Novel mathematical approaches to CT image analysis in asthma

Asthma is a complex respiratory disease characterised by spatial ventilation heterogeneity (VH) in the lung. Multiple breath washout (MBW) and forced oscillation technique (FOT) testing has been shown to quantify VH at the mouth. Methods to provide fresh insight into the mechanisms driving VH are urgently needed to support treatment development. Computed tomography (CT) with parametric response map (PRM) analysis provides spatial and functional lung data. Integrated data sets of imaging features and VH markers present the problem of extracting meaningful information from high dimensional objects; topological data analysis (TDA) has demonstrated recent success in solving this problem. In this thesis topological methods are applied to extract information about lung anatomy and function from imaging data to study association with VH in innately high dimensional integrated data sets. It was sought to describe the spatial distributions of voxel based metrics, visualise the lungs using TDA methods, and combine PRM with simulated airway tree models to improve computational modelling of FOT. Data was obtained from a clinical trial involving 52 subjects, 41 asthmatic (11 healthy). An algorithm was developed to quantify directional Hounsfield unit change (ΔHU) gradients. TDA was applied to integrated data sets and voxel sets with measures of airway tree depth. FOT modelling was augmented with ΔHU about simulated acinar airways.Inferior-to-superior ΔHU gradient best differentiated VH markers. Visualisations of the lungs illustrated gradient reversal and increased heterogeneity in ΔHU in asthmatics. FOT modelling using ΔHU parameterisation showed increased correlation between clinically measured and simulated FOT small airway resistance (R5-R20). In this thesis additional insight is presented into mechanisms affecting VH markers derived from MBW and FOT. Topological methods to analyse imaging data were developed and implemented, including workflows to visualise the lungs and lung function. Linking simulated airway tree geometry with ΔHU showed improvement in FOT modelling.