Cerebral Near Infrared Spectroscopy Monitoring in Term Infants With Hypoxic Ischemic Encephalopathy—A Systematic Review

BACKGROUND: Neonatal hypoxic ischemic encephalopathy (HIE) remains a significant cause of mortality and morbidity worldwide. Cerebral near infrared spectroscopy (NIRS) can provide cot side continuous information about changes in brain hemodynamics, oxygenation and metabolism in real time. OBJECTIVE: To perform a systematic review of cerebral NIRS monitoring in term and near-term infants with HIE. SEARCH METHODS: A systematic search was performed in Ovid EMBASE and Medline database from inception to November 2019. The search combined three broad categories: measurement (NIRS monitoring), disease condition [hypoxic ischemic encephalopathy (HIE)] and subject category (newborn infants) using a stepwise approach as per PRISMA guidance. SELECTION CRITERIA: Only human studies published in English were included. DATA COLLECTION AND ANALYSIS: Two authors independently selected, assessed the quality, and extracted data from the studies for this review. RESULTS: Forty-seven studies on term and near-term infants following HIE were identified. Most studies measured multi-distance NIRS based cerebral tissue saturation using monitors that are referred to as cerebral oximeters. Thirty-nine studies were published since 2010; eight studies were published before this. Fifteen studies reviewed the neurodevelopmental outcome in relation to NIRS findings. No randomized study was identified. CONCLUSION: Commercial NIRS cerebral oximeters can provide important information regarding changes in cerebral oxygenation and hemodynamics following HIE and can be particularly helpful when used in combination with other neuromonitoring tools. Optical measurements of brain metabolism using broadband NIRS and cerebral blood flow using diffuse correlation spectroscopy add additional pathophysiological information. Further randomized clinical trials and large observational studies are necessary with proper study design to assess the utility of NIRS in predicting neurodevelopmental outcome and guiding therapeutic interventions

Relationship Between Cerebral Oxygenation and Metabolism During Rewarming in Newborn Infants After Therapeutic Hypothermia Following Hypoxic-Ischemic Brain Injury

Therapeutic hypothermia (TH) has become a standard of care following hypoxic ischemic encephalopathy (HIE). After TH, body temperature is brought back to 37 °C over 14 h. Lactate/N-acetylasperatate (Lac/NAA) peak area ratio on proton magnetic resonance spectroscopy ((1)H MRS) is the best available outcome biomarker following HIE. We hypothesized that broadband near infrared spectroscopy (NIRS) measured changes in the oxidation state of cytochrome-c-oxidase concentration (Δ[oxCCO]) and cerebral hemodynamics during rewarming would relate to Lac/NAA. Broadband NIRS and systemic data were collected during rewarming from 14 infants following HIE over a mean period of 12.5 h. (1)H MRS was performed on day 5-9. Heart rate increased by 20/min during rewarming while blood pressure and peripheral oxygen saturation (SpO2) remained stable. The relationship between mitochondrial metabolism and oxygenation (measured as Δ[oxCCO] and Δ[HbD], respectively) was calculated by linear regression analysis. This was reviewed in three groups: Lac/NAA values 1. Mean regression coefficient (r (2)) values in these groups were 0.41 (±0.27), 0.22 (±0.21) and 0.01, respectively. The relationship between mitochondrial metabolism and oxygenation became impaired with rising Lac/NAA. Cardiovascular parameters remained stable during rewarming

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

Changes in Cerebral Oxidative Metabolism during Neonatal Seizures Following Hypoxic-Ischemic Brain Injury.

Seizures are common following hypoxic-ischemic brain injury in newborn infants. Prolonged or recurrent seizures have been shown to exacerbate neuronal damage in the developing brain; however, the precise mechanism is not fully understood. Cytochrome-c-oxidase is responsible for more than 90% of ATP production inside mitochondria. Using a novel broadband near-infrared spectroscopy system, we measured the concentration changes in the oxidation state of cerebral cytochrome-c-oxidase (Δ[oxCCO]) and hemodynamics during recurrent neonatal seizures following hypoxic-ischemic encephalopathy in a newborn infant. A rapid increase in Δ[oxCCO] was noted at the onset of seizures along with a rise in the baseline of amplitude-integrated electroencephalogram. Cerebral oxygenation and cerebral blood volume fell just prior to the seizure onset but recovered rapidly during seizures. Δ[oxCCO] during seizures correlated with changes in mean electroencephalogram voltage indicating an increase in neuronal activation and energy demand. The progressive decline in the Δ[oxCCO] baseline during seizures suggests a progressive decrease of mitochondrial oxidative metabolism

An assessment of road-verge grass as a feedstock for farm-fed anaerobic digestion plants

Cuttings from road-verge grass could provide biomass for energy generation, but currently this potential is not exploited. This research assessed the technical, practical and financial feasibility of using grass harvested from road verges as a feedstock in farm-fed anaerobic digestion (AD) plants. The methane potential (191 mL CH4 gDM−1) and digestion characteristics of verge grass were similar to those of current farm feedstocks; indicating suitability for AD. Ensiling had no significant impact on the biomethane generated. Testing co-digestions of verge grass with current farm feedstocks showed enhanced methane yields, suggesting that verge grass could be a valuable addition to AD feedstock mixes. In a case study of the UK county of Lincolnshire, potential volumes and locations of verge grass biomass were estimated, with capacities and locations of existing AD plants, to assess the potential to supply practical grass volumes. Grass harvesting costs were modelled and compared with other feedstock costs. Finally, the attitudes of AD operators to using verge grass were investigated to understand whether a market for verge grass exists. In a small survey all operators were willing to use it as a feedstock and most were prepared to pay over the estimated harvesting cost. If verge grass was legally recognised as a waste product it could be attractive to AD operators especially where financial incentives to use waste feedstocks are in place. In rural areas, verge grass could be harvested and co-digested by existing farm-fed AD plants, potentially reducing the cost of road verge maintenance and increasing biodiversity

Quantification of the severity of hypoxic-ischemic brain injury in a neonatal preclinical model using measurements of cytochrome-c-oxidase from a miniature broadband-near-infrared spectroscopy system

We describe the development of a miniaturized broadband near-infrared spectroscopy system (bNIRS), which measures changes in cerebral tissue oxyhemoglobin (  [  HbO₂ ]  ) and deoxyhemoglobin ([HHb]) plus tissue metabolism via changes in the oxidation state of cytochrome-c-oxidase ([oxCCO]). The system is based on a small light source and a customized mini-spectrometer. We assessed the instrument in a preclinical study in 27 newborn piglets undergoing transient cerebral hypoxia-ischemia (HI). We aimed to quantify the recovery of the HI insult and estimate the severity of the injury. The recovery in brain oxygenation (Δ  [  HbDiff  ]    =  Δ  [  HbO₂  ]    −  Δ  [  HHb  ]  ), blood volume (Δ  [  HbT  ]    =  Δ  [  HbO₂  ]    +  Δ  [  HHb  ]  ), and metabolism (Δ  [  oxCCO  ]  ) for up to 30 min after the end of HI were quantified in percentages using the recovery fraction (RF) algorithm, which quantifies the recovery of a signal with respect to baseline. The receiver operating characteristic analysis was performed on bNIRS-RF measurements compared to proton (H1) magnetic resonance spectroscopic (MRS)-derived thalamic lactate/N-acetylaspartate (Lac/NAA) measured at 24-h post HI insult; Lac/NAA peak area ratio is an accurate surrogate marker of neurodevelopmental outcome in babies with neonatal HI encephalopathy. The Δ  [  oxCCO  ]  -RF cut-off threshold of 79% within 30 min of HI predicted injury severity based on Lac/NAA with high sensitivity (100%) and specificity (93%). A significant difference in thalamic Lac/NAA was noticed (p  <  0.0001) between the two groups based on this cut-off threshold of 79% Δ  [  oxCCO  ]  -RF. The severe injury group (n  =  13) had ∼30  %   smaller recovery in Δ  [  HbDiff  ]  -RF (p  =  0.0001) and no significant difference was observed in Δ  [  HbT  ]  -RF between groups. At 48 h post HI, significantly higher P31-MRS-measured inorganic phosphate/exchangeable phosphate pool (epp) (p  =  0.01) and reduced phosphocreatine/epp (p  =  0.003) were observed in the severe injury group indicating persistent cerebral energy depletion. Based on these results, the bNIRS measurement of the oxCCO recovery fraction offers a noninvasive real-time biomarker of brain injury severity within 30 min following HI insult

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

Systems Biology Model of Cerebral Oxygen Delivery and Metabolism During Therapeutic Hypothermia: Application to the Piglet Model

Hypoxic ischaemic encephalopathy (HIE) is a significant cause of death and disability. Therapeutic hypothermia (TH) is the only available standard of treatment, but 45-55% of cases still result in death or neurodevelopmental disability following TH. This work has focussed on developing a new brain tissue physiology and biochemistry systems biology model that includes temperature effects, as well as a Bayesian framework for analysis of model parameter estimation. Through this, we can simulate the effects of temperature on brain tissue oxygen delivery and metabolism, as well as analyse clinical and experimental data to identify mechanisms to explain differing behaviour and outcome. Presented here is an application of the model to data from two piglets treated with TH following hypoxic-ischaemic injury showing different responses and outcome following treatment. We identify the main mechanism for this difference as the Q10 temperature coefficient for metabolic reactions, with the severely injured piglet having a median posterior value of 0.133 as opposed to the mild injury value of 5.48. This work demonstrates the use of systems biology models to investigate underlying mechanisms behind the varying response to hypothermic treatment

Acetic acid stress response of the acidophilic sulfate reducer Acididesulfobacillus acetoxydans

Acid mine drainage (AMD) waters are a severe environmental threat, due to their high metal content and low pH (pH <3). Current technologies treating AMD utilize neutrophilic sulfate-reducing microorganisms (SRMs), but acidophilic SRM could offer advantages. As AMDs are low in organics these processes require electron donor addition, which is often incompletely oxidized into organic acids (e.g., acetic acid). At low pH, acetic acid is undissociated and toxic to microorganisms. We investigated the stress response of the acetotrophic Acididesulfobacillus acetoxydans to acetic acid. A. acetoxydans was cultivated in bioreactors at pH 5.0 (optimum). For stress experiments, triplicate reactors were spiked until 7.5 mM of acetic acid and compared with (non-spiked) triplicate reactors for physiological, transcriptomic, and membrane lipid changes. After acetic acid spiking, the optical density initially dropped, followed by an adaptation phase during which growth resumed at a lower growth rate. Transcriptome analysis revealed a downregulation of genes involved in glutamate and aspartate synthesis following spiking. Membrane lipid analysis revealed a decrease in iso and anteiso fatty acid relative abundance; and an increase of acetyl-CoA as a fatty acid precursor. These adaptations allow A. acetoxydans to detoxify acetic acid, creating milder conditions for other microorganisms in AMD environments

Garden and landscape-scale correlates of moths of differing conservation status: significant effects of urbanization and habitat diversity

Moths are abundant and ubiquitous in vegetated terrestrial environments and are pollinators, important herbivores of wild plants, and food for birds, bats and rodents. In recent years, many once abundant and widespread species have shown sharp declines that have been cited by some as indicative of a widespread insect biodiversity crisis. Likely causes of these declines include agricultural intensification, light pollution, climate change, and urbanization; however, the real underlying cause(s) is still open to conjecture. We used data collected from the citizen science Garden Moth Scheme (GMS) to explore the spatial association between the abundance of 195 widespread British species of moth, and garden habitat and landscape features, to see if spatial habitat and landscape associations varied for species of differing conservation status. We found that associations with habitat and landscape composition were species-specific, but that there were consistent trends in species richness and total moth abundance. Gardens with more diverse and extensive microhabitats were associated with higher species richness and moth abundance; gardens near to the coast were associated with higher richness and moth abundance; and gardens in more urbanized locations were associated with lower species richness and moth abundance. The same trends were also found for species classified as increasing, declining and vulnerable under IUCN (World Conservation Union) criteria