多光子显微镜在皮肤科中的应用

doi:10.35541/cjd.20230022

中华皮肤科杂志 ›› 2023, e20230022.doi: 10.35541/cjd.20230022

多光子显微镜在皮肤科中的应用

张嘉琪¹ 吴凡¹ 韩雨晴¹ 刘琦² 盘瑶¹

¹北京工商大学化学与材料工程学院化妆品系，北京 100048；²北京颐唯实检测技术有限公司，北京 100048

收稿日期:2023-01-13 修回日期:2023-06-15 发布日期:2023-09-04
通讯作者: 盘瑶 E-mail:panyao@btbu.edu.cn

Application of multi-photon microscopy in dermatology

Zhang Jiaqi¹, Wu Fan¹, Han Yuqing¹, Liu Qi², Pan Yao¹

¹Department of Cosmetics, College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing 100048, China; ²Beijing Yiweishi Testing Technology Limited Liability Company, Beijing 100048, China

Received:2023-01-13 Revised:2023-06-15 Published:2023-09-04
Contact: Pan Yao E-mail:panyao@btbu.edu.cn

摘要/Abstract

摘要： 【摘要】多光子显微镜利用近红外激光，通过选择不同的激发波长，使特定皮肤组织中的内源性荧光物或外源性荧光标记物发出荧光，对皮肤组织进行成像。这种在体、无创、精准的三维皮肤成像方法已经应用于皮肤肿瘤、皮肤炎症性疾病、创伤愈合和皮肤衰老等的研究中，是一种有效的成像辅助诊断工具。本文综述了多光子显微镜在皮肤科的应用和进展。

关键词: 皮肤肿瘤, 皮肤疾病, 皮肤衰老, 多光子显微镜, 皮肤创伤愈合

Abstract: 【Abstract】 Multi-photon microscopy has been used for skin tissue imaging based on the principle that endogenous fluorescent components in specific skin tissues or exogenous fluorescence-labeled substances could emit fluorescence under different excitation wavelengths of near-infrared lasers. It is an effective imaging technique for the auxiliary diagnosis of skin neoplasms, inflammatory skin diseases, wound healing and skin aging, with the advantages of in vivo, non-invasive and accurate three-dimensional skin imaging. This review summarizes the application of and progress in multi-photon microscopy in clinical practice in dermatology.

Key words: Skin neoplasms, Skin diseases, Skin aging, Multi-photon microscopy, Skin wound healing

张嘉琪吴凡韩雨晴刘琦盘瑶. 多光子显微镜在皮肤科中的应用[J]. 中华皮肤科杂志, 2023,e20230022. doi:10.35541/cjd.20230022

Zhang Jiaqi, Wu Fan, Han Yuqing, Liu Qi, Pan Yao. Application of multi-photon microscopy in dermatology[J]. Chinese Journal of Dermatology,2023,e20230022. doi:10.35541/cjd.20230022

参考文献 48

［1］	王诗琪, 刘洁. 深度学习辅助皮肤影像自动分类的研究进展［J］. 中华皮肤科杂志, 2020,53（12）:1037⁃1040. doi: 10.35541/cjd.20190660.
［2］	Giovannacci I, Meleti M, Garbarino F, et al. Correlation between autofluorescence intensity and histopathological features in non⁃melanoma skin cancer: an ex vivo study［J］. Cancers （Basel）, 2021,13（16）:3974. doi: 10.3390/cancers13163974.
［3］	Liu C, Jiang Z, Wang X, et al. Continuous optical zoom microscope with extended depth of field and 3D reconstruction［J］. PhotoniX, 2022,3（1）:1⁃18.https://doi.org/10.1186/s43074⁃022⁃00066⁃0.
［4］	Lunter D, Klang V, Kocsis D, et al. Novel aspects of Raman spectroscopy in skin research［J］. Exp Dermatol, 2022,31（9）:1311⁃1329. doi: 10.1111/exd.14645.
［5］	李少强, 耿俊娴, 李艳萍. 多光子成像技术的生物医学应用新进展［J］. 物理学报, 2020,69（22）:264⁃281. doi: 10.7498/aps. 69.20201039.
［6］	Stachowiak D, Bogusławski J, Głuszek A, et al. Frequency⁃doubled femtosecond Er⁃doped fiber laser for two⁃photon excited fluorescence imaging［J］. Biomed Opt Express, 2020,11（8）:4431⁃4442. doi: 10.1364/BOE.396878.
［7］	Chi HH, Lee JC, Chen CC, et al. An index combining lost and remaining nerve fibers correlates with pain hypersensitivity in mice［J］. Cells, 2020,9（11）. doi: 10.3390/cells9112414.
［8］	宋艳青, 盘瑶, 赵华. 化妆品透皮吸收试验方法概述［J］. 日用化学工业, 2019,49（12）:824⁃829. doi: 10.3969/j.issn.1001⁃1803. 2019.12.010.
［9］	应亚宸, 张广杰, 贾荟琳, 等. 多光子皮肤成像技术及其应用［J］. 中国光学, 2019,12（1）:104⁃111. doi: 10.3788/CO.20191201. 0104.
［10］	Khan S, Farabi B, Navarrete⁃Dechent C, et al. Applications of reflectance confocal microscopy in the diagnosis of fungal infections: a systematic review［J］. J Fungi （Basel）, 2022,9（1）:39. doi: 10.3390/jof9010039.
［11］	Atak MF, Farabi B, Navarrete⁃Dechent C, et al. Confocal microscopy for diagnosis and management of cutaneous malignancies: clinical impacts and innovation［J］. Diagnostics （Basel）, 2023,13（5）:854. doi: 10.3390/diagnostics13050854.
［12］	Owida HA. Developments and clinical applications of noninvasive optical technologies for skin cancer diagnosis ［J］. J Skin Cancer, 2022:9218847. doi: 10.1155/2022/9218847.
［13］	Hwang SM, Pan HC, Hwang MK, et al. Malignant skin tumor misdiagnosed as a benign skin lesion［J］. Arch Craniofac Surg, 2016,17（2）:86⁃89. doi: 10.7181/acfs.2016.17.2.86.
［14］	Lim CS, Choi JW, Kim YC, et al. Analyzing nonmelanoma skin cancer using enzyme⁃activatable two⁃photon probes［J］. Bull. Korean Chem. Soc., 2021,42（1）:103⁃106. doi: 10.1002/bkcs.12150.
［15］	Park WY, Kim B, Chun JH, et al. High⁃contrast visualization of human skin cancers with combined reflectance confocal and moxifloxacin⁃based two⁃photon microscopy: an ex vivo study［J］. Lasers Surg Med, 2022,54（9）:1226⁃1237. doi: 10.1002/lsm.23600.
［16］	Rajadhyaksha M, Menaker G, Flotte T, et al. Confocal examination of nonmelanoma cancers in thick skin excisions to potentially guide mohs micrographic surgery without frozen histopathology［J］. J Invest Dermatol, 2001,117（5）:1137⁃1143. doi: 10.1046/j.0022⁃202x.2001.01524.x.
［17］	Dobre EG, Surcel M, Constantin C, et al. Skin cancer pathobiology at a glance: a focus on imaging techniques and their potential for improved diagnosis and surveillance in clinical cohorts［J］. Int J Mol Sci, 2023,24（2）:1079. doi: 10. 3390/ijms24021079.
［18］	Hristu R, Eftimie LG, Stanciu SG, et al. Assessment of extramammary paget disease by two⁃photon microscopy［J］. Front Med （Lausanne）, 2022,9:839786. doi: 10.3389/fmed.2022. 839786.
［19］	Kim B, Le H, Oh BH, et al. High⁃speed combined reflectance confocal and moxifloxacin based two⁃photon microscopy［J］. Biomed Opt Express, 2020,11（3）:1555⁃1567. doi: 10.1364/BOE. 385763.
［20］	Ghezzi M, Pescina S, Delledonne A, et al. Improvement of imiquimod solubilization and skin retention via TPGS micelles: Exploiting the co⁃solubilizing effect of oleic acid［J］. Pharmaceutics, 2021,13（9）. doi: 10.3390/pharmaceutics13091476.
［21］	Otomo K, Goto A, Yamanaka Y, et al. High⁃peak⁃power 918⁃nm laser light source based two⁃photon spinning⁃disk microscopy for green fluorophores［J］. Biochem Biophys Res Commun, 2020,529（2）:238⁃242. doi: 10.1016/j.bbrc.2020.05.213.
［22］	Wang K, Pan Y, Tong S, et al. Deep⁃skin multiphoton microscopy in vivo excited at 1 600 nm: a comparative investigation with silicone oil and deuterium dioxide immersion［J］. J Biophotonics, 2021,14（10）:e202100076. doi: 10.1002/jbio.2021 00076.
［23］	Bánvölgyi A, Lőrincz K, Kiss N, et al. Efficiency of long⁃term high⁃dose intravenous ascorbic acid therapy in locally advanced basal cell carcinoma ⁃ a pilot study［J］. Postepy Dermatol Alergol, 2020,37（4）:548⁃558. doi: 10.5114/ada.2019.83027.
［24］	Ching⁃Roa VD, Huang CZ, Ibrahim SF, et al. Real⁃time analysis of skin biopsy specimens with 2⁃photon fluorescence microscopy［J］. JAMA Dermatol, 2022,158（10）:1175⁃1182. doi: 10.1001/jamadermatol.2022.3628.
［25］	Pena AM, Decencière E, Brizion S, et al. In vivo melanin 3D quantification and z⁃epidermal distribution by multiphoton FLIM, phasor and pseudo⁃FLIM analyses［J］. Sci Rep, 2022,12（1）:1642. doi: 10.1038/s41598⁃021⁃03114⁃0.
［26］	König K, Breunig HG, Batista A, et al. Translation of two⁃photon microscopy to the clinic: multimodal multiphoton CARS tomography of in vivo human skin［J］. J Biomed Opt, 2020,25（1）:1⁃12. doi: 10.1117/1.JBO.25.1.014515.
［27］	Žurauskas M, Barkalifa R, Alex A, et al. Assessing the severity of psoriasis through multivariate analysis of optical images from non⁃lesional skin［J］. Sci Rep, 2020,10（1）:9154. doi: 10.1038/s41598⁃020⁃65689⁃4.
［28］	Perevedentseva E, Ali N, Lin YC, et al. Au nanostar nanoparticle as a bio⁃imaging agent and its detection and visualization in biosystems［J］. Biomed Opt Express, 2020,11（10）:5872⁃5885. doi: 10.1364/BOE.401462.
［29］	Gaudenzio N, Marichal T, Galli S J, et al. Genetic and imaging approaches reveal pro⁃inflammatory and immunoregulatory roles of mast cells in contact hypersensitivity［J］. Front Immunol, 2018,9:1275. doi: 10.3389/fimmu.2018.01275.
［30］	Kocsis D, Horváth S, Kemény Á, et al. Drug delivery through the psoriatic epidermal barrier⁃a "skin⁃on⁃a⁃chip" permeability study and ex vivo optical imaging［J］. Int J Mol Sci, 2022,23（8）. doi: 10.3390/ijms23084237.
［31］	Jeong S, Hermsmeier M, Osseiran S, et al. Visualization of drug distribution of a topical minocycline gel in human facial skin［J］. Biomed Opt Express, 2018,9（7）:3434⁃3448. doi: 10.1364/BOE. 9.003434.
［32］	Lin Y, Lin H, Zhu X, et al. Three⁃dimensional characterizations of two⁃photon excitation fluorescence images of elastic fibers affected by cutaneous scar duration［J］. Quant Imaging Med Surg, 2021,11（8）:3584⁃3594. doi: 10.21037/qims⁃20⁃1051.
［33］	Morone D, Autilia F, Schorn T, et al. Author correction: evaluation of cell metabolic adaptation in wound and tumour by fluorescence lifetime imaging microscopy［J］. Sci Rep, 2020,10（1）:14138. doi: 10.1038/s41598⁃020⁃71164⁃x.
［34］	Maluki A, Breitschwerdt E, Bemis L, et al. Imaging analysis of Bartonella species in the skin using single⁃photon and multi⁃photon （second harmonic generation） laser scanning microscopy［J］. Clin Case Rep, 2020,8（8）:1564⁃1570. doi: 10.1002/ccr3. 2939.
［35］	Meador WD, Sugerman GP, Tepole AB, et al. Biaxial mechanics of thermally denaturing skin ⁃ Part 1: Experiments［J］. Acta Biomater, 2022,140:412⁃420. doi: 10.1016/j.actbio.2021.09.033.
［36］	Seeger M, Dehner C, Jüstel D, et al. Label⁃free concurrent 5⁃modal microscopy （Co5M） resolves unknown spatio⁃temporal processes in wound healing［J］. Commun Biol, 2021,4（1）:1040. doi: 10.1038/s42003⁃021⁃02573⁃5.
［37］	He G, Cao Y, Tang J, et al. Assessing skin healing and angiogenesis of deep burns in vivo using two⁃photon microscopy in mice［J］. Front. Phys, 2022,10. doi: 10.3389/fphy.2022.931419.
［38］	Wang J, Zhen Z, Wang Y, et al. Non⁃invasive skin imaging assessment of human stress during head⁃down bed rest using a portable handheld two⁃photon microscope［J］. Front Physiol, 2022,13:899830. doi: 10.3389/fphys.2022.899830.
［39］	Wang H, Shyr T, Fevola MJ, et al. Age⁃related morphological changes of the dermal matrix in human skin documented in vivo by multiphoton microscopy［J］. J Biomed Opt, 2018,23（3）:1⁃4. doi: 10.1117/1.JBO.23.3.030501.
［40］	McCabe MC, Hill RC, Calderone K, et al. Alterations in extracellular matrix composition during aging and photoaging of the skin［J］. Matrix Biol Plus, 2020,8:100041. doi: 10.1016/j.mbplus.2020.100041.
［41］	Ipponjima S, Umino Y, Nagayama M, et al. Live imaging of alterations in cellular morphology and organelles during cornification using an epidermal equivalent model［J］. Sci Rep, 2020,10（1）:5515. doi: 10.1038/s41598⁃020⁃62240⁃3.
［42］	Sun Y, Li L, Ma S, et al. In vivo visualization of collagen transdermal absorption by second⁃harmonic generation and two⁃photon excited fluorescence microscopy［J］. Front Chem, 2022,10:925931. doi: 10.3389/fchem.2022.925931.
［43］	Lee SH, Bae I, Lee E, et al. Glucose exerts an anti⁃melanogenic effect by indirect inactivation of tyrosinase in melanocytes and a human skin equivalent［J］.Int J Mol Sci, 2020,21（5）:1736. doi: 10.3390/ijms21051736.
［44］	Pham DL, Miller CR, Myers MS, et al. Development and characterization of phasor⁃based analysis for FLIM to evaluate the metabolic and epigenetic impact of HER2 inhibition on squamous cell carcinoma cultures［J］. J Biomed Opt, 2021,26（10）. doi: 10.1117/1.JBO.26.10.106501.
［45］	Ung T, Lim S, Solinas X, et al. Simultaneous NAD（P）H and FAD fluorescence lifetime microscopy of long UVA⁃induced metabolic stress in reconstructed human skin［J］. Sci Rep, 2021,11（1）:22171. doi: 10.1038/s41598⁃021⁃00126⁃8.
［46］	Liu Z, Chiang CY, Nip J, et al. Nicotinamide effects on the metabolism of human fibroblasts and keratinocytes assessed by quantitative, label⁃free fluorescence imaging［J］. Biomed Opt Express, 2021,12（10）:6375⁃6390. doi: 10.1364/BOE.432561.
［47］	Seidenari S, Arginelli F, Bassoli S, et al. Multiphoton laser microscopy and fluorescence lifetime imaging for the evaluation of the skin［J］. Dermatol Res Pract, 2012,2012:810749. doi: 10.1155/2012/810749.
［48］	Vicente JR, Durkin A, Shrestha K, et al. In vivo imaging with a fast large⁃area multiphoton exoscope （FLAME） captures the melanin distribution heterogeneity in human skin［J］. Sci Rep, 2022,12（1）:8106. doi: 10.1038/s41598⁃022⁃12317⁃y.

[1]	Michèle Verschoore 牛悦青 Stéphane Commo Léopold Muller 魏宇昊甄雅贤刘玮. [开放获取] 中华医学会-欧莱雅中国人健康皮肤/毛发研究项目成果总结——皮肤篇[J]. 中华皮肤科杂志, 2024, 57(5): 464-467.
[2]	王艺萌吴雯婷张倩张春雷李薇薇. 肛周外生殖器部位原发性实性肿瘤389例临床和病理诊断分析[J]. 中华皮肤科杂志, 2024, 57(4): 316-323.
[3]	洪永镇王倩梁俊琴. 二代测序技术在非遗传性皮肤病领域中的运用[J]. 中华皮肤科杂志, 2024, 0(3): 20220436-e20220436.
[4]	郭蕾曹春艳方晓雅冯素英. 自身免疫性大疱病患者创面感染多重耐药菌现况及危险因素分析[J]. 中华皮肤科杂志, 2024, 57(2): 155-160.
[5]	王晨薛晨红宋静卉李建国李振鲁张守民李明王建波. 阿达木单抗治疗Blau综合征1家系3例[J]. 中华皮肤科杂志, 2024, 0(2): 20220239-e20220239.
[6]	荆可王媛李锁冯素英. 表现为环状红斑水疱的自身免疫性表皮下水疱病25例回顾性分析[J]. 中华皮肤科杂志, 2023, 56(9): 832-838.
[7]	陈耀龙刘辉姚志荣高兴华. 提升皮肤病领域指南和共识质量的策略与建议[J]. 中华皮肤科杂志, 2023, 56(9): 805-808.
[8]	孙小洁刘毅. 抗雄激素药物治疗皮肤病研究进展[J]. 中华皮肤科杂志, 2023, 56(9): 882-885.
[9]	岳超段梦莹王涛章满玉戴叶芹彭建中宋秀祖. 上睑眼轮匝肌岛状皮瓣修复眼睑及眶周皮肤肿瘤切除后继发缺损28例回顾性分析[J]. 中华皮肤科杂志, 2023, 56(9): 862-865.
[10]	刘璐, 尹翠元, 胡红忠何琳琳, . 胶原蛋白肽抗皮肤自然老化作用机制与临床研究进展[J]. 中华皮肤科杂志, 2023, 56(5): 455-458.
[11]	连盼盼刘军苏忠兰王宏伟. 过氧化物酶体增殖物激活受体γ对皮肤生理功能和病理过程的影响[J]. 中华皮肤科杂志, 2023, 56(4): 365-368.
[12]	杨小丽邓丹琪. 牙周炎与免疫性皮肤病的研究进展[J]. 中华皮肤科杂志, 2023, 0(2): 20230059-e20230059.
[13]	刘力豪胡煜陈崑. 光生物调节作用在皮肤科应用的研究与进展[J]. 中华皮肤科杂志, 2023, 0(2): 20230312-e20230312.
[14]	陈良宏孙艳王敬玉吴严. 本维莫德在皮肤病中的研究进展[J]. 中华皮肤科杂志, 2023, 0(2): 20210875-e20210875.
[15]	郑娜娜曾荣, 陶盈凯李岷, . 环状RNA与皮肤肿瘤相关性研究进展[J]. 中华皮肤科杂志, 2023, 0(2): 20210893-e20210893.

多光子显微镜在皮肤科中的应用

Application of multi-photon microscopy in dermatology

PDF

PDF (Mobile)

可视化

摘要/Abstract

引用本文

使用本文

参考文献 48

相关文章 15

Metrics

本文评价

推荐阅读 10