In vivo monitoring of cystic fibrosis-like lung disease in mice by volumetric computed tomography

Eur Respir J. 2011 Nov;38(5):1060-70. doi: 10.1183/09031936.00149810. Epub 2011 Apr 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Airway Obstruction / diagnostic imaging
  • Animals
  • Bronchography
  • Cone-Beam Computed Tomography*
  • Cystic Fibrosis / complications
  • Cystic Fibrosis / diagnostic imaging*
  • Cystic Fibrosis / pathology
  • Cystic Fibrosis / physiopathology
  • Disease Progression
  • Lung / diagnostic imaging*
  • Lung / pathology
  • Mice
  • Mice, Transgenic
  • Mucus
  • Pulmonary Emphysema / diagnostic imaging
  • Pulmonary Emphysema / etiology
  • Pulmonary Emphysema / physiopathology
  • Trachea / diagnostic imaging