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Title: Development of optical instrumentation and methods to monitor brain oxygen metabolism : application to neonatal brain injury
Author: Bale, G. M.
ISNI:       0000 0004 7230 4062
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2016
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Hypoxic ischemic encephalopathy (HIE) is a relatively common and potentially devastating form of perinatal brain injury, associated with neurodevelopmental problems and mortality. HIE is an evolving process. There is a need for real-time, in-vivo measurements of brain oxygenation and metabolism for clinical assessment in the first days of life, to detect those at risk of further brain injury who may benefit from redirection of care. This thesis describes the development of a broadband near-infrared spectroscopy (NIRS) system to monitor changes in metabolism and haemodynamics in HIE infants at the cotside. This system uses multiple wavelengths (λ=136,770-905nm) to monitor changes in concentration of the oxidation state of cytochrome-c-oxidase (oxCCO) as well as haemoglobin oxygenation. Changes in oxCCO are indicative of CCO redox state changes within mitochondria and therefore represent oxygen utilization. The 2-channel system incorporates a broadband source, optical fibres, spectrograph and CCD. This set up is flexible and robustly monitors changes in haemoglobin and oxCCO. The system was developed specifically for the neonatal intensive care unit (NICU) and has been demonstrated on 38 brain-injured newborn infants (28 with HIE). Data was continuously collected over the frontal lobe simultaneously with systemic data for multimodal analysis. This allows the study of cerebral changes in response to global pathophysiological events. HIE was assessed by magnetic resonance spectroscopy measurement of lactate to NAA ratio (Lac/NAA), the gold standard for neurodevelopmental outcome. Initially the analysis focussed on spontaneous hypoxias. The relationship between haemoglobin oxygenation and oxCCO during hypoxic events was significantly associated with Lac/NAA (n=22,r=0.51,p=0.02). Further investigation of the dynamics of the cerebral changes during hypoxias found oxCCO differences with injury severity (not observed in haemoglobins). Finally, the relationship between cerebral signals and systemic physiology was investigated with a multivariate statistical technique. A strong relationship between oxCCO and systemic changes indicated severe brain injury (n=12,p=0.04).
Supervisor: Tachtsidis, I. ; Meek, J. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available