Automatic Segmentation of Cells of Different Types in Fluorescence Microscopy Images

Recognition of different cell compartments, types of cells, and their interactions is a critical aspect of quantitative cell biology. This provides a valuable insight for understanding cellular and subcellular interactions and mechanisms of biological processes, such as cancer cell dissemination, organ development and wound healing. Quantitative analysis of cell images is also the mainstay of numerous clinical diagnostic and grading procedures, for example in cancer, immunological, infectious, heart and lung disease. Computer automation of cellular biological samples quantification requires segmenting different cellular and sub-cellular structures in microscopy images. However, automating this problem has proven to be non-trivial, and requires solving multi-class image segmentation tasks that are challenging owing to the high similarity of objects from different classes and irregularly shaped structures. This thesis focuses on the development and application of probabilistic graphical models to multi-class cell segmentation. Graphical models can improve the segmentation accuracy by their ability to exploit prior knowledge and model inter-class dependencies. Directed acyclic graphs, such as trees have been widely used to model top-down statistical dependencies as a prior for improved image segmentation. However, using trees, a few inter-class constraints can be captured. To overcome this limitation, polytree graphical models are proposed in this thesis that capture label proximity relations more naturally compared to tree-based approaches. Polytrees can effectively impose the prior knowledge on the inclusion of different classes by capturing both same-level and across-level dependencies. A novel recursive mechanism based on two-pass message passing is developed to efficiently calculate closed form posteriors of graph nodes on polytrees. Furthermore, since an accurate and sufficiently large ground truth is not always available for training segmentation algorithms, a weakly supervised framework is developed to employ polytrees for multi-class segmentation that reduces the need for training with the aid of modeling the prior knowledge during segmentation. Generating a hierarchical graph for the superpixels in the image, labels of nodes are inferred through a novel efficient message-passing algorithm and the model parameters are optimized with Expectation Maximization (EM). Results of evaluation on the segmentation of simulated data and multiple publicly available fluorescence microscopy datasets indicate the outperformance of the proposed method compared to state-of-the-art. The proposed method has also been assessed in predicting the possible segmentation error and has been shown to outperform trees. This can pave the way to calculate uncertainty measures on the resulting segmentation and guide subsequent segmentation refinement, which can be useful in the development of an interactive segmentation framework

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

Artificial Intelligence in Cervical Cancer Research and Applications

Cervical cancer remains a leading cause of death among females, posing a severe threat to women's health. Due to the uneven distribution of resources in different regions, there are challenges regarding physicians' experience, quantity, and medical conditions. Early screening, diagnosis, and treatment of cervical cancer still face significant obstacles. In recent years, artificial intelligence (AI) has been increasingly applied to various diseases' screening, diagnosis, and treatment. Currently, AI has many research applications in cervical cancer screening, diagnosis, treatment, and prognosis, assisting doctors and clinical experts in decision-making, improving efficiency and accuracy. This study discusses the application of AI in cervical cancer screening, including HPV typing and detection, cervical cytology screening, and colposcopy screening, as well as AI in cervical cancer diagnosis and treatment, including magnetic resonance imaging (MRI) and computed tomography (CT). Finally, the study briefly describes the current challenges faced by AI applications in cervical cancer and proposes future research directions

Deep Learning in Medical Image Analysis

The accelerating power of deep learning in diagnosing diseases will empower physicians and speed up decision making in clinical environments. Applications of modern medical instruments and digitalization of medical care have generated enormous amounts of medical images in recent years. In this big data arena, new deep learning methods and computational models for efficient data processing, analysis, and modeling of the generated data are crucially important for clinical applications and understanding the underlying biological process. This book presents and highlights novel algorithms, architectures, techniques, and applications of deep learning for medical image analysis

Contributions to Medical Image Segmentation and Signal Analysis Utilizing Model Selection Methods

This thesis presents contributions to model selection techniques, especially based on information theoretic criteria, with the goal of solving problems appearing in signal analysis and in medical image representation, segmentation, and compression.The field of medical image segmentation is wide and is quickly developing to make use of higher available computational power. This thesis concentrates on several applications that allow the utilization of parametric models for image and signal representation. One important application is cell nuclei segmentation from histological images. We model nuclei contours by ellipses and thus the complicated problem of separating overlapping nuclei can be rephrased as a model selection problem, where the number of nuclei, their shapes, and their locations define one segmentation. In this thesis, we present methods for model selection in this parametric setting, where the intuitive algorithms are combined with more principled ones, namely those based on the minimum description length (MDL) principle. The results of the introduced unsupervised segmentation algorithm are compared with human subject segmentations, and are also evaluated with the help of a pathology expert.Another considered medical image application is lossless compression. The objective has been to add the task of image segmentation to that of image compression such that the image regions can be transmitted separately, depending on the region of interest for diagnosis. The experiments performed on retinal color images show that our modeling, in which the MDL criterion selects the structure of the linear predictive models, outperforms publicly available image compressors such as the lossless version of JPEG 2000.For time series modeling, the thesis presents an algorithm which allows detection of changes in time series signals. The algorithm is based on one of the most recent implementations of the MDL principle, the sequentially normalized maximum likelihood (SNML) models.This thesis produces contributions in the form of new methods and algorithms, where the simplicity of information theoretic principles are combined with a rather complex and problem dependent modeling formulation, resulting in both heuristically motivated and principled algorithmic solutions