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Combined nonlinear imaging technique reveals interaction of chemical agent with dermal collagen

Some chemical agents, including dimethyl-sulfoxide (DMSO), induce temporary transparency of the skin. This process, known as skin optical clearing, provides a direct solution for a problem well known to dermatologists: a limited view of what lies underneath the skin's upper layer. By making the skin's upper layer temporarily transparent, application of DMSO can thus aid the diagnosis of skin conditions.

Despite its usefulness, the actual mechanism of DMSO induced skin clearing is not understood. This lack of understanding also limits the application of the skin clearing method. It is, therefore, important to find out what the interactions are between DMSO and skin components that underlie the observed optical clearing effect. Experiments in vitro have suggested that the interaction of DMSO with collagen may play an important role in the clearing process. To confirm this hypothesis, BLI LAMMP researchers have now performed accurate experiments in skin in situ.

Laser scanning microscope system on which the
experiments were performed.

Measuring both the local concentration of the clearing agent and the dermal collagen in intact skin samples is not trivial. Students Max Zimmerley and Anthony McClure, in a joint project with LAMMP principal investigators Bernard Choi and Eric Potma, accomplished such measurements by combining second harmonic generation (SHG) microscopy with coherent anti-Stokes Raman scattering (CARS) imaging. Whereas SHG exhibits excellent sensitivity to collagen, CARS allows a sensitive registration of the local DMSO concentration.

By performing careful measurements, the research team managed to determine the overall decrease of fibrous collagen as a function of DMSO concentration in the human dermis. When a correlation with the skin's light scattering properties was made, the measurements revealed a likely correlation between skin optical clearing and the DMSO induced changes to the fibrous collagen matrix.

The results of this study, which are published in the April issue of Applied Optics, provide an important step to a comprehensive understanding of the skin optical clearing process. Future studies will focus on the reversibility of this process and on establishing clear benchmarks for the clinical applicability of DMSO as an optical clearing agent.

For more information please contact
Bernard Choi (choib@uci.edu)
Eric Potma (epotma@uci.edu)