Abstract

BackgroundOne challenge to train deep convolutional neural network (CNNs) models with whole slide images (WSIs) is providing the required large number of costly, manually annotated image regions. Strategies to alleviate the scarcity of annotated data include: using transfer learning, data augmentation and training the models with less expensive image-level annotations (weakly-supervised learning). However, it is not clear how to combine the use of transfer learning in a CNN model when different data sources are available for training or how to leverage from the combination of large amounts of weakly annotated images with a set of local region annotations. This paper aims to evaluate CNN training strategies based on transfer learning to leverage the combination of weak and strong annotations in heterogeneous data sources. The trade-off between classification performance and annotation effort is explored by evaluating a CNN that learns from strong labels (region annotations) and is later fine-tuned on a dataset with less expensive weak (image-level) labels.ResultsAs expected, the model performance on strongly annotated data steadily increases as the percentage of strong annotations that are used increases, reaching a performance comparable to pathologists (kappa = 0.691 pm 0.02). Nevertheless, the performance sharply decreases when applied for the WSI classification scenario with kappa = 0.307 pm 0.133. Moreover, it only provides a lower performance regardless of the number of annotations used. The model performance increases when fine-tuning the model for the task of Gleason scoring with the weak WSI labels kappa = 0.528 pm 0.05.ConclusionCombining weak and strong supervision improves strong supervision in classification of Gleason patterns using tissue microarrays (TMA) and WSI regions. Our results contribute very good strategies for training CNN models combining few annotated data and heterogeneous data sources. The performance increases in the controlled TMA scenario with the number of annotations used to train the model. Nevertheless, the performance is hindered when the trained TMA model is applied directly to the more challenging WSI classification problem. This demonstrates that a good pre-trained model for prostate cancer TMA image classification may lead to the best downstream model if fine-tuned on the WSI target dataset. We have made available the source code repository for reproducing the experiments in the paper: https://github.com/ilmaro8/Digital_Pathology_Transfer_Learning

Highlights

  • One challenge to train deep convolutional neural network (CNNs) models with whole slide images (WSIs) is providing the required large number of costly, manually annotated image regions

  • For answering the questions we evaluate the trade-off of using small amounts of strong annotations from one data source, jointly with weak annotations from another data source to train supervised Convolutional Neural Network (CNN) models

  • In this paper, transfer learning strategies that combine strong and weak supervision are evaluated in two cases of prostate cancer image classification in histopathology: tissue microarrays of prostate tissue and prostatectomy WSIs

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Summary

Introduction

One challenge to train deep convolutional neural network (CNNs) models with whole slide images (WSIs) is providing the required large number of costly, manually annotated image regions. It is not clear how to combine the use of transfer learning in a CNN model when different data sources are available for training or how to leverage from the combination of large amounts of weakly annotated images with a set of local region annotations. This paper aims to evaluate CNN training strategies based on transfer learning to leverage the combination of weak and strong annotations in heterogeneous data sources. The trade-off between classification performance and annotation effort is explored by evaluating a CNN that learns from strong labels (region annotations) and is later fine-tuned on a dataset with less expensive weak (image-level) labels. The gold standard for the diagnosis of PCa is the visual inspection of tissue samples from needle biopsies or prostatectomies. The Gleason scoring assigns a number given the architectural patterns shown in prostate tissue samples observed under a microscope. The revised Gleason score from the International Society of Urological Pathology (ISUP) is used in pathology routine [3]

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