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6Optical clearing as a new approach to increasing the efficiency of laser thermolysis of adipose tissue
I.Yu. Yanina1'2*' D.K. Tuchina1'2, P.A. Timoshina1'2, E.A. Genina1'2, V.V. Tuchin1'2
1- Saratov State University (National Research University), Institute of Physics, 83 Astrakhanskaya str., Saratov
410012, Russia
2- Tomsk State University (National Research University), Laboratory of laser molecular imaging and machine
learning, 36Lenin's av., Tomsk 634050, Russia
The technique based on the combination of photochemical and photothermal effects induces adipose tissue optical clearing (OC) on the cell level [1-6]. In this technique, to control the optical scattering properties of the adipose tissue laser radiation is used. Depending on the intensity of laser radiation, the biological response of the cell may lead to reversible or irreversible injury of the cell membrane, which results in the creation of new pores or enlargement of the already existing ones, through which efficient exchange between the cell content and the environment takes place. For adipocytes, the presence of pores promotes lipolysis, as a result of which the intercellular space is filled with the contents of the cells and their decay products (triglycerides, fatty acids, water and glycerol) [2,7]. The appearance in the intercellular space of such an immersion fluid contributes to the process of OC of adipose tissue [8]. However, application of this technique can be accompanied by necrosis of irradiated adipocytes. Thus, it is necessary to reduce the side effects of OC procedure.
The possibility of temperature monitoring within adipose tissue in a wide temperature range, from room to human body temperatures and above by using of thermosensitive luminescent upconversion nanoparticles (UCNPs) [NaYF4:Yb3+, Er3+] [9]. The increase of luminescent intensity at high temperatures can be explained by OC associated with the phase transition of lipids. Application of optical clearing agents (OCAs) leads to a significant increase of detected intensity of laser-induced luminescence from the UCNPs. The obtained results confirm a high sensitivity of the luminescent UCNPs to the temperature variations within tissues and show a strong potential for providing of the controlled adipose tissue thermolysis. Also at immersion OC, a more reliable temperature measurement technique in tissues can be proposed by using luminescence from laser induced UCNPs.
The paper focuses on the technology of OC of abdominal fat tissue ex vivo using different complex hyperosmotic OCAs (dimethyl sulfoxide, diatrizoic acid, metrizoic acid, sucrose, and fructose solutions) and tissue permeability enhancers (fractional laser microablation and sonophoresis with various modes and their combinations). Kinetics and efficacy of the OC was evaluated using spatially resolved back reflectance measurements. Tissue morphology modification was monitored using the histological studies. Maximal clearing effect (83.5%) was observed for the samples subjected to the fructose-ethanol solution action during 90 min with gentle modes of fractional laser microablation and sonophoresis.
The study was supported by a grant Russian Science Foundation No. 24-44-00082, https://rscf.ru/project/24-44-00082/.
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