Paling, DJ;
(2014)
Novel MRI techniques to investigate the pathophysiological mechanisms underlying disease progression and disability in multiple sclerosis.
Doctoral thesis , UCL (University College London).
Abstract
Most patients with multiple sclerosis (MS) develop progressive disease. Progression is ominous as there are no drugs able to alter this inexorable accrual of disability. In this thesis the literature on the pathology of MS is reviewed. Experimental and pathological studies that suggest energy failure may be a significant cause of the neuroaxonal loss underlying progression are discussed. The thesis then describes magnetic resonance imaging studies designed to investigate the importance of energy failure in vivo. R2’ is a measure of magnetic field inhomogeneity, and is increased by deoxyhaemaglobin within the vasculature. Whole brain R2’ mapping found that R2’ in was reduced in lesions and in normal appearing white matter suggesting that oxidative metabolism may be decreased. Energy failure may also be secondary to insufficient blood flow to tissue. This was investigated using an arterial spin labelled MRI sequence. This study showed that blood flow and bolus arrival time were actually increased in white matter in MS. These results suggest that there may be widespread vasodilation, particularly in white matter, despite possible reduction in oxidative metabolism. Lastly, since sodium is maintained at a low concentration in cells by an energy intensive pump, increase in sodium concentration could indicate cellular energy failure. Whole brain sodium imaging showed increase in sodium concentration in lesions and cortical grey matter in all subgroups of MS, but increases in normal appearing white matter and deep grey matter in progressive MS only. Associations were seen between sodium concentrations and disability suggesting that sodium imaging is sensitive to the pathology underlying progression. As a whole the results suggest that in MS there are widespread metabolic abnormalities effecting all parts of the brain. Particularly with sodium MRI, it provides preliminary validation that this may be a technique sensitive to early, clinically relevant, and potentially reversible pathophysiology.
| Type: | Thesis (Doctoral) |
|---|---|
| Title: | Novel MRI techniques to investigate the pathophysiological mechanisms underlying disease progression and disability in multiple sclerosis |
| Language: | English |
| Keywords: | Multiple sclerosis, Magnetic resonance imaging, Neuroaxonal loss, Disability, Progression, Sodium, Iron, Perfusion, Arterial transit time, Bolus arrival time, Cerebral blood flow, Mitochondria, Energy failure, Relaxation mapping, Spectroscopy, Atrophy, Deep grey matter, Basal ganglia |
| UCL classification: | UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1420448 |
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