Simulation of Preterm Neonatal Brain Metabolism During Functional Neuronal Activation Using a Computational Model

We present a computational model of metabolism in the preterm neonatal brain. The model has the capacity to mimic haemodynamic and metabolic changes during functional activation and simulate functional near-infrared spectroscopy (fNIRS) data. As an initial test of the model's efficacy, we simulate data obtained from published studies investigating functional activity in preterm neonates. In addition we simulated recently collected data from preterm neonates during visual activation. The model is well able to predict the haemodynamic and metabolic changes from these observations. In particular, we found that changes in cerebral blood flow and blood pressure may account for the observed variability of the magnitude and sign of stimulus-evoked haemodynamic changes reported in preterm infants

Brain Cortical Mapping by Simultaneous Recording of Functional Near Infrared Spectroscopy and Electroencephalograms from the Whole Brain During Right Median Nerve Stimulation

To investigate relationships between hemodynamic responses and neural activities in the somatosensory cortices, hemodynamic responses by near infrared spectroscopy (NIRS) and electroencephalograms (EEGs) were recorded simultaneously while subjects received electrical stimulation in the right median nerve. The statistical significance of the hemodynamic responses was evaluated by a general linear model (GLM) with the boxcar design matrix convoluted with Gaussian function. The resulting NIRS and EEGs data were stereotaxically superimposed on the reconstructed brain of each subject. The NIRS data indicated that changes in oxy-hemoglobin concentration increased at the contralateral primary somatosensory (SI) area; responses then spread to the more posterior and ipsilateral somatosensory areas. The EEG data indicated that positive somatosensory evoked potentials peaking at 22 ms latency (P22) were recorded from the contralateral SI area. Comparison of these two sets of data indicated that the distance between the dipoles of P22 and NIRS channels with maximum hemodynamic responses was less than 10 mm, and that the two topographical maps of hemodynamic responses and current source density of P22 were significantly correlated. Furthermore, when onset of the boxcar function was delayed 5–15 s (onset delay), hemodynamic responses in the bilateral parietal association cortices posterior to the SI were more strongly correlated to electrical stimulation. This suggests that GLM analysis with onset delay could reveal the temporal ordering of neural activation in the hierarchical somatosensory pathway, consistent with the neurophysiological data. The present results suggest that simultaneous NIRS and EEG recording is useful for correlating hemodynamic responses to neural activity

Dual role of cerebral blood flow in regional brain temperature control in the healthy newborn infant.

Small shifts in brain temperature after hypoxia-ischaemia affect cell viability. The main determinants of brain temperature are cerebral metabolism, which contributes to local heat production, and brain perfusion, which removes heat. However, few studies have addressed the effect of cerebral metabolism and perfusion on regional brain temperature in human neonates because of the lack of non-invasive cot-side monitors. This study aimed (i) to determine non-invasive monitoring tools of cerebral metabolism and perfusion by combining near-infrared spectroscopy and echocardiography, and (ii) to investigate the dependence of brain temperature on cerebral metabolism and perfusion in unsedated newborn infants. Thirty-two healthy newborn infants were recruited. They were studied with cerebral near-infrared spectroscopy, echocardiography, and a zero-heat flux tissue thermometer. A surrogate of cerebral blood flow (CBF) was measured using superior vena cava flow adjusted for cerebral volume (rSVC flow). The tissue oxygenation index, fractional oxygen extraction (FOE), and the cerebral metabolic rate of oxygen relative to rSVC flow (CMRO2 index) were also estimated. A greater rSVC flow was positively associated with higher brain temperatures, particularly for superficial structures. The CMRO2 index and rSVC flow were positively coupled. However, brain temperature was independent of FOE and the CMRO2 index. A cooler ambient temperature was associated with a greater temperature gradient between the scalp surface and the body core. Cerebral oxygen metabolism and perfusion were monitored in newborn infants without using tracers. In these healthy newborn infants, cerebral perfusion and ambient temperature were significant independent variables of brain temperature. CBF has primarily been associated with heat removal from the brain. However, our results suggest that CBF is likely to deliver heat specifically to the superficial brain. Further studies are required to assess the effect of cerebral metabolism and perfusion on regional brain temperature in low-cardiac output conditions, fever, and with therapeutic hypothermia

Optical imaging in vivo with a focus on paediatric disease: technical progress, current preclinical and clinical applications and future perspectives

To obtain information on the occurrence and location of molecular events as well as to track target-specific probes such as antibodies or peptides, drugs or even cells non-invasively over time, optical imaging (OI) technologies are increasingly applied. Although OI strongly contributes to the advances made in preclinical research, it is so far, with the exception of optical coherence tomography (OCT), only very sparingly applied in clinical settings. Nevertheless, as OI technologies evolve and improve continuously and represent relatively inexpensive and harmful methods, their implementation as clinical tools for the assessment of children disease is increasing. This review focuses on the current preclinical and clinical applications as well as on the future potential of OI in the clinical routine. Herein, we summarize the development of different fluorescence and bioluminescence imaging techniques for microscopic and macroscopic visualization of microstructures and biological processes. In addition, we discuss advantages and limitations of optical probes with distinct mechanisms of target-detection as well as of different bioluminescent reporter systems. Particular attention has been given to the use of near-infrared (NIR) fluorescent probes enabling observation of molecular events in deeper tissue

Relación entre la actividad EEG y la oxigenación cerebral en recién nacidos prematuros

This study investigates the relationship between brain oxygenation, assessed by means of near infrared spectroscopy (NIRS), and brain function, assessed by means of electroencephalography (EEG). Using NIRS signals measuring the regional cerebral oxygen saturation (rScO2) and computing the fractional tissue oxygen extraction (FTOE), we compared how these variables relate to different features extracted from the EEG, such as the inter-burst interval (IBI) duration and amplitude, the amplitude of the EEG, and the amplitude of the burst. A cohort of 22 neonates undergoing sedation by propofol was studied and a regression of the NIRS-derived values to the different EEG features was made. We found that higher values of FTOE were related to higher values of EEG amplitude. These results might be of used in the monitoring of proper brain function in neonates

Relation between EEG activity and brain oxygenation in preterm neonates

This study investigates the relationship between brain oxygenation, assessed by means of near infrared spectroscopy (NIRS), and brain function, assessed by means of electroencephalography (EEG). Using NIRS signals measuring the regional cerebral oxygen saturation (rScO2) and computing the fractional tissue oxygen extraction (FTOE), we compared how these variables relate to different features extracted from the EEG, such as the inter-burst interval (IBI) duration and amplitude, the amplitude of the EEG, and the amplitude of the burst. A cohort of 22 neonates undergoing sedation by propofol was studied and a regression of the NIRS-derived values to the different EEG features was made. We found that higher values of FTOE were related to higher values of EEG amplitude. These results might be of used in the monitoring of proper brain function in neonates.status: publishe

The confounding effect of systemic physiology on the hemodynamic response in newborns

During neural activity, increases in glucose and oxygen consumption and release of vasoactive neurotransmitters cause a local increase in cerebral blood fl ow (CBF) [1] and cerebral blood volume (CBV). Increases in oxygen consumption are signifi-cantly lower than increases in CBF and as a result we see a net increase in the amount of oxygen in the blood and tissue [2]. Typical measures of neural activity in adults with near-infrared spectroscopy (NIRS) show a local increase in oxy-hemoglobin concentration (HbO) and a decrease in deoxy-hemoglobin concentration (HbR), which corresponds to a local increase in BOLD signal measured with fMRI. In many neonatal functional studies inversions of these hemoglobin signals have been reported, across visual [3, 4], olfactory [5], sensory-motor [6] and auditory [7] cortices. In general, the inversion starts at a few weeks of age. The reason for such an inversion in the functional hemodynamic signals is not yet understood. We hypothesize that changes in hematocrit during the transition from fetal to adult hemoglobin and the consequent period of low hematocrit cause such an inversion. To test this hypothesis, we performed a longitudinal auditory functional study in premature infants

Effect of different assumptions for brain water content on absolute measures of cerebral oxygenation determined by frequency-domain near-infrared spectroscopy in preterm infants: an observational study

BACKGROUND Brain-water content (BWC) decreases with maturation of the brain and potentially affects parameters of cerebral oxygenation determined by near-infrared spectroscopy (NIRS). Most commercially available devices do not take these maturational changes into account. The aim of this study was to determine the effect of different assumptions for BWC on parameters of cerebral oxygenation in preterm infants. METHODS Concentrations of oxy-, deoxy- and total hemoglobin and regional cerebral oxygen saturation (rcStO2) were calculated based on absolute coefficients of absorption and scattering determined by multi-distance Frequency-Domain-NIRS assuming BWCs of 75-95%, which may be encountered in newborn infants depending on gestational and postnatal age. RESULTS This range of BWC gave rise to a linear modification of the assessed NIRS parameters with a maximum change of 10%. This may result in an absolute overestimation of rcStO2 by (median (range)) 4 (1-8)%, if the calculation is based on the lowest BWC (75%) in an extremely preterm infant with an anticipated BWC of 95%. CONCLUSION Clinicians wishing to rely on parameters of cerebral oxygenation determined by NIRS should consider that maturational changes in BWC not taken into account by most devices may result in a deviation of cerebral oxygenation readings by up to 8% from the correct value