Brain GABA editing by localized in vivo1H magnetic resonance spectroscopy

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Abstract
Editing of GABA by 1H MRS in a specific brain area is a unique tool for in vivo non‐invasive investigation of neurotransmission disorders. Selective GABA detection is achieved using sequences based on double quantum coherence (DQC). Our pulse sequence makes accurate measurements without artefacts due to spatial localization. The sequence was tested on a phantom solution. The effect of vigabatrin, a specific inhibitor of GABA transaminase, was measured in rat brain and GABA detection was performed in vivo in monkey brain using this procedure. Rats were spilt into two groups. In the control group, the rats had access to water and, in the other group (vigabatrin, VGB, rats), animals were allowed free access to drinking water containing vigabatrin. After 3 weeks of treatment, rats were anesthetized for in vivo NMR spectroscopy investigation. At the end of the experiment, brains were quickly removed, freeze‐clamped and extracted with 4% perchloric acid. One part of the acid extract was used for GABA concentrations assessment by ion exchange chromatography with ninhydrin detection. The second was used for high‐resolution NMR analysis. By chromatography measurements, the GABA concentration was 1.23±0.06 μmol/g for controls, while for vigabatrin‐treated rats the GABA concentration was 4.89±1.60 μmol/g. The NMR in vivo results were closely correlated with the NMR ex vivo (r=0.99, pr=0.98, pex vivo results and chromatography results was also high (r=0.99, pin vivo GABA editing scheme can thus be proposed for accurate measurement of brain GABA concentrations. Copyright © 2004 John Wiley & Sons, Ltd.