Rugg-Gunn, Fergus James; (2004) Imaging the neocortex in epilepsy with advanced MRI techniques. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

Current optimal MRI reveals an identifiable abnormality in up to 80% of patients with refractory focal epilepsy. The remaining 20% are classified as "MRI-negative" and surgical treatment of such patients is often associated with a poor outcome. The identification of a cerebral lesion is, therefore, an important goal in the management of these patients. The aim of this thesis was to implement four novel advanced MRI techniques - diffusion tensor imaging (DTI), magnetisation transfer imaging (MTI), T2-mapping (T2M) and double inversion recovery (DIR), to provide insights into the structural basis of seizure disorders that are currently cryptogenic. For each technique, normative data from 30 healthy control subjects were obtained. These were compared on a statistical voxel-by- voxel basis to imaging data derived from patients with refractory epilepsy and non-progressive acquired cerebral lesions, malformations of cortical development (MCD), or normal conventional MR imaging ("MRI-negative patients"). In patients with acquired lesions (infarcts, cerebral trauma, intracranial infections), and MCD (gyral abnormalities, heterotopias and focal cortical dysplasia) the advanced MRI techniques were sensitive in identifying abnormalities which had previously been visualised on conventional MRI. More importantly, however, there were areas that appeared normal on conventional imaging but which were identified as abnormal with the advanced MRI techniques, indicating additional sensitivity from the new methods. Individual analyses of the MRI-negative patients identified abnormalities which concurred with the presumed seizure foci in approximately 33% (DTI - 23%, MTI - 36%, T2M - 44% and DIR 30%). The areas of abnormality in the MRI-negative patients are most likely caused by disruption in the microstructural environment due to aetiological factors such as, occult dysgenesis or acquired damage, or as a result of repeated seizures, for example, atrophy, gliosis, and neuronal loss. In an MRI-negative patient with refractory focal epilepsy, histopathological examination of surgically excised tissue which displayed abnormal diffusion revealed extensive white matter gliosis. Further histopathological correlative data is required to validate these advanced MRI techniques more definitively. It is likely that that our positive findings in individual patients represent the most structurally abnormal of all the MRI-negative patients. With improvements in these techniques, further occult epileptogenic regions may be identified, which may guide invasive diagnostic procedures and possible epilepsy surgery.

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