Unsupervised Fiber Bundles Registration using Weighted Measures Geometric Demons

International audienceBrain image registration aims at reducing anatomical variability across subjects to create a common space for group analysis. Multi-modal approaches intend to minimize cortex shape variations along with internal structures, such as fiber bundles. A di ficulty is that it requires a prior identi fication of these structures, which remains a challenging task in the absence of a complete reference atlas. We propose an extension of the log-Geometric Demons for jointly registering images and fi ber bundles without the need of point or ber correspondences. By representing fi ber bundles as Weighted Measures we can register subjects with di fferent numbers of fiber bundles. The ef ficacy of our algorithm is demonstrated by registering simultaneously T1 images and between 37 and 88 ber bundles depending on each of the ten subject used. We compare results with a multi-modal T1 + Fractional Anisotropy (FA) and a tensor-based registration algorithms and obtain superior performance with our approach

Development of High Angular Resolution Diffusion Imaging Analysis Paradigms for the Investigation of Neuropathology

Diffusion weighted magnetic resonance imaging (DW-MRI), provides unique insight into the microstructure of neural white matter tissue, allowing researchers to more fully investigate white matter disorders. The abundance of clinical research projects incorporating DW-MRI into their acquisition protocols speaks to the value this information lends to the study of neurological disease. However, the most widespread DW-MRI technique, diffusion tensor imaging (DTI), possesses serious limitations which restrict its utility in regions of complex white matter. Fueled by advances in DW-MRI acquisition protocols and technologies, a group of exciting new DW-MRI models, developed to address these concerns, are now becoming available to clinical researchers. The emergence of these new imaging techniques, categorized as high angular resolution diffusion imaging (HARDI), has generated the need for sophisticated computational neuroanatomic techniques able to account for the high dimensionality and structure of HARDI data. The goal of this thesis is the development of such techniques utilizing prominent HARDI data models. Specifically, methodologies for spatial normalization, population atlas building and structural connectivity have been developed and validated. These methods form the core of a comprehensive analysis paradigm allowing the investigation of local white matter microarcitecture, as well as, systemic properties of neuronal connectivity. The application of this framework to the study of schizophrenia and the autism spectrum disorders demonstrate its sensitivity sublte differences in white matter organization, as well as, its applicability to large population DW-MRI studies

Unsupervised Clustering of Neural Pathways

International audienceDiffusion-weighted Magnetic Resonance Imaging (dMRI) can unveil the microstructure of the brain white matter. The analysis of the anisotropy observed in the dMRI and highlighted by tractography methods can help to understand the pattern of connections between brain regions and characterize neurological diseases. Because of the amount of information produced by such analyses and the errors carried by the reconstruction step, it is necessary to simplify this output. Clustering algorithms can be used to group samples that are similar according to a given metric.In this work, we address important questions related to the use of clustering for brain fibers obtained by dMRI, namely: i) what is the most adequate metric to quantify the similarity between brain fiber tracts? ii) How to select the best clustering algorithm and parametrization among standard possibilities? While trying to solve these questions, we perform a new contribution: we show how to combine the well-known K-means clustering algorithm with various metrics while keeping an efficient procedure. We analyze the performance and usability of the ensuing algorithms on a dataset of ten subjects. We show that the association of K-means with Point Density Model, a recently proposed metric to analyze geometric structures, outperforms other state-of-the-art solutions

Atlas Construction for Measuring the Variability of Complex Anatomical Structures

RÉSUMÉ La recherche sur l'anatomie humaine, en particulier sur le cœur et le cerveau, est d'un intérêt particulier car leurs anomalies entraînent des pathologies qui sont parmi les principales causes de décès dans le monde et engendrent des coûts substantiels. Heureusement, les progrès en imagerie médicale permettent des diagnostics et des traitements autrefois impossibles. En contrepartie, la quantité phénoménale de données produites par ces technologies nécessite le développement d'outils efficaces pour leur traitement. L'objectif de cette thèse est de proposer un ensemble d'outils permettant de normaliser des mesures prélevées sur différents individus, essentiels à l'étude des caractéristiques de structures anatomiques complexes. La normalisation de mesures consiste à rassembler une collection d'images dans une référence commune, aussi appelée construction d'atlas numériques, afin de combiner des mesures provenant de différents patients. Le processus de construction inclut deux étapes principales; la segmentation d'images pour trouver des régions d'intérêts et le recalage d'images afin de déterminer les correspondances entres régions d'intérêts. Les méthodes actuelles de constructions d'atlas peuvent nécessiter des interventions manuelles, souvent fastidieuses, variables, et sont en outre limitées par leurs mécanismes internes. Principalement, le recalage d'images dépend d'une déformation incrémentales d'images sujettes a des minimums locaux. Le recalage n'est ainsi pas optimal lors de grandes déformations et ces limitations requièrent la nécessite de proposer de nouvelles approches pour la construction d'atlas. Les questions de recherche de cette thèse se concentrent donc sur l'automatisation des méthodes actuelles ainsi que sur la capture de déformations complexes de structures anatomiques, en particulier sur le cœur et le cerveau. La méthodologie adoptée a conduit à trois objectifs de recherche spécifiques. Le premier prévoit un nouveau cadre de construction automatise d'atlas afin de créer le premier atlas humain de l'architecture de fibres cardiaques. Le deuxième vise à explorer une nouvelle approche basée sur la correspondance spectrale, nommée FOCUSR, afin de capturer une grande variabilité de formes sur des maillages. Le troisième aboutit finalement à développer une approche fondamentalement différente pour le recalage d'images à fortes déformations, nommée les démons spectraux. Le premier objectif vise plus particulièrement à construire un atlas statistique de l'architecture des fibres cardiaques a partir de 10 cœurs ex vivo humains. Le système développé a mené à deux contributions techniques et une médicale, soit l'amélioration de la segmentation de structures cardiaques et l'automatisation du calcul de forme moyenne, ainsi que notamment la première étude chez l'homme de la variabilité de l'architecture des fibres cardiaques. Pour résumer les principales conclusions, les fibres du cœur humain moyen varient de +- 12 degrés, l'angle d'helix s'étend entre -41 degrés (+- 26 degrés) sur l'épicarde à +66 degrés (+- 15 degrés) sur l'endocarde, tandis que l'angle transverse varie entre +9 degrés (+- 12 degrés) et +34 degrés (+- 29 degrés) à travers le myocarde. Ces résultats sont importants car ces fibres jouent un rôle clef dans diverses fonctions mécaniques et électrophysiologiques du cœur. Le deuxième objectif cherche à capturer une grande variabilité de formes entre structures anatomiques complexes, plus particulièrement entre cortex cérébraux à cause de l'extrême variabilité de ces surfaces et de leur intérêt pour l'étude de fonctions cognitives. La nouvelle méthode de correspondance surfacique, nommée FOCUSR, exploite des représentations spectrales car l'appariement devient plus facile et rapide dans le domaine spectral plutôt que dans l'espace Euclidien classique. Dans sa forme la plus simple, FOCUSR améliore les méthodes spectrales actuelles par un recalage non rigide des représentations spectrales, toutefois, son plein potentiel est atteint en exploitant des données supplémentaires lors de la mise en correspondance. Par exemple, les résultats ont montré que la profondeur des sillons et de la courbure du cortex cérébral améliore significativement la correspondance de surfaces de cerveaux. Enfin, le troisième objectif vise à améliorer le recalage d'images d'organes ayant des fortes variabilités entre individus ou subis de fortes déformations, telles que celles créées par le mouvement cardiaque. La méthodologie amenée par la correspondance spectrale permet d'améliorer les approches conventionnelles de recalage d'images. En effet, les représentations spectrales, capturant des similitudes géométriques globales entre différentes formes, permettent de surmonter les limitations actuelles des méthodes de recalage qui restent guidées par des forces locales. Le nouvel algorithme, nommé démons spectraux, peut ainsi supporter de très grandes déformations locales et complexes entre images, et peut être tout autant adapté a d'autres approches, telle que dans un cadre de recalage conjoint d'images. Il en résulte un cadre complet de construction d'atlas, nommé démons spectraux multijoints, où la forme moyenne est calculée directement lors du processus de recalage plutôt qu'avec une approche séquentielle de recalage et de moyennage. La réalisation de ces trois objectifs spécifiques a permis des avancées dans l'état de l'art au niveau des méthodes de correspondance spectrales et de construction d'atlas, en permettant l'utilisation d'organes présentant une forte variabilité de formes. Dans l'ensemble, les différentes stratégies fournissent de nouvelles contributions sur la façon de trouver et d'exploiter des descripteurs globaux d'images et de surfaces. D'un point de vue global, le développement des objectifs spécifiques établit un lien entre : a) la première série d'outils, mettant en évidence les défis à recaler des images à fortes déformations, b) la deuxième série d'outils, servant à capturer de fortes déformations entre surfaces mais qui ne reste pas directement applicable a des images, et c) la troisième série d'outils, faisant un retour sur le traitement d'images en permettant la construction d'atlas a partir d'images ayant subies de fortes déformations. Il y a cependant plusieurs limitations générales qui méritent d'être investiguées, par exemple, les données partielles (tronquées ou occluses) ne sont pas actuellement prises en charge les nouveaux outils, ou encore, les stratégies algorithmiques utilisées laissent toujours place à l'amélioration. Cette thèse donne de nouvelles perspectives dans les domaines de l'imagerie cardiaque et de la neuroimagerie, toutefois, les nouveaux outils développés sont assez génériques pour être appliqués a tout recalage d'images ou de surfaces. Les recommandations portent sur des recherches supplémentaires qui établissent des liens avec la segmentation à base de graphes, pouvant conduire à un cadre complet de construction d'atlas où la segmentation, le recalage, et le moyennage de formes seraient tous interdépendants. Il est également recommandé de poursuivre la recherche sur la construction de meilleurs modèles électromécaniques cardiaques à partir des résultats de cette thèse. En somme, les nouveaux outils offrent de nouvelles bases de recherche et développement pour la normalisation de formes, ce qui peut potentiellement avoir un impact sur le diagnostic, ainsi que la planification et la pratique d'interventions médicales.----------ABSTRACT Research on human anatomy, in particular on the heart and the brain, is a primary concern for society since their related diseases are among top killers across the globe and have exploding associated costs. Fortunately, recent advances in medical imaging offer new possibilities for diagnostics and treatments. On the other hand, the growth in data produced by these relatively new technologies necessitates the development of efficient tools for processing data. The focus of this thesis is to provide a set of tools for normalizing measurements across individuals in order to study complex anatomical characteristics. The normalization of measurements consists of bringing a collection of images into a common reference, also known as atlas construction, in order to combine measurements made on different individuals. The process of constructing an atlas involves the topics of segmentation, which finds regions of interest in the data (e.g., an organ, a structure), and registration, which finds correspondences between regions of interest. Current frameworks may require tedious and hardly reproducible user interactions, and are additionally limited by their computational schemes, which rely on slow iterative deformations of images, prone to local minima. Image registration is, therefore, not optimal with large deformations. Such limitations indicate the need to research new approaches for atlas construction. The research questions are consequently addressing the problems of automating current frameworks and capturing global and complex deformations between anatomical structures, in particular between human hearts and brains. More precisely, the methodology adopted in the thesis led to three specific research objectives. Briefly, the first step aims at developing a new automated framework for atlas construction in order to build the first human atlas of the cardiac fiber architecture. The second step intends to explore a new approach based on spectral correspondence, named FOCUSR, in order to precisely capture large shape variability. The third step leads, finally, to a fundamentally new approach for image registration with large deformations, named the Spectral Demons algorithm. The first objective aims more specifically at constructing a statistical atlas of the cardiac fiber architecture from a unique human dataset of 10 ex vivo hearts. The developed framework made two technical, and one medical, contributions, that are the improvement of the segmentation of cardiac structures, the automation of the shape averaging process, and more importantly, the first human study on the variability of the cardiac fiber architecture. To summarize the main finding, the fiber orientations in human hearts has been found to vary with about +- 12 degrees, the range of the helix angle spans from -41 degrees (+- 26 degrees) on the epicardium to +66 degrees (+- 15 degrees) on the endocardium, while, the range of the transverse angle spans from +9 degrees (+- 12 degrees) to +34 degrees (+- 29 degrees) across the myocardial wall. These findings are significant in cardiology since the fiber architecture plays a key role in cardiac mechanical functions and in electrophysiology. The second objective intends to capture large shape variability between complex anatomical structures, in particular between cerebral cortices due to their highly convoluted surfaces and their high anatomical and functional variability across individuals. The new method for surface correspondence, named FOCUSR, exploits spectral representations since matching is easier in the spectral domain rather than in the conventional Euclidean space. In its simplest form, FOCUSR improves current spectral approaches by refining spectral representations with a nonrigid alignment; however, its full power is demonstrated when using additional features during matching. For instance, the results showed that sulcal depth and cortical curvature improve significantly the accuracy of cortical surface matching. Finally, the third objective is to improve image registration for organs with a high inter-subject variability or undergoing very large deformations, such as the heart. The new approach brought by the spectral matching technique allows the improvement of conventional image registration methods. Indeed, spectral representations, which capture global geometric similarities and large deformations between different shapes, may be used to overcome a major limitation of current registration methods, which are in fact guided by local forces and restrained to small deformations. The new algorithm, named Spectral Demons, can capture very large and complex deformations between images, and can additionally be adapted to other approaches, such as in a groupwise configuration. This results in a complete framework for atlas construction, named Groupwise Spectral Demons, where the average shape is computed during the registration process rather than in sequential steps. The achievements of these three specific objectives permitted advances in the state-of-the-art of spectral matching methods and of atlas construction, enabling the registration of organs with significant shape variability. Overall, the investigation of these different strategies provides new contributions on how to find and exploit global descriptions of images and surfaces. From a global perspective, these objectives establish a link between: a) the first set of tools, that highlights the challenges in registering images with very large deformations, b) the second set of tools, that captures very large deformations between surfaces but are not applicable to images, and c) the third set of tools, that comes back on processing images and allows a natural construction of atlases from images with very large deformations. There are, however, several general remaining limitations, for instance, partial data (truncated or occluded) is currently not supported by the new tools, or also, the strategy for computing and using spectral representations still leaves room for improvement. This thesis gives new perspectives in cardiac and neuroimaging, yet at the same time, the new tools remain general enough for virtually any application that uses surface or image registration. It is recommended to research additional links with graph-based segmentation methods, which may lead to a complete framework for atlas construction where segmentation, registration and shape averaging are all interlinked. It is also recommended to pursue research on building better cardiac electromechanical models from the findings of this thesis. Nevertheless, the new tools provide new grounds for research and application of shape normalization, which may potentially impact diagnostic, as well as planning and performance of medical interventions

Spectral Log-Demons: Diffeomorphic Image Registration with Very Large Deformations

International audienceThis paper presents a new framework for capturing large and complex deformations in image registration and atlas construction. This challenging and recurrent problem in computer vision and medical imaging currently relies on iterative and local approaches, which are prone to local minima and, therefore, limit present methods to relatively small deformations. Our general framework introduces to this effect a new direct feature matching technique that finds global correspondences between images via simple nearest-neighbor searches. More specifically, very large image deformations are captured in Spectral Forces, which are derived from an improved graph spectral representation. We illustrate the benefits of our framework through a new enhanced version of the popular Log-Demons algorithm, named the Spectral Log-Demons, as well as through a groupwise extension, named the Groupwise Spectral Log-Demons, which is relevant for atlas construction. The evaluations of these extended versions demonstrate substantial improvements in accuracy and robustness to large deformations over the conventional Demons approaches

Connectomics across development:towards mapping brain structure from birth to childhood

The brain is probably the most complex system of the human body, composed of numerous neural units interconnected at dierent scales. This highly structured architecture provides the ability to communicate, synthesize information and perform the analytical tasks of human beings. Its development starts during the transition between the embryonic and fetal periods, from a simple tubular to a highly complex folded structure. It is globally organized as early as birth. This developing process is highly vulnerable to antenatal adverse conditions. Indeed, extreme prematurity and intra uterine growth restriction are major risk factors for long-term morbidities, including developmental ailments such as cerebral palsy, mental retardation and a wide spectrum of learning disabilities and behavior disorders. In this context, the characterization of the brainâs normative wiring pattern is crucial for our understanding of its architecture and workings, as the origin of many neurological and neurobehavioral disorders is found in early structural brain development. Diusion magnetic resonance imaging (dMRI) allows the in vivo assessment of biological tissues at the microstructural level. It has emerged as a powerful tool to study brain connectivity and analyse the underlying substrate of the human brain, comprising its structurally integrated and functionally specialized architecture. dMRI has been widely used in adult studies. Nevertheless, due to technical constraints, this mapping at earlier stages of development has not yet been accomplished. Yet, this time period is of extreme importance to comprehend the structural and functional integrity of the brain. This thesis is motivated by this shortfall, and intends to fill the gap between the clinical and neuroscience demands and the methodological developments needed to fulfill them. In our work, we comprehensibly study the brain structural connectivity of children born extremely prematurely and/or with additional prenatal restriction at school-age. We provide evidence that brain systems that mature early in development are the most vulnerable to antenatal insults. Interestingly, the alterations highlighted in these systems correlate with the neurobehavioral and cognitive impairments seen in these children at school-age. The overall brain organization appear also altered after preterm birth and prenatal restriction. Indeed, these children show dierent brain network modular topology, with a reduction in the overall network capacity. What remains unclear is whether the alterations seen at school age are already present at birth and, if yes, to what extent. In this thesis we set the technical basis to enable the connectome analysis as early as at birth. This task is challenging when dealing with neonatal data. Indeed, most of the assumptions used in adult data processing methods do not hold, due to the inverted image contrast and other MRI artefacts such as motion, partial volume and intensity inhomogeneities. Here, we propose a novel technique for surface reconstruction, and provide a fully-automatic procedure to delineate the newborn cortical surface, opening the way to establish the newborn connectome

Proceedings of the Second International Workshop on Mathematical Foundations of Computational Anatomy (MFCA'08) - Geometrical and Statistical Methods for Modelling Biological Shape Variability

International audienceThe goal of computational anatomy is to analyze and to statistically model the anatomy of organs in different subjects. Computational anatomic methods are generally based on the extraction of anatomical features or manifolds which are then statistically analyzed, often through a non-linear registration. There are nowadays a growing number of methods that can faithfully deal with the underlying biomechanical behavior of intra-subject deformations. However, it is more difficult to relate the anatomies of different subjects. In the absence of any justified physical model, diffeomorphisms provide a general mathematical framework that enforce topological consistency. Working with such infinite dimensional space raises some deep computational and mathematical problems, in particular for doing statistics. Likewise, modeling the variability of surfaces leads to rely on shape spaces that are much more complex than for curves. To cope with these, different methodological and computational frameworks have been proposed (e.g. smooth left-invariant metrics, focus on well-behaved subspaces of diffeomorphisms, modeling surfaces using courants, etc.) The goal of the Mathematical Foundations of Computational Anatomy (MFCA) workshop is to foster the interactions between the mathematical community around shapes and the MICCAI community around computational anatomy applications. It targets more particularly researchers investigating the combination of statistical and geometrical aspects in the modeling of the variability of biological shapes. The workshop aims at being a forum for the exchange of the theoretical ideas and a source of inspiration for new methodological developments in computational anatomy. A special emphasis is put on theoretical developments, applications and results being welcomed as illustrations. Following the very successful first edition of this workshop in 2006 (see http://www.inria.fr/sophia/asclepios/events/MFCA06/), the second edition was held in New-York on September 6, in conjunction with MICCAI 2008. Contributions were solicited in Riemannian and group theoretical methods, Geometric measurements of the anatomy, Advanced statistics on deformations and shapes, Metrics for computational anatomy, Statistics of surfaces. 34 submissions were received, among which 9 were accepted to MICCAI and had to be withdrawn from the workshop. Each of the remaining 25 paper was reviewed by three members of the program committee. To guaranty a high level program, 16 papers only were selected