CT-derived Biomechanical Metrics Improve Agreement Between Spirometry and Emphysema

Abstract

Rationale and objectives: Many patients with chronic obstructive pulmonary disease (COPD) have marked discordance between forced expiratory volume in 1 second (FEV1) and degree of emphysema on computed tomography (CT). Biomechanical differences between these patients have not been studied. We aimed to identify reasons for the discordance between CT and spirometry in some patients with COPD.

Materials and methods: Subjects with Global initiative for chronic Obstructive Lung Disease stages I-IV from a large multicenter study (The Genetic Epidemiology of COPD) were arranged by percentiles of %predicted FEV1 and emphysema on CT. Three categories were created using differences in percentiles: Catspir with predominant airflow obstruction/minimal emphysema, CatCT with predominant emphysema/minimal airflow obstruction, and Catmatched with matched FEV1 and emphysema. Image registration was used to derive Jacobian determinants, a measure of lung elasticity, anisotropy, and strain tensors, to assess biomechanical differences between groups. Regression models were created with the previously mentioned categories as outcome variable, adjusting for demographics, scanner type, quantitative CT-derived emphysema, gas trapping, and airway thickness (model 1), and after adding biomechanical CT metrics (model 2).

Results: Jacobian determinants, anisotropy, and strain tensors were strongly associated with FEV1. With Catmatched as control, model 2 predicted Catspir and CatCT better than model 1 (Akaike information criterion 255.8 vs. 320.8). In addition to demographics, the strongest independent predictors of FEV1 were Jacobian mean (β = 1.60,95%confidence intervals [CI] = 1.16 to 1.98; P < 0.001), coefficient of variation (CV) of Jacobian (β = 1.45,95%CI = 0.86 to 2.03; P < 0.001), and CV of strain (β = 1.82,95%CI = 0.68 to 2.95; P = 0.001). CVs of Jacobian and strain are both potential markers of biomechanical lung heterogeneity.

Conclusions: CT-derived measures of lung mechanics improve the link between quantitative CT and spirometry, offering the potential for new insights into the linkage between regional parenchymal destruction and global decrement in lung function in patients with COPD.

Trial registration: ClinicalTrials.gov NCT00608764.

Keywords: COPD; Emphysema; discordance; spirometry.

Figure 1

Panel A shows computed tomographic (CT) images for subject with severe airflow obstruction (FEV₁ %predicted 32.6) but with relatively minimal emphysema (1.5% volume <−950HU on end inspiratory images). Panel B shows features for subject with severe emphysema on CT (20.8%) but with relatively minimal airflow obstruction (FEV₁ %predicted 99.6). Top row represents the overlay of emphysema voxels on the CT images. Middle row represents the overlay of Jacobian color map on the CT images from each category. Jacobian value (=1) represents no deformation; >1 represents local expansion; <1 local contraction. Bottom row represents 3D visualization of emphysema voxels in each category with flow volume loop.