Age-related mechanical changes to the lung: A multi-scale modelling approach

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dc.contributor.advisor Tawhai, M en
dc.contributor.advisor Kumar, H en
dc.contributor.advisor Clark, A en Subramaniam, Karthikeya en 2017-07-06T22:02:52Z en 2017 en
dc.identifier.uri en
dc.description.abstract As a normal part of mature ageing lung tissue undergoes microstructural changes such as alveolar airspace enlargement, redistribution of collagen and elastin, a decrease in tissue elastic recoil, and an increase in interstitial fibrosis. Such changes, however, are also common early indicators of pulmonary disease. Old-age lungs are also expected to show a reduction in overall density, in addition to structural changes to alveoli and ducts. While these changes are common in pulmonary diseases such as emphysema, there is variation in how localised these phenomena are, and the mechanisms by which they occur, leading to heterogeneity in the pattern of degeneration of the parenchyma. Linking these age-related microstructural changes to mechanical changes at the whole-organ scale has proven difficult, and current understanding of the complex interactions between lung tissue structure and function is poor. This is largely due to the lung’s behaviour on a wholeorgan scale bearing little resemblance to its micromechanical behaviour. To date, models of lung tissue mechanics have focused on the general case of the young healthy lung, and have yet to address the healthy ageing lung. Pulmonary function tests are commonly used to assess lung health, but are often unable to distinguish between early signs of pathology and normal age-related changes. Difficulty in distinguishing between early signs of pathology and normal ageing extends to imaging as well. Therefore, developing models that link microstructural changes to the mechanical behaviour of the ageing lung could be of great value in reducing misdiagnosis in the elderly, as well as improving and customising therapies such as radiation treatment, where an understanding of the organ’s mechanics is essential. This thesis presents multi-scale biophysical models that can elucidate structurefunction soft tissue mechanics relationships in the healthy young and old adult lung, and proposes methodologies to make models more ‘subject-specific’, with the aim that these frameworks aid in the development of clinical diagnostic tools. Biophysical models are developed to analyse the roles played by morphometric alveolar changes and the redistribution of load-bearing elements in duct/alveoli structures, both of which occur as a result of ageing. Heterogeneity in young and old lungs is studied using two different image analysis algorithms. Results show no significant difference in mean lung density (MLD) with respect to age at end expiration, however, at end inspiration the young cohort shows higher MLD. Gradients of tissue deformation along the gravitational axis show no significant difference between young and older cohorts. The two measurements of heterogeneity – fractal dimension and quadtree decomposition – show no correlation with age, however both metrics show strong correlations with body mass index (BMI). Alveolar-duct models are then used to address the effects of age-related alveolar morphometric changes and redistribution of collagen and elastin on elastic recoil and bulk modulus at a microstructural scale. Results support published data that suggest that airspace enlargement in old age contributes to loss of tissue elastic recoil. Results further show that redistribution of elastic proteins away from the alveolar duct walls to the septae can decrease tissue elastic recoil. Finally, a methodology for linking pulmonary function test pressurevolume data and tissue material test data to lung tissue mechanics is introduced. The effects of old age on soft-tissue deformation due to gravity are simulated using finite element models that are parameterised using this method. en
dc.publisher ResearchSpace@Auckland en
dc.relation.ispartof PhD Thesis - University of Auckland en
dc.relation.isreferencedby UoA99264959414102091 en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri en
dc.rights.uri en
dc.title Age-related mechanical changes to the lung: A multi-scale modelling approach en
dc.type Thesis en Bioengineering en The University of Auckland en Doctoral en PhD en
dc.rights.holder Copyright: The author en
dc.rights.accessrights en
pubs.elements-id 635584 en
pubs.record-created-at-source-date 2017-07-07 en

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