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Non-invasive imaging of CSF-mediated brain clearance pathways via assessment of perivascular fluid movement with DTI MRI

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Cite this article as: eLife 2018;7:e34028 doi: 10.7554/eLife.34028

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).

The following data sets were generated

Article and author information

Author details

  1. Ian F Harrison

    UCL Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1250-4911
  2. Bernard Siow

    UCL Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Aisha B Akilo

    UCL Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Phoebe G Evans

    UCL Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Ozama Ismail

    UCL Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Yolanda Ohene

    UCL Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Payam Nahavandi

    UCL Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. David L Thomas

    Department of Brain Repair and Rehabilitation, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1491-1641
  9. Mark F Lythgoe

    UCL Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Jack A Wells

    UCL Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom
    For correspondence
    jack.wells@ucl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4171-3539

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.

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.

Reviewing Editor

  1. Thomas W. Okell

Publication history

  1. Received: December 5, 2017
  2. Accepted: July 30, 2018
  3. Accepted Manuscript published: July 31, 2018 (version 1)
  4. 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.

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