Ovarian Toxicity Assessment in Histopathological Images Using Deep Learning.

Journal: Toxicologic pathology
PMID:

Abstract

As ovarian toxicity is often a safety concern for cancer therapeutics, identification of ovarian pathology is important in early stages of preclinical drug development, particularly when the intended patient population include women of child-bearing potential. Microscopic evaluation by pathologists of hematoxylin and eosin (H&E)-stained tissues is the current gold standard for the assessment of organs in toxicity studies. However, digital pathology and advanced image analysis are being explored with greater frequency and broader applicability to tissue evaluations in toxicologic pathology. Our objective in this work was to develop an automated method that rapidly enumerates rat ovarian corpora lutea on standard H&E-stained slides with comparable accuracy to the gold standard assessment by a pathologist. Herein, we describe an algorithm generated by a deep learning network and tested on 5 rat toxicity studies, which included studies that both had and had not previously been diagnosed with effects on number of ovarian corpora lutea. Our algorithm could not only enumerate corpora lutea accurately in all studies but also revealed distinct trends for studies with and without reproductive toxicity. Our method could be a widely applied tool to aid analysis in general toxicity studies.

Authors

  • Fangyao Hu
    Department of Safety Assessment, Genentech, South San Francisco, CA, USA.
  • Leah Schutt
    Department of Safety Assessment, Genentech, South San Francisco, CA, USA.
  • Cleopatra Kozlowski
    Department of Development Sciences, Genentech Inc., South San Francisco, CA, USA.
  • Karen Regan
    Regan Path/Tox Services, Ashland, OH, USA.
  • Noel Dybdal
    Department of Safety Assessment, Genentech, South San Francisco, CA, USA.
  • Melissa M Schutten
    Department of Safety Assessment, Genentech, South San Francisco, CA, USA.