Scattering detection in multi-layer tissue: phantom experiments and in vivo applications

Deep tissue imaging using visible light is challenging due to its turbid nature. Nevertheless, clinical information can be detected by sensing changes in the tissue's optical properties with low spatial resolution. The most challenging aspect is the spectral dependent scattering, which varies with physiological state and tissue layer. In this paper, we present the multi-layer study of the reflection-based iterative multiplane optical property extraction (IMOPE) technique. The IMOPE is a noninvasive nanophotonics technique that detects medium scattering properties based on the reemitted light phase. The extracted scattering properties are used as indicators of the internal tissue information and the presence of additional nanoparticles (NPs) in it. The technique is a combination of a theoretical model, an experimental setup, and the phase retrieval Gerchberg-Saxton algorithm. The IMOPE experimental setup records light intensity images at different locations, in order to reconstruct the phase by the multi-plane GS algorithm. Once the phase distribution is reconstructed, its root mean square (RMS) is calculated and compared to a theoretical model for obtaining the reduced scattering coefficient. This work presents the study of single-layer and two-layer tissue-like phantoms and a new phase image analysis that provides detection of different scattering layers with 0.2mm-1 sensitivity at different depths, following layers up to 6mm thickness. The IMOPE with the new phase image analysis was applied for the detection of the novel iron-based NPs drug (Nano-Leish-IL) in mice leishmaniasis lesions, where it was detected in the epidermis (∼1/413μm) and dermis (∼1/4160μm) at different stages of the disease.