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

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 bnormal 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.

keywords: X-ray Microtomography, Bleomycin, Fibrosis, Mice

Reference

Gross TJ, Hunninghake GW. Idiopathic pulmonary fibrosis. N Engl J Med 2001;345:517-25.

Moeller A, Ask K, Warburton D, Gauldie J, Kolb M. The bleomycin animal model: a useful tool to investigate treatment options for idiopathic pulmonary fibrosis? Int J Biochem Cell Biol 2008;40:362-82.

Sleijfer S. Bleomycin-induced pneumonitis. Chest 2001;120:617-24.

Ritman EL. Micro-computed tomography of the lungs and pulmonary-vascular system. Proc Am Thorac Soc 2005;2:477-80, 501.

Ritman EL. Micro-computed tomography-current status and developments. Annu Rev Biomed Eng 2004;6:185-208.

Johnson KA. Imaging techniques for small animal imaging models of pulmonary disease: micro-CT. Toxicol Pathol 2007;35:59-64.

Lee HJ, Goo JM, Kim NR, Kim MA, Chung DH, Son KR, et al. Semiquantitative measurement of murine bleomycin-induced lung fibrosis in in vivo and postmortem conditions using microcomputed tomography: correlation with pathologic scores--initial results. Invest Radiol 2008;43:453-60.

Cavanaugh D, Travis EL, Price RE, Gladish G, White RA, Wang M, et al. Quantification of bleomycin-induced murine lung damage in vivo with micro-computed tomography. Acad Radiol 2006;13:1505-12.

Genovese T, Cuzzocrea S, Di Paola R, Mazzon E, Mastruzzo C, Catalano P, et al. Effect of rosiglitazone and 15-deoxy-Delta12, 14-prostaglandin J2 on bleomycin- induced lung injury. Eur Respir J 2005;25:225-34.

10.

Ashcroft T, Simpson JM, Timbrell V. Simple method of estimating severity of pulmonary fibrosis on a numerical scale. J Clin Pathol 1988;41:467-70.

11.

Langheinrich AC, Leithäuser B, Greschus S, Von Gerlach S, Breithecker A, Matthias FR, et al. Acute rat lung injury: feasibility of assessment with micro-CT. Radiology 2004;233:165-71.

12.

Ford NL, Wheatley AR, Holdsworth DW, Drangova M. Optimization of a retrospective technique for respiratory- gated high speed micro-CT of free-breathing rodents. Phys Med Biol 2007;52:5749-69.

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Article Contents

Vol.67 No.5

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

Abstract

Reference

Tuberculosis & Respiratory Diseases