Benchmarking artificial intelligence methods for end-to-end computational pathology
bioRxiv (Cold Spring Harbor Laboratory)
Abstract
Abstract Artificial intelligence (AI) can extract subtle visual information from digitized histopathology slides and yield scientific insight on genotype-phenotype interactions as well as clinically actionable recommendations. Classical weakly supervised pipelines use an end-to-end approach with residual neural networks (ResNets), modern convolutional neural networks such as EfficientNet, or non-convolutional architectures such as vision transformers (ViT). In addition, multiple-instance learning (MIL) and clustering-constrained attention MIL (CLAM) are being used for pathology image analysis. However, it is unclear how these different approaches perform relative to each other. Here, we implement and systematically compare all five methods in six clinically relevant end-to-end prediction tasks using data from N=4848 patients with rigorous external validation. We show that histological tumor subtyping of renal cell carcinoma is an easy task which approaches successfully solved with an area under the receiver operating curve (AUROC) of above 0.9 without any significant differences between approaches. In contrast, we report significant performance differences for mutation prediction in colorectal, gastric and bladder cancer. Weakly supervised ResNet-and ViT-based workflows significantly outperformed other methods, in particular MIL and CLAM for mutation prediction. As a reason for this higher performance we identify the ability of ResNet and ViT to assign high prediction scores to highly informative image regions with plausible histopathological image features. We make all source codes publicly available at https://github.com/KatherLab/HIA , allowing easy application of all methods on any end-to-end problem in computational pathology.
Authors 23
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
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Brigham and Women's Hospital · Harvard University
Affiliation as printed
Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
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Brigham and Women's Hospital · Harvard University
Affiliation as printed
Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
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Johannes Kepler University of Linz · Kepler Universitätsklinikum
Affiliation as printed
Institute of Pathology and Molecular Pathology, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria
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Affiliation as printed
Institute of Pathology, University of Bern, Switzerland
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Institute of Pathology, University Hospital RWTH Aachen, Aachen, Germany
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University of Leeds · Maastricht University Medical Centre · Maastricht University
Affiliation as printed
Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands
Pathology & Data Analytics, Leeds Institute of Medical Research at St James’s, University of Leeds, Leeds, UK
Pathology & Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
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German Cancer Research Center · National Center for Tumor Diseases · Deutsches Konsortium für Translationale Krebsforschung
Affiliation as printed
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
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Universität Hamburg · German Cancer Research Center · University Medical Center Hamburg-Eppendorf · University Cancer Center Hamburg
Affiliation as printed
Cancer Epidemiology Group, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
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Affiliation as printed
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
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Affiliation as printed
Digital Biomarkers for Oncology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Department of Radiology, University Hospital RWTH Aachen, Aachen, Germany
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Department of Radiology, University Hospital RWTH Aachen, Aachen, Germany
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Institute of Pathology, University Hospital RWTH Aachen, Aachen, Germany
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Institute of Pathology, University Hospital RWTH Aachen, Aachen, Germany
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Affiliation as printed
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
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Volkmar Schulz Aachen Comprehensive Diagnostic Center Aachen (CDCA) Department of Physics of Molecular Imaging Systems
Universitätsklinikum Aachen · Fraunhofer Institute for Digital Medicine · RWTH Aachen University
Affiliation as printed
Comprehensive Diagnostic Center Aachen (CDCA), University Hospital Aachen, Aachen, Germany
Department of Physics of Molecular Imaging Systems, Experimental Molecular Imaging, RWTH Aachen University, Aachen, Germany
Fraunhofer Institute for Digital Medicine MEVIS, Bremen, Germany
Hyperion Hybrid Imaging Systems GmbH, Aachen, Germany
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University of Leeds · Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
Pathology & Data Analytics, Leeds Institute of Medical Research at St James’s, University of Leeds, Leeds, UK
Pathology & Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
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