Abstract

We present a dual-color laser scanning endomicroscope capable of fluorescence lifetime endomicroscopy at one frame per second (FPS). The scanning system uses a coherent imaging fiber with 30,000 cores. High-speed lifetime imaging is achieved by distributing the signal over an array of 1024 parallel single-photon avalanche diode detectors (SPADs), minimizing detection dead-time maximizing the number of photons detected per excitation pulse without photon pile-up to achieve the high frame rate. This also enables dual color fluorescence imaging by temporally shifting the dual excitation lasers, with respect to each other, to separate the two spectrally distinct fluorescent decays in time. Combining the temporal encoding, to provide spectral separation, with lifetime measurements we show a one FPS, multi-channel endomicroscopy platform for clinical applications and diagnosis. We demonstrate the potential of the system by imaging SmartProbe labeled bacteria in ex vivo samples of human lung using lifetimeto differentiate bacterial fluorescence from the strong background lung autofluorescence which was used to provide structural information.

Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.

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    [Crossref]
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    [Crossref]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref]
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  20. N. Krstajić, S. Poland, J. Levitt, R. Walker, A. Erdogan, S. Ameer-Beg, and R. K. Henderson, “0.5 billion events per second time correlated single photon counting using cmos spad arrays,” Opt. Lett. 40, 4305–4308 (2015).
    [Crossref]
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    [Crossref]
  22. A. Perperidis, H. E. Parker, A. Karam-Eldaly, Y. Altmann, K. Dhaliwal, R. R. Thomson, M. G. Tanner, and S. McLaughlin, “Characterization and modelling of inter-core coupling in coherent fiber bundles,” Opt. Express 25, 11932–11953 (2017).
    [Crossref] [PubMed]
  23. F. Ceccarelli, A. Gulinatti, I. Labanca, I. Rech, and M. Ghioni, “Development and characterization of an 8x8 spad-array module for gigacount per second applications,” in Photon Counting Applications 2017, (Proc. SPIE 10229, 2017), p. 102290E.
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    [Crossref]
  29. S. Behnel, R. Bradshaw, C. Citro, L. Dalcin, D. S. Seljebotn, and K. Smith, “Cython: The best of both worlds,” Computing in Science & Engineering 13, 31–39 (2011).
    [Crossref]

2018 (4)

A. R. Akram, S. V. Chankeshwara, E. Scholefield, T. Aslam, N. McDonald, A. Megia-Fernandez, A. Marshall, B. Mills, N. Avlonitis, T. H. Craven, A. M. Smyth, D. S. Collie, C. Gray, N. Hirani, A. T. Hill, J. R. Govan, T. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “In situ identification of gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid a,” Science Translational Medicine 10, eaal0033(2018).
[Crossref] [PubMed]

N. Krstajić, B. Mills, I. Murray, A. Marshall, D. Norberg, T. H. Craven, P. Emanuel, T. R. Choudhary, G. O. S. Williams, E. Scholefield, A. R. Akram, A. Davie, N. Hirani, A. Bruce, A. Moore, M. Bradley, and K. Dhaliwal, “Low-cost high sensitivity pulsed endomicroscopy to visualize tricolor optical signatures,” Journal of Biomedical Optics 23, 076005 (2018).
[Crossref]

T. H. Craven, N. Avlonitis, N. McDonald, T. Walton, E. Scholefield, A. R. Akram, T. S. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “Super-silent fret sensor enables live cell imaging and flow cytometric stratification of intracellular serine protease activity in neutrophils,” Scientific reports 8, 13490 (2018).
[Crossref] [PubMed]

A. Alfonso-Garcia, A. K. Haudenschild, and L. Marcu, “Label-free assessment of carotid artery biochemical composition using fiber-based fluorescence lifetime imaging,” Biomedical Optics Express 9, 4064–4076 (2018).
[Crossref]

2017 (2)

A. Megia-Fernandez, B. Mills, C. Michels, S. V. Chankeshwara, K. Dhaliwal, and M. Bradley, “Highly selective and rapidly activatable fluorogenic thrombin sensors and application in human lung tissue,” Organic & biomolecular chemistry 15, 4344–4350 (2017).
[Crossref]

A. Perperidis, H. E. Parker, A. Karam-Eldaly, Y. Altmann, K. Dhaliwal, R. R. Thomson, M. G. Tanner, and S. McLaughlin, “Characterization and modelling of inter-core coupling in coherent fiber bundles,” Opt. Express 25, 11932–11953 (2017).
[Crossref] [PubMed]

2016 (2)

S. Poland, A. Erdogan, N. Krstajic, J. Levitt, V. Devauges, R. Walker, D. Li, S. Ameer-Beg, and R. Henderson, “A new high-speed centre of mass method incorporating background subtraction for accurate determination of fluorescence lifetime,” Optics Express 24, 6899–6915 (2016).
[Crossref]

N. Krstajić, A. R. Akram, T. R. Choudhary, N. McDonald, M. G. Tanner, E. Pedretti, P. A. Dalgarno, E. Scholefield, J. M. Girkin, A. Moore, M. Bradley, and K. Dhaliwal, “Two-color widefield fluorescence microendoscopy enables multiplexed molecular imaging in the alveolar space of human lung tissue,” Journal of Biomedical Optics 21, 046009 (2016).
[Crossref]

2015 (1)

2014 (1)

D. R. Yankelevich, D. Ma, J. Liu, Y. Sun, Y. Sun, J. Bec, D. S. Elson, and L. Marcu, “Design and evaluation of a device for fast multispectral time-resolved fluorescence spectroscopy and imaging,” Review of Scientific Instruments 85, 034303 (2014).
[Crossref] [PubMed]

2013 (1)

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,” Microscopy and Microanalysis 19, 791–798 (2013).
[Crossref] [PubMed]

2012 (1)

J. Bec, H. Xie, D. R. Yankelevich, F. Zhou, Y. Sun, N. Ghata, R. Aldredge, and L. Marcu, “Design, construction, and validation of a rotary multifunctional intravascular diagnostic catheter combining multispectral fluorescence lifetime imaging and intravascular ultrasound,” Journal of biomedical optics 17, 1060121 (2012).
[Crossref]

2011 (2)

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,” Proceedings of the National Academy of Sciences 108, 13582–13587 (2011).
[Crossref]

S. Behnel, R. Bradshaw, C. Citro, L. Dalcin, D. S. Seljebotn, and K. Smith, “Cython: The best of both worlds,” Computing in Science & Engineering 13, 31–39 (2011).
[Crossref]

2010 (1)

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

2009 (1)

Y. Sun, J. Phipps, D. S. Elson, H. Stoy, S. Tinling, J. Meier, B. Poirier, F. S. Chuang, D. G. Farwell, and L. Marcu, “Fluorescence lifetime imaging microscopy: in vivo application to diagnosis of oral carcinoma,” Optics letters 34, 2081–2083 (2009).
[Crossref] [PubMed]

2008 (1)

Y. Sun, R. Liu, D. S. Elson, C. W. Hollars, J. A. Jo, J. Park, Y. Sun, and L. Marcu, “Simultaneous time-and wavelength-resolved fluorescence spectroscopy for near real-time tissue diagnosis,” Optics letters 33, 630–632 (2008).
[Crossref]

2007 (2)

F. Pérez and B. E. Granger, “IPython: a system for interactive scientific computing,” Computing in Science and Engineering 9, 21–29 (2007).
[Crossref]

J. D. Hunter, “Matplotlib: A 2d graphics environment,” Computing In Science & Engineering 9, 90–95 (2007).
[Crossref]

2005 (1)

H. Wallrabe and A. Periasamy, “Imaging protein molecules using fret and flim microscopy,” Current opinion in biotechnology 16, 19–27 (2005).
[Crossref] [PubMed]

2003 (1)

E. Gratton, S. Breusegem, J. D. Sutin, Q. Ruan, and N. P. Barry, “Fluorescence lifetime imaging for the two-photon microscope: time-domain and frequency-domain methods,” Journal of biomedical optics 8, 381–391 (2003).
[Crossref] [PubMed]

1981 (1)

D. C. Wells, E. W. Greisen, and R. H. Harten, “FITS - a Flexible Image Transport System,” A&AS 44, 363 (1981).

Akram, A. R.

A. R. Akram, S. V. Chankeshwara, E. Scholefield, T. Aslam, N. McDonald, A. Megia-Fernandez, A. Marshall, B. Mills, N. Avlonitis, T. H. Craven, A. M. Smyth, D. S. Collie, C. Gray, N. Hirani, A. T. Hill, J. R. Govan, T. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “In situ identification of gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid a,” Science Translational Medicine 10, eaal0033(2018).
[Crossref] [PubMed]

N. Krstajić, B. Mills, I. Murray, A. Marshall, D. Norberg, T. H. Craven, P. Emanuel, T. R. Choudhary, G. O. S. Williams, E. Scholefield, A. R. Akram, A. Davie, N. Hirani, A. Bruce, A. Moore, M. Bradley, and K. Dhaliwal, “Low-cost high sensitivity pulsed endomicroscopy to visualize tricolor optical signatures,” Journal of Biomedical Optics 23, 076005 (2018).
[Crossref]

T. H. Craven, N. Avlonitis, N. McDonald, T. Walton, E. Scholefield, A. R. Akram, T. S. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “Super-silent fret sensor enables live cell imaging and flow cytometric stratification of intracellular serine protease activity in neutrophils,” Scientific reports 8, 13490 (2018).
[Crossref] [PubMed]

N. Krstajić, A. R. Akram, T. R. Choudhary, N. McDonald, M. G. Tanner, E. Pedretti, P. A. Dalgarno, E. Scholefield, J. M. Girkin, A. Moore, M. Bradley, and K. Dhaliwal, “Two-color widefield fluorescence microendoscopy enables multiplexed molecular imaging in the alveolar space of human lung tissue,” Journal of Biomedical Optics 21, 046009 (2016).
[Crossref]

Aldredge, R.

J. Bec, H. Xie, D. R. Yankelevich, F. Zhou, Y. Sun, N. Ghata, R. Aldredge, and L. Marcu, “Design, construction, and validation of a rotary multifunctional intravascular diagnostic catheter combining multispectral fluorescence lifetime imaging and intravascular ultrasound,” Journal of biomedical optics 17, 1060121 (2012).
[Crossref]

Alfonso-Garcia, A.

A. Alfonso-Garcia, A. K. Haudenschild, and L. Marcu, “Label-free assessment of carotid artery biochemical composition using fiber-based fluorescence lifetime imaging,” Biomedical Optics Express 9, 4064–4076 (2018).
[Crossref]

Altmann, Y.

Ameer-Beg, S.

S. Poland, A. Erdogan, N. Krstajic, J. Levitt, V. Devauges, R. Walker, D. Li, S. Ameer-Beg, and R. Henderson, “A new high-speed centre of mass method incorporating background subtraction for accurate determination of fluorescence lifetime,” Optics Express 24, 6899–6915 (2016).
[Crossref]

N. Krstajić, S. Poland, J. Levitt, R. Walker, A. Erdogan, S. Ameer-Beg, and R. K. Henderson, “0.5 billion events per second time correlated single photon counting using cmos spad arrays,” Opt. Lett. 40, 4305–4308 (2015).
[Crossref]

Aslam, T.

A. R. Akram, S. V. Chankeshwara, E. Scholefield, T. Aslam, N. McDonald, A. Megia-Fernandez, A. Marshall, B. Mills, N. Avlonitis, T. H. Craven, A. M. Smyth, D. S. Collie, C. Gray, N. Hirani, A. T. Hill, J. R. Govan, T. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “In situ identification of gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid a,” Science Translational Medicine 10, eaal0033(2018).
[Crossref] [PubMed]

Avlonitis, N.

A. R. Akram, S. V. Chankeshwara, E. Scholefield, T. Aslam, N. McDonald, A. Megia-Fernandez, A. Marshall, B. Mills, N. Avlonitis, T. H. Craven, A. M. Smyth, D. S. Collie, C. Gray, N. Hirani, A. T. Hill, J. R. Govan, T. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “In situ identification of gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid a,” Science Translational Medicine 10, eaal0033(2018).
[Crossref] [PubMed]

T. H. Craven, N. Avlonitis, N. McDonald, T. Walton, E. Scholefield, A. R. Akram, T. S. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “Super-silent fret sensor enables live cell imaging and flow cytometric stratification of intracellular serine protease activity in neutrophils,” Scientific reports 8, 13490 (2018).
[Crossref] [PubMed]

Barry, N. P.

E. Gratton, S. Breusegem, J. D. Sutin, Q. Ruan, and N. P. Barry, “Fluorescence lifetime imaging for the two-photon microscope: time-domain and frequency-domain methods,” Journal of biomedical optics 8, 381–391 (2003).
[Crossref] [PubMed]

Bec, J.

D. R. Yankelevich, D. Ma, J. Liu, Y. Sun, Y. Sun, J. Bec, D. S. Elson, and L. Marcu, “Design and evaluation of a device for fast multispectral time-resolved fluorescence spectroscopy and imaging,” Review of Scientific Instruments 85, 034303 (2014).
[Crossref] [PubMed]

J. Bec, H. Xie, D. R. Yankelevich, F. Zhou, Y. Sun, N. Ghata, R. Aldredge, and L. Marcu, “Design, construction, and validation of a rotary multifunctional intravascular diagnostic catheter combining multispectral fluorescence lifetime imaging and intravascular ultrasound,” Journal of biomedical optics 17, 1060121 (2012).
[Crossref]

Becker, W.

W. Becker, Advanced time-correlated single photon counting techniques, vol. 81 (SpringerScience & Business Media, 2005).
[Crossref]

Behnel, S.

S. Behnel, R. Bradshaw, C. Citro, L. Dalcin, D. S. Seljebotn, and K. Smith, “Cython: The best of both worlds,” Computing in Science & Engineering 13, 31–39 (2011).
[Crossref]

Borghetti, F.

J. Richardson, R. Walker, L. Grant, D. Stoppa, F. Borghetti, E. Charbon, M. Gersbach, and R. K. Henderson, “A 32× 32 50ps resolution 10 bit time to digital converter array in 130nm cmos for time correlated imaging,” in Custom Integrated Circuits Conference, 2009. CICC’09. IEEE, (IEEE, 2009), pp. 77–80.

Bradley, M.

N. Krstajić, B. Mills, I. Murray, A. Marshall, D. Norberg, T. H. Craven, P. Emanuel, T. R. Choudhary, G. O. S. Williams, E. Scholefield, A. R. Akram, A. Davie, N. Hirani, A. Bruce, A. Moore, M. Bradley, and K. Dhaliwal, “Low-cost high sensitivity pulsed endomicroscopy to visualize tricolor optical signatures,” Journal of Biomedical Optics 23, 076005 (2018).
[Crossref]

T. H. Craven, N. Avlonitis, N. McDonald, T. Walton, E. Scholefield, A. R. Akram, T. S. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “Super-silent fret sensor enables live cell imaging and flow cytometric stratification of intracellular serine protease activity in neutrophils,” Scientific reports 8, 13490 (2018).
[Crossref] [PubMed]

A. R. Akram, S. V. Chankeshwara, E. Scholefield, T. Aslam, N. McDonald, A. Megia-Fernandez, A. Marshall, B. Mills, N. Avlonitis, T. H. Craven, A. M. Smyth, D. S. Collie, C. Gray, N. Hirani, A. T. Hill, J. R. Govan, T. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “In situ identification of gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid a,” Science Translational Medicine 10, eaal0033(2018).
[Crossref] [PubMed]

A. Megia-Fernandez, B. Mills, C. Michels, S. V. Chankeshwara, K. Dhaliwal, and M. Bradley, “Highly selective and rapidly activatable fluorogenic thrombin sensors and application in human lung tissue,” Organic & biomolecular chemistry 15, 4344–4350 (2017).
[Crossref]

N. Krstajić, A. R. Akram, T. R. Choudhary, N. McDonald, M. G. Tanner, E. Pedretti, P. A. Dalgarno, E. Scholefield, J. M. Girkin, A. Moore, M. Bradley, and K. Dhaliwal, “Two-color widefield fluorescence microendoscopy enables multiplexed molecular imaging in the alveolar space of human lung tissue,” Journal of Biomedical Optics 21, 046009 (2016).
[Crossref]

T. R. Choudhary, M. Bradley, R. R. Duncan, and K. Dhaliwal, “Towards in vivo bacterial detection in human lung (conference presentation),” in Optical Techniques in Pulmonary Medicine II, (Proc. SPIE 10041, 2017), p. 100410M.

T. R. Choudhary, M. G. Tanner, A. Megia-Fernandez, K. Harrington, H. A. Wood, S. Chankeshwara, P. Zhu, D. Choudhury, F. Yu, R. R. Thomson, R. R. Duncan, K. Dhaliwal, and M. Bradley, “Multiplexed fibre optic sensing in the distal lung (conference presentation),” in Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications XVII, (Proc. SPIE 10058, 2017), p. 100580E.

Bradshaw, R.

S. Behnel, R. Bradshaw, C. Citro, L. Dalcin, D. S. Seljebotn, and K. Smith, “Cython: The best of both worlds,” Computing in Science & Engineering 13, 31–39 (2011).
[Crossref]

Breusegem, S.

E. Gratton, S. Breusegem, J. D. Sutin, Q. Ruan, and N. P. Barry, “Fluorescence lifetime imaging for the two-photon microscope: time-domain and frequency-domain methods,” Journal of biomedical optics 8, 381–391 (2003).
[Crossref] [PubMed]

Bruce, A.

N. Krstajić, B. Mills, I. Murray, A. Marshall, D. Norberg, T. H. Craven, P. Emanuel, T. R. Choudhary, G. O. S. Williams, E. Scholefield, A. R. Akram, A. Davie, N. Hirani, A. Bruce, A. Moore, M. Bradley, and K. Dhaliwal, “Low-cost high sensitivity pulsed endomicroscopy to visualize tricolor optical signatures,” Journal of Biomedical Optics 23, 076005 (2018).
[Crossref]

Ceccarelli, F.

F. Ceccarelli, A. Gulinatti, I. Labanca, I. Rech, and M. Ghioni, “Development and characterization of an 8x8 spad-array module for gigacount per second applications,” in Photon Counting Applications 2017, (Proc. SPIE 10229, 2017), p. 102290E.

Chankeshwara, S.

T. R. Choudhary, M. G. Tanner, A. Megia-Fernandez, K. Harrington, H. A. Wood, S. Chankeshwara, P. Zhu, D. Choudhury, F. Yu, R. R. Thomson, R. R. Duncan, K. Dhaliwal, and M. Bradley, “Multiplexed fibre optic sensing in the distal lung (conference presentation),” in Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications XVII, (Proc. SPIE 10058, 2017), p. 100580E.

Chankeshwara, S. V.

A. R. Akram, S. V. Chankeshwara, E. Scholefield, T. Aslam, N. McDonald, A. Megia-Fernandez, A. Marshall, B. Mills, N. Avlonitis, T. H. Craven, A. M. Smyth, D. S. Collie, C. Gray, N. Hirani, A. T. Hill, J. R. Govan, T. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “In situ identification of gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid a,” Science Translational Medicine 10, eaal0033(2018).
[Crossref] [PubMed]

A. Megia-Fernandez, B. Mills, C. Michels, S. V. Chankeshwara, K. Dhaliwal, and M. Bradley, “Highly selective and rapidly activatable fluorogenic thrombin sensors and application in human lung tissue,” Organic & biomolecular chemistry 15, 4344–4350 (2017).
[Crossref]

Charbon, E.

J. Richardson, R. Walker, L. Grant, D. Stoppa, F. Borghetti, E. Charbon, M. Gersbach, and R. K. Henderson, “A 32× 32 50ps resolution 10 bit time to digital converter array in 130nm cmos for time correlated imaging,” in Custom Integrated Circuits Conference, 2009. CICC’09. IEEE, (IEEE, 2009), pp. 77–80.

Choudhary, T. R.

N. Krstajić, B. Mills, I. Murray, A. Marshall, D. Norberg, T. H. Craven, P. Emanuel, T. R. Choudhary, G. O. S. Williams, E. Scholefield, A. R. Akram, A. Davie, N. Hirani, A. Bruce, A. Moore, M. Bradley, and K. Dhaliwal, “Low-cost high sensitivity pulsed endomicroscopy to visualize tricolor optical signatures,” Journal of Biomedical Optics 23, 076005 (2018).
[Crossref]

N. Krstajić, A. R. Akram, T. R. Choudhary, N. McDonald, M. G. Tanner, E. Pedretti, P. A. Dalgarno, E. Scholefield, J. M. Girkin, A. Moore, M. Bradley, and K. Dhaliwal, “Two-color widefield fluorescence microendoscopy enables multiplexed molecular imaging in the alveolar space of human lung tissue,” Journal of Biomedical Optics 21, 046009 (2016).
[Crossref]

T. R. Choudhary, M. Bradley, R. R. Duncan, and K. Dhaliwal, “Towards in vivo bacterial detection in human lung (conference presentation),” in Optical Techniques in Pulmonary Medicine II, (Proc. SPIE 10041, 2017), p. 100410M.

T. R. Choudhary, M. G. Tanner, A. Megia-Fernandez, K. Harrington, H. A. Wood, S. Chankeshwara, P. Zhu, D. Choudhury, F. Yu, R. R. Thomson, R. R. Duncan, K. Dhaliwal, and M. Bradley, “Multiplexed fibre optic sensing in the distal lung (conference presentation),” in Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications XVII, (Proc. SPIE 10058, 2017), p. 100580E.

Choudhury, D.

T. R. Choudhary, M. G. Tanner, A. Megia-Fernandez, K. Harrington, H. A. Wood, S. Chankeshwara, P. Zhu, D. Choudhury, F. Yu, R. R. Thomson, R. R. Duncan, K. Dhaliwal, and M. Bradley, “Multiplexed fibre optic sensing in the distal lung (conference presentation),” in Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications XVII, (Proc. SPIE 10058, 2017), p. 100580E.

Chuang, F. S.

Y. Sun, J. Phipps, D. S. Elson, H. Stoy, S. Tinling, J. Meier, B. Poirier, F. S. Chuang, D. G. Farwell, and L. Marcu, “Fluorescence lifetime imaging microscopy: in vivo application to diagnosis of oral carcinoma,” Optics letters 34, 2081–2083 (2009).
[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,” Proceedings of the National Academy of Sciences 108, 13582–13587 (2011).
[Crossref]

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,” Proceedings of the National Academy of Sciences 108, 13582–13587 (2011).
[Crossref]

Citro, C.

S. Behnel, R. Bradshaw, C. Citro, L. Dalcin, D. S. Seljebotn, and K. Smith, “Cython: The best of both worlds,” Computing in Science & Engineering 13, 31–39 (2011).
[Crossref]

Collie, D. S.

A. R. Akram, S. V. Chankeshwara, E. Scholefield, T. Aslam, N. McDonald, A. Megia-Fernandez, A. Marshall, B. Mills, N. Avlonitis, T. H. Craven, A. M. Smyth, D. S. Collie, C. Gray, N. Hirani, A. T. Hill, J. R. Govan, T. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “In situ identification of gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid a,” Science Translational Medicine 10, eaal0033(2018).
[Crossref] [PubMed]

Craven, T. H.

A. R. Akram, S. V. Chankeshwara, E. Scholefield, T. Aslam, N. McDonald, A. Megia-Fernandez, A. Marshall, B. Mills, N. Avlonitis, T. H. Craven, A. M. Smyth, D. S. Collie, C. Gray, N. Hirani, A. T. Hill, J. R. Govan, T. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “In situ identification of gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid a,” Science Translational Medicine 10, eaal0033(2018).
[Crossref] [PubMed]

N. Krstajić, B. Mills, I. Murray, A. Marshall, D. Norberg, T. H. Craven, P. Emanuel, T. R. Choudhary, G. O. S. Williams, E. Scholefield, A. R. Akram, A. Davie, N. Hirani, A. Bruce, A. Moore, M. Bradley, and K. Dhaliwal, “Low-cost high sensitivity pulsed endomicroscopy to visualize tricolor optical signatures,” Journal of Biomedical Optics 23, 076005 (2018).
[Crossref]

T. H. Craven, N. Avlonitis, N. McDonald, T. Walton, E. Scholefield, A. R. Akram, T. S. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “Super-silent fret sensor enables live cell imaging and flow cytometric stratification of intracellular serine protease activity in neutrophils,” Scientific reports 8, 13490 (2018).
[Crossref] [PubMed]

Dalcin, L.

S. Behnel, R. Bradshaw, C. Citro, L. Dalcin, D. S. Seljebotn, and K. Smith, “Cython: The best of both worlds,” Computing in Science & Engineering 13, 31–39 (2011).
[Crossref]

Dalgarno, P. A.

N. Krstajić, A. R. Akram, T. R. Choudhary, N. McDonald, M. G. Tanner, E. Pedretti, P. A. Dalgarno, E. Scholefield, J. M. Girkin, A. Moore, M. Bradley, and K. Dhaliwal, “Two-color widefield fluorescence microendoscopy enables multiplexed molecular imaging in the alveolar space of human lung tissue,” Journal of Biomedical Optics 21, 046009 (2016).
[Crossref]

Davie, A.

N. Krstajić, B. Mills, I. Murray, A. Marshall, D. Norberg, T. H. Craven, P. Emanuel, T. R. Choudhary, G. O. S. Williams, E. Scholefield, A. R. Akram, A. Davie, N. Hirani, A. Bruce, A. Moore, M. Bradley, and K. Dhaliwal, “Low-cost high sensitivity pulsed endomicroscopy to visualize tricolor optical signatures,” Journal of Biomedical Optics 23, 076005 (2018).
[Crossref]

Devauges, V.

S. Poland, A. Erdogan, N. Krstajic, J. Levitt, V. Devauges, R. Walker, D. Li, S. Ameer-Beg, and R. Henderson, “A new high-speed centre of mass method incorporating background subtraction for accurate determination of fluorescence lifetime,” Optics Express 24, 6899–6915 (2016).
[Crossref]

Dhaliwal, K.

N. Krstajić, B. Mills, I. Murray, A. Marshall, D. Norberg, T. H. Craven, P. Emanuel, T. R. Choudhary, G. O. S. Williams, E. Scholefield, A. R. Akram, A. Davie, N. Hirani, A. Bruce, A. Moore, M. Bradley, and K. Dhaliwal, “Low-cost high sensitivity pulsed endomicroscopy to visualize tricolor optical signatures,” Journal of Biomedical Optics 23, 076005 (2018).
[Crossref]

T. H. Craven, N. Avlonitis, N. McDonald, T. Walton, E. Scholefield, A. R. Akram, T. S. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “Super-silent fret sensor enables live cell imaging and flow cytometric stratification of intracellular serine protease activity in neutrophils,” Scientific reports 8, 13490 (2018).
[Crossref] [PubMed]

A. R. Akram, S. V. Chankeshwara, E. Scholefield, T. Aslam, N. McDonald, A. Megia-Fernandez, A. Marshall, B. Mills, N. Avlonitis, T. H. Craven, A. M. Smyth, D. S. Collie, C. Gray, N. Hirani, A. T. Hill, J. R. Govan, T. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “In situ identification of gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid a,” Science Translational Medicine 10, eaal0033(2018).
[Crossref] [PubMed]

A. Megia-Fernandez, B. Mills, C. Michels, S. V. Chankeshwara, K. Dhaliwal, and M. Bradley, “Highly selective and rapidly activatable fluorogenic thrombin sensors and application in human lung tissue,” Organic & biomolecular chemistry 15, 4344–4350 (2017).
[Crossref]

A. Perperidis, H. E. Parker, A. Karam-Eldaly, Y. Altmann, K. Dhaliwal, R. R. Thomson, M. G. Tanner, and S. McLaughlin, “Characterization and modelling of inter-core coupling in coherent fiber bundles,” Opt. Express 25, 11932–11953 (2017).
[Crossref] [PubMed]

N. Krstajić, A. R. Akram, T. R. Choudhary, N. McDonald, M. G. Tanner, E. Pedretti, P. A. Dalgarno, E. Scholefield, J. M. Girkin, A. Moore, M. Bradley, and K. Dhaliwal, “Two-color widefield fluorescence microendoscopy enables multiplexed molecular imaging in the alveolar space of human lung tissue,” Journal of Biomedical Optics 21, 046009 (2016).
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A. Perperidis, K. Dhaliwal, S. McLaughlin, and T. Vercauteren, “Image computing for fibre-bundle endomicroscopy: A review,” ArXiv e-prints (2018).

T. R. Choudhary, M. Bradley, R. R. Duncan, and K. Dhaliwal, “Towards in vivo bacterial detection in human lung (conference presentation),” in Optical Techniques in Pulmonary Medicine II, (Proc. SPIE 10041, 2017), p. 100410M.

T. R. Choudhary, M. G. Tanner, A. Megia-Fernandez, K. Harrington, H. A. Wood, S. Chankeshwara, P. Zhu, D. Choudhury, F. Yu, R. R. Thomson, R. R. Duncan, K. Dhaliwal, and M. Bradley, “Multiplexed fibre optic sensing in the distal lung (conference presentation),” in Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications XVII, (Proc. SPIE 10058, 2017), p. 100580E.

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,” Proceedings of the National Academy of Sciences 108, 13582–13587 (2011).
[Crossref]

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,” Proceedings of the National Academy of Sciences 108, 13582–13587 (2011).
[Crossref]

Duncan, R. R.

T. R. Choudhary, M. Bradley, R. R. Duncan, and K. Dhaliwal, “Towards in vivo bacterial detection in human lung (conference presentation),” in Optical Techniques in Pulmonary Medicine II, (Proc. SPIE 10041, 2017), p. 100410M.

T. R. Choudhary, M. G. Tanner, A. Megia-Fernandez, K. Harrington, H. A. Wood, S. Chankeshwara, P. Zhu, D. Choudhury, F. Yu, R. R. Thomson, R. R. Duncan, K. Dhaliwal, and M. Bradley, “Multiplexed fibre optic sensing in the distal lung (conference presentation),” in Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications XVII, (Proc. SPIE 10058, 2017), p. 100580E.

Dunsby, C.

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

Elson, D.

G. Kennedy, H. Manning, D. Elson, M. Neil, G. Stamp, B. Viellerobe, F. Lacombe, C. Dunsby, and P. French, “A fluorescence lifetime imaging scanning confocal endomicroscope,” Journal of Biophotonics 3, 103–107 (2010).
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Elson, D. S.

D. R. Yankelevich, D. Ma, J. Liu, Y. Sun, Y. Sun, J. Bec, D. S. Elson, and L. Marcu, “Design and evaluation of a device for fast multispectral time-resolved fluorescence spectroscopy and imaging,” Review of Scientific Instruments 85, 034303 (2014).
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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,” Microscopy and Microanalysis 19, 791–798 (2013).
[Crossref] [PubMed]

Y. Sun, J. Phipps, D. S. Elson, H. Stoy, S. Tinling, J. Meier, B. Poirier, F. S. Chuang, D. G. Farwell, and L. Marcu, “Fluorescence lifetime imaging microscopy: in vivo application to diagnosis of oral carcinoma,” Optics letters 34, 2081–2083 (2009).
[Crossref] [PubMed]

Y. Sun, R. Liu, D. S. Elson, C. W. Hollars, J. A. Jo, J. Park, Y. Sun, and L. Marcu, “Simultaneous time-and wavelength-resolved fluorescence spectroscopy for near real-time tissue diagnosis,” Optics letters 33, 630–632 (2008).
[Crossref]

Emanuel, P.

N. Krstajić, B. Mills, I. Murray, A. Marshall, D. Norberg, T. H. Craven, P. Emanuel, T. R. Choudhary, G. O. S. Williams, E. Scholefield, A. R. Akram, A. Davie, N. Hirani, A. Bruce, A. Moore, M. Bradley, and K. Dhaliwal, “Low-cost high sensitivity pulsed endomicroscopy to visualize tricolor optical signatures,” Journal of Biomedical Optics 23, 076005 (2018).
[Crossref]

Erdogan, A.

S. Poland, A. Erdogan, N. Krstajic, J. Levitt, V. Devauges, R. Walker, D. Li, S. Ameer-Beg, and R. Henderson, “A new high-speed centre of mass method incorporating background subtraction for accurate determination of fluorescence lifetime,” Optics Express 24, 6899–6915 (2016).
[Crossref]

N. Krstajić, S. Poland, J. Levitt, R. Walker, A. Erdogan, S. Ameer-Beg, and R. K. Henderson, “0.5 billion events per second time correlated single photon counting using cmos spad arrays,” Opt. Lett. 40, 4305–4308 (2015).
[Crossref]

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,” Microscopy and Microanalysis 19, 791–798 (2013).
[Crossref] [PubMed]

Y. Sun, J. Phipps, D. S. Elson, H. Stoy, S. Tinling, J. Meier, B. Poirier, F. S. Chuang, D. G. Farwell, and L. Marcu, “Fluorescence lifetime imaging microscopy: in vivo application to diagnosis of oral carcinoma,” Optics letters 34, 2081–2083 (2009).
[Crossref] [PubMed]

French, P.

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

Gersbach, M.

J. Richardson, R. Walker, L. Grant, D. Stoppa, F. Borghetti, E. Charbon, M. Gersbach, and R. K. Henderson, “A 32× 32 50ps resolution 10 bit time to digital converter array in 130nm cmos for time correlated imaging,” in Custom Integrated Circuits Conference, 2009. CICC’09. IEEE, (IEEE, 2009), pp. 77–80.

Ghata, N.

J. Bec, H. Xie, D. R. Yankelevich, F. Zhou, Y. Sun, N. Ghata, R. Aldredge, and L. Marcu, “Design, construction, and validation of a rotary multifunctional intravascular diagnostic catheter combining multispectral fluorescence lifetime imaging and intravascular ultrasound,” Journal of biomedical optics 17, 1060121 (2012).
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Ghioni, M.

F. Ceccarelli, A. Gulinatti, I. Labanca, I. Rech, and M. Ghioni, “Development and characterization of an 8x8 spad-array module for gigacount per second applications,” in Photon Counting Applications 2017, (Proc. SPIE 10229, 2017), p. 102290E.

Girkin, J. M.

N. Krstajić, A. R. Akram, T. R. Choudhary, N. McDonald, M. G. Tanner, E. Pedretti, P. A. Dalgarno, E. Scholefield, J. M. Girkin, A. Moore, M. Bradley, and K. Dhaliwal, “Two-color widefield fluorescence microendoscopy enables multiplexed molecular imaging in the alveolar space of human lung tissue,” Journal of Biomedical Optics 21, 046009 (2016).
[Crossref]

Govan, J. R.

A. R. Akram, S. V. Chankeshwara, E. Scholefield, T. Aslam, N. McDonald, A. Megia-Fernandez, A. Marshall, B. Mills, N. Avlonitis, T. H. Craven, A. M. Smyth, D. S. Collie, C. Gray, N. Hirani, A. T. Hill, J. R. Govan, T. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “In situ identification of gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid a,” Science Translational Medicine 10, eaal0033(2018).
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Granger, B. E.

F. Pérez and B. E. Granger, “IPython: a system for interactive scientific computing,” Computing in Science and Engineering 9, 21–29 (2007).
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Grant, L.

J. Richardson, R. Walker, L. Grant, D. Stoppa, F. Borghetti, E. Charbon, M. Gersbach, and R. K. Henderson, “A 32× 32 50ps resolution 10 bit time to digital converter array in 130nm cmos for time correlated imaging,” in Custom Integrated Circuits Conference, 2009. CICC’09. IEEE, (IEEE, 2009), pp. 77–80.

Gratton, E.

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,” Proceedings of the National Academy of Sciences 108, 13582–13587 (2011).
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E. Gratton, S. Breusegem, J. D. Sutin, Q. Ruan, and N. P. Barry, “Fluorescence lifetime imaging for the two-photon microscope: time-domain and frequency-domain methods,” Journal of biomedical optics 8, 381–391 (2003).
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Gray, C.

A. R. Akram, S. V. Chankeshwara, E. Scholefield, T. Aslam, N. McDonald, A. Megia-Fernandez, A. Marshall, B. Mills, N. Avlonitis, T. H. Craven, A. M. Smyth, D. S. Collie, C. Gray, N. Hirani, A. T. Hill, J. R. Govan, T. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “In situ identification of gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid a,” Science Translational Medicine 10, eaal0033(2018).
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Greisen, E. W.

D. C. Wells, E. W. Greisen, and R. H. Harten, “FITS - a Flexible Image Transport System,” A&AS 44, 363 (1981).

Gulinatti, A.

F. Ceccarelli, A. Gulinatti, I. Labanca, I. Rech, and M. Ghioni, “Development and characterization of an 8x8 spad-array module for gigacount per second applications,” in Photon Counting Applications 2017, (Proc. SPIE 10229, 2017), p. 102290E.

Harrington, K.

T. R. Choudhary, M. G. Tanner, A. Megia-Fernandez, K. Harrington, H. A. Wood, S. Chankeshwara, P. Zhu, D. Choudhury, F. Yu, R. R. Thomson, R. R. Duncan, K. Dhaliwal, and M. Bradley, “Multiplexed fibre optic sensing in the distal lung (conference presentation),” in Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications XVII, (Proc. SPIE 10058, 2017), p. 100580E.

Harten, R. H.

D. C. Wells, E. W. Greisen, and R. H. Harten, “FITS - a Flexible Image Transport System,” A&AS 44, 363 (1981).

Haslett, C.

A. R. Akram, S. V. Chankeshwara, E. Scholefield, T. Aslam, N. McDonald, A. Megia-Fernandez, A. Marshall, B. Mills, N. Avlonitis, T. H. Craven, A. M. Smyth, D. S. Collie, C. Gray, N. Hirani, A. T. Hill, J. R. Govan, T. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “In situ identification of gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid a,” Science Translational Medicine 10, eaal0033(2018).
[Crossref] [PubMed]

T. H. Craven, N. Avlonitis, N. McDonald, T. Walton, E. Scholefield, A. R. Akram, T. S. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “Super-silent fret sensor enables live cell imaging and flow cytometric stratification of intracellular serine protease activity in neutrophils,” Scientific reports 8, 13490 (2018).
[Crossref] [PubMed]

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,” Microscopy and Microanalysis 19, 791–798 (2013).
[Crossref] [PubMed]

Haudenschild, A. K.

A. Alfonso-Garcia, A. K. Haudenschild, and L. Marcu, “Label-free assessment of carotid artery biochemical composition using fiber-based fluorescence lifetime imaging,” Biomedical Optics Express 9, 4064–4076 (2018).
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Henderson, R.

S. Poland, A. Erdogan, N. Krstajic, J. Levitt, V. Devauges, R. Walker, D. Li, S. Ameer-Beg, and R. Henderson, “A new high-speed centre of mass method incorporating background subtraction for accurate determination of fluorescence lifetime,” Optics Express 24, 6899–6915 (2016).
[Crossref]

Henderson, R. K.

N. Krstajić, S. Poland, J. Levitt, R. Walker, A. Erdogan, S. Ameer-Beg, and R. K. Henderson, “0.5 billion events per second time correlated single photon counting using cmos spad arrays,” Opt. Lett. 40, 4305–4308 (2015).
[Crossref]

J. Richardson, R. Walker, L. Grant, D. Stoppa, F. Borghetti, E. Charbon, M. Gersbach, and R. K. Henderson, “A 32× 32 50ps resolution 10 bit time to digital converter array in 130nm cmos for time correlated imaging,” in Custom Integrated Circuits Conference, 2009. CICC’09. IEEE, (IEEE, 2009), pp. 77–80.

Hill, A. T.

A. R. Akram, S. V. Chankeshwara, E. Scholefield, T. Aslam, N. McDonald, A. Megia-Fernandez, A. Marshall, B. Mills, N. Avlonitis, T. H. Craven, A. M. Smyth, D. S. Collie, C. Gray, N. Hirani, A. T. Hill, J. R. Govan, T. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “In situ identification of gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid a,” Science Translational Medicine 10, eaal0033(2018).
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Hirani, N.

A. R. Akram, S. V. Chankeshwara, E. Scholefield, T. Aslam, N. McDonald, A. Megia-Fernandez, A. Marshall, B. Mills, N. Avlonitis, T. H. Craven, A. M. Smyth, D. S. Collie, C. Gray, N. Hirani, A. T. Hill, J. R. Govan, T. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “In situ identification of gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid a,” Science Translational Medicine 10, eaal0033(2018).
[Crossref] [PubMed]

N. Krstajić, B. Mills, I. Murray, A. Marshall, D. Norberg, T. H. Craven, P. Emanuel, T. R. Choudhary, G. O. S. Williams, E. Scholefield, A. R. Akram, A. Davie, N. Hirani, A. Bruce, A. Moore, M. Bradley, and K. Dhaliwal, “Low-cost high sensitivity pulsed endomicroscopy to visualize tricolor optical signatures,” Journal of Biomedical Optics 23, 076005 (2018).
[Crossref]

Hollars, C. W.

Y. Sun, R. Liu, D. S. Elson, C. W. Hollars, J. A. Jo, J. Park, Y. Sun, and L. Marcu, “Simultaneous time-and wavelength-resolved fluorescence spectroscopy for near real-time tissue diagnosis,” Optics letters 33, 630–632 (2008).
[Crossref]

Hunter, J. D.

J. D. Hunter, “Matplotlib: A 2d graphics environment,” Computing In Science & Engineering 9, 90–95 (2007).
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Jo, J. A.

Y. Sun, R. Liu, D. S. Elson, C. W. Hollars, J. A. Jo, J. Park, Y. Sun, and L. Marcu, “Simultaneous time-and wavelength-resolved fluorescence spectroscopy for near real-time tissue diagnosis,” Optics letters 33, 630–632 (2008).
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Jones, E.

E. Jones, T. Oliphant, and P. Peterson, “Scipy: Open source scientific tools for python,” (2001).

Karam-Eldaly, A.

Kennedy, G.

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

Krstajic, N.

N. Krstajić, B. Mills, I. Murray, A. Marshall, D. Norberg, T. H. Craven, P. Emanuel, T. R. Choudhary, G. O. S. Williams, E. Scholefield, A. R. Akram, A. Davie, N. Hirani, A. Bruce, A. Moore, M. Bradley, and K. Dhaliwal, “Low-cost high sensitivity pulsed endomicroscopy to visualize tricolor optical signatures,” Journal of Biomedical Optics 23, 076005 (2018).
[Crossref]

N. Krstajić, A. R. Akram, T. R. Choudhary, N. McDonald, M. G. Tanner, E. Pedretti, P. A. Dalgarno, E. Scholefield, J. M. Girkin, A. Moore, M. Bradley, and K. Dhaliwal, “Two-color widefield fluorescence microendoscopy enables multiplexed molecular imaging in the alveolar space of human lung tissue,” Journal of Biomedical Optics 21, 046009 (2016).
[Crossref]

S. Poland, A. Erdogan, N. Krstajic, J. Levitt, V. Devauges, R. Walker, D. Li, S. Ameer-Beg, and R. Henderson, “A new high-speed centre of mass method incorporating background subtraction for accurate determination of fluorescence lifetime,” Optics Express 24, 6899–6915 (2016).
[Crossref]

N. Krstajić, S. Poland, J. Levitt, R. Walker, A. Erdogan, S. Ameer-Beg, and R. K. Henderson, “0.5 billion events per second time correlated single photon counting using cmos spad arrays,” Opt. Lett. 40, 4305–4308 (2015).
[Crossref]

Labanca, I.

F. Ceccarelli, A. Gulinatti, I. Labanca, I. Rech, and M. Ghioni, “Development and characterization of an 8x8 spad-array module for gigacount per second applications,” in Photon Counting Applications 2017, (Proc. SPIE 10229, 2017), p. 102290E.

Lacombe, F.

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

Levitt, J.

S. Poland, A. Erdogan, N. Krstajic, J. Levitt, V. Devauges, R. Walker, D. Li, S. Ameer-Beg, and R. Henderson, “A new high-speed centre of mass method incorporating background subtraction for accurate determination of fluorescence lifetime,” Optics Express 24, 6899–6915 (2016).
[Crossref]

N. Krstajić, S. Poland, J. Levitt, R. Walker, A. Erdogan, S. Ameer-Beg, and R. K. Henderson, “0.5 billion events per second time correlated single photon counting using cmos spad arrays,” Opt. Lett. 40, 4305–4308 (2015).
[Crossref]

Li, D.

S. Poland, A. Erdogan, N. Krstajic, J. Levitt, V. Devauges, R. Walker, D. Li, S. Ameer-Beg, and R. Henderson, “A new high-speed centre of mass method incorporating background subtraction for accurate determination of fluorescence lifetime,” Optics Express 24, 6899–6915 (2016).
[Crossref]

Liu, J.

D. R. Yankelevich, D. Ma, J. Liu, Y. Sun, Y. Sun, J. Bec, D. S. Elson, and L. Marcu, “Design and evaluation of a device for fast multispectral time-resolved fluorescence spectroscopy and imaging,” Review of Scientific Instruments 85, 034303 (2014).
[Crossref] [PubMed]

Liu, R.

Y. Sun, R. Liu, D. S. Elson, C. W. Hollars, J. A. Jo, J. Park, Y. Sun, and L. Marcu, “Simultaneous time-and wavelength-resolved fluorescence spectroscopy for near real-time tissue diagnosis,” Optics letters 33, 630–632 (2008).
[Crossref]

Ma, D.

D. R. Yankelevich, D. Ma, J. Liu, Y. Sun, Y. Sun, J. Bec, D. S. Elson, and L. Marcu, “Design and evaluation of a device for fast multispectral time-resolved fluorescence spectroscopy and imaging,” Review of Scientific Instruments 85, 034303 (2014).
[Crossref] [PubMed]

Manning, H.

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

Marcu, L.

A. Alfonso-Garcia, A. K. Haudenschild, and L. Marcu, “Label-free assessment of carotid artery biochemical composition using fiber-based fluorescence lifetime imaging,” Biomedical Optics Express 9, 4064–4076 (2018).
[Crossref]

D. R. Yankelevich, D. Ma, J. Liu, Y. Sun, Y. Sun, J. Bec, D. S. Elson, and L. Marcu, “Design and evaluation of a device for fast multispectral time-resolved fluorescence spectroscopy and imaging,” Review of Scientific Instruments 85, 034303 (2014).
[Crossref] [PubMed]

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,” Microscopy and Microanalysis 19, 791–798 (2013).
[Crossref] [PubMed]

J. Bec, H. Xie, D. R. Yankelevich, F. Zhou, Y. Sun, N. Ghata, R. Aldredge, and L. Marcu, “Design, construction, and validation of a rotary multifunctional intravascular diagnostic catheter combining multispectral fluorescence lifetime imaging and intravascular ultrasound,” Journal of biomedical optics 17, 1060121 (2012).
[Crossref]

Y. Sun, J. Phipps, D. S. Elson, H. Stoy, S. Tinling, J. Meier, B. Poirier, F. S. Chuang, D. G. Farwell, and L. Marcu, “Fluorescence lifetime imaging microscopy: in vivo application to diagnosis of oral carcinoma,” Optics letters 34, 2081–2083 (2009).
[Crossref] [PubMed]

Y. Sun, R. Liu, D. S. Elson, C. W. Hollars, J. A. Jo, J. Park, Y. Sun, and L. Marcu, “Simultaneous time-and wavelength-resolved fluorescence spectroscopy for near real-time tissue diagnosis,” Optics letters 33, 630–632 (2008).
[Crossref]

Marshall, A.

A. R. Akram, S. V. Chankeshwara, E. Scholefield, T. Aslam, N. McDonald, A. Megia-Fernandez, A. Marshall, B. Mills, N. Avlonitis, T. H. Craven, A. M. Smyth, D. S. Collie, C. Gray, N. Hirani, A. T. Hill, J. R. Govan, T. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “In situ identification of gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid a,” Science Translational Medicine 10, eaal0033(2018).
[Crossref] [PubMed]

N. Krstajić, B. Mills, I. Murray, A. Marshall, D. Norberg, T. H. Craven, P. Emanuel, T. R. Choudhary, G. O. S. Williams, E. Scholefield, A. R. Akram, A. Davie, N. Hirani, A. Bruce, A. Moore, M. Bradley, and K. Dhaliwal, “Low-cost high sensitivity pulsed endomicroscopy to visualize tricolor optical signatures,” Journal of Biomedical Optics 23, 076005 (2018).
[Crossref]

McDonald, N.

T. H. Craven, N. Avlonitis, N. McDonald, T. Walton, E. Scholefield, A. R. Akram, T. S. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “Super-silent fret sensor enables live cell imaging and flow cytometric stratification of intracellular serine protease activity in neutrophils,” Scientific reports 8, 13490 (2018).
[Crossref] [PubMed]

A. R. Akram, S. V. Chankeshwara, E. Scholefield, T. Aslam, N. McDonald, A. Megia-Fernandez, A. Marshall, B. Mills, N. Avlonitis, T. H. Craven, A. M. Smyth, D. S. Collie, C. Gray, N. Hirani, A. T. Hill, J. R. Govan, T. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “In situ identification of gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid a,” Science Translational Medicine 10, eaal0033(2018).
[Crossref] [PubMed]

N. Krstajić, A. R. Akram, T. R. Choudhary, N. McDonald, M. G. Tanner, E. Pedretti, P. A. Dalgarno, E. Scholefield, J. M. Girkin, A. Moore, M. Bradley, and K. Dhaliwal, “Two-color widefield fluorescence microendoscopy enables multiplexed molecular imaging in the alveolar space of human lung tissue,” Journal of Biomedical Optics 21, 046009 (2016).
[Crossref]

McLaughlin, S.

Megia-Fernandez, A.

A. R. Akram, S. V. Chankeshwara, E. Scholefield, T. Aslam, N. McDonald, A. Megia-Fernandez, A. Marshall, B. Mills, N. Avlonitis, T. H. Craven, A. M. Smyth, D. S. Collie, C. Gray, N. Hirani, A. T. Hill, J. R. Govan, T. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “In situ identification of gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid a,” Science Translational Medicine 10, eaal0033(2018).
[Crossref] [PubMed]

A. Megia-Fernandez, B. Mills, C. Michels, S. V. Chankeshwara, K. Dhaliwal, and M. Bradley, “Highly selective and rapidly activatable fluorogenic thrombin sensors and application in human lung tissue,” Organic & biomolecular chemistry 15, 4344–4350 (2017).
[Crossref]

T. R. Choudhary, M. G. Tanner, A. Megia-Fernandez, K. Harrington, H. A. Wood, S. Chankeshwara, P. Zhu, D. Choudhury, F. Yu, R. R. Thomson, R. R. Duncan, K. Dhaliwal, and M. Bradley, “Multiplexed fibre optic sensing in the distal lung (conference presentation),” in Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications XVII, (Proc. SPIE 10058, 2017), p. 100580E.

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,” Microscopy and Microanalysis 19, 791–798 (2013).
[Crossref] [PubMed]

Y. Sun, J. Phipps, D. S. Elson, H. Stoy, S. Tinling, J. Meier, B. Poirier, F. S. Chuang, D. G. Farwell, and L. Marcu, “Fluorescence lifetime imaging microscopy: in vivo application to diagnosis of oral carcinoma,” Optics letters 34, 2081–2083 (2009).
[Crossref] [PubMed]

Michels, C.

A. Megia-Fernandez, B. Mills, C. Michels, S. V. Chankeshwara, K. Dhaliwal, and M. Bradley, “Highly selective and rapidly activatable fluorogenic thrombin sensors and application in human lung tissue,” Organic & biomolecular chemistry 15, 4344–4350 (2017).
[Crossref]

Mills, B.

N. Krstajić, B. Mills, I. Murray, A. Marshall, D. Norberg, T. H. Craven, P. Emanuel, T. R. Choudhary, G. O. S. Williams, E. Scholefield, A. R. Akram, A. Davie, N. Hirani, A. Bruce, A. Moore, M. Bradley, and K. Dhaliwal, “Low-cost high sensitivity pulsed endomicroscopy to visualize tricolor optical signatures,” Journal of Biomedical Optics 23, 076005 (2018).
[Crossref]

A. R. Akram, S. V. Chankeshwara, E. Scholefield, T. Aslam, N. McDonald, A. Megia-Fernandez, A. Marshall, B. Mills, N. Avlonitis, T. H. Craven, A. M. Smyth, D. S. Collie, C. Gray, N. Hirani, A. T. Hill, J. R. Govan, T. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “In situ identification of gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid a,” Science Translational Medicine 10, eaal0033(2018).
[Crossref] [PubMed]

A. Megia-Fernandez, B. Mills, C. Michels, S. V. Chankeshwara, K. Dhaliwal, and M. Bradley, “Highly selective and rapidly activatable fluorogenic thrombin sensors and application in human lung tissue,” Organic & biomolecular chemistry 15, 4344–4350 (2017).
[Crossref]

Moore, A.

N. Krstajić, B. Mills, I. Murray, A. Marshall, D. Norberg, T. H. Craven, P. Emanuel, T. R. Choudhary, G. O. S. Williams, E. Scholefield, A. R. Akram, A. Davie, N. Hirani, A. Bruce, A. Moore, M. Bradley, and K. Dhaliwal, “Low-cost high sensitivity pulsed endomicroscopy to visualize tricolor optical signatures,” Journal of Biomedical Optics 23, 076005 (2018).
[Crossref]

N. Krstajić, A. R. Akram, T. R. Choudhary, N. McDonald, M. G. Tanner, E. Pedretti, P. A. Dalgarno, E. Scholefield, J. M. Girkin, A. Moore, M. Bradley, and K. Dhaliwal, “Two-color widefield fluorescence microendoscopy enables multiplexed molecular imaging in the alveolar space of human lung tissue,” Journal of Biomedical Optics 21, 046009 (2016).
[Crossref]

Murray, I.

N. Krstajić, B. Mills, I. Murray, A. Marshall, D. Norberg, T. H. Craven, P. Emanuel, T. R. Choudhary, G. O. S. Williams, E. Scholefield, A. R. Akram, A. Davie, N. Hirani, A. Bruce, A. Moore, M. Bradley, and K. Dhaliwal, “Low-cost high sensitivity pulsed endomicroscopy to visualize tricolor optical signatures,” Journal of Biomedical Optics 23, 076005 (2018).
[Crossref]

Neil, M.

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

Norberg, D.

N. Krstajić, B. Mills, I. Murray, A. Marshall, D. Norberg, T. H. Craven, P. Emanuel, T. R. Choudhary, G. O. S. Williams, E. Scholefield, A. R. Akram, A. Davie, N. Hirani, A. Bruce, A. Moore, M. Bradley, and K. Dhaliwal, “Low-cost high sensitivity pulsed endomicroscopy to visualize tricolor optical signatures,” Journal of Biomedical Optics 23, 076005 (2018).
[Crossref]

Oliphant, T.

E. Jones, T. Oliphant, and P. Peterson, “Scipy: Open source scientific tools for python,” (2001).

Park, J.

Y. Sun, R. Liu, D. S. Elson, C. W. Hollars, J. A. Jo, J. Park, Y. Sun, and L. Marcu, “Simultaneous time-and wavelength-resolved fluorescence spectroscopy for near real-time tissue diagnosis,” Optics letters 33, 630–632 (2008).
[Crossref]

Parker, H. E.

Pedretti, E.

N. Krstajić, A. R. Akram, T. R. Choudhary, N. McDonald, M. G. Tanner, E. Pedretti, P. A. Dalgarno, E. Scholefield, J. M. Girkin, A. Moore, M. Bradley, and K. Dhaliwal, “Two-color widefield fluorescence microendoscopy enables multiplexed molecular imaging in the alveolar space of human lung tissue,” Journal of Biomedical Optics 21, 046009 (2016).
[Crossref]

Pérez, F.

F. Pérez and B. E. Granger, “IPython: a system for interactive scientific computing,” Computing in Science and Engineering 9, 21–29 (2007).
[Crossref]

Periasamy, A.

H. Wallrabe and A. Periasamy, “Imaging protein molecules using fret and flim microscopy,” Current opinion in biotechnology 16, 19–27 (2005).
[Crossref] [PubMed]

Perperidis, A.

Peterson, P.

E. Jones, T. Oliphant, and P. Peterson, “Scipy: Open source scientific tools for python,” (2001).

Phipps, J.

Y. Sun, J. Phipps, D. S. Elson, H. Stoy, S. Tinling, J. Meier, B. Poirier, F. S. Chuang, D. G. Farwell, and L. Marcu, “Fluorescence lifetime imaging microscopy: in vivo application to diagnosis of oral carcinoma,” Optics letters 34, 2081–2083 (2009).
[Crossref] [PubMed]

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,” Microscopy and Microanalysis 19, 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,” Microscopy and Microanalysis 19, 791–798 (2013).
[Crossref] [PubMed]

Y. Sun, J. Phipps, D. S. Elson, H. Stoy, S. Tinling, J. Meier, B. Poirier, F. S. Chuang, D. G. Farwell, and L. Marcu, “Fluorescence lifetime imaging microscopy: in vivo application to diagnosis of oral carcinoma,” Optics letters 34, 2081–2083 (2009).
[Crossref] [PubMed]

Poland, S.

S. Poland, A. Erdogan, N. Krstajic, J. Levitt, V. Devauges, R. Walker, D. Li, S. Ameer-Beg, and R. Henderson, “A new high-speed centre of mass method incorporating background subtraction for accurate determination of fluorescence lifetime,” Optics Express 24, 6899–6915 (2016).
[Crossref]

N. Krstajić, S. Poland, J. Levitt, R. Walker, A. Erdogan, S. Ameer-Beg, and R. K. Henderson, “0.5 billion events per second time correlated single photon counting using cmos spad arrays,” Opt. Lett. 40, 4305–4308 (2015).
[Crossref]

Rech, I.

F. Ceccarelli, A. Gulinatti, I. Labanca, I. Rech, and M. Ghioni, “Development and characterization of an 8x8 spad-array module for gigacount per second applications,” in Photon Counting Applications 2017, (Proc. SPIE 10229, 2017), p. 102290E.

Richardson, J.

J. Richardson, R. Walker, L. Grant, D. Stoppa, F. Borghetti, E. Charbon, M. Gersbach, and R. K. Henderson, “A 32× 32 50ps resolution 10 bit time to digital converter array in 130nm cmos for time correlated imaging,” in Custom Integrated Circuits Conference, 2009. CICC’09. IEEE, (IEEE, 2009), pp. 77–80.

Ruan, Q.

E. Gratton, S. Breusegem, J. D. Sutin, Q. Ruan, and N. P. Barry, “Fluorescence lifetime imaging for the two-photon microscope: time-domain and frequency-domain methods,” Journal of biomedical optics 8, 381–391 (2003).
[Crossref] [PubMed]

Scholefield, E.

A. R. Akram, S. V. Chankeshwara, E. Scholefield, T. Aslam, N. McDonald, A. Megia-Fernandez, A. Marshall, B. Mills, N. Avlonitis, T. H. Craven, A. M. Smyth, D. S. Collie, C. Gray, N. Hirani, A. T. Hill, J. R. Govan, T. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “In situ identification of gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid a,” Science Translational Medicine 10, eaal0033(2018).
[Crossref] [PubMed]

T. H. Craven, N. Avlonitis, N. McDonald, T. Walton, E. Scholefield, A. R. Akram, T. S. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “Super-silent fret sensor enables live cell imaging and flow cytometric stratification of intracellular serine protease activity in neutrophils,” Scientific reports 8, 13490 (2018).
[Crossref] [PubMed]

N. Krstajić, B. Mills, I. Murray, A. Marshall, D. Norberg, T. H. Craven, P. Emanuel, T. R. Choudhary, G. O. S. Williams, E. Scholefield, A. R. Akram, A. Davie, N. Hirani, A. Bruce, A. Moore, M. Bradley, and K. Dhaliwal, “Low-cost high sensitivity pulsed endomicroscopy to visualize tricolor optical signatures,” Journal of Biomedical Optics 23, 076005 (2018).
[Crossref]

N. Krstajić, A. R. Akram, T. R. Choudhary, N. McDonald, M. G. Tanner, E. Pedretti, P. A. Dalgarno, E. Scholefield, J. M. Girkin, A. Moore, M. Bradley, and K. Dhaliwal, “Two-color widefield fluorescence microendoscopy enables multiplexed molecular imaging in the alveolar space of human lung tissue,” Journal of Biomedical Optics 21, 046009 (2016).
[Crossref]

Seljebotn, D. S.

S. Behnel, R. Bradshaw, C. Citro, L. Dalcin, D. S. Seljebotn, and K. Smith, “Cython: The best of both worlds,” Computing in Science & Engineering 13, 31–39 (2011).
[Crossref]

Smith, K.

S. Behnel, R. Bradshaw, C. Citro, L. Dalcin, D. S. Seljebotn, and K. Smith, “Cython: The best of both worlds,” Computing in Science & Engineering 13, 31–39 (2011).
[Crossref]

Smyth, A. M.

A. R. Akram, S. V. Chankeshwara, E. Scholefield, T. Aslam, N. McDonald, A. Megia-Fernandez, A. Marshall, B. Mills, N. Avlonitis, T. H. Craven, A. M. Smyth, D. S. Collie, C. Gray, N. Hirani, A. T. Hill, J. R. Govan, T. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “In situ identification of gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid a,” Science Translational Medicine 10, eaal0033(2018).
[Crossref] [PubMed]

Stamp, G.

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

Stoppa, D.

J. Richardson, R. Walker, L. Grant, D. Stoppa, F. Borghetti, E. Charbon, M. Gersbach, and R. K. Henderson, “A 32× 32 50ps resolution 10 bit time to digital converter array in 130nm cmos for time correlated imaging,” in Custom Integrated Circuits Conference, 2009. CICC’09. IEEE, (IEEE, 2009), pp. 77–80.

Stoy, H.

Y. Sun, J. Phipps, D. S. Elson, H. Stoy, S. Tinling, J. Meier, B. Poirier, F. S. Chuang, D. G. Farwell, and L. Marcu, “Fluorescence lifetime imaging microscopy: in vivo application to diagnosis of oral carcinoma,” Optics letters 34, 2081–2083 (2009).
[Crossref] [PubMed]

Stringari, C.

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,” Proceedings of the National Academy of Sciences 108, 13582–13587 (2011).
[Crossref]

Sun, Y.

D. R. Yankelevich, D. Ma, J. Liu, Y. Sun, Y. Sun, J. Bec, D. S. Elson, and L. Marcu, “Design and evaluation of a device for fast multispectral time-resolved fluorescence spectroscopy and imaging,” Review of Scientific Instruments 85, 034303 (2014).
[Crossref] [PubMed]

D. R. Yankelevich, D. Ma, J. Liu, Y. Sun, Y. Sun, J. Bec, D. S. Elson, and L. Marcu, “Design and evaluation of a device for fast multispectral time-resolved fluorescence spectroscopy and imaging,” Review of Scientific Instruments 85, 034303 (2014).
[Crossref] [PubMed]

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,” Microscopy and Microanalysis 19, 791–798 (2013).
[Crossref] [PubMed]

J. Bec, H. Xie, D. R. Yankelevich, F. Zhou, Y. Sun, N. Ghata, R. Aldredge, and L. Marcu, “Design, construction, and validation of a rotary multifunctional intravascular diagnostic catheter combining multispectral fluorescence lifetime imaging and intravascular ultrasound,” Journal of biomedical optics 17, 1060121 (2012).
[Crossref]

Y. Sun, J. Phipps, D. S. Elson, H. Stoy, S. Tinling, J. Meier, B. Poirier, F. S. Chuang, D. G. Farwell, and L. Marcu, “Fluorescence lifetime imaging microscopy: in vivo application to diagnosis of oral carcinoma,” Optics letters 34, 2081–2083 (2009).
[Crossref] [PubMed]

Y. Sun, R. Liu, D. S. Elson, C. W. Hollars, J. A. Jo, J. Park, Y. Sun, and L. Marcu, “Simultaneous time-and wavelength-resolved fluorescence spectroscopy for near real-time tissue diagnosis,” Optics letters 33, 630–632 (2008).
[Crossref]

Y. Sun, R. Liu, D. S. Elson, C. W. Hollars, J. A. Jo, J. Park, Y. Sun, and L. Marcu, “Simultaneous time-and wavelength-resolved fluorescence spectroscopy for near real-time tissue diagnosis,” Optics letters 33, 630–632 (2008).
[Crossref]

Sutin, J. D.

E. Gratton, S. Breusegem, J. D. Sutin, Q. Ruan, and N. P. Barry, “Fluorescence lifetime imaging for the two-photon microscope: time-domain and frequency-domain methods,” Journal of biomedical optics 8, 381–391 (2003).
[Crossref] [PubMed]

Tanner, M. G.

A. Perperidis, H. E. Parker, A. Karam-Eldaly, Y. Altmann, K. Dhaliwal, R. R. Thomson, M. G. Tanner, and S. McLaughlin, “Characterization and modelling of inter-core coupling in coherent fiber bundles,” Opt. Express 25, 11932–11953 (2017).
[Crossref] [PubMed]

N. Krstajić, A. R. Akram, T. R. Choudhary, N. McDonald, M. G. Tanner, E. Pedretti, P. A. Dalgarno, E. Scholefield, J. M. Girkin, A. Moore, M. Bradley, and K. Dhaliwal, “Two-color widefield fluorescence microendoscopy enables multiplexed molecular imaging in the alveolar space of human lung tissue,” Journal of Biomedical Optics 21, 046009 (2016).
[Crossref]

T. R. Choudhary, M. G. Tanner, A. Megia-Fernandez, K. Harrington, H. A. Wood, S. Chankeshwara, P. Zhu, D. Choudhury, F. Yu, R. R. Thomson, R. R. Duncan, K. Dhaliwal, and M. Bradley, “Multiplexed fibre optic sensing in the distal lung (conference presentation),” in Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications XVII, (Proc. SPIE 10058, 2017), p. 100580E.

Thomson, R. R.

A. Perperidis, H. E. Parker, A. Karam-Eldaly, Y. Altmann, K. Dhaliwal, R. R. Thomson, M. G. Tanner, and S. McLaughlin, “Characterization and modelling of inter-core coupling in coherent fiber bundles,” Opt. Express 25, 11932–11953 (2017).
[Crossref] [PubMed]

T. R. Choudhary, M. G. Tanner, A. Megia-Fernandez, K. Harrington, H. A. Wood, S. Chankeshwara, P. Zhu, D. Choudhury, F. Yu, R. R. Thomson, R. R. Duncan, K. Dhaliwal, and M. Bradley, “Multiplexed fibre optic sensing in the distal lung (conference presentation),” in Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications XVII, (Proc. SPIE 10058, 2017), p. 100580E.

Tinling, S.

Y. Sun, J. Phipps, D. S. Elson, H. Stoy, S. Tinling, J. Meier, B. Poirier, F. S. Chuang, D. G. Farwell, and L. Marcu, “Fluorescence lifetime imaging microscopy: in vivo application to diagnosis of oral carcinoma,” Optics letters 34, 2081–2083 (2009).
[Crossref] [PubMed]

Vercauteren, T.

A. Perperidis, K. Dhaliwal, S. McLaughlin, and T. Vercauteren, “Image computing for fibre-bundle endomicroscopy: A review,” ArXiv e-prints (2018).

Viellerobe, B.

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

Walker, R.

S. Poland, A. Erdogan, N. Krstajic, J. Levitt, V. Devauges, R. Walker, D. Li, S. Ameer-Beg, and R. Henderson, “A new high-speed centre of mass method incorporating background subtraction for accurate determination of fluorescence lifetime,” Optics Express 24, 6899–6915 (2016).
[Crossref]

N. Krstajić, S. Poland, J. Levitt, R. Walker, A. Erdogan, S. Ameer-Beg, and R. K. Henderson, “0.5 billion events per second time correlated single photon counting using cmos spad arrays,” Opt. Lett. 40, 4305–4308 (2015).
[Crossref]

J. Richardson, R. Walker, L. Grant, D. Stoppa, F. Borghetti, E. Charbon, M. Gersbach, and R. K. Henderson, “A 32× 32 50ps resolution 10 bit time to digital converter array in 130nm cmos for time correlated imaging,” in Custom Integrated Circuits Conference, 2009. CICC’09. IEEE, (IEEE, 2009), pp. 77–80.

Wallrabe, H.

H. Wallrabe and A. Periasamy, “Imaging protein molecules using fret and flim microscopy,” Current opinion in biotechnology 16, 19–27 (2005).
[Crossref] [PubMed]

Walsh, T.

A. R. Akram, S. V. Chankeshwara, E. Scholefield, T. Aslam, N. McDonald, A. Megia-Fernandez, A. Marshall, B. Mills, N. Avlonitis, T. H. Craven, A. M. Smyth, D. S. Collie, C. Gray, N. Hirani, A. T. Hill, J. R. Govan, T. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “In situ identification of gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid a,” Science Translational Medicine 10, eaal0033(2018).
[Crossref] [PubMed]

Walsh, T. S.

T. H. Craven, N. Avlonitis, N. McDonald, T. Walton, E. Scholefield, A. R. Akram, T. S. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “Super-silent fret sensor enables live cell imaging and flow cytometric stratification of intracellular serine protease activity in neutrophils,” Scientific reports 8, 13490 (2018).
[Crossref] [PubMed]

Walton, T.

T. H. Craven, N. Avlonitis, N. McDonald, T. Walton, E. Scholefield, A. R. Akram, T. S. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “Super-silent fret sensor enables live cell imaging and flow cytometric stratification of intracellular serine protease activity in neutrophils,” Scientific reports 8, 13490 (2018).
[Crossref] [PubMed]

Wells, D. C.

D. C. Wells, E. W. Greisen, and R. H. Harten, “FITS - a Flexible Image Transport System,” A&AS 44, 363 (1981).

Williams, G. O. S.

N. Krstajić, B. Mills, I. Murray, A. Marshall, D. Norberg, T. H. Craven, P. Emanuel, T. R. Choudhary, G. O. S. Williams, E. Scholefield, A. R. Akram, A. Davie, N. Hirani, A. Bruce, A. Moore, M. Bradley, and K. Dhaliwal, “Low-cost high sensitivity pulsed endomicroscopy to visualize tricolor optical signatures,” Journal of Biomedical Optics 23, 076005 (2018).
[Crossref]

Wood, H. A.

T. R. Choudhary, M. G. Tanner, A. Megia-Fernandez, K. Harrington, H. A. Wood, S. Chankeshwara, P. Zhu, D. Choudhury, F. Yu, R. R. Thomson, R. R. Duncan, K. Dhaliwal, and M. Bradley, “Multiplexed fibre optic sensing in the distal lung (conference presentation),” in Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications XVII, (Proc. SPIE 10058, 2017), p. 100580E.

Xie, H.

J. Bec, H. Xie, D. R. Yankelevich, F. Zhou, Y. Sun, N. Ghata, R. Aldredge, and L. Marcu, “Design, construction, and validation of a rotary multifunctional intravascular diagnostic catheter combining multispectral fluorescence lifetime imaging and intravascular ultrasound,” Journal of biomedical optics 17, 1060121 (2012).
[Crossref]

Yankelevich, D. R.

D. R. Yankelevich, D. Ma, J. Liu, Y. Sun, Y. Sun, J. Bec, D. S. Elson, and L. Marcu, “Design and evaluation of a device for fast multispectral time-resolved fluorescence spectroscopy and imaging,” Review of Scientific Instruments 85, 034303 (2014).
[Crossref] [PubMed]

J. Bec, H. Xie, D. R. Yankelevich, F. Zhou, Y. Sun, N. Ghata, R. Aldredge, and L. Marcu, “Design, construction, and validation of a rotary multifunctional intravascular diagnostic catheter combining multispectral fluorescence lifetime imaging and intravascular ultrasound,” Journal of biomedical optics 17, 1060121 (2012).
[Crossref]

Yu, F.

T. R. Choudhary, M. G. Tanner, A. Megia-Fernandez, K. Harrington, H. A. Wood, S. Chankeshwara, P. Zhu, D. Choudhury, F. Yu, R. R. Thomson, R. R. Duncan, K. Dhaliwal, and M. Bradley, “Multiplexed fibre optic sensing in the distal lung (conference presentation),” in Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications XVII, (Proc. SPIE 10058, 2017), p. 100580E.

Zhou, F.

J. Bec, H. Xie, D. R. Yankelevich, F. Zhou, Y. Sun, N. Ghata, R. Aldredge, and L. Marcu, “Design, construction, and validation of a rotary multifunctional intravascular diagnostic catheter combining multispectral fluorescence lifetime imaging and intravascular ultrasound,” Journal of biomedical optics 17, 1060121 (2012).
[Crossref]

Zhu, P.

T. R. Choudhary, M. G. Tanner, A. Megia-Fernandez, K. Harrington, H. A. Wood, S. Chankeshwara, P. Zhu, D. Choudhury, F. Yu, R. R. Thomson, R. R. Duncan, K. Dhaliwal, and M. Bradley, “Multiplexed fibre optic sensing in the distal lung (conference presentation),” in Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications XVII, (Proc. SPIE 10058, 2017), p. 100580E.

A&AS (1)

D. C. Wells, E. W. Greisen, and R. H. Harten, “FITS - a Flexible Image Transport System,” A&AS 44, 363 (1981).

Biomedical Optics Express (1)

A. Alfonso-Garcia, A. K. Haudenschild, and L. Marcu, “Label-free assessment of carotid artery biochemical composition using fiber-based fluorescence lifetime imaging,” Biomedical Optics Express 9, 4064–4076 (2018).
[Crossref]

Computing In Science & Engineering (1)

J. D. Hunter, “Matplotlib: A 2d graphics environment,” Computing In Science & Engineering 9, 90–95 (2007).
[Crossref]

S. Behnel, R. Bradshaw, C. Citro, L. Dalcin, D. S. Seljebotn, and K. Smith, “Cython: The best of both worlds,” Computing in Science & Engineering 13, 31–39 (2011).
[Crossref]

Computing in Science and Engineering (1)

F. Pérez and B. E. Granger, “IPython: a system for interactive scientific computing,” Computing in Science and Engineering 9, 21–29 (2007).
[Crossref]

Current opinion in biotechnology (1)

H. Wallrabe and A. Periasamy, “Imaging protein molecules using fret and flim microscopy,” Current opinion in biotechnology 16, 19–27 (2005).
[Crossref] [PubMed]

Journal of biomedical optics (2)

J. Bec, H. Xie, D. R. Yankelevich, F. Zhou, Y. Sun, N. Ghata, R. Aldredge, and L. Marcu, “Design, construction, and validation of a rotary multifunctional intravascular diagnostic catheter combining multispectral fluorescence lifetime imaging and intravascular ultrasound,” Journal of biomedical optics 17, 1060121 (2012).
[Crossref]

E. Gratton, S. Breusegem, J. D. Sutin, Q. Ruan, and N. P. Barry, “Fluorescence lifetime imaging for the two-photon microscope: time-domain and frequency-domain methods,” Journal of biomedical optics 8, 381–391 (2003).
[Crossref] [PubMed]

N. Krstajić, A. R. Akram, T. R. Choudhary, N. McDonald, M. G. Tanner, E. Pedretti, P. A. Dalgarno, E. Scholefield, J. M. Girkin, A. Moore, M. Bradley, and K. Dhaliwal, “Two-color widefield fluorescence microendoscopy enables multiplexed molecular imaging in the alveolar space of human lung tissue,” Journal of Biomedical Optics 21, 046009 (2016).
[Crossref]

N. Krstajić, B. Mills, I. Murray, A. Marshall, D. Norberg, T. H. Craven, P. Emanuel, T. R. Choudhary, G. O. S. Williams, E. Scholefield, A. R. Akram, A. Davie, N. Hirani, A. Bruce, A. Moore, M. Bradley, and K. Dhaliwal, “Low-cost high sensitivity pulsed endomicroscopy to visualize tricolor optical signatures,” Journal of Biomedical Optics 23, 076005 (2018).
[Crossref]

Journal of Biophotonics (1)

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

Microscopy and Microanalysis (1)

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,” Microscopy and Microanalysis 19, 791–798 (2013).
[Crossref] [PubMed]

Opt. Express (1)

Opt. Lett. (1)

Optics Express (1)

S. Poland, A. Erdogan, N. Krstajic, J. Levitt, V. Devauges, R. Walker, D. Li, S. Ameer-Beg, and R. Henderson, “A new high-speed centre of mass method incorporating background subtraction for accurate determination of fluorescence lifetime,” Optics Express 24, 6899–6915 (2016).
[Crossref]

Optics letters (2)

Y. Sun, J. Phipps, D. S. Elson, H. Stoy, S. Tinling, J. Meier, B. Poirier, F. S. Chuang, D. G. Farwell, and L. Marcu, “Fluorescence lifetime imaging microscopy: in vivo application to diagnosis of oral carcinoma,” Optics letters 34, 2081–2083 (2009).
[Crossref] [PubMed]

Y. Sun, R. Liu, D. S. Elson, C. W. Hollars, J. A. Jo, J. Park, Y. Sun, and L. Marcu, “Simultaneous time-and wavelength-resolved fluorescence spectroscopy for near real-time tissue diagnosis,” Optics letters 33, 630–632 (2008).
[Crossref]

Organic & biomolecular chemistry (1)

A. Megia-Fernandez, B. Mills, C. Michels, S. V. Chankeshwara, K. Dhaliwal, and M. Bradley, “Highly selective and rapidly activatable fluorogenic thrombin sensors and application in human lung tissue,” Organic & biomolecular chemistry 15, 4344–4350 (2017).
[Crossref]

Proceedings of the National Academy of Sciences (1)

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,” Proceedings of the National Academy of Sciences 108, 13582–13587 (2011).
[Crossref]

Review of Scientific Instruments (1)

D. R. Yankelevich, D. Ma, J. Liu, Y. Sun, Y. Sun, J. Bec, D. S. Elson, and L. Marcu, “Design and evaluation of a device for fast multispectral time-resolved fluorescence spectroscopy and imaging,” Review of Scientific Instruments 85, 034303 (2014).
[Crossref] [PubMed]

Science Translational Medicine (1)

A. R. Akram, S. V. Chankeshwara, E. Scholefield, T. Aslam, N. McDonald, A. Megia-Fernandez, A. Marshall, B. Mills, N. Avlonitis, T. H. Craven, A. M. Smyth, D. S. Collie, C. Gray, N. Hirani, A. T. Hill, J. R. Govan, T. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “In situ identification of gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid a,” Science Translational Medicine 10, eaal0033(2018).
[Crossref] [PubMed]

Scientific reports (1)

T. H. Craven, N. Avlonitis, N. McDonald, T. Walton, E. Scholefield, A. R. Akram, T. S. Walsh, C. Haslett, M. Bradley, and K. Dhaliwal, “Super-silent fret sensor enables live cell imaging and flow cytometric stratification of intracellular serine protease activity in neutrophils,” Scientific reports 8, 13490 (2018).
[Crossref] [PubMed]

Other (7)

A. Perperidis, K. Dhaliwal, S. McLaughlin, and T. Vercauteren, “Image computing for fibre-bundle endomicroscopy: A review,” ArXiv e-prints (2018).

T. R. Choudhary, M. Bradley, R. R. Duncan, and K. Dhaliwal, “Towards in vivo bacterial detection in human lung (conference presentation),” in Optical Techniques in Pulmonary Medicine II, (Proc. SPIE 10041, 2017), p. 100410M.

J. Richardson, R. Walker, L. Grant, D. Stoppa, F. Borghetti, E. Charbon, M. Gersbach, and R. K. Henderson, “A 32× 32 50ps resolution 10 bit time to digital converter array in 130nm cmos for time correlated imaging,” in Custom Integrated Circuits Conference, 2009. CICC’09. IEEE, (IEEE, 2009), pp. 77–80.

W. Becker, Advanced time-correlated single photon counting techniques, vol. 81 (SpringerScience & Business Media, 2005).
[Crossref]

F. Ceccarelli, A. Gulinatti, I. Labanca, I. Rech, and M. Ghioni, “Development and characterization of an 8x8 spad-array module for gigacount per second applications,” in Photon Counting Applications 2017, (Proc. SPIE 10229, 2017), p. 102290E.

E. Jones, T. Oliphant, and P. Peterson, “Scipy: Open source scientific tools for python,” (2001).

T. R. Choudhary, M. G. Tanner, A. Megia-Fernandez, K. Harrington, H. A. Wood, S. Chankeshwara, P. Zhu, D. Choudhury, F. Yu, R. R. Thomson, R. R. Duncan, K. Dhaliwal, and M. Bradley, “Multiplexed fibre optic sensing in the distal lung (conference presentation),” in Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications XVII, (Proc. SPIE 10058, 2017), p. 100580E.

Supplementary Material (1)

NameDescription
» Visualization 1       10 FPS movie from ex vivo lung tissue taken in in non time–resolved modality using the APD detector. Some monocyte cells labeled with Calcein are visible in the foreground. The image intensity represents the voltage output of the APD.

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Figures (8)

Fig. 1
Fig. 1 Optics diagram and block diagram of the laser-scanning endomicroscope. A USB controlled DAQ generates the scanning waveforms and acquires the analog signal from the APD when in pure intensity scanning mode. The MF32 camera for FLIM data acquisition is controlled through a separate USB interface. Center right shows the trigger signal path originating in the 640 nm laser, passing through a delay box, triggering the 485 nm laser and finally triggering the MF32 camera. The emission dichroic and excitation filters are the XF454 set from Horiba. The schematic shows a raw histogram as acquired from the MF32 camera, showing the red fluorescence decay and the temporally shifted green fluorescence decay (bottom right).
Fig. 2
Fig. 2 Fluorescent image sequence acquired in non time-resolved mode of a 1951 USAF resolution test chart as a standardized test of the imaging system performance at varying field of view. The sequence starts left with the highest resolution and ends right with lower resolution, zooming out of group 7, element 2. The single cores of the imaging fiber (5 μ m) are visible in the highest resolution image.
Fig. 3
Fig. 3 A multi-core fiber loaded with four different fluorescent microspheres acquired at 1 FPS. Top shows the green channel and bottom the red channel. The left hand column shows a fluorescence image, the center column a lifetime image. The plots show the lifetime measured from two distinct areas of 9 × 9 elements in the figures, marked by red and purple squares on the top row and black and yellow squares on the bottom row. The plots and the uncertainties were obtained using a single exponential fit with the scipy.optimize.leastsq module [25]. The FLIM images use the center-of-mass method [18]. The effect of varying intensity observed in the left panels is noticed as varying transparency in the middle (lifetime) panels.
Fig. 4
Fig. 4 Above are three frames extracted from a 10 FPS movie from ex vivo lung tissue taken in in non time-resolved modality using the APD detector. Monocytes labeled with Calcein are visible in the foreground. The image intensity represents the voltage output of the APD (in response to fluorescence intensity) on the indicated color scale. The field of view is 500 μm. Parameters were kept constant throughout the image frames giving good contrast of lung tissue, howeversome saturation of brighter features is therefore present (see Visualization 1 in the supplementary materials for the full-length movie).
Fig. 5
Fig. 5 Ex vivo human lung tissue. The top row shows human lung and bottom row shows human lung plus E.coli and NBD–PMX SmartProbe. The rightmost plots show the lifetime measured from two distinct 9 × 9 element areas in the figures, represented by red and purple squares.
Fig. 6
Fig. 6 Top left is ex vivo lung and top right is ex vivo lung with NBD–PMX SmartProbe labeled bacteria, both displayed as intensity with a threshold applied based on lifetime to highlight labeled bacteria. The bottom panel shows two histograms of the lifetime distribution over the whole images. The red histogram is from the left image without SmartProbes and the purple histogram from the right image with SmartProbes. A threshold of 3 ns was applied to the FLIM data to identify regions where the SmartProbes were active. The red dots on the intensity images represent regions where lifetime was larger than 3 ns and counts were larger than 50.
Fig. 7
Fig. 7 Sequence of eight images extracted from a ten-frames, 1 FPS FLIM movie. Microspheres covalently bound to Fluorescein (green), TAMRA (orange), NBD (yellow) and CY5 (red) dyes were deposited in a microscope slide. The imaging fiber was mounted on a XYZ translation stage and moved a few μ m across the surface of the slide.
Fig. 8
Fig. 8 Sequence of eight images extracted from a ten-frames, 1 FPS FLIM movie. Microspheres covalently bound to Fluorescein (green), TAMRA (orange), NBD (yellow) and CY5 (red) dyes were loaded onto a multi-core fiber. The fiber was placed in water during recording, causing most microspheres to show a decrease in lifetime.

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