Curvilinear Structure Enhancement in Biomedical Images

Curvilinear structures can appear in many different areas and at a variety of scales. They can be axons and dendrites in the brain, blood vessels in the fundus, streets, rivers or fractures in buildings, and others. So, it is essential to study curvilinear structures in many fields such as neuroscience, biology, and cartography regarding image processing. Image processing is an important field for the help to aid in biomedical imaging especially the diagnosing the disease. Image enhancement is the early step of image analysis. In this thesis, I focus on the research, development, implementation, and validation of 2D and 3D curvilinear structure enhancement methods, recently established. The proposed methods are based on phase congruency, mathematical morphology, and tensor representation concepts. First, I have introduced a 3D contrast independent phase congruency-based enhancement approach. The obtained results demonstrate the proposed approach is robust against the contrast variations in 3D biomedical images. Second, I have proposed a new mathematical morphology-based approach called the bowler-hat transform. In this approach, I have combined the mathematical morphology with a local tensor representation of curvilinear structures in images. The bowler-hat transform is shown to give better results than comparison methods on challenging data such as retinal/fundus images. The bowler-hat transform is shown to give better results than comparison methods on challenging data such as retinal/fundus images. Especially the proposed method is quite successful while enhancing of curvilinear structures at junctions. Finally, I have extended the bowler-hat approach to the 3D version to prove the applicability, reliability, and ability of it in 3D

A Multi-task Network to Detect Junctions in Retinal Vasculature

Junctions in the retinal vasculature are key points to be able to extract its topology, but they vary in appearance, depending on vessel density, width and branching/crossing angles. The complexity of junction patterns is usually accompanied by a scarcity of labels, which discourages the usage of very deep networks for their detection. We propose a multi-task network, generating labels for vessel interior, centerline, edges and junction patterns, to provide additional information to facilitate junction detection. After the initial detection of potential junctions in junction-selective probability maps, candidate locations are re-examined in centerline probability maps to verify if they connect at least 3 branches. The experiments on the DRIVE and IOSTAR showed that our method outperformed a recent study in which a popular deep network was trained as a classifier to find junctions. Moreover, the proposed approach is applicable to unseen datasets with the same degree of success, after training it only once.Comment: MICCAI 2018 Camera Ready Versio

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

Reconstructing Curvilinear Networks using Path Classifiers and Integer Programming

We propose a novel Bayesian approach to automated delineation of curvilinear structures that form complex and potentially loopy networks. By representing the image data as a graph of potential paths, we first show how to weight these paths using discriminatively-trained classifiers that are both robust and generic enough to be applied to very different imaging modalities. We then present an Integer Programming approach to finding the optimal subset of paths, subject to structural and topological constraints that eliminate implausible solutions. Unlike earlier approaches that assume a tree topology for the networks, ours explicitly models the fact that the networks may contain loops, and can reconstruct both cyclic and acyclic ones. We demonstrate the effectiveness of our approach on a variety of challenging datasets including aerial images of road networks and micrographs of neural arbors, and show that it outperforms state-of-the-art techniques

Learning Approach to Delineation of Curvilinear Structures in 2D and 3D Images

Detection of curvilinear structures has long been of interest due to its wide range of applications. Large amounts of imaging data could be readily used in many fields, but it is practically not possible to analyze them manually. Hence, the need for automated delineation approaches. In the recent years Computer Vision witnessed a paradigm shift from mathematical modelling to data-driven methods based on Machine Learning. This led to improvements in performance and robustness of the detection algorithms. Nonetheless, most Machine Learning methods are general-purpose and they do not exploit the specificity of the delineation problem. In this thesis, we present learning methods suited for this task and we apply them to various kinds of microscopic and natural images, proving the general applicability of the presented solutions. First, we introduce a topology loss - a new training loss term, which captures higher-level features of curvilinear networks such as smoothness, connectivity and continuity. This is in contrast to most Deep Learning segmentation methods that do not take into account the geometry of the resulting prediction. In order to compute the new loss term, we extract topology features of prediction and ground-truth using a pre-trained network, whose filters are activated by structures at different scales and orientations. We show that this approach yields better results in terms of conventional segmentation metrics and overall topology of the resulting delineation. Although segmentation of curvilinear structures provides useful information, it is not always sufficient. In many cases, such as neuroscience and cartography, it is crucial to estimate the network connectivity. In order to find the graph representation of the structure depicted in the image, we propose an approach for joint segmentation and connection classification. Apart from pixel probabilities, this approach also returns the likelihood of a proposed path being a part of the reconstructed network. We show that segmentation and path classification are closely related tasks and can benefit from the synergy. The aforementioned methods rely on Machine Learning, which requires significant amounts of annotated ground-truth data to train models. The labelling process often requires expertise, it is costly and tiresome. To alleviate this problem, we introduce an Active Learning method that significantly decreases the time spent on annotating images. It queries the annotator only about the most informative examples, in this case the hypothetical paths belonging to the structure of interest. Contrary to conventional Active Learning methods, our approach exploits local consistency of linear paths to pick the ones that stand out from their neighborhood. Our final contribution is a method suited for both Active Learning and proofreading the result, which often requires more time than the automated delineation itself. It investigates edges of the delineation graph and determines the ones that are especially significant for the global reconstruction by perturbing their weights. Our Active Learning and proofreading strategies are combined with a new efficient formulation of an optimal subgraph computation and reduce the annotation effort by up to 80%

Model-based Curvilinear Network Extraction and Tracking toward Quantitative Analysis of Biopolymer Networks

Curvilinear biopolymer networks pervade living systems. They are routinely imaged by fluorescence microscopy to gain insight into their structural, mechanical, and dynamic properties. Image analysis can facilitate understanding the mechanisms of their formation and their biological functions from a quantitative viewpoint. Due to the variability in network geometry, topology and dynamics as well as often low resolution and low signal-to-noise ratio in images, segmentation and tracking networks from these images is challenging. In this dissertation, we propose a complete framework for extracting the geometry and topology of curvilinear biopolymer networks, and also tracking their dynamics from multi-dimensional images. The proposed multiple Stretching Open Active Contours (SOACs) can identify network centerlines and junctions, and infer plausible network topology. Combined with a $k$-partite matching algorithm, temporal correspondences among all the detected filaments can be established. This work enables statistical analysis of structural parameters of biopolymer networks as well as their dynamics. Quantitative evaluation using simulated and experimental images demonstrate its effectiveness and efficiency. Moreover, a principled method of optimizing key parameters without ground truth is proposed for attaining the best extraction result for any type of images. The proposed methods are implemented into a usable open source software ``SOAX\u27\u27. Besides network extraction and tracking, SOAX provides a user-friendly cross-platform GUI for interactive visualization, manual editing and quantitative analysis. Using SOAX to analyze several types of biopolymer networks demonstrates the potential of the proposed methods to help answer key questions in cell biology and biophysics from a quantitative viewpoint

Multiscale Centerline Extraction Based on Regression and Projection onto the Set of Elongated Structures

Automatically extracting linear structures from images is a fundamental low-level vision problem with numerous applications in different domains. Centerline detection and radial estimation are the first crucial steps in most Computer Vision pipelines aiming to reconstruct linear structures. Existing techniques rely either on hand-crafted filters, designed to respond to ideal profiles of the linear structure, or on classification-based approaches, which automatically learn to detect centerline points from data. Hand-crafted methods are the most accurate when the content of the image fulfills the ideal model they rely on. However, they lose accuracy in the presence of noise or when the linear structures are irregular and deviate from the ideal case. Machine learning techniques can alleviate this problem. However, they are mainly based on a classification framework. In this thesis, we show that classification is not the best formalism to solve the centerline detection problem. In fact, since the appearance of a centerline point is very similar to the points immediately next to it, the output of a classifier trained to detect centerlines presents low localization accuracy and double responses on the body of the linear structure. To solve this problem, we propose a regression-based formulation for centerline detection. We rely on the distance transform of the centerlines to automatically learn a function whose local maxima correspond to centerline points. The output of our method can be used to directly estimate the location of the centerline, by a simple Non-Maximum Suppression operation, or it can be used as input to a tracing pipeline to reconstruct the graph of the linear structure. In both cases, our method gives more accurate results than state-of-the-art techniques on challenging 2D and 3D datasets. Our method relies on features extracted by means of convolutional filters. In order to process large amount of data efficiently, we introduce a general filter bank approximation scheme. In particular, we show that a generic filter bank can be approximated by a linear combination of a smaller set of separable filters. Thanks to this method, we can greatly reduce the computation time of the convolutions, without loss of accuracy. Our approach is general, and we demonstrate its effectiveness by applying it to different Computer Vision problems, such as linear structure detection and image classification with Convolutional Neural Networks. We further improve our regression-based method for centerline detection by taking advantage of contextual image information. We adopt a multiscale iterative regression approach to efficiently include a large image context in our algorithm. Compared to previous approaches, we use context both in the spatial domain and in the radial one. In this way, our method is also able to return an accurate estimation of the radii of the linear structures. The idea of using regression can also be beneficial for solving other related Computer Vision problems. For example, we show an improvement compared to previous works when applying it to boundary and membrane detection. Finally, we focus on the particular geometric properties of the linear structures. We observe that most methods for detecting them treat each pixel independently and do not model the strong relation that exists between neighboring pixels. As a consequence, their output is geometrically inconsistent. In this thesis, we address this problem by considering the projection of the score map returned by our regressor onto the set of all geometrically admissible ground truth images. We propose an efficient patch-wise approximation scheme to compute the projection. Moreover, we provide conditions under which the projection is exact. We demonstrate the advantage of our method by applying it to four different problems

Methods for Automated Neuron Image Analysis

Knowledge of neuronal cell morphology is essential for performing specialized analyses in the endeavor to understand neuron behavior and unravel the underlying principles of brain function. Neurons can be captured with a high level of detail using modern microscopes, but many neuroscientific studies require a more explicit and accessible representation than offered by the resulting images, underscoring the need for digital reconstruction of neuronal morphology from the images into a tree-like graph structure. This thesis proposes new computational methods for automated detection and reconstruction of neurons from fluorescence microscopy images. Specifically, the successive chapters describe and evaluate original solutions to problems such as the detection of landmarks (critical points) of the neuronal tree, complete tracing and reconstruction of the tree, and the detection of regions containing neurons in high-content screens