Keereweer, S. | Search bioRxiv

bioRxiv2026

Whole-Slide Mapping of Tumor Tissue Fiber Architecture via Computational Scattered Light Imaging

Mapping peritumoral collagen fiber directionality in solid tumors may assist in determining cancer progression and support more personalized prognoses. However, existing microscopy techniques are often limited by a restricted field of view, high cost, or incompatibility with paraffin-treated tissues. Computational scattered light imaging (ComSLI) is a cost-effective whole-slide microscopy technique that reveals fiber orientations independent of sample preparation. Using glioma, colorectal, and head and neck cancer samples, we show for the first time that ComSLI maps fiber orientations in paraffin-treated tumor tissues, visualizes tumor growth pathways and desmoplastic reactions, and allows the study of collagen orientations relative to tumor boundaries.

cancer biology↗

bioRxiv2024

Uncovering microstructural architecture from histology

Mapping the brains 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 (FODs). 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 tissues 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.

pathology↗