Model and Appearance Based Analysis of Neuronal Morphology from Different Microscopy Imaging Modalities

The neuronal morphology analysis is key for understanding how a brain works. This process requires the neuron imaging system with single-cell resolution; however, there is no feasible system for the human brain. Fortunately, the knowledge can be inferred from the model organism, Drosophila melanogaster, to the human system. This dissertation explores the morphology analysis of Drosophila larvae at single-cell resolution in static images and image sequences, as well as multiple microscopy imaging modalities. Our contributions are on both computational methods for morphology quantification and analysis of the influence of the anatomical aspect. We develop novel model-and-appearance-based methods for morphology quantification and illustrate their significance in three neuroscience studies. Modeling of the structure and dynamics of neuronal circuits creates understanding about how connectivity patterns are formed within a motor circuit and determining whether the connectivity map of neurons can be deduced by estimations of neuronal morphology. To address this problem, we study both boundary-based and centerline-based approaches for neuron reconstruction in static volumes. Neuronal mechanisms are related to the morphology dynamics; so the patterns of neuronal morphology changes are analyzed along with other aspects. In this case, the relationship between neuronal activity and morphology dynamics is explored to analyze locomotion procedures. Our tracking method models the morphology dynamics in the calcium image sequence designed for detecting neuronal activity. It follows the local-to-global design to handle calcium imaging issues and neuronal movement characteristics. Lastly, modeling the link between structural and functional development depicts the correlation between neuron growth and protein interactions. This requires the morphology analysis of different imaging modalities. It can be solved using the part-wise volume segmentation with artificial templates, the standardized representation of neurons. Our method follows the global-to-local approach to solve both part-wise segmentation and registration across modalities. Our methods address common issues in automated morphology analysis from extracting morphological features to tracking neurons, as well as mapping neurons across imaging modalities. The quantitative analysis delivered by our techniques enables a number of new applications and visualizations for advancing the investigation of phenomena in the nervous system

Comparative Uncertainty Visualization for High-Level Analysis of Scalar- and Vector-Valued Ensembles

With this thesis, I contribute to the research field of uncertainty visualization, considering parameter dependencies in multi valued fields and the uncertainty of automated data analysis. Like uncertainty visualization in general, both of these fields are becoming more and more important due to increasing computational power, growing importance and availability of complex models and collected data, and progress in artificial intelligence. I contribute in the following application areas: Uncertain Topology of Scalar Field Ensembles. The generalization of topology-based visualizations to multi valued data involves many challenges. An example is the comparative visualization of multiple contour trees, complicated by the random nature of prevalent contour tree layout algorithms. I present a novel approach for the comparative visualization of contour trees - the Fuzzy Contour Tree. Uncertain Topological Features in Time-Dependent Scalar Fields. Tracking features in time-dependent scalar fields is an active field of research, where most approaches rely on the comparison of consecutive time steps. I created a more holistic visualization for time-varying scalar field topology by adapting Fuzzy Contour Trees to the time-dependent setting. Uncertain Trajectories in Vector Field Ensembles. Visitation maps are an intuitive and well-known visualization of uncertain trajectories in vector field ensembles. For large ensembles, visitation maps are not applicable, or only with extensive time requirements. I developed Visitation Graphs, a new representation and data reduction method for vector field ensembles that can be calculated in situ and is an optimal basis for the efficient generation of visitation maps. This is accomplished by bringing forward calculation times to the pre-processing. Visually Supported Anomaly Detection in Cyber Security. Numerous cyber attacks and the increasing complexity of networks and their protection necessitate the application of automated data analysis in cyber security. Due to uncertainty in automated anomaly detection, the results need to be communicated to analysts to ensure appropriate reactions. I introduce a visualization system combining device readings and anomaly detection results: the Security in Process System. To further support analysts I developed an application agnostic framework that supports the integration of knowledge assistance and applied it to the Security in Process System. I present this Knowledge Rocks Framework, its application and the results of evaluations for both, the original and the knowledge assisted Security in Process System. For all presented systems, I provide implementation details, illustrations and applications

A survey of visual preprocessing and shape representation techniques

Many recent theories and methods proposed for visual preprocessing and shape representation are summarized. The survey brings together research from the fields of biology, psychology, computer science, electrical engineering, and most recently, neural networks. It was motivated by the need to preprocess images for a sparse distributed memory (SDM), but the techniques presented may also prove useful for applying other associative memories to visual pattern recognition. The material of this survey is divided into three sections: an overview of biological visual processing; methods of preprocessing (extracting parts of shape, texture, motion, and depth); and shape representation and recognition (form invariance, primitives and structural descriptions, and theories of attention)

Implicit deformable models for biomedical image segmentation.

In this thesis, new methods for the efficient segmentation of images are presented. The proposed methods are based on the deformable model approach, and can be used efficiently in the segmentation of complex geometries from various imaging modalities. A novel deformable model that is based on a geometrically induced external force field which can be conveniently generalized to arbitrary dimensions is presented. This external force field is based on hypothesized interactions between the relative geometries of the deformable model and the object boundary characterized by image gradient. The evolution of the deformable model is solved using the level set method so that topological changes are handled automatically. The relative geometrical configurations between the deformable model and the object boundaries contributes to a dynamic vector force field that changes accordingly as the deformable model evolves. The geometrically induced dynamic interaction force has been shown to greatly improve the deformable model performance in acquiring complex geometries and highly concave boundaries, and give the deformable model a high invariance in initialization configurations. The voxel interactions across the whole image domain provides a global view of the object boundary representation, giving the external force a long attraction range. The bidirectionality of the external force held allows the new deformable model to deal with arbitrary cross-boundary initializations, and facilitates the handling of weak edges and broken boundaries. In addition, it is shown that by enhancing the geometrical interaction field with a nonlocal edge-preserving algorithm, the new deformable model can effectively overcome image noise. A comparative study on the segmentation of various geometries with different topologies from both synthetic and real images is provided, and the proposed method is shown to achieve significant improvements against several existing techniques. A robust framework for the segmentation of vascular geometries is described. In particular, the framework consists of image denoising, optimal object edge representation, and segmentation using implicit deformable model. The image denoising is based on vessel enhancing diffusion which can be used to smooth out image noise and enhance the vessel structures. The image object boundaries are derived using an edge detection technique which can produce object edges of single pixel width. The image edge information is then used to derive the geometric interaction field for optimal object edge representation. The vascular geometries are segmented using an implict deformable model. A region constraint is added to the deformable model which allows it to easily get around calcified regions and propagate across the vessels to segment the structures efficiently. The presented framework is ai)plied in the accurate segmentation of carotid geometries from medical images. A new segmentation model with statistical shape prior using a variational approach is also presented in this thesis. The proposed model consists of an image attraction force that propagates contours towards image object boundaries, and a global shape force that attracts the model towards similar shapes in the statistical shape distribution. The image attraction force is derived from gradient vector interactions across the whole image domain, which makes the model more robust to image noise, weak edges and initializations. The statistical shape information is incorporated using kernel density estimation, which allows the shape prior model to handle arbitrary shape variations. It is shown that the proposed model with shape prior can be used to segment object shapes from images efficiently

A comparative evaluation for liver segmentation from spir images and a novel level set method using signed pressure force function

Thesis (Doctoral)--Izmir Institute of Technology, Electronics and Communication Engineering, Izmir, 2013Includes bibliographical references (leaves: 118-135)Text in English; Abstract: Turkish and Englishxv, 145 leavesDeveloping a robust method for liver segmentation from magnetic resonance images is a challenging task due to similar intensity values between adjacent organs, geometrically complex liver structure and injection of contrast media, which causes all tissues to have different gray level values. Several artifacts of pulsation and motion, and partial volume effects also increase difficulties for automatic liver segmentation from magnetic resonance images. In this thesis, we present an overview about liver segmentation methods in magnetic resonance images and show comparative results of seven different liver segmentation approaches chosen from deterministic (K-means based), probabilistic (Gaussian model based), supervised neural network (multilayer perceptron based) and deformable model based (level set) segmentation methods. The results of qualitative and quantitative analysis using sensitivity, specificity and accuracy metrics show that the multilayer perceptron based approach and a level set based approach which uses a distance regularization term and signed pressure force function are reasonable methods for liver segmentation from spectral pre-saturation inversion recovery images. However, the multilayer perceptron based segmentation method requires a higher computational cost. The distance regularization term based automatic level set method is very sensitive to chosen variance of Gaussian function. Our proposed level set based method that uses a novel signed pressure force function, which can control the direction and velocity of the evolving active contour, is faster and solves several problems of other applied methods such as sensitivity to initial contour or variance parameter of the Gaussian kernel in edge stopping functions without using any regularization term

Segmentation of cell structures in fluorescence confocal microscopy images

During the past several years, image segmentation techniques have been developed and extensively used in biomedical applications as an important tool to extract objects and boundaries of interest. In biological field, cytoskeleton analysis is a complicated problem and the analysing technique is still immature. Cytoskeleton plays an important role in normal cell activities, including motion and division, which make the cell cytoskeleton important to investigate. The objective of this project is to investigate and evaluate level set segmentation methods for segmentation of both cell nuclei and membrane segmentation of microfilament images captured by fluorescent confocal microscopy. Based on some background investigations, the active contour methodology has been selected as the fundamental method for image segmentation. This thesis presents the methods used and reports on the results achieved for cell and nuclei segmentation using the hybrid level-set method and cell membrane segmentation using the subjective surfaces model. In addition, some initial results of nuclei segmentation in 3-D case based on the hybrid method will be presented as well. Also included in this thesis are the method and the initial categorisation of microtubule images based on the multi-template method. At the end of the thesis, possible directions for potential future work are presented. It is envisaged that the segmentation tools produced by the project will make cell cytoskeleton data analysis much more convenient. In particular, the segmentation of cell membranes will help biologists to perform quantitative analysis of fluorescent confocal microscopy images by measuring the cell properties. With more useful information of cytoskeleton being provided, the work contained in this thesis has the potential to contribute to evaluation and prediction of the possibility of cell canceration

Modeling small objects under uncertainties : novel algorithms and applications.

Active Shape Models (ASM), Active Appearance Models (AAM) and Active Tensor Models (ATM) are common approaches to model elastic (deformable) objects. These models require an ensemble of shapes and textures, annotated by human experts, in order identify the model order and parameters. A candidate object may be represented by a weighted sum of basis generated by an optimization process. These methods have been very effective for modeling deformable objects in biomedical imaging, biometrics, computer vision and graphics. They have been tried mainly on objects with known features that are amenable to manual (expert) annotation. They have not been examined on objects with severe ambiguities to be uniquely characterized by experts. This dissertation presents a unified approach for modeling, detecting, segmenting and categorizing small objects under uncertainty, with focus on lung nodules that may appear in low dose CT (LDCT) scans of the human chest. The AAM, ASM and the ATM approaches are used for the first time on this application. A new formulation to object detection by template matching, as an energy optimization, is introduced. Nine similarity measures of matching have been quantitatively evaluated for detecting nodules less than 1 em in diameter. Statistical methods that combine intensity, shape and spatial interaction are examined for segmentation of small size objects. Extensions of the intensity model using the linear combination of Gaussians (LCG) approach are introduced, in order to estimate the number of modes in the LCG equation. The classical maximum a posteriori (MAP) segmentation approach has been adapted to handle segmentation of small size lung nodules that are randomly located in the lung tissue. A novel empirical approach has been devised to simultaneously detect and segment the lung nodules in LDCT scans. The level sets methods approach was also applied for lung nodule segmentation. A new formulation for the energy function controlling the level set propagation has been introduced taking into account the specific properties of the nodules. Finally, a novel approach for classification of the segmented nodules into categories has been introduced. Geometric object descriptors such as the SIFT, AS 1FT, SURF and LBP have been used for feature extraction and matching of small size lung nodules; the LBP has been found to be the most robust. Categorization implies classification of detected and segmented objects into classes or types. The object descriptors have been deployed in the detection step for false positive reduction, and in the categorization stage to assign a class and type for the nodules. The AAMI ASMI A TM models have been used for the categorization stage. The front-end processes of lung nodule modeling, detection, segmentation and classification/categorization are model-based and data-driven. This dissertation is the first attempt in the literature at creating an entirely model-based approach for lung nodule analysis

Inferring Geodesic Cerebrovascular Graphs: Image Processing, Topological Alignment and Biomarkers Extraction

A vectorial representation of the vascular network that embodies quantitative features - location, direction, scale, and bifurcations - has many potential neuro-vascular applications. Patient-specific models support computer-assisted surgical procedures in neurovascular interventions, while analyses on multiple subjects are essential for group-level studies on which clinical prediction and therapeutic inference ultimately depend. This first motivated the development of a variety of methods to segment the cerebrovascular system. Nonetheless, a number of limitations, ranging from data-driven inhomogeneities, the anatomical intra- and inter-subject variability, the lack of exhaustive ground-truth, the need for operator-dependent processing pipelines, and the highly non-linear vascular domain, still make the automatic inference of the cerebrovascular topology an open problem. In this thesis, brain vessels’ topology is inferred by focusing on their connectedness. With a novel framework, the brain vasculature is recovered from 3D angiographies by solving a connectivity-optimised anisotropic level-set over a voxel-wise tensor field representing the orientation of the underlying vasculature. Assuming vessels joining by minimal paths, a connectivity paradigm is formulated to automatically determine the vascular topology as an over-connected geodesic graph. Ultimately, deep-brain vascular structures are extracted with geodesic minimum spanning trees. The inferred topologies are then aligned with similar ones for labelling and propagating information over a non-linear vectorial domain, where the branching pattern of a set of vessels transcends a subject-specific quantized grid. Using a multi-source embedding of a vascular graph, the pairwise registration of topologies is performed with the state-of-the-art graph matching techniques employed in computer vision. Functional biomarkers are determined over the neurovascular graphs with two complementary approaches. Efficient approximations of blood flow and pressure drop account for autoregulation and compensation mechanisms in the whole network in presence of perturbations, using lumped-parameters analog-equivalents from clinical angiographies. Also, a localised NURBS-based parametrisation of bifurcations is introduced to model fluid-solid interactions by means of hemodynamic simulations using an isogeometric analysis framework, where both geometry and solution profile at the interface share the same homogeneous domain. Experimental results on synthetic and clinical angiographies validated the proposed formulations. Perspectives and future works are discussed for the group-wise alignment of cerebrovascular topologies over a population, towards defining cerebrovascular atlases, and for further topological optimisation strategies and risk prediction models for therapeutic inference. Most of the algorithms presented in this work are available as part of the open-source package VTrails

Novel Techniques for Automated Dental Identification

Automated dental identification is one of the best candidates for postmortem identification. With the large number of victims encountered in mass disasters, automating the process of postmortem identification is receiving an increased attention. This dissertation introduces new approaches for different stages of Automated Dental Identification system: These stages include segmentations, classification, labeling, and matching:;We modified the seam carving technique to adapt the problem of segmenting dental image records into individual teeth. We propose a two-stage teeth segmentation approach for segmenting the dental images. In the first stage, the teeth images are preprocessed by a two-step thresholding technique, which starts with an iterative thresholding followed by an adaptive thresholding to binarize the teeth images. In the second stage, we adapt the seam carving technique on the binary images, using both horizontal and vertical seams, to separate each individual tooth. We have obtained an optimality rate of 54.02% for the bitewing type images, which is superior to all existing fully automated dental segmentation algorithms in the literature, and a failure rate of 1.05%. For the periapical type images, we have obtained a high optimality rate of 58.13% and a low failure rate of 0.74 which also surpasses the performance of existing techniques. An important problem in automated dental identification is automatic classification of teeth into four classes (molars, premolars, canines, and incisors). A dental chart is a key to avoiding illogical comparisons that inefficiently consume the limited computational resources, and may mislead decision-making. We tackle this composite problem using a two-stage approach. The first stage, utilizes low computational-cost, appearance-based features, using Orthogonal Locality Preserving Projections (OLPP) for assigning an initial class. The second stage applies a string matching technique, based on teeth neighborhood rules, to validate initial teeth-classes and hence to assign each tooth a number corresponding to its location in the dental chart, even in the presence of a missed tooth. The experimental results of teeth classification show that on a large dataset of bitewing and periapical films, the proposed approach achieves overall classification accuracy of 77% and teeth class validation enhances the overall teeth classification accuracy to 87% which is slightly better than the performance obtained from previous methods based on EigenTeeth the performance of which is 75% and 86%, respectively.;We present a new technique that searches the dental database to find a candidate list. We use dental records of the FBI\u27s Criminal Justice Service (CJIC) ADIS database, that contains 104 records (about 500 bitewing and periapical films) involving more than 2000 teeth, 47 Antemortem (AM) records and 57 Postmortem (PM) records with 20 matched records.;The proposed approach consists of two main stages, the first stage is to preprocess the dental records (segmentation and teeth labeling classification) in order to get a reliable, appearance-based, low computational-cost feature. In the second stage, we developed a technique based on LaplacianTeeth using OLPP algorithm to produce a candidate list. The proposed technique can correctly retrieve the dental records 65% in the 5 top ranks while the method based on EigenTeeth remains at 60%. The proposed approach takes about 0.17 seconds to make record to record comparison while the other method based on EigenTeeth takes about 0.09 seconds.;Finally, we address the teeth matching problem by presenting a new technique for dental record retrieval. The technique is based on the matching of the Scale Invariant feature Transform (SIFT) descriptors guided by the teeth contour between the subject and reference dental records. Our fundamental objective is to accomplish a relatively short match list, with a high probability of having the correct match reference. The proposed technique correctly retrieves the dental records with performance rates of 35% and 75% in the 1 and 5 top ranks respectively, and takes only an average time of 4.18 minutes to retrieve a match list. This compares favorably with the existing technique shape-based (edge direction histogram) method which has the performance rates of 29% and 46% in the 1 and 5 top ranks respectively.;In summary, the proposed ADIS system accurately retrieves the dental record with an overall rate of 80% in top 5 ranks when a candidate list of 20 is used (from potential match search) whereas a candidate size of 10 yields an overall rate of 84% in top 5 ranks and takes only a few minutes to search the database, which compares favorably against most of the existing methods in the literature, when both accuracy and computational complexity are considered