Optical contrast is often the limiting factor in the imaging of live biological tissue. Studies were conducted in postmortem human brain to identify clinical applications where the structures of interest possess high intrinsic optical contrast and where the real-time, high-resolution imaging capabilities of optical coherence tomography (OCT) may be critical. Myelinated fiber tracts and blood vessels are two structures with high optical contrast. The ability to image these two structures in real time may improve the efficacy and safety of a neurosurgical procedure to treat Parkinson’s disease called deep brain stimulation (DBS). OCT was evaluated as a potential optical guidance system for DBS in 25 human brains. The results suggest that catheter-based OCT has the resolution and contrast necessary for DBS targeting. The results also demonstrate the ability of OCT to detect blood vessels with high sensitivity, suggesting a possible means to avoid their laceration during DBS. Other microscopic structures in the human brain with high optical contrast are pathological vacuoles associated with transmissible spongiform encephalopathy (TSE). TSE include diseases such as Mad Cow disease and Creutzfeldt-Jakob disease (CJD) in humans. OCT performed on the brain from a woman who died of CJD was able to detect clearly the pathological vacuoles.