Brain imaging biomarkers in Multiple Sclerosis
Background: Iron rim lesions (IRLs), white matter lesions (WMLs) accumulation and linear brain atrophy measurements have been suggested to be important imaging biomarkers in multiple sclerosis (MS). The extent to which these markers are related to MS diagnosis and predict disease prognosis remains u...
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| Format: | Thesis (University of Nottingham only) |
| Language: | English |
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2023
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| Online Access: | https://eprints.nottingham.ac.uk/73561/ |
| _version_ | 1848800790149332992 |
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| author | Altokhis, Amjad |
| author_facet | Altokhis, Amjad |
| author_sort | Altokhis, Amjad |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Background: Iron rim lesions (IRLs), white matter lesions (WMLs) accumulation and linear brain atrophy measurements have been suggested to be important imaging biomarkers in multiple sclerosis (MS). The extent to which these markers are related to MS diagnosis and predict disease prognosis remains unclear. Furthermore, research Magnetic Resonance Imaging (MRI) findings need validation in clinical settings before they can be incorporated into clinical practice.
Methods: I conducted two reviews one was a mapping review on IRLs and the other was a meta-analysis on WMLs in MS. I then tested the diagnostic and prognostic usefulness of the IRL in two studies: (1) a large, cross-sectional, multi-centre study of patients with MS and mimicking disorders using 3T MRI, (2) a retrospective single-centre study of patients with first presentation of a clinically isolated syndrome (CIS) or at the early stage of the disease using 7T MRI. I also explored the utility of routine, non-standardised MRI scans measuring WMLs number, volume and linear measures of atrophy at the early stage of the disease and examined their role in predicting long-term disability.
Results: The IRLs achieved high specificity (up to 99%) in diagnosing MS compared to MS-mimics but low sensitivity of 24%. All patients with IRLs showing a central vein sign (CVS) had MS or CIS, giving a diagnostic specificity of 100% but equally low sensitivity of 21%. Moreover, the presence of IRLs was also a predictor of long-term disability, especially in patients with ≥4 IRLs. IRLs had a greater impact on disability compared to the WMLs number and volume. Linear brain atrophy of Inter-Caudate Distance (ICD) and Third Ventricle Width (TVW) had a significant impact in predicting disability after 10 years.
Conclusions: The perilesional IRLs may reduce diagnostic uncertainty in MS by being a highly specific imaging diagnostic biomarker, especially when used in conjunction with the CVS. Also, the presence and number of IRLs hold prognostic value for long-term physical disability in MS. Simple and reliable assessment of brain atrophy remains challenging in clinical practice. |
| first_indexed | 2025-11-14T20:57:09Z |
| format | Thesis (University of Nottingham only) |
| id | nottingham-73561 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T20:57:09Z |
| publishDate | 2023 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-735612023-07-31T04:41:06Z https://eprints.nottingham.ac.uk/73561/ Brain imaging biomarkers in Multiple Sclerosis Altokhis, Amjad Background: Iron rim lesions (IRLs), white matter lesions (WMLs) accumulation and linear brain atrophy measurements have been suggested to be important imaging biomarkers in multiple sclerosis (MS). The extent to which these markers are related to MS diagnosis and predict disease prognosis remains unclear. Furthermore, research Magnetic Resonance Imaging (MRI) findings need validation in clinical settings before they can be incorporated into clinical practice. Methods: I conducted two reviews one was a mapping review on IRLs and the other was a meta-analysis on WMLs in MS. I then tested the diagnostic and prognostic usefulness of the IRL in two studies: (1) a large, cross-sectional, multi-centre study of patients with MS and mimicking disorders using 3T MRI, (2) a retrospective single-centre study of patients with first presentation of a clinically isolated syndrome (CIS) or at the early stage of the disease using 7T MRI. I also explored the utility of routine, non-standardised MRI scans measuring WMLs number, volume and linear measures of atrophy at the early stage of the disease and examined their role in predicting long-term disability. Results: The IRLs achieved high specificity (up to 99%) in diagnosing MS compared to MS-mimics but low sensitivity of 24%. All patients with IRLs showing a central vein sign (CVS) had MS or CIS, giving a diagnostic specificity of 100% but equally low sensitivity of 21%. Moreover, the presence of IRLs was also a predictor of long-term disability, especially in patients with ≥4 IRLs. IRLs had a greater impact on disability compared to the WMLs number and volume. Linear brain atrophy of Inter-Caudate Distance (ICD) and Third Ventricle Width (TVW) had a significant impact in predicting disability after 10 years. Conclusions: The perilesional IRLs may reduce diagnostic uncertainty in MS by being a highly specific imaging diagnostic biomarker, especially when used in conjunction with the CVS. Also, the presence and number of IRLs hold prognostic value for long-term physical disability in MS. Simple and reliable assessment of brain atrophy remains challenging in clinical practice. 2023-07-31 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en cc_by https://eprints.nottingham.ac.uk/73561/1/PhD%20Thesis_Amjad%20Altokhis%20%2820198140%29%20.pdf Altokhis, Amjad (2023) Brain imaging biomarkers in Multiple Sclerosis. PhD thesis, University of Nottingham. MRI Magnetic Resonance Imaging Brain MS Multiple Sclerosis rim |
| spellingShingle | MRI Magnetic Resonance Imaging Brain MS Multiple Sclerosis rim Altokhis, Amjad Brain imaging biomarkers in Multiple Sclerosis |
| title | Brain imaging biomarkers in Multiple Sclerosis |
| title_full | Brain imaging biomarkers in Multiple Sclerosis |
| title_fullStr | Brain imaging biomarkers in Multiple Sclerosis |
| title_full_unstemmed | Brain imaging biomarkers in Multiple Sclerosis |
| title_short | Brain imaging biomarkers in Multiple Sclerosis |
| title_sort | brain imaging biomarkers in multiple sclerosis |
| topic | MRI Magnetic Resonance Imaging Brain MS Multiple Sclerosis rim |
| url | https://eprints.nottingham.ac.uk/73561/ |