Consistent sulcal parcellation of longitudinal cortical surfaces

Automated accurate and consistent sulcal parcellation of longitudinal cortical surfaces is of great importance in studying longitudinal morphological and functional changes of human brains, since longitudinal cortical changes are normally very subtle, especially in aging brains. However, applying the existing methods (which were typically developed for cortical sulcal parcellation of a single cortical surface) independently to longitudinal cortical surfaces might generate longitudinally-inconsistent results. To overcome this limitation, this paper presents a novel energy function based method for accurate and consistent sulcal parcellation of longitudinal cortical surfaces. Specifically, both spatial and temporal smoothness are imposed in the energy function to obtain consistent longitudinal sulcal parcellation results. The energy function is efficiently minimized by a graph cuts method. The proposed method has been successfully applied to sulcal parcellation of both real and simulated longitudinal inner cortical surfaces of human brain MR images. Both qualitative and quantitative evaluation results demonstrate the validity of the proposed method

Computational Methods on Study of Differentially Expressed Proteins in Maize Proteomes Associated with Resistance to Aflatoxin Accumulation

Plant breeders have focused on improving maize resistance to Aspergillus flavus infection and aflatoxin accumulation by breeding with genotypes having the desirable traits. Various maize inbred lines have been developed for the breeding of resistance. Identification of differentially expressed proteins among such maize inbred lines will facilitate the development of gene markers and expedite the breeding process. Computational biology and proteomics approaches on the investigation of differentially expressed proteins were explored in this research. The major research objectives included 1) application of computational methods in homology and comparative modeling to study 3D protein structures and identify single nucleotide polymorphisms (SNPs) involved in changes of protein structures and functions, which can in turn increase the efficiency of the development of DNA markers; 2) investigation of methods on total protein profiling including purification, separation, visualization, and computational analysis at the proteome level. Special research goals were set on the development of open source computational methods using Matlab image processing tools to quantify and compare protein expression levels visualized by 2D protein electrophoresis gel techniques

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

Global brain connectivity analysis by diffusion MR tractography:algorithms, validation and applications

The human cerebral cortex consists of approximately 1010 neurons that are organized into a complex network of local circuits and long-range connections. During the past years there has been an increasing interest from the neuro-scientific community towards the study of this network, referred to as the human connectome. Due to its ability to probe the tissue microstructure in vivo and non invasively, diffusion MRI has revealed to be a helpful tool for the analysis of brain axonal pathways at the millimeter scale. Whereas the neuronal level remains unreachable, diffusion MRI enables the mapping of a low-resolution estimate of the human connectome, which should give a new breath to the study of normal or pathologic neuroanatomy. After a short introduction on diffusion MRI and tractography, the process by which fiber tracts are reconstructed from the diffusion images, we present a methodology allowing the creation of normalized whole-brain structural connection matrices derived from tractography and representing the human connectome. Based on the developed framework we then investigate the potential of front propagation algorithms in tractography. We compare their performance with classical tractography approaches on several well-known associative fiber pathways, and we discuss their advantages and limitations. Several solutions are proposed in order to evaluate and validate the connectome-related methodology. We develop a method to estimate the respective contributions of diffusion contrast versus other effects to a tractography result. Using this methodology, we show that whereas we can have a strong confidence in mid- and long-range connections, short-range connectivity has to be interpreted with care. Next, we demonstrate the strong relationship between the structural connectivity obtained from diffusion MR tractography and the functional connectivity measured with functional MRI. Then, we compare the performance of several diffusion MRI techniques through connectome-based measurements. We find that diffusion spectrum imaging is more sensitive and therefore enhances the results of tractography. Finally, we present two network-oriented applications. We use the human connectome to reveal the small-world architecture of the brain, a very efficient network topology in terms of wiring and power supply. We identify the cortical areas that belong to the core of structural connectivity. We show that these regions also belong to the default mode network, a set of dynamically coupled brain regions that are found to be more highly activated at rest. As a conclusion, we emphasize the potential of human connectome mapping for clinical applications and pathological studies

Statistical analysis for longitudinal MR imaging of dementia

Serial Magnetic Resonance (MR) Imaging can reveal structural atrophy in the brains of subjects with neurodegenerative diseases such as Alzheimer’s Disease (AD). Methods of computational neuroanatomy allow the detection of statistically significant patterns of brain change over time and/or over multiple subjects. The focus of this thesis is the development and application of statistical and supporting methodology for the analysis of three-dimensional brain imaging data. There is a particular emphasis on longitudinal data, though much of the statistical methodology is more general. New methods of voxel-based morphometry (VBM) are developed for serial MR data, employing combinations of tissue segmentation and longitudinal non-rigid registration. The methods are evaluated using novel quantitative metrics based on simulated data. Contributions to general aspects of VBM are also made, and include a publication concerning guidelines for reporting VBM studies, and another examining an issue in the selection of which voxels to include in the statistical analysis mask for VBM of atrophic conditions. Research is carried out into the statistical theory of permutation testing for application to multivariate general linear models, and is then used to build software for the analysis of multivariate deformation- and tensor-based morphometry data, efficiently correcting for the multiple comparison problem inherent in voxel-wise analysis of images. Monte Carlo simulation studies extend results available in the literature regarding the different strategies available for permutation testing in the presence of confounds. Theoretical aspects of longitudinal deformation- and tensor-based morphometry are explored, such as the options for combining within- and between-subject deformation fields. Practical investigation of several different methods and variants is performed for a longitudinal AD study

Geodesic Active Fields:A Geometric Framework for Image Registration

Image registration is the concept of mapping homologous points in a pair of images. In other words, one is looking for an underlying deformation field that matches one image to a target image. The spectrum of applications of image registration is extremely large: It ranges from bio-medical imaging and computer vision, to remote sensing or geographic information systems, and even involves consumer electronics. Mathematically, image registration is an inverse problem that is ill-posed, which means that the exact solution might not exist or not be unique. In order to render the problem tractable, it is usual to write the problem as an energy minimization, and to introduce additional regularity constraints on the unknown data. In the case of image registration, one often minimizes an image mismatch energy, and adds an additive penalty on the deformation field regularity as smoothness prior. Here, we focus on the registration of the human cerebral cortex. Precise cortical registration is required, for example, in statistical group studies in functional MR imaging, or in the analysis of brain connectivity. In particular, we work with spherical inflations of the extracted hemispherical surface and associated features, such as cortical mean curvature. Spatial mapping between cortical surfaces can then be achieved by registering the respective spherical feature maps. Despite the simplified spherical geometry, inter-subject registration remains a challenging task, mainly due to the complexity and inter-subject variability of the involved brain structures. In this thesis, we therefore present a registration scheme, which takes the peculiarities of the spherical feature maps into particular consideration. First, we realize that we need an appropriate hierarchical representation, so as to coarsely align based on the important structures with greater inter-subject stability, before taking smaller and more variable details into account. Based on arguments from brain morphogenesis, we propose an anisotropic scale-space of mean-curvature maps, built around the Beltrami framework. Second, inspired by concepts from vision-related elements of psycho-physical Gestalt theory, we hypothesize that anisotropic Beltrami regularization better suits the requirements of image registration regularization, compared to traditional Gaussian filtering. Different objects in an image should be allowed to move separately, and regularization should be limited to within the individual Gestalts. We render the regularization feature-preserving by limiting diffusion across edges in the deformation field, which is in clear contrast to the indifferent linear smoothing. We do so by embedding the deformation field as a manifold in higher-dimensional space, and minimize the associated Beltrami energy which represents the hyperarea of this embedded manifold as measure of deformation field regularity. Further, instead of simply adding this regularity penalty to the image mismatch in lieu of the standard penalty, we propose to incorporate the local image mismatch as weighting function into the Beltrami energy. The image registration problem is thus reformulated as a weighted minimal surface problem. This approach has several appealing aspects, including (1) invariance to re-parametrization and ability to work with images defined on non-flat, Riemannian domains (e.g., curved surfaces, scalespaces), and (2) intrinsic modulation of the local regularization strength as a function of the local image mismatch and/or noise level. On a side note, we show that the proposed scheme can easily keep up with recent trends in image registration towards using diffeomorphic and inverse consistent deformation models. The proposed registration scheme, called Geodesic Active Fields (GAF), is non-linear and non-convex. Therefore we propose an efficient optimization scheme, based on splitting. Data-mismatch and deformation field regularity are optimized over two different deformation fields, which are constrained to be equal. The constraint is addressed using an augmented Lagrangian scheme, and the resulting optimization problem is solved efficiently using alternate minimization of simpler sub-problems. In particular, we show that the proposed method can easily compete with state-of-the-art registration methods, such as Demons. Finally, we provide an implementation of the fast GAF method on the sphere, so as to register the triangulated cortical feature maps. We build an automatic parcellation algorithm for the human cerebral cortex, which combines the delineations available on a set of atlas brains in a Bayesian approach, so as to automatically delineate the corresponding regions on a subject brain given its feature map. In a leave-one-out cross-validation study on 39 brain surfaces with 35 manually delineated gyral regions, we show that the pairwise subject-atlas registration with the proposed spherical registration scheme significantly improves the individual alignment of cortical labels between subject and atlas brains, and, consequently, that the estimated automatic parcellations after label fusion are of better quality

Dense deformation field estimation for atlas registration using the active contour framework

A key research area in computer vision is image segmentation. Image segmentation aims at extracting objects of interest in images or video sequences. These objects contain relevant information for a given application. For example, a video surveillance application generally requires to extract moving objects (vehicles, persons or animals) from a sequence of images in order to check that their path stays conformed to the regulation rules set for the observed scene. Image segmentation is not an easy task. In many applications, the contours of the objects of interest are difficult to delineate, even manually. The problems linked to segmentation are often due to low contrast, fuzzy contours or too similar intensities with adjacent objects. In some cases, the objects to be extracted have no real contours in the image. This kind of objects is called virtual objects. Virtual objects appear especially in medical applications. To draw them, medical experts usually estimate their position from surrounding objects. The problems related to image segmentation can be greatly simplified with information known in advance on the objects to be extracted (the prior knowledge). A widely used method consists to extract the needed prior knowledge from a reference image often called atlas. The goal of the atlas is to describe the image to be segmented like a map would describe the components of a geographical area. An atlas can contain three types of information on each object being part of the image: an estimation of its position in the image, a description of its shape and texture, and the features of its adjacent objects. The atlas-based segmentation method is rather used when the atlas can characterize a range of images. This method is thus especially adapted to medical images due to the existing consistency between anatomical structures of same type. There exist two types of atlas: the determinist atlas and the statistical atlas. The determinist atlas is an image which has been selected or computed, to be the most representative of an image category to be segmented. This image is called intensity atlas. The contours of the objects of interest (the objects to be extracted in images of the same type) have been traced manually on the intensity atlas, or by using a semi-automatic method. A label is often attributed to each one of these objects in order to differentiate them. In this way, we obtain a labeled version of the atlas called labeled atlas. The statistical atlas is an atlas created from a database of images in order to be the most representative of a certain type of images to be segmented. In this atlas, the position and the features of the objects of interest depend on statistical measures. In this thesis, we are focused on the use of determinist atlases for image segmentation. The segmentation process with a determinist atlas consists to deform the objects delineated in the atlas in order to better align them with their corresponding objects in the image to be segmented. To perform this task, we have distinguished two types of approaches in the literature. The first approach consists to reduce the segmentation problem in an image registration problem. First of all, a dense deformation field that registers (i.e. puts in point-to-point spatial correspondence) the atlas to the image to be segmented, is explicitly computed. Then, this transformation is used to project the assigned labels onto each atlas structure on the image to be segmented. The advantage of this approach is that the deformation field computed from the registration of visible contours allows to easily estimate the position of virtual objects or objects with fuzzy contours. However, the methods currently used for the atlas registration are often only based on the intensity atlas. That means that they do not exploit the object-based information that can be obtained by combining the intensity atlas with its labeled version. In the second approach, the atlas contours selected by the labeled atlas are directly deformed without using a geometrical deformation. For that, this approach is based on matching contour techniques, generally called deformable models. In this thesis, we are interested to a particular type of deformable models, which are the active contour segmentation models. The advantage of the active contour method is that this segmentation technique has been designed to exploit the image information directly linked to the object to be delineated. By using object-based information, active contour models are frequently able to extract regions where the atlas-based segmentation method by registration fails. On the other hand, the result of this local segmentation method is very sensitive to the initial atlas contour position regarding to the target contours. On the other hand, this local segmentation method is very sensitive to the initial position of the atlas contours: the closer they are to the contours to be detected, the more robust the active contour-based segmentation will be. Besides, this segmentation technique needs prior shape models to be able to estimate the position of virtual objects. The main objective of this thesis is to design an algorithm for atlas-based segmentation which combines the advantages of the dense deformation field computed by the registration algorithms, with local segmentation constraints coming from the active contour framework. This implies to design a model where the registration and segmentation by active contours are jointly performed. The atlas registration algorithm that we propose is based on a formulation allowing the integration of any segmentation or contour regularization forces derived from the theory of the active contours in a non parametric registration process. Our algorithm led us to introduce the concept of hierarchical atlas registration. Its principle is that the registration of the main image objects helps the registration of depending objects. This allows to bring progressively the atlas contours closer to their target and thus, to limit the risk to be stuck in a local minimum. Our model had been designed to be easily adaptable to various types of segmentation problems. At the end of the thesis, we present several examples of atlas registration applications in medical imaging. These applications highlight the integration of manual constraints in an atlas registration process, the modeling of a tumor growth in the atlas, the labelization of the thalamus for a statistical study on neuronal connections, the localization of the subthalamic nucleus (STN) for deep brain stimulation (DBS) and the compensation of intra-operative brain shift for neuronavigation systems

De la neurochirurgie guidée par l'image,<br />au processus neurochirurgical assisté par la connaissance et l'information

La totalité des services français de neurochirurgie est aujourd'hui équipée de systèmes de neuronavigation. Ces systèmes de chirurgie guidée par l'image permettent le lien direct entre le patient, en salle d'opération, et ses images pré opératoires ; c'est-à-dire que le neurochirurgien, en salle d'opération et à tout instant, connaît, à partir d'un point désigné sur le patient par un outil, le point correspondant dans ses images d'IRM ou de Scanner X. Ceci est possible grâce à des localisateurs tridimensionnels et des logiciels de recalage d'images. Les bénéfices de tels systèmes pour le patient ont déjà été montrés. Ils rendent notamment la chirurgie plus sûre et moins invasive.Il est important de considérer le concept de chirurgie guidée par l'image comme un processus qui ne se réduit pas à la seule étape de réalisation du geste chirurgical. Depuis près d'une dizaine d'années, il existe un consensus sur l'importance de l'étape de préparation pour anticiper la réalisation du geste. Ce processus peut aussi inclure des étapes de choix de la stratégie chirurgicale, de simulation ou de répétition du geste et de suivi post opératoire du patient. Chaque étape de ce processus se fonde sur des observations liées au patient, comme ses images pré opératoires, sur des connaissances génériques explicites, comme des livres ou des atlas numériques d'anatomie, et sur des connaissances implicites résultant de l'expérience du chirurgien. Malgré cela, dans les systèmes actuels de chirurgie guidée par l'image, la seule information explicite utilisée est, le plus souvent, réduite à une simple imagerie anatomique. Alors que si l'on introduisait dans ces systèmes les images multimodales du patient, on prendrait mieux en compte la complexité anatomique, physiologique et métabolique des structures cérébrales. Sans compter que dans ces systèmes, la préparation de la procédure chirurgicale se réduit principalement à la définition de la cible et d'une trajectoire d'accès rectiligne. Si l'on considérait la procédure comme une succession d'étapes et d'actions, on permettrait au neurochirurgien de mieux préparer et, donc, de mieux réaliser son geste. Son savoir-faire implicite pourrait être explicité. Enfin, ces systèmes ne tiennent pas compte des déformations anatomiques intra opératoires dues, notamment, au geste chirurgical. Ainsi, les images pré opératoires du patient deviennent rapidement obsolètes et ne correspondent plus à la réalité anatomique du patient.Il existe donc un fossé entre la chirurgie telle qu'elle est vue par ces systèmes et la réalité chirurgicale. C'est ce fossé que je cherche à combler.Mes travaux de recherche se situent dans le domaine du génie biologique et médical. Ils incluent des aspects liés au traitement d'images et à l'informatique médicale. Le domaine d'application est la neurochirurgie. Les méthodes mises en oeuvre dans les travaux que je présenterai s'appuient sur un concept de coopération entre observations et connaissances. Ainsi, sur l'aspect observations, je présenterai l'introduction d'images multimodales du patient, dans le processus chirurgical, qu'elles soient pré ou intra opératoires. Sur l'aspect connaissances, je présenterai une démarche qui permet de formaliser certaines connaissances relatives à la neurochirurgie.La méthodologie de recherche que j'ai utilisée suit une approche itérative, où l'application clinique est centrale. A partir des connaissances médicales, les spécifications d'un nouveau projet sont définies. Ces spécifications entraînent le développement de nouvelles méthodes et leur implémentation par le biais d'un prototype d'application. Ce prototype permet, grâce àune utilisation pré clinique, d'évaluer ces méthodes. Cette implémentation et cette phase d'utilisation autorisent aussi un retour vers la méthode, pour vérifier la pertinence des choix réalisés et pour contribuer à son amélioration. Enfin, cette boucle permet une validation des connaissances initiales et un possible enrichissement de celles-ci. Les objectifs de mes recherches sont donc, à la fois, l'élaboration de nouveaux systèmes d'intérêt thérapeutique et la génération de nouvelles connaissances chirurgicales.Ce document aborde trois domaines principaux : la neurochirurgie guidée par l'image, la neurochirurgie guidée par l'information et la validation des outils de traitement d'images médicales en chirurgie guidée par l'image. Pour chacun de ces domaines, je présenterai le contexte et l'état de l'art, les contributions personnelles apportées au domaine et ses perspectives d'évolution.Dans le premier chapitre, je présenterai comment l'imagerie médicale peut assister la chirurgie. Pour cela, j'introduirai les méthodes de traitement d'images, plus particulièrement le recalage et la fusion d'images médicales. Ces dernières sont incontournables en neurochirurgie guidée par l'image, le principe même de ce type de chirurgie étant cette mise en correspondance géométrique entre repère des images et repère du patient. Puis, je présenterai le principe du processus chirurgical assisté par l'image, en décrivant les différentes étapes mises en jeu dans un tel processus. Je présenterai mes contributions : 1) l'introduction du concept de neuronavigation multimodale et multi informationnelle, et 2) l'introduction du concept de virtualité augmentée, en complément aux approches de réalité augmentée.Dans le deuxième chapitre, je présenterai le concept récent de chirurgie guidée par l'information, qui s'appuie sur une formalisation du processus chirurgical et des connaissances associées. Nous verrons que ce processus peut être étudié selon différents angles, chaque angle d'étude correspondant à un objectif applicatif précis. Je présenterai une méthodologie complète permettant supervision et apprentissage par : 1) la prise en compte, dans le processus de chirurgie guidée par l'image multimodale, de certaines connaissances implicites du chirurgien, notamment liées à son expertise chirurgicale, en les rendant explicites, et 2) la génération de connaissances sur la chirurgie.Les deux premiers chapitres démontrent comment il peut être intéressant de faire coopérer images et connaissances. Dans le troisième chapitre, nous proposerons d'appliquer ce concept de coopération entre observations et connaissances au contexte des déformations anatomiques intra opératoires. Nous montrerons la complexité de ce phénomène, et de ses causes, et les limites des méthodes présentées dans la littérature. Nous décrirons succinctement comment ce concept pourra être appliqué dans le cadre d'un projet de recherche qui débute.Dans le quatrième chapitre, j'insisterai sur l'importance de la validation des outils de traitement d'images en chirurgie guidée par l'image. J'introduirai la terminologie et la méthodologie liées à la validation principalement technique des outils de traitement d'images, en soulignant le besoin de standardisation. Je présenterai mes contributions au domaine : la définition d'une méthodologie standardisée pour la validation des méthodes de recalage d'images médicales, basée sur la comparaison avec une référence.Je terminerai, dans le cinquième chapitre, par une ébauche de description des évolutions à court et à long terme de la chirurgie, s'inspirant des réflexions et résultats des chapitres précédents