Reconstructing micrometer-scale fiber pathways in the brain: multi-contrast optical coherence tomography based tractography.

Comprehensive understanding of connective neural pathways in the brain has put great challenges on the current imaging techniques, for which three-dimensional (3D) visualization of fiber tracts with high spatiotemporal resolution is desirable. Here we present optical imaging and tractography of rat brain ex-vivo using multi-contrast optical coherence tomography (MC-OCT), which is capable of simultaneously generating depth-resolved images of reflectivity, phase retardance, optic axis orientation and, for in-vivo studies, blood flow images. Using the birefringence property of myelin sheath, nerve fiber tracts as small as a few tens of micrometers can be resolved and neighboring fiber tracts with different orientations can be distinguished in cross-sectional optical slices, 2D en-face images and 3D volumetric images. Combinational contrast of MC-OCT images enables visualization of the spatial architecture and nerve fiber orientations in the brain with unprecedented detail. The results suggest that optical tractography, by virtue of its direct accessibility to nerve fibers, has the potential to validate diffusion magnetic resonance images and investigate structural connections in normal brain and neurological disorders. In addition, an endoscopic MC-OCT may be useful in neurosurgical interventions to aid in placement of deep brain stimulating electrodes.