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Additionally, tissue processed for histopathology suffers from poor nucleic acid quality and\/or quantity for downstream molecular profiling. Targeted micro-sampling of tissue can ensure accurate diagnosis and molecular profiling in the presence of spatial heterogeneity, especially in tumors, and facilitate acquisition of fresh tissue for molecular analysis. In this study, we explored the feasibility of performing 1\u20132\u00a0mm precision biopsies guided by high-resolution reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), and reflective metallic grids for accurate spatial targeting. Accurate sampling was confirmed with either histopathology or molecular profiling through next generation sequencing (NGS) in 9 skin cancers in 7 patients. Imaging-guided 1\u20132\u00a0mm biopsies enabled spatial targeting for in vivo diagnosis, feature correlation and depth assessment, which were confirmed with histopathology. In vivo 1-mm targeted biopsies achieved adequate quantity and high quality of DNA for next-generation sequencing. Subsequent mutational profiling was confirmed on 1 melanoma in situ and 2 invasive melanomas, using a 505-gene mutational panel\u00a0called Memorial Sloan Kettering-Integrated mutational profiling of actionable cancer targets (MSK-IMPACT). Differential mutational landscapes, in terms of number and types of mutations, were found between invasive and in situ melanomas in a single patient. Our findings demonstrate feasibility of accurate sampling of regions of interest for downstream histopathological diagnoses and molecular pathology in both in vivo and ex vivo settings with broad diagnostic, therapeutic and research potential in cutaneous diseases accessible by RCM-OCT imaging.<\/jats:p>","DOI":"10.1038\/s41598-021-01447-4","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T12:53:32Z","timestamp":1638276812000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["In vivo optical imaging-guided targeted sampling for precise diagnosis and molecular pathology"],"prefix":"10.1038","volume":"11","author":[{"given":"Aditi","family":"Sahu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuna","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Peterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Cordova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Navarrete-Dechent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Gill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christi","family":"Alessi-Fox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvador","family":"Gonzalez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Phillips","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Afzalneia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raven","family":"Rose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abu-Akeel","family":"Mohsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Bello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashfaq","family":"Marghoob","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jedd D.","family":"Wolchok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taha","family":"Merghoub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Rotemberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Shan","family":"Jason Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milind","family":"Rajadhyaksha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,30]]},"reference":[{"key":"1447_CR1","doi-asserted-by":"publisher","first-page":"5009","DOI":"10.1200\/JCO.2007.13.2142","volume":"25","author":"H Singh","year":"2007","unstructured":"Singh, H., Sethi, S., Raber, M. & Petersen, L. 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Christi Alessi-Fox was previously employed by and owns equity in Caliber Imaging and Diagnostics Inc (formerly Lucid Inc), the company that manufactures and sells the VivaScope confocal microscope. Dr. Rossi reports travel accommodation from Mavig; he is also a consultant for Merz, DynaMed, Canfield Scientific, Evolus, Biofrontera, QuantiaMD, Lam Therapeutics, and Cutera; and is on the advisory board of Allergan. Ashfaq A. Marghoob: received honorarium from 3GEN for dermoscopy lectures, received royalties from publishing companies for books and book chapters, received dermoscopy equipment for testing and feedback, received payment from the American Dermoscopy Meeting for organizing and lecturing at the annual meeting. JDW is a consultant for: Amgen; Apricity; Ascentage Pharma; Arsenal IO; Astellas; AstraZeneca; Bayer; Bicara Therapeutics; Boehringer Ingelheim; Bristol Myers Squibb; Chugai; Daiichi Sankyo, Dragonfly; Eli Lilly; F Star; Georgiamune; Idera; Imvaq; Kyowa Hakko Kirin; Maverick Therapeutics; Merck; Neon Therapeutics; Psioxus; Recepta; Tizona; Trieza; Truvax; Trishula; Sellas; Surface Oncology; Syndax; Syntalogic, Werewolf Therapeutics. JDW receives Grant\/Research Support from: Bristol Myers Squibb; Sephora. JDW has Equity in: Tizona Pharmaceuticals; Adaptive Biotechnologies; Imvaq; Beigene; Linneaus, Apricity, Arsenal IO; Georgiamune; Trieza; Maverick; Ascentage. TM is a consultant for Immunos Therapeutics and Pfizer; is a co-founder with equity in IMVAQ therapeutics; receives research funding from Bristol-Myers Squibb, Surface Oncology, Kyn Therapeutics, Infinity Pharmaceuticals Inc., Peregrine Pharmaceuticals Inc., Adaptive Biotechnologies, Leap Therapeutics Inc., and Aprea; is an inventor on patent applications related to work on Oncolytic Viral therapy, Alpha Virus Based Vaccine, Neo Antigen Modeling, CD40, GITR, OX40, PD-1 and CTLA-4.\u00a0Chih-Shan Jason Chen: received research funding from Apollo Medical Optics, Inc. Milind Rajadhyaksha is a former employee of and owns equity in Caliber Imaging and Diagnostics. The VivaScope is the commercial version of an original laboratory prototype that he developed at Massachusetts General Hospital, Harvard Medical School. VR is an expert advisor for Inhabit Brands, Inc. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"23124"}}