Label-free optical imaging for human mesoscale connectivity with a focus on deep brain stimulation targets

PROJECT SUMMARY AND ABSTRACT Many neurological and psychiatric disorders are essentially connectionist disorders: certain sets of neurons have abnormally increased or decreased connectivity with other sets of neurons. Deep brain stimulation (DBS) therapies target small, unique populations of axons and/or cell bodies in order to treat brain disorders and normalize connectivity. Thus, mapping the wiring diagram of the brain is an important goal. Macroscale connectivity has been studied indirectly in humans using noninvasive neuroimaging. In order to develop a much higher resolution connectivity map of the brain, this project will develop depth-resolved polarized light imaging to visualize axons and fiber tracts. Since brain imaging and mapping at microscopic resolution is feasible with intrinsic optical contrasts (e.g. polarization-based) and depth-resolved block-face imaging is desired before histological processing, we have developed the serial optical coherence scanner (SOCS) for large-scale or whole brain imaging with microscopic resolution. SOCS combines a polarization-maintaining fiber based polarization-sensitive optical coherence tomography and a tissue slicer. This project will create a novel SOCS system that can image axonal tracts at the micron scale spatial resolution using unbiased optical contrasts (Aim 1). The approach will be evaluated, refined, and compared in the same brain tissue to neural tract-tracer labeling of tracts associated with DBS targets for brain disorders, in nonhuman animal models (Aim 2). The approach will then be applied to DBS targets in the human brain (Aim 3). The physical scales at which this project investigates the brain microstructure are unique (1-10 μm resolution across centimeters of tissue). This project will pave the way for the foundation of a future human connectome at the micron scale, which is the highest resolution achievable with current optical technology for imaging an entire human brain.