Manifold Integration of Lung Emphysema Signatures (MILES): A Radiomic-Based Study

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, and emphysema is present in the majority of affected patients and can be identified on computed tomography (CT). This study investigated whether radiomic features derived from automatically and adaptively segmented low-attenuation lung regions can capture distinct imaging characteristics of COPD beyond conventional emphysema measures. Radiomic features were extracted from 6078 chest CT scans of 2243 participants from the COPDGene cohort. Emphysematous regions were segmented using the MimSeg method based on Gaussian mixture modelling with patient-adjusted thresholding, and radiomic features were computed for individual lesion clusters and aggregated per patient using summary statistics, yielding 780 features per subject. Uniform Manifold Approximation and Projection (UMAP) was used to generate a low-dimensional embedding, and feature contributions were evaluated using SHAP analysis and statistical testing. The resulting embedding demonstrated structured patterns broadly aligned with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages, with greater overlap among GOLD 0–2 and more consolidated groupings for GOLD 3 and 4, reflecting differences in disease severity. The most influential features were predominantly derived from Grey Level Run Length Matrix measures, capturing textural heterogeneity and spatial organisation of emphysematous changes that are not directly described by standard density-based metrics. These findings suggest that radiomic analysis of adaptively segmented CT data may provide complementary and structurally distinct information relative to conventional emphysema measures, supporting a more nuanced characterisation of emphysema patterns in COPD.