Quantitative computed tomography (QCT) enables objective assessment of lung structure and may provide information complementary to spirometry in chronic airflow limitation (CAL). Inspiratory and expiratory chest CT can assess lung volume, lung density, low-attenuation volume, and ventilation-related changes. However, their role in population-based cohorts remains less extensively studied, particularly in individuals without established lung disease or with mild airflow limitation. Furthermore, regional analysis requires accurate lung lobe segmentation, and the value of radiomic and deep learning-derived features for identifying CAL remains incompletely understood.
The overall aim of this thesis was to extract, analyse, automate, and regionalise quantitative measures from inspiratory and expiratory chest CT images, and to study their relationship with normal lung structure, ventilation-related changes, and spirometry-defined CAL. Data were obtained from the Stockholm cohort of the Swedish CArdioPulmonary bioImage Study (SCAPIS), a population-based cohort of men and women aged 50–64 years. Inspiratory and expiratory chest CT, post-bronchodilator spirometry, and questionnaire data were used. CAL was defined as a post-bronchodilator FEV1/FVC ratio < 0.70.
Study I evaluated global inspiratory and expiratory CT-derived lung volumes, mean lung density, low-attenuation volume, and density gradients. Inspiratory CT lung volumes were lower than literature-based total lung capacity reference values, whereas expiratory CT lung volumes exceeded residual volume reference values. Participants with CAL had higher inspiratory and expiratory lung volumes, lower mean lung density, and greater low-attenuation volume than participants without CAL. Expiratory CT measures showed better discriminatory performance than inspiratory measures, with the highest performance observed for expiratory low-attenuation measures. A dorsal–ventral attenuation gradient was observed during expiration in participants without CAL but not in participants with CAL.
Study II trained and evaluated a deep learning-based lung lobe segmentation method incorporating prior anatomical information from lung vessel connectivity. The method was evaluated in both inspiratory and expiratory CT, including expiratory scans, in which segmentation is typically more demanding. Prior anatomical information mainly improved boundary accuracy, with the clearest benefit in expiratory CT. The best overall segmentation performance was achieved using a multitask model segmenting both lung lobes and fissures. Complementary downstream analyses showed that the choice of segmentation method had a limited effect on CAL discrimination in the full cohort, although variability was greater in smaller cohorts.
Study III extended the global analyses in Study I to lobar CT measures in a larger cohort. Participants with CAL had higher inspiratory and expiratory lung volumes, higher low-attenuation volumes, and more negative mean lung density than participants without CAL. Expiratory measures again showed stronger discriminatory ability than inspiratory measures. Lobar analyses demonstrated regional heterogeneity in lung volume, density, and low-attenuation measures, while complementary thesis analyses examined dorsal–ventral variation. In regularised logistic regression models, combined inspiratory–expiratory measures contributed to CAL discrimination; performance improved when expiratory measures were added to inspiratory measures and showed a slight additional improvement with lobar variables. The best Study III model achieved an area under the ROC curve (AUC) of 0.81.
Study IV assessed whether lobe-level radiomic and deep learning-derived features improved CAL discrimination beyond established quantitative CT measures. Classical radiomics, SegResNet, and 3D U-Net feature models were compared using inspiratory, expiratory, and combined inspiratory–expiratory data. Expiratory feature models consistently outperformed inspiratory models. The best performance was achieved by the classical radiomics model combining inspiratory and expiratory features, which outperformed the handcrafted quantitative CT model from Study III. Feature selection showed that classical radiomics relied mainly on expiratory texture features, whereas deep learning-derived models showed more balanced contributions from inspiratory and expiratory images. Combining radiomic, deep learning-derived, and handcrafted feature sets did not improve performance beyond the best individual model.
In conclusion, inspiratory and expiratory chest CT provide quantitative measures associated with spirometry-defined CAL in a population-based cohort. Expiratory CT was consistently more informative for discriminating CAL than inspiratory CT, supporting its value for assessing ventilation-related abnormalities and CAL-related lung changes relevant to early COPD. However, regression analyses showed that combinations of inspiratory and expiratory measures contributed to CAL classification, suggesting that the two respiratory phases provided complementary information. Automated lung lobe segmentation enabled scalable regional analysis, while lobar and radiomic approaches added information beyond whole-lung measures. Together, the findings support QCT as a complementary imaging-based approach for describing lung structure, regional heterogeneity, and CAL-related abnormalities in population-based research.