title: In vivo monitoring of cystic fibrosis-like lung disease in mice by volumetric computed tomography.
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.
authors.affiliation: Dept of Radiology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: M O
authors.initials: MO
authors.lastname: Wielpütz
authors.forename: M
authors.initials: M
authors.lastname: Eichinger
authors.forename: Z
authors.initials: Z
authors.lastname: Zhou
authors.forename: K
authors.initials: K
authors.lastname: Leotta
authors.forename: S
authors.initials: S
authors.lastname: Hirtz
authors.forename: S H
authors.initials: SH
authors.lastname: Bartling
authors.forename: W
authors.initials: W
authors.lastname: Semmler
authors.forename: H-U
authors.initials: HU
authors.lastname: Kauczor
authors.forename: M
authors.initials: M
authors.lastname: Puderbach
authors.forename: M A
authors.initials: MA
authors.lastname: Mall
mesh_terms: D000402:Airway Obstruction / Q000000981:diagnostic imaging; D000818:Animals; D001995:Bronchography; D054893:Cone-Beam Computed Tomography; D003550:Cystic Fibrosis / Q000150:complications / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D008168:Lung / Q000000981:diagnostic imaging* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009093:Mucus; D011656:Pulmonary Emphysema / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology; D014132:Trachea / Q000000981:diagnostic imaging