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Quantifying the effects of data augmentation and stain color normalization in convolutional neural networks for computational pathology

Open access
Tellez, David, Litjens, Geert, Bándi, Péter, Bulten, Wouter, Bokhorst, John-Melle, Ciompi, Francesco, van der Laak, Jeroen·2019·Medical Image Analysis

Abstract

Stain variation is a phenomenon observed when distinct pathology laboratories stain tissue slides that exhibit similar but not identical color appearance. Due to this color shift between laboratories, convolutional neural networks (CNNs) trained with images from one lab often underperform on unseen images from the other lab. Several techniques have been proposed to reduce the generalization error, mainly grouped into two categories: stain color augmentation and stain color normalization. The former simulates a wide variety of realistic stain variations during training, producing stain-invariant CNNs. The latter aims to match training and test color distributions in order to reduce stain variation. For the first time, we compared some of these techniques and quantified their effect on CNN classification performance using a heterogeneous dataset of hematoxylin and eosin histopathology images from 4 organs and 9 pathology laboratories. Additionally, we propose a novel unsupervised method to perform stain color normalization using a neural network. Based on our experimental results, we provide practical guidelines on how to use stain color augmentation and stain color normalization in future computational pathology applications.

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Crossref · 10.1016/j.media.2019.101544

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  1. Haeberli, 1994, Image processing by linear interpolation and extrapolation, IRIS Uni. Mag., 28, 8

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Metadata

Authors
Tellez, D., Litjens, G., Bándi, P., Bulten, W., Bokhorst, J.-M., Ciompi, F., & van der Laak, J.
Affiliations
Radboud University Medical Center (NL)
Corresponding author
Tellez, David
Venue
Medical Image Analysis
Publisher
Elsevier BV
Published
2019-12
Volume
58
Pages
101544
ISSN
1361-8415 (ISSN-L)
OpenAlex
W2969278648
Cited by
649
References
40
Citations by year
2026: 142 · 2025: 108 · 2024: 80 · 2023: 92 · 2022: 89 · 2021: 81 · 2020: 42 · 2019: 14
FWCI
25.50
Type
journal article
Language
en
Open access
Locations
  • Medical Image Analysis (publishedVersion)
  • PubMed (publishedVersion)
  • arXiv (Cornell University) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion, other-oa)
  • arXiv (Cornell University)
Funders
  • KWF Kankerbestrijding
  • Radboud Universitair Medisch Centrum
  • Horizon 2020
Topics
  • Physical Sciences › Computer Science › Artificial Intelligence › AI in cancer detection
  • Physical Sciences › Computer Science › Computer Vision and Pattern Recognition › Digital Imaging for Blood Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Cell Image Analysis Techniques
Keywords
computational pathology, convolutional neural networks, histopathological image classification
MeSH terms
Unsupervised Machine Learning, Color, Eosine Yellowish-(YS), Hematoxylin, Humans, Pathology, Clinical, Staining and Labeling, Neural Networks, Computer, Datasets as Topic

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