WAVELET FRAMES ON THE SPHERE, HIGH ANGULAR RESOLUTION DIFFUSION IMAGINING AND L_1-REGULARIZED OPTIMIZATION ON STIEFEL MANIFOLDS

Ph.DDOCTOR OF PHILOSOPH

Reconstruction et description des fonctions de distribution d'orientation en imagerie de diffusion à haute résolution angulaire

This thesis concerns the reconstruction and description of orientation distribution functions (ODFs) in high angular resolution diffusion imaging (HARDI) such as q-ball imaging (QBI). QBI is used to analyze more accurately fiber structures (crossing, bending, fanning, etc.) in a voxel. In this field, the ODF reconstructed from QBI is widely used for resolving complex intravoxel fiber configuration problem. However, until now, the assessment of the characteristics or quality of ODFs remains mainly visual and qualitative, although the use of a few objective quality metrics is also reported that are directly borrowed from classical signal and image processing theory. At the same time, although some metrics such as generalized anisotropy (GA) and generalized fractional anisotropy (GFA) have been proposed for classifying intravoxel fiber configurations, the classification of the latters is still a problem. On the other hand, QBI often needs an important number of acquisitions (usually more than 60 directions) to compute accurately ODFs. So, reducing the quantity of QBI data (i.e. shortening acquisition time) while maintaining ODF quality is a real challenge. In this context, we have addressed the problems of how to reconstruct high-quality ODFs and assess their characteristics. We have proposed a new paradigm allowing describing the characteristics of ODFs more quantitatively. It consists of regarding an ODF as a general three-dimensional (3D) point cloud, projecting a 3D point cloud onto an angle-distance map (ADM), constructing an angle-distance matrix (ADMAT), and calculating morphological characteristics of the ODF such as length ratio, separability and uncertainty. In particular, a new metric, called PEAM (PEAnut Metric), which is based on computing the deviation of ODFs from a single fiber ODF represented by a peanut, was proposed and used to classify intravoxel fiber configurations. Several ODF reconstruction methods have also been compared using the proposed metrics. The results showed that the characteristics of 3D point clouds can be well assessed in a relatively complete and quantitative manner. Concerning the reconstruction of high-quality ODFs with reduced data, we have proposed two methods. The first method is based on interpolation by Delaunay triangulation and imposing constraints in both q-space and spatial space. The second method combines random gradient diffusion direction sampling, compressed sensing, resampling density increasing, and missing diffusion signal recovering. The results showed that the proposed missing diffusion signal recovering approaches enable us to obtain accurate ODFs with relatively fewer number of diffusion signals.Ce travail de thèse porte sur la reconstruction et la description des fonctions de distribution d'orientation (ODF) en imagerie de diffusion à haute résolution angulaire (HARDI) telle que l’imagerie par q-ball (QBI). Dans ce domaine, la fonction de distribution d’orientation (ODF) en QBI est largement utilisée pour étudier le problème de configuration complexe des fibres. Toutefois, jusqu’à présent, l’évaluation des caractéristiques ou de la qualité des ODFs reste essentiellement visuelle et qualitative, bien que l’utilisation de quelques mesures objectives de qualité ait également été reportée dans la littérature, qui sont directement empruntées de la théorie classique de traitement du signal et de l’image. En même temps, l’utilisation appropriée de ces mesures pour la classification des configurations des fibres reste toujours un problème. D'autre part, le QBI a souvent besoin d'un nombre important d’acquisitions pour calculer avec précision les ODFs. Ainsi, la réduction du temps d’acquisition des données QBI est un véritable défi. Dans ce contexte, nous avons abordé les problèmes de comment reconstruire des ODFs de haute qualité et évaluer leurs caractéristiques. Nous avons proposé un nouveau paradigme permettant de décrire les caractéristiques des ODFs de manière plus quantitative. Il consiste à regarder un ODF comme un nuage général de points tridimensionnels (3D), projeter ce nuage de points 3D sur un plan angle-distance (ADM), construire une matrice angle-distance (ADMAT), et calculer des caractéristiques morphologiques de l'ODF telles que le rapport de longueurs, la séparabilité et l'incertitude. En particulier, une nouvelle métrique, appelé PEAM (PEAnut Metric) et qui est basée sur le calcul de l'écart des ODFs par rapport à l’ODF (représenté par une forme arachide) d’une seule fibre, a été proposée et utilisée pour classifier des configurations intravoxel des fibres. Plusieurs méthodes de reconstruction des ODFs ont également été comparées en utilisant les paramètres proposés. Les résultats ont montré que les caractéristiques du nuage de points 3D peuvent être évaluées d'une manière relativement complète et quantitative. En ce qui concerne la reconstruction de l'ODF de haute qualité avec des données réduites, nous avons proposé deux méthodes. La première est basée sur une interpolation par triangulation de Delaunay et sur des contraintes imposées à la fois dans l’espace-q et dans l'espace spatial. La deuxième méthode combine l’échantillonnage aléatoire des directions de gradient de diffusion, le compressed sensing, l’augmentation de la densité de ré-échantillonnage, et la reconstruction des signaux de diffusion manquants. Les résultats ont montré que les approches de reconstruction des signaux de diffusion manquants proposées nous permettent d'obtenir des ODFs précis à partir d’un nombre relativement faible de signaux de diffusion

NOVEL PHANTOMS AND POST-PROCESSING FOR DIFFUSION SPECTRUM IMAGING

High Angular Resolution Diffusion Imaging (HARDI) techniques, including Diffusion Spectrum Imaging (DSI), have been proposed to resolve crossing and other complex fiber architecture in the human brain white matter. In these methods, directional information of diffusion is inferred from the peaks in the orientation distribution function (ODF). Extensive studies using histology on macaque brain, cat cerebellum, rat hippocampus and optic tracts, and bovine tongue are qualitatively in agreement with the DSI-derived ODFs and tractography. However, there are only two studies in the literature which validated the DSI results using physical phantoms and both these studies were not performed on a clinical MRI scanner. Also, the limited studies which optimized DSI in a clinical setting, did not involve a comparison against physical phantoms. Finally, there is lack of consensus on the necessary pre- and post-processing steps in DSI; and ground truth diffusion fiber phantoms are not yet standardized. Therefore, the aims of this dissertation were to design and construct novel diffusion phantoms, employ post-processing techniques in order to systematically validate and optimize (DSI)-derived fiber ODFs in the crossing regions on a clinical 3T MR scanner, and develop user-friendly software for DSI data reconstruction and analysis. Phantoms with a fixed crossing fiber configuration of two crossing fibers at 90° and 45° respectively along with a phantom with three crossing fibers at 60°, using novel hollow plastic capillaries and novel placeholders, were constructed. T2-weighted MRI results on these phantoms demonstrated high SNR, homogeneous signal, and absence of air bubbles. Also, a technique to deconvolve the response function of an individual peak from the overall ODF was implemented, in addition to other DSI post-processing steps. This technique greatly improved the angular resolution of the otherwise unresolvable peaks in a crossing fiber ODF. The effects of DSI acquisition parameters and SNR on the resultant angular accuracy of DSI on the clinical scanner were studied and quantified using the developed phantoms. With a high angular direction sampling and reasonable levels of SNR, quantification of a crossing region in the 90°, 45° and 60° phantoms resulted in a successful detection of angular information with mean ± SD of 86.93°±2.65°, 44.61°±1.6° and 60.03°±2.21° respectively, while simultaneously enhancing the ODFs in regions containing single fibers. For the applicability of these validated methodologies in DSI, improvement in ODFs and fiber tracking from known crossing fiber regions in normal human subjects were demonstrated; and an in-house software package in MATLAB which streamlines the data reconstruction and post-processing for DSI, with easy to use graphical user interface was developed. In conclusion, the phantoms developed in this dissertation offer a means of providing ground truth for validation of reconstruction and tractography algorithms of various diffusion models (including DSI). Also, the deconvolution methodology (when applied as an additional DSI post-processing step) significantly improved the angular accuracy of the ODFs obtained from DSI, and should be applicable to ODFs obtained from the other high angular resolution diffusion imaging techniques

Super Resolution of HARDI images Using Compressed Sensing Techniques

Effective techniques of inferring the condition of neural tracts in the brain is invaluable for clinicians and researchers towards investigation of neurological disorders in patients. It was not until the advent of diffusion Magnetic Resonance Imaging (dMRI), a noninvasive imaging method used to detect the diffusion of water molecules, that scientists have been able to assess the characteristics of cerebral diffusion in vivo. Among different dMRI methods, High Angular Resolution Diffusion Imaging (HARDI) is well known for striking a balance between ability to distinguish crossing neural fibre tracts while requiring a modest number of diffusion measurements (which is directly related to acquisition time). HARDI data provides insight into the directional properties of water diffusion in cerebral matter as a function of spatial coordinates. Ideally, one would be interested in having this information available at fine spatial resolution while minimizing the probing along different spatial orientations (so as to minimize the acquisition time). Unfortunately, availability of such datasets in reasonable acquisition times are hindered by limitations in current hardware and scanner protocols. On the other hand, post processing techniques prove promising in increasing the effective spatial resolution, allowing more detailed depictions of cerebral matter, while keeping the number of diffusion measurements within a feasible range. In light of the preceding developments, the main purpose of this research is to look into super resolution of HARDI data, using the modern theory of compressed sensing. The method proposed in this thesis allows an accurate approximation of HARDI signals at a higher spatial resolution compared to data obtained with a typical scanner. At the same time, ideas for reducing the number of diffusion measurements in the angular domain to improve the acquisition time are explored. Accordingly, the novel method of applying two distinct compressed sensing approaches in both spatial and angular domain, and combining them into a single framework for performing super resolution forms the main contribution provided by this thesis

Signal processing in diffusion MRI : high quality signal reconstruction

Magnetic Resonance Imaging (MRI) is a medical imaging technique which is especially sensitive to different soft tissues, producing a good contrast between them. It allows for in vivo visualisation of internal structures in detail and became an indispensable tool in diagnosing and monitoring the brain related diseases and pathologies. Amongst others, MRI can be used to measure random incoherent motion of water molecules, which in turn allows to infer structural information. One of the main challenges in processing and analysing four dimensional diffusion MRI images is low signal quality. To improve the signal quality, either denoising algorithm or angular and spatial regularisations are utilised. Regularisation method based on Laplace--Beltrami smoothing operator was successfully applied to diffusion signal. In this thesis, a new regularisation strength selection scheme for diffusion signal regularisation is introduced. A mathematical model of diffusion signal is used in Monte--Carlo simulations, and a regularisation strength that optimally reconstructs the diffusion signal is sought. The regularisation values found in this research show a different trend than the currently used L-curve analysis, and further improve reconstruction accuracy. Additionally, as an alternative to regularisation methods a backward elimination regression for spherical harmonics is proposed. Instead of using the regularisation term as a low-pass filter, the statistical t-test is classifying regression terms into reliable and corrupted. Four algorithms that use this information are further introduced. As the result, a selective filtering is constructed that retains the angular sharpness of the signal, while at the same time reducing corruptive effect of measurement noise. Finally, a statistical approach for estimating diffusion signal is investigated. Based on the physical properties of water diffusion a prior knowledge for the diffusion signal is constructed. The spherical harmonic transform is then formulated as a Bayesian regression problem. Diffusion signal reconstructed with the addition of such prior knowledge is accurate, noise resilient, and of high quality

Signal processing in diffusion MRI : high quality signal reconstruction

Magnetic Resonance Imaging (MRI) is a medical imaging technique which is especially sensitive to different soft tissues, producing a good contrast between them. It allows for in vivo visualisation of internal structures in detail and became an indispensable tool in diagnosing and monitoring the brain related diseases and pathologies. Amongst others, MRI can be used to measure random incoherent motion of water molecules, which in turn allows to infer structural information. One of the main challenges in processing and analysing four dimensional diffusion MRI images is low signal quality. To improve the signal quality, either denoising algorithm or angular and spatial regularisations are utilised. Regularisation method based on Laplace--Beltrami smoothing operator was successfully applied to diffusion signal. In this thesis, a new regularisation strength selection scheme for diffusion signal regularisation is introduced. A mathematical model of diffusion signal is used in Monte--Carlo simulations, and a regularisation strength that optimally reconstructs the diffusion signal is sought. The regularisation values found in this research show a different trend than the currently used L-curve analysis, and further improve reconstruction accuracy. Additionally, as an alternative to regularisation methods a backward elimination regression for spherical harmonics is proposed. Instead of using the regularisation term as a low-pass filter, the statistical t-test is classifying regression terms into reliable and corrupted. Four algorithms that use this information are further introduced. As the result, a selective filtering is constructed that retains the angular sharpness of the signal, while at the same time reducing corruptive effect of measurement noise. Finally, a statistical approach for estimating diffusion signal is investigated. Based on the physical properties of water diffusion a prior knowledge for the diffusion signal is constructed. The spherical harmonic transform is then formulated as a Bayesian regression problem. Diffusion signal reconstructed with the addition of such prior knowledge is accurate, noise resilient, and of high quality

Compendio de métodos para caracterizar la geometría de los tejidos cerebrales a partir de imágenes de resonancia magnética por difusión del agua.

221 p.FIDMAG Hermanas Hospitalarias Research Foundation; CIBERSAM:Centro de Investigación Biomédica en Re

Impacts des étapes de pré-traitement des données de diffusion sur la tractographie - Imagerie de diffusion

Ce mémoire présente l'ensemble des étapes de pré-traitement appliquées aux images provenant de l'imagerie par résonance magnétique de diffusion afin de conseiller les meilleurs paramètres dans une étude de tractographie. L'imagerie de diffusion nous donne l'information locale des déplacements moyens des molécules d'eau dans le cerveau. Cette information nous permet d'inférer l'architecture de la matière blanche. La reconstruction du signal de diffusion fait appel à différentes méthodes plus ou moins aptes à restituer la complexité des configurations de fibres. Dans ce mémoire, nous proposons une nouvelle méthode de reconstruction du phénomène de diffusion basée sur la décomposition en ondelettes sphériques. Ensuite, en combinant ces informations à tous les points du cerveau nous reconstruisons le réseau de fibres de la matière blanche par un algorithme de tractographie déterministe. Afin d'initier cet algorithme, nous proposons une nouvelle méthode d'initialisation dans le but de mieux gérer la complexité des configurations de fibres au sein d'un seul voxel. Les fibres reconstruites sont très difficiles à évaluer dans le cerveau car nous ne connaissons pas la configuration réelle des fibres. Pour être en mesure d'évaluer nos méthodes de reconstruction, nous utilisons un fantôme calquant la complexité des configurations de fibres trouvées dans le cerveau. Dans ce mémoire, nous proposons un ensemble de métriques et un système de notations permettant d'évaluer automatiquement la qualité des résultats d'une tractographie. Nous concluons l'étude concernant les données synthétiques par un ensemble de conseils sur les paramètres à utiliser afin d'obtenir des résultats de tractographie optimaux. Finalement, nous évaluons qualitativement les résultats de tractographie issus de données réelles afin de confirmer nos choix sur les données fantômes