Quantitative assessment of pulmonary vascular alterations in chronic obstructive lung disease: Associations with pulmonary function test and survival in the KOLD cohort

Purpose: Despite the high prevalence of pulmonary vascular alterations and their substantial impact on chronic obstructive pulmonary disease (COPD), tools for the direct in vivo assessment of pulmonary vascular alterations remain limited. Thus, the purpose of this study was to automatically extract pulmonary vessels from volumetric chest CT and evaluate the associations between the derived quantitative pulmonary vessel features and clinical parameters, including survival, in COPD patients. Methods: This study included 344 adult COPD patients. Pulmonary vessels were automatically extracted from volumetric chest CT data. Quantitative pulmonary vessel features were obtained from various lung surface areas (LSAs), which are theoretical surface areas drawn at different depths from the pleural borders. The total number of vessels (N-total) and number of vessels with vessel area (VA) less than 5 mm(2) (N (<) (5mm)) were counted as both robust values and as values per 10 cm(2) of LSA (N-total/LSA; N (< 5mm)/LSA). The average VA (VA(mean)) and percentage of measured VA in the corresponding LSA (%VA) were measured. Associations between quantitative pulmonary vessel features and clinical parameters, including survival and the pulmonary function test (PFT), were evaluated. Results: The pulmonary vessels were automatically extracted with 100% technical success. Cox regression analysis showed N-total/LSA, N (< 5mm)/LSA, VA(mean), and %VA to be significant predictors of survival (hazard ratio (HR), 0.80, 0.75, 0.70, 0.49, respectively). Patients classified into high-risk groups by %VA(18mm) (cut-off = 3.258), chosen because it demonstrated the strongest statistical influence on survival in a univariate Cox analysis, were associated with worse overall survival before (HR, 4.83; p < 0.001) and after adjustment for patient age and BMI (HR, 2.18; p = 0.014). Of the quantitative pulmonary vessel features, N-total/LSA, N (< 5mm)/LSA, and %VA were correlated with FEV1, FEV1/FVC, and DLCO in all LSAs. The strongest correlation with PFTs was noted at LSA(9mm) for both N-total (FEV1, r = 0.33; FEV1/FVC, r = 0.51) and N (<) (5mm) (FEV1, r = 0.35; FEV1/FVC, r = 0.52). For %VA, the association was most evident at LSA(18mm) (FEV1, r = 0.27; FEV1/FVC, r = 0.47). Significant moderate to strong correlations were consistently observed between the extent of emphysema and quantitative pulmonary vessel features (r = 0.44-0.66; all p < 0.001). Conclusions: The automated extraction of pulmonary vessels and their quantitative assessment are technically feasible. Various quantitative pulmonary vessel features demonstrated significant relationships with survival and PFT in COPD patients. Of the various quantitative features, the percentage of total VA measured at 18 mm depth from the pleural surface (%VA(18mm)) and the number of small vessels counted per 10 cm(2) of LSA at 9 mm depth from the pleural surface (N (< 5mm)/LSA(9mm)) had the strongest predictability for the clinical parameters.