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

Doctor of Philosophy

dissertationDiffusion magnetic resonance imaging (dMRI) has become a popular technique to detect brain white matter structure. However, imaging noise, imaging artifacts, and modeling techniques, etc., create many uncertainties, which may generate misleading information for further analysis or applications, such as surgical planning. Therefore, how to analyze, effectively visualize, and reduce these uncertainties become very important research questions. In this dissertation, we present both rank-k decomposition and direct decomposition approaches based on spherical deconvolution to decompose the fiber directions more accurately for high angular resolution diffusion imaging (HARDI) data, which will reduce the uncertainties of the fiber directions. By applying volume rendering techniques to an ensemble of 3D orientation distribution function (ODF) glyphs, which we call SIP functions of diffusion shapes, one can elucidate the complex heteroscedastic structural variation in these local diffusion shapes. Furthermore, we quantify the extent of this variation by measuring the fraction of the volume of these shapes, which is consistent across all noise levels, the certain volume ratio. To better understand the uncertainties in white matter fiber tracks, we propose three metrics to quantify the differences between the results of diffusion tensor magnetic resonance imaging (DT-MRI) fiber tracking algorithms: the area between corresponding fibers of each bundle, the Earth Mover's Distance (EMD) between two fiber bundle volumes, and the current distance between two fiber bundle volumes. Based on these metrics, we discuss an interactive fiber track comparison visualization toolkit we have developed to visualize these uncertainties more efficiently. Physical phantoms, with high repeatability and reproducibility, are also designed with the hope of validating the dMRI techniques. In summary, this dissertation provides a better understanding about uncertainties in diffusion magnetic resonance imaging: where and how much are the uncertainties? How do we reduce these uncertainties? How can we possibly validate our algorithms

Diffusion Tensor Imaging Tractography of the Facial Nerve for the Pre-Surgical Plan in Patients with Vestibular Schwannoma

Patients with vestibular schwannoma (VS) may experience facial nerve (FN) damage after surgery. The aim of this thesis is to evaluate the feasibility to use DTI fiber tracking for the preoperative determination of FN course in patients with VS and to optimize the DTI sequence to decrease the acquisition time. The results show that the probabilistic iFOD2 algorithm, applied to multi-shell DTI protocol, is the most suitable for FN reconstruction in all the five patients analyzed

Fast diffusion MRI based on sparse acquisition and reconstruction for long-term population imaging

Diffusion weighted magnetic resonance imaging (dMRI) is a unique MRI modality to probe the diffusive molecular transport in biological tissue. Due to its noninvasiveness and its ability to investigate the living human brain at submillimeter scale, dMRI is frequently performed in clinical and biomedical research to study the brain’s complex microstructural architecture. Over the last decades large prospective cohort studies have been set up with the aim to gain new insights into the development and progression of brain diseases across the life span and to discover biomarkers for disease prediction and potentially prevention. To allow for diverse brain imaging using different MRI modalities, stringent scan time limits are typically imposed in population imaging. Nevertheless, population studies aim to apply advanced and thereby time consuming dMRI protocols that deliver high quality data with great potential for future analysis. To allow for time-efficient but also versatile diffusion imaging, this thesis contributes to the investigation of accelerating diffusion spectrum imaging (DSI), an advanced dMRI technique that acquires imaging data with high intra-voxel resolution of tissue microstructure. Combining state-of-the-art parallel imaging and the theory of compressed sensing (CS) enables the acceleration of spatial encoding and diffusion encoding in dMRI. In this way, the otherwise long acquisition times in DSI can be reduced significantly. In this thesis, first, suitable q-space sampling strategies and basis functions are explored that fulfill the requirements of CS theory for accurate sparse DSI reconstruction. Novel 3D q-space sample distributions are investigated for CS-DSI. Moreover, conventional CS-DSI based on the discrete Fourier transform is compared for the first time to CS-DSI based on the continuous SHORE (simple harmonic oscillator based reconstruction and estimation) basis functions. Based on these findings, a CS-DSI protocol is proposed for application in a prospective cohort study, the Rhineland Study. A pilot study was designed and conducted to evaluate the CS-DSI protocol in comparison with state-of-the-art 3-shell dMRI and dedicated protocols for diffusion tensor imaging (DTI) and for the combined hindered and restricted model of diffusion (CHARMED). Population imaging requires processing techniques preferably with low computational cost to process and analyze the acquired big data within a reasonable time frame. Therefore, a pipeline for automated processing of CS-DSI acquisitions was implemented including both in-house developed and existing state-of-the-art processing tools. The last contribution of this thesis is a novel method for automatic detection and imputation of signal dropout due to fast bulk motion during the diffusion encoding in dMRI. Subject motion is a common source of artifacts, especially when conducting clinical or population studies with children, the elderly or patients. Related artifacts degrade image quality and adversely affect data analysis. It is, thus, highly desired to detect and then exclude or potentially impute defective measurements prior to dMRI analysis. Our proposed method applies dMRI signal modeling in the SHORE basis and determines outliers based on the weighted model residuals. Signal imputation reconstructs corrupted and therefore discarded measurements from the sparse set of inliers. This approach allows for fast and robust correction of imaging artifacts in dMRI which is essential to estimate accurate and precise model parameters that reflect the diffusive transport of water molecules and the underlying microstructural environment in brain tissue.Die diffusionsgewichtete Magnetresonanztomographie (dMRT) ist ein einzigartiges MRTBildgebungsverfahren, um die Diffusionsbewegung von Wassermolekülen in biologischem Gewebe zu messen. Aufgrund der Möglichkeit Schichtbilder nicht invasiv aufzunehmen und das lebende menschliche Gehirn im Submillimeter-Bereich zu untersuchen, ist die dMRT ein häufig verwendetes Bildgebungsverfahren in klinischen und biomedizinischen Studien zur Erforschung der komplexen mikrostrukturellen Architektur des Gehirns. In den letzten Jahrzehnten wurden große prospektive Kohortenstudien angelegt, um neue Einblicke in die Entwicklung und den Verlauf von Gehirnkrankheiten über die Lebenspanne zu erhalten und um Biomarker zur Krankheitserkennung und -vorbeugung zu bestimmen. Um durch die Verwendung unterschiedlicher MRT-Verfahren verschiedenartige Schichtbildaufnahmen des Gehirns zu ermöglich, müssen Scanzeiten typischerweise stark begrenzt werden. Dennoch streben Populationsstudien die Anwendung von fortschrittlichen und daher zeitintensiven dMRT-Protokollen an, um Bilddaten in hoher Qualität und mit großem Potential für zukünftige Analysen zu akquirieren. Um eine zeiteffizente und gleichzeitig vielseitige Diffusionsbildgebung zu ermöglichen, leistet diese Dissertation Beiträge zur Untersuchung von Beschleunigungsverfahren für die Bildgebung mittels diffusion spectrum imaging (DSI). DSI ist ein fortschrittliches dMRT-Verfahren, das Bilddaten mit hoher intra-voxel Auflösung der Gewebestruktur erhebt. Werden modernste Verfahren zur parallelen MRT-Bildgebung mit der compressed sensing (CS) Theorie kombiniert, ermöglicht dies eine Beschleunigung der räumliche Kodierung und der Diffusionskodierung in der dMRT. Dadurch können die ansonsten langen Aufnahmezeiten für DSI erheblich reduziert werden. In dieser Arbeit werden zuerst geeigenete Strategien zur Abtastung des q-space sowie Basisfunktionen untersucht, welche die Anforderungen der CS-Theorie für eine korrekte Signalrekonstruktion der dünnbesetzten DSI-Daten erfüllen. Neue 3D-Verteilungen von Messpunkten im q-space werden für die Verwendung in CS-DSI untersucht. Außerdem wird konventionell auf der diskreten Fourier-Transformation basierendes CS-DSI zum ersten Mal mit einem CS-DSI Verfahren verglichen, welches kontinuierliche SHORE (simple harmonic oscillator based reconstruction and estimation) Basisfunktionen verwendet. Aufbauend auf diesen Ergebnissen wird ein CS-DSI-Protokoll zur Anwendung in einer prospektiven Kohortenstudie, der Rheinland Studie, vorgestellt. Eine Pilotstudie wurde entworfen und durchgeführt, um das CS-DSI-Protokoll im Vergleich mit modernster 3-shell-dMRT und mit dedizierten Protokollen für diffusion tensor imaging (DTI) und für das combined hindered and restricted model of diffusion (CHARMED) zu evaluieren. Populationsbildgebung erfordert Prozessierungsverfahren mit möglichst geringem Rechenaufwand, um große akquirierte Datenmengen in einem angemessenen Zeitrahmen zu verarbeiten und zu analysieren. Dafür wurde eine Pipeline zur automatisierten Verarbeitung von CS-DSI-Daten implementiert, welche sowohl eigenentwickelte als auch bereits existierende moderene Verarbeitungsprogramme enthält. Der letzte Beitrag dieser Arbeit ist eine neue Methode zur automatischen Detektion und Imputation von Signalabfall, welcher durch schnelle Bewegungen während der Diffusionskodierung in der dMRT entsteht. Bewegungen der Probanden während der dMRT-Aufnahme sind eine häufige Ursache für Bildfehler, vor allem in klinischen oder Populationsstudien mit Kindern, alten Menschen oder Patienten. Diese Artefakte vermindern die Datenqualität und haben einen negativen Einfluss auf die Datenanalyse. Daher ist es das Ziel, fehlerhafte Messungen vor der dMRI-Analyse zu erkennen und dann auszuschließen oder wenn möglich zu ersetzen. Die vorgestellte Methode verwendet die SHORE-Basis zur dMRT-Signalmodellierung und bestimmt Ausreißer mit Hilfe von gewichteten Modellresidualen. Die Datenimputation rekonstruiert die unbrauchbaren und daher verworfenen Messungen mit Hilfe der verbleibenden, dünnbesetzten Menge an Messungen. Dieser Ansatz ermöglicht eine schnelle und robuste Korrektur von Bildartefakten in der dMRT, welche erforderlich ist, um korrekte und präzise Modellparameter zu schätzen, die die Diffusionsbewegung von Wassermolekülen und die zugrundeliegende Mikrostruktur des Gehirngewebes reflektieren

Anisotropy Across Fields and Scales

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

Anisotropy Across Fields and Scales

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

Robust processing of diffusion weighted image data

The work presented in this thesis comprises a proposed robust diffusion weighted magnetic resonance imaging (DW-MRI) pipeline, each chapter detailing a step designed to ultimately transform raw DW-MRI data into segmented bundles of coherent fibre ready for more complex analysis or manipulation. In addition to this pipeline we will also demonstrate, where appropriate, ways in which each step could be optimized for the maxillofacial region, setting the groundwork for a wider maxillofacial modelling project intended to aid surgical planning. Our contribution begins with RESDORE, an algorithm designed to automatically identify corrupt DW-MRI signal elements. While slower than the closest alternative, RESDORE is also far more robust to localised changes in SNR and pervasive image corruptions. The second step in the pipeline concerns the retrieval of accurate fibre orientation distribution functions (fODFs) from the DW-MRI signal. Chapter 4 comprises a simulation study exploring the application of spherical deconvolution methods to `generic' fibre; finding that the commonly used constrained spherical harmonic deconvolution (CSHD) is extremely sensitive to calibration but, if handled correctly, might be able to resolve muscle fODFs in vivo. Building upon this information, Chapter 5 conducts further simulations and in vivo image experimentation demonstrating that this is indeed the case, allowing us to demonstrate, for the first time, anatomically plausible reconstructions of several maxillofacial muscles. To complete the proposed pipeline, Chapter 6 then introduces a method for segmenting whole volume streamline tractographies into anatomically valid bundles. In addition to providing an accurate segmentation, this shape-based method does not require computationally expensive inter-streamline comparisons employed by other approaches, allowing the algorithm to scale linearly with respect to the number of streamlines within the dataset. This is not often true for comparison based methods which in the best case scale in higher linear time but more often by O(N2) complexity