Mitchell, Tejal Navin; (2004) Quantitative MRI in cerebral developmental disorders and epilepsy. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

Despite recent advances in MRI, the structural basis for epilepsy in a significant proportion of patients remains unknown. This work investigates methods of MRI analysis that improve our detection of subtle structural abnormalities that are not seen on visual assessment of high resolution MRI. The additional information obtained from quantitative MRI analysis may also be informative in advancing knowledge about human cerebral development. We have developed automated methods for extracting information from MRI to derive quantitative measures, qMRI, of cerebral structure (grey and white matter volume, cortical thickness), connectivity (white matter surface area, callosal cross-sectional area) and complexity (gyrification index, fractal dimension). These methods were applied to control subjects (100) to investigate the structural relationships that exist within the normal brain and obtain a normal range for each measure in each region, revealing sex differences and regional asymmetries. Four adult subject groups were studied to explore the developmental and biological basis and clinical implications of these measures. These were subjects with known malformations of cerebral development (MCD) on visual MRI (82); PAX6 gene mutation (14); epilepsy patients in whom histopathological examination of cerebral tissue was available (100), of which 97 had undergone surgical resection for hippocampal sclerosis or focal cortical dysplasia and 3 in whom post mortem material was available; and patients with localisation-related epilepsy and normal visual MRI (51). The distribution and type of quantitative abnormalities did not correlate with the current classification of MCD, although those with diffuse MCD had more widespread quantitative structural abnormalities than those with focal MCD, even in visually normal areas. Subjects with PAX6 mutation had anatomical changes not previously described in humans. We were not able to detect microdysgenesis using our methods. Patients with quantitative structural abnormalities had a greater chance of having continuing seizures following surgical resection than could have been predicted on presurgical assessment. A third of patients with localisation-related epilepsy and normal qualitative MRI had quantitative abnormalities concordant with electroclinical data.

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