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Most of the methods used in clinics to diagnose skin are invasive and require a biopsy for histological examination. In the last 10-15 years, the multiphoton tomography (MPT) with fluorescence lifetime imaging (FLIM) have advanced so much that it allow to obtain results comparable in sensitivity and specificity with histological analysis. MPT is based on non-linear optical effects, such as the optical harmonics generation, mainly the second harmonic generation (SHG), two-photon excited auto fluorescence (TPEAF) and coherent anti-Stokes Raman scattering (CARS). These effects are observed when ultrashort (usually femtosecond) laser pulses are used as a pump. The use of such pulses can increase the penetration depth of radiation into the skin. MPT is an imaging technique allowing not only to analyze the architecture of the tissue, but also to selectively detect certain types of molecules using their spectral or fluorescence lifetime-based signature, thus allowing to perform imaging of metabolic processes. However, MPT capabilities are currently limited to several specific applications, e.g. assessment of epidermal cells and collagen type I in the upper dermis, while a number of clinically relevant structures and processes remain not investigated. Recently, we suggested the MPT/FLIM based approach to assess blood vessels and structural proteins localization in the upper dermis. This stimulated further research of the area around superficial capillaries, which is metabolically active due to exchange of chemicals through the capillary wall. The first question we addressed was the manifestation of fluid retention, i.e. the edemateous syndrome, in the properties of perivascular zone for patients suffering from heart failure. It was shown that the increased amount of interstitial fluid controls the intercellular space and the size of viable epidermis. Next, migration and localization of cells in the vicinity of blood vessels in the papillary dermis was investigated, and the question about the possibility of mast cells imaging was addressed. Finally, transcapillary diffusion of model substances was studied in the papillary dermis, and the origin of two-photon and one-photon fluorescence of blood cells is discussed. The work was supported by the Russian Science Foundataion (grant №17-75- 10215)