Segmentation of Fuzzy and Touching Cells Based on Modified Minimum Spanning Tree and Concave Point Detection

In order to segment fuzzy and touching cell images accurately, an improved algorithm is proposed based on minimum spanning tree (MST) and concave point detection. First, the cell images are smoothed and enhanced by a Gaussian filter. Then, the improved minimum spanning tree algorithm is used to segment the cell images. The MST algorithm is modified from three aspects, namely, weight function of edges, difference function of internal and inter region, and threshold function and parameter k. Furthermore, the problem of cell touching is solved by means of concave point detection. According to the rugged topography of touching cells, the concave points are found from the concave regions in the touching cell images, which are used to find the separation points quickly and accurately. Experimental results indicate that the new algorithm is ideal and effective

Nuclei/Cell Detection in Microscopic Skeletal Muscle Fiber Images and Histopathological Brain Tumor Images Using Sparse Optimizations

Nuclei/Cell detection is usually a prerequisite procedure in many computer-aided biomedical image analysis tasks. In this thesis we propose two automatic nuclei/cell detection frameworks. One is for nuclei detection in skeletal muscle fiber images and the other is for brain tumor histopathological images. For skeletal muscle fiber images, the major challenges include: i) shape and size variations of the nuclei, ii) overlapping nuclear clumps, and iii) a series of z-stack images with out-of-focus regions. We propose a novel automatic detection algorithm consisting of the following components: 1) The original z-stack images are first converted into one all-in-focus image. 2) A sufficient number of hypothetical ellipses are then generated for each nuclei contour. 3) Next, a set of representative training samples and discriminative features are selected by a two-stage sparse model. 4) A classifier is trained using the refined training data. 5) Final nuclei detection is obtained by mean-shift clustering based on inner distance. The proposed method was tested on a set of images containing over 1500 nuclei. The results outperform the current state-of-the-art approaches. For brain tumor histopathological images, the major challenges are to handle significant variations in cell appearance and to split touching cells. The proposed novel automatic cell detection consists of: 1) Sparse reconstruction for splitting touching cells. 2) Adaptive dictionary learning for handling cell appearance variations. The proposed method was extensively tested on a data set with over 2000 cells. The result outperforms other state-of-the-art algorithms with F1 score = 0.96

Nuclei & Glands Instance Segmentation in Histology Images: A Narrative Review

Instance segmentation of nuclei and glands in the histology images is an important step in computational pathology workflow for cancer diagnosis, treatment planning and survival analysis. With the advent of modern hardware, the recent availability of large-scale quality public datasets and the community organized grand challenges have seen a surge in automated methods focusing on domain specific challenges, which is pivotal for technology advancements and clinical translation. In this survey, 126 papers illustrating the AI based methods for nuclei and glands instance segmentation published in the last five years (2017-2022) are deeply analyzed, the limitations of current approaches and the open challenges are discussed. Moreover, the potential future research direction is presented and the contribution of state-of-the-art methods is summarized. Further, a generalized summary of publicly available datasets and a detailed insights on the grand challenges illustrating the top performing methods specific to each challenge is also provided. Besides, we intended to give the reader current state of existing research and pointers to the future directions in developing methods that can be used in clinical practice enabling improved diagnosis, grading, prognosis, and treatment planning of cancer. To the best of our knowledge, no previous work has reviewed the instance segmentation in histology images focusing towards this direction.Comment: 60 pages, 14 figure

Automated Clump Splitting for Biological Cell Segmentation in Microscopy Using Image Analysis

Formation of clumps due to touching or overlapping of individual objects in an image is common. The process is natural in some cell cultures, for instance, yeast cells typically grow in clumps. Automated analysis of images containing such clumps requires the capability to split them into their constituent objects. Failure of the segmentation methods to split the clumps leads to the requirement of developing clump splitting methods to be used as post-processing step towards overall segmentation. The goal of this thesis work is to study and develop an automated method for splitting cell clumps in images of biological cells. To achieve this goal we studied previous clump splitting methods found in the literature. One of the best methods is based on defining split lines by detecting and linking concavity points. We found that this method has deficiencies in it and first modified it to achieve improved clump splitting results. We also developed a novel method for clump splitting following a similar approach. Like any other concavity point-based clump splitting method, both these methods start with finding all the concavity points on the contour of the clumps. Contrary to the original method, these methods look for every possible valid concavity point in a concavity region using curvature analysis, thus minimizing false split lines as well as under-segmentation. The modified method then uses Delaunay triangulation to narrow down the list of all the possible split lines between all the concavity points to a list of candidate split lines. Finally, it uses a set of features such as saliency and alignment to define a cost function. The best split line is found for each concavity point yielding the minimum value for the cost function. On the other hand, the novel method uses variable size rectangular window to search for the concavity point-pairs forming the split lines. This makes the method less dependent on user-defined parameters. We also propose some post-processing steps that remove some non-cellular objects based on a priori information on cell shapes. We compared the performance of these two methods with the performance of the original method and of a widely used method that is based on the watershed transform. Three different sets of images of yeast cells were used. Precision and recall analysis was used to show that the two methods proposed in this thesis outperform the two methods taken from the literature. Although the targeted application of the methods is splitting of cell clumps, it can be applied to split clumps of other convex objects as well. /Kir1

Computer-aided acute leukemia blast cells segmentation in peripheral blood images

Computer-aided diagnosis system of leukemic cells is vital tool, which can assist domain experts in the diagnosis and evaluation procedure. Accurate blast cells segmentation is the initial stage in building a successful computer-aided diagnosis system. Blast cells segmentation is still an open research topic due to several problems such as variation of blats cells in terms of color, shape and texture, touching and overlapping of cells, inconsistent image quality, etc. Although numerous blast cells segmentation methods have been developed, only few studies attempted to address these problems simultaneously. This paper presents a new image segmentation method to extract acute leukemia blast cells in peripheral blood. The first aim is to segment the leukemic cells by mean of color transformation and mathematical morphology. The method also introduces an approach to split overlapping cells using the marker-controlled watershed algorithm based on a new marker selection scheme. Furthermore, the paper presents a powerful approach to separate the nucleus region and the cytoplasm region based on the seeded region growing algorithm powered by histogram equalization and arithmetic addition to handle the issue of non-homogenous nuclear chromatin pattern. The robustness of the proposed method is tested on two datasets comprise of 1024 peripheral blood images acquired from two different medical centers. The quantitative evaluation reveals that the proposed method obtain a better segmentation performance compared with its counterparts and achieves remarkable segmentation results of approximately 96 % in blast cell extraction and 94 % in nucleus/cytoplasm separation

Improving cancer subtype diagnosis and grading using clinical decision support system based on computer-aided tissue image analysis

This research focuses towards the development of a clinical decision support system (CDSS) based on cellular and tissue image analysis and classification system that improves consistency and facilitates the clinical decision making process. In a typical cancer examination, pathologists make diagnosis by manually reading morphological features in patient biopsy images, in which cancer biomarkers are highlighted by using different staining techniques. This process is subjected to pathologist's training and experience, especially when the same cancer has several subtypes (i.e. benign tumor subtype vs. malignant subtype) and the same cancer tissue biopsy contains heterogeneous morphologies in different locations. The variability in pathologist's manual reading may result in varying cancer diagnosis and treatment. This Ph.D. research aims to reduce the subjectivity and variation existing in traditional histo-pathological reading of patient tissue biopsy slides through Computer-Aided Diagnosis (CAD). Using the CAD, quantitative molecular profiling of cancer biomarkers of stained biopsy images are obtained by extracting and analyzing texture and cellular structure features. In addition, cancer sub-type classification and a semi-automatic grade scoring (i.e. clinical decision making) for improved consistency over a large number of cancer subtype images can be performed. The CAD tools do have their own limitations and in certain cases the clinicians, however, prefer systems which are flexible and take into account their individuality when necessary by providing some control rather than fully automated system. Therefore, to be able to introduce CDSS in health care, we need to understand users' perspectives and preferences on the new information technology. This forms as the basis for this research where we target to present the quantitative information acquired through the image analysis, annotate the images and provide suitable visualization which can facilitate the process of decision making in a clinical setting.PhDCommittee Chair: Dr. May D. Wang; Committee Member: Dr. Andrew N. Young; Committee Member: Dr. Anthony J. Yezzi; Committee Member: Dr. Edward J. Coyle; Committee Member: Dr. Paul Benkese

Attributed relational graphs for cell nucleus segmentation in fluorescence microscopy Images

Cataloged from PDF version of article.More rapid and accurate high-throughput screening in molecular cellular biology research has become possible with the development of automated microscopy imaging, for which cell nucleus segmentation commonly constitutes the core step. Although several promising methods exist for segmenting the nuclei of monolayer isolated and less-confluent cells, it still remains an open problem to segment the nuclei of more-confluent cells, which tend to grow in overlayers. To address this problem, we propose a new model-based nucleus segmentation algorithm. This algorithm models how a human locates a nucleus by identifying the nucleus boundaries and piecing them together. In this algorithm, we define four types of primitives to represent nucleus boundaries at different orientations and construct an attributed relational graph on the primitives to represent their spatial relations. Then, we reduce the nucleus identification problem to finding predefined structural patterns in the constructed graph and also use the primitives in region growing to delineate the nucleus borders. Working with fluorescence microscopy images, our experiments demonstrate that the proposed algorithm identifies nuclei better than previous nucleus segmentation algorithms