{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:47:30Z","timestamp":1791229650168,"version":"4.1.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Gouvernement du Canada | Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP130548 and PJT-166023"],"award-info":[{"award-number":["MOP130548 and PJT-166023"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007475","name":"Canadian Dermatology Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007475","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004489","name":"Mitacs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004489","id-type":"DOI","asserted-by":"publisher"}]},{"name":"VGH & UBC Hospital Foundation BC Hydro Employees Community Services Fund CIHR Skin Research Training Centre doctoral scholarship"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"DOI":"10.1038\/s42003-025-07614-x","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T15:52:06Z","timestamp":1738770726000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Motion-tolerant 3D volumetric multimodality microscopy imaging of human skin with subcellular resolution and extended field-of-view"],"prefix":"10.1038","volume":"8","author":[{"given":"Zhenguo","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxian","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harvey","family":"Lui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil","family":"Kalia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3557-2407","authenticated-orcid":false,"given":"Haishan","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,5]]},"reference":[{"key":"7614_CR1","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1111\/1523-1747.ep12606215","volume":"104","author":"M Rajadhyaksha","year":"1995","unstructured":"Rajadhyaksha, M., Grossman, M., Esterowitz, D., Webb, R. H. & Anderson, R. R. In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast. J. Invest. Dermatol. 104, 946\u2013952 (1995).","journal-title":"J. Invest. Dermatol."},{"key":"7614_CR2","doi-asserted-by":"publisher","first-page":"e73","DOI":"10.1016\/j.jaad.2011.08.021","volume":"68","author":"C Longo","year":"2013","unstructured":"Longo, C., Casari, A., Beretti, F., Cesinaro, A. M. & Pellacani, G. Skin aging: in vivo microscopic assessment of epidermal and dermal changes by means of confocal microscopy. J. Am. Acad. Dermatol. 68, e73\u2013e82 (2013).","journal-title":"J. Am. Acad. Dermatol."},{"key":"7614_CR3","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1117\/1.1577349","volume":"8","author":"K Konig","year":"2003","unstructured":"Konig, K. & Riemann, I. High-resolution multiphoton tomography of human skin with subcellular spatial resolution and picosecond time resolution. J. Biomed. Opt. 8, 432\u2013439 (2003).","journal-title":"J. Biomed. Opt."},{"key":"7614_CR4","doi-asserted-by":"publisher","first-page":"7857","DOI":"10.1364\/OE.18.007857","volume":"18","author":"H. G Breunig","year":"2010","unstructured":"Breunig, H. G., Studier, H. & K\u00f6nig, K. Multiphoton excitation characteristics of cellular fluorophores of human skin in vivo. Opt. Express 18, 7857\u20137871 (2010).","journal-title":"Opt. Express"},{"key":"7614_CR5","doi-asserted-by":"publisher","first-page":"367ra169","DOI":"10.1126\/scitranslmed.aag2202","volume":"8","author":"D Pouli","year":"2016","unstructured":"Pouli, D. et al. Imaging mitochondrial dynamics in human skin reveals depth-dependent hypoxia and malignant potential for diagnosis. Sci. Transl. Med. 8, 367ra169\u2013367ra169 (2016).","journal-title":"Sci. Transl. Med."},{"key":"7614_CR6","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-18657-z","volume":"12","author":"A. M Pena","year":"2022","unstructured":"Pena, A. M. et al. In vivo multiphoton multiparametric 3D quantification of human skin aging on forearm and face. Sci. Rep. 12, 14863 (2022).","journal-title":"Sci. Rep."},{"key":"7614_CR7","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1002\/lsm.22788","volume":"50","author":"A. J Deegan","year":"2018","unstructured":"Deegan, A. J. et al. Optical coherence tomography angiography of normal skin and inflammatory dermatologic conditions. Laser Surg. Med. 50, 183\u2013193 (2018).","journal-title":"Laser Surg. Med."},{"key":"7614_CR8","doi-asserted-by":"publisher","first-page":"040901","DOI":"10.1117\/1.JBO.23.4.040901","volume":"23","author":"J Olsen","year":"2018","unstructured":"Olsen, J., Holmes, J. & Jemec, G. B. Advances in optical coherence tomography in dermatology\u2014a review. J. Biomed. Opt. 23, 040901 (2018).","journal-title":"J. Biomed. Opt."},{"key":"7614_CR9","doi-asserted-by":"crossref","unstructured":"Huck, V. et al. From morphology to biochemical state\u2013intravital multiphoton fluorescence lifetime imaging of inflamed human skin. Sci. Rep. 6, 22789 (2016).","DOI":"10.1038\/srep22789"},{"key":"7614_CR10","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1001\/jamadermatol.2015.0453","volume":"151","author":"M Balu","year":"2015","unstructured":"Balu, M. et al. In vivo multiphoton microscopy of basal cell carcinoma. JAMA Dermatol. 151, 1068\u20131074 (2015).","journal-title":"JAMA Dermatol."},{"key":"7614_CR11","doi-asserted-by":"publisher","first-page":"2688","DOI":"10.1158\/0008-5472.CAN-13-2582","volume":"74","author":"M Balu","year":"2014","unstructured":"Balu, M. et al. Distinguishing between benign and malignant melanocytic nevi by in vivo multiphoton microscopy. Cancer Res. 74, 2688\u20132697 (2014).","journal-title":"Cancer Res."},{"key":"7614_CR12","doi-asserted-by":"publisher","first-page":"2386","DOI":"10.1038\/jid.2012.172","volume":"132","author":"P Guitera","year":"2012","unstructured":"Guitera, P. et al. In vivo confocal microscopy for diagnosis of melanoma and basal cell carcinoma using a two-step method: analysis of 710 consecutive clinically equivocal cases. J. Invest. Dermatol. 132, 2386\u20132394 (2012).","journal-title":"J. Invest. Dermatol."},{"key":"7614_CR13","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1111\/bjd.13148","volume":"171","author":"G Pellacani","year":"2014","unstructured":"Pellacani, G., Pepe, P., Casari, A. & Longo, C. Reflectance confocal microscopy as a second-level examination in skin oncology improves diagnostic accuracy and saves unnecessary excisions: a longitudinal prospective study. Br J. Dermatol. 171, 1044\u20131051 (2014).","journal-title":"Br J. Dermatol."},{"key":"7614_CR14","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-90328-x","volume":"11","author":"A Bozkurt","year":"2021","unstructured":"Bozkurt, A. et al. Skin strata delineation in reflectance confocal microscopy images using recurrent convolutional networks with attention. Sci. Rep. 11, 12576 (2021).","journal-title":"Sci. Rep."},{"key":"7614_CR15","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-12317-y","volume":"12","author":"J. R Vicente","year":"2022","unstructured":"Vicente, J. R., Durkin, A., Shrestha, K. & Balu, M. In vivo imaging with a fast large-area multiphoton exoscope (FLAME) captures the melanin distribution heterogeneity in human skin. Sci. Rep. 12, 8106 (2022).","journal-title":"Sci. Rep."},{"key":"7614_CR16","doi-asserted-by":"crossref","unstructured":"Ogien, J., Daures, A., Cazalas, M., Perrot, J.-L. & Dubois, A. Line-field confocal optical coherence tomography for three-dimensional skin imaging. Front. Optoelectron.13, 381\u2013392 (2020).","DOI":"10.1007\/s12200-020-1096-x"},{"key":"7614_CR17","doi-asserted-by":"publisher","first-page":"4375","DOI":"10.1364\/BOE.7.004375","volume":"7","author":"M Balu","year":"2016","unstructured":"Balu, M., Mikami, H., Hou, J., Potma, E. O. & Tromberg, B. J. Rapid mesoscale multiphoton microscopy of human skin. Biomed. Opt. Express 7, 4375\u20134387 (2016).","journal-title":"Biomed. Opt. Express"},{"key":"7614_CR18","doi-asserted-by":"publisher","first-page":"2865","DOI":"10.1364\/OL.36.002865","volume":"36","author":"A Lee","year":"2011","unstructured":"Lee, A. et al. In vivo video rate multiphoton microscopy imaging of human skin. Opt. Lett. 36, 2865\u20132867 (2011).","journal-title":"Opt. Lett."},{"key":"7614_CR19","doi-asserted-by":"publisher","first-page":"106007","DOI":"10.1117\/1.JBO.23.10.106007","volume":"23","author":"A Dubois","year":"2018","unstructured":"Dubois, A. et al. Line-field confocal optical coherence tomography for high-resolution noninvasive imaging of skin tumors. J. Biomed. Opt. 23, 106007 (2018).","journal-title":"J. Biomed. Opt."},{"key":"7614_CR20","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-11072-9","volume":"7","author":"K Kose","year":"2017","unstructured":"Kose, K. et al. Automated video-mosaicking approach for confocal microscopic imaging in vivo: an approach to address challenges in imaging living tissue and extend field of view. Sci. Rep. 7, 10759 (2017).","journal-title":"Sci. Rep."},{"key":"7614_CR21","doi-asserted-by":"publisher","first-page":"61227","DOI":"10.1117\/1.JBO.18.6.061227","volume":"18","author":"S Abeytunge","year":"2013","unstructured":"Abeytunge, S. et al. Confocal microscopy with strip mosaicing for rapid imaging over large areas of excised tissue. J. Biomed. Opt. 18, 61227 (2013).","journal-title":"J. Biomed. Opt."},{"key":"7614_CR22","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/j.bpj.2012.11.3809","volume":"104","author":"M Balu","year":"2013","unstructured":"Balu, M. et al. In vivo multiphoton NADH fluorescence reveals depth-dependent keratinocyte metabolism in human skin. Biophys. J. 104, 258\u2013267 (2013).","journal-title":"Biophys. J."},{"key":"7614_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-75172-9","volume":"10","author":"A Fast","year":"2020","unstructured":"Fast, A. et al. Fast, large area multiphoton exoscope (FLAME) for macroscopic imaging with microscopic resolution of human skin. Sci. Rep. 10, 18093 (2020).","journal-title":"Sci. Rep."},{"key":"7614_CR24","doi-asserted-by":"publisher","first-page":"25161","DOI":"10.1364\/OE.19.025161","volume":"19","author":"H Mansoor","year":"2011","unstructured":"Mansoor, H. et al. Vertical optical sectioning using a magnetically driven confocal microscanner aimed for in vivo clinical imaging. Opt. Express 19, 25161\u201325172 (2011).","journal-title":"Opt. Express"},{"key":"7614_CR25","doi-asserted-by":"publisher","first-page":"4281","DOI":"10.1364\/BOE.5.004281","volume":"5","author":"G Thomas","year":"2014","unstructured":"Thomas, G. et al. In vivo nonlinear spectral imaging as a tool to monitor early spectroscopic and metabolic changes in a murine cutaneous squamous cell carcinoma model. Biomed. Opt. Express 5, 4281 (2014).","journal-title":"Biomed. Opt. Express"},{"key":"7614_CR26","doi-asserted-by":"publisher","first-page":"085602","DOI":"10.1088\/1612-2011\/12\/8\/085602","volume":"12","author":"C Czekalla","year":"2015","unstructured":"Czekalla, C. et al. Technical parameters of vertical in vivo multiphoton microscopy: a critical evaluation of the flyscanning method. Laser Phys. Lett. 12, 085602 (2015).","journal-title":"Laser Phys. Lett."},{"key":"7614_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-76908-7","volume":"14","author":"K. L Montgomery","year":"2024","unstructured":"Montgomery, K. L., Novoa, R. A., Ko, J. M. & Sanchez, G. N. Handheld multiphoton and pinhole-free reflectance confocal microscopy enables noninvasive, real-time cross-sectional imaging in skin. Sci. Rep. 14, 26129 (2024).","journal-title":"Sci. Rep."},{"key":"7614_CR28","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1002\/jbio.201200067","volume":"6","author":"H Wang","year":"2013","unstructured":"Wang, H. et al. Perfectly registered multiphoton and reflectance confocal video rate imaging of in vivo human skin. J. Biophoton.6, 305\u2013309 (2013).","journal-title":"J. Biophoton."},{"key":"7614_CR29","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1001\/jamadermatol.2022.0924","volume":"158","author":"I Saknite","year":"2022","unstructured":"Saknite, I. et al. Association of Leukocyte Adhesion And Rolling In Skin With Patient Outcomes After Hematopoietic Cell Transplantation Using Noninvasive Reflectance Confocal Videomicroscopy. JAMA Dermatol. 158, 661\u2013669 (2022).","journal-title":"JAMA Dermatol."},{"key":"7614_CR30","doi-asserted-by":"publisher","first-page":"908","DOI":"10.3390\/s19040908","volume":"19","author":"C Massaroni","year":"2019","unstructured":"Massaroni, C. et al. Contact-based methods for measuring respiratory rate. Sensors 19, 908 (2019).","journal-title":"Sensors"},{"key":"7614_CR31","doi-asserted-by":"publisher","first-page":"07TR01","DOI":"10.1088\/1361-6579\/ab299e","volume":"40","author":"H Liu","year":"2019","unstructured":"Liu, H., Allen, J., Zheng, D. & Chen, F. Recent development of respiratory rate measurement technologies. Physiol. Meas. 40, 07TR01 (2019).","journal-title":"Physiol. Meas."},{"key":"7614_CR32","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1111\/j.0022-202X.2004.23569.x","volume":"124","author":"A Gerger","year":"2005","unstructured":"Gerger, A. et al. Diagnostic applicability of in vivo confocal laser scanning microscopy in melanocytic skin tumors. J. Invest. Dermatol. 124, 493\u2013498 (2005).","journal-title":"J. Invest. Dermatol."},{"key":"7614_CR33","doi-asserted-by":"publisher","first-page":"2759","DOI":"10.1038\/sj.jid.5700993","volume":"127","author":"G Pellacani","year":"2007","unstructured":"Pellacani, G. et al. The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions. J. Invest. Dermatol. 127, 2759\u20132765 (2007).","journal-title":"J. Invest. Dermatol."},{"key":"7614_CR34","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1111\/bjd.16364","volume":"179","author":"S. Borsari","year":"2018","unstructured":"Borsari, S., et al. In vivo dermoscopic and confocal microscopy multistep algorithm to detect in situ melanomas. Br. J. Dermatol. 179, 163\u2013172 (2018).","journal-title":"Br. J. Dermatol."},{"key":"7614_CR35","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1016\/j.optcom.2007.10.007","volume":"281","author":"E. J Botcherby","year":"2008","unstructured":"Botcherby, E. J., Ju\u0161kaitis, R., Booth, M. J. & Wilson, T. An optical technique for remote focusing in microscopy. Opt. Commun. 281, 880\u2013887 (2008).","journal-title":"Opt. Commun."},{"key":"7614_CR36","doi-asserted-by":"publisher","first-page":"2919","DOI":"10.1073\/pnas.1111662109","volume":"109","author":"E. J Botcherby","year":"2012","unstructured":"Botcherby, E. J. et al. Aberration-free three-dimensional multiphoton imaging of neuronal activity at kHz rates. Proc. Natl Acad. Sci. USA 109, 2919\u20132924 (2012).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"7614_CR37","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1002\/lsm.22600","volume":"49","author":"M Rajadhyaksha","year":"2017","unstructured":"Rajadhyaksha, M., Marghoob, A., Rossi, A., Halpern, A. C. & Nehal, K. S. Reflectance confocal microscopy of skin in vivo: from bench to bedside. Laser Surg. Med. 49, 7\u201319 (2017).","journal-title":"Laser Surg. Med."},{"key":"7614_CR38","doi-asserted-by":"crossref","unstructured":"Zong, W. et al. Fast high-resolution miniature two-photon microscopy for brain imaging in freely behaving mice. Nat. Methods 14, 713\u2013719 (2017).","DOI":"10.1038\/nmeth.4305"},{"key":"7614_CR39","unstructured":"Sanderson, M. J. Acquisition of multiple real-time images for laser scanning microscopy. Microsc. Anal. 18, 17\u201323 (2004)."},{"key":"7614_CR40","doi-asserted-by":"publisher","unstructured":"Wu, Z. & Zeng, H. Motion correction and volume reconstruction software for: motion-tolerant 3D volumetric multimodality microscopy imaging of human skin with subcellular resolution and extended field-of-view. Zenodo https:\/\/doi.org\/10.5281\/zenodo.14648379 (2025).","DOI":"10.5281\/zenodo.14648379"}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-07614-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-07614-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-07614-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T15:52:13Z","timestamp":1738770733000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-07614-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,5]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["7614"],"URL":"https:\/\/doi.org\/10.1038\/s42003-025-07614-x","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,5]]},"assertion":[{"value":"7 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 February 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The BC Cancer Research Institute has filed a US patent application with H.Z., Z.W., H.L., and Y.T. as co-inventors. Details are as following: Haishan Zeng, Zhenguo Wu, Harvey Lui, Yuxian Tian: Volumetric Multi-modal Microscopy Methods and Systems. Application # US 2022\/0015638A1, November 22, 2018. The BC Cancer Research Institute, H.Z., Z.W., H.L., and Y.T. will receive royalties from any commercialization of this patent. All other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"186"}}