Changes in Brain Tissue Oxygenation and Metabolism During Rewarming After Neonatal Encephalopathy are Related to Electrical Abnormality.

Hypoxic ischemic encephalopathy (HIE) leads to significant mortality and morbidity, and therapeutic hypothermia (TH) has become a standard of care following HIE. After TH, the body temperature is brought back to 37 °C. Early electroencephalography (EEG) is a reliable outcome biomarker following HIE. We hypothesized that changes in cerebral oxidative metabolism, measured as Δ[oxCCO], in relation to changes in brain tissue oxygenation (measured as Δ[HbD]) during rewarming will correlate with injury severity as evidenced on amplitude integrated EEG/EEG at initial presentation. Broadband near-infrared spectroscopy (NIRS) and systemic data were collected during rewarming from 14 infants following HIE over a mean period of 12.5 h. All infants were monitored with video EEG telemetry using a standard neonatal montage. aEEG and EEG background was classified into mild, moderate and severely abnormal groups based on the background pattern. Two infants had mild, 6 infants had moderate and another 6 infants had severe abnormality at presentation. The relationship between [oxCCO] and [HbD] was evaluated between two groups of infants with abnormal electrical activity (mild vs moderate to severe). A significant difference was noted between the groups in the relationship between [oxCCO] and [HbD] (as r2) (p = 0.02). This result indicates that the mitochondrial injury and deranged oxidative metabolism persists in the moderate to severely abnormal group during rewarming.

Correction to: Improvements in Skeletal Muscle Can Be Detected Using Broadband NIRS in First-Time Marathon Runners.

This chapter was inadvertently published as an open access chapter. However, the open access for this chapter has now been reverted.

Near-Infrared Spectroscopy Measured Cerebral Blood Flow from Spontaneous Oxygenation Changes in Neonatal Brain Injury.

Neonates with hypoxic-ischaemic (HI) brain injury were monitored using a broadband near-infrared spectroscopy (NIRS) system in the neonatal intensive care unit. The aim of this work is to use the NIRS cerebral oxygenation data (HbD = oxygenated-haemoglobin - deoxygenated-haemoglobin) combined with arterial saturation (SaO2) from pulse oximetry to calculate cerebral blood flow (CBF) based on the oxygen swing method, during spontaneous desaturation episodes. The method is based on Fick's principle and uses HbD as a tracer; when a sudden change in SaO2 occurs, the change in HbD represents a change in tracer concentration, and thus it is possible to estimate CBF. CBF was successfully calculated with broadband NIRS in 11 HIE infants (3 with severe injury) for 70 oxygenation events on the day of birth. The average CBF was 18.0 ± 12.7 ml 100 g-1 min-1 with a range of 4 ml 100 g-1 min-1 to 60 ml 100 g-1 min-1. For infants with severe HIE (as determined by magnetic resonance spectroscopy) CBF was significantly lower (p = 0.038, d = 1.35) than those with moderate HIE on the day of birth.

Improvements in Skeletal Muscle Can Be Detected Using Broadband NIRS in First-Time Marathon Runners.

Skeletal muscle metabolic function is known to respond positively to endurance exercise interventions, such as marathon training. Studies investigating skeletal muscle have typically used muscle biopsy samples or magnetic resonance spectroscopy (MRS) to interrogate metabolic function. We aimed to non-invasively detect exercise-training-induced improvements in muscle function using broadband near-infrared spectroscopy (NIRS). We used NIRS to determine concentration changes in oxygenated haemoglobin (HbO2) and the oxidation state of cytochrome-c-oxidase (oxCCO) in gastrocnemius during arterial occlusion in 14 volunteers. We also used a cardio-pulmonary exercise test (CPET) to assess peak total body oxygen uptake (peakVO2; a measure of fitness). Measurements were made at baseline (BL) which was prior to a period of at least 16 weeks of training for the 2017 London Marathon, and then within 3 weeks after completion of the marathon, follow-up (FU). We observed an increase in locally measured muscle oxygen consumption and rate of oxCCO concentration change, but not in cardio-respiratory fitness measured as whole-body peak oxygen consumption (peakVO2).

ABroAD: A Machine Learning Based Approach to Detect Broadband NIRS Artefacts.

Artefacts are a common and unwanted aspect of any measurement process, especially in a clinical environment, with multiple causes such as environmental changes or motion. In near-infrared spectroscopy (NIRS), there are several existing methods that can be used to identify and remove artefacts to improve the quality of collected data.We have developed a novel Automatic Broadband Artefact Detection (ABroAD) process, using machine learning methods alongside broadband NIRS data to detect common measurement artefacts using the broadband intensity spectrum. Data were collected from eight subjects, using a broadband NIRS monitoring over the frontal lobe with two sensors. Six different artificial artefacts - vertical head movement, horizontal head movement, frowning, pressure, ambient light, torch light - were simulated using movement and light changes on eight subjects in a block test design. It was possible to identify both light artefacts to a good degree, as well as pressure artefacts. This is promising and, by expanding this work to larger datasets, it may be possible to create and train a machine learning pipeline to automate the detection of various artefacts, making the analysis of collected data more reliable.

Functional NIRS Measurement of Cytochrome-C-Oxidase Demonstrates a More Brain-Specific Marker of Frontal Lobe Activation Compared to the Haemoglobins.

Functional near-infrared spectroscopy (fNIRS) is an increasingly common neuromonitoring technique used to observe evoked haemodynamic changes in the brain in response to a stimulus. The measurement is typically in terms of concentration changes of oxy- (∆HbO2) and deoxy- (∆HHb) haemoglobin. However, noise from systemic fluctuations in the concentration of these chromophores can contaminate stimulus-evoked haemodynamic responses, leading to misinterpretation of results. Short-separation channels can be used to regress out extracerebral haemodynamics to better reveal cerebral changes, significantly improving the reliability of fNIRS. Broadband NIRS can be used to additionally monitor concentration changes of the oxidation state of cytochrome-c-oxidase (∆oxCCO). Recent studies have shown ∆oxCCO to be a depth-dependent and hence brain-specific signal. This study aims to investigate whether ∆oxCCO can produce a more robust marker of functional activation. Continuous frontal lobe NIRS measurements were collected from 17 healthy adult volunteers. Short 1 cm source-detector separation channels were regressed from longer separation channels in order to minimise the extracerebral contribution to standard fNIRS channels. Significant changes in ∆HbO2 and ∆HHb were seen at 1 cm channels but were not observed in ∆oxCCO. An improvement in the haemodynamic signals was achieved with regression of the 1 cm channel. Broadband NIRS-measured concentration changes of the oxidation state of cytochrome-c-oxidase has the potential to be an alternative and more brain-specific marker of functional activation.

Interrelationship Between Broadband NIRS Measurements of Cerebral Cytochrome C Oxidase and Systemic Changes Indicates Injury Severity in Neonatal Encephalopathy.

Perinatal hypoxic ischaemic encephalopathy (HIE) is associated with severe neurodevelopmental problems and mortality. There is a clinical need for techniques to provide cotside assessment of the injury extent. This study aims to use non-invasive cerebral broadband near-infrared spectroscopy (NIRS) in combination with systemic physiology to assess the severity of HIE injury. Broadband NIRS is used to measure the changes in haemodynamics, oxygenation and the oxidation state of cytochrome c oxidase (oxCCO). We used canonical correlation analysis (CCA), a multivariate statistical technique, to measure the relationship between cerebral broadband NIRS measurements and systemic physiology. A strong relationship between the metabolic marker, oxCCO, and systemic changes indicated severe brain injury; if more than 60 % of the oxCCO signal could be explained by the systemic variations, then the neurodevelopmental outcome was poor. This boundary has high sensitivity and specificity (100 and 83 %, respectively). Broadband NIRS measured concentration changes of the oxidation state of cytochrome c oxidase has the potential to become a useful cotside tool for assessment of injury severity following hypoxic ischaemic brain injury.

Broadband-NIRS System Identifies Epileptic Focus in a Child with Focal Cortical Dysplasia-A Case Study.

Epileptic seizures are transiently occurring symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Previous functional near-infrared spectroscopy (fNIRS) studies during seizures have focused in only monitoring the brain oxygenation and haemodynamic changes. However, few tools are available to measure actual cellular metabolism during seizures, especially at the bedside. Here we use an in-house developed multichannel broadband NIRS (or bNIRS) system, that, alongside the changes in oxy-, deoxy- haemoglobin concentration (HbO2, HHb), also quantifies the changes in oxidised cytochrome-c-oxidase Δ(oxCCO), a marker of cellular oxygen metabolism, simultaneously over 16 different brain locations. We used bNIRS to measure metabolic activity alongside brain tissue haemodynamics/oxygenation during 17 epileptic seizures at the bedside of a 3-year-old girl with seizures due to an extensive malformation of cortical development in the left posterior quadrant. Simultaneously Video-EEG data was recorded from 12 channels. Whilst we did observe the expected increase in brain tissue oxygenation (HbD) during seizures, it was almost diminished in the area of the focal cortical dysplasia. Furthermore, in the area of seizure origination (epileptic focus) ΔoxCCO decreased significantly at the time of seizure generalization when compared to the mean change in all other channels. We hypothesize that this indicates an incapacity to sustain and increase brain tissue metabolism during seizures in the region of the epileptic focus.

Oxygen dependency of mitochondrial metabolism indicates outcome of newborn brain injury.

There is a need for a method of real-time assessment of brain metabolism during neonatal hypoxic-ischaemic encephalopathy (HIE). We have used broadband near-infrared spectroscopy (NIRS) to monitor cerebral oxygenation and metabolic changes in 50 neonates with HIE undergoing therapeutic hypothermia treatment. In 24 neonates, 54 episodes of spontaneous decreases in peripheral oxygen saturation (desaturations) were recorded between 6 and 81 h after birth. We observed differences in the cerebral metabolic responses to these episodes that were related to the predicted outcome of the injury, as determined by subsequent magnetic resonance spectroscopy derived lactate/N-acetyl-aspartate. We demonstrated that a strong relationship between cerebral metabolism (broadband NIRS-measured cytochrome-c-oxidase (CCO)) and cerebral oxygenation was associated with unfavourable outcome; this is likely to be due to a lower cerebral metabolic rate and mitochondrial dysfunction in severe encephalopathy. Specifically, a decrease in the brain tissue oxidation state of CCO greater than 0.06 µM per 1 µM brain haemoglobin oxygenation drop was able to predict the outcome with 64% sensitivity and 79% specificity (receiver operating characteristic area under the curve = 0.73). With further work on the implementation of this methodology, broadband NIRS has the potential to provide an early, cotside, non-invasive, clinically relevant metabolic marker of perinatal hypoxic-ischaemic injury.

Investigation of the Pattern of the Hemodynamic Response as Measured by Functional Near-Infrared Spectroscopy (fNIRS) Studies in Newborns, Less Than a Month Old: A Systematic Review.

It has been 20 years since functional near-infrared spectroscopy (fNIRS) was first used to investigate the evoked hemodynamic response to a stimulus in newborns. The hemodynamic response to functional activation is well-established in adults, with an observed increase in concentration change of oxygenated hemoglobin (Δ[HbO2]) and decrease in deoxygenated hemoglobin (Δ[HHb]). However, functional studies in newborns have revealed a mixed response, particularly with Δ[HHb] where an inconsistent change in direction is observed. The reason for this heterogeneity is unknown, with potential explanations arising from differing physiology in the developing brain, or differences in instrumentation or methodology. The aim of this review is to collate the findings from studies that have employed fNIRS to monitor cerebral hemodynamics in term newborn infants aged 1 day-1 month. A total of 46 eligible studies were identified; some studies investigated more than one stimulus type, resulting in a total of 51 reported results. The NIRS parameters reported varied across studies with 50/51 cases reporting Δ[HbO2], 39/51 reporting Δ[HHb], and 13/51 reporting total hemoglobin concentration Δ[HbT] (Δ[HbO2] + Δ[HHb]). However, of the 39 cases reporting Δ[HHb] in graphs or tables, only 24 studies explicitly discussed the response (i.e., direction of change) of this variable. In the studies where the fNIRS responses were discussed, 46/51 cases observed an increase in Δ[HbO2], 7/51 observed an increase or varied Δ[HHb], and 2/51 reported a varied or negative Δ[HbT]. An increase in Δ[HbO2] and decrease or no change in Δ[HHb] was observed in 15 studies. By reviewing this body of literature, we have identified that the majority of research articles reported an increase in Δ[HbO2] across various functional tasks and did not report the response of Δ[HHb]. Confirming the normal, healthy hemodynamic response in newborns will allow identification of unhealthy patterns and their association to normal neurodevelopment.