PT - JOURNAL ARTICLE AU - Chris J. Scotton AU - Brian Hayes AU - Robert Alexander AU - Arnab Datta AU - Ellen J. Forty AU - Paul F. Mercer AU - Andy Blanchard AU - Rachel C. Chambers TI - <em>Ex vivo</em> micro-computed tomography analysis of bleomycin-induced lung fibrosis for preclinical drug evaluation AID - 10.1183/09031936.00182412 DP - 2013 Dec 01 TA - European Respiratory Journal PG - 1633--1645 VI - 42 IP - 6 4099 - http://erj.ersjournals.com/content/42/6/1633.short 4100 - http://erj.ersjournals.com/content/42/6/1633.full SO - Eur Respir J2013 Dec 01; 42 AB - Research into the pathogenesis underlying the development of idiopathic pulmonary fibrosis is hampered by a repertoire of animal models that fail to recapitulate all the features of the human disease. Better use and understanding of what the animal models represent may improve clinical predictability. We interrogated ex vivo micro-computed tomography (CT) as a novel end-point measure in the mouse model of bleomycin-induced lung fibrosis (BILF), and to evaluate a therapeutic dosing regimen for preclinical drug evaluation. A detailed characterisation of BILF was performed using standard end-point measures (lung hydroxyproline and histology). High resolution micro-CT (∼13.7 μm voxel size) was evaluated for quantifying the extent and severity of lung fibrosis. The period from 14 to 28 days following bleomycin instillation represents progression of established fibrosis. A therapeutic dosing regimen during this period was validated using a transforming growth factor-β receptor-1 kinase inhibitor, and micro-CT provided a highly sensitive and quantitative measure of fibrosis. Moreover, fibrotic lesions did not completely resolve, but instead persisted for ≥6 months following a single insult with bleomycin. Ex vivo micro-CT analysis of BILF allows robust evaluation of therapeutic dosing once fibrosis is already well established, requiring fewer mice than conventional biochemical end-points. Micro-CT has improved out understanding of the bleomycin model of fibrotic lung disease for preclinical drug evaluation http://ow.ly/p73De