Saudi Cultural Missions Theses & Dissertations
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Item Restricted Olfactory Mesenchymal Stromal Cells: A Potential Therapeutic Approach for Central Nervous System Repair(University of Glasgow, 2024) Alamoudi, Wesal; Lindsay, SusanMultiple sclerosis (MS) is an autoimmune mediated demyelinating disease that occurs in the central nervous system (CNS). The loss of myelin creates a disturbance in the flow of the electrical signals in the nerve cells leading to a range of neurological symptoms. Currently, only the inflammatory component is managed with no cure for the disease itself. A possible therapeutic approach is stem-cell based therapies. Bone marrow derived mesenchymal stromal cells (BM-MSCs) have been considered, but have limitations in promoting myelination. A newer approach is to utilize olfactory mucosa-derived MSCs (OM-MSCs) since they exist in a neurogenetic niche and provide more myelination enhancement. In this investigation, an in vitro and in vivo comparison of BM-MSCs and OM-MSCs was undertaken. OM-MSC condition media (CM) showed significant outcomes regarding OPC differentiation and the promotion of myelination in vitro. In the animal model of MS, experimental autoimmune encephalomyelitis (EAE), OM-MSC transplanted animals had reduced inflammation, myelin loss and astrocyte reactivity unlike BM-MSCs. This study also investigated the effect of OM-MSC-CM on IL-16-induced astrocyte reactivity in vitro. However, there was no significant effect. Taken together, our findings suggest that OM-MSCs should be considered as a therapeutic candidate to promote myelin repair in MS.16 0Item Restricted Assessment of advanced MRI techniques within the spinal cord as applied to Multiple sclerosis patients(University of Exeter, 2024-06-26) Al-shaari, Hussein; Fulford, JonathanRationale: Multiple sclerosis (MS) is a complex inflammatory autoimmune disease of the central nervous system (CNS) characterized by inflammation, demyelination, and axonal damage. Magnetic resonance imaging (MRI) is a non-invasive technique that has become integral to the clinical management of MS over the past 20 years. While conventional MRI has played an important role in MS diagnosis and disease progression, its relationship with clinical signs remains limited, because of a lack of specificity. Recognizing this limitation, new advances in MRI technology present exciting opportunities for more accurate insights into MS pathophysiology. Techniques like diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) have emerged as effective tools. Unlike conventional MRI, these advanced methods have a better association with the subtle pathology alterations associated with MS. DTI allows for the visualization of microstructural abnormalities in white matter tracts, providing more detailed information of demyelination and axonal integrity. On the other hand, MTI offers novel insights into the dynamics of bound and free water, offering information on the underlying pathophysiology. Research on techniques such as DTI and MTI, typically focuses on imaging of the brain and its findings frequently do not have a direct application to the spinal cord. Thus, there is currently a lack of knowledge regarding spinal cord changes in patients with MS using these techniques. Aims: The aim of this thesis was to evaluate the potential of DTI and MTI for determining cervical spinal cord (CSC) changes when using automated data processing software such as spinal cord toolbox (SCT) in assessing changes in the CSC in patients with relapsing remitting multiple sclerosis (RRMS). Method: The assessment of the cervical spinal cord (CSC) using these MRI techniques was investigated for each inter-vertebral level, spanning four vertebral segments between the upper limit of the vertebral body of C2 and lower limit of the vertebral body of C5 over the regions of interest within the whole cord white matter (WM), ventral column (VC), lateral column (LC), and dorsal column (DC). This thesis was developed to explore two parts. The first part focused on the assessment of the reliability of DTI and MTI in the CSC. A total of 20 healthy participants were recruited and scanned on two separate visits. The second part focused on the potential of DTI and MTI to evaluate changes in tissue structure in relapsing-remitting multiple sclerosis (RRMS) patients in comparison to the same healthy participants recruited for the reliability study. For this, 13 patients with RRMS were recruited through the MS clinic. Expanded disability status scale (EDSS) was used as a clinical measure to examine the correlation with DTI and MTI parameters. Results: The reliability assessment of both DTI and MTI in the CSC found that the relative within-participants reliability varied depending on location of the ROIs. There was difference in the mean values of the DTI measures magnetic transfer ratio (MTR) value between the RRMS group and controls, however the significance of these differences differed depending on the ROI location. The correlation between DTI and MTI metrics and EDSS did not reach significant levels. Conclusion: This thesis has demonstrated the potential of DTI and MTI to identify alterations in RRMS patients. The results will be helpful in guiding diagnosis as well as future research into MS disease therapies and patient monitoring.20 0Item Restricted Brain Imaging Biomarkers in Multiple Sclerosis(2023-05-10) Altokhis, Amjad; Evangelou , Nikos; Constantinescu, CrisBackground: 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.18 0