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15MOUSE: ADVANCED APPROACHES TO SKIN IN VIVO OPTICAL CLEARING
ELINA A. GENINA1,2, ALEXEY N. BASHKATOV1,2, VALERY V. TUCHIN1,2,3, AND VLADIMIR P. ZHAROV1,4
1Saratov State University, Russia 2National Research Tomsk State University, Russia 3Institute of Precision Mechanics and Control RAS, Russia 4Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences, USA
eagenina@yandex.ru
Abstract
Immersion optical clearing of biological tissue that reduces the influence of light scattering on the quality of optical imaging led to breakthrough in biophotonic studies of tissue properties ex vivo [1, 2]. However, applications of these techniques in human skinin vivo is challenging due to low efficiency, toxicity concerns, and time consuming procedure. The use of biocompatible optical clearing agents makes it possible to some increase the probing depth of non-invasive optical diagnostic methods [3, 4]. However, the protective epidermal barrier of the skin prevents the penetration of immersion liquids into the deeper layers of the skin.
Based on our discoveries described here, we propose to solve the indicated above problems by combination of physical factors such as microdermabrasion and sonophoresis, which all are approved for application in humans. Our ultimate goal was to clarify the contribution of the Microdermabrasion, Oleic acid and UltraSound Effect (MOUSE) on optical clearing of human skin measured by OCT in vivo separately and in various combinations and to compare results obtained for light (II-type) and dark (VI-type) skin.
This study involved healthy volunteers 19-23 years old with II and VI skin types. Microdermabrasion associated with mechanical peeling and massage was performed applied using a commercially available device with sapphire tip and vacuum massager. Sonophoresis was performed using a commercially available ultrasonic therapeutic device.Optical coherence tomography (OCT) allowed to differentiate the contribution of each factors separately and in different combinations.
Results have demonstrated that topical application of MOUSE can provide increasing the optical penetration depth inhuman skin in vivo during short time. After optimization, OCT-signal amplitude increased more than3-fold with twice improved depth penetration for light skin during 30 minutes that significantly exceed the results obtained earlier (Fig. 1a,b). All optical clearing approaches were tested on skin with VI phototype (deeply pigmented dark brown to black skin according to Fitzpatrick Skin Type ClassificationScale). After combined optical clearing 1.3-fold increase in OCT-signal amplitude was achieved for dark skin (Fig. 1a,c).
These results show a high potential of the advanced clearing techniques for broad application in the optical diagnostics of skin and peripheral blood and lymphatic systems. MOUSE has not required a multicomponent composition of the OCA and has not caused dehydration and shrinkage of the skin, which are induced by hyperosmotic hydrophilic agents. Consequently, there is a low risk of side effects. A comparison of the presented results has shown that the use of MOUSE for optical clearing of epidermis has significant advantages compared with separate use of microdermabrasion and sonophoresis for both light and dark skin. MOUSE has allowed significant increasing OCT signal amplitude during only 15-20 min that has been not demonstrated with other approaches. The novelty of this work is also discovering that OCT optical probing depth increases in skin due to only ultrasound impact without optical clearing agent application. Comparison of the MOUSE in light and dark skin has revealed similarity of the optical clearing mechanisms and differences in the magnitude of the effect. The obtained OCT optical probing depth increase of dark skin is a novel result, which is practically and socially relevant.
Intact skin
30 min
after
MOUSE
j^j
a
Depth (urn) Depth (urn)
b c
Figure 1: OCT B-scans of light and dark skin before and after MOUSE (a). Results are presented for volunteers ## 3-6. OCT-signal amplitude for light (a) and dark (b) skin before and 30 min after applicationof oleic acid (OA) on an intact skin surface (Group I); microdermabrasion followed by a single application of OA (Group II); combined application of OA and sonophoresis (Group III); microdermabrasion followed by application of OA and sonophoresis - MOUSE (Group IV). Results are averaged. Braces with asterisks combine groups with statistically significant differences between the OCT and the background signal (p<0.05). Figure is adapted from figures published in Ref. [5]. Bars correspond to 200 ^m.
References
[1] D. Zhu et al, Laser & Photonics Reviews 7, 732-757, 2013.
[2] P. Matryba et al, Laser Photon. Rev.13, 1800292, 2019.
[3] I. Costantini et al, Biomed. Opt. Express 10, 5251-5267, 2019.
[4] Q. Zhao et al, Sci. Rep. 6, 34954, 2016.
[5] E.A.Genina, et al, IEEE Trans Med Imaging 39, 3198-3206, 2020.
