Whole-brain reconstruction of fiber tracts based on cytoarchitectonic organization

Mapping of axon trajectories is crucial for understanding brain organization. Using whole-brain high-throughput fluorescence imaging, we developed a cytoarchitecture-based link estimation (CABLE) method for accurate fiber tract mapping at cellular resolution. This method infers the fiber direction from the inherent anisotropy of the nucleus or soma shape and spatial arrangement of adjacent cells. The inferred fiber tracts were validated by tracing virally labeled individual axons in the monkey brain. This CABLE method could disentangle complex intersecting or bending fibers that were uncertain in diffusion magnetic resonance imaging tractography, allowing accurate brain-wide fiber tract reconstruction in marmoset and macaque brains. Finally, we applied CABLE for rapid mapping of axon fiber abnormalities in diseased neonatal human brain tissues, establishing a path for high-resolution brain mapping of fiber tracts in the human brain.