Imaging crossing fibers in mouse, pig, monkey, and human brain using small-angle X-ray scattering

Area of Science:

• Neuroscience
• Biophysics
• Medical Imaging

Background:

• Accurate mapping of the brain's structural connectome requires resolving complex nerve fiber trajectories, including crossings.
• Current methods like diffusion MRI can struggle with specificity and accurately detecting these crossings.
• Myelinated axons, crucial for signal transmission, possess a unique structural periodicity exploitable for specific detection.

Purpose of the Study:

• To demonstrate the capability of small-angle X-ray scattering (SAXS) for specifically detecting myelinated axon fiber crossings.
• To validate SAXS as a potential ground truth method for neuroimaging.
• To explore the application of SAXS in various species and compare it with existing techniques.

Main Methods:

• Utilized small-angle X-ray scattering (SAXS) to probe the myelin sheath's periodicity.
• Created artificial double- and triple-crossing fiber geometries using human corpus callosum strips.
• Applied SAXS to ex vivo brain tissue from mouse, pig, vervet monkey, and human.

Main Results:

• SAXS successfully detected artificial and in vivo myelinated, axon-specific fiber crossings.
• Results were compared with polarized light imaging, tracer experiments, and diffusion MRI, highlighting SAXS's specificity.
• Demonstrated SAXS's capability for 3D sampling and high-resolution analysis of fiber orientations.

Conclusions:

• SAXS offers a non-destructive, myelin-specific method for resolving nerve fiber crossings.
• This technique can serve as a gold standard for validating other neuroimaging modalities.
• SAXS has the potential to significantly advance the accuracy of structural connectome mapping.