spectroscopic information for all MRS-detectable species. However, for metabolites found at low concentration, a direct, in vivo, comprehensive methods comparison is challenging and has not been reported to date. Here, we document an assessment of comparability between 2D (1)H MRS and J-editing methods for measuring GABA in human brain. This clinical study is unique in that it involved chronic administration a GABA-amino transferase (AT) inhibitor (CPP-115), which induces substantial increases in brain GABA concentration, with normalization after washout. We report a qualitative and quantitative comparison between these two measurement techniques. In general, GABA concentration changes detected using J-editing were closely mirrored by the 2D (1)H MRS time courses. The data presented are particularly encouraging considering recent 2D (1)H MRS methodological advances are continuing to improve temporal resolution and spatial coverage for achieving whole-brain, multi-metabolite mapping.