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In-silico investigation of the neonatal brain physiology using a systems biology approach: modelling birth asphyxia and neuroprotective strategies

Russell-Buckland, Joshua; (2020) In-silico investigation of the neonatal brain physiology using a systems biology approach: modelling birth asphyxia and neuroprotective strategies. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Hypoxic ischaemic encephelopathy (HIE), often resulting from intrapartum hypoxic-ischemic injury, is a significant cause of death and morbidity before, during and after birth. In order to identify and monitor HIE, clinicians use non-invasive techniques including magnetic resonance spectroscopy (MRS) and near-infrared spectroscopy (NIRS). However, interpretation of these signals, particularly to determine the effectiveness of treatment and the severity of injury, is a challenging and difficult task. This thesis describes an attempt to use a systems biology approach to better understand the mechanisms behind HIE and its outcomes, using mathematical and computational techniques to analyse multimodal data, including broadband near-infrared spectroscopy (bNIRS). These models incorporate submodels of cerebral blood flow, oxygen transport and metabolism into a single cohesive model that attempts to simulate the observed measurements of tissue oxygenation and metabolism. The scope of this work is to both develop a set of computational tools that can be used to better understand existing systems biology models of the brain and to develop a new model which is able to incorporate the effects of therapeutic hypothermia, a common treatment for HIE, on the underlying physiology and its dynamics. The work begins by redeveloping the existing framework used for running and analysing systems biology models as used previously, before going on to develop a Bayesian framework which allows a better and more comprehensive interpretation of the results. This framework is then used to analyse three new models that incorporate the impact of therapeutic hypothermia on the piglet brain. The model determined to be most effective is then applied to clinical data from neonates that experience spontaneous desaturations in blood oxygen whilst undergoing hypothermic treatment. In all cases data from subjects with both mild and severe injuries are compared to determine if separate parameter spaces (and therefore physiological mechanisms) can be identified for each.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: In-silico investigation of the neonatal brain physiology using a systems biology approach: modelling birth asphyxia and neuroprotective strategies
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2020. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science > CoMPLEX: Mat&Phys in Life Sci and Exp Bio
URI: https://discovery.ucl.ac.uk/id/eprint/10117821
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