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

Background The intratracheal instillation of bleomycin in mice induces early damage to alveolar epithelial cells and development of inflammation followed by fibrotic tissue changes and represents the most widely used model of pulmonary fibrosis to investigate human IPF. Histopathology is the gold st...

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Published in:Multidisciplinary respiratory medicine Vol. 12; no. 1; pp. 8 - 10
Main Authors: Ruscitti, Francesca, Ravanetti, Francesca, Essers, Jeroen, Ridwan, Yanto, Belenkov, Sasha, Vos, Wim, Ferreira, Francisca, KleinJan, Alex, van Heijningen, Paula, Van Holsbeke, Cedric, Cacchioli, Antonio, Villetti, Gino, Stellari, Franco Fabio
Format: Journal Article
Language:English
Published: London BioMed Central 10.04.2017
BioMed Central Ltd
PAGEPress Publications
Mattioli 1885
Subjects:
Automation
Bleomycin
Critical Care Medicine
Disease
Intensive
Laboratory animals
Lung fibrosis
Lungs
Medical imaging
Medical prognosis
Medicine
Medicine & Public Health
Mice
Micro-CT
Original
Original Research Article
Pharmaceutical industry
Pneumology/Respiratory System
Pulmonary fibrosis
Rodents
Thoracic Surgery
Tomography
Micro-CT
Mice
Bleomycin
Lung fibrosis
ISSN:2049-6958, 1828-695X, 2049-6958
Online Access:Get full text
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Summary:Background The intratracheal instillation of bleomycin in mice induces early damage to alveolar epithelial cells and development of inflammation followed by fibrotic tissue changes and represents the most widely used model of pulmonary fibrosis to investigate human IPF. Histopathology is the gold standard for assessing lung fibrosis in rodents, however it precludes repeated and longitudinal measurements of disease progression and does not provide information on spatial and temporal distribution of tissue damage. Here we investigated the use of the Micro-CT technique to allow the evaluation of disease onset and progression at different time-points in the mouse bleomycin model of lung fibrosis. Micro-CT was throughout coupled with histological analysis for the validation of the imaging results. Methods In bleomycin-instilled and control mice, airways and lung morphology changes were assessed and reconstructed at baseline, 7, 14 and 21 days post-treatment based on Micro-CT images. Ashcroft score, percentage of collagen content and percentage of alveolar air area were detected on lung slides processed by histology and subsequently compared with Micro-CT parameters. Results Extent (%) of fibrosis measured by Micro-CT correlated with Ashcroft score, the percentage of collagen content and the percentage of alveolar air area ( r 2  = 0.91; 0.77; 0.94, respectively). Distal airway radius also correlated with the Ashcroft score, the collagen content and alveolar air area percentage ( r 2  = 0.89; 0.78; 0.98, respectively). Conclusions Micro-CT data were in good agreement with histological read-outs as micro-CT was able to quantify effectively and non-invasively disease progression longitudinally and to reduce the variability and number of animals used to assess the damage. This suggests that this technique is a powerful tool for understanding experimental pulmonary fibrosis and that its use could translate into a more efficient drug discovery process, also helping to fill the gap between preclinical setting and clinical practice.
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ISSN:2049-6958
1828-695X
2049-6958
DOI:10.1186/s40248-017-0089-0