Target lung tissue selection remains a challenging task to perform for treating severe emphysema with lung volume reduction (LVR). In order to target the treatment candidate, the percentage of low attenuation volume (LAV%) representing the proportion of emphysema volume to whole lung volume is measured using computed tomography (CT) images. Although LAV% have shown to have a correlation with lung function in patients with chronic obstructive pulmonary disease (COPD), similar measurements of LAV% in whole lung or lobes may have large variations in lung function due to emphysema heterogeneity. The functional information of regional emphysema destruction is required for supporting the choice of optimal target. The purpose of this study is to develop an emphysema heterogeneity descriptor for the three-dimensional emphysematous bullae according to the size variations of emphysematous density (ED) and their spatial distribution. The second purpose is to derive a predictive model of airflow limitation based on the regional emphysema heterogeneity. Deriving the bullous representation and grouping them into four scales in the upper and lower lobes, a predictive model is computed using the linear model fitting to estimate the severity of lung function. A total of 99 subjects, 87 patients with mild to very severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I~IV) and 12 control participants with normal lung functions (forced expiratory volume in one second (FEV₁)/forced vital capacity (FVC) > 0.7) were evaluated. The final model was trained with stratified cross-validation on randomly selected 75% of the dataset (n = 76) and tested on the remaining dataset (n = 23). The dispersed cases of LAV% inconsistent with their lung function outcome were evaluated, and the correlation study suggests that comparing to LAV of larger bullae, the widely spread smaller bullae with equivalent LAV has a larger impact on lung function. The testing dataset has the correlation of r = -0.76 (p < 0.01) between the whole lung LAV% and FEV₁/FVC, whereas using two ED % of scales and location-dependent variables to predict the emphysema-associated FEV₁/FVC, the results shows their correlation of 0.82 (p < 0.001) with clinical FEV₁/FVC.

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