{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T15:50:14Z","timestamp":1789487414334,"version":"build-2803163510"},"reference-count":30,"publisher":"Optica Publishing Group","issue":"10","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1364\/OA_License_v2#VOR-OA"},{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/opg.optica.org\/policies\/opg-tdm-policy.json"}],"funder":[{"name":"the Fujian Provincial Natural Science Foundation of China","award":["2024J011644"],"award-info":[{"award-number":["2024J011644"]}]},{"name":"the Fujian Provincial Science and Technology Innovation Joint Funds","award":["2024Y9023"],"award-info":[{"award-number":["2024Y9023"]}]},{"name":"National Natural Science Foundation of China","award":["62575072"],"award-info":[{"award-number":["62575072"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":["opg.optica.org"],"crossmark-restriction":false},"short-container-title":["Biomed. Opt. Express"],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:p>Lung adenocarcinoma (LUAD) requires accurate subtyping for prognosis and treatment, yet conventional histopathology is time-consuming and subjective. This study applies label-free multiphoton microscopy (MPM) to quantify extracellular matrix remodeling, imaging collagen via SHG and elastin via TPEF in 88 specimens from 72 patients. We introduce a SHG\/TPEF ratio (STR) system to assess tumor invasiveness. Results show progressive \u201cfiber desertification,\u201d reduced fiber content, and decreased collagen alignment in high-grade LUAD subtypes. STR metrics strongly correlate with pathological grading and effectively distinguish aggressive patterns. This MPM-based framework enables rapid, objective intraoperative identification of high-grade LUAD, improving diagnostic precision and clinical decision-making.<\/jats:p>","DOI":"10.1364\/boe.601927","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T08:00:16Z","timestamp":1782720016000},"page":"5179","update-policy":"https:\/\/doi.org\/10.1364\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Label-free, multiphoton microscopy-based strategy for intraoperative grading of lung adenocarcinoma via quantitative extracellular matrix analysis"],"prefix":"10.1364","volume":"17","author":[{"given":"Houqiang","family":"Li","sequence":"first","affiliation":[{"name":"Fuzhou University Affiliated Provincial Hospital"},{"name":"Shengli Clinical Medical College of Fujian Medical University"},{"name":"Fuzhou University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouzhi","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/011xvna82","id-type":"ROR","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiming","family":"He","sequence":"additional","affiliation":[{"name":"Fuzhou University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianshun","family":"Chen","sequence":"additional","affiliation":[{"name":"Fuzhou University Affiliated Provincial Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Huang","sequence":"additional","affiliation":[{"name":"Fujian Normal University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhan","family":"Zhuang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Fujian Medical University"},{"name":"Fujian Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangmei","family":"Tong","sequence":"additional","affiliation":[{"name":"Fuzhou University Affiliated Provincial Hospital"},{"name":"Shengli Clinical Medical College of Fujian Medical University"},{"name":"Fuzhou University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunbin","family":"Yu","sequence":"additional","affiliation":[{"name":"Fuzhou University Affiliated Provincial Hospital"},{"name":"Shengli Clinical Medical College of Fujian Medical University"},{"name":"Fuzhou University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Lin","sequence":"additional","affiliation":[{"name":"Fuzhou University Affiliated Provincial Hospital"},{"name":"Shengli Clinical Medical College of Fujian Medical University"},{"name":"Fuzhou University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyao","family":"Yan","sequence":"additional","affiliation":[{"name":"Fuzhou University Affiliated Provincial Hospital"},{"name":"Shengli Clinical Medical College of Fujian Medical University"},{"name":"Fuzhou University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8519-4462","authenticated-orcid":true,"given":"Jianxin","family":"Chen","sequence":"additional","affiliation":[{"name":"Fujian Normal University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0829-5694","authenticated-orcid":true,"given":"Shu","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/011xvna82","id-type":"ROR","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Li","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Fujian Medical University"},{"name":"Fujian Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"Fuzhou University Affiliated Provincial Hospital"},{"name":"Shengli Clinical Medical College of Fujian Medical University"},{"name":"Fuzhou University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"285","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"boe-17-10-5179-R1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","type":"journal-article","volume":"71","author":"Sung","year":"2021","journal-title":"CA: a Cancer Journal for Clinicians"},{"key":"boe-17-10-5179-R2","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1016\/S0140-6736(17)33326-3","type":"journal-article","volume":"391","author":"Allemani","year":"2018","journal-title":"Lancet"},{"key":"boe-17-10-5179-R3","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1016\/j.jtho.2021.04.007","type":"journal-article","volume":"16","author":"Yotsukura","year":"2021","journal-title":"J. Thorac. Oncol."},{"key":"boe-17-10-5179-R5","doi-asserted-by":"publisher","first-page":"1599","DOI":"10.1016\/j.jtho.2020.06.001","type":"journal-article","volume":"15","author":"Moreira","year":"2020","journal-title":"J. Thorac. Oncol."},{"key":"boe-17-10-5179-R6","first-page":"1081","type":"journal-article","volume":"53","author":"Xie","year":"2024","journal-title":"Zhonghua Bing Li Xue Za Zhi\u2009=\u2009Chinese Journal of Pathology"},{"key":"boe-17-10-5179-R7","doi-asserted-by":"publisher","first-page":"8334","DOI":"10.1038\/s41598-018-26673-1","type":"journal-article","volume":"8","author":"Luo","year":"2018","journal-title":"Sci. Rep."},{"key":"boe-17-10-5179-R8","doi-asserted-by":"publisher","first-page":"659","DOI":"10.2174\/1566524033479447","type":"journal-article","volume":"3","author":"Cairns","year":"2003","journal-title":"Curr. Mol. Med."},{"key":"boe-17-10-5179-R9","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1038\/onc.2016.358","type":"journal-article","volume":"36","author":"Peng","year":"2017","journal-title":"Oncogene"},{"key":"boe-17-10-5179-R10","doi-asserted-by":"publisher","first-page":"7715","DOI":"10.1038\/s41598-019-44156-9","type":"journal-article","volume":"9","author":"Natal","year":"2019","journal-title":"Sci. Rep."},{"key":"boe-17-10-5179-R11","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1111\/his.12308","type":"journal-article","volume":"64","author":"Castonguay","year":"2014","journal-title":"Histopathology"},{"key":"boe-17-10-5179-R12","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1136\/jclinpath-2021-207779","type":"journal-article","volume":"75","author":"Shen","year":"2022","journal-title":"J. Clin. Pathol."},{"key":"boe-17-10-5179-R13","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.jtho.2015.09.009","type":"journal-article","volume":"11","author":"Goldstraw","year":"2016","journal-title":"J. Thorac. Oncol."},{"key":"boe-17-10-5179-R14","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/j.jtho.2022.11.026","type":"journal-article","volume":"18","author":"Thunnissen","year":"2023","journal-title":"J. Thorac. Oncol."},{"key":"boe-17-10-5179-R15","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1038\/s41377-024-01597-w","type":"journal-article","volume":"13","author":"Wang","year":"2024","journal-title":"Light: Sci. Appl."},{"key":"boe-17-10-5179-R16","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1007\/s11102-018-0882-6","type":"journal-article","volume":"21","author":"Lin","year":"2018","journal-title":"Pituitary"},{"key":"boe-17-10-5179-R17","doi-asserted-by":"publisher","first-page":"1802","DOI":"10.1002\/ijc.34855","type":"journal-article","volume":"154","author":"Han","year":"2024","journal-title":"Int. J. Cancer"},{"key":"boe-17-10-5179-R18","doi-asserted-by":"publisher","first-page":"6595","DOI":"10.7150\/thno.77532","type":"journal-article","volume":"12","author":"Wang","year":"2022","journal-title":"Theranostics"},{"key":"boe-17-10-5179-R19","doi-asserted-by":"publisher","first-page":"086014","DOI":"10.1117\/1.JBO.19.8.086014","type":"journal-article","volume":"19","author":"Tilbury","year":"2014","journal-title":"J. Biomed. Opt."},{"key":"boe-17-10-5179-R20","doi-asserted-by":"publisher","first-page":"20713","DOI":"10.1038\/s41598-022-24973-1","type":"journal-article","volume":"12","author":"Mirsanaye","year":"2022","journal-title":"Sci. Rep."},{"key":"boe-17-10-5179-R21","doi-asserted-by":"publisher","first-page":"1851","DOI":"10.1364\/BOE.387744","type":"journal-article","volume":"11","author":"Golaraei","year":"2020","journal-title":"Biomed. Opt. Express"},{"key":"boe-17-10-5179-R22","doi-asserted-by":"publisher","first-page":"044034","DOI":"10.1117\/1.3210768","type":"journal-article","volume":"14","author":"Wang","year":"2009","journal-title":"J. Biomed. Opt."},{"key":"boe-17-10-5179-R23","doi-asserted-by":"publisher","first-page":"e202300172","DOI":"10.1002\/jbio.202300172","type":"journal-article","volume":"16","author":"Xi","year":"2023","journal-title":"J. Biophotonics"},{"key":"boe-17-10-5179-R24","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.5858\/arpa.2013-0122-OA","type":"journal-article","volume":"138","author":"Jain","year":"2014","journal-title":"Arch. Pathol. Lab. Med."},{"key":"boe-17-10-5179-R25","doi-asserted-by":"publisher","first-page":"100633","DOI":"10.1016\/j.modpat.2024.100633","type":"journal-article","volume":"38","author":"van Huizen","year":"2025","journal-title":"Mod. Pathol."},{"key":"boe-17-10-5179-R26","doi-asserted-by":"publisher","first-page":"198","DOI":"10.3389\/fbioe.2020.00198","type":"journal-article","volume":"8","author":"Liu","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"boe-17-10-5179-R27","first-page":"429","article-title":"Methods for quantifying fibrillar collagen alignment","author":"Liu","year":"2017"},{"key":"boe-17-10-5179-R28","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1111\/his.14537","type":"journal-article","volume":"80","author":"Thunnissen","year":"2022","journal-title":"Histopathology"},{"key":"boe-17-10-5179-R29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1109\/JSTQE.2021.3058175","type":"journal-article","volume":"27","author":"Wang","year":"2021","journal-title":"IEEE J. Sel. Top. Quantum Electron."},{"key":"boe-17-10-5179-R30","doi-asserted-by":"publisher","first-page":"3229","DOI":"10.7150\/thno.55921","type":"journal-article","volume":"11","author":"Xi","year":"2021","journal-title":"Theranostics"},{"key":"boe-17-10-5179-R31","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1200\/JCO.2015.63.4907","type":"journal-article","volume":"34","author":"Liu","year":"2016","journal-title":"J. Clin. Oncol."}],"container-title":["Biomedical Optics Express"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/opg.optica.org\/viewmedia.cfm?URI=boe-17-10-5179&seq=0","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T14:25:43Z","timestamp":1789482343000},"score":1,"resource":{"primary":{"URL":"https:\/\/opg.optica.org\/abstract.cfm?URI=boe-17-10-5179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":30,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026]]},"published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1364\/boe.601927","relation":{},"ISSN":["2156-7085","2156-7085"],"issn-type":[{"value":"2156-7085","type":"print"},{"value":"2156-7085","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]},"assertion":[{"value":"Optica Publishing Group","name":"publisher","label":"This article is maintained by"},{"value":"https:\/\/doi.org\/10.1364\/BOE.601927","name":"articlelink","label":"Crossref DOI link to publisher maintained version"},{"value":"research-article","name":"content_type","label":"Article type"},{"value":"Screened by Similarity Check","name":"cross_check","label":"Similarity check"},{"value":"Yes","order":0,"name":"peer_reviewed","label":"Peer reviewed","group":{"name":"peer_review","label":"Peer review"}},{"value":"Single blind","order":1,"name":"review_process","label":"Review process","group":{"name":"peer_review","label":"Peer review"}},{"value":"20 April 2026","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"19 June 2026","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"15 September 2026","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}},{"value":"\u00a9 2026 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement","name":"copyright","label":"Copyright"}]}}