Improving the Tractography Pipeline: on Evaluation, Segmentation, and Visualization

Recent advances in tractography allow for connectomes to be constructed in vivo. These have applications for example in brain tumor surgery and understanding of brain development and diseases. The large size of the data produced by these methods lead to a variety problems, including how to evaluate tractography outputs, development of faster processing algorithms for tractography and clustering, and the development of advanced visualization methods for verification and exploration. This thesis presents several advances in these fields. First, an evaluation is presented for the robustness to noise of multiple commonly used tractography algorithms. It employs a Monte–Carlo simulation of measurement noise on a constructed ground truth dataset. As a result of this evaluation, evidence for obustness of global tractography is found, and algorithmic sources of uncertainty are identified. The second contribution is a fast clustering algorithm for tractography data based on k–means and vector fields for representing the flow of each cluster. It is demonstrated that this algorithm can handle large tractography datasets due to its linear time and memory complexity, and that it can effectively integrate interrupted fibers that would be rejected as outliers by other algorithms. Furthermore, a visualization for the exploration of structural connectomes is presented. It uses illustrative rendering techniques for efficient presentation of connecting fiber bundles in context in anatomical space. Visual hints are employed to improve the perception of spatial relations. Finally, a visualization method with application to exploration and verification of probabilistic tractography is presented, which improves on the previously presented Fiber Stippling technique. It is demonstrated that the method is able to show multiple overlapping tracts in context, and correctly present crossing fiber configurations

Tractographie par apprentissage par renforcement

L'Imagerie par Résonance Magnétique de diffusion (IRMd) est présentement la seule technique non-invasive permettant d'étudier la structure de la matière blanche dans le cerveau humain. L'IRMd permet une reconstruction indirecte de la matière blanche grâce à la modélisation du mouvement de l'eau et la tractographie. La tractographie a été décrite comme un problème mal-posé; malgré les nombreux algorithmes développés, il demeure très difficile d'évaluer la connectivité globale du cerveau selon des actions basées sur des informations locales. Motivées par l'explosion des performances de l'apprentissage profond supervisé, des tentatives ont été faites afin d'utiliser cet outil pour concevoir des algorithmes de tractographie exempts des problèmes affligeant la tractographie classique. Cependant ces méthodes, apprenant de données provenant des algorithmes classiques, sont à ce jour vouées à reproduire les même erreurs. Parallèlement, l'apprentissage profond par renforcement a récemment connu des avancées extraordinaires menant à des percées telles que AlphaGo. L'apprentissage profond par renforcement, par opposition à l'apprentissage profond supervisé, permet à l'algorithme d'apprendre par exploration, ne requérant qu'un signal récompensant les actions adéquates de l'agent apprenant. Dans ce mémoire, nous aborderons la possibilité d'apprendre à un algorithme d'apprentissage profond par renforcement à reconstruire les chemins de la matière blanche sans avoir recourt à des données biaisées par les algorithmes classiques. Nous poserons le problème de la tractographie dans le contexte de l'apprentissage par renforcement, décrirons les pièges à éviter lors de la conception d'un tel algorithme, puis proposerons une méthode permettant d'obtenir des résultats compétitifs aux algorithmes de tractographie existants

An improvement to Global Tractography Using Anatomical Priors

Tractography is a visualization technique which reconstructs and models neural fibers in the white matter of the brain based on data from diffusion magnetic resonance imaging. It is already used locally to model parts of dominant fiber pathways but global methods are also emerging which aim to reconstruct all the brain fibers simultaneously. In this thesis we have attempted to improve the current state of the art of Global Tractography by introducing three principles: * Anatomical Priors * Introduction of fiber weights * Reduced complexity Our approach uses an optimization method based on Markov Chain Monte Carlo (MCMC) and Simulated annealing in order to fit a set of plausible initial fiber trajectories to a dataset acquired by diffusion MRI. Our method was compared to the state of the art global tractography method known as the Gibbs Tracker in a phantom study using conventional global tractography evaluation methods. In a second test, we also try the method on an in-vivo dataset of a human brain and derive the connectivity matrix with corresponding network parameters. Our approach showed considerable improvements in decreasing the amount of wrong fibers and reduced computational time. However the method still struggles to eliminate certain false but plausible connections. To remedy this, several improvements to the MCMC sampler are suggested for future work

Hitting the right target : noninvasive localization of the subthalamic nucleus motor part for specific deep brain stimulation

Deep brain stimulation of the subthalamic nucleus (STN) has gained momentum as a therapy for advanced Parkinson’s disease. The stimulation effectively alleviates the patients’ typical motor symptoms on a long term, but can give rise to cognitive and psychiatric adverse effects as well. Based on primate studies, the STN has been divided into three functionally different parts, which were distinguished by their afferent and efferent connections. The largest part is the motor area, followed by an associative and a limbic area. The serious adverse effects on cognition and behavior occurring after deep brain stimulation are assumed to be caused by electrical current spread to the associative and limbic areas of the STN. Therefore, selective stimulation of the motor part of the STN seems crucial, both to obtain the best possible therapeutic effect on the motor symptoms and to minimize the debilitating effects on cognition and behavior. However, current medical imaging techniques do not yet facilitate the required accurate identification of the STN itself, let alone its different functional areas. The final target for DBS is still often adjusted using intraoperative electrophysiology. Therefore, in this thesis we aimed to improve imaging for deep brain stimulation using noninvasive MRI protocols, in order to identify the STN and its motor part. We studied the advantages and drawbacks of already available noninvasive methods to target the STN. This review did not lead to a straightforward conclusion; identification of the STN motor part remained an open question. In follow-up on this question, we investigated the possibility to distinguish the different functional STN parts based on their connectivity information. Three types of information were carefully analyzed in this thesis. First, we looked into the clustering of local diffusion information within the STN region. We visually inspected the complex diffusion profiles, derived from postmortem rat brain data with high angular resolution, and augmented this manual segmentation method using k-means and graph cuts clustering. Because the weighing of different orders of diffusion information in the traditionally used L2 norm on the orientation distribution functions (ODFs) remained an open issue, we developed a specialized distance measure, the so-called Sobolev norm. This norm does not only take into account the amplitudes of the diffusion profiles, but also their extrema. We showed it to perform better than the L2 norm on synthetic phantom data and real brain (thalamus) data. The research done on this topic facilitates better classification by clustering of gray matter structures in the (deep) brain. Secondly, we were the first to analyze the STN’s full structural connectivity, based on probabilistic fiber tracking in diffusion MRI data of healthy volunteers. The results correspond well to topical literature on STN projections. Furthermore, we assessed the structural connectivity per voxel of the STN seed region and discovered a gradient in connectivity to the premotor cortex within the STN. While going from the medial to the lateral part of the STN, the connectivity increases, confirming the expected lateral location of the STN motor part. Finally, the connectivity analysis produced evidence for the existence of a "hyperdirect" pathway between the motor cortex and the STN in humans, which is very useful for future research into stimulation targets. The results of these experiments indicate that it is possible to find the motor part of the STN as specific target for deep brain stimulation using structural connectivity information acquired in a noninvasive way. Third and last, we studied functional connectivity using resting state functional MRI data of healthy volunteers. The resulting significant clusters provided us with the first complete description of the STN’s resting state functional connectivity, which corresponds with the expectations based on available literature. Moreover, we performed a reverse regression procedure with the average time series signals in motor and limbic areas as principal regressors. The results were analyzed for each STN voxel separately and also showed mediolateral gradients in functional connectivity within the STN. The lateral STN part exhibited more motor connectivity, while the medial part seemed to be more functionally connected to limbic brain areas, as described in neuronal tracer studies. These results show that functional connectivity analysis also is a viable noninvasive method to find the motor part of the STN. The work on noninvasive MRI methods for identification of the STN and its functional parts, as presented in this thesis, thus contributes to future specific stimulation of the motor part of the STN for deep brain stimulation in patients with Parkinson’s disease. This may help to maximize the motor effects and minimize severe cognitive and psychiatric side effects

Disconnected aging: cerebral white matter integrity and age-related differences in cognition.

Cognition arises as a result of coordinated processing among distributed brain regions and disruptions to communication within these neural networks can result in cognitive dysfunction. Cortical disconnection may thus contribute to the declines in some aspects of cognitive functioning observed in healthy aging. Diffusion tensor imaging (DTI) is ideally suited for the study of cortical disconnection as it provides indices of structural integrity within interconnected neural networks. The current review summarizes results of previous DTI aging research with the aim of identifying consistent patterns of age-related differences in white matter integrity, and of relationships between measures of white matter integrity and behavioral performance as a function of adult age. We outline a number of future directions that will broaden our current understanding of these brain-behavior relationships in aging. Specifically, future research should aim to (1) investigate multiple models of age-brain-behavior relationships; (2) determine the tract-specificity versus global effect of aging on white matter integrity; (3) assess the relative contribution of normal variation in white matter integrity versus white matter lesions to age-related differences in cognition; (4) improve the definition of specific aspects of cognitive functioning related to age-related differences in white matter integrity using information processing tasks; and (5) combine multiple imaging modalities (e.g., resting-state and task-related functional magnetic resonance imaging; fMRI) with DTI to clarify the role of cerebral white matter integrity in cognitive aging

Visualisation en imagerie par résonance magnétique de diffusion : tractographie en temps réel des fibres de la matière blanche du cerveau

L'imagerie par résonance magnétique de diffusion est une technique non-invasive permettant de mesurer la diffusion des molécules d'eau selon plusieurs directions. Le résultat d'une telle acquisition contient de l'information implicite sur les structures microbiologiques qui composent le cerveau humain. La tractographie consiste à déterminer et visualiser, en trois dimensions, l'ensemble des connections neuronales de la matière blanche du cerveau en suivant la diffusion préférentielle de l'eau présente en chaque voxel. Les fibres de la matière blanche sont responsables de connecter les différentes aires fonctionnelles du cerveau entre-elles. En présence d'une tumeur, elles peuvent se réorganiser de multiples façons et refaire des connections pour assurer le suivi des fonctions importantes. L'imagerie du câblage cérébral est utilisée lors d'interventions neurochirurgicales afin d'aider le neurochirurgien à planifier son angle d'attaque pour réséquer le maximum de la tumeur sans léser la fonction du patient. La tractographie prend donc tout son sens pour le neurochirurgien avant et pendant l'opération. Dans ce mémoire, il sera question de tractographie en temps réel. La plupart des algorithmes de tractographie utilisent des paramètres fixes et prédéfinis pour l'ensemble du cerveau. Nous croyons que ces paramètres devraient être accessibles et modifiables afin de voir l'impact que ceux-ci ont sur la reconstruction des connections cérébrales. Nous proposons une méthode de visualisation de fibres en temps réel, permettant de calculer et d'afficher instantanément le résultat d'un nouvel algorithme de tractographie qui sera confronté aux méthodes existantes. Le nouveau module permet d'effectuer la tractographie des fibres de la matière blanche de manière interactive en offrant la possibilité d'ajuster les paramètres impliqués dans le processus de tractographie. Il a notamment été introduit plus d'une vingtaine de fois lors d'interventions neurochirurgicales au Centre Hospitalier Universitaire de Sherbrooke, grâce à la supervision du Dr. David Fortin. La tractographie en temps réel a changé la manière dont les données sont préparées en vue d'une intervention en bloc opératoire. Dans un contexte où le temps entre le traitement des données et l'intervention chirurgicale est une contrainte majeure, l'élimination de l'étape de tractographie du processus de prétraitement est un avantage non-négligeable

Tractographie de la matière blanche par réseaux de neurones récurrents

La matière blanche du cerveau fait encore l'objet de nombreuses études. Grâce à l'IRM de diffusion, on peut étudier de façon non invasive la connectivité du cerveau avec une précision sans précédent. La reconstruction de la matière blanche --- la tractographie --- n'est pas parfaite cependant. En effet, la tractographie tend à reconstruire tous les chemins possibles au sein de la matière blanche; l'expertise des neuroanatomistes est donc requise pour distinguer les chemins qui sont possibles anatomiquement de ceux qui résultent d'une mauvaise reconstruction. Cette connaissance est difficile à exprimer et à codifier sous forme de règles logiques. L'intelligence artificielle a refait surface dans les années 1990 --- suite à une amélioration remarquable de la vitesse des processeurs --- en tant que solution viable à plusieurs problèmes qui étaient considérés comme fondamentalement > et quasi impossibles à résoudre pour une machine. Celle-ci représente un outil unique pour intégrer l'expertise des neuroanatomistes dans le processus de reconstruction de la matière blanche, sans avoir à fournir de règles explicitement. Un modèle peut ainsi apprendre la définition d'un chemin valide à partir d'exemples valides, pour ensuite reproduire ce qu'il a appris, sans répéter les erreurs classiques. Plus particulièrement, les réseaux de neurones récurrents sont une famille de modèles créés spécifiquement pour le traitement de séquences de données. Comme une fibre de matière blanche est représentée par une séquence de points, le lien se fait naturellement. Malgré leur potentiel énorme, l'application des réseaux récurrents à la tractographie fait face à plusieurs problèmes techniques. Cette thèse se veut très exploratoire, et détaille donc les débuts de l'utilisation des réseaux de neurones récurrents pour la tractographie par apprentissage, des problèmes qui sont apparus suite à la création d'une multitude d'algorithmes basés sur l'intelligence artificielle, ainsi que des solutions développées pour répondre à ces problèmes. Les résultats de cette thèse ont démontré le potentiel des réseaux de neurones récurrents pour la reconstruction de la matière blanche, en plus de contribuer à l’avancement du domaine grâce à la création d’une base de données publique pour la tractographie par apprentissage

Homogeneity based segmentation and enhancement of Diffusion Tensor Images : a white matter processing framework

In diffusion magnetic resonance imaging (DMRI) the Brownian motion of the water molecules, within biological tissue, is measured through a series of images. In diffusion tensor imaging (DTI) this diffusion is represented using tensors. DTI describes, in a non-invasive way, the local anisotropy pattern enabling the reconstruction of the nervous fibers - dubbed tractography. DMRI constitutes a powerful tool to analyse the structure of the white matter within a voxel, but also to investigate the anatomy of the brain and its connectivity. DMRI has been proved useful to characterize brain disorders, to analyse the differences on white matter and consequences in brain function. These procedures usually involve the virtual dissection of white matters tracts of interest. The manual isolation of these bundles requires a great deal of neuroanatomical knowledge and can take up to several hours of work. This thesis focuses on the development of techniques able to automatically perform the identification of white matter structures. To segment such structures in a tensor field, the similarity of diffusion tensors must be assessed for partitioning data into regions, which are homogeneous in terms of tensor characteristics. This concept of tensor homogeneity is explored in order to achieve new methods for segmenting, filtering and enhancing diffusion images. First, this thesis presents a novel approach to semi-automatically define the similarity measures that better suit the data. Following, a multi-resolution watershed framework is presented, where the tensor field’s homogeneity is used to automatically achieve a hierarchical representation of white matter structures in the brain, allowing the simultaneous segmentation of different structures with different sizes. The stochastic process of water diffusion within tissues can be modeled, inferring the homogeneity characteristics of the diffusion field. This thesis presents an accelerated convolution method of diffusion images, where these models enable the contextual processing of diffusion images for noise reduction, regularization and enhancement of structures. These new methods are analysed and compared on the basis of their accuracy, robustness, speed and usability - key points for their application in a clinical setting. The described methods enrich the visualization and exploration of white matter structures, fostering the understanding of the human brain

Anisotropy Across Fields and Scales

This open access book focuses on processing, modeling, and visualization of anisotropy information, which are often addressed by employing sophisticated mathematical constructs such as tensors and other higher-order descriptors. It also discusses adaptations of such constructs to problems encountered in seemingly dissimilar areas of medical imaging, physical sciences, and engineering. Featuring original research contributions as well as insightful reviews for scientists interested in handling anisotropy information, it covers topics such as pertinent geometric and algebraic properties of tensors and tensor fields, challenges faced in processing and visualizing different types of data, statistical techniques for data processing, and specific applications like mapping white-matter fiber tracts in the brain. The book helps readers grasp the current challenges in the field and provides information on the techniques devised to address them. Further, it facilitates the transfer of knowledge between different disciplines in order to advance the research frontiers in these areas. This multidisciplinary book presents, in part, the outcomes of the seventh in a series of Dagstuhl seminars devoted to visualization and processing of tensor fields and higher-order descriptors, which was held in Dagstuhl, Germany, on October 28–November 2, 2018