Semiquantitative measurement of murine bleomycin-induced lung fibrosis in in vivo and postmortem conditions using microcomputed tomography: correlation with pathologic scores--initial results.
ABSTRACT To evaluate whether the semiquantification of lung inflammation and fibrosis in murine bleomycin-induced lung fibrosis using micro-computed tomography (micro-CT) in in vivo and postmortem conditions is feasible, and to correlate micro-CT and pathologic scores.
Bleomycin-induced lung fibrosis was created by intratracheally instilling 3 mg/kg of bleomycin into C57BL/6 mice. Mice were allocated randomly to 2-week, 4-week, and 8-week follow-up groups. In each group, in vivo and follow-up postmortem micro-CT were performed using a voxel size of 35 x 35 x 35 microm. Ground-glass opacity (GGO), consolidation, parenchymal lines, honeycombing, and peripheral bronchial dilatation were scored on micro-CT images in a semiquantitative fashion, whereas inflammation and fibrosis were scored histopathologically. The confidence levels of micro-CT findings were also scored. Correlations between micro-CT and pathologic findings were examined using Spearman rank correlation analysis, and differences between CT scores and confidence levels for in vivo and postmortem micro-CT were subjected to Wilcoxon signed rank testing. Agreements between in vivo and postmortem micro-CT scores were tested using weighted kappa statistics.
Consolidation in vivo (r = 0.46) and at postmortem (r = 0.39) and GGO in vivo (r = 0.31) by micro-CT showed fair to moderate correlation with pathologic inflammation scores (P < 0.001). By in vivo and postmortem micro-CT, parenchymal lines (r = 0.72 vs. 0.83) showed good to excellent and peripheral bronchial dilatation (r = 0.47 vs. 0.68) showed moderate to good correlation with pathologic fibrosis scores (P < 0.001). For GGO, consolidation, peripheral bronchial dilatation, and parenchymal lines, fair to moderate agreement was obtained between in vivo and postmortem micro-CT. However, confidence levels for peripheral bronchial dilatation, parenchymal lines, and honeycombing were significantly higher by postmortem micro-CT (P < 0.001).
Micro-CT scores and pathologic scores were found to be well correlated by in vivo and postmortem micro-CT. Although agreements between in vivo and postmortem micro-CT were significant, the confidence levels for fibrosis-related CT findings were significantly higher by postmortem micro-CT.
Article: Micro-computed tomography of pulmonary fibrosis in mice induced by adenoviral gene transfer of biologically active transforming growth factor-β1.[show abstract] [hide abstract]
ABSTRACT: Micro-computed tomography (micro-CT) is a novel tool for monitoring acute and chronic disease states in small laboratory animals. Its value for assessing progressive lung fibrosis in mice has not been reported so far. Here we examined the importance of in vivo micro-CT as non-invasive tool to assess progression of pulmonary fibrosis in mice over time. Pulmonary fibrosis was induced in mice by intratracheal delivery of an adenoviral gene vector encoding biologically active TGF-β1 (AdTGF-β1). Respiratory gated and ungated micro-CT scans were performed at 1, 2, 3, and 4 weeks post pulmonary adenoviral gene or control vector delivery, and were then correlated with respective histopathology-based Ashcroft scoring of pulmonary fibrosis in mice. Visual assessment of image quality and consolidation was performed by 3 observers and a semi-automated quantification algorithm was applied to quantify aerated pulmonary volume as an inverse surrogate marker for pulmonary fibrosis. We found a significant correlation between classical Ashcroft scoring and micro-CT assessment using both visual assessment and the semi-automated quantification algorithm. Pulmonary fibrosis could be clearly detected in micro-CT, image quality values were higher for respiratory gated exams, although differences were not significant. For assessment of fibrosis no significant difference between respiratory gated and ungated exams was observed. Together, we show that micro-CT is a powerful tool to assess pulmonary fibrosis in mice, using both visual assessment and semi-automated quantification algorithms. These data may be important in view of pre-clinical pharmacologic interventions for the treatment of lung fibrosis in small laboratory animals.Respiratory research 01/2010; 11:181. · 3.36 Impact Factor