Moyoko Tomiyasu

Neonatal Brain Metabolite Concentrations: An In Vivo Magnetic Resonance Spectroscopy Study with a Clinical MR System at 3 Tesla

Brain metabolite concentrations change dynamically throughout development, especially during early childhood. The purpose of this study was to investigate the brain metabolite concentrations of neonates (postconceptional age (PCA): 30 to 43 weeks) using single-voxel magnetic resonance spectroscopy (MRS) and to discuss the relationships between the changes in the concentrations of such metabolites and brain development during the neonatal period. A total of 83 neonatal subjects were included using the following criteria: the neonates had to be free of radiological abnormalities, organic illness, and neurological symptoms; the MR spectra had to have signal-to-noise ratios ≥ 4; and the estimated metabolite concentrations had to display Cramér-Rao lower bounds of ≤ 30%. MRS data (echo time/repetition time, 30/5000 ms; 3T) were acquired from the basal ganglia (BG), centrum semiovale (CS), and the cerebellum. The concentrations of five metabolites were measured: creatine, choline, N-acetylaspartate, myo-inositol, and glutamate/glutamine complex (Glx). One hundred and eighty-four MR spectra were obtained (83 BG, 77 CS, and 24 cerebellum spectra). Creatine, N-acetylaspartate, and Glx displayed increases in their concentrations with PCA. Choline was not correlated with PCA in any region. As for myo-inositol, its concentration decreased with PCA in the BG, whereas it increased with PCA in the cerebellum. Quantitative brain metabolite concentrations and their changes during the neonatal period were assessed. Although the observed changes were partly similar to those detected in previous reports, our results are with more subjects (n = 83), and higher magnetic field (3T). The metabolite concentrations examined in this study and their changes are clinically useful indices of neonatal brain development.

A multi-compartmental SE-BOLD interpretation for stimulus-related signal changes in diffusion-weighted functional MRI.

A new interpretation is proposed for stimulus‐induced signal changes in diffusion‐weighted functional MRI. T2‐weighted spin‐echo echo‐planar images were acquired at different diffusion‐weightings while visual stimulation was presented to human volunteers. The amplitudes of the positive stimulus‐correlated response and post‐stimulus undershoot (PSU) in the functional time‐courses were found to follow different trends as a function of b‐value. Data were analysed using a three‐compartment signal model, with one compartment being purely vascular and the other two dominated by fast‐ and slow‐diffusing molecules in the brain tissue. The diffusion coefficients of the tissue were assumed to be constant throughout the experiments. It is shown that the stimulus‐induced signal changes can be decomposed into independent contributions originating from each of the three compartments. After decomposition, the fast‐diffusion phase displays a substantial PSU, while the slow‐diffusion phase demonstrates a highly reproducible and stimulus‐correlated time‐course with minimal undershoot. The decomposed responses are interpreted in terms of the spin‐echo blood oxygenation level dependent (SE‐BOLD) effect, and it is proposed that the signal produced by fast‐ and slow‐diffusing molecules reflect a sensitivity to susceptibility changes in arteriole/venule‐ and capillary‐sized vessels, respectively. This interpretation suggests that diffusion‐weighted SE‐BOLD imaging may provide subtle information about the haemodynamic and neuronal responses. Copyright

Monitoring the brain metabolites of children with acute encephalopathy caused by the H1N1 virus responsible for the 2009 influenza pandemic: a quantitative in vivo 1H MR spectroscopy study

BACKGROUND AND PURPOSE Influenza viral infection, which results in central nervous system dysfunction, is a major cause of acute encephalopathy (AE). The purpose of this study was to investigate the changes in the concentrations of brain metabolites in children with AE using single-voxel magnetic resonance spectroscopy (MRS) and to provide diagnostic information about the relationship between the symptoms of AE and metabolite concentrations. MATERIALS AND METHODS The subjects were 10 children (mean age: 6.2 years; range: 1-13) with AE caused by the novel influenza A virus responsible for the 2009 influenza pandemic. The serial MRS data (TE/TR=30/5000 ms, 3 T) acquired from the basal ganglia (BG) and centrum semiovale (CS) of each patient were categorized into three periods: (1) initial neurological symptom presentation and the start of treatment (n=10), (2) short-term follow-up (n=9) and (3) long-term follow-up (n=3). As controls, the magnetic resonance (MR) spectra of eight age-matched children were also investigated. RESULTS In both regions, the concentrations of the major metabolites (N-acetylaspartate, creatine, choline, myo-inositol, glutamate/glutamine complex and glutamate) only showed minor fluctuations between the three periods. On the other hand, higher levels of taurine (Tau) were observed in the BG during the second period (P=.005), and increased levels of glucose were observed in the CS during the first (P=.005) and second (P=.036) periods. CONCLUSIONS Serial monitoring of brain metabolite changes was carried out with a clinical MR system. The concentrations of major metabolites only displayed very minor fluctuations in response to mild H1N1-related AE. However, a higher Tau concentration was found to be associated with neurological symptoms. Further studies are required to improve our understanding of the detailed activity of Tau in AE.

Monitoring of liver glycogen synthesis in diabetic patients using carbon-13 MR spectroscopy

To investigate the relationship between liver glucose, glycogen, and plasma glucose in diabetic patients, in vivo liver carbon-13 magnetic resonance spectroscopy ((13)C MRS) with a clinical 3.0T MR system was performed. Subjects were healthy male volunteers (n=5) and male type-2 diabetic patients (n=5). Pre- and during oral glucose tolerance tests (OGTT), (13)C MR spectra without proton decoupling were acquired in a monitoring period of over 6h, and in total seven spectra were obtained from each subject. For OGTT, 75g of glucose, including 5g of [1-(13)C]glucose, was administered. The MR signals of liver [1-(13)C]glucose and glycogen were detected and their time-course changes were assessed in comparison with the plasma data obtained at screening. The correlations between the fasting plasma glucose level and liver glycogen/glucose rate (Spearman: rho=-0.68, p<0.05, n=10) and the fasting plasma glucose level and liver glycogen peak/fasting rate (Spearman: rho=-0.67, p<0.05, n=10) indicated that (13)C MRS can perform noninvasive measurement of glycogen storage/degradation ability in the liver individually and can assist in tailor-made therapy for diabetes. In conclusion, (13)C MRS has a potential to become a powerful tool in diagnosing diabetes multilaterally.

Neonatal case of classic maple syrup urine disease: Usefulness of 1 H-MRS in early diagnosis

We describe a male neonate with classic maple syrup urine disease (MSUD) in metabolic crisis. On day 7 of life, he was referred to hospital because of coma and metabolic acidosis with maple syrup odor. On day 4 after admission, brain magnetic resonance imaging findings were consistent with encephalopathy due to MSUD. Proton magnetic resonance spectroscopy (1H‐MRS) showed a large methyl resonance peak at 0.9 p.p.m. The diagnosis of MSUD was confirmed on low branched‐chain α‐keto acid dehydrogenase complex activity in lymphocyte. 1H‐MR spectra were obtained in 10 min, while it took at least several days to obtain the results of other diagnostic examinations. In convalescence, the peak at 0.9 p.p.m. decreased. The large methyl resonance peak at 0.9 p.p.m. in brain 1H‐MRS would be one of the earliest clues to the diagnosis of classic MSUD in the neonatal period, especially in metabolic crisis.

Transient ischemic attack-like episodes without stroke-like lesions in MELAS

A stroke-like episode is a core symptom in mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Proton magnetic resonance spectroscopy (1H-MRS) is useful in the diagnosis of mitochondrial diseases. We report an 8-year-old girl with MELAS, presenting with a seizure and blindness. 1H-MRS showed a strikingly elevated lactate peak in the right occipital region, where no abnormal signals appeared on either T2-W or diffusion-weighted MRI. She recovered completely within a day. We describe this mild clinical condition with abnormal lactate peak in normal-appearing gray matter as a transient ischemic attack-like episode in MELAS.

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.

In vivo estimation of gamma‐aminobutyric acid levels in the neonatal brain

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.

A Phantom Study On Component Segregation for MR Images Using ICA

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. MATERIALS 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. RESULTS 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. CONCLUSIONS 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.

Changes in Brain Metabolite Concentrations after Neonatal Hypoxic-ischemic Encephalopathy

Purpose To investigate the time-course changes and predictive utility of brain metabolite concentrations in neonatal hypoxic-ischemic encephalopathy (HIE). Materials and Methods Sixty-eight neonates (age, 35-41 gestational weeks) with HIE were admitted to a neonatal intensive care unit between September 2009 and March 2016 and examined by using proton MR spectroscopy at 18-96 hours (n = 25) and 7-14 days (n = 64) after birth (35-43 postmenstrual weeks) to estimate metabolite concentrations in the deep gray matter. Adverse outcome was defined as death or neurodevelopmental impairment at 18-22 months of age. Areas under the receiver operating characteristic curves were calculated to evaluate the prognostic values of metabolites. Results At 18-96 hours, N-acetylaspartate and creatine concentrations were lower, whereas lactate, and glutamate and glutamine (Glx) concentrations were higher in neonates with adverse outcomes than in those with favorable outcomes. Metabolite concentrations at 18-96 hours decreased during days 7-14 in neonates with adverse outcomes but did not change in those with favorable outcomes. For N-acetylaspartate, creatine, lactate, and Glx concentrations measured at 18-96 hours to predict adverse outcomes, areas under the receiver operating characteristic curve were 0.98, 0.89, 0.96, and 0.88, respectively, whereas at 7-14 days, the areas under the receiver operating characteristic curve were 0.97, 0.97, 0.59, and 0.36, respectively. Conclusion Time-dependent reductions in N-acetylaspartate and creatine concentrations at both 18-96 hours and 7-14 days accurately predicted adverse outcomes. However, higher lactate and glutamate and glutamine concentrations were often transient.