Reconstructing diffusion kurtosis tensors from sparse noisy measurements

Diffusion kurtosis imaging (DKI) is a recent MRI based method that can quantify deviation from Gaussian behavior using a kurtosis tensor. DKI has potential value for the assessment of neurologic diseases. Existing techniques for diffusion kurtosis imaging typically need to capture hundreds of MRI images, which is not clinically feasible on human subjects. In this paper, we develop robust denoising and model fitting methods that make it possible to accurately reconstruct a kurtosis tensor from 75 or less noisy measurements. Our denoising method is based on subspace learning for multi-dimensional signals and our model fitting technique uses iterative reweighting to effectively discount the influences of outliers. The total data acquisition time thus drops significantly, making diffusion kurtosis imaging feasible for many clinical applications involving human subjects. © 2010 IEEE.published_or_final_versionThe 17th IEEE International Conference on Image Processing (ICIP 2010), Hong Kong, China, 26-29 September 2010. In Proceedings of the 17th ICIP, 2010, p. 4185-418

Diffusion kurtosis imaging based on adaptive spherical integral

Diffusion kurtosis imaging (DKI) is a recent approach in medical engineering that has potential value for both neurological diseases and basic neuroscience research. In this letter, we develop a robust method based on adaptive spherical integral that can compute kurtosis based quantities more precisely and efficiently. Our method integrates spherical trigonometry with a recursive computational scheme to make numerical estimations in kurtosis imaging convergent. Our algorithm improves the efficiency of computing integral invariants based on reconstructed diffusion kurtosis tensors and makes DKI better prepared for further clinical applications. © 2011 IEEE.link_to_subscribed_fulltex

Unsupervised methods for large-scale, cell-resolution neural data analysis

In order to keep up with the volume of data, as well as the complexity of experiments and models in modern neuroscience, we need scalable and principled analytic programmes that take into account the scientific goals and the challenges of biological experiments. This work focuses on algorithms that tackle problems throughout the whole data analysis process. I first investigate how to best transform two-photon calcium imaging microscopy recordings – sets of contiguous images – into an easier-to-analyse matrix containing time courses of individual neurons. For this I first estimate how the true fluorescence signal gets transformed by tissue artefacts and the microscope setup, by learning the parameters of a realistic physical model from recorded data. Next, I describe how individual neural cell bodies may be segmented from the images, based on a cost function tailored to neural characteristics. Finally, I describe an interpretable non-linear dynamical model of neural population activity, which provides immediate scientific insight into complex system behaviour, and may spawn a new way of investigating stochastic non-linear dynamical systems. I hope the algorithms described here will not only be integrated into analytic pipelines of neural recordings, but also point out that algorithmic design should be informed by communication with the broader community, understanding and tackling the challenges inherent in experimental biological science

Spherical deconvolution of multichannel diffusion MRI data with non-Gaussian noise models and spatial regularization

Spherical deconvolution (SD) methods are widely used to estimate the intra-voxel white-matter fiber orientations from diffusion MRI data. However, while some of these methods assume a zero-mean Gaussian distribution for the underlying noise, its real distribution is known to be non-Gaussian and to depend on the methodology used to combine multichannel signals. Indeed, the two prevailing methods for multichannel signal combination lead to Rician and noncentral Chi noise distributions. Here we develop a Robust and Unbiased Model-BAsed Spherical Deconvolution (RUMBA-SD) technique, intended to deal with realistic MRI noise, based on a Richardson-Lucy (RL) algorithm adapted to Rician and noncentral Chi likelihood models. To quantify the benefits of using proper noise models, RUMBA-SD was compared with dRL-SD, a well-established method based on the RL algorithm for Gaussian noise. Another aim of the study was to quantify the impact of including a total variation (TV) spatial regularization term in the estimation framework. To do this, we developed TV spatially-regularized versions of both RUMBA-SD and dRL-SD algorithms. The evaluation was performed by comparing various quality metrics on 132 three-dimensional synthetic phantoms involving different inter-fiber angles and volume fractions, which were contaminated with noise mimicking patterns generated by data processing in multichannel scanners. The results demonstrate that the inclusion of proper likelihood models leads to an increased ability to resolve fiber crossings with smaller inter-fiber angles and to better detect non-dominant fibers. The inclusion of TV regularization dramatically improved the resolution power of both techniques. The above findings were also verified in brain data

Towards non-parametric reconstruction of axon diameter distributions using diffusion MRI and regularized discrete linear modeling

The distribution of axon diameters (ADD) is an important white matter feature: it influences action potential speed, it has been shown to evolve during development, and also to be affected during pathological processes. Diffusion Magnetic Resonance Imaging is a powerful non-invasive tool that is sensitive to the displacement of water molecules. In theory, as axon diameters are well bellow the imaging resolution, the ADD can be estimated indirectly by fitting a biophysical model to the measured signal. Such an approach is the basis of microstructure imaging. Microstructure imaging usually relies on compartment models, splitting the signal into the intra-axonal or the extra-axonal compartments. However, in practice, ADD reconstruction remains a challenging problem, mainly due to model degeneracy (different solutions can have similar signals), the diameter lower bound which dictates the smallest diameter visible by the scanner, and the difficulty in modeling properly the extra-axonal signal. In this thesis, we addressed the challenges at stake by focusing on the intra-axonal and extra-axonal compartments separately. Model performance was evaluated by comparing estimates with the ground-truth provided by Monte Carlo simulations. Model degeneracy was addressed by introducing Laplacian regularization, which was shown to provide better ADD estimates when considering the intra-axonal signal only. Sensitivity to small diameters was improved by using a richer diffusion protocol designed to maximize sensitivity to a set of diameters, which was shown to provide reconstruction of unimodal and bimodal distributions, with sensitivity to population specific changes. Regarding the extra-axonal space, using a mixture of higher order tensors improved reconstruction of the signal compared to standard models. The proposed model is flexible enough to adapt to a variety of simulated signals, outperforming current models of hindered diffusion. Combining the results for both compartments slightly improved estimates for some of the simulated signals. We highlighted the similarity between the intra-axonal and extra-axonal signals, which might be the main limiting factor when using single Pulsed Gradient Spin Echo sequences

Nonparametric tests of structure for high angular resolution diffusion imaging in Q-space

High angular resolution diffusion imaging data is the observed characteristic function for the local diffusion of water molecules in tissue. This data is used to infer structural information in brain imaging. Nonparametric scalar measures are proposed to summarize such data, and to locally characterize spatial features of the diffusion probability density function (PDF), relying on the geometry of the characteristic function. Summary statistics are defined so that their distributions are, to first-order, both independent of nuisance parameters and also analytically tractable. The dominant direction of the diffusion at a spatial location (voxel) is determined, and a new set of axes are introduced in Fourier space. Variation quantified in these axes determines the local spatial properties of the diffusion density. Nonparametric hypothesis tests for determining whether the diffusion is unimodal, isotropic or multi-modal are proposed. More subtle characteristics of white-matter microstructure, such as the degree of anisotropy of the PDF and symmetry compared with a variety of asymmetric PDF alternatives, may be ascertained directly in the Fourier domain without parametric assumptions on the form of the diffusion PDF. We simulate a set of diffusion processes and characterize their local properties using the newly introduced summaries. We show how complex white-matter structures across multiple voxels exhibit clear ellipsoidal and asymmetric structure in simulation, and assess the performance of the statistics in clinically-acquired magnetic resonance imaging data.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS441 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

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

Denoising and fast diffusion imaging with physically constrained sparse dictionary learning

International audienceDiffusion-weighted imaging (DWI) allows imaging the geometry of water diffusion in biological tissues. However, DW images are noisy at high b-values and acquisitions are slow when using a large number of measurements, such as in Diffusion Spectrum Imaging (DSI). This work aims to denoise DWI and reduce the number of required measurements, while maintaining data quality. To capture the structure of DWI data, we use sparse dictionary learning constrained by the physical properties of the signal: symmetry and positivity. The method learns a dictionary of diffusion profiles on all the DW images at the same time and then scales to full brain data. Its performance is investigated with simulations and two real DSI datasets. We obtain better signal estimates from noisy measurements than by applying mirror symmetry through the q-space origin, Gaussian denoising or state-of- the-art non-local means denoising. Using a high-resolution dictionary learnt on another subject, we show that we can reduce the number of images acquired while still generating high resolution DSI data. Using dictionary learning, one can denoise DW images effectively and perform faster acquisitions. Higher b-value acquisitions and DSI techniques are possible with approximately 40 measurements. This opens important perspectives for the connectomics community using DSI

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