title: Noninvasive assessment of bleomycin-induced lung injury and the effects of short-term glucocorticosteroid treatment in rats using MRI.
abstract: OBJECTIVE
  To demonstrate the feasibility of proton MRI to noninvasively quantify bleomycin-induced injury and the effects of glucocorticosteroids in a rat model of lung fibrosis.
  
  
  METHODS
  Sprague-Dawley rats received bleomycin intra-tracheally and underwent MRI up to day 70 following injury onset. A subgroup of animals was treated with budesonide.
  
  
  RESULTS
  The response in the first 2 weeks post-bleomycin, characterized by diffuse MRI signals, was related primarily to inflammation as confirmed by histology. Later, increased signals reflected principally tissue remodeling involved in fibrosis development, as suggested by histological analysis revealing collagen deposition in the same areas where MRI signals had been detected. Budesonide administration at days 6 and 13 after bleomycin resulted in decreased MRI signals 24 h after each corticosteroid application. However, no complete signal resolution was observed. Histology showed that budesonide affected inflammation but not fibrosis.
  
  
  CONCLUSIONS
  The ability of MRI to noninvasively quantify lung injury in bleomycin-treated rats will facilitate in vivo pharmacological studies in this model of pulmonary fibrosis. Repetitive measurements open new avenues in testing compounds as the responses at several time points during the course of treatment can be easily compared. Specifically, studies at the chronic phase, when fibrosis is already established, become amenable.
authors.affiliation: Global Imaging Group Novartis Institutes for BioMedical Research, CH-4056 Basel, Switzerland.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Babin
authors.forename: Catherine
authors.initials: C
authors.lastname: Cannet
authors.forename: Christelle
authors.initials: C
authors.lastname: Gérard
authors.forename: Daniel
authors.initials: D
authors.lastname: Wyss
authors.forename: Clive P
authors.initials: CP
authors.lastname: Page
authors.forename: Nicolau
authors.initials: N
authors.lastname: Beckmann
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects; D001761:Bleomycin / Q000009:adverse effects*; D019819:Budesonide / Q000009:adverse effects; D003094:Collagen / Q000737:chemistry; D005355:Fibrosis / Q000139:chemically induced* / Q000473:pathology; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects*; D055370:Lung Injury / Q000139:chemically induced*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000903:Antibiotics, Antineoplastic; D005938:Glucocorticoids; D001761:Bleomycin; D019819:Budesonide; D003094:Collagen