Spirometric assessment of emphysema presence and severity as measured by quantitative CT and CT-based radiomics in COPD

Abstract

Background: The mechanisms underlying airflow obstruction in COPD cannot be distinguished by standard spirometry. We ascertain whether mathematical modeling of airway biomechanical properties, as assessed from spirometry, could provide estimates of emphysema presence and severity, as quantified by computed tomography (CT) metrics and CT-based radiomics.

Methods: We quantified presence and severity of emphysema by standard CT metrics (VIDA) and co-registration analysis (ImbioLDA) of inspiratory-expiratory CT in 194 COPD patients who underwent pulmonary function testing. According to percentages of low attenuation area below - 950 Hounsfield Units (%LAA_-950insp) patients were classified as having no emphysema (NE) with %LAA_-950insp < 6, moderate emphysema (ME) with %LAA_-950insp ≥ 6 and < 14, and severe emphysema (SE) with %LAA_-950insp ≥ 14. We also obtained stratified clusters of emphysema CT features by an automated unsupervised radiomics approach (CALIPER). An emphysema severity index (ESI), derived from mathematical modeling of the maximum expiratory flow-volume curve descending limb, was compared with pulmonary function data and the three CT classifications of emphysema presence and severity as derived from CT metrics and radiomics.

Results: ESI mean values and pulmonary function data differed significantly in the subgroups with different emphysema degree classified by VIDA, ImbioLDA and CALIPER (p < 0.001 by ANOVA). ESI differentiated NE from ME/SE CT-classified patients (sensitivity 0.80, specificity 0.85, AUC 0.86) and SE from ME CT-classified patients (sensitivity 0.82, specificity 0.87, AUC 0.88).

Conclusions: Presence and severity of emphysema in patients with COPD, as quantified by CT metrics and radiomics can be estimated by mathematical modeling of airway function as derived from standard spirometry.

Keywords: Area under curve; COPD; Pulmonary emphysema; Radiomics; Respiratory function tests; Small airway disease; Spirometry; Tomography.

Fig. 1

Lung parenchyma representations at CT scan after post-processing with different software programs in a patient with severe emphysema. a. Axial CT scan shows advanced destructive emphysema with a giant bulla in the right lower lobe adjacent to an area of passive atelectasis. b. Volume rendering of the densitometric analysis performed by VIDA shows the location and severity of emphysema at inspiratory scan (threshold -950HU) displaying spheres whose diameter is proportional to the relative volume of emphysema in each region. c-d. Coronal and Sagittal 2D images obtained by co-registration of inspiratory and expiratory CT scans by Imbio LDA show the location of emphysema (red), functional airways gas trapping (yellow), and normal lung (green). e. Volume rendering of the lung texture analysis performed by CALIPER shows the 3D distribution of the different lung patterns, including Normal (dark green), Mild Low Attenuation Area (LAA, light green), Moderate LAA (light blue), Severe LAA (dark blue), Ground-glass (yellow), Reticular (orange). The glyph f provided by CALIPER summarizes the location and amount of the different lung patterns. The overall area of the glyph represents the computed total lung volume, the partitions with thick radial lines illustrate the relative volumes of the left (L) and right (R) lungs, which are further divided with thin radial lines into three regions, each representing the upper (U), middle (M), lower (L) lung zones. In this patient severe LAA dominates in the right lower and middle lung zones, whereas middle and lower left zones are characterized by mild and moderate LAA

Fig. 2

The three clusters of COPD patients stratified represented as glyphs. Clusters (G1 to G3) were the result of quantitative unsupervised clustering based on a dissimilarity matrix that captures the distribution of classified parenchymal patterns recognized by CALIPER. G1 was characterized by predominant Normal (dark green) and Mild LAA (light green) patterns, whereas G2 by predominant Moderate LAA (light blue) pattern and G3 by predominant Severe (dark blue) and Moderate LAA (light blue) patterns

Fig. 3

ROC curve over the range of the ESI model output for severe emphysema a and no emphysema b. Severe emphysema was defined at CT scan as %LAA_-950insp ≥ 14 by VIDA whereas no emphysema was defined at CT scan as %LAA_-950insp < 6 by VIDA. The total AUC area was of 0.88 for severe emphysema and 0.86 for no emphysema

Fig. 4

Maximal expiratory flow-volume curves of two representative subjects with severe emphysema or no emphysema. Patient with severe emphysema (left panel) had %LAA_-950insp = 24 whereas the patient with no emphysema (right panel) had %LAA_-950insp = 4 at CT. Note the flatter slope in the former when flow was plotted against expired volume (black lines) but not pletysmographic thoracic volume (grey lines), indicating greater thoracic gas compression at high-to-mid lung volumes