PointNu-Net: Simultaneous Multi-tissue Histology Nuclei Segmentation and Classification in the Clinical Wild

Automatic nuclei segmentation and classification plays a vital role in digital pathology. However, previous works are mostly built on data with limited diversity and small sizes, making the results questionable or misleading in actual downstream tasks. In this paper, we aim to build a reliable and robust method capable of dealing with data from the 'the clinical wild'. Specifically, we study and design a new method to simultaneously detect, segment, and classify nuclei from Haematoxylin and Eosin (H&E) stained histopathology data, and evaluate our approach using the recent largest dataset: PanNuke. We address the detection and classification of each nuclei as a novel semantic keypoint estimation problem to determine the center point of each nuclei. Next, the corresponding class-agnostic masks for nuclei center points are obtained using dynamic instance segmentation. By decoupling two simultaneous challenging tasks, our method can benefit from class-aware detection and class-agnostic segmentation, thus leading to a significant performance boost. We demonstrate the superior performance of our proposed approach for nuclei segmentation and classification across 19 different tissue types, delivering new benchmark results.Comment: 10 pages,7 figures, journa

Diffusion-based Data Augmentation for Nuclei Image Segmentation

Nuclei segmentation is a fundamental but challenging task in the quantitative analysis of histopathology images. Although fully-supervised deep learning-based methods have made significant progress, a large number of labeled images are required to achieve great segmentation performance. Considering that manually labeling all nuclei instances for a dataset is inefficient, obtaining a large-scale human-annotated dataset is time-consuming and labor-intensive. Therefore, augmenting a dataset with only a few labeled images to improve the segmentation performance is of significant research and application value. In this paper, we introduce the first diffusion-based augmentation method for nuclei segmentation. The idea is to synthesize a large number of labeled images to facilitate training the segmentation model. To achieve this, we propose a two-step strategy. In the first step, we train an unconditional diffusion model to synthesize the Nuclei Structure that is defined as the representation of pixel-level semantic and distance transform. Each synthetic nuclei structure will serve as a constraint on histopathology image synthesis and is further post-processed to be an instance map. In the second step, we train a conditioned diffusion model to synthesize histopathology images based on nuclei structures. The synthetic histopathology images paired with synthetic instance maps will be added to the real dataset for training the segmentation model. The experimental results show that by augmenting 10% labeled real dataset with synthetic samples, one can achieve comparable segmentation results with the fully-supervised baseline.Comment: MICCAI 2023, released code: https://github.com/lhaof/Nudif

Unsupervised tissue segmentation via deep constrained Gaussian network

Tissue segmentation is the mainstay of pathological examination, whereas the manual delineation is unduly burdensome. To assist this time-consuming and subjective manual step, researchers have devised methods to automatically segment structures in pathological images. Recently, automated machine and deep learning based methods dominate tissue segmentation research studies. However, most machine and deep learning based approaches are supervised and developed using a large number of training samples, in which the pixel-wise annotations are expensive and sometimes can be impossible to obtain. This paper introduces a novel unsupervised learning paradigm by integrating an end-to-end deep mixture model with a constrained indicator to acquire accurate semantic tissue segmentation. This constraint aims to centralise the components of deep mixture models during the calculation of the optimisation function. In so doing, the redundant or empty class issues, which are common in current unsupervised learning methods, can be greatly reduced. By validation on both public and in-house datasets, the proposed deep constrained Gaussian network achieves significantly (Wilcoxon signed-rank test) better performance (with the average Dice scores of 0.737 and 0.735, respectively) on tissue segmentation with improved stability and robustness, compared to other existing unsupervised segmentation approaches. Furthermore, the proposed method presents a similar performance (p-value > 0.05) compared to the fully supervised U-Net

A Survey on Deep Learning-based Architectures for Semantic Segmentation on 2D images

Semantic segmentation is the pixel-wise labelling of an image. Since the problem is defined at the pixel level, determining image class labels only is not acceptable, but localising them at the original image pixel resolution is necessary. Boosted by the extraordinary ability of convolutional neural networks (CNN) in creating semantic, high level and hierarchical image features; excessive numbers of deep learning-based 2D semantic segmentation approaches have been proposed within the last decade. In this survey, we mainly focus on the recent scientific developments in semantic segmentation, specifically on deep learning-based methods using 2D images. We started with an analysis of the public image sets and leaderboards for 2D semantic segmantation, with an overview of the techniques employed in performance evaluation. In examining the evolution of the field, we chronologically categorised the approaches into three main periods, namely pre-and early deep learning era, the fully convolutional era, and the post-FCN era. We technically analysed the solutions put forward in terms of solving the fundamental problems of the field, such as fine-grained localisation and scale invariance. Before drawing our conclusions, we present a table of methods from all mentioned eras, with a brief summary of each approach that explains their contribution to the field. We conclude the survey by discussing the current challenges of the field and to what extent they have been solved.Comment: Updated with new studie

A Comprehensive Overview of Computational Nuclei Segmentation Methods in Digital Pathology

In the cancer diagnosis pipeline, digital pathology plays an instrumental role in the identification, staging, and grading of malignant areas on biopsy tissue specimens. High resolution histology images are subject to high variance in appearance, sourcing either from the acquisition devices or the H\&E staining process. Nuclei segmentation is an important task, as it detects the nuclei cells over background tissue and gives rise to the topology, size, and count of nuclei which are determinant factors for cancer detection. Yet, it is a fairly time consuming task for pathologists, with reportedly high subjectivity. Computer Aided Diagnosis (CAD) tools empowered by modern Artificial Intelligence (AI) models enable the automation of nuclei segmentation. This can reduce the subjectivity in analysis and reading time. This paper provides an extensive review, beginning from earlier works use traditional image processing techniques and reaching up to modern approaches following the Deep Learning (DL) paradigm. Our review also focuses on the weak supervision aspect of the problem, motivated by the fact that annotated data is scarce. At the end, the advantages of different models and types of supervision are thoroughly discussed. Furthermore, we try to extrapolate and envision how future research lines will potentially be, so as to minimize the need for labeled data while maintaining high performance. Future methods should emphasize efficient and explainable models with a transparent underlying process so that physicians can trust their output.Comment: 47 pages, 27 figures, 9 table

Exploring Unsupervised Cell Recognition with Prior Self-activation Maps

The success of supervised deep learning models on cell recognition tasks relies on detailed annotations. Many previous works have managed to reduce the dependency on labels. However, considering the large number of cells contained in a patch, costly and inefficient labeling is still inevitable. To this end, we explored label-free methods for cell recognition. Prior self-activation maps (PSM) are proposed to generate pseudo masks as training targets. To be specific, an activation network is trained with self-supervised learning. The gradient information in the shallow layers of the network is aggregated to generate prior self-activation maps. Afterward, a semantic clustering module is then introduced as a pipeline to transform PSMs to pixel-level semantic pseudo masks for downstream tasks. We evaluated our method on two histological datasets: MoNuSeg (cell segmentation) and BCData (multi-class cell detection). Compared with other fully-supervised and weakly-supervised methods, our method can achieve competitive performance without any manual annotations. Our simple but effective framework can also achieve multi-class cell detection which can not be done by existing unsupervised methods. The results show the potential of PSMs that might inspire other research to deal with the hunger for labels in medical area.Comment: MICCAI 2023. arXiv admin note: substantial text overlap with arXiv:2210.0786

Hover-Net : simultaneous segmentation and classification of nuclei in multi-tissue histology images

Nuclear segmentation and classification within Haematoxylin & Eosin stained histology images is a fundamental prerequisite in the digital pathology work-flow. The development of automated methods for nuclear segmentation and classification enables the quantitative analysis of tens of thousands of nuclei within a whole-slide pathology image, opening up possibilities of further analysis of large-scale nuclear morphometry. However, automated nuclear segmentation and classification is faced with a major challenge in that there are several different types of nuclei, some of them exhibiting large intra-class variability such as the nuclei of tumour cells. Additionally, some of the nuclei are often clustered together. To address these challenges, we present a novel convolutional neural network for simultaneous nuclear segmentation and classification that leverages the instance-rich information encoded within the vertical and horizontal distances of nuclear pixels to their centres of mass. These distances are then utilised to separate clustered nuclei, resulting in an accurate segmentation, particularly in areas with overlapping instances. Then, for each segmented instance the network predicts the type of nucleus via a devoted up-sampling branch. We demonstrate state-of-the-art performance compared to other methods on multiple independent multi-tissue histology image datasets. As part of this work, we introduce a new dataset of Haematoxylin & Eosin stained colorectal adenocarcinoma image tiles, containing 24,319 exhaustively annotated nuclei with associated class labels

CoNIC Challenge: Pushing the Frontiers of Nuclear Detection, Segmentation, Classification and Counting

Nuclear detection, segmentation and morphometric profiling are essential in helping us further understand the relationship between histology and patient outcome. To drive innovation in this area, we setup a community-wide challenge using the largest available dataset of its kind to assess nuclear segmentation and cellular composition. Our challenge, named CoNIC, stimulated the development of reproducible algorithms for cellular recognition with real-time result inspection on public leaderboards. We conducted an extensive post-challenge analysis based on the top-performing models using 1,658 whole-slide images of colon tissue. With around 700 million detected nuclei per model, associated features were used for dysplasia grading and survival analysis, where we demonstrated that the challenge's improvement over the previous state-of-the-art led to significant boosts in downstream performance. Our findings also suggest that eosinophils and neutrophils play an important role in the tumour microevironment. We release challenge models and WSI-level results to foster the development of further methods for biomarker discovery

Deep learning for unsupervised domain adaptation in medical imaging: Recent advancements and future perspectives

Deep learning has demonstrated remarkable performance across various tasks in medical imaging. However, these approaches primarily focus on supervised learning, assuming that the training and testing data are drawn from the same distribution. Unfortunately, this assumption may not always hold true in practice. To address these issues, unsupervised domain adaptation (UDA) techniques have been developed to transfer knowledge from a labeled domain to a related but unlabeled domain. In recent years, significant advancements have been made in UDA, resulting in a wide range of methodologies, including feature alignment, image translation, self-supervision, and disentangled representation methods, among others. In this paper, we provide a comprehensive literature review of recent deep UDA approaches in medical imaging from a technical perspective. Specifically, we categorize current UDA research in medical imaging into six groups and further divide them into finer subcategories based on the different tasks they perform. We also discuss the respective datasets used in the studies to assess the divergence between the different domains. Finally, we discuss emerging areas and provide insights and discussions on future research directions to conclude this survey.Comment: Under Revie