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

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

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

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

A new multichannel broadband NIRS system for quantitative monitoring of brain hemodynamics and metabolism during seizures

We present a newly developed multichannel broadband NIRS (or bNIRS) system that has the capacity to measure changes in light attenuation of 308 NIR wavelengths (610nm to 918nm) simultaneously over 16 different brain locations. To achieve this the instrument uses a lens based spectrometer with a front-illuminated CCD that has a sensor size of 26.8x26mm. This large CCD detector allows the simultaneous binning of 16 detector fibres. The software uses the UCLn algorithm to quantify the changes in oxy-, deoxy- haemoglobin concentration (HbO2, HHb) and oxidised cytochrome-coxidase (oxCCO) simultaneously over 16 different brain locations with 1second sampling rate. We demonstrate the use of the instrument in quantifying brain tissue oxygenation and metabolic activity simultaneously with electrical changes as measured with EEG in children with seizures

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 Confounding Factors in Measuring Tissue Saturation with NIRS Spatially Resolved Spectroscopy

Performing absolute measurements of tissue saturation of the brain with near-infrared spectroscopy (NIRS) is a clinically desirable brain monitoring tool. Tissue oxygenation index (TOI) is an indicator of absolute tissue mixed arterial and venous oxygen saturation, and can be calculated using a NIRS technique called spatially resolved spectroscopy (SRS). SRS instruments measure the change of light attenuation with distance by using multiple light source-detector distances at two or more wavelengths. The aim of the study is to use broadband NIRS SRS data to investigate the effects on the calculation of TOI of different parameters: wavelength selection, scattering dependence, source-detector distance, and resolving for water. In total, 55 neonates with hypoxic-ischemic encephalopathy were monitored using a broadband multi-distance continuous wave NIRS system; 172 datasets were recorded. Using a “Standard” approach, TOI values between 0 and 100% (“good”) were calculated in 157/172 datasets with a mean TOI of 50%. By changing the wavelength selection, the number of “good” data sets increases to 165/172 with a mean of 60%. Alteration of the dependence of scattering on wavelength acts as a constant which shifts the absolute value of TOI significantly (p < 0.05), demonstrating the importance of having a subject-appropriate estimation of scattering dependence. In general, changing the combination of source-detector distances does not significantly alter the TOI (the mean TOI ranges from 41% to 53%) which suggests that the algorithm is robust to different source-detector combinations. The study shows the broadband NIRS SRS algorithm gives the opportunity to explore the calculation of TOI and could further improve the measurement of tissue saturation in a clinical setting

Isomorphisms of algebras of Colombeau generalized functions

We show that for smooth manifolds X and Y, any isomorphism between the special algebra of Colombeau generalized functions on X, resp. Y is given by composition with a unique Colombeau generalized function from Y to X. We also identify the multiplicative linear functionals from the special algebra of Colombeau generalized functions on X to the ring of Colombeau generalized numbers. Up to multiplication with an idempotent generalized number, they are given by an evaluation map at a compactly supported generalized point on X.Comment: 10 page

Taxing the Informal Economy: The Current State of Knowledge and Agendas for Future Research

This paper reviews the literature on taxation of the informal economy, taking stock of key debates and drawing attention to recent innovations. Conventionally, the debate on whether to tax has frequently focused on the limited revenue potential, high cost of collection, and potentially adverse impact on small firms. Recent arguments have increasingly emphasised the more indirect benefits of informal taxation in relation to economic growth, broader tax compliance, and governance. More research is needed, we argue, into the relevant costs and benefits for all, including quasi-voluntary compliance, political and administrative incentives for reform, and citizen-state bargaining over taxation