The highly disordered refractive index distribution in biological tissue causes multiple-scattering of incident light and inhibits optical penetration depth. “Tissue optical clearing” increases penetration depth of near-collimated light in biological tissue, potentially resulting in improved optical analysis and treatment techniques. Numerous methods of tissue optical clearing have been hypothesized using hyperosmostic agents [1]. These methods propose reduction in light scattering by means of dehydration of tissue constituents, replacement of interstitial or intracellular water with higher refractive agents, or structural modification or dissociation of collagen fibers [2,3]. It has been suggested that dehydration of tissue constituents alone can reduce light scattering by expulsing water between collagen fibrils, increasing protein and sugar concentrations, and decreasing refractive index mismatch [4].