Using NIRS to monitor in-vivo brain tissue metabolism via quantification of the oxidation changes in cytochrome-c-oxidase: how and why?

Gemma Bale and Ilias Tachtsidis, University College London

Duration: 90 min

Capacity: 50

Level: Introductory

Demo Tech

Requirements: None

Synopsis: fNIRS uses hemoglobin oxygen changes as a surrogate for brain activity, but by measuring another NIR absorber, it is possible to monitor cellular metabolism more directly. Cytochrome-c-oxidase (CCO)is an enzyme within the mitochondria which is involved in 95% of oxygen metabolism. It has a unique NIR absorption spectrum which is dependent on its oxidation state, therefore it is possible to use NIRS to resolve changes in oxygen turnover at the mitochondrial level. This direct metabolic marker has uses in clinical monitoring of disease and atypical function, but also has advantages in fNIRS studies as the signal is more brain-specific than haemoglobin and is more localised to neuronal activity. However, measuring CCO that is one tenth of the hemoglobin concentration involves solving several technical challenges.

Rationale: Participants will learn how and why CCO is measured using NIRS; and will be introduced to broadband NIRS or bNIRS. We will introduce mitochondrial physiology, the electron transport chain and the possible relationship of CCO with neurovascular coupling. The optics, in terms of the hardware and analysis, will be covered. A live fNIRS measurement with a portable, miniature bNIRS device will be demonstrated and analysed. The interpretation of the signal will be discussed, with examples from recent clinical NIRS studies, as well as a look into the future of CCO measurements and potential applications.

Learning objectives:

Why measure cytochrome-c-oxidase?
Physiology – mitochondrial and cytochrome-c-oxidase
Applications – clinical and neuroscience
How can you measure cytochrome-c-oxidase?
Instrumentation: broadband NIRS (with live demo)
Algorithm (UCLn: modified Beer-Lambert law)
Interpretation of cytochrome-c-oxidase signal
Recent results with cytochrome-c-oxidase