Novel imaging biomarkers for the diagnosis and study of Neuromyelitis optica

Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing demyelinating neurological condition that requires prompt diagnosis and treatment to prevent the accrual of significant disability, such as blindness and immobility. It is caused by antibodies to the aquaporin-4 water channel, which can be detected within the serum of patients and are therefore a highly specific biomarker for the condition. However NMOSD can have overlapping clinical features with the more prevalent demyelinating disease relapsing remitting multiple sclerosis (RRMS). Thus in the situation of a negative aquaporin-4 antibody assay result diagnostic distinction can be difficult to achieve. This in turn leads to a treatment dilemma as NMOSD requires long term immunosuppression, and disease modifying therapies used in RRMS can worsen disease activity in NMOSD.The work presented in this thesis aimed to find further biomarkers of NMOSD, focusing on conventional and quantitative magnetic resonance imaging, and markers of neurodegeneration. The principle findings are:Lesion probability mapping analysis revealed that T2 lesion distribution and morphology can distinguish RRMS from NMO with a 92% sensitivity and 96% specificity. Radiological criteria to aid diagnosis have been proposed.Quantitative imaging methods that provide complementary micro-structural measures within CNS tissue have shown that RRMS is associated with widespread neurodegenerative changes in the normal appearing tissue, where as NMO is lesion focused.NMO is not associated with diffuse global neurodegeneration in the non-lesioned CNS tissue over a one-year period as determined by serial MRI.Normalised thalamic and whole brain volume can be used in a function to help discriminate NMOSD and RRMSThis thesis therefore contributes the knowledge that conventional and quantitative imaging can distinguish NMOSD and RRMS, and provides practical methods in which to apply this to patient management. It is the first longitudinal quantitative imaging study of NMOSD and lends further proof that global or diffuse neurodegeneration of the normal appearing brain or spinal cord tissue is not a feature of this condition.This thesis is not currently available via ORA