Single particle tracking through a multimode fiber endoscope for exploring the extracellular space in mouse brain

Multimode fiber (MMF) endoscopes have emerged as tools for minimally invasive imaging with optical resolution at depth in tissue, due to their small, 100 um, diameter. They have found use in imaging in brain in animal models, and have potential for clinical use for in situ diagnosis in sensitive tissues. In this project we will develop a method for single particle tracking (SPT)through a MMF, overcoming limitations of the lack of a practical way of implementing wide-field imaging in MMFs. SPT is used to investigate transport and diffusion in biological systems, as well as mapping spaces with a resolution of 10s of nm. Here, we will demonstrate the use of STP through a MMF to measure diffusion and map out the extra cellular space (ECS) in mouse brain. The ECS is critical for communication between neurons and it is relatively unexplored because of technical difficulties in imaging the network of thin (50-400nm) channels, especially in vivo. The project will also explore new, potentially faster tracking methods in few mode fibers by utilizing their mode structure.