Weakly Supervised Contrastive Learning for Histopathology Patch Embeddings
Department of Electrical and Computer Engineering, University of Utah（电气与计算机工程系，犹他大学）；Scientific Computing and Imaging Institute, University of Utah（科学计算与成像研究所，犹他大学）；Department of Pathology, University of Utah（病理学系，犹他大学）
Digital histopathology whole slide images (WSIs) provide gigapixel-scale high-resolution images that are highly useful for disease diagnosis. However, digital histopathology image analysis faces significant challenges due to the limited training labels, since manually annotating specific regions or small patches cropped from large WSIs requires substantial time and effort. Weakly supervised multiple instance learning (MIL) offers a practical and efficient solution by requiring only bag-level (slide-level) labels, while each bag typically contains multiple instances (patches). Most MIL methods directly use frozen image patch features generated by various image encoders as inputs and primarily focus on feature aggregation. However, feature representation learning for encoder pretraining in MIL settings has largely been neglected.
In our work, we propose a novel feature representation learning framework called weakly supervised contrastive learning (WeakSupCon) that incorporates bag-level label information during training. Our method does not rely on instance-level pseudo-labeling, yet it effectively separates patches with different labels in the feature space. Experimental results demonstrate that the image features generated by our WeakSupCon method lead to improved downstream MIL performance compared to self-supervised contrastive learning approaches in three datasets. Our related code is available at github.com/BzhangURU/Paper_WeakSupCon_for_MIL
Beihang University（北京航空航天大学）；Hefei University of Technology（合肥工业大学）
Local representation learning has been a key challenge to promote the performance of the histopathological whole slide images analysis. The previous representation learning methods followed the supervised learning paradigm. However, manual annotation for large-scale WSIs is time-consuming and labor-intensive. Hence, the self-supervised contrastive learning has recently attracted intensive attention. The present contrastive learning methods treat each sample as a single class, which suffers from class collision problems, especially in the domain of histopathology image analysis. In this paper, …
University of Rochester（罗切斯特大学）；HistoWiz Inc.（HistoWiz公司）
Automated whole slide image (WSI) tagging has become a growing demand due to the increasing volume and diversity of WSIs collected nowadays in histopathology. Various methods have been studied to classify WSIs with single tags but none of them focuses on labeling WSIs with multiple tags. To this end, we propose a novel end-to-end trainable deep neural network named Patch Transformer which can effectively predict multiple slide-level tags from WSI patches based on both the correlations and the uniqueness between the tags. Specifically, the proposed method learns patch characteristics considerin…
University of Toronto（多伦多大学）；University of British Columbia（不列颠哥伦比亚大学）；Sunnybrook Research Institute（森尼布鲁克研究所）
Unsupervised learning has been a long-standing goal of machine learning and is especially important for medical image analysis, where the learning can compensate for the scarcity of labeled datasets. A promising subclass of unsupervised learning is self-supervised learning, which aims to learn salient features using the raw input as the learning signal. In this paper, we use a contrastive self-supervised learning method called SimCLR that achieved state-of-the-art results on natural-scene images and apply this method to digital histopathology by collecting and pretraining on 57 histopathology …
Learning from the Right Patches: A Two-Stage Wavelet-Driven Masked Autoencoder for Histopathology Representation Learning
PLRI Medical Informatics Institute（PLRI医学信息学研究所）；CAIMed Reserch Center（CAIMed研究中心）；Hannover Medical School（汉诺威医学院）；Computer Science Institute（计算机科学研究所）；Leibniz University Hannover（莱比锡大学汉诺威分校）；Sanford Burnham Prebys Medical Discovery Institute（桑福医疗发现研究所）；Rady Children’s Institute for Genomic Medicine（拉迪儿童基因医学研究所）；University of California San Diego（加州大学圣地亚哥分校）
Central South University（中南大学）；Nanjing Tech University（南京工业大学）；The third affiliated hospital of Soochow University（苏州大学第三附属医院）
Digital pathological analysis is run as the main examination used for cancer diagnosis. Recently, deep learning-driven feature extraction from pathology images is able to detect genetic variations and tumor environment, but few studies focus on differential gene expression in tumor cells. In this paper, we propose a self-supervised contrastive learning framework, HistCode, to infer differential gene expressions from whole slide images (WSIs). We leveraged contrastive learning on large-scale unannotated WSIs to derive slide-level histopathological feature in latent space, and then transfer it t…
There is a strong need for automated systems to improve diagnostic quality and reduce the analysis time in histopathology image processing. Automated detection and classification of pathological tissue characteristics with computer-aided diagnostic systems are a critical step in the early diagnosis and treatment of diseases. Once a pathology image is scanned by a microscope and loaded onto a computer, it can be used for automated detection and classification of diseases. In this study, the DenseNet-161 and ResNet-50 pre-trained CNN models have been used to classify digital histopathology patch…
Advancement in digital pathology and artificial intelligence has enabled deep learning-based computer vision techniques for automated disease diagnosis and prognosis. However, WSIs present unique computational and algorithmic challenges. WSIs are gigapixel-sized, making them infeasible to be used directly for training deep neural networks. Hence, for modeling, a two-stage approach is adopted: Patch representations are extracted first, followed by the aggregation for WSI prediction. These approaches require detailed pixel-level annotations for training the patch encoder. However, obtaining thes…
Clinically-Informed Modeling for Pediatric Brain Tumor Classification from Whole-Slide Histopathology Images
Dept. of Computer Science（计算机科学系）；University of Texas at Austin（德克萨斯大学奥斯汀分校）；School of Information（信息学院）；Dell Children's Medical Center（德尔儿童医学中心）；Dept. of OREI（OREI部门）；University of Nevada, Reno（内华达大学里诺分校）
Unsupervised learning has made substantial progress over the last few years, especially by means of contrastive self-supervised learning. The dominating dataset for benchmarking self-supervised learning has been ImageNet, for which recent methods are approaching the performance achieved by fully supervised training. The ImageNet dataset is however largely object-centric, and it is not clear yet what potential those methods have on widely different datasets and tasks that are not object-centric, such as in digital pathology. While self-supervised learning has started to be explored within this …
University of Waterloo（滑铁卢大学）；Amirkabir University of Technology（阿米尔卡比尔理工大学）
We explore the problem of classification within a medical image data-set based on a feature vector extracted from the deepest layer of pre-trained Convolution Neural Networks. We have used feature vectors from several pre-trained structures, including networks with/without transfer learning to evaluate the performance of pre-trained deep features versus CNNs which have been trained by that specific dataset as well as the impact of transfer learning with a small number of samples. All experiments are done on Kimia Path24 dataset which consists of 27,055 histopathology training patches in 24 tis…
Spatial Transcriptomics Expression Prediction from Histopathology Based on Cross-Modal Mask Reconstruction and Contrastive Learning
University of Regensburg（雷根斯堡大学）；Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)（埃尔朗根-纽伦堡弗里德里希-亚历山大大学）；Beijing Friendship Hospital, Capital Medical University（首都医科大学附属北京友谊医院）；Hanover Medical School（汉诺威医学院）；University Clinic Freiburg（弗莱堡大学附属医院）；Fraunhofer Institute for Digital Medicine MEVIS（弗劳恩霍夫数字医学研究所）
Weakly Supervised Spatial Grounding for Discriminative Attention-Based Ultrasound-Histopathology Alignment in Prostate Cancer Grading
University of British Columbia（不列颠哥伦比亚大学）；Vector Institute（向量研究所）；Ordensklinikum Linz（林茨教团医院）；University of Alberta（阿尔伯塔大学）；Exact Imaging（Exact Imaging公司）
Vector Institute（向量研究所）；Pierre and Marie Curie University（皮埃尔和玛丽·居里大学）；Sorbonne University（索邦大学）；University of Waterloo（滑铁卢大学）
Whole Slide Imaging (WSI) has become an important topic during the last decade. Even though significant progress in both medical image processing and computational resources has been achieved, there are still problems in WSI that need to be solved. A major challenge is the scan size. The dimensions of digitized tissue samples may exceed 100,000 by 100,000 pixels causing memory and efficiency obstacles for real-time processing. The main contribution of this work is representing a WSI by selecting a small number of patches for algorithmic processing (e.g., indexing and search). As a result, we r…
North Shore Country Day（北岸乡村日校）；Northwestern University（西北大学）
Data labeling is often the most challenging task when developing computational pathology models. Pathologist participation is necessary to generate accurate labels, and the limitations on pathologist time and demand for large, labeled datasets has led to research in areas including weakly supervised learning using patient-level labels, machine assisted annotation and active learning. In this paper we explore self-supervised learning to reduce labeling burdens in computational pathology. We explore this in the context of classification of breast cancer tissue using the Barlow Twins approach, an…
We analyze the effect of offline and online triplet mining for colorectal cancer (CRC) histopathology dataset containing 100,000 patches. We consider the extreme, i.e., farthest and nearest patches to a given anchor, both in online and offline mining. While many works focus solely on selecting the triplets online (batch-wise), we also study the effect of extreme distances and neighbor patches before training in an offline fashion. We analyze extreme cases' impacts in terms of embedding distance for offline versus online mining, including easy positive, batch semi-hard, batch hard triplet minin…
The Pennsylvania State University（宾夕法尼亚州立大学）；Lister Hill National Center for Biomedical Communications（利斯特希尔国家生物医学通信中心）；National Library of Medicine（国家医学图书馆）；Penn State Health Milton S. Hershey Medical Center（宾夕法尼亚州立大学健康米尔顿·S·赫尔希医学中心）；Penn State College Of Medicine（宾夕法尼亚州立大学医学院）
Histopathological analysis is the present gold standard for precancerous lesion diagnosis. The goal of automated histopathological classification from digital images requires supervised training, which requires a large number of expert annotations that can be expensive and time-consuming to collect. Meanwhile, accurate classification of image patches cropped from whole-slide images is essential for standard sliding window based histopathology slide classification methods. To mitigate these issues, we propose a carefully designed conditional GAN model, namely HistoGAN, for synthesizing realisti…
Histopathology digital scans are large-size images that contain valuable information at the pixel level. Content-based comparison of these images is a challenging task. This study proposes a content-based similarity measure for high-resolution gigapixel histopathology images. The proposed similarity measure is an expansion of cosine vector similarity to a matrix. Each image is divided into same-size patches with a meaningful amount of information (i.e., contained enough tissue). The similarity is measured by the extraction of patch-level deep embeddings of the last pooling layer of a pre-train…
University of British Columbia（不列颠哥伦比亚大学）；BC Cancer Agency（不列颠哥伦比亚省癌症局）；Deeley Research Centre（迪利研究中心）
In clinical practice, many diagnosis tasks rely on the identification of cells in histopathology images. While supervised machine learning techniques require labels, providing manual cell annotations is time-consuming due to the large number of cells. In this paper, we propose a self-supervised framework (VOLTA) for cell representation learning in histopathology images using a novel technique that accounts for the cell's mutual relationship with its environment for improved cell representations. We subjected our model to extensive experiments on the data collected from multiple institutions ar…
Isfahan University of Technology（伊斯法罕理工大学）；McMaster University（麦克马斯特大学）
Digital pathology is one of the most significant developments in modern medicine. Pathological examinations are the gold standard of medical protocols and play a fundamental role in diagnosis. Recently, with the advent of digital scanners, tissue histopathology slides can now be digitized and stored as digital images. As a result, digitized histopathological tissues can be used in computer-aided image analysis programs and machine learning techniques. Detection and segmentation of nuclei are some of the essential steps in the diagnosis of cancers. Recently, deep learning has been used for nucl…
Automated classification of histopathological whole-slide images (WSI) of breast tissue requires analysis at very high resolutions with a large contextual area. In this paper, we present context-aware stacked convolutional neural networks (CNN) for classification of breast WSIs into normal/benign, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC). We first train a CNN using high pixel resolution patches to capture cellular level information. The feature responses generated by this model are then fed as input to a second CNN, stacked on top of the first. Training of this stac…
Low-resource finetuning of foundation models beats state-of-the-art in histopathology
School of Computation and Information Technology, Technical University of Munich（慕尼黑工业大学计算与信息技术学院）；Helmholtz Zentrum München - German Research Center for Environmental Health（慕尼黑亥姆霍兹中心——德国环境健康研究中心）；School of Biomedical Engineering and Imaging Sciences, King’s College London（伦敦国王学院生物医学工程与影像科学学院）
SIGMMA: Hierarchical Graph-Based Multi-Scale Multi-modal Contrastive Alignment of Histopathology Image and Spatial Transcriptome
Wellcome Sanger Institute（沃森桑格研究所）；Cambridge Centre for AI in Medicine（剑桥人工智能医学中心）；Institute of AI for Health（人工智能与健康研究所）；Cambridge Stem Cell Institute（剑桥干细胞研究所）
Cross-Modal Contrastive Learning from Histopathology and CT for Automated Renal Cell Carcinoma Grading
Dartmouth College（达特茅斯学院）；Geisel School of Medicine at Dartmouth（达特茅斯盖泽尔医学院）；Massachusetts General Hospital（麻省总医院）；Dartmouth-Hitchcock Medical Center（达特茅斯-希契科克医疗中心）；Memorial Sloan Kettering Cancer Center（纪念斯隆-凯特琳癌症中心）
University of Waterloo（滑铁卢大学）；Vector Institute（向量研究所）
Representation learning for Whole Slide Images (WSIs) is pivotal in developing image-based systems to achieve higher precision in diagnostic pathology. We propose a two-stage framework for WSI representation learning. We sample relevant patches using a color-based method and use graph neural networks to learn relations among sampled patches to aggregate the image information into a single vector representation. We introduce attention via graph pooling to automatically infer patches with higher relevance. We demonstrate the performance of our approach for discriminating two sub-types of lung ca…
Faculty of Informatics and Data Science, University of Regensburg, Germany（信息学与数据科学学院，雷根萨大学）；Indian Institute of Information Technology Bhopal, India（比哈尔信息学院）
Stony Brook University（石溪大学）；Oak Ridge National Laboratory（橡树岭国家实验室）；Stony Brook University Hospital（石溪大学医院）
Histopathology images are crucial to the study of complex diseases such as cancer. The histologic characteristics of nuclei play a key role in disease diagnosis, prognosis and analysis. In this work, we propose a sparse Convolutional Autoencoder (CAE) for fully unsupervised, simultaneous nucleus detection and feature extraction in histopathology tissue images. Our CAE detects and encodes nuclei in image patches in tissue images into sparse feature maps that encode both the location and appearance of nuclei. Our CAE is the first unsupervised detection network for computer vision applications. T…
A deep learning pipeline for PAM50 subtype classification using histopathology images and multi-objective patch selection
Austrian Center for Medical Innovation and Technology（奥地利医学创新与技术中心）；Danube Private University（多瑙河私立大学）；Medical University of Vienna（维也纳医科大学）；Patho im Zentrum（中心病理机构）；Institute for Systems and Robotics (ISR-Lisboa/LARSyS)（系统与机器人研究所（里斯本系统与机器人研究所/卢西塔尼亚机器人与系统协会））；Instituto Superior Técnico（高等技术学院）；University of Lisbon（里斯本大学）；The University of Texas MD Anderson Cancer Center（德克萨斯大学MD安德森癌症中心）
Hierarchical Text-to-Vision Self Supervised Alignment for Improved Histopathology Representation Learning
Mohamed Bin Zayed University of Artificial Intelligence（穆罕默德·本·扎耶德人工智能大学）；Stony Brook University（石溪大学）；Shaukat Khanum Cancer Hospital（肖卡特·卡努姆癌症医院）；Australian National University（澳大利亚国立大学）
The distribution and appearance of nuclei are essential markers for the diagnosis and study of cancer. Despite the importance of nuclear morphology, there is a lack of large scale, accurate, publicly accessible nucleus segmentation data. To address this, we developed an analysis pipeline that segments nuclei in whole slide tissue images from multiple cancer types with a quality control process. We have generated nucleus segmentation results in 5,060 Whole Slide Tissue images from 10 cancer types in The Cancer Genome Atlas. One key component of our work is that we carried out a multi-level qual…
Promptable Representation Distribution Learning and Data Augmentation for Gigapixel Histopathology WSI Analysis
Beihang University（北京航空航天大学）；Tianmushan Laboratory（天目山实验室）；Hefei University of Technology（合肥工业大学）；the First Affiliated Hospital of USTC（中国科学技术大学附属第一医院）；University of Science and Technology of China（中国科学技术大学）
Due to the recent advancements in machine vision, digital pathology has gained significant attention. Histopathology images are distinctly rich in visual information. The tissue glass slide images are utilized for disease diagnosis. Researchers study many methods to process histopathology images and facilitate fast and reliable diagnosis; therefore, the availability of high-quality slides becomes paramount. The quality of the images can be negatively affected when the glass slides are ink-marked by pathologists to delineate regions of interest. As an example, in one of the largest public histo…
Histopathology image analysis can be considered as a Multiple instance learning (MIL) problem, where the whole slide histopathology image (WSI) is regarded as a bag of instances (i.e, patches) and the task is to predict a single class label to the WSI. However, in many real-life applications such as computational pathology, discovering the key instances that trigger the bag label is of great interest because it provides reasons for the decision made by the system. In this paper, we propose a deep convolutional neural network (CNN) model that addresses the primary task of a bag classification o…
Pennsylvania State University（宾夕法尼亚州立大学）；National Library of Medicine, National Institutes of Health（美国国立卫生研究院国家医学图书馆）
Cervical intraepithelial neoplasia (CIN) grade of histopathology images is a crucial indicator in cervical biopsy results. Accurate CIN grading of epithelium regions helps pathologists with precancerous lesion diagnosis and treatment planning. Although an automated CIN grading system has been desired, supervised training of such a system would require a large amount of expert annotations, which are expensive and time-consuming to collect. In this paper, we investigate the CIN grade classification problem on segmented epithelium patches. We propose to use conditional Generative Adversarial Netw…
Vector Institute（向量研究所）；University of Waterloo（滑铁卢大学）
Whole slide imaging (WSI) refers to the digitization of a tissue specimen which enables pathologists to explore high-resolution images on a monitor rather than through a microscope. The formation of tissue folds occur during tissue processing. Their presence may not only cause out-of-focus digitization but can also negatively affect the diagnosis in some cases. In this paper, we have compared five pre-trained convolutional neural networks (CNNs) of different depths as feature extractors to characterize tissue folds. We have also explored common classifiers to discriminate folded tissue against…
Breast cancer has the highest mortality among cancers in women. Computer-aided pathology to analyze microscopic histopathology images for diagnosis with an increasing number of breast cancer patients can bring the cost and delays of diagnosis down. Deep learning in histopathology has attracted attention over the last decade of achieving state-of-the-art performance in classification and localization tasks. The convolutional neural network, a deep learning framework, provides remarkable results in tissue images analysis, but lacks in providing interpretation and reasoning behind the decisions. …
Northeastern University（东北大学）；Shenyang Institute of Automation, Chinese Academy of Sciences（中国科学院沈阳自动化研究所）；Stevens Institute of Technology（史蒂文斯理工学院）；China Medical University（中国医科大学）；Liaoning Cancer Hospital and Institute（辽宁省肿瘤医院暨研究所）；Chengdu University of Information Technology（成都信息工程大学）
In the Gastric Histopathology Image Classification (GHIC) tasks, which are usually weakly supervised learning missions, there is inevitably redundant information in the images. Therefore, designing networks that can focus on effective distinguishing features has become a popular research topic. In this paper, to accomplish the tasks of GHIC superiorly and to assist pathologists in clinical diagnosis, an intelligent Hierarchical Conditional Random Field based Attention Mechanism (HCRF-AM) model is proposed. The HCRF-AM model consists of an Attention Mechanism (AM) module and an Image Classifica…
