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Single nucleus segmentation is a frequent challenge of microscopy image processing, since it is the first step of many quantitative data analysis pipelines. The quality of tracking single cells, extracting features or classifying cellular phenotypes strongly depends on segmentation accuracy. Worldwide competitions have been held, aiming to improve segmentation, and recent years have definitely brought significant improvements: large annotated datasets are now freely available, several 2D segmentation strategies have been extended to 3D, and deep learning approaches have increased accuracy. However, even today, no generally accepted solution and benchmarking platform exist. We review the most recent single-cell segmentation tools, and provide an interactive method browser to select the most appropriate solution. Nucleus segmentation is one of the first steps of many microscopy image analysis pipelines. Several large-scale competitions have yielded annotated datasets that are available for training and testing specific methods. The 2D segmentation strategies cover a diverse range of image modalities; some of these are also available for 3D datasets. Simple cases of segmentation, especially for 2D, are straightforward, while in more challenging cases improved accuracy has been achieved recently. Deep learning has established a new level of image analysis, but the lack of uniform evaluation strategies makes quantitative comparison and relative performance determination highly challenging. [ABSTRACT FROM AUTHOR]

Histopathological images reveal a lot of information about tissue health. The task of nucleus segmentation can be applied to more diverse studies. The potential of deep learning has been demonstrated for the task of nuclei segmentation. However, the cost and time required for labeling data, as well as the lack of annotators, makes it difficult to keep up with the continuous generation of new pathological images. This paper proposes a method that combines attention mechanisms and self-supervised learning to train a model for nuclei segmentation on unlabeled data. The method is mainly divided into two stages. After the initial preprocessing of the image, the enhanced image of the nucleus area can be obtained in the first stage. Subsequently, the original image and the augmented image needed for self-supervised learning undergo feature extraction in the second stage. The results of this study show that the proposed method can achieve dice scores exceeding 0.7 in the nucleus binary segmentation task without labels. Fine-tuning the model for downstream tasks can also achieve the effect of F1 score 0.7 multi-category segmentation. Using the same experimental setting, the method proposed in this study achieves a dice score of 0.779 on the MoNuSeg dataset, which is only 0.03 lower than the highest dice score of 0.809 achieved by the compared supervised learning methods. In comparison to other unsupervised models, this method demonstrates superior segmentation performance. Moreover, this study applies the training weights to other histopathology image datasets, enabling the generation of the same binary segmentation effect. © 2017 Elsevier Inc. All rights reserved. [ABSTRACT FROM AUTHOR]

It is a challenging problem to achieve generalized nuclear segmentation in digital histopathology images. Existing techniques, using either handcrafted features in learning-based models or traditional image analysis-based approaches, do not effectively tackle the challenging cases, such as crowded nuclei, chromatin-sparse, and heavy background clutter. In contrast, deep networks have achieved state-of-the-art performance in modeling various nuclear appearances. However, their success is limited due to the size of the considered networks. We solve these problems by reformulating nuclear segmentation in terms of a cascade 2-class classification problem and propose a multi-layer boosting sparse convolutional (ML-BSC) model. In the proposed ML-BSC model, discriminative probabilistic binary decision trees (PBDTs) are designed as weak learners in each layer to cope with challenging cases. A sparsity-constrained cascade structure enables the ML-BSC model to improve representation learning. Comparing to the existing techniques, our method can accurately separate individual nuclei in complex histopathology images, and it is more robust against chromatin-sparse and heavy background clutter. An evaluation carried out using three disparate datasets demonstrates the superiority of our method over the state-of-the-art supervised approaches in terms of segmentation accuracy. [ABSTRACT FROM AUTHOR]

Accurate segmentation of hepatocellular carcinoma (HCC) nuclei is of great importance in automatic pathologic diagnosis. This paper proposes structure convolutional extreme learning machine (SC-ELM) and case-based shape template (CBST) methods for HCC nucleus segmentation, which could tackle complex nucleus scenarios including adhesion or overlap. First, SC-ELM is developed for global segmentation of pathology images, which is used for coarse segmentation. Then, each connected region is considered as a nucleus clump and a probability model with three energy functions is proposed for contour refinement of nucleus clumps. Finally, for complex nucleus clumps, the CBST method combined with pixel-based classification is utilized for unclear or lost boundary inference. Experimentations with 127 liver pathology images demonstrate the performance advantages of our proposed method as compared with related work. [ABSTRACT FROM AUTHOR]

Medical image segmentation methods based on encoder-decoder network structure have gained great success. However, these methods inevitably cause feature loss due to the pooling operation on the features during the encoding stage. Furthermore, there exists semantic gaps caused by the difference between low-level features and high-level features in the encoder-decoder network structure. By fusing the contextual features through simple skip-connections, it will limit the segmentation performance. To address these problems, this paper presents a new network for medical image segmentation, termed as NMNet, which mainly consists of a reverse encoder-decoder major structure with new attention modules. Specifically, in this network, we first design an N -shaped reverse encoder-decoder medical image segmentation structure (NNet), which can effectively reduce the impact of feature loss during the encoding process by performing feature representation compensation from the scale extension domain. Then, we build a Multi-scale Cross-attention Mechanism (MSC) in the skip-connections, which can enhance low-level features to bridge the semantic gaps. Extensive experiments on three benchmark datasets show that our NMNet performs favorably against most state-of-the-art methods under different evaluation metrics. [ABSTRACT FROM AUTHOR]

The detection and segmentation of individual cells or nuclei is often involved in image analysis across a variety of biology and biomedical applications as an indispensable prerequisite. However, the ubiquitous presence of crowd clusters with morphological variations often hinders successful instance segmentation. In this paper, nuclei cluster focused annotation strategies and frameworks are proposed to overcome this challenging practical problem. Specifically, we design a nucleus segmentation framework, namely ClusterSeg, to tackle nuclei clusters, which consists of a convolutional-transformer hybrid encoder and a 2.5-path decoder for precise predictions of nuclei instance mask, contours, and clustered-edges. Additionally, an annotation-efficient clustered-edge pointed strategy pinpoints the salient and error-prone boundaries, where a partially-supervised PS-ClusterSeg is presented using ClusterSeg as the segmentation backbone. The framework is evaluated with four privately curated image sets and two public sets with characteristic severely clustered nuclei across a variety range of image modalities, e.g., microscope, cytopathology, and histopathology images. The proposed ClusterSeg and PS-ClusterSeg are modality-independent and generalizable, and superior to current state-of-the-art approaches in multiple metrics empirically. Our collected data, the elaborate annotations to both public and private set, as well the source code, are released publicly at https://github.com/lu-yizhou/ClusterSeg. • A convolution and transformer hybrid framework for cluster-aware nuclei segmentation. • A partially supervised framework for cluster-focused partial annotation and training. • Pixel-wise annotation on our clinical collection of microscope and pathology image. [ABSTRACT FROM AUTHOR]

Semen analysis is the first step in the evaluation of an infertile couple. Within this process, an accurate and objective morphological analysis becomes more critical as it is based on the correct detection and segmentation of human sperm components. In this paper, we present an improved two-stage framework for detection and segmentation of human sperm head characteristics (including acrosome and nucleus) that uses three different color spaces. The first stage detects regions of interest that define sperm heads, using k -means, then candidate heads are refined using mathematical morphology. In the second stage, we work on each region of interest to segment accurately the sperm head as well as nucleus and acrosome, using clustering and histogram statistical analysis techniques. Our proposal is also characterized by being fully automatic, where a user intervention is not required. Our experimental evaluation shows that our proposed method outperforms the state-of-the-art. This is supported by the results of different evaluation metrics. In addition, we propose a gold-standard built with the cooperation of a referent expert in the field, aiming to compare methods for detecting and segmenting sperm cells. Our results achieve notable improvement getting above 98% in the sperm head detection process at the expense of having significantly fewer false positives obtained by the state-of-the-art method. Our results also show an accurate head, acrosome and nucleus segmentation achieving over 80% overlapping against hand-segmented gold-standard. Our method achieves higher Dice coefficient, lower Hausdorff distance and less dispersion with respect to the results achieved by the state-of-the-art method. [ABSTRACT FROM AUTHOR]

Abstract: We examined the classification and prognostic scoring performances of several computer methods on different feature sets to obtain objective and reproducible analysis of estrogen receptor status in breast cancer tissue samples. Radial basis function network, k-nearest neighborhood search, support vector machines, naive bayes, functional trees, and k-means clustering algorithm were applied to the test datasets. Several features were employed and the classification accuracies of each method for these features were examined. The assessment results of the methods on test images were also experimentally compared with those of two experts. According to the results of our experimental work, a combination of functional trees and the naive bayes classifier gave the best prognostic scores indicating very good kappa agreement values (κ =0.899 and κ =0.949, p <0.001) with the experts. This combination also gave the best dichotomization rate (96.3%) for assessment of estrogen receptor status. Wavelet color features provided better classification accuracy than Laws texture energy and co-occurrence matrix features. [Copyright &y& Elsevier]

Abstract: In order to automate cervical cancer screening tests, one of the most important and longstanding challenges is the segmentation of cell nuclei in the stained specimens. Though nuclei of isolated cells in high-quality acquisitions often are easy to segment, the problem lies in the segmentation of large numbers of nuclei with various characteristics under differing acquisition conditions in high-resolution scans of the complete microscope slides. We implemented a system that enables processing of full resolution images, and proposes a new algorithm for segmenting the nuclei under adequate control of the expert user. The system can work automatically or interactively guided, to allow for segmentation within the whole range of slide and image characteristics. It facilitates data storage and interaction of technical and medical experts, especially with its web-based architecture. The proposed algorithm localizes cell nuclei using a voting scheme and prior knowledge, before it determines the exact shape of the nuclei by means of an elastic segmentation algorithm. After noise removal with a mean-shift and a median filtering takes place, edges are extracted with a Canny edge detection algorithm. Motivated by the observation that cell nuclei are surrounded by cytoplasm and their shape is roughly elliptical, edges adjacent to the background are removed. A randomized Hough transform for ellipses finds candidate nuclei, which are then processed by a level set algorithm. The algorithm is tested and compared to other algorithms on a database containing 207 images acquired from two different microscope slides, with promising results. [Copyright &y& Elsevier]

Abstract: This paper presents a new segmentation method of complex nucleus configurations. The specificity of this work is to introduce prior information about the usual shape of cells nuclei, in order to optimize the selection of markers from which the flooding will start, during the watershed-based segmentation. [Copyright &y& Elsevier]

• A generalized white blood cell (WBC) nucleus segmentation method is proposed. • We localize WBC by showing a statistical analysis on four public databases. • We compare the proposed WBC nucleus segmentation method on four public databases. • A new CNN model is proposed to classify four types of white blood cell. • We evaluate and compare the proposed CNN model by using nine evaluation metrics. White blood cells (WBCs) play a remarkable role in the human immune system. To diagnose blood-related diseases, pathologists need to consider the characteristics of WBC. The characteristics of WBC can be defined based on the morphological properties of WBC nucleus. Therefore, nucleus segmentation plays a vital role to classify the WBC image and it is an important part of the medical diagnosis system. In this study, color space conversion and k-means algorithm based new WBC nucleus segmentation method is proposed. Then we localize the WBC based on the location of segmented nucleus to separate them from the entire blood smear image. To classify the localized WBC image, we propose a new convolutional neural network (CNN) model by combining the concept of fusing the features of first and last convolutional layers, and propagating the input image to the convolutional layer. We also use a dropout layer for preventing the model from overfitting problem. We show the effectiveness of our proposed nucleus segmentation method by evaluating with seven quality metrics and comparing with other methods on four public databases. We achieve average accuracy of 98.61% and more than 97% on each public database. We also evaluate our proposed CNN model by using nine classification metrics and achieve an overall accuracy of 96% on BCCD test database. To validate the generalization capability of our proposed CNN model, we show the training and testing accuracy and loss curves for random test set of BCCD database. Further, we compare the performance of our proposed CNN model with four state-of-the-art CNN models (biomedical image classifier) by measuring the value of evaluation metrics. [ABSTRACT FROM AUTHOR]