Micron-resolution fiber mapping in histology independent of sample preparation

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.

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Publication Details

Journal
Nature Communications
Published
2025-11-05
DOI
https://doi.org/10.1038/s41467-025-64896-9
Citations
2
Primary Topic
Advanced Neuroimaging Techniques and Applications
Type
article
Field-Weighted Citation Impact
2.72
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article

Micron-resolution fiber mapping in histology independent of sample preparation

Michael Zeineh, Marios Georgiadis, Katrin Amunts, Jeffrey Nirschl et al.
2 citations
Nature Communications
Advanced Neuroimaging Techniques and Applications
2.72
article

Micron-resolution fiber mapping in histology independent of sample preparation

Michael Zeineh, Marios Georgiadis, Katrin Amunts, Jeffrey Nirschl, Hamed Abbasi, William Hai Dang Ho, Markus Axer, Sjors A. Koppes, Congyu Liao, Mackenzie Carlson, Stijn Keereweer, Miriam Menzel, Hossein Moein Taghavi, Raymond A. Sobel, Kawin Setsompop, Franca auf der Heiden, Loes Ettema, Moe Wakatsuki, Andy Liu, Michail Doukas
article en
2 citations

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.

Nature CommunicationsVol. 16(1)
University of Wuppertal (DE), Forschungszentrum Jülich (DE), Erasmus MC (NL), Düsseldorf University Hospital (DE), Stanford Medicine (US), Heinrich Heine University Düsseldorf (DE), Erasmus University Rotterdam (NL), Stanford University (US), Delft University of Technology (NL)
Openalex Percentile: Top 8%
Advanced Neuroimaging Techniques and Applications
2.72
DOIOpen Access PDFOpenAlex
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