Magnetic resonance imaging of disease progression and resolution in a transgenic mouse model of pulmonary fibrosis

We examined the ability of magnetic resonance imaging (MRI) to noninvasively assess lung fibrosis progression and resolution in a doxycycline (Dox) regulatable, transgenic mouse model that overexpresses transforming growth factor-α (TGF-α) under control of a lung-epithelial-specific promoter. During 7 wk of Dox treatment, fibrotic lesions were readily observed as high-signal tissue. Mean weighted signal and percent signal volume were found to be the most robust MRI-derived measures of fibrosis, and these metrics correlated significantly with pleural thickness, histology scores, and hydroxyproline content (R = 0.75–0.89). When applied longitudinally, percent high signal volume increased by 1.5% wk–1 (P < 0.001) and mean weighted signal increased at a rate of 0.0065 wk–1 (P = 0.0062). Following Dox treatment, lesions partially resolved, with percent high signal volume decreasing by –3.2% wk–1 (P = 0.0034) and weighted mean signal decreasing at –0.015 wk–1 (P = 0.0028). Additionally, longitudinal MRI revealed dynamic remodeling in a subset of lesions, a previously unobserved behavior in this model. These results demonstrate MRI can noninvasively assess experimental lung fibrosis progression and resolution and provide unique insights into its pathobiology.
Source: AJP: Lung Cellular and Molecular Physiology - Category: Respiratory Medicine Authors: Tags: RESEARCH ARTICLE Source Type: research