{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T22:26:23Z","timestamp":1776810383913,"version":"3.51.2"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018693","name":"HORIZON EUROPE Framework Programme","doi-asserted-by":"publisher","award":["871212"],"award-info":[{"award-number":["871212"]}],"id":[{"id":"10.13039\/100018693","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019854","name":"Greater Copenhagen Health Science Partners","doi-asserted-by":"publisher","award":["SCIN CAG"],"award-info":[{"award-number":["SCIN CAG"]}],"id":[{"id":"10.13039\/501100019854","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"Skin cancer is one of the most common types of cancer, frequently resulting from excessive exposure to ultraviolet radiation (UVR). Early detection and effective prevention of photodamage are important to mitigate the long-term risks of skin cancer. In this study, we investigate the use of optical coherence tomography (OCT) for assessing photodamage over time and the efficacy of photodamage prevention treatments non-invasively. Of the n<\/jats:italic>\u2009=\u200981 hairless mice, 75 of them were exposed to ultraviolet radiation (UVR) three times per week to induce photodamage. Two different systemic photodamage prevention treatments were tested: nicotinamide mononucleotide (NMN) and polypodium leucotomos (PL). OCT images were acquired monthly on the back, side, and stomach of the mice over 7 months. Two OCT-derived metrics, skin thickness and the attenuation coefficient, \u03bc<\/mml:mi>O<\/mml:mi>C<\/mml:mi>T<\/mml:mi><\/mml:mrow><\/mml:msub><\/mml:mrow><\/mml:math><\/jats:alternatives><\/jats:inline-formula>, were quantified using a custom-developed algorithm to evaluate photodamage. Significant differences in skin thickness (p<\/jats:italic>\u2009=\u20090.038) and attenuation coefficient (p<\/jats:italic><0.001) were observed between the UVR control group and the non-irradiated control group after 7 months at the back. At month 7, no significant difference was observed in the attenuation coefficient between the UVR control group and the UVR + PL group, however, a significant difference was observed between the UVR control group and the UVR + NMN group. Additionally, our OCT-derived skin thickness was well correlated with the skin thickness measured from histology, demonstrating a strong alignment with these invasive ground truth findings. Altogether, our results indicate that OCT could be a useful tool for non-invasive monitoring of photodamage in skin and for monitoring the efficacy of photodamage prevention treatments.<\/jats:p>","DOI":"10.1371\/journal.pone.0328647","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T17:45:45Z","timestamp":1754934345000},"page":"e0328647","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Assessing changes in ultraviolet radiation-exposed mouse skin using optical coherence tomography"],"prefix":"10.1371","volume":"20","author":[{"given":"Anna V.","family":"Vejlsby","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0848-9096","authenticated-orcid":true,"given":"Celina","family":"Pihl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rozarin Delal","family":"Kara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1250-2035","authenticated-orcid":true,"given":"Merete","family":"Haedersdal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter E.","family":"Andersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catharina M.","family":"Lerche","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6334-0625","authenticated-orcid":true,"given":"Gavrielle R.","family":"Untracht","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,8,11]]},"reference":[{"issue":"7","key":"pone.0328647.ref001","doi-asserted-by":"crossref","first-page":"3478","DOI":"10.3390\/ijms23073478","article-title":"Molecular mechanisms of cutaneous squamous cell carcinoma","volume":"23","author":"ML Hedberg","year":"2022","journal-title":"Int J Mol Sci."},{"issue":"5","key":"pone.0328647.ref002","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1001\/jamadermatol.2013.2139","article-title":"Factors predictive of recurrence and death from cutaneous squamous cell carcinoma: a 10-year, single-institution cohort study","volume":"149","author":"CD Schmults","year":"2013","journal-title":"JAMA Dermatol."},{"issue":"9","key":"pone.0328647.ref003","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1056\/NEJMoa2203086","article-title":"Nicotinamide for skin-cancer chemoprevention in transplant recipients","volume":"388","author":"NC Allen","year":"2023","journal-title":"N Engl J Med."},{"issue":"10","key":"pone.0328647.ref004","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.3390\/cancers16101800","article-title":"Cutaneous squamous cell carcinoma: an updated review","volume":"16","author":"R Jiang","year":"2024","journal-title":"Cancers (Basel)."},{"issue":"15","key":"pone.0328647.ref005","doi-asserted-by":"crossref","first-page":"3684","DOI":"10.3390\/cancers13153684","article-title":"Keratinocyte carcinoma and photoprevention: the protective actions of repurposed pharmaceuticals, phytochemicals and vitamins","volume":"13","author":"C Pihl","year":"2021","journal-title":"Cancers (Basel)."},{"issue":"4","key":"pone.0328647.ref006","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1111\/phpp.12870","article-title":"The combination of oral and topical photoprotection with a standardized Polypodium leucotomos extract is beneficial against actinic keratosis","volume":"39","author":"G Pellacani","year":"2023","journal-title":"Photodermatol Photoimmunol Photomed."},{"issue":"1","key":"pone.0328647.ref007","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/lsm.23613","article-title":"Repeated exposure to fractional CO2 laser delays squamous cell carcinoma formation and prevents clinical and subclinical photodamage visualized by line-field confocal optical coherence tomography and histology","volume":"55","author":"UH Olesen","year":"2023","journal-title":"Lasers Surg Med."},{"issue":"1","key":"pone.0328647.ref008","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/lsm.23750","article-title":"Line-field confocal optical coherence tomography for in vivo visualization of morphological characteristics of squamous cell carcinoma in a murine model","volume":"56","author":"UH Olesen","year":"2024","journal-title":"Lasers Surg Med."},{"issue":"1","key":"pone.0328647.ref009","doi-asserted-by":"crossref","first-page":"17912","DOI":"10.1038\/s41598-017-17398-8","article-title":"Universal in vivo textural model for human skin based on optical coherence tomograms","volume":"7","author":"S Adabi","year":"2017","journal-title":"Sci Rep."},{"issue":"22","key":"pone.0328647.ref010","doi-asserted-by":"crossref","first-page":"336","DOI":"10.5897\/JMPR2018.6651","article-title":"Comparison of several hydrophilic extracts of Polypodium leucotomos reveals different antioxidant moieties and photoprotective effects in vitro","volume":"12","author":"G Salvador","year":"2018","journal-title":"J Med Plants Res."},{"key":"pone.0328647.ref011","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/j.1600-0781.1997.tb00108.x","article-title":"Topical or oral administration with an extract of Polypodium leucotomos prevents acute sunburn and psoralen-induced phototoxic reactions as well as depletion of Langerhans cells in human skin","volume":"13","author":"S Gonz\u00e1lez","year":"1997","journal-title":"Photodermatol Photoimmunol Photomed."},{"issue":"6","key":"pone.0328647.ref012","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.cmet.2016.09.013","article-title":"Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice","volume":"24","author":"KF Mills","year":"2016","journal-title":"Cell Metab."},{"key":"pone.0328647.ref013","doi-asserted-by":"crossref","first-page":"112760","DOI":"10.1016\/j.jphotobiol.2023.112760","article-title":"Oral phytochemicals as photoprotectants in UVR exposed hairless mice: a study of hesperidin methyl chalcone, phloroglucinol, and syringic acid","volume":"246","author":"C Pihl","year":"2023","journal-title":"J Photochem Photobiol B."},{"issue":"7","key":"pone.0328647.ref014","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.3390\/ijms17071026","article-title":"Fernblock (polypodium leucotomos extract): molecular mechanisms and pleiotropic effects in light-related skin conditions, photoaging and skin cancers, a review","volume":"17","author":"C Parrado","year":"2016","journal-title":"Int J Mol Sci."},{"issue":"6","key":"pone.0328647.ref015","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1039\/d0pp00124d","article-title":"The role of the aqueous extract Polypodium leucotomos in photoprotection","volume":"19","author":"C Parrado","year":"2020","journal-title":"Photochem Photobiol Sci."},{"key":"pone.0328647.ref016","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.jare.2021.08.003","article-title":"Nicotinamide mononucleotide (NMN) as an anti-aging health product - Promises and safety concerns","volume":"37","author":"H Nadeeshani","year":"2021","journal-title":"J Adv Res."},{"issue":"1","key":"pone.0328647.ref017","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/s41598-020-57506-9","article-title":"Extracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity","volume":"10","author":"A Wilk","year":"2020","journal-title":"Sci Rep."},{"issue":"10","key":"pone.0328647.ref018","doi-asserted-by":"crossref","first-page":"100601","DOI":"10.1117\/1.JBO.26.10.100601","article-title":"Enhanced medical diagnosis for dOCTors: a perspective of optical coherence tomography","volume":"26","author":"R Leitgeb","year":"2021","journal-title":"J Biomed Opt."},{"issue":"3","key":"pone.0328647.ref019","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1159\/000444706","article-title":"Dynamic optical coherence tomography in dermatology","volume":"232","author":"M Ulrich","year":"2016","journal-title":"Dermatology."},{"issue":"4","key":"pone.0328647.ref020","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1111\/srt.12468","article-title":"OCT image atlas of healthy skin on sun-exposed areas","volume":"24","author":"S O\u2019Leary","year":"2018","journal-title":"Skin Res Technol."},{"issue":"5","key":"pone.0328647.ref021","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s00403-021-02245-8","article-title":"Optical coherence tomography quantifying photo aging: skin microvasculature depth, epidermal thickness and UV exposure","volume":"314","author":"J Olsen","year":"2022","journal-title":"Arch Dermatol Res."},{"issue":"9","key":"pone.0328647.ref022","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1117\/1.JBO.24.9.090901","article-title":"Review of methods and applications of attenuation coefficient measurements with optical coherence tomography","volume":"24","author":"S Chang","year":"2019","journal-title":"J Biomed Opt."},{"issue":"7","key":"pone.0328647.ref023","doi-asserted-by":"crossref","DOI":"10.1111\/exd.15141","article-title":"Metabolomic profiling and accurate diagnosis of basal cell carcinoma by MALDI imaging and machine learning","volume":"33","author":"LF Brorsen","year":"2024","journal-title":"Exp Dermatol."},{"issue":"1","key":"pone.0328647.ref024","doi-asserted-by":"crossref","first-page":"11091","DOI":"10.1038\/s41598-024-62023-0","article-title":"Cutaneous squamous cell carcinoma characterized by MALDI mass spectrometry imaging in combination with machine learning","volume":"14","author":"LF Brorsen","year":"2024","journal-title":"Sci Rep."},{"issue":"9","key":"pone.0328647.ref025","doi-asserted-by":"crossref","first-page":"4947","DOI":"10.1364\/BOE.496080","article-title":"Unleashing the power of optical attenuation coefficients to facilitate segmentation strategies in OCT imaging of age-related macular degeneration: perspective","volume":"14","author":"PJ Rosenfeld","year":"2023","journal-title":"Biomed Opt Express."},{"issue":"8","key":"pone.0328647.ref026","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1158\/0008-5472.CAN-18-2791","article-title":"Optical radiomic signatures derived from optical coherence tomography images improve identification of melanoma","volume":"79","author":"Z Turani","year":"2019","journal-title":"Cancer Res."},{"key":"pone.0328647.ref027","doi-asserted-by":"crossref","unstructured":"Untracht GR, Mortensen LB, Emini L, J\u00f8rgensen NR, Andersen PE. OCT-derived attenuation coefficient can differentiate between healthy and diabetic bone in a mouse model. In: Optical Coherence Imaging Techniques and Imaging in Scattering Media V, 2023. 17. https:\/\/doi.org\/10.1117\/12.2670587","DOI":"10.1117\/12.2670587"},{"issue":"292","key":"pone.0328647.ref028","article-title":"Detection of human brain cancer infiltration ex vivo and in vivo using quantitative optical coherence tomography","volume":"7","author":"C Kut","year":"2015","journal-title":"Sci Transl Med."},{"key":"pone.0328647.ref029","doi-asserted-by":"crossref","first-page":"44909","DOI":"10.1038\/srep44909","article-title":"Robust and fast characterization of OCT-based optical attenuation using a novel frequency-domain algorithm for brain cancer detection","volume":"7","author":"W Yuan","year":"2017","journal-title":"Sci Rep."},{"issue":"5","key":"pone.0328647.ref030","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/phpp.12181","article-title":"Black tattoos protect against UVR-induced skin cancer in mice","volume":"31","author":"CM Lerche","year":"2015","journal-title":"Photodermatol Photoimmunol Photomed."},{"issue":"9","key":"pone.0328647.ref031","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1002\/lsm.23406","article-title":"Tumor clearance and immune cell recruitment in UV-induced murine squamous cell carcinoma exposed to ablative fractional laser and imiquimod treatment","volume":"53","author":"S Fontenete","year":"2021","journal-title":"Lasers Surg Med."},{"issue":"4","key":"pone.0328647.ref032","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1117\/1.JBO.25.4.040901","article-title":"Parametric imaging of attenuation by optical coherence tomography: review of models, methods, and clinical translation","volume":"25","author":"P Gong","year":"2020","journal-title":"J Biomed Opt."},{"issue":"3","key":"pone.0328647.ref033","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1159\/000538445","article-title":"Efficacy of combinational treatment versus nicotinamide monotherapy in the prevention of ultraviolet radiation-induced skin cancer","volume":"240","author":"C Pihl","year":"2024","journal-title":"Dermatology."},{"issue":"1","key":"pone.0328647.ref034","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/j.1600-0781.1995.tb00131.x","article-title":"In vivo estimation of pigmentation in ultraviolet-exposed hairless mice","volume":"11","author":"AB Hansen","year":"1995","journal-title":"Photodermatol Photoimmunol Photomed."},{"key":"pone.0328647.ref035","unstructured":"R Core Team. R: A language and environment for statistical computing. 2021. https:\/\/www.R-project.org\/"},{"issue":"1","key":"pone.0328647.ref036","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.jdermsci.2008.08.012","article-title":"The hairless mouse in skin research","volume":"53","author":"F Benavides","year":"2009","journal-title":"J Dermatol Sci."},{"issue":"1","key":"pone.0328647.ref037","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/jid.1952.67","article-title":"The skin of hairless mice. I. The formation of cysts and the distribution of lipids","volume":"19","author":"W Montagna","year":"1952","journal-title":"J Invest Dermatol."},{"issue":"7","key":"pone.0328647.ref038","doi-asserted-by":"crossref","first-page":"2929","DOI":"10.3390\/molecules28072929","article-title":"Pirfenidone protects from UVB-induced photodamage in hairless mice","volume":"28","author":"Y Martinez-Alvarado","year":"2023","journal-title":"Molecules."},{"key":"pone.0328647.ref039","doi-asserted-by":"crossref","unstructured":"Welch AJ, van Gemert MJC. Optical-thermal response of laser-irradiated tissue. Springer Netherlands. 2011. https:\/\/doi.org\/10.1007\/978-90-481-8831-4","DOI":"10.1007\/978-90-481-8831-4"},{"issue":"11","key":"pone.0328647.ref040","doi-asserted-by":"crossref","DOI":"10.1088\/0031-9155\/58\/11\/R37","article-title":"Optical properties of biological tissues: a review","volume":"58","author":"SL Jacques","year":"2013","journal-title":"Phys Med Biol."},{"issue":"3","key":"pone.0328647.ref041","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1364\/JOSAA.17.000484","article-title":"Analysis of optical coherence tomography systems based on the extended Huygens-Fresnel principle","volume":"17","author":"L Thrane","year":"2000","journal-title":"J Opt Soc Am A Opt Image Sci Vis."},{"issue":"12","key":"pone.0328647.ref042","doi-asserted-by":"crossref","first-page":"121314","DOI":"10.1117\/1.JBO.20.12.121314","article-title":"Validation of quantitative attenuation and backscattering coefficient measurements by optical coherence tomography in the concentration-dependent and multiple scattering regime","volume":"20","author":"M Almasian","year":"2015","journal-title":"J Biomed Opt."},{"issue":"30","key":"pone.0328647.ref043","doi-asserted-by":"crossref","first-page":"6032","DOI":"10.1364\/AO.32.006032","article-title":"Measurement of optical properties of biological tissues by low-coherence reflectometry","volume":"32","author":"JM Schmitt","year":"1993","journal-title":"Appl Opt."},{"issue":"4","key":"pone.0328647.ref044","doi-asserted-by":"crossref","first-page":"131","DOI":"10.2478\/v10249-011-0029-5","article-title":"Optical properties of the human skin\/Opti\u010dke osobine ljudske ko\u017ee","volume":"2","author":"Z Gajinov","year":"2010","journal-title":"Serbian Journal of Dermatology and Venerology."},{"issue":"2","key":"pone.0328647.ref045","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1364\/OPEX.12.000249","article-title":"Determination of optical scattering properties of highly-scattering media in optical coherence tomography images","volume":"12","author":"D Levitz","year":"2004","journal-title":"Opt Express."},{"issue":"2","key":"pone.0328647.ref046","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1364\/BOE.382493","article-title":"Robust, accurate depth-resolved attenuation characterization in optical coherence tomography","volume":"11","author":"K Li","year":"2020","journal-title":"Biomed Opt Express."},{"key":"pone.0328647.ref047","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1007\/s43630-025-00736-5","article-title":"Oral nicotinamide mononucleotide (NMN) increases tissue NAD+ content in mice but neither NMN nor Polypodium leucotomos protect against UVR-induced skin cancer","volume":"24","author":"C Pihl","year":"2025","journal-title":"Photochem Photobiol Sci"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0328647","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T17:45:54Z","timestamp":1754934354000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0328647"}},"subtitle":[],"editor":[{"given":"Wenxuan","family":"Liang","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,8,11]]},"references-count":47,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0328647","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,11]]}}}