• M O Wielpütz, M Eichinger, Z Zhou, K Leotta, S Hirtz, S H Bartling, W Semmler, H-U Kauczor, M Puderbach, and M A Mall.
• Dept of Radiology, German Cancer Research Center, Heidelberg, Germany.
• Eur. Respir. J. 2011 Nov 1;38(5):1060-70.

AbstractThe 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.

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