Paper Info
Title
Non-invasive MRI of brain clearance pathways using multiple echo time arterial spin labelling: An Aquaporin-4 study.
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 (T), 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 (δ), 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.
Year
DOI
Venue
2019
10.1016/j.jalz.2018.06.2055
Alzheimer's & Dementia
Keywords
DocType
Volume
ASL,Aquaporin-4,Blood-brain barrier,Blood-brain interface,Glymphatic system,Multiple echo-time,Water permeability
Journal
14
Issue
ISSN
Citations 
7
1552-5260
0
PageRank 
References 
Authors
0.34
0
10
Name
Order
Citations
PageRank
Yolanda Ohene100.34
I. F. Harrison2142.07
Payam Nahavandi300.34
O. Ismail4202.26
Eleanor V Bird500.34
Ole Petter Ottersen671.30
Erlend A Nagelhus7132.35
David Thomas863.37
Mark F. Lythgoe913912.63
Jack A. Wells10364.51