[1] W. Chen, R. Zheng, P. D. Baade, S. Zhang, H. Zeng, F. Bray, A. Jemal, X. Q. Yu, J. He, “Cancer statistics in China, 2015," CA-Cancer J. Clin. 66, 115–132 (2016).

[2] F. Bray, J. Ferlay, I. Soerjomataram, R. L. Siegel, L. A. Torre, A. Jemal, “Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries," CACancer J. Clin. 68, 394–424 (2018).

[3] J. Yan, G. Chen, J. Chen, N. Liu, S. Zhuo, H. Yu, M. Ying, “A pilot study of using multiphoton microscopy to diagnose gastric cancer," Surg. Endosc. 25, 1425–1430 (2011).

[4] Z. Wang, W. Zheng, J. Lin, Z. Huang, “Simultaneous quadruple-modal nonlinear optical imaging for gastric diseases diagnosis and characterization," Conf. Multiphoton Microscopy in the Biomedical Sciences XV, SPIE, Vol. 9329, p. 93291P (2015).

[5] W. Denk, J. H. Strickler, W. W. Webb, “Twophoton laser scanning fluorescence microscopy," Science 248, 73–76 (1990).

[6] F. Helmchen, W. Denk, “Deep tissue two-photon microscopy," Nat. Methods 2, 932–940 (2005).

[7] M. J. Pittet, R. Weissleder, “Intravital imaging," Cell 147, 983–991 (2011).

[8] W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, W. W. Webb, “Live tissue intrinsic emission microscopy using multiphotonexcited native fluorescence and second harmonic generation," Proc. Natl Acad. Sci. USA 100, 7075–7080 (2003).

[9] B. G. Wang, K. Konig, K. J. Halbhuber, “Twophoton microscopy of deep intravital tissues and its merits in clinical research," J. Microsc. 238, 1–20 (2010).

[10] L. Marcu, “Fluorescence lifetime techniques in medical applications," Ann. Biomed. Eng. 40, 304–331 (2012).

[11] M. Y. Berezin, S. Achilefu, “Fluorescence lifetime measurements and biological imaging," Chem. Rev. 110, 2641–2684 (2010).

[12] 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, 175–193 (2009).

[13] L. K. Seah, P. Wang, V. M. Murukeshan, Z. X. Chao, “Application of fluorescence lifetime imaging (FLIM) in latent finger mark detection," Forensic Sci. Int. 160, 109–114 (2006).

[14] W. Becker, A. Bergmann, Handbook of Biomedical Nonlinear Optical Microscopy, Oxford University Press, Oxford (2008).

[15] J. R. Lakowicz, Principles of Fluorescence Spectroscopy, 3rd Edition, Springer, New York (2006).

[16] K. Konig, “Clinical multiphoton tomography," J. Biophoton. 1, 13–23 (2008).

[17] 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," Conf. Multiphoton Microscopy in the Biomedical Sciences XIV, SPIE, Vol. 8948, p. 89482E (2014).

[18] W. Pan, J. Qu, T. Chen, L. Sun, and J. Qi, “FLIM and emission spectral analysis of caspase-3 activation inside single living cell during anticancer drug-induced cell death," Eur. Biophys. J. 38, 447–456 (2009).

[19] S. R. Kantelhardt, J. Leppert, J. Krajewski, N. Petkus, E. Reusche, V. M. Tronnier, G. Huttmann, and A. Giese, “Imaging of brain and brain tumor specimens by time-resolved multiphoton excitation microscopy ex vivo," Neuro. Oncol. 9, 103–112 (2007).

[20] M. C. Skala, K.M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, N. Ramanujam, “In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia," Proc. Natl Acad. Sci. USA 104, 19494–19499 (2007).

[21] S. R. Kantelhardt, D. Kalasauskas, K. Konig, E. Kim, M. Weinigel, A. Uchugonova, A. Giese, “In vivo multiphoton tomography and fluorescence lifetime imaging of human brain tumor tissue," J. Neurooncol. 127, 473–482 (2016).

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

[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, 919–930 (2015).

[24] R. Niesner, K.-H. Gericke, “Fluorescence lifetime imaging in biosciences: Technologies and applications," Front. Phys. China 3, 88–104 (2008).

[25] W. Becker, Advanced Time-Correlated Single-Photon Counting Techniques, Springer, Berlin, Heidelberg, New York (2005).

[26] W. H. Koppenol, P. L. Bounds, C. V. Dang, “Otto Warburg's contributions to current concepts of cancer metabolism," Nat. Rev. Cancer 11, 325–337 (2011).

[27] Y. Wu, W. Zheng, J. Y. Qu, “Sensing cell metabolism by time-resolved autofluorescence," Opt. Lett. 31, 3122–3124 (2006).

[28] D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH," Cancer Res. 65, 8766–8773 (2005).

[29] B. Chance, B. Schoener, R. Oshino, F. Itshak, Y. Nakase, “Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals," J. Biol. Chem. 254, 4764–4771 (1979).

[30] B. Chance, P. Cohen, F. Jobsis, B. Schoener, “Intracellular oxidation-reduction states in vivo," Science 137, 499–508 (1962).

[31] T. Galeotti, G. D. V. van Rossum, D. H. Mayer, B. Chance, “On the fluorescence of NAD(P)H in whole-cell preparations of tumours and normal tissues," Eur. J. Biochem. 17, 485–496 (1970).

[32] J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, M. L. Johnson, “Fluorescence lifetime imaging of free and protein-bound NADH," Proc. Natl Acad. Sci. USA 89, 1271–1275 (1992).

[33] M. J. Colditz, K. Leyen, R. L. Jeffree, “Aminolevulinic acid (ALA)-protoporphyrin IX fluorescence guided tumour resection. Part 2: theoretical, biochemical and practical aspects," J. Clin. Neurosci. 19, 1611–1616 (2012).

[34] J. Leppert, J. Krajewski, S. R. Kantelhardt, S. Schlaffer, N. Petkus, E. Reusche, G. Huttmann, A. Giese, “Multiphoton excitation of auto-fluorescence for microscopy of glioma tissue," Neurosurgery 58, 759–767 (2006).

[35] P. P. Provenzano, C. T. Rueden, S. M. Trier, L. Yan, S. M. Ponik, D. R. Inman, P. J. Keely, K. W. Eliceiri, “Nonlinear optical imaging and spectral-lifetime computational analysis of endogenous and exogenous fluorophores in breast cancer," J. Biomed. Opt. 13, 031220 (2008).

[36] J. A. Russell, K. R. Diamond, T. J. Collins, H. F. Tiedje, J. E. Hayward, T. J. Farrell, M. S. Patterson, Q. Fang, “Characterization of fluorescence lifetime of photofrin and delta-aminolevulinic acid induced protoporphyrin IX in living cells using single-and two-photon excitation," IEEE J. Sel. Top. Quantum 14, 158–166 (2008).

[37] S. R. Kantelhardt, H. Diddens, J. Leppert, V. Rohde, G. Huttmann, A. Giese, “Multiphoton excitation fluorescence microscopy of 5-aminolevulinic acid induced fluorescence in experimental gliomas," Lasers Surg. Med. 40, 273–281 (2008).

[38] S. X. Zhang, An Atlas of Histology, Springer-Verlag, New York (1999).

[39] A. Ruck, C. Hauser, S. Mosch, S. Kalinina, “Spectrally resolved fluorescence lifetime imaging to investigate cell metabolism in malignant and nonmalignant oral mucosa cells," J. Biomed. Opt. 19, 96005 (2014).

[40] M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, N. Ramanujam, “In vivo multiphoton fluorescence lifetime imaging of protein-bound and free nicotinamide adenine dinucleotide in normal and precancerous epithelia," J. Biomed. Opt. 12, 024014 (2007).

[41] S. K. Teh, W. Zheng, S. Li, D. Li, Y. Zeng, Y. Yang, J. Y. Qu, “Multimodal nonlinear optical microscopy improves the accuracy of early diagnosis of squamous intraepithelial neoplasia," J. Biomed. Opt. 18, 036001 (2013).

[42] Y. F. Shen, M. R. Tsai, S. C. Chen, Y. S. Leung, C. T. Hsieh, Y. S. Chen, F. L. Huang, R. P. Obena, M. M. Zulueta, H. Y. Huang, W. J. Lee, K. C. Tang, C. T. Kung, M. H. Chen, D. B. Shieh, Y. J. Chen, T. M. Liu, P. T. Chou, C. K. Sun, “Imaging endogenous bilirubins with two-photon fluorescence of bilirubin dimers," Anal. Chem. 87, 7575–7582 (2015).

[43] P. H. Lakner, M. G. Monaghan, Y. Moller, M. A. Olayioye, K. Schenke-Layland, “Applying phasor approach analysis of multiphoton FLIM measurements to probe the metabolic activity of three-dimensional in vitro cell culture models," Sci. Rep. 7, 42730 (2017).

[44] J. Adur, V. B. Pelegati, M. Bianchi, A. A. de Thomaz, M. O. Baratti, H. F. Carvalho, V. H. Casco, C. L. Cesar, “Multimodal nonlinear optical microscopy used to discriminate human colon cancer," Conf. Multiphoton Microscopy in the Biomedical Sciences XIII, SPIE, Vol. 8588, p. 85881J (2013).

[45] H. Bao, A. Boussioutas, J. Reynolds, S. Russell, M. Gu, “Imaging of goblet cells as a marker for intestinal metaplasia of the stomach by one-photon and two-photon fluorescence endomicroscopy," J. Biomed. Opt. 14, 064031 (2009).

[46] J. N. Rogart, J. Nagata, C. S. Loeser, R. D. Roorda, H. Aslanian, M. E. Robert, W. R. Zipfel, M. H. Nathanson, “Multiphoton imaging can be used for microscopic examination of intact human gastrointestinal mucosa ex vivo," Clin. Gastroenterol Hepatol. 6, 95–101 (2008).

[47] R. Cicchi, A. Sturiale, G. Nesi, D. Kapsokalyvas, G. Alemanno, F. Tonelli, F. S. Pavone, “Multiphoton morpho-functional imaging of healthy colon mucosa, adenomatous polyp and adenocarcinoma," Biomed. Opt. Expr. 4, 1204–1213 (2013).

[48] L. E. Grosberg, A. J. Radosevich, S. Asfaha, T. C. Wang, E. M. Hillman, “Spectral characterization and unmixing of intrinsic contrast in intact normal and diseased gastric tissues using hyperspectral twophoton microscopy," PLoS One 6, e19925 (2011).

[49] X. Li, H. Li, X. Z. He, T. G. Chen, X. Y. Xia, C. X. Yang, W. Zheng, “Spectrum- and time-resolved endogenous multiphoton signals reveal quantitative differentiation of premalignant and malignant gastric mucosa," Biomed. Opt. Expr. 9, 453–471 (2018).

[50] W. Zheng, Y. C. Wu, D. Li, J. N. Y. Qu, “Autofluorescence of epithelial tissue: Single-photon versus two-photon excitation," J. Biomed. Opt. 13, 8 (2008).

[51] R. Patalay, C. Talbot, Y. Alexandrov, I. Munro, M. A. A. Neil, K. Koenig, P. M. W. French, A. Chu, G. W. Stamp, C. Dunsby, “Quantification of cellular autofluorescence of human skin using multiphoton tomography and fluorescence lifetime imaging in two spectral detection channels," Biomed. Opt. Expr. 2, 3295–3308 (2011).

[52] M. S. Roberts, Y. Dancik, T. W. Prow, C. A. Thorling, L. L. Lin, J. E. Grice, T. A. Robertson, K. Konig, 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, 469–488 (2011).

[53] R. Datta, C. Heylman, S. C. George, E. Gratton, “Label-free imaging of metabolism and oxidative stress in human induced pluripotent stem cellderived cardiomyocytes," Biomed. Opt. Expr. 7, 1690–1701 (2016).