title: Micro-computed tomography of pulmonary fibrosis in mice induced by adenoviral gene transfer of biologically active transforming growth factor-β1.
abstract: BACKGROUND
  Micro-computed tomography (micro-CT) is a novel tool for monitoring acute and chronic disease states in small laboratory animals. Its value for assessing progressive lung fibrosis in mice has not been reported so far. Here we examined the importance of in vivo micro-CT as non-invasive tool to assess progression of pulmonary fibrosis in mice over time.
  
  
  METHODS
  Pulmonary fibrosis was induced in mice by intratracheal delivery of an adenoviral gene vector encoding biologically active TGF-β1 (AdTGF-β1). Respiratory gated and ungated micro-CT scans were performed at 1, 2, 3, and 4 weeks post pulmonary adenoviral gene or control vector delivery, and were then correlated with respective histopathology-based Ashcroft scoring of pulmonary fibrosis in mice. Visual assessment of image quality and consolidation was performed by 3 observers and a semi-automated quantification algorithm was applied to quantify aerated pulmonary volume as an inverse surrogate marker for pulmonary fibrosis.
  
  
  RESULTS
  We found a significant correlation between classical Ashcroft scoring and micro-CT assessment using both visual assessment and the semi-automated quantification algorithm. Pulmonary fibrosis could be clearly detected in micro-CT, image quality values were higher for respiratory gated exams, although differences were not significant. For assessment of fibrosis no significant difference between respiratory gated and ungated exams was observed.
  
  
  CONCLUSIONS
  Together, we show that micro-CT is a powerful tool to assess pulmonary fibrosis in mice, using both visual assessment and semi-automated quantification algorithms. These data may be important in view of pre-clinical pharmacologic interventions for the treatment of lung fibrosis in small laboratory animals.
authors.affiliation: Department of Radiology, Hannover Medical School, Hannover, Germany. rodt.thomas@mh-hannover.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Rodt
authors.forename: Christian
authors.initials: C
authors.lastname: von Falck
authors.forename: Sabine
authors.initials: S
authors.lastname: Dettmer
authors.forename: Roman
authors.initials: R
authors.lastname: Halter
authors.forename: Regina
authors.initials: R
authors.lastname: Maus
authors.forename: Kjetil
authors.initials: K
authors.lastname: Ask
authors.forename: Martin
authors.initials: M
authors.lastname: Kolb
authors.forename: Jack
authors.initials: J
authors.lastname: Gauldie
authors.forename: Florian
authors.initials: F
authors.lastname: Länger
authors.forename: Ludwig
authors.initials: L
authors.lastname: Hoy
authors.forename: Tobias
authors.initials: T
authors.lastname: Welte
authors.forename: Michael
authors.initials: M
authors.lastname: Galanski
authors.forename: Ulrich A
authors.initials: UA
authors.lastname: Maus
authors.forename: Jürgen
authors.initials: J
authors.lastname: Borlak
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D005260:Female; D008168:Lung / Q000000981:diagnostic imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000000981:diagnostic imaging* / Q000235:genetics / Q000662:veterinary*; D012680:Sensitivity and Specificity; D014057:Tomography, X-Ray Computed / Q000662:veterinary*; D014162:Transfection / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D016212:Transforming Growth Factor beta