Towards efficient neurosurgery: Image analysis for interventional MRI

Interventional magnetic resonance imaging (iMRI) is being increasingly used for performing imageguided neurosurgical procedures. Intermittent imaging through iMRI can help a neurosurgeon visualise the target and eloquent brain areas during neurosurgery and lead to better patient outcome. MRI plays an important role in planning and performing neurosurgical procedures because it can provide highresolution anatomical images that can be used to discriminate between healthy and diseased tissue, as well as identify location and extent of functional areas. This is of significant clinical utility as it helps the surgeons maximise target resection and avoid damage to functionally important brain areas. There is clinical interest in propagating the pre-operative surgical information to the intra-operative image space as this allows the surgeons to utilise the pre-operatively generated surgical plans during surgery. The current state of the art neuronavigation systems achieve this by performing rigid registration of pre-operative and intra-operative images. As the brain undergoes non-linear deformations after craniotomy (brain shift), the rigidly registered pre-operative images do not accurately align anymore with the intra-operative images acquired during surgery. This limits the accuracy of these neuronavigation systems and hampers the surgeon’s ability to perform more aggressive interventions. In addition, intra-operative images are typically of lower quality with susceptibility artefacts inducing severe geometric and intensity distortions around areas of resection in echo planar MRI images, significantly reducing their utility in the intraoperative setting. This thesis focuses on development of novel methods for an image processing workflow that aims to maximise the utility of iMRI in neurosurgery. I present a fast, non-rigid registration algorithm that can leverage information from both structural and diffusion weighted MRI images to localise target lesions and a critical white matter tract, the optic radiation, during surgical management of temporal lobe epilepsy. A novel method for correcting susceptibility artefacts in echo planar MRI images is also developed, which combines fieldmap and image registration based correction techniques. The work developed in this thesis has been validated and successfully integrated into the surgical workflow at the National Hospital for Neurology and Neurosurgery in London and is being clinically used to inform surgical decisions

Feasibility of functional MRI on point-of-care MR platforms

Magnetic resonance imaging (MRI) has proven to be a clinically valuable tool that can produce anatomical and functional images with improved soft tissue contrast compared to other imaging modalities. There has recently been a surge in low- and mid-field scanners due to hardware developments and innovative acquisition techniques. These compact scanners are accessible, offer reduced siting requirements and can be made operational at a reduced cost. This thesis aims to implement blood-oxygen-level-dependent (BOLD) resting-state functional MRI (fMRI) at such a mid-field point-of-care scanner. The availability of this technique can be beneficial to get neurological information in cases of traumatic brain injury, stroke, epilepsy, and dementia. This technique was previously not implemented at low- and mid-field since signal-to-noise ratio and the contrast scale with field strength. Studies were conducted to gauge the performance of an independent component analysis (ICA) based platform (GraphICA) to analyze artificially added noisy resting state functional data previously collected with a 3T scanner. This platform was used in later chapters to preprocess and perform functional connectivity studies with data from a mid-field scanner. A single echo gradient echo echoplanar imaging (GE-EPI) sequence is typically used for BOLD-based fMRI. Task-based fMRI experiments were performed with this sequence to gauge the feasibility of this technique on a mid-field scanner. Once the feasibility was established, the sequence was further optimized to suit mid-field scanners by considering all the imaging parameters. Resting-state experiments were conducted with an optimized single echo GE-EPI sequence with reduced dead time on a mid-field scanner. Temporal and image signal-to-noise ratio were calculated for different cortical regions. Along with that, functional connectivity studies and identification of resting-state networks were performed with GraphICA which demonstrated the feasibility of this resting-state fMRI at mid-field. The reliability and repeatability of the identified networks were assessed by comparing the networks identified with 3T data. Resting-state experiments were conducted with a multi-echo GE-EPI sequence to use the dead time due to long T2* at mid-field effectively. Temporal signal-to-noise was calculated for different cortical regions. Along with that, functional connectivity studies and identification of resting-state networks were performed with GraphICA which demonstrated the feasibility of this resting-state fMRI at mid-field

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

Preclinical MRI of the Kidney

This Open Access volume provides readers with an open access protocol collection and wide-ranging recommendations for preclinical renal MRI used in translational research. The chapters in this book are interdisciplinary in nature and bridge the gaps between physics, physiology, and medicine. They are designed to enhance training in renal MRI sciences and improve the reproducibility of renal imaging research. Chapters provide guidance for exploring, using and developing small animal renal MRI in your laboratory as a unique tool for advanced in vivo phenotyping, diagnostic imaging, and research into potential new therapies. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and thorough, Preclinical MRI of the Kidney: Methods and Protocols is a valuable resource and will be of importance to anyone interested in the preclinical aspect of renal and cardiorenal diseases in the fields of physiology, nephrology, radiology, and cardiology. This publication is based upon work from COST Action PARENCHIMA, supported by European Cooperation in Science and Technology (COST). COST (www.cost.eu) is a funding agency for research and innovation networks. COST Actions help connect research initiatives across Europe and enable scientists to grow their ideas by sharing them with their peers. This boosts their research, career and innovation. PARENCHIMA (renalmri.org) is a community-driven Action in the COST program of the European Union, which unites more than 200 experts in renal MRI from 30 countries with the aim to improve the reproducibility and standardization of renal MRI biomarkers

Experimental and Model-based Approaches to Directional Thalamic Deep Brain Stimulation

University of Minnesota Ph.D. dissertation. September 2016. Major: Biomedical Engineering. Advisor: Matthew Johnson. 1 computer file (PDF); xii, 181 pages.Deep brain stimulation (DBS) is an effective surgical procedure for the treatment of several brain disorders. However, the clinical successes of DBS hinges on several factors. Here, we describe the development of tools and methodologies in the context of thalamic DBS for essential tremor (ET) to address three key challenges: 1) accurate localization of nuclei and fiber pathways for stimulation, 2) model-based programming of high-density DBS electrode arrays (DBSA) and 3) in vivo assessment of computational DBS model predictions. We approached the first challenge through a multimodal imaging approach, utilizing high-field (7T) susceptibility-weighted imaging and diffusion-weighted imaging data. A nonlinear image deformation algorithm was used in conjunction with probabilistic fiber tractography to segment individual thalamic sub-nuclei and reconstruct their afferent fiber pathways. We addressed the second challenge by developing subject-specific computational model-based algorithms built on maximizing population activating function values within a target region using convex optimization principles. The algorithms converged within seconds and only required as many finite-element simulations as the number of electrodes on the DBSA being modeled. For the third challenge, we recorded (in two non-human primates) unit-spike data from neurons in the vicinity of chronically implanted thalamic DBSAs before, during and after high-frequency stimulation. A novel entropy-based method was developed to quantify the degree and significance of stimulation-induced changes in neuronal firing pattern. Results indicated that neurons modulated by thalamic DBS were distributed and not confined to the immediate proximity of the active electrode. For those that were modulated by DBS, their responses increasingly shifted from firing rate modulation to firing pattern modulation with increased stimulation amplitude. Additionally, strong low-pass filtering effect was observed where <4% of DBS pulses produced phase-locked spikes in cells exhibiting significant excitatory firing pattern modulation. Finally, we quantified the spatial distribution of neurons modulated by DBS by developing a novel spherical statistical framework for analysis. Together, these tools and methodologies are poised to improve our understanding of DBS mechanisms and improve the efficacy and efficiency of DBS therapy

Preclinical MRI of the kidney : methods and protocols

This Open Access volume provides readers with an open access protocol collection and wide-ranging recommendations for preclinical renal MRI used in translational research. The chapters in this book are interdisciplinary in nature and bridge the gaps between physics, physiology, and medicine. They are designed to enhance training in renal MRI sciences and improve the reproducibility of renal imaging research. Chapters provide guidance for exploring, using and developing small animal renal MRI in your laboratory as a unique tool for advanced in vivo phenotyping, diagnostic imaging, and research into potential new therapies. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and thorough, Preclinical MRI of the Kidney: Methods and Protocols is a valuable resource and will be of importance to anyone interested in the preclinical aspect of renal and cardiorenal diseases in the fields of physiology, nephrology, radiology, and cardiology. This publication is based upon work from COST Action PARENCHIMA, supported by European Cooperation in Science and Technology (COST). COST (www.cost.eu) is a funding agency for research and innovation networks. COST Actions help connect research initiatives across Europe and enable scientists to grow their ideas by sharing them with their peers. This boosts their research, career and innovation. PARENCHIMA (renalmri.org) is a community-driven Action in the COST program of the European Union, which unites more than 200 experts in renal MRI from 30 countries with the aim to improve the reproducibility and standardization of renal MRI biomarkers

Contributions of Continuous Max-Flow Theory to Medical Image Processing

Discrete graph cuts and continuous max-flow theory have created a paradigm shift in many areas of medical image processing. As previous methods limited themselves to analytically solvable optimization problems or guaranteed only local optimizability to increasingly complex and non-convex functionals, current methods based now rely on describing an optimization problem in a series of general yet simple functionals with a global, but non-analytic, solution algorithms. This has been increasingly spurred on by the availability of these general-purpose algorithms in an open-source context. Thus, graph-cuts and max-flow have changed every aspect of medical image processing from reconstruction to enhancement to segmentation and registration. To wax philosophical, continuous max-flow theory in particular has the potential to bring a high degree of mathematical elegance to the field, bridging the conceptual gap between the discrete and continuous domains in which we describe different imaging problems, properties and processes. In Chapter 1, we use the notion of infinitely dense and infinitely densely connected graphs to transfer between the discrete and continuous domains, which has a certain sense of mathematical pedantry to it, but the resulting variational energy equations have a sense of elegance and charm. As any application of the principle of duality, the variational equations have an enigmatic side that can only be decoded with time and patience. The goal of this thesis is to show the contributions of max-flow theory through image enhancement and segmentation, increasing incorporation of topological considerations and increasing the role played by user knowledge and interactivity. These methods will be rigorously grounded in calculus of variations, guaranteeing fuzzy optimality and providing multiple solution approaches to addressing each individual problem