title: Development and Analysis of Patient-Based Complete Conducting Airways Models.
abstract: The analysis of high-resolution computed tomography (CT) images of the lung is dependent on inter-subject differences in airway geometry. The application of computational models in understanding the significance of these differences has previously been shown to be a useful tool in biomedical research. Studies using image-based geometries alone are limited to the analysis of the central airways, down to generation 6-10, as other airways are not visible on high-resolution CT. However, airways distal to this, often termed the small airways, are known to play a crucial role in common airway diseases such as asthma and chronic obstructive pulmonary disease (COPD). Other studies have incorporated an algorithmic approach to extrapolate CT segmented airways in order to obtain a complete conducting airway tree down to the level of the acinus. These models have typically been used for mechanistic studies, but also have the potential to be used in a patient-specific setting. In the current study, an image analysis and modelling pipeline was developed and applied to a number of healthy (n = 11) and asthmatic (n = 24) CT patient scans to produce complete patient-based airway models to the acinar level (mean terminal generation 15.8 ± 0.47). The resulting models are analysed in terms of morphometric properties and seen to be consistent with previous work. A number of global clinical lung function measures are compared to resistance predictions in the models to assess their suitability for use in a patient-specific setting. We show a significant difference (p < 0.01) in airways resistance at all tested flow rates in complete airway trees built using CT data from severe asthmatics (GINA 3-5) versus healthy subjects. Further, model predictions of airways resistance at all flow rates are shown to correlate with patient forced expiratory volume in one second (FEV1) (Spearman ρ = -0.65, p < 0.001) and, at low flow rates (0.00017 L/s), FEV1 over forced vital capacity (FEV1/FVC) (ρ = -0.58, p < 0.001). We conclude that the pipeline and anatomical models can be used directly in mechanistic modelling studies and can form the basis for future patient-based modelling studies.
authors.affiliation: Computational Biology, Department of Computer Science, University of Oxford, Oxford, United Kingdom.
authors.forename: Rafel
authors.initials: R
authors.lastname: Bordas
authors.affiliation: ARTEMIS Department, CNRS UMR 8145, Telecom SudParis, Institut Mines-Telecom, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Lefevre
authors.affiliation: Materialise NV, Leuven, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Veeckmans
authors.affiliation: Computational Biology, Department of Computer Science, University of Oxford, Oxford, United Kingdom.
authors.forename: Joe
authors.initials: J
authors.lastname: Pitt-Francis
authors.affiliation: ARTEMIS Department, CNRS UMR 8145, Telecom SudParis, Institut Mines-Telecom, Paris, France.
authors.forename: Catalin
authors.initials: C
authors.lastname: Fetita
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Brightling
authors.affiliation: Computational Biology, Department of Computer Science, University of Oxford, Oxford, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Kay
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: Salman
authors.initials: S
authors.lastname: Siddiqui
authors.affiliation: Computational Biology, Department of Computer Science, University of Oxford, Oxford, United Kingdom.
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Burrowes
mesh_terms: D000368:Aged; D000403:Airway Resistance; D005260:Female; D006801:Humans; D008168:Lung / Q000033:anatomy & histology* / Q000000981:diagnostic imaging / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D008953:Models, Anatomic; D014057:Tomography, X-Ray Computed