Microstructural tissue organization underlies the complex connectivity of
the brain and controls the properties of connective, muscle, and
epithelial tissue. However, discerning microstructural architecture with
high resolution for large fields of view remains prohibitive. We address
this challenge with computational scattered light imaging (ComSLI), which
exploits the anisotropic light scattering of aligned structures. Using a
rotating light source and a high-resolution camera, ComSLI determines
fiber architecture with micrometer resolution from histological sections
across preparation and staining protocols. We show complex fiber
architecture in brain and non-brain sections, including histological
paraffin-embedded sections with various stains, and demonstrate its
applicability on animal and human tissue, including disease cases with
altered microstructure. ComSLI opens new avenues for investigating fiber
architecture in new and archived sections across organisms, tissues, and
diseases.