A study of the mechanisms of damage and recovery of the central nervous system in demyelinating diseases using diffusion tensor imaging and functional magnetic resonance imaging
The aim of this thesis was to develop and apply Diffusion Tensor Imaging (DTI) and functional Magnetic Resonance Imaging (fMRI) in patients with demyelinating diseases in order to provide further insights into the mechanisms of damage and recovery. We used DTI to investigate pathological changes in the normal-appearing (NA) brain of patients with multiple sclerosis (MS), using regions of interest. Our results showed that diffusion changes were associated with disability and progression in MS, and that the NA white matter damage related to focal lesions. We then extended the investigation to the whole white matter tracts, using the novel technique of diffusion-based tractography, in three separate studies. In the frst study, we assessed the reproducibility of fast marching tractography in quantifying the major white-matter pathways. In the second, we created probabilistic group maps of these tracts in healthy volunteers, in order to estimate their normal inter-subjects variability. In the third study, we employed these group mapping techniques to investigate pathologic changes in the optic radiations of patients affected by optic neuritis, and found that patients had a lower voxel-scale connectivity in the optic radiations when compared with controls. To complement these studies, we developed a motor paradigm that allows investigation of the brain functional response to active and passive movements of the foot. We then used this paradigm to determine the role of cortical reorganisation in patients with primary progressive MS, and concluded that brain functional changes, in our cohort of patients, represented both adaptive and non-adaptive responses to central nervous system damage. Finally, we combined the data obtained from tractography with those obtained by fMRI, in patients with optic neuritis, and demonstrated the potential of this methodology to understand the relationship between structural and functional mechanisms.