Systematic investigation of changes in oxidized cerebral cytochrome c oxidase concentration during frontal lobe activation in healthy adults

Using transcranial near-infrared spectroscopy (NIRS) to measure changes in the redox state of cerebral cytochrome c oxidase (Δ[oxCCO]) during functional activation in healthy adults is hampered by instrumentation and algorithm issues. This study reports the Δ[oxCCO] response measured in such a setting and investigates possible confounders of this measurement. Continuous frontal lobe NIRS measurements were collected from 11 healthy volunteers during a 6-minute anagram-solving task, using a hybrid optical spectrometer (pHOS) that combines multi-distance frequency and broadband components. Only data sets showing a hemodynamic response consistent with functional activation were interrogated for a Δ[oxCCO] response. Simultaneous systemic monitoring data were also available. Possible influences on the Δ[oxCCO] response were systematically investigated and there was no effect of: 1) wavelength range chosen for fitting the measured attenuation spectra; 2) constant or measured, with the pHOS in real-time, differential pathlength factor; 3) systemic hemodynamic changes during functional activation; 4) changes in optical scattering during functional activation. The Δ[oxCCO] response measured in the presence of functional activation was heterogeneous, with the majority of subjects showing significant increase in oxidation, but others having a decrease. We conclude that the heterogeneity in the Δ[oxCCO] response is physiological and not induced by confounding factors in the measurements. © 2012 Optical Society of America

Functional Optical Topography Analysis Using Statistical Parametric Mapping (SPM) Methodology with and without Physiological Confounds

Functional optical topography (OT) measures the changes in oxygenated and deoxygenated hemoglobin (HbO(2), HHb) across multiple brain sites which occur in response to neuronal activation of the cerebral cortex. However, identification of areas of cortical activation is a complex task due to intrinsic physiological noise and systemic interference and careful statistical analysis is therefore required. A total of 10 young healthy adults were studied. The activation paradigm comprised of anagrams followed by finger tapping. 12 channels of the OT system were positioned over the frontal cortex and 12 channels over the motor cortex while the systemic physiology (mean blood pressure (MBP), heart rate (HR), scalp flux) was simultaneously monitored. Analysis was done using the functional Optical Signal Analysis (fOSA) software and Statistical Parametric Mapping (SPM), where we utilized two approaches: (i) using only HbO(2) as a regressor in the general linear model (GLM) and (ii) using all of the explanatory variables (HbO(2), MBP, HR and scalp flux) as regressors. Group analysis using SPM showed significant correlation in a large number of OT channels between HbO(2) and systemic regressors; however no differences in activation areas were seen between the two approaches

Taking the lid off ambitions for optical imaging of the human brain: a conversation with Clare Elwell

Ilias Tachtsidis, professor of biomedical engineering, senior member of the Biomedical Optics Research Laboratory, and head of the Multi-Modal Spectroscopy Group at University College London (UCL), interviewed his colleague and mentor Clare Elwell, professor of medical physics at UCL and Vice Dean of Impact for UCL Engineering, about her pioneering work in fNIRS and brain imaging for global health

Investigation of frontal lobe activation with fNIRS and systemic changes during video gaming.

Frontal lobe activation caused by tasks such as videogames can be investigated using multichannel near-infrared spectroscopy (fNIRS), sometimes called optical topography. The aims of this study are to investigate the effects of video gaming (fighting and puzzle games) in the brain and the systemic physiology and to determine whether systemic responses during the gaming task are associated with the measurement of localised cerebral haemodynamic changes as measured by fNIRS. We used a continuous-wave 8-channel fNIRS system to measure the changes in concentration of oxy-haemoglobin (HbO2) and deoxy-haemoglobin (HHb) and changes in total haemoglobin (ΔtHb = ΔHbO2 + ΔHHb) over the frontal lobe in 30 healthy volunteers. The Portapres system was used to measure mean blood pressure (MBP) and heart rate (HR), and a laser Doppler was employed to measure the changes in scalp blood flow (or flux). Even though we observed significant changes in systemic variables during gaming, in particular in scalp flow, we also managed to see localised activation patterns over the frontal polar (FP1) region. However, in some channels over the frontal lobe, we also observed significant correlations between the HbO2 and systemic variables

False positives and false negatives in functional near-infrared spectroscopy: issues, challenges, and the way forward

We highlight a significant problem that needs to be considered and addressed when performing functional near-infrared spectroscopy (fNIRS) studies, namely the possibility of inadvertently measuring fNIRS hemodynamic responses that are not due to neurovascular coupling. These can be misinterpreted as brain activity, i.e., "false positives" (errors caused by wrongly assigning a detected hemodynamic response to functional brain activity), or mask brain activity, i.e., "false negatives" (errors caused by wrongly assigning a not observed hemodynamic response in the presence of functional brain activity). Here, we summarize the possible physiological origins of these issues and suggest ways to avoid and remove them

Cerebral and Peripheral Tissue Oxygenation in Children Supported on ECMO for Cardio-Respiratory Failure

Extracorporeal membrane oxygenation (ECMO) is a rescue therapy for patients with cardio-respiratory failure. Establishing, maintaining and weaning from ECMO may increase the risk for intracranial injury. We used a dual channel near infrared system to monitor cerebral and peripheral tissue oxygenation in 3 venoarterial (VA) and 1 venovenous (VV) ECMO patients undergoing manipulations in the ECMO circuit flows. Spectral analysis was performed on the oxyhaemoglobin data collected from these patients with the aim of comparing oscillations at range of frequencies appearing in the two measurement sites

A Hybrid Multi-Distance Phase and Broadband Spatially Resolved Spectrometer and Algorithm for Resolving Absolute Concentrations of Chromophores in the Near-Infrared Light Spectrum

For resolving absolute concentration of tissue chromophores in the human adult brain with near-infrared spectroscopy it is necessary to calculate the light scattering and absorption, at multiple wavelengths with some depth resolution. To achieve this we propose an instrumentation configuration that combines multi-distance frequency and broadband spectrometers to quantify chromophores in turbid media by using a hybrid spatially resolved algorithm. Preliminary results in solid phantoms as well as liquid dynamic homogeneous and inhomogeneous phantoms and in-vivo muscle measurements showed encouraging results

Chapter Developing a Model to Simulate the Effect of Hypothermia on Cerebral Blood Flow and Metabolism

Hypoxic ischemic encephalopathy (HIE) is a significant cause of death and neurological disability in newborns. Therapeutic hypothermia at 33.5 °C is one of the most common treatments in HIE and generally improves outcome; however 45–55% of injuries still result in death or severe neurodevelopmental disability. We have developed a systems biology model of cerebral oxygen transport and metabolism to model the impact of hypothermia on the piglet brain (the neonatal preclinical animal model) tissue physiology. This computational model is an extension of the BrainSignals model of the adult brain. The model predicts that during hypothermia there is a 5.1% decrease in cerebral metabolism, 1.1% decrease in blood flow and 2.3% increase in cerebral tissue oxygenation saturation. The model can be used to simulate effects of hypothermia on the brain and to help interpret bedside recordings

Analysis of the Changes in the Oxidation of Brain Tissue Cytochrome-c-Oxidase in Traumatic Brain Injury Patients during Hypercapnoea A Broadband NIRS Study

Using broadband near-infrared spectroscopy (NIRS) and cerebral micro-dialysis (MD), we investigated cerebral cellular metabolism and mitochondrial redox states, following hypercapnoea in 6 patients with traumatic brain injury (TBI). In all patients hypercapnoea increased intracranial pressure and cerebral blood flow velocity measured with transcranial Doppler. Despite the likely increase in cerebral oxygen delivery, we did not see an increase in the oxidation status of cytochrome-c-oxidase [oxCCO] in every patient. Analysis of the NIRS data demonstrated two patterns of the changes; Group A (n = 4) showed an increase in [oxCCO] of 0.34(+/-0.34)mu M and Group B (n = 2) a decrease of 0.40(+/- 0.41)mu M. Although no obvious association was seen between the Delta[oxCCO] and the MD, measured changes in lactate and pyruvate concentrations. Further work using model informed data interpretation may be helpful in understanding the multimodal signals acquired in this heterogeneous patient group

The Use of Supercontinuum Laser Sources in Biomedical Diffuse Optics: Unlocking the Power of Multispectral Imaging

Optical techniques based on diffuse optics have been around for decades now and are making their way into the day-to-day medical applications. Even though the physics foundations of these techniques have been known for many years, practical implementation of these technique were hindered by technological limitations, mainly from the light sources and/or detection electronics. In the past 20 years, the developments of supercontinuum laser (SCL) enabled to unlock some of these limitations, enabling the development of system and methodologies relevant for medical use, notably in terms of spectral monitoring. In this review, we focus on the use of SCL in biomedical diffuse optics, from instrumentation and methods developments to their use for medical applications. A total of 95 publications were identified, from 1993 to 2021. We discuss the advantages of the SCL to cover a large spectral bandwidth with a high spectral power and fast switching against the disadvantages of cost, bulkiness, and long warm up times. Finally, we summarize the utility of using such light sources in the development and application of diffuse optics in biomedical sciences and clinical applications