A fully automated image analysis method to quantify lung fibrosis in the bleomycin-induced rat model

PLoS One. 2018 Mar 16;13(3):e0193057. doi: 10.1371/journal.pone.0193057. eCollection 2018.

Abstract

Intratracheal administration of bleomycin induces fibrosis in the lung, which is mainly assessed by histopathological grading that is subjective. Current literature highlights the need of reproducible and quantitative pulmonary fibrosis analysis. If some quantitative studies looked at fibrosis parameters separately, none of them quantitatively assessed both aspects: lung tissue remodeling and collagenization. To ensure reliable quantification, support vector machine learning was used on digitalized images to design a fully automated method that analyzes two important aspects of lung fibrosis: (i) areas having substantial tissue remodeling with appearance of dense fibrotic masses and (ii) collagen deposition. Fibrotic masses were identified on low magnification images and collagen detection was performed at high magnification. To insure a fully automated application the tissue classifier was trained on several independent studies that were performed over a period of four years. The detection method generates two different values that can be used to quantify lung fibrosis development: (i) percent area of fibrotic masses and (ii) percent of alveolar collagen. These two parameters were validated using independent studies from bleomycin- and saline-treated animals. A significant change of these lung fibrosis quantification parameters- increased amount of fibrotic masses and increased collagen deposition- were observed upon intratracheal administration of bleomycin and subsequent significant beneficial treatments effects were observed with BIBF-1120 and pirfenidone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bleomycin / administration & dosage*
  • Bleomycin / pharmacology
  • Collagen / metabolism*
  • Disease Models, Animal
  • Image Processing, Computer-Assisted / methods*
  • Male
  • Pulmonary Alveoli* / metabolism
  • Pulmonary Alveoli* / pathology
  • Pulmonary Fibrosis* / chemically induced
  • Pulmonary Fibrosis* / metabolism
  • Pulmonary Fibrosis* / pathology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Bleomycin
  • Collagen

Grants and funding

The authors [S.S., M.S., E.V., O.N., P.H., P.MA.G., A.K.S.] received no specific funding for this work. All authors are employed by Idorsia Pharmaceuticals Ltd who provided support in the form of author salaries, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of the authors are articulated in the ‘author contributions’ section.