Longitudinal assessment of bleomycin-induced lung fibrosis by Micro-CT correlates with histological evaluation in mice
Abstract 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 th...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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PAGEPress Publications
2017-04-01
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| Series: | Multidisciplinary Respiratory Medicine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40248-017-0089-0 |
| _version_ | 1797287119383691264 |
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| author | Francesca Ruscitti Francesca Ravanetti Jeroen Essers Yanto Ridwan Sasha Belenkov Wim Vos Francisca Ferreira Alex KleinJan Paula van Heijningen Cedric Van Holsbeke Antonio Cacchioli Gino Villetti Franco Fabio Stellari |
| author_facet | Francesca Ruscitti Francesca Ravanetti Jeroen Essers Yanto Ridwan Sasha Belenkov Wim Vos Francisca Ferreira Alex KleinJan Paula van Heijningen Cedric Van Holsbeke Antonio Cacchioli Gino Villetti Franco Fabio Stellari |
| author_sort | Francesca Ruscitti |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-07T18:28:18Z |
| format | Article |
| id | doaj.art-c9605a10554646ebb94302e2d11f1a67 |
| institution | Directory Open Access Journal |
| issn | 2049-6958 |
| language | English |
| last_indexed | 2024-03-07T18:28:18Z |
| publishDate | 2017-04-01 |
| publisher | PAGEPress Publications |
| record_format | Article |
| series | Multidisciplinary Respiratory Medicine |
| spelling | doaj.art-c9605a10554646ebb94302e2d11f1a672024-03-02T06:54:36ZengPAGEPress PublicationsMultidisciplinary Respiratory Medicine2049-69582017-04-0112111010.1186/s40248-017-0089-0Longitudinal assessment of bleomycin-induced lung fibrosis by Micro-CT correlates with histological evaluation in miceFrancesca Ruscitti0Francesca Ravanetti1Jeroen Essers2Yanto Ridwan3Sasha Belenkov4Wim Vos5Francisca Ferreira6Alex KleinJan7Paula van Heijningen8Cedric Van Holsbeke9Antonio Cacchioli10Gino Villetti11Franco Fabio Stellari12Chiesi S.p.A., Pre-Clinical R & DDipartimento di Scienze Medico Veterinarie, Università di ParmaDepartment of Molecular Genetics, Vascular Surgery, and Radiation Oncology, Erasmus MCDepartment of Molecular Genetics, Vascular Surgery, and Radiation Oncology, Erasmus MCPerkinElmer, IncFluidda NVFluidda NVDepartment of Pulmonary Medicine Erasmus MCDepartment of Molecular Genetics, Vascular Surgery, and Radiation Oncology, Erasmus MCFluidda NVDipartimento di Scienze Medico Veterinarie, Università di ParmaChiesi S.p.A., Pre-Clinical R & DChiesi S.p.A., Pre-Clinical R & DAbstract 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.http://link.springer.com/article/10.1186/s40248-017-0089-0BleomycinLung fibrosisMicro-CTMice |
| spellingShingle | Francesca Ruscitti Francesca Ravanetti Jeroen Essers Yanto Ridwan Sasha Belenkov Wim Vos Francisca Ferreira Alex KleinJan Paula van Heijningen Cedric Van Holsbeke Antonio Cacchioli Gino Villetti Franco Fabio Stellari Longitudinal assessment of bleomycin-induced lung fibrosis by Micro-CT correlates with histological evaluation in mice Multidisciplinary Respiratory Medicine Bleomycin Lung fibrosis Micro-CT Mice |
| title | Longitudinal assessment of bleomycin-induced lung fibrosis by Micro-CT correlates with histological evaluation in mice |
| title_full | Longitudinal assessment of bleomycin-induced lung fibrosis by Micro-CT correlates with histological evaluation in mice |
| title_fullStr | Longitudinal assessment of bleomycin-induced lung fibrosis by Micro-CT correlates with histological evaluation in mice |
| title_full_unstemmed | Longitudinal assessment of bleomycin-induced lung fibrosis by Micro-CT correlates with histological evaluation in mice |
| title_short | Longitudinal assessment of bleomycin-induced lung fibrosis by Micro-CT correlates with histological evaluation in mice |
| title_sort | longitudinal assessment of bleomycin induced lung fibrosis by micro ct correlates with histological evaluation in mice |
| topic | Bleomycin Lung fibrosis Micro-CT Mice |
| url | http://link.springer.com/article/10.1186/s40248-017-0089-0 |
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