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Title: High-field and ultra high-field MR imaging in clinical and subclinical inflammatory demyelination
Author: Lim , Su-Yin
ISNI:       0000 0004 6351 3495
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2014
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This thesis explores the use of quantitative magnetic resonance imaging (MRI) at high-field (3T) and ultra high-field (7T) to detect abnormal changes in the normal-appearing grey (NAGM) and white matter (NAWM) in clinically isolated syndrome (CIS), relapsing-remitting multiple sclerosis (RRMS) and rheumatology patients who have had TNF-inhibitor (TNFi) therapy. This was investigated through an exploratory study at 7T comprising of a cohort of 27 CIS and 14 RRMS patients followed-up for 12 months, and a pilot cohort study at 3T comprising of 15 rheumatology patients (with rheumatoid arthritis or ankylosing spondylitis) alongside 7 RRMS control patients. The study at 7T focused on quantitative T1 relaxation (T1RT) in the normal-appearing brain tissues (NABT). Quantitative T1 relaxation values of normal-appearing brain tissue correlate with demyelination and neuroaxonal loss pathologically, and neurological disability clinically. Volumetric analysis of the deep grey matter (DGM) nuclei, which is implicated in clinical disability and disease conversion from CIS to RRMS, was also studied. In Chapter 3, T1RT in NABT regions at 7T is described, providing useful data to aid in future planning of 7T T1 studies. Additional observations were made noting the loss of physiological gender and regional NAWM T1 changes in CIS and RRMS patients, and the correlation between NAWM T1RT and T1 lesion load. In Chapter 4, the association between 7T imaging parameters and disability was explored. and the correlation between thalamic T1 RT and fatigue in RRMS patients was demonstrated, amongst other MRI and clinical measures. In Chapter 5, the prognostic value of baseline MRI measures (including T1 RT) at 7T in disability progression and disease conversion to clinically definite MS was investigated. 1 Changes in the NAWM T1RT and DGM volumes were observed longitudinally. Baseline caudate volume were shown to correlate with worsened EDSS score in CIS patients at follow-up. Trials of TNFi treatment have shown detrimental effects in MS patients, and rare but increasing numbers of cases of CNS demyelination are being reported in association with TNFi therapy. Reported clinical cases of demyelination following TNFi therapy and pharmacovigilance data however do not conclusively support a causal link between treatment and onset of demyelination. In Chapter 6, T1RT and MTR of lesions and NABT were measured in TNFi-treated rheumatology patients and compared to that of healthy subjects and RRMS controls, showing that TNFi-treated patients who were free of neurological symptoms do not demonstrate evidence of subclinical inflammatory demyelination in their white matter on MR imaging. This work has advanced knowledge in several aspects of imaging of clinical and subclinical demyelinating conditions. First, we provide evidence of the robustness of T1 imaging at 7T, its utility as an indicator of non-lesional brain tissue integrity, and the range of longitudinal change in CIS and MS. These findings will be helpful for the design and sample size estimations of future ultra high-field studies in MS. Second, we show for the first time that widespread subclinical demyelination does not occur in patients undergoing anti-TNF treatment. This is a reassuring finding for the majority of patients benefiting from this treatment.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available