Penetration-enhanced optical coherence tomography angiography with optical clearing agent for clinical evaluation of human skin

• The novel optical clearing agent (OCA) had an ability to improve optical coherence tomography angiography (OCTA) imaging in terms of depth and contrast. • The capability of OCTA and the efficacy of the OCA for in vivo imaging of the skin structure and vasculature in healthy volunteers and patients with port wine stains was investigated. • It highlights the great potential of OCTA and OCA as well as their contribution in the diagnosis of PWS lesions. Optical coherence tomography angiography (OCTA) is an emerging imaging technique which shows its advantages over visualizing microcirculation with free label. However, its shortcomings in imaging depth limit its development in dermatological field. Nowadays, the newly optical clearing agent (OCA) designed for skin optical imaging demonstrates its potential. In our study, whether this OCA can improve the imaging ability of OCTA in healthy human skin and whether the combination of them is beneficial to compare the lesions and the contralateral normal skins in the patients with port wine stains (PWS) have been investigated. Five healthy volunteers and 3 PWS patients were recruited in this study. In terms of healthy people, the opisthenar area which has same structure information as facial skin was taken for investigating the OCA’s ability of enhancing OCTA imaging depth on healthy human skin, besides, in order to verifying whether the exists of skin corneum interfere OCA’s function, we compared the effect of only using OCA with that of comprehensive using pre-processing skin and OCA. There are one physical removing corneum method by using medical tape to strip opisthenar skin for over 20-time and one chemical way through applying exfoliating cream. For PWS patient, the combining using OCA and OCTA was applied at the lesion area and the contralateral normal area for the purpose of verifying their ability to provide the information of vessels. This novel OCA had excellent efficacy to increase the penetration depth of human opisthenar skin for the OCTA imaging by approximately 0.16 ± 0.03 mm. Pre-processing of stratum corneum with an exfoliating cream or medical tape stripping did not further benefit the penetrating efficacy of the OCA. Moreover, according to a comprehensive analysis of the OCTA images enhanced by the OCA, the PWS lesions usually have larger density and diameter of the vessels which located in deep layers (beyond 0.21 mm) than the contralateral normal skin. The OCTA imaging depth and contrast were significantly improved by the OCA. The OCA application is a simple and efficient clinical procedure for OCTA enhancement. Moreover, it demonstrated great clinical value to compare the normal skin and the PWS lesions in the patients by the enhanced OCTA imaging.