@article{discovery1395037,
           month = {January},
            year = {2014},
          number = {1},
            note = {{\copyright} 2013 The Authors. Published by Elsevier Inc. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction
in any medium, provided the original author and source are credited.},
          volume = {85},
           pages = {234--244},
           title = {Cytochrome c oxidase response to changes in cerebral oxygen delivery in the adult brain shows higher brain-specificity than haemoglobin},
         journal = {Neuroimage},
        keywords = {Cytochrome c oxidase;
    Hypoxia;
    Hyperoxia;
    Hypocapnia;
    Hypercapnia;
    Near-infrared spectroscopy;},
        abstract = {The redox state of cerebral mitochondrial cytochrome c oxidase monitored with near-infrared spectroscopy ({\ensuremath{\Delta}}{{[}}oxCCO]) is a signal with strong potential as a non-invasive, bedside biomarker of cerebral metabolic status. We hypothesised that the higher mitochondrial density of brain compared to skin and skull would lead to evidence of brain-specificity of the {\ensuremath{\Delta}}{{[}}oxCCO] signal when measured with a multi-distance near-infrared spectroscopy (NIRS) system. Measurements of {\ensuremath{\Delta}}{{[}}oxCCO] as well as of concentration changes in oxygenated ({\ensuremath{\Delta}}{{[}}HbO2]) and deoxygenated haemoglobin ({\ensuremath{\Delta}}{{[}}HHb]) were taken at multiple source-detector distances during systemic hypoxia and hypocapnia (decrease in cerebral oxygen delivery), and hyperoxia and hypercapnia (increase in cerebral oxygen delivery) from 15 adult healthy volunteers. Increasing source-detector spacing is associated with increasing light penetration depth and thus higher sensitivity to cerebral changes. An increase in {\ensuremath{\Delta}}{{[}}oxCCO] was observed during the challenges that increased cerebral oxygen delivery and the opposite was observed when cerebral oxygen delivery decreased. A consistent pattern of statistically significant increasing amplitude of the {\ensuremath{\Delta}}{{[}}oxCCO] response with increasing light penetration depth was observed in all four challenges, a behaviour that was distinctly different from that of the haemoglobin chromophores, which did not show this statistically significant depth gradient. This depth-dependence of the {\ensuremath{\Delta}}{{[}}oxCCO] signal corroborates the notion of higher concentrations of CCO being present in cerebral tissue compared to extracranial components and highlights the value of NIRS-derived {\ensuremath{\Delta}}{{[}}oxCCO] as a brain-specific signal of cerebral metabolism, superior in this aspect to haemoglobin.},
             url = {http://dx.doi.org/10.1016/j.neuroimage.2013.05.070},
          author = {Kolyva, C and Ghosh, A and Tachtsidis, I and Highton, D and Cooper, CE and Smith, M and Elwell, CE},
            issn = {1053-8119}
}