IDIOPATHIC PULMONARY FIBROSIS
Current literature on pulmonary fibrosis observed in rodents highlights the need to develop accurate, reliable, reproducible and observer-independent assessment of quantitative analysis of fibrosis. That cannot be satisfactorily achieved by conventional scoring evaluation. To successfully meet these needs, Biocellvia developed a multiparametric image analysis using proprietary software tools which have been combined into one assay: the Biocellvia’s IPF assay.
FEATURES OF BIOCELLVIA’S IPF ASSAY
- It is based on computer analysis of digital images of entire lung lobe sections, at high resolution (pixel size: 0.452 µm), obtained from the scan of histological slides.
- Fully automatic quantitative analysis of fibrosis is performed by assessing multiple key morphometric parameters of parenchymal tissue:
(1) Density of parenchymal tissue
(2) Percentage of pulmonary foci
(3) Density of airspaces
(4) Number of airspaces/mm² of parenchymal tissue
(5) Collagen content expressed specifically into pulmonary foci
- Morphometric parameters have been validated as endpoint measures by comparison to other image analysis methods (e.g. Ashcroft scoring, micro-CT imaging) and functional in vivo standard evaluation methods. Some results gave rise to a publication in PLOS ONE in collaboration with Boehringer Ingelheim.
- The quantification of pulmonary fibrosis is fully automatic – from the scanning of slides to the complete evaluation of morphometric parameters and statistical analysis.
- Biocellvia’s analysis is very rapid (about 1 hour for 120 whole lung sections) and avoids any intra- and inter-variabilities from the subjective manipulation of the experimenter.
- The assessment of multiple morphometric parameters has been validated as endpoint measurements in several rodent models in which pulmonary fibrosis can be induced by bleomycin, irradiation, silica, as well as in genetically modified mice.
(1) Density of parenchymal tissue
(2) Percentage of fibrotic foci
Representative native images and their corresponding tissue density mapping of lung sections from saline control and BLM-treated mice.
Mapping of tissue density is performed from individual pixels characterized by a distinct density value. Low density values were pseudo colored in blue and high density values in yellow. Note that high density values were focalized specifically in fibrotic foci. A quantification of fibrotic foci is determined from the frequency of high density values. Bars: 1 mm.
On this figure, you can observe quantification of all the morphological parameters of our digital image analysis program dedicated to IPF with 3 different groups. The blue one is the control group, the red one is the group with bleomycin, the green one is the group with bleomycin and pirfenidone.
All parameters are calculated from the same lung section stained in Picrosirius red.
IMAGE ANALYSIS OF COLLAGEN CONTENT
- Concurrent to the evaluation of morphometric parameters, an automatic software image analysis was developed to quantify the expression of collagen in the whole lung section. We showed that this quantification of lung collagen – from Masson trichrome or picrosirius red stained sections – is far superior than the standard hydroxyproline or Sircol methods.
(6) Collagen content expressed specifically into pulmonary foci
TOP 4 REASONS TO CHOOSE BIOCELLVIA’S IPF ASSAY
- Biocellvia’s IPF (idiopathic pulmonary fibrosis) assay is a fully automatic software analysis of pulmonary fibrosis, totally observer-independent, and therefore free of any intra- and inter-experimental variabilities.
- Quantitative assessment of the severity of fibrosis is performed by matching multiple morphometric parameters of both parenchymal tissue and airspaces, leading to a significantly more comprehensive analysis of structural changes than the standard scoring evaluation.
- The accuracy and reliability of Biocellvia’s analysis means that much lower concentrations of bleomycin is needed for fibrosis induction (4-5X lower than the usual dose). Thus, molecule candidates can be tested in vivo using animals in better condition, contributing to greater robustness in the efficacy studies.
- Biocellvia’s IPF assay is coupled to the measurement of collagen content in whole lung sections. Therefore, morphological changes can be closely associated with collagen expression in the same sample, which cannot be performed as finely by hydroxyproline or Sircol assays.
Biocellvia’s cutting-edge digital IPF assay is unparalleled in its robustness and accuracy, and is your best and most reliable choice in preclinical drug evaluation, empowering your Go/No decisions.
The related results on pulmonary fibrosis gave rise to a scientific article in 2017 in PlosOne.
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