Tuberc Respir Dis.  2009 Nov;67(5):436-444.

Utility of Micro CT in a Murine Model of Bleomycin-Induced Lung Fibrosis

• Lee JA
• Jin GY
• Bok SM
• Han YM
• Park SJ
• Lee YC
• Chung MJ
• Youn GH

Abstract

BACKGROUND
Micro computed tomography (CT) is rapidly developing as an imaging tool, especially for mice, which have become the experimental animal of choice for many pulmonary disease studies. We evaluated the usefulness of micro CT for evaluating lung fibrosis in the murine model of bleomycin-induced lung inflammation and fibrosis.
METHODS
The control mice (n=10) were treated with saline. The murine model of lung fibrosis (n=60) was established by administering bleomycin intra-tracheally. Among the 70 mice, only 20 mice had successful imaging analyses. We analyzed the micro CT and pathological findings and examined the correlation between imaging scoring in micro CT and histological scoring of pulmonary inflammation or fibrosis.
RESULTS
The control group showed normal findings on micro CT. The abnormal findings on micro CT performed at 3 weeks after the administration of bleomycin were ground-glass opacity (GGO) and consolidation. At 6 weeks after bleomycin administration, micro CT showed various patterns such as GGO, consolidation, bronchiectasis, small nodules, and reticular opacity. GGO (r=0.84) and consolidation (r=0.69) on micro CT were significantly correlated with histological scoring that reflected pulmonary inflammation (p<0.05). In addition, bronchiectasis (r=0.63) and reticular opacity (r=0.83) on micro CT shown at 6 weeks after bleomycin administration correlated with histological scoring that reflected lung fibrosis (p<0.05).
CONCLUSION
These results suggest that micro CT findings from a murine model of bleomycin-induced lung fibrosis reflect pathologic findings, and micro CT may be useful for predicting bleomycin-induced lung inflammation and fibrosis in mice.

Keyword

X-ray Microtomography, Bleomycin; Fibrosis; Mice

MeSH Terms

Animals
Bleomycin
Bronchiectasis
Fibrosis
Lung
Lung Diseases
Mice
Pneumonia
Bleomycin

Figure

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  Figure 1 Micro CT finding (A) and pathologic finding (B) of saline-treated mice. Both micro CT scan and lung tissue show normal findings (H&E stain, ×25).

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  Figure 2 Micro CT finding (A) and pathologic finding (B) of bleomycin-treated mice that is classified as small nodule according to the pattern of micro CT finding. Micro CT scanning and histological sampling were performed at 6 weeks after the administration of bleomycin solution. (A) Micro CT shows two small nodules (white arrow) in right lower lobe on micro CT. (B) Histological finding shows an aggregation of inflammatory cells (black arrow) with fibroblast around bronchus (H&E stain, ×25).

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  Figure 3 Micro CT finding (A) and pathologic finding (B) of bleomycin-treated mice that is classified as consolidation according to the pattern of micro CT finding. Micro CT scanning and histological sampling were performed at 3 weeks after the administration of bleomycin solution. (A) Micro CT shows the consolidation (white arrow) in left lower lobe. (B) Histological finding shows many inflammatory cells around bronchi, alveoli (black arrow), and alveolar septa (H&E stain, ×25).

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  Figure 4 Micro CT finding (A) and pathologic finding (B) of bleomycin-treated mice that show many patterns related with lung fibrosis on micro CT. Micro CT scanning and histological sampling were performed at 6 weeks after the administration of bleomycin solution. (A) Micro CT shows diffuse ground-glass opacity, reticular opacity (white arrow), bronchiolectasis, and small nodule in left lower lobe. (B) Histological finding shows dense collagen deposition and interstitial fibrosis (black arrow) (H&E stain, ×25).

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  Figure 5 Micro CT finding (A) and pathologic finding (B) of bleomycin-treated mice that have severe lung fibrosis. Micro CT scanning and histological sampling were performed at 6 weeks after the administration of bleomycin solution. (A) Micro CT shows diffuse ground-glass opacity with reticular pattern (white arrow) in left lower lobe. (B) Histological finding shows a reticular pattern (black arrow) due to severe interstitial fibrosis with destruction (H&E stain, ×25).

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  Figure 6 Correlation between imaging scoring (extent of lung with abnormal findings) in micro CT and histological scoring of pulmonary inflammation or fibrosis.

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