<i>In Vivo</i>Virtual Biopsy of Human Skin by Using Noninvasive Higher Harmonic Generation Microscopy

Abstract

Higher harmonic generation microscopy (HHGM), combining both second- and third-harmonic generation (SHG and THG) modalities, is a new paradigm for <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in vivo</i> noninvasive virtual biopsy. With the ability to achieve noninvasiveness, high resolution, and high penetrability at the same time, HHGM is a promising tool for future noninvasive diagnosis of skin diseases. In this paper, we report our preliminary pilot clinical trial results on <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in vivo</i> virtual biopsy of human skin by using HHGM. <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">In vivo</i> virtual biopsy imaging has been performed on 21 volunteers' inside and outside forearm skin along with the damage evaluation. Together with an embryo viability study, our results not only indicate a superior viability performance of the developed system, but also a much improved penetrability in different skin types. <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Ex vivo</i> studies further confirm the capability of the developed virtual biopsy system to pathohistologically distinguish different skin diseases. Our <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in vivo</i> HHGM biopsy study of human skin with different colors also reveals the central role of melanin in the epi-THG resonance enhancement and attenuation. With a unique capability to molecular image the melanin distribution, epi-THG microscopy is also highly valuable for diagnosing and screening early melanocytic lesions.