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

Machine learning methods for automated classification of tumors with papillary thyroid carcinoma-like nuclei : A quantitative analysis

When approaching thyroid gland tumor classification, the differentiation between samples with and without “papillary thyroid carcinoma-like” nuclei is a daunting task with high inter-observer variability among pathologists. Thus, there is increasing interest in the use of machine learning approaches to provide pathologists real-time decision support. In this paper, we optimize and quantitatively compare two automated machine learning methods for thyroid gland tumor classification on two datasets to assist pathologists in decision-making regarding these methods and their parameters. The first method is a feature-based classification originating from common image processing and consists of cell nucleus segmentation, feature extraction, and subsequent thyroid gland tumor classification utilizing different classifiers. The second method is a deep learning-based classification which directly classifies the input images with a convolutional neural network without the need for cell nucleus segmentation. On the Tharun and Thompson dataset, the feature-based classification achieves an accuracy of 89.7% (Cohen’s Kappa 0.79), compared to the deep learning-based classification of 89.1% (Cohen’s Kappa 0.78). On the Nikiforov dataset, the feature-based classification achieves an accuracy of 83.5% (Cohen’s Kappa 0.46) compared to the deep learning-based classification 77.4% (Cohen’s Kappa 0.35). Thus, both automated thyroid tumor classification methods can reach the classification level of an expert pathologist. To our knowledge, this is the first study comparing feature-based and deep learning-based classification regarding their ability to classify samples with and without papillary thyroid carcinoma-like nuclei on two large-scale datasets

Computerized cancer malignancy grading of fine needle aspirates

According to the World Health Organization, breast cancer is a leading cause of death among middle-aged women. Precise diagnosis and correct treatment significantly reduces the high number of deaths caused by breast cancer. Being successful in the treatment strictly relies on the diagnosis. Specifically, the accuracy of the diagnosis and the stage at which a cancer was diagnosed. Precise and early diagnosis has a major impact on the survival rate, which indicates how many patients will live after the treatment. For many years researchers in medical and computer science fields have been working together to find the approach for precise diagnosis. For this thesis, precise diagnosis means finding a cancer at as early a stage as possible by developing new computer aided diagnostic tools. These tools differ depending on the type of cancer and the type of the examination that is used for diagnosis. This work concentrates on cytological images of breast cancer that are produced during fine needle aspiration biopsy examination. This kind of examination allows pathologists to estimate the malignancy of the cancer with very high accuracy. Malignancy estimation is very important when assessing a patients survival rate and the type of treatment. To achieve precise malignancy estimation, a classification framework is presented. This framework is able to classify breast cancer malignancy into two malignancy classes and is based on features calculated according to the Bloom-Richardson grading scheme. This scheme is commonly used by pathologists when grading breast cancer tissue. In Bloom-Richardson scheme two types of features are assessed depending on the magnification. Low magnification images are used for examining the dispersion of the cells in the image while the high magnification images are used for precise analysis of the cells' nuclear features. In this thesis, different types of segmentation algorithms were compared to estimate the algorithm that allows for relatively fast and accurate nuclear segmentation. Based on that segmentation a set of 34 features was extracted for further malignancy classification. For classification purposes 6 different classifiers were compared. From all of the tests a set of the best preforming features were chosen. The presented system is able to classify images of fine needle aspiration biopsy slides with high accurac

Medical Image Segmentation by Deep Convolutional Neural Networks

Medical image segmentation is a fundamental and critical step for medical image analysis. Due to the complexity and diversity of medical images, the segmentation of medical images continues to be a challenging problem. Recently, deep learning techniques, especially Convolution Neural Networks (CNNs) have received extensive research and achieve great success in many vision tasks. Specifically, with the advent of Fully Convolutional Networks (FCNs), automatic medical image segmentation based on FCNs is a promising research field. This thesis focuses on two medical image segmentation tasks: lung segmentation in chest X-ray images and nuclei segmentation in histopathological images. For the lung segmentation task, we investigate several FCNs that have been successful in semantic and medical image segmentation. We evaluate the performance of these different FCNs on three publicly available chest X-ray image datasets. For the nuclei segmentation task, since the challenges of this task are difficulty in segmenting the small, overlapping and touching nuclei, and limited ability of generalization to nuclei in different organs and tissue types, we propose a novel nuclei segmentation approach based on a two-stage learning framework and Deep Layer Aggregation (DLA). We convert the original binary segmentation task into a two-step task by adding nuclei-boundary prediction (3-classes) as an intermediate step. To solve our two-step task, we design a two-stage learning framework by stacking two U-Nets. The first stage estimates nuclei and their coarse boundaries while the second stage outputs the final fine-grained segmentation map. Furthermore, we also extend the U-Nets with DLA by iteratively merging features across different levels. We evaluate our proposed method on two public diverse nuclei datasets. The experimental results show that our proposed approach outperforms many standard segmentation architectures and recently proposed nuclei segmentation methods, and can be easily generalized across different cell types in various organs

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

Advances in Image Processing, Analysis and Recognition Technology

For many decades, researchers have been trying to make computers’ analysis of images as effective as the system of human vision is. For this purpose, many algorithms and systems have previously been created. The whole process covers various stages, including image processing, representation and recognition. The results of this work can be applied to many computer-assisted areas of everyday life. They improve particular activities and provide handy tools, which are sometimes only for entertainment, but quite often, they significantly increase our safety. In fact, the practical implementation of image processing algorithms is particularly wide. Moreover, the rapid growth of computational complexity and computer efficiency has allowed for the development of more sophisticated and effective algorithms and tools. Although significant progress has been made so far, many issues still remain, resulting in the need for the development of novel approaches