Longitudinal assessment of lung fibrosis by micro CT correlates with histological evaluation in bleomycin-induced mice

Abstract

Introduction Intratracheal bleomycin instillation in mice induces early damage to alveolar epithelial cells and development of inflammation followed by fibrotic tissue changes, mimicking human IPF. Even if histology is the gold standard to quantify lung fibrosis in mice, it precludes repeated and longitudinal measurements of disease progression and does not provide information on 3D distribution of tissue damage. Methods We performed a comparative longitudinal study of bleomycin-induced lung fibrosis progression in C57Bl/6 mice using Mirco CT throughout coupled with histology evaluated by Masson9s Trichrome. Airways, and lung morphology changes were assessed and reconstructed at baseline, 7, 14, and 21 days based on mCT images. Ashcroft score, % of collagen and % of air area were detected on lung histology and compared to mCT parameters. Results Extent (%) of fibrosis measured by µCT correlated with Ashcroft score, % of collagen and air area (r 2 =0.89; 0.94; 0.99 respectively). Left and right airway radius correlated with Ashcroft score (Left: r 2 =0.75; Right 0.81), % of collagen (Left: r 2 =0.9; Right 0.84) and air area (Left: r 2 =0.74; Right: 0.74) respectively. Conclusions µCT can quantify disease progression longitudinally, reducing the variability and number of animals used, potentially creating a bridge between preclinical and clinical settings.