Kou Kawada

Developmental changes of optical properties in neonates determined by near-infrared time-resolved spectroscopy.

Near-infrared spectroscopy has been used for measurement of changes in cerebral Hb concentrations in infants to study cerebral oxygenation and hemodynamics. In this study, measurements by time-resolved spectroscopy (TRS) were performed in 22 neonates to estimate the values of light absorption coefficient and reduced scattering coefficient (μs), cerebral Hb oxygen saturation (Sco2), cerebral blood volume (CBV), and differential pathlength factor (DPF), and the relationships between postconceptional age and μs, Sco2, CBV, and DPF were investigated. A portable three-wavelength TRS system with a probe attached to the head of the neonate was used. The mean μs values at 761, 795, and 835 nm in neonates were estimated to be (mean ± SD) 6.46 ± 1.21, 5.90 ± 1.15 and 6.40 ± 1.16/cm, respectively. There was a significant positive relationship between postconceptional age and μs at those three wavelengths. The mean Sco2 value was calculated to be 70.0 ± 4.6%, and postconceptional age and Sco2 showed a negative linear relationship. The mean value of CBV was 2.31 ± 0.56 mL/100 g. There was a significant positive relationship between postconceptional age and CBV. The mean DPF values at 761, 795, and 835 nm were estimated to be 4.58 ± 0.41, 4.64 ± 0.46, and 4.31 ± 0.42, respectively. There was no relationship between postconceptional age and DPF at those three wavelengths. The results demonstrated that our near-infrared TRS method can be used to monitor μs, Sco2, CBV, and DPF in the neonatal brain at the bedside in an intensive care unit.

Noninvasive optical imaging in the visual cortex in young infants.

During the developmental stage, the brain undergoes anatomic, functional, and metabolic changes necessary to support the complex adaptive behavior of a mature individual. Estimation of developmental changes occurring in different regions of the brain would provide a means of relating various behavioral phenomena to maturation‐specific brain structures, thereby providing useful information on structure‐function relationships in both normal and disease states. We used multichannel near‐infrared spectroscopy (MNIRS), a new noninvasive imaging technique for revealing the course of neural activity in selected brain regions, to monitor the activities of the visual cortex as mirrored by hemodynamic responses in infants subjected to photostimulation during natural sleep. In the infants, oxyhemoglobin and total hemoglobin decreased and deoxyhemoglobin increased in the visual cortex with photostimulation. This pattern of responses was different from the response pattern in adults reported previously. The different patterns of responses to photostimulation in the visual cortices of infants and adults might reflect developmental and behavioral differences. It may reflect a different functional organization of the visual cortex in infants or ongoing retinal development. Our results demonstrated that regional hemodynamic change could be detected in a small area around the visual cortex. MNIRS offers considerable potential for research and noninvasive clinical applications. Hum. Brain Mapping 22:124–134, 2004.

Pharmacokinetics of zonisamide in perinatal period

Zonisamide is widely used for intractable epilepsy and the effects of this drug on fetuses and neonates through the mother taking it for epilepsy need to be clarified. We measured the zonisamide concentration in plasma and breast milk using high-performance liquid chromatography to investigate the transfer of zonisamide through the placenta and breast milk, as well as its pharmacokinetics, in two neonates born to epileptic mothers receiving zonisamide. The transfer rates were 92% via the placenta and 41-57% through the breast milk. The first-order kinetics of zonisamide in the two infants was elimination half-lives of 109 and 61h, respectively.

Changes in cerebral hemoglobin concentration and oxygen saturation immediately after birth in the human neonate using full-spectrum near infrared spectroscopy

Using full-spectrum near infrared spectroscopy (fsNIRS), we measured changes in oxy- and deoxyhemoglobin (HbO2 and Hb), total hemoglobin (T-Hb) concentration, and hemoglobin oxygen saturation (SbO2) in the brain tissue of seven neonates immediately following birth. It was found that HbO2 rose rapidly within 2-3 min after birth. During the same time, there was a transient increase in T-Hb concentration, after which it decreased together with Hb. SbO2 increased rapidly after birth, from 18% at 1.5 min to about 55% at 5-6 min, followed by a gradual increase of about 10%. Oxygenation in the brain occurred much sooner in three subjects given oxygen for a short time immediately after birth than in those who did not receive oxygen. This preliminary study indicated that dynamic changes occur in cerebral circulation and oxygenation as part of the physiological changes taking place soon after birth.

Pharmacokinetics of prophylactic micafungin in very-low-birth-weight infants.

We evaluated the use of micafungin as a prophylaxis in very-low-birth-weight infants. Micafungin was first administered to 25 very-low-birth-weight infants 12 to 24 hours after birth at a dose of 1 mg/kg/d. the apparent volume of distribution, the apparent elimination rate constant, the elimination half-life, and the total body clearance (mean ± SD) were 0.76 ± 0.28 L/kg, 0.12 ± 0.041 1/h, 6.7 ± 2.2 h, and 0.089 ± 0.047 L/kg/h, respectively.

Henoch-Schönlein purpura with intracerebral hemorrhage

We describe a case of Henoch-Schönlein purpura (HSP) with massive intracerebral hemorrhage (ICH) in a 7-year-old-girl. A cranial CT scan revealed extensive ICH in the left parietal region and right parieto-temporal through occipital regions. At the time of ICH onset, hypertension and coagulation abnormality were not observed, but factor XIII activity was markedly reduced 9%. ICH was thought to have resulted from a marked decrease in factor XIII. Factor XIII preparation was administered immediately after the onset of ICH, and enlargement of the hemorrhagic region was not seen. The present case is the only reported case of HSP complicated by ICH in which factor XIII level was measured.

Relationship between Cerebral Interstitial Levels of Amino Acids and Phosphorylation Potential during Secondary Energy Failure in Hypoxic-Ischemic Newborn Piglets

The aim of this study was to determine the validity of the hypothesis that excitatory amino acids are related to phosphorylation potential during primary and secondary cerebral energy failure observed in asphyxiated infants. We report here the results of experiments using newborn piglets subjected to severe transient cerebral hypoxia-ischemia followed by resuscitation. We examined cerebral energy metabolism by phosphorus nuclear magnetic resonance spectroscopy and changes in levels of amino acid neurotransmitters in the cortex by microdialysis before, during, and up to 24 h after the hypoxic-ischemic insult. The concentrations of aspartate, glutamate, taurine, and γ-aminobutyric acid were significantly elevated during the hypoxic-ischemic insult compared with prebaseline values. Shortly after resuscitation, glutamate, taurine, and γ-aminobutyric acid concentrations decreased but then began to increase again. These secondary elevations were greater than the primary elevations. A negative linear correlation was found between primary interstitial levels of glutamate and taurine and minimum values of phosphocreatine/inorganic phosphate during the secondary energy failure. The cerebral energy state depended on the time course of changes in excitatory amino acids, suggesting that amino acids play distinct roles during the early and delayed phases of injury.

Influence of Glucuronosyl Bilirubin and (EZ)-Cyclobilirubin on Determination of Serum Unbound Bilirubin by UB-Analyser

Background In the enzyme reaction for the determination of the unbound (free) bilirubin concentration by glucose oxidase and peroxidase, materials with low affinity for serum protein are reactive. The influence of these materials on the determination of serum unbound bilirubin was investigated. Methods Serum samples from patients with neonatal hyperbilirubinaemia were analysed by high-performance liquid chromatography for total glucuronosyl bilirubin concentration (TGC) and (E2)-cyclobilirubin concentration [(EZ)-C]. Based on these measurements, the samples were classified into three groups: group I [13 samples, TGC < 2 μmol/L and (EZ)-C < 2·5 μmol/L]; group II [four samples, TGC < 2 μmol/L and (EZ)-C ≥ 2·5 μmol/L]; and group III (five samples, TGC ≥ 2 μmol/L). The concentrations of total bilirubin and unbound bilirubin were measured in these same samples with a UB-analyser. When the absorbance at 460 nm was monitored, the decrease in absorbance was non-linear (concave curve). The degree of concavity was estimated (D15 value) as the deviation from linearity at 15 s. Results The D15 value was significantly higher in groups II and III than in group I. D15 value correlated significantly with TGC, (EZ)-C and unbound bilirubin concentration, and the unbound bilirubin concentration correlated significantly with TGC and (EZ)-C. Conclusion These results indicated that determination of serum unbound bilirubin concentration using the UB-analyser could be positively skewed by high concentrations of TGC and (EZ)-C.

Estimation of circulating blood volume in infants using the pulse dye densitometry method

Background:  Estimation of hemodynamics is important for critically ill infants. Pulse dye densitometry (PDD) using indocyanine green (ICG), which enables measurements of circulating blood volume at the bedside, has recently been developed for adults.

Extrauterine environment affects the cortical responses to verbal stimulation in preterm infants.

Using optical topography, changes in the cerebral oxygenation were compared in the parieto-temporal lobe of preterm and term infants of equal postconceptional age in response to verbal stimulation. Eight preterm infants of gestational age 23-34 weeks were studied at postconceptional term age (38-46 weeks). Ten term infants were studied at 2-11 days after birth. Twenty-four-channel near-infrared optical topography (NIOT) was used to measure changes in concentration of oxyhemoglobin ([oxyHb]), deoxyhemoglobin ([deoxyHb]) and total hemoglobin ([totalHb]) in the bilateral temporal cortices. Verbal stimulation was provided by a recording of a Japanese fairy tale. The latency in response to verbal stimulation was significantly shorter in the preterm infants than in the term infants. This time is thought to reflect brain development, particularly the development of the neuro-vascular coupling mechanisms in the cerebral cortex. The present results indicate that the number of days after birth is more closely related to development of auditory system and neuro-vascular coupling than is postconceptional age. Thus, this suggests that early extrauterine environment affects the cortical responses to verbal stimulation in preterm infants.