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

Journal Article · · Nature Communications
ORCiD logo [1];  [2]; ORCiD logo [3]; ORCiD logo [4]; ORCiD logo [5];  [6]; ORCiD logo [6]; ORCiD logo [7];  [8];  [8];  [8]; ORCiD logo [8]; ORCiD logo [8];  [9];  [10];  [6];  [11];  [2]; ORCiD logo [2]; ORCiD logo [2] more »;  [12];  [12]; ORCiD logo [4]; ORCiD logo [10];  [8]; ORCiD logo [8]; ORCiD logo [6]; ORCiD logo [8];  [13] « less
  1. Eidgenoessische Technische Hochschule (ETH), Zurich (Switzerland); New York Univ. (NYU), NY (United States); Stanford Univ., CA (United States)
  2. Eidgenoessische Technische Hochschule (ETH), Zurich (Switzerland)
  3. Eidgenoessische Technische Hochschule (ETH), Zurich (Switzerland); Paul Scherrer Inst. (PSI), Villigen (Switzerland)
  4. Paul Scherrer Inst. (PSI), Villigen (Switzerland)
  5. Chalmers Univ. of Technology, Gothenburg (Sweden)
  6. Stanford Univ., CA (United States)
  7. Univ. of Denver, CO (United States)
  8. New York Univ. (NYU), NY (United States)
  9. Johns Hopkins Univ., Baltimore, MD (United States); Univ. of Maryland, Baltimore, MD (United States)
  10. Brookhaven National Lab. (BNL), Upton, NY (United States)
  11. Univ. of Zurich (Switzerland)
  12. SLAC National Accelerator Lab., Menlo Park, CA (United States)
  13. Eidgenoessische Technische Hochschule (ETH), Zurich (Switzerland); Univ. of Zurich (Switzerland)
+ Show Author Affiliations

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.

Research Organization:
SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States); Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES); Swiss National Science Foundation (SNSF); National Institutes of Health (NIH)
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
OSTI ID:
1808596
Alternate ID(s):
OSTI ID: 1817356
Report Number(s):
BNL-222056-2021-JAAM; TRN: US2212914
Journal Information:
Nature Communications, Vol. 12, Issue 1; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
imaging
imaging techniques
Myelin biology and repair
nervous system
SAXS
36 MATERIALS SCIENCE