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 mining, neighborhood component analysis loss, its proxy version, and distance weighted sampling. We also investigate online approaches based on extreme distance and comprehensively compare offline, and online mining performance based on the data patterns and explain offline mining as a tractable generalization of the online mining with large mini-batch size. As well, we discuss the relations of different colorectal tissue types in terms of extreme distances. We found that offline and online mining approaches have comparable performances for a specific architecture, such as ResNet-18 in this study. Moreover, we found the assorted case, including different extreme distances, is promising, especially in the online approach.
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…
University of Toronto（多伦多大学）；National Cancer Research Centre（国家癌症研究中心）；Institute for Oncology and Radiology（肿瘤与放射学研究所）
Accurate diagnosis of breast cancer in histopathology images is challenging due to the heterogeneity of cancer cell growth as well as of a variety of benign breast tissue proliferative lesions. In this paper, we propose a practical and self-interpretable invasive cancer diagnosis solution. With minimum annotation information, the proposed method mines contrast patterns between normal and malignant images in unsupervised manner and generates a probability map of abnormalities to verify its reasoning. Particularly, a fully convolutional autoencoder is used to learn the dominant structural patter…
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…
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…
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…
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…
University of Waterloo（滑铁卢大学）；Huron Digital Pathology（休伦数字病理学公司）；University of Pittsburgh Medical Center（匹兹堡大学医学中心）；Vector Institute（矢量研究所）
With the emergence of digital pathology, searching for similar images in large archives has gained considerable attention. Image retrieval can provide pathologists with unprecedented access to the evidence embodied in already diagnosed and treated cases from the past. This paper proposes a search engine specialized for digital pathology, called Yottixel, a portmanteau for "one yotta pixel," alluding to the big-data nature of histopathology images. The most impressive characteristic of Yottixel is its ability to represent whole slide images (WSIs) in a compact manner. Yottixel can perform milli…
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…
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…
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）
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. …
Helmholtz Munich（亥姆霍兹慕尼黑中心）；Technical University of Munich（慕尼黑工业大学）；Johns Hopkins University（约翰斯·霍普金斯大学）
In many histopathology tasks, sample classification depends on morphological details in tissue or single cells that are only visible at the highest magnification. For a pathologist, this implies tedious zooming in and out, while for a computational decision support algorithm, it leads to the analysis of a huge number of small image patches per whole slide image (WSI). Attention-based multiple instance learning (MIL), where attention estimation is learned in a weakly supervised manner, has been successfully applied in computational histopathology, but it is challenged by large numbers of irrele…
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…
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）
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…
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…
Computational histopathology has made significant strides in the past few years, slowly getting closer to clinical adoption. One area of benefit would be the automatic generation of diagnostic reports from H\&E-stained whole slide images which would further increase the efficiency of the pathologists' routine diagnostic workflows. In this study, we compiled a dataset (PatchGastricADC22) of histopathological captions of stomach adenocarcinoma endoscopic biopsy specimens, which we extracted from diagnostic reports and paired with patches extracted from the associated whole slide images. The data…
Multiple Instance Learning Framework with Masked Hard Instance Mining for Gigapixel Histopathology Image Analysis
Hong Kong University of Science and Technology（香港科学与技术大学）；Hefei University of Technology（合肥工业大学）；Nanjing University of Posts and Telecommunications（南京邮电大学）
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…
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…
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）
Technische Hochschule Ingolstadt（英戈尔施塔特工业大学）；University Hospital Erlangen（埃尔朗根大学医院）；University of Veterinary Medicine Vienna（维也纳兽医大学）；Friedrich-Alexander-Universität Erlangen-Nürnberg（弗里德里希-亚历山大-埃尔朗根-纽伦堡大学）
Meningioma is one of the most prevalent brain tumors in adults. To determine its malignancy, it is graded by a pathologist into three grades according to WHO standards. This grade plays a decisive role in treatment, and yet may be subject to inter-rater discordance. In this work, we present and compare three approaches towards fully automatic meningioma grading from histology whole slide images. All approaches are following a two-stage paradigm, where we first identify a region of interest based on the detection of mitotic figures in the slide using a state-of-the-art object detection deep lea…
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…
Scientific Computing and Imaging Institute, University of Utah（犹他大学科学计算与成像研究所）；University of Utah（犹他大学）
Pathologists diagnose and grade prostate cancer by examining tissue from needle biopsies on glass slides. The cancer's severity and risk of metastasis are determined by the Gleason grade, a score based on the organization and morphology of prostate cancer glands. For diagnostic work-up, pathologists first locate glands in the whole biopsy core, and -- if they detect cancer -- they assign a Gleason grade. This time-consuming process is subject to errors and significant inter-observer variability, despite strict diagnostic criteria. This paper proposes an automated workflow that follows patholog…
Huron Digital Pathology（休伦数字病理学公司）；University of Waterloo（滑铁卢大学）；Vector Institute（矢量研究所）；McMaster University（麦克马斯特大学）；University of Pittsburgh Medical Center（匹兹堡大学医学中心）
The emergence of digital pathology has opened new horizons for histopathology and cytology. Artificial-intelligence algorithms are able to operate on digitized slides to assist pathologists with diagnostic tasks. Whereas machine learning involving classification and segmentation methods have obvious benefits for image analysis in pathology, image search represents a fundamental shift in computational pathology. Matching the pathology of new patients with already diagnosed and curated cases offers pathologist a novel approach to improve diagnostic accuracy through visual inspection of similar c…
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 Connecticut（康涅狄格大学）；University of Connecticut Health Center（康涅狄格大学健康中心）
Prostate cancer is the most common cancer in men worldwide and the second leading cause of cancer death in the United States. One of the prognostic features in prostate cancer is the Gleason grading of histopathology images. The Gleason grade is assigned based on tumor architecture on Hematoxylin and Eosin (H&E) stained whole slide images (WSI) by the pathologists. This process is time-consuming and has known interobserver variability. In the past few years, deep learning algorithms have been used to analyze histopathology images, delivering promising results for grading prostate cancer. Howev…
DepViT-CAD: Deployable Vision Transformer-Based Cancer Diagnosis in Histopathology
University of Padova, Italy（意大利帕多瓦大学）；Unit of Surgical Pathology and Cytopathology, Ospedale dell’Angelo, Italy（意大利奥斯佩达莱-安吉洛外科病理学与细胞病理学单位）；Pathological Anatomy Unit, Padova University-Hospital, Italy（意大利帕多瓦大学医院病理学解剖单位）；Department of Medicine, University of Padova, Italy（意大利帕多瓦大学医学系）；Department of Integrated Diagnostics, Azienda Ospedale-Università Padova, Italy（意大利帕多瓦医院-大学整合诊断系）
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）
PathFinder: A Multi-Modal Multi-Agent System for Medical Diagnostic Decision-Making Applied to Histopathology
University of Washington（华盛顿大学）；Microsoft Research（微软研究院）；David Geffen School of Medicine, UCLA（加州大学洛杉矶分校大卫·格芬医学院）；Allen Institute for AI (AI2)（艾伦人工智能研究所）
University of Liverpool（利物浦大学）；Cixi Institute of Biomedical Engineering, Chinese Academy of Sciences（中国科学院慈溪生物医学工程研究所）；China Science IntelliCloud Technology Co., Ltd（中科智云科技有限公司）；Remark AI UK Limited（Remark AI英国有限公司）
Multiple instance learning (MIL) has been increasingly used in the classification of histopathology whole slide images (WSIs). However, MIL approaches for this specific classification problem still face unique challenges, particularly those related to small sample cohorts. In these, there are limited number of WSI slides (bags), while the resolution of a single WSI is huge, which leads to a large number of patches (instances) cropped from this slide. To address this issue, we propose to virtually enlarge the number of bags by introducing the concept of pseudo-bags, on which a double-tier MIL f…
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…
University Hospital and University of Zurich（苏黎世大学医院和苏黎世大学）
Making histopathology image classifiers robust to a wide range of real-world variability is a challenging task. Here, we describe a candidate deep learning solution for the Mitosis Domain Generalization Challenge 2022 (MIDOG) to address the problem of generalization for mitosis detection in images of hematoxylin-eosin-stained histology slides under high variability (scanner, tissue type and species variability). Our approach consists in training a rotation-invariant deep learning model using aggressive data augmentation with a training set enriched with hard negative examples and automatically…
Taiwan AI Labs（台湾人工智能实验室）；National Taiwan University College of Medicine（台湾大学医学院）；Taipei Veterans General Hospital（台北荣民总医院）；Academia Sinica（中央研究院）
Delineation of cancerous regions in gigapixel whole slide images (WSIs) is a crucial diagnostic procedure in digital pathology. This process is time-consuming because of the large search space in the gigapixel WSIs, causing chances of omission and misinterpretation at indistinct tumor lesions. To tackle this, the development of an automated cancerous region segmentation method is imperative. We frame this issue as a modeling problem with partial label WSIs, where some cancerous regions may be misclassified as benign and vice versa, producing patches with noisy labels. To learn from these patch…
Label-free Concept Based Multiple Instance Learning for Gigapixel Histopathology
University of Tübingen（蒂宾根大学）；University of Lucerne（卢塞恩大学）；Radboud University Medical Center（拉德堡德大学医学中心）；Institut du Cancer de l’Ouest（西部癌症研究所）；Oncode Institute（Oncode研究所）
Multi-Resolution Histopathology Patch Graphs for Ovarian Cancer Subtyping
Centre for Computational Imaging and Simulation Technologies in Biomedicine (CISTIB)（生物医学计算成像与模拟技术中心）；School of Computing, University of Leeds（利兹大学计算机学院）；Leeds Institute of Medical Research at St James’s, School of Medicine, University of Leeds（利兹大学医学院圣詹姆斯利兹医学研究所）；Leeds Cancer Centre, St James’s University Hospital（圣詹姆斯大学医院利兹癌症中心）
GRAPHITE: Graph-Based Interpretable Tissue Examination for Enhanced Explainability in Breast Cancer Histopathology
School of Computer Science and Engineering（计算机科学与工程学院）；University of New South Wales（新南威尔士大学）；St. George and Sutherland Clinical School（圣乔治与萨瑟兰临床学院）；Department of Anatomical Pathology（解剖病理学部）；NSW Health Pathology（新南威尔士州卫生病理学）；Cancer Care Centre（癌症护理中心）
