Label-free optical imaging to study brain connectivity and neuropathology

Abstract

The brain is composed of billions of neurons that communicate through an intricate network of axons and dendrites. The difficulty of tracing the 3D neuronal pathways, however, has been a challenge to study the brain connectivity in normal and diseased brains. Polarization-sensitive optical coherence tomography (PS-OCT) provides label-free and depth-resolved contrasts of tissue microstructure. For brain imaging, nerve fiber tracts that are as small as tens of micrometers can be highlighted by polarization-based contrasts due to the birefringent nature of myelin sheath. We applied optical imaging to investigate the anatomical changes associated with neurodegeneration and neuro-oncology. The former includes spinocerebellar ataxia type 1 (SCA1), a fatal inherited genetic disease. The intrinsic optical properties revealed the neuropathology in SCA1 mouse models. To investigate the role of nerve fiber tracts in glioblastoma invasion, we combined PS-OCT with confocal fluorescence microscopy to characterize glioma cell migration behavior in mouse brain slices. Moreover, PS-OCT can be adapted to quantify the inclination angles of nerve fibers and further developed to delineate the complete 3D neuronal pathways. This method and its future advances open up intriguing applications in neurological and psychiatric disorders.