In Vivo Imaging of Human Skin Aging: A Narrative Review of Reflectance Confocal Microscopy, Multiphoton Microscopy, Optical Coherence Tomography and High Frequency Ultrasound (Preprint)

BACKGROUND Skin biopsy provides detailed microscopic information about skin aging; however, its invasive nature makes it unsuitable for longitudinal monitoring. Noninvasive imaging modalities allow real-time, in vivo evaluation of skin aging without the need for biopsy. OBJECTIVE To evaluate and compare the strengths and limitations of reflectance confocal microscopy (RCM), multiphoton microscopy (MPM), optical coherence tomography (OCT) and high-frequency ultrasound (HFUS) for noninvasive assessment of human skin aging. METHODS PubMed, Scopus, Web of Science and Google Scholar were searched for studies evaluating in vivo human skin aging using HFUS, OCT, RCM and MPM. Additional technical data was obtained from websites of device manufacturers. This yielded 81 references. RESULTS RCM (~$100,000) provides high-resolution 2D grayscale images with a field of view (FOV) up to 750 × 750 µm and penetration depth up to papillary dermis. MPM (~$500,000) offers high-resolution 3D color images with a FOV of 350 × 350 µm and penetration depth up to reticular dermis. OCT (~$40,000–150,000) provides moderate-resolution 2D and 3D grayscale images, with a FOV up to 2,000 x 10,000 µm and penetration depth up to papillary dermis. HFUS (~$2,500–150,000) delivers lower-resolution grayscale 3D images, variable FOV and penetration depth up to subcutis. CONCLUSIONS RCM, MPM, OCT and HFUS have complementary strengths for noninvasive, real-time assessment of skin aging. Their combined use, along with AI-assisted analysis, could improve early detection of aging-related changes which can guide skin cancer risk stratification, and inform research on anti-aging interventions.