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Moving beyond the tensor: Advanced characterisation of white matter microstructure in Huntington’s Disease using translational neuroimaging

Casella, Chiara 2021. Moving beyond the tensor: Advanced characterisation of white matter microstructure in Huntington’s Disease using translational neuroimaging. PhD Thesis, Cardiff University.
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Abstract

Huntington’s disease (HD) is a genetic neurodegenerative disorder leading to devastating cognitive, psychiatric and motor symptoms. Currently, this disease cannot be cured, and a research priority is to increase the understanding of its pathogenesis and to provide biomarkers for evaluating the efficacy of targeted therapies. Subtle and progressive white matter (WM) alterations have been observed early in HD progression, before clinical onset of the disease. However the aetiology of WM degeneration and its role in disease pathogenesis remain unclear. The assessment of early WM microstructural changes in the HD brain is therefore of fundamental importance, as this might prove useful for the identification of disease-related biomarkers and for measuring responsiveness to pharmaceutical and other therapeutic approaches. The primary aim of this work was to exploit both ultra-strong gradients (300 mT/m) and ultra-high field (7 Tesla, 9.4 Tesla) to assess WM microstructure in HD, using a variety of MRI techniques in premanifest and manifest patients, as well as in a mouse model of the disease. Specifically, this Thesis moved beyond the diffusion tensor framework, with the application of advanced WM microstructural imaging. Using these advanced MR techniques I was able to provide a comprehensive and detailed characterisation of WM microstructural alterations in the HD brain, and to better tease apart changes in apparent myelin from alterations in axon microstructure. Assessing both human patients and a mouse model of HD allowed for direct cross-species comparisons and bi-directional translation of results. Additionally, I was able to exploit the improved compartmental specificity obtained by complementing standard DTI metrics with advanced MRI measurements, to study the effects of two months of a novel drumming training on WM plasticity in patients with manifest HD.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Medicine
Psychology
Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Funders: Wellcome Trust
Date of First Compliant Deposit: 23 March 2021
Date of Acceptance: 23 March 2021
Last Modified: 31 Mar 2021 09:13
URI: https://orca.cardiff.ac.uk/id/eprint/140041

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