Micron-resolution fiber mapping in histology independent of sample preparation

Marios Georgiadis (), Franca auf der Heiden, Hamed Abbasi, Loes Ettema, Jeffrey Nirschl, Hossein Moein Taghavi, Moe Wakatsuki, Andy Liu, William Hai Dang Ho, Mackenzie Carlson, Michail Doukas, Sjors A. Koppes, Stijn Keereweer, Raymond A. Sobel, Kawin Setsompop, Congyu Liao, Katrin Amunts, Markus Axer, Michael Zeineh and Miriam Menzel ()
Additional contact information
Marios Georgiadis: Stanford University
Franca auf der Heiden: Forschungszentrum Jülich GmbH
Hamed Abbasi: Delft University of Technology
Loes Ettema: Delft University of Technology
Jeffrey Nirschl: Stanford University
Hossein Moein Taghavi: Stanford University
Moe Wakatsuki: Stanford University
Andy Liu: Stanford University
William Hai Dang Ho: Stanford University
Mackenzie Carlson: Stanford University
Michail Doukas: University Medical Center Rotterdam
Sjors A. Koppes: University Medical Center Rotterdam
Stijn Keereweer: University Medical Center Rotterdam
Raymond A. Sobel: Stanford University
Kawin Setsompop: Stanford University
Congyu Liao: Stanford University
Katrin Amunts: Forschungszentrum Jülich GmbH
Markus Axer: Forschungszentrum Jülich GmbH
Michael Zeineh: Stanford University
Miriam Menzel: Forschungszentrum Jülich GmbH

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract Mapping the brain’s fiber network is crucial for understanding its function and malfunction, but resolving nerve trajectories over large fields of view is challenging. Here, we show that computational scattered light imaging (ComSLI) can map fiber networks in histology independent of sample preparation, also in formalin-fixed paraffin-embedded (FFPE) tissues including whole human brain sections. We showcase this method in new and archived, animal and human brain sections, for different sample preparations (in paraffin, deparaffinized, various stains, unstained fresh-frozen). We convert microscopic orientations to microstructure-informed fiber orientation distributions (μFODs). Adapting tractography tools from diffusion magnetic resonance imaging (dMRI), we trace axonal trajectories revealing white and gray matter connectivity. These allow us to identify altered microstructure or deficient tracts in demyelinating or neurodegenerating pathology, and to show key advantages over dMRI, polarization microscopy, and structure tensor analysis. Finally, we map fibers in non-brain tissues, including muscle, bone, and blood vessels, unveiling the tissue’s function. Our cost-effective, versatile approach enables micron-resolution studies of intricate fiber networks across tissues, species, diseases, and sample preparations, offering new dimensions to neuroscientific and biomedical research.

Date: 2025
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DOI: 10.1038/s41467-025-64896-9

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