Computerized Analysis of Magnetic Resonance Images to Study Cerebral Anatomy in Developing Neonates

The study of cerebral anatomy in developing neonates is of great importance for the understanding of brain development during the early period of life. This dissertation therefore focuses on three challenges in the modelling of cerebral anatomy in neonates during brain development. The methods that have been developed all use Magnetic Resonance Images (MRI) as source data. To facilitate study of vascular development in the neonatal period, a set of image analysis algorithms are developed to automatically extract and model cerebral vessel trees. The whole process consists of cerebral vessel tracking from automatically placed seed points, vessel tree generation, and vasculature registration and matching. These algorithms have been tested on clinical Time-of- Flight (TOF) MR angiographic datasets. To facilitate study of the neonatal cortex a complete cerebral cortex segmentation and reconstruction pipeline has been developed. Segmentation of the neonatal cortex is not effectively done by existing algorithms designed for the adult brain because the contrast between grey and white matter is reversed. This causes pixels containing tissue mixtures to be incorrectly labelled by conventional methods. The neonatal cortical segmentation method that has been developed is based on a novel expectation-maximization (EM) method with explicit correction for mislabelled partial volume voxels. Based on the resulting cortical segmentation, an implicit surface evolution technique is adopted for the reconstruction of the cortex in neonates. The performance of the method is investigated by performing a detailed landmark study. To facilitate study of cortical development, a cortical surface registration algorithm for aligning the cortical surface is developed. The method first inflates extracted cortical surfaces and then performs a non-rigid surface registration using free-form deformations (FFDs) to remove residual alignment. Validation experiments using data labelled by an expert observer demonstrate that the method can capture local changes and follow the growth of specific sulcus

Genus Computing for 3D digital objects: algorithm and implementation

This paper deals with computing topological invariants such as connected components, boundary surface genus, and homology groups. For each input data set, we have designed or implemented algorithms to calculate connected components, boundary surfaces and their genus, and homology groups. Due to the fact that genus calculation dominates the entire task for 3D object in 3D space, in this paper, we mainly discuss the calculation of the genus. The new algorithms designed in this paper will perform: (1) pathological cases detection and deletion, (2) raster space to point space (dual space) transformation, (3) the linear time algorithm for boundary point classification, and (4) genus calculation.Comment: 12 pages 7 figures. In Proceedings of the Workshop on Computational Topology in image context 2009, Aug. 26-28, Austria, Edited by W. Kropatsch, H. M. Abril and A. Ion, 200

Décomposition volumique d'images pour l'étude de la microstructure de la neige

Les avalanches de neige sont des phénomènes naturels complexes dont l'occurrence s'explique principalement par la structure et les propriétés du manteau neigeux. Afin de mieux comprendre les évolutions de ces propriétés au cours du temps, il est important de pouvoir caractériser la microstructure de la neige, notamment en termes de grains et de ponts de glace les reliant. Dans ce contexte, l'objectif de cette thèse est la décomposition d'échantillons de neige en grains individuels à partir d'images 3-D de neige obtenues par microtomographie X. Nous présentons ici deux méthodes de décomposition utilisant des algorithmes de géométrie discrète. Sur la base des résultats de ces segmentations, certains paramètres, comme la surface spécifique et la surface spécifique de contact entre grains sont ensuite estimés sur des échantillons de neiges variées. Ces méthodes de segmentation ouvrent de nouvelles perspectives pour la caractérisation de la microstructure de la neige, de ses propriétés, ainsi que de leur évolution au cours du temps.Snow avalanches are complex natural phenomena whose occurrence is mainly due to the structure and properties of the snowpack. To better understand the evolution of these properties over time, it is important to characterize the microstructure of snow, especially in terms of grains and ice necks that connect them. In this context, the objective of this thesis is the decomposition of snow samples into individual grains from 3-D images of snow obtained by X-ray microtomography. We present two decomposition methods using algorithms of discrete geometry. Based on the results of these segmentations, some parameters such as the specific surface area and the specific contact area between grains are then estimated from samples of several snow types. These segmentation methods offer new outlooks for the characterization of the microstructure of snow, its properties, and its time evolution

Cell Nuclear Morphology Analysis Using 3D Shape Modeling, Machine Learning and Visual Analytics

Quantitative analysis of morphological changes in a cell nucleus is important for the understanding of nuclear architecture and its relationship with cell differentiation, development, proliferation, and disease. Changes in the nuclear form are associated with reorganization of chromatin architecture related to altered functional properties such as gene regulation and expression. Understanding these processes through quantitative analysis of morphological changes is important not only for investigating nuclear organization, but also has clinical implications, for example, in detection and treatment of pathological conditions such as cancer. While efforts have been made to characterize nuclear shapes in two or pseudo-three dimensions, several studies have demonstrated that three dimensional (3D) representations provide better nuclear shape description, in part due to the high variability of nuclear morphologies. 3D shape descriptors that permit robust morphological analysis and facilitate human interpretation are still under active investigation. A few methods have been proposed to classify nuclear morphologies in 3D, however, there is a lack of publicly available 3D data for the evaluation and comparison of such algorithms. There is a compelling need for robust 3D nuclear morphometric techniques to carry out population-wide analyses. In this work, we address a number of these existing limitations. First, we present a largest publicly available, to-date, 3D microscopy imaging dataset for cell nuclear morphology analysis and classification. We provide a detailed description of the image analysis protocol, from segmentation to baseline evaluation of a number of popular classification algorithms using 2D and 3D voxel-based morphometric measures. We proposed a specific cross-validation scheme that accounts for possible batch effects in data. Second, we propose a new technique that combines mathematical modeling, machine learning, and interpretation of morphometric characteristics of cell nuclei and nucleoli in 3D. Employing robust and smooth surface reconstruction methods to accurately approximate 3D object boundary enables the establishment of homologies between different biological shapes. Then, we compute geometric morphological measures characterizing the form of cell nuclei and nucleoli. We combine these methods into a highly parallel computational pipeline workflow for automated morphological analysis of thousands of nuclei and nucleoli in 3D. We also describe the use of visual analytics and deep learning techniques for the analysis of nuclear morphology data. Third, we evaluate proposed methods for 3D surface morphometric analysis of our data. We improved the performance of morphological classification between epithelial vs mesenchymal human prostate cancer cells compared to the previously reported results due to the more accurate shape representation and the use of combined nuclear and nucleolar morphometry. We confirmed previously reported relevant morphological characteristics, and also reported new features that can provide insight in the underlying biological mechanisms of pathology of prostate cancer. We also assessed nuclear morphology changes associated with chromatin remodeling in drug-induced cellular reprogramming. We computed temporal trajectories reflecting morphological differences in astroglial cell sub-populations administered with 2 different treatments vs controls. We described specific changes in nuclear morphology that are characteristic of chromatin re-organization under each treatment, which previously has been only tentatively hypothesized in literature. Our approach demonstrated high classification performance on each of 3 different cell lines and reported the most salient morphometric characteristics. We conclude with the discussion of the potential impact of method development in nuclear morphology analysis on clinical decision-making and fundamental investigation of 3D nuclear architecture. We consider some open problems and future trends in this field.PHDBioinformaticsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/147598/1/akalinin_1.pd

Characterising population variability in brain structure through models of whole-brain structural connectivity

Models of whole-brain connectivity are valuable for understanding neurological function. This thesis seeks to develop an optimal framework for extracting models of whole-brain connectivity from clinically acquired diffusion data. We propose new approaches for studying these models. The aim is to develop techniques which can take models of brain connectivity and use them to identify biomarkers or phenotypes of disease. The models of connectivity are extracted using a standard probabilistic tractography algorithm, modified to assess the structural integrity of tracts, through estimates of white matter anisotropy. Connections are traced between 77 regions of interest, automatically extracted by label propagation from multiple brain atlases followed by classifier fusion. The estimates of tissue integrity for each tract are input as indices in 77x77 ”connectivity” matrices, extracted for large populations of clinical data. These are compared in subsequent studies. To date, most whole-brain connectivity studies have characterised population differences using graph theory techniques. However these can be limited in their ability to pinpoint the locations of differences in the underlying neural anatomy. Therefore, this thesis proposes new techniques. These include a spectral clustering approach for comparing population differences in the clustering properties of weighted brain networks. In addition, machine learning approaches are suggested for the first time. These are particularly advantageous as they allow classification of subjects and extraction of features which best represent the differences between groups. One limitation of the proposed approach is that errors propagate from segmentation and registration steps prior to tractography. This can cumulate in the assignment of false positive connections, where the contribution of these factors may vary across populations, causing the appearance of population differences where there are none. The final contribution of this thesis is therefore to develop a common co-ordinate space approach. This combines probabilistic models of voxel-wise diffusion for each subject into a single probabilistic model of diffusion for the population. This allows tractography to be performed only once, ensuring that there is one model of connectivity. Cross-subject differences can then be identified by mapping individual subjects’ anisotropy data to this model. The approach is used to compare populations separated by age and gender

Minkowski Tensors of Anisotropic Spatial Structure

This article describes the theoretical foundation of and explicit algorithms for a novel approach to morphology and anisotropy analysis of complex spatial structure using tensor-valued Minkowski functionals, the so-called Minkowski tensors. Minkowski tensors are generalisations of the well-known scalar Minkowski functionals and are explicitly sensitive to anisotropic aspects of morphology, relevant for example for elastic moduli or permeability of microstructured materials. Here we derive explicit linear-time algorithms to compute these tensorial measures for three-dimensional shapes. These apply to representations of any object that can be represented by a triangulation of its bounding surface; their application is illustrated for the polyhedral Voronoi cellular complexes of jammed sphere configurations, and for triangulations of a biopolymer fibre network obtained by confocal microscopy. The article further bridges the substantial notational and conceptual gap between the different but equivalent approaches to scalar or tensorial Minkowski functionals in mathematics and in physics, hence making the mathematical measure theoretic method more readily accessible for future application in the physical sciences

Surface-guided computing to analyze subcellular morphology and membrane-associated signals in 3D

Signal transduction and cell function are governed by the spatiotemporal organization of membrane-associated molecules. Despite significant advances in visualizing molecular distributions by 3D light microscopy, cell biologists still have limited quantitative understanding of the processes implicated in the regulation of molecular signals at the whole cell scale. In particular, complex and transient cell surface morphologies challenge the complete sampling of cell geometry, membrane-associated molecular concentration and activity and the computing of meaningful parameters such as the cofluctuation between morphology and signals. Here, we introduce u-Unwrap3D, a framework to remap arbitrarily complex 3D cell surfaces and membrane-associated signals into equivalent lower dimensional representations. The mappings are bidirectional, allowing the application of image processing operations in the data representation best suited for the task and to subsequently present the results in any of the other representations, including the original 3D cell surface. Leveraging this surface-guided computing paradigm, we track segmented surface motifs in 2D to quantify the recruitment of Septin polymers by blebbing events; we quantify actin enrichment in peripheral ruffles; and we measure the speed of ruffle movement along topographically complex cell surfaces. Thus, u-Unwrap3D provides access to spatiotemporal analyses of cell biological parameters on unconstrained 3D surface geometries and signals.Comment: 49 pages, 10 figure

Direct occlusion handling for high level image processing algorithms

Many high-level computer vision algorithms suffer in the presence of occlusions caused by multiple objects overlapping in a view. Occlusions remove the direct correspondence between visible areas of objects and the objects themselves by introducing ambiguity in the interpretation of the shape of the occluded object. Ignoring this ambiguity allows the perceived geometry of overlapping objects to be deformed or even fractured. Supplementing the raw image data with a vectorized structural representation which predicts object completions could stabilize high-level algorithms which currently disregard occlusions. Studies in the neuroscience community indicate that the feature points located at the intersection of junctions may be used by the human visual system to produce these completions. Geiger, Pao, and Rubin have successfully used these features in a purely rasterized setting to complete objects in a fashion similar to what is demonstrated by human perception. This work proposes using these features in a vectorized approach to solving the mid-level computer vision problem of object stitching. A system has been implemented which is able extract L and T-junctions directly from the edges of an image using scale-space and robust statistical techniques. The system is sensitive enough to be able to isolate the corners on polygons with 24 sides or more, provided sufficient image resolution is available. Areas of promising development have been identified and several directions for further research are proposed