Abstract

Third-harmonic generation (THG) microscopy has been reported to provide intrinsic contrast in elastic fibers, cytoplasmic membrane, nucleus, actin filaments, lipid bodies, hemoglobin, and melanin in human skin. For advanced molecular imaging, exogenous contrast agents are developed for a higher structural or molecular specificity. We demonstrate the potential of the commonly adopted tattoo dye as a THG contrast agent for in vivo optical biopsy of human skin. Spectroscopy and microscopy experiments were performed on cultured cells with tattoo dyes, in tattooed mouse skin, and in tattooed human skin to demonstrate the THG enhancement effect. Compared with other absorbing dyes or nanoparticles used as exogenous THG contrast agents, tattoo dyes are widely adopted in human skin so that future clinical biocompatibility evaluation is relatively achievable. Combined with the demonstrated THG enhancement effect, tattoo dyes show their promise for future clinical imaging applications.

Highlights

  • Harmonic generation microscopy (HGM) has emerged as an important imaging modality in biological study,[1,2,3,4,5,6,7,8,9] especially in in vivo applications[10,11,12,13,14,15,16,17] because of its nonlinear and noninvasive nature

  • We suggest that the black tattoo dye is suitable as a third-harmonic generation (THG) contrast agent through the multiphoton resonance enhancement

  • In contrast to previously reported nanoparticles,[27,28,29] lipidenclosed quantum dots and iron oxides,[30,33] or the hematoxylin dye[31] as THG exogenous contrast agents, tattoo dye is the only exogenous contrast agent currently allowed to be applied on human skin so that the establishment of the clinical database for future biocompatibility evaluation is relatively achievable

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Summary

Introduction

Harmonic generation microscopy (HGM) has emerged as an important imaging modality in biological study,[1,2,3,4,5,6,7,8,9] especially in in vivo applications[10,11,12,13,14,15,16,17] because of its nonlinear and noninvasive nature. We demonstrate the potential of the commonly adopted tattoo dye as a THG contrast agent for in vivo optical virtual biopsy of human skin through multiphoton resonance enhancement.

Results
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