期刊
EUROPEAN RESPIRATORY JOURNAL
卷 38, 期 5, 页码 1060-1070出版社
EUROPEAN RESPIRATORY SOC JOURNALS LTD
DOI: 10.1183/09031936.00149810
关键词
Computed tomography; cystic fibrosis; epithelial Na+ channel; lung disease; lung imaging; transgenic mouse model
资金
- Deutsche Forschungsgemeinschaft [DFG MA 2081/3-2, MA 2081/4-1]
- European Commission [MEXT-CT-2004-013666]
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 beta-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 mm), beta ENaC-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 beta ENaC-TG mice. Furthermore, we show that early tracheal mucus obstruction predicted mortality in beta ENaC-TG mice and that the density of lung parenchyma was significantly reduced at all time-points in beta ENaC-TG compared with WT mice (median+/-SEM -558+/-8 HUinWT versus -686+/-16 HU in beta ENaC-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.
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