Noninvasive assessment of bleomycin-induced lung injury and the effects of short-term glucocorticosteroid treatment in rats using MRI

Abstract

Purpose: 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. Materials and 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. Conclusion: 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. © 2011 Wiley-Liss, Inc.