Cross-Polarization Optical Coherence Tomography for Clinical Evaluation of Dermal Lesion Degrees in Vulvar Lichen Sclerosus

The aim of the study was to identify different degrees of dermal lesions in vulvar lichen sclerosus (VLS) using cross-polarization optical coherence tomography (CP OCT) based on attenuation coefficient to detect disease early manifestations and to monitor the effectiveness of treatment.

Materials and Methods. The study included 10 patients without pathology and 39 patients with VLS diagnosed histologically. CP OCT was performed in vivo on the inner surface of the labia minora, in the main lesion area. From each scanning point, a 3.4×3.4×1.25-mm³ 3D data array was obtained in 26 s. CP OCT examination results were compared with histological examination of specimens stained with Van Gieson’s picrofuchsin.

Quantitative analysis of OCT images was performed by measuring the attenuation coefficient in co-polarization and cross-polarization. For visual analysis, color-coded charts were developed based on OCT attenuation coefficients.

Results. According to histological examination, all patients with VLS were divided into 4 groups as per dermal lesion degree: initial (8 patients); mild (7 patients); moderate (9 patients); severe (15 patients). Typical features of different degrees were interfibrillary edema up to 250 μm deep for initial degree, thickened collagen bundles without edema up to 350 μm deep for mild degree, dermis homogenization up to 700 μm deep for moderate degree, dermis homogenization and total edema up to 1200 μm deep for severe degree.

Pathological processes in dermis during VLS like interfibrillary edema and collagen bundles homogenization were visualized using CP OCT method based on values of attenuation coefficient in co- and cross-polarization channels. However, CP OCT method appeared to be less sensitive to changes of collagen bundles thickness not allowing to distinguish thickened collagen bundles from normal ones with enough statistical significance. The CP OCT method was able to differentiate all degrees of dermal lesions among themselves. OCT attenuation coefficients differed from normal condition with statistical significance for all degrees of lesions, except for mild.

Conclusion. For the first time, quantitative parameters for each degrees of dermis lesion in VLS, including initial degree, were determined by CP OCT method allowing to detect the disease at an early stage and to monitor the applied clinical treatment effectiveness.

1. Terlou A., Santegoets L.A., van der Meijden W.I., Heijmans-Antonissen C., Swagemakers S.M., van der Spek P.J., Ewing P.C., van Beurden M., Helmerhorst T.J., Blok L.J. An autoimmune phenotype in vulvar lichen sclerosus and lichen planus: a Th1 response and high levels of microRNA-155. J Invest Dermatol 2012; 132(3 Pt 1): 658–666, https://doi.org/10.1038/jid.2011.369.
2. Wijaya M., Lee G., Fischer G. Quality of life of women with untreated vulval lichen sclerosus assessed with vulval quality of life index (VQLI). Australas J Dermatol 2021; 62(2): 177–182, https://doi.org/10.1111/ajd.13530.
3. Kirtschig G., Cooper S., Aberer W., Günthert A., Becker K., Jasaitiene D., Chi C.C., Kreuter A., Rall K.K., Riechardt S., Casabona F., Powell J., Brackenbury F., Erdmann R., Lazzeri M., Barbagli G., Wojnarowska F. Evidence-based (S3) guideline on (anogenital) lichen sclerosus. J Eur Acad Dermatol Venereol 2017; 31(2): e81–e83, https://doi.org/10.1111/jdv.13740.
4. Spekreijse J.J., Streng B.M.M., Vermeulen R.F.M., Voss F.O., Vermaat H., van Beurden M. The risk of developing squamous cell carcinoma in patients with anogenital lichen sclerosis: a systematic review. Gynecol Oncol 2020; 157(3): 671–677, https://doi.org/10.1016/j.ygyno.2020.02.020.
5. Lee A., Bradford J., Fischer G. Long-term management of adult vulvar lichen sclerosus: a prospective cohort study of 507 women. JAMA Dermatol 2015; 151(10): 1061–1067, https://doi.org/10.1001/jamadermatol.2015.0643.
6. Lewis F.M., Tatnall F.M., Velangi S.S., Bunker C.B., Kumar A., Brackenbury F., Mohd Mustapa M.F., Exton L.S. British Association of Dermatologists guidelines for the management of lichen sclerosus, 2018. Br J Dermatol 2018; 178(4): 839–853, https://doi.org/10.1111/bjd.16241.
7. Vulvar pathology. 2015th edition. Hoang M.P., Selim M.A. (editors). New York, NY: Springer New York; 2015.
8. Potapov A.L., Sirotkina M.A., Matveev L.A., Dudenkova V.V., Elagin V.V., Kuznetsov S.S., Karabut M.M., Komarova A.D., Vagapova N.N., Safonov I.K., Kuznetsova I.A., Radenska-Lopovok S.G., Zagaynova E.V., Gladkova N.D. Multiphoton microscopy assessment of the structure and variability changes of dermal connective tissue in vulvar lichen sclerosus: a pilot study. J Biophotonics 2022; 15(9): e202200036, https://doi.org/10.1002/jbio.202200036.
9. Cox G., Kable E., Jones A., Fraser I., Manconi F., Gorrell M.D. 3-dimensional imaging of collagen using second harmonic generation. J Struct Biol 2003; 141(1): 53–62, https://doi.org/10.1016/s1047-8477(02)00576-2.
10. Leitgeb R., Placzek F., Rank E., Krainz L., Haindl R., Li Q., Liu M., Andreana M., Unterhuber A., Schmoll T., Drexler W. Enhanced medical diagnosis for dOCTors: a perspective of optical coherence tomography. J Biomed Opt 2021; 26(10): 100601, https://doi.org/10.1117/1.jbo.26.10.100601.
11. Wan B., Ganier C., Du-Harpur X., Harun N., Watt F.M., Patalay R., Lynch M.D. Applications and future directions for optical coherence tomography in dermatology. Br J Dermatol 2021; 184(6): 1014–1022, https://doi.org/10.1111/bjd.19553.
12. Sirotkina M.A., Potapov A.L., Vagapova N.N., Safonov I.K., Karashtin D.A., Matveev L.A., Radenska-Lopovok S.G., Timakova A.A., Kuznetsov S.S., Zagaynova E.V., Kuznetsova I.A., Gladkova N.D. Multimodal optical coherence tomography: imaging of blood and lymphatic vessels of the vulva. Sovremennye tehnologii v medicine 2019; 11(4): 26, https://doi.org/10.17691/stm2019.11.4.03.
13. Moiseev A.A., Achkasova K.A., Kiseleva E.B., Yashin K.S., Potapov A.L., Bederina E.L., Kuznetsov S.S., Sherstnev E.P., Shabanov D.V., Gelikonov G.V., Ostrovskaya Y.V., Gladkova N.D. Brain white matter morphological structure correlation with its optical properties estimated from optical coherence tomography (OCT) data. Biomed Opt Express 2022; 13(4): 2393–2413, https://doi.org/10.1364/boe.457467.
14. Schmitt J.M., Xiang S.H. Cross-polarized backscatter in optical coherence tomography of biological tissue. Opt Lett 1998; 23(13): 1060–1062, https://doi.org/10.1364/ol.23.001060.
15. Yashin K.S., Kiseleva E.B., Moiseev A.A., Kuznetsov S.S., Timofeeva L.B., Pavlova N.P., Gelikonov G.V., Medyanik I.А., Kravets L.Y., Zagaynova E.V., Gladkova N.D. Quantitative nontumorous and tumorous human brain tissue assessment using microstructural co- and cross-polarized optical coherence tomography. Sci Rep 2019; 9(1): 2024, https://doi.org/10.1038/s41598-019-38493-y.
16. Gong P., McLaughlin R.A., Liew Y.M., Munro P.R., Wood F.M., Sampson D.D. Assessment of human burn scars with optical coherence tomography by imaging the attenuation coefficient of tissue after vascular masking. J Biomed Opt 2014; 19(2): 21111, https://doi.org/10.1117/1.jbo.19.2.021111.
17. Gong P., Almasian M., van Soest G., de Bruin D.M., van Leeuwen T.G., Sampson D.D., Faber D.J. Parametric imaging of attenuation by optical coherence tomography: review of models, methods, and clinical translation. J Biomed Opt 2020; 25(4): 1–34, https://doi.org/10.1117/1.jbo.25.4.040901.
18. Vingan N.R., Parsa S., Barillas J., Culver A., Kenkel J.M. Evaluation and characterization of facial skin aging using optical coherence tomography. Lasers Surg Med 2023; 55(1): 22–34, https://doi.org/10.1002/lsm.23611.
19. Boone M.A.L.M., Suppa M., Dhaenens F., Miyamoto M., Marneffe A., Jemec G.B.E., Del Marmol V., Nebosis R. In vivo assessment of optical properties of melanocytic skin lesions and differentiation of melanoma from non-malignant lesions by high-definition optical coherence tomography. Arch Dermatol Res 2016; 308(1): 7–20, https://doi.org/10.1007/s00403-015-1608-5.
20. Boone M., Suppa M., Miyamoto M., Marneffe A., Jemec G., Del Marmol V. In vivo assessment of optical properties of basal cell carcinoma and differentiation of BCC subtypes by high-definition optical coherence tomography. Biomed Opt Express 2016; 7(6): 2269–2284, https://doi.org/10.1364/boe.7.002269.
21. Shilyagin P.A., Gelikonov G.V., Gelikonov V.M., Moiseev A.A., Terpelov D.A. Achromatic registration of quadrature components of the optical spectrum in spectral domain optical coherence tomography. Quantum Electron 2014; 44(7): 664, https://doi.org/10.1070/qe2014v044n07abeh015465.
22. Shilyagin P.A., Ksenofontov S.Yu., Moiseev A.A., Terpelov D.A., Matkivsky V.A., Kasatkina I.V., Mamaev Yu.A., Gelikonov G.V., Gelikonov V.M. Equidistant recording of the spectral components in ultra-wideband spectral-domain optical coherence tomography. Radiophys Quantum Electron 2018; 60(10): 769–778, https://doi.org/10.1007/s11141-018-9845-z.
23. Gelikonov V.M., Romashov V.N., Shabanov D.V., Ksenofontov S.Yu., Terpelov D.A., Shilyagin P.A., Gelikonov G.V., Vitkin I.A. Cross-polarization optical coherence tomography with active maintenance of the circular polarization of a sounding wave in a common path system. Radiophys Quantum Electron 2018; 60(11): 897–911, https://doi.org/10.1007/s11141-018-9856-9.
24. McLaughlin R.A., Scolaro L., Robbins P., Saunders C., Jacques S.L., Sampson D.D. Parametric imaging of cancer with optical coherence tomography. J Biomed Opt 2010; 15(4): 046029, https://doi.org/10.1117/1.3479931.
25. Vermeer K.A., Mo J., Weda J.J.A., Lemij H.G., de Boer J.F. Depth-resolved model-based reconstruction of attenuation coefficients in optical coherence tomography. Biomed Opt Express 2013; 5(1): 322–337, https://doi.org/10.1364/boe.5.000322.
26. Gubarkova E.V., Moiseev A.A., Kiseleva E.B., Vorontsov D.A., Kuznetsov S.S., Vorontsov A.Y., Gelikonov G.V., Sirotkina M.A., Gladkova N.D. Tissue optical properties estimation from cross-polarization OCT data for breast cancer margin assessment. Laser Phys Lett 2020; 17(7): 075602, https://doi.org/10.1088/1612-202x/ab9091.
27. Kut C., Chaichana K.L., Xi J., Raza S.M., Ye X., McVeigh E.R., Rodriguez F.J., Quiñones-Hinojosa A., Li X. Detection of human brain cancer infiltration ex vivo and in vivo using quantitative optical coherence tomography. Sci Transl Med 2015; 7(292): 292ra100, https://doi.org/10.1126/scitranslmed.3010611.
28. Sirotkina M.A., Potapov A.L., Vagapova N.N., Safonov I.K., Karabut M.M., Kuznetsova I.A., Karashtin D.A., Matveev L.A., Radenska-Lopovok S.G., Timakova A.A., Zagaynova E.V., Gladkova N.D. In vivo study of vulvar mucosa microcirculation in norm and diseases. Proceedings Volume 11362, Clinical Biophotonics 2020; 1136205, https://doi.org/10.1117/12.2555366.
29. Welzel J., Bruhns M., Wolff H.H. Optical coherence tomography in contact dermatitis and psoriasis. Arch Dermatol Res 2003; 295(2): 50–55, https://doi.org/10.1007/s00403-003-0390-y.
30. Phillips K.G., Wang Y., Levitz D., Choudhury N., Swanzey E., Lagowski J., Kulesz-Martin M., Jacques S.L. Dermal reflectivity determined by optical coherence tomography is an indicator of epidermal hyperplasia and dermal edema within inflamed skin. J Biomed Opt 2011;16(4): 040503, https://doi.org/10.1117/1.3567082.

Potapov A.L., Loginova M.M., Moiseev A.A., Radenska-Lopovok S.G., Kuznetsov S.S., Kuznetsova I.A., Mustafina N.N., Safonov I.K., Gladkova N.D., Sirotkina M.A. Cross-Polarization Optical Coherence Tomography for Clinical Evaluation of Dermal Lesion Degrees in Vulvar Lichen Sclerosus. Sovremennye tehnologii v medicine 2023; 15(1): 53, https://doi.org/10.17691/stm2023.15.1.06