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

Políticas de Copyright de Publicações Científicas em Repositórios Institucionais: O Caso do INESC TEC

A progressiva transformação das práticas científicas, impulsionada pelo desenvolvimento das novas Tecnologias de Informação e Comunicação (TIC), têm possibilitado aumentar o acesso à informação, caminhando gradualmente para uma abertura do ciclo de pesquisa. Isto permitirá resolver a longo prazo uma adversidade que se tem colocado aos investigadores, que passa pela existência de barreiras que limitam as condições de acesso, sejam estas geográficas ou financeiras. Apesar da produção científica ser dominada, maioritariamente, por grandes editoras comerciais, estando sujeita às regras por estas impostas, o Movimento do Acesso Aberto cuja primeira declaração pública, a Declaração de Budapeste (BOAI), é de 2002, vem propor alterações significativas que beneficiam os autores e os leitores. Este Movimento vem a ganhar importância em Portugal desde 2003, com a constituição do primeiro repositório institucional a nível nacional. Os repositórios institucionais surgiram como uma ferramenta de divulgação da produção científica de uma instituição, com o intuito de permitir abrir aos resultados da investigação, quer antes da publicação e do próprio processo de arbitragem (preprint), quer depois (postprint), e, consequentemente, aumentar a visibilidade do trabalho desenvolvido por um investigador e a respetiva instituição. O estudo apresentado, que passou por uma análise das políticas de copyright das publicações científicas mais relevantes do INESC TEC, permitiu não só perceber que as editoras adotam cada vez mais políticas que possibilitam o auto-arquivo das publicações em repositórios institucionais, como também que existe todo um trabalho de sensibilização a percorrer, não só para os investigadores, como para a instituição e toda a sociedade. A produção de um conjunto de recomendações, que passam pela implementação de uma política institucional que incentive o auto-arquivo das publicações desenvolvidas no âmbito institucional no repositório, serve como mote para uma maior valorização da produção científica do INESC TEC.The progressive transformation of scientific practices, driven by the development of new Information and Communication Technologies (ICT), which made it possible to increase access to information, gradually moving towards an opening of the research cycle. This opening makes it possible to resolve, in the long term, the adversity that has been placed on researchers, which involves the existence of barriers that limit access conditions, whether geographical or financial. Although large commercial publishers predominantly dominate scientific production and subject it to the rules imposed by them, the Open Access movement whose first public declaration, the Budapest Declaration (BOAI), was in 2002, proposes significant changes that benefit the authors and the readers. This Movement has gained importance in Portugal since 2003, with the constitution of the first institutional repository at the national level. Institutional repositories have emerged as a tool for disseminating the scientific production of an institution to open the results of the research, both before publication and the preprint process and postprint, increase the visibility of work done by an investigator and his or her institution. The present study, which underwent an analysis of the copyright policies of INESC TEC most relevant scientific publications, allowed not only to realize that publishers are increasingly adopting policies that make it possible to self-archive publications in institutional repositories, all the work of raising awareness, not only for researchers but also for the institution and the whole society. The production of a set of recommendations, which go through the implementation of an institutional policy that encourages the self-archiving of the publications developed in the institutional scope in the repository, serves as a motto for a greater appreciation of the scientific production of INESC TEC

Digital Forensics AI: on Practicality, Optimality, and Interpretability of Digital Evidence Mining Techniques

Digital forensics as a field has progressed alongside technological advancements over the years, just as digital devices have gotten more robust and sophisticated. However, criminals and attackers have devised means for exploiting the vulnerabilities or sophistication of these devices to carry out malicious activities in unprecedented ways. Their belief is that electronic crimes can be committed without identities being revealed or trails being established. Several applications of artificial intelligence (AI) have demonstrated interesting and promising solutions to seemingly intractable societal challenges. This thesis aims to advance the concept of applying AI techniques in digital forensic investigation. Our approach involves experimenting with a complex case scenario in which suspects corresponded by e-mail and deleted, suspiciously, certain communications, presumably to conceal evidence. The purpose is to demonstrate the efficacy of Artificial Neural Networks (ANN) in learning and detecting communication patterns over time, and then predicting the possibility of missing communication(s) along with potential topics of discussion. To do this, we developed a novel approach and included other existing models. The accuracy of our results is evaluated, and their performance on previously unseen data is measured. Second, we proposed conceptualizing the term “Digital Forensics AI” (DFAI) to formalize the application of AI in digital forensics. The objective is to highlight the instruments that facilitate the best evidential outcomes and presentation mechanisms that are adaptable to the probabilistic output of AI models. Finally, we enhanced our notion in support of the application of AI in digital forensics by recommending methodologies and approaches for bridging trust gaps through the development of interpretable models that facilitate the admissibility of digital evidence in legal proceedings

Digital Forensics AI: on Practicality, Optimality, and Interpretability of Digital Evidence Mining Techniques

Digital forensics as a field has progressed alongside technological advancements over the years, just as digital devices have gotten more robust and sophisticated. However, criminals and attackers have devised means for exploiting the vulnerabilities or sophistication of these devices to carry out malicious activities in unprecedented ways. Their belief is that electronic crimes can be committed without identities being revealed or trails being established. Several applications of artificial intelligence (AI) have demonstrated interesting and promising solutions to seemingly intractable societal challenges. This thesis aims to advance the concept of applying AI techniques in digital forensic investigation. Our approach involves experimenting with a complex case scenario in which suspects corresponded by e-mail and deleted, suspiciously, certain communications, presumably to conceal evidence. The purpose is to demonstrate the efficacy of Artificial Neural Networks (ANN) in learning and detecting communication patterns over time, and then predicting the possibility of missing communication(s) along with potential topics of discussion. To do this, we developed a novel approach and included other existing models. The accuracy of our results is evaluated, and their performance on previously unseen data is measured. Second, we proposed conceptualizing the term “Digital Forensics AI” (DFAI) to formalize the application of AI in digital forensics. The objective is to highlight the instruments that facilitate the best evidential outcomes and presentation mechanisms that are adaptable to the probabilistic output of AI models. Finally, we enhanced our notion in support of the application of AI in digital forensics by recommending methodologies and approaches for bridging trust gaps through the development of interpretable models that facilitate the admissibility of digital evidence in legal proceedings

Tracing retinal vessel trees by transductive inference

Background Structural study of retinal blood vessels provides an early indication of diseases such as diabetic retinopathy, glaucoma, and hypertensive retinopathy. These studies require accurate tracing of retinal vessel tree structure from fundus images in an automated manner. However, the existing work encounters great difficulties when dealing with the crossover issue commonly-seen in vessel networks. Results In this paper, we consider a novel graph-based approach to address this tracing with crossover problem: After initial steps of segmentation and skeleton extraction, its graph representation can be established, where each segment in the skeleton map becomes a node, and a direct contact between two adjacent segments is translated to an undirected edge of the two corresponding nodes. The segments in the skeleton map touching the optical disk area are considered as root nodes. This determines the number of trees to-be-found in the vessel network, which is always equal to the number of root nodes. Based on this undirected graph representation, the tracing problem is further connected to the well-studied transductive inference in machine learning, where the goal becomes that of properly propagating the tree labels from those known root nodes to the rest of the graph, such that the graph is partitioned into disjoint sub-graphs, or equivalently, each of the trees is traced and separated from the rest of the vessel network. This connection enables us to address the tracing problem by exploiting established development in transductive inference. Empirical experiments on public available fundus image datasets demonstrate the applicability of our approach. Conclusions We provide a novel and systematic approach to trace retinal vessel trees with the present of crossovers by solving a transductive learning problem on induced undirected graphs.Published versio