Abstract
The onset and spontaneous development of cystic fibrosis (CF) lung disease remain poorly understood. In the present study, we used volumetric computed tomography (VCT) as a new method for longitudinal in vivo monitoring of early lesions and disease progression in CF-like lung disease in β-epithelial Na+ channel (ENaC)-transgenic (TG) mice.
Using a VCT scanner prototype (80 kV, 50 mA·s, scan time 19 s and spatial resolution 200 μm), βENaC-TG mice and wild-type (WT) littermates were examined longitudinally at 10 time-points from neonatal to adult ages, and VCT images were assessed by qualitative and quantitative morphological parameters.
We demonstrate that VCT detected early-onset airway mucus obstruction, diffuse infiltrates, atelectasis and air trapping as characteristic abnormalities in βENaC-TG mice. Furthermore, we show that early tracheal mucus obstruction predicted mortality in βENaC-TG mice and that the density of lung parenchyma was significantly reduced at all time-points in βENaC-TG compared with WT mice (median±sem -558±8 HU in WT versus -686±16 HU in βENaC-TG at 6 weeks of age; p<0.005).
Our study demonstrates that VCT is a sensitive, noninvasive technique for early detection and longitudinal monitoring of morphological abnormalities of CF-like lung disease in mice, and may thus provide a useful tool for pre-clinical in vivo evaluation of novel treatment strategies for CF.
- Computed tomography
- cystic fibrosis
- epithelial Na+ channel
- lung disease
- lung imaging
- transgenic mouse model
Footnotes
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Support Statement
This study was supported by the Deutsche Forschungsgemeinschaft (grant numbers DFG MA 2081/3-2 and MA 2081/4-1) and the European Commission (grant number MEXT-CT-2004-013666).
Statement of Interest
A statement of interest for M.A. Mall can be found at www.erj.ersjournals.com/site/misc/statements.xhtml
- Received September 23, 2010.
- Accepted March 20, 2011.
- ©ERS 2011