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Open Access Research

Micro-computed tomography of pulmonary fibrosis in mice induced by adenoviral gene transfer of biologically active transforming growth factor-β1

Thomas Rodt12*, Christian von Falck12, Sabine Dettmer1, Roman Halter2, Regina Maus3, Kjetil Ask4, Martin Kolb4, Jack Gauldie4, Florian Länger5, Ludwig Hoy6, Tobias Welte7, Michael Galanski1, Ulrich A Maus3 and Jürgen Borlak2

Author Affiliations

1 Department of Radiology, Hannover Medical School, Hannover, Germany

2 Department of Molecular Medicine and Medical Biotechnology, Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover Germany

3 Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany

4 Department of Medicine, Pathology and Molecular Medicine, McMaster University, Hamilton, Canada

5 Institute of Pathology, Hannover Medical School, Hannover, Germany

6 Institute of Biometry, Hannover Medical School, Hannover, Germany

7 Clinic for Pneumology, Hannover Medical School, Hannover, Germany

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Respiratory Research 2010, 11:181  doi:10.1186/1465-9921-11-181

Published: 22 December 2010

Abstract

Background

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.

Methods

Pulmonary fibrosis was induced in mice by intratracheal delivery of an adenoviral gene vector encoding biologically active TGF-ß1 (AdTGF-ß1). 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.

Results

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.

Conclusions

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.