Alzheimer's Imaging Consortium.

Area of Science:

• Neuroscience
• Biophysics
• Medical Imaging

Background:

• Neurodegenerative diseases disrupt the brain's nerve fiber network, hindering connectivity studies.
• Existing methods for mapping nerve fibers have limitations in resolution, volume, or sample preparation.
• Computational scattered light imaging (ComSLI) offers a novel solution for resolving neuronal trajectories.

Purpose of the Study:

• To introduce and validate computational scattered light imaging (ComSLI) for high-resolution mapping of neuronal fiber trajectories.
• To demonstrate ComSLI's capability in studying neurodegeneration, specifically in hippocampal tracts.
• To establish ComSLI as a versatile and cost-effective tool for histological analysis.

Main Methods:

• Utilized standard formalin-fixed paraffin-embedded (FFPE) and older celloidin-embedded human brain sections.
• Employed a rotating LED light source and a micron-resolution camera system for scattered light imaging.
• Applied SLIX software for orientation quantification and MRtrix3 for tractography.

Main Results:

• ComSLI generated micron-resolution whole-brain fiber orientation maps, resolving detailed structures like the corpus callosum and corona radiata.
• The method demonstrated consistent results across various sample preparation protocols and staining methods.
• ComSLI successfully visualized significant changes in neurodegenerating tracts, such as the hippocampal perforant pathway in sclerotic and Alzheimer's disease models.

Conclusions:

• ComSLI provides a cost-effective approach for studying complex fiber networks at micron resolution in diverse histological samples.
• The technique is capable of identifying subtle alterations associated with neurodegeneration.
• ComSLI overcomes previous technical barriers, enabling large-scale connectivity analysis in neurological research.