Histopathological image classification constitutes a pivotal task in computer-aided diagnostics. The precise identification and categorization of histopathological images are of paramount significance for early disease detection and treatment. In the diagnostic process of pathologists, a multi-tiered approach is typically employed to assess abnormalities in cell regions at different magnifications. However, feature extraction is often performed at a single granularity, overlooking the multi-granular characteristics of cells. To address this issue, we propose the Fuzzy-guided Multi-granularity Deep Neural Network (FMDNN). Inspired by the multi-granular diagnostic approach of pathologists, we perform feature extraction on cell structures at coarse, medium, and fine granularity, enabling the model to fully harness the information in histopathological images. We incorporate the theory of fuzzy logic to address the challenge of redundant key information arising during multi-granular feature extraction. Cell features are described from different perspectives using multiple fuzzy membership functions, which are fused to create universal fuzzy features. A fuzzy-guided cross-attention module guides universal fuzzy features toward multi-granular features. We propagate these features through an encoder to all patch tokens, aiming to achieve enhanced classification accuracy and robustness. In experiments on multiple public datasets, our model exhibits a significant improvement in accuracy over commonly used classification methods for histopathological image classification and shows commendable interpretability.
Histopathological images are widely used for the analysis of diseased (tumor) tissues and patient treatment selection. While the majority of microscopy image processing was previously done manually by pathologists, recent advances in computer vision allow for accurate recognition of lesion regions with deep learning-based solutions. Such models, however, usually require extensive annotated datasets for training, which is often not the case in the considered task, where the number of available patient data samples is very limited. To deal with this problem, we propose a novel DeepCMorph model pre-trained to learn cell morphology and identify a large number of different cancer types. The model consists of two modules: the first one performs cell nuclei segmentation and annotates each cell type, and is trained on a combination of 8 publicly available datasets to ensure its high generalizability and robustness. The second module combines the obtained segmentation map with the original microscopy image and is trained for the downstream task. We pre-trained this module on the Pan-Cancer TCGA dataset consisting of over 270K tissue patches extracted from 8736 diagnostic slides from 7175 patients. The proposed solution achieved a new state-of-the-art performance on the dataset under consideration, detecting 32 cancer types with over 82% accuracy and outperforming all previously proposed solutions by more than 4%. We demonstrate that the resulting pre-trained model can be easily fine-tuned on smaller microscopy datasets, yielding superior results compared to the current top solutions and models initialized with ImageNet weights. The codes and pre-trained models presented in this paper are available at: https://github.com/aiff22/DeepCMorph
Invasive ductal carcinoma (IDC) is the most prevalent form of breast cancer. Breast tissue histopathological examination is critical in diagnosing and classifying breast cancer. Although existing methods have shown promising results, there is still room for improvement in the classification accuracy and generalization of IDC using histopathology images. We present a novel approach, Supervised Contrastive Vision Transformer (SupCon-ViT), for improving the classification of invasive ductal carcinoma in terms of accuracy and generalization by leveraging the inherent strengths and advantages of both transfer learning, i.e., pre-trained vision transformer, and supervised contrastive learning. Our results on a benchmark breast cancer dataset demonstrate that SupCon-Vit achieves state-of-the-art performance in IDC classification, with an F1-score of 0.8188, precision of 0.7692, and specificity of 0.8971, outperforming existing methods. In addition, the proposed model demonstrates resilience in scenarios with minimal labeled data, making it highly efficient in real-world clinical settings where labelled data is limited. Our findings suggest that supervised contrastive learning in conjunction with pre-trained vision transformers appears to be a viable strategy for an accurate classification of IDC, thus paving the way for a more efficient and reliable diagnosis of breast cancer through histopathological image analysis.
Active Learning (AL) has the potential to solve a major problem of digital pathology: the efficient acquisition of labeled data for machine learning algorithms. However, existing AL methods often struggle in realistic settings with artifacts, ambiguities, and class imbalances, as commonly seen in the medical field. The lack of precise uncertainty estimations leads to the acquisition of images with a low informative value. To address these challenges, we propose Focused Active Learning (FocAL), which combines a Bayesian Neural Network with Out-of-Distribution detection to estimate different uncertainties for the acquisition function. Specifically, the weighted epistemic uncertainty accounts for the class imbalance, aleatoric uncertainty for ambiguous images, and an OoD score for artifacts. We perform extensive experiments to validate our method on MNIST and the real-world Panda dataset for the classification of prostate cancer. The results confirm that other AL methods are 'distracted' by ambiguities and artifacts which harm the performance. FocAL effectively focuses on the most informative images, avoiding ambiguities and artifacts during acquisition. For both experiments, FocAL outperforms existing AL approaches, reaching a Cohen's kappa of 0.764 with only 0.69% of the labeled Panda data.
Breast cancer classification stands as a pivotal pillar in ensuring timely diagnosis and effective treatment. This study with histopathological images underscores the profound significance of harnessing the synergistic capabilities of colour space ensembling and quantum-classical stacking to elevate the precision of breast cancer classification. By delving into the distinct colour spaces of RGB, HSV and CIE L*u*v, the authors initiated a comprehensive investigation guided by advanced methodologies. Employing the DenseNet121 architecture for feature extraction the authors have capitalized on the robustness of Random Forest, SVM, QSVC, and VQC classifiers. This research encompasses a unique feature fusion technique within the colour space ensemble. This approach not only deepens our comprehension of breast cancer classification but also marks a milestone in personalized medical assessment. The amalgamation of quantum and classical classifiers through stacking emerges as a potent catalyst, effectively mitigating the inherent constraints of individual classifiers, paving a robust path towards more dependable and refined breast cancer identification. Through rigorous experimentation and meticulous analysis, fusion of colour spaces like RGB with HSV and RGB with CIE L*u*v, presents an classification accuracy, nearing the value of unity. This underscores the transformative potential of our approach, where the fusion of diverse colour spaces and the synergy of quantum and classical realms converge to establish a new horizon in medical diagnostics. Thus the implications of this research extend across medical disciplines, offering promising avenues for advancing diagnostic accuracy and treatment efficacy.
Histopathological image classification is an important task in medical image analysis. Recent approaches generally rely on weakly supervised learning due to the ease of acquiring case-level labels from pathology reports. However, patch-level classification is preferable in applications where only a limited number of cases are available or when local prediction accuracy is critical. On the other hand, acquiring extensive datasets with localized labels for training is not feasible. In this paper, we propose a semi-supervised patch-level histopathological image classification model, named CLASS-M, that does not require extensively labeled datasets. CLASS-M is formed by two main parts: a contrastive learning module that uses separated Hematoxylin and Eosin images generated through an adaptive stain separation process, and a module with pseudo-labels using MixUp. We compare our model with other state-of-the-art models on two clear cell renal cell carcinoma datasets. We demonstrate that our CLASS-M model has the best performance on both datasets. Our code is available at github.com/BzhangURU/Paper_CLASS-M/tree/main
Deep learning for histopathology has been successfully used for disease classification, image segmentation and more. However, combining image and text modalities using current state-of-the-art (SOTA) methods has been a challenge due to the high resolution of histopathology images. Automatic report generation for histopathology images is one such challenge. In this work, we show that using an existing pre-trained Vision Transformer (ViT) to encode 4096x4096 sized patches of the Whole Slide Image (WSI) and a pre-trained Bidirectional Encoder Representations from Transformers (BERT) model for language modeling-based decoder for report generation, we can build a performant and portable report generation mechanism that takes into account the whole high resolution image. Our method allows us to not only generate and evaluate captions that describe the image, but also helps us classify the image into tissue types and the gender of the patient as well. Our best performing model achieves a 89.52% accuracy in Tissue Type classification with a BLEU-4 score of 0.12 in our caption generation task.
Healthcare is one of the foremost applications of machine learning (ML). Traditionally, ML models are trained by central servers, which aggregate data from various distributed devices to forecast the results for newly generated data. This is a major concern as models can access sensitive user information, which raises privacy concerns. A federated learning (FL) approach can help address this issue: A global model sends its copy to all clients who train these copies, and the clients send the updates (weights) back to it. Over time, the global model improves and becomes more accurate. Data privacy is protected during training, as it is conducted locally on the clients' devices. However, the global model is susceptible to data poisoning. We develop a privacy-preserving FL technique for a skin cancer dataset and show that the model is prone to data poisoning attacks. Ten clients train the model, but one of them intentionally introduces flipped labels as an attack. This reduces the accuracy of the global model. As the percentage of label flipping increases, there is a noticeable decrease in accuracy. We use a stochastic gradient descent optimization algorithm to find the most optimal accuracy for the model. Although FL can protect user privacy for healthcare diagnostics, it is also vulnerable to data poisoning, which must be addressed.
Convolutional neural networks excel in histopathological image classification, yet their pixel-level focus hampers explainability. Conversely, emerging graph convolutional networks spotlight cell-level features and medical implications. However, limited by their shallowness and suboptimal use of high-dimensional pixel data, GCNs underperform in multi-class histopathological image classification. To make full use of pixel-level and cell-level features dynamically, we propose an asymmetric co-training framework combining a deep graph convolutional network and a convolutional neural network for multi-class histopathological image classification. To improve the explainability of the entire framework by embedding morphological and topological distribution of cells, we build a 14-layer deep graph convolutional network to handle cell graph data. For the further utilization and dynamic interactions between pixel-level and cell-level information, we also design a co-training strategy to integrate the two asymmetric branches. Notably, we collect a private clinically acquired dataset termed LUAD7C, including seven subtypes of lung adenocarcinoma, which is rare and more challenging. We evaluated our approach on the private LUAD7C and public colorectal cancer datasets, showcasing its superior performance, explainability, and generalizability in multi-class histopathological image classification.
The rapid identification and accurate diagnosis of breast cancer, known as the killer of women, have become greatly significant for those patients. Numerous breast cancer histopathological image classification methods have been proposed. But they still suffer from two problems. (1) These methods can only hand high-resolution (HR) images. However, the low-resolution (LR) images are often collected by the digital slide scanner with limited hardware conditions. Compared with HR images, LR images often lose some key features like texture, which deeply affects the accuracy of diagnosis. (2) The existing methods have fixed receptive fields, so they can not extract and fuse multi-scale features well for images with different magnification factors. To fill these gaps, we present a \textbf{S}ingle \textbf{H}istopathological \textbf{I}mage \textbf{S}uper-\textbf{R}esolution \textbf{C}lassification network (SHISRCNet), which consists of two modules: Super-Resolution (SR) and Classification (CF) modules. SR module reconstructs LR images into SR ones. CF module extracts and fuses the multi-scale features of SR images for classification. In the training stage, we introduce HR images into the CF module to enhance SHISRCNet's performance. Finally, through the joint training of these two modules, super-resolution and classified of LR images are integrated into our model. The experimental results demonstrate that the effects of our method are close to the SOTA methods with taking HR images as inputs.
Breast cancer is a prevalent form of cancer among women, with over 1.5 million women being diagnosed each year. Unfortunately, the survival rates for breast cancer patients in certain third-world countries, like South Africa, are alarmingly low, with only 40% of diagnosed patients surviving beyond five years. The inadequate availability of resources, including qualified pathologists, delayed diagnoses, and ineffective therapy planning, contribute to this low survival rate. To address this pressing issue, medical specialists and researchers have turned to domain-specific AI approaches, specifically deep learning models, to develop end-to-end solutions that can be integrated into computer-aided diagnosis (CAD) systems. By improving the workflow of pathologists, these AI models have the potential to enhance the detection and diagnosis of breast cancer. This research focuses on evaluating the performance of various cutting-edge convolutional neural network (CNN) architectures in comparison to a relatively new model called the Vision Trans-former (ViT). The objective is to determine the superiority of these models in terms of their accuracy and effectiveness. The experimental results reveal that the ViT models outperform the other selected state-of-the-art CNN architectures, achieving an impressive accuracy rate of 95.15%. This study signifies a significant advancement in the field, as it explores the utilization of data augmentation and other relevant preprocessing techniques in conjunction with deep learning models for the detection and diagnosis of breast cancer using datasets of Breast Cancer Histopathological Image Classification.
Deep learning methods have emerged as powerful tools for analyzing histopathological images, but current methods are often specialized for specific domains and software environments, and few open-source options exist for deploying models in an interactive interface. Experimenting with different deep learning approaches typically requires switching software libraries and reprocessing data, reducing the feasibility and practicality of experimenting with new architectures. We developed a flexible deep learning library for histopathology called Slideflow, a package which supports a broad array of deep learning methods for digital pathology and includes a fast whole-slide interface for deploying trained models. Slideflow includes unique tools for whole-slide image data processing, efficient stain normalization and augmentation, weakly-supervised whole-slide classification, uncertainty quantification, feature generation, feature space analysis, and explainability. Whole-slide image processing is highly optimized, enabling whole-slide tile extraction at 40X magnification in 2.5 seconds per slide. The framework-agnostic data processing pipeline enables rapid experimentation with new methods built with either Tensorflow or PyTorch, and the graphical user interface supports real-time visualization of slides, predictions, heatmaps, and feature space characteristics on a variety of hardware devices, including ARM-based devices such as the Raspberry Pi.
Whole Slide Image (WSI) analysis is a powerful method to facilitate the diagnosis of cancer in tissue samples. Automating this diagnosis poses various issues, most notably caused by the immense image resolution and limited annotations. WSIs commonly exhibit resolutions of 100Kx100K pixels. Annotating cancerous areas in WSIs on the pixel level is prohibitively labor-intensive and requires a high level of expert knowledge. Multiple instance learning (MIL) alleviates the need for expensive pixel-level annotations. In MIL, learning is performed on slide-level labels, in which a pathologist provides information about whether a slide includes cancerous tissue. Here, we propose Self-ViT-MIL, a novel approach for classifying and localizing cancerous areas based on slide-level annotations, eliminating the need for pixel-wise annotated training data. Self-ViT- MIL is pre-trained in a self-supervised setting to learn rich feature representation without relying on any labels. The recent Vision Transformer (ViT) architecture builds the feature extractor of Self-ViT-MIL. For localizing cancerous regions, a MIL aggregator with global attention is utilized. To the best of our knowledge, Self-ViT- MIL is the first approach to introduce self-supervised ViTs in MIL-based WSI analysis tasks. We showcase the effectiveness of our approach on the common Camelyon16 dataset. Self-ViT-MIL surpasses existing state-of-the-art MIL-based approaches in terms of accuracy and area under the curve (AUC).
In recent years, colorectal cancer has become one of the most significant diseases that endanger human health. Deep learning methods are increasingly important for the classification of colorectal histopathology images. However, existing approaches focus more on end-to-end automatic classification using computers rather than human-computer interaction. In this paper, we propose an IL-MCAM framework. It is based on attention mechanisms and interactive learning. The proposed IL-MCAM framework includes two stages: automatic learning (AL) and interactivity learning (IL). In the AL stage, a multi-channel attention mechanism model containing three different attention mechanism channels and convolutional neural networks is used to extract multi-channel features for classification. In the IL stage, the proposed IL-MCAM framework continuously adds misclassified images to the training set in an interactive approach, which improves the classification ability of the MCAM model. We carried out a comparison experiment on our dataset and an extended experiment on the HE-NCT-CRC-100K dataset to verify the performance of the proposed IL-MCAM framework, achieving classification accuracies of 98.98% and 99.77%, respectively. In addition, we conducted an ablation experiment and an interchangeability experiment to verify the ability and interchangeability of the three channels. The experimental results show that the proposed IL-MCAM framework has excellent performance in the colorectal histopathological image classification tasks.
Test-time adaptation (TTA) has increasingly been an important topic to efficiently tackle the cross-domain distribution shift at test time for medical images from different institutions. Previous TTA methods have a common limitation of using a fixed learning rate for all the test samples. Such a practice would be sub-optimal for TTA, because test data may arrive sequentially therefore the scale of distribution shift would change frequently. To address this problem, we propose a novel dynamic learning rate adjustment method for test-time adaptation, called DLTTA, which dynamically modulates the amount of weights update for each test image to account for the differences in their distribution shift. Specifically, our DLTTA is equipped with a memory bank based estimation scheme to effectively measure the discrepancy of a given test sample. Based on this estimated discrepancy, a dynamic learning rate adjustment strategy is then developed to achieve a suitable degree of adaptation for each test sample. The effectiveness and general applicability of our DLTTA is extensively demonstrated on three tasks including retinal optical coherence tomography (OCT) segmentation, histopathological image classification, and prostate 3D MRI segmentation. Our method achieves effective and fast test-time adaptation with consistent performance improvement over current state-of-the-art test-time adaptation methods. Code is available at: https://github.com/med-air/DLTTA.
The gold standard for gastric cancer detection is gastric histopathological image analysis, but there are certain drawbacks in the existing histopathological detection and diagnosis. In this paper, based on the study of computer aided diagnosis system, graph based features are applied to gastric cancer histopathology microscopic image analysis, and a classifier is used to classify gastric cancer cells from benign cells. Firstly, image segmentation is performed, and after finding the region, cell nuclei are extracted using the k-means method, the minimum spanning tree (MST) is drawn, and graph based features of the MST are extracted. The graph based features are then put into the classifier for classification. In this study, different segmentation methods are compared in the tissue segmentation stage, among which are Level-Set, Otsu thresholding, watershed, SegNet, U-Net and Trans-U-Net segmentation; Graph based features, Red, Green, Blue features, Grey-Level Co-occurrence Matrix features, Histograms of Oriented Gradient features and Local Binary Patterns features are compared in the feature extraction stage; Radial Basis Function (RBF) Support Vector Machine (SVM), Linear SVM, Artificial Neural Network, Random Forests, k-NearestNeighbor, VGG16, and Inception-V3 are compared in the classifier stage. It is found that using U-Net to segment tissue areas, then extracting graph based features, and finally using RBF SVM classifier gives the optimal results with 94.29%.
Self-supervised learning (SSL) has drawn increasing attention in histopathological image analysis in recent years. Compared to contrastive learning which is troubled with the false negative problem, i.e., semantically similar images are selected as negative samples, masked autoencoders (MAE) building SSL from a generative paradigm is probably a more appropriate pre-training. In this paper, we introduce MAE and verify the effect of visible patches for histopathological image understanding. Moreover, a novel SD-MAE model is proposed to enable a self-distillation augmented MAE. Besides the reconstruction loss on masked image patches, SD-MAE further imposes the self-distillation loss on visible patches to enhance the representational capacity of the encoder located shallow layer. We apply SD-MAE to histopathological image classification, cell segmentation and object detection. Experiments demonstrate that SD-MAE shows highly competitive performance when compared with other SSL methods in these tasks.
Progress in digital pathology is hindered by high-resolution images and the prohibitive cost of exhaustive localized annotations. The commonly used paradigm to categorize pathology images is patch-based processing, which often incorporates multiple instance learning (MIL) to aggregate local patch-level representations yielding image-level prediction. Nonetheless, diagnostically relevant regions may only take a small fraction of the whole tissue, and current MIL-based approaches often process images uniformly, discarding the inter-patches interactions. To alleviate these issues, we propose ScoreNet, a new efficient transformer that exploits a differentiable recommendation stage to extract discriminative image regions and dedicate computational resources accordingly. The proposed transformer leverages the local and global attention of a few dynamically recommended high-resolution regions at an efficient computational cost. We further introduce a novel mixing data-augmentation, namely ScoreMix, by leveraging the image's semantic distribution to guide the data mixing and produce coherent sample-label pairs. ScoreMix is embarrassingly simple and mitigates the pitfalls of previous augmentations, which assume a uniform semantic distribution and risk mislabeling the samples. Thorough experiments and ablation studies on three breast cancer histology datasets of Haematoxylin & Eosin (H&E) have validated the superiority of our approach over prior arts, including transformer-based models on tumour regions-of-interest (TRoIs) classification. ScoreNet equipped with proposed ScoreMix augmentation demonstrates better generalization capabilities and achieves new state-of-the-art (SOTA) results with only 50% of the data compared to other mixing augmentation variants. Finally, ScoreNet yields high efficacy and outperforms SOTA efficient transformers, namely TransPath and SwinTransformer.
The classification of histopathological images is of great value in both cancer diagnosis and pathological studies. However, multiple reasons, such as variations caused by magnification factors and class imbalance, make it a challenging task where conventional methods that learn from image-label datasets perform unsatisfactorily in many cases. We observe that tumours of the same class often share common morphological patterns. To exploit this fact, we propose an approach that learns similarity-based multi-scale embeddings (SMSE) for magnification-independent histopathological image classification. In particular, a pair loss and a triplet loss are leveraged to learn similarity-based embeddings from image pairs or image triplets. The learned embeddings provide accurate measurements of similarities between images, which are regarded as a more effective form of representation for histopathological morphology than normal image features. Furthermore, in order to ensure the generated models are magnification-independent, images acquired at different magnification factors are simultaneously fed to networks during training for learning multi-scale embeddings. In addition to the SMSE, to eliminate the impact of class imbalance, instead of using the hard sample mining strategy that intuitively discards some easy samples, we introduce a new reinforced focal loss to simultaneously punish hard misclassified samples while suppressing easy well-classified samples. Experimental results show that the SMSE improves the performance for histopathological image classification tasks for both breast and liver cancers by a large margin compared to previous methods. In particular, the SMSE achieves the best performance on the BreakHis benchmark with an improvement ranging from 5% to 18% compared to previous methods using traditional features.
Cancer diseases constitute one of the most significant societal challenges. In this paper, we introduce a novel histopathological dataset for prostate cancer detection. The proposed dataset, consisting of over 2.6 million tissue patches extracted from 430 fully annotated scans, 4675 scans with assigned binary diagnoses, and 46 scans with diagnoses independently provided by a group of histopathologists can be found at https://github.com/michalkoziarski/DiagSet. Furthermore, we propose a machine learning framework for detection of cancerous tissue regions and prediction of scan-level diagnosis, utilizing thresholding to abstain from the decision in uncertain cases. The proposed approach, composed of ensembles of deep neural networks operating on the histopathological scans at different scales, achieves 94.6% accuracy in patch-level recognition and is compared in a scan-level diagnosis with 9 human histopathologists showing high statistical agreement.