Nanostructure-specific X-ray tomography reveals myelin levels, integrity and axon orientations in mouse and human nervous tissue
Marios Georgiadis, Aileen Schroeter, Zirui Gao, Manuel Guizar‐Sicairos, Marianne Liebi, Christoph Leuze, Jennifer A. McNab, Aleezah Balolia, Jelle Veraart, Benjamin Ades‐Aron, Sung-Lyoung Kim, Timothy M. Shepherd, Choong H. Lee, Piotr Walczak, Shirish Chodankar, Phillip DiGiacomo, Gergely Dávid, M Augath, Valerio Zerbi, Stefan Sommer, Ivan Rajković, Thomas Weiß, Oliver Bunk, Lin Yang, Jiangyang Zhang, Dmitry S. Novikov, Michael Zeineh, Els Fieremans, Markus Rudin
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.