Changes in Cytochrome-C-Oxidase Account for Changes in Attenuation of Near-Infrared Light in the Healthy Infant Brain.

M F Siddiqui,M H Johnson,I Tachtsidis,P Kaynezhad,C E Elwell,S Lloyd-Fox

doi:10.1007/978-3-319-91287-5_2

Abstract

A novel multi-wavelength broadband near infrared spectroscopy (NIRS) system has been employed to simultaneously measure haemodynamic changes alongside changes in cellular oxygen utilization by measurement of oxidation state of mitochondrial enzyme cytochrome-c-oxidase (oxCCO). The aim of this study was to investigate the role of oxCCO in neural responses to functional activation in infants. Studies were performed using a NIRS broadband system in 33 typically developing infants aged between 4 and 6 months. Responses were recorded over the right temporal lobe while infants were presented with engaging videos containing social and nonsocial content. Changes in the concentration of oxyhaemoglobin (Δ[HbO2]), deoxyhaemoglobin (Δ[HHb]) and Δ[oxCCO] were calculated using changes in attenuation of light at 120 wavelengths between 780 and 900 nm using the UCLn algorithm. The algorithm was also used to fit (a) HbO2 and HHb spectra (2 component fit) and (b) HbO2, HHb and oxCCO (3 component fit) to the change in attenuation occurring within an experimental block in different participants. Residuals resulting from these two fits were compared with oxidized-minus reduced CCO spectrum, calculated using the CCO specific extinction coefficient. A significant increase in oxCCO was found in response to the social stimuli (maximum increase 0.238 ± 0.13 μM). Residuals analysis showed that the best fits were achieved when oxCCO was included as a tissue chromophore. These results are the first reported significant change in oxCCO to stimulus-evoked activation in infants and may reveal vital information about oxygen metabolism during functional activation in the developing human brain.

Highlights

near infrared spectroscopy (NIRS) is a non-invasive optical technique that provides valuable measures of cerebral oxygenation and haemodynamic changes through quantification of changes in oxygenated and deoxygenated haemoglobin Δ[HbO2] and Δ[HHb], by absorption of near-infrared light by underlying brain tissue
Recent technological advances in NIRS have allowed the measurement of cellular energy metabolism through measurement of mitochondrial respiratory chain enzyme cytochrome-c-oxidase (CCO)
The total concentration of CCO in healthy individuals remains constant, the NIRS measurement provides a marker of the oxidation state of CCO

Summary

Introduction

NIRS is a non-invasive optical technique that provides valuable measures of cerebral oxygenation and haemodynamic changes through quantification of changes in oxygenated and deoxygenated haemoglobin Δ[HbO2] and Δ[HHb], by absorption of near-infrared light by underlying brain tissue. NIRS measures of cerebral haemodynamic changes provide useful information about oxygen delivery in the brain. Recent technological advances in NIRS have allowed the measurement of cellular energy metabolism through measurement of mitochondrial respiratory chain enzyme cytochrome-c-oxidase (CCO). CCO is the terminal electron acceptor in the electron transport chain and is responsible for over 95% of oxygen metabolism in the body. Compared to haemoglobin based measures, oxCCO can potentially provide a more direct marker of brain activation, and animal studies [6] have found a significant correlation between oxCCO measures and phosphorus magnetic resonance spectroscopy biomarkers of cerebral energy metabolism

Objectives

Methods

Results

Conclusion