430 research outputs found

    A Survey of Multimedia Technologies and Robust Algorithms

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    Multimedia technologies are now more practical and deployable in real life, and the algorithms are widely used in various researching areas such as deep learning, signal processing, haptics, computer vision, robotics, and medical multimedia processing. This survey provides an overview of multimedia technologies and robust algorithms in multimedia data processing, medical multimedia processing, human facial expression tracking and pose recognition, and multimedia in education and training. This survey will also analyze and propose a future research direction based on the overview of current robust algorithms and multimedia technologies. We want to thank the research and previous work done by the Multimedia Research Centre (MRC), the University of Alberta, which is the inspiration and starting point for future research.Comment: arXiv admin note: text overlap with arXiv:2010.1296

    Fast and Robust Automatic Segmentation Methods for MR Images of Injured and Cancerous Tissues

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    Magnetic Resonance Imaging: MRI) is a key medical imaging technology. Through in vivo soft tissue imaging, MRI allows clinicians and researchers to make diagnoses and evaluations that were previously possible only through biopsy or autopsy. However, analysis of MR images by domain experts can be time-consuming, complex, and subject to bias. The development of automatic segmentation techniques that make use of robust statistical methods allows for fast and unbiased analysis of MR images. In this dissertation, I propose segmentation methods that fall into two classes---(a) segmentation via optimization of a parametric boundary, and: b) segmentation via multistep, spatially constrained intensity classification. These two approaches are applicable in different segmentation scenarios. Parametric boundary segmentation is useful and necessary for segmentation of noisy images where the tissue of interest has predictable shape but poor boundary delineation, as in the case of lung with heavy or diffuse tumor. Spatially constrained intensity classification is appropriate for segmentation of noisy images with moderate contrast between tissue regions, where the areas of interest have unpredictable shapes, as is the case in spinal injury and brain tumor. The proposed automated segmentation techniques address the need for MR image analysis in three specific applications:: 1) preclinical rodent studies of primary and metastatic lung cancer: approach: a)),: 2) preclinical rodent studies of spinal cord lesion: approach: b)), and: 3) postclinical analysis of human brain cancer: approach: b)). In preclinical rodent studies of primary and metastatic lung cancer, respiratory-gated MRI is used to quantitatively measure lung-tumor burden and monitor the time-course progression of individual tumors. I validate a method for measuring tumor burden based upon average lung-image intensity. The method requires accurate lung segmentation; toward this end, I propose an automated lung segmentation method that works for varying tumor burden levels. The method includes development of a novel, two-dimensional parametric model of the mouse lungs and a multifaceted cost function to optimally fit the model parameters to each image. Results demonstrate a strong correlation: 0.93), comparable with that of fully manual expert segmentation, between the automated method\u27s tumor-burden metric and the tumor burden measured by lung weight. In preclinical rodent studies of spinal cord lesion, MRI is used to quantify tissues in control and injured mouse spinal cords. For this application, I propose a novel, multistep, multidimensional approach, utilizing the Classification Expectation Maximization: CEM) algorithm, for automatic segmentation of spinal cord tissues. In contrast to previous methods, my proposed method incorporates prior knowledge of cord geometry and the distinct information contained in the different MR images gathered. Unlike previous approaches, the algorithm is shown to remain accurate for whole spinal cord, white matter, and hemorrhage segmentation, even in the presence of significant injury. The results of the method are shown to be on par with expert manual segmentation. In postclinical analysis of human brain cancer, access to large collections of MRI data enables scientifically rigorous study of cancers like glioblastoma multiforme, the most common form of malignant primary brain tumor. For this application, I propose an efficient and effective automated segmentation method, the Enhanced Classification Expectation Maximization: ECEM) algorithm. The ECEM algorithm is novel in that it introduces spatial information directly into the classical CEM algorithm, which is otherwise spatially unaware, with low additional computational complexity. I compare the ECEM\u27s performance on simulated data to the standard finite Gaussian mixture EM algorithm, which is not spatially aware, and to the hidden-Markov random field EM algorithm, a commonly-used spatially aware automated segmentation method for MR brain images. I also show sample results demonstrating the ECEM algorithm\u27s ability to segment MR images of glioblastoma

    Spinal Cord Segmentation by One Dimensional Normalized Template Matching: A Novel, Quantitative Technique to Analyze Advanced Magnetic Resonance Imaging Data

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    Spinal cord segmentation is a developing area of research intended to aid the processing and interpretation of advanced magnetic resonance imaging (MRI). For example, high resolution three-dimensional volumes can be segmented to provide a measurement of spinal cord atrophy. Spinal cord segmentation is difficult due to the variety of MRI contrasts and the variation in human anatomy. In this study we propose a new method of spinal cord segmentation based on one-dimensional template matching and provide several metrics that can be used to compare with other segmentation methods. A set of ground-truth data from 10 subjects was manually-segmented by two different raters. These ground truth data formed the basis of the segmentation algorithm. A user was required to manually initialize the spinal cord center-line on new images, taking less than one minute. Template matching was used to segment the new cord and a refined center line was calculated based on multiple centroids within the segmentation. Arc distances down the spinal cord and cross-sectional areas were calculated. Inter-rater validation was performed by comparing two manual raters (n = 10). Semi-automatic validation was performed by comparing the two manual raters to the semi-automatic method (n = 10). Comparing the semi-automatic method to one of the raters yielded a Dice coefficient of 0.91 +/- 0.02 for ten subjects, a mean distance between spinal cord center lines of 0.32 +/- 0.08 mm, and a Hausdorff distance of 1.82 +/- 0.33 mm. The absolute variation in cross-sectional area was comparable for the semi-automatic method versus manual segmentation when compared to inter-rater manual segmentation. The results demonstrate that this novel segmentation method performs as well as a manual rater for most segmentation metrics. It offers a new approach to study spinal cord disease and to quantitatively track changes within the spinal cord in an individual case and across cohorts of subjects

    Quantification of spinal cord atrophy in magnetic resonance images

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    Quantifying the volume of the spinal cord is of vital interest for studying and understanding diseases of the central nervous system such as multiple sclerosis (MS). In this thesis, which is motivated by MS research, we propose methods for measuring the spinal cord cross-sectional area and volume in magnetic resonance (MR) images. These measurements are used for determining neural atrophy and for performing both longitudinal and cross-sectional comparisons in clinical trials. We present three evolutionary steps of our approach: In the first step, we use graph cut–based image segmentation on the intensities of T1-weighted MR images. In the second step, we combine a continuous max flow segmentation algorithm with a cross-sectional similarity prior and Hessian-based structural features, which we apply to T1- and T2-weighted images. The prior leverages the fact that the spinal cord is an elongated structure by constraining its cross-sectional shape to vary only slowly along one image axis. In conjunction with the additional features, the segmentation robustness is thus increased. In the third step, we combine continuous max flow with anisotropic total variation regularization, which enables us to direct the regularization of the cross-sectional shape of the spinal cord more flexibly. We implement the proposed approach as a semi-automatic software toolchain that automatically segments the spinal cord, reconstructs its surface, and acquires the desired measurements. The software employs a user-provided anatomical landmark as well as hints for the location of the spinal cord and its surroundings. It accounts for the bending of the spine, MR-induced image distortions, and noise. We evaluate the proposed methods in experiments on phantom, healthy subject, and patient data. Our measurement accuracy and precision are on par with the state of the art. At the same time, our measurements on MS patient data are in accordance with the medical literature

    Segmentation automatique de la moelle épinière sur des images de résonance magnétique par propagation de modèles déformables

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    RÉSUMÉ Les lésions de la moelle épinière, induites par des traumas (e.g. accident de la route) ou par des maladies neurodégénératives, touchent plus 85 000 personnes au Canada avec environ 4250 nouveaux cas chaque année1. Elles ont de plus un impact majeur sur la vie quotidienne des personnes atteintes, en provoquant des pertes de sensibilité et de contrôle moteur dont la gravité dépend de la taille et de l’emplacement des lésions. Bien qu’il existe des approches thérapeutiques permettant d’améliorer la réhabilitation fonctionnelle des patients, toutes ces approches se heurtent à une inconnue majeure : l’étendue des dégâts causés par les lésions. Un diagnostic précoce et précis des maladies neurodégénératives touchant la moelle épinière permettrait d’améliorer grandement l’efficacité de leurs traitements. Depuis de nombreuses années, l’IRM a prouvé son potentiel dans le diagnostic et le pronostic des lésions de la moelle épinière (Cadotte, 2011; Cohen-Adad et al., 2011). Ce domaine manque cependant encore d’outils complètement automatisés permettant l’extraction et la comparaison de métriques cliniques reliées à la structure de la moelle (aire de section transverse, volume, etc.). La segmentation de la moelle épinière sur des images IRM anatomiques peut fournir des mesures d’aires et de volumes de la moelle (Losseff et al., 1996) et peut quantifier son atrophie en cas de maladies neurodégénératives telles que la sclérose en plaques (Chen et al., 2013) et la sclérose latérale amyotrophique (Cohen-Adad et al., 2011). Ce projet de maîtrise vise à développer une méthode de segmentation complètement automatique de la moelle épinière, fonctionnant sur plusieurs types d’images IRM (pondérées en T1 et en T2) et sur n’importe quel champ de vue (cervical ou thoracique), et permettant d’extraire et de comparer des mesures précises de la moelle épinière. La revue de la littérature a permis de mettre en évidence le manque de méthode de segmentation automatique de la moelle épinière fonctionnant sur n’importe quel type de contraste et de champ de vue. Elle a toutefois fait ressortir une série de propriétés intéressantes, dans les méthodes semi-automatiques existantes, pouvant être combinées pour former une méthode complètement automatisée.----------ABSTRACT Spinal cord lesions affects more than 85,000 people in Canada with about 4,250 new cases every year. Lesions can be caused by traumatic injuries or by neurodegenerative diseases such as multiple sclerosis. They have an important impact on a patient’s daily life, inducing loss of sensibility or motor control in the human body. The extent of damages caused by a lesion varies with the number of damaged spinal cord tracks, and depends on the size and the position of the lesion within the spinal cord. Although therapeutic approaches for patient functional rehabilitation exist, they all face an unknown variable: the extent of spinal cord lesions. A precise and early diagnosis of neurodegenerative diseases would improve their treatment efficiency. For a number of years, MRI has demonstrated its potential in the diagnosis and prognosis of spinal cord lesions (Cadotte, 2011; Cohen-Adad et al., 2010). However, this research field still lacks of fully automatized tools for the extraction and comparison of clinical metrics related to the spinal cord structure (e.g. cross-sectional area, volumes). Spinal cord segmentation on anatomical MR images can provide accurate area and volume measurements (Losseff et al., 1996) and could quantify spinal cord atrophy caused by neurodegenerative diseases such as multiple sclerosis (Chen et al., 2013) or amyotrophic lateral sclerosis (Cohen-Adad et al., 2011). The objective of this Master’s project is to develop a fully automatic spinal cord segmentation method, working on multiple MR contrasts and any field of view, able to extract and compare accurate spinal cord measurements. The literature review pointed out the lack of such a method but highlighted several interesting features in existing methods, that can be combined to develop a new automatic segmentation algorithm. The method developed in this project is based on the multi-resolution propagation of a deformable model. First, the spinal cord position and orientation is detected in the image using an elliptical Hough transform on multiple adjacent axial slices. A low-resolution tubular mesh is then build around the detection point and direction and deformed on spinal cord edges by minimizing an energy equation. An iterative process, composed by the duplication, translation, orientation and deformation of the mesh, propagates the surface along the spinal cord. Finally, a refinement and a global deformation of the surface provide accurate segmentation of the spinal cord. Measurements can be directly extracted from the segmentation surface. The spinal canal can also be segmented with our method by simply inversing the gradient in the image an

    Deformable Image Registration in the Analysis of Multiple Sclerosis

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    In medical image analysis, image registration is the task of finding corresponding features in two or more images, and using them to solve for the transformation that best aligns the images. Knowing the alignment allows information, such as landmarks and functional metrics, to be easily transferred between images, and allows them to be analyzed together. This dissertation focuses on the development of deformable image registration techniques for the analysis of multiple sclerosis (MS), a neurodegenerative disease that damages the myelin sheath of nervous tissue. MS is known to affect the entire central nervous system (CNS), and can result in the loss of sensorimotor control, cognition, and vision. Hence, the four primary contributions of this dissertation are on the development and application of deformable image registration in the three areas of the CNS that are most currently studied for MS -- the spinal cord, the retina, and the brain. First, for spinal cord magnetic resonance imaging (MRI), an approach is presented that uses deformable registration to provide atlas priors for automatic topology-preserving segmentation of the spinal cord and cerebrospinal fluid. The method shows high accuracy and robustness when compared to manual raters, and allows spinal cord atrophy to be analyzed on large datasets without manual segmentations. Second, for spinal cord diffusion tensor imaging, a pipeline is presented that uses deformable registration to correct for susceptibility distortions in the images. The pipeline allows for accurate computation of spinal cord diffusion metrics, which are shown to be significantly correlated with clinical measures of sensorimotor function and disability levels. Third, for optical coherence tomography (OCT) of the retina, a deformable registration technique is presented that constrains the transformation to follow the OCT acquisition geometry. 3D voxel-based analysis using the algorithm found significant differences between healthy and MS cohorts in regions of the retina that is consistent with previous findings using 2D analysis. Lastly, for brain MRI, a multi-channel registration framework is presented that can use distance transforms and image synthesis to improve registration accuracy. Together, these techniques have enabled several types of analysis that were previously unavailable for the study of MS

    Spinal cord volume quantification and clinical application in multiple sclerosis

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    Magnetic resonance imaging of the spinal cord is a valuable part of the diagnostic work-up in patients with multiple sclerosis and other neurological disorders. Currently, mainly signal intensity changes within the cord in MR-images are considered in the clinical management of disorders of the central nervous system. However, cross-sectional or longitudinal measurements of spinal cord volume may deliver additional valuable information. Hence, the overall goal of this doctoral thesis was twofold: i) to clinically validate methods for quantification of spinal cord volume and spinal cord compartments, which are suitable for longitudinal assessment of large patient cohorts and clinical practice and ii) to evaluate spinal cord volume as a potential valuable biomarker and provide new insights into the role of spinal cord damage in multiple sclerosis. The first part focuses on the validation of quantification methods for spinal cord volume and includes two projects. While several MRI-based approaches of semi- and fully automatic techniques for volumetric spinal cord measurements have been proposed, up to now no gold standard exists and only a few methods have been validated and/or evaluated on patient follow-up scans to demonstrate their applicability in longitudinal settings. One of the latter segmentation methods was recently developed in-house and showed excellent reliability for cervical cord segmentation (Cordial, the cord image analyzer). In a first project, we extended its applicability to the lumbar cord, since no other software has been tested so far within this anatomical region of interest. On a well-selected dataset of 10 healthy controls (scanned in a scan-rescan fashion) we were able to show that - even within this technically challenging region - this segmentation algorithm provides excellent inter- and intra-session reproducibility showing high potential for application in longitudinal trials. In a second project, we aimed at obtaining volumetric information on particular compartments of the spinal cord such as the cord grey and white matter, since recent studies in multiple sclerosis provided evidence that measuring spinal cord grey matter volume changes may be a better biomarker for disease progression than quantifying cord white matter pathology or even volumetric brain measures. We therefore implemented a novel imaging approach, the averaged magnetization inversion recovery acquisitions sequence, for better grey and white matter visualization within the cord and scanned 24 healthy controls in a scan-rescan fashion. Further we applied an innovative fully automatic variational segmentation algorithm with a shape prior modified for 3D data with a slice similarity prior to segment the spinal cord grey and white matter. This pipeline allowed for highly accurate and reproducible grey and white matter segmentation within the cord. In view of its features, our automatic segmentation method seems promising for further application in both cross-sectional and longitudinal and in large multi-center studies. The second goal of this thesis was the clinical application of the above-mentioned methods for the evaluation of spinal cord volume changes as a potential biomarker in multiple sclerosis patients. For this purpose, we quantified spinal cord volume change in a large cohort of 243 multiple sclerosis patients, followed over a period of 6 years with annual clinical and MRI examinations. Spinal cord volume proved to be a strong predictor of physical disability and disease progression, indicating that it may be a suitable marker for monitoring disease activity and severity in all disease types but especially in progressive multiple sclerosis. Spinal cord volume also proved to be the only MRI metric to strongly explain the clinical progression over time as opposed to brain atrophy and lesion measures

    Multi-scale active shape description in medical imaging

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    Shape description in medical imaging has become an increasingly important research field in recent years. Fast and high-resolution image acquisition methods like Magnetic Resonance (MR) imaging produce very detailed cross-sectional images of the human body - shape description is then a post-processing operation which abstracts quantitative descriptions of anatomically relevant object shapes. This task is usually performed by clinicians and other experts by first segmenting the shapes of interest, and then making volumetric and other quantitative measurements. High demand on expert time and inter- and intra-observer variability impose a clinical need of automating this process. Furthermore, recent studies in clinical neurology on the correspondence between disease status and degree of shape deformations necessitate the use of more sophisticated, higher-level shape description techniques. In this work a new hierarchical tool for shape description has been developed, combining two recently developed and powerful techniques in image processing: differential invariants in scale-space, and active contour models. This tool enables quantitative and qualitative shape studies at multiple levels of image detail, exploring the extra image scale degree of freedom. Using scale-space continuity, the global object shape can be detected at a coarse level of image detail, and finer shape characteristics can be found at higher levels of detail or scales. New methods for active shape evolution and focusing have been developed for the extraction of shapes at a large set of scales using an active contour model whose energy function is regularized with respect to scale and geometric differential image invariants. The resulting set of shapes is formulated as a multiscale shape stack which is analysed and described for each scale level with a large set of shape descriptors to obtain and analyse shape changes across scales. This shape stack leads naturally to several questions in regard to variable sampling and appropriate levels of detail to investigate an image. The relationship between active contour sampling precision and scale-space is addressed. After a thorough review of modem shape description, multi-scale image processing and active contour model techniques, the novel framework for multi-scale active shape description is presented and tested on synthetic images and medical images. An interesting result is the recovery of the fractal dimension of a known fractal boundary using this framework. Medical applications addressed are grey-matter deformations occurring for patients with epilepsy, spinal cord atrophy for patients with Multiple Sclerosis, and cortical impairment for neonates. Extensions to non-linear scale-spaces, comparisons to binary curve and curvature evolution schemes as well as other hierarchical shape descriptors are discussed

    Development of an MRI Template and Analysis Pipeline for the Spinal Cord and Application in Patients with Spinal Cord Injury

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    La moelle épinière est un organe fondamental du corps humain. Étant le lien entre le cerveau et le système nerveux périphérique, endommager la moelle épinière, que ce soit suite à un trauma ou une maladie neurodégénérative, a des conséquences graves sur la qualité de vie des patients. En effet, les maladies et traumatismes touchant la moelle épinière peuvent affecter l’intégrité des neurones et provoquer des troubles neurologiques et/ou des handicaps fonctionnels. Bien que de nombreuses voies thérapeutiques pour traiter les lésions de la moelle épinière existent, la connaissance de l’étendue des dégâts causés par ces lésions est primordiale pour améliorer l’efficacité de leur traitement et les décisions cliniques associées. L’imagerie par résonance magnétique (IRM) a démontré un grand potentiel pour le diagnostic et pronostic des maladies neurodégénératives et traumas de la moelle épinière. Plus particulièrement, l’analyse par template de données IRM du cerveau, couplée à des outils de traitement d’images automatisés, a permis une meilleure compréhension des mécanismes sous-jacents de maladies comme l’Alzheimer et la Sclérose en Plaques. Extraire automatiquement des informations pertinentes d’images IRM au sein de régions spécifiques de la moelle épinière présente toutefois de plus grands défis que dans le cerveau. Il n’existe en effet qu’un nombre limité de template de la moelle épinière dans la littérature, et aucun ne couvre toute la moelle épinière ou n’est lié à un template existant du cerveau. Ce manque de template et d’outils automatisés rend difficile la tenue de larges études d’analyse de la moelle épinière sur des populations variées. L’objectif de ce projet est donc de proposer un nouveau template IRM couvrant toute la moelle épinière, recalé avec un template existant du cerveau, et intégrant des atlas de la structure interne de la moelle épinière (e.g., matière blanche et grise, tracts de la matière blanche). Ce template doit venir avec une série d’outils automatisés permettant l’extraction d’information IRM au sein de régions spécifiques de la moelle épinière. La question générale de recherche de ce projet est donc « Comment créer un template générique de la moelle épinière, qui permettrait l’analyse non biaisée et reproductible de données IRM de la moelle épinière ? ». Plusieurs contributions originales ont été proposées pour répondre à cette question et vont être décrites dans les prochains paragraphes. La première contribution de ce projet est le développement du logiciel Spinal Cord Toolbox (SCT). SCT est un logiciel open-source de traitement d’images IRM multi-parametrique de la moelle épinière (De Leener, Lévy, et al., 2016). Ce logiciel intègre notamment des outils pour la détection et la segmentation automatique de la moelle épinière et de sa structure interne (i.e., matière blanche et matière grise), l’identification et la labellisation des niveaux vertébraux, le recalage d’images IRM multimodales sur un template générique de la moelle épinière (précédemment le template MNI-Poly-AMU, maintenant le template PAM50, proposé içi). En se basant sur un atlas de la moelle, SCT intègre également des outils pour extraire des données IRM de régions spécifiques de la moelle épinière, comme la matière blanche et grise et les tracts de la matière blanche, ainsi que sur des niveaux vertébraux spécifiques. D’autres outils additionnels ont aussi été proposés, comme des outils de correction de mouvement et de traitement basiques d’images appliqués le long de la moelle épinière. Chaque outil intégré à SCT a été validé sur un jeu de données multimodales. La deuxième contribution de ce projet est le développement d’une nouvelle méthode de recalage d’images IRM de la moelle épinière (De Leener, Mangeat, et al., 2017). Cette méthode a été développée pour un usage particulier : le redressement d’images IRM de la moelle épinière, mais peut également être utilisé pour recaler plusieurs images de la moelle épinière entre elles, tout en tenant compte de la distribution vertébrale de chaque sujet. La méthode proposée se base sur une approximation globale de la courbure de la moelle épinière dans l’espace et sur la résolution analytique des champs de déformation entre les deux images. La validation de cette nouvelle méthode a été réalisée sur une population de sujets sains et de patients touchés par une compression de la moelle épinière. La contribution majeure de ce projet est le développement d’un système de création de template IRM de la moelle épinière et la proposition du template PAM50 comme template de référence pour les études d’analyse par template de données IRM de la moelle épinière. Le template PAM50 a été créé à partir d’images IRM tiré de 50 sujets sains, et a été généré en utilisant le redressement d’images présenté ci-dessus et une méthode de recalage d’images itératif non linéaire, après plusieurs étapes de prétraitement d’images. Ces étapes de prétraitement incluent la segmentation automatique de la moelle épinière, l’extraction manuelle du bord antérieur du tronc cérébral, la détection et l’identification des disques intervertébraux, et la normalisation d’intensité le long de la moelle. Suite au prétraitement, la ligne centrale moyenne de la moelle et la distribution vertébrale ont été calculées sur la population entière de sujets et une image initiale de template a été générée. Après avoir recalé toutes les images sur ce template initial, le template PAM50 a été créé en utilisant un processus itératif de recalage d’image, utilisé pour générer des templates de cerveau. Le PAM50 couvre le tronc cérébral et la moelle épinière en entier, est disponible pour les contrastes IRM pondérés en T1, T2 et T2*, et intègre des cartes probabilistes et atlas de la structure interne de la moelle épinière. De plus, le PAM50 a été recalé sur le template ICBM152 du cerveau, permettant ainsi la tenue d’analyse par template simultanément dans le cerveau et dans la moelle épinière. Finalement, plusieurs résultats complémentaires ont été présentés dans cette dissertation. Premièrement, une étude de validation de la répétabilité et reproductibilité de mesures de l’aire de section de la moelle épinière a été menée sur une population de patients touchés par la sclérose en plaques. Les résultats démontrent une haute fiabilité des mesures ainsi que la possibilité de détecter des changements très subtiles de l’aire de section transverse de la moelle, importants pour mesurer l’atrophie de la moelle épinière précoce due à des maladies neurodégénératives comme la sclérose en plaques. Deuxièmement, un nouveau biomarqueur IRM des lésions de la moelle épinière a été proposé, en collaboration avec Allan Martin, de l’Université de Toronto. Ce biomarqueur, calculé à partir du ratio d’intensité entre la matière blanche et grise sur des images IRM pondérées en T2*, utilise directement les développements proposés dans ce projet, notamment en utilisant le recalage du template de la moelle épinière et les méthodes de segmentation de la moelle. La faisabilité d’extraire des mesures de données IRM multiparamétrique dans des régions spécifiques de la moelle épinière a également été démontrée, permettant d’améliorer le diagnostic et pronostic de lésions et compression de la moelle épinière. Finalement, une nouvelle méthode d’extraction de la morphométrie de la moelle épinière a été proposée et utilisée sur une population de patients touchés par une compression asymptomatique de la moelle épinière, démontrant de grandes capacités de diagnostic (> 99%). Le développement du template PAM50 comble le manque de template de la moelle épinière dans la littérature mais présente cependant plusieurs limitations. En effet, le template proposé se base sur une population de 50 sujets sains et jeunes (âge moyen = 27 +- 6.5) et est donc biaisée vers cette population particulière. Adapter les analyses par template pour un autre type de population (âge, race ou maladie différente) peut être réalisé directement sur les méthodes d’analyse mais aussi sur le template en lui-même. Tous le code pour générer le template a en effet été mis en ligne (https://github.com/neuropoly/template) pour permettre à tout groupe de recherche de développer son propre template. Une autre limitation de ce projet est le choix d’un système de coordonnées basé sur la position des vertèbres. En effet, les vertèbres ne représentent pas complètement le caractère fonctionnel de la moelle épinière, à cause de la différence entre les niveaux vertébraux et spinaux. Le développement d’un système de coordonnées spinal, bien que difficile à caractériser dans des images IRM, serait plus approprié pour l’analyse fonctionnelle de la moelle épinière. Finalement, il existe encore de nombreux défis pour automatiser l’ensemble des outils développés dans ce projet et les rendre robuste pour la majorité des contrastes et champs de vue utilisés en IRM conventionnel et clinique. Ce projet a présenté plusieurs développements importants pour l’analyse de données IRM de la moelle épinière. De nombreuses améliorations du travail présenté sont cependant requises pour amener ces outils dans un contexte clinique et pour permettre d’améliorer notre compréhension des maladies affectant la moelle épinière. Les applications cliniques requièrent notamment l’amélioration de la robustesse et de l’automatisation des méthodes d’analyse d’images proposées. La caractérisation de la structure interne de la moelle épinière, incluant la matière blanche et la matière grise, présente en effet de grands défis, compte tenu de la qualité et la résolution des images IRM standard acquises en clinique. Les outils développés et validés au cours de ce projet ont un grand potentiel pour la compréhension et la caractérisation des maladies affectant la moelle épinière et aura un impact significatif sur la communauté de la neuroimagerie.----------ABSTRACT The spinal cord plays a fundamental role in the human body, as part of the central nervous system and being the vector between the brain and the peripheral nervous system. Damaging the spinal cord, through traumatic injuries or neurodegenerative diseases, can significantly affect the quality of life of patients. Indeed, spinal cord injuries and diseases can affect the integrity of neurons, and induce neurological impairments and/or functional disabilities. While various treatment procedures exist, assessing the extent of damages and understanding the underlying mechanisms of diseases would improve treatment efficiency and clinical decisions. Over the last decades, magnetic resonance imaging (MRI) has demonstrated a high potential for the diagnosis and prognosis of spinal cord injury and neurodegenerative diseases. Particularly, template-based analysis of brain MRI data has been very helpful for the understanding of neurological diseases, using automated analysis of large groups of patients. However, extracting MRI information within specific regions of the spinal cord with minimum bias and using automated tools is still a challenge. Indeed, only a limited number of MRI template of the spinal cord exists, and none covers the full spinal cord, thereby preventing large multi-centric template-based analysis of the spinal cord. Moreover, no template integrates both the spinal cord and the brain region, thereby preventing simultaneous cerebrospinal studies. The objective of this project was to propose a new MRI template of the full spinal cord, which allows simultaneous brain and spinal cord studies, that integrates atlases of the spinal cord internal structures (e.g., white and gray matter, white matter pathways) and that comes with tools for extracting information within these subregions. More particularly, the general research question of the project was “How to create generic MRI templates of the spinal cord that would enable unbiased and reproducible template-based analysis of spinal cord MRI data?”. Several original contributions have been made to answer this question and to enable template-based analysis of spinal cord MRI data. The first contribution was the development of the Spinal Cord Toolbox (SCT), a comprehensive and open-source software for processing multi-parametric MRI data of the spinal cord (De Leener, Lévy, et al., 2016). SCT includes tools for the automatic segmentation of the spinal cord and its internal structure (white and gray matter), vertebral labeling, registration of multimodal MRI data (structural and non-structural) on a spinal cord MRI template (initially the MNI-Poly-AMU template, later the PAM50 template), co-registration of spinal cord MRI images, as well as the robust extraction of MRI metric within specific regions of the spinal cord (i.e., white and gray matter, white matter tracts, gray matter subregions) and specific vertebral levels using a spinal cord atlas (Lévy et al., 2015). Additional tools include robust motion correction and image processing along the spinal cord. Each tool included in SCT has been validated on a multimodal dataset. The second contribution of this project was the development of a novel registration method dedicated to spinal cord images, with an interest in the straightening of the spinal cord, while preserving its topology (De Leener, Mangeat et al., 2017). This method is based on the global approximation of the spinal cord and the analytical computation of deformation fields perpendicular to the centerline. Validation included calculation of distance measurements after straightening on a population of healthy subjects and patients with spinal cord compression. The major contribution of this project was the development of a framework for generating MRI template of the spinal cord and the PAM50 template, an unbiased and symmetrical MRI template of the brainstem and full spinal cord. Based on 50 healthy subjects, the PAM50 template was generated using an iterative nonlinear registration process, after applying normalization and straightening of all images. Pre-processing included segmentation of the spinal cord, manual delineation of the brainstem anterior edge, detection and identification of intervertebral disks, and normalization of intensity along the spinal cord. Next, the average centerline and vertebral distribution was computed to create an initial straight template space. Then, all images were registered to the initial template space and an iterative nonlinear registration framework was applied to create the final symmetrical template. The PAM50 covers the brainstem and the full spinal cord, from C1 to L2, is available for T1-, T2- and T2*-weighted contrasts, and includes probabilistic maps of the white and the gray matter and atlases of the white matter pathways and gray matter subregions. Additionally, the PAM50 template has been merged with the ICBM152 brain template, thereby allowing for simultaneous cerebrospinal template-based analysis. Finally, several complementary results, focused on clinical validation and applications, are presented. First, a reproducibility and repeatability study of cross-sectional area measurements using SCT (De Leener, Granberg, Fink, Stikov, & Cohen-Adad, 2017) was performed on a Multiple Sclerosis population (n=9). The results demonstrated the high reproducibility and repeatability of SCT and its ability to detect very subtle atrophy of the spinal cord. Second, a novel biomarker of spinal cord injury has been proposed. Based on the T2*-weighted intensity ratio between the white and the gray matter, this new biomarker is computed by registering MRI images with the PAM50 template and extracting metrics using probabilistic atlases. Additionally, the feasibility of extracting multiparametric MRI metrics from subregions of the spinal cord has been demonstrated and the diagnostic potential of this approach has been assessed on a degenerative cervical myelopathy (DCM) population. Finally, a method for extracting shape morphometrics along the spinal cord has been proposed, including spinal cord flattening, indentation and torsion. These metrics demonstrated high capabilities for the diagnostic of asymptomatic spinal cord compression (AUC=99.8% for flattening, 99.3% for indentation, and 98.4% for torsion). The development of the PAM50 template enables unbiased template-based analysis of the spinal cord. However, the PAM50 template has several limitations. Indeed, the proposed template has been generated with multimodal MRI images from 50 healthy and young individuals (age = 27+/- 6.5 y.o.). Therefore, the template is specific to this particular population and could not be directly usable for age- or disease-specific populations. One solution is to open-source the templategeneration code so that research groups can generate and use their own spinal cord MRI template. The code is available on https://github.com/neuropoly/template. While this project introduced a generic referential coordinate system, based on vertebral levels and the pontomedullary junction as origin, one limitation is the choice of this coordinate system. Another coordinate system, based spinal segments would be more suitable for functional analysis. However, the acquisition of MRI images with high enough resolution to delineate the spinal roots is still challenging. Finally, several challenges in the automation of spinal cord MRI processing remains, including the robust detection and identification of vertebral levels, particularly in case of small fields-of-view. This project introduced key developments for the analysis of spinal cord MRI data. Many more developments are still required to bring them into clinics and to improve our understanding of diseases affecting the spinal cord. Indeed, clinical applications require the improvement of the robustness and the automation of the proposed processing and analysis tools. Particularly, the detection and segmentation of spinal cord structures, including vertebral labeling and white/gray matter segmentation, is still challenging, given the lowest quality and resolution of standard clinical MRI acquisition. The tools developed and validated here have the potential to improve our understanding and the characterization of diseases affecting the spinal cord and will have a significant impact on the neuroimaging community
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