Adult Brain

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As an optical laboratory we have employed several NIRS systems for monitoring non-invasively cerebral oxygenation and hemodynamics in adults. These systems are not only used for research purposes, but they are daily put into use at the neurosurgical intensive care unit, typically combined with conventional multi-modal patient monitoring.

Since a deficit in cerebral oxygenation can be caused both by a reduction in oxygen delivery below critical levels and an inability to utilise the delivered oxygen because of impaired cellular metabolism, measuring only haemoglobin-based NIRS variables, such as haemoglobin concentrations and tissue oxygenation index, fails to provide essential information on how oxygen is being utilised at the cellular level. Our work in human adults aims to explore cerebral oxygen delivery and utilisation in healthy volunteers and adults.

Potentially ideal markers of cellular oxygen metabolism are the mitochondrial cytochromes, which have similar NIR specific extinction coefficients to haemoglobin, but are present in about 10-fold lower concentrations, hence making a much lower contribution to the tissue NIR spectrum. Cytochrome c oxidase (CCO) is the terminal enzyme of the mitochondrial respiratory chain and contains a unique Cu-Cu dimer (termed CuA) that is a strong NIR absorber at 830nm and therefore it can be measured using NIRS techniques. Over 95% of oxygen metabolism is catalysed by CCO and its redox state can potentially be used to monitor alterations in cellular oxygen utilisation and energy production in the brain. Unlike haemoglobin, during the time course of a typical NIR study the total concentration of mitochondrial CCO does not change. However, changes in the redox state (difference of oxidised minus reduced CCO) are detectable [1-3].

Clearly the combination of cerebral tissue measurements of changes in haemoglobin concentration and intracellular CCO redox state can identify abnormalities of brain tissue haemodynamics and tissue oxygen utilisation, which can potentially be used to define thresholds for tissue wellbeing.

References

  1. Cooper C.E., Cope M., Springett R., Amess P.N., Penrice J., Tyszczuk L., Punwani S., Ordidge R., Wyatt J., Delpy D., “Use of mitochondrial inhibitors to demonstrate that sytochrome oxidase near-infrared spectroscopy can meassure mitochondrial dysfunction noninvasively in the brain."Journal of Cerebral Blood Flow and Metabolism (1999) 19:27-38 [URL]
  2. Cooper C.E., Springett R., “Measurement of cytochrome oxidase and mitochondrial energetics by near-infrared spectroscopy.” Philosophical Transactions of the Royal Society London B. Biological Sciences (1997) 352(1354):669-676 [URL]
  3. Springett R., Newman J., Cope M., Delpy D.T., “Oxygen dependency and precision of cytochrome oxidase signal from full spectral NIRS of the piglet brain.” American Journal of Physiology: Heart and Circulatory Physiology (2000) 279(5):H2202-H2209 [URL]

Personnel

  • Clare Elwell, Group Leader and Professor of Medical Physics
  • Martin Smith, Consultant and Honorary Professor in Neurocritical Care
  • Terence Leung, EPSRC Career Acceleration Fellow and Head of Acousto-Optic Group

Research Fellows
  • Christina Kolyva
  • Maria Papademetriou
  • Beth Jelfs
  • Murad Banaji
Clinical Research Fellows
  • Arnab Ghosh
  • David Highton

Previous Members of NIRS

  • Anna Blasi
  • Jasmina Panovska-Griffiths

External Academic Collaborators

  • Prof. Chris Cooper
  • Dr. Stephen Payne
  • Prof. Mark Johnson
  • Sarah Lloyd-Fox
  • Dr. Daniel Leff