Evaluation of Progressive Architectural Distortion in Idiopathic Pulmonary Fibrosis Using Deformable Registration of Sequential CT Images

Abstract

Background: Monitoring the progression of idiopathic pulmonary fibrosis (IPF) using CT primarily focuses on assessing the extent of fibrotic lesions, without considering the distortion of lung architecture.

Objectives: To evaluate three-dimensional average displacement (3D-AD) quantification of lung structures using deformable registration of serial CT images as a parameter of local lung architectural distortion and predictor of IPF prognosis.

Materials and methods: Patients with IPF evaluated between January 2016 and March 2017 who had undergone CT at least twice were retrospectively included (n = 114). The 3D-AD was obtained by deformable registration of baseline and follow-up CT images. A computer-aided quantification software measured the fibrotic lesion volume. Cox regression analysis evaluated these variables to predict mortality.

Results: The 3D-AD and the fibrotic lesion volume change were significantly larger in the subpleural lung region (5.2 mm (interquartile range (IQR): 3.6-7.1 mm) and 0.70% (IQR: 0.22-1.60%), respectively) than those in the inner region (4.7 mm (IQR: 3.0-6.4 mm) and 0.21% (IQR: 0.004-1.12%), respectively). Multivariable logistic analysis revealed that subpleural region 3D-AD and fibrotic lesion volume change were independent predictors of mortality (hazard ratio: 1.12 and 1.23; 95% confidence interval: 1.02-1.22 and 1.10-1.38; p = 0.01 and p < 0.001, respectively).

Conclusions: The 3D-AD quantification derived from deformable registration of serial CT images serves as a marker of lung architectural distortion and a prognostic predictor in patients with IPF.

Keywords: computed tomography; deformable image registration; idiopathic pulmonary fibrosis; progressive pulmonary fibrosis; three-dimensional average displacement.

Figure 1

Flowchart of the study population selection and exclusion criteria. IPF, idiopathic pulmonary fibrosis. * Other idiopathic interstitial pneumonias include cryptogenic organizing pneumonias and interstitial pneumonia with autoimmune features.

Figure 2

Creation of the three-dimensional average displacement (3D-AD) color map. Following the rigid registration of the initial and follow-up computed tomography (CT) images, follow-up CT images were deformably registered to match initial CT images with extracted landmarks, such as bones, large vessels, bronchial trees, and peripheral pulmonary vessels. Deformable registration was performed to overlap these paired landmarks completely. The 3D-AD of each pixel was calculated and shown as a 3D-AD color map. The color bar indicates the range of displacement.

Figure 3

Computed tomography (CT) images of a 69-year-old man with idiopathic pulmonary fibrosis and three-dimensional average displacement (3D-AD) color maps. (a) Initial CT image of the lung base showed mild subpleural reticulation. (b) Follow-up CT image of the lung base after one year shows increased subpleural reticulation. The fissure deviated backward, indicating the decreased lower lobe volume (thick arrows). The distance between the peripheral bronchi (arrows) and pleura also decreased (yellow lines). (c,d) Color map of the 3D-AD demonstrates greater deviation (red in the color map), corresponding to the subpleural reticulation in the original CT images. In this case, 3D-AD in the subpleural/inner region = 7.4 mm/7.2 mm.

Figure 4

Computed tomography (CT) images of a 68-year-old man with idiopathic pulmonary fibrosis and three-dimensional average displacement (3D-AD) color maps. (a) Initial CT image shows subpleural reticulation in the lung base. (b) Follow-up CT image after one year shows an increase in subpleural reticulations predominantly in the posterior areas of the left lung base. (c,d) Color map of the 3D-AD shows a greater deviation (red in the color map) in the posterior areas of the left lung base (white arrow), corresponding to the original CT images. In this case, 3D-AD in the whole lung/lower lobe of the left lung = 5.9 mm/14 mm.

Figure 5

Computed tomography (CT) images of a 77-year-old man with idiopathic pulmonary fibrosis and three-dimensional average displacement (3D-AD) color maps. (a) Initial CT image of the lung base showed subpleural interstitial abnormality. (b) Follow-up CT image after one year shows a little increase of subpleural lesions in the posterior areas of the right lung base. (c) Follow-up CT image after two years shows obvious progression of fibrosis at the lung base. (d,e) The 3D-AD color map shows yellow scale in the posterior areas of the right lung base. (f,g) Color map of the 3D-AD shows a greater deviation (red in the color map) observed. Local displacement of peripheral structures is evident before lung abnormalities and lung volume loss are clearly visible at the follow-up CT.

Figure 6

Graphs show Kaplan–Meier distribution of survival time. Comparison between two groups on the basis of 3D-AD (3D-AD ≥ 4.29 mm and 3D-AD < 4.29 mm; Log-rank p < 0.001).