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Title: Multimodal magnetic resonance investigation of childhood metabolic neurodegenerative disease
Author: Davison, James Edward
ISNI:       0000 0004 2720 0424
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2012
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Background: The central nervous system is frequently affected in children with inherited metabolic disorders (IMD). The causes of the brain insult are incompletely understood, and novel methods are required for disease diagnosis and monitoring response to novel therapies. Aims & Methods: The study aimed to improve understanding of the pathogenesis of IMD-related neurodegeneration, and to identify potential disease biomarkers in specific IMD, by directly investigating alterations in brain tissue metabolite profiles using non-invasive in vivo magnetic resonance spectroscopy (MRS) in conjunction with conventional MRI brain scans. Results: MRI/MRS studies were performed on over 300 children. Normal brain metabolite profiles were established from a standard comparator cohort. A detailed quality analysis enabled combination of data from different scanner systems. Non-standard brain metabolites were detected in 2.3% of children. Metabolite-based methods of disease progression monitoring were evaluated in Hunter Syndrome. Mechanisms leading to strokes in patients with propionic acidaemia and to learning difficulties and epilepsy in argininosuccinic aciduria were explored using brain tissue metabolite profiling. Conclusions: Non-invasive in vivo brain tissue metabolite profiling is achievable using quantitative magnetic resonance spectroscopy in the routine clinical paediatric setting, and has utility in disease diagnostics, in monitoring disease progression and in investigating disease pathogenesis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QH301 Biology ; QH426 Genetics ; R Medicine (General) ; RB Pathology ; RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry ; RJ Pediatrics