Using Artificial Intelligence to Detect, Classify, and Objectively Score Severity of Rodent Cardiomyopathy.

Journal: Toxicologic pathology
Published Date:

Abstract

Rodent progressive cardiomyopathy (PCM) encompasses a constellation of microscopic findings commonly seen as a spontaneous background change in rat and mouse hearts. Primary histologic features of PCM include varying degrees of cardiomyocyte degeneration/necrosis, mononuclear cell infiltration, and fibrosis. Mineralization can also occur. Cardiotoxicity may increase the incidence and severity of PCM, and toxicity-related morphologic changes can overlap with those of PCM. Consequently, sensitive and consistent detection and quantification of PCM features are needed to help differentiate spontaneous from test article-related findings. To address this, we developed a computer-assisted image analysis algorithm, facilitated by a fully convolutional network deep learning technique, to detect and quantify the microscopic features of PCM (degeneration/necrosis, fibrosis, mononuclear cell infiltration, mineralization) in rat heart histologic sections. The trained algorithm achieved high values for accuracy, intersection over union, and dice coefficient for each feature. Further, there was a strong positive correlation between the percentage area of the heart predicted to have PCM lesions by the algorithm and the median severity grade assigned by a panel of veterinary toxicologic pathologists following light microscopic evaluation. By providing objective and sensitive quantification of the microscopic features of PCM, deep learning algorithms could assist pathologists in discerning cardiotoxicity-associated changes.

Authors

  • Debra A Tokarz
    Experimental Pathology Laboratories, Inc, Research Triangle Park, NC, USA.
  • Thomas J Steinbach
    Experimental Pathology Laboratories, Inc, Research Triangle Park, NC, USA.
  • Avinash Lokhande
  • Gargi Srivastava
    AIRA Matrix Private Limited, Mumbai, India.
  • Rajesh Ugalmugle
    AIRA Matrix Private Limited, Mumbai, India.
  • Caroll A Co
    3063Social and Scientific Systems, Durham, NC, USA.
  • Keith R Shockley
    Biostatistics and Computational Biology Branch, Division of Intramural Research, 6857National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
  • Emily Singletary
    Experimental Pathology Laboratories, Inc, Research Triangle Park, NC, USA.
  • Mark F Cesta
    National Toxicology Program, 6857National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
  • Heath C Thomas
    205955Aclairo Pharmaceutical Development Group, Vienna, VA, USA.
  • Vivian S Chen
    Charles River Laboratories Inc, Durham, NC, USA.
  • Kristen Hobbie
    298616Integrated Laboratory Systems, LLC, Research Triangle Park, NC, USA.
  • Torrie A Crabbs
    Experimental Pathology Laboratories, Inc, Research Triangle Park, NC, USA.