In VivoVirtual Biopsy of Human Skin by Using Noninvasive Higher Harmonic Generation Microscopy

Higher harmonic generation microscopy (HHGM), combining both second- and third-harmonic generation (SHG and THG) modalities, is a new paradigm forin vivononinvasive 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 onin vivovirtual biopsy of human skin by using HHGM.In vivovirtual 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.Ex vivostudies further confirm the capability of the developed virtual biopsy system to pathohistologically distinguish different skin diseases. Ourin vivoHHGM 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.