Learning to detect lymphocytes in immunohistochemistry with deep learning

Zaneta Swiderska-Chadaj, Hans Pinckaers, Mart van Rijthoven, Maschenka Balkenhol, Margarita Melnikova, Oscar Geessink, Quirine Manson, Mark Sherman, Antonio Polonia, Jeremy Parry, Mustapha Abubakar, Geert Litjens, Jeroen van der Laak, Francesco Ciompi

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

The immune system is of critical importance in the development of cancer. The evasion of destruction by the immune system is one of the emerging hallmarks of cancer. We have built a dataset of 171,166 manually annotated CD3+ and CD8+ cells, which we used to train deep learning algorithms for automatic detection of lymphocytes in histopathology images to better quantify immune response. Moreover, we investigate the effectiveness of four deep learning based methods when different subcompartments of the whole-slide image are considered: normal tissue areas, areas with immune cell clusters, and areas containing artifacts. We have compared the proposed methods in breast, colon and prostate cancer tissue slides collected from nine different medical centers. Finally, we report the results of an observer study on lymphocyte quantification, which involved four pathologists from different medical centers, and compare their performance with the automatic detection. The results give insights on the applicability of the proposed methods for clinical use. U-Net obtained the highest performance with an F1-score of 0.78 and the highest agreement with manual evaluation (κ=0.72), whereas the average pathologists agreement with reference standard was κ=0.64. The test set and the automatic evaluation procedure are publicly available at lyon19.grand-challenge.org.

Original languageEnglish (US)
Article number101547
JournalMedical Image Analysis
Volume58
DOIs
StatePublished - Dec 2019

Keywords

  • Computational pathology
  • Deep learning
  • Immune cell detection
  • Immunohistochemistry

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Computer Vision and Pattern Recognition
  • Health Informatics
  • Computer Graphics and Computer-Aided Design

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    Swiderska-Chadaj, Z., Pinckaers, H., van Rijthoven, M., Balkenhol, M., Melnikova, M., Geessink, O., Manson, Q., Sherman, M., Polonia, A., Parry, J., Abubakar, M., Litjens, G., van der Laak, J., & Ciompi, F. (2019). Learning to detect lymphocytes in immunohistochemistry with deep learning. Medical Image Analysis, 58, [101547]. https://doi.org/10.1016/j.media.2019.101547