Detecting cells and analyzing their behaviors in microscopy images using deep neural networks

The computer-aided analysis in the medical imaging field has attracted a lot of attention for the past decade. The goal of computer-vision based medical image analysis is to provide automated tools to relieve the burden of human experts such as radiologists and physicians. More specifically, these computer-aided methods are to help identify, classify and quantify patterns in medical images. Recent advances in machine learning, more specifically, in the way of deep learning, have made a big leap to boost the performance of various medical applications. The fundamental core of these advances is exploiting hierarchical feature representations by various deep learning models, instead of handcrafted features based on domain-specific knowledge. In the work presented in this dissertation, we are particularly interested in exploring the power of deep neural network in the Circulating Tumor Cells detection and mitosis event detection. We will introduce the Convolutional Neural Networks and the designed training methodology for Circulating Tumor Cells detection, a Hierarchical Convolutional Neural Networks model and a Two-Stream Bidirectional Long Short-Term Memory model for mitosis event detection and its stage localization in phase-contrast microscopy images”--Abstract, page iii

A Survey on Deep Learning in Medical Image Analysis

Deep learning algorithms, in particular convolutional networks, have rapidly become a methodology of choice for analyzing medical images. This paper reviews the major deep learning concepts pertinent to medical image analysis and summarizes over 300 contributions to the field, most of which appeared in the last year. We survey the use of deep learning for image classification, object detection, segmentation, registration, and other tasks and provide concise overviews of studies per application area. Open challenges and directions for future research are discussed.Comment: Revised survey includes expanded discussion section and reworked introductory section on common deep architectures. Added missed papers from before Feb 1st 201

Assessment of algorithms for mitosis detection in breast cancer histopathology images

The proliferative activity of breast tumors, which is routinely estimated by counting of mitotic figures in hematoxylin and eosin stained histology sections, is considered to be one of the most important prognostic markers. However, mitosis counting is laborious, subjective and may suffer from low inter-observer agreement. With the wider acceptance of whole slide images in pathology labs, automatic image analysis has been proposed as a potential solution for these issues. In this paper, the results from the Assessment of Mitosis Detection Algorithms 2013 (AMIDA13) challenge are described. The challenge was based on a data set consisting of 12 training and 11 testing subjects, with more than one thousand annotated mitotic figures by multiple observers. Short descriptions and results from the evaluation of eleven methods are presented. The top performing method has an error rate that is comparable to the inter-observer agreement among pathologists

SFCN-OPI: Detection and Fine-grained Classification of Nuclei Using Sibling FCN with Objectness Prior Interaction

Cell nuclei detection and fine-grained classification have been fundamental yet challenging problems in histopathology image analysis. Due to the nuclei tiny size, significant inter-/intra-class variances, as well as the inferior image quality, previous automated methods would easily suffer from limited accuracy and robustness. In the meanwhile, existing approaches usually deal with these two tasks independently, which would neglect the close relatedness of them. In this paper, we present a novel method of sibling fully convolutional network with prior objectness interaction (called SFCN-OPI) to tackle the two tasks simultaneously and interactively using a unified end-to-end framework. Specifically, the sibling FCN branches share features in earlier layers while holding respective higher layers for specific tasks. More importantly, the detection branch outputs the objectness prior which dynamically interacts with the fine-grained classification sibling branch during the training and testing processes. With this mechanism, the fine-grained classification successfully focuses on regions with high confidence of nuclei existence and outputs the conditional probability, which in turn benefits the detection through back propagation. Extensive experiments on colon cancer histology images have validated the effectiveness of our proposed SFCN-OPI and our method has outperformed the state-of-the-art methods by a large margin.Comment: Accepted at AAAI 201

Spatiotemporal Identification of Cell Divisions Using Symmetry Properties in Time-Lapse Phase Contrast Microscopy

A variety of biological and pharmaceutical studies, such as for anti-cancer drugs, require the quantification of cell responses over long periods of time. This is performed with time-lapse video microscopy that gives a long sequence of frames. For this purpose, phase contrast imaging is commonly used since it is minimally invasive. The cell responses of interest in this study are the mitotic cell divisions. Their manual measurements are tedious, subjective, and restrictive. This study introduces an automated method for these measurements. The method starts with preprocessing for restoration and reconstruction of the phase contrast time-lapse sequences. The data are first restored from intensity non-uniformities. Subsequently, the circular symmetry of the contour of the mitotic cells in phase contrast images is used by applying a Circle Hough Transform (CHT) to reconstruct the entire cells. The CHT is also enhanced with the ability to “vote” exclusively towards the center of curvature. The CHT image sequence is then registered for misplacements between successive frames. The sequence is subsequently processed to detect cell centroids in individual frames and use them as starting points to form spatiotemporal trajectories of cells along the positive as well as along the negative time directions, that is, anti-causally. The connectivities of different trajectories enhanced by the symmetry of the trajectories of the daughter cells provide as topological by-products the events of cell divisions together with the corresponding entries into mitoses as well as exits from cytokineses. The experiments use several experimental video sequences from three different cell lines with many cells undergoing mitoses and divisions. The quantitative validations of the results of the processing demonstrate the high performance and efficiency of the method