The unique nature of histopathology images opens the door to domain-specific formulations of image translation models. We propose a difficulty translation model that modifies colorectal histopathology images to be more challenging to classify. Our model comprises a scorer, which provides an output confidence to measure the difficulty of images, and an image translator, which learns to translate images from easy-to-classify to hard-to-classify using a training set defined by the scorer. We present three findings. First, generated images were indeed harder to classify for both human pathologists and machine learning classifiers than their corresponding source images. Second, image classifiers trained with generated images as augmented data performed better on both easy and hard images from an independent test set. Finally, human annotator agreement and our model's measure of difficulty correlated strongly, implying that for future work requiring human annotator agreement, the confidence score of a machine learning classifier could be used as a proxy.
Dartmouth College（达特茅斯学院）；Dartmouth-Hitchcock Medical Center（达特茅斯-希区柯克医疗中心）
Applying curriculum learning requires both a range of difficulty in data and a method for determining the difficulty of examples. In many tasks, however, satisfying these requirements can be a formidable challenge. In this paper, we contend that histopathology image classification is a compelling use case for curriculum learning. Based on the nature of histopathology images, a range of difficulty inherently exists among examples, and, since medical datasets are often labeled by multiple annotators, annotator agreement can be used as a natural proxy for the difficulty of a given example. Hence,…
Rotation-invariance is a desired property of machine-learning models for medical image analysis and in particular for computational pathology applications. We propose a framework to encode the geometric structure of the special Euclidean motion group SE(2) in convolutional networks to yield translation and rotation equivariance via the introduction of SE(2)-group convolution layers. This structure enables models to learn feature representations with a discretized orientation dimension that guarantees that their outputs are invariant under a discrete set of rotations. Conventional approaches fo…
Dartmouth College（达特茅斯学院）；Dartmouth-Hitchcock Medical Center（达特茅斯-希区柯克医疗中心）
We present an image translation approach to generate augmented data for mitigating data imbalances in a dataset of histopathology images of colorectal polyps, adenomatous tumors that can lead to colorectal cancer if left untreated. By applying cycle-consistent generative adversarial networks (CycleGANs) to a source domain of normal colonic mucosa images, we generate synthetic colorectal polyp images that belong to diagnostically less common polyp classes. Generated images maintain the general structure of their source image but exhibit adenomatous features that can be enhanced with our propose…
The classification of histopathology images fundamentally differs from traditional image classification tasks because histopathology images naturally exhibit a range of diagnostic features, resulting in a diverse range of annotator agreement levels. However, examples with high annotator disagreement are often either assigned the majority label or discarded entirely when training histopathology image classifiers. This widespread practice often yields classifiers that do not account for example difficulty and exhibit poor model calibration. In this paper, we ask: can we improve model calibration…
The diagnosis of cancer is mainly performed by visual analysis of the pathologists, through examining the morphology of the tissue slices and the spatial arrangement of the cells. If the microscopic image of a specimen is not stained, it will look colorless and textured. Therefore, chemical staining is required to create contrast and help identify specific tissue components. During tissue preparation due to differences in chemicals, scanners, cutting thicknesses, and laboratory protocols, similar tissues are usually varied significantly in appearance. This diversity in staining, in addition to…
In the clinical setting of histopathology, whole-slide image (WSI) artifacts frequently arise, distorting regions of interest, and having a pernicious impact on WSI analysis. Image-to-image translation networks such as CycleGANs are in principle capable of learning an artifact removal function from unpaired data. However, we identify a surjection problem with artifact removal, and propose an weakly-supervised extension to CycleGAN to address this. We assemble a pan-cancer dataset comprising artifact and clean tiles from the TCGA database. Promising results highlight the soundness of our method…
NYU Grossman School of Medicine（纽约大学格罗斯曼医学院）；University of Toronto（多伦多大学）；Microsoft Research（微软研究院）
Scarcity of labeled histopathology data limits the applicability of deep learning methods to under-profiled cancer types and labels. Transfer learning allows researchers to overcome the limitations of small datasets by pre-training machine learning models on larger datasets similar to the small target dataset. However, similarity between datasets is often determined heuristically. In this paper, we propose a principled notion of distance between histopathology datasets based on a hierarchical generalization of optimal transport distances. Our method does not require any training, is agnostic t…
University of Strasbourg（斯特拉斯堡大学）；University of Belgrade（贝尔格莱德大学）；University of Kragujevac（克拉古耶瓦茨大学）
Domain shift in digital histopathology can occur when different stains or scanners are used, during stain translation, etc. A deep neural network trained on source data may not generalise well to data that has undergone some domain shift. An important step towards being robust to domain shift is the ability to detect and measure it. This article demonstrates that the PixelCNN and domain shift metric can be used to detect and quantify domain shift in digital histopathology, and they demonstrate a strong correlation with generalisation performance. These findings pave the way for a mechanism to …
Single-Stage Hierarchical Rectification for Weakly Supervised Histopathology Segmentation
VinUni-Illinois Smart Health Center, VinUniversity, Hanoi, Vietnam（越南河内VinUniversity VinUni-Illinois智慧健康中心）；The Computer Vision and Medical AI Lab, VinUniversity, Hanoi, Vietnam（越南河内VinUniversity计算机视觉与医学人工智能实验室）；Posts and Telecommunications Institute of Technology, Hanoi, Vietnam（越南河内邮电技术学院）
DeNuC: Decoupling Nuclei Detection and Classification in Histopathology
School of Automation and Electrical Engineering, University of Science and Technology Beijing（自动化与电气工程学院，北京科技大学）；University of Science and Technology Beijing（北京科技大学）；Beijing Engineering Research Center of Industrial Spectrum Imaging（工业光谱成像工程研究中心）
Histopathology whole slide images (WSIs) can reveal significant inter-hospital variability such as illumination, color or optical artifacts. These variations, caused by the use of different scanning protocols across medical centers (staining, scanner), can strongly harm algorithms generalization on unseen protocols. This motivates development of new methods to limit such drop of performances. In this paper, to enhance robustness on unseen target protocols, we propose a new test-time data augmentation based on multi domain image-to-image translation. It allows to project images from unseen prot…
Unsupervised and unpaired domain translation using generative adversarial neural networks, and more precisely CycleGAN, is state of the art for the stain translation of histopathology images. It often, however, suffers from the presence of cycle-consistent but non structure-preserving errors. We propose an alternative approach to the set of methods which, relying on segmentation consistency, enable the preservation of pathology structures. Focusing on immunohistochemistry (IHC) and multiplexed immunofluorescence (mIF), we introduce a simple yet effective guidance scheme as a loss function that…
Joint analysis of multiple biomarker images and tissue morphology is important for disease diagnosis, treatment planning and drug development. It requires cross-staining comparison among Whole Slide Images (WSIs) of immuno-histochemical and hematoxylin and eosin (H&E) microscopic slides. However, automatic, and fast cross-staining alignment of enormous gigapixel WSIs at single-cell precision is challenging. In addition to morphological deformations introduced during slide preparation, there are large variations in cell appearance and tissue morphology across different staining. In this paper, …
Equivariant Imaging Biomarkers for Robust Unsupervised Segmentation of Histopathology
Department of Biomedical Engineering, Yale University（生物医学工程系，耶鲁大学）；Department of Radiology & Biomedical Imaging, Yale University（放射科与生物医学成像系，耶鲁大学）；Department of Urology, Yale University（泌尿外科系，耶鲁大学）；Medical Scientist Training Program, Yale University（医学科学家培训计划，耶鲁大学）
Pathological diagnosis is the gold standard for cancer diagnosis, but it is labor-intensive, in which tasks such as cell detection, classification, and counting are particularly prominent. A common solution for automating these tasks is using nucleus segmentation technology. However, it is hard to train a robust nucleus segmentation model, due to several challenging problems, the nucleus adhesion, stacking, and excessive fusion with the background. Recently, some researchers proposed a series of automatic nucleus segmentation methods based on point annotation, which can significant improve the…
From Generic to Specialized: A Subspecialty Diagnostic System Powered by Self-Supervised Learning for Cervical Histopathology
Tsinghua University（清华大学）；Ningbo Clinical Pathology Diagnosis Center（宁波市临床病理诊断中心）；University of Oxford（牛津大学）；Research Institute of Tsinghua University in Shenzhen（清华大学深圳研究院）；Greater Bay Area National Center of Technology Innovation（粤港澳大湾区国家技术创新中心）；Zhejiang University School of Medicine（浙江大学医学院）；Hangzhou Adicon Clinical Laboratories Co., Ltd.（杭州艾迪康医学检验中心有限公司）；Wuhan University of Science and Technology（武汉科技大学）；Guangdong Women and Children Hospital（广东省妇幼保健院）；Maternal and Child Health Hospital of Hubei Province（湖北省妇幼保健院）；Shenzhen Shengqiang Technology Co., Ltd.（深圳盛强科技有限公司）；Pengcheng Laboratory（鹏城实验室）；Jinfeng Laboratory（金凤实验室）；The 920th Hospital of the Joint Logistics Support Force of PLA（中国人民解放军联勤保障部队第九二〇医院）；The Integrated Engineering Research Center of Cell Biological Medicine of State and Regions（细胞生物医学国家与区域整合工程研究中心）；Fuzhou University（福州大学）
IBM Research（IBM研究院）；EPFL（洛桑联邦理工学院）；ETH（苏黎世联邦理工学院）
Advances in entity-graph based analysis of histopathology images have brought in a new paradigm to describe tissue composition, and learn the tissue structure-to-function relationship. Entity-graphs offer flexible and scalable representations to characterize tissue organization, while allowing the incorporation of prior pathological knowledge to further support model interpretability and explainability. However, entity-graph analysis requires prerequisites for image-to-graph translation and knowledge of state-of-the-art machine learning algorithms applied to graph-structured data, which can po…
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）
We propose a framework for rotation and translation covariant deep learning using $SE(2)$ group convolutions. The group product of the special Euclidean motion group $SE(2)$ describes how a concatenation of two roto-translations results in a net roto-translation. We encode this geometric structure into convolutional neural networks (CNNs) via $SE(2)$ group convolutional layers, which fit into the standard 2D CNN framework, and which allow to generically deal with rotated input samples without the need for data augmentation. We introduce three layers: a lifting layer which lifts a 2D (vector va…
Rethinking Multiple Instance Learning: Developing an Instance-Level Classifier via Weakly-Supervised Self-Training
Digital Medical Research Center, School of Basic Medical Science, Fudan University（复旦大学基础医学院数字医学研究中心）；Shanghai Key Laboratory of Medical Image Computing and Computer Assisted Intervention（上海市医学影像计算与计算机辅助介入重点实验室）
F2FLDM: Latent Diffusion Models with Histopathology Pre-Trained Embeddings for Unpaired Frozen Section to FFPE Translation
University of Utah（犹他大学）；The Catholic University of Korea College of Medicine（韩国天主教大学医学院）；Huntsman Cancer Institute（亨茨曼癌症研究所）；Scientific Computing and Imaging Institute（科学计算与成像研究所）
The analysis of the tumor environment on digital histopathology slides is becoming key for the understanding of the immune response against cancer, supporting the development of novel immuno-therapies. We introduce here a novel deep learning solution to the related problem of tumor epithelium segmentation. While most existing deep learning segmentation approaches are trained on time-consuming and costly manual annotation on single stain domain (PD-L1), we leverage here semi-automatically labeled images from a second stain domain (Cytokeratin-CK). We introduce an end-to-end trainable network th…
Leveraging Pre-trained Models for FF-to-FFPE Histopathological Image Translation
Shenzhen International Graduate School, Tsinghua University（清华大学深圳国际研究生院）；The First Affiliated Hospital of Sun Yat-sen University（中山大学附属第一医院）；Jinfeng Laboratory（金凤实验室）
University of Strasbourg（斯特拉斯堡大学）；University of Belgrade（贝尔格莱德大学）；University of Kragujevac（克拉古耶瓦茨大学）；Hannover Medical School（汉诺威医学院）
It has been shown that unpaired image-to-image translation methods constrained by cycle-consistency hide the information necessary for accurate input reconstruction as imperceptible noise. We demonstrate that, when applied to histopathology data, this hidden noise appears to be related to stain specific features and show that this is the case with two immunohistochemical stainings during translation to Periodic acid- Schiff (PAS), a histochemical staining method commonly applied in renal pathology. Moreover, by perturbing this hidden information, the translation models produce different, plaus…
Shanghai Jiao Tong University（上海交通大学）；University of Technology Sydney（悉尼科技大学）；Xian Jiao Tong University（西安交通大学）
Prevailing image-translation frameworks mostly seek to process images via the end-to-end style, which has achieved convincing results. Nonetheless, these methods lack interpretability and are not scalable on different image-translation tasks (e.g., style transfer, HDR, etc.). In this paper, we propose an interpretable knowledge-based image-translation framework, which realizes the image-translation through knowledge retrieval and transfer. In details, the framework constructs a plug-and-play and model-agnostic general purpose knowledge library, remembering task-specific styles, tones, texture …
Beijing University of Posts and Telecommunications（北京邮电大学）；Kuaishou Technology（快手科技）
Unpaired image-to-image translation is to translate an image from a source domain to a target domain without paired training data. By utilizing CNN in extracting local semantics, various techniques have been developed to improve the translation performance. However, CNN-based generators lack the ability to capture long-range dependency to well exploit global semantics. Recently, Vision Transformers have been widely investigated for recognition tasks. Though appealing, it is inappropriate to simply transfer a recognition-based vision transformer to image-to-image translation due to the generati…
RWTH Aachen University（亚琛工业大学）；RWTH Aachen University Hospital（亚琛工业大学医院）；Fraunhofer Institute for Digital Medicine MEVIS（弗劳恩霍夫数字医学MEVIS研究所）
In digital pathology, many image analysis tasks are challenged by the need for large and time-consuming manual data annotations to cope with various sources of variability in the image domain. Unsupervised domain adaptation based on image-to-image translation is gaining importance in this field by addressing variabilities without the manual overhead. Here, we tackle the variation of different histological stains by unsupervised stain-to-stain translation to enable a stain-independent applicability of a deep learning segmentation model. We use CycleGANs for stain-to-stain translation in kidney …
We present a novel method for exemplar-based image translation, called matching interleaved diffusion models (MIDMs). Most existing methods for this task were formulated as GAN-based matching-then-generation framework. However, in this framework, matching errors induced by the difficulty of semantic matching across cross-domain, e.g., sketch and photo, can be easily propagated to the generation step, which in turn leads to degenerated results. Motivated by the recent success of diffusion models overcoming the shortcomings of GANs, we incorporate the diffusion models to overcome these limitatio…
University of Bucharest（布加勒斯特大学）；Institute of Mathematics of the Romanian Academy（罗马尼亚科学院数学研究所）；University “Politehnica” of Bucharest（布加勒斯特理工大学）
Despite the significant advances in recent years, Generative Adversarial Networks (GANs) are still notoriously hard to train. In this paper, we propose three novel curriculum learning strategies for training GANs. All strategies are first based on ranking the training images by their difficulty scores, which are estimated by a state-of-the-art image difficulty predictor. Our first strategy is to divide images into gradually more difficult batches. Our second strategy introduces a novel curriculum loss function for the discriminator that takes into account the difficulty scores of the real imag…
University of Science and Technology of China（中国科学技术大学）；JD AI Research（京东人工智能研究院）
Unsupervised image-to-image translation is the task of translating an image from one domain to another in the absence of any paired training examples and tends to be more applicable to practical applications. Nevertheless, the extension of such synthesis from image-to-image to video-to-video is not trivial especially when capturing spatio-temporal structures in videos. The difficulty originates from the aspect that not only the visual appearance in each frame but also motion between consecutive frames should be realistic and consistent across transformation. This motivates us to explore both a…
University of Tsukuba（筑波大学）；RIKEN Center for Advanced Intelligence Project（理化学研究所先进智能项目中心）
We investigate policy transfer using image-to-semantics translation to mitigate learning difficulties in vision-based robotics control agents. This problem assumes two environments: a simulator environment with semantics, that is, low-dimensional and essential information, as the state space, and a real-world environment with images as the state space. By learning mapping from images to semantics, we can transfer a policy, pre-trained in the simulator, to the real world, thereby eliminating real-world on-policy agent interactions to learn, which are costly and risky. In addition, using image-t…
The mood of a text and the intention of the writer can be reflected in the typeface. However, in designing a typeface, it is difficult to keep the style of various characters consistent, especially for languages with lots of morphological variations such as Chinese. In this paper, we propose a Typeface Completion Network (TCN) which takes one character as an input, and automatically completes the entire set of characters in the same style as the input characters. Unlike existing models proposed for image-to-image translation, TCN embeds a character image into two separate vectors representing …
