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Nanostructure-specific X-ray tomography reveals myelin levels, integrity and axon orientations in mouse and human nervous tissue

Author

Listed:
  • Marios Georgiadis

    (ETH Zurich
    New York University School of Medicine
    Stanford School of Medicine)

  • Aileen Schroeter

    (ETH Zurich)

  • Zirui Gao

    (ETH Zurich
    Swiss Light Source, Paul Scherrer Institute)

  • Manuel Guizar-Sicairos

    (Swiss Light Source, Paul Scherrer Institute)

  • Marianne Liebi

    (Chalmers University of Technology)

  • Christoph Leuze

    (Stanford School of Medicine)

  • Jennifer A. McNab

    (Stanford School of Medicine)

  • Aleezah Balolia

    (University of Colorado Denver)

  • Jelle Veraart

    (New York University School of Medicine)

  • Benjamin Ades-Aron

    (New York University School of Medicine)

  • Sunglyoung Kim

    (New York University School of Medicine)

  • Timothy Shepherd

    (New York University School of Medicine)

  • Choong H. Lee

    (New York University School of Medicine)

  • Piotr Walczak

    (Johns Hopkins Medicine
    University of Maryland)

  • Shirish Chodankar

    (Brookhaven National Laboratory)

  • Phillip DiGiacomo

    (Stanford School of Medicine)

  • Gergely David

    (University of Zurich)

  • Mark Augath

    (ETH Zurich)

  • Valerio Zerbi

    (ETH Zurich)

  • Stefan Sommer

    (ETH Zurich)

  • Ivan Rajkovic

    (SLAC National Accelerator Laboratory)

  • Thomas Weiss

    (SLAC National Accelerator Laboratory)

  • Oliver Bunk

    (Swiss Light Source, Paul Scherrer Institute)

  • Lin Yang

    (Brookhaven National Laboratory)

  • Jiangyang Zhang

    (New York University School of Medicine)

  • Dmitry S. Novikov

    (New York University School of Medicine)

  • Michael Zeineh

    (Stanford School of Medicine)

  • Els Fieremans

    (New York University School of Medicine)

  • Markus Rudin

    (ETH Zurich
    University of Zurich)

Abstract

Myelin insulates neuronal axons and enables fast signal transmission, constituting a key component of brain development, aging and disease. Yet, myelin-specific imaging of macroscopic samples remains a challenge. Here, we exploit myelin’s nanostructural periodicity, and use small-angle X-ray scattering tensor tomography (SAXS-TT) to simultaneously quantify myelin levels, nanostructural integrity and axon orientations in nervous tissue. Proof-of-principle is demonstrated in whole mouse brain, mouse spinal cord and human white and gray matter samples. Outcomes are validated by 2D/3D histology and compared to MRI measurements sensitive to myelin and axon orientations. Specificity to nanostructure is exemplified by concomitantly imaging different myelin types with distinct periodicities. Finally, we illustrate the method’s sensitivity towards myelin-related diseases by quantifying myelin alterations in dysmyelinated mouse brain. This non-destructive, stain-free molecular imaging approach enables quantitative studies of myelination within and across samples during development, aging, disease and treatment, and is applicable to other ordered biomolecules or nanostructures.

Suggested Citation

  • Marios Georgiadis & Aileen Schroeter & Zirui Gao & Manuel Guizar-Sicairos & Marianne Liebi & Christoph Leuze & Jennifer A. McNab & Aleezah Balolia & Jelle Veraart & Benjamin Ades-Aron & Sunglyoung Kim, 2021. "Nanostructure-specific X-ray tomography reveals myelin levels, integrity and axon orientations in mouse and human nervous tissue," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22719-7
    DOI: 10.1038/s41467-021-22719-7
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