Abstract

In situ fluorescence lifetime imaging microscopy (FLIM) in an endoscopic configuration of the endogenous biomarker nicotinamide adenine dinucleotide (NADH) has a great potential for malignant tissue diagnosis. Moreover, two-photon nonlinear excitation provides intrinsic optical sectioning along with enhanced imaging depth. We demonstrate, for the first time to our knowledge, nonlinear endogenous FLIM in a fibered microscope with proximal detection, applied to NADH in cultured cells, as a first step to a nonlinear endomicroscope, using a double-clad microstructured fiber with convenient fiber length (> 3 m) and excitation pulse duration (≈50 fs). Fluorescence photons are collected by the fiber inner cladding and we show that its contribution to the impulse response function (IRF), which originates from its intermodal and chromatic dispersions, is small (< 600 ps) and stable for lengths up to 8 m and allows for short lifetime measurements. We use the phasor representation as a quick visualization tool adapted to the endoscopy speed requirements.

© 2017 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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2017 (1)

2016 (2)

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2016).
[Crossref] [PubMed]

R. Datta, C. Heylman, S. C. George, and E. Gratton, “Label-free imaging of metabolism and oxidative stress in human induced pluripotent stem cell-derived cardiomyocytes,” Biomed. Opt. Express 7(5), 1690–1701 (2016).
[Crossref] [PubMed]

2015 (3)

R. Datta, A. Alfonso-García, R. Cinco, and E. Gratton, “Fluorescence lifetime imaging of endogenous biomarker of oxidative stress,” Sci. Rep. 5(1), 9848 (2015).
[Crossref] [PubMed]

H. Sparks, S. Warren, J. Guedes, N. Yoshida, T. C. Charn, N. Guerra, T. Tatla, C. Dunsby, and P. French, “A flexible wide-field FLIM endoscope utilising blue excitation light for label-free contrast of tissue,” J. Biophotonics 8(1-2), 168–178 (2015).
[Crossref] [PubMed]

W. Becker, “The bh TCSPC Handbook,” Scanning 2015, 1–768 (2015).

2014 (2)

J. Carpenter, B. J. Eggleton, and J. Schröder, “110x110 optical mode transfer matrix inversion,” Opt. Express 22(1), 96–101 (2014).
[Crossref] [PubMed]

K. O. Alfarouk, D. Verduzco, C. Rauch, A. K. Muddathir, A. H. Bashir, G. O. Elhassan, M. E. Ibrahim, J. D. Orozco, R. A. Cardone, S. J. Reshkin, and S. Harguindey, “Glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based etiopathogenic perspective and therapeutic approach to an old cancer question,” Oncoscience 2(4), 317 (2014).
[Crossref] [PubMed]

2013 (5)

Y. Sun, J. E. Phipps, J. Meier, N. Hatami, B. Poirier, D. S. Elson, D. G. Farwell, and L. Marcu, “Endoscopic fluorescence lifetime imaging for in vivo intraoperative diagnosis of oral carcinoma,” Microsc. Microanal. 19(4), 791–798 (2013).
[Crossref] [PubMed]

S. Cheng, J. J. Rico-Jimenez, J. Jabbour, B. Malik, K. C. Maitland, J. Wright, Y.-S. L. Cheng, and J. A. Jo, “Flexible endoscope for continuous in vivo multispectral fluorescence lifetime imaging,” Opt. Lett. 38(9), 1515–1517 (2013).
[Crossref] [PubMed]

A. Leray, S. Padilla-Parra, J. Roul, L. Héliot, and M. Tramier, “827Spatio-Temporal Quantification of FRET in Living Cells by Fast Time-Domain FLIM: A Comparative Study of Non-Fitting Methods,” PLoS One 8, e69335 (2013).
[Crossref]

K. Jung, P. Kim, F. Leuschner, R. Gorbatov, J. K. Kim, T. Ueno, M. Nahrendorf, and S. H. Yun, “Endoscopic time-lapse imaging of immune cells in infarcted mouse hearts,” Circ. Res. 112(6), 891–899 (2013).
[Crossref] [PubMed]

J. L. Rinnenthal, C. Börnchen, H. Radbruch, V. Andresen, A. Mossakowski, V. Siffrin, T. Seelemann, H. Spiecker, I. Moll, J. Herz, A. E. Hauser, F. Zipp, M. J. Behne, and R. Niesner, “Parallelized TCSPC for Dynamic Intravital Fluorescence Lifetime Imaging: Quantifying Neuronal Dysfunction in Neuroinflammation,” PLoS One 8(4), e60100 (2013).
[Crossref] [PubMed]

2012 (6)

D. A. Peyrot, C. Lefort, M. Steffenhagen, T. Mansuryan, G. Ducourthial, D. Abi-Haidar, N. Sandeau, C. Vever-Bizet, S. G. Kruglik, L. Thiberville, F. Louradour, and G. Bourg-Heckly, “Development of a nonlinear fiber-optic spectrometer for human lung tissue exploration,” Biomed. Opt. Express 3(5), 840–853 (2012).
[Crossref] [PubMed]

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref] [PubMed]

C. S. Garbe, A. Buttgereit, S. Schürmann, and O. Friedrich, “Automated multiscale morphometry of muscle disease from second harmonic generation microscopy using tensor-based image processing,” IEEE Trans. Biomed. Eng. 59(1), 39–44 (2012).
[Crossref] [PubMed]

F. Knorr, D. R. Yankelevich, J. Liu, S. Wachsmann-Hogiu, and L. Marcu, “Two-photon excited fluorescence lifetime measurements through a double-clad photonic crystal fiber for tissue micro-endoscopy,” J. Biophotonics 5(1), 14–19 (2012).
[Crossref] [PubMed]

M. Kalashyan, C. Lefort, L. Martínez-León, T. Mansuryan, L. Mouradian, and F. Louradour, “Ultrashort pulse fiber delivery with optimized dispersion control by reflection grisms at 800 nm,” Opt. Express 20(23), 25624–25635 (2012).
[Crossref] [PubMed]

C. Stringari, J. L. Nourse, L. A. Flanagan, and E. Gratton, “Phasor Fluorescence Lifetime Microscopy of Free and Protein-Bound NADH Reveals Neural Stem Cell Differentiation Potential,” PLoS One 7(11), e48014 (2012).
[Crossref] [PubMed]

2011 (4)

K. König, A. Uchugonova, and E. Gorjup, “Multiphoton fluorescence lifetime imaging of 3D-stem cell spheroids during differentiation,” Microsc. Res. Tech. 74(1), 9–17 (2011).
[Crossref] [PubMed]

J. T. C. Liu, N. O. Loewke, M. J. Mandella, R. M. Levenson, J. M. Crawford, and C. H. Contag, “Point-of-care pathology with miniature microscopes,” Anal. Cell Pathol. (Amst.) 34(3), 81–98 (2011).
[Crossref] [PubMed]

C. Stringari, A. Cinquin, O. Cinquin, M. A. Digman, P. J. Donovan, and E. Gratton, “Phasor approach to fluorescence lifetime microscopy distinguishes different metabolic states of germ cells in a live tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(33), 13582–13587 (2011).
[Crossref] [PubMed]

C. H. Hage, B. Kibler, E. R. Andresen, S. Michel, H. Rigneault, A. Courjaud, E. Mottay, J. M. Dudley, G. Millot, and C. Finot, “Optimization and characterization of a femtosecond tunable light source based on the soliton self-frequency shift in photonic crystal fiber,” Proc. SPIE 8071, 80710I (2011).
[Crossref]

2010 (2)

G. O. Fruhwirth, S. Ameer-Beg, R. Cook, T. Watson, T. Ng, and F. Festy, “Fluorescence lifetime endoscopy using TCSPC for the measurement of FRET in live cells,” Opt. Express 18(11), 11148–11158 (2010).
[Crossref] [PubMed]

G. T. Kennedy, H. B. Manning, D. S. Elson, M. A. A. Neil, G. W. Stamp, B. Viellerobe, F. Lacombe, C. Dunsby, and P. M. W. French, “A fluorescence lifetime imaging scanning confocal endomicroscope,” J. Biophotonics 3(1-2), 103–107 (2010).
[Crossref] [PubMed]

2009 (1)

Q. Yu and A. A. Heikal, “Two-photon autofluorescence dynamics imaging reveals sensitivity of intracellular NADH concentration and conformation to cell physiology at the single-cell level,” J. Photochem. Photobiol. B 95(1), 46–57 (2009).
[Crossref] [PubMed]

2008 (1)

M. A. Digman, V. R. Caiolfa, M. Zamai, and E. Gratton, “The phasor approach to fluorescence lifetime imaging analysis,” Biophys. J. 94(2), L14–L16 (2008).
[Crossref] [PubMed]

2007 (3)

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and 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(2), 024014 (2007).
[Crossref] [PubMed]

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of {NADH} and {FAD} redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A. 104(49), 19494–19499 (2007).
[Crossref] [PubMed]

P. G. Bush, D. L. Wokosin, and A. C. Hall, “Two-versus one photon excitation laser scanning microscopy: critical importance of excitation wavelength,” Front. Biosci. 12(1), 2646–2657 (2007).
[Crossref] [PubMed]

2006 (2)

J. M. Dudley and S. Coen, “Supercontinuum generation in photonic crystal fiber,” Rev. Mod. Phys. 78(4), 1135–1184 (2006).
[Crossref]

S. Jerebtsov, A. Kolomenskii, M. Poudel, F. Zhu, and H. Schuessler, “Lifetime and anisotropy decay of excited Coumarin 30 measured by a femtosecond pump–probe technique,” J. Mod. Opt. 53(16-17), 2609–2617 (2006).
[Crossref]

2005 (1)

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[Crossref] [PubMed]

2004 (1)

2003 (1)

J. Condeelis and J. E. Segall, “Intravital imaging of cell movement in tumours,” Nat. Rev. Cancer 3(12), 921–930 (2003).
[Crossref] [PubMed]

2002 (2)

S. Huang, A. A. Heikal, and W. W. Webb, “Two-photon fluorescence spectroscopy and microscopy of NAD(P)H and flavoprotein,” Biophys. J. 82(5), 2811–2825 (2002).
[Crossref] [PubMed]

I. Georgakoudi, B. C. Jacobson, M. G. Müller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62(3), 682–687 (2002).
[PubMed]

1999 (1)

J. M. Squirrell, D. L. Wokosin, J. G. White, and B. D. Bavister, “Long-term two-photon fluorescence imaging of mammalian embryos without compromising viability,” Nat. Biotechnol. 17(8), 763–767 (1999).
[Crossref] [PubMed]

1998 (2)

J. N. Kutz, J. A. Cox, and D. Smith, “Mode mixing and power diffusion in multimode optical fibers,” J. Lightwave Technol. 16(7), 1195–1202 (1998).
[Crossref]

A. V. Kuznetsov, O. Mayboroda, D. Kunz, K. Winkler, W. Schubert, and W. S. Kunz, “Functional imaging of mitochondria in saponin-permeabilized mice muscle fibers,” J. Cell Biol. 140(5), 1091–1099 (1998).
[Crossref] [PubMed]

1996 (1)

C. Xu, W. Zipfel, J. B. Shear, R. M. Williams, and W. W. Webb, “Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy,” Proc. Natl. Acad. Sci. U.S.A. 93(20), 10763–10768 (1996).
[Crossref] [PubMed]

1992 (1)

J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, and M. L. Johnson, “Fluorescence lifetime imaging of free and protein-bound NADH,” Proc. Natl. Acad. Sci. U.S.A. 89(4), 1271–1275 (1992).
[Crossref] [PubMed]

1965 (1)

Abi-Haidar, D.

Alfarouk, K. O.

K. O. Alfarouk, D. Verduzco, C. Rauch, A. K. Muddathir, A. H. Bashir, G. O. Elhassan, M. E. Ibrahim, J. D. Orozco, R. A. Cardone, S. J. Reshkin, and S. Harguindey, “Glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based etiopathogenic perspective and therapeutic approach to an old cancer question,” Oncoscience 2(4), 317 (2014).
[Crossref] [PubMed]

Alfonso-García, A.

R. Datta, A. Alfonso-García, R. Cinco, and E. Gratton, “Fluorescence lifetime imaging of endogenous biomarker of oxidative stress,” Sci. Rep. 5(1), 9848 (2015).
[Crossref] [PubMed]

Ambichl, P.

Ameer-Beg, S.

Andresen, E. R.

C. H. Hage, B. Kibler, E. R. Andresen, S. Michel, H. Rigneault, A. Courjaud, E. Mottay, J. M. Dudley, G. Millot, and C. Finot, “Optimization and characterization of a femtosecond tunable light source based on the soliton self-frequency shift in photonic crystal fiber,” Proc. SPIE 8071, 80710I (2011).
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Andresen, V.

J. L. Rinnenthal, C. Börnchen, H. Radbruch, V. Andresen, A. Mossakowski, V. Siffrin, T. Seelemann, H. Spiecker, I. Moll, J. Herz, A. E. Hauser, F. Zipp, M. J. Behne, and R. Niesner, “Parallelized TCSPC for Dynamic Intravital Fluorescence Lifetime Imaging: Quantifying Neuronal Dysfunction in Neuroinflammation,” PLoS One 8(4), e60100 (2013).
[Crossref] [PubMed]

Badizadegan, K.

I. Georgakoudi, B. C. Jacobson, M. G. Müller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62(3), 682–687 (2002).
[PubMed]

Bashir, A. H.

K. O. Alfarouk, D. Verduzco, C. Rauch, A. K. Muddathir, A. H. Bashir, G. O. Elhassan, M. E. Ibrahim, J. D. Orozco, R. A. Cardone, S. J. Reshkin, and S. Harguindey, “Glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based etiopathogenic perspective and therapeutic approach to an old cancer question,” Oncoscience 2(4), 317 (2014).
[Crossref] [PubMed]

Batrin, R.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2016).
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Bavister, B. D.

J. M. Squirrell, D. L. Wokosin, J. G. White, and B. D. Bavister, “Long-term two-photon fluorescence imaging of mammalian embryos without compromising viability,” Nat. Biotechnol. 17(8), 763–767 (1999).
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Becker, W.

W. Becker, “The bh TCSPC Handbook,” Scanning 2015, 1–768 (2015).

Behne, M. J.

J. L. Rinnenthal, C. Börnchen, H. Radbruch, V. Andresen, A. Mossakowski, V. Siffrin, T. Seelemann, H. Spiecker, I. Moll, J. Herz, A. E. Hauser, F. Zipp, M. J. Behne, and R. Niesner, “Parallelized TCSPC for Dynamic Intravital Fluorescence Lifetime Imaging: Quantifying Neuronal Dysfunction in Neuroinflammation,” PLoS One 8(4), e60100 (2013).
[Crossref] [PubMed]

Bird, D. K.

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and 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(2), 024014 (2007).
[Crossref] [PubMed]

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[Crossref] [PubMed]

Boone, C. W.

I. Georgakoudi, B. C. Jacobson, M. G. Müller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62(3), 682–687 (2002).
[PubMed]

Börnchen, C.

J. L. Rinnenthal, C. Börnchen, H. Radbruch, V. Andresen, A. Mossakowski, V. Siffrin, T. Seelemann, H. Spiecker, I. Moll, J. Herz, A. E. Hauser, F. Zipp, M. J. Behne, and R. Niesner, “Parallelized TCSPC for Dynamic Intravital Fluorescence Lifetime Imaging: Quantifying Neuronal Dysfunction in Neuroinflammation,” PLoS One 8(4), e60100 (2013).
[Crossref] [PubMed]

Bourg-Heckly, G.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2016).
[Crossref] [PubMed]

D. A. Peyrot, C. Lefort, M. Steffenhagen, T. Mansuryan, G. Ducourthial, D. Abi-Haidar, N. Sandeau, C. Vever-Bizet, S. G. Kruglik, L. Thiberville, F. Louradour, and G. Bourg-Heckly, “Development of a nonlinear fiber-optic spectrometer for human lung tissue exploration,” Biomed. Opt. Express 3(5), 840–853 (2012).
[Crossref] [PubMed]

Braud, F.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2016).
[Crossref] [PubMed]

Brevier, J.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2016).
[Crossref] [PubMed]

Bromberg, Y.

Brown, C. M.

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref] [PubMed]

Bush, P. G.

P. G. Bush, D. L. Wokosin, and A. C. Hall, “Two-versus one photon excitation laser scanning microscopy: critical importance of excitation wavelength,” Front. Biosci. 12(1), 2646–2657 (2007).
[Crossref] [PubMed]

Buttgereit, A.

C. S. Garbe, A. Buttgereit, S. Schürmann, and O. Friedrich, “Automated multiscale morphometry of muscle disease from second harmonic generation microscopy using tensor-based image processing,” IEEE Trans. Biomed. Eng. 59(1), 39–44 (2012).
[Crossref] [PubMed]

Caiolfa, V. R.

M. A. Digman, V. R. Caiolfa, M. Zamai, and E. Gratton, “The phasor approach to fluorescence lifetime imaging analysis,” Biophys. J. 94(2), L14–L16 (2008).
[Crossref] [PubMed]

Cao, H.

Cardone, R. A.

K. O. Alfarouk, D. Verduzco, C. Rauch, A. K. Muddathir, A. H. Bashir, G. O. Elhassan, M. E. Ibrahim, J. D. Orozco, R. A. Cardone, S. J. Reshkin, and S. Harguindey, “Glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based etiopathogenic perspective and therapeutic approach to an old cancer question,” Oncoscience 2(4), 317 (2014).
[Crossref] [PubMed]

Carpenter, J.

Carr-Locke, D. L.

I. Georgakoudi, B. C. Jacobson, M. G. Müller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62(3), 682–687 (2002).
[PubMed]

Charn, T. C.

H. Sparks, S. Warren, J. Guedes, N. Yoshida, T. C. Charn, N. Guerra, T. Tatla, C. Dunsby, and P. French, “A flexible wide-field FLIM endoscope utilising blue excitation light for label-free contrast of tissue,” J. Biophotonics 8(1-2), 168–178 (2015).
[Crossref] [PubMed]

Cheng, S.

Cheng, Y.-S. L.

Cinco, R.

R. Datta, A. Alfonso-García, R. Cinco, and E. Gratton, “Fluorescence lifetime imaging of endogenous biomarker of oxidative stress,” Sci. Rep. 5(1), 9848 (2015).
[Crossref] [PubMed]

Cinquin, A.

C. Stringari, A. Cinquin, O. Cinquin, M. A. Digman, P. J. Donovan, and E. Gratton, “Phasor approach to fluorescence lifetime microscopy distinguishes different metabolic states of germ cells in a live tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(33), 13582–13587 (2011).
[Crossref] [PubMed]

Cinquin, O.

C. Stringari, A. Cinquin, O. Cinquin, M. A. Digman, P. J. Donovan, and E. Gratton, “Phasor approach to fluorescence lifetime microscopy distinguishes different metabolic states of germ cells in a live tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(33), 13582–13587 (2011).
[Crossref] [PubMed]

Coen, S.

J. M. Dudley and S. Coen, “Supercontinuum generation in photonic crystal fiber,” Rev. Mod. Phys. 78(4), 1135–1184 (2006).
[Crossref]

Condeelis, J.

J. Condeelis and J. E. Segall, “Intravital imaging of cell movement in tumours,” Nat. Rev. Cancer 3(12), 921–930 (2003).
[Crossref] [PubMed]

Contag, C. H.

J. T. C. Liu, N. O. Loewke, M. J. Mandella, R. M. Levenson, J. M. Crawford, and C. H. Contag, “Point-of-care pathology with miniature microscopes,” Anal. Cell Pathol. (Amst.) 34(3), 81–98 (2011).
[Crossref] [PubMed]

Cook, R.

Courjaud, A.

C. H. Hage, B. Kibler, E. R. Andresen, S. Michel, H. Rigneault, A. Courjaud, E. Mottay, J. M. Dudley, G. Millot, and C. Finot, “Optimization and characterization of a femtosecond tunable light source based on the soliton self-frequency shift in photonic crystal fiber,” Proc. SPIE 8071, 80710I (2011).
[Crossref]

Cox, J. A.

Crawford, J. M.

J. T. C. Liu, N. O. Loewke, M. J. Mandella, R. M. Levenson, J. M. Crawford, and C. H. Contag, “Point-of-care pathology with miniature microscopes,” Anal. Cell Pathol. (Amst.) 34(3), 81–98 (2011).
[Crossref] [PubMed]

Crum, C. P.

I. Georgakoudi, B. C. Jacobson, M. G. Müller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62(3), 682–687 (2002).
[PubMed]

Dasari, R. R.

I. Georgakoudi, B. C. Jacobson, M. G. Müller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62(3), 682–687 (2002).
[PubMed]

Datta, R.

Digman, M. A.

C. Stringari, A. Cinquin, O. Cinquin, M. A. Digman, P. J. Donovan, and E. Gratton, “Phasor approach to fluorescence lifetime microscopy distinguishes different metabolic states of germ cells in a live tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(33), 13582–13587 (2011).
[Crossref] [PubMed]

M. A. Digman, V. R. Caiolfa, M. Zamai, and E. Gratton, “The phasor approach to fluorescence lifetime imaging analysis,” Biophys. J. 94(2), L14–L16 (2008).
[Crossref] [PubMed]

Donovan, P. J.

C. Stringari, A. Cinquin, O. Cinquin, M. A. Digman, P. J. Donovan, and E. Gratton, “Phasor approach to fluorescence lifetime microscopy distinguishes different metabolic states of germ cells in a live tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(33), 13582–13587 (2011).
[Crossref] [PubMed]

Druilhe, A.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2016).
[Crossref] [PubMed]

Ducourthial, G.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2016).
[Crossref] [PubMed]

D. A. Peyrot, C. Lefort, M. Steffenhagen, T. Mansuryan, G. Ducourthial, D. Abi-Haidar, N. Sandeau, C. Vever-Bizet, S. G. Kruglik, L. Thiberville, F. Louradour, and G. Bourg-Heckly, “Development of a nonlinear fiber-optic spectrometer for human lung tissue exploration,” Biomed. Opt. Express 3(5), 840–853 (2012).
[Crossref] [PubMed]

Dudley, J. M.

C. H. Hage, B. Kibler, E. R. Andresen, S. Michel, H. Rigneault, A. Courjaud, E. Mottay, J. M. Dudley, G. Millot, and C. Finot, “Optimization and characterization of a femtosecond tunable light source based on the soliton self-frequency shift in photonic crystal fiber,” Proc. SPIE 8071, 80710I (2011).
[Crossref]

J. M. Dudley and S. Coen, “Supercontinuum generation in photonic crystal fiber,” Rev. Mod. Phys. 78(4), 1135–1184 (2006).
[Crossref]

Dunsby, C.

H. Sparks, S. Warren, J. Guedes, N. Yoshida, T. C. Charn, N. Guerra, T. Tatla, C. Dunsby, and P. French, “A flexible wide-field FLIM endoscope utilising blue excitation light for label-free contrast of tissue,” J. Biophotonics 8(1-2), 168–178 (2015).
[Crossref] [PubMed]

G. T. Kennedy, H. B. Manning, D. S. Elson, M. A. A. Neil, G. W. Stamp, B. Viellerobe, F. Lacombe, C. Dunsby, and P. M. W. French, “A fluorescence lifetime imaging scanning confocal endomicroscope,” J. Biophotonics 3(1-2), 103–107 (2010).
[Crossref] [PubMed]

Eggleton, B. J.

Eickhoff, J.

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and 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(2), 024014 (2007).
[Crossref] [PubMed]

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of {NADH} and {FAD} redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A. 104(49), 19494–19499 (2007).
[Crossref] [PubMed]

Elhassan, G. O.

K. O. Alfarouk, D. Verduzco, C. Rauch, A. K. Muddathir, A. H. Bashir, G. O. Elhassan, M. E. Ibrahim, J. D. Orozco, R. A. Cardone, S. J. Reshkin, and S. Harguindey, “Glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based etiopathogenic perspective and therapeutic approach to an old cancer question,” Oncoscience 2(4), 317 (2014).
[Crossref] [PubMed]

Eliceiri, K. W.

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and 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(2), 024014 (2007).
[Crossref] [PubMed]

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of {NADH} and {FAD} redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A. 104(49), 19494–19499 (2007).
[Crossref] [PubMed]

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[Crossref] [PubMed]

Elson, D. S.

Y. Sun, J. E. Phipps, J. Meier, N. Hatami, B. Poirier, D. S. Elson, D. G. Farwell, and L. Marcu, “Endoscopic fluorescence lifetime imaging for in vivo intraoperative diagnosis of oral carcinoma,” Microsc. Microanal. 19(4), 791–798 (2013).
[Crossref] [PubMed]

G. T. Kennedy, H. B. Manning, D. S. Elson, M. A. A. Neil, G. W. Stamp, B. Viellerobe, F. Lacombe, C. Dunsby, and P. M. W. French, “A fluorescence lifetime imaging scanning confocal endomicroscope,” J. Biophotonics 3(1-2), 103–107 (2010).
[Crossref] [PubMed]

Fabert, M.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2016).
[Crossref] [PubMed]

Farwell, D. G.

Y. Sun, J. E. Phipps, J. Meier, N. Hatami, B. Poirier, D. S. Elson, D. G. Farwell, and L. Marcu, “Endoscopic fluorescence lifetime imaging for in vivo intraoperative diagnosis of oral carcinoma,” Microsc. Microanal. 19(4), 791–798 (2013).
[Crossref] [PubMed]

Feld, M. S.

I. Georgakoudi, B. C. Jacobson, M. G. Müller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62(3), 682–687 (2002).
[PubMed]

Festy, F.

Finot, C.

C. H. Hage, B. Kibler, E. R. Andresen, S. Michel, H. Rigneault, A. Courjaud, E. Mottay, J. M. Dudley, G. Millot, and C. Finot, “Optimization and characterization of a femtosecond tunable light source based on the soliton self-frequency shift in photonic crystal fiber,” Proc. SPIE 8071, 80710I (2011).
[Crossref]

Flanagan, L. A.

C. Stringari, J. L. Nourse, L. A. Flanagan, and E. Gratton, “Phasor Fluorescence Lifetime Microscopy of Free and Protein-Bound NADH Reveals Neural Stem Cell Differentiation Potential,” PLoS One 7(11), e48014 (2012).
[Crossref] [PubMed]

French, P.

H. Sparks, S. Warren, J. Guedes, N. Yoshida, T. C. Charn, N. Guerra, T. Tatla, C. Dunsby, and P. French, “A flexible wide-field FLIM endoscope utilising blue excitation light for label-free contrast of tissue,” J. Biophotonics 8(1-2), 168–178 (2015).
[Crossref] [PubMed]

French, P. M. W.

G. T. Kennedy, H. B. Manning, D. S. Elson, M. A. A. Neil, G. W. Stamp, B. Viellerobe, F. Lacombe, C. Dunsby, and P. M. W. French, “A fluorescence lifetime imaging scanning confocal endomicroscope,” J. Biophotonics 3(1-2), 103–107 (2010).
[Crossref] [PubMed]

Friedrich, O.

C. S. Garbe, A. Buttgereit, S. Schürmann, and O. Friedrich, “Automated multiscale morphometry of muscle disease from second harmonic generation microscopy using tensor-based image processing,” IEEE Trans. Biomed. Eng. 59(1), 39–44 (2012).
[Crossref] [PubMed]

Fruhwirth, G. O.

Garbe, C. S.

C. S. Garbe, A. Buttgereit, S. Schürmann, and O. Friedrich, “Automated multiscale morphometry of muscle disease from second harmonic generation microscopy using tensor-based image processing,” IEEE Trans. Biomed. Eng. 59(1), 39–44 (2012).
[Crossref] [PubMed]

Gendron-Fitzpatrick, A.

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of {NADH} and {FAD} redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A. 104(49), 19494–19499 (2007).
[Crossref] [PubMed]

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and 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(2), 024014 (2007).
[Crossref] [PubMed]

Georgakoudi, I.

I. Georgakoudi, B. C. Jacobson, M. G. Müller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62(3), 682–687 (2002).
[PubMed]

George, S. C.

Göbel, W.

Gorbatov, R.

K. Jung, P. Kim, F. Leuschner, R. Gorbatov, J. K. Kim, T. Ueno, M. Nahrendorf, and S. H. Yun, “Endoscopic time-lapse imaging of immune cells in infarcted mouse hearts,” Circ. Res. 112(6), 891–899 (2013).
[Crossref] [PubMed]

Gorjup, E.

K. König, A. Uchugonova, and E. Gorjup, “Multiphoton fluorescence lifetime imaging of 3D-stem cell spheroids during differentiation,” Microsc. Res. Tech. 74(1), 9–17 (2011).
[Crossref] [PubMed]

Gratton, E.

R. Datta, C. Heylman, S. C. George, and E. Gratton, “Label-free imaging of metabolism and oxidative stress in human induced pluripotent stem cell-derived cardiomyocytes,” Biomed. Opt. Express 7(5), 1690–1701 (2016).
[Crossref] [PubMed]

R. Datta, A. Alfonso-García, R. Cinco, and E. Gratton, “Fluorescence lifetime imaging of endogenous biomarker of oxidative stress,” Sci. Rep. 5(1), 9848 (2015).
[Crossref] [PubMed]

C. Stringari, J. L. Nourse, L. A. Flanagan, and E. Gratton, “Phasor Fluorescence Lifetime Microscopy of Free and Protein-Bound NADH Reveals Neural Stem Cell Differentiation Potential,” PLoS One 7(11), e48014 (2012).
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C. Stringari, A. Cinquin, O. Cinquin, M. A. Digman, P. J. Donovan, and E. Gratton, “Phasor approach to fluorescence lifetime microscopy distinguishes different metabolic states of germ cells in a live tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(33), 13582–13587 (2011).
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M. A. Digman, V. R. Caiolfa, M. Zamai, and E. Gratton, “The phasor approach to fluorescence lifetime imaging analysis,” Biophys. J. 94(2), L14–L16 (2008).
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Guedes, J.

H. Sparks, S. Warren, J. Guedes, N. Yoshida, T. C. Charn, N. Guerra, T. Tatla, C. Dunsby, and P. French, “A flexible wide-field FLIM endoscope utilising blue excitation light for label-free contrast of tissue,” J. Biophotonics 8(1-2), 168–178 (2015).
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Habert, R.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2016).
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Hage, C. H.

C. H. Hage, B. Kibler, E. R. Andresen, S. Michel, H. Rigneault, A. Courjaud, E. Mottay, J. M. Dudley, G. Millot, and C. Finot, “Optimization and characterization of a femtosecond tunable light source based on the soliton self-frequency shift in photonic crystal fiber,” Proc. SPIE 8071, 80710I (2011).
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P. G. Bush, D. L. Wokosin, and A. C. Hall, “Two-versus one photon excitation laser scanning microscopy: critical importance of excitation wavelength,” Front. Biosci. 12(1), 2646–2657 (2007).
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K. O. Alfarouk, D. Verduzco, C. Rauch, A. K. Muddathir, A. H. Bashir, G. O. Elhassan, M. E. Ibrahim, J. D. Orozco, R. A. Cardone, S. J. Reshkin, and S. Harguindey, “Glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based etiopathogenic perspective and therapeutic approach to an old cancer question,” Oncoscience 2(4), 317 (2014).
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Hatami, N.

Y. Sun, J. E. Phipps, J. Meier, N. Hatami, B. Poirier, D. S. Elson, D. G. Farwell, and L. Marcu, “Endoscopic fluorescence lifetime imaging for in vivo intraoperative diagnosis of oral carcinoma,” Microsc. Microanal. 19(4), 791–798 (2013).
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Hauser, A. E.

J. L. Rinnenthal, C. Börnchen, H. Radbruch, V. Andresen, A. Mossakowski, V. Siffrin, T. Seelemann, H. Spiecker, I. Moll, J. Herz, A. E. Hauser, F. Zipp, M. J. Behne, and R. Niesner, “Parallelized TCSPC for Dynamic Intravital Fluorescence Lifetime Imaging: Quantifying Neuronal Dysfunction in Neuroinflammation,” PLoS One 8(4), e60100 (2013).
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Heikal, A. A.

Q. Yu and A. A. Heikal, “Two-photon autofluorescence dynamics imaging reveals sensitivity of intracellular NADH concentration and conformation to cell physiology at the single-cell level,” J. Photochem. Photobiol. B 95(1), 46–57 (2009).
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S. Huang, A. A. Heikal, and W. W. Webb, “Two-photon fluorescence spectroscopy and microscopy of NAD(P)H and flavoprotein,” Biophys. J. 82(5), 2811–2825 (2002).
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Héliot, L.

A. Leray, S. Padilla-Parra, J. Roul, L. Héliot, and M. Tramier, “827Spatio-Temporal Quantification of FRET in Living Cells by Fast Time-Domain FLIM: A Comparative Study of Non-Fitting Methods,” PLoS One 8, e69335 (2013).
[Crossref]

Helmchen, F.

Herz, J.

J. L. Rinnenthal, C. Börnchen, H. Radbruch, V. Andresen, A. Mossakowski, V. Siffrin, T. Seelemann, H. Spiecker, I. Moll, J. Herz, A. E. Hauser, F. Zipp, M. J. Behne, and R. Niesner, “Parallelized TCSPC for Dynamic Intravital Fluorescence Lifetime Imaging: Quantifying Neuronal Dysfunction in Neuroinflammation,” PLoS One 8(4), e60100 (2013).
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Heylman, C.

Huang, S.

S. Huang, A. A. Heikal, and W. W. Webb, “Two-photon fluorescence spectroscopy and microscopy of NAD(P)H and flavoprotein,” Biophys. J. 82(5), 2811–2825 (2002).
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K. O. Alfarouk, D. Verduzco, C. Rauch, A. K. Muddathir, A. H. Bashir, G. O. Elhassan, M. E. Ibrahim, J. D. Orozco, R. A. Cardone, S. J. Reshkin, and S. Harguindey, “Glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based etiopathogenic perspective and therapeutic approach to an old cancer question,” Oncoscience 2(4), 317 (2014).
[Crossref] [PubMed]

Jabbour, J.

Jacobson, B. C.

I. Georgakoudi, B. C. Jacobson, M. G. Müller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62(3), 682–687 (2002).
[PubMed]

Jerebtsov, S.

S. Jerebtsov, A. Kolomenskii, M. Poudel, F. Zhu, and H. Schuessler, “Lifetime and anisotropy decay of excited Coumarin 30 measured by a femtosecond pump–probe technique,” J. Mod. Opt. 53(16-17), 2609–2617 (2006).
[Crossref]

Jo, J. A.

Johnson, M. L.

J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, and M. L. Johnson, “Fluorescence lifetime imaging of free and protein-bound NADH,” Proc. Natl. Acad. Sci. U.S.A. 89(4), 1271–1275 (1992).
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Jung, K.

K. Jung, P. Kim, F. Leuschner, R. Gorbatov, J. K. Kim, T. Ueno, M. Nahrendorf, and S. H. Yun, “Endoscopic time-lapse imaging of immune cells in infarcted mouse hearts,” Circ. Res. 112(6), 891–899 (2013).
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Kalashyan, M.

Keely, P. J.

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and 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(2), 024014 (2007).
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D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
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Kennedy, G. T.

G. T. Kennedy, H. B. Manning, D. S. Elson, M. A. A. Neil, G. W. Stamp, B. Viellerobe, F. Lacombe, C. Dunsby, and P. M. W. French, “A fluorescence lifetime imaging scanning confocal endomicroscope,” J. Biophotonics 3(1-2), 103–107 (2010).
[Crossref] [PubMed]

Kerr, J. N. D.

Kibler, B.

C. H. Hage, B. Kibler, E. R. Andresen, S. Michel, H. Rigneault, A. Courjaud, E. Mottay, J. M. Dudley, G. Millot, and C. Finot, “Optimization and characterization of a femtosecond tunable light source based on the soliton self-frequency shift in photonic crystal fiber,” Proc. SPIE 8071, 80710I (2011).
[Crossref]

Kim, J. K.

K. Jung, P. Kim, F. Leuschner, R. Gorbatov, J. K. Kim, T. Ueno, M. Nahrendorf, and S. H. Yun, “Endoscopic time-lapse imaging of immune cells in infarcted mouse hearts,” Circ. Res. 112(6), 891–899 (2013).
[Crossref] [PubMed]

Kim, P.

K. Jung, P. Kim, F. Leuschner, R. Gorbatov, J. K. Kim, T. Ueno, M. Nahrendorf, and S. H. Yun, “Endoscopic time-lapse imaging of immune cells in infarcted mouse hearts,” Circ. Res. 112(6), 891–899 (2013).
[Crossref] [PubMed]

Knorr, F.

F. Knorr, D. R. Yankelevich, J. Liu, S. Wachsmann-Hogiu, and L. Marcu, “Two-photon excited fluorescence lifetime measurements through a double-clad photonic crystal fiber for tissue micro-endoscopy,” J. Biophotonics 5(1), 14–19 (2012).
[Crossref] [PubMed]

Kolomenskii, A.

S. Jerebtsov, A. Kolomenskii, M. Poudel, F. Zhu, and H. Schuessler, “Lifetime and anisotropy decay of excited Coumarin 30 measured by a femtosecond pump–probe technique,” J. Mod. Opt. 53(16-17), 2609–2617 (2006).
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König, K.

K. König, A. Uchugonova, and E. Gorjup, “Multiphoton fluorescence lifetime imaging of 3D-stem cell spheroids during differentiation,” Microsc. Res. Tech. 74(1), 9–17 (2011).
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Kruglik, S. G.

Kudlinski, A.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2016).
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Kunz, D.

A. V. Kuznetsov, O. Mayboroda, D. Kunz, K. Winkler, W. Schubert, and W. S. Kunz, “Functional imaging of mitochondria in saponin-permeabilized mice muscle fibers,” J. Cell Biol. 140(5), 1091–1099 (1998).
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Kunz, W. S.

A. V. Kuznetsov, O. Mayboroda, D. Kunz, K. Winkler, W. Schubert, and W. S. Kunz, “Functional imaging of mitochondria in saponin-permeabilized mice muscle fibers,” J. Cell Biol. 140(5), 1091–1099 (1998).
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Kutz, J. N.

Kuznetsov, A. V.

A. V. Kuznetsov, O. Mayboroda, D. Kunz, K. Winkler, W. Schubert, and W. S. Kunz, “Functional imaging of mitochondria in saponin-permeabilized mice muscle fibers,” J. Cell Biol. 140(5), 1091–1099 (1998).
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Lacombe, F.

G. T. Kennedy, H. B. Manning, D. S. Elson, M. A. A. Neil, G. W. Stamp, B. Viellerobe, F. Lacombe, C. Dunsby, and P. M. W. French, “A fluorescence lifetime imaging scanning confocal endomicroscope,” J. Biophotonics 3(1-2), 103–107 (2010).
[Crossref] [PubMed]

Lakowicz, J. R.

J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, and M. L. Johnson, “Fluorescence lifetime imaging of free and protein-bound NADH,” Proc. Natl. Acad. Sci. U.S.A. 89(4), 1271–1275 (1992).
[Crossref] [PubMed]

Leclerc, P.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2016).
[Crossref] [PubMed]

Lefort, C.

Leray, A.

A. Leray, S. Padilla-Parra, J. Roul, L. Héliot, and M. Tramier, “827Spatio-Temporal Quantification of FRET in Living Cells by Fast Time-Domain FLIM: A Comparative Study of Non-Fitting Methods,” PLoS One 8, e69335 (2013).
[Crossref]

Leuschner, F.

K. Jung, P. Kim, F. Leuschner, R. Gorbatov, J. K. Kim, T. Ueno, M. Nahrendorf, and S. H. Yun, “Endoscopic time-lapse imaging of immune cells in infarcted mouse hearts,” Circ. Res. 112(6), 891–899 (2013).
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J. T. C. Liu, N. O. Loewke, M. J. Mandella, R. M. Levenson, J. M. Crawford, and C. H. Contag, “Point-of-care pathology with miniature microscopes,” Anal. Cell Pathol. (Amst.) 34(3), 81–98 (2011).
[Crossref] [PubMed]

Liu, J.

F. Knorr, D. R. Yankelevich, J. Liu, S. Wachsmann-Hogiu, and L. Marcu, “Two-photon excited fluorescence lifetime measurements through a double-clad photonic crystal fiber for tissue micro-endoscopy,” J. Biophotonics 5(1), 14–19 (2012).
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J. T. C. Liu, N. O. Loewke, M. J. Mandella, R. M. Levenson, J. M. Crawford, and C. H. Contag, “Point-of-care pathology with miniature microscopes,” Anal. Cell Pathol. (Amst.) 34(3), 81–98 (2011).
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J. T. C. Liu, N. O. Loewke, M. J. Mandella, R. M. Levenson, J. M. Crawford, and C. H. Contag, “Point-of-care pathology with miniature microscopes,” Anal. Cell Pathol. (Amst.) 34(3), 81–98 (2011).
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Louradour, F.

Maitland, K. C.

Malik, B.

Malitson, I. H.

Mandella, M. J.

J. T. C. Liu, N. O. Loewke, M. J. Mandella, R. M. Levenson, J. M. Crawford, and C. H. Contag, “Point-of-care pathology with miniature microscopes,” Anal. Cell Pathol. (Amst.) 34(3), 81–98 (2011).
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Manning, H. B.

G. T. Kennedy, H. B. Manning, D. S. Elson, M. A. A. Neil, G. W. Stamp, B. Viellerobe, F. Lacombe, C. Dunsby, and P. M. W. French, “A fluorescence lifetime imaging scanning confocal endomicroscope,” J. Biophotonics 3(1-2), 103–107 (2010).
[Crossref] [PubMed]

Mansuryan, T.

Marcu, L.

Y. Sun, J. E. Phipps, J. Meier, N. Hatami, B. Poirier, D. S. Elson, D. G. Farwell, and L. Marcu, “Endoscopic fluorescence lifetime imaging for in vivo intraoperative diagnosis of oral carcinoma,” Microsc. Microanal. 19(4), 791–798 (2013).
[Crossref] [PubMed]

F. Knorr, D. R. Yankelevich, J. Liu, S. Wachsmann-Hogiu, and L. Marcu, “Two-photon excited fluorescence lifetime measurements through a double-clad photonic crystal fiber for tissue micro-endoscopy,” J. Biophotonics 5(1), 14–19 (2012).
[Crossref] [PubMed]

Martínez-León, L.

Mayboroda, O.

A. V. Kuznetsov, O. Mayboroda, D. Kunz, K. Winkler, W. Schubert, and W. S. Kunz, “Functional imaging of mitochondria in saponin-permeabilized mice muscle fibers,” J. Cell Biol. 140(5), 1091–1099 (1998).
[Crossref] [PubMed]

Meier, J.

Y. Sun, J. E. Phipps, J. Meier, N. Hatami, B. Poirier, D. S. Elson, D. G. Farwell, and L. Marcu, “Endoscopic fluorescence lifetime imaging for in vivo intraoperative diagnosis of oral carcinoma,” Microsc. Microanal. 19(4), 791–798 (2013).
[Crossref] [PubMed]

Michel, S.

C. H. Hage, B. Kibler, E. R. Andresen, S. Michel, H. Rigneault, A. Courjaud, E. Mottay, J. M. Dudley, G. Millot, and C. Finot, “Optimization and characterization of a femtosecond tunable light source based on the soliton self-frequency shift in photonic crystal fiber,” Proc. SPIE 8071, 80710I (2011).
[Crossref]

Millot, G.

C. H. Hage, B. Kibler, E. R. Andresen, S. Michel, H. Rigneault, A. Courjaud, E. Mottay, J. M. Dudley, G. Millot, and C. Finot, “Optimization and characterization of a femtosecond tunable light source based on the soliton self-frequency shift in photonic crystal fiber,” Proc. SPIE 8071, 80710I (2011).
[Crossref]

Mohanan, S.

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref] [PubMed]

Moll, I.

J. L. Rinnenthal, C. Börnchen, H. Radbruch, V. Andresen, A. Mossakowski, V. Siffrin, T. Seelemann, H. Spiecker, I. Moll, J. Herz, A. E. Hauser, F. Zipp, M. J. Behne, and R. Niesner, “Parallelized TCSPC for Dynamic Intravital Fluorescence Lifetime Imaging: Quantifying Neuronal Dysfunction in Neuroinflammation,” PLoS One 8(4), e60100 (2013).
[Crossref] [PubMed]

Mossakowski, A.

J. L. Rinnenthal, C. Börnchen, H. Radbruch, V. Andresen, A. Mossakowski, V. Siffrin, T. Seelemann, H. Spiecker, I. Moll, J. Herz, A. E. Hauser, F. Zipp, M. J. Behne, and R. Niesner, “Parallelized TCSPC for Dynamic Intravital Fluorescence Lifetime Imaging: Quantifying Neuronal Dysfunction in Neuroinflammation,” PLoS One 8(4), e60100 (2013).
[Crossref] [PubMed]

Mottay, E.

C. H. Hage, B. Kibler, E. R. Andresen, S. Michel, H. Rigneault, A. Courjaud, E. Mottay, J. M. Dudley, G. Millot, and C. Finot, “Optimization and characterization of a femtosecond tunable light source based on the soliton self-frequency shift in photonic crystal fiber,” Proc. SPIE 8071, 80710I (2011).
[Crossref]

Mouradian, L.

Muddathir, A. K.

K. O. Alfarouk, D. Verduzco, C. Rauch, A. K. Muddathir, A. H. Bashir, G. O. Elhassan, M. E. Ibrahim, J. D. Orozco, R. A. Cardone, S. J. Reshkin, and S. Harguindey, “Glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based etiopathogenic perspective and therapeutic approach to an old cancer question,” Oncoscience 2(4), 317 (2014).
[Crossref] [PubMed]

Müller, M. G.

I. Georgakoudi, B. C. Jacobson, M. G. Müller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62(3), 682–687 (2002).
[PubMed]

Nahrendorf, M.

K. Jung, P. Kim, F. Leuschner, R. Gorbatov, J. K. Kim, T. Ueno, M. Nahrendorf, and S. H. Yun, “Endoscopic time-lapse imaging of immune cells in infarcted mouse hearts,” Circ. Res. 112(6), 891–899 (2013).
[Crossref] [PubMed]

Neil, M. A. A.

G. T. Kennedy, H. B. Manning, D. S. Elson, M. A. A. Neil, G. W. Stamp, B. Viellerobe, F. Lacombe, C. Dunsby, and P. M. W. French, “A fluorescence lifetime imaging scanning confocal endomicroscope,” J. Biophotonics 3(1-2), 103–107 (2010).
[Crossref] [PubMed]

Ng, T.

Niesner, R.

J. L. Rinnenthal, C. Börnchen, H. Radbruch, V. Andresen, A. Mossakowski, V. Siffrin, T. Seelemann, H. Spiecker, I. Moll, J. Herz, A. E. Hauser, F. Zipp, M. J. Behne, and R. Niesner, “Parallelized TCSPC for Dynamic Intravital Fluorescence Lifetime Imaging: Quantifying Neuronal Dysfunction in Neuroinflammation,” PLoS One 8(4), e60100 (2013).
[Crossref] [PubMed]

Nimmerjahn, A.

Nourse, J. L.

C. Stringari, J. L. Nourse, L. A. Flanagan, and E. Gratton, “Phasor Fluorescence Lifetime Microscopy of Free and Protein-Bound NADH Reveals Neural Stem Cell Differentiation Potential,” PLoS One 7(11), e48014 (2012).
[Crossref] [PubMed]

Nowaczyk, K.

J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, and M. L. Johnson, “Fluorescence lifetime imaging of free and protein-bound NADH,” Proc. Natl. Acad. Sci. U.S.A. 89(4), 1271–1275 (1992).
[Crossref] [PubMed]

Orozco, J. D.

K. O. Alfarouk, D. Verduzco, C. Rauch, A. K. Muddathir, A. H. Bashir, G. O. Elhassan, M. E. Ibrahim, J. D. Orozco, R. A. Cardone, S. J. Reshkin, and S. Harguindey, “Glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based etiopathogenic perspective and therapeutic approach to an old cancer question,” Oncoscience 2(4), 317 (2014).
[Crossref] [PubMed]

Ouzounov, D. G.

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref] [PubMed]

Padilla-Parra, S.

A. Leray, S. Padilla-Parra, J. Roul, L. Héliot, and M. Tramier, “827Spatio-Temporal Quantification of FRET in Living Cells by Fast Time-Domain FLIM: A Comparative Study of Non-Fitting Methods,” PLoS One 8, e69335 (2013).
[Crossref]

Pavlova, I.

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref] [PubMed]

Peyrot, D. A.

Phipps, J. E.

Y. Sun, J. E. Phipps, J. Meier, N. Hatami, B. Poirier, D. S. Elson, D. G. Farwell, and L. Marcu, “Endoscopic fluorescence lifetime imaging for in vivo intraoperative diagnosis of oral carcinoma,” Microsc. Microanal. 19(4), 791–798 (2013).
[Crossref] [PubMed]

Poirier, B.

Y. Sun, J. E. Phipps, J. Meier, N. Hatami, B. Poirier, D. S. Elson, D. G. Farwell, and L. Marcu, “Endoscopic fluorescence lifetime imaging for in vivo intraoperative diagnosis of oral carcinoma,” Microsc. Microanal. 19(4), 791–798 (2013).
[Crossref] [PubMed]

Poudel, M.

S. Jerebtsov, A. Kolomenskii, M. Poudel, F. Zhu, and H. Schuessler, “Lifetime and anisotropy decay of excited Coumarin 30 measured by a femtosecond pump–probe technique,” J. Mod. Opt. 53(16-17), 2609–2617 (2006).
[Crossref]

Radbruch, H.

J. L. Rinnenthal, C. Börnchen, H. Radbruch, V. Andresen, A. Mossakowski, V. Siffrin, T. Seelemann, H. Spiecker, I. Moll, J. Herz, A. E. Hauser, F. Zipp, M. J. Behne, and R. Niesner, “Parallelized TCSPC for Dynamic Intravital Fluorescence Lifetime Imaging: Quantifying Neuronal Dysfunction in Neuroinflammation,” PLoS One 8(4), e60100 (2013).
[Crossref] [PubMed]

Ramanujam, N.

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of {NADH} and {FAD} redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A. 104(49), 19494–19499 (2007).
[Crossref] [PubMed]

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and 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(2), 024014 (2007).
[Crossref] [PubMed]

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[Crossref] [PubMed]

Rauch, C.

K. O. Alfarouk, D. Verduzco, C. Rauch, A. K. Muddathir, A. H. Bashir, G. O. Elhassan, M. E. Ibrahim, J. D. Orozco, R. A. Cardone, S. J. Reshkin, and S. Harguindey, “Glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based etiopathogenic perspective and therapeutic approach to an old cancer question,” Oncoscience 2(4), 317 (2014).
[Crossref] [PubMed]

Redding, B.

Reshkin, S. J.

K. O. Alfarouk, D. Verduzco, C. Rauch, A. K. Muddathir, A. H. Bashir, G. O. Elhassan, M. E. Ibrahim, J. D. Orozco, R. A. Cardone, S. J. Reshkin, and S. Harguindey, “Glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based etiopathogenic perspective and therapeutic approach to an old cancer question,” Oncoscience 2(4), 317 (2014).
[Crossref] [PubMed]

Riching, K. M.

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and 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(2), 024014 (2007).
[Crossref] [PubMed]

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of {NADH} and {FAD} redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A. 104(49), 19494–19499 (2007).
[Crossref] [PubMed]

Rico-Jimenez, J. J.

Rigneault, H.

C. H. Hage, B. Kibler, E. R. Andresen, S. Michel, H. Rigneault, A. Courjaud, E. Mottay, J. M. Dudley, G. Millot, and C. Finot, “Optimization and characterization of a femtosecond tunable light source based on the soliton self-frequency shift in photonic crystal fiber,” Proc. SPIE 8071, 80710I (2011).
[Crossref]

Rinnenthal, J. L.

J. L. Rinnenthal, C. Börnchen, H. Radbruch, V. Andresen, A. Mossakowski, V. Siffrin, T. Seelemann, H. Spiecker, I. Moll, J. Herz, A. E. Hauser, F. Zipp, M. J. Behne, and R. Niesner, “Parallelized TCSPC for Dynamic Intravital Fluorescence Lifetime Imaging: Quantifying Neuronal Dysfunction in Neuroinflammation,” PLoS One 8(4), e60100 (2013).
[Crossref] [PubMed]

Rivera, D. R.

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref] [PubMed]

Rotter, S.

Roul, J.

A. Leray, S. Padilla-Parra, J. Roul, L. Héliot, and M. Tramier, “827Spatio-Temporal Quantification of FRET in Living Cells by Fast Time-Domain FLIM: A Comparative Study of Non-Fitting Methods,” PLoS One 8, e69335 (2013).
[Crossref]

Sandeau, N.

Schröder, J.

Schubert, W.

A. V. Kuznetsov, O. Mayboroda, D. Kunz, K. Winkler, W. Schubert, and W. S. Kunz, “Functional imaging of mitochondria in saponin-permeabilized mice muscle fibers,” J. Cell Biol. 140(5), 1091–1099 (1998).
[Crossref] [PubMed]

Schuessler, H.

S. Jerebtsov, A. Kolomenskii, M. Poudel, F. Zhu, and H. Schuessler, “Lifetime and anisotropy decay of excited Coumarin 30 measured by a femtosecond pump–probe technique,” J. Mod. Opt. 53(16-17), 2609–2617 (2006).
[Crossref]

Schürmann, S.

C. S. Garbe, A. Buttgereit, S. Schürmann, and O. Friedrich, “Automated multiscale morphometry of muscle disease from second harmonic generation microscopy using tensor-based image processing,” IEEE Trans. Biomed. Eng. 59(1), 39–44 (2012).
[Crossref] [PubMed]

Seelemann, T.

J. L. Rinnenthal, C. Börnchen, H. Radbruch, V. Andresen, A. Mossakowski, V. Siffrin, T. Seelemann, H. Spiecker, I. Moll, J. Herz, A. E. Hauser, F. Zipp, M. J. Behne, and R. Niesner, “Parallelized TCSPC for Dynamic Intravital Fluorescence Lifetime Imaging: Quantifying Neuronal Dysfunction in Neuroinflammation,” PLoS One 8(4), e60100 (2013).
[Crossref] [PubMed]

Segall, J. E.

J. Condeelis and J. E. Segall, “Intravital imaging of cell movement in tumours,” Nat. Rev. Cancer 3(12), 921–930 (2003).
[Crossref] [PubMed]

Shear, J. B.

C. Xu, W. Zipfel, J. B. Shear, R. M. Williams, and W. W. Webb, “Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy,” Proc. Natl. Acad. Sci. U.S.A. 93(20), 10763–10768 (1996).
[Crossref] [PubMed]

Sheets, E. E.

I. Georgakoudi, B. C. Jacobson, M. G. Müller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62(3), 682–687 (2002).
[PubMed]

Siffrin, V.

J. L. Rinnenthal, C. Börnchen, H. Radbruch, V. Andresen, A. Mossakowski, V. Siffrin, T. Seelemann, H. Spiecker, I. Moll, J. Herz, A. E. Hauser, F. Zipp, M. J. Behne, and R. Niesner, “Parallelized TCSPC for Dynamic Intravital Fluorescence Lifetime Imaging: Quantifying Neuronal Dysfunction in Neuroinflammation,” PLoS One 8(4), e60100 (2013).
[Crossref] [PubMed]

Skala, M. C.

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of {NADH} and {FAD} redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A. 104(49), 19494–19499 (2007).
[Crossref] [PubMed]

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and 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(2), 024014 (2007).
[Crossref] [PubMed]

Smith, D.

Sparks, H.

H. Sparks, S. Warren, J. Guedes, N. Yoshida, T. C. Charn, N. Guerra, T. Tatla, C. Dunsby, and P. French, “A flexible wide-field FLIM endoscope utilising blue excitation light for label-free contrast of tissue,” J. Biophotonics 8(1-2), 168–178 (2015).
[Crossref] [PubMed]

Spiecker, H.

J. L. Rinnenthal, C. Börnchen, H. Radbruch, V. Andresen, A. Mossakowski, V. Siffrin, T. Seelemann, H. Spiecker, I. Moll, J. Herz, A. E. Hauser, F. Zipp, M. J. Behne, and R. Niesner, “Parallelized TCSPC for Dynamic Intravital Fluorescence Lifetime Imaging: Quantifying Neuronal Dysfunction in Neuroinflammation,” PLoS One 8(4), e60100 (2013).
[Crossref] [PubMed]

Squirrell, J. M.

J. M. Squirrell, D. L. Wokosin, J. G. White, and B. D. Bavister, “Long-term two-photon fluorescence imaging of mammalian embryos without compromising viability,” Nat. Biotechnol. 17(8), 763–767 (1999).
[Crossref] [PubMed]

Stamp, G. W.

G. T. Kennedy, H. B. Manning, D. S. Elson, M. A. A. Neil, G. W. Stamp, B. Viellerobe, F. Lacombe, C. Dunsby, and P. M. W. French, “A fluorescence lifetime imaging scanning confocal endomicroscope,” J. Biophotonics 3(1-2), 103–107 (2010).
[Crossref] [PubMed]

Steffenhagen, M.

Stringari, C.

C. Stringari, J. L. Nourse, L. A. Flanagan, and E. Gratton, “Phasor Fluorescence Lifetime Microscopy of Free and Protein-Bound NADH Reveals Neural Stem Cell Differentiation Potential,” PLoS One 7(11), e48014 (2012).
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C. Stringari, A. Cinquin, O. Cinquin, M. A. Digman, P. J. Donovan, and E. Gratton, “Phasor approach to fluorescence lifetime microscopy distinguishes different metabolic states of germ cells in a live tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(33), 13582–13587 (2011).
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Sun, Y.

Y. Sun, J. E. Phipps, J. Meier, N. Hatami, B. Poirier, D. S. Elson, D. G. Farwell, and L. Marcu, “Endoscopic fluorescence lifetime imaging for in vivo intraoperative diagnosis of oral carcinoma,” Microsc. Microanal. 19(4), 791–798 (2013).
[Crossref] [PubMed]

Szmacinski, H.

J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, and M. L. Johnson, “Fluorescence lifetime imaging of free and protein-bound NADH,” Proc. Natl. Acad. Sci. U.S.A. 89(4), 1271–1275 (1992).
[Crossref] [PubMed]

Tatla, T.

H. Sparks, S. Warren, J. Guedes, N. Yoshida, T. C. Charn, N. Guerra, T. Tatla, C. Dunsby, and P. French, “A flexible wide-field FLIM endoscope utilising blue excitation light for label-free contrast of tissue,” J. Biophotonics 8(1-2), 168–178 (2015).
[Crossref] [PubMed]

Thiberville, L.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2016).
[Crossref] [PubMed]

D. A. Peyrot, C. Lefort, M. Steffenhagen, T. Mansuryan, G. Ducourthial, D. Abi-Haidar, N. Sandeau, C. Vever-Bizet, S. G. Kruglik, L. Thiberville, F. Louradour, and G. Bourg-Heckly, “Development of a nonlinear fiber-optic spectrometer for human lung tissue exploration,” Biomed. Opt. Express 3(5), 840–853 (2012).
[Crossref] [PubMed]

Tramier, M.

A. Leray, S. Padilla-Parra, J. Roul, L. Héliot, and M. Tramier, “827Spatio-Temporal Quantification of FRET in Living Cells by Fast Time-Domain FLIM: A Comparative Study of Non-Fitting Methods,” PLoS One 8, e69335 (2013).
[Crossref]

Uchugonova, A.

K. König, A. Uchugonova, and E. Gorjup, “Multiphoton fluorescence lifetime imaging of 3D-stem cell spheroids during differentiation,” Microsc. Res. Tech. 74(1), 9–17 (2011).
[Crossref] [PubMed]

Ueno, T.

K. Jung, P. Kim, F. Leuschner, R. Gorbatov, J. K. Kim, T. Ueno, M. Nahrendorf, and S. H. Yun, “Endoscopic time-lapse imaging of immune cells in infarcted mouse hearts,” Circ. Res. 112(6), 891–899 (2013).
[Crossref] [PubMed]

Van Dam, J.

I. Georgakoudi, B. C. Jacobson, M. G. Müller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62(3), 682–687 (2002).
[PubMed]

Vaughan, E. M.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[Crossref] [PubMed]

Verduzco, D.

K. O. Alfarouk, D. Verduzco, C. Rauch, A. K. Muddathir, A. H. Bashir, G. O. Elhassan, M. E. Ibrahim, J. D. Orozco, R. A. Cardone, S. J. Reshkin, and S. Harguindey, “Glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based etiopathogenic perspective and therapeutic approach to an old cancer question,” Oncoscience 2(4), 317 (2014).
[Crossref] [PubMed]

Vever-Bizet, C.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2016).
[Crossref] [PubMed]

D. A. Peyrot, C. Lefort, M. Steffenhagen, T. Mansuryan, G. Ducourthial, D. Abi-Haidar, N. Sandeau, C. Vever-Bizet, S. G. Kruglik, L. Thiberville, F. Louradour, and G. Bourg-Heckly, “Development of a nonlinear fiber-optic spectrometer for human lung tissue exploration,” Biomed. Opt. Express 3(5), 840–853 (2012).
[Crossref] [PubMed]

Viellerobe, B.

G. T. Kennedy, H. B. Manning, D. S. Elson, M. A. A. Neil, G. W. Stamp, B. Viellerobe, F. Lacombe, C. Dunsby, and P. M. W. French, “A fluorescence lifetime imaging scanning confocal endomicroscope,” J. Biophotonics 3(1-2), 103–107 (2010).
[Crossref] [PubMed]

Vrotsos, K. M.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[Crossref] [PubMed]

Wachsmann-Hogiu, S.

F. Knorr, D. R. Yankelevich, J. Liu, S. Wachsmann-Hogiu, and L. Marcu, “Two-photon excited fluorescence lifetime measurements through a double-clad photonic crystal fiber for tissue micro-endoscopy,” J. Biophotonics 5(1), 14–19 (2012).
[Crossref] [PubMed]

Warren, S.

H. Sparks, S. Warren, J. Guedes, N. Yoshida, T. C. Charn, N. Guerra, T. Tatla, C. Dunsby, and P. French, “A flexible wide-field FLIM endoscope utilising blue excitation light for label-free contrast of tissue,” J. Biophotonics 8(1-2), 168–178 (2015).
[Crossref] [PubMed]

Watson, T.

Webb, W. W.

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref] [PubMed]

S. Huang, A. A. Heikal, and W. W. Webb, “Two-photon fluorescence spectroscopy and microscopy of NAD(P)H and flavoprotein,” Biophys. J. 82(5), 2811–2825 (2002).
[Crossref] [PubMed]

C. Xu, W. Zipfel, J. B. Shear, R. M. Williams, and W. W. Webb, “Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy,” Proc. Natl. Acad. Sci. U.S.A. 93(20), 10763–10768 (1996).
[Crossref] [PubMed]

White, J. G.

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of {NADH} and {FAD} redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A. 104(49), 19494–19499 (2007).
[Crossref] [PubMed]

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[Crossref] [PubMed]

J. M. Squirrell, D. L. Wokosin, J. G. White, and B. D. Bavister, “Long-term two-photon fluorescence imaging of mammalian embryos without compromising viability,” Nat. Biotechnol. 17(8), 763–767 (1999).
[Crossref] [PubMed]

Williams, R. M.

C. Xu, W. Zipfel, J. B. Shear, R. M. Williams, and W. W. Webb, “Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy,” Proc. Natl. Acad. Sci. U.S.A. 93(20), 10763–10768 (1996).
[Crossref] [PubMed]

Williams, W. O.

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref] [PubMed]

Winkler, K.

A. V. Kuznetsov, O. Mayboroda, D. Kunz, K. Winkler, W. Schubert, and W. S. Kunz, “Functional imaging of mitochondria in saponin-permeabilized mice muscle fibers,” J. Cell Biol. 140(5), 1091–1099 (1998).
[Crossref] [PubMed]

Wokosin, D. L.

P. G. Bush, D. L. Wokosin, and A. C. Hall, “Two-versus one photon excitation laser scanning microscopy: critical importance of excitation wavelength,” Front. Biosci. 12(1), 2646–2657 (2007).
[Crossref] [PubMed]

J. M. Squirrell, D. L. Wokosin, J. G. White, and B. D. Bavister, “Long-term two-photon fluorescence imaging of mammalian embryos without compromising viability,” Nat. Biotechnol. 17(8), 763–767 (1999).
[Crossref] [PubMed]

Wright, J.

Xiong, W.

Xu, C.

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref] [PubMed]

C. Xu, W. Zipfel, J. B. Shear, R. M. Williams, and W. W. Webb, “Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy,” Proc. Natl. Acad. Sci. U.S.A. 93(20), 10763–10768 (1996).
[Crossref] [PubMed]

Yan, L.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[Crossref] [PubMed]

Yankelevich, D. R.

F. Knorr, D. R. Yankelevich, J. Liu, S. Wachsmann-Hogiu, and L. Marcu, “Two-photon excited fluorescence lifetime measurements through a double-clad photonic crystal fiber for tissue micro-endoscopy,” J. Biophotonics 5(1), 14–19 (2012).
[Crossref] [PubMed]

Yoshida, N.

H. Sparks, S. Warren, J. Guedes, N. Yoshida, T. C. Charn, N. Guerra, T. Tatla, C. Dunsby, and P. French, “A flexible wide-field FLIM endoscope utilising blue excitation light for label-free contrast of tissue,” J. Biophotonics 8(1-2), 168–178 (2015).
[Crossref] [PubMed]

Yu, Q.

Q. Yu and A. A. Heikal, “Two-photon autofluorescence dynamics imaging reveals sensitivity of intracellular NADH concentration and conformation to cell physiology at the single-cell level,” J. Photochem. Photobiol. B 95(1), 46–57 (2009).
[Crossref] [PubMed]

Yun, S. H.

K. Jung, P. Kim, F. Leuschner, R. Gorbatov, J. K. Kim, T. Ueno, M. Nahrendorf, and S. H. Yun, “Endoscopic time-lapse imaging of immune cells in infarcted mouse hearts,” Circ. Res. 112(6), 891–899 (2013).
[Crossref] [PubMed]

Zamai, M.

M. A. Digman, V. R. Caiolfa, M. Zamai, and E. Gratton, “The phasor approach to fluorescence lifetime imaging analysis,” Biophys. J. 94(2), L14–L16 (2008).
[Crossref] [PubMed]

Zhu, F.

S. Jerebtsov, A. Kolomenskii, M. Poudel, F. Zhu, and H. Schuessler, “Lifetime and anisotropy decay of excited Coumarin 30 measured by a femtosecond pump–probe technique,” J. Mod. Opt. 53(16-17), 2609–2617 (2006).
[Crossref]

Zipfel, W.

C. Xu, W. Zipfel, J. B. Shear, R. M. Williams, and W. W. Webb, “Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy,” Proc. Natl. Acad. Sci. U.S.A. 93(20), 10763–10768 (1996).
[Crossref] [PubMed]

Zipp, F.

J. L. Rinnenthal, C. Börnchen, H. Radbruch, V. Andresen, A. Mossakowski, V. Siffrin, T. Seelemann, H. Spiecker, I. Moll, J. Herz, A. E. Hauser, F. Zipp, M. J. Behne, and R. Niesner, “Parallelized TCSPC for Dynamic Intravital Fluorescence Lifetime Imaging: Quantifying Neuronal Dysfunction in Neuroinflammation,” PLoS One 8(4), e60100 (2013).
[Crossref] [PubMed]

Anal. Cell Pathol. (Amst.) (1)

J. T. C. Liu, N. O. Loewke, M. J. Mandella, R. M. Levenson, J. M. Crawford, and C. H. Contag, “Point-of-care pathology with miniature microscopes,” Anal. Cell Pathol. (Amst.) 34(3), 81–98 (2011).
[Crossref] [PubMed]

Biomed. Opt. Express (2)

Biophys. J. (2)

S. Huang, A. A. Heikal, and W. W. Webb, “Two-photon fluorescence spectroscopy and microscopy of NAD(P)H and flavoprotein,” Biophys. J. 82(5), 2811–2825 (2002).
[Crossref] [PubMed]

M. A. Digman, V. R. Caiolfa, M. Zamai, and E. Gratton, “The phasor approach to fluorescence lifetime imaging analysis,” Biophys. J. 94(2), L14–L16 (2008).
[Crossref] [PubMed]

Cancer Res. (2)

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[Crossref] [PubMed]

I. Georgakoudi, B. C. Jacobson, M. G. Müller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62(3), 682–687 (2002).
[PubMed]

Circ. Res. (1)

K. Jung, P. Kim, F. Leuschner, R. Gorbatov, J. K. Kim, T. Ueno, M. Nahrendorf, and S. H. Yun, “Endoscopic time-lapse imaging of immune cells in infarcted mouse hearts,” Circ. Res. 112(6), 891–899 (2013).
[Crossref] [PubMed]

Front. Biosci. (1)

P. G. Bush, D. L. Wokosin, and A. C. Hall, “Two-versus one photon excitation laser scanning microscopy: critical importance of excitation wavelength,” Front. Biosci. 12(1), 2646–2657 (2007).
[Crossref] [PubMed]

IEEE Trans. Biomed. Eng. (1)

C. S. Garbe, A. Buttgereit, S. Schürmann, and O. Friedrich, “Automated multiscale morphometry of muscle disease from second harmonic generation microscopy using tensor-based image processing,” IEEE Trans. Biomed. Eng. 59(1), 39–44 (2012).
[Crossref] [PubMed]

J. Biomed. Opt. (2)

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref] [PubMed]

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W. Becker, “The bh TCSPC Handbook,” Scanning 2015, 1–768 (2015).

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W. Liang, G. Meng, I. Gannot, M.-J. Li, and X. Li, “Real-time Fluorescence Lifetime Imaging by a Fiber-optic Two-photon Endomicroscopy System,” in Biomedical Optics 2016, OSA Technical Digest (Online) (Optical Society of America, 2016), p. TTu4B.3.

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Figures (5)

Fig. 1
Fig. 1 Experimental setup. (a) Characterization vs imaging arrangement. (b) FUT microstructure (taken from [21]). (c) Experimental setup. SSFS: Soliton Self-Frequency Shift, SC: SuperContinuum, SHG: Second Harmonic Generation, LPF: long-pass filter, BPF: band-pass filter, SPF: short-pass filter, TCSPC: Time Correlated Single Photon Counting, IRF: Impulse Response Function, CCD: Coupled Charge Device, FUT: Fiber Under Test. (d) Typical excitation signals: SSFS ultrashort pulses (left) and spectrally broad supercontinuum (right). (e) Current scanning head for the imaging experiment.
Fig. 2
Fig. 2 Fiber dispersion influence estimation and characterization. (a) Calculated chromatic delay for a signal with a 50 (plain) and 80 (dashed) nm spectral bandwidth centered on 450 nm. (b) Calculated intermodal delay for a 400 nm carrier wavelength – 0.24 NA fiber (dashed black), 500 nm carrier wavelength – 0.24 NA fiber (plain grey) and a 450 nm carrier wavelength – 0.2 NA fiber (plain black). (c to e): Measured free-space (red) and fiber (green) IRFs. (c) Fiber A1 (0.24 NA, 4m). (d) Fiber A2 (0.24 NA, 8.15m). (e) Fiber B (0.2 NA, 6 m). On each plot, from left to right: 430 nm/100 fs pulses, 475 nm/100 fs pulses, 425-510 nm/2 ps supercontinuum. The fiber A2 was no longer available when using the supercontinuum.
Fig. 3
Fig. 3 Coumarin 515 fluorescence measurements through the fiber A2. Red = free-space. Green = fiber. (a) Typical TCSPC histograms. (b) Phasor representation. Coumarin fluorescence phasors are located near g = 0.5 and the IRFs near g = 0.95. Black cross: phasor corresponding to ref [41].
Fig. 4
Fig. 4 Fast digitalizer suitability assessment using a 4-m/0.24 fiber. Red = PicoQuant reference device, green = Fast digitalizer. (a) IRF measurement using the Picoquant device (red), and the Fast digitalizer (dashed green) in free space, and the fast digitalizer in the fibered configuration (plain green). (b) Phasor of the IRFs (stars) and the raw coumarin histograms (crosses).
Fig. 5
Fig. 5 HT29 cell lifetime imaging. (a1,a2) Before and (b1,b2) after addition of sodium cyanide (NaCN). (a1,b1) Intensity images, no binning. (a2,b2) Mean lifetime images, 3x3 pixels binning. (c) Phasor representation, 5x5 pixels binning. Free and bound NADH positions are taken from [5,6]. (d) Signal intensity evolution over the acquisitions. Scalebar = 20 µm. 200x200 px, 10 µs dwell time. Green = before and red = after NaCN addition.

Tables (3)

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Table 1 Tested fibers main properties

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Table 2 Fibers’ characterization metrics calculated dispersions compared to the deconvolved IRFs (rows 1 and 2), comparison between free-space and fiber coumarin 515 average lifetime (row 3).

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Table 3 Influence of the fiber movements and curvature radius on the intermodal dispersion. The value represents the maximum difference between the different centers of mass (in picoseconds).

Equations (6)

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g( ω )= 0 + I(t)cos(ωt)dt 0 + I(t)dt
s( ω )= 0 + I(t)sin(ωt)dt 0 + I(t)dt
IR F total =IR F detection *IR F fiber =IR F detection *(IR F chromatic *IR F intermodal )
max(IR F chromatic FWHM ,IR F intermodal FWHM ) IR F fiber FWHM IR F chromatic FWHM +IR F intermodal FWHM
Δt=max( L n 0 (λ) c ( 1 cos(θ) 1 ) ), 0θ θ c (λ)
IRF IR F chromatic 2 +IR F intermodal 2

Metrics