3D COLORED MESH STRUCTURE-PRESERVING FILTERING WITH ADAPTIVE P-LAPLACIAN ON DIRECTED GRAPHS

International audienceEditing of 3D colored meshes represents a fundamental component of nowadays computer vision and computer graphics applications. In this paper, we propose a framework based on the p-laplacian on directed graphs for structure-preserving filtering. This relies on a novel objective function composed of a fitting term, a smoothness term with a spatially-variant pTV norm, and a structure-preserving term. The last two terms can be related to formulations of the p-Laplacian on directed graphs. This enables to impose different forms of processing onto different graph areas for better smoothing quality

Doctor of Philosophy

dissertationConfocal microscopy has become a popular imaging technique in biology research in recent years. It is often used to study three-dimensional (3D) structures of biological samples. Confocal data are commonly multichannel, with each channel resulting from a different fluorescent staining. This technique also results in finely detailed structures in 3D, such as neuron fibers. Despite the plethora of volume rendering techniques that have been available for many years, there is a demand from biologists for a flexible tool that allows interactive visualization and analysis of multichannel confocal data. Together with biologists, we have designed and developed FluoRender. It incorporates volume rendering techniques such as a two-dimensional (2D) transfer function and multichannel intermixing. Rendering results can be enhanced through tone-mappings and overlays. To facilitate analyses of confocal data, FluoRender provides interactive operations for extracting complex structures. Furthermore, we developed the Synthetic Brainbow technique, which takes advantage of the asynchronous behavior in Graphics Processing Unit (GPU) framebuffer loops and generates random colorizations for different structures in single-channel confocal data. The results from our Synthetic Brainbows, when applied to a sequence of developing cells, can then be used for tracking the movements of these cells. Finally, we present an application of FluoRender in the workflow of constructing anatomical atlases

Leveraging Microtechnology to Study Multicellular Microvascular Systems and Macromolecular Interaction

Biological systems are large-scale, complex systems comprised of many hierarchical subsystems interacting physico-chemically in a dynamic and coordinated fashion. The complex interactions of subsystems (in micro-scale) lead to the formation of emergent properties (in macro-scale); these are properties that are not visible if individual subsystems are studied. The inherent high-throughput characteristics of microfabrication technology (microtechnology) along with its ability to manipulate biological species at the micro-scale makes it an ideal tool to elucidate the mechanisms leading to the formation of emergent properties at the macro-scale. In this dissertation, by combining microtechnologies with advanced computational algorithms, we demonstrate system-level analysis of biological systems in development and disease. The abundance of high quality molecular and genetic data along with the drastic increase in computational power resulted in considerable progress in genomics, epigenomics and proteomics, but not for the so-called cellomics as we define it here: high-throughput study of single-cell phenotype and heterotypic cell-cell interaction via micromanipulation and bioinformatics analysis. Lack of high-throughput robust experimental tools is the major roadblock to cellomics. Using microtechnologies, in the context of developmental biology we studied vascular tissue morphogenesis (vasculogenesis). Formation of microvessels is of critical significance in development and for vascularizing newly engineered tissues in regenerative medicine. First, we sought to map the heterogeneous morphodynamic behavior of individual clonal cells in the process of capillary-like structure (CLS) formation (Chapter 2 and 3). Then we looked into deciphering the role of extracellular matrix (ECM) mediated mechanical signals in deriving the process of CLS formation (Chapter 4). In the second half of this thesis, we demonstrated the capabilities of microtechnologies and advanced computational algorithms in tackling the challenging problems in disease: global health diagnostics and cancer drug screening. First, we studied the performance of microfluidic-based diagnostic as a large-scale complex system under real-world constraints (Chapter 5). Then, we present the development of two microfluidic-based platforms to study the heterotypic interaction of cells in both a biomimetic in vitro and a realistic in vivo setting. We developed an implantable construct carrying a densely-packed heterogeneous panel of tumor cells. This platform could ultimately be used to test anti-cancer drug efficacy against a large number of genotypes in an in vivo setting (Appendices A and B). Together, these methods provide a powerful suite of tools for high-throughput analysis of biological species at the micro-scale and could potentially unlock the mysteries behind the emergent properties observed at the macro-scale

Fluorescence microscopy image analysis of retinal neurons using deep learning

An essential goal of neuroscience is to understand the brain by simultaneously identifying, measuring, and analyzing activity from individual cells within a neural population in live brain tissue. Analyzing fluorescence microscopy (FM) images in real-time with computational algorithms is essential for achieving this goal. Deep learning techniques have shown promise in this area, but face domain-specific challenges due to limited training data, significant amounts of voxel noise in FM images, and thin structures present in large 3D images. In this thesis, I address these issues by introducing a novel deep learning pipeline to analyze static FM images of neurons with minimal data requirements and demonstrate the pipeline’s ability to segment neurons from low signal-to-noise ratio FM images with few training samples. The first step of this pipeline employs a Generative Adversarial Network (GAN) equipped to learn imaging properties from a small set of static FM images acquired for a given neuroscientific experiment. Operating like an actual microscope, our fully-trained GAN can then generate realistic static FM images from volumetric reconstructions of neurons with added control over the intensity and noise of the generated images. For the second step in our pipeline, a novel segmentation network is trained on GAN-generated images with reconstructed neurons serving as “gold standard” ground truths. While training on a large dataset of FM images is optimal, a 15\% improvement in neuron segmentation accuracy from noisy FM images is shown when architectures are fine-tuned only on a small subsample of real image data. To evaluate the overall feasibility of our pipeline and the utility of generated images, 2 novel synthetic and 3 newly acquired FM image datasets are introduced along with a new evaluation protocol for FM image ”realness” that incorporates content, texture, and expert opinion metrics. While this pipeline's primary application is to segment neurons from highly noisy FM images, its utility can be extended to automate other FM tasks such as synapse identification, neuron classification, or super-resolution

3DTeethSeg'22: 3D Teeth Scan Segmentation and Labeling Challenge

Teeth localization, segmentation, and labeling from intra-oral 3D scans are essential tasks in modern dentistry to enhance dental diagnostics, treatment planning, and population-based studies on oral health. However, developing automated algorithms for teeth analysis presents significant challenges due to variations in dental anatomy, imaging protocols, and limited availability of publicly accessible data. To address these challenges, the 3DTeethSeg'22 challenge was organized in conjunction with the International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) in 2022, with a call for algorithms tackling teeth localization, segmentation, and labeling from intraoral 3D scans. A dataset comprising a total of 1800 scans from 900 patients was prepared, and each tooth was individually annotated by a human-machine hybrid algorithm. A total of 6 algorithms were evaluated on this dataset. In this study, we present the evaluation results of the 3DTeethSeg'22 challenge. The 3DTeethSeg'22 challenge code can be accessed at: https://github.com/abenhamadou/3DTeethSeg22_challengeComment: 29 pages, MICCAI 2022 Singapore, Satellite Event, Challeng

Statistical and Graph-Based Signal Processing: Fundamental Results and Application to Cardiac Electrophysiology

The goal of cardiac electrophysiology is to obtain information about the mechanism, function, and performance of the electrical activities of the heart, the identification of deviation from normal pattern and the design of treatments. Offering a better insight into cardiac arrhythmias comprehension and management, signal processing can help the physician to enhance the treatment strategies, in particular in case of atrial fibrillation (AF), a very common atrial arrhythmia which is associated to significant morbidities, such as increased risk of mortality, heart failure, and thromboembolic events. Catheter ablation of AF is a therapeutic technique which uses radiofrequency energy to destroy atrial tissue involved in the arrhythmia sustenance, typically aiming at the electrical disconnection of the of the pulmonary veins triggers. However, recurrence rate is still very high, showing that the very complex and heterogeneous nature of AF still represents a challenging problem. Leveraging the tools of non-stationary and statistical signal processing, the first part of our work has a twofold focus: firstly, we compare the performance of two different ablation technologies, based on contact force sensing or remote magnetic controlled, using signal-based criteria as surrogates for lesion assessment. Furthermore, we investigate the role of ablation parameters in lesion formation using the late-gadolinium enhanced magnetic resonance imaging. Secondly, we hypothesized that in human atria the frequency content of the bipolar signal is directly related to the local conduction velocity (CV), a key parameter characterizing the substrate abnormality and influencing atrial arrhythmias. Comparing the degree of spectral compression among signals recorded at different points of the endocardial surface in response to decreasing pacing rate, our experimental data demonstrate a significant correlation between CV and the corresponding spectral centroids. However, complex spatio-temporal propagation pattern characterizing AF spurred the need for new signals acquisition and processing methods. Multi-electrode catheters allow whole-chamber panoramic mapping of electrical activity but produce an amount of data which need to be preprocessed and analyzed to provide clinically relevant support to the physician. Graph signal processing has shown its potential on a variety of applications involving high-dimensional data on irregular domains and complex network. Nevertheless, though state-of-the-art graph-based methods have been successful for many tasks, so far they predominantly ignore the time-dimension of data. To address this shortcoming, in the second part of this dissertation, we put forth a Time-Vertex Signal Processing Framework, as a particular case of the multi-dimensional graph signal processing. Linking together the time-domain signal processing techniques with the tools of GSP, the Time-Vertex Signal Processing facilitates the analysis of graph structured data which also evolve in time. We motivate our framework leveraging the notion of partial differential equations on graphs. We introduce joint operators, such as time-vertex localization and we present a novel approach to significantly improve the accuracy of fast joint filtering. We also illustrate how to build time-vertex dictionaries, providing conditions for efficient invertibility and examples of constructions. The experimental results on a variety of datasets suggest that the proposed tools can bring significant benefits in various signal processing and learning tasks involving time-series on graphs. We close the gap between the two parts illustrating the application of graph and time-vertex signal processing to the challenging case of multi-channels intracardiac signals

Using positional information to provide context for biological image analysis with MorphoGraphX 2.0

Positional information is a central concept in developmental biology. In developing organs, positional information can be idealized as a local coordinate system that arises from morphogen gradients controlled by organizers at key locations. This offers a plausible mechanism for the integration of the molecular networks operating in individual cells into the spatially-coordinated multicellular responses necessary for the organization of emergent forms. Understanding how positional cues guide morphogenesis requires the quantification of gene expression and growth dynamics in the context of their underlying coordinate systems. Here we present recent advances in the MorphoGraphX software (Barbier de Reuille et al., 2015)⁠ that implement a generalized framework to annotate developing organs with local coordinate systems. These coordinate systems introduce an organ-centric spatial context to microscopy data, allowing gene expression and growth to be quantified and compared in the context of the positional information thought to control them

Anatomical Modeling of Cerebral Microvascular Structures: Application to Identify Biomarkers of Microstrokes

Les réseaux microvasculaires corticaux sont responsables du transport de l’oxygène et des substrats énergétiques vers les neurones. Ces réseaux réagissent dynamiquement aux demandes énergétiques lors d’une activation neuronale par le biais du couplage neurovasculaire. Afin d’élucider le rôle de la composante microvasculaire dans ce processus de couplage, l’utilisation de la modélisation in-formatique pourrait se révéler un élément clé. Cependant, la manque de méthodologies de calcul appropriées et entièrement automatisées pour modéliser et caractériser les réseaux microvasculaires reste l’un des principaux obstacles. Le développement d’une solution entièrement automatisée est donc important pour des explorations plus avancées, notamment pour quantifier l’impact des mal-formations vasculaires associées à de nombreuses maladies cérébrovasculaires. Une observation courante dans l’ensemble des troubles neurovasculaires est la formation de micro-blocages vascu-laires cérébraux (mAVC) dans les artérioles pénétrantes de la surface piale. De récents travaux ont démontré l’impact de ces événements microscopiques sur la fonction cérébrale. Par conséquent, il est d’une importance vitale de développer une approche non invasive et comparative pour identifier leur présence dans un cadre clinique. Dans cette thèse,un pipeline de traitement entièrement automatisé est proposé pour aborder le prob-lème de la modélisation anatomique microvasculaire. La méthode de modélisation consiste en un réseau de neurones entièrement convolutif pour segmenter les capillaires sanguins, un générateur de modèle de surface 3D et un algorithme de contraction de la géométrie pour produire des mod-èles graphiques vasculaires ne comportant pas de connections multiples. Une amélioration de ce pipeline est développée plus tard pour alléger l’exigence de maillage lors de la phase de représen-tation graphique. Un nouveau schéma permettant de générer un modèle de graphe est développé avec des exigences d’entrée assouplies et permettant de retenir les informations sur les rayons des vaisseaux. Il est inspiré de graphes géométriques déformants construits en respectant les morpholo-gies vasculaires au lieu de maillages de surface. Un mécanisme pour supprimer la structure initiale du graphe à chaque exécution est implémenté avec un critère de convergence pour arrêter le pro-cessus. Une phase de raffinement est introduite pour obtenir des modèles vasculaires finaux. La modélisation informatique développée est ensuite appliquée pour simuler les signatures IRM po-tentielles de mAVC, combinant le marquage de spin artériel (ASL) et l’imagerie multidirectionnelle pondérée en diffusion (DWI). L’hypothèse est basée sur des observations récentes démontrant une réorientation radiale de la microvascularisation dans la périphérie du mAVC lors de la récupéra-tion chez la souris. Des lits capillaires synthétiques, orientés aléatoirement et radialement, et des angiogrammes de tomographie par cohérence optique (OCT), acquis dans le cortex de souris (n = 5) avant et après l’induction d’une photothrombose ciblée, sont analysés. Les graphes vasculaires informatiques sont exploités dans un simulateur 3D Monte-Carlo pour caractériser la réponse par résonance magnétique (MR), tout en considérant les effets des perturbations du champ magnétique causées par la désoxyhémoglobine, et l’advection et la diffusion des spins nucléaires. Le pipeline graphique proposé est validé sur des angiographies synthétiques et réelles acquises avec différentes modalités d’imagerie. Comparé à d’autres méthodes effectuées dans le milieu de la recherche, les expériences indiquent que le schéma proposé produit des taux d’erreur géométriques et topologiques amoindris sur divers angiogrammes. L’évaluation confirme également l’efficacité de la méthode proposée en fournissant des modèles représentatifs qui capturent tous les aspects anatomiques des structures vasculaires. Ensuite, afin de trouver des signatures de mAVC basées sur le signal IRM, la modélisation vasculaire proposée est exploitée pour quantifier le rapport de perte de signal intravoxel minimal lors de l’application de plusieurs directions de gradient, à des paramètres de séquence variables avec et sans ASL. Avec l’ASL, les résultats démontrent une dif-férence significative (p <0,05) entre le signal calculé avant et 3 semaines après la photothrombose. La puissance statistique a encore augmenté (p <0,005) en utilisant des angiogrammes capturés à la semaine suivante. Sans ASL, aucun changement de signal significatif n’est trouvé. Des rapports plus élevés sont obtenus à des intensités de champ magnétique plus faibles (par exemple, B0 = 3) et une lecture TE plus courte (<16 ms). Cette étude suggère que les mAVC pourraient être carac-térisés par des séquences ASL-DWI, et fournirait les informations nécessaires pour les validations expérimentales postérieures et les futurs essais comparatifs.----------ABSTRACT Cortical microvascular networks are responsible for carrying the necessary oxygen and energy substrates to our neurons. These networks react to the dynamic energy demands during neuronal activation through the process of neurovascular coupling. A key element in elucidating the role of the microvascular component in the brain is through computational modeling. However, the lack of fully-automated computational frameworks to model and characterize these microvascular net-works remains one of the main obstacles. Developing a fully-automated solution is thus substantial for further explorations, especially to quantify the impact of cerebrovascular malformations associ-ated with many cerebrovascular diseases. A common pathogenic outcome in a set of neurovascular disorders is the formation of microstrokes, i.e., micro occlusions in penetrating arterioles descend-ing from the pial surface. Recent experiments have demonstrated the impact of these microscopic events on brain function. Hence, it is of vital importance to develop a non-invasive and translatable approach to identify their presence in a clinical setting. In this thesis, a fully automatic processing pipeline to address the problem of microvascular anatom-ical modeling is proposed. The modeling scheme consists of a fully-convolutional neural network to segment microvessels, a 3D surface model generator and a geometry contraction algorithm to produce vascular graphical models with a single connected component. An improvement on this pipeline is developed later to alleviate the requirement of water-tight surface meshes as inputs to the graphing phase. The novel graphing scheme works with relaxed input requirements and intrin-sically captures vessel radii information, based on deforming geometric graphs constructed within vascular boundaries instead of surface meshes. A mechanism to decimate the initial graph struc-ture at each run is formulated with a convergence criterion to stop the process. A refinement phase is introduced to obtain final vascular models. The developed computational modeling is then ap-plied to simulate potential MRI signatures of microstrokes, combining arterial spin labeling (ASL) and multi-directional diffusion-weighted imaging (DWI). The hypothesis is driven based on recent observations demonstrating a radial reorientation of microvasculature around the micro-infarction locus during recovery in mice. Synthetic capillary beds, randomly- and radially oriented, and op-tical coherence tomography (OCT) angiograms, acquired in the barrel cortex of mice (n=5) before and after inducing targeted photothrombosis, are analyzed. The computational vascular graphs are exploited within a 3D Monte-Carlo simulator to characterize the magnetic resonance (MR) re-sponse, encompassing the effects of magnetic field perturbations caused by deoxyhemoglobin, and the advection and diffusion of the nuclear spins. The proposed graphing pipeline is validated on both synthetic and real angiograms acquired with different imaging modalities. Compared to other efficient and state-of-the-art graphing schemes, the experiments indicate that the proposed scheme produces the lowest geometric and topological error rates on various angiograms. The evaluation also confirms the efficiency of the proposed scheme in providing representative models that capture all anatomical aspects of vascular struc-tures. Next, searching for MRI-based signatures of microstokes, the proposed vascular modeling is exploited to quantify the minimal intravoxel signal loss ratio when applying multiple gradient di-rections, at varying sequence parameters with and without ASL. With ASL, the results demonstrate a significant difference (p<0.05) between the signal-ratios computed at baseline and 3 weeks after photothrombosis. The statistical power further increased (p<0.005) using angiograms captured at week 4. Without ASL, no reliable signal change is found. Higher ratios with improved significance are achieved at low magnetic field strengths (e.g., at 3 Tesla) and shorter readout TE (<16 ms). This study suggests that microstrokes might be characterized through ASL-DWI sequences, and provides necessary insights for posterior experimental validations, and ultimately, future transla-tional trials