Ohene, Yolanda;
(2020)
Development of non-invasive MRI to measure water permeability across the blood-brain interface.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
The blood-brain interface (BBI) is a physical and biochemical barrier that protects and maintains healthy brain function. Disruption of the BBI is indicative of the early stages of certain neurodegenerative diseases, such as Alzheimer’s Disease. However, there is currently a lack of sensitive tools available to accurately quantify the early alterations to the integrity of the BBI. This thesis describes the development and implementation of multiple echo time arterial spin labelling (multi-TE ASL) MRI technique in the mouse brain to measure vascular water permeability across the BBI. The technique was implemented in two high-field MRI system to demonstrate the consistency of the imaging protocols and the sensitivity of the measures of BBI water permeability. The multi-TE ASL technique was used to probe the function of aquaporin-4 (AQP4) water channels, which play a key role in the clearance of the deleterious proteins from the brain. This non-invasive technique was able to demonstrate its sensitivity to targeting AQP4 by measuring a 31% slowing of cortical BBI water permeability with the removal of the AQP4 water channels. The technique also measured a 34% slowing in the BBI water permeability in the cerebellum brain region with a reduction of AQP4 channels at the BBI. Finally, the technique measured a 32% increase in cortical BBI permeability to water in a mouse model of ageing. The non-invasive imaging measurements were 7 associated with a 2-fold increase in mRNA expression of pericytes, while other BBI markers such as tight junction proteins were maintained. Overall, this work has demonstrated the scope of novel MRI technique to target changes to BBI water permeability, with potential for clinical translation for the early detection and understanding of neurodegenerative disease.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Development of non-invasive MRI to measure water permeability across the blood-brain interface |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2020. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10091166 |
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