Magnetic resonance measurements of cellular and sub-cellular membrane structures in live and fixed neural tissue

  1. Nathan H Williamson
  2. Rea Ravin
  3. Dan Benjamini
  4. Hellmut Merkle
  5. Melanie Falgairolle
  6. Michael James O'Donovan
  7. Dvir Blivis
  8. Dave Ide
  9. Teddy X Cai
  10. Nima S Ghorashi
  11. Ruiliang Bai
  12. Peter J Basser  Is a corresponding author
  1. Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States
  2. National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States
  3. National Institute of Mental Health, National Institutes of Health, United States
  4. National Heart, Lung, and Blood Institute, National Institutes of Health, United States
  5. Zhejiang University, China

Abstract

We develop magnetic resonance (MR) methods for real-time measurement of tissue microstructure and membrane permeability of live and fixed excised neonatal mouse spinal cords. Diffusion and exchange MR measurements are performed using the strong static gradient produced by a single-sided permanent magnet. Using tissue delipidation methods, we show that water diffusion is restricted solely by lipid membranes. Most of the diffusion signal can be assigned to water in tissue which is far from membranes. The remaining 25% can be assigned to water restricted on length scales of roughly a micron or less, near or within membrane structures at the cellular, organelle, and vesicle levels. Diffusion exchange spectroscopy measures water exchanging between membrane structures and free environments at 100 s-1.

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Source data for all Figures 1-9 in the manuscript have been provided as supporting files.

Article and author information

Author details

  1. Nathan H Williamson

    Section on Quantitative Imaging and Tissue Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0221-9121
  2. Rea Ravin

    Section on Quantitative Imaging and Tissue Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Dan Benjamini

    Section on Quantitative Imaging and Tissue Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Hellmut Merkle

    National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Melanie Falgairolle

    National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5243-4714
  6. Michael James O'Donovan

    National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2487-7547
  7. Dvir Blivis

    National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6203-7325
  8. Dave Ide

    National Institute of Mental Health, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Teddy X Cai

    Section on Quantitative Imaging and Tissue Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Nima S Ghorashi

    Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Ruiliang Bai

    Interdisciplinary Institute of Neuroscience and Technology, Qiushi Academy for Advanced Studies; College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  12. Peter J Basser

    Section on Quantitative Imaging and Tissue Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    For correspondence
    pjbasser@helix.nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4795-6088

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development (Intramural Research Program (IRP))

  • Nathan H Williamson
  • Rea Ravin
  • Dan Benjamini
  • Teddy X Cai
  • Ruiliang Bai
  • Peter J Basser

National Institute of Neurological Disorders and Stroke (IRP)

  • Hellmut Merkle
  • Melanie Falgairolle
  • Michael James O'Donovan
  • Dvir Blivis
  • Dave Ide

National Institute of Mental Health (IRP)

  • Dave Ide

National Heart, Lung, and Blood Institute (IRP)

  • Nima S Ghorashi

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 carried out in compliance with the National Institute of Neurological Disorders and Stroke Animal Care and Use Committee (Animal Protocol Number 1267-18).

Reviewing Editor

  1. Inna Slutsky, Tel Aviv University, Israel

Publication history

  1. Received: August 15, 2019
  2. Accepted: December 11, 2019
  3. Accepted Manuscript published: December 12, 2019 (version 1)
  4. Version of Record published: January 23, 2020 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Nathan H Williamson
  2. Rea Ravin
  3. Dan Benjamini
  4. Hellmut Merkle
  5. Melanie Falgairolle
  6. Michael James O'Donovan
  7. Dvir Blivis
  8. Dave Ide
  9. Teddy X Cai
  10. Nima S Ghorashi
  11. Ruiliang Bai
  12. Peter J Basser
(2019)
Magnetic resonance measurements of cellular and sub-cellular membrane structures in live and fixed neural tissue
eLife 8:e51101.
https://doi.org/10.7554/eLife.51101

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