The goal of this research project is to expand the capabilities of optical sensing and monitoring technology for in vivo functional and molecular sensing and imaging through use of reducing light scattering in tissue. This work proposes to increase the light penetration in tissue through introduction of clearing agents (glycerol and others) which dehydrate tissue and provide a better index of refraction match with collagen, the primary cause of light scattering in tissue. Specific aims are to characterize the transport of hyper-osmotic agents, demonstrate enhanced light propagation and optical sensing, and extend applications of the tissue clearing process to molecular and functional sensing and imaging.