Experimental Evaluation of Human Skin Optical Clearing in vivo Efficiency Using Biocompatible Agents and Optical Coherence Tomography

The clinical use of optical methods for in vivo skin imaging is limited by skin strong scattering properties, which reduce image contrast and probing depth. The efficiency of optical methods can be improved by optical clearing (OC). However, for the use of optical clearing agents (OCAs) in a clinical setting, compliance with acceptable non-toxic concentrations is required. Optical clearing of in vivo human skin, combined with physical and chemical methods to enhance skin permeability to OCAs, was performed to determine the clearing-effectiveness of biocompatible OCAs using Line-field Confocal Optical Coherence Tomography (LC-OCT) imaging. Nine types of OCAs mixtures were used in combination with dermabrasion and sonophoresis for optical clearing protocol on three volunteers hand skin. From 3D images obtained every five minutes for 40 minutes, the intensity and contrast parameters were extracted to assess their changes during the clearing process and evaluate each OCAs mixture's clearing efficacy. LC-OCT images average intensity and contrast increased over the entire skin depth with all OCAs. The best image contrast and intensity improvement was observed using the Polyethylene Glycol, Oleic Acid and Propylene Glycol mixture. To estimate the overall completion of the clearing process after the end of the active experimental phase, the experimental data were fitted using the Biphasic Exponential Association model. The fitting results largely agreed with the experimental results. Complex OCAs featuring reduced component concentrations that meet drug regulation-established biocompatibility requirements were developed and proved to induce significant skin tissues clearing. By allowing deeper observations and higher contrast, such OCAs in combination with physical and chemical permeation enhancers may improve LC-OCT diagnostic efficacy.