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Modelling oxygen transport and tissue damage in the human brain

Xue, Yidan ORCID: 2022. Modelling oxygen transport and tissue damage in the human brain. PhD Thesis, University of Oxford.

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Healthy brain function depends on continuous blood flow carrying oxygen and metabolites. Ischaemic stroke, caused by an occlusion in the cerebral artery that disrupts blood and oxygen supply and leads to irreversible tissue damage, is one of the leading causes of death and disability in the world. To complement clinical trials to improve the functional outcomes of stroke patients, computational models have been developed to build a virtual platform (i.e. an in silico trial) to test the feasibility of new treatments. However, the role of the human cerebrovascular system in oxygen transport and tissue health remains poorly understood, which limits the utility of current brain models. Therefore, it is necessary to develop new models of oxygen transport and tissue damage for the human brain to improve our understanding of brain physiology and diseases. This thesis first models oxygen transport in human capillary networks using a Green’s function method. The effects of microembolism on oxygen delivery are simulated to derive a quantitative relationship between tissue hypoxia and vessel blockage. In human cortical columns supplied by a single penetrating arteriole, oxygen transport is simulated after the arteriole tree is occluded by a 25 μm microthrombus to mimic a rodent experiment of microembolism. Reasonable agreement has been shown between simulations and experiments measuring the spatial correlation between hypoxic regions and occlusion sites. A novel 3-state cell death model and a thrombus extravasation model are then proposed to simulate the irreversible tissue damage caused by cerebral microvascular occlusions. The cell death model is further developed to simulate brain tissue damage over time under different ischaemic conditions. A full in silico trial of ischaemic stroke can thus be built by coupling the cell death model with existing whole brain models of cerebral blood flow and ischaemic stroke.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Published
Schools: Mathematics
Publisher: University of Oxford
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Last Modified: 08 Jan 2024 16:33

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