title: Spatial Distribution of Changes in Oxidised Cytochrome C Oxidase During Visual Stimulation Using Broadband Near Infrared Spectroscopy Imaging.
abstract: Functional hyperaemia, characterised as an increase in concentration of oxyhaemoglobin [HbO2] and a decrease in concentration of deoxyhaemoglobin [HHb] in response to neuronal activity, can be precisely mapped using diffuse optical spectroscopy. However, such techniques do not directly measure changes in metabolic activity during neuronal activation. Changes in the redox state of cerebral oxidised cytochrome c oxidase Δ[oxCCO] measured by broadband spectroscopy may be a more specific marker of neuronal metabolic activity. This study aims to investigate the spatial distribution of Δ[oxCCO] responses during the activation of the visual cortex in the healthy adult human brain, and reconstruct images of these changes.Multi-channel broadband NIRS measurements were collected from the left visual cortex of four healthy volunteers using an in-house broadband spectrometer during an inverting checkerboard visual stimulation paradigm. Δ[HbO2], Δ[HHb] and Δ[oxCCO] were calculated by fitting the broadband spectra between 780 and 900 nm using the UCLn algorithm. Centre of gravity analysis was applied to the concentration data to determine the centres of activation for [HbO2], [HHb] and [oxCCO].All four subjects showed similar changes in [oxCCO] in the presence of a typical visual-evoked haemodynamic response in channels overlying the visual cortex. Image reconstruction of the optical data showed a clear and spatially localized activation for all three chromophores. Centre of gravity analysis showed different localisation of the changes in each of the three chromophores across the visual cortex with the x-y coordinates of the mean centres of gravity (across 4 subjects) of HbO2, HHb and oxCCO at (63.1 mm; 24.8 mm), (56.2 mm; 21.0 mm) and (63.7 mm; 23.8 mm), respectively.The spatial distribution of Δ[oxCCO] response appears distinct from the haemodynamic response in the human visual cortex. Image reconstruction of Δ[oxCCO] shows considerable promise as a technique to visualise regional variation in [oxCCO] in a range of scenarios.
authors.affiliation: Department of Medical Physics and Biomedical Engineering, University College London, London, UK. thanh.phan.11@ucl.ac.uk.
authors.forename: P
authors.initials: P
authors.lastname: Phan
authors.affiliation: Neurocritical Care, National Hospital for Neurology and Neurosurgery, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Highton
authors.affiliation: Department of Medical Physics and Biomedical Engineering, University College London, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Brigadoi
authors.affiliation: Department of Medical Physics and Biomedical Engineering, University College London, London, UK.
authors.forename: I
authors.initials: I
authors.lastname: Tachtsidis
authors.affiliation: Department of Medical Physics and Biomedical Engineering, University College London, London, UK.|Neurocritical Care, National Hospital for Neurology and Neurosurgery, London, UK.|NIHR University College London Hospitals Biomedical Research Centre, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Smith
authors.affiliation: Department of Medical Physics and Biomedical Engineering, University College London, London, UK.
authors.forename: C E
authors.initials: CE
authors.lastname: Elwell
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001931:Brain Mapping / Q000379:methods*; D003576:Electron Transport Complex IV / Q000378:metabolism*; D064368:Healthy Volunteers; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D010084:Oxidation-Reduction; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D010108:Oxyhemoglobins / Q000378:metabolism; D010775:Photic Stimulation; D011237:Predictive Value of Tests; D019265:Spectroscopy, Near-Infrared; D014793:Visual Cortex / Q000201:enzymology*
chemical_list: D015415:Biomarkers; D006454:Hemoglobins; D010108:Oxyhemoglobins; C100003:deoxyhemoglobin; D003576:Electron Transport Complex IV; D010100:Oxygen
keywords: Cytochrome coxidase; Diffuse optical imaging; Functional imaging; Near infrared spectroscopy; Visual cortex