Abstract

The pathophysiological progression of chronic diseases, including atherosclerosis and cancer, is closely related to compositional changes in biological tissues containing endogenous fluorophores such as collagen, elastin, and NADH, which exhibit strong autofluorescence under ultraviolet excitation. Fluorescence lifetime imaging (FLIm) provides robust detection of the compositional changes by measuring fluorescence lifetime, which is an inherent property of a fluorophore. In this paper, we present a dual-modality system combining a multispectral analog-mean-delay (AMD) FLIm and a high-speed swept-source optical coherence tomography (OCT) to simultaneously visualize the cross-sectional morphology and biochemical compositional information of a biological tissue. Experiments using standard fluorescent solutions showed that the fluorescence lifetime could be measured with a precision of less than 40 psec using the multispectral AMD-FLIm without averaging. In addition, we performed ex vivo imaging on rabbit iliac normal-looking and atherosclerotic specimens to demonstrate the feasibility of the combined FLIm-OCT system for atherosclerosis imaging. We expect that the combined FLIm-OCT will be a promising next-generation imaging technique for diagnosing atherosclerosis and cancer due to the advantages of the proposed label-free high-precision multispectral lifetime measurement.

© 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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2017 (3)

G. Pasterkamp, H. M. den Ruijter, and P. Libby, “Temporal shifts in clinical presentation and underlying mechanisms of atherosclerotic disease,” Nat. Rev. Cardiol. 14(1), 21–29 (2017).
[Crossref] [PubMed]

J. Bec, J. E. Phipps, D. Gorpas, D. Ma, H. Fatakdawala, K. B. Margulies, J. A. Southard, and L. Marcu, “In vivo label-free structural and biochemical imaging of coronary arteries using an integrated ultrasound and multispectral fluorescence lifetime catheter system,” Sci. Rep. 7(1), 8960 (2017).
[Crossref] [PubMed]

B. E. Sherlock, J. E. Phipps, J. Bec, and L. Marcu, “Simultaneous, label-free, multispectral fluorescence lifetime imaging and optical coherence tomography using a double-clad fiber,” Opt. Lett. 42(19), 3753–3756 (2017).
[Crossref] [PubMed]

2016 (4)

S. Shrestha, M. J. Serafino, J. Rico-Jimenez, J. Park, X. Chen, S. Zhaorigetu, B. L. Walton, J. A. Jo, and B. E. Applegate, “Multimodal optical coherence tomography and fluorescence lifetime imaging with interleaved excitation sources for simultaneous endogenous and exogenous fluorescence,” Biomed. Opt. Express 7(9), 3184–3197 (2016).
[Crossref] [PubMed]

J. Ryu, J. Kim, H. Kim, J. H. Jeong, H. J. Lee, H. Yoo, and D. G. Gweon, “High-speed time-resolved laser-scanning microscopy using the line-to-pixel referencing method,” Appl. Opt. 55(32), 9033–9041 (2016).
[Crossref] [PubMed]

A. Alfonso-García, T. D. Smith, R. Datta, T. U. Luu, E. Gratton, E. O. Potma, and W. F. Liu, “Label-free identification of macrophage phenotype by fluorescence lifetime imaging microscopy,” J. Biomed. Opt. 21(4), 046005 (2016).
[Crossref] [PubMed]

S. Kim, M. W. Lee, T. S. Kim, J. W. Song, H. S. Nam, H. S. Cho, S. J. Jang, J. Ryu, D. J. Oh, D. G. Gweon, S. H. Park, K. Park, W. Y. Oh, H. Yoo, and J. W. Kim, “Intracoronary dual-modal optical coherence tomography-near-infrared fluorescence structural-molecular imaging with a clinical dose of indocyanine green for the assessment of high-risk plaques and stent-associated inflammation in a beating coronary artery,” Eur. Heart J. 37(37), 2833–2844 (2016).
[Crossref] [PubMed]

2015 (2)

H. Fatakdawala, D. Gorpas, J. W. Bishop, J. Bec, D. Ma, J. A. Southard, K. B. Margulies, and L. Marcu, “Fluorescence lifetime imaging combined with conventional intravascular ultrasound for enhanced assessment of atherosclerotic plaques: an ex vivo study in human coronary arteries,” J. Cardiovasc. Transl. Res. 8(4), 253–263 (2015).
[Crossref] [PubMed]

J. A. Jo, J. Park, P. Pande, S. Shrestha, M. J. Serafino, J. J. Rico Jimenez, F. Clubb, B. Walton, L. M. Buja, J. E. Phipps, M. D. Feldman, J. Adame, and B. E. Applegate, “Simultaneous morphological and biochemical endogenous optical imaging of atherosclerosis,” Eur. Heart J. Cardiovasc. Imaging 16(8), 910–918 (2015).
[Crossref] [PubMed]

2014 (5)

D. Ma, J. Bec, D. R. Yankelevich, D. Gorpas, H. Fatakdawala, and L. Marcu, “Rotational multispectral fluorescence lifetime imaging and intravascular ultrasound: bimodal system for intravascular applications,” J. Biomed. Opt. 19(6), 066004 (2014).
[Crossref] [PubMed]

A. C. Croce and G. Bottiroli, “Autofluorescence spectroscopy and imaging: a tool for biomedical research and diagnosis,” Eur. J. Histochem. 58(4), 2461 (2014).
[Crossref] [PubMed]

H. S. Cho, S.-J. Jang, K. Kim, A. V. Dan-Chin-Yu, M. Shishkov, B. E. Bouma, and W.-Y. Oh, “High frame-rate intravascular optical frequency-domain imaging in vivo,” Biomed. Opt. Express 5(1), 223–232 (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,” Rev. Sci. Instrum. 85(3), 034303 (2014).
[Crossref] [PubMed]

S. Lee, M. W. Lee, H. S. Cho, J. W. Song, H. S. Nam, D. J. Oh, K. Park, W.-Y. Oh, H. Yoo, and J. W. Kim, “Fully integrated high-speed intravascular optical coherence tomography/near-infrared fluorescence structural/molecular imaging in vivo using a clinically available near-infrared fluorescence-emitting indocyanine green to detect inflamed lipid-rich atheromata in coronary-sized vessels,” Circ. Cardiovasc. Interv. 7(4), 560–569 (2014).
[Crossref] [PubMed]

2013 (3)

G. J. Ughi, T. Adriaenssens, P. Sinnaeve, W. Desmet, and J. D’hooge, “Automated tissue characterization of in vivo atherosclerotic plaques by intravascular optical coherence tomography images,” Biomed. Opt. Express 4(7), 1014–1030 (2013).
[Crossref] [PubMed]

L. A. Sordillo, Y. Pu, P. P. Sordillo, Y. Budansky, and R. R. Alfano, “Optical spectral fingerprints of tissues from patients with different breast cancer histologies using a novel fluorescence spectroscopic device,” Technol. Cancer Res. Treat. 12(5), 455–461 (2013).
[Crossref] [PubMed]

J. M. Jabbour, S. Cheng, B. H. Malik, R. Cuenca, J. A. Jo, J. Wright, Y.-S. L. Cheng, and K. C. Maitland, “Fluorescence lifetime imaging and reflectance confocal microscopy for multiscale imaging of oral precancer,” J. Biomed. Opt. 18(4), 046012 (2013).
[Crossref] [PubMed]

2012 (3)

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,” J. Biomed. Opt. 17(10), 1060121 (2012).
[Crossref] [PubMed]

J. Park, P. Pande, S. Shrestha, F. Clubb, B. E. Applegate, and J. A. Jo, “Biochemical characterization of atherosclerotic plaques by endogenous multispectral fluorescence lifetime imaging microscopy,” Atherosclerosis 220(2), 394–401 (2012).
[Crossref] [PubMed]

G. J. Tearney, E. Regar, T. Akasaka, T. Adriaenssens, P. Barlis, H. G. Bezerra, B. Bouma, N. Bruining, J. M. Cho, S. Chowdhary, M. A. Costa, R. de Silva, J. Dijkstra, C. Di Mario, D. Dudek, E. Falk, M. D. Feldman, P. Fitzgerald, H. M. Garcia-Garcia, N. Gonzalo, J. F. Granada, G. Guagliumi, N. R. Holm, Y. Honda, F. Ikeno, M. Kawasaki, J. Kochman, L. Koltowski, T. Kubo, T. Kume, H. Kyono, C. C. Lam, G. Lamouche, D. P. Lee, M. B. Leon, A. Maehara, O. Manfrini, G. S. Mintz, K. Mizuno, M. A. Morel, S. Nadkarni, H. Okura, H. Otake, A. Pietrasik, F. Prati, L. Räber, M. D. Radu, J. Rieber, M. Riga, A. Rollins, M. Rosenberg, V. Sirbu, P. W. Serruys, K. Shimada, T. Shinke, J. Shite, E. Siegel, S. Sonoda, M. Suter, S. Takarada, A. Tanaka, M. Terashima, T. Thim, S. Uemura, G. J. Ughi, H. M. van Beusekom, A. F. van der Steen, G. A. van Es, G. van Soest, R. Virmani, S. Waxman, N. J. Weissman, G. Weisz, and International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT), “Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation,” J. Am. Coll. Cardiol. 59(12), 1058–1072 (2012).
[Crossref] [PubMed]

2011 (3)

2010 (9)

Y. J. Won, S. Moon, W. T. Han, and D. Y. Kim, “Referencing techniques for the analog mean-delay method in fluorescence lifetime imaging,” J. Opt. Soc. Am. A 27(11), 2402–2410 (2010).
[Crossref] [PubMed]

J. McGinty, N. P. Galletly, C. Dunsby, I. Munro, D. S. Elson, J. Requejo-Isidro, P. Cohen, R. Ahmad, A. Forsyth, A. V. Thillainayagam, M. A. Neil, P. M. French, and G. W. Stamp, “Wide-field fluorescence lifetime imaging of cancer,” Biomed. Opt. Express 1(2), 627–640 (2010).
[Crossref] [PubMed]

P. V. Butte, Q. Fang, J. A. Jo, W. H. Yong, B. K. Pikul, K. L. Black, and L. Marcu, “Intraoperative delineation of primary brain tumors using time-resolved fluorescence spectroscopy,” J. Biomed. Opt. 15(2), 027008 (2010).
[Crossref] [PubMed]

S. Shrestha, B. E. Applegate, J. Park, X. Xiao, P. Pande, and J. A. Jo, “High-speed multispectral fluorescence lifetime imaging implementation for in vivo applications,” Opt. Lett. 35(15), 2558–2560 (2010).
[Crossref] [PubMed]

M. Y. Berezin and S. Achilefu, “Fluorescence lifetime measurements and biological imaging,” Chem. Rev. 110(5), 2641–2684 (2010).
[Crossref] [PubMed]

Y. Pu, W. Wang, G. Tang, and R. R. Alfano, “Changes of collagen and nicotinamide adenine dinucleotide in human cancerous and normal prostate tissues studied using native fluorescence spectroscopy with selective excitation wavelength,” J. Biomed. Opt. 15(4), 047008 (2010).
[Crossref] [PubMed]

Y. Sun, N. Hatami, M. Yee, J. Phipps, D. S. Elson, F. Gorin, R. J. Schrot, and L. Marcu, “Fluorescence lifetime imaging microscopy for brain tumor image-guided surgery,” J. Biomed. Opt. 15(5), 056022 (2010).
[Crossref] [PubMed]

J. Park, J. A. Jo, S. Shrestha, P. Pande, Q. Wan, and B. E. Applegate, “A dual-modality optical coherence tomography and fluorescence lifetime imaging microscopy system for simultaneous morphological and biochemical tissue characterization,” Biomed. Opt. Express 1(1), 186–200 (2010).
[Crossref] [PubMed]

A. V. Finn, M. Nakano, J. Narula, F. D. Kolodgie, and R. Virmani, “Concept of vulnerable/unstable plaque,” Arterioscler. Thromb. Vasc. Biol. 30(7), 1282–1292 (2010).
[Crossref] [PubMed]

2009 (4)

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,” Opt. Lett. 34(13), 2081–2083 (2009).
[Crossref] [PubMed]

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J.-H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[Crossref] [PubMed]

S. Moon, Y. Won, and D. Y. Kim, “Analog mean-delay method for high-speed fluorescence lifetime measurement,” Opt. Express 17(4), 2834–2849 (2009).
[Crossref] [PubMed]

A. Leray, F. B. Riquet, E. Richard, C. Spriet, D. Trinel, and L. Héliot, “Optimized protocol of a frequency domain fluorescence lifetime imaging microscope for FRET measurements,” Microsc. Res. Tech. 72(5), 371–379 (2009).
[Crossref] [PubMed]

2008 (4)

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,” Opt. Lett. 33(6), 630–632 (2008).
[Crossref] [PubMed]

A. Žukauskas, P. Vitta, N. Kurilčik, S. Juršėnas, and E. Bakienė, “Characterization of biological materials by frequency-domain fluorescence lifetime measurements using ultraviolet light-emitting diodes,” Opt. Mater. 30(5), 800–805 (2008).
[Crossref]

V. C. Cappendijk, A. G. Kessels, S. Heeneman, K. B. Cleutjens, G. W. H. Schurink, R. J. T. J. Welten, W. H. Mess, R. J. van Suylen, T. Leiner, M. J. Daemen, J. M. van Engelshoven, and M. E. Kooi, “Comparison of lipid-rich necrotic core size in symptomatic and asymptomatic carotid atherosclerotic plaque: Initial results,” J. Magn. Reson. Imaging 27(6), 1356–1361 (2008).
[Crossref] [PubMed]

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

2007 (1)

C. W. Chang, D. Sud, and M. A. Mycek, “Fluorescence lifetime imaging microscopy,” Methods Cell Biol. 81, 495–524 (2007).
[Crossref] [PubMed]

2006 (1)

R. Virmani, A. P. Burke, A. Farb, and F. D. Kolodgie, “Pathology of the vulnerable plaque,” J. Am. Coll. Cardiol. 47(8Suppl), C13–C18 (2006).
[Crossref] [PubMed]

2005 (4)

L. Marcu, Q. Fang, J. A. Jo, T. Papaioannou, A. Dorafshar, T. Reil, J.-H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “In vivo detection of macrophages in a rabbit atherosclerotic model by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 181(2), 295–303 (2005).
[Crossref] [PubMed]

G. K. Hansson, “Inflammation, atherosclerosis, and coronary artery disease,” N. Engl. J. Med. 352(16), 1685–1695 (2005).
[Crossref] [PubMed]

J. Cai, T. S. Hatsukami, M. S. Ferguson, W. S. Kerwin, T. Saam, B. Chu, N. Takaya, N. L. Polissar, and C. Yuan, “In vivo quantitative measurement of intact fibrous cap and lipid-rich necrotic core size in atherosclerotic carotid plaque: comparison of high-resolution, contrast-enhanced magnetic resonance imaging and histology,” Circulation 112(22), 3437–3444 (2005).
[Crossref] [PubMed]

J. J. Boyle, “Macrophage activation in atherosclerosis: pathogenesis and pharmacology of plaque rupture,” Curr. Vasc. Pharmacol. 3(1), 63–68 (2005).
[Crossref] [PubMed]

2004 (2)

G. Finet, J. Ohayon, and G. Rioufol, “Biomechanical interaction between cap thickness, lipid core composition and blood pressure in vulnerable coronary plaque: impact on stability or instability,” Coron. Artery Dis. 15(1), 13–20 (2004).
[Crossref] [PubMed]

J. A. Jo, Q. Fang, T. Papaioannou, and L. Marcu, “Fast model-free deconvolution of fluorescence decay for analysis of biological systems,” J. Biomed. Opt. 9(4), 743–752 (2004).
[Crossref] [PubMed]

2003 (4)

T. J. Pfefer, D. Y. Paithankar, J. M. Poneros, K. T. Schomacker, and N. S. Nishioka, “Temporally and spectrally resolved fluorescence spectroscopy for the detection of high grade dysplasia in Barrett’s esophagus,” Lasers Surg. Med. 32(1), 10–16 (2003).
[Crossref] [PubMed]

H. Pal, S. Nad, and M. Kumbhakar, “Photophysical properties of coumarin-120: Unusual behavior in nonpolar solvents,” J. Chem. Phys. 119(1), 443–452 (2003).
[Crossref]

G. J. Tearney, H. Yabushita, S. L. Houser, H. T. Aretz, I. K. Jang, K. H. Schlendorf, C. R. Kauffman, M. Shishkov, E. F. Halpern, and B. E. Bouma, “Quantification of macrophage content in atherosclerotic plaques by optical coherence tomography,” Circulation 107(1), 113–119 (2003).
[Crossref] [PubMed]

J. Siegel, D. S. Elson, S. E. Webb, K. C. Lee, A. Vlandas, G. L. Gambaruto, S. Lévêque-Fort, M. J. Lever, P. J. Tadrous, G. W. Stamp, A. L. Wallace, A. Sandison, T. F. Watson, F. Alvarez, and P. M. French, “Studying biological tissue with fluorescence lifetime imaging: microscopy, endoscopy, and complex decay profiles,” Appl. Opt. 42(16), 2995–3004 (2003).
[Crossref] [PubMed]

2002 (2)

K. Arakawa, K. Isoda, T. Ito, K. Nakajima, T. Shibuya, and F. Ohsuzu, “Fluorescence analysis of biochemical constituents identifies atherosclerotic plaque with a thin fibrous cap,” Arterioscler. Thromb. Vasc. Biol. 22(6), 1002–1007 (2002).
[Crossref] [PubMed]

R. Virmani, A. P. Burke, F. D. Kolodgie, and A. Farb, “Vulnerable plaque: the pathology of unstable coronary lesions,” J. Interv. Cardiol. 15(6), 439–446 (2002).
[Crossref] [PubMed]

2001 (1)

G. S. Mintz, S. E. Nissen, W. D. Anderson, S. R. Bailey, R. Erbel, P. J. Fitzgerald, F. J. Pinto, K. Rosenfield, R. J. Siegel, E. M. Tuzcu, and P. G. Yock, “American College of Cardiology clinical expert consensus document on standards for acquisition, measurement and reporting of intravascular ultrasound studies (ivus): A report of the american college of cardiology task force on clinical expert consensus documents developed in collaboration with the european society of cardiology endorsed by the society of cardiac angiography and interventions,” J. Am. Coll. Cardiol. 37(5), 1478–1492 (2001).
[Crossref] [PubMed]

1999 (3)

P. I. Bastiaens and A. Squire, “Fluorescence lifetime imaging microscopy: spatial resolution of biochemical processes in the cell,” Trends Cell Biol. 9(2), 48–52 (1999).
[Crossref] [PubMed]

R. E. Shadwick, “Mechanical design in arteries,” J. Exp. Biol. 202(Pt 23), 3305–3313 (1999).
[PubMed]

D. Magde, G. E. Rojas, and P. G. Seybold, “Solvent dependence of the fluorescence lifetimes of xanthene dyes,” Photochem. Photobiol. 70(5), 737–744 (1999).
[Crossref]

1992 (3)

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

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

H. M. Loree, R. D. Kamm, R. G. Stringfellow, and R. T. Lee, “Effects of fibrous cap thickness on peak circumferential stress in model atherosclerotic vessels,” Circ. Res. 71(4), 850–858 (1992).
[Crossref] [PubMed]

1991 (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

1983 (1)

M. S. Brown and J. L. Goldstein, “Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis,” Annu. Rev. Biochem. 52(1), 223–261 (1983).
[Crossref] [PubMed]

Achilefu, S.

M. Y. Berezin and S. Achilefu, “Fluorescence lifetime measurements and biological imaging,” Chem. Rev. 110(5), 2641–2684 (2010).
[Crossref] [PubMed]

Adame, J.

J. A. Jo, J. Park, P. Pande, S. Shrestha, M. J. Serafino, J. J. Rico Jimenez, F. Clubb, B. Walton, L. M. Buja, J. E. Phipps, M. D. Feldman, J. Adame, and B. E. Applegate, “Simultaneous morphological and biochemical endogenous optical imaging of atherosclerosis,” Eur. Heart J. Cardiovasc. Imaging 16(8), 910–918 (2015).
[Crossref] [PubMed]

Adriaenssens, T.

G. J. Ughi, T. Adriaenssens, P. Sinnaeve, W. Desmet, and J. D’hooge, “Automated tissue characterization of in vivo atherosclerotic plaques by intravascular optical coherence tomography images,” Biomed. Opt. Express 4(7), 1014–1030 (2013).
[Crossref] [PubMed]

G. J. Tearney, E. Regar, T. Akasaka, T. Adriaenssens, P. Barlis, H. G. Bezerra, B. Bouma, N. Bruining, J. M. Cho, S. Chowdhary, M. A. Costa, R. de Silva, J. Dijkstra, C. Di Mario, D. Dudek, E. Falk, M. D. Feldman, P. Fitzgerald, H. M. Garcia-Garcia, N. Gonzalo, J. F. Granada, G. Guagliumi, N. R. Holm, Y. Honda, F. Ikeno, M. Kawasaki, J. Kochman, L. Koltowski, T. Kubo, T. Kume, H. Kyono, C. C. Lam, G. Lamouche, D. P. Lee, M. B. Leon, A. Maehara, O. Manfrini, G. S. Mintz, K. Mizuno, M. A. Morel, S. Nadkarni, H. Okura, H. Otake, A. Pietrasik, F. Prati, L. Räber, M. D. Radu, J. Rieber, M. Riga, A. Rollins, M. Rosenberg, V. Sirbu, P. W. Serruys, K. Shimada, T. Shinke, J. Shite, E. Siegel, S. Sonoda, M. Suter, S. Takarada, A. Tanaka, M. Terashima, T. Thim, S. Uemura, G. J. Ughi, H. M. van Beusekom, A. F. van der Steen, G. A. van Es, G. van Soest, R. Virmani, S. Waxman, N. J. Weissman, G. Weisz, and International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT), “Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation,” J. Am. Coll. Cardiol. 59(12), 1058–1072 (2012).
[Crossref] [PubMed]

Ahmad, R.

Akasaka, T.

G. J. Tearney, E. Regar, T. Akasaka, T. Adriaenssens, P. Barlis, H. G. Bezerra, B. Bouma, N. Bruining, J. M. Cho, S. Chowdhary, M. A. Costa, R. de Silva, J. Dijkstra, C. Di Mario, D. Dudek, E. Falk, M. D. Feldman, P. Fitzgerald, H. M. Garcia-Garcia, N. Gonzalo, J. F. Granada, G. Guagliumi, N. R. Holm, Y. Honda, F. Ikeno, M. Kawasaki, J. Kochman, L. Koltowski, T. Kubo, T. Kume, H. Kyono, C. C. Lam, G. Lamouche, D. P. Lee, M. B. Leon, A. Maehara, O. Manfrini, G. S. Mintz, K. Mizuno, M. A. Morel, S. Nadkarni, H. Okura, H. Otake, A. Pietrasik, F. Prati, L. Räber, M. D. Radu, J. Rieber, M. Riga, A. Rollins, M. Rosenberg, V. Sirbu, P. W. Serruys, K. Shimada, T. Shinke, J. Shite, E. Siegel, S. Sonoda, M. Suter, S. Takarada, A. Tanaka, M. Terashima, T. Thim, S. Uemura, G. J. Ughi, H. M. van Beusekom, A. F. van der Steen, G. A. van Es, G. van Soest, R. Virmani, S. Waxman, N. J. Weissman, G. Weisz, and International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT), “Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation,” J. Am. Coll. Cardiol. 59(12), 1058–1072 (2012).
[Crossref] [PubMed]

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,” J. Biomed. Opt. 17(10), 1060121 (2012).
[Crossref] [PubMed]

Alfano, R. R.

L. A. Sordillo, Y. Pu, P. P. Sordillo, Y. Budansky, and R. R. Alfano, “Optical spectral fingerprints of tissues from patients with different breast cancer histologies using a novel fluorescence spectroscopic device,” Technol. Cancer Res. Treat. 12(5), 455–461 (2013).
[Crossref] [PubMed]

Y. Pu, W. Wang, G. Tang, and R. R. Alfano, “Changes of collagen and nicotinamide adenine dinucleotide in human cancerous and normal prostate tissues studied using native fluorescence spectroscopy with selective excitation wavelength,” J. Biomed. Opt. 15(4), 047008 (2010).
[Crossref] [PubMed]

Alfonso-García, A.

A. Alfonso-García, T. D. Smith, R. Datta, T. U. Luu, E. Gratton, E. O. Potma, and W. F. Liu, “Label-free identification of macrophage phenotype by fluorescence lifetime imaging microscopy,” J. Biomed. Opt. 21(4), 046005 (2016).
[Crossref] [PubMed]

Alvarez, F.

Anderson, W. D.

G. S. Mintz, S. E. Nissen, W. D. Anderson, S. R. Bailey, R. Erbel, P. J. Fitzgerald, F. J. Pinto, K. Rosenfield, R. J. Siegel, E. M. Tuzcu, and P. G. Yock, “American College of Cardiology clinical expert consensus document on standards for acquisition, measurement and reporting of intravascular ultrasound studies (ivus): A report of the american college of cardiology task force on clinical expert consensus documents developed in collaboration with the european society of cardiology endorsed by the society of cardiac angiography and interventions,” J. Am. Coll. Cardiol. 37(5), 1478–1492 (2001).
[Crossref] [PubMed]

Applegate, B. E.

S. Shrestha, M. J. Serafino, J. Rico-Jimenez, J. Park, X. Chen, S. Zhaorigetu, B. L. Walton, J. A. Jo, and B. E. Applegate, “Multimodal optical coherence tomography and fluorescence lifetime imaging with interleaved excitation sources for simultaneous endogenous and exogenous fluorescence,” Biomed. Opt. Express 7(9), 3184–3197 (2016).
[Crossref] [PubMed]

J. A. Jo, J. Park, P. Pande, S. Shrestha, M. J. Serafino, J. J. Rico Jimenez, F. Clubb, B. Walton, L. M. Buja, J. E. Phipps, M. D. Feldman, J. Adame, and B. E. Applegate, “Simultaneous morphological and biochemical endogenous optical imaging of atherosclerosis,” Eur. Heart J. Cardiovasc. Imaging 16(8), 910–918 (2015).
[Crossref] [PubMed]

J. Park, P. Pande, S. Shrestha, F. Clubb, B. E. Applegate, and J. A. Jo, “Biochemical characterization of atherosclerotic plaques by endogenous multispectral fluorescence lifetime imaging microscopy,” Atherosclerosis 220(2), 394–401 (2012).
[Crossref] [PubMed]

J. Park, J. A. Jo, S. Shrestha, P. Pande, Q. Wan, and B. E. Applegate, “A dual-modality optical coherence tomography and fluorescence lifetime imaging microscopy system for simultaneous morphological and biochemical tissue characterization,” Biomed. Opt. Express 1(1), 186–200 (2010).
[Crossref] [PubMed]

S. Shrestha, B. E. Applegate, J. Park, X. Xiao, P. Pande, and J. A. Jo, “High-speed multispectral fluorescence lifetime imaging implementation for in vivo applications,” Opt. Lett. 35(15), 2558–2560 (2010).
[Crossref] [PubMed]

Arakawa, K.

K. Arakawa, K. Isoda, T. Ito, K. Nakajima, T. Shibuya, and F. Ohsuzu, “Fluorescence analysis of biochemical constituents identifies atherosclerotic plaque with a thin fibrous cap,” Arterioscler. Thromb. Vasc. Biol. 22(6), 1002–1007 (2002).
[Crossref] [PubMed]

Aretz, H. T.

G. J. Tearney, H. Yabushita, S. L. Houser, H. T. Aretz, I. K. Jang, K. H. Schlendorf, C. R. Kauffman, M. Shishkov, E. F. Halpern, and B. E. Bouma, “Quantification of macrophage content in atherosclerotic plaques by optical coherence tomography,” Circulation 107(1), 113–119 (2003).
[Crossref] [PubMed]

Bailey, S. R.

G. S. Mintz, S. E. Nissen, W. D. Anderson, S. R. Bailey, R. Erbel, P. J. Fitzgerald, F. J. Pinto, K. Rosenfield, R. J. Siegel, E. M. Tuzcu, and P. G. Yock, “American College of Cardiology clinical expert consensus document on standards for acquisition, measurement and reporting of intravascular ultrasound studies (ivus): A report of the american college of cardiology task force on clinical expert consensus documents developed in collaboration with the european society of cardiology endorsed by the society of cardiac angiography and interventions,” J. Am. Coll. Cardiol. 37(5), 1478–1492 (2001).
[Crossref] [PubMed]

Baker, J. D.

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J.-H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[Crossref] [PubMed]

L. Marcu, Q. Fang, J. A. Jo, T. Papaioannou, A. Dorafshar, T. Reil, J.-H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “In vivo detection of macrophages in a rabbit atherosclerotic model by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 181(2), 295–303 (2005).
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Bakiene, E.

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G. J. Tearney, E. Regar, T. Akasaka, T. Adriaenssens, P. Barlis, H. G. Bezerra, B. Bouma, N. Bruining, J. M. Cho, S. Chowdhary, M. A. Costa, R. de Silva, J. Dijkstra, C. Di Mario, D. Dudek, E. Falk, M. D. Feldman, P. Fitzgerald, H. M. Garcia-Garcia, N. Gonzalo, J. F. Granada, G. Guagliumi, N. R. Holm, Y. Honda, F. Ikeno, M. Kawasaki, J. Kochman, L. Koltowski, T. Kubo, T. Kume, H. Kyono, C. C. Lam, G. Lamouche, D. P. Lee, M. B. Leon, A. Maehara, O. Manfrini, G. S. Mintz, K. Mizuno, M. A. Morel, S. Nadkarni, H. Okura, H. Otake, A. Pietrasik, F. Prati, L. Räber, M. D. Radu, J. Rieber, M. Riga, A. Rollins, M. Rosenberg, V. Sirbu, P. W. Serruys, K. Shimada, T. Shinke, J. Shite, E. Siegel, S. Sonoda, M. Suter, S. Takarada, A. Tanaka, M. Terashima, T. Thim, S. Uemura, G. J. Ughi, H. M. van Beusekom, A. F. van der Steen, G. A. van Es, G. van Soest, R. Virmani, S. Waxman, N. J. Weissman, G. Weisz, and International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT), “Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation,” J. Am. Coll. Cardiol. 59(12), 1058–1072 (2012).
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G. Pasterkamp, H. M. den Ruijter, and P. Libby, “Temporal shifts in clinical presentation and underlying mechanisms of atherosclerotic disease,” Nat. Rev. Cardiol. 14(1), 21–29 (2017).
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Desmet, W.

Di Mario, C.

G. J. Tearney, E. Regar, T. Akasaka, T. Adriaenssens, P. Barlis, H. G. Bezerra, B. Bouma, N. Bruining, J. M. Cho, S. Chowdhary, M. A. Costa, R. de Silva, J. Dijkstra, C. Di Mario, D. Dudek, E. Falk, M. D. Feldman, P. Fitzgerald, H. M. Garcia-Garcia, N. Gonzalo, J. F. Granada, G. Guagliumi, N. R. Holm, Y. Honda, F. Ikeno, M. Kawasaki, J. Kochman, L. Koltowski, T. Kubo, T. Kume, H. Kyono, C. C. Lam, G. Lamouche, D. P. Lee, M. B. Leon, A. Maehara, O. Manfrini, G. S. Mintz, K. Mizuno, M. A. Morel, S. Nadkarni, H. Okura, H. Otake, A. Pietrasik, F. Prati, L. Räber, M. D. Radu, J. Rieber, M. Riga, A. Rollins, M. Rosenberg, V. Sirbu, P. W. Serruys, K. Shimada, T. Shinke, J. Shite, E. Siegel, S. Sonoda, M. Suter, S. Takarada, A. Tanaka, M. Terashima, T. Thim, S. Uemura, G. J. Ughi, H. M. van Beusekom, A. F. van der Steen, G. A. van Es, G. van Soest, R. Virmani, S. Waxman, N. J. Weissman, G. Weisz, and International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT), “Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation,” J. Am. Coll. Cardiol. 59(12), 1058–1072 (2012).
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Dijkstra, J.

G. J. Tearney, E. Regar, T. Akasaka, T. Adriaenssens, P. Barlis, H. G. Bezerra, B. Bouma, N. Bruining, J. M. Cho, S. Chowdhary, M. A. Costa, R. de Silva, J. Dijkstra, C. Di Mario, D. Dudek, E. Falk, M. D. Feldman, P. Fitzgerald, H. M. Garcia-Garcia, N. Gonzalo, J. F. Granada, G. Guagliumi, N. R. Holm, Y. Honda, F. Ikeno, M. Kawasaki, J. Kochman, L. Koltowski, T. Kubo, T. Kume, H. Kyono, C. C. Lam, G. Lamouche, D. P. Lee, M. B. Leon, A. Maehara, O. Manfrini, G. S. Mintz, K. Mizuno, M. A. Morel, S. Nadkarni, H. Okura, H. Otake, A. Pietrasik, F. Prati, L. Räber, M. D. Radu, J. Rieber, M. Riga, A. Rollins, M. Rosenberg, V. Sirbu, P. W. Serruys, K. Shimada, T. Shinke, J. Shite, E. Siegel, S. Sonoda, M. Suter, S. Takarada, A. Tanaka, M. Terashima, T. Thim, S. Uemura, G. J. Ughi, H. M. van Beusekom, A. F. van der Steen, G. A. van Es, G. van Soest, R. Virmani, S. Waxman, N. J. Weissman, G. Weisz, and International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT), “Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation,” J. Am. Coll. Cardiol. 59(12), 1058–1072 (2012).
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Dorafshar, A.

L. Marcu, Q. Fang, J. A. Jo, T. Papaioannou, A. Dorafshar, T. Reil, J.-H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “In vivo detection of macrophages in a rabbit atherosclerotic model by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 181(2), 295–303 (2005).
[Crossref] [PubMed]

Dudek, D.

G. J. Tearney, E. Regar, T. Akasaka, T. Adriaenssens, P. Barlis, H. G. Bezerra, B. Bouma, N. Bruining, J. M. Cho, S. Chowdhary, M. A. Costa, R. de Silva, J. Dijkstra, C. Di Mario, D. Dudek, E. Falk, M. D. Feldman, P. Fitzgerald, H. M. Garcia-Garcia, N. Gonzalo, J. F. Granada, G. Guagliumi, N. R. Holm, Y. Honda, F. Ikeno, M. Kawasaki, J. Kochman, L. Koltowski, T. Kubo, T. Kume, H. Kyono, C. C. Lam, G. Lamouche, D. P. Lee, M. B. Leon, A. Maehara, O. Manfrini, G. S. Mintz, K. Mizuno, M. A. Morel, S. Nadkarni, H. Okura, H. Otake, A. Pietrasik, F. Prati, L. Räber, M. D. Radu, J. Rieber, M. Riga, A. Rollins, M. Rosenberg, V. Sirbu, P. W. Serruys, K. Shimada, T. Shinke, J. Shite, E. Siegel, S. Sonoda, M. Suter, S. Takarada, A. Tanaka, M. Terashima, T. Thim, S. Uemura, G. J. Ughi, H. M. van Beusekom, A. F. van der Steen, G. A. van Es, G. van Soest, R. Virmani, S. Waxman, N. J. Weissman, G. Weisz, and International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT), “Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation,” J. Am. Coll. Cardiol. 59(12), 1058–1072 (2012).
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Dunsby, C.

J. McGinty, N. P. Galletly, C. Dunsby, I. Munro, D. S. Elson, J. Requejo-Isidro, P. Cohen, R. Ahmad, A. Forsyth, A. V. Thillainayagam, M. A. Neil, P. M. French, and G. W. Stamp, “Wide-field fluorescence lifetime imaging of cancer,” Biomed. Opt. Express 1(2), 627–640 (2010).
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N. P. Galletly, J. McGinty, C. Dunsby, F. Teixeira, J. Requejo-Isidro, I. Munro, D. S. Elson, M. A. Neil, A. C. Chu, P. M. French, and G. W. Stamp, “Fluorescence lifetime imaging distinguishes basal cell carcinoma from surrounding uninvolved skin,” Br. J. Dermatol. 159(1), 152–161 (2008).
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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,” Rev. Sci. Instrum. 85(3), 034303 (2014).
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Y. Sun, N. Hatami, M. Yee, J. Phipps, D. S. Elson, F. Gorin, R. J. Schrot, and L. Marcu, “Fluorescence lifetime imaging microscopy for brain tumor image-guided surgery,” J. Biomed. Opt. 15(5), 056022 (2010).
[Crossref] [PubMed]

J. McGinty, N. P. Galletly, C. Dunsby, I. Munro, D. S. Elson, J. Requejo-Isidro, P. Cohen, R. Ahmad, A. Forsyth, A. V. Thillainayagam, M. A. Neil, P. M. French, and G. W. Stamp, “Wide-field fluorescence lifetime imaging of cancer,” Biomed. Opt. Express 1(2), 627–640 (2010).
[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,” Opt. Lett. 34(13), 2081–2083 (2009).
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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,” Opt. Lett. 33(6), 630–632 (2008).
[Crossref] [PubMed]

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

J. Siegel, D. S. Elson, S. E. Webb, K. C. Lee, A. Vlandas, G. L. Gambaruto, S. Lévêque-Fort, M. J. Lever, P. J. Tadrous, G. W. Stamp, A. L. Wallace, A. Sandison, T. F. Watson, F. Alvarez, and P. M. French, “Studying biological tissue with fluorescence lifetime imaging: microscopy, endoscopy, and complex decay profiles,” Appl. Opt. 42(16), 2995–3004 (2003).
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Erbel, R.

G. S. Mintz, S. E. Nissen, W. D. Anderson, S. R. Bailey, R. Erbel, P. J. Fitzgerald, F. J. Pinto, K. Rosenfield, R. J. Siegel, E. M. Tuzcu, and P. G. Yock, “American College of Cardiology clinical expert consensus document on standards for acquisition, measurement and reporting of intravascular ultrasound studies (ivus): A report of the american college of cardiology task force on clinical expert consensus documents developed in collaboration with the european society of cardiology endorsed by the society of cardiac angiography and interventions,” J. Am. Coll. Cardiol. 37(5), 1478–1492 (2001).
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et,

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
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Falk, E.

G. J. Tearney, E. Regar, T. Akasaka, T. Adriaenssens, P. Barlis, H. G. Bezerra, B. Bouma, N. Bruining, J. M. Cho, S. Chowdhary, M. A. Costa, R. de Silva, J. Dijkstra, C. Di Mario, D. Dudek, E. Falk, M. D. Feldman, P. Fitzgerald, H. M. Garcia-Garcia, N. Gonzalo, J. F. Granada, G. Guagliumi, N. R. Holm, Y. Honda, F. Ikeno, M. Kawasaki, J. Kochman, L. Koltowski, T. Kubo, T. Kume, H. Kyono, C. C. Lam, G. Lamouche, D. P. Lee, M. B. Leon, A. Maehara, O. Manfrini, G. S. Mintz, K. Mizuno, M. A. Morel, S. Nadkarni, H. Okura, H. Otake, A. Pietrasik, F. Prati, L. Räber, M. D. Radu, J. Rieber, M. Riga, A. Rollins, M. Rosenberg, V. Sirbu, P. W. Serruys, K. Shimada, T. Shinke, J. Shite, E. Siegel, S. Sonoda, M. Suter, S. Takarada, A. Tanaka, M. Terashima, T. Thim, S. Uemura, G. J. Ughi, H. M. van Beusekom, A. F. van der Steen, G. A. van Es, G. van Soest, R. Virmani, S. Waxman, N. J. Weissman, G. Weisz, and International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT), “Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation,” J. Am. Coll. Cardiol. 59(12), 1058–1072 (2012).
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Fang, Q.

P. V. Butte, Q. Fang, J. A. Jo, W. H. Yong, B. K. Pikul, K. L. Black, and L. Marcu, “Intraoperative delineation of primary brain tumors using time-resolved fluorescence spectroscopy,” J. Biomed. Opt. 15(2), 027008 (2010).
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L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J.-H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[Crossref] [PubMed]

L. Marcu, Q. Fang, J. A. Jo, T. Papaioannou, A. Dorafshar, T. Reil, J.-H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “In vivo detection of macrophages in a rabbit atherosclerotic model by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 181(2), 295–303 (2005).
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J. A. Jo, Q. Fang, T. Papaioannou, and L. Marcu, “Fast model-free deconvolution of fluorescence decay for analysis of biological systems,” J. Biomed. Opt. 9(4), 743–752 (2004).
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Farb, A.

R. Virmani, A. P. Burke, A. Farb, and F. D. Kolodgie, “Pathology of the vulnerable plaque,” J. Am. Coll. Cardiol. 47(8Suppl), C13–C18 (2006).
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R. Virmani, A. P. Burke, F. D. Kolodgie, and A. Farb, “Vulnerable plaque: the pathology of unstable coronary lesions,” J. Interv. Cardiol. 15(6), 439–446 (2002).
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Farwell, D. G.

Fatakdawala, H.

J. Bec, J. E. Phipps, D. Gorpas, D. Ma, H. Fatakdawala, K. B. Margulies, J. A. Southard, and L. Marcu, “In vivo label-free structural and biochemical imaging of coronary arteries using an integrated ultrasound and multispectral fluorescence lifetime catheter system,” Sci. Rep. 7(1), 8960 (2017).
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H. Fatakdawala, D. Gorpas, J. W. Bishop, J. Bec, D. Ma, J. A. Southard, K. B. Margulies, and L. Marcu, “Fluorescence lifetime imaging combined with conventional intravascular ultrasound for enhanced assessment of atherosclerotic plaques: an ex vivo study in human coronary arteries,” J. Cardiovasc. Transl. Res. 8(4), 253–263 (2015).
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D. Ma, J. Bec, D. R. Yankelevich, D. Gorpas, H. Fatakdawala, and L. Marcu, “Rotational multispectral fluorescence lifetime imaging and intravascular ultrasound: bimodal system for intravascular applications,” J. Biomed. Opt. 19(6), 066004 (2014).
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Feldman, M. D.

J. A. Jo, J. Park, P. Pande, S. Shrestha, M. J. Serafino, J. J. Rico Jimenez, F. Clubb, B. Walton, L. M. Buja, J. E. Phipps, M. D. Feldman, J. Adame, and B. E. Applegate, “Simultaneous morphological and biochemical endogenous optical imaging of atherosclerosis,” Eur. Heart J. Cardiovasc. Imaging 16(8), 910–918 (2015).
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G. J. Tearney, E. Regar, T. Akasaka, T. Adriaenssens, P. Barlis, H. G. Bezerra, B. Bouma, N. Bruining, J. M. Cho, S. Chowdhary, M. A. Costa, R. de Silva, J. Dijkstra, C. Di Mario, D. Dudek, E. Falk, M. D. Feldman, P. Fitzgerald, H. M. Garcia-Garcia, N. Gonzalo, J. F. Granada, G. Guagliumi, N. R. Holm, Y. Honda, F. Ikeno, M. Kawasaki, J. Kochman, L. Koltowski, T. Kubo, T. Kume, H. Kyono, C. C. Lam, G. Lamouche, D. P. Lee, M. B. Leon, A. Maehara, O. Manfrini, G. S. Mintz, K. Mizuno, M. A. Morel, S. Nadkarni, H. Okura, H. Otake, A. Pietrasik, F. Prati, L. Räber, M. D. Radu, J. Rieber, M. Riga, A. Rollins, M. Rosenberg, V. Sirbu, P. W. Serruys, K. Shimada, T. Shinke, J. Shite, E. Siegel, S. Sonoda, M. Suter, S. Takarada, A. Tanaka, M. Terashima, T. Thim, S. Uemura, G. J. Ughi, H. M. van Beusekom, A. F. van der Steen, G. A. van Es, G. van Soest, R. Virmani, S. Waxman, N. J. Weissman, G. Weisz, and International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT), “Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation,” J. Am. Coll. Cardiol. 59(12), 1058–1072 (2012).
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Fergus, R.

M. D. Zeiler and R. Fergus, “Visualizing and understanding convolutional networks,” in European Conference on Computer Vision (Springer, 2014), 818–833.

Ferguson, M. S.

J. Cai, T. S. Hatsukami, M. S. Ferguson, W. S. Kerwin, T. Saam, B. Chu, N. Takaya, N. L. Polissar, and C. Yuan, “In vivo quantitative measurement of intact fibrous cap and lipid-rich necrotic core size in atherosclerotic carotid plaque: comparison of high-resolution, contrast-enhanced magnetic resonance imaging and histology,” Circulation 112(22), 3437–3444 (2005).
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Finet, G.

G. Finet, J. Ohayon, and G. Rioufol, “Biomechanical interaction between cap thickness, lipid core composition and blood pressure in vulnerable coronary plaque: impact on stability or instability,” Coron. Artery Dis. 15(1), 13–20 (2004).
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Finn, A. V.

A. V. Finn, M. Nakano, J. Narula, F. D. Kolodgie, and R. Virmani, “Concept of vulnerable/unstable plaque,” Arterioscler. Thromb. Vasc. Biol. 30(7), 1282–1292 (2010).
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Fishbein, M. C.

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J.-H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[Crossref] [PubMed]

L. Marcu, Q. Fang, J. A. Jo, T. Papaioannou, A. Dorafshar, T. Reil, J.-H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “In vivo detection of macrophages in a rabbit atherosclerotic model by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 181(2), 295–303 (2005).
[Crossref] [PubMed]

Fitzgerald, P.

G. J. Tearney, E. Regar, T. Akasaka, T. Adriaenssens, P. Barlis, H. G. Bezerra, B. Bouma, N. Bruining, J. M. Cho, S. Chowdhary, M. A. Costa, R. de Silva, J. Dijkstra, C. Di Mario, D. Dudek, E. Falk, M. D. Feldman, P. Fitzgerald, H. M. Garcia-Garcia, N. Gonzalo, J. F. Granada, G. Guagliumi, N. R. Holm, Y. Honda, F. Ikeno, M. Kawasaki, J. Kochman, L. Koltowski, T. Kubo, T. Kume, H. Kyono, C. C. Lam, G. Lamouche, D. P. Lee, M. B. Leon, A. Maehara, O. Manfrini, G. S. Mintz, K. Mizuno, M. A. Morel, S. Nadkarni, H. Okura, H. Otake, A. Pietrasik, F. Prati, L. Räber, M. D. Radu, J. Rieber, M. Riga, A. Rollins, M. Rosenberg, V. Sirbu, P. W. Serruys, K. Shimada, T. Shinke, J. Shite, E. Siegel, S. Sonoda, M. Suter, S. Takarada, A. Tanaka, M. Terashima, T. Thim, S. Uemura, G. J. Ughi, H. M. van Beusekom, A. F. van der Steen, G. A. van Es, G. van Soest, R. Virmani, S. Waxman, N. J. Weissman, G. Weisz, and International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT), “Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation,” J. Am. Coll. Cardiol. 59(12), 1058–1072 (2012).
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Fitzgerald, P. J.

G. S. Mintz, S. E. Nissen, W. D. Anderson, S. R. Bailey, R. Erbel, P. J. Fitzgerald, F. J. Pinto, K. Rosenfield, R. J. Siegel, E. M. Tuzcu, and P. G. Yock, “American College of Cardiology clinical expert consensus document on standards for acquisition, measurement and reporting of intravascular ultrasound studies (ivus): A report of the american college of cardiology task force on clinical expert consensus documents developed in collaboration with the european society of cardiology endorsed by the society of cardiac angiography and interventions,” J. Am. Coll. Cardiol. 37(5), 1478–1492 (2001).
[Crossref] [PubMed]

Flotte, T.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Forsyth, A.

Freischlag, J. A.

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J.-H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[Crossref] [PubMed]

L. Marcu, Q. Fang, J. A. Jo, T. Papaioannou, A. Dorafshar, T. Reil, J.-H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “In vivo detection of macrophages in a rabbit atherosclerotic model by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 181(2), 295–303 (2005).
[Crossref] [PubMed]

French, P. M.

Galletly, N. P.

J. McGinty, N. P. Galletly, C. Dunsby, I. Munro, D. S. Elson, J. Requejo-Isidro, P. Cohen, R. Ahmad, A. Forsyth, A. V. Thillainayagam, M. A. Neil, P. M. French, and G. W. Stamp, “Wide-field fluorescence lifetime imaging of cancer,” Biomed. Opt. Express 1(2), 627–640 (2010).
[Crossref] [PubMed]

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

Gambaruto, G. L.

Garcia-Garcia, H. M.

G. J. Tearney, E. Regar, T. Akasaka, T. Adriaenssens, P. Barlis, H. G. Bezerra, B. Bouma, N. Bruining, J. M. Cho, S. Chowdhary, M. A. Costa, R. de Silva, J. Dijkstra, C. Di Mario, D. Dudek, E. Falk, M. D. Feldman, P. Fitzgerald, H. M. Garcia-Garcia, N. Gonzalo, J. F. Granada, G. Guagliumi, N. R. Holm, Y. Honda, F. Ikeno, M. Kawasaki, J. Kochman, L. Koltowski, T. Kubo, T. Kume, H. Kyono, C. C. Lam, G. Lamouche, D. P. Lee, M. B. Leon, A. Maehara, O. Manfrini, G. S. Mintz, K. Mizuno, M. A. Morel, S. Nadkarni, H. Okura, H. Otake, A. Pietrasik, F. Prati, L. Räber, M. D. Radu, J. Rieber, M. Riga, A. Rollins, M. Rosenberg, V. Sirbu, P. W. Serruys, K. Shimada, T. Shinke, J. Shite, E. Siegel, S. Sonoda, M. Suter, S. Takarada, A. Tanaka, M. Terashima, T. Thim, S. Uemura, G. J. Ughi, H. M. van Beusekom, A. F. van der Steen, G. A. van Es, G. van Soest, R. Virmani, S. Waxman, N. J. Weissman, G. Weisz, and International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT), “Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation,” J. Am. Coll. Cardiol. 59(12), 1058–1072 (2012).
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H. Fatakdawala, D. Gorpas, J. W. Bishop, J. Bec, D. Ma, J. A. Southard, K. B. Margulies, and L. Marcu, “Fluorescence lifetime imaging combined with conventional intravascular ultrasound for enhanced assessment of atherosclerotic plaques: an ex vivo study in human coronary arteries,” J. Cardiovasc. Transl. Res. 8(4), 253–263 (2015).
[Crossref] [PubMed]

D. Ma, J. Bec, D. R. Yankelevich, D. Gorpas, H. Fatakdawala, and L. Marcu, “Rotational multispectral fluorescence lifetime imaging and intravascular ultrasound: bimodal system for intravascular applications,” J. Biomed. Opt. 19(6), 066004 (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,” Rev. Sci. Instrum. 85(3), 034303 (2014).
[Crossref] [PubMed]

Maehara, A.

G. J. Tearney, E. Regar, T. Akasaka, T. Adriaenssens, P. Barlis, H. G. Bezerra, B. Bouma, N. Bruining, J. M. Cho, S. Chowdhary, M. A. Costa, R. de Silva, J. Dijkstra, C. Di Mario, D. Dudek, E. Falk, M. D. Feldman, P. Fitzgerald, H. M. Garcia-Garcia, N. Gonzalo, J. F. Granada, G. Guagliumi, N. R. Holm, Y. Honda, F. Ikeno, M. Kawasaki, J. Kochman, L. Koltowski, T. Kubo, T. Kume, H. Kyono, C. C. Lam, G. Lamouche, D. P. Lee, M. B. Leon, A. Maehara, O. Manfrini, G. S. Mintz, K. Mizuno, M. A. Morel, S. Nadkarni, H. Okura, H. Otake, A. Pietrasik, F. Prati, L. Räber, M. D. Radu, J. Rieber, M. Riga, A. Rollins, M. Rosenberg, V. Sirbu, P. W. Serruys, K. Shimada, T. Shinke, J. Shite, E. Siegel, S. Sonoda, M. Suter, S. Takarada, A. Tanaka, M. Terashima, T. Thim, S. Uemura, G. J. Ughi, H. M. van Beusekom, A. F. van der Steen, G. A. van Es, G. van Soest, R. Virmani, S. Waxman, N. J. Weissman, G. Weisz, and International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT), “Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation,” J. Am. Coll. Cardiol. 59(12), 1058–1072 (2012).
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Magde, D.

D. Magde, G. E. Rojas, and P. G. Seybold, “Solvent dependence of the fluorescence lifetimes of xanthene dyes,” Photochem. Photobiol. 70(5), 737–744 (1999).
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Maitland, K. C.

J. M. Jabbour, S. Cheng, B. H. Malik, R. Cuenca, J. A. Jo, J. Wright, Y.-S. L. Cheng, and K. C. Maitland, “Fluorescence lifetime imaging and reflectance confocal microscopy for multiscale imaging of oral precancer,” J. Biomed. Opt. 18(4), 046012 (2013).
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Malik, B. H.

J. M. Jabbour, S. Cheng, B. H. Malik, R. Cuenca, J. A. Jo, J. Wright, Y.-S. L. Cheng, and K. C. Maitland, “Fluorescence lifetime imaging and reflectance confocal microscopy for multiscale imaging of oral precancer,” J. Biomed. Opt. 18(4), 046012 (2013).
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Manfrini, O.

G. J. Tearney, E. Regar, T. Akasaka, T. Adriaenssens, P. Barlis, H. G. Bezerra, B. Bouma, N. Bruining, J. M. Cho, S. Chowdhary, M. A. Costa, R. de Silva, J. Dijkstra, C. Di Mario, D. Dudek, E. Falk, M. D. Feldman, P. Fitzgerald, H. M. Garcia-Garcia, N. Gonzalo, J. F. Granada, G. Guagliumi, N. R. Holm, Y. Honda, F. Ikeno, M. Kawasaki, J. Kochman, L. Koltowski, T. Kubo, T. Kume, H. Kyono, C. C. Lam, G. Lamouche, D. P. Lee, M. B. Leon, A. Maehara, O. Manfrini, G. S. Mintz, K. Mizuno, M. A. Morel, S. Nadkarni, H. Okura, H. Otake, A. Pietrasik, F. Prati, L. Räber, M. D. Radu, J. Rieber, M. Riga, A. Rollins, M. Rosenberg, V. Sirbu, P. W. Serruys, K. Shimada, T. Shinke, J. Shite, E. Siegel, S. Sonoda, M. Suter, S. Takarada, A. Tanaka, M. Terashima, T. Thim, S. Uemura, G. J. Ughi, H. M. van Beusekom, A. F. van der Steen, G. A. van Es, G. van Soest, R. Virmani, S. Waxman, N. J. Weissman, G. Weisz, and International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT), “Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation,” J. Am. Coll. Cardiol. 59(12), 1058–1072 (2012).
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Marcu, L.

J. Bec, J. E. Phipps, D. Gorpas, D. Ma, H. Fatakdawala, K. B. Margulies, J. A. Southard, and L. Marcu, “In vivo label-free structural and biochemical imaging of coronary arteries using an integrated ultrasound and multispectral fluorescence lifetime catheter system,” Sci. Rep. 7(1), 8960 (2017).
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B. E. Sherlock, J. E. Phipps, J. Bec, and L. Marcu, “Simultaneous, label-free, multispectral fluorescence lifetime imaging and optical coherence tomography using a double-clad fiber,” Opt. Lett. 42(19), 3753–3756 (2017).
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H. Fatakdawala, D. Gorpas, J. W. Bishop, J. Bec, D. Ma, J. A. Southard, K. B. Margulies, and L. Marcu, “Fluorescence lifetime imaging combined with conventional intravascular ultrasound for enhanced assessment of atherosclerotic plaques: an ex vivo study in human coronary arteries,” J. Cardiovasc. Transl. Res. 8(4), 253–263 (2015).
[Crossref] [PubMed]

D. Ma, J. Bec, D. R. Yankelevich, D. Gorpas, H. Fatakdawala, and L. Marcu, “Rotational multispectral fluorescence lifetime imaging and intravascular ultrasound: bimodal system for intravascular applications,” J. Biomed. Opt. 19(6), 066004 (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,” Rev. Sci. Instrum. 85(3), 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,” J. Biomed. Opt. 17(10), 1060121 (2012).
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P. V. Butte, Q. Fang, J. A. Jo, W. H. Yong, B. K. Pikul, K. L. Black, and L. Marcu, “Intraoperative delineation of primary brain tumors using time-resolved fluorescence spectroscopy,” J. Biomed. Opt. 15(2), 027008 (2010).
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Y. Sun, N. Hatami, M. Yee, J. Phipps, D. S. Elson, F. Gorin, R. J. Schrot, and L. Marcu, “Fluorescence lifetime imaging microscopy for brain tumor image-guided surgery,” J. Biomed. Opt. 15(5), 056022 (2010).
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L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J.-H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
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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,” Opt. Lett. 34(13), 2081–2083 (2009).
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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,” Opt. Lett. 33(6), 630–632 (2008).
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J. A. Jo, Q. Fang, T. Papaioannou, and L. Marcu, “Fast model-free deconvolution of fluorescence decay for analysis of biological systems,” J. Biomed. Opt. 9(4), 743–752 (2004).
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Margulies, K. B.

J. Bec, J. E. Phipps, D. Gorpas, D. Ma, H. Fatakdawala, K. B. Margulies, J. A. Southard, and L. Marcu, “In vivo label-free structural and biochemical imaging of coronary arteries using an integrated ultrasound and multispectral fluorescence lifetime catheter system,” Sci. Rep. 7(1), 8960 (2017).
[Crossref] [PubMed]

H. Fatakdawala, D. Gorpas, J. W. Bishop, J. Bec, D. Ma, J. A. Southard, K. B. Margulies, and L. Marcu, “Fluorescence lifetime imaging combined with conventional intravascular ultrasound for enhanced assessment of atherosclerotic plaques: an ex vivo study in human coronary arteries,” J. Cardiovasc. Transl. Res. 8(4), 253–263 (2015).
[Crossref] [PubMed]

McCarthy, J. R.

H. Yoo, J. W. Kim, M. Shishkov, E. Namati, T. Morse, R. Shubochkin, J. R. McCarthy, V. Ntziachristos, B. E. Bouma, F. A. Jaffer, and G. J. Tearney, “Intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo,” Nat. Med. 17(12), 1680–1684 (2011).
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McGinty, J.

J. McGinty, N. P. Galletly, C. Dunsby, I. Munro, D. S. Elson, J. Requejo-Isidro, P. Cohen, R. Ahmad, A. Forsyth, A. V. Thillainayagam, M. A. Neil, P. M. French, and G. W. Stamp, “Wide-field fluorescence lifetime imaging of cancer,” Biomed. Opt. Express 1(2), 627–640 (2010).
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Meier, J.

Mess, W. H.

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Mizuno, K.

G. J. Tearney, E. Regar, T. Akasaka, T. Adriaenssens, P. Barlis, H. G. Bezerra, B. Bouma, N. Bruining, J. M. Cho, S. Chowdhary, M. A. Costa, R. de Silva, J. Dijkstra, C. Di Mario, D. Dudek, E. Falk, M. D. Feldman, P. Fitzgerald, H. M. Garcia-Garcia, N. Gonzalo, J. F. Granada, G. Guagliumi, N. R. Holm, Y. Honda, F. Ikeno, M. Kawasaki, J. Kochman, L. Koltowski, T. Kubo, T. Kume, H. Kyono, C. C. Lam, G. Lamouche, D. P. Lee, M. B. Leon, A. Maehara, O. Manfrini, G. S. Mintz, K. Mizuno, M. A. Morel, S. Nadkarni, H. Okura, H. Otake, A. Pietrasik, F. Prati, L. Räber, M. D. Radu, J. Rieber, M. Riga, A. Rollins, M. Rosenberg, V. Sirbu, P. W. Serruys, K. Shimada, T. Shinke, J. Shite, E. Siegel, S. Sonoda, M. Suter, S. Takarada, A. Tanaka, M. Terashima, T. Thim, S. Uemura, G. J. Ughi, H. M. van Beusekom, A. F. van der Steen, G. A. van Es, G. van Soest, R. Virmani, S. Waxman, N. J. Weissman, G. Weisz, and International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT), “Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation,” J. Am. Coll. Cardiol. 59(12), 1058–1072 (2012).
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Morel, M. A.

G. J. Tearney, E. Regar, T. Akasaka, T. Adriaenssens, P. Barlis, H. G. Bezerra, B. Bouma, N. Bruining, J. M. Cho, S. Chowdhary, M. A. Costa, R. de Silva, J. Dijkstra, C. Di Mario, D. Dudek, E. Falk, M. D. Feldman, P. Fitzgerald, H. M. Garcia-Garcia, N. Gonzalo, J. F. Granada, G. Guagliumi, N. R. Holm, Y. Honda, F. Ikeno, M. Kawasaki, J. Kochman, L. Koltowski, T. Kubo, T. Kume, H. Kyono, C. C. Lam, G. Lamouche, D. P. Lee, M. B. Leon, A. Maehara, O. Manfrini, G. S. Mintz, K. Mizuno, M. A. Morel, S. Nadkarni, H. Okura, H. Otake, A. Pietrasik, F. Prati, L. Räber, M. D. Radu, J. Rieber, M. Riga, A. Rollins, M. Rosenberg, V. Sirbu, P. W. Serruys, K. Shimada, T. Shinke, J. Shite, E. Siegel, S. Sonoda, M. Suter, S. Takarada, A. Tanaka, M. Terashima, T. Thim, S. Uemura, G. J. Ughi, H. M. van Beusekom, A. F. van der Steen, G. A. van Es, G. van Soest, R. Virmani, S. Waxman, N. J. Weissman, G. Weisz, and International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT), “Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation,” J. Am. Coll. Cardiol. 59(12), 1058–1072 (2012).
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Morse, T.

H. Yoo, J. W. Kim, M. Shishkov, E. Namati, T. Morse, R. Shubochkin, J. R. McCarthy, V. Ntziachristos, B. E. Bouma, F. A. Jaffer, and G. J. Tearney, “Intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo,” Nat. Med. 17(12), 1680–1684 (2011).
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J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, and M. L. Johnson, “Fluorescence lifetime imaging of free and protein-bound NADH,” Proc. Natl. Acad. Sci. U.S.A. 89(4), 1271–1275 (1992).
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H. Yoo, J. W. Kim, M. Shishkov, E. Namati, T. Morse, R. Shubochkin, J. R. McCarthy, V. Ntziachristos, B. E. Bouma, F. A. Jaffer, and G. J. Tearney, “Intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo,” Nat. Med. 17(12), 1680–1684 (2011).
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J. Park, P. Pande, S. Shrestha, F. Clubb, B. E. Applegate, and J. A. Jo, “Biochemical characterization of atherosclerotic plaques by endogenous multispectral fluorescence lifetime imaging microscopy,” Atherosclerosis 220(2), 394–401 (2012).
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J. Park, J. A. Jo, S. Shrestha, P. Pande, Q. Wan, and B. E. Applegate, “A dual-modality optical coherence tomography and fluorescence lifetime imaging microscopy system for simultaneous morphological and biochemical tissue characterization,” Biomed. Opt. Express 1(1), 186–200 (2010).
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S. Shrestha, B. E. Applegate, J. Park, X. Xiao, P. Pande, and J. A. Jo, “High-speed multispectral fluorescence lifetime imaging implementation for in vivo applications,” Opt. Lett. 35(15), 2558–2560 (2010).
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Räber, L.

G. J. Tearney, E. Regar, T. Akasaka, T. Adriaenssens, P. Barlis, H. G. Bezerra, B. Bouma, N. Bruining, J. M. Cho, S. Chowdhary, M. A. Costa, R. de Silva, J. Dijkstra, C. Di Mario, D. Dudek, E. Falk, M. D. Feldman, P. Fitzgerald, H. M. Garcia-Garcia, N. Gonzalo, J. F. Granada, G. Guagliumi, N. R. Holm, Y. Honda, F. Ikeno, M. Kawasaki, J. Kochman, L. Koltowski, T. Kubo, T. Kume, H. Kyono, C. C. Lam, G. Lamouche, D. P. Lee, M. B. Leon, A. Maehara, O. Manfrini, G. S. Mintz, K. Mizuno, M. A. Morel, S. Nadkarni, H. Okura, H. Otake, A. Pietrasik, F. Prati, L. Räber, M. D. Radu, J. Rieber, M. Riga, A. Rollins, M. Rosenberg, V. Sirbu, P. W. Serruys, K. Shimada, T. Shinke, J. Shite, E. Siegel, S. Sonoda, M. Suter, S. Takarada, A. Tanaka, M. Terashima, T. Thim, S. Uemura, G. J. Ughi, H. M. van Beusekom, A. F. van der Steen, G. A. van Es, G. van Soest, R. Virmani, S. Waxman, N. J. Weissman, G. Weisz, and International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT), “Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation,” J. Am. Coll. Cardiol. 59(12), 1058–1072 (2012).
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G. J. Tearney, E. Regar, T. Akasaka, T. Adriaenssens, P. Barlis, H. G. Bezerra, B. Bouma, N. Bruining, J. M. Cho, S. Chowdhary, M. A. Costa, R. de Silva, J. Dijkstra, C. Di Mario, D. Dudek, E. Falk, M. D. Feldman, P. Fitzgerald, H. M. Garcia-Garcia, N. Gonzalo, J. F. Granada, G. Guagliumi, N. R. Holm, Y. Honda, F. Ikeno, M. Kawasaki, J. Kochman, L. Koltowski, T. Kubo, T. Kume, H. Kyono, C. C. Lam, G. Lamouche, D. P. Lee, M. B. Leon, A. Maehara, O. Manfrini, G. S. Mintz, K. Mizuno, M. A. Morel, S. Nadkarni, H. Okura, H. Otake, A. Pietrasik, F. Prati, L. Räber, M. D. Radu, J. Rieber, M. Riga, A. Rollins, M. Rosenberg, V. Sirbu, P. W. Serruys, K. Shimada, T. Shinke, J. Shite, E. Siegel, S. Sonoda, M. Suter, S. Takarada, A. Tanaka, M. Terashima, T. Thim, S. Uemura, G. J. Ughi, H. M. van Beusekom, A. F. van der Steen, G. A. van Es, G. van Soest, R. Virmani, S. Waxman, N. J. Weissman, G. Weisz, and International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT), “Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation,” J. Am. Coll. Cardiol. 59(12), 1058–1072 (2012).
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H. Yoo, J. W. Kim, M. Shishkov, E. Namati, T. Morse, R. Shubochkin, J. R. McCarthy, V. Ntziachristos, B. E. Bouma, F. A. Jaffer, and G. J. Tearney, “Intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo,” Nat. Med. 17(12), 1680–1684 (2011).
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J. Cai, T. S. Hatsukami, M. S. Ferguson, W. S. Kerwin, T. Saam, B. Chu, N. Takaya, N. L. Polissar, and C. Yuan, “In vivo quantitative measurement of intact fibrous cap and lipid-rich necrotic core size in atherosclerotic carotid plaque: comparison of high-resolution, contrast-enhanced magnetic resonance imaging and histology,” Circulation 112(22), 3437–3444 (2005).
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M. D. Zeiler and R. Fergus, “Visualizing and understanding convolutional networks,” in European Conference on Computer Vision (Springer, 2014), 818–833.

Zhaorigetu, S.

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,” J. Biomed. Opt. 17(10), 1060121 (2012).
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Žukauskas, A.

A. Žukauskas, P. Vitta, N. Kurilčik, S. Juršėnas, and E. Bakienė, “Characterization of biological materials by frequency-domain fluorescence lifetime measurements using ultraviolet light-emitting diodes,” Opt. Mater. 30(5), 800–805 (2008).
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K. Arakawa, K. Isoda, T. Ito, K. Nakajima, T. Shibuya, and F. Ohsuzu, “Fluorescence analysis of biochemical constituents identifies atherosclerotic plaque with a thin fibrous cap,” Arterioscler. Thromb. Vasc. Biol. 22(6), 1002–1007 (2002).
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J. Park, P. Pande, S. Shrestha, F. Clubb, B. E. Applegate, and J. A. Jo, “Biochemical characterization of atherosclerotic plaques by endogenous multispectral fluorescence lifetime imaging microscopy,” Atherosclerosis 220(2), 394–401 (2012).
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L. Marcu, Q. Fang, J. A. Jo, T. Papaioannou, A. Dorafshar, T. Reil, J.-H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “In vivo detection of macrophages in a rabbit atherosclerotic model by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 181(2), 295–303 (2005).
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L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J.-H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
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M. Y. Berezin and S. Achilefu, “Fluorescence lifetime measurements and biological imaging,” Chem. Rev. 110(5), 2641–2684 (2010).
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S. Lee, M. W. Lee, H. S. Cho, J. W. Song, H. S. Nam, D. J. Oh, K. Park, W.-Y. Oh, H. Yoo, and J. W. Kim, “Fully integrated high-speed intravascular optical coherence tomography/near-infrared fluorescence structural/molecular imaging in vivo using a clinically available near-infrared fluorescence-emitting indocyanine green to detect inflamed lipid-rich atheromata in coronary-sized vessels,” Circ. Cardiovasc. Interv. 7(4), 560–569 (2014).
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G. J. Tearney, H. Yabushita, S. L. Houser, H. T. Aretz, I. K. Jang, K. H. Schlendorf, C. R. Kauffman, M. Shishkov, E. F. Halpern, and B. E. Bouma, “Quantification of macrophage content in atherosclerotic plaques by optical coherence tomography,” Circulation 107(1), 113–119 (2003).
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J. Biomed. Opt. (8)

P. V. Butte, Q. Fang, J. A. Jo, W. H. Yong, B. K. Pikul, K. L. Black, and L. Marcu, “Intraoperative delineation of primary brain tumors using time-resolved fluorescence spectroscopy,” J. Biomed. Opt. 15(2), 027008 (2010).
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J. A. Jo, Q. Fang, T. Papaioannou, and L. Marcu, “Fast model-free deconvolution of fluorescence decay for analysis of biological systems,” J. Biomed. Opt. 9(4), 743–752 (2004).
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A. Alfonso-García, T. D. Smith, R. Datta, T. U. Luu, E. Gratton, E. O. Potma, and W. F. Liu, “Label-free identification of macrophage phenotype by fluorescence lifetime imaging microscopy,” J. Biomed. Opt. 21(4), 046005 (2016).
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Y. Pu, W. Wang, G. Tang, and R. R. Alfano, “Changes of collagen and nicotinamide adenine dinucleotide in human cancerous and normal prostate tissues studied using native fluorescence spectroscopy with selective excitation wavelength,” J. Biomed. Opt. 15(4), 047008 (2010).
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Y. Sun, N. Hatami, M. Yee, J. Phipps, D. S. Elson, F. Gorin, R. J. Schrot, and L. Marcu, “Fluorescence lifetime imaging microscopy for brain tumor image-guided surgery,” J. Biomed. Opt. 15(5), 056022 (2010).
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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,” J. Biomed. Opt. 17(10), 1060121 (2012).
[Crossref] [PubMed]

D. Ma, J. Bec, D. R. Yankelevich, D. Gorpas, H. Fatakdawala, and L. Marcu, “Rotational multispectral fluorescence lifetime imaging and intravascular ultrasound: bimodal system for intravascular applications,” J. Biomed. Opt. 19(6), 066004 (2014).
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J. M. Jabbour, S. Cheng, B. H. Malik, R. Cuenca, J. A. Jo, J. Wright, Y.-S. L. Cheng, and K. C. Maitland, “Fluorescence lifetime imaging and reflectance confocal microscopy for multiscale imaging of oral precancer,” J. Biomed. Opt. 18(4), 046012 (2013).
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J. Cardiovasc. Transl. Res. (1)

H. Fatakdawala, D. Gorpas, J. W. Bishop, J. Bec, D. Ma, J. A. Southard, K. B. Margulies, and L. Marcu, “Fluorescence lifetime imaging combined with conventional intravascular ultrasound for enhanced assessment of atherosclerotic plaques: an ex vivo study in human coronary arteries,” J. Cardiovasc. Transl. Res. 8(4), 253–263 (2015).
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Microsc. Res. Tech. (1)

A. Leray, F. B. Riquet, E. Richard, C. Spriet, D. Trinel, and L. Héliot, “Optimized protocol of a frequency domain fluorescence lifetime imaging microscope for FRET measurements,” Microsc. Res. Tech. 72(5), 371–379 (2009).
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G. K. Hansson, “Inflammation, atherosclerosis, and coronary artery disease,” N. Engl. J. Med. 352(16), 1685–1695 (2005).
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H. Yoo, J. W. Kim, M. Shishkov, E. Namati, T. Morse, R. Shubochkin, J. R. McCarthy, V. Ntziachristos, B. E. Bouma, F. A. Jaffer, and G. J. Tearney, “Intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo,” Nat. Med. 17(12), 1680–1684 (2011).
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Opt. Express (2)

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A. Žukauskas, P. Vitta, N. Kurilčik, S. Juršėnas, and E. Bakienė, “Characterization of biological materials by frequency-domain fluorescence lifetime measurements using ultraviolet light-emitting diodes,” Opt. Mater. 30(5), 800–805 (2008).
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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,” Rev. Sci. Instrum. 85(3), 034303 (2014).
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J. Bec, J. E. Phipps, D. Gorpas, D. Ma, H. Fatakdawala, K. B. Margulies, J. A. Southard, and L. Marcu, “In vivo label-free structural and biochemical imaging of coronary arteries using an integrated ultrasound and multispectral fluorescence lifetime catheter system,” Sci. Rep. 7(1), 8960 (2017).
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Supplementary Material (1)

NameDescription
» Visualization 1       Measured fluorescence emission pulses sequence waveform in practice

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Figures (5)

Fig. 1
Fig. 1 A schematic diagram of the combined FLIm-OCT system with the OCT subsystem (orange), the FLIm subsystem (sky-blue), the combining optics of FLIm and OCT (green), and the workstation and data acquisition system (navy). Gray and black lines are electronic wires and optical fibers, respectively. DM: dichroic mirror; L: lens; F: filter; GVM: galvano mirror; DC: dispersion compensator; FS: acousto-optic frequency shifter; PC: polarization controller.
Fig. 2
Fig. 2 Workflow of signal and image processing for the combined FLIm-OCT image visualization, which is split into six steps: two-channel raw data acquisition, raw data deinterleaving, OCT processing, FLIm processing, data conversion, and combined image visualization. Each box represents a task.
Fig. 3
Fig. 3 Monte-Carlo simulation results for the multispectral AMD-FLIm subsystem. (a) Simulated pulse sequence waveforms for the different fluorescence lifetimes (0, 2, 4, 6 nsec) with the optical delay-line lengths of 1 m (IRF), 16 m (Ch 1), 31 m (Ch 2), and 46 m (Ch 3). (b) Results of the simulation for fluorescence lifetime measurements according to the length difference between the two optical delay-lines for the fluorescence emission pulse and the IRF from 0 m to 50 m. (c) Compensation results for the increase in measured fluorescence lifetime due to the use of optical delay-lines. Solid lines and dashed lines in (b) and (c) denote the expected value and the standard deviation (precision) of each simulation with the different fluorescence lifetimes.
Fig. 4
Fig. 4 A combined FLIm-OCT imaging result for a normal-looking rabbit iliac artery tissue specimen. (a) An OCT image of the normal-looking specimen combined with the co-registered fluorescence lifetime distribution of the three spectral channels. (b-d) Pseudocolor en face maps of fluorescence lifetime distribution of channels (b) 1, (c) 2, and (d) 3, which are represented in HSV color space. Each red dashed line indicates the corresponding position to the image in (a). (e-h) The corresponding histopathological sections: (e) H&E staining, (f) ORO staining, (g) PSR staining, and (h) RAM11 immunostaining. Red arrowheads in (a) and (e-h) show the exact match between the combined FLIm-OCT image and the histological sections. Scale bars are 1 mm.
Fig. 5
Fig. 5 A combined FLIm-OCT imaging result for an atherosclerotic rabbit iliac artery tissue specimen. (a) An OCT image of the atherosclerotic specimen combined with the co-registered fluorescence lifetime distribution of the three spectral channels. (b-d) Pseudocolor en face maps of fluorescence lifetime distribution of channels (b) 1, (c) 2 and (d) 3, which are represented in HSV color space. Each red dashed line indicates the corresponding position to the image in (a). (e-h) The corresponding histopathological sections: (e) H&E staining, (f) ORO staining, (g) PSR staining, and (h) RAM11 immunostaining. Red arrowheads in (a) and (e-h) show the exact match between the combined FLIm-OCT image and the histological sections. Scale bars are 1 mm.

Tables (2)

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Table 1 Fluorescence emission peak and fluorescence lifetime of solutions for performance validation of the FLIm subsystem

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Table 2 Results of fluorescence lifetime measurements for the solutions with known fluorescence lifetimes

Equations (1)

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τ=M D decay =M D em M D irf =(M D ex +M D decay +M D pd )(M D ex +M D pd ) =( t i em (t)dt i em (t)dt )( t i irf (t)dt i irf (t)dt )

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