Quantitation in MRI : application to ageing and epilepsy

Multi-atlas propagation and label fusion techniques have recently been developed for segmenting the human brain into multiple anatomical regions. In this thesis, I investigate possible adaptations of these current state-of-the-art methods. The aim is to study ageing on the one hand, and on the other hand temporal lobe epilepsy as an example for a neurological disease. Overall effects are a confounding factor in such anatomical analyses. Intracranial volume (ICV) is often preferred to normalize for global effects as it allows to normalize for estimated maximum brain size and is hence independent of global brain volume loss, as seen in ageing and disease. I describe systematic differences in ICV measures obtained at 1.5T versus 3T, and present an automated method of measuring intracranial volume, Reverse MNI Brain Masking (RBM), based on tissue probability maps in MNI standard space. I show that this is comparable to manual measurements and robust against field strength differences. Correct and robust segmentation of target brains which show gross abnormalities, such as ventriculomegaly, is important for the study of ageing and disease. We achieved this with incorporating tissue classification information into the image registration process. The best results in elderly subjects, patients with TLE and healthy controls were achieved using a new approach using multi-atlas propagation with enhanced registration (MAPER). I then applied MAPER to the problem of automatically distinguishing patients with TLE with (TLE-HA) and without (TLE-N) hippocampal atrophy on MRI from controls, and determine the side of seizure onset. MAPER-derived structural volumes were used for a classification step consisting of selecting a set of discriminatory structures and applying support vector machine on the structural volumes as well as morphological similarity information such as volume difference obtained with spectral analysis. Acccuracies were 91-100 %, indicating that the method might be clinically useful. Finally, I used the methods developed in the previous chapters to investigate brain regional volume changes across the human lifespan in over 500 healthy subjects between 20 to 90 years of age, using data from three different scanners (2x 1.5T, 1x 3T), using the IXI database. We were able to confirm several known changes, indicating the veracity of the method. In addition, we describe the first multi-region, whole-brain database of normal ageing

Multivariate Analysis of MR Images in Temporal Lobe Epilepsy

Epilepsy stands aside from other neurological diseases because clinical patterns of progression are unknown: The etiology of each epilepsy case is unique and so it is the individual prognosis. Temporal lobe epilepsy (TLE) is the most frequent type of focal epilepsy and the surgical excision of the hippocampus and the surrounding tissue is an accepted treatment in refractory cases, specially when seizures become frequent increasingly affecting the performance of daily tasks and significantly decreasing the quality of life of the patient. The sensitivity of clinical imaging is poor for patients with no hippocampal involvement and invasive procedures such as the Wada test and intracranial EEG are required to detect and lateralize epileptogenic tissue. This thesis develops imaging processing techniques using quantitative relaxometry and diffusion tensor imaging with the aiming to provide a less invasive alternative when detectability is low. Chapter 2 develops the concept of individual feature maps on regions of interest. A laterality score on these maps correctly distinguished left TLE from right TLE in 12 out of 15 patients. Chapter 3 explores machine learning models to detect TLE, obtaining perfect classification for left patients, and 88.9% accuracy for right TLE patients. Chapter 4 focuses on temporal lobe asymmetry developing a voxel-based method for assessing asymmetry and verifying its applicability to individual predictions (92% accuracy) and group-wise statistical analyses. Informative ROI and voxel-based informative features are described for each experiment, demonstrating the relative importance of mean diffusivity over other MR imaging alternatives in identification and lateralization of TLE patients. Finally, the conclusion chapter discuss contributions, main limitations and outlining options for future research

Clinical Application of Machine Learning Models for Brain Imaging in Epilepsy: A Review

Epilepsy is a common neurological disorder characterized by recurrent and disabling seizures. An increasing number of clinical and experimental applications of machine learning (ML) methods for epilepsy and other neurological and psychiatric disorders are available. ML methods have the potential to provide a reliable and optimal performance for clinical diagnoses, prediction, and personalized medicine by using mathematical algorithms and computational approaches. There are now several applications of ML for epilepsy, including neuroimaging analyses. For precise and reliable clinical applications in epilepsy and neuroimaging, the diverse ML methodologies should be examined and validated. We review the clinical applications of ML models for brain imaging in epilepsy obtained from a PubMed database search in February 2021. We first present an overview of typical neuroimaging modalities and ML models used in the epilepsy studies and then focus on the existing applications of ML models for brain imaging in epilepsy based on the following clinical aspects: (i) distinguishing individuals with epilepsy from healthy controls, (ii) lateralization of the temporal lobe epilepsy focus, (iii) the identification of epileptogenic foci, (iv) the prediction of clinical outcomes, and (v) brain-age prediction. We address the practical problems and challenges described in the literature and suggest some future research directions

Optimizing Pilot Overhead for Ultra-Reliable Short-Packet Transmission

In this paper we optimize the pilot overhead for ultra-reliable short-packet transmission and investigate the dependence of this overhead on packet size and error probability. In particular, we consider a point-to-point communication in which one sensor sends messages to a central node, or base-station, over AWGN with Rayleigh fading channel. We formalize the optimization in terms of approximate achievable rates at a given block length, pilot length, and error probability. This leads to more accurate pilot overhead optimization. Simulation results show that it is important to take into account the packet size and the error probability when optimizing the pilot overhead.Comment: To be published on IEEE ICC 2017 Communication Theory Symposiu

Magnetoencephalography

This is a practical book on MEG that covers a wide range of topics. The book begins with a series of reviews on the use of MEG for clinical applications, the study of cognitive functions in various diseases, and one chapter focusing specifically on studies of memory with MEG. There are sections with chapters that describe source localization issues, the use of beamformers and dipole source methods, as well as phase-based analyses, and a step-by-step guide to using dipoles for epilepsy spike analyses. The book ends with a section describing new innovations in MEG systems, namely an on-line real-time MEG data acquisition system, novel applications for MEG research, and a proposal for a helium re-circulation system. With such breadth of topics, there will be a chapter that is of interest to every MEG researcher or clinician

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

Cortical Morphology and MRI Signal Intensity Analysis in Paediatric Epilepsy

Epilepsy encompasses a great variety of aetiologies, and as such is not a single disease but a group of diseases characterised by unprovoked seizures.The primary aim of the work presented in this thesis was to use multimodal structural imaging to improve understanding of epilepsy related brain pathology, both the epileptogenic lesions themselves and extralesional pathology, in order to improve pre-surgical planning in medicationresistant epilepsy and improve understanding of the underlying pathogenic mechanisms. The work focuses on 2 epilepsy aetiologies: focal cortical dysplasia (FCD) (chapters 2 and 3) and mesial temporal lobe epilepsy (chapters 4 & 5). Chapter 2 of this thesis develops surface-based, structural MRI post-processing techniques that can be applied to clinical T1 and FLAIR images to complement current MRI-based diagnosis of focal cortical dysplasias. Chapter 3 uses the features developed in Chapter 2 within a machine learning framework to automatically detect FCDs, obtaining 73% sensitivity using a neural network. Chapter 4 develops an in vivo method to explore neocortical gliosis in adults with TLE, while Chapter 5 applies this method to a paediatric cohort. Finally, the concluding chapter discusses contributions, main limitations and outlines options for future research