Quantifying oriented myelin in mouse and human brain

Myelin “insulates” our neurons enabling fast signal transduction in our brain; myelin levels, integrity, and neuron orientations are important determinants of brain development and disease. However, myelin imaging methods used in clinics or research are non-specific or destructive.

Using small-angle X-ray scattering tensor tomography (SAXS-TT), we exploited myelin’s ~17nm periodicity to non-invasively derive 3D myelin and neuron orientation maps in macroscopic tissue volumes (Figure). We demonstrated the method on a mouse brain (a-d), a mouse spinal cord, a human visual cortex and two human white matter specimens. We validated the readouts with 2D and 3D histology, and correlated the results with MRI contrasts.

Myelin’s ~3nm periodicity difference in the central and peripheral nervous system (CNS/PNS) enabled multiplexed imaging of the mouse brain and peripheral nerves (e,f). We also imaged control and diseased (dysmyelinated) mouse brains (g), highlighting SAXS-TT’s ability to tomographically image even minute amounts of myelin, and probe myelin structural integrity.

This non-destructive, stain-free imaging enables quantitative studies of myelination and neuron orientations within and across samples during development, aging, disease and treatment, and is applicable to other ordered biomolecules or nanostructures.