A new case of GABA transaminase deficiency facilitated by proton MR spectroscopy

BACKGROUND: Deficiency of 4-aminobutyrate aminotransferase (GABA-T) is a rare disorder of GABA catabolism, with only a single sibship reported. We report on a third case, a Japanese female infant with severe psychomotor retardation and recurrent episodic lethargy with intractable seizures, with the diagnosis facilitated by proton magnetic resonance (MR) spectroscopy ((1)H-MRS). METHODS: Neuroimaging was performed at the first episode of lethargy. For (1)H-MRS, locations were placed in the semioval center and the basal ganglia. Quantification of metabolite concentrations were derived using the LCModel. We confirmed the diagnosis subsequently by enzyme and molecular studies, which involved direct DNA sequence analysis and the development of a novel multiplex ligation-dependent probe amplification test. RESULTS: (1)H-MRS analysis revealed an elevated GABA concentration in the basal ganglia (2.9 mmol/l). Based on the results of quantitative (1)H-MRS and clinical findings, GABA-T deficiency was suspected and confirmed in cultured lymphoblasts. Molecular studies of the GABA-T gene revealed compound heterozygosity for a deletion of one exon and a missense mutation, 275G>A, which was not detected in 210 control chromosomes. CONCLUSIONS: Our results suggest that excessive prenatal GABA exposure in the central nervous system (CNS) was responsible for the clinical manifestations of GABA transaminase deficiency. Our findings suggest the dual nature of GABA as an excitatory molecule early in life, followed by a functional switch to an inhibitory species later in development. Furthermore, quantitative (1)H-MRS appears to be a useful, noninvasive tool for detecting inborn errors of GABA metabolism in the CNS

In vivo Human MR Spectroscopy Using a Clinical Scanner: Development, Applications, and Future Prospects.

MR spectroscopy (MRS) is a unique and useful method for noninvasively evaluating biochemical metabolism in human organs and tissues, but its clinical dissemination has been slow and often limited to specialized institutions or hospitals with experts in MRS technology. The number of 3-T clinical MR scanners is now increasing, representing a major opportunity to promote the use of clinical MRS. In this review, we summarize the theoretical background and basic knowledge required to understand the results obtained with MRS and introduce the general consensus on the clinical utility of proton MRS in routine clinical practice. In addition, we present updates to the consensus guidelines on proton MRS published by the members of a working committee of the Japan Society of Magnetic Resonance in Medicine in 2013. Recent research into multinuclear MRS equipped in clinical MR scanners is explained with an eye toward future development. This article seeks to provide an overview of the current status of clinical MRS and to promote the understanding of when it can be useful. In the coming years, MRS-mediated biochemical evaluation is expected to become available for even routine clinical practice

A phantom study on component segregation for MR images using ICA(1)

RATIONALE AND OBJECTIVES: A phantom set was devised to evaluate capability of independent component analysis (ICA) as an image filter for magnetic resonance (MR) images to segregate components. \nMATERIALS AND METHODS: Four components (free water [FW], olive oil [OL], 2% and 4% agar gels [2A and 4A, respectively]) were arranged in a phantom set. Seven MR images were obtained with different echo time and repetition time. ICA was performed on 23 combinations of four components. A segregation rate higher than 70% was defined as effective. \nRESULTS: Four-component segregation was obtained in 5 of 23 combinations. The best result showed a mean of 87% across the four components. For each component, there were 20 of 23 for FW, 22 for OL, 9 for 2A, and 16 for 4A.\nCONCLUSIONS: The results demonstrated ICA works as an image filter and provides new contrast images that unambiguously segregate components in MR images. For practical application, the best performance should be obtained when T(1)W, T(2)W, and proton density images are included in the dataset for ICA

Combination of two fat saturation pulses improves detectability of glucose signals in carbon-13 MR spectroscopy

In order to improve the fat suppression performance of in vivo 13C-MRS operating at 3.0 Tesla, a phantom model study was conducted using a combination of two fat suppression techniques; a set of pulses for frequency (chemical shift) selective suppression (CHESS), and spatial saturation (SAT). By optimizing the slab thickness for SAT and the irradiation bandwidth for CHESS, the signals of the -13CH3 peak at 49 ppm and the -13CH2- peak at 26ppm simulating fat components were suppressed to 5% and 19%, respectively. Combination of these two fat suppression pulses achieved a 53% increase of the height ratio of the glucose C1O peak compared with the sum of all other peaks, indicating better sensitivity for glucose signal detection. This method will be applicable for in vivo 13C-MRS by additional adjustment with the in vivo relaxation times of the metabolites

Acute hemicerebellitis in a pediatric patient: a case report of a serial MR spectroscopy study

The changes in the signals for brain metabolites in the left cerebellum of a 14-year-old boy with acute hemicerebellitis were monitored using proton magnetic resonance spectroscopy (MRS). From the onset of disease treatment to long-term follow-up, MRS data were serially acquired from the left and right cerebella, basal ganglia (BG), and centrum semiovale (CS). Large fluctuations in his MRS signals were observed in the left cerebellum. At onset (first day), his glutamate/glutamine complex signals were increased (>mean +- 2 standard deviations [SD] of the control), and those for N-acetylaspartate/N-acetylaspartylglutamate and myo-inositol were decreased (<2SD). By the 25th day, these signals had recovered to normal levels, while those for choline (Cho) were increased. In other locations, the signals for mIns in the BG and Cho in the CS were decreased on the seventh day. By the 201st day, the levels of all metabolites in all locations had recovered to within +- 2SD of the control levels. In vivo proton MRS monitoring demonstrated reversible metabolite changes associated with acute hemicerebellitis, which should contribute to its differential diagnosis from brain tumors