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Multimodal magnetic resonance investigation of childhood metabolic neurodegenerative disease

Davison, James Edward (2012)
Ph.D. thesis, University of Birmingham.

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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.

Type of Work:Ph.D. thesis.
Supervisor(s):Gissen, Paul and Peet, Andrew
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Clinical and Experimental Medicine
Subjects:QP Physiology
RB Pathology
RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
RJ Pediatrics
Institution:University of Birmingham
ID Code:3612
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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