Kosuke Koyano

Functional lateralization of sensorimotor cortex in infants measured using multichannel near-infrared spectroscopy.

Multichannel near-infrared spectroscopy (MNIRS) was used for the functional imaging of the sensorimotor cortex of newborn infants during passive knee and elbow movement under sedated sleep. Contralateral knee and elbow movement caused a marked increase in the concentration of oxyhemoglobin ([oxyHb]) from the baseline values at site within the sensorimotor area in all infants. During ipsilateral knee and elbow movement, [oxyHb] showed smaller changes, equivalent to 64 ± 23 and 66 ± 28% of the changes that occurred with contralateral stimulation, respectively. The mean times corresponding to maximal changes in [oxyHb] were 16.1 ± 3.3 s for contralateral knee movement and 17.9 ± 5.7 s for contralateral elbow movement. No significant difference was noted between the mean latencies showing the maximal changes in [oxyHb] between contralateral and ipsilateral movement. There was a significant difference in the area and degree of response between the contralateral and ipsilateral movement. MNIRS could be a useful tool to understand the pathophysiology of the developing brain and monitor cortical responses in various clinical situations.

HDlive imaging of intra-amniotic umbilical vein varix with thrombosis

We present a case of intra-amniotic umbilical vein varix with thrombosis using conventional two-dimensional (2D) sonography, power Doppler, three-dimensional (3D) HD-flow, and HDlive at 35 weeks of gestation. 2D sonography showed a large banana-like umbilical cord enlargement (100 × 43.3 × 45.9 mm) including umbilical vein varix (maximum vein diameter = 25.5 mm) with massive thrombosis. Power Doppler and 3D HD-flow revealed bidirectional turbulent blood flow inside the varix. The HDlive clearly demonstrated fragile massive thrombosis inside the varix. Elective cesarean section was performed on the same day in order to avoid additional risks of umbilical cord complications and umbilical venous embolism. A male infant weighing 2501 g was delivered with an umbilical artery pH of 7.334, and Apgar score of 8/9 at 1 and 5 min, respectively. The macroscopic and microscopic findings revealed umbilical cord vein varix with thrombosis. On the basis of the laboratory date of the neonate, the diagnosis of consumptive coagulopathy was made. However, the neonate followed a favorable course after delivery.

Relationship between cerebral oxygenation and phosphorylation potential during secondary energy failure in hypoxic-ischemic newborn piglets.

The aim of this study was to evaluate the hypothesis that cerebral hemoglobin (Hb) oxygenation is related to phosphorylation potential during primary and secondary cerebral energy failure in newborn infants who have experienced birth asphyxia. We subjected newborn piglets to severe transient cerebral hypoxic-ischemia followed by resuscitation and examined cerebral energy metabolism by 31P-magnetic resonance spectroscopy and evaluated changes in cerebral Hb oxygen saturation (ScO2) using full-spectrum near-infrared spectroscopy before, during, and up to 54 h after the hypoxic-ischemic insult. ScO2 was significantly decreased during the hypoxic-ischemic insult compared with baseline values. During secondary energy failure, piglets were separated based on the relationship between the ratio of phosphocreatine to inorganic phosphate and ScO2; those with a negative correlation were less injured than those with a positive correlation. These results indicate that changes in ScO2 as measured by near-infrared spectroscopy are related to phosphorylation potential during secondary energy failure in asphyxiated infants.

The effect of blood transfusion on cerebral hemodynamics in preterm infants

Anemia of prematurity commonly occurs in infants with very low birth weight; blood transfusion is an important treatment. However, there is no clear evidence to support the criteria currently widely used, based on blood hemoglobin (bHb) and hematocrit indices. Previous studies showed that overtransfusion or a low threshold for transfusion could induce complications or neurologic sequelae, respectively. We hypothesized that a cerebral hemodynamic index may provide an appropriate criterion for determining the need for transfusion in anemic preterm infants.

Simultaneous measurement of cerebral hemoglobin oxygen saturation and blood volume in asphyxiated neonates by near-infrared time-resolved spectroscopy.

BACKGROUND Hypoxic-ischemic encephalopathy (HIE) usually results in a poor clinical outcome even when treated with hypothermic therapy (HT). Early postnatal changes in cerebral blood oxygenation and hemodynamics may be critical determinants of brain injury and the efficacy of HT. OBJECTIVES We measured cerebral hemoglobin oxygen saturation (ScO2) and cerebral blood volume (CBV) by near-infrared time-resolved spectroscopy (TRS) in HT-treated and non-HT-treated neonatal HIE patients to assess the influence of these parameters on clinical outcome. METHODS We retrospectively compared ScO2, CBV, and clinical outcomes of 11 neonates with HIE: 5 were treated by HT (HT-treated; 33.5°C±0.5°C for 72h starting approximately 6h after delivery) and 6 were not (non-HT-treated). Both CBV and ScO2 were measured by TRS at 6, 24, 48, and 72h after birth. Magnetic resonance imaging (MRI) was performed 1-2weeks after birth to assess brain injury. RESULTS Five neonates had adverse outcomes (3 HT-treated, 2 non-HT-treated). Of these, 1 died within 3days of birth and 4 had abnormal MRI findings, including basal ganglia, white matter, and/or thalamic lesions. The other 6 neonates had normal MRI findings (favorable outcome). At 6h after birth, CBV was significantly higher in neonates with adverse outcomes compared with those with a favorable outcome. At 24h after birth, ScO2 was significantly higher in neonates with adverse outcomes. Furthermore, we found that combined CBV at 24h after birth plus ScO2 had the best predictive ability for neurological outcome: sensitivity, specificity, positive predictive value, and negative predictive value were all 100%. CONCLUSION Early postnatal CBV and ScO2 elevations were predictive of a poor outcome in HIE. Therefore, measuring combined CBV plus ScO2 at 24h after birth can allow more precise prediction of neurological outcome. Control of postnatal CBV and ScO2 is critical for effective HIE treatment.

Four-Dimensional Power Doppler Sonography With the HDlive Silhouette Mode in Antenatal Diagnosis of a Right Aortic Arch With an Aberrant Left Subclavian Artery

Aortic arch anomalies develop as a result of abnormal regression of one of the pharyngeal arches, resulting in abnormalities in the aortic arch position or branching pattern.1 They may present alone or associated with other congenital heart defects. The most common type is the right aortic arch (RAA), with an estimated incidence of approximately 0.1%.2 An association of a right aortic arch with 22q11 microdeletion has been reported.1,3 There have been numerous reports on the antenatal diagnosis of a right aortic arch with an aberrant left subclavian artery using 2dimensional (2D) echocardiography, 2D color Doppler sonography, and 3-dimensional (3D) power Doppler sonography.1,2,4–6 However, to the best of our knowledge, the use of 4-dimensional (4D) power Doppler sonography with the HDlive silhouette mode (GE Healthcare Japan, Tokyo, Japan) for the antenatal diagnosis of a right aortic arch with an aberrant left subclavian artery has not been reported previously. A 37-year-old primigravida was referred to our ultrasound clinic at 29 weeks’ gestation because of a suspected right-sided descending arch. Two-dimensional sonography (Voluson E8; GE Healthcare Japan) showed a single living fetus with biometric measurements consistent with gestational age. Two-dimensional fetal echocardiography showed an abnormal 3-vessel and trachea view, and the aortic arch was present on the right side of the trachea, with the ductus arteriosus on the left side of the trachea, connected by a vascular segment behind the trachea (diverticulum of Kommerell). An aberrant left subclavian artery originating from the diverticulum of Kommerell was suspected. There was no other fetal abnormality. At 34 weeks, 2D power Doppler sonography with a 3vessel and trachea view (Voluson E10) showed the pulmonary artery, right aortic arch, superior vena cava, and a vascular ring around the trachea. Also, the azygos vein and right pulmonary vessels were visualized (Figure 1A). Fourdimensional power Doppler sonography with the HDlive silhouette mode clearly showed the vascular ring around the trachea at the level of the upper mediastinum in addition to the spatial 3-vessel view (Figure 1B and Video 1). The descending aorta was noted on the right anterior side of the spine. An aberrant left subclavian artery originating from the diverticulum of Kommerell was clearly identified (Figure 1C and Video 2). A diagnosis of a right aortic arch with an aberrant left subclavian artery was made. At 41 weeks’ gestation, a cesarean delivery was performed because of rupture of membranes while the head was unengaged, resulting in a male neonate weighing 4054 g with a height of 51 cm. The Apgar scores were 8 at 1 minute and 9 at 5 minutes, and the umbilical artery pH was 7.301. Neonatal echocardiography confirmed the diagnosis of a right aortic arch with an aberrant left subclavian artery. The diagnosis of aortic arch anomalies is a challenging task for obstetricians. The axial view of the upper mediastinum (namely, 3-vessel and trachea view) is an approach to evaluating the aortic arch by visualizing the V-shaped configuration formed by the junction of the aortic and ductal arches, with the trachea present posteriorly under normal conditions.2 However, detailed and precise detection of the branching pattern is mandatory to differentiate a right aortic arch from other aortic arch anomalies.7 Aortic arch anomalies have also been reported to be closely associated with genetic disorders and multiple congenital cardiac anomalies; therefore, accurate identification of the anatomic changes is needed for improved postnatal management. In this case, 2D echocardiography showed the loss of the V-shaped confluence of the 3-vessel and trachea view. Two-dimensional power Doppler sonography was beneficial, as it showed the vascular ring around the trachea formed by the ductus arteriosus, descending aorta, diverticulum of Kommerell, and right aortic arch. Fourdimensional power Doppler sonography with the HDlive silhouette mode facilitated a spatial 3-vessel view, which showed the relationship and size comparison among them. Therefore, 3D reconstruction of a typical vascular ring was clearly shown. Moreover, an aberrant left subclavian artery was clearly shown, as well as the azygos vein and right pulmonary vessels. The key point is that the relationship of these vessels with the spine could be understood because the spine can be seen by using the HDlive silhouette mode. The descending aorta was noted on the right anterior side of the spine. This finding is another important diagnostic clue in cases of a right aortic arch,1 which cannot be obtained with conventional 3D power Doppler sonography. Therefore, accurate localization and description of the branching patterns of great arteries and an improved understanding of the spatial relationship are easily possible. Fourdimensional power Doppler sonography with the HDlive silhouette mode combines the advantages of a spatial view of great vessels in addition to visualization of the spine as a landmark. Its use may provide potential advantages in the

Relationship between early changes in cerebral blood volume and electrocortical activity after hypoxic–ischemic insult in newborn piglets

BACKGROUND Early changes in cerebral hemodynamics and depressed electrocortical activity have been reported after a hypoxic-ischemic (HI) insult. However, the relationship between these two parameters is unclear. This study aimed to examine the relationship between changes in cerebral blood volume (CBV) and cerebral Hb oxygen saturation (ScO2) after a HI insult and the low amplitude-integrated electroencephalography (aEEG) duration concomitantly observed. METHODS Sixteen newborn piglets obtained within 24h of birth were used (n=3 controls). Thirteen piglets were subjected to a HI insult of 20-min low-amplitude aEEG (<5 μV, LAEEG), after which a low mean arterial blood pressure (<70% of baseline) was maintained for 10 min. We measured changes in CBV and ScO2 using near-infrared time-resolved spectroscopy (TRS) and cerebral electrocortical activities using aEEG until 6h after the insult. RESULTS A positive correlation was observed between the LAEEG duration and CBV increase, but not ScO2, after the insult. CONCLUSION These results suggest that a larger increase in CBV reflected a more severe failure in cerebral circulation to maintain cell membrane action potentials, which induced a more extended recovery period of electrocortical activity after the insult. We conclude that an early increase in CBV and longer LAEEG indicate severe brain injury.

Extrauterine environment influences spontaneous low-frequency oscillations in the preterm brain

Low-frequency oscillations in cerebral blood flow that are suggestive of resting-state brain activity have recently been reported, but no study on the development of resting-state brain activity in preterm infants has been performed. The objective of this study was to measure the cerebral blood flow oscillations, which are assumed to represent brain function in the resting state, in preterm and term infants of the same postconceptional age. The subjects were 9 preterm infants who had reached full term (gestational age (GA): 23-34 weeks, postconceptional age: 37-46 weeks) and 10 term infants (GA: 37-40 weeks, postconceptional age: 37-41 weeks). Their changes in concentration of oxyhemoglobin ([oxyHb]) and deoxyhemoglobin ([deoxyHb]) were measured in the parieto-temporal region during quiet sleep using multi-channel near-infrared spectroscopy, and the power spectral densities (PSD) of the oscillations in the concentrations of these molecules were analyzed and compared. The preterm infants displayed a higher proportion of 0.06-0.10 Hz low frequency oscillations of [oxyHb] and [deoxyHb] than the term infants, and the gestational age and the proportion of low frequency oscillations were inversely correlated. These findings suggest that resting-state cerebral blood flow oscillations differ between preterm and term infants, and that the development of circulatory regulation and nerve activity in preterm infants are influenced by the extrauterine environment.

Influence of bilirubin photoisomers on unbound bilirubin measurement in clinical settings

Background Measured unbound bilirubin concentration is influenced by bilirubin photoisomers. Bilirubin photoisomers are produced even with only a slight light exposure, and clinical samples are inevitably exposed to light. The objective of the study was to evaluate the influence of bilirubin photoisomers on the measurement of unbound bilirubin using serum of jaundiced neonates during blue light phototherapy. Methods Five neonates treated with phototherapy for hyperbilirubinaemia were enrolled. The samples were taken 12 h after initiation of phototherapy. Samples were processed by irradiation with blue light, by indoor ceiling light, by both blue light and indoor ceiling light or shaded. Bilirubin subfractions, total bilirubin and unbound bilirubin were measured. Results Compared with the non-irradiated samples, the (EZ)-cyclobilirubin concentration and (ZE)-bilirubin/(ZZ)-bilirubin ratio significantly increased in the blue light-irradiated samples, the (ZE)-bilirubin/(ZZ)-bilirubin ratio significantly increased in the indoor ceiling light-irradiated samples, and the (EZ)-cyclobilirubin, (EZ)-bilirubin and (ZE)-bilirubin/(ZZ)-bilirubin ratio significantly increased in the samples irradiated with both lights. No change was noted in unbound bilirubin in any group. Conclusions We consider that changes in bilirubin photoisomers induced by light exposure during clinical practice do not influence the measured unbound bilirubin concentration.

Cerebral blood volume measurement using near-infrared time-resolved spectroscopy and histopathological evaluation after hypoxic-ischemic insult in newborn piglets

The aim of this study was to assess the relationship between the cerebral blood volume (CBV) measured by near‐infrared time‐resolved spectroscopy (TRS) and pathological change of the brain in a hypoxic‐ischemic (HI) piglet model.