Aneurysm Identification in Cerebral Models with Multiview Convolutional Neural Network

Stroke is the third most common cause of death and a major contributor to long-term disability worldwide. Severe stroke is most often caused by the rupture of a cerebral aneurysm, a weakened area in a blood vessel. The detection and quantification of cerebral aneurysms are essential for the prevention and treatment of aneurysmal rupture and cerebral infarction. Here, we propose a novel aneurysm detection method in a three-dimensional (3D) cerebrovascular model based on convolutional neural networks (CNNs). The multiview method is used to obtain a sequence of 2D images on the cerebral vessel branch model. The pretrained CNN is used with transfer learning to overcome the small training sample problem. The data augmentation strategy with rotation, mirroring and flipping helps improve the performance dramatically, particularly on our small datasets. The hyperparameter of the view number is determined in the task. We have applied the labeling task on 56 3D mesh models with aneurysms (positive) and 65 models without aneurysms (negative). The average accuracy of individual projected images is 87.86%, while that of the model is 93.4% with the best view number. The framework is highly effective with quick training efficiency that can be widely extended to detect other organ anomalies

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

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

Systems Radiology and Personalized Medicine

Medicine has evolved into a high level of specialization using the very detailed imaging of organs. This has impressively solved a multitude of acute health-related problems linked to single-organ diseases. Many diseases and pathophysiological processes, however, involve more than one organ. An organ-based approach is challenging when considering disease prevention and caring for elderly patients, or those with systemic chronic diseases or multiple co-morbidities. In addition, medical imaging provides more than a pretty picture. Much of the data are now revealed by quantitating algorithms with or without artificial intelligence. This Special Issue on “Systems Radiology and Personalized Medicine” includes reviews and original studies that show the strengths and weaknesses of structural and functional whole-body imaging for personalized medicine

Digital Twin of Cardiovascular Systems

Patient specific modelling using numerical methods is widely used in understanding diseases and disorders. It produces medical analysis based on the current state of patient’s health. Concurrently, as a parallel development, emerging data driven Artificial Intelligence (AI) has accelerated patient care. It provides medical analysis using algorithms that rely upon knowledge from larger human population data. AI systems are also known to have the capacity to provide a prognosis with overallaccuracy levels that are better than those provided by trained professionals. When these two independent and robust methods are combined, the concept of human digital twins arise. A Digital Twin is a digital replica of any given system or process. They combine knowledge from general data with subject oriented knowledge for past, current and future analyses and predictions. Assumptions made during numerical modelling are compensated using knowledge from general data. For humans, they can provide an accurate current diagnosis as well as possible future outcomes. This allows forprecautions to be taken so as to avoid further degradation of patient’s health.In this thesis, we explore primary forms of human digital twins for the cardiovascular system, that are capable of replicating various aspects of the cardiovascular system using different types of data. Since different types of medical data are available, such as images, videos and waveforms, and the kinds of analysis required may be offline or online in nature, digital twin systems should be uniquely designed to capture each type of data for different kinds of analysis. Therefore, passive, active and semi-active digital twins, as the three primary forms of digital twins, for different kinds of applications are proposed in this thesis. By the virtue of applications and the kind of data involved ineach of these applications, the performance and importance of human digital twins for the cardiovascular system are demonstrated. The idea behind these twins is to allow for the application of the digital twin concept for online analysis, offline analysis or a combination of the two in healthcare. In active digital twins active data, such as signals, is analysed online in real-time; in semi-active digital twin some of the components being analysed are active but the analysis itself is carried out offline; and finally, passive digital twins perform offline analysis of data that involves no active component.For passive digital twin, an automatic workflow to calculate Fractional Flow Reserve (FFR) is proposed and tested on a cohort of 25 patients with acceptable results. For semi-active digital twin, detection of carotid stenosis and its severity using face videos is proposed and tested with satisfactory results from one carotid stenosis patient and a small cohort of healthy adults. Finally, for the active digital twin, an enabling model is proposed using inverse analysis and its application in the detection of Abdominal Aortic Aneurysm (AAA) and its severity, with the help of a virtual patient database. This enabling model detected artificially generated AAA with an accuracy as high as 99.91% and classified its severity with acceptable accuracy of 97.79%. Further, for active digital twin, a truly active model is proposed for continuous cardiovascular state monitoring. It is tested on a small cohort of five patients from a publicly available database for three 10-minute periods, wherein this model satisfactorily replicated and forecasted patients’ cardiovascular state. In addition to the three forms of human digital twins for the cardiovascular system, an additional work on patient prioritisation in pneumonia patients for ITU care using data-driven digital twin is also proposed. The severity indices calculated by these models are assessed using the standard benchmark of Area Under Receiving Operating Characteristic Curve (AUROC). The results indicate that using these models, the ITU and mechanical ventilation can be prioritised correctly to an AUROC value as high as 0.89