Non-invasive imaging of CSF-mediated brain clearance pathways via assessment of perivascular fluid movement with DTI MRI
Abstract
The glymphatics system describes a CSF-mediated clearance pathway for the removal of potentially harmful molecules, such as amyloid beta, from the brain. As such, its components may represent new therapeutic targets to alleviate aberrant protein accumulation that defines the most prevalent neurodegenerative conditions. Currently, however, the absence of any non-invasive measurement technique prohibits detailed understanding of glymphatic function in the human brain and in turn, it's role in pathology. Here, we present the first non-invasive technique for the assessment of glymphatic inflow by using an ultra-long echo time, low b-value, multi-direction diffusion weighted MRI sequence to assess perivascular fluid movement (which represents a critical component of the glymphatic pathway) in the rat brain. This novel, quantitative and non-invasive approach may represent a valuable biomarker of CSF-mediated brain clearance, working towards the clinical need for reliable and early diagnostic indicators of neurodegenerative conditions such as Alzheimer's disease.
Data availability
All the data has been deposited on Dryad (https://dx.doi.org/10.5061/dryad.121hs31).
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Data from: Non-invasive imaging of CSF-mediated brain clearance pathways via assessment of perivascular fluid movement with diffusion tensor MRIAvailable at Dryad Digital Repository under a CC0 Public Domain Dedication.
Article and author information
Author details
Funding
Wellcome (Sir Henry Dale Fellowship 204624/Z/16/Z)
- Phoebe G Evans
- Jack A Wells
Royal Society (Sir Henry Dale Fellowship 204624/Z/16/Z)
- Phoebe G Evans
- Jack A Wells
Engineering and Physical Sciences Research Council (EP/N034864/1)
- Ian F Harrison
- David L Thomas
- Mark F Lythgoe
National Institute for Health Research
- Mark F Lythgoe
Medical Research Council (MR/K026739/1)
- Mark F Lythgoe
Department of Health
- Mark F Lythgoe
Leonard Wolfson Experimental Neurology Centre (PR/ylr/18575)
- David L Thomas
Engineering and Physical Sciences Research Council (UCL Centre for Doctoral Training in Medical Imaging (EP/L016478/1)
- Yolanda Ohene
- Payam Nahavandi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Thomas W. Okell
Ethics
Animal experimentation: All experiments were performed in accordance with the UK Home Office's Animals (Scientific Procedures) Act (1986). All procedures were minimally invasive and with a relatively high level of isoflurane for deep anesthesia throughout imaging.
Version history
- Received: December 5, 2017
- Accepted: July 30, 2018
- Accepted Manuscript published: July 31, 2018 (version 1)
- Version of Record published: August 30, 2018 (version 2)
Copyright
© 2018, Harrison et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.