Learning from crowds in digital pathology using scalable variational Gaussian processes

This work was supported by the Agencia Estatal de Investigacion of the Spanish Ministerio de Ciencia e Innovacion under contract PID2019-105142RB-C22/AEI/10.13039/501100011033, and the United States National Institutes of Health National Cancer Institute Grants U01CA220401 and U24CA19436201. P.M. contribution was mostly before joining Microsoft Research, when he was supported by La Caixa Banking Foundation (ID 100010434, Barcelona, Spain) through La Caixa Fellowship for Doctoral Studies LCF/BQ/ES17/11600011.The volume of labeled data is often the primary determinant of success in developing machine learning algorithms. This has increased interest in methods for leveraging crowds to scale data labeling efforts, and methods to learn from noisy crowd-sourced labels. The need to scale labeling is acute but particularly challenging in medical applications like pathology, due to the expertise required to generate quality labels and the limited availability of qualified experts. In this paper we investigate the application of Scalable Variational Gaussian Processes for Crowdsourcing (SVGPCR) in digital pathology. We compare SVGPCR with other crowdsourcing methods using a large multi-rater dataset where pathologists, pathology residents, and medical students annotated tissue regions breast cancer. Our study shows that SVGPCR is competitive with equivalent methods trained using goldstandard pathologist generated labels, and that SVGPCR meets or exceeds the performance of other crowdsourcing methods based on deep learning. We also show how SVGPCR can effectively learn the class-conditional reliabilities of individual annotators and demonstrate that Gaussian-process classifiers have comparable performance to similar deep learning methods. These results suggest that SVGPCR can meaningfully engage non-experts in pathology labeling tasks, and that the classconditional reliabilities estimated by SVGPCR may assist in matching annotators to tasks where they perform well.Agencia Estatal de Investigacion of the Spanish Ministerio de Ciencia e Innovacion PID2019-105142RB-C22/AEI/10.13039/501100011033United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) U01CA220401 U24CA19436201La Caixa Banking Foundation (Barcelona, Spain) Barcelona, Spain) through La Caixa Fellowship 100010434 LCF/BQ/ES17/1160001

The U-Net-based Active Learning Framework for Enhancing Cancer Immunotherapy

Breast cancer is the most common cancer in the world. According to the U.S. Breast Cancer Statistics, about 281,000 new cases of invasive breast cancer are expected to be diagnosed in 2021 (Smith et al., 2019). The death rate of breast cancer is higher than any other cancer type. Early detection and treatment of breast cancer have been challenging over the last few decades. Meanwhile, deep learning algorithms using Convolutional Neural Networks to segment images have achieved considerable success in recent years. These algorithms have continued to assist in exploring the quantitative measurement of cancer cells in the tumor microenvironment. However, detecting cancerous regions in whole-slide images has been challenging as it requires substantial annotation and training efforts from clinicians and biologists. In this thesis, a notable instructing process named U-Net-based Active Learning is proposed to improve the annotation and training procedure in a feedback learning process by utilizing a Deep Convolutional Neural Networks model. The proposed approach reduces the amount of time and effort required to analyze the whole slide images. During the Active Learning process, highly uncertain samples are iteratively selected to strategically supply characteristics of the whole slide images to the training process using a low-confidence sample selection algorithm. The performance results of the proposed approach indicated that the U-Net-based Active Learning framework has promising outcomes in the feedback learning process as it reaches 88.71% AUC-ROC when only using 64 image patches, while random lymphocyte prediction reaches 84.12% AUC-ROC at maximum

One Model is All You Need: Multi-Task Learning Enables Simultaneous Histology Image Segmentation and Classification

The recent surge in performance for image analysis of digitised pathology slides can largely be attributed to the advance of deep learning. Deep models can be used to initially localise various structures in the tissue and hence facilitate the extraction of interpretable features for biomarker discovery. However, these models are typically trained for a single task and therefore scale poorly as we wish to adapt the model for an increasing number of different tasks. Also, supervised deep learning models are very data hungry and therefore rely on large amounts of training data to perform well. In this paper we present a multi-task learning approach for segmentation and classification of nuclei, glands, lumen and different tissue regions that leverages data from multiple independent data sources. While ensuring that our tasks are aligned by the same tissue type and resolution, we enable simultaneous prediction with a single network. As a result of feature sharing, we also show that the learned representation can be used to improve downstream tasks, including nuclear classification and signet ring cell detection. As part of this work, we use a large dataset consisting of over 600K objects for segmentation and 440K patches for classification and make the data publicly available. We use our approach to process the colorectal subset of TCGA, consisting of 599 whole-slide images, to localise 377 million, 900K and 2.1 million nuclei, glands and lumen respectively. We make this resource available to remove a major barrier in the development of explainable models for computational pathology

Scale-Equivariant UNet for Histopathology Image Segmentation

Digital histopathology slides are scanned and viewed under different magnifications and stored as images at different resolutions. Convolutional Neural Networks (CNNs) trained on such images at a given scale fail to generalise to those at different scales. This inability is often addressed by augmenting training data with re-scaled images, allowing a model with sufficient capacity to learn the requisite patterns. Alternatively, designing CNN filters to be scale-equivariant frees up model capacity to learn discriminative features. In this paper, we propose the Scale-Equivariant UNet (SEUNet) for image segmentation by building on scale-space theory. The SEUNet contains groups of filters that are linear combinations of Gaussian basis filters, whose scale parameters are trainable but constrained to span disjoint scales through the layers of the network. Extensive experiments on a nuclei segmentation dataset and a tissue type segmentation dataset demonstrate that our method outperforms other approaches, with much fewer trainable parameters.Comment: This paper was accepted by GeoMedIA 202

FrOoDo: Framework for Out-of-Distribution Detection

FrOoDo is an easy-to-use and flexible framework for Out-of-Distribution detection tasks in digital pathology. It can be used with PyTorch classification and segmentation models, and its modular design allows for easy extension. The goal is to automate the task of OoD Evaluation such that research can focus on the main goal of either designing new models, new methods or evaluating a new dataset. The code can be found at https://github.com/MECLabTUDA/FrOoDo