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

• Published in: Nature communications Vol. 12; no. 1; pp. 2941 - 13
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19.05.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 101/1; 14/19; 59/57; 631/1647/245; 631/378/2606; 631/535/1261; 639/925/930/2735; 692/698/1688; 96/34; Aging; Animals; Axons; Axons - metabolism; Axons - ultrastructure; BASIC BIOLOGICAL SCIENCES; Biomolecules; Brain; Brain - metabolism; Brain - ultrastructure; Central Nervous System - diagnostic imaging; Central Nervous System - metabolism; Central Nervous System - ultrastructure; Child, Preschool; Female; Histology; Humanities and Social Sciences; Humans; imaging; imaging techniques; Integrity; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Male; MATERIALS SCIENCE; Mathematical analysis; Medical imaging; Mice; Mice, Inbred C57BL; Mice, Knockout; multidisciplinary; Myelin; Myelin biology and repair; Myelin Proteins - metabolism; Myelin Sheath - metabolism; Myelin Sheath - ultrastructure; Myelination; Nanostructure; Nanostructures - chemistry; Nanostructures - ultrastructure; nervous system; Nervous tissues; Neuroimaging; Neuroimaging - methods; Periodicity; Proof of Concept Study; Quantitative research; SAXS; Scattering, Small Angle; Science; Science (multidisciplinary); Signal transmission; Small angle X ray scattering; Spinal cord; Spinal Cord - metabolism; Spinal Cord - ultrastructure; Substantia grisea; Tensors; Tomography; Tomography, X-Ray Computed - methods; X-ray scattering; X-rays
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-22719-7

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. Small-angle X-ray scattering (SAXS) combines the high tissue penetration of X-rays with specificity to periodic nanostructures. The authors use SAXS tensor tomography (SAXS-TT) on intact mouse and human brain tissue samples, to quantify myelin levels and determine myelin integrity, myelinated axon orientation, and fibre tracts non-destructively.