Congle Zhou

Research on the relationship between brain anoxia at different regional oxygen saturations and brain damage using near-infrared spectroscopy

The objective of this paper is to investigate the difference in physiological parameters, EEG and morphology of brain tissues in newborn pigs with different regional oxygen saturations of brain (rSO(2)) and provide a basis for the determination of brain injury and degree of injury with the rSO(2) in clinical practice. A noninvasive near-infrared spectroscopy (NIRS) technique was used to monitor the rSO(2) of 27 newborn pigs. After mechanical ventilation and inhalation of 3-11% oxygen for 30 min by the newborn pigs, the pigs were grouped according to the rSO(2) in the brain caused by inhalation of different concentrations of oxygen. There were six animals each in rSO(2) < 30%, 30-35%, 35-40%, 40-50% groups and three animals in the rSO(2) > 60% group (normal control). The physiological parameters and the EEG were monitored during the experiment. The animals were sacrificed by decollation at 72 hours after brain injury, and light microscope examination and pathological analysis of the ultrastructure were conducted on the brain tissues in the CA1 zone of hippocampi. In rSO(2) > 40% groups, the mean arterial pressure (MAP) was stable and there were no significant changes in blood lactic acid, amplitudes of the EEG, light microscopic findings and ultrastructure after hypoxia. When the rSO(2) was between 30% and 40%, the MAP was stable, the level of blood lactic acid increased, metabolic acidosis occurred, there was no significant change in the amplitudes of the EEG, there were ischemic changes in brain tissues under a light microscope and there was an injury of mitochondria in the neurons in the CA1 zone of hippocampi. When the rSO(2) was less than 30%, circulatory failure occurred, the level of blood lactic acid increased, there was serious metabolic acidosis, the amplitudes of the EEG significantly decreased, there were vacuolization and broken fragments of cells under the light microscope and the mitochondria in the neurons in the CA1 zone of hippocampi were seriously injured. Under varying degrees of hypoxia, when the rSO(2) is between 30% and 40%, brain injury occurs and the functional zones of mitochondria are injured in newborn pigs. When the rSO(2) is less than 30%, the brain functions are seriously abnormal, and the serious morphological impairment in the functional zones of mitochondria is the basis for the disturbance of energy metabolism in brain neurocytes after hypoxia and the sequelae of the nervous system.

Reference Values for Amplitude-Integrated EEGs in Infants From Preterm to 3.5 Months of Age

OBJECTIVES: Amplitude-integrated electroencephalogram (aEEG) is a valuable tool for the continuous evaluation of functional brain maturation in infants. The amplitudes of the upper and lower margins of aEEGs are postulated to change with maturation and correlate with postmenstrual age (PMA). In this study we aimed to establish reliable reference values of aEEG amplitudes, which provide quantitative guidelines for assessing brain maturation as indicated by aEEG results in neonates and young infants. METHODS: aEEGs from healthy infants (n = 274) with PMAs that ranged from 30 to 55 weeks were divided into 10 groups according to their PMAs. Two 5-minute segments were selected from each aEEG and were used to automatically calculate the upper and lower margins and bandwidths of the aEEG tracings. RESULTS: Interobserver agreement was achieved with an overall correlation of 0.99. The upper and lower margins of the aEEGs in both active and quiet sleep clearly rose in infants after the neonatal period. The bandwidth defined as the graphic distance decreased almost monotonically throughout the PMA range from 30 to 55 weeks. The lower margin of the aEEG was positively correlated with PMA, with a larger rank correlation coefficient during quiet sleep (r = 0.89) than during active sleep (r = 0.49). CONCLUSIONS: Reference values of aEEG amplitudes were obtained for infants with a wide range of PMAs and constituted the basis for the quantitative assessment of aEEG changes with maturation in neonates and young infants. The normative amplitudes of aEEG margins, especially of the lower margin in quiet sleep, are recommended as a source of reference data for the identification of potentially abnormal aEEG results.

Assessment of the hypoxic-ischemic encephalopathy in neonates using non-invasive near-infrared spectroscopy

This paper introduces a method of monitoring cerebral oxygenation for healthy neonates and neonates with hypoxic-ischemic encephalopathy (HIE) using near-infrared spectroscopy. The object of this study was to investigate whether or not there were differences between the HIE group and the healthy group in terms of NIRS parameters. The subjects were all term neonates, their age ranging from 2 to 18 days. The healthy group included 25 subjects while the HIE group consisted of 16 patients. A prototype NIRS instrument, which provides the data of tissue oxygenation including regional oxygen saturation (rSO2), the increment of oxyhemoglobin concentration and hemoglobin (deltaHbO2 and deltaHb) was used, and the data of rSO2 was compared with the data from the blood gas analyzer. The result shows that: (1) the mean+/-SD of rSO2 for the healthy group was 62 +/- 4% in the frontal region under the quiet sleep condition, but the mean+/-SD of rSO2 for the HIE group was 53 +/- 3%. (2) As all subjects inhaled pure oxygen in 21 min(-1) for a period of 60 s, rSO2 for the healthy group increased rapidly, with the increase in rSO2 (deltarSO2) being 7 +/- 2.3%, but the increase in rSO2 for the HIE neonates was 3 +/- 1.5%. After inhaling oxygen, deltaHbO2 and deltaHb between the two groups were also significantly different. (3) During all the experiments SpO2 was monitored, the value of SpO2 was not significantly different between the two groups. The above observations suggest that the rSO2 in quiet condition and the values of change of rSO2, HbO2 and Hb during the inhalation of oxygen may be used as the parameters to discover and assess the HIE infants.

Neurodevelopment in newborns: a sample entropy analysis of electroencephalogram.

The present paper investigates the neural ontogeny of newborns in view of electroencephalogram (EEG) complexity during active sleep (AS) and quiet sleep (QS). Sample entropy (SampEn) is applied to EEG recordings from 168 newborns with postmenstrual age (PMA) ranging from 25 to 60 weeks. The relationship between neurodevelopment and PMA is then explored according to the statistical analysis of the median and interquartile range of SampEn curves. It is found that SampEn of EEG during AS is higher than that during QS. SampEn increases during both AS and QS before about 42 weeks in PMA while it ceases its increase in QS and even decreases in AS after newborns reaching term age. A distinct decrease in the interquartile range of SampEn is found with increasing PMA (from 25 to about 50 weeks), followed by maintenance of low fluctuation in SampEn curves. The study in this paper sets the stage for exhaustive investigation of the SampEn of EEG during brain maturation in newborns. And it could be hoped that SampEn in sleep EEG might be a useful parameter against which delays and aberrations in brain maturation might be tested. The SampEn changes during brain maturation also offer functional clues about neurodevelopment, based on which further explorations could be done. The significance of this paper is the discovery of the decrease in EEG complexity after newborns reaching term. Although some potential neurophysiologic reasons are given, this new discovery might require more study to investigate. In addition, the fluctuation of EEG complexity is analyzed for the first time, which helps to understand the EEG maturation in neurodevelopment.

The utility of amplitude-integrated EEG and NIRS measurements as indices of hypoxic ischaemia in the newborn pig

OBJECTIVE The early detection and stratification of potential hypoxic ischaemia (HI) injury in neonates are crucial for reducing the risk of neural disability. This study investigates early changes in brain function caused by acute HI of varying severities in the neonatal pig. METHODS Two non-invasive techniques, amplitude-integrated electroencephalogram (aEEG) and near-infrared spectroscopy (NIRS), were used to monitor electrocortical and cerebral haemodynamic function, respectively. The fraction of inspired oxygen (FiO(2)) was varied to produce different HI severities. The sensitivity and HI correlation of these methods were systematically analysed to assess their abilities to both detect injury early and assess HI severity accurately. RESULTS The tissue oxygen index measured via NIRS detected acute changes in cerebral oxygenation and was highly sensitive to HI (sensitivity=0.97), whereas aEEG was comparatively insensitive to HI. On the other hand, aEEG measurements correlated well with FiO(2) during the entire HI event as well as the 3-h recovery period (R=0.43-0.61). NIRS measurements did not correlate well with FiO(2). CONCLUSIONS Parameters measured via aEEG and NIRS displayed different time profiles during and following the HI event. SIGNIFICANCE These results highlight the potential advantage of using aEEG and NIRS in conjunction to monitor neonatal brain function, and provide an objective and rigorous method for the characterisation of cerebral function both during and following HI insults.

The Prognostic Value of Amplitude-Integrated EEG in Full-Term Neonates with Seizures

Neonatal seizures pose a high risk for adverse outcome in survived infants. While the prognostic value of amplitude-integrated electroencephalogram (aEEG) is well established in neonates with encephalopathy and asphyxia, neonatal seizure studies focusing on the direct correlation between early aEEG measurement and subsequent neurologic outcome are scarce. In this study, the prognostic value of aEEG features was systematically analyzed in 143 full-term neonates to identify prognostic indicators of neurodevelopmental outcome. Neonatal aEEG features of background pattern, cyclicity, and seizure activity, as well as the etiology of neonatal seizures, were significantly associated with neurodevelopmental outcome at one year of age. aEEG background pattern was highly associated with neurologic outcomes (χ2 = 116.9), followed by aEEG cyclicity (χ2 = 87.2) and seizure etiology (χ2 = 79.3). Multiple linear regression showed that the four predictors explained 71.2% of the variation in neurological outcome, with standardized β coefficients of 0.44, 0.24, 0.22, and 0.14 for the predictors of aEEG background pattern, cyclicity, etiology, and aEEG seizure activity, respectively. This clinically applicable scoring system based on etiology and three aEEG indices would allow pediatricians to assess the risk for neurodevelopmental impairment and facilitate an early intervention in newborns developing seizures.

NIRS study of cerebral oxygenation and hemodynamics in neonate at birth

To study the changes of cerebral oxygenation and hemodynamics in normal neonates at 2–5 min post-birth and understand the effects of pregnancy-induced hypertension (PIH) upon cerebral oxygenation and hemodynamics in newborn neonates. The near infrared spectroscopy (NIRS) was employed to measure the absolute quantity of brain tissue oxygen saturation (rSO2) in newborn neonates and the changes of concentrations of deoxyhemoglobin (Hb) and oxygenation hemoglobin (HbO2) with time relative to initial values to further obtain the changes of total hemoglobin (tHb) and cerebral perfusion (denoted by HbD). In normal neonates at 2–5 min post-birth, rSO2 increased while tHb remained relatively stable and HbD increased. In neonates born of PIH mothers at 3–5 min post-birth, the changes of tHb were markedly higher than those in the normal infants, p<0.05; at 2–5 min post-birth, the changes were markedly lower than the normal term infants. We concluded that NIRS can detect the changes of cerebral oxygenation and blood flow in a non-invasive and effective way.

Burst Suppression EEG in Neonatal Convulsions

Convulsions represent a characteristic signal of neurological disease in the newborn period. Single-channel EEG is a convenient tool for continuous evaluation of neonatal convulsions and gives valuable prognostic information on neurological recovery. Among various abnormal EEG waveforms during convulsions, burst suppression (BS) pattern is distinctive and usually indicates an urgent state that therapeutic interventions should be performed appropriately and instantly. Four temporal variables (i.e. burst suppression ratio, burst frequency, burst amplitude, and suppression amplitude) were selected as BS features in this paper to describe the convulsive EEG signals from 47 full term neonates. Subjects were divided into mild convulsive group (22 neonates) and serious convulsive group (25 neonates) according to their standard clinical diagnoses. Wilcoxon rank sum test shows that both the burst suppression ratio and burst amplitude are significantly different between mild and serious groups (p << 0.01) while burst frequency and suppression amplitude exhibit similar values in two groups (p = 0.76 and p = 0.46). According to linear discriminant analysis, nearest neighbor rule (NNR) is used to perform pattern classification in the plane supported by the first two discriminant BS features (i.e. burst suppression ratio and burst amplitude). The leave-one-out recognition rate of NNR is 0.96. Results in the present paper indicate that burst suppression ratio and burst amplitude are effective discriminant BS features which help to guarantee a rigorous evaluation of neonatal convulsions.

Clinical Manifestations and Amplitude-integrated Encephalogram in Neonates with Early-onset Epileptic Encephalopathy

Background: The patients with early-onset epileptic encephalopathy (EOEE) suffer from neurodevelopmental delay. The aim of this study was to analyze the clinical manifestations and amplitude-integrated encephalogram (aEEG) characteristics of infants with EOEE with onset within the neonatal period, to make early diagnosis to improve the prognosis. Methods: One-hundred and twenty-eight patients with neonatal seizure were enrolled and followed up till 1 year old. Sixty-six neonates evolved into EOEE were as the EOEE group, the other 62 were as the non-EOEE (nEOEE) group. Then we compared the clinical and aEEG characteristics between the two groups to analyze the manifestations in neonates with EOEE. Results: Compared to the nEOEE group, the incidence of daily seizure attacks, more than two types of convulsions, more than two antiepileptic drugs (AEDs) application, severely abnormal aEEG background, absence of cyclicity, and more than two seizures detection were significantly higher in the EOEE group (P < 0.05) (97% vs. 54.8%; 30.3% vs. 14.5%; 97.0% vs. 25.4%; 39.4% vs. 3.2%; 57.6% vs. 9.7%; and 56% vs. 3.2%, respectively). Severely abnormal background pattern (odds ratio [OR] = 0.081, 95% confidence interval [CI]: 0.009–0.729, P = 0.025) and more than two seizures detection by aEEG (OR = 0.158, 95% CI: 0.043–0.576, P = 0.005) were the independent risk factors for the evolvement into EOEE. The upper and lower margins of active sleep (AS) and quiet sleep (QS) were significantly higher in EOEE group than those of the control group (P < 0.05) (34.3 ± 13.6 vs. 21.3 ± 6.4; 9.9 ± 3.7 vs. 6.7 ± 2.2; 41.2 ± 15.1 vs. 30.4 ± 11.4; and 11.9 ± 4.4 vs. 9.4 ± 4.0; unit: &mgr;V, respectively). AS upper margin was demonstrated a higher diagnostic specificity and sensitivity for EOEE than another three parameters according to the receiver operating characteristic curves; the area under the curve was 0.827. Conclusions: The clinical characteristics of the neonatal seizure which will evolve into EOEE were more than two AEDs application, high seizure frequency (daily attack), and more than two types of the seizure. Significant high voltage, severely abnormal background, absence of cyclicity, and more than two seizures detected on aEEG were the meaningful indicators to the prediction of EOEE.

Using noninvasive NIRS to evaluate the metabolic capability of infant brain

The value of cerebral oxygenation saturation is important for optimal treatment and prognosis in neonates during perinatal period. The purpose of this study was to investigate the cerebral oxygen in newborn infants and obtain clinical characteristic parameters by using steady state spatially resolved near infrared spectroscopy. The subjects consist of 239 infants selected from two hospital. The results show that the values of regional cerebral oxygen saturation (rSO2) for preterm infants with gestational ages of 27 - 32 weeks were different from term infants and the value of rSO2 for sick term infants after treatment were better than that of before treatment. Above results suggest that the value of rSO2 may be used as a clinical parameter to assess cerebral oxygen for preterm and sick infants avoiding hypoxia.