Abstract
Metabolite-specific, scalar spin-spin coupling constant (J)-editing 1H MRS methods have become gold-standard for measuring brain γ-amino butyric acid (GABA) levels in human brain. Localized, two-dimensional (2D) 1H 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 1H 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 1H MRS time courses. The data presented are particularly encouraging considering recent 2D 1H MRS methodological advances are continuing to improve temporal resolution and spatial coverage for achieving whole-brain, multi-metabolite mapping.
Highlights
(J)-coupling effects, which act to complicate gold-standard for measuring brain γ-amino butyric acid (GABA) MRS resonance structures and reduce signal-to-noise ratio (SNR)
The Coefficient of variation (CV) values presented were obtained by first determining the CV for each subject, and calculating the mean within-subject CV for each cohort
Efforts to reduce total 2D MRS measurement time have recently found traction through the introduction of non-uniform weighted sampling (NUWS) procedures[57,58,59,60], and quantitative treatment of 2D 1H MRS data has been advanced through automated methods such as prior knowledge fitting (ProFit)[35]
Summary
(J)-coupling effects, which act to complicate GABA MRS resonance structures and reduce signal-to-noise ratio (SNR). A second class of 1H MRS metabolite-specific editing methods for isolating the GABA C4 proton resonance involves the excitation and filtration of higher-order multiple quantum coherences (MQC). On the principle that MQCs can be stimulated for J-coupled proton nuclei but not for uncoupled singlet species, including the Cre methyl nuclei For human studies, this typically has been achieved by incorporating a double-quantum filter (DQF) within single-voxel[20,21,22,23,24] or multi-voxel spatial localization schemes[25]. Localized 2D 1H MRS brain studies have been reported for both healthy brain[29,37,38], psychiatric illness[39,40,41], and substance abuse disorders[7]
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