39 research outputs found

    Segmentation and Characterization of Small Retinal Vessels in Fundus Images Using the Tensor Voting Approach

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    RÉSUMÉ La rétine permet de visualiser facilement une partie du réseau vasculaire humain. Elle offre ainsi un aperçu direct sur le développement et le résultat de certaines maladies liées au réseau vasculaire dans son entier. Chaque complication visible sur la rétine peut avoir un impact sur la capacité visuelle du patient. Les plus petits vaisseaux sanguins sont parmi les premières structures anatomiques affectées par la progression d’une maladie, être capable de les analyser est donc crucial. Les changements dans l’état, l’aspect, la morphologie, la fonctionnalité, ou même la croissance des petits vaisseaux indiquent la gravité des maladies. Le diabète est une maladie métabolique qui affecte des millions de personnes autour du monde. Cette maladie affecte le taux de glucose dans le sang et cause des changements pathologiques dans différents organes du corps humain. La rétinopathie diabétique décrit l’en- semble des conditions et conséquences du diabète au niveau de la rétine. Les petits vaisseaux jouent un rôle dans le déclenchement, le développement et les conséquences de la rétinopa- thie. Dans les dernières étapes de cette maladie, la croissance des nouveaux petits vaisseaux, appelée néovascularisation, présente un risque important de provoquer la cécité. Il est donc crucial de détecter tous les changements qui ont lieu dans les petits vaisseaux de la rétine dans le but de caractériser les vaisseaux sains et les vaisseaux anormaux. La caractérisation en elle-même peut faciliter la détection locale d’une rétinopathie spécifique. La segmentation automatique des structures anatomiques comme le réseau vasculaire est une étape cruciale. Ces informations peuvent être fournies à un médecin pour qu’elles soient considérées lors de son diagnostic. Dans les systèmes automatiques d’aide au diagnostic, le rôle des petits vaisseaux est significatif. Ne pas réussir à les détecter automatiquement peut conduire à une sur-segmentation du taux de faux positifs des lésions rouges dans les étapes ultérieures. Les efforts de recherche se sont concentrés jusqu’à présent sur la localisation précise des vaisseaux de taille moyenne. Les modèles existants ont beaucoup plus de difficultés à extraire les petits vaisseaux sanguins. Les modèles existants ne sont pas robustes à la grande variance d’apparence des vaisseaux ainsi qu’à l’interférence avec l’arrière-plan. Les modèles de la littérature existante supposent une forme générale qui n’est pas suffisante pour s’adapter à la largeur étroite et la courbure qui caractérisent les petits vaisseaux sanguins. De plus, le contraste avec l’arrière-plan dans les régions des petits vaisseaux est très faible. Les méthodes de segmentation ou de suivi produisent des résultats fragmentés ou discontinus. Par ailleurs, la segmentation des petits vaisseaux est généralement faite aux dépends de l’amplification du bruit. Les modèles déformables sont inadéquats pour segmenter les petits vaisseaux. Les forces utilisées ne sont pas assez flexibles pour compenser le faible contraste, la largeur, et vii la variance des vaisseaux. Enfin, les approches de type apprentissage machine nécessitent un entraînement avec une base de données étiquetée. Il est très difficile d’obtenir ces bases de données dans le cas des petits vaisseaux. Cette thèse étend les travaux de recherche antérieurs en fournissant une nouvelle mé- thode de segmentation des petits vaisseaux rétiniens. La détection de ligne à échelles multiples (MSLD) est une méthode récente qui démontre une bonne performance de segmentation dans les images de la rétine, tandis que le vote tensoriel est une méthode proposée pour reconnecter les pixels. Une approche combinant un algorithme de détection de ligne et de vote tensoriel est proposée. L’application des détecteurs de lignes a prouvé son efficacité à segmenter les vais- seaux de tailles moyennes. De plus, les approches d’organisation perceptuelle comme le vote tensoriel ont démontré une meilleure robustesse en combinant les informations voisines d’une manière hiérarchique. La méthode de vote tensoriel est plus proche de la perception humain que d’autres modèles standards. Comme démontré dans ce manuscrit, c’est un outil pour segmenter les petits vaisseaux plus puissant que les méthodes existantes. Cette combinaison spécifique nous permet de surmonter les défis de fragmentation éprouvés par les méthodes de type modèle déformable au niveau des petits vaisseaux. Nous proposons également d’utiliser un seuil adaptatif sur la réponse de l’algorithme de détection de ligne pour être plus robuste aux images non-uniformes. Nous illustrons également comment une combinaison des deux méthodes individuelles, à plusieurs échelles, est capable de reconnecter les vaisseaux sur des distances variables. Un algorithme de reconstruction des vaisseaux est également proposé. Cette dernière étape est nécessaire car l’information géométrique complète est requise pour pouvoir utiliser la segmentation dans un système d’aide au diagnostic. La segmentation a été validée sur une base de données d’images de fond d’oeil à haute résolution. Cette base contient des images manifestant une rétinopathie diabétique. La seg- mentation emploie des mesures de désaccord standards et aussi des mesures basées sur la perception. En considérant juste les petits vaisseaux dans les images de la base de données, l’amélioration dans le taux de sensibilité que notre méthode apporte par rapport à la méthode standard de détection multi-niveaux de lignes est de 6.47%. En utilisant les mesures basées sur la perception, l’amélioration est de 7.8%. Dans une seconde partie du manuscrit, nous proposons également une méthode pour caractériser les rétines saines ou anormales. Certaines images contiennent de la néovascula- risation. La caractérisation des vaisseaux en bonne santé ou anormale constitue une étape essentielle pour le développement d’un système d’aide au diagnostic. En plus des défis que posent les petits vaisseaux sains, les néovaisseaux démontrent eux un degré de complexité encore plus élevé. Ceux-ci forment en effet des réseaux de vaisseaux à la morphologie com- plexe et inhabituelle, souvent minces et à fortes courbures. Les travaux existants se limitent viii à l’utilisation de caractéristiques de premier ordre extraites des petits vaisseaux segmentés. Notre contribution est d’utiliser le vote tensoriel pour isoler les jonctions vasculaires et d’uti- liser ces jonctions comme points d’intérêts. Nous utilisons ensuite une statistique spatiale de second ordre calculée sur les jonctions pour caractériser les vaisseaux comme étant sains ou pathologiques. Notre méthode améliore la sensibilité de la caractérisation de 9.09% par rapport à une méthode de l’état de l’art. La méthode développée s’est révélée efficace pour la segmentation des vaisseaux réti- niens. Des tenseurs d’ordre supérieur ainsi que la mise en œuvre d’un vote par tenseur via un filtrage orientable pourraient être étudiés pour réduire davantage le temps d’exécution et résoudre les défis encore présents au niveau des jonctions vasculaires. De plus, la caractéri- sation pourrait être améliorée pour la détection de la rétinopathie proliférative en utilisant un apprentissage supervisé incluant des cas de rétinopathie diabétique non proliférative ou d’autres pathologies. Finalement, l’incorporation des méthodes proposées dans des systèmes d’aide au diagnostic pourrait favoriser le dépistage régulier pour une détection précoce des rétinopathies et d’autres pathologies oculaires dans le but de réduire la cessité au sein de la population.----------ABSTRACT As an easily accessible site for the direct observation of the circulation system, human retina can offer a unique insight into diseases development or outcome. Retinal vessels are repre- sentative of the general condition of the whole systematic circulation, and thus can act as a "window" to the status of the vascular network in the whole body. Each complication on the retina can have an adverse impact on the patient’s sight. In this direction, small vessels’ relevance is very high as they are among the first anatomical structures that get affected as diseases progress. Moreover, changes in the small vessels’ state, appearance, morphology, functionality, or even growth indicate the severity of the diseases. This thesis will focus on the retinal lesions due to diabetes, a serious metabolic disease affecting millions of people around the world. This disorder disturbs the natural blood glucose levels causing various pathophysiological changes in different systems across the human body. Diabetic retinopathy is the medical term that describes the condition when the fundus and the retinal vessels are affected by diabetes. As in other diseases, small vessels play a crucial role in the onset, the development, and the outcome of the retinopathy. More importantly, at the latest stage, new small vessels, or neovascularizations, growth constitutes a factor of significant risk for blindness. Therefore, there is a need to detect all the changes that occur in the small retinal vessels with the aim of characterizing the vessels to healthy or abnormal. The characterization, in turn, can facilitate the detection of a specific retinopathy locally, like the sight-threatening proliferative diabetic retinopathy. Segmentation techniques can automatically isolate important anatomical structures like the vessels, and provide this information to the physician to assist him in the final decision. In comprehensive systems for the automatization of DR detection, small vessels role is significant as missing them early in a CAD pipeline might lead to an increase in the false positive rate of red lesions in subsequent steps. So far, the efforts have been concentrated mostly on the accurate localization of the medium range vessels. In contrast, the existing models are weak in case of the small vessels. The required generalization to adapt an existing model does not allow the approaches to be flexible, yet robust to compensate for the increased variability in the appearance as well as the interference with the background. So far, the current template models (matched filtering, line detection, and morphological processing) assume a general shape for the vessels that is not enough to approximate the narrow, curved, characteristics of the small vessels. Additionally, due to the weak contrast in the small vessel regions, the current segmentation and the tracking methods produce fragmented or discontinued results. Alternatively, the small vessel segmentation can be accomplished at the expense of x background noise magnification, in the case of using thresholding or the image derivatives methods. Furthermore, the proposed deformable models are not able to propagate a contour to the full extent of the vasculature in order to enclose all the small vessels. The deformable model external forces are ineffective to compensate for the low contrast, the low width, the high variability in the small vessel appearance, as well as the discontinuities. Internal forces, also, are not able to impose a global shape constraint to the contour that could be able to approximate the variability in the appearance of the vasculature in different categories of vessels. Finally, machine learning approaches require the training of a classifier on a labelled set. Those sets are difficult to be obtained, especially in the case of the smallest vessels. In the case of the unsupervised methods, the user has to predefine the number of clusters and perform an effective initialization of the cluster centers in order to converge to the global minimum. This dissertation expanded the previous research work and provides a new segmentation method for the smallest retinal vessels. Multi-scale line detection (MSLD) is a recent method that demonstrates good segmentation performance in the retinal images, while tensor voting is a method first proposed for reconnecting pixels. For the first time, we combined the line detection with the tensor voting framework. The application of the line detectors has been proved an effective way to segment medium-sized vessels. Additionally, perceptual organization approaches like tensor voting, demonstrate increased robustness by combining information coming from the neighborhood in a hierarchical way. Tensor voting is closer than standard models to the way human perception functions. As we show, it is a more powerful tool to segment small vessels than the existing methods. This specific combination allows us to overcome the apparent fragmentation challenge of the template methods at the smallest vessels. Moreover, we thresholded the line detection response adaptively to compensate for non-uniform images. We also combined the two individual methods in a multi-scale scheme in order to reconnect vessels at variable distances. Finally, we reconstructed the vessels from their extracted centerlines based on pixel painting as complete geometric information is required to be able to utilize the segmentation in a CAD system. The segmentation was validated on a high-resolution fundus image database that in- cludes diabetic retinopathy images of varying stages, using standard discrepancy as well as perceptual-based measures. When only the smallest vessels are considered, the improve- ments in the sensitivity rate for the database against the standard multi-scale line detection method is 6.47%. For the perceptual-based measure, the improvement is 7.8% against the basic method. The second objective of the thesis was to implement a method for the characterization of isolated retinal areas into healthy or abnormal cases. Some of the original images, from which xi these patches are extracted, contain neovascularizations. Investigation of image features for the vessels characterization to healthy or abnormal constitutes an essential step in the direction of developing CAD system for the automatization of DR screening. Given that the amount of data will significantly increase under CAD systems, the focus on this category of vessels can facilitate the referral of sight-threatening cases to early treatment. In addition to the challenges that small healthy vessels pose, neovessels demonstrate an even higher degree of complexity as they form networks of convolved, twisted, looped thin vessels. The existing work is limited to the use of first-order characteristics extracted from the small segmented vessels that limits the study of patterns. Our contribution is in using the tensor voting framework to isolate the retinal vascular junctions and in turn using those junctions as points of interests. Second, we exploited second-order statistics computed on the junction spatial distribution to characterize the vessels as healthy or neovascularizations. In fact, the second-order spatial statistics extracted from the junction distribution are combined with widely used features to improve the characterization sensitivity by 9.09% over the state of art. The developed method proved effective for the segmentation of the retinal vessels. Higher order tensors along with the implementation of tensor voting via steerable filtering could be employed to further reduce the execution time, and resolve the challenges at vascular junctions. Moreover, the characterization could be advanced to the detection of prolifera- tive retinopathy by extending the supervised learning to include non-proliferative diabetic retinopathy cases or other pathologies. Ultimately, the incorporation of the methods into CAD systems could facilitate screening for the effective reduction of the vision-threatening diabetic retinopathy rates, or the early detection of other than ocular pathologies

    Evaluation of yarn characteristics using computer vision and image processing

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    Irregularity, hairiness and twist are among the most important characteristics that define yarn quality. This thesis describes computer vision and image processing techniques developed to evaluate these characteristics. The optical and electronic aspects such as the illumination, lens parameters and aberrations play crucial role on the quality of yam images and on the overall performance of image processing. The depth of field limitation being the most important restraint in yam imaging as well as image distortion in line scan cameras arising from digitisation and yam movement are modelled mathematically and verified through experiments both for front-lit and back-lit illuminations. Various light sources and arrangements are tested and relative advantages and disadvantages are discussed based on the image quality. Known problems in defining the hair-core boundaries and determining the total hairiness from yam images are addressed and image enhancement and processing algorithms developed to overcome these problems are explained. A method to simulate various yam scanning resolution conditions is described. Using this method, the minimum scanning resolution limits to measure the hairiness and irregularity are investigated. [Continues.

    Optimizing fMRI analysis in Schizophrenia research: methodology improvements

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    La Resonancia Magnética funcional (RMf) es una técnica moderna de neuroimagen que permite la localización de actividad neuronal con una alta resolución espacial. La técnica de RMf emplea los cambios locales de oxigenación en la sangre, reflejados como pequeños cambios en la intensidad en un tipo concreto de imagen de Resonancia Magnética. La habilidad de esta técnica en la detección de cambios en la función en el cerebro sano y enfermo, y la localización de función anormal convierte a la RMf en una técnica ideal para el tratamiento de numerosas enfermedades y lesiones neuronales. Ya se ha aplicado clínicamente en la localización de áreas funcionales afectadas por tumores, pre- y post- operativamente. La esquizofrenia, una vasta enfermedad que se encuentra presente en el uno por cien de la población global, es una dolencia que se ha estudiado recientemente mediante técnicas de neuroimagen funcional, con más de 300 estudios publicados en revistas sobre esquizofrenia y RMf. La comprensión de los sustratos neuronales de la esquizofrenia requiere una determinación precisa de la extensión y la distribución de anormalidades en la función y anatomía cerebrales. Ya que los síntomas tienen una distribución dispersa, se debería emplear una aproximación fenomemológica a esta enfermedad para relacionar anormalidades, síntomas y prognosis con precisión. Los pacientes que tienen principalmente síntomas positivos, tales como alucinaciones auditivas y delirios, pueden tener anomalías cerebrales diferentes a aquellos que tienen síntomas negativos pronunciados. Por tanto, en el presente estudios se ha seleccionado un síntoma positivo, la presencia de alucinaciones auditivas en pacientes esquizofrénicos, como el criterio de selección de un grupo homogéneo de pacientes esquizofrénicos auditivos. Esta tesis presenta la aplicación de la RMf al estudio de la enfermedad de la esquizofrenia. Finalmente, un nuevo método de filtrado de datos de RMf, el NL-means, se ha propuesto y se sugiere suLull Noguera, JJ. (2008). Optimizing fMRI analysis in Schizophrenia research: methodology improvements [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/48597Palanci

    Pattern Formation and Organization of Epithelial Tissues

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    Developmental biology is a study of how elaborate patterns, shapes, and functions emerge as an organism grows and develops its body plan. From the physics point of view this is very much a self-organization process. The genetic blueprint contained in the DNA does not explicitly encode shapes and patterns an animal ought to make as it develops from an embryo. Instead, the DNA encodes various proteins which, among other roles, specify how different cells function and interact with each other. Epithelial tissues, from which many organs are sculpted, serve as experimentally- and analytically-tractable systems to study patterning mechanisms in animal development. Despite extensive studies in the past decade, the mechanisms that shape epithelial tissues into functioning organs remain incompletely understood. This thesis summarizes various studies we have done on epithelial organization and patterning, both in abstract theory and in close contact with experiments. A novel mechanism to establish cellular left-right asymmetry based on planar polarity instabilities is discussed. Tissue chirality is often assumed to originate from handedness of biological molecules. Here we propose an alternative where it results from spontaneous symmetry breaking of planar polarity mechanisms. We show that planar cell polarity (PCP), a class of well-studied mechanisms that allows epithelia to spontaneously break rotational symmetry, is also generically capable of spontaneously breaking reflection symmetry. Our results provide a clear interpretation of many mutant phenotypes, especially those that result in incomplete inversion. To bridge theory and experiments, we develop quantitative methods to analyze fluorescence microscopy images. Included in this thesis are algorithms to selectively project intensities from a surface in z-stack images, analysis of cells forming short chain fragments, analysis of thick fluorescent bands using steerable ridge detector, and analysis of cell recoil in laser ablation experiments. These techniques, though developed in the context of zebrafish retina mosaic, are general and can be adapted to other systems. Finally we explore correlated noise in morphogenesis of fly pupa notum. Here we report unexpected correlation of noise in cell movements between left and right halves of developing notum, suggesting that feedback or other mechanisms might be present to counteract stochastic noise and maintain left-right symmetry.PHDPhysicsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/138800/1/hjeremy_1.pd

    Multi-scale techniques for multi-dimensional data analysis

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    Large datasets of geometric data of various nature are becoming more and more available as sensors become cheaper and more widely used. Due to both their size and their noisy nature, special techniques must be employed to deal with them correctly. In order to efficiently handle this amount of data and to tackle the technical challenges they pose, we propose techniques that analyze a scalar signal by means of its critical points (i.e. maxima and minima), ranking them on a scale of importance, by which we can extrapolate important information of the input signal separating it from noise, thus dramatically reducing the complexity of the problem. In order to obtain a ranking of critical points we employ multi-scale techniques. The standard scale-space approach, however, is not sufficient when trying to track critical points across various scales. We start from an implementation of the scale-space which computes a linear interpolation between scales in order to make tracking of critical points easier. The linear interpolation of a process which is not itself linear, though, does not fulfill some theoretical properties of scale-space, thus making the tracking of critical points much harder. We propose an extension of this piecewiselinear scale-space implementation, which recovers the theoretical properties (e.g., to avoid the generation of new critical points as the scale increases) and keeps the tracking consistent. Next we combine the scale-space with another technique that comes from the topology theory: the classification of critical points based on their persistence value. While the scale-space applies a filtering in the frequency domain, by progressively smoothing the input signal with low-pass filters of increasing size, the computation of the persistence can be seen as a filtering applied in the amplitude domain, which progressively removes pairs of critical points based on their difference in amplitude. The two techniques, while being both relevant to the concept of scale, express different qualities of the critical points of the input signal; depending on the application domain we can use either of them, or, since they both have non-zero values only at critical points, they can be used together with a linear combination. The thesis will be structured as follows: In Chapter 1 we will present an overview on the problem of analyzing huge geometric datasets, focusing on the problem of dealing with their size and noise, and of reducing the problem to a subset of relevant samples. The Chapter 2 will contain a study of the state of the art in scale-space algorithms, followed by a more in-depth analysis of the virtually continuous framework used as base technique will be presented. In its last part, we will propose methods to extend these techniques in order to satisfy the axioms present in the continuous version of the scale-space and to have a stronger and more reliable tracking of critical points across scales, and the extraction of the persistence of critical points of a signal as a variant to the standard scale-space approach; we will show the differences between the two and discuss how to combine them. The Chapter 3 will introduce an ever growing source of data, the motion capture systems; we will motivate its importance by discussing the many applications in which it has been used for the past two decades. We will briefly summarize the different systems existing and then we will focus on a particular one, discussing its peculiarities and its output data. In Chapter 4, we will discuss the problem of studying intra-personal synchronization computed on data coming from such motion-capture systems. We will show how multi-scale approaches can be used to identify relevant instants in the motion and how these instants can be used to precisely study synchronization between the different parts of the body from which they are extracted. We will apply these techniques to the problem of generating a classifier to discriminate between martial artists of different skills who have been recorded doing karate\u2019s movements. In Chapter 5 will present a work on the automatic detection of relevant points of the human face from 3D data. We will show that the Gaussian curvature of the 3D surface is a good feature to distinguish the so-called fiducial points, but also that multi-scale techniques must be used to extract only relevant points and get rid of the noise. In closing, Chapter 6 will discuss an ongoing work about motion segmentation; after an introduction about the meaning and different possibilities of motion segmentation we will present the data we work with, the approach used to identify segments and some preliminary tools and results

    Modeling and performance analysis of a UAV-based sensor network for improved ATR

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    Automatic Target Recognition (ATR) is computer processing of images or signals acquired by sensors with the purpose to identify objects of interest (targets). This technology is a critical element for surveillance missions. Over the past several years there has been an increasing trend towards fielding swarms of unattended aerial vehicles (UAVs) operating as sensor networks in the air. This trend offers opportunities of integration ATR systems with a UAV-based sensor network to improve the recognition performance. This dissertation addresses some of design issues of ATR systems, explores recognition capabilities of sensor networks in the presence of various distortions and analyzes the limiting recognition performance of sensor networks.;We assume that each UAV is equipped with an optical camera. A model based recognition method for single and multiple frames is introduced. A complete ATR system, including detection, segmentation, recognition and clutter rejection, is designed and tested using synthetic and realistic images. The effects of environmental conditions on target recognition are also investigated.;To analyze and predict ATR performance of a recognition sensor network, a general methodology from information theory view point is used. Given the encoding method, the recognition system is analyzed using a recognition channel. The concepts of recognition capacity, error exponents and probability of outage are defined and derived for a PCA-based ATR system. Both the case of a single encoded image and the case of encoded correlated multiple frames are analyzed. Numerical evaluations are performed. Finally we discuss the joint recognition and communication problems. Three scenarios of a two node recognition sensor network are analyzed. The communication and recognition performances for each scenario are evaluated numerically

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

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    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

    Automated Segmentation for Connectomics Utilizing Higher-Order Biological Priors

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    This thesis presents novel methodological approaches for the automated segmentation of neurons from electron microscopic image volumes using machine learning techniques. New potentials for neural segmentation are revealed by incorporating (high-level) biological prior knowledge. This goes beyond the modeling of neural tissue which has been applied for the purpose of its segmentation, so far. Firstly, the V-Multicut algorithm is introduced which enables the consideration of topological constraints for segmented membranes. In this way, biologically implausible appearances of membranes are corrected. Secondly, this thesis proves that, in addition to local evidence and topological requirements for the detection of neural membranes, the consideration of high-level biological prior knowledge is beneficial. For this task, both the recently proposed Asymmetric Multiway Cut and the introduced Semantic Agglomerative Clustering algorithm are implemented and quantitatively evaluated. To be precise, the spatial separation of dendrites and axons in mammals is exploited to significantly improve the segmentation quality. Additionally, new ways to improve the scalability of the used algorithms are presented. All in all this thesis serves as another step towards fully automated segmentation of neurons and contributes to the field of connectomics
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