Accurate assessment of multiple sclerosis pathology using high-field magnetic resonance and quantitative histology. (360G-Wellcome-075941_Z_04_A)

Using quantitative high-field magnetic resonance (MR) applied to post mortem multiple sclerosis (MS) brain tissue this project aims to establish accurate non-invasive measures for three fundamental pathological features of MS that are potentially of importance for the development of disability and recovery of clinical symptoms in people with this condition: (i) remyelination, (ii) lesions in the grey matter and (iii) gliosis. Furthermore we will explore the possible link between Glutamate as assessed by high-field MR spectroscopy (MRS) and quantitative histological measures (glutaminase activity, axonal count) in MS. Results from this project will have significant impact for the optimisation of MR studies in patients with MS in vivo. It will also facilitate the understanding of the mechanisms that cause disability in MS. T2-weighted (T2W) MR imaging (MRI) of the brain and spinal cord at a field strength of 1.5Tesla is sensitive in the detection of MS white matter (WM) lesions and thereby useful for diagnosis. However, T2W MRI is not specific for the individual pathological substrates of MS, e.g. demyelination, remyelination, axonal loss, gliosis, inflammation. Quantitative MR (qMR) techniques have the potential to be more specific for certain pathological components in MS brain and may therefore improve the monitoring of patients in natural history studies and treatment trials. In order to establish the specificity of qMR measurements, research into the pathological substrates of qMR measures is much needed. Several studies using standard magnetic field strengths have explored the relationship between signal changes detected on MRI and histopathological findings by investigating brain or spinal cord specimens of MS patients. However, the assessment by MR techniques of important aspects of MS pathology, such as lesions in the grey matter or the detailed investigation of WM lesions for signs of remyelination is limited, mainly by the low image resolution at 1.5T.