A Kernel-based Approach to Diffusion Tensor and Fiber Clustering in the Human Skeletal Muscle

In this report, we present a kernel-based approach to the clustering of diffusion tensors in images of the human skeletal muscle. Based on the physical intuition of tensors as a means to represent the uncertainty of the position of water protons in the tissues, we propose a Mercer (i.e. positive definite) kernel over the tensor space where both spatial and diffusion information are taken into account. This kernel highlights implicitly the connectivity along fiber tracts. We show that using this kernel in a kernel-PCA setting compounded with a landmark-Isomap embedding and k-means clustering provides a tractable framework for tensor clustering. We extend this kernel to deal with fiber tracts as input using the multi-instance kernel by considering the fiber as set of tensors centered in the sampled points of the tract. The obtained kernel reflects not only interactions between points along fiber tracts, but also the interactions between diffusion tensors. We give an interpretation of the obtained kernel as a comparison of soft fiber representations and show that it amounts to a generalization of the Gaussian kernel Correlation. As in the tensor case, we use the kernel-PCA setting and k-means for grouping of fiber tracts. This unsupervised method is further extended by way of an atlas-based registration of diffusion-free images, followed by a classification of fibers based on non-linear kernel Support Vector Machines (SVMs) and kernel diffusion. The experimental results on a dataset of diffusion tensor images of the calf muscle of 25 patients (of which 5 affected by myopathies, i.e. neuromuscular diseases) show the potential of our method in segmenting the calf in anatomically relevant regions both at the tensor and fiber level

MODELING AND QUANTITATIVE ANALYSIS OF WHITE MATTER FIBER TRACTS IN DIFFUSION TENSOR IMAGING

Diffusion tensor imaging (DTI) is a structural magnetic resonance imaging (MRI) technique to record incoherent motion of water molecules and has been used to detect micro structural white matter alterations in clinical studies to explore certain brain disorders. A variety of DTI based techniques for detecting brain disorders and facilitating clinical group analysis have been developed in the past few years. However, there are two crucial issues that have great impacts on the performance of those algorithms. One is that brain neural pathways appear in complicated 3D structures which are inappropriate and inaccurate to be approximated by simple 2D structures, while the other involves the computational efficiency in classifying white matter tracts. The first key area that this dissertation focuses on is to implement a novel computing scheme for estimating regional white matter alterations along neural pathways in 3D space. The mechanism of the proposed method relies on white matter tractography and geodesic distance mapping. We propose a mask scheme to overcome the difficulty to reconstruct thin tract bundles. Real DTI data are employed to demonstrate the performance of the pro- posed technique. Experimental results show that the proposed method bears great potential to provide a sensitive approach for determining the white matter integrity in human brain. Another core objective of this work is to develop a class of new modeling and clustering techniques with improved performance and noise resistance for separating reconstructed white matter tracts to facilitate clinical group analysis. Different strategies are presented to handle different scenarios. For whole brain tractography reconstructed white matter tracts, a Fourier descriptor model and a clustering algorithm based on multivariate Gaussian mixture model and expectation maximization are proposed. Outliers are easily handled in this framework. Real DTI data experimental results show that the proposed algorithm is relatively effective and may offer an alternative for existing white matter fiber clustering methods. For a small amount of white matter fibers, a modeling and clustering algorithm with the capability of handling white matter fibers with unequal length and sharing no common starting region is also proposed and evaluated with real DTI data

Density-based algorithms for active and anytime clustering

Data intensive applications like biology, medicine, and neuroscience require effective and efficient data mining technologies. Advanced data acquisition methods produce a constantly increasing volume and complexity. As a consequence, the need of new data mining technologies to deal with complex data has emerged during the last decades. In this thesis, we focus on the data mining task of clustering in which objects are separated in different groups (clusters) such that objects inside a cluster are more similar than objects in different clusters. Particularly, we consider density-based clustering algorithms and their applications in biomedicine. The core idea of the density-based clustering algorithm DBSCAN is that each object within a cluster must have a certain number of other objects inside its neighborhood. Compared with other clustering algorithms, DBSCAN has many attractive benefits, e.g., it can detect clusters with arbitrary shape and is robust to outliers, etc. Thus, DBSCAN has attracted a lot of research interest during the last decades with many extensions and applications. In the first part of this thesis, we aim at developing new algorithms based on the DBSCAN paradigm to deal with the new challenges of complex data, particularly expensive distance measures and incomplete availability of the distance matrix. Like many other clustering algorithms, DBSCAN suffers from poor performance when facing expensive distance measures for complex data. To tackle this problem, we propose a new algorithm based on the DBSCAN paradigm, called Anytime Density-based Clustering (A-DBSCAN), that works in an anytime scheme: in contrast to the original batch scheme of DBSCAN, the algorithm A-DBSCAN first produces a quick approximation of the clustering result and then continuously refines the result during the further run. Experts can interrupt the algorithm, examine the results, and choose between (1) stopping the algorithm at any time whenever they are satisfied with the result to save runtime and (2) continuing the algorithm to achieve better results. Such kind of anytime scheme has been proven in the literature as a very useful technique when dealing with time consuming problems. We also introduced an extended version of A-DBSCAN called A-DBSCAN-XS which is more efficient and effective than A-DBSCAN when dealing with expensive distance measures. Since DBSCAN relies on the cardinality of the neighborhood of objects, it requires the full distance matrix to perform. For complex data, these distances are usually expensive, time consuming or even impossible to acquire due to high cost, high time complexity, noisy and missing data, etc. Motivated by these potential difficulties of acquiring the distances among objects, we propose another approach for DBSCAN, called Active Density-based Clustering (Act-DBSCAN). Given a budget limitation B, Act-DBSCAN is only allowed to use up to B pairwise distances ideally to produce the same result as if it has the entire distance matrix at hand. The general idea of Act-DBSCAN is that it actively selects the most promising pairs of objects to calculate the distances between them and tries to approximate as much as possible the desired clustering result with each distance calculation. This scheme provides an efficient way to reduce the total cost needed to perform the clustering. Thus it limits the potential weakness of DBSCAN when dealing with the distance sparseness problem of complex data. As a fundamental data clustering algorithm, density-based clustering has many applications in diverse fields. In the second part of this thesis, we focus on an application of density-based clustering in neuroscience: the segmentation of the white matter fiber tracts in human brain acquired from Diffusion Tensor Imaging (DTI). We propose a model to evaluate the similarity between two fibers as a combination of structural similarity and connectivity-related similarity of fiber tracts. Various distance measure techniques from fields like time-sequence mining are adapted to calculate the structural similarity of fibers. Density-based clustering is used as the segmentation algorithm. We show how A-DBSCAN and A-DBSCAN-XS are used as novel solutions for the segmentation of massive fiber datasets and provide unique features to assist experts during the fiber segmentation process.Datenintensive Anwendungen wie Biologie, Medizin und Neurowissenschaften erfordern effektive und effiziente Data-Mining-Technologien. Erweiterte Methoden der Datenerfassung erzeugen stetig wachsende Datenmengen und Komplexit\"at. In den letzten Jahrzehnten hat sich daher ein Bedarf an neuen Data-Mining-Technologien f\"ur komplexe Daten ergeben. In dieser Arbeit konzentrieren wir uns auf die Data-Mining-Aufgabe des Clusterings, in der Objekte in verschiedenen Gruppen (Cluster) getrennt werden, so dass Objekte in einem Cluster untereinander viel \"ahnlicher sind als Objekte in verschiedenen Clustern. Insbesondere betrachten wir dichtebasierte Clustering-Algorithmen und ihre Anwendungen in der Biomedizin. Der Kerngedanke des dichtebasierten Clustering-Algorithmus DBSCAN ist, dass jedes Objekt in einem Cluster eine bestimmte Anzahl von anderen Objekten in seiner Nachbarschaft haben muss. Im Vergleich mit anderen Clustering-Algorithmen hat DBSCAN viele attraktive Vorteile, zum Beispiel kann es Cluster mit beliebiger Form erkennen und ist robust gegen\"uber Ausrei{\ss}ern. So hat DBSCAN in den letzten Jahrzehnten gro{\ss}es Forschungsinteresse mit vielen Erweiterungen und Anwendungen auf sich gezogen. Im ersten Teil dieser Arbeit wollen wir auf die Entwicklung neuer Algorithmen eingehen, die auf dem DBSCAN Paradigma basieren, um mit den neuen Herausforderungen der komplexen Daten, insbesondere teurer Abstandsma{\ss}e und unvollst\"andiger Verf\"ugbarkeit der Distanzmatrix umzugehen. Wie viele andere Clustering-Algorithmen leidet DBSCAN an schlechter Per- formanz, wenn es teuren Abstandsma{\ss}en f\"ur komplexe Daten gegen\"uber steht. Um dieses Problem zu l\"osen, schlagen wir einen neuen Algorithmus vor, der auf dem DBSCAN Paradigma basiert, genannt Anytime Density-based Clustering (A-DBSCAN), der mit einem Anytime Schema funktioniert. Im Gegensatz zu dem urspr\"unglichen Schema DBSCAN, erzeugt der Algorithmus A-DBSCAN zuerst eine schnelle Ann\"aherung des Clusterings-Ergebnisses und verfeinert dann kontinuierlich das Ergebnis im weiteren Verlauf. Experten k\"onnen den Algorithmus unterbrechen, die Ergebnisse pr\"ufen und w\"ahlen zwischen (1) Anhalten des Algorithmus zu jeder Zeit, wann immer sie mit dem Ergebnis zufrieden sind, um Laufzeit sparen und (2) Fortsetzen des Algorithmus, um bessere Ergebnisse zu erzielen. Eine solche Art eines "Anytime Schemas" ist in der Literatur als eine sehr n\"utzliche Technik erprobt, wenn zeitaufwendige Problemen anfallen. Wir stellen auch eine erweiterte Version von A-DBSCAN als A-DBSCAN-XS vor, die effizienter und effektiver als A-DBSCAN beim Umgang mit teuren Abstandsma{\ss}en ist. Da DBSCAN auf der Kardinalit\"at der Nachbarschaftsobjekte beruht, ist es notwendig, die volle Distanzmatrix auszurechen. F\"ur komplexe Daten sind diese Distanzen in der Regel teuer, zeitaufwendig oder sogar unm\"oglich zu errechnen, aufgrund der hohen Kosten, einer hohen Zeitkomplexit\"at oder verrauschten und fehlende Daten. Motiviert durch diese m\"oglichen Schwierigkeiten der Berechnung von Entfernungen zwischen Objekten, schlagen wir einen anderen Ansatz f\"ur DBSCAN vor, namentlich Active Density-based Clustering (Act-DBSCAN). Bei einer Budgetbegrenzung B, darf Act-DBSCAN nur bis zu B ideale paarweise Distanzen verwenden, um das gleiche Ergebnis zu produzieren, wie wenn es die gesamte Distanzmatrix zur Hand h\"atte. Die allgemeine Idee von Act-DBSCAN ist, dass es aktiv die erfolgversprechendsten Paare von Objekten w\"ahlt, um die Abst\"ande zwischen ihnen zu berechnen, und versucht, sich so viel wie m\"oglich dem gew\"unschten Clustering mit jeder Abstandsberechnung zu n\"ahern. Dieses Schema bietet eine effiziente M\"oglichkeit, die Gesamtkosten der Durchf\"uhrung des Clusterings zu reduzieren. So schr\"ankt sie die potenzielle Schw\"ache des DBSCAN beim Umgang mit dem Distance Sparseness Problem von komplexen Daten ein. Als fundamentaler Clustering-Algorithmus, hat dichte-basiertes Clustering viele Anwendungen in den unterschiedlichen Bereichen. Im zweiten Teil dieser Arbeit konzentrieren wir uns auf eine Anwendung des dichte-basierten Clusterings in den Neurowissenschaften: Die Segmentierung der wei{\ss}en Substanz bei Faserbahnen im menschlichen Gehirn, die vom Diffusion Tensor Imaging (DTI) erfasst werden. Wir schlagen ein Modell vor, um die \"Ahnlichkeit zwischen zwei Fasern als einer Kombination von struktureller und konnektivit\"atsbezogener \"Ahnlichkeit von Faserbahnen zu beurteilen. Verschiedene Abstandsma{\ss}e aus Bereichen wie dem Time-Sequence Mining werden angepasst, um die strukturelle \"Ahnlichkeit von Fasern zu berechnen. Dichte-basiertes Clustering wird als Segmentierungsalgorithmus verwendet. Wir zeigen, wie A-DBSCAN und A-DBSCAN-XS als neuartige L\"osungen f\"ur die Segmentierung von sehr gro{\ss}en Faserdatens\"atzen verwendet werden, und bieten innovative Funktionen, um Experten w\"ahrend des Fasersegmentierungsprozesses zu unterst\"utzen

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

Quantitation in MRI : application to ageing and epilepsy

Multi-atlas propagation and label fusion techniques have recently been developed for segmenting the human brain into multiple anatomical regions. In this thesis, I investigate possible adaptations of these current state-of-the-art methods. The aim is to study ageing on the one hand, and on the other hand temporal lobe epilepsy as an example for a neurological disease. Overall effects are a confounding factor in such anatomical analyses. Intracranial volume (ICV) is often preferred to normalize for global effects as it allows to normalize for estimated maximum brain size and is hence independent of global brain volume loss, as seen in ageing and disease. I describe systematic differences in ICV measures obtained at 1.5T versus 3T, and present an automated method of measuring intracranial volume, Reverse MNI Brain Masking (RBM), based on tissue probability maps in MNI standard space. I show that this is comparable to manual measurements and robust against field strength differences. Correct and robust segmentation of target brains which show gross abnormalities, such as ventriculomegaly, is important for the study of ageing and disease. We achieved this with incorporating tissue classification information into the image registration process. The best results in elderly subjects, patients with TLE and healthy controls were achieved using a new approach using multi-atlas propagation with enhanced registration (MAPER). I then applied MAPER to the problem of automatically distinguishing patients with TLE with (TLE-HA) and without (TLE-N) hippocampal atrophy on MRI from controls, and determine the side of seizure onset. MAPER-derived structural volumes were used for a classification step consisting of selecting a set of discriminatory structures and applying support vector machine on the structural volumes as well as morphological similarity information such as volume difference obtained with spectral analysis. Acccuracies were 91-100 %, indicating that the method might be clinically useful. Finally, I used the methods developed in the previous chapters to investigate brain regional volume changes across the human lifespan in over 500 healthy subjects between 20 to 90 years of age, using data from three different scanners (2x 1.5T, 1x 3T), using the IXI database. We were able to confirm several known changes, indicating the veracity of the method. In addition, we describe the first multi-region, whole-brain database of normal ageing

Analyse et reconstruction de faisceaux de la matière blanche

L'imagerie par résonance magnétique de diffusion (IRMd) est une modalité d'acquisition permettant de sonder les tissus biologiques et d'en extraire une variété d'informations sur le mouvement microscopique des molécules d'eau. Plus spécifiquement à l'imagerie médicale, l'IRMd permet l'investigation des structures fibreuses de nombreux organes et facilite la compréhension des processus cognitifs ou au diagnostic. Dans le domaine des neurosciences, l'IRMd est cruciale à l'exploration de la connectivité structurelle de la matière blanche. Cette thèse s'intéresse plus particulièrement à la reconstruction de faisceaux de la matière blanche ainsi qu'à leur analyse. Toute la complexité du traitement des données commençant au scanneur jusqu'à la création d'un tractogramme est extrêmement importante. Par contre, l'application spécifique de reconstruction des faisceaux anatomiques plausibles est ultimement le véritable défi de l'IRMd. L'optimisation des paramètres de la tractographie, le processus de segmentation manuelle ou automatique ainsi que l'interprétation des résultats liée à ces faisceaux sont toutes des étapes du processus avec leurs lots de difficultés

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