eprintid: 10166552 rev_number: 13 eprint_status: archive userid: 699 dir: disk0/10/16/65/52 datestamp: 2023-05-05 11:04:30 lastmod: 2024-02-05 14:48:06 status_changed: 2023-05-05 11:04:30 type: thesis metadata_visibility: show sword_depositor: 699 creators_name: Perera, Charith title: Development and Application of MRI Techniques for Non-Invasive Assessment of Blood-Cerebrospinal Fluid Barrier Function ispublished: inpress divisions: UCL divisions: B02 divisions: C10 divisions: D17 divisions: FI6 note: Copyright © The Author 2023. 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. abstract: The choroid plexus (CP) tissue forms the blood-cerebrospinal fluid barrier (BCSFB) - a unique interface which plays a critical role in effective homeostasis of the central nervous system. To date, exploration of the BCSFB’s role in health and disease has been hindered by a lack of non-invasive, translatable methodologies. The recent development of BCSFB-ASL MRI by Evans et al. has permitted the non-invasive, surrogate measurement of BCSFB function. The work presented herein develops and applies the BCSFB-ASL method to investigate BCSFB function in rodent models of ageing and disease. Chapter 2 describes a novel platform for simultaneous recording of BCSFB function and brain tissue perfusion using interleaved echo-time ASL, which provided insight into alterations of vessel tone at the BBB and BCSFB under the influence of pharmacological agents, as well as how reactivity towards a vasopressin challenge is impaired in the aged mouse brain. In Chapter 3, I reproduce, optimise, and characterise the BCSFB-ASL MRI approach on a Bruker 9.4T system, that was heretofore applied only on an Agilent 9.4T MRI system. This work seeks to utilise the improved hardware and software on the Bruker system to increase measurement precision with minimised scan times. Chapter 4 describes efforts to further characterise the contributing sources and kinetics of ultra-long echo-time ASL signals arising from brain-wide CSF regions. These experiments seek to determine the reliability of the estimated labelled blood water delivery rates, alongside potential factors which may contribute to the appearance of these signals, in regions distal to the caudal lateral ventricles. In Chapter 5, BCSFB function was then investigated in the context of systemic hypertension. Spontaneously hypertensive rats displayed a reduction in BCSFB function, which highlights the potential for such measures to serve as a sensitive early biomarker for hypertension-driven neurodegeneration. Overall, we demonstrate the scope of BCSFB-ASL to capture changes to BCSFB function, which not only has value in providing a useful biomarker for downstream neurodegeneration, but also provides an insight into mechanisms which may increase the brain’s susceptibility towards neurodegenerative outcomes. date: 2023-03-28 date_type: published oa_status: green full_text_type: other thesis_class: doctoral_open thesis_award: Ph.D language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2010845 lyricists_name: Perera, Peduru lyricists_id: PACPE68 actors_name: Perera, Peduru actors_id: PACPE68 actors_role: owner full_text_status: public pages: 200 institution: UCL (University College London) department: Imaging thesis_type: Doctoral editors_name: Wells, Jack A editors_name: Thomas, David L citation: Perera, Charith; (2023) Development and Application of MRI Techniques for Non-Invasive Assessment of Blood-Cerebrospinal Fluid Barrier Function. Doctoral thesis (Ph.D), UCL (University College London). Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10166552/1/Peduru%20A.%20Charith%20Perera%20-%20Doctoral%20Thesis%2C%20final.pdf