Combination of tissular multimodal spectro-imaging and optical clearing methods to improve detection depth in skin in vivo ; Combinaison de méthodes de spectro-imagerie tissulaire multimodalités et de clarification optique pour améliorer la profondeur de détection dans la peau in vivo

This thesis presents the results of research in the context of improved analysis of the skin optical properties using various optical techniques, such as multimodal tissular spectroscopy and optical coherence tomography (OCT) imaging. Since many years optical techniques of skin characterization are an effective alternative to traditional invasive diagnostic methods as they allow to get information about the structural and biochemical skin composition in vivo in real time, which led to their extensive implementation in the clinical practice of skin lesions analysis. In the last decades it was demonstrated that combined use of several optical techniques allows to increase the diagnostic accuracy by increasing the variety of data acquired in one measurement. Spatial resolution may also increase the diagnostic potential by providing depth discrimination (resolution) between assessed layers. Even though the main limitation for the use of the optical methods in skin diagnostics is the strong absorption and scattering of the latter, skin optical properties can be changed using the method of skin optical clearing (OC). The combination of optical clearing agents (OCA) with various chemical and physical enhancers of skin permeability may significantly improve the potential of multimodal optical approaches with spatial resolution. The aim of the first experimental study within this thesis framework was (i) to investigate the effect of the OC process applied to ex vivo human skin samples on spatially resolved (SR) diffuse reflectance (DR) and autofluorescence (AF) spectra using two combinations of OCA and chemical permeation enhancers (CPE), and (ii) to quantify the clearing- like effect of drying and of spectroscopic probe pressure on skin. A spatially resolved multimodal spectroscopic device was used on a two- layered “hybrid” model made of ex vivo skin and fluorescent gel. Time kinetics of fluorescence and diffuse reflectance spectra demonstrate d an increase in the gel fluorescence back reflected intensity after optical ...