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

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.

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October 2018
Data Policy information about availability of data All manuscripts must include a data availability statement. This statement should provide the following information, where applicable: This study includes proof-of-principle experiments and feasibility demonstrations. We used: one mouse brain, one mouse spinal cord, two human white matter and one cortex specimen for proof-of-principle experiments, two mouse brains (one control and one dysmyelinated) for demonstration of sensitivity of the method to myelin levels and nanostructural alterations no data were excluded These proof of principle experiments do not aim to show population differences, but demonstrate the capabilities of the method. These were shown in multiple samples and sample ROIs.
Study contains proof of principle experiments. Samples were chosen randomly.
These proof of principle experiments do not aim to show population differences, but demonstrate the capabilities of the method. Sequence & imaging parameters one 5-month-old C57BL/6 female mouse, one 50-day-old Rag2-/-male mouse, one 50-day-old Rag2-/-sh-/-male mouse Housing conditions are described in the manuscript.
the study did not involve wild animals the study did not involve samples collected from the field C57BL/6 mouse: animal license ZH242/14 of the Animal Imaging Center of ETH Zurich/University of Zurich 50-day-old Rag2-/-and Rag2-/-sh-/-mice: Johns Hopkins University animal care and use committee protocol number MO16M313