Persistent homology analysis of longitudinal CT fibrotic features in COPD

Backgrounds Fibrosis may coexist with emphysema in chronic obstructive pulmonary disease (COPD), but computed tomography (CT) quantification is challenging. Persistent homology (PH), a topological data analysis technique, provides interpretable structural features in grayscale images. By using PH, this CT study aimed to quantify fibrotic lesions in nonemphysematous and emphysematous lungs and to investigate clinical implications of PH-based fibrosis quantification in patients with COPD. Methods The study included subjects from the Lung Cancer Screening (LCS) cohort (n=346) and two prospective COPD cohorts (Kyoto University KU, n=234; Kyoto-Himeji, n=166). Based on CT value patterns and spatial topology, PH assigned each voxel as fibrotic or non-fibrotic and calculated the percentage of fibrotic lung volume (PH-fibrosis%) in association with visually identified interstitial lung abnormality (ILA) and COPD outcomes. Results Higher PH-fibrosis% was associated with ILAs in the LCS and KU cohorts. The two COPD cohorts consistently showed significant associations between higher baseline PH-fibrosis% and future exacerbation risk independent of emphysema and airway wall thickness (hazard ratios HR: 1.39 and 3.35 for KU and Kyoto-Himeji, respectively). In the KU cohort, higher PH-fibrosis% was significantly associated with increased mortality (HR: 1.94), with a similar trend in the Kyoto-Himeji cohort (HR: 1.86). Longitudinal increases in PH-fibrosis% over median 4.98 years were associated with higher exacerbation frequency and patients experiencing greater increase in PH-fibrosis% subsequently exhibited higher mortality in the KU cohort. Conclusions PH can be used to quantify fibrotic lesions on CT and PH-fibrosis% could be a prognostic imaging marker in patients with COPD.