Alignment of Tractograms As Graph Matching

The white matter pathways of the brain can be reconstructed as 3D polylines, called streamlines, through the analysis of diffusion magnetic resonance imaging (dMRI) data. The whole set of streamlines is called tractogram and represents the structural connectome of the brain. In multiple applications, like group-analysis, segmentation, or atlasing, tractograms of different subjects need to be aligned. Typically, this is done with registration methods, that transform the tractograms in order to increase their similarity. In contrast with transformation-based registration methods, in this work we propose the concept of tractogram correspondence, whose aim is to find which streamline of one tractogram corresponds to which streamline in another tractogram, i.e., a map from one tractogram to another. As a further contribution, we propose to use the relational information of each streamline, i.e., its distances from the other streamlines in its own tractogram, as the building block to define the optimal correspondence. We provide an operational procedure to find the optimal correspondence through a combinatorial optimization problem and we discuss its similarity to the graph matching problem. In this work, we propose to represent tractograms as graphs and we adopt a recent inexact sub-graph matching algorithm to approximate the solution of the tractogram correspondence problem. On tractograms generated from the Human Connectome Project dataset, we report experimental evidence that tractogram correspondence, implemented as graph matching, provides much better alignment than affine registration and comparable if not better results than non-linear registration of volumes

Computational methods to create and analyze a digital gene expression atlas of embryo development from microscopy images

Abstract The creation of atlases, or digital models where information from different subjects can be combined, is a field of increasing interest in biomedical imaging. When a single image does not contain enough information to appropriately describe the organism under study, it is then necessary to acquire images of several individuals, each of them containing complementary data with respect to the rest of the components in the cohort. This approach allows creating digital prototypes, ranging from anatomical atlases of human patients and organs, obtained for instance from Magnetic Resonance Imaging, to gene expression cartographies of embryo development, typically achieved from Light Microscopy. Within such context, in this PhD Thesis we propose, develop and validate new dedicated image processing methodologies that, based on image registration techniques, bring information from multiple individuals into alignment within a single digital atlas model. We also elaborate a dedicated software visualization platform to explore the resulting wealth of multi-dimensional data and novel analysis algo-rithms to automatically mine the generated resource in search of bio¬logical insights. In particular, this work focuses on gene expression data from developing zebrafish embryos imaged at the cellular resolution level with Two-Photon Laser Scanning Microscopy. Disposing of quantitative measurements relating multiple gene expressions to cell position and their evolution in time is a fundamental prerequisite to understand embryogenesis multi-scale processes. However, the number of gene expressions that can be simultaneously stained in one acquisition is limited due to optical and labeling constraints. These limitations motivate the implementation of atlasing strategies that can recreate a virtual gene expression multiplex. The developed computational tools have been tested in two different scenarios. The first one is the early zebrafish embryogenesis where the resulting atlas constitutes a link between the phenotype and the genotype at the cellular level. The second one is the late zebrafish brain where the resulting atlas allows studies relating gene expression to brain regionalization and neurogenesis. The proposed computational frameworks have been adapted to the requirements of both scenarios, such as the integration of partial views of the embryo into a whole embryo model with cellular resolution or the registration of anatom¬ical traits with deformable transformation models non-dependent on any specific labeling. The software implementation of the atlas generation tool (Match-IT) and the visualization platform (Atlas-IT) together with the gene expression atlas resources developed in this Thesis are to be made freely available to the scientific community. Lastly, a novel proof-of-concept experiment integrates for the first time 3D gene expression atlas resources with cell lineages extracted from live embryos, opening up the door to correlate genetic and cellular spatio-temporal dynamics. La creación de atlas, o modelos digitales, donde la información de distintos sujetos puede ser combinada, es un campo de creciente interés en imagen biomédica. Cuando una sola imagen no contiene suficientes datos como para describir apropiadamente el organismo objeto de estudio, se hace necesario adquirir imágenes de varios individuos, cada una de las cuales contiene información complementaria respecto al resto de componentes del grupo. De este modo, es posible crear prototipos digitales, que pueden ir desde atlas anatómicos de órganos y pacientes humanos, adquiridos por ejemplo mediante Resonancia Magnética, hasta cartografías de la expresión genética del desarrollo de embrionario, típicamente adquiridas mediante Microscopía Optica. Dentro de este contexto, en esta Tesis Doctoral se introducen, desarrollan y validan nuevos métodos de procesado de imagen que, basándose en técnicas de registro de imagen, son capaces de alinear imágenes y datos provenientes de múltiples individuos en un solo atlas digital. Además, se ha elaborado una plataforma de visualization específicamente diseñada para explorar la gran cantidad de datos, caracterizados por su multi-dimensionalidad, que resulta de estos métodos. Asimismo, se han propuesto novedosos algoritmos de análisis y minería de datos que permiten inspeccionar automáticamente los atlas generados en busca de conclusiones biológicas significativas. En particular, este trabajo se centra en datos de expresión genética del desarrollo embrionario del pez cebra, adquiridos mediante Microscopía dos fotones con resolución celular. Disponer de medidas cuantitativas que relacionen estas expresiones genéticas con las posiciones celulares y su evolución en el tiempo es un prerrequisito fundamental para comprender los procesos multi-escala característicos de la morfogénesis. Sin embargo, el número de expresiones genéticos que pueden ser simultáneamente etiquetados en una sola adquisición es reducido debido a limitaciones tanto ópticas como del etiquetado. Estas limitaciones requieren la implementación de estrategias de creación de atlas que puedan recrear un multiplexado virtual de expresiones genéticas. Las herramientas computacionales desarrolladas han sido validadas en dos escenarios distintos. El primer escenario es el desarrollo embrionario temprano del pez cebra, donde el atlas resultante permite constituir un vínculo, a nivel celular, entre el fenotipo y el genotipo de este organismo modelo. El segundo escenario corresponde a estadios tardíos del desarrollo del cerebro del pez cebra, donde el atlas resultante permite relacionar expresiones genéticas con la regionalización del cerebro y la formación de neuronas. La plataforma computacional desarrollada ha sido adaptada a los requisitos y retos planteados en ambos escenarios, como la integración, a resolución celular, de vistas parciales dentro de un modelo consistente en un embrión completo, o el alineamiento entre estructuras de referencia anatómica equivalentes, logrado mediante el uso de modelos de transformación deformables que no requieren ningún marcador específico. Está previsto poner a disposición de la comunidad científica tanto la herramienta de generación de atlas (Match-IT), como su plataforma de visualización (Atlas-IT), así como las bases de datos de expresión genética creadas a partir de estas herramientas. Por último, dentro de la presente Tesis Doctoral, se ha incluido una prueba conceptual innovadora que permite integrar los mencionados atlas de expresión genética tridimensionales dentro del linaje celular extraído de una adquisición in vivo de un embrión. Esta prueba conceptual abre la puerta a la posibilidad de correlar, por primera vez, las dinámicas espacio-temporales de genes y células

On pattern recognition of brain connectivity in resting-state functional MRI

Dissertação de mestrado integrado em Biomedical Engineering (specialization on Medical Informatics)The human urge and pursuit for information have led to the development of increasingly complex technologies, and new means to study and understand the most advanced and intricate biological system: the human brain. Large-scale neuronal communication within the brain, and how it relates to human behaviour can be inferred by delving into the brain network, and searching for patterns in connectivity. Functional connectivity is a steady characteristic of the brain, and it has been proved to be very useful for examining how mental disorders affect connections within the brain. The detection of abnormal behaviour in brain networks is performed by experts, such as physicians, who limit the process with human subjectivity, and unwittingly introduce errors in the interpretation. The continuous search for alternatives to obtain faster and robuster results have put Machine Learning and Deep Learning in the leading position of computer vision, as they enable the extraction of meaningful patterns, some beyond human perception. The aim of this dissertation is to design and develop an experiment setup to analyse functional connectivity at a voxel level, in order to find functional patterns. For the purpose, a pipeline was outlined to include steps from data download to data analysis, resulting in four methods: Data Download, Data Preprocessing, Dimensionality Reduction, and Analysis. The proposed experiment setup was modeled using as materials resting state fMRI data from two sources: Life and Health Sciences Research Institute (Portugal), and Human Connectome Project (USA). To evaluate its performance, a case study was performed using the In-House data for concerning a smaller number of subjects to study. The pipeline was successful at delivering results, although limitations concerning the memory of the machine used restricted some aspects of this experiment setup’s testing. With appropriate resources, this experiment setup may support the process of analysing and extracting patterns from any resting state functional connectivity data, and aid in the detection of mental disorders.O desejo e a busca intensos do ser humano por informação levaram ao desenvolvimento de tecnologias cada vez mais complexas e novos meios para estudar e entender o sistema biológico mais avançado e intrincado: o cérebro humano. A comunicação neuronal em larga escala no cérebro, e como ela se relaciona com o comportamento humano, pode ser inferida investigando a rede neuronal cerebral e procurando por padrões de conectividade. A conectividade funcional é uma característica constante do cérebro e provou ser muito útil para examinar como os distúrbios mentais afetam as conexões cerebrais. A deteção de anormalidades em imagens de ressonância magnética é realizada por especialistas, como médicos, que limitam o processo com a subjetividade humana e, inadvertidamente, introduzem erros na interpretação. A busca contínua de alternativas para obter resultados mais rápidos e robustos colocou as técnicas de machine learning e deep learning na posição de liderança de visão computacional, pois permitem a extração de padrões significativos e alguns deles para além da percepção humana. O objetivo desta dissertação é projetar e desenvolver uma configuração experimental para analisar a conectividade funcional ao nível do voxel, a fim de encontrar padrões funcionais. Nesse sentido, foi delineado um pipeline para incluir etapas a começar no download de dados até à análise desses mesmos dados, resultando assim em quatro métodos: Download de Dados, Pré-processamento de Dados, Redução de Dimensionalidade e Análise. A configuração experimental proposta foi modelada usando dados de ressonância magnética funcional de resting-state de duas fontes: Instituto de Ciências da Vida e Saúde (Portugal) e Human Connectome Project (EUA). Para avaliar o seu desempenho, foi realizado um estudo de caso usando os dados internos por considerar um número menor de participantes a serem estudados. O pipeline foi bem-sucedido em fornecer resultados, embora limitações relacionadas com a memória da máquina usada tenham restringido alguns aspetos do teste desta configuração experimental. Com recursos apropriados, esta configuração experimental poderá servir de suporte para o processo de análise e extração de padrões de qualquer conjunto de dados de conectividade funcional em resting-state e auxiliar na deteção de transtornos mentais

Visibility computation through image generalization

This dissertation introduces the image generalization paradigm for computing visibility. The paradigm is based on the observation that an image is a powerful tool for computing visibility. An image can be rendered efficiently with the support of graphics hardware and each of the millions of pixels in the image reports a visible geometric primitive. However, the visibility solution computed by a conventional image is far from complete. A conventional image has a uniform sampling rate which can miss visible geometric primitives with a small screen footprint. A conventional image can only find geometric primitives to which there is direct line of sight from the center of projection (i.e. the eye) of the image; therefore, a conventional image cannot compute the set of geometric primitives that become visible as the viewpoint translates, or as time changes in a dynamic dataset. Finally, like any sample-based representation, a conventional image can only confirm that a geometric primitive is visible, but it cannot confirm that a geometric primitive is hidden, as that would require an infinite number of samples to confirm that the primitive is hidden at all of its points. ^ The image generalization paradigm overcomes the visibility computation limitations of conventional images. The paradigm has three elements. (1) Sampling pattern generalization entails adding sampling locations to the image plane where needed to find visible geometric primitives with a small footprint. (2) Visibility sample generalization entails replacing the conventional scalar visibility sample with a higher dimensional sample that records all geometric primitives visible at a sampling location as the viewpoint translates or as time changes in a dynamic dataset; the higher-dimensional visibility sample is computed exactly, by solving visibility event equations, and not through sampling. Another form of visibility sample generalization is to enhance a sample with its trajectory as the geometric primitive it samples moves in a dynamic dataset. (3) Ray geometry generalization redefines a camera ray as the set of 3D points that project at a given image location; this generalization supports rays that are not straight lines, and enables designing cameras with non-linear rays that circumvent occluders to gather samples not visible from a reference viewpoint. ^ The image generalization paradigm has been used to develop visibility algorithms for a variety of datasets, of visibility parameter domains, and of performance-accuracy tradeoff requirements. These include an aggressive from-point visibility algorithm that guarantees finding all geometric primitives with a visible fragment, no matter how small primitive\u27s image footprint, an efficient and robust exact from-point visibility algorithm that iterates between a sample-based and a continuous visibility analysis of the image plane to quickly converge to the exact solution, a from-rectangle visibility algorithm that uses 2D visibility samples to compute a visible set that is exact under viewpoint translation, a flexible pinhole camera that enables local modulations of the sampling rate over the image plane according to an input importance map, an animated depth image that not only stores color and depth per pixel but also a compact representation of pixel sample trajectories, and a curved ray camera that integrates seamlessly multiple viewpoints into a multiperspective image without the viewpoint transition distortion artifacts of prior art methods

Contributions in computational intelligence with results in functional neuroimaging

This thesis applies computational intelligence methodologies to study functional brain images. It is a state-of-the-art application relative to unsupervised learning domain to functional neuroimaging. There are also contributions related to computational intelligence on topics relative to clustering validation and spatio-temporal clustering analysis. Speci_cally, there are the presentation of a new separation measure based on fuzzy sets theory to establish the validity of the fuzzy clustering outcomes and the presentation of a framework to approach the parcellation of functional neuroimages taking in account both spatial and temporal patterns. These contributions have been applied to neuroimages obtained with functional Magnetic Resonance Imaging, using both active and passive paradigm and using both in-house data and fMRI repository. The results obtained shown, globally, an improvement on the quality of the neuroimaging analysis using the methodological contributions proposed

Automated morphometric analysis and phenotyping of mouse brains from structural µMR images

In light of the utility and increasing ubiquity of mouse models of genetic and neurological disease, I describefully automated pipelines for the investigation of structural microscopic magnetic resonance images of mouse brains – for both high-throughput phenotyping, and monitoring disease. Mouse models offer unparalleled insight into genetic function and brain plasticity, in phenotyping studies; and neurodegenerative disease onset and progression, in therapeutic trials. I developed two cohesive, automatic software tools, for Voxel- and Tensor-Based Morphometry (V/TBM) and the Boundary Shift Integral (BSI), in the mouse brain. V/TBM are advantageous for their ability to highlight morphological differences between groups, without laboriously delineating regions of interest. The BSI is a powerful and sensitive imaging biomarker for the detection of atrophy. The resulting pipelines are described in detail. I show the translation and application of open-source software developed for clinical MRI analysis to mouse brain data: for tissue segmentation into high-quality, subject-specific maps, using contemporary multi-atlas techniques; and for symmetric, inverse-consistent registration. I describe atlases and parameters suitable for the preclinical paradigm, and illustrate and discuss image processing challenges encountered and overcome during development. As proof of principle and to illustrate robustness, I used both pipelines with in and ex vivo mouse brain datasets to identify differences between groups, representing the morphological influence of genes, and subtle, longitudinal changes over time, in particular relation to Down syndrome and Alzheimer’s disease. I also discuss the merits of transitioning preclinical analysis from predominately ex vivo MRI to in vivo, where morphometry is still viable and fewer mice are necessary. This thesis conveys the cross-disciplinary translation of up-to-date image analysis techniques to the preclinical paradigm; the development of novel methods and adaptations to robustly process large cohorts of data; and the sensitive detection of phenotypic differences and neurodegenerative changes in the mouse brai

The anthropometric, environmental and genetic determinants of right ventricular structure and function

BACKGROUND Measures of right ventricular (RV) structure and function have significant prognostic value. The right ventricle is currently assessed by global measures, or point surrogates, which are insensitive to regional and directional changes. We aim to create a high-resolution three-dimensional RV model to improve understanding of its structural and functional determinants. These may be particularly of interest in pulmonary hypertension (PH), a condition in which RV function and outcome are strongly linked. PURPOSE To investigate the feasibility and additional benefit of applying three-dimensional phenotyping and contemporary statistical and genetic approaches to large patient populations. METHODS Healthy subjects and incident PH patients were prospectively recruited. Using a semi-automated atlas-based segmentation algorithm, 3D models characterising RV wall position and displacement were developed, validated and compared with anthropometric, physiological and genetic influences. Statistical techniques were adapted from other high-dimensional approaches to deal with the problems of multiple testing, contiguity, sparsity and computational burden. RESULTS 1527 healthy subjects successfully completed high-resolution 3D CMR and automated segmentation. Of these, 927 subjects underwent next-generation sequencing of the sarcomeric gene titin and 947 subjects completed genotyping of common variants for genome-wide association study. 405 incident PH patients were recruited, of whom 256 completed phenotyping. 3D modelling demonstrated significant reductions in sample size compared to two-dimensional approaches. 3D analysis demonstrated that RV basal-freewall function reflects global functional changes most accurately and that a similar region in PH patients provides stronger survival prediction than all anthropometric, haemodynamic and functional markers. Vascular stiffness, titin truncating variants and common variants may also contribute to changes in RV structure and function. CONCLUSIONS High-resolution phenotyping coupled with computational analysis methods can improve insights into the determinants of RV structure and function in both healthy subjects and PH patients. Large, population-based approaches offer physiological insights relevant to clinical care in selected patient groups.Open Acces

Ray Tracing Gems

This book is a must-have for anyone serious about rendering in real time. With the announcement of new ray tracing APIs and hardware to support them, developers can easily create real-time applications with ray tracing as a core component. As ray tracing on the GPU becomes faster, it will play a more central role in real-time rendering. Ray Tracing Gems provides key building blocks for developers of games, architectural applications, visualizations, and more. Experts in rendering share their knowledge by explaining everything from nitty-gritty techniques that will improve any ray tracer to mastery of the new capabilities of current and future hardware. What you'll learn: The latest ray tracing techniques for developing real-time applications in multiple domains Guidance, advice, and best practices for rendering applications with Microsoft DirectX Raytracing (DXR) How to implement high-performance graphics for interactive visualizations, games, simulations, and more Who this book is for: Developers who are looking to leverage the latest APIs and GPU technology for real-time rendering and ray tracing Students looking to learn about best practices in these areas Enthusiasts who want to understand and experiment with their new GPU

Pacific Symposium on Biocomputing 2023

The Pacific Symposium on Biocomputing (PSB) 2023 is an international, multidisciplinary conference for the presentation and discussion of current research in the theory and application of computational methods in problems of biological significance. Presentations are rigorously peer reviewed and are published in an archival proceedings volume. PSB 2023 will be held on January 3-7, 2023 in Kohala Coast, Hawaii. Tutorials and workshops will be offered prior to the start of the conference.PSB 2023 will bring together top researchers from the US, the Asian Pacific nations, and around the world to exchange research results and address open issues in all aspects of computational biology. It is a forum for the presentation of work in databases, algorithms, interfaces, visualization, modeling, and other computational methods, as applied to biological problems, with emphasis on applications in data-rich areas of molecular biology.The PSB has been designed to be responsive to the need for critical mass in sub-disciplines within biocomputing. For that reason, it is the only meeting whose sessions are defined dynamically each year in response to specific proposals. PSB sessions are organized by leaders of research in biocomputing's 'hot topics.' In this way, the meeting provides an early forum for serious examination of emerging methods and approaches in this rapidly changing field