Quantitative MRI correlates of hippocampal and neocortical pathology in intractable temporal lobe epilepsy

Intractable or drug-resistant epilepsy occurs in over 30% of epilepsy patients, with many of these patients undergoing surgical excision of the affected brain region to achieve seizure control. Advances in MRI have the potential to improve surgical treatment of epilepsy through improved identification and delineation of lesions. However, validation is currently needed to investigate histopathological correlates of these new imaging techniques. The purpose of this work is to investigate histopathological correlates of quantitative relaxometry and DTI from hippocampal and neocortical specimens of intractable TLE patients. To achieve this goal I developed and evaluated a pipeline for histology to in-vivo MRI image registration, which finds dense spatial correspondence between both modalities. This protocol was divided in two steps whereby sparsely sectioned histology from temporal lobe specimens was first registered to the intermediate ex-vivo MRI which is then registered to the in-vivo MRI, completing a pipeline for histology to in-vivo MRI registration. When correlating relaxometry and DTI with neuronal density and morphology in the temporal lobe neocortex, I found T1 to be a predictor of neuronal density in the neocortical GM and demonstrated that employing multi-parametric MRI (combining T1 and FA together) provided a significantly better fit than each parameter alone in predicting density of neurons. This work was the first to relate in-vivo T1 and FA values to the proportion of neurons in GM. When investigating these quantitative multimodal parameters with histological features within the hippocampal subfields, I demonstrated that MD correlates with neuronal density and size, and can act as a marker for neuron integrity within the hippocampus. More importantly, this work was the first to highlight the potential of subfield relaxometry and diffusion parameters (mainly T2 and MD) as well as volumetry in predicting the extent of cell loss per subfield pre-operatively, with a precision so far unachievable. These results suggest that high-resolution quantitative MRI sequences could impact clinical practice for pre-operative evaluation and prediction of surgical outcomes of intractable epilepsy

Translation of Novel Imaging Techniques into Clinical Use for Patients with Epilepsy

Temporal lobe epilepsy is the most common focal epilepsy. Up to 40% of patients are refractory to medication. Anterior temporal lobe resection (ATLR) is an effective treatment but damage to the optic radiation can result in a visual field deficit (VFD) that precludes driving, a key goal of surgery. Diffusion tensor imaging tractography allows the in vivo delineation of white matter tracts such as the optic radiation. This thesis addresses the role of optic radiation tractography in planning and subsequently improving the safety of epilepsy surgery. I show how tractography assists risk stratification and surgical planning in patients with lesions near the optic radiation and assess the utility of different tractography methods for surgical planning. To derive the greatest benefit, tractography information should be available during surgery which requires correction for intraoperative brain shift and other sources of image distortion. I apply software developed at UCL in a clinical population underlying ATLR to show that postoperative imaging can predict the VFD and then use this software in real time during surgery in an intraoperative MRI suite. Updated anatomical scans can be acquired during surgery and tractography data accurately mapped on to these and displayed on the operating microscope display. I demonstrate that this image guidance allows the neurosurgeon to avoid significant VFD without affecting the seizure outcome. Diffusion imaging can also probe tissue microstructure. I explore how structural changes within the frontoparietal working memory network and temporal lobes are related to working memory impairment in TLE. I describe the structural changes that occur following ATLR showing both Wallerian degeneration and structural plasticity. Finally, I show how a novel diffusion model (NODDI) could aid the clinical assessment of patients with focal cortical dysplasia. The emphasis throughout this thesis is how diffusion imaging can be clinically useful and address clinically relevant outcomes

Enhancing Registration for Image-Guided Neurosurgery

Pharmacologically refractive temporal lobe epilepsy and malignant glioma brain tumours are examples of pathologies that are clinically managed through neurosurgical intervention. The aims of neurosurgery are, where possible, to perform a resection of the surgical target while minimising morbidity to critical structures in the vicinity of the resected brain area. Image-guidance technology aims to assist this task by displaying a model of brain anatomy to the surgical team, which may include an overlay of surgical planning information derived from preoperative scanning such as the segmented resection target and nearby critical brain structures. Accurate neuronavigation is hindered by brain shift, the complex and non-rigid deformation of the brain that arises during surgery, which invalidates assumed rigid geometric correspondence between the neuronavigation model and the true shifted positions of relevant brain areas. Imaging using an interventional MRI (iMRI) scanner in a next-generation operating room can serve as a reference for intraoperative updates of the neuronavigation. An established clinical image processing workflow for iMRI-based guidance involves the correction of relevant imaging artefacts and the estimation of deformation due to brain shift based on non-rigid registration. The present thesis introduces two refinements aimed at enhancing the accuracy and reliability of iMRI-based guidance. A method is presented for the correction of magnetic susceptibility artefacts, which affect diffusion and functional MRI datasets, based on simulating magnetic field variation in the head from structural iMRI scans. Next, a method is presented for estimating brain shift using discrete non-rigid registration and a novel local similarity measure equipped with an edge-preserving property which is shown to improve the accuracy of the estimated deformation in the vicinity of the resected area for a number of cases of surgery performed for the management of temporal lobe epilepsy and glioma

Development of an Atlas-Based Segmentation of Cranial Nerves Using Shape-Aware Discrete Deformable Models for Neurosurgical Planning and Simulation

Twelve pairs of cranial nerves arise from the brain or brainstem and control our sensory functions such as vision, hearing, smell and taste as well as several motor functions to the head and neck including facial expressions and eye movement. Often, these cranial nerves are difficult to detect in MRI data, and thus represent problems in neurosurgery planning and simulation, due to their thin anatomical structure, in the face of low imaging resolution as well as image artifacts. As a result, they may be at risk in neurosurgical procedures around the skull base, which might have dire consequences such as the loss of eyesight or hearing and facial paralysis. Consequently, it is of great importance to clearly delineate cranial nerves in medical images for avoidance in the planning of neurosurgical procedures and for targeting in the treatment of cranial nerve disorders. In this research, we propose to develop a digital atlas methodology that will be used to segment the cranial nerves from patient image data. The atlas will be created from high-resolution MRI data based on a discrete deformable contour model called 1-Simplex mesh. Each of the cranial nerves will be modeled using its centerline and radius information where the centerline is estimated in a semi-automatic approach by finding a shortest path between two user-defined end points. The cranial nerve atlas is then made more robust by integrating a Statistical Shape Model so that the atlas can identify and segment nerves from images characterized by artifacts or low resolution. To the best of our knowledge, no such digital atlas methodology exists for segmenting nerves cranial nerves from MRI data. Therefore, our proposed system has important benefits to the neurosurgical community

Segmentation d'images IRM du cerveau pour la construction d'un modèle anatomique destiné à la simulation bio-mécanique

Comment obtenir des données anatomiques pendant une neurochirurgie ? a été ce qui a guidé le travail développé dans le cadre de cette thèse. Les IRM sont actuellement utilisées en amont de l'opération pour fournir cette information, que ce soit pour le diagnostique ou pour définir le plan de traitement. De même, ces images pre-opératoires peuvent aussi être utilisées pendant l'opération, pour pallier la difficulté et le coût des images per-opératoires. Pour les rendre utilisables en salle d'opération, un recalage doit être effectué avec la position du patient. Cependant, le cerveau subit des déformations pendant la chirurgie, phénomène appelé Brain Shift, ce qui altère la qualité du recalage. Pour corriger cela, d'autres données per-opératoires peuvent être acquises, comme la localisation de la surface corticale, ou encore des images US localisées en 3D. Ce nouveau recalage permet de compenser ce problème, mais en partie seulement. Ainsi, des modèles mécaniques ont été développés, entre autres pour apporter des solutions à l'amélioration de ce recalage. Ils permettent ainsi d'estimer les déformations du cerveau. De nombreuses méthodes existent pour implémenter ces modèles, selon différentes lois de comportement et différents paramètres physiologiques. Dans tous les cas, cela requiert un modèle anatomique patient-spécifique. Actuellement, ce modèle est obtenu par contourage manuel, ou quelquefois semi-manuel. Le but de ce travail de thèse est donc de proposer une méthode automatique pour obtenir un modèle du cerveau adapté sur l'anatomie du patient, et utilisable pour une simulation mécanique. La méthode implémentée se base sur les modèles déformables pour segmenter les structures anatomiques les plus pertinentes dans une modélisation bio-mécanique. En effet, les membranes internes du cerveau sont intégrées: falx cerebri and tentorium cerebelli. Et bien qu'il ait été démontré que ces structures jouent un rôle primordial, peu d'études les prennent en compte. Par ailleurs, la segmentation résultante de notre travail est validée par comparaison avec des données disponibles en ligne. De plus, nous construisons un modèle 3D, dont les déformations seront simulées en utilisant une méthode de résolution par Éléments Finis. Ainsi, nous vérifions par des expériences l'importance des membranes, ainsi que celle des paramètres physiologiques.The general problem that motivates the work developed in this thesis is: how to obtain anatomical information during a neurosurgery?. Magnetic Resonance (MR) images are usually acquired before the surgery to provide anatomical information for diagnosis and planning. Also, the same images are commonly used during the surgery, because to acquire MRI images in the operating room is complex and expensive. To make these images useful inside the operating room, a registration between them and the patient's position has to be processed. The problem is that the brain suffers deformations during the surgery, in a process called brain shift, degrading the quality of registration. To correct this, intra-operative information may be used, for example, the position of the brain surface or US images localized in 3D. The new registration will compensate this problem, but only to a certain extent. Mechanical models of the brain have been developed as a solution to improve this registration. They allow to estimate brain deformation under certain boundary conditions. In the literature, there are a variety of methods for implementing these models, different equation laws used for continuum mechanic, and different reported mechanical properties of the tissues. However, a patient specific anatomical model is always required. Currently, most mechanical models obtain the associated anatomical model by manual or semi-manual segmentation. The aim of this thesis is to propose and implement an automatic method to obtain a model of the brain fitted to the patient's anatomy and suitable for mechanical modeling. The implemented method uses deformable model techniques to segment the most relevant anatomical structures for mechanical modeling. Indeed, the internal membranes of the brain are included: falx cerebri and tentorium cerebelli. Even though the importance of these structures is stated in the literature, only a few of publications include them in the model. The segmentation obtained by our method is assessed using the most used online databases. In addition, a 3D model is constructed to validate the usability of the anatomical model in a Finite Element Method (FEM). And the importance of the internal membranes and the variation of the mechanical parameters is studied.SAVOIE-SCD - Bib.électronique (730659901) / SudocGRENOBLE1/INP-Bib.électronique (384210012) / SudocGRENOBLE2/3-Bib.électronique (384219901) / SudocSudocFranceF

Computational modelling of brain shift in stereotactic neurosurgery

Navigation in stereotactic neurosurgery relies solely on preoperative images, with the location of anatomical targets defined relative to the skull. Displacement of the anatomical target from its expected position is a common complication during surgery; however, the magnitude of this deviation is currently unpredictable. One potential source of this error occurs with reorientation of the head alone and is known as positional brain shift (PBS). PBS is the focus of this thesis, which aims to better understand the phenomenon through computational methods. A finite element (FE) model was generated in FEBio, incorporating a novel spring element/fluid structure-interaction representation of the pia-arachnoid complex (PAC). The model was loaded to represent gravity in the prone and supine positions. Material parameter identification and sensitivity analysis were performed using statistical software, comparing the FE results to human in-vivo measurements. Results for the brain Ogden parameters