Controling the scattering of Intralipid by using optical clearing agents

Optical clearing agents (OCAs) with high refractive indices and hyperosmolarity can enhance the penetration of light in tissues by reducing scattering in tissues. However, the mechanism of tissue optical clearing is not much clear for the complex interaction between tissues and OCAs. In this work, Intralipid was mixed with different concentrations of OCAs, i.e. dimethyl sulfoxide (DMSO), glycerol, 1,4-butanediol, 1,2-propanediol, poly-ethylene glycol 200 (PEG200) and poly-ethylene glycol 400 (PEG400). Except for PEG200 and PEG400 that make aggregation of particles, the others kept the mixture uniform. The reduced scattering coefficients of uniform mixtures were predicted with Mie theory and measured by a commercially available spectrophotometer with an integrating sphere. The results show that all of the OCAs used enhance the optical clearing effect of Intralipid. If OCAs do not change the structure of Intralipid, Mie theory prediction matches well with the measurements. And the higher the refractive index of OCA, the smaller the reduced scattering coefficient. A simple formula deduced can quantitatively predict the optical clearing effect caused by OCAs. This work is helpful for clarifying the mechanism of tissue optical clearing, which will make the effect of optical clearing of tissue predictable and controllable.