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Objective: To determine the optimal quantitative magnetic resonance (MR) biomarker in neonatal encephalopathy following therapeutic hypothermia based on scan timing. Study design: This retrospective study included 98 neonates (35-41 weeks of gestation) with neonatal encephalopathy, who underwent therapeutic hypothermia; diffusion-weighted imaging and proton MR spectroscopy were performed at 24-96 hours (n = 56) and 7-14 days (n = 92) after birth, respectively, to estimate apparent diffusion coefficient (ADC) values, N-acetylaspartate and N-acetylaspartylglutamate (tNAA), lactate, and choline concentrations, and lactate/tNAA, tNAA/choline ratios in the deep gray matter. Adverse outcomes included death or neurodevelopmental impairment at 18-22 months of age. We used receiver operating characteristic curves to examine the prognostic accuracy of each MR biomarker. Results: Deep gray matter tNAA concentrations showed the best prognostic value, with an area under the curve (AUC) of 0.97 and 1.00 at 24-96 hours and 7-14 days after birth, respectively. At 24-96 hours of age, ADC values, lactate concentrations, and lactate/tNAA ratios showed prognostic value with AUCs of 0.90, 0.95, and 0.97, respectively. At 7-14 days of age, the AUCs of ADC values, lactate, and lactate/tNAA ratios were 0.61, 0.67, and 0.80, respectively; these were lower than those at 24-96 hours of age. Conclusions: During the first 2 weeks of life, the deep gray matter tNAA concentration was the most accurate quantitative MR biomarker. Although ADC values, lactate levels, and lactate/tNAA ratios also showed high prognostic value during 24-96 hours of life, only tNAA retained high prognostic value in the second week of life.

A very-low-birth-weight (VLBW) preterm infants is associated with an increased risk of impaired neurodevelopmental outcomes. In this study, we investigated how neonatal brain metabolite concentrations changed with postmenstrual age and examined the relationship between changes in concentration (slopes) and neurodevelopmental level at 3-4 years.

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.

Introduction: In nonketotic hyperglycinemia (NKH), 1H-MRS shows a striking increase in brain glycine levels. However, the signal overlap of glycine with myo-inositol makes it difficult to quantify each metabolite separately. Our aim was to investigate glycine measurement with 1H-MRS using different echo times (TE) in a neonate with NKH. Methods: Serial single-voxel 1H-MRS in the centrum semiovale was performed with TE of 30 and 270ms in a neonate with NKH on 6, 19, 44 days of age, and the peak area ratios of glycine plus myo-inositol to creatine ((Gly+mIns)/Cr) was evaluated. Glycine levels of plasma and cerebral spinal fluid (CSF) were also measured on 5, 19, and 44 days of ages. Results: In both TEs, (Gly+mIns)/Cr showed higher values at first, then decreased subsequently; TE 30msec: 1.43, 1.19, and 1.11, TE 270 msec: 1.05, 0.55, and 0.49, respectively. Both glycine levels of plasma and CSF showed similar decreasing: plasma: 1803.9, 353.0, and 140.0 μmol/L, CSF: 321.6, 135.3, and 69.7 μmol/L, respectively. On 6 days, the patient was comatose, and had no spontaneous respiration. On 19 days, he was lethargic but had spontaneous respirations. On 44 days, his consciousness was almost clear. Conclusion: The continuing reduction of (Gly+mIns)/Cr with long-TE corresponded more reliably with glycine levels of plasma and CSF than the change with short-TE. In addition to T2 relaxation time effect, myo-inositol also has J-coupling induced-dephasing effect, which results in small signal in long TE. Therefore myo-inositol signal may have a relatively less contribution to (Gly+mIns) in TE 270ms., The 20th Annual Meeting of Infantile Seizure Society (ISS)

[Purpose] It is well known that the premature birth is associated with increased risk of neurological and physical problems. The purpose of this study is to investigate whether the brain metabolite concentration (conc) and/or volumes in neonates can be an index of the prognosis for the premature birth. [Methods] Twenty-six subjects with premature birth (gestational age: 23-33 weeks) were included. At their postconceptional age of 34-40 weeks, they had brain MRI (Siemens 3T) including MRS (PRESS, TE 30ms, TR 5s). The metabolite conc were calculated using LCModel with water conc of 46.9M. Using T2W images (TE 119-123ms, TR 5s), the volumes were measured using ROI editor (John Hopkins). At a corrected age of 1.5 years, they had developmental quotient (DQ) by Kyoto Scale of Psychological Development. Correlations between the conc and DQ, and the volume and DQ were investigated using Spearman’s rank correlation coefficients. The conc change with development was considered. [Results] The creatine, choline, N-acetylaspartate, myo-inositol, and glutamate/glutamine complex conc were 5.4-9.0, 1.3-2.6, 3.0-6.4, 4.8-8.8, and 3.8-11.5mM, in the basal ganglia, respectively, and 3.8-5.9, 1.5-2.3, 2.4-6.1, 5.7-9.3, and 3.9-8.9mM, in the centrum semiovale. The supratentorial, cerebellum, and intracranial volumes were 222-332, 13-22, and 352-550mL, respectively; The DQ were 44-119. No correlations were found between the metabolite conc or volumes and DQ. [Discussion] The DQ is overall index, and in this study fine classification of the DQ was not considered. Also, the volume change with development was not considered. Although we could not find any correlation, more detail studies are needed to confirm whether the MR data in neonates can be an index of the prognosis for premature birth., 第44回日本磁気共鳴医学会大会