Three-dimensional CT imaging in an animal model of emphysema

¹ Dept of Pathology and Molecular Medicine, Center for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada
² Dept of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, Ontario, Canada
³ Dept of Nuclear Medicine, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada
⁴ Developmental Biology Program, Saban Research Institute, Children's Hospital Los Angeles, University of Southern California
⁵ Dept of Pathology and Molecular Medicine, Center for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada; and Dept of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, Ontario, Canada

^* To whom correspondence should be addressed. E-mail: kolbm{at}mcmaster.ca.

	Abstract

Emphysema is a major health problem and novel drugs are needed. Animal disease models are pivotal in their development, but validity and sensitivity of current tools to evaluate drug efficacy are limited. We investigated the usefulness of micro computed tomography (CT) as an innovative tool to assess emphysema in a mouse model.

Serial CT was performed in two-weekly intervals in Smad 3 knockout (KO) mice, which spontaneously develop airspace enlargement. Lung density was quantified in 2D and 3D images and correlated to mean linear intercept and lung compliance.

CT-scans of Smad3 KO lungs revealed a significant decrease in lung density at 8 weeks age and progression towards 14 weeks with respect to age matched wildtype (WT) animals. Emphysema could be reliably assessed with both the 2D and 3D approach, but 3D was superior due to normalization to lung volumes and less variability. Lung compliance by week 14 was 0.053 +/- 0.005 and 0.034 +/- 0.002 % max vol/cmH₂O for KO and WT mice (p<0.007), reflecting physiologically relevant emphysema.

Small animal CT-imaging and density quantification in a reconstructed 3D image is a useful tool to quantify emphysematous changes in an animal disease model. It adds significant information to conventional assessment.

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