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Non-invasive MRI of brain clearance pathways using multiple echo time arterial spin labelling: an aquaporin-4 study

Ohene, Y; Harrison, IF; Nahavandi, P; Ismail, O; Bird, EV; Ottersen, OP; Nagelhus, EA; ... Wells, JA; + view all (2019) Non-invasive MRI of brain clearance pathways using multiple echo time arterial spin labelling: an aquaporin-4 study. NeuroImage , 188 pp. 515-523. 10.1016/j.neuroimage.2018.12.026. Green open access

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Abstract

There is currently a lack of non-invasive tools to assess water transport in healthy and pathological brain tissue. Aquaporin-4 (AQP4) water channels are central to many water transport mechanisms, and emerging evidence also suggests that AQP4 plays a key role in amyloid-β (Aβ) clearance, possibly via the glymphatic system. Here, we present the first non-invasive technique sensitive to AQP4 channels polarised at the blood-brain interface (BBI). We apply a multiple echo time (multi-TE) arterial spin labelling (ASL) MRI technique to the mouse brain to assess BBI water permeability via calculation of the exchange time (Texw), the time for magnetically labelled intravascular water to exchange across the BBI. We observed a 31% increase in exchange time in AQP4-deficient (Aqp4-/-) mice (452 ± 90 ms) compared to their wild-type counterparts (343 ± 91 ms) (p = 0.01), demonstrating the sensitivity of the technique to the lack of AQP4 water channels. More established, quantitative MRI parameters: arterial transit time (δa), cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) detected no significant changes with the removal of AQP4. This clinically relevant tool may be crucial to better understand the role of AQP4 in water transport across the BBI, as well as clearance of proteins in neurodegenerative conditions such as Alzheimer's disease.

Type: Article
Title: Non-invasive MRI of brain clearance pathways using multiple echo time arterial spin labelling: an aquaporin-4 study
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.neuroimage.2018.12.026
Publisher version: https://doi.org/10.1016/j.neuroimage.2018.12.026
Language: English
Additional information: Copyright © 2018 Published by Elsevier Inc. Open access article via CCBY 4.0. This work is supported by the Medical Research Council (MR/K501268/1), the EPSRC-funded UCL Centre for Doctoral Training in Medical Imaging (EP/L016478/1) and the UCL Leonard Wolfson Experimental Neurology Centre (PR/YLR/18575). JW is supported by the Wellcome Trust/Royal Society Sir Henry Dale Fellowship (204624/Z/16/Z).
Keywords: ASL, Aquaporin-4, Blood-brain barrier, Blood-brain interface, Glymphatic system, Multiple echo-time, Water permeability
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 Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation
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 > Department of Imaging
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/10065171
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