Deep Learning-Based Image Analysis of Liver Steatosis in Mouse Models.

Journal: The American journal of pathology
Published Date:

Abstract

The incidence of nonalcoholic fatty liver disease is a continuously growing health problem worldwide, along with obesity. Therefore, novel methods to both efficiently study the manifestation of nonalcoholic fatty liver disease and to analyze drug efficacy in preclinical models are needed. The present study developed a deep neural network-based model to quantify microvesicular and macrovesicular steatosis in the liver on hematoxylin-eosin-stained whole slide images, using the cloud-based platform, Aiforia Create. The training data included a total of 101 whole slide images from dietary interventions of wild-type mice and from two genetically modified mouse models with steatosis. The algorithm was trained for the following: to detect liver parenchyma, to exclude the blood vessels and any artefacts generated during tissue processing and image acquisition, to recognize and differentiate the areas of microvesicular and macrovesicular steatosis, and to quantify the recognized tissue area. The results of the image analysis replicated well the evaluation by expert pathologists and correlated well with the liver fat content measured by EchoMRI ex vivo, and the correlation with total liver triglycerides was notable. In conclusion, the developed deep learning-based model is a novel tool for studying liver steatosis in mouse models on paraffin sections and, thus, can facilitate reliable quantification of the amount of steatosis in large preclinical study cohorts.

Authors

  • Laura Mairinoja
    Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine and Turku Center for Disease Modeling, University of Turku, Turku, Finland. Electronic address: lajomai@utu.fi.
  • Hanna Heikelä
    Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine and Turku Center for Disease Modeling, University of Turku, Turku, Finland.
  • Sami Blom
    Biomedicum, Fimmic Oy, Helsinki, Finland.
  • Darshan Kumar
    Aiforia Technologies Oyj, Helsinki, Finland.
  • Anna Knuuttila
    Aiforia Technologies Oy, Tukholmankatu 8, 000290, Helsinki, Finland.
  • Sonja Boyd
    Department of Pathology, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 3, 00290, Helsinki, Finland.
  • Nelli Sjöblom
    Department of Pathology, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 3, 00290, Helsinki, Finland. nelli.sjoblom@hus.fi.
  • Eva-Maria Birkman
    Department of Pathology, Turku University Hospital and University of Turku, Turku, Finland.
  • Petteri Rinne
    Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine and Turku Center for Disease Modeling, University of Turku, Turku, Finland.
  • Pekka Ruusuvuori
    BioMediTech and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
  • Leena Strauss
    Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine and Turku Center for Disease Modeling, University of Turku, Turku, Finland.
  • Matti Poutanen
    Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine and Turku Center for Disease Modeling, University of Turku, Turku, Finland; Department of Internal Medicine and Clinical Nutrition, Centre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.