Multi-Scale Label-Free Human Brain Imaging with Integrated Serial Sectioning Polarization Sensitive Optical Coherence...

Area of Science:

• Neuroscience
• Biomedical Engineering
• Optical Imaging

Background:

• Aging and neurodegenerative diseases require understanding brain cytoarchitecture, myeloarchitecture, and vasculature.
• Standard histological processing causes tissue distortion, hindering deformation-free brain reconstruction.
• Computational advances allow volumetric reconstruction but are limited by processing artifacts.

Purpose of the Study:

• To develop an integrated imaging system for label-free, multi-contrast analysis of intact human brain structures.
• To enable high-throughput, deformation-free reconstruction and comprehensive analysis of brain tissue.
• To quantitatively characterize pathological features associated with aging and neurodegeneration.

Main Methods:

• Integrated serial sectioning polarization-sensitive optical coherence tomography (PSOCT) and two-photon microscopy (2PM).
• Label-free multi-contrast imaging of scattering, birefringence, and autofluorescence.
• High-throughput reconstruction of 4 × 4 × 2cm³ sample blocks with simple image registration.

Main Results:

• Demonstrated high-throughput reconstruction of large brain tissue blocks.
• Enabled comprehensive analysis of myelin content, vascular structure, and cellular information.
• Revealed detailed cortical and white matter structures, including fibers, capillaries, and lipofuscin-filled cell bodies.
• Enabled quantitative characterization of myelin degradation, lipofuscin accumulation, and microvascular changes.

Conclusions:

• The integrated PSOCT and 2PM system provides label-free, multi-contrast imaging for detailed brain analysis.
• This technology facilitates the study of pathological features in aging and neurodegenerative diseases.
• Opens new avenues for research into the mechanisms of neurodegeneration.