Elsarraj, Afaf
(2016)
Advanced MRI techniques in studying multiple sclerosis pathology and lesion progression.
PhD thesis, University of Nottingham.
Abstract
There is an intimate spatial and functional relationship between cerebral microvasculature and the neuroglial tissues. It is known that both cerebrovascular and neuroglial alterations occur in multiple sclerosis (MS), but the pathophysiological relationships between these alterations, and the functional consequences, are not well characterised in vivo. Evidence from previous literature indicates that there are subtle changes in blood brain barrier (BBB) in normal appearing white matter (NAWM) of MS. However, lesion development due to subtle BBB leakage remains unclear. Additionally, the haemodynamic alteration and microstructural changes in grey matter (GM) is a well-known feature in MS. Nevertheless, the structural and functional relevance of GM perfusion and diffusion necessitate more exploration.
The main objective of this study was further interpretation of lesion development in MS, using advanced MRI techniques. Moreover, the study also aimed to provide valuable understandings into the association of different MRI measures with structural changes and clinical performance in MS, using advanced image analysis methods. The study has focused on the following goals: to determine BBB permeability in NAWM of MS and its correlation with microstructural damage, the relationship of subtle BBB leakage to lesion development, the association of grey matter perfusion with structural changes and functional performance and finally, the cortical diffusion alteration and its relevance with functional performance. Therefore, the main hypothesises of this thesis are: firstly, MS patients have impaired BBB permeability in NAWM compared to healthy controls. Secondly, that mean diffusivity (MD) in NAWM will correlate with BBB permeability in MS. Thirdly, that subtle BBB leakage in NAWM may precede lesion progression in MS. Fourthly, that cortical and deep GM perfusion is reduced in MS patients compared to healthy controls. Fifthly, that cortical perfusion correlates inversely with cortical atrophy in MS and finally, pattern of regional cortical MD variability will explain performance in different functional domains in MS.
All MS and healthy participants included in this study underwent an MRI scan at 3T. Functional and cognitive assessment was performed on MS. Dynamic contrast enhance-MRI was used to generate perfusion and permeability maps. The microstructural changes were measured using diffusion imaging. The cortical perfusion and diffusion changes were explored by Surface based analysis approach.
Increased BBB permeability in NAWM of MS was detected when compared to healthy controls (p<0.05) and it revealed an association with MD in NAWM (r= 0.48, p = 0.01). The findings also revealed subtle BBB breakdown indicated by an increase in the permeability parameter (Ktrans) in prelesion NAWM. GM hypoperfusion was shown in MS when compared to healthy controls (P<0.05). However, surface based analysis revealed no correlation between cortical hypoperfusion with cortical atrophy and microstructural damage in MS. Furthermore, there was no association between GM perfusion and clinical scores. In addition, the cortical diffusion alteration revealed vertex-wise correlation with functional scores in MS (P<0.05).
In conclusion, advanced MRI and advanced image analysis in this study has delivered novel insights on lesion development and other pathological changes affecting GM and WM in MS, which might have prognostic and therapeutic importance in MS.
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