Deep learning-based image-analysis algorithm for classification and quantification of multiple histopathological lesions in rat liver

• Published in: Journal of Toxicologic Pathology Vol. 35; no. 2; pp. 135 - 147
• Main Authors: Shimazaki, Taishi, Deshpande, Ameya, Hajra, Anindya, Thomas, Tijo, Muta, Kyotaka, Yamada, Naohito, Yasui, Yuzo, Shoda, Toshiyuki
• Format: Journal Article
• Language: English
• Published: Japan JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY 01.01.2022; The Japanese Society of Toxicologic Pathology; Japan Science and Technology Agency; Japanese Society of Toxicologic Pathology
• Subjects: Algorithms; Artificial intelligence; Bile ducts; Boundaries; Deep learning; digital pathology; Hepatocytes; hepatotoxicity; Hyperplasia; Hypertrophy; Image analysis; Image classification; Image processing; lesion detection and quantification; Liver; Machine learning; Necrosis; Original; pharmaceutical development; Pharmaceutical industry; Toxicity; toxicity study; Toxicology; pharmaceutical development; toxicity study; machine learning; digital pathology; hepatotoxicity; lesion detection and quantification
• ISSN: 0914-9198; 1881-915X; 1347-7404
• DOI: 10.1293/tox.2021-0053

Artificial intelligence (AI)-based image analysis is increasingly being used for preclinical safety-assessment studies in the pharmaceutical industry. In this paper, we present an AI-based solution for preclinical toxicology studies. We trained a set of algorithms to learn and quantify multiple typical histopathological findings in whole slide images (WSIs) of the livers of young Sprague Dawley rats by using a U-Net-based deep learning network. The trained algorithms were validated using 255 liver WSIs to detect, classify, and quantify seven types of histopathological findings (including vacuolation, bile duct hyperplasia, and single-cell necrosis) in the liver. The algorithms showed consistently good performance in detecting abnormal areas. Approximately 75% of all specimens could be classified as true positive or true negative. In general, findings with clear boundaries with the surrounding normal structures, such as vacuolation and single-cell necrosis, were accurately detected with high statistical scores. The results of quantitative analyses and classification of the diagnosis based on the threshold values between “no findings” and “abnormal findings” correlated well with diagnoses made by professional pathologists. However, the scores for findings ambiguous boundaries, such as hepatocellular hypertrophy, were poor. These results suggest that deep learning-based algorithms can detect, classify, and quantify multiple findings simultaneously on rat liver WSIs. Thus, it can be a useful supportive tool for a histopathological evaluation, especially for primary screening in rat toxicity studies.