Evans, Phoebe Grace;
(2023)
Development of a novel non-invasive MRI technique to quantitatively assess perivascular function.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
In the last decade, a number of studies have highlighted the importance of perivascular spaces (PVS) in cerebrospinal fluid (CSF) transport in the brain via the newly discovered glymphatic system. Alterations to the structure and function of the PVS has been associated with neurological diseases, such as dementia and stroke. Despite momentous advances in PVS research, there is still a lack of understanding of the exact role in brain homeostasis and pathophysiological implications in human diseases. The main pitfall being a lack of non-invasive methods to probe perivascular function with the potential for clinical translation. Thus, there is a need to develop techniques that can be implemented in both preclinical models and clinical studies, to disentangle the mechanisms underlying CSF transport in the PVS and alterations that occur in pathology. This thesis is dedicated to the development and implementation of a novel and non-invasive MRI method to measure perivascular function, i.e., fluid movement, in the rodent brain. A diffusion-weighted MRI sequence was developed to measure ΔD*, a quantitative surrogate measure of the directionality of perivascular fluid movement in the PVS. The novel MRI method was implemented across two high-field MRI systems thus demonstrating the consistency and sensitivity of the technique to quantify perivascular function despite MRI hardware differences. The MR method was sensitive to cardiac pulsation driven perivascular fluid movement, measuring a 45% increase during the heart’s systole phase. The technique was applied to models of arterial hypertension and was sensitive to blood-pressure driven changes to perivascular function, measuring a 38% decrease in an acute pharmacological elevation of blood pressure. In genetic chronic models of hypertension, there was a significant increase in perivascular function compared to normotensive controls, measured on the Bruker 9.4T MRI scanner. Finally, there were no significant increases in perivascular function after inducing hyperosmolality as a method for enhancing drug delivery to the brain via the glymphatic pathway. Overall, this thesis has demonstrated the scope of novel MRI method to quantify perivascular fluid movement and it’s potential to be clinically translated for investigation into the mechanisms causing small vessel disease (SVD).
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Development of a novel non-invasive MRI technique to quantitatively assess perivascular function |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/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 > 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 |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10164282 |
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