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Two-Photon Microscopy for Evaluating UVA-1 Treatment of Sclerotic Skin Disease

Jianhua Zhao, MD, University of British Columbia, Vancouver, BC

Morphea (localized scleroderma) comprises a group of distinct conditions that involve the skin and subcutaneous tissues. They range from very small circumscribed plaques involving only the skin to diseases that may cause significant functional and cosmetic deformity. The disease is more prevalent in women than in men with the exception of linear morphea, which has no gender preference. The prevalence increases with age. Over the years, many treatments have been tried for morphea. These have included topical, intra- lesional and systemic corticosteroids, and phototherapy of UVA light with and without psoralens. Unfortunately, there are no effective methods to quantify or assess the outcomes of these treatment modalities. Two-photon microscopy (TPM) is a nonlinear fluorescence imaging technique, which has the capability of imaging human skin in vivo up to 1 millimeter. It has advantages over confocal microscopy and optical coherence tomography (OCT). TPM is particularly suitable for studying collagen and elastin related skin disorders. In this proposal, we will design a new in vivo TPM system and method for non- invasive evaluation and monitoring the process of UVA-1 treatment of morphea.


Peer-Reviewed Publications Supported by the Canadian Dermatology Foundation

1. Huang, Z, Lui H, Chen MXK, McLean DI, Zeng, H.: Raman Spectroscopy of In Vivo Cutaneous Melanin. J. of Biomedical Optics, 9(6):1198-1205, 2004.

2. Hamzavi, I.,Jain, H., McLean, D.I., Shapiro, J., Zeng, H., Lui, H.: Parametric Modelling of Narrow Band UV-B Phototherapy for Vitiligo Using a Novel Quantitative Tool, Arch. Dermatol. 140: 677-683, 2004.

3. Tang L, Cao L, Sundberg JP, LUI H, Shapiro J. Restoration of hair growth in mice with an alopecia areata-like disease using topical anthralin. Exp Dermatol 2004; 13:5-10.

4. Huang, Z, Lui, H., McLean, DI, Korbelik, Zeng, H: Raman Spectroscopy in Combination with Background Near-Infrared Autofluorescence Enhances the In Vivo Assessment of Malignant Tissues. Photochemistry and Photobiology, 81: 1219-1226, 2005

5. Lau DP, Huang Z, Lui H, Anderson DW, Berean K, Morrison MD, Shen L, Zeng H. Raman spectroscopy for optical diagnosis in the larynx: preliminary findings. Lasers Surg Med. 37(3):192-200. (2005).

6. Hamzavi, I.,Shiff, N., Martinka, M., Huang, Z., McLean, DI., Zeng, H., Lui, H.: Spectroscopic Assessment of Dermal Melanin using Blue Vitiligo as an in vivo Model. Photodermatology, Photoimmunology & Photomedicine, 22:46-51, 2006.

7. Short, M.A., Lui, H., McLean, D.I., Zeng, H., Alajlan, A., Chen, M.X.: Demonstrating Changes in Nuclei and Peritumoral Collagen within Nodular Basal Cell Carcinomas Via Confocal Micro-Raman Spectroscopy, J of Biomedical Optics, 11: 034004, 2006.

8. Huang Z, Zeng H, Hamzavi I, Alajlan A, Tan E, McLean DI, LUI H. Cutaneous Melanin Exhibits Fluorescence Emission Under Near-Infrared Light Excitation. J. of Biomedical Optics, 11: 034010, 2006.

9. Markhvida, I, Tchvialeva, L, Lee, TK, and Zeng, H.: The Influence of Geometry on Polychromatic Speckle Contrast, Journal of OSA A, 24 (1), 93-97 (2006).

10. Chen, R., Huang, Z., Lui, H., Hamzavi, I., McLean, D.I., Xie, S., Zeng, H.: Monte Carlo simulation of cutaneous reflectance and fluorescence measurements —— the effect of melanin contents and localization, Journal of photochemistry and photobiology B: Biology, 86 (3): 219-226 (2007)

11. J. Zhao, H. Lui, D. I. McLean, and H. Zeng, "Automated fluorescence background subtraction in biomedical Raman spectra", Applied Spectroscopy 61, 1225 (2007)

12. J. Zhao, H. Lui, D. I. McLean, and H. Zeng, "Towards instrument independent quantitative measurement of fluorescence intensity in fiber optic spectrometer system", Applied Optics 46, 7132-7140 (2007)

13 J. Zhao, H. Lui, D. I. McLean, and H. Zeng, "Integrated real-time Raman system for clinical in vivo skin analysis", Skin Research and Technology 14, 484-492 (2008)

14. Zeng H, Zhao J, Short M, McLean D, Lam S, McWilliams A, and LUI H. Raman Spectroscopy for in vivo Tissue Analysis and Diagnosis – from Instrument Development to Clinical Applications. J Innovative Optical Health Research 1, 95- 106 (2008). Two-Photon Microscopy for Evaluating UVA-1 Treatment of Sclerotic Skin Disease Nominated PI: Jianhua Zhao Requested amount: $52,435

15. Tchvialeva, L, Lee, TK, Markhvida, I, Mclean, DI, Lui, H. and Zeng, H.: Using a zone model to incorporate the influence of geometry on polychromatic speckle contrast, Optical Engineering, 47(7): 074201, 2008.

16. Cluff, GM, Short, MA, Lui, H, McLean, DI, Zeng, H, Korbelik, M, Chen, MX: Comparison of Connective Tissue Invaded by Lewis Lung Carcinoma to Healthy Connective Tissue by Means of Micro-Raman Spectroscopy, J. of Raman Spectroscopy, 2008 (Accepted).

17. Han, X., Lui, H., McLean, DI, Zeng, H.: Near-infrared autofluorescence imaging of cutaneous melanins and human skin in vivo, J. of Biomedical Optics, 2009 (Accepted).

© 2009