Development of a portable multi-channel broadband near infrared spectroscopy instrument to measure brain tissue oxygenation and metabolism during functional activation and seizures

Epilepsy is a common neurological disorder often developed during childhood, characterised by abnormal neuronal discharges. These spontaneous recurrent seizures can be associated with poor long-term neurological development. Near-infrared spectroscopy (NIRS) is a non-invasive tech- nique able to monitor cerebral concentration changes in oxygenated- (∆[HbO2]) and deoxygenated- (∆[HHb]) haemoglobin. However, current commercial NIRS systems use only a few wavelengths, limiting their use to haemodynamic monitoring. Broadband NIRS (bNIRS) systems use a larger number of wavelengths enabling changes in concentration of the oxidation state of cytochrome-c- oxidase (∆[oxCCO]) to be determined, a marker of cellular metabolism. This thesis describes the development and miniaturisation of an existing bNIRS system to monitor haemodynamic and metabolic changes in children with epilepsy. Using the latest technological advancements, the bulk and complexity of the system was reduced while increasing the number of measurement channels. Two miniature tungsten halogen light sources were utilised with time- multiplexing capabilities implemented (0.5Hz). Bifurcated optical fibre bundles (2.8mm diameter) connected to each light source and twelve detector fibre bundles (1mm diameter) arranged linearly into a ferrule (25mm diameter); modification of the interface between the detectors and lens-based spectrograph ensured compatibility with the increased detector number. Light was collimated to a diffraction grating with a wider 308nm bandwidth and the largest CCD image sensor available (1340x1300 array, 26.8x26mm) was integrated into the system. LabVIEW software was updated to enable simultaneous, real-time collection and display of intensity and concentration changes. Extensive testing of the system was performed; in-vivo testing in healthy adults using a Stroop task demonstrated a typical haemodynamic response with regional variation in metabolism. Si- multaneous bNIRS and electroencephalography data were collected from 12 children with epilepsy in the Neurology Unit. One patient case study is presented in detail, with temporal data from 17 seizures collected. A large decrease in metabolism was observed in the left posterior region, corresponding to a region of cortical malformation, suggesting an energetic deficiency in this re- gion. This indicates the potential for ∆[oxCCO] as an investigative marker in monitoring seizures, providing localised information about cellular oxygen utilisation

Whole-Body Regeneration

This Open Access volume provides a comprehensive overview of the latest tools available to scientists to study the many facets of whole-body regeneration (WBR). The chapters in this book are organized into six parts. Part One provides a historical overview on the study of the WBR phenomena focusing on the primary challenges of this research. Parts Two and Three explore a series of non-vertebrate zoological contexts that provide experimental models for WBR, showing how they can be approached with cellular tools. Parts Four, Five, and Six discuss the future advancements of WBR, reporting about the cutting-edge techniques in genetics and omics used to dissect the underlying mechanisms of WBR, and systems biology approaches to reach a synthetic view of WBR. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and thorough, Whole-Body Regeneration: Methods and Protocols is a valuable resource for scientists and researchers who want to learn more about this important and developing field

Chapter 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

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations

Estimating global injuries morbidity and mortality : methods and data used in the Global Burden of Disease 2017 study

Background While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. Methods In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. Results GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. Conclusions GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future.Peer reviewe

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic

Mapping inequalities in exclusive breastfeeding in low- and middle-income countries, 2000–2018

Exclusive breastfeeding (EBF)—giving infants only breast-milk for the first 6 months of life—is a component of optimal breastfeeding practices effective in preventing child morbidity and mortality. EBF practices are known to vary by population and comparable subnational estimates of prevalence and progress across low- and middle-income countries (LMICs) are required for planning policy and interventions. Here we present a geospatial analysis of EBF prevalence estimates from 2000 to 2018 across 94 LMICs mapped to policy-relevant administrative units (for example, districts), quantify subnational inequalities and their changes over time, and estimate probabilities of meeting the World Health Organization’s Global Nutrition Target (WHO GNT) of ≥70% EBF prevalence by 2030. While six LMICs are projected to meet the WHO GNT of ≥70% EBF prevalence at a national scale, only three are predicted to meet the target in all their district-level units by 2030

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

La interrelación entre las mediciones NIRS de banda ancha de la citocromo C oxidasa cerebral y los cambios sistémicos indican la gravedad de la lesión en la encefalopatía neonatal

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

Chapter 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