Segmentation of primary breast tumor nuclei in histological images

Breast cancer (BCa) is a heterogeneous and diverse disease. They are sub-classified into four major subtypes – luminal A, luminal B, Her2-overexpressing and basal-like. It has been seen that the phenotypic variability between BCa occurs within, but not across these major subtypes. These subtypes not only have distinct behaviors but also differ in responses to therapy which highlights the importance of identifying each subtype of BCa for appropriate therapeutic decisions. In order to determine pathologic staging, pathologists routinely evaluate various features like Regional lymph node metastasis status and histologic grade. Such histological analysis though useful and cost-effective, largely depends on the experience of the pathologist performing the analysis. To achieve a better reproducibility and reduced dependence on the pathologist, there is a need to develop a system to objectively predict tumor subtype which was previously possible only through expensive molecular testing and immunohistochemistry (IHC). In order to establish an Image analysis paradigm to generate predictions of tumor sub-type objectively, a reliable method to segment nuclei to analyze their properties individually has been discussed. The performance of this method is evaluated and is seen to perform better - qualitatively and quantitatively compared to a preliminary segmentation

Plasmodium life cycle stage classification based quantification of malaria parasitaemia in thin blood smears.

Visual inspection for the quantification of malaria parasitaemiain (MP) and classification of life cycle stage are hard and time taking. Even though, automated techniques for the quantification of MP and their classification are reported in the literature. However, either reported techniques are imperfect or cannot deal with special issues such as anemia and hemoglobinopathies due to clumps of red blood cells (RBCs). The focus of the current work is to examine the thin blood smear microscopic images stained with Giemsa by digital image processing techniques, grading MP on independent factors (RBCs morphology) and classification of its life cycle stage. For the classification of the life cycle of malaria parasite the k-nearest neighbor, Naïve Bayes and multi-class support vector machine are employed for classification based on histograms of oriented gradients and local binary pattern features. The proposed methodology is based on inductive technique, segment malaria parasites through the adaptive machine learning techniques. The quantification accuracy of RBCs is enhanced; RBCs clumps are split by analysis of concavity regions for focal points. Further, classification of infected and non-infected RBCs has been made to grade MP precisely. The training and testing of the proposed approach on benchmark dataset with respect to ground truth data, yield 96.75% MP sensitivity and 94.59% specificity. Additionally, the proposed approach addresses the process with independent factors (RBCs morphology). Finally, it is an economical solution for MP grading in immense testing

Image analysis and statistical modeling for applications in cytometry and bioprocess control

Today, signal processing has a central role in many of the advancements in systems biology. Modern signal processing is required to provide efficient computational solutions to unravel complex problems that are either arduous or impossible to obtain using conventional approaches. For example, imaging-based high-throughput experiments enable cells to be examined at even subcellular level yielding huge amount of image data. Cytometry is an integral part of such experiments and involves measurement of different cell parameters which requires extraction of quantitative experimental values from cell microscopy images. In order to do that for such large number of images, fast and accurate automated image analysis methods are required. In another example, modeling of bioprocesses and their scale-up is a challenging task where different scales have different parameters and often there are more variables than the available number of observations thus requiring special methodology. In many biomedical cell microscopy studies, it is necessary to analyze the images at single cell or even subcellular level since owing to the heterogeneity of cell populations the population-averaged measurements are often inconclusive. Moreover, the emergence of imaging-based high-content screening experiments, especially for drug design, has put single cell analysis at the forefront since it is required to study the dynamics of single-cell gene expressions for tracking and quantification of cell phenotypic variations. The ability to perform single cell analysis depends on the accuracy of image segmentation in detecting individual cells from images. However, clumping of cells at both nuclei and cytoplasm level hinders accurate cell image segmentation. Part of this thesis work concentrates on developing accurate automated methods for segmentation of bright field as well as multichannel fluorescence microscopy images of cells with an emphasis on clump splitting so that cells are separated from each other as well as from background. The complexity in bioprocess development and control crave for the usage of computational modeling and data analysis approaches for process optimization and scale-up. This is also asserted by the fact that obtaining a priori knowledge needed for the development of traditional scale-up criteria may at times be difficult. Moreover, employment of efficient process modeling may provide the added advantage of automatic identification of influential control parameters. Determination of the values of the identified parameters and the ability to predict them at different scales help in process control and in achieving their scale-up. Bioprocess modeling and control can also benefit from single cell analysis where the latter could add a new dimension to the former once imaging-based in-line sensors allow for monitoring of key variables governing the processes. In this thesis we exploited signal processing techniques for statistical modeling of bioprocess and its scale-up as well as for development of fully automated methods for biomedical cell microscopy image segmentation beginning from image pre-processing and initial segmentation to clump splitting and image post-processing with the goal to facilitate the high-throughput analysis. In order to highlight the contribution of this work, we present three application case studies where we applied the developed methods to solve the problems of cell image segmentation and bioprocess modeling and scale-up

Robust detection and classification of biomedical cell specimens from light microscope images

Ph.DDOCTOR OF PHILOSOPH

High Resolution, Quantitative Optical Coherence Tomography for Tissue Imaging

Master'sMASTER OF SCIENC

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

Bildfolgenbasierte Gewinnung und Nutzung partikelindividueller Bewegungsinformation in der optischen Schüttgutsortierung

Die sensorgestützte Sortierung ermöglicht die Trennung einzelner Partikel aus einem Materialstrom. In dieser Arbeit wird eine neue Gattung eines Schüttgutsortiersystems mit Flächenkamera erforscht. Der Einsatz von Hochgeschwindigkeitskameras als Inspektionssensorik wirft aus Sicht der Informatik spannende Forschungsfragen hinsichtlich der Gewinnung und Nutzung weitergehender Merkmale, insbesondere von Bewegungsinformation über zu sortierende Materialien, auf