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Combining novel optics and analysis strategies for non-invasive investigation of cerebral haemodynamic regulation

Highton, David Thomas; (2018) Combining novel optics and analysis strategies for non-invasive investigation of cerebral haemodynamic regulation. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Cerebral autoregulation defines the brain’s ability to sustain blood flow despite changes in perfusion pressure, and established techniques can characterise this from slow <0.05Hz waves in cerebral haemodynamics. This thesis examines changes in slow waves of cerebral haemodynamics and metabolism following acute brain injury using near infrared spectroscopy (NIRS). Impaired autoregulation is implicated in energy dysfunction following acute brain injury, and continuous autoregulation monitoring (including NIRS) demonstrates an “optimal” perfusion pressure in many patients which has future potential as a therapeutic target to avoid hypoperfusion and ischaemia. However the metabolic impact of impaired autoregulation (and its optimisation) is controversial and challenging to quantify. The aim, and novelty of this work is for the first time to characterise slow metabolic waves via NIRS-derived cytochrome c oxidase in adult acute brain injury using a similar paradigm. NIRS is a non-invasive, optical technique that measures cerebral haemodynamics and, using optimised broadband systems, mitochondrial oxidation via the oxidation status of cytochrome c oxidase ([oxCCO]). I hypothesise that [oxCCO] exhibits similar perfusion pressure related changes to established haemodynamic variables, suggesting impaired metabolism in the setting of dysfunctional autoregulation. The analysis of these relationships is challenged by the dynamic measured signals, multivariate influences from systemic and cerebral physiology (autoregulation, neurovascular coupling, systemic carbon dioxide and oxygenation), and optical confounding factors. This thesis describes the combination of customised spectroscopy hardware and advanced analytical techniques to address these issues. First I describe a novel wavelet technique that addresses dynamic analysis, then define optical confounders using a custom made NIRS system optimised for the detection of [oxCCO]. I show that [oxCCO] is sensitive to changes in both blood pressure (autoregulation) and neuronal activity (neurovascular coupling). I then quantify the normal response of [oxCCO] to different energy demands for comparison to the brain injured state. Finally, I define changes in autoregulation, neurovascular coupling and [oxCCO] following acute brain injury, consistent with ischaemia. My findings support the rationale for autoregulation-directed therapy after acute brain injury, and [oxCCO] as a promising biomarker for haemodynamic regulation.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Combining novel optics and analysis strategies for non-invasive investigation of cerebral haemodynamic regulation
Event: UCL (University College London)
Language: English
URI: http://discovery.ucl.ac.uk/id/eprint/10053798
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