Evaluating the accuracy of diffusion MRI models in white matter

Models of diffusion MRI within a voxel are useful for making inferences about the properties of the tissue and inferring fiber orientation distribution used by tractography algorithms. A useful model must fit the data accurately. However, evaluations of model-accuracy of some of the models that are commonly used in analyzing human white matter have not been published before. Here, we evaluate model-accuracy of the two main classes of diffusion MRI models. The diffusion tensor model (DTM) summarizes diffusion as a 3-dimensional Gaussian distribution. Sparse fascicle models (SFM) summarize the signal as a linear sum of signals originating from a collection of fascicles oriented in different directions. We use cross-validation to assess model-accuracy at different gradient amplitudes (b-values) throughout the white matter. Specifically, we fit each model to all the white matter voxels in one data set and then use the model to predict a second, independent data set. This is the first evaluation of model-accuracy of these models. In most of the white matter the DTM predicts the data more accurately than test-retest reliability; SFM model-accuracy is higher than test-retest reliability and also higher than the DTM, particularly for measurements with (a) a b-value above 1000 in locations containing fiber crossings, and (b) in the regions of the brain surrounding the optic radiations. The SFM also has better parameter-validity: it more accurately estimates the fiber orientation distribution function (fODF) in each voxel, which is useful for fiber tracking

Diffusion directions imaging (high resolution reconstruction of white matter fascicles from low angular resolution diffusion MRI)

L'objectif de cette thèse est de fournir une chaine de traitement complète pour la reconstruction des faisceaux de la matière blanche à partir d'images pondérées en diffusion caractérisées par une faible résolution angulaire. Cela implique (i) d'inférer en chaque voxel un modèle de diffusion à partir des images de diffusion et (ii) d'accomplir une ''tractographie", i.e., la reconstruction des faisceaux à partir de ces modèles locaux. Notre contribution en modélisation de la diffusion est une nouvelle distribution statistique dont les propriétés sont étudiées en détail. Nous modélisons le phénomène de diffusion par un mélange de telles distributions incluant un outil de sélection de modèle destiné à estimer le nombre de composantes du mélange. Nous montrons que le modèle peut être correctement estimé à partir d'images de diffusion ''single-shell" à faible résolution angulaire et qu'il fournit des biomarqueurs spécifiques pour l'étude des tumeurs. Notre contribution en tractographie est un algorithme qui approxime la distribution des faisceaux émanant d'un voxel donné. Pour cela, nous élaborons un filtre particulaire mieux adapté aux distributions multi-modales que les filtres traditionnels. Pour démontrer l'applicabilité de nos outils en usage clinique, nous avons participé aux trois éditions du MICCAI DTI Tractography challenge visant à reconstruire le faisceau cortico-spinal à partir d'images de diffusion ''single-shell" à faibles résolutions angulaire et spatiale. Les résultats montrent que nos outils permettent de reconstruire toute l'étendue de ce faisceau.The objective of this thesis is to provide a complete pipeline that achieves an accurate reconstruction of the white matter fascicles using clinical diffusion images characterized by a low angular resolution. This involves (i) a diffusion model inferred in each voxel from the diffusion images and (ii) a tractography algorithm fed with these local models to perform the actual reconstruction of fascicles. Our contribution in diffusion modeling is a new statistical distribution, the properties of which are extensively studied. We model the diffusion as a mixture of such distributions, for which we design a model selection tool that estimates the number of mixture components. We show that the model can be accurately estimated from single shell low angular resolution diffusion images and that it provides specific biomarkers for studying tumors. Our contribution in tractography is an algorithm that approximates the distribution of fascicles emanating from a seed voxel. We achieve that by means of a particle filter better adapted to multi-modal distributions than the traditional filters. To demonstrate the clinical applicability of our tools, we participated to all three editions of the MICCAI DTI Tractography challenge aiming at reconstructing the cortico-spinal tract from single-shell low angular and low spatial resolution diffusion images. Results show that our pipeline provides a reconstruction of the full extent of the CST.RENNES1-Bibl. électronique (352382106) / SudocSudocFranceF

Unsupervised deep learning of human brain diffusion magnetic resonance imaging tractography data

L'imagerie par résonance magnétique de diffusion est une technique non invasive permettant de connaître la microstructure organisationnelle des tissus biologiques. Les méthodes computationnelles qui exploitent la préférence orientationnelle de la diffusion dans des structures restreintes pour révéler les voies axonales de la matière blanche du cerveau sont appelées tractographie. Ces dernières années, diverses méthodes de tractographie ont été utilisées avec succès pour découvrir l'architecture de la matière blanche du cerveau. Pourtant, ces techniques de reconstruction souffrent d'un certain nombre de défauts dérivés d'ambiguïtés fondamentales liées à l'information orientationnelle. Cela a des conséquences dramatiques, puisque les cartes de connectivité de la matière blanche basées sur la tractographie sont dominées par des faux positifs. Ainsi, la grande proportion de voies invalides récupérées demeure un des principaux défis à résoudre par la tractographie pour obtenir une description anatomique fiable de la matière blanche. Des approches méthodologiques innovantes sont nécessaires pour aider à résoudre ces questions. Les progrès récents en termes de puissance de calcul et de disponibilité des données ont rendu possible l'application réussie des approches modernes d'apprentissage automatique à une variété de problèmes, y compris les tâches de vision par ordinateur et d'analyse d'images. Ces méthodes modélisent et trouvent les motifs sous-jacents dans les données, et permettent de faire des prédictions sur de nouvelles données. De même, elles peuvent permettre d'obtenir des représentations compactes des caractéristiques intrinsèques des données d'intérêt. Les approches modernes basées sur les données, regroupées sous la famille des méthodes d'apprentissage profond, sont adoptées pour résoudre des tâches d'analyse de données d'imagerie médicale, y compris la tractographie. Dans ce contexte, les méthodes deviennent moins dépendantes des contraintes imposées par les approches classiques utilisées en tractographie. Par conséquent, les méthodes inspirées de l'apprentissage profond conviennent au changement de paradigme requis, et peuvent ouvrir de nouvelles possibilités de modélisation, en améliorant ainsi l'état de l'art en tractographie. Dans cette thèse, un nouveau paradigme basé sur les techniques d'apprentissage de représentation est proposé pour générer et analyser des données de tractographie. En exploitant les architectures d'autoencodeurs, ce travail tente d'explorer leur capacité à trouver un code optimal pour représenter les caractéristiques des fibres de la matière blanche. Les contributions proposées exploitent ces représentations pour une variété de tâches liées à la tractographie, y compris (i) le filtrage et (ii) le regroupement efficace sur les résultats générés par d'autres méthodes, ainsi que (iii) la reconstruction proprement dite des fibres de la matière blanche en utilisant une méthode générative. Ainsi, les méthodes issues de cette thèse ont été nommées (i) FINTA (Filtering in Tractography using Autoencoders), (ii) CINTA (Clustering in Tractography using Autoencoders), et (iii) GESTA (Generative Sampling in Bundle Tractography using Autoencoders), respectivement. Les performances des méthodes proposées sont évaluées par rapport aux méthodes de l'état de l'art sur des données de diffusion synthétiques et des données de cerveaux humains chez l'adulte sain in vivo. Les résultats montrent que (i) la méthode de filtrage proposée offre une sensibilité et spécificité supérieures par rapport à d'autres méthodes de l'état de l'art; (ii) le regroupement des tractes dans des faisceaux est fait de manière consistante; et (iii) l'approche générative échantillonnant des tractes comble mieux l'espace de la matière blanche dans des régions difficiles à reconstruire. Enfin, cette thèse révèle les possibilités des autoencodeurs pour l'analyse des données des fibres de la matière blanche, et ouvre la voie à fournir des données de tractographie plus fiables.Abstract : Diffusion magnetic resonance imaging is a non-invasive technique providing insights into the organizational microstructure of biological tissues. The computational methods that exploit the orientational preference of the diffusion in restricted structures to reveal the brain's white matter axonal pathways are called tractography. In recent years, a variety of tractography methods have been successfully used to uncover the brain's white matter architecture. Yet, these reconstruction techniques suffer from a number of shortcomings derived from fundamental ambiguities inherent to the orientation information. This has dramatic consequences, since current tractography-based white matter connectivity maps are dominated by false positive connections. Thus, the large proportion of invalid pathways recovered remains one of the main challenges to be solved by tractography to obtain a reliable anatomical description of the white matter. Methodological innovative approaches are required to help solving these questions. Recent advances in computational power and data availability have made it possible to successfully apply modern machine learning approaches to a variety of problems, including computer vision and image analysis tasks. These methods model and learn the underlying patterns in the data, and allow making accurate predictions on new data. Similarly, they may enable to obtain compact representations of the intrinsic features of the data of interest. Modern data-driven approaches, grouped under the family of deep learning methods, are being adopted to solve medical imaging data analysis tasks, including tractography. In this context, the proposed methods are less dependent on the constraints imposed by current tractography approaches. Hence, deep learning-inspired methods are suit for the required paradigm shift, may open new modeling possibilities, and thus improve the state of the art in tractography. In this thesis, a new paradigm based on representation learning techniques is proposed to generate and to analyze tractography data. By harnessing autoencoder architectures, this work explores their ability to find an optimal code to represent the features of the white matter fiber pathways. The contributions exploit such representations for a variety of tractography-related tasks, including efficient (i) filtering and (ii) clustering on results generated by other methods, and (iii) the white matter pathway reconstruction itself using a generative method. The methods issued from this thesis have been named (i) FINTA (Filtering in Tractography using Autoencoders), (ii) CINTA (Clustering in Tractography using Autoencoders), and (iii) GESTA (Generative Sampling in Bundle Tractography using Autoencoders), respectively. The proposed methods' performance is assessed against current state-of-the-art methods on synthetic data and healthy adult human brain in vivo data. Results show that the (i) introduced filtering method has superior sensitivity and specificity over other state-of-the-art methods; (ii) the clustering method groups streamlines into anatomically coherent bundles with a high degree of consistency; and (iii) the generative streamline sampling technique successfully improves the white matter coverage in hard-to-track bundles. In summary, this thesis unlocks the potential of deep autoencoder-based models for white matter data analysis, and paves the way towards delivering more reliable tractography data

The Human Connectome Project's neuroimaging approach

Noninvasive human neuroimaging has yielded many discoveries about the brain. Numerous methodological advances have also occurred, though inertia has slowed their adoption. This paper presents an integrated approach to data acquisition, analysis and sharing that builds upon recent advances, particularly from the Human Connectome Project (HCP). The 'HCP-style' paradigm has seven core tenets: (i) collect multimodal imaging data from many subjects; (ii) acquire data at high spatial and temporal resolution; (iii) preprocess data to minimize distortions, blurring and temporal artifacts; (iv) represent data using the natural geometry of cortical and subcortical structures; (v) accurately align corresponding brain areas across subjects and studies; (vi) analyze data using neurobiologically accurate brain parcellations; and (vii) share published data via user-friendly databases. We illustrate the HCP-style paradigm using existing HCP data sets and provide guidance for future research. Widespread adoption of this paradigm should accelerate progress in understanding the brain in health and disease

Learning, Arts, and the Brain: The Dana Consortium Report on Arts and Cognition

Reports findings from multiple neuroscientific studies on the impact of arts training on the enhancement of other cognitive capacities, such as reading acquisition, sequence learning, geometrical reasoning, and memory

Structure-Function Relationships in the Brain: Applications in Neurosurgery

Multimodal brain imaging allows the study of structure-function relationships of the brain at the individual level, a key subject in basic neuroscience with important applications in neurosurgery. The current thesis aims to better understand these relationships by (1) examining how cortical morphology metrics influence measures of brain function, (2) their visualization in augmented reality (AR), and (3) their application in neurosurgical planning. To achieve these objectives, we made use of multimodal magnetic resonance imaging (MRI) data: diffusion weighted imaging, resting-state functional MRI (rs-fMRI), task-based fMRI, and T1-weighted images. Various metrics were calculated: cortical thickness (CT), blood oxygen level dependent signal variability (BOLDSD), structural connectivity (SC), functional connectivity (FC), etc.. We found that BOLDSD measures are confounded by CT, developed an application to visualize SC and FC in AR, and used rs-fMRI to map language for epilepsy surgery. Overall, these studies provided a better understanding of structure-function relationships in the brain

Advanced Methods for Discovering Genetic Markers Associated with High Dimensional Imaging Data

Imaging genetic studies have been widely applied to discover genetic factors of inherited neuropsychiatric diseases. Despite the notable contribution of genome-wide association studies (GWAS) in neuroimaging research, it has always been difficult to efficiently perform association analysis on imaging phenotypes. There are several challenges arising from this topic, such as the large dimensionality of imaging data and genetic data, the potential spatial dependency of imaging phenotypes and the computational burden of the GWAS problem. All the aforementioned issues motivate us to investigate new statistical methods in neuroimaging genetic analysis. In the first project, we develop a hierarchical functional principal regression model (HFPRM) to simultaneously study diffusion tensor bundle statistics on multiple fiber tracts. Theoretically, the asymptotic distribution of the global test statistic on the common factors has been studied. Simulations are conducted to evaluate the finite sample performance of HFPRM. Finally, we apply our method to a GWAS of a neonate population to explore important genetic architecture in early human brain development. In the second project, we consider an association test between functional data acquired on a single curve and scalar variables in a varying coefficient model. We propose a functional projection regression model and an associated global test statistic to aggregate weak signals across the domain of functional data. Theoretically, we examine the asymptotic distribution of the global test statistic and provide a strategy to adaptively select the tuning parameter. Simulation experiments show that the proposed test outperforms existing state-of-the-art methods in functional statistical inference. We also apply the proposed method to a GWAS in the UK Biobank dataset. In the third project, we introduce an adaptive projection regression model (APRM) to perform statistical inference on high dimensional imaging responses in the presence of high correlations. Dimension reduction of the phenotypes is achieved through a linear projection regression model. We also implement an adaptive inference procedure to detect signals at multiple levels. Numerical simulations demonstrate that APRM outperforms many state-of-the-art methods in high dimensional inference. Finally, we apply APRM to a GWAS of volumetric data on 93 regions of interest in the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset.Doctor of Philosoph