Calvi, Alberto;
(2023)
Chronic active lesions in multiple sclerosis: novel MRI markers.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
The heterogeneity of multiple sclerosis (MS) clinical spectrum is in part explained by the differential distribution and accumulation of distinct demyelinating lesion types. At their onset, new lesions are recognised in early MS, while in the late disease stages the chronic active lesions predominate and are associated with disability progression. Pathologically, those lesions are characterised by activated iron-enriched macrophages-microglia at the border promoting radial expansion, and severe neuroaxonal loss in the core. Despite the availability of magnetic resonance imaging (MRI) markers for chronic inflammatory activity, their contribution to MS prognostication of disability progression is still unknown. In this work, the initial focus was on the pathobiology and radiological correlations, which was realised as a literature review on the topic of imaging chronic active lesions in MS. Then, a novel technique based on deformation field computation to detect slowly expanding lesions (SELs) was implemented. Firstly, the association between SELs and other MRI markers for MS inflammatory activity and neurodegeneration was analysed in a secondary-progressive MS trial to establish their impact on disability. Then, the work was extended to relapse-onset MS, including a combined analysis of SELs and persisting black holes (PBHs), as a surrogate of structural tissue damage using hypointensity on T1-weighted scans. In a further analysis, SELs and paramagnetic rim lesions (PRLs) at susceptibility imaging, as an alternative marker of chronic active lesions, were investigated in an early relapse-onset MS cohort. Finally, an evaluation of the volumetric evolution of the newly developed lesions, and including the evaluation of treatment effects, was conducted on a primary-progressive MS trial. The clinical impact of all the imaging markers assessed was combined with physical and cognitive data, to assess the evolution of MS disability. Overall, this work has provided an overview of the currently available imaging markers to evaluate chronic inflammatory activity in MS.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Chronic active lesions in multiple sclerosis: novel MRI markers |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL 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/10162952 |
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