Abstract

Fibre-based optical endomicroscopy (OEM) permits high resolution fluorescence microscopy in endoscopically accessible tissues. Fibred OEM has the potential to visualise pathologies targeted with fluorescent imaging probes and provide an in vivo in situ molecular pathology platform to augment disease understanding, diagnosis and stratification. Here we present an inexpensive widefield ratiometric fibred OEM system capable of enhancing the contrast between similar spectra of pathologically relevant fluorescent signals without the burden of complex spectral unmixing. As an exemplar, we demonstrate the potential of the platform to detect fluorescently labelled Gram-negative bacteria in the challenging environment of highly autofluorescent lung tissue in whole ex vivo human lungs.

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2018 (6)

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,” J. Biomed. Opt. 23(7), 1–12 (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,” Sci. Rep. 8(1), 13490 (2018).
[Crossref] [PubMed]

A. Megia-Fernandez, B. Mills, C. Michels, S. V. Chankeshwara, N. Krstajić, C. Haslett, K. Dhaliwal, and M. Bradley, “Bimodal fluorogenic sensing of matrix proteolytic signatures in lung cancer,” Org. Biomol. Chem. 16(43), 8056–8063 (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,” Sci. Transl. Med. 10(464), eaal0033 (2018).
[Crossref] [PubMed]

S. Seth, A. R. Akram, K. Dhaliwal, and C. K. I. Williams, “Estimating Bacterial and Cellular Load in FCFM Imaging,” J. Imaging 4(1), 11 (2018).
[Crossref]

E. Pedretti, M. G. Tanner, T. R. Choudhary, N. Krstajić, A. Megia-Fernandez, R. K. Henderson, M. Bradley, R. R. Thomson, J. M. Girkin, K. Dhaliwal, and P. A. Dalgarno, “High-speed dual color fluorescence lifetime endomicroscopy for highly-multiplexed pulmonary diagnostic applications and detection of labeled bacteria,” Biomed. Opt. Express 10(1), 181–195 (2018).
[Crossref] [PubMed]

2017 (5)

J. M. Stone, H. A. C. Wood, K. Harrington, and T. A. Birks, “Low index contrast imaging fibers,” Opt. Lett. 42(8), 1484–1487 (2017).
[Crossref] [PubMed]

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(10), 11932–11953 (2017).
[Crossref] [PubMed]

A. S. Luthman, S. Dumitru, I. Quiros-Gonzalez, J. Joseph, and S. E. Bohndiek, “Fluorescence hyperspectral imaging (fHSI) using a spectrally resolved detector array,” J. Biophotonics 10(6-7), 840–853 (2017).
[Crossref] [PubMed]

M. A. van der Putten, L. E. MacKenzie, A. L. Davies, J. Fernandez-Ramos, R. A. Desai, K. J. Smith, and A. R. Harvey, “A multispectral microscope for in vivo oximetry of rat dorsal spinal cord vasculature,” Physiol. Meas. 38(2), 205–218 (2017).
[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,” Org. Biomol. Chem. 15(20), 4344–4350 (2017).
[Crossref] [PubMed]

2016 (2)

N. Krstajic, 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,” J. Biomed. Opt. 21(4), 46009 (2016).
[Crossref] [PubMed]

A. Lopez, D. V. Zlatev, K. E. Mach, D. Bui, J. J. Liu, R. V. Rouse, T. Harris, J. T. Leppert, and J. C. Liao, “Intraoperative Optical Biopsy during Robotic Assisted Radical Prostatectomy Using Confocal Endomicroscopy,” J. Urol. 195(4 Pt 1), 1110–1117 (2016).
[Crossref] [PubMed]

2015 (2)

A. R. Akram, N. Avlonitis, A. Lilienkampf, A. M. Perez-Lopez, N. McDonald, S. V. Chankeshwara, E. Scholefield, C. Haslett, M. Bradley, and K. Dhaliwal, “A labelled-ubiquicidin antimicrobial peptide for immediate in situ optical detection of live bacteria in human alveolar lung tissue,” Chem. Sci. (Camb.) 6(12), 6971–6979 (2015).
[Crossref] [PubMed]

T. Aslam, A. Miele, S. V. Chankeshwara, A. Megia-Fernandez, C. Michels, A. R. Akram, N. McDonald, N. Hirani, C. Haslett, M. Bradley, and K. Dhaliwal, “Optical molecular imaging of lysyl oxidase activity - detection of active fibrogenesis in human lung tissue,” Chem. Sci. (Camb.) 6(8), 4946–4953 (2015).
[Crossref] [PubMed]

2014 (3)

G. Lu and B. Fei, “Medical hyperspectral imaging: a review,” J. Biomed. Opt. 19(1), 10901 (2014).
[Crossref] [PubMed]

T. Cheng, Q. Liu, R. Zhang, Y. Zhang, J. Chen, R. Yu, and G. Ge, “Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation,” J. Mol. Cell Biol. 6(6), 506–515 (2014).
[Crossref] [PubMed]

S. van der Walt, J. L. Schönberger, J. Nunez-Iglesias, F. Boulogne, J. D. Warner, N. Yager, E. Gouillart, T. Yu, and scikit-image contributors, “scikit-image: image processing in Python,” PeerJ 2, e453 (2014).
[Crossref] [PubMed]

2013 (2)

M. Hughes, T. P. Chang, and G.-Z. Yang, “Fiber bundle endocytoscopy,” Biomed. Opt. Express 4(12), 2781–2794 (2013).
[Crossref] [PubMed]

Y. Pan, J. P. Volkmer, K. E. Mach, J. J. Liu, R. V. Rouse, D. Sahoo, T. C. Chang, M. Van De Rijn, E. Skinner, S. S. Gambhir, I. Weissman, and J. C. Liao, “Endoscopic molecular imaging of human bladder cancer using a CD47 antibody,” Mol. Imaging Biol. 15(S1), 2–1590 (2013).
[Crossref]

2012 (2)

A. Churg, S. Zhou, and J. L. Wright, “Series “matrix metalloproteinases in lung health and disease”: Matrix metalloproteinases in COPD,” Eur. Respir. J. 39(1), 197–209 (2012).
[Crossref] [PubMed]

A. D. Elliott, L. Gao, A. Ustione, N. Bedard, R. Kester, D. W. Piston, and T. S. Tkaczyk, “Real-time hyperspectral fluorescence imaging of pancreatic β-cell dynamics with the image mapping spectrometer,” J. Cell Sci. 125(Pt 20), 4833–4840 (2012).
[Crossref] [PubMed]

2011 (1)

A. Davey, D. F. McAuley, and C. M. O’Kane, “Matrix metalloproteinases in acute lung injury: mediators of injury and drivers of repair,” Eur. Respir. J. 38(4), 959–970 (2011).
[Crossref] [PubMed]

2009 (1)

M. B. Wallace and P. Fockens, “Probe-based confocal laser endomicroscopy,” Gastroenterology 136(5), 1509–1513 (2009).
[Crossref] [PubMed]

2007 (2)

J. D. Hunter, “Matplotlib: A 2D graphics environment,” Comput. Sci. Eng. 9(3), 90–95 (2007).
[Crossref]

L. Thiberville, S. Moreno-Swirc, T. Vercauteren, E. Peltier, C. Cavé, and G. Bourg Heckly, “In vivo imaging of the bronchial wall microstructure using fibered confocal fluorescence microscopy,” Am. J. Respir. Crit. Care Med. 175(1), 22–31 (2007).
[Crossref] [PubMed]

2006 (1)

F. Chua and G. J. Laurent, “Neutrophil elastase: mediator of extracellular matrix destruction and accumulation,” Proc. Am. Thorac. Soc. 3(5), 424–427 (2006).
[Crossref] [PubMed]

2005 (2)

J. W. Lichtman and J.-A. Conchello, “Fluorescence microscopy,” Nat. Methods 2(12), 910–919 (2005).
[Crossref] [PubMed]

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2(12), 941–950 (2005).
[Crossref] [PubMed]

2002 (2)

J. Zhang, R. E. Campbell, A. Y. Ting, and R. Y. Tsien, “Creating new fluorescent probes for cell biology,” Nat. Rev. Mol. Cell Biol. 3(12), 906–918 (2002).
[Crossref] [PubMed]

Y. Hiraoka, T. Shimi, and T. Haraguchi, “Multispectral imaging fluorescence microscopy for living cells,” Cell Struct. Funct. 27(5), 367–374 (2002).
[Crossref] [PubMed]

Akram, A. 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,” J. Biomed. Opt. 23(7), 1–12 (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,” Sci. Rep. 8(1), 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,” Sci. Transl. Med. 10(464), eaal0033 (2018).
[Crossref] [PubMed]

S. Seth, A. R. Akram, K. Dhaliwal, and C. K. I. Williams, “Estimating Bacterial and Cellular Load in FCFM Imaging,” J. Imaging 4(1), 11 (2018).
[Crossref]

N. Krstajic, 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,” J. Biomed. Opt. 21(4), 46009 (2016).
[Crossref] [PubMed]

A. R. Akram, N. Avlonitis, A. Lilienkampf, A. M. Perez-Lopez, N. McDonald, S. V. Chankeshwara, E. Scholefield, C. Haslett, M. Bradley, and K. Dhaliwal, “A labelled-ubiquicidin antimicrobial peptide for immediate in situ optical detection of live bacteria in human alveolar lung tissue,” Chem. Sci. (Camb.) 6(12), 6971–6979 (2015).
[Crossref] [PubMed]

T. Aslam, A. Miele, S. V. Chankeshwara, A. Megia-Fernandez, C. Michels, A. R. Akram, N. McDonald, N. Hirani, C. Haslett, M. Bradley, and K. Dhaliwal, “Optical molecular imaging of lysyl oxidase activity - detection of active fibrogenesis in human lung tissue,” Chem. Sci. (Camb.) 6(8), 4946–4953 (2015).
[Crossref] [PubMed]

Altmann, Y.

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,” Sci. Transl. Med. 10(464), eaal0033 (2018).
[Crossref] [PubMed]

T. Aslam, A. Miele, S. V. Chankeshwara, A. Megia-Fernandez, C. Michels, A. R. Akram, N. McDonald, N. Hirani, C. Haslett, M. Bradley, and K. Dhaliwal, “Optical molecular imaging of lysyl oxidase activity - detection of active fibrogenesis in human lung tissue,” Chem. Sci. (Camb.) 6(8), 4946–4953 (2015).
[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,” Sci. Transl. Med. 10(464), 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,” Sci. Rep. 8(1), 13490 (2018).
[Crossref] [PubMed]

A. R. Akram, N. Avlonitis, A. Lilienkampf, A. M. Perez-Lopez, N. McDonald, S. V. Chankeshwara, E. Scholefield, C. Haslett, M. Bradley, and K. Dhaliwal, “A labelled-ubiquicidin antimicrobial peptide for immediate in situ optical detection of live bacteria in human alveolar lung tissue,” Chem. Sci. (Camb.) 6(12), 6971–6979 (2015).
[Crossref] [PubMed]

Bedard, N.

A. D. Elliott, L. Gao, A. Ustione, N. Bedard, R. Kester, D. W. Piston, and T. S. Tkaczyk, “Real-time hyperspectral fluorescence imaging of pancreatic β-cell dynamics with the image mapping spectrometer,” J. Cell Sci. 125(Pt 20), 4833–4840 (2012).
[Crossref] [PubMed]

Birks, T. A.

Bohndiek, S. E.

A. S. Luthman, S. Dumitru, I. Quiros-Gonzalez, J. Joseph, and S. E. Bohndiek, “Fluorescence hyperspectral imaging (fHSI) using a spectrally resolved detector array,” J. Biophotonics 10(6-7), 840–853 (2017).
[Crossref] [PubMed]

Boulogne, F.

S. van der Walt, J. L. Schönberger, J. Nunez-Iglesias, F. Boulogne, J. D. Warner, N. Yager, E. Gouillart, T. Yu, and scikit-image contributors, “scikit-image: image processing in Python,” PeerJ 2, e453 (2014).
[Crossref] [PubMed]

Bourg Heckly, G.

L. Thiberville, S. Moreno-Swirc, T. Vercauteren, E. Peltier, C. Cavé, and G. Bourg Heckly, “In vivo imaging of the bronchial wall microstructure using fibered confocal fluorescence microscopy,” Am. J. Respir. Crit. Care Med. 175(1), 22–31 (2007).
[Crossref] [PubMed]

Bradley, 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,” Sci. Transl. Med. 10(464), 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,” Sci. Rep. 8(1), 13490 (2018).
[Crossref] [PubMed]

A. Megia-Fernandez, B. Mills, C. Michels, S. V. Chankeshwara, N. Krstajić, C. Haslett, K. Dhaliwal, and M. Bradley, “Bimodal fluorogenic sensing of matrix proteolytic signatures in lung cancer,” Org. Biomol. Chem. 16(43), 8056–8063 (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,” J. Biomed. Opt. 23(7), 1–12 (2018).
[Crossref] [PubMed]

E. Pedretti, M. G. Tanner, T. R. Choudhary, N. Krstajić, A. Megia-Fernandez, R. K. Henderson, M. Bradley, R. R. Thomson, J. M. Girkin, K. Dhaliwal, and P. A. Dalgarno, “High-speed dual color fluorescence lifetime endomicroscopy for highly-multiplexed pulmonary diagnostic applications and detection of labeled bacteria,” Biomed. Opt. Express 10(1), 181–195 (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,” Org. Biomol. Chem. 15(20), 4344–4350 (2017).
[Crossref] [PubMed]

N. Krstajic, 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,” J. Biomed. Opt. 21(4), 46009 (2016).
[Crossref] [PubMed]

A. R. Akram, N. Avlonitis, A. Lilienkampf, A. M. Perez-Lopez, N. McDonald, S. V. Chankeshwara, E. Scholefield, C. Haslett, M. Bradley, and K. Dhaliwal, “A labelled-ubiquicidin antimicrobial peptide for immediate in situ optical detection of live bacteria in human alveolar lung tissue,” Chem. Sci. (Camb.) 6(12), 6971–6979 (2015).
[Crossref] [PubMed]

T. Aslam, A. Miele, S. V. Chankeshwara, A. Megia-Fernandez, C. Michels, A. R. Akram, N. McDonald, N. Hirani, C. Haslett, M. Bradley, and K. Dhaliwal, “Optical molecular imaging of lysyl oxidase activity - detection of active fibrogenesis in human lung tissue,” Chem. Sci. (Camb.) 6(8), 4946–4953 (2015).
[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,” J. Biomed. Opt. 23(7), 1–12 (2018).
[Crossref] [PubMed]

Bui, D.

A. Lopez, D. V. Zlatev, K. E. Mach, D. Bui, J. J. Liu, R. V. Rouse, T. Harris, J. T. Leppert, and J. C. Liao, “Intraoperative Optical Biopsy during Robotic Assisted Radical Prostatectomy Using Confocal Endomicroscopy,” J. Urol. 195(4 Pt 1), 1110–1117 (2016).
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J. Zhang, R. E. Campbell, A. Y. Ting, and R. Y. Tsien, “Creating new fluorescent probes for cell biology,” Nat. Rev. Mol. Cell Biol. 3(12), 906–918 (2002).
[Crossref] [PubMed]

Cavé, C.

L. Thiberville, S. Moreno-Swirc, T. Vercauteren, E. Peltier, C. Cavé, and G. Bourg Heckly, “In vivo imaging of the bronchial wall microstructure using fibered confocal fluorescence microscopy,” Am. J. Respir. Crit. Care Med. 175(1), 22–31 (2007).
[Crossref] [PubMed]

Chang, T. C.

Y. Pan, J. P. Volkmer, K. E. Mach, J. J. Liu, R. V. Rouse, D. Sahoo, T. C. Chang, M. Van De Rijn, E. Skinner, S. S. Gambhir, I. Weissman, and J. C. Liao, “Endoscopic molecular imaging of human bladder cancer using a CD47 antibody,” Mol. Imaging Biol. 15(S1), 2–1590 (2013).
[Crossref]

Chang, T. P.

Chankeshwara, S. V.

A. Megia-Fernandez, B. Mills, C. Michels, S. V. Chankeshwara, N. Krstajić, C. Haslett, K. Dhaliwal, and M. Bradley, “Bimodal fluorogenic sensing of matrix proteolytic signatures in lung cancer,” Org. Biomol. Chem. 16(43), 8056–8063 (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,” Sci. Transl. Med. 10(464), 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,” Org. Biomol. Chem. 15(20), 4344–4350 (2017).
[Crossref] [PubMed]

T. Aslam, A. Miele, S. V. Chankeshwara, A. Megia-Fernandez, C. Michels, A. R. Akram, N. McDonald, N. Hirani, C. Haslett, M. Bradley, and K. Dhaliwal, “Optical molecular imaging of lysyl oxidase activity - detection of active fibrogenesis in human lung tissue,” Chem. Sci. (Camb.) 6(8), 4946–4953 (2015).
[Crossref] [PubMed]

A. R. Akram, N. Avlonitis, A. Lilienkampf, A. M. Perez-Lopez, N. McDonald, S. V. Chankeshwara, E. Scholefield, C. Haslett, M. Bradley, and K. Dhaliwal, “A labelled-ubiquicidin antimicrobial peptide for immediate in situ optical detection of live bacteria in human alveolar lung tissue,” Chem. Sci. (Camb.) 6(12), 6971–6979 (2015).
[Crossref] [PubMed]

Chen, J.

T. Cheng, Q. Liu, R. Zhang, Y. Zhang, J. Chen, R. Yu, and G. Ge, “Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation,” J. Mol. Cell Biol. 6(6), 506–515 (2014).
[Crossref] [PubMed]

Cheng, T.

T. Cheng, Q. Liu, R. Zhang, Y. Zhang, J. Chen, R. Yu, and G. Ge, “Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation,” J. Mol. Cell Biol. 6(6), 506–515 (2014).
[Crossref] [PubMed]

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B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2(12), 941–950 (2005).
[Crossref] [PubMed]

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E. Pedretti, M. G. Tanner, T. R. Choudhary, N. Krstajić, A. Megia-Fernandez, R. K. Henderson, M. Bradley, R. R. Thomson, J. M. Girkin, K. Dhaliwal, and P. A. Dalgarno, “High-speed dual color fluorescence lifetime endomicroscopy for highly-multiplexed pulmonary diagnostic applications and detection of labeled bacteria,” Biomed. Opt. Express 10(1), 181–195 (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,” J. Biomed. Opt. 23(7), 1–12 (2018).
[Crossref] [PubMed]

N. Krstajic, 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,” J. Biomed. Opt. 21(4), 46009 (2016).
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F. Chua and G. J. Laurent, “Neutrophil elastase: mediator of extracellular matrix destruction and accumulation,” Proc. Am. Thorac. Soc. 3(5), 424–427 (2006).
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A. Churg, S. Zhou, and J. L. Wright, “Series “matrix metalloproteinases in lung health and disease”: Matrix metalloproteinases in COPD,” Eur. Respir. J. 39(1), 197–209 (2012).
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Cocker, E. D.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2(12), 941–950 (2005).
[Crossref] [PubMed]

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,” Sci. Transl. Med. 10(464), eaal0033 (2018).
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J. W. Lichtman and J.-A. Conchello, “Fluorescence microscopy,” Nat. Methods 2(12), 910–919 (2005).
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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,” Sci. Transl. Med. 10(464), 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,” Sci. Rep. 8(1), 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,” J. Biomed. Opt. 23(7), 1–12 (2018).
[Crossref] [PubMed]

Dalgarno, P. A.

E. Pedretti, M. G. Tanner, T. R. Choudhary, N. Krstajić, A. Megia-Fernandez, R. K. Henderson, M. Bradley, R. R. Thomson, J. M. Girkin, K. Dhaliwal, and P. A. Dalgarno, “High-speed dual color fluorescence lifetime endomicroscopy for highly-multiplexed pulmonary diagnostic applications and detection of labeled bacteria,” Biomed. Opt. Express 10(1), 181–195 (2018).
[Crossref] [PubMed]

N. Krstajic, 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,” J. Biomed. Opt. 21(4), 46009 (2016).
[Crossref] [PubMed]

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A. Davey, D. F. McAuley, and C. M. O’Kane, “Matrix metalloproteinases in acute lung injury: mediators of injury and drivers of repair,” Eur. Respir. J. 38(4), 959–970 (2011).
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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,” J. Biomed. Opt. 23(7), 1–12 (2018).
[Crossref] [PubMed]

Davies, A. L.

M. A. van der Putten, L. E. MacKenzie, A. L. Davies, J. Fernandez-Ramos, R. A. Desai, K. J. Smith, and A. R. Harvey, “A multispectral microscope for in vivo oximetry of rat dorsal spinal cord vasculature,” Physiol. Meas. 38(2), 205–218 (2017).
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Desai, R. A.

M. A. van der Putten, L. E. MacKenzie, A. L. Davies, J. Fernandez-Ramos, R. A. Desai, K. J. Smith, and A. R. Harvey, “A multispectral microscope for in vivo oximetry of rat dorsal spinal cord vasculature,” Physiol. Meas. 38(2), 205–218 (2017).
[Crossref] [PubMed]

Dhaliwal, K.

S. Seth, A. R. Akram, K. Dhaliwal, and C. K. I. Williams, “Estimating Bacterial and Cellular Load in FCFM Imaging,” J. Imaging 4(1), 11 (2018).
[Crossref]

E. Pedretti, M. G. Tanner, T. R. Choudhary, N. Krstajić, A. Megia-Fernandez, R. K. Henderson, M. Bradley, R. R. Thomson, J. M. Girkin, K. Dhaliwal, and P. A. Dalgarno, “High-speed dual color fluorescence lifetime endomicroscopy for highly-multiplexed pulmonary diagnostic applications and detection of labeled bacteria,” Biomed. Opt. Express 10(1), 181–195 (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,” J. Biomed. Opt. 23(7), 1–12 (2018).
[Crossref] [PubMed]

A. Megia-Fernandez, B. Mills, C. Michels, S. V. Chankeshwara, N. Krstajić, C. Haslett, K. Dhaliwal, and M. Bradley, “Bimodal fluorogenic sensing of matrix proteolytic signatures in lung cancer,” Org. Biomol. Chem. 16(43), 8056–8063 (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,” Sci. Rep. 8(1), 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,” Sci. Transl. Med. 10(464), 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,” Org. Biomol. Chem. 15(20), 4344–4350 (2017).
[Crossref] [PubMed]

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(10), 11932–11953 (2017).
[Crossref] [PubMed]

N. Krstajic, 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,” J. Biomed. Opt. 21(4), 46009 (2016).
[Crossref] [PubMed]

A. R. Akram, N. Avlonitis, A. Lilienkampf, A. M. Perez-Lopez, N. McDonald, S. V. Chankeshwara, E. Scholefield, C. Haslett, M. Bradley, and K. Dhaliwal, “A labelled-ubiquicidin antimicrobial peptide for immediate in situ optical detection of live bacteria in human alveolar lung tissue,” Chem. Sci. (Camb.) 6(12), 6971–6979 (2015).
[Crossref] [PubMed]

T. Aslam, A. Miele, S. V. Chankeshwara, A. Megia-Fernandez, C. Michels, A. R. Akram, N. McDonald, N. Hirani, C. Haslett, M. Bradley, and K. Dhaliwal, “Optical molecular imaging of lysyl oxidase activity - detection of active fibrogenesis in human lung tissue,” Chem. Sci. (Camb.) 6(8), 4946–4953 (2015).
[Crossref] [PubMed]

Dumitru, S.

A. S. Luthman, S. Dumitru, I. Quiros-Gonzalez, J. Joseph, and S. E. Bohndiek, “Fluorescence hyperspectral imaging (fHSI) using a spectrally resolved detector array,” J. Biophotonics 10(6-7), 840–853 (2017).
[Crossref] [PubMed]

Elliott, A. D.

A. D. Elliott, L. Gao, A. Ustione, N. Bedard, R. Kester, D. W. Piston, and T. S. Tkaczyk, “Real-time hyperspectral fluorescence imaging of pancreatic β-cell dynamics with the image mapping spectrometer,” J. Cell Sci. 125(Pt 20), 4833–4840 (2012).
[Crossref] [PubMed]

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,” J. Biomed. Opt. 23(7), 1–12 (2018).
[Crossref] [PubMed]

Fei, B.

G. Lu and B. Fei, “Medical hyperspectral imaging: a review,” J. Biomed. Opt. 19(1), 10901 (2014).
[Crossref] [PubMed]

Fernandez-Ramos, J.

M. A. van der Putten, L. E. MacKenzie, A. L. Davies, J. Fernandez-Ramos, R. A. Desai, K. J. Smith, and A. R. Harvey, “A multispectral microscope for in vivo oximetry of rat dorsal spinal cord vasculature,” Physiol. Meas. 38(2), 205–218 (2017).
[Crossref] [PubMed]

Flusberg, B. A.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2(12), 941–950 (2005).
[Crossref] [PubMed]

Fockens, P.

M. B. Wallace and P. Fockens, “Probe-based confocal laser endomicroscopy,” Gastroenterology 136(5), 1509–1513 (2009).
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Gambhir, S. S.

Y. Pan, J. P. Volkmer, K. E. Mach, J. J. Liu, R. V. Rouse, D. Sahoo, T. C. Chang, M. Van De Rijn, E. Skinner, S. S. Gambhir, I. Weissman, and J. C. Liao, “Endoscopic molecular imaging of human bladder cancer using a CD47 antibody,” Mol. Imaging Biol. 15(S1), 2–1590 (2013).
[Crossref]

Gao, L.

A. D. Elliott, L. Gao, A. Ustione, N. Bedard, R. Kester, D. W. Piston, and T. S. Tkaczyk, “Real-time hyperspectral fluorescence imaging of pancreatic β-cell dynamics with the image mapping spectrometer,” J. Cell Sci. 125(Pt 20), 4833–4840 (2012).
[Crossref] [PubMed]

Ge, G.

T. Cheng, Q. Liu, R. Zhang, Y. Zhang, J. Chen, R. Yu, and G. Ge, “Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation,” J. Mol. Cell Biol. 6(6), 506–515 (2014).
[Crossref] [PubMed]

Girkin, J. M.

E. Pedretti, M. G. Tanner, T. R. Choudhary, N. Krstajić, A. Megia-Fernandez, R. K. Henderson, M. Bradley, R. R. Thomson, J. M. Girkin, K. Dhaliwal, and P. A. Dalgarno, “High-speed dual color fluorescence lifetime endomicroscopy for highly-multiplexed pulmonary diagnostic applications and detection of labeled bacteria,” Biomed. Opt. Express 10(1), 181–195 (2018).
[Crossref] [PubMed]

N. Krstajic, 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,” J. Biomed. Opt. 21(4), 46009 (2016).
[Crossref] [PubMed]

Gouillart, E.

S. van der Walt, J. L. Schönberger, J. Nunez-Iglesias, F. Boulogne, J. D. Warner, N. Yager, E. Gouillart, T. Yu, and scikit-image contributors, “scikit-image: image processing in Python,” PeerJ 2, e453 (2014).
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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,” Sci. Transl. Med. 10(464), eaal0033 (2018).
[Crossref] [PubMed]

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,” Sci. Transl. Med. 10(464), eaal0033 (2018).
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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,” Sci. Transl. Med. 10(464), eaal0033 (2018).
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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,” Sci. Rep. 8(1), 13490 (2018).
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T. Aslam, A. Miele, S. V. Chankeshwara, A. Megia-Fernandez, C. Michels, A. R. Akram, N. McDonald, N. Hirani, C. Haslett, M. Bradley, and K. Dhaliwal, “Optical molecular imaging of lysyl oxidase activity - detection of active fibrogenesis in human lung tissue,” Chem. Sci. (Camb.) 6(8), 4946–4953 (2015).
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A. R. Akram, N. Avlonitis, A. Lilienkampf, A. M. Perez-Lopez, N. McDonald, S. V. Chankeshwara, E. Scholefield, C. Haslett, M. Bradley, and K. Dhaliwal, “A labelled-ubiquicidin antimicrobial peptide for immediate in situ optical detection of live bacteria in human alveolar lung tissue,” Chem. Sci. (Camb.) 6(12), 6971–6979 (2015).
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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,” Sci. Transl. Med. 10(464), eaal0033 (2018).
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Y. Hiraoka, T. Shimi, and T. Haraguchi, “Multispectral imaging fluorescence microscopy for living cells,” Cell Struct. Funct. 27(5), 367–374 (2002).
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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,” J. Biomed. Opt. 23(7), 1–12 (2018).
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A. Megia-Fernandez, B. Mills, C. Michels, S. V. Chankeshwara, N. Krstajić, C. Haslett, K. Dhaliwal, and M. Bradley, “Bimodal fluorogenic sensing of matrix proteolytic signatures in lung cancer,” Org. Biomol. Chem. 16(43), 8056–8063 (2018).
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A. Lopez, D. V. Zlatev, K. E. Mach, D. Bui, J. J. Liu, R. V. Rouse, T. Harris, J. T. Leppert, and J. C. Liao, “Intraoperative Optical Biopsy during Robotic Assisted Radical Prostatectomy Using Confocal Endomicroscopy,” J. Urol. 195(4 Pt 1), 1110–1117 (2016).
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Y. Pan, J. P. Volkmer, K. E. Mach, J. J. Liu, R. V. Rouse, D. Sahoo, T. C. Chang, M. Van De Rijn, E. Skinner, S. S. Gambhir, I. Weissman, and J. C. Liao, “Endoscopic molecular imaging of human bladder cancer using a CD47 antibody,” Mol. Imaging Biol. 15(S1), 2–1590 (2013).
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A. Lopez, D. V. Zlatev, K. E. Mach, D. Bui, J. J. Liu, R. V. Rouse, T. Harris, J. T. Leppert, and J. C. Liao, “Intraoperative Optical Biopsy during Robotic Assisted Radical Prostatectomy Using Confocal Endomicroscopy,” J. Urol. 195(4 Pt 1), 1110–1117 (2016).
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Y. Pan, J. P. Volkmer, K. E. Mach, J. J. Liu, R. V. Rouse, D. Sahoo, T. C. Chang, M. Van De Rijn, E. Skinner, S. S. Gambhir, I. Weissman, and J. C. Liao, “Endoscopic molecular imaging of human bladder cancer using a CD47 antibody,” Mol. Imaging Biol. 15(S1), 2–1590 (2013).
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M. A. van der Putten, L. E. MacKenzie, A. L. Davies, J. Fernandez-Ramos, R. A. Desai, K. J. Smith, and A. R. Harvey, “A multispectral microscope for in vivo oximetry of rat dorsal spinal cord vasculature,” Physiol. Meas. 38(2), 205–218 (2017).
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Marshall, 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,” J. Biomed. Opt. 23(7), 1–12 (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,” Sci. Transl. Med. 10(464), eaal0033 (2018).
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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,” Sci. Transl. Med. 10(464), eaal0033 (2018).
[Crossref] [PubMed]

N. Krstajic, 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,” J. Biomed. Opt. 21(4), 46009 (2016).
[Crossref] [PubMed]

A. R. Akram, N. Avlonitis, A. Lilienkampf, A. M. Perez-Lopez, N. McDonald, S. V. Chankeshwara, E. Scholefield, C. Haslett, M. Bradley, and K. Dhaliwal, “A labelled-ubiquicidin antimicrobial peptide for immediate in situ optical detection of live bacteria in human alveolar lung tissue,” Chem. Sci. (Camb.) 6(12), 6971–6979 (2015).
[Crossref] [PubMed]

T. Aslam, A. Miele, S. V. Chankeshwara, A. Megia-Fernandez, C. Michels, A. R. Akram, N. McDonald, N. Hirani, C. Haslett, M. Bradley, and K. Dhaliwal, “Optical molecular imaging of lysyl oxidase activity - detection of active fibrogenesis in human lung tissue,” Chem. Sci. (Camb.) 6(8), 4946–4953 (2015).
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McLaughlin, S.

Megia-Fernandez, A.

E. Pedretti, M. G. Tanner, T. R. Choudhary, N. Krstajić, A. Megia-Fernandez, R. K. Henderson, M. Bradley, R. R. Thomson, J. M. Girkin, K. Dhaliwal, and P. A. Dalgarno, “High-speed dual color fluorescence lifetime endomicroscopy for highly-multiplexed pulmonary diagnostic applications and detection of labeled bacteria,” Biomed. Opt. Express 10(1), 181–195 (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,” Sci. Transl. Med. 10(464), eaal0033 (2018).
[Crossref] [PubMed]

A. Megia-Fernandez, B. Mills, C. Michels, S. V. Chankeshwara, N. Krstajić, C. Haslett, K. Dhaliwal, and M. Bradley, “Bimodal fluorogenic sensing of matrix proteolytic signatures in lung cancer,” Org. Biomol. Chem. 16(43), 8056–8063 (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,” Org. Biomol. Chem. 15(20), 4344–4350 (2017).
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T. Aslam, A. Miele, S. V. Chankeshwara, A. Megia-Fernandez, C. Michels, A. R. Akram, N. McDonald, N. Hirani, C. Haslett, M. Bradley, and K. Dhaliwal, “Optical molecular imaging of lysyl oxidase activity - detection of active fibrogenesis in human lung tissue,” Chem. Sci. (Camb.) 6(8), 4946–4953 (2015).
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Michels, C.

A. Megia-Fernandez, B. Mills, C. Michels, S. V. Chankeshwara, N. Krstajić, C. Haslett, K. Dhaliwal, and M. Bradley, “Bimodal fluorogenic sensing of matrix proteolytic signatures in lung cancer,” Org. Biomol. Chem. 16(43), 8056–8063 (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,” Org. Biomol. Chem. 15(20), 4344–4350 (2017).
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T. Aslam, A. Miele, S. V. Chankeshwara, A. Megia-Fernandez, C. Michels, A. R. Akram, N. McDonald, N. Hirani, C. Haslett, M. Bradley, and K. Dhaliwal, “Optical molecular imaging of lysyl oxidase activity - detection of active fibrogenesis in human lung tissue,” Chem. Sci. (Camb.) 6(8), 4946–4953 (2015).
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Mills, B.

A. Megia-Fernandez, B. Mills, C. Michels, S. V. Chankeshwara, N. Krstajić, C. Haslett, K. Dhaliwal, and M. Bradley, “Bimodal fluorogenic sensing of matrix proteolytic signatures in lung cancer,” Org. Biomol. Chem. 16(43), 8056–8063 (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,” J. Biomed. Opt. 23(7), 1–12 (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,” Sci. Transl. Med. 10(464), 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,” Org. Biomol. Chem. 15(20), 4344–4350 (2017).
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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,” J. Biomed. Opt. 23(7), 1–12 (2018).
[Crossref] [PubMed]

N. Krstajic, 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,” J. Biomed. Opt. 21(4), 46009 (2016).
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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,” J. Biomed. Opt. 23(7), 1–12 (2018).
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S. van der Walt, J. L. Schönberger, J. Nunez-Iglesias, F. Boulogne, J. D. Warner, N. Yager, E. Gouillart, T. Yu, and scikit-image contributors, “scikit-image: image processing in Python,” PeerJ 2, e453 (2014).
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A. Davey, D. F. McAuley, and C. M. O’Kane, “Matrix metalloproteinases in acute lung injury: mediators of injury and drivers of repair,” Eur. Respir. J. 38(4), 959–970 (2011).
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E. Jones, T. Oliphant, P. Peterson, and et al., “SciPy: Open source scientific tools for Python,” Comput. Sci. Eng. (2007).

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Y. Pan, J. P. Volkmer, K. E. Mach, J. J. Liu, R. V. Rouse, D. Sahoo, T. C. Chang, M. Van De Rijn, E. Skinner, S. S. Gambhir, I. Weissman, and J. C. Liao, “Endoscopic molecular imaging of human bladder cancer using a CD47 antibody,” Mol. Imaging Biol. 15(S1), 2–1590 (2013).
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Parker, H. E.

Pedretti, E.

E. Pedretti, M. G. Tanner, T. R. Choudhary, N. Krstajić, A. Megia-Fernandez, R. K. Henderson, M. Bradley, R. R. Thomson, J. M. Girkin, K. Dhaliwal, and P. A. Dalgarno, “High-speed dual color fluorescence lifetime endomicroscopy for highly-multiplexed pulmonary diagnostic applications and detection of labeled bacteria,” Biomed. Opt. Express 10(1), 181–195 (2018).
[Crossref] [PubMed]

N. Krstajic, 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,” J. Biomed. Opt. 21(4), 46009 (2016).
[Crossref] [PubMed]

Peltier, E.

L. Thiberville, S. Moreno-Swirc, T. Vercauteren, E. Peltier, C. Cavé, and G. Bourg Heckly, “In vivo imaging of the bronchial wall microstructure using fibered confocal fluorescence microscopy,” Am. J. Respir. Crit. Care Med. 175(1), 22–31 (2007).
[Crossref] [PubMed]

Perez-Lopez, A. M.

A. R. Akram, N. Avlonitis, A. Lilienkampf, A. M. Perez-Lopez, N. McDonald, S. V. Chankeshwara, E. Scholefield, C. Haslett, M. Bradley, and K. Dhaliwal, “A labelled-ubiquicidin antimicrobial peptide for immediate in situ optical detection of live bacteria in human alveolar lung tissue,” Chem. Sci. (Camb.) 6(12), 6971–6979 (2015).
[Crossref] [PubMed]

Perperidis, A.

Peterson, P.

E. Jones, T. Oliphant, P. Peterson, and et al., “SciPy: Open source scientific tools for Python,” Comput. Sci. Eng. (2007).

Piston, D. W.

A. D. Elliott, L. Gao, A. Ustione, N. Bedard, R. Kester, D. W. Piston, and T. S. Tkaczyk, “Real-time hyperspectral fluorescence imaging of pancreatic β-cell dynamics with the image mapping spectrometer,” J. Cell Sci. 125(Pt 20), 4833–4840 (2012).
[Crossref] [PubMed]

Piyawattanametha, W.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2(12), 941–950 (2005).
[Crossref] [PubMed]

Quiros-Gonzalez, I.

A. S. Luthman, S. Dumitru, I. Quiros-Gonzalez, J. Joseph, and S. E. Bohndiek, “Fluorescence hyperspectral imaging (fHSI) using a spectrally resolved detector array,” J. Biophotonics 10(6-7), 840–853 (2017).
[Crossref] [PubMed]

Rouse, R. V.

A. Lopez, D. V. Zlatev, K. E. Mach, D. Bui, J. J. Liu, R. V. Rouse, T. Harris, J. T. Leppert, and J. C. Liao, “Intraoperative Optical Biopsy during Robotic Assisted Radical Prostatectomy Using Confocal Endomicroscopy,” J. Urol. 195(4 Pt 1), 1110–1117 (2016).
[Crossref] [PubMed]

Y. Pan, J. P. Volkmer, K. E. Mach, J. J. Liu, R. V. Rouse, D. Sahoo, T. C. Chang, M. Van De Rijn, E. Skinner, S. S. Gambhir, I. Weissman, and J. C. Liao, “Endoscopic molecular imaging of human bladder cancer using a CD47 antibody,” Mol. Imaging Biol. 15(S1), 2–1590 (2013).
[Crossref]

Sahoo, D.

Y. Pan, J. P. Volkmer, K. E. Mach, J. J. Liu, R. V. Rouse, D. Sahoo, T. C. Chang, M. Van De Rijn, E. Skinner, S. S. Gambhir, I. Weissman, and J. C. Liao, “Endoscopic molecular imaging of human bladder cancer using a CD47 antibody,” Mol. Imaging Biol. 15(S1), 2–1590 (2013).
[Crossref]

Schnitzer, M. J.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2(12), 941–950 (2005).
[Crossref] [PubMed]

Scholefield, E.

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,” J. Biomed. Opt. 23(7), 1–12 (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,” Sci. Transl. Med. 10(464), 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,” Sci. Rep. 8(1), 13490 (2018).
[Crossref] [PubMed]

N. Krstajic, 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,” J. Biomed. Opt. 21(4), 46009 (2016).
[Crossref] [PubMed]

A. R. Akram, N. Avlonitis, A. Lilienkampf, A. M. Perez-Lopez, N. McDonald, S. V. Chankeshwara, E. Scholefield, C. Haslett, M. Bradley, and K. Dhaliwal, “A labelled-ubiquicidin antimicrobial peptide for immediate in situ optical detection of live bacteria in human alveolar lung tissue,” Chem. Sci. (Camb.) 6(12), 6971–6979 (2015).
[Crossref] [PubMed]

Schönberger, J. L.

S. van der Walt, J. L. Schönberger, J. Nunez-Iglesias, F. Boulogne, J. D. Warner, N. Yager, E. Gouillart, T. Yu, and scikit-image contributors, “scikit-image: image processing in Python,” PeerJ 2, e453 (2014).
[Crossref] [PubMed]

Seth, S.

S. Seth, A. R. Akram, K. Dhaliwal, and C. K. I. Williams, “Estimating Bacterial and Cellular Load in FCFM Imaging,” J. Imaging 4(1), 11 (2018).
[Crossref]

Shimi, T.

Y. Hiraoka, T. Shimi, and T. Haraguchi, “Multispectral imaging fluorescence microscopy for living cells,” Cell Struct. Funct. 27(5), 367–374 (2002).
[Crossref] [PubMed]

Skinner, E.

Y. Pan, J. P. Volkmer, K. E. Mach, J. J. Liu, R. V. Rouse, D. Sahoo, T. C. Chang, M. Van De Rijn, E. Skinner, S. S. Gambhir, I. Weissman, and J. C. Liao, “Endoscopic molecular imaging of human bladder cancer using a CD47 antibody,” Mol. Imaging Biol. 15(S1), 2–1590 (2013).
[Crossref]

Smith, K. J.

M. A. van der Putten, L. E. MacKenzie, A. L. Davies, J. Fernandez-Ramos, R. A. Desai, K. J. Smith, and A. R. Harvey, “A multispectral microscope for in vivo oximetry of rat dorsal spinal cord vasculature,” Physiol. Meas. 38(2), 205–218 (2017).
[Crossref] [PubMed]

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,” Sci. Transl. Med. 10(464), eaal0033 (2018).
[Crossref] [PubMed]

Stone, J. M.

Tanner, M. G.

Thiberville, L.

L. Thiberville, S. Moreno-Swirc, T. Vercauteren, E. Peltier, C. Cavé, and G. Bourg Heckly, “In vivo imaging of the bronchial wall microstructure using fibered confocal fluorescence microscopy,” Am. J. Respir. Crit. Care Med. 175(1), 22–31 (2007).
[Crossref] [PubMed]

Thomson, R. R.

Ting, A. Y.

J. Zhang, R. E. Campbell, A. Y. Ting, and R. Y. Tsien, “Creating new fluorescent probes for cell biology,” Nat. Rev. Mol. Cell Biol. 3(12), 906–918 (2002).
[Crossref] [PubMed]

Tkaczyk, T. S.

A. D. Elliott, L. Gao, A. Ustione, N. Bedard, R. Kester, D. W. Piston, and T. S. Tkaczyk, “Real-time hyperspectral fluorescence imaging of pancreatic β-cell dynamics with the image mapping spectrometer,” J. Cell Sci. 125(Pt 20), 4833–4840 (2012).
[Crossref] [PubMed]

Tsien, R. Y.

J. Zhang, R. E. Campbell, A. Y. Ting, and R. Y. Tsien, “Creating new fluorescent probes for cell biology,” Nat. Rev. Mol. Cell Biol. 3(12), 906–918 (2002).
[Crossref] [PubMed]

Ustione, A.

A. D. Elliott, L. Gao, A. Ustione, N. Bedard, R. Kester, D. W. Piston, and T. S. Tkaczyk, “Real-time hyperspectral fluorescence imaging of pancreatic β-cell dynamics with the image mapping spectrometer,” J. Cell Sci. 125(Pt 20), 4833–4840 (2012).
[Crossref] [PubMed]

Van De Rijn, M.

Y. Pan, J. P. Volkmer, K. E. Mach, J. J. Liu, R. V. Rouse, D. Sahoo, T. C. Chang, M. Van De Rijn, E. Skinner, S. S. Gambhir, I. Weissman, and J. C. Liao, “Endoscopic molecular imaging of human bladder cancer using a CD47 antibody,” Mol. Imaging Biol. 15(S1), 2–1590 (2013).
[Crossref]

van der Putten, M. A.

M. A. van der Putten, L. E. MacKenzie, A. L. Davies, J. Fernandez-Ramos, R. A. Desai, K. J. Smith, and A. R. Harvey, “A multispectral microscope for in vivo oximetry of rat dorsal spinal cord vasculature,” Physiol. Meas. 38(2), 205–218 (2017).
[Crossref] [PubMed]

van der Walt, S.

S. van der Walt, J. L. Schönberger, J. Nunez-Iglesias, F. Boulogne, J. D. Warner, N. Yager, E. Gouillart, T. Yu, and scikit-image contributors, “scikit-image: image processing in Python,” PeerJ 2, e453 (2014).
[Crossref] [PubMed]

Vercauteren, T.

L. Thiberville, S. Moreno-Swirc, T. Vercauteren, E. Peltier, C. Cavé, and G. Bourg Heckly, “In vivo imaging of the bronchial wall microstructure using fibered confocal fluorescence microscopy,” Am. J. Respir. Crit. Care Med. 175(1), 22–31 (2007).
[Crossref] [PubMed]

Volkmer, J. P.

Y. Pan, J. P. Volkmer, K. E. Mach, J. J. Liu, R. V. Rouse, D. Sahoo, T. C. Chang, M. Van De Rijn, E. Skinner, S. S. Gambhir, I. Weissman, and J. C. Liao, “Endoscopic molecular imaging of human bladder cancer using a CD47 antibody,” Mol. Imaging Biol. 15(S1), 2–1590 (2013).
[Crossref]

Wallace, M. B.

M. B. Wallace and P. Fockens, “Probe-based confocal laser endomicroscopy,” Gastroenterology 136(5), 1509–1513 (2009).
[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,” Sci. Transl. Med. 10(464), 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,” Sci. Rep. 8(1), 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,” Sci. Rep. 8(1), 13490 (2018).
[Crossref] [PubMed]

Warner, J. D.

S. van der Walt, J. L. Schönberger, J. Nunez-Iglesias, F. Boulogne, J. D. Warner, N. Yager, E. Gouillart, T. Yu, and scikit-image contributors, “scikit-image: image processing in Python,” PeerJ 2, e453 (2014).
[Crossref] [PubMed]

Weissman, I.

Y. Pan, J. P. Volkmer, K. E. Mach, J. J. Liu, R. V. Rouse, D. Sahoo, T. C. Chang, M. Van De Rijn, E. Skinner, S. S. Gambhir, I. Weissman, and J. C. Liao, “Endoscopic molecular imaging of human bladder cancer using a CD47 antibody,” Mol. Imaging Biol. 15(S1), 2–1590 (2013).
[Crossref]

Williams, C. K. I.

S. Seth, A. R. Akram, K. Dhaliwal, and C. K. I. Williams, “Estimating Bacterial and Cellular Load in FCFM Imaging,” J. Imaging 4(1), 11 (2018).
[Crossref]

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,” J. Biomed. Opt. 23(7), 1–12 (2018).
[Crossref] [PubMed]

Wood, H. A. C.

Wright, J. L.

A. Churg, S. Zhou, and J. L. Wright, “Series “matrix metalloproteinases in lung health and disease”: Matrix metalloproteinases in COPD,” Eur. Respir. J. 39(1), 197–209 (2012).
[Crossref] [PubMed]

Yager, N.

S. van der Walt, J. L. Schönberger, J. Nunez-Iglesias, F. Boulogne, J. D. Warner, N. Yager, E. Gouillart, T. Yu, and scikit-image contributors, “scikit-image: image processing in Python,” PeerJ 2, e453 (2014).
[Crossref] [PubMed]

Yang, G.-Z.

Yu, R.

T. Cheng, Q. Liu, R. Zhang, Y. Zhang, J. Chen, R. Yu, and G. Ge, “Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation,” J. Mol. Cell Biol. 6(6), 506–515 (2014).
[Crossref] [PubMed]

Yu, T.

S. van der Walt, J. L. Schönberger, J. Nunez-Iglesias, F. Boulogne, J. D. Warner, N. Yager, E. Gouillart, T. Yu, and scikit-image contributors, “scikit-image: image processing in Python,” PeerJ 2, e453 (2014).
[Crossref] [PubMed]

Zhang, J.

J. Zhang, R. E. Campbell, A. Y. Ting, and R. Y. Tsien, “Creating new fluorescent probes for cell biology,” Nat. Rev. Mol. Cell Biol. 3(12), 906–918 (2002).
[Crossref] [PubMed]

Zhang, R.

T. Cheng, Q. Liu, R. Zhang, Y. Zhang, J. Chen, R. Yu, and G. Ge, “Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation,” J. Mol. Cell Biol. 6(6), 506–515 (2014).
[Crossref] [PubMed]

Zhang, Y.

T. Cheng, Q. Liu, R. Zhang, Y. Zhang, J. Chen, R. Yu, and G. Ge, “Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation,” J. Mol. Cell Biol. 6(6), 506–515 (2014).
[Crossref] [PubMed]

Zhou, S.

A. Churg, S. Zhou, and J. L. Wright, “Series “matrix metalloproteinases in lung health and disease”: Matrix metalloproteinases in COPD,” Eur. Respir. J. 39(1), 197–209 (2012).
[Crossref] [PubMed]

Zlatev, D. V.

A. Lopez, D. V. Zlatev, K. E. Mach, D. Bui, J. J. Liu, R. V. Rouse, T. Harris, J. T. Leppert, and J. C. Liao, “Intraoperative Optical Biopsy during Robotic Assisted Radical Prostatectomy Using Confocal Endomicroscopy,” J. Urol. 195(4 Pt 1), 1110–1117 (2016).
[Crossref] [PubMed]

Am. J. Respir. Crit. Care Med. (1)

L. Thiberville, S. Moreno-Swirc, T. Vercauteren, E. Peltier, C. Cavé, and G. Bourg Heckly, “In vivo imaging of the bronchial wall microstructure using fibered confocal fluorescence microscopy,” Am. J. Respir. Crit. Care Med. 175(1), 22–31 (2007).
[Crossref] [PubMed]

Biomed. Opt. Express (2)

Cell Struct. Funct. (1)

Y. Hiraoka, T. Shimi, and T. Haraguchi, “Multispectral imaging fluorescence microscopy for living cells,” Cell Struct. Funct. 27(5), 367–374 (2002).
[Crossref] [PubMed]

Chem. Sci. (Camb.) (2)

A. R. Akram, N. Avlonitis, A. Lilienkampf, A. M. Perez-Lopez, N. McDonald, S. V. Chankeshwara, E. Scholefield, C. Haslett, M. Bradley, and K. Dhaliwal, “A labelled-ubiquicidin antimicrobial peptide for immediate in situ optical detection of live bacteria in human alveolar lung tissue,” Chem. Sci. (Camb.) 6(12), 6971–6979 (2015).
[Crossref] [PubMed]

T. Aslam, A. Miele, S. V. Chankeshwara, A. Megia-Fernandez, C. Michels, A. R. Akram, N. McDonald, N. Hirani, C. Haslett, M. Bradley, and K. Dhaliwal, “Optical molecular imaging of lysyl oxidase activity - detection of active fibrogenesis in human lung tissue,” Chem. Sci. (Camb.) 6(8), 4946–4953 (2015).
[Crossref] [PubMed]

Comput. Sci. Eng. (1)

J. D. Hunter, “Matplotlib: A 2D graphics environment,” Comput. Sci. Eng. 9(3), 90–95 (2007).
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Eur. Respir. J. (2)

A. Davey, D. F. McAuley, and C. M. O’Kane, “Matrix metalloproteinases in acute lung injury: mediators of injury and drivers of repair,” Eur. Respir. J. 38(4), 959–970 (2011).
[Crossref] [PubMed]

A. Churg, S. Zhou, and J. L. Wright, “Series “matrix metalloproteinases in lung health and disease”: Matrix metalloproteinases in COPD,” Eur. Respir. J. 39(1), 197–209 (2012).
[Crossref] [PubMed]

Gastroenterology (1)

M. B. Wallace and P. Fockens, “Probe-based confocal laser endomicroscopy,” Gastroenterology 136(5), 1509–1513 (2009).
[Crossref] [PubMed]

J. Biomed. Opt. (3)

G. Lu and B. Fei, “Medical hyperspectral imaging: a review,” J. Biomed. Opt. 19(1), 10901 (2014).
[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,” J. Biomed. Opt. 23(7), 1–12 (2018).
[Crossref] [PubMed]

N. Krstajic, 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,” J. Biomed. Opt. 21(4), 46009 (2016).
[Crossref] [PubMed]

J. Biophotonics (1)

A. S. Luthman, S. Dumitru, I. Quiros-Gonzalez, J. Joseph, and S. E. Bohndiek, “Fluorescence hyperspectral imaging (fHSI) using a spectrally resolved detector array,” J. Biophotonics 10(6-7), 840–853 (2017).
[Crossref] [PubMed]

J. Cell Sci. (1)

A. D. Elliott, L. Gao, A. Ustione, N. Bedard, R. Kester, D. W. Piston, and T. S. Tkaczyk, “Real-time hyperspectral fluorescence imaging of pancreatic β-cell dynamics with the image mapping spectrometer,” J. Cell Sci. 125(Pt 20), 4833–4840 (2012).
[Crossref] [PubMed]

J. Imaging (1)

S. Seth, A. R. Akram, K. Dhaliwal, and C. K. I. Williams, “Estimating Bacterial and Cellular Load in FCFM Imaging,” J. Imaging 4(1), 11 (2018).
[Crossref]

J. Mol. Cell Biol. (1)

T. Cheng, Q. Liu, R. Zhang, Y. Zhang, J. Chen, R. Yu, and G. Ge, “Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation,” J. Mol. Cell Biol. 6(6), 506–515 (2014).
[Crossref] [PubMed]

J. Urol. (1)

A. Lopez, D. V. Zlatev, K. E. Mach, D. Bui, J. J. Liu, R. V. Rouse, T. Harris, J. T. Leppert, and J. C. Liao, “Intraoperative Optical Biopsy during Robotic Assisted Radical Prostatectomy Using Confocal Endomicroscopy,” J. Urol. 195(4 Pt 1), 1110–1117 (2016).
[Crossref] [PubMed]

Mol. Imaging Biol. (1)

Y. Pan, J. P. Volkmer, K. E. Mach, J. J. Liu, R. V. Rouse, D. Sahoo, T. C. Chang, M. Van De Rijn, E. Skinner, S. S. Gambhir, I. Weissman, and J. C. Liao, “Endoscopic molecular imaging of human bladder cancer using a CD47 antibody,” Mol. Imaging Biol. 15(S1), 2–1590 (2013).
[Crossref]

Nat. Methods (2)

J. W. Lichtman and J.-A. Conchello, “Fluorescence microscopy,” Nat. Methods 2(12), 910–919 (2005).
[Crossref] [PubMed]

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2(12), 941–950 (2005).
[Crossref] [PubMed]

Nat. Rev. Mol. Cell Biol. (1)

J. Zhang, R. E. Campbell, A. Y. Ting, and R. Y. Tsien, “Creating new fluorescent probes for cell biology,” Nat. Rev. Mol. Cell Biol. 3(12), 906–918 (2002).
[Crossref] [PubMed]

Opt. Express (1)

Opt. Lett. (1)

Org. Biomol. Chem. (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,” Org. Biomol. Chem. 15(20), 4344–4350 (2017).
[Crossref] [PubMed]

A. Megia-Fernandez, B. Mills, C. Michels, S. V. Chankeshwara, N. Krstajić, C. Haslett, K. Dhaliwal, and M. Bradley, “Bimodal fluorogenic sensing of matrix proteolytic signatures in lung cancer,” Org. Biomol. Chem. 16(43), 8056–8063 (2018).
[Crossref] [PubMed]

PeerJ (1)

S. van der Walt, J. L. Schönberger, J. Nunez-Iglesias, F. Boulogne, J. D. Warner, N. Yager, E. Gouillart, T. Yu, and scikit-image contributors, “scikit-image: image processing in Python,” PeerJ 2, e453 (2014).
[Crossref] [PubMed]

Physiol. Meas. (1)

M. A. van der Putten, L. E. MacKenzie, A. L. Davies, J. Fernandez-Ramos, R. A. Desai, K. J. Smith, and A. R. Harvey, “A multispectral microscope for in vivo oximetry of rat dorsal spinal cord vasculature,” Physiol. Meas. 38(2), 205–218 (2017).
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F. Chua and G. J. Laurent, “Neutrophil elastase: mediator of extracellular matrix destruction and accumulation,” Proc. Am. Thorac. Soc. 3(5), 424–427 (2006).
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Sci. Rep. (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,” Sci. Rep. 8(1), 13490 (2018).
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Sci. Transl. Med. (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,” Sci. Transl. Med. 10(464), eaal0033 (2018).
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J. M. Stone, T. Choudhary, H. Parker, B. Mills, A. Marshall, D. Choudhury, M. G. Tanner, H. A. Wood, K. Harrington, J. C. Knight, T. A. Birks, K. Dhaliwal, and M. Bradley, “A multifunctional endoscope for imaging, fluid delivery and fluid extraction (Conference Presentation),” in Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications XVIII (2018), 10488, p. 29.

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Supplementary Material (2)

NameDescription
» Visualization 1       Ratiometric fibre-based fluorescent imaging of lung tissue
» Visualization 2       Ratiometric fibre-based imaging of lung tissue and fluorescently labelled bacteria

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Figures (8)

Fig. 1
Fig. 1 Ratiometric imaging system. Panoptes imaging fibre (a) consisting of a tessellated array of 8100 cores (b). A blue LED (c) is coupled via a dichroic mirror (d) into the fibre bundle. The fluorescence emission is separated by a second dichroic mirror (e) about 605 nm. The long wavelength path is interrupted by an optical chopper (f) and recombined with another dichroic mirror (g) onto a monochromatic camera (h). A PC (j) is used to control a triggering unit (i) with outputs to the camera and the chopper.
Fig. 2
Fig. 2 (left) Example fluorescence emission of SmartProbe labelled P. aeruginosa (black) and human lung (red) at excitation of 470 nm at 5.5 µW acquired using a spectrometer (USB2000 + VIS-NIR-ES, Ocean Optics) coupled into a spectroscopy setup analogous to our imaging arrangement. SmartProbe labelled bacteria have greater short wavelength contributions than typical lung tissue autofluorescence. Profile of dichroic mirrors used to separate the short and long channels determines the short channel wavelength range (green fill) and the long channel wavelength range (red fill). (right) Relative visibility of SmartProbe labelled bacteria defined as the relative spectral ratio value of SmartProbe labelled bacteria to lung tissue for a range of potential cut-off wavelengths.
Fig. 3
Fig. 3 Initial, semi-supervised processing of data set that sets out parameters for core data extraction.
Fig. 4
Fig. 4 Schematic of processing methodology used to analyse data and produce final images. (a) How wavelength dependent propagation of light through different cores is accounted for through normalisation of the data with a brightfield image. (b) How spectral ratio values are calculated following a core matching protocol and interpolation.
Fig. 5
Fig. 5 (a) Images from negative USAF target with (left to right) 100% 1 mM NBD, 25% 1 mM NBD 75% 1 mM fluorescein, and 100% 1 mM fluorescein with spectral ratio values clipped to 0.75 - 4. (b) Spectra of the three solutions taken at an illumination wavelength of 470 nm at 5.5 µW, using a commercial spectrometer (USB2000 + VIS-NIR-ES, Ocean Optics). (c) Histograms of the spectral ratio values contained within USAF images summed over the whole image for ten sequential frames. The histograms have been weighted by intensity and normalised by area for ease of comparison. Broadening of the 100% fluorescein histogram is due to a low signal to noise ratio above the cut-off wavelength at 605 nm. Note that a shift of the spectra towards shorter wavelengths corresponds to an increase in the spectral ratio calculated.
Fig. 6
Fig. 6 (top three rows) Typical examples of imaging lung tissue in an ex vivo lung perfusion (EVLP) model prior to instillation of labelled bacteria. (bottom three rows) Typical examples of EVLP lung imaging after in situ delivery of SmartProbe labelled P. aeruginosa. All images are the same FOV presented in four modes. (from left to right) Intensity image as would appear on a widefield fluorescence fibred OEM system; spectral ratio image (auto-scaled); combined image with auto-scaling; combined image with scaling clipped from a spectral ratio of 0.3 to 0.4 to enhance SmartProbe labelled P. aeruginosa visibility (see Visualization 2); histograms of the spectral ratio contained with the image. Selected images are shown enlarged in Fig. 7.
Fig. 7
Fig. 7 (Top) Typical ex vivo imaging of lung tissue from EVLP model in alveolar space before and after in situ instillation of pre-labelled bacteria. Greyscale images show how imaging appears in the widefield imaging system without spectral ratio analysis enabled. Coloured images display spectral ratio and intensity with rescaling of spectral ratio to 0.3 - 0.4 to enhance SmartProbe labelled P. aeruginosa visibility. (Bottom) Typical histogram of spectral ratio across 300 frame videos of lung before and after delivery of labelled bacteria. A tabulated series of images can be seen in Fig. 6.
Fig. 8
Fig. 8 Typical examples of skin tissue. From left to right, intensity only image; spectral ratio only image with auto-contrast; combined image; histogram of the spectral ratio within the image weighted by intensity.

Equations (1)

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R=  I sc I lc = [ i=1 n p i ( m sct ) ] [ i=1 n p i ( m scb ) ] 1 [ i=1 n p i ( m lct ) ] [ i=1 n p i ( m lcb ) ] 1