Magnollay, LC; (2017) Neuromyelitis optica (NMO): identifying imaging markers to improve diagnosis and inform therapeutic innovation. Doctoral thesis , UCL (University College London).

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Abstract

The main objective of the thesis is to use advanced MRI techniques to look for biomarkers that separate neuromyelitis optica spectrum disorders (NMOSD) from MS to improve diagnosis. NMOSD, a severe inflammatory disease which causes demyelination of the central nervous system, is characterised by optic neuritis (ON) and acute myelitis. Because of similarities with MS, NMOSD is not always correctly diagnosed at onset. As it is both more aggressive and faster progressing than MS, an early accurate diagnosis is crucial. For this thesis, three different MRI techniques were used, together with clinical assessments, to gain a better understanding of the differences between the two diseases. The first was neurite orientation dispersion and density imaging (NODDI), a diffusion MR technique used to analyse the microstructure of dendrites and axons. When applied to a single-shell dataset of RRMS patients, it was shown to detect more regions of diffusion abnormalities than FA maps. The second technique used is phase-sensitive inversion recovery (PSIR), to look for grey matter lesions. This first application to NMOSD patients led to the detection of grey matter lesions in nearly 50% of this group, as well as showing differences in leucocortical and juxtacortical lesions between NMOSD and MS, with juxtacortical lesions emerging as potential markers to differentiate between these diseases. The final part applies magnetisation transfer ratio (MTR) to the optic nerve to assess myelin integrity in both MS and NMOSD patients, together with optic coherence tomography (OCT) for the macula the retinal nerve fibre layer and visual assessments. Significant differences in MTR and OCT values were found in MS and NMOSD patients with ON compared to healthy controls (HC). Significant differences were found between the unaffected nerve of NMOSD patients and HC, but not between groups for either MTR values (after correction for age) and OCT measurements.

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