Skip to main content
Log in

Methods for Optical Skin Clearing in Molecular Optical Imaging in Dermatology

  • Review
  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

This short review describes recent progress in using optical clearing (OC) technique in skin studies. Optical clear-ing is an efficient tool for enhancing the probing depth and data quality in multiphoton microscopy and Raman spec-troscopy. Here, we discuss the main mechanisms of OC, its safety, advantages, and limitations. The data on the OC effect on the skin water content are presented. It was demonstrated that 70% glycerol and 100% OmnipaqueTM 300 reduce the water content in the skin. Both OC agents (OCAs) significantly affect the strongly bound and weakly bound water. However, OmnipaqueTM 300 causes considerably less skin dehydration than glycerol. In addition, the results of examination of the OC effect on autofluorescence in two-photon excitation and background fluorescence in Raman scattering at different skin depths are presented. It is shown that OmnipaqueTM 300 is a promising OCA due to its ability to reduce background fluo-rescence in the upper skin layers. The possibility of multimodal imaging combining optical methods and OC technique is discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

AF:

autofluorescence

CARS:

coherent anti-Stokes Raman spectroscopy

DMSO:

dimethyl sulfoxide

MPT:

multiphoton tomography

OC:

optical clearing

OCA:

optical clearing agent

OCT:

optical coherence tomography

PA:

photoacoustics

PAT:

PA tomography

PEG:

polyethylene glycol

RS:

Raman spectroscopy

RM:

Raman microscopy

SERS:

surface enhanced Raman scattering

SHG:

second har-monic generation

References

  1. Agache, P., and Humbert, P. (2004) Measuring the Skin, Springer Science Business Media, Berlin.

    Book  Google Scholar 

  2. Potts, R. (1997) Skin barrier: principles of percutaneous absorption, Arch. Dermatol., 133, 924–924.

    Article  Google Scholar 

  3. Yokota, M., and Tokudome, Y. (2016) The effect of glyca–tion on epidermal lipid content, its metabolism and change in barrier function, Skin Pharmacol. Physiol., 29, 231–242.

    Article  CAS  PubMed  Google Scholar 

  4. Proksch, E., Brandner, J. M., and Jensen, J. M. (2008) The skin: an indispensable barrier, Exp. Dermatol., 17, 1063–1072.

    Article  PubMed  Google Scholar 

  5. Van Smeden, J., Janssens, M., Kaye, E. C., Caspers, P. J., Lavrijsen, A. P., Vreeken, R. J., and Bouwstra, J. A. (2014) The importance of free fatty acid chain length for the skin barrier function in atopic eczema patients, Exp. Dermatol., 23, 45–52.

    Article  CAS  PubMed  Google Scholar 

  6. Fercher, A. F. (1996) Optical coherence tomography, J. Biomed. Opt., 1, 157–173.

    Article  CAS  PubMed  Google Scholar 

  7. Gambichler, T., Pljakic, A., and Schmitz, L. (2015) Recent advances in clinical application of optical coherence tomography of human skin, Clin. Cosmet. Invest. Dermatol., 8, 345–354.

    Article  Google Scholar 

  8. Darvin, M. E., Gersonde, I., Albrecht, H., Gonchukov, S. A., Sterry, W., and Lademann, J. (2005) Determination of beta carotene and lycopene concentrations in human skin using resonance Raman spectroscopy, Laser Phys., 15, 295–299.

    CAS  Google Scholar 

  9. Vyumvuhore, R., Tfayli, A., Piot, O., Le Guillou, M., Guichard, N., Manfait, M., and Baillet–Guffroy, A. (2014) Raman spectroscopy: in vivo quick response code of skin physiological status, J. Biomed. Opt., 19, 111603.

    Article  CAS  PubMed  Google Scholar 

  10. Krafft, C., and Popp, J. (2015) The many facets of Raman spectroscopy for biomedical analysis, Anal. Bioanal. Chem., 407, 699–717.

    Article  CAS  PubMed  Google Scholar 

  11. Choe, C., Lademann, J., and Darvin, M. E. (2016) A depth–dependent profile of the lipid conformation and lat–eral packing order of the stratum corneum in vivo measured using Raman microscopy, Analyst, 141, 1981–1987.

    Article  CAS  PubMed  Google Scholar 

  12. Darvin, M. E., Sterry, W., Lademann, J., and Vergou, T. (2011) The role of carotenoids in human skin, Molecules, 16, 10491–10506.

    Article  PubMed Central  Google Scholar 

  13. Konig, K., and Riemann, I. (2003) High–resolution multi–photon tomography of human skin with subcellular spatial resolution and picosecond time resolution, J. Biomed. Opt., 8, 432–439.

    Article  PubMed  Google Scholar 

  14. Balu, M., Mikami, H., Hou, J., Potma, E. O., and Tromberg, B. J. (2016) Rapid mesoscale multiphoton microscopy of human skin, Biomed. Opt. Express, 7, 4375–4387.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Shirshin, E. A., Gurfinkel, Y. I., Priezzhev, A. V., Fadeev, V. V., Lademann, J., and Darvin, M. E. (2017) Two–photon autofluorescence lifetime imaging of human skin papillary dermis in vivo: assessment of blood capillaries and structur–al proteins localization, Sci. Rep., 7, 1171.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Shirshin, E. A., Gurfinkel, Y. I., Matskeplishvili, S. T., Sasonko, M. L., Omelyanenko, N. P., Yakimov, B. P., Lademann, J., and Darvin, M. E. (2018) In vivo optical imaging of the viable epidermis around the nailfold capil–laries for the assessment of heart failure severity in humans, J. Biophotonics, 11, e201800066.

    Google Scholar 

  17. Abookasis, D., and Moshe, T. (2014) Feasibility study of hid–den flow imaging based on laser speckle technique using mul–tiperspectives contrast images, Opt. Laser Eng., 62, 38–45.

    Article  Google Scholar 

  18. Sdobnov, A., Bykov, A., Molodij, G., Kalchenko, V., Jarvinen, T., Popov, A., Kordas, K., and Meglinski, I. (2018) Speckle dynamics under ergodicity breaking, J. Phys. D. Appl. Phys., 51, 155401.

    Article  CAS  Google Scholar 

  19. Ferulova, I., Lihachev, A., and Spigulis, J. (2015) Photobleaching effects on in vivo skin autofluorescence lifetime, J. Biomed. Opt., 20, 051031.

    Article  PubMed  Google Scholar 

  20. Maciel, V. H., Correr, W. R., Kurachi, C., Bagnato, V. S., and da Silva Souza, C. (2017) Fluorescence spectroscopy as a tool to in vivo discrimination of distinctive skin disorders, Photodiagn. Photodyn. Ther., 19, 45–50.

    Article  CAS  Google Scholar 

  21. Lademann, J., Patzelt, A., Darvin, M., Richter, H., Antoniou, C., Sterry, W., and Koch, S. (2008) Application of optical non–invasive methods in skin physiology, Laser Phys. Lett., 5, 335–346.

    Article  CAS  Google Scholar 

  22. Ulrich, M., Klemp, M., Darvin, M. E., Konig, K., Lademann, J., and Meinke, M. C. (2013) In vivo detection of basal cell carcinoma: comparison of a reflectance confo–cal microscope and a multiphoton tomograph, J. Biomed. Opt., 18, 61229.

    Article  PubMed  Google Scholar 

  23. Darvin, M. E., Richter, H., Meinke, M. C., Knorr, F., Lademann, J., Zhu, Y. J., Gonchukov, S. A., and Koenig, K. (2014) Comparison of in vivo and ex vivo laser scanning microscopy and muliphoton tomography application for human and porcine skin imaging, Quantum Electron., 44, 646–651.

    Article  CAS  Google Scholar 

  24. Marti–Bonmati, L., Sopena, R., Bartumeus, P., and Sopena, P. (2010) Multimodality imaging techniques, Contrast Media Mol. Imaging, 5, 180–189.

    Article  CAS  PubMed  Google Scholar 

  25. Chen, Z., Rank, E., Meiburger, K. M., Sinz, C., Hodul, A., Zhang, E., Hoover, E., Minneman, M., Ensher, J., Beard, P. C., Kittler, H., Leitgeb, R. A., Drexler, W., and Liu, M. Y. (2017) Non–invasive multimodal optical coher–ence and photoacoustic tomography for human skin imag–ing, Sci. Rep., 7, 17975.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Konig, K., Speicher, M., Buckle, R., Reckfort, J., McKenzie, G., Welzel, J., Koehler, M. J., Elsner, P., and Kaatz, M. (2009) Clinical optical coherence tomography combined with multiphoton tomography of patients with skin diseases, J. Biophotonics, 2, 389–397.

    Article  PubMed  Google Scholar 

  27. Fan, B., Neel, V. A., and Yaroslavsky, A. N. (2017) Multimodal imaging for nonmelanoma skin cancer margin delineation, Laser Surg. Med., 49, 319–326.

    Article  Google Scholar 

  28. Peng, T., Xie, H., Ding, Y. C., Wang, W. C., Li, Z. M., Jin, D. Y., Tang, Y. H., Ren, Q. S., and Xi, P. (2012) CRAFT: multimodality confocal skin imaging for early cancer diag–nosis, J. Biophotonics, 5, 469–476.

    Article  PubMed  Google Scholar 

  29. Konig, K., Raphael, A. P., Lin, L., Grice, J. E., Soyer, H. P., Breunig, H. G., Roberts, M. S., and Prow, T. W. (2011) Applications of multiphoton tomographs and femtosecond laser nanoprocessing microscopes in drug delivery research, Adv. Drug Deliver Rev., 63, 388–404.

    Article  CAS  Google Scholar 

  30. Patalay, R., Talbot, C., Alexandrov, Y., Munro, I., Neil, M. A. A., Konig, K., French, P. M. W., Chu, A., Stamp, G. W., and Dunsby, C. (2011) Quantification of cellular autofluo–rescence of human skin using multiphoton tomography and fluorescence lifetime imaging in two spectral detection channels, Biomed. Opt. Express, 2, 3295–3308.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Darvin, M. E., Konig, K., Kellner–Hoefer, M., Breunig, H. G., Werncke, W., Meinke, M. C., Patzelt, A., Sterry, W., and Lademann, J. (2012) Safety assessment by multi–photon fluorescence/second harmonic generation/hyper–rayleigh scattering tomography of ZnO nanoparticles used in cosmetic products, Skin Pharmacol. Physiol., 25, 219–226.

    Article  CAS  PubMed  Google Scholar 

  32. Sanchez, W. Y., Obispo, C., Ryan, E., Grice, J. E., and Roberts, M. S. (2013) Changes in the redox state and endogenous fluorescence of in vivo human skin due to intrinsic and photo–aging, measured by multiphoton tomography with fluorescence lifetime imaging, J. Biomed. Opt., 18, 061217.

    Article  PubMed  Google Scholar 

  33. Breunig, H. G., Weinigel, M., Buckle, R., Kellner–Hofer, M., Lademann, J., Darvin, M. E., Sterry, W., and Konig, K. (2013) Clinical coherent anti–Stokes Raman scattering and multiphoton tomography of human skin with a fem–tosecond laser and photonic crystal fiber, Laser Phys. Lett., 10, 025604.

    Article  CAS  Google Scholar 

  34. Tuchin, V. V. (2015) Tissue Optics: Light Scattering Methods and Instruments for Medical Diagnostics, SPIE Press, Bellingham.

    Book  Google Scholar 

  35. Gratton, E. (2011) Deeper tissue imaging with total detec–tion, Science, 331, 1016–1017.

    Article  PubMed  Google Scholar 

  36. Tuchin, V. V., Maksimova, I. L., Zimnyakov, D. A., Kon, I. L., Mavlyutov, A. H., and Mishin, A. A. (1997) Light prop–agation in tissues with controlled optical properties, J. Biomed. Opt., 2, 401–417.

    Article  CAS  PubMed  Google Scholar 

  37. Tuchin, V. V. (2006) Optical Clearing of Tissues and Blood, SPIE Press, Bellingham.

    Google Scholar 

  38. Sdobnov, A. Y., Darvin, M. E., Genina, E. A., Bashkatov, A. N., Lademann, J., and Tuchin, V. V. (2018) Recent progress in tissue optical clearing for spectroscopic applica–tion, Spectrochim. Acta, A. Mol. Biomol. Spectrosc., 197, 216–229.

    Article  CAS  Google Scholar 

  39. Jiang, J., Boese, M., Turner, P., and Wang, R. K. (2008) Penetration kinetics of dimethyl sulphoxide and glycerol in dynamic optical clearing of porcine skin tissue in vitro stud–ied by Fourier transform infrared spectroscopic imaging, J. Biomed. Opt., 13, 021105.

    Article  CAS  PubMed  Google Scholar 

  40. Larin, K. V., and Tuchin, V. V. (2008) Functional imaging and assessment of the glucose diffusion rate in epithelial tis–sues in optical coherence tomography, Quantum Electron., 38, 551–556.

    Article  CAS  Google Scholar 

  41. Tuchina, D. K., Shi, R., Bashkatov, A. N., Genina, E. A., Zhu, D., Luo, Q., and Tuchin, V. V. (2015) Ex vivo optical measurements of glucose diffusion kinetics in native and diabetic mouse skin, J. Biophotonics, 8, 332–346.

    Article  CAS  PubMed  Google Scholar 

  42. Bui, A. K., McClure, R. A., Chang, J., Stoianovici, C., Hirshburg, J., Yeh, A. T., and Choi, B. (2009) Revisiting optical clearing with dimethyl sulfoxide (DMSO), Lasers Surg. Med., 41, 142–148.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Tuchin, V. V., Xu, X. Q., and Wang, R. K. (2002) Dynamic optical coherence tomography in studies of optical clear–ing, sedimentation, and aggregation of immersed blood, Appl. Optics, 41, 258–271.

    Article  CAS  Google Scholar 

  44. Bykov, A., Hautala, T., Kinnunen, M., Popov, A., Karhula, S., Saarakkala, S., Nieminen, M. T., Tuchin, V., and Meglinski, I. (2016) Imaging of subchondral bone by opti–cal coherence tomography upon optical clearing of articu–lar cartilage, J. Biophotonics, 9, 270–275.

    Article  PubMed  Google Scholar 

  45. Cicchi, R., Pavone, F. S., Massi, D., and Sampson, D. D. (2005) Contrast and depth enhancement in two–photon microscopy of human skin ex vivo by use of optical clearing agents, Opt. Express, 13, 2337–2344.

    Article  CAS  PubMed  Google Scholar 

  46. Sdobnov, A., Darvin, M. E., Lademann, J., and Tuchin, V. (2017) A comparative study of ex vivo skin optical clearing using two–photon microscopy, J. Biophotonics, 10, 1115–1123.

    Article  CAS  PubMed  Google Scholar 

  47. Schulmerich, M. V., Cole, J. H., Dooley, K. A., Morris, M. D., Kreider, J. M., and Goldstein, S. A. (2008) Optical clearing in transcutaneous Raman spectroscopy of murine cortical bone tissue, J. Biomed. Opt., 13, 021108.

    Article  CAS  PubMed  Google Scholar 

  48. Sdobnov, A. Y., Tuchin, V. V., Lademann, J., and Darvin, M. E. (2017) Confocal Raman microscopy supported by optical clearing treatment of the skin–influence on colla–gen hydration, J. Phys. D. Appl. Phys., 50, 285401.

    Article  CAS  Google Scholar 

  49. Liopo, A., Su, R., Tsyboulski, D. A., and Oraevsky, A. A. (2016) Optical clearing of skin enhanced with hyaluronic acid for increased contrast of optoacoustic imaging, J. Biomed. Opt., 21, 081208.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Liu, Y. Y., Yang, X. Q., Zhu, D., Shi, R., and Luo, Q. M. (2013) Optical clearing agents improve photoacoustic imaging in the optical diffusive regime, Opt. Lett., 38, 4236–4239.

    Article  CAS  PubMed  Google Scholar 

  51. Zhao, Q. L., Li, L., Li, Q., Jiang, X., Ren, Q. S., Chai, X. Y., and Zhou, C. Q. (2014) Concentration dependence of optical clearing on the enhancement of laser–scanning optical–resolution photoacoustic microscopy imaging, J. Biomed. Opt., 19, 36019.

    Article  PubMed  Google Scholar 

  52. Zhou, Y., Yao, J. J., and Wang, L. H. V. (2013) Optical clearing–aided photoacoustic microscopy with enhanced resolution and imaging depth, Opt. Lett., 38, 2592–2595.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Yang, X. Q., Liu, Y. Y., Zhu, D., Shi, R., and Luo, Q. M. (2014) Dynamic monitoring of optical clearing of skin using photoacoustic microscopy and ultrasonography, Opt. Express, 22, 1094–1104.

    Article  CAS  PubMed  Google Scholar 

  54. Yang, X. Q., Zhang, Y., Zhao, K., Zhao, Y. J., Liu, Y. Y., Gong, H., Luo, Q. M., and Zhu, D. (2016) Skull optical clearing solution for enhancing ultrasonic and photoa–coustic imaging, IEEE Trans. Med. Imaging, 35, 1903–1906.

    Article  PubMed  Google Scholar 

  55. Menyaev, Y. A., Nedosekin, D. A., Sarimollaoglu, M., Juratli, M. A., Galanzha, E. I., Tuchin, V. V., and Zharov, V. P. (2013) Optical clearing in photoacoustic flow cytome–try, Biomed. Opt. Express, 4, 3030–3041.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Tuchin, V. V., Wang, L., and Zimnyakov, D. A. (2006) Optical Polarization in Biomedical Applications, Springer Science and Business Media, Berlin.

    Book  Google Scholar 

  57. Drezek, R., Dunn, A., and Richards–Kortum, R. (1999) Light scattering from cells: finite–difference time–domain simulations and goniometric measurements, Appl. Optics, 38, 3651–3661.

    Article  CAS  Google Scholar 

  58. Friebel, M., and Meinke, M. (2006) Model function to cal–culate the refractive index of native hemoglobin in the wavelength range of 250–1100 nm dependent on concentra–tion, Appl. Optics, 45, 2838–2842.

    Article  CAS  Google Scholar 

  59. Lazareva, E. N., and Tuchin, V. V. (2018) Measurement of refractive index of hemoglobin in the visible/NIR spectral range, J. Biomed. Opt., 23, 1–9.

    Article  PubMed  Google Scholar 

  60. Leonard, D. W., and Meek, K. M. (1997) Refractive indices of the collagen fibrils and extrafibrillar material of the corneal stroma, Biophys. J., 72, 1382–1387.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Genina, E. A., Bashkatov, A. N., and Tuchin, V. V. (2010) Tissue optical immersion clearing, Expert Rev. Med. Devices, 7, 825–842.

    Article  PubMed  Google Scholar 

  62. Larin, K. V., Ghosn, M. G., Bashkatov, A. N., Genina, E. A., Trunina, N. A., and Tuchin, V. V. (2012) Optical clear–ing for OCT image enhancement and in–depth monitoring of molecular diffusion, IEEE J. Sel. Top. Quantum Electron., 18, 1244–1259.

    Article  CAS  Google Scholar 

  63. Hama, H., Hioki, H., Namiki, K., Hoshida, T., Kurokawa, H., Ishidate, F., Kaneko, T., Akagi, T., Saito, T., Saido, T., and Miyawaki, A. (2015) Sca/eS: an optical clearing palette for biological imaging, Nat. Neurosci., 18, 1518–1529.

    Article  CAS  PubMed  Google Scholar 

  64. Hama, H., Kurokawa, H., Kawano, H., Ando, R., Shimogori, T., Noda, H., Fukami, K., Sakaue–Sawano, A., and Miyawaki, A. (2011) Scale: a chemical approach for fluorescence imaging and reconstruction of transparent mouse brain, Nat. Neurosci., 14, 1481–1488.

    Article  CAS  PubMed  Google Scholar 

  65. Zhu, D., Larin, K. V., Luo, Q. M., and Tuchin, V. V. (2013) Recent progress in tissue optical clearing, Laser Photonics Rev., 7, 732–757.

    Article  CAS  Google Scholar 

  66. Bui, A. K., McClure, R. A., Chang, J., Stoianovici, C., Hirshburg, J., Yeh, A. T., and Choi, B. (2009) Revisiting optical clearing with dimethyl sulfoxide (DMSO), Laser Surg. Med., 41, 142–148.

    Article  Google Scholar 

  67. Tuchin, V. V. (2007) A clear vision for laser diagnostics (review), IEEE J. Sel. Top. Quantum Electron., 13, 1621–1628.

    Article  Google Scholar 

  68. Wen, X., Mao, Z. Z., Han, Z. Z., Tuchin, V. V., and Zhu, D. (2010) In vivo skin optical clearing by glycerol solutions: mechanism, J. Biophotonics, 3, 44–52.

    Article  CAS  PubMed  Google Scholar 

  69. Hirshburg, J., Choi, B., Nelson, J. S., and Yeh, A. T. (2006) Collagen solubility correlates with skin optical clearing, J. Biomed. Opt., 11, 040501.

    Article  PubMed  Google Scholar 

  70. Hirshburg, J., Choi, B., Nelson, J. S., and Yeh, A. T. (2007) Correlation between collagen solubility and skin optical clearing using sugars, Laser Surg. Med., 39, 140–144.

    Article  Google Scholar 

  71. Hirshburg, J. M., Ravikumar, K. M., Hwang, W., and Yeh, A. T. (2010) Molecular basis for optical clearing of collage–nous tissues, J. Biomed. Opt., 15, 055002.

    Article  CAS  PubMed  Google Scholar 

  72. Yeh, A. T., Choi, B., Nelson, J. S., and Tromberg, B. J. (2003) Reversible dissociation of collagen in tissues, J. Invest. Dermatol., 121, 1332–1335.

    Article  CAS  PubMed  Google Scholar 

  73. Berezin, K. V., Dvoretski, K. N., Chernavina, M. L., Likhter, A. M., Smirnov, V. V., Shagautdinova, I. T., Antonova, E. M., Stepanovich, E. Y., Dzhalmuhambetova, E. A., and Tuchin, V. V. (2018) Molecular modeling of immersion optical clearing of biological tissues, J. Mol. Model., 24, 45.

    Article  CAS  PubMed  Google Scholar 

  74. Askar’yan, G. A. (1982). Enhancement of transmission of laser and other radiation by soft turbid physical and biolog–ical media, Soviet J. Quantum Electron., 12, 877–880.

    Google Scholar 

  75. Chan, E. K., Sorg, B., Protsenko, D., O’Neil, M., Motamedi, M., and Welch, A. J. (1996) Effects of com–pression on soft tissue optical properties, IEEE J. Sel. Top. Quantum Electron., 2, 943–950.

    Article  CAS  Google Scholar 

  76. Ding, H. F., Lu, J. Q., Wooden, W. A., Kragel, P. J., and Hu, X. H. (2006) Refractive indices of human skin tissues at eight wavelengths and estimated dispersion relations between 300 and 1600 nm, Phys. Med. Biol., 51, 1479–1489.

    Article  PubMed  Google Scholar 

  77. Hoyt, L. F. (1934) New table of the refractive index of pure glycerol at 20°C, Ind. Eng. Chem., 26, 329–332.

    Article  CAS  Google Scholar 

  78. Genina, E. A., Bashkatov, A. N., Kochubey, V. I., and Tuchin, V. V. (2005) Optical clearing of human dura mater, Opt. Spectrosc., 98, 470–476.

    Article  CAS  Google Scholar 

  79. Vargas, O., Chan, E. K., Barton, J. K., Rylander, H. G., and Welch, A. J. (1999) Use of an agent to reduce scatter–ing in skin, Laser Surg. Med., 24, 133–141.

    Article  CAS  Google Scholar 

  80. Bashkatov, A. N., Genina, E. A., Sinichkin, Y. P., Kochubey, V. I., Lakodina, N. A., and Tuchin, V. V. (2003) Glucose and mannitol diffusion in human dura mater, Biophys. J., 85, 3310–3318.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Bashkatov, A. N., Genina, E. A., and Tuchin, V. V. (2009) in Handbook of Optical Sensing of Glucose in Biological Fluids and Tissues (Tuchin, V. V., ed.), CRC Press, Boca Raton.

    Google Scholar 

  82. Vargas, G., Barton, J. K., and Welch, A. J. (2008) Use of hyperosmotic chemical agent to improve the laser treat–ment of cutaneous vascular lesions, J. Biomed. Opt., 13, 021114.

    Article  PubMed  Google Scholar 

  83. Sun, R. W., Tuchin, V. V., Zharov, V. P., Galanzha, E. I., and Richter, G. T. (2018). Current status, pitfalls and future directions in the diagnosis and therapy of lymphatic mal–formation, J. Biophotonics, 11, e201700124.

    Google Scholar 

  84. Genina, E. A., Bashkatov, A. N., Sinichkin, Yu. P., and Tuchin, V. V. (2006) Optical clearing of eye sclera in vivo caused by glucose, Quantum Electron., 36, 1119–1124.

    Article  CAS  Google Scholar 

  85. Bashkatov, A. N., Korolevich, A. N., Tuchin, V. V., Sinichkin, Yu. P., Genina, E. A., Stolnitz, M. M., Dubina, N. S., Vecherinski, S. I., and Belsley, M. S. (2006) In vivo investigation of human skin optical clearing and blood microcirculation under the action of glucose solution, Asian J. Phys., 15, 1–14.

    CAS  Google Scholar 

  86. Galanzha, E. I., Tuchin, V. V., Solovieva, A. V., Stepanova, T. V., Luo, Q., and Cheng, H. (2003) Skin backreflect–ance and microvascular system functioning at the action of osmotic agents, J. Phys. D: Appl. Phys., 36, 1739–1746.

    Article  CAS  Google Scholar 

  87. Zhu, D., Zhang, J., Cui, H., Mao, Z., Li, P., and Luo, Q. (2008) Short–term and long–term effects of optical clearing agents on blood vessels in chick chorioallantoic membrane, J. Biomed. Opt., 13, 021106.

    Article  CAS  PubMed  Google Scholar 

  88. Zhu, Z. G., Wu, G. Y., Wei, H. J., Yang, H. Q., He, Y. H., Xie, S. S., Zhao, Q. L., and Guo, X. (2012) Investigation of the permeability and optical clearing ability of different analytes in human normal and cancerous breast tissues by spectral domain OCT, J. Biophotonics, 5, 536–543.

    Article  CAS  PubMed  Google Scholar 

  89. Genina, E. A., Bashkatov, A. N., Korobko, A. A., Zubkova, E. A., Tuchin, V. V., Yaroslavsky, I., and Altshuler, G. B. (2008) Optical clearing of human skin: comparative study of permeability and dehydration of intact and photothermally perforated skin, J. Biomed. Opt., 13, 021102.

    Article  CAS  PubMed  Google Scholar 

  90. Genina, E. A., Bashkatov, A. N., Sinichkin, Yu. P., and Tuchin, V. V. (2010) Optical clearing of skin under action of glycerol: ex vivo and in vivo investigations, Opt. Spectrosc., 109, 225–231.

    Article  CAS  Google Scholar 

  91. Choi, B., Tsu, L., Chen, E., Ishak, T. S., Iskandar, S. M., Chess, S., and Nelson, J. S. (2005) Determination of chemical agent optical clearing potential using in vitro human skin, Laser Surg. Med., 36, 72–75.

    Article  Google Scholar 

  92. Khan, M. H., Choi, B., Chess, S., Kelly, K. M., McCullough, J., and Nelson, J. S. (2004) Optical clearing of in vivo human skin: implications for light–based diag–nostic imaging and therapeutics, Laser Surg. Med., 34, 83–85.

    Article  Google Scholar 

  93. Mao, Z., Zhu, D., Hu, Y., Wen, X., and Han, Z. (2008) Influence of alcohols on the optical clearing effect of skin in vitro, J. Biomed. Opt., 13, 021104.

    Article  CAS  PubMed  Google Scholar 

  94. Proskurin, S. G., and Meglinski, I. V. (2007) Optical coherence tomography imaging depth enhancement by superficial skin optical clearing, Laser Phys. Lett., 4, 824–826.

    Article  Google Scholar 

  95. Genina, E. A., Bashkatov, A. N., and Tuchin, V. V. (2008) Optical clearing of cranial bone, Adv. Opt. Technol., 2008, 1–8.

    Article  Google Scholar 

  96. Ghosn, M. G., Tuchin, V. V., and Larin, K. V. (2006) Depth–resolved monitoring of glucose diffusion in tissues by using optical coherence tomography, Opt. Lett., 31, 2314–2316.

    Article  PubMed  Google Scholar 

  97. Wang, J., Ma, N., Shi, R., Zhang, Y., Yu, T. T., and Zhu, D. (2014) Sugar–induced skin optical clearing: from molecular dynamics simulation to experimental demon–stration, IEEE J. Sel. Top. Quant. Electron., 20, 7101007.

    Google Scholar 

  98. Bashkatov, A. N., Genina, E. A., Sinichkin, Yu. P., Kochubei, I. V., Lakodina, N. A., and Tuchin, V. V. (2003) Determination of glucose diffusion coefficient in human eye sclera, Biophysics, 48, 309–313.

    CAS  Google Scholar 

  99. Tuchina, D. K., Timoshina, P. A., Tuchin, V. V., Bashkatov, A. N., and Genina, E. A. (2019). Kinetics of rat skin optical clearing at topical application of 40% glucose: ex vivo and in vivo studies, IEEE J. Sel. Top. Quant. Electron., 25, 1–8.

    Google Scholar 

  100. Jiang, J. Y., and Wang, R. K. K. (2004) Comparing the synergistic effects of oleic acid and dimethyl sulfoxide as vehicles for optical clearing of skin tissue in vitro, Phys. Med. Biol., 49, 5283–5294.

    Article  CAS  PubMed  Google Scholar 

  101. Xu, X. Q., and Wang, R. K. K. (2004) Synergistic effect of hyperosmotic agents of dimethyl sulfoxide and glycerol on optical clearing of gastric tissue studied with near infrared spectroscopy, Phys. Med. Biol., 49, 457–468.

    Article  PubMed  Google Scholar 

  102. Ding, Y. M., Wang, J., Fan, Z. C., Wei, D., Shi, R., Luo, Q. M., Zhu, D., and Wei, X. B. (2013) Signal and depth enhancement for in vivo flow cytometer measurement of ear skin by optical clearing agents, Biomed. Opt. Express, 4, 2518–2526.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Shi, R., Guo, L., Zhang, C., Feng, W., Li, P., Ding, Z., and Zhu, D. (2016) A useful way to develop effective in vivo skin optical clearing agents, J. Biophotonics, 10, 887–895.

    Article  CAS  PubMed  Google Scholar 

  104. Deng, Z., Jing, L., Wu, N., Jiang, X., Ren, Q., and Li, C. (2014) Viscous optical clearing agent for in vivo optical imaging, J. Biomed. Opt., 19, 76019.

    Article  PubMed  Google Scholar 

  105. Guo, L., Shi, R., Zhang, C., Zhu, D., Ding, Z., and Li, P. (2016) Optical coherence tomography angiography offers comprehensive evaluation of skin optical clearing in vivo by quantifying optical properties and blood flow imaging simultaneously, J. Biomed. Opt., 21, 081202.

    Article  PubMed  Google Scholar 

  106. Jin, X., Deng, Z., Wang, J., Ye, Q., Mei, J., Zhou, W., Zhang, C., and Tian, J. (2016) Study of the inhibition effect of thiazone on muscle optical clearing, J. Biomed. Opt., 21, 105004.

    Article  PubMed  Google Scholar 

  107. Wang, J., Shi, R., and Zhu, D. (2012) Switchable skin win–dow induced by optical clearing method for dermal blood flow imaging, J. Biomed. Opt., 18, 061209.

    Article  Google Scholar 

  108. Zhong, H. Q., Guo, Z. Y., Wei, H. J., Guo, L., Wang, C. X., He, Y. H., Xiong, H. L., and Liu, S. H. (2010) Synergistic effect of ultrasound and thiazone–PEG 400 on human skin optical clearing in vivo, Photochem. Photobiol., 86, 732–737.

    Article  CAS  PubMed  Google Scholar 

  109. Shi, R., Chen, M., Tuchin, V. V., and Zhu, D. (2015) Accessing to arteriovenous blood flow dynamics response using combined laser speckle contrast imaging and skin optical clearing, Biomed. Opt. Express, 6, 1977–1989.

    Article  PubMed  PubMed Central  Google Scholar 

  110. Plotnikov, S., Juneja, V., Isaacson, A. B., Mohler, W. A., and Campagnola, P. J. (2006) Optical clearing for improved contrast in second harmonic generation imaging of skeletal muscle, Biophys. J., 90, 328–339.

    Article  CAS  PubMed  Google Scholar 

  111. Wen, X., Jacques, S. L., Tuchin, V. V., and Zhu, D. (2012) Enhanced optical clearing of skin in vivo and optical coherence tomography in–depth imaging, J. Biomed. Opt., 17, 066022.

    Article  CAS  PubMed  Google Scholar 

  112. Vargas, G., Readinger, A., Dozier, S. S., and Welch, A. J. (2003) Morphological changes in blood vessels pro–duced by hyperosmotic agents and measured by optical coherence tomography, Photochem. Photobiol., 77, 541–549.

    Article  CAS  PubMed  Google Scholar 

  113. Larina, I. V., Carbajal, E. F., Tuchin, V. V., Dickinson, M. E., and Larin, K. V. (2008) Enhanced OCT imaging of embryonic tissue with optical clearing, Laser Phys. Lett., 5, 476–479.

    Article  CAS  Google Scholar 

  114. Sudheendran, N., Mohamed, M., Ghosn, M. G., Tuchin, V. V., and Larin, K. V. (2010) Assessment of tissue optical clearing as a function of glucose concentration using opti–cal coherence tomography, J. Innov. Opt. Heal. Sci., 3, 169–176.

    Article  Google Scholar 

  115. Xu, X. Q., and Zhu, Q. H. (2007) Evaluation of skin opti–cal clearing enhancement with Azone as a penetration enhancer, Opt. Commun., 279, 223–228.

    Article  CAS  Google Scholar 

  116. Zhi, Z. W., Han, Z. Z., Luo, Q. M., and Zhu, D. (2009) Improve optical clearing of skin in vitro with propylene gly–col as a penetration enhancer, J. Innov. Opt. Heal. Sci., 2, 269–278.

    Article  Google Scholar 

  117. Caspers, P. J., Williams, A. C., Carter, E. A., Edwards, H. G., Barry, B. W., Bruining, H. A., and Puppels, G. J. (2002) Monitoring the penetration enhancer dimethyl sul–foxide in human stratum corneum in vivo by confocal Raman spectroscopy, Pharm. Res., 19, 1577–1580.

    Article  CAS  PubMed  Google Scholar 

  118. Notman, R., den Otter, W. K., Noro, M. G., Briels, W. J., and Anwar, J. (2007) The permeability enhancing mecha–nism of DMSO in ceramide bilayers simulated by molecu–lar dynamics, Biophys. J., 93, 2056–2068.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Vejnovic, I., Simmler, L., and Betz, G. (2010) Investigation of different formulations for drug delivery through the nail plate, Int. J. Pharm., 386, 185–194.

    Article  CAS  PubMed  Google Scholar 

  120. Kuriharabergstrom, T., Knutson, K., Denoble, L. J., and Goates, C. Y. (1990) Percutaneous absorption enhance–ment of an ionic molecule by ethanol–water systems in human skin, Pharm. Res., 7, 762–766.

    Article  CAS  Google Scholar 

  121. Timoshina, P. A., Zinchenko, E. M., Tuchina, D. K., Sagatova, M. M., Semyachkina–Glushkovskaya, O. V., and Tuchin, V. V. (2017) Laser speckle contrast imaging of cerebral blood flow of newborn mice at optical clearing, Proc. SPIE, 10336, 1033610.

    Article  Google Scholar 

  122. Liu, P., Huang, Y., Guo, Z., Wang, J., Zhuang, Z., and Liu, S. (2013) Discrimination of dimethyl sulphoxide dif–fusion coefficient in the process of optical clearing by con–focal micro–Raman spectroscopy, J. Biomed. Opt., 18, 20507.

    Article  CAS  PubMed  Google Scholar 

  123. Samatham, R., Phillips, K. G., and Jacques, S. L. (2010) Assessment of optical clearing agents using reflectance–mode confocal scanning laser microscopy, J. Innov. Opt. Heal. Sci., 3, 183–188.

    Article  Google Scholar 

  124. Millon, S. R., Roldan–Perez, K. M., Riching, K. M., Palmer, G. M., and Ramanujam, N. (2006) Effect of opti–cal clearing agents on the in vivo optical properties of squa–mous epithelial tissue, Laser Surg. Med., 38, 920–927.

    Article  Google Scholar 

  125. Vargas, G., Chan, K. F., Thomsen, S. L., and Welch, A. J. (2001) Use of osmotically active agents to alter optical properties of tissue: effects on the detected fluorescence signal measured through skin, Laser Surg. Med., 29, 213–220.

    Article  CAS  Google Scholar 

  126. Weigmann, H. J., Lademann, J., Schanzer, S., Lindemann, U., von Pelchrzim, R., Schaefer, H., Sterry, W., and Shah, V. (2001) Correlation of the local distribu–tion of topically applied substances inside the stratum corneum determined by tape–stripping to differences in bioavailability, Skin Pharmacol. Appl. Skin Physiol., 14 (Suppl. 1), 98–102.

    Google Scholar 

  127. Stumpp, O., Chen, B., and Welch, A. J. (2006) Using sandpaper for noninvasive transepidermal optical skin clearing agent delivery, J. Biomed. Opt., 11, 041118.

    Article  CAS  PubMed  Google Scholar 

  128. Lee, W. R., Tsai, R. Y., Fang, C. L., Liu, C. J., Hu, C. H., and Fang, J. Y. (2006) Microdermabrasion as a novel tool to enhance drug delivery via the skin: an animal study, Dermatol. Surg., 32, 1013–1022.

    CAS  PubMed  Google Scholar 

  129. Tuchin, V. V., Altshuler, G. B., Gavrilova, A. A., Pravdin, A. B., Tabatadze, D., Childs, J., and Yaroslavsky, I. V. (2006) Optical clearing of skin using flashlamp–induced enhancement of epidermal permeability, Laser Surg. Med., 38, 824–836.

    Article  CAS  Google Scholar 

  130. Stumpp, O. F., Welch, A. J., Milner, T. E., and Neev, J. (2005) Enhancement of transepidermal skin clearing agent delivery using a 980 nm diode laser, Laser Surg. Med., 37, 278–285.

    Article  CAS  Google Scholar 

  131. Liu, C., Zhi, Z., Tuchin, V. V., and Zhu, D. (2009) Combined laser and glycerol enhancing skin optical clear–ing, Proc. SPIE, 7186, 71860D.

    Google Scholar 

  132. Nugroho, A. K., Li, G. L., Danhof, M., and Bouwstra, J. A. (2004) Transdermal iontophoresis of rotigotine across human stratum corneum in vitro: influence of pH and NaCl concentration, Pharm. Res., 21, 844–850.

    Article  CAS  PubMed  Google Scholar 

  133. Tezel, A., and Mitragotri, S. (2003) Interactions of inertial cavitation bubbles with stratum corneum lipid bilayers during low–frequency sonophoresis, Biophys. J., 85, 3502–3512.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Konig, K. (2008) Clinical multiphoton tomography, J. Biophotonics, 1, 13–23.

    Article  PubMed  Google Scholar 

  135. Tseng, S. J., Lee, Y. H., Chen, Z. H., Lin, H. H., Lin, C. Y., and Tang, S. C. (2009) Integration of optical clearing and optical sectioning microscopy for three–dimensional imaging of natural biomaterial scaffolds in thin sections, J. Biomed. Opt., 14, 044004.

    Article  CAS  PubMed  Google Scholar 

  136. Chiang, Ann–Shyn, Aqueous tissue clearing solution, US Patent No. 6,472,216, October 29, 2002.

  137. Cicchi, R., Sestini, S., De Giorgi, V., Massi, D., Lotti, T., and Pavone, F. S. (2008) Nonlinear laser imaging of skin lesions, J. Biophotonics, 1, 62–73.

    Article  CAS  PubMed  Google Scholar 

  138. Klemp, M., Meinke, M. C., Weinigel, M., Rowert–Huber, H. J., Konig, K., Ulrich, M., Lademann, J., and Darvin, M. E. (2016) Comparison of morphologic criteria for actinic keratosis and squamous cell carcinoma using in vivo multiphoton tomography, Exp. Dermatol., 25, 218–222.

    Article  PubMed  Google Scholar 

  139. Hovhannisyan, V. A., Hu, P. S., Chen, S. J., Kim, C. S., and Dong, C. Y. (2013) Elucidation of the mechanisms of optical clearing in collagen tissue with multiphoton imag–ing, J. Biomed. Opt., 18, 046004.

    Article  PubMed  Google Scholar 

  140. Migacheva, E. V., Pravdin, A. B., and Tuchin, V. V. (2010) Alterations in autofluorescence signal from rat skin ex vivo under optical immersion clearing, J. Innov. Opt. Heal. Sci., 3, 147–152.

    Article  Google Scholar 

  141. Kong, K., Kendall, C., Stone, N., and Notingher, I. (2015) Raman spectroscopy for medical diagnostics–from in vitro biofluid assays to in vivo cancer detection, Adv. Drug Deliver Rev., 89, 121–134.

    Article  CAS  Google Scholar 

  142. Krafft, C., Schmitt, M., Schie, I. W., Cialla–May, D., Matthaus, C., Bocklitz, T., and Popp, J. (2017) Label–free molecular imaging of biological cells and tissues by linear and nonlinear Raman spectroscopic approaches, Angew. Chem. Int. Edit., 56, 4392–4430.

    Article  CAS  Google Scholar 

  143. Jermyn, M., Desroches, J., Aubertin, K., St–Arnaud, K., Madore, W. J., De Montigny, E., Guiot, M. C., Trudel, D., Wilson, B. C., Petrecca, K., and Leblond, F. (2016) A review of Raman spectroscopy advances with an emphasis on clinical translation challenges in oncology, Phys. Med. Biol., 61, R370–R400.

    Book  Google Scholar 

  144. Binder, L., SheikhRezaei, S., Baierl, A., Gruber, L., Wolzt, M., and Valenta, C. (2017) Confocal Raman spec–troscopy: in vivo measurement of physiological skin parameters–a pilot study, J. Dermatol. Sci., 88, 280–288.

    Article  CAS  PubMed  Google Scholar 

  145. Choe, C., Schleusener, J., Lademann, J., and Darvin, M. E. (2017) Age related depth profiles of human stratum corneum barrier–related molecular parameters by confocal Raman microscopy in vivo, Mech. Ageing Dev., 172, 6–12.

    Article  CAS  PubMed  Google Scholar 

  146. Darvin, M. E., Gersonde, I., Ey, S., Brandt, N. N., Albrecht, H., Gonchukov, S. A., Sterry, W., and Lademann, J. (2004) Noninvasive detection of beta–carotene and lycopene in human skin using Raman spec–troscopy, Laser Phys., 14, 231–233.

    CAS  Google Scholar 

  147. Richters, R. J., Falcone, D., Uzunbajakava, N. E., Varghese, B., Caspers, P. J., Puppels, G. J., van Erp, P. E., and van de Kerkhof, P. C. (2017) Sensitive skin: assess–ment of the skin barrier using confocal Raman microspec–troscopy, Skin Pharmac. Physiol., 30, 1–12.

    Article  CAS  Google Scholar 

  148. Choe, C., Lademann, J., and Darvin, M. E. (2015) Analysis of human and porcine skin in vivo/ex vivo for pen–etration of selected oils by confocal Raman microscopy, Skin Pharmac. Physiol., 28, 318–330.

    Article  CAS  Google Scholar 

  149. Binder, L., Kulovits, E. M., Petz, R., Ruthofer, J., Baurecht, D., Klang, V., and Valenta, C. (2018) Penetration monitoring of drugs and additives by ATR–FTIR spectroscopy/tape stripping and confocal Raman spectroscopy–a comparative study, Eur. J. Pharm. Biopharm., 130, 214–223.

    Article  CAS  PubMed  Google Scholar 

  150. Mujica Ascencio, S., Choe, C., Meinke, M. C., Muller, R. H., Maksimov, G. V., Wigger–Alberti, W., Lademann, J., and Darvin, M. E. (2016) Confocal Raman microscopy and multivariate statistical analysis for determination of different penetration abilities of caffeine and propylene glycol applied simultaneously in a mixture on porcine skin ex vivo, Eur. J. Pharm. Biopharm., 104, 51–58.

    Article  CAS  PubMed  Google Scholar 

  151. Enejder, A. M. K., Scecina, T. G., Oh, J., Hunter, M., Shih, W. C., Sasic, S., Horowitz, G. L., and Feld, M. S. (2005) Raman spectroscopy for noninvasive glucose meas–urements, J. Biomed. Opt., 10, 031114.

    Article  CAS  PubMed  Google Scholar 

  152. McNichols, R. J., and Cote, G. L. (2000) Optical glucose sensing in biological fluids: an overview, J. Biomed. Opt., 5, 5–16.

    Article  CAS  PubMed  Google Scholar 

  153. Quatela, A., Miloudi, L., Tfayli, A., and Baillet–Guffroy, A. (2016) In vivo Raman microspectroscopy: intra–and intersubject variability of stratum corneum spectral mark–ers, Skin Pharmacol. Physiol., 29, 102–109.

    Article  CAS  PubMed  Google Scholar 

  154. Zimmerley, M., McClure, R. A., Choi, B., and Potma, E. O. (2009) Following dimethyl sulfoxide skin optical clear–ing dynamics with quantitative nonlinear multimodal microscopy, Appl. Optics, 48, D79–D87.

    Google Scholar 

  155. Huang, D., Zhang, W., Zhong, H., Xiong, H., Guo, X., and Guo, Z. (2012) Optical clearing of porcine skin tissue in vitro studied by Raman microspectroscopy, J. Biomed. Opt., 17, 015004.

    Article  CAS  PubMed  Google Scholar 

  156. Kim, S., Byun, K. M., and Lee, S. Y. (2017) Influence of water content on Raman spectroscopy characterization of skin sample, Biomed. Opt. Express, 8, 1130–1138.

    Article  PubMed  PubMed Central  Google Scholar 

  157. Choe, C., Schleusener, J., Lademann, J., and Darvin, M. E. (2018) Human skin in vivo has a higher skin barrier function than porcine skin ex vivo–comprehensive Raman microscopic study of the stratum corneum, J. Biophotonics, 11, e201700355.

    Book  Google Scholar 

  158. Hokr, B. H., and Yakovlev, V. V. (2013) Raman signal enhancement via elastic light scattering, Opt. Express, 21, 11757–11762.

    Article  PubMed  PubMed Central  Google Scholar 

  159. Matousek, P. (2007) Raman signal enhancement in deep spectroscopy of turbid media, Appl. Spectrosc., 61, 845–854.

    Article  CAS  PubMed  Google Scholar 

  160. Oelkrug, D., Boldrini, B., and Rebner, K. (2017) Comparative Raman study of transparent and turbid mate–rials: models and experiments in the remote sensing mode, Anal. Bioanal. Chem., 409, 673–681.

    Article  CAS  PubMed  Google Scholar 

  161. Zhu, Y., Choe, C. S., Ahlberg, S., Meinke, M. C., Alexiev, U., Lademann, J., and Darvin, M. E. (2015) Penetration of silver nanoparticles into porcine skin ex vivo using fluo–rescence lifetime imaging microscopy, Raman microscopy, and surface–enhanced Raman scattering microscopy, J. Biomed. Opt., 20, 051006.

    PubMed  Google Scholar 

  162. Wang, Y., Ji, W., Yu, Z., Li, R., Wang, X., Song, W., Ruan, W. D., Zhao, B., and Ozaki, Y. (2014) Contribution of hydrogen bonding to charge–transfer induced surface–enhanced Raman scattering of an intermolecular system comprising p–aminothiophenol and benzoic acid, Phys. Chem. Chem. Phys., 16, 3153–3161.

    Article  CAS  PubMed  Google Scholar 

  163. Yamamoto, Y. S., Ishikawa, M., Ozaki, Y., and Itoh, T. (2014) Fundamental studies on enhancement and blinking mechanism of surface–enhanced Raman scattering (SERS) and basic applications of SERS biological sensing, Front. Phys. (Beijing), 9, 31–46.

    Article  Google Scholar 

  164. Zhang, Y. F., Li, D. Q., Zhou, X. Y., Gao, X. H., Zhao, S. Y., and Li, C. (2016) Enhancing sensitivity of SERRS nanoprobes by modifying heptamethine cyanine–based reporter molecules, J. Innov. Opt. Heal. Sci., 9, 1642005.

    Article  CAS  Google Scholar 

  165. Ozaki, Y., Kneipp, K., and Aroca, R. (2014) Frontiers of Surface–Enhanced Raman Scattering: Single Nanoparticles and Single Cells, John Wiley & Sons, Chichester.

    Book  Google Scholar 

  166. Zhang, Y., Liu, H., Tang, J., Li, Z., Zhou, X., Zhang, R., Chen, L., Mao, Y., and Li, C. (2017) Noninvasively imag–ing subcutaneous tumor xenograft by a handheld Raman detector, with the assistance of an optical clearing agent, ACS Appl. Mater. Interfaces, 9, 17769–17776.

    Article  CAS  PubMed  Google Scholar 

  167. Darvin, M. E., Schleusener, J., Parenz, F., Seidel, O., Krafft, C., Popp, J., and Lademann, J. (2018) Confocal Raman microscopy combined with optical clearing for identification of inks in multicolored tattooed skin in vivo, Analyst, 143, 4990–4999.

    Article  CAS  PubMed  Google Scholar 

  168. Choe, C., Lademann, J., and Darvin, M. E. (2016) Depth profiles of hydrogen bound water molecule types and their relation to lipid and protein interaction in the human stra–tum corneum in vivo, Analyst, 141, 6329–6337.

    Article  CAS  PubMed  Google Scholar 

  169. Choe, C., Schleusener, J., Lademann, J., and Darvin, M. E. (2017) Keratin–water–NMF interaction as a three layer model in the human stratum corneum using in vivo confocal Raman microscopy, Sci. Rep., 7, 15900.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Sdobnov, A. Y., Darvin, M. E., Schleusener, J., Lademann, J., and Tuchin, V. V. (2018) Hydrogen bound water profiles in the skin influenced by optical clearing molecular agents–quantitative analysis using confocal Raman microscopy, J. Biophotonics, e201800283; doi: 10.1002/jbio.201800283.

    Google Scholar 

  171. Nakagawa, N., Matsumoto, M., and Sakai, S. (2010) In vivo measurement of the water content in the dermis by confocal Raman spectroscopy, Skin Res. Technol., 16, 137–141.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. Yu. Sdobnov.

Additional information

Russian Text © A. Yu. Sdobnov, J. Lademann, M. E. Darvin, V. V. Tuchin, 2019, published in Uspekhi Biologicheskoi Khimii, 2019, Vol. 59, pp. 295–322.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sdobnov, A.Y., Lademann, J., Darvin, M.E. et al. Methods for Optical Skin Clearing in Molecular Optical Imaging in Dermatology. Biochemistry Moscow 84 (Suppl 1), 144–158 (2019). https://doi.org/10.1134/S0006297919140098

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297919140098

Keywords

Navigation