首页 > 论文 > Journal of Innovative Optical Health Sciences > 12卷 > 5期(pp:1930004--1)

Fluorescence lifetime imaging microscopy and its applications in skin cancer diagnosis

Fluorescence lifetime imaging microscopy and its applications in skin cancer diagnosis

  • 摘要
  • 论文信息
  • 参考文献
  • 被引情况
  • PDF全文


Fluorescence lifetime (FLT) of fluorophores is sensitive to the changes in their surrounding microenvironment, and hence it can quantitatively reveal the physiological characterization of the tissue under investigation. Fluorescence lifetime imaging microscopy (FLIM) provides not only morphological but also functional information of the tissue by producing spatially resolved image of fluorophore lifetime, which can be used as a signature of disorder and/or malignancy in diseased tissues. In this paper, we begin by introducing the basic principle and common detection methods of FLIM. Then the recent advances in the FLIM-based diagnosis of three different skin cancers, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and malignant melanoma (MM) are reviewed. Furthermore, the potential advantages of FLIM in skin cancer diagnosis and the challenges that may be faced in the future are prospected.



基金项目:This work has been partially supported by The 111 Project (B17035), Open Research Fund Program of the State Key Laboratory of Low Dimensional Quantum Physics (KF201713), State Key Laboratory of Transient Optics and Photonics, Chinese Academy of Sciences (SKLST201804) and the Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province (GD201711).




作者单位    点击查看

Lixin Liu:School of Physics and Optoelectronic Engineering, Xidian University, Xi'an 710071, P. R. China
Qianqian Yang:School of Physics and Optoelectronic Engineering, Xidian University, Xi'an 710071, P. R. China
Meiling Zhang:School of Physics and Optoelectronic Engineering, Xidian University, Xi'an 710071, P. R. China
Zhaoqing Wu:School of Physics and Optoelectronic Engineering, Xidian University, Xi'an 710071, P. R. China
Ping Xue:State Key Laboratory of Low-Dimensional Quantum Physics, Department of Physics, Tsinghua University, Beijing 100084, P. R. China

联系人作者:Lixin Liu(lxliu@xidian.edu.cn)

【1】Z. Apalla, A. Lallas, E. Sotiriou, L. Elizabeth, I. Demetrios, “Epidemiological trends in skin cancer," Dermatol. Pract. Concept. 7(2), 1–6 (2017).

【2】Z. Apalla, D. Nashan, R. B. Weller, X. Castellsague, “Skin cancer: Epidemiology, disease burden, pathophysiology, diagnosis, and therapeutic approaches," Dermatol. Ther. 7(1), 5–19 (2017).

【3】American Cancer Society, Cancer Facts & Figures 2018, https://www.cancer.org/research/cancer-factsstatistics/all-cancer-facts-figures/cancer-facts-figures-2018.html (2018).

【4】National Cancer Institute, SEER stats fact sheets: melanoma of the skin, https://seer.cancer.gov/statfacts/html/melan.html (2018).

【5】J. Yang, S. Xiong, “Diagnosis and treatment of human basal cell carcinoma and squamous cell carcinoma," China Mod. Med. 18(11), 13–15 (2011).

【6】A. Luu, L. Doerwald-Munoz, O. Stapiak, “An evaluation of two approaches to skin bolus design for patients receiving radiotherapy for head and neck cancers," J. Med. Imaging Radiat. Sci. 46(3), 37–42 (2014).

【7】Z. Tang, J. Shi, M. Cai, D. Xue, “An analysis of skin melanoma incidence and its influencing factors in China," China Cancer 23(10), 829–833 (2014).

【8】Y. Lu, X. Peng, S. Fan, S. Liu, J. Qu, “Application of new optical methods in skin cancer research," Int. J. Dermatol. Venereol. 40(6), 383–385 (2014).

【9】M. Y. Berezin, S. Achilefu, “Fluorescence lifetime measurements and biological imaging," Chem. Rev. 110(5), 2641–2684 (2010).

【10】V. Ntziachristos, “Going deeper than microscopy: The optical imaging frontier in biology," Nat. Methods 7(8), 603–614 (2010).

【11】K. Nienhaus, G. U. Nienhaus, “Where do we stand with super-resolution optical microscopy," J. Mol. Biol. 428(2), 308–322 (2016).

【12】K. Konig, “Clinical multiphoton tomography," J. Biophoton. 1(1), 13–23 (2008).

【13】S. G. Stanciu, M. Costache, D. E. Tranca, R. Hristu, M. Popescu, V. Enache, G. A. Stanciu, “Towards imaging skin cancer by apertureless scanning near-field optical microscopy," U.P.B. Sci. Bull., Ser. A. Appl. Math. Phys. 78(2), 235–244 (2016).

【14】X. Zhang, “Imaging technology in modern microsystems," Opt. Instrum. 37(6), 550–560 (2015).

【15】V. V. Ghukasyan, F. J. Kao, “Monitoring cellular metabolism with fluorescence lifetime of reduced nicotinamide adenine dinucleotide," J. Phys. Chem. 113(27), 11532–11540 (2009).

【16】M. W. Conklin, P. P. Provenzano, K. W. Eliceiri, R. Sullivan, P. J. Keely, “Fluorescence lifetime imaging of endogenous fluorophores in histopathology sections reveals differences between normal and tumor epithelium in carcinoma in situ of the breast," Cell Biochem. Biophys. 53(3), 145–157 (2009).

【17】L. Marcu, “Fluorescence lifetime techniques in medical applications," Ann. Biomed. Eng. 40(2), 304–331 (2012).

【18】D. Chorvat, A. Chorvatova, “Multi-wavelength fluorescence lifetime spectroscopy: A new approach to the study of endogenous fluorescence in living cells and tissues," Laser Phys. Lett. 6(3), 175–193 (2009).

【19】M. S. Roberts, Y. Dancik, T. W. Prow, C. A. Thorling, L. L. Lin, J. E. Grice, T. A. Robertson, K. K€onig, W. Becker, “Non-invasive imaging of skin physiology and percutaneous penetration using fluorescence spectral and lifetime imaging with multiphoton and confocal microscopy," Eur. J. Pharm. Biopharm. 77(3), 469–488 (2011).

【20】J. Leppert, J. Krajewski, S. R. Kantelhardt, S. M. Schlaffer, N. Petkus, E. Reusche, G. Hüttmann, A. Giese, “Multiphoton excitation of autofluorescence for microscopy of glioma tissue," Neurosurgery 58(4), 759–767 (2006).

【21】I. Riemann, A. Ehlers, R. Le Harzic, E. Dimitrow, M. Kaatz, P. Elsner, R. Bückle, K. Koenig, “Noninvasive analysis/diagnosis of human normal and melanoma skin tissues with two-photon FLIM in vivo," Proc. SPIE 6842, 684205 (2008).

【22】S. Fan, X. Peng, L. Liu, S. Liu, Y. Lu, J. Qu, “Diagnosis of basal cell carcinoma by two photon excited fluorescence combined with lifetime imaging," Proc. SPIE 8948, 89482E (2014).

【23】A. Pliss, X. Peng, L. Liu, A. Kuzmin, Y. Wang, J. Qu, Y. Li, P. N. Prasad, “Single cell assay for molecular diagnostics and medicine: Monitoring intracellular concentrations of macromolecules by two-photon fluorescence lifetime imaging," Theranostics 5(9), 919–930 (2015).

【24】A. Pliss, S. M. Levchenko, L. Liu, X. Peng, T. Y. Ohulchanskyy, I. Roy, A. N. Kuzmin, J. Qu, P. N. Prasad, “Cycles of protein condensation and discharge in nuclear organelles studied by fluorescence lifetime imaging," Nat. Commun. 10(1), 455 (2019).

【25】TuanVo-Dinh, Biomedical Photonics Handbook, CRC Publishing Company, Florida (2003).

【26】A. T. N. Kumar, S. B. Raymond, B. J. Bacskai, D. A. Boas, “Comparison of frequency-domain and time-domain fluorescence lifetime tomography," Opt. Lett. 33(5), 470–472 (2008).

【27】E. Gratton, S. Breusegem, J. Sutin, Q. Q. Ruan, N. Barry, “Fluorescence lifetime imaging of twophoton microscopy: Time domain and frequency domain method," J. Biomed. Opt. 8(3), 381–390 (2003).

【28】L. Liu, J. Qu, Z. Lin, B. Guo, H. Niu, “Fluorescence lifetime imaging and its biomedical applications," J. Shenzhen Univ. Sci. Eng. 22(2), 133–141 (2005).

【29】W. Becker, A. Bergmann, K. Koenig, U. Tirlapur, “Picosecond fluorescence lifetime microscopy by TCSPC imaging," Proc. SPIE 4262, 414–419 (2001).

【30】X. Liu, D. Lin, Q. Wu, W. Yan, T. Luo, Z. Yang, J. Qu, “Recent progress of fluorescence lifetime imaging microscopy technology and its application," Acta Phys. Sin. 67(17), 27–40 (2018).

【31】K. Suhling, L. M. Hirvonen, J. A. Levitt, P. H. Chung, C. Tregido, A. Le Marois, D. Rusakov, K. Zheng, S. Ameer-Beg, S. Poland, S. Coelho, R. Dimble, “Fluorescence lifetime imaging (FLIM): Basic concepts and recent applications," Springer Ser. Chem. Phys. 111, 119–188 (2015).

【32】L. Liu, A. Pliss, X. Peng, A. Kuzmin, J. Qu, P. N. Prasa, “Mapping of intracellular concentrations of macromolecules by twophoton excited fluorescence lifetime imaging," Proc. SPIE 9712, 971221 (2016).

【33】S. A. Gandhi, J. Kampp, “Skin cancer epidemiology, detection, and management," Med. Clin. N. Am. 99(6), 1323–1335 (2015).

【34】N. P. Galletly, J. Mcginty, C. Dunsby, F. Teixeira, J. Requejo-Isidro, I. Munro, D. S. Elson, M. A. Neil, A. C. Chu, P. M. French, G. W. Stamp, “Fluorescence lifetime imaging distinguishes basal cell carcinoma from surrounding uninvolved skin," Br. J. Dermatol. 159(1), 152–161 (2008).

【35】R. Patalay, C. B. Talbot, L. Munro, H. G. Breunig, “Fluorescence lifetime imaging of skin cancer," Proc. SPIE 7883, 78830A (2011).

【36】R. Patalay, C. Talbot, Y. Alexandrov, I. Munro, M. A. Neil, K. K€onig, P. M. French, A. Chu, G. W. Stamp, C. Dunsby, “Quantification of cellular autofluorescence of human skin using multiphoton tomogr aphy and fluorescence lifetime imaging in two spectral detection channels," Biomed. Opt. Exp. 2(12), 3295–3308 (2012).

【37】S. Seidenari, F. Arginelli, C. Dunsby, P. French, K. Koenig, C. Magnoni, M. Manfredini, C. Talbot, G. Ponti, “Multiphoton laser tomography and fluorescence lifetime imaging of basal cell carcinoma: Morphologic features for non-invasive diagnostics," Exp. Dermatol. 21(11), 831–836 (2012).

【38】T. Luo, Y. Lu, S. Liu, D. Lin, J. Qu, “Phasor-FLIM as a screening tool for the differential diagnosis of actinic keratosis, Bowen''s disease and basal cell carcinoma," Anal. Chem. 89(15), 8104–8111 (2017).

【39】T. Zhao, J. Zheng, “Advances in the research of cutaneous squamous cell carcinoma," Int. J. Dermatol. 32(4), 247–250 (2006).

【40】E. Martín-Villar, B. Fernandez-Munoz, M. Parsons, M. M. Yurrita, D. Megías, E. Perez-Gómez, G. E. Jones, M. Quintanilla, “Podoplanin associates with cd44 to promote directional cell migration," Mol. Biol. Cell 21(24), 4387–4399 (2010).

【41】C. R. Miller, M. G. Nichols, “Metabolic profiling of the skin to monitor the onset and progression of squamous cell carcinoma through time- and wavelength-resolved fluorescence lifetime imaging," Biophys. J. 108(2), 478a (2015).

【42】J. P. Miller, L. M. Habimana-Gri±n, T. S. Edwards, S. Achilefu, “Multimodal fluorescence molecular imaging for in vivo characterization of skin cancer using endogenous and exogenous fluorophores," J. Biomed. Opt. 22(6), 066007 (2017).

【43】S. LevêqueFort, M. P. Fontaineaupart, G. Roger, P. Georges, “Fluorescence-lifetime imaging with a multifocal two-photon microscope," Opt. Lett. 29(24), 2884–2886 (2004).

【44】R. Cicchi, S. Sestini, V. D. Giorgi, D. Massi, T. Lotti, F. S. Pavone, “Multidimensional two-photon imaging of diseased skin," Proc. SPIE 6859, 685903 (2008).

【45】E. Dimitrow, I. Riemann, A. Ehlers, M. J. Koehler, J. Norgauer, P. Elsner, K. Koenig, M. Kaatz, “Spectral fluorescence lifetime detection and selective melanin imaging by multiphoton laser tomography for melanoma diagnosis," Exp. Dermatol. 18(6), 509–515 (2009).

【46】L. Pires, M. S. Nogueira, S. Pratavieira, L. Moriyama, C. Kurachi, “Time-resolved fluorescence lifetime for cutaneous melanoma detection," Biomed. Opt. Express 5(9), 3080–3089 (2014).

【47】M. N. Pastore, H. Studier, C. S. Bonder, M. Roberts, “Non-invasive metabolic imaging of melanoma progression," Exp. Dermatol. 26(7), 607–614 (2017).


Lixin Liu,Qianqian Yang,Meiling Zhang,Zhaoqing Wu,Ping Xue. Fluorescence lifetime imaging microscopy and its applications in skin cancer diagnosis[J]. Journal of Innovative Optical Health Sciences, 2019, 12(5): 1930004

Lixin Liu,Qianqian Yang,Meiling Zhang,Zhaoqing Wu,Ping Xue. Fluorescence lifetime imaging microscopy and its applications in skin cancer diagnosis[J]. Journal of Innovative Optical Health Sciences, 2019, 12(5): 1930004

您的浏览器不支持PDF插件,请使用最新的(Chrome/Fire Fox等)浏览器.或者您还可以点击此处下载该论文PDF