Nanostructure-specific X-ray tomography reveals myelin levels, integrity and axon orientations in mouse and human nervous tissue
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.
- Authors:
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[1];
[3];
[4];
[5];
[6];
[7];
[8];
[8];
[2];
[2]
more »
- Eidgenoessische Technische Hochschule (ETH), Zurich (Switzerland); New York Univ. (NYU), NY (United States); Stanford Univ., CA (United States)
- Eidgenoessische Technische Hochschule (ETH), Zurich (Switzerland)
- Eidgenoessische Technische Hochschule (ETH), Zurich (Switzerland); Paul Scherrer Inst. (PSI), Villigen (Switzerland)
- Paul Scherrer Inst. (PSI), Villigen (Switzerland)
- Chalmers Univ. of Technology, Gothenburg (Sweden)
- Stanford Univ., CA (United States)
- Univ. of Denver, CO (United States)
- New York Univ. (NYU), NY (United States)
- Johns Hopkins Univ., Baltimore, MD (United States); Univ. of Maryland, Baltimore, MD (United States)
- Brookhaven National Lab. (BNL), Upton, NY (United States)
- Univ. of Zurich (Switzerland)
- SLAC National Accelerator Lab., Menlo Park, CA (United States)
- Eidgenoessische Technische Hochschule (ETH), Zurich (Switzerland); Univ. of Zurich (Switzerland)
- Publication Date:
- Research Org.:
- SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States); Brookhaven National Laboratory (BNL), Upton, NY (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES); Swiss National Science Foundation (SNSF); National Institutes of Health (NIH)
- OSTI Identifier:
- 1808596
- Alternate Identifier(s):
- OSTI ID: 1817356
- Report Number(s):
- BNL-222056-2021-JAAM
Journal ID: ISSN 2041-1723; TRN: US2212914
- Grant/Contract Number:
- AC02-76SF00515; SC0012704; KP1605010; P400PM_180773; P2EZP3_168920; P41GM103393; R01 NS088040; R01 AG06112001; S10OD021512; NIGMS T34 6M096958; NIH/NCI 5P30CA016087; NIH/NIBIB P41GM103393; S10 OD012331
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature Communications
- Additional Journal Information:
- Journal Volume: 12; Journal Issue: 1; Journal ID: ISSN 2041-1723
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; imaging; imaging techniques; Myelin biology and repair; nervous system; SAXS; 36 MATERIALS SCIENCE
Citation Formats
Georgiadis, Marios, Schroeter, Aileen, Gao, Zirui, Guizar-Sicairos, Manuel, Liebi, Marianne, Leuze, Christoph, McNab, Jennifer A., Balolia, Aleezah, Veraart, Jelle, Ades-Aron, Benjamin, Kim, Sunglyoung, Shepherd, Timothy, Lee, Choong H., Walczak, Piotr, Chodankar, Shirish, DiGiacomo, Phillip, David, Gergely, Augath, Mark, Zerbi, Valerio, Sommer, Stefan, Rajkovic, Ivan, Weiss, Thomas, Bunk, Oliver, Yang, Lin, Zhang, Jiangyang, Novikov, Dmitry S., Zeineh, Michael, Fieremans, Els, and Rudin, Markus. Nanostructure-specific X-ray tomography reveals myelin levels, integrity and axon orientations in mouse and human nervous tissue. United States: N. p., 2021.
Web. doi:10.1038/s41467-021-22719-7.
Georgiadis, Marios, Schroeter, Aileen, Gao, Zirui, Guizar-Sicairos, Manuel, Liebi, Marianne, Leuze, Christoph, McNab, Jennifer A., Balolia, Aleezah, Veraart, Jelle, Ades-Aron, Benjamin, Kim, Sunglyoung, Shepherd, Timothy, Lee, Choong H., Walczak, Piotr, Chodankar, Shirish, DiGiacomo, Phillip, David, Gergely, Augath, Mark, Zerbi, Valerio, Sommer, Stefan, Rajkovic, Ivan, Weiss, Thomas, Bunk, Oliver, Yang, Lin, Zhang, Jiangyang, Novikov, Dmitry S., Zeineh, Michael, Fieremans, Els, & Rudin, Markus. Nanostructure-specific X-ray tomography reveals myelin levels, integrity and axon orientations in mouse and human nervous tissue. United States. https://doi.org/10.1038/s41467-021-22719-7
Georgiadis, Marios, Schroeter, Aileen, Gao, Zirui, Guizar-Sicairos, Manuel, Liebi, Marianne, Leuze, Christoph, McNab, Jennifer A., Balolia, Aleezah, Veraart, Jelle, Ades-Aron, Benjamin, Kim, Sunglyoung, Shepherd, Timothy, Lee, Choong H., Walczak, Piotr, Chodankar, Shirish, DiGiacomo, Phillip, David, Gergely, Augath, Mark, Zerbi, Valerio, Sommer, Stefan, Rajkovic, Ivan, Weiss, Thomas, Bunk, Oliver, Yang, Lin, Zhang, Jiangyang, Novikov, Dmitry S., Zeineh, Michael, Fieremans, Els, and Rudin, Markus. Wed .
"Nanostructure-specific X-ray tomography reveals myelin levels, integrity and axon orientations in mouse and human nervous tissue". United States. https://doi.org/10.1038/s41467-021-22719-7. https://www.osti.gov/servlets/purl/1808596.
@article{osti_1808596,
title = {Nanostructure-specific X-ray tomography reveals myelin levels, integrity and axon orientations in mouse and human nervous tissue},
author = {Georgiadis, Marios and Schroeter, Aileen and Gao, Zirui and Guizar-Sicairos, Manuel and Liebi, Marianne and Leuze, Christoph and McNab, Jennifer A. and Balolia, Aleezah and Veraart, Jelle and Ades-Aron, Benjamin and Kim, Sunglyoung and Shepherd, Timothy and Lee, Choong H. and Walczak, Piotr and Chodankar, Shirish and DiGiacomo, Phillip and David, Gergely and Augath, Mark and Zerbi, Valerio and Sommer, Stefan and Rajkovic, Ivan and Weiss, Thomas and Bunk, Oliver and Yang, Lin and Zhang, Jiangyang and Novikov, Dmitry S. and Zeineh, Michael and Fieremans, Els and Rudin, Markus},
abstractNote = {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.},
doi = {10.1038/s41467-021-22719-7},
journal = {Nature Communications},
number = 1,
volume = 12,
place = {United States},
year = {Wed May 19 00:00:00 EDT 2021},
month = {Wed May 19 00:00:00 EDT 2021}
}
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