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In vivo estimation of gamma‐aminobutyric acid levels in the neonatal brain
Authors:Moyoko Tomiyasu  Noriko Aida  Jun Shibasaki  Masahiro Umeda  Katsutoshi Murata  Keith Heberlein  Mark A Brown  Eiji Shimizu  Hiroshi Tsuji  Takayuki Obata
Institution:1. Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, Chiba, Japan;2. Research Center for Child Mental Development, Chiba University, Chiba, Japan;3. Department of Radiology, Kanagawa Children's Medical Center, Yokohama, Japan;4. Department of Neonatology, Kanagawa Children's Medical Center, Yokohama, Japan;5. Medical MR Center, Meiji University of Integrative Medicine, Kyoto, Japan;6. Imaging and Therapy System Division, Siemens Japan, Tokyo, Japan;7. Biomedical Imaging Technology Center, Burlington, Massachusetts, USA;8. Siemens Medical Solutions USA, Cary, North Carolina, USA
Abstract:Gamma‐aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain, and plays a key role in brain development. However, the in vivo levels of brain GABA in early life are unknown. Using edited MRS, in vivo GABA can be detected as GABA+ signal with contamination of macromolecule signals. GABA+ is evaluated as the peak ratio of GABA+/reference compound, for which creatine (Cr) or water is typically used. However, the concentrations and T1 and T2 relaxation times of these references change during development. Thus, the peak ratio comparison between neonates and children may be inaccurate. The aim of this study was to measure in vivo neonatal brain GABA+ levels, and to investigate the dependency of GABA levels on brain region and age. The basal ganglia and cerebellum of 38 neonates and 12 children were measured using GABA‐edited MRS. Two different approaches were used to obtain GABA+ levels: (i) multiplying the GABA/water ratio by the water concentration; and (ii) multiplying the GABA+/Cr by the Cr concentration. Neonates exhibited significantly lower GABA+ levels compared with children in both regions, regardless of the approach employed, consistent with previous ex vivo data. A similar finding of lower GABA+/water and GABA+/Cr in neonates compared with children was observed, except for GABA+/Cr in the cerebellum. This contrasting finding resulted from significantly lower Cr concentrations in the neonate cerebellum, which were approximately 52% of those of children. In conclusion, care should be taken to consider Cr concentrations when comparing GABA+/Cr levels between different‐aged subjects.
Keywords:gamma‐aminobutyric acid (GABA)  human study  MEGA‐PRESS  neonates  normal brain  spectroscopic quantitation
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