Quantitative measurement of bleomycin-induced lung fibrosis in rabbits using sequential in vivo regional analysis and high-resolution computed tomography: correlation with pathologic findings

Abstract

Rationale and objectives: To examine the feasibility of quantitative high-resolution computed tomography (HRCT) findings to monitor the stage of bleomycin-induced pulmonary fibrosis in rabbits by correlating HRCT and pathologic scores and analyzing sequential changes on HRCT images using regional volume histograms.

Materials and methods: Lung fibrosis was induced by injecting bleomycin intratracheally into 23 Japanese white rabbits. Rabbits were randomly separated into seven groups depending on follow-up period (12-hour, 24-hour, 3-day, 7-day, 14-day, 21-day, and 28-day). Four-row HRCT examinations were performed at any of the seven time points in each follow-up period and just after bleomycin administration in addition to pre-bleomycin administration as the baseline scan. Scores of consolidation, homogenous ground-glass opacity (GGO), inhomogeneous GGO, reticulolinear shadow, and honey-comb formation were recorded as ratio of affected area to total cross-section in four transaxial planes. Inflammatory and fibrous changes were scored histopathologically. Correlations between HRCT and pathologic findings were assessed. Sequential changes on HRCT images in areas with pathologically confirmed fibrosis were assessed on volume histograms of cubic regions of interest (ROI) using quantitative parameters.

Results: Consolidation and inhomogeneous GGO exhibited fair correlations with inflammation scores (r = 0.273, P = .009, and r = 0.393, P < .001); reticulolinear shadow and inhomogeneous GGO had a fair and good correlation, respectively, with fibrous scores (r = 0.327, P = .001, and r = 0.579, P < .001). Inhomogeneous GGO was hardly detected on regional images at 21 and 28 days after bleomycin administration. As to mean computed tomography attenuation, skewness, and kurtosis, inhomogeneous GGO differed from reticulolinear shadow and consolidation.

Conclusion: Using appropriate ROI settings, quantitative assessment of inhomogeneous GGO with regional volume histograms enables us to monitor the progression of lung fibrosis by sequential observations.