Abstract

Barrett’s esophagus (BE) is a metaplastic disorder where dysplastic and early cancerous changes are invisible to the naked eye and where the practice of blind biopsy is hampered by large sampling errors. Multi-photon microscopy (MPM) has emerged as an alternative solution for fast and label-free diagnostic capability for identifying the histological features with sub-micron accuracy. We developed a compact, inexpensive MPM system by using a handheld mode-locked fiber laser operating at 1560nm to study mucosal biopsies of BE. The combination of back-scattered THG, back-reflected forward THG and SHG signals generate images of cell nuclei and collagen, leading to label-free diagnosis in Barrett’s.

© 2015 Optical Society of America

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2015 (9)

J. H. Park, W. Sun, and M. Cui, “High-resolution in vivo imaging of mouse brain through the intact skull,” Proc. Natl. Acad. Sci. U.S.A. 112(30), 9236–9241 (2015).
[Crossref] [PubMed]

E. J. Lee, B. Kim, H. G. Ahn, S. H. Park, E. Cheong, and S. Lee, “In-vivo and label-free imaging of cellular and tissue structures in mouse ear skin by using second- and third-harmonic generation microscopy,” J Korean Phys Soc, Vol. 66(4), 597–601 (2015).
[Crossref]

L. Jay, J. M. Bourget, B. Goyer, K. Singh, I. Brunette, T. Ozaki, and S. Proulx, “Characterization of tissue-engineered posterior corneas using second- and third-harmonic generation microscopy,” PLoS One 10(4), e0125564 (2015).
[Crossref] [PubMed]

E. Gavgiotaki, G. Filippidis, M. Kalognomou, A. A. Tsouko, I. Skordos, C. Fotakis, and I. Athanassakis, “Third harmonic generation microscopy as a reliable diagnostic tool for evaluating lipid body modification during cell activation: the example of BV-2 microglia cells,” J. Struct. Biol. 189(2), 105–113 (2015).
[Crossref] [PubMed]

O. Masihzadeh, T. C. Lei, S. R. Domingue, M. Y. Kahook, R. A. Bartels, and D. A. Ammar, “Third harmonic generation microscopy of a mouse retina,” Mol. Vis. 21, 538–547 (2015).
[PubMed]

M. Yildirim, N. Durr, and A. Ben-Yakar, “Tripling the maximum imaging depth with third-harmonic generation microscopy,” J. Biomed. Opt. 20(9), 096013 (2015).
[Crossref] [PubMed]

Y. C. Chen, S. Y. Lee, Y. Wu, K. Brink, D. B. Shieh, T. D. Huang, R. R. Reisz, and C. K. Sun, “Third-harmonic generation microscopy reveals dental anatomy in ancient fossils,” Opt. Lett. 40(7), 1354–1357 (2015).
[Crossref] [PubMed]

S. Kumar, T. Kamali, J. M. Levitte, O. Katz, B. Hermann, R. Werkmeister, B. Považay, W. Drexler, A. Unterhuber, and Y. Silberberg, “Single-pulse CARS based multimodal nonlinear optical microscope for bioimaging,” Opt. Express 23(10), 13082–13098 (2015).
[Crossref] [PubMed]

J. Trägårdh, G. Robb, K. K. E. Gadalla, S. Cobb, C. Travis, G. L. Oppo, and G. McConnell, “Label-free imaging of thick tissue at 1550 nm using a femtosecond optical parametric generator,” Opt. Lett. 40(15), 3484–3487 (2015).
[Crossref] [PubMed]

2014 (3)

J. Chen, S. Wong, M. H. Nathanson, and D. Jain, “Evaluation of Barrett esophagus by multi-photon microscopy,” Arch Pathol Lab Med. 138(8), 582 (2014).

S. J. Spechler and R. F. Souza, “Barrett’s esophagus,” N. Engl. J. Med. 371(9), 836–845 (2014).
[Crossref] [PubMed]

O. Pech, A. May, H. Manner, A. Behrens, J. Pohl, M. Weferling, U. Hartmann, N. Manner, J. Huijsmans, L. Gossner, T. Rabenstein, M. Vieth, M. Stolte, and C. Ell, “Long-term efficacy and safety of endoscopic resection for patients with mucosal adenocarcinoma of the esophagus,” Gastroenterology 146(3), 652–660 (2014).
[Crossref] [PubMed]

2013 (3)

P. Sharma, R. H. Hawes, A. Bansal, N. Gupta, W. Curvers, A. Rastogi, M. Singh, M. Hall, S. C. Mathur, S. B. Wani, B. Hoffman, S. Gaddam, P. Fockens, and J. J. Bergman, “Standard endoscopy with random biopsies versus narrow band imaging targeted biopsies in Barrett’s oesophagus: a prospective, international, randomised controlled trial,” Gut 62(1), 15–21 (2013).
[Crossref] [PubMed]

K. Kieu, S. Mehravar, R. Gowda, R. A. Norwood, and N. Peyghambarian, “Label-free multi-photon imaging using a compact femtosecond fiber laser mode-locked by carbon nanotube saturable absorber,” Biomed. Opt. Express 4(10), 2187–2195 (2013).
[Crossref] [PubMed]

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

2012 (3)

E. L. Bird-Lieberman, A. A. Neves, P. Lao-Sirieix, M. O’Donovan, M. Novelli, L. B. Lovat, W. S. Eng, L. K. Mahal, K. M. Brindle, and R. C. Fitzgerald, “Molecular imaging using fluorescent lectins permits rapid endoscopic identification of dysplasia in Barrett’s esophagus,” Nat. Med. 18(2), 315–321 (2012).
[Crossref] [PubMed]

E. Chabrun, M. Marty, and F. Zerbib, “Development of esophageal adenocarcinoma on buried glands following radiofrequency ablation for Barrett’s esophagus,” Endoscopy 44(S 02Suppl 2 UCTN), E392 (2012).
[Crossref] [PubMed]

B. Lin, S. Urayama, R. M. G. Saroufeem, D. L. Matthews, and S. G. Demos, “Establishment of rules for interpreting ultraviolet autofluorescence microscopy images for noninvasive detection of Barrett’s esophagus and dysplasia,” J. Biomed. Opt. 17(1), 016013 (2012).
[Crossref] [PubMed]

2011 (2)

N. A. Gray, R. D. Odze, and S. J. Spechler, “Buried metaplasia after endoscopic ablation of Barrett’s esophagus: a systematic review,” Am. J. Gastroenterol. 106(11), 1899–1909 (2011).
[Crossref] [PubMed]

M. J. Farrar, F. W. Wise, J. R. Fetcho, and C. B. Schaffer, “In vivo imaging of myelin in the vertebrate central nervous system using third harmonic generation microscopy,” Biophys. J. 100, 1362–1371 (2011).

2010 (2)

T. L. Sun, Y. Liu, M. C. Sung, H. C. Chen, C. H. Yang, V. Hovhannisyan, W. C. Lin, Y. M. Jeng, W. L. Chen, L. L. Chiou, G. T. Huang, K. H. Kim, P. T. C. So, Y. F. Chen, H. S. Lee, and C. Y. Dong, “Ex vivo imaging and quantification of liver fibrosis using second-harmonic generation microscopy,” J. Biomed. Opt. 15(3), 036002 (2010).
[Crossref] [PubMed]

S. Zhuo, J. Chen, G. Wu, S. S. Xie, L. Q. Zheng, X. S. Jiang, and X. Q. Zhu, “Quantitatively linking collagen alteration and epithelial tumor progression by second harmonic generation microscopy,” Appl. Phys. Lett. 96(21), 213704 (2010).
[Crossref]

2009 (4)

D. C. Adler, C. Zhou, T. H. Tsai, H. C. Lee, L. Becker, J. M. Schmitt, Q. Huang, J. G. Fujimoto, and H. Mashimo, “Three-dimensional optical coherence tomography of Barrett’s esophagus and buried glands beneath neosquamous epithelium following radiofrequency ablation,” Endoscopy 41(9), 773–776 (2009).
[Crossref] [PubMed]

S. Preibisch, S. Saalfeld, and P. Tomancak, “Globally optimal stitching of tiled 3D microscopic image acquisitions,” Bioinformatics 25(11), 1463–1465 (2009).
[Crossref] [PubMed]

N. J. Shaheen, P. Sharma, B. F. Overholt, H. C. Wolfsen, R. E. Sampliner, K. K. Wang, J. A. Galanko, M. P. Bronner, J. R. Goldblum, A. E. Bennett, B. A. Jobe, G. M. Eisen, M. B. Fennerty, J. G. Hunter, D. E. Fleischer, V. K. Sharma, R. H. Hawes, B. J. Hoffman, R. I. Rothstein, S. R. Gordon, H. Mashimo, K. J. Chang, V. R. Muthusamy, S. A. Edmundowicz, S. J. Spechler, A. A. Siddiqui, R. F. Souza, A. Infantolino, G. W. Falk, M. B. Kimmey, R. D. Madanick, A. Chak, and C. J. Lightdale, “Radiofrequency ablation in Barrett’s esophagus with dysplasia,” N. Engl. J. Med. 360(22), 2277–2288 (2009).
[Crossref] [PubMed]

G. W. Falk, “Risk factors for esophageal cancer development,” Surg. Oncol. Clin. N. Am. 18(3), 469–485 (2009).
[Crossref] [PubMed]

2008 (3)

R. D. Odze and G. Y. Lauwers, “Histopathology of Barrett’s esophagus after ablation and endoscopic mucosal resection therapy,” Endoscopy 40(12), 1008–1015 (2008).
[Crossref] [PubMed]

T. J. Muldoon, S. Anandasabapathy, D. Maru, and R. Richards-Kortum, “High-resolution imaging in Barrett’s esophagus: a novel, low-cost endoscopic microscope,” Gastrointest. Endosc. 68(4), 737–744 (2008).
[Crossref] [PubMed]

J. N. Rogart, J. Nagata, C. S. Loeser, R. D. Roorda, H. Aslanian, M. E. Robert, W. R. Zipfel, and M. H. Nathanson, “Multiphoton imaging can be used for microscopic examination of intact human gastrointestinal mucosa ex vivo,” Clin. Gastroenterol. Hepatol. 6(1), 95–101 (2008).
[Crossref] [PubMed]

2007 (1)

2006 (1)

2005 (1)

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, J. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, “Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues,” Cancer Res. 65(4), 1180–1186 (2005).
[Crossref] [PubMed]

2004 (1)

M. Solaymani-Dodaran, R. F. Logan, J. West, T. Card, and C. Coupland, “Risk of oesophageal cancer in Barrett’s oesophagus and gastro-oesophageal reflux,” Gut 53(8), 1070–1074 (2004).
[Crossref] [PubMed]

2003 (5)

D. J. Kearney, C. Crump, C. Maynard, and E. J. Boyko, “A case-control study of endoscopy and mortality from adenocarcinoma of the esophagus or gastric cardia in persons with GERD,” Gastrointest. Endosc. 57(7), 823–829 (2003).
[Crossref] [PubMed]

D. Chatelain and J. F. Fléjou, “High-grade dysplasia and superficial adenocarcinoma in Barrett’s esophagus: histological mapping and expression of p53, p21 and Bcl-2 oncoproteins,” Virchows Arch. 442(1), 18–24 (2003).
[PubMed]

M. J. Connor and P. Sharma, “Chromoendoscopy and magnification endoscopy in Barrett’s esophagus,” Gastrointest. Endosc. Clin. N. Am. 13(2), 269–277 (2003).
[Crossref] [PubMed]

H. Lantz and N. Vakil, “Barrett’s esophagus and argon plasma coagulation: buried trouble?” Am. J. Gastroenterol. 98(7), 1647–1649 (2003).
[PubMed]

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: Multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
[Crossref] [PubMed]

2002 (1)

J. R. Goldblum and G. Y. Lauwers, “Dysplasia arising in barrett’s esophagus: diagnostic pitfalls and natural history,” Semin. Diagn. Pathol. 19(1), 12–19 (2002).
[PubMed]

2001 (1)

E. Montgomery, M. P. Bronner, J. R. Goldblum, J. K. Greenson, M. M. Haber, J. Hart, L. W. Lamps, G. Y. Lauwers, A. J. Lazenby, D. N. Lewin, M. E. Robert, A. Y. Toledano, Y. Shyr, and K. Washington, “Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation,” Hum. Pathol. 32(4), 368–378 (2001).
[Crossref] [PubMed]

1999 (1)

1994 (1)

P. Whittaker, R. A. Kloner, D. R. Boughner, and J. G. Pickering, “Quantitative assessment of myocardial collagen with picrosirius red staining and circularly polarized light,” Basic Res. Cardiol. 89(5), 397–410 (1994).
[Crossref] [PubMed]

1990 (1)

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[Crossref] [PubMed]

1988 (1)

B. J. Reid, R. C. Haggitt, C. E. Rubin, G. Roth, C. M. Surawicz, G. Van Belle, K. Lewin, W. M. Weinstein, D. A. Antonioli, H. Goldman, W. Macdonald, and D. Owen, “Observer variation in the diagnosis of dysplasia in Barrett’s esophagus,” Hum. Pathol. 19(2), 166–178 (1988).
[Crossref] [PubMed]

1979 (1)

L. C. Junqueira, G. Bignolas, and R. R. Brentani, “Picrosirius staining plus polarization microscopy, a specific method for collagen detection in tissue sections,” Histochem. J. 11(4), 447–455 (1979).
[Crossref] [PubMed]

1973 (1)

H. Puchtler, F. S. Waldrop, and L. S. Valentine, “Polarization microscopic studies of connective tissue stained with picro-sirius red FBA,” Beitr. Pathol. 150(2), 174–187 (1973).
[Crossref] [PubMed]

Adler, D. C.

D. C. Adler, C. Zhou, T. H. Tsai, H. C. Lee, L. Becker, J. M. Schmitt, Q. Huang, J. G. Fujimoto, and H. Mashimo, “Three-dimensional optical coherence tomography of Barrett’s esophagus and buried glands beneath neosquamous epithelium following radiofrequency ablation,” Endoscopy 41(9), 773–776 (2009).
[Crossref] [PubMed]

Ahn, H. G.

E. J. Lee, B. Kim, H. G. Ahn, S. H. Park, E. Cheong, and S. Lee, “In-vivo and label-free imaging of cellular and tissue structures in mouse ear skin by using second- and third-harmonic generation microscopy,” J Korean Phys Soc, Vol. 66(4), 597–601 (2015).
[Crossref]

Ammar, D. A.

O. Masihzadeh, T. C. Lei, S. R. Domingue, M. Y. Kahook, R. A. Bartels, and D. A. Ammar, “Third harmonic generation microscopy of a mouse retina,” Mol. Vis. 21, 538–547 (2015).
[PubMed]

Anandasabapathy, S.

T. J. Muldoon, S. Anandasabapathy, D. Maru, and R. Richards-Kortum, “High-resolution imaging in Barrett’s esophagus: a novel, low-cost endoscopic microscope,” Gastrointest. Endosc. 68(4), 737–744 (2008).
[Crossref] [PubMed]

Antonioli, D. A.

B. J. Reid, R. C. Haggitt, C. E. Rubin, G. Roth, C. M. Surawicz, G. Van Belle, K. Lewin, W. M. Weinstein, D. A. Antonioli, H. Goldman, W. Macdonald, and D. Owen, “Observer variation in the diagnosis of dysplasia in Barrett’s esophagus,” Hum. Pathol. 19(2), 166–178 (1988).
[Crossref] [PubMed]

Aslanian, H.

J. N. Rogart, J. Nagata, C. S. Loeser, R. D. Roorda, H. Aslanian, M. E. Robert, W. R. Zipfel, and M. H. Nathanson, “Multiphoton imaging can be used for microscopic examination of intact human gastrointestinal mucosa ex vivo,” Clin. Gastroenterol. Hepatol. 6(1), 95–101 (2008).
[Crossref] [PubMed]

Athanassakis, I.

E. Gavgiotaki, G. Filippidis, M. Kalognomou, A. A. Tsouko, I. Skordos, C. Fotakis, and I. Athanassakis, “Third harmonic generation microscopy as a reliable diagnostic tool for evaluating lipid body modification during cell activation: the example of BV-2 microglia cells,” J. Struct. Biol. 189(2), 105–113 (2015).
[Crossref] [PubMed]

Aus-der-Au, J.

Bansal, A.

P. Sharma, R. H. Hawes, A. Bansal, N. Gupta, W. Curvers, A. Rastogi, M. Singh, M. Hall, S. C. Mathur, S. B. Wani, B. Hoffman, S. Gaddam, P. Fockens, and J. J. Bergman, “Standard endoscopy with random biopsies versus narrow band imaging targeted biopsies in Barrett’s oesophagus: a prospective, international, randomised controlled trial,” Gut 62(1), 15–21 (2013).
[Crossref] [PubMed]

Bartels, R. A.

O. Masihzadeh, T. C. Lei, S. R. Domingue, M. Y. Kahook, R. A. Bartels, and D. A. Ammar, “Third harmonic generation microscopy of a mouse retina,” Mol. Vis. 21, 538–547 (2015).
[PubMed]

Becker, L.

D. C. Adler, C. Zhou, T. H. Tsai, H. C. Lee, L. Becker, J. M. Schmitt, Q. Huang, J. G. Fujimoto, and H. Mashimo, “Three-dimensional optical coherence tomography of Barrett’s esophagus and buried glands beneath neosquamous epithelium following radiofrequency ablation,” Endoscopy 41(9), 773–776 (2009).
[Crossref] [PubMed]

Behrens, A.

O. Pech, A. May, H. Manner, A. Behrens, J. Pohl, M. Weferling, U. Hartmann, N. Manner, J. Huijsmans, L. Gossner, T. Rabenstein, M. Vieth, M. Stolte, and C. Ell, “Long-term efficacy and safety of endoscopic resection for patients with mucosal adenocarcinoma of the esophagus,” Gastroenterology 146(3), 652–660 (2014).
[Crossref] [PubMed]

Bennett, A. E.

N. J. Shaheen, P. Sharma, B. F. Overholt, H. C. Wolfsen, R. E. Sampliner, K. K. Wang, J. A. Galanko, M. P. Bronner, J. R. Goldblum, A. E. Bennett, B. A. Jobe, G. M. Eisen, M. B. Fennerty, J. G. Hunter, D. E. Fleischer, V. K. Sharma, R. H. Hawes, B. J. Hoffman, R. I. Rothstein, S. R. Gordon, H. Mashimo, K. J. Chang, V. R. Muthusamy, S. A. Edmundowicz, S. J. Spechler, A. A. Siddiqui, R. F. Souza, A. Infantolino, G. W. Falk, M. B. Kimmey, R. D. Madanick, A. Chak, and C. J. Lightdale, “Radiofrequency ablation in Barrett’s esophagus with dysplasia,” N. Engl. J. Med. 360(22), 2277–2288 (2009).
[Crossref] [PubMed]

Ben-Yakar, A.

M. Yildirim, N. Durr, and A. Ben-Yakar, “Tripling the maximum imaging depth with third-harmonic generation microscopy,” J. Biomed. Opt. 20(9), 096013 (2015).
[Crossref] [PubMed]

Bergman, J. J.

P. Sharma, R. H. Hawes, A. Bansal, N. Gupta, W. Curvers, A. Rastogi, M. Singh, M. Hall, S. C. Mathur, S. B. Wani, B. Hoffman, S. Gaddam, P. Fockens, and J. J. Bergman, “Standard endoscopy with random biopsies versus narrow band imaging targeted biopsies in Barrett’s oesophagus: a prospective, international, randomised controlled trial,” Gut 62(1), 15–21 (2013).
[Crossref] [PubMed]

Bignolas, G.

L. C. Junqueira, G. Bignolas, and R. R. Brentani, “Picrosirius staining plus polarization microscopy, a specific method for collagen detection in tissue sections,” Histochem. J. 11(4), 447–455 (1979).
[Crossref] [PubMed]

Bird-Lieberman, E. L.

E. L. Bird-Lieberman, A. A. Neves, P. Lao-Sirieix, M. O’Donovan, M. Novelli, L. B. Lovat, W. S. Eng, L. K. Mahal, K. M. Brindle, and R. C. Fitzgerald, “Molecular imaging using fluorescent lectins permits rapid endoscopic identification of dysplasia in Barrett’s esophagus,” Nat. Med. 18(2), 315–321 (2012).
[Crossref] [PubMed]

Boughner, D. R.

P. Whittaker, R. A. Kloner, D. R. Boughner, and J. G. Pickering, “Quantitative assessment of myocardial collagen with picrosirius red staining and circularly polarized light,” Basic Res. Cardiol. 89(5), 397–410 (1994).
[Crossref] [PubMed]

Bourget, J. M.

L. Jay, J. M. Bourget, B. Goyer, K. Singh, I. Brunette, T. Ozaki, and S. Proulx, “Characterization of tissue-engineered posterior corneas using second- and third-harmonic generation microscopy,” PLoS One 10(4), e0125564 (2015).
[Crossref] [PubMed]

Boyko, E. J.

D. J. Kearney, C. Crump, C. Maynard, and E. J. Boyko, “A case-control study of endoscopy and mortality from adenocarcinoma of the esophagus or gastric cardia in persons with GERD,” Gastrointest. Endosc. 57(7), 823–829 (2003).
[Crossref] [PubMed]

Brentani, R. R.

L. C. Junqueira, G. Bignolas, and R. R. Brentani, “Picrosirius staining plus polarization microscopy, a specific method for collagen detection in tissue sections,” Histochem. J. 11(4), 447–455 (1979).
[Crossref] [PubMed]

Brindle, K. M.

E. L. Bird-Lieberman, A. A. Neves, P. Lao-Sirieix, M. O’Donovan, M. Novelli, L. B. Lovat, W. S. Eng, L. K. Mahal, K. M. Brindle, and R. C. Fitzgerald, “Molecular imaging using fluorescent lectins permits rapid endoscopic identification of dysplasia in Barrett’s esophagus,” Nat. Med. 18(2), 315–321 (2012).
[Crossref] [PubMed]

Brink, K.

Bronner, M. P.

N. J. Shaheen, P. Sharma, B. F. Overholt, H. C. Wolfsen, R. E. Sampliner, K. K. Wang, J. A. Galanko, M. P. Bronner, J. R. Goldblum, A. E. Bennett, B. A. Jobe, G. M. Eisen, M. B. Fennerty, J. G. Hunter, D. E. Fleischer, V. K. Sharma, R. H. Hawes, B. J. Hoffman, R. I. Rothstein, S. R. Gordon, H. Mashimo, K. J. Chang, V. R. Muthusamy, S. A. Edmundowicz, S. J. Spechler, A. A. Siddiqui, R. F. Souza, A. Infantolino, G. W. Falk, M. B. Kimmey, R. D. Madanick, A. Chak, and C. J. Lightdale, “Radiofrequency ablation in Barrett’s esophagus with dysplasia,” N. Engl. J. Med. 360(22), 2277–2288 (2009).
[Crossref] [PubMed]

E. Montgomery, M. P. Bronner, J. R. Goldblum, J. K. Greenson, M. M. Haber, J. Hart, L. W. Lamps, G. Y. Lauwers, A. J. Lazenby, D. N. Lewin, M. E. Robert, A. Y. Toledano, Y. Shyr, and K. Washington, “Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation,” Hum. Pathol. 32(4), 368–378 (2001).
[Crossref] [PubMed]

Brunette, I.

L. Jay, J. M. Bourget, B. Goyer, K. Singh, I. Brunette, T. Ozaki, and S. Proulx, “Characterization of tissue-engineered posterior corneas using second- and third-harmonic generation microscopy,” PLoS One 10(4), e0125564 (2015).
[Crossref] [PubMed]

Card, T.

M. Solaymani-Dodaran, R. F. Logan, J. West, T. Card, and C. Coupland, “Risk of oesophageal cancer in Barrett’s oesophagus and gastro-oesophageal reflux,” Gut 53(8), 1070–1074 (2004).
[Crossref] [PubMed]

Chabrun, E.

E. Chabrun, M. Marty, and F. Zerbib, “Development of esophageal adenocarcinoma on buried glands following radiofrequency ablation for Barrett’s esophagus,” Endoscopy 44(S 02Suppl 2 UCTN), E392 (2012).
[Crossref] [PubMed]

Chak, A.

N. J. Shaheen, P. Sharma, B. F. Overholt, H. C. Wolfsen, R. E. Sampliner, K. K. Wang, J. A. Galanko, M. P. Bronner, J. R. Goldblum, A. E. Bennett, B. A. Jobe, G. M. Eisen, M. B. Fennerty, J. G. Hunter, D. E. Fleischer, V. K. Sharma, R. H. Hawes, B. J. Hoffman, R. I. Rothstein, S. R. Gordon, H. Mashimo, K. J. Chang, V. R. Muthusamy, S. A. Edmundowicz, S. J. Spechler, A. A. Siddiqui, R. F. Souza, A. Infantolino, G. W. Falk, M. B. Kimmey, R. D. Madanick, A. Chak, and C. J. Lightdale, “Radiofrequency ablation in Barrett’s esophagus with dysplasia,” N. Engl. J. Med. 360(22), 2277–2288 (2009).
[Crossref] [PubMed]

Chang, K. J.

N. J. Shaheen, P. Sharma, B. F. Overholt, H. C. Wolfsen, R. E. Sampliner, K. K. Wang, J. A. Galanko, M. P. Bronner, J. R. Goldblum, A. E. Bennett, B. A. Jobe, G. M. Eisen, M. B. Fennerty, J. G. Hunter, D. E. Fleischer, V. K. Sharma, R. H. Hawes, B. J. Hoffman, R. I. Rothstein, S. R. Gordon, H. Mashimo, K. J. Chang, V. R. Muthusamy, S. A. Edmundowicz, S. J. Spechler, A. A. Siddiqui, R. F. Souza, A. Infantolino, G. W. Falk, M. B. Kimmey, R. D. Madanick, A. Chak, and C. J. Lightdale, “Radiofrequency ablation in Barrett’s esophagus with dysplasia,” N. Engl. J. Med. 360(22), 2277–2288 (2009).
[Crossref] [PubMed]

Chatelain, D.

D. Chatelain and J. F. Fléjou, “High-grade dysplasia and superficial adenocarcinoma in Barrett’s esophagus: histological mapping and expression of p53, p21 and Bcl-2 oncoproteins,” Virchows Arch. 442(1), 18–24 (2003).
[PubMed]

Chen, H. C.

T. L. Sun, Y. Liu, M. C. Sung, H. C. Chen, C. H. Yang, V. Hovhannisyan, W. C. Lin, Y. M. Jeng, W. L. Chen, L. L. Chiou, G. T. Huang, K. H. Kim, P. T. C. So, Y. F. Chen, H. S. Lee, and C. Y. Dong, “Ex vivo imaging and quantification of liver fibrosis using second-harmonic generation microscopy,” J. Biomed. Opt. 15(3), 036002 (2010).
[Crossref] [PubMed]

Chen, J.

J. Chen, S. Wong, M. H. Nathanson, and D. Jain, “Evaluation of Barrett esophagus by multi-photon microscopy,” Arch Pathol Lab Med. 138(8), 582 (2014).

S. Zhuo, J. Chen, G. Wu, S. S. Xie, L. Q. Zheng, X. S. Jiang, and X. Q. Zhu, “Quantitatively linking collagen alteration and epithelial tumor progression by second harmonic generation microscopy,” Appl. Phys. Lett. 96(21), 213704 (2010).
[Crossref]

Chen, W. L.

T. L. Sun, Y. Liu, M. C. Sung, H. C. Chen, C. H. Yang, V. Hovhannisyan, W. C. Lin, Y. M. Jeng, W. L. Chen, L. L. Chiou, G. T. Huang, K. H. Kim, P. T. C. So, Y. F. Chen, H. S. Lee, and C. Y. Dong, “Ex vivo imaging and quantification of liver fibrosis using second-harmonic generation microscopy,” J. Biomed. Opt. 15(3), 036002 (2010).
[Crossref] [PubMed]

Chen, Y. C.

Chen, Y. F.

T. L. Sun, Y. Liu, M. C. Sung, H. C. Chen, C. H. Yang, V. Hovhannisyan, W. C. Lin, Y. M. Jeng, W. L. Chen, L. L. Chiou, G. T. Huang, K. H. Kim, P. T. C. So, Y. F. Chen, H. S. Lee, and C. Y. Dong, “Ex vivo imaging and quantification of liver fibrosis using second-harmonic generation microscopy,” J. Biomed. Opt. 15(3), 036002 (2010).
[Crossref] [PubMed]

Cheong, E.

E. J. Lee, B. Kim, H. G. Ahn, S. H. Park, E. Cheong, and S. Lee, “In-vivo and label-free imaging of cellular and tissue structures in mouse ear skin by using second- and third-harmonic generation microscopy,” J Korean Phys Soc, Vol. 66(4), 597–601 (2015).
[Crossref]

Chiou, L. L.

T. L. Sun, Y. Liu, M. C. Sung, H. C. Chen, C. H. Yang, V. Hovhannisyan, W. C. Lin, Y. M. Jeng, W. L. Chen, L. L. Chiou, G. T. Huang, K. H. Kim, P. T. C. So, Y. F. Chen, H. S. Lee, and C. Y. Dong, “Ex vivo imaging and quantification of liver fibrosis using second-harmonic generation microscopy,” J. Biomed. Opt. 15(3), 036002 (2010).
[Crossref] [PubMed]

Clark, C. G.

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

Clay, G. O.

Cobb, S.

Connor, M. J.

M. J. Connor and P. Sharma, “Chromoendoscopy and magnification endoscopy in Barrett’s esophagus,” Gastrointest. Endosc. Clin. N. Am. 13(2), 269–277 (2003).
[Crossref] [PubMed]

Coupland, C.

M. Solaymani-Dodaran, R. F. Logan, J. West, T. Card, and C. Coupland, “Risk of oesophageal cancer in Barrett’s oesophagus and gastro-oesophageal reflux,” Gut 53(8), 1070–1074 (2004).
[Crossref] [PubMed]

Crump, C.

D. J. Kearney, C. Crump, C. Maynard, and E. J. Boyko, “A case-control study of endoscopy and mortality from adenocarcinoma of the esophagus or gastric cardia in persons with GERD,” Gastrointest. Endosc. 57(7), 823–829 (2003).
[Crossref] [PubMed]

Cui, M.

J. H. Park, W. Sun, and M. Cui, “High-resolution in vivo imaging of mouse brain through the intact skull,” Proc. Natl. Acad. Sci. U.S.A. 112(30), 9236–9241 (2015).
[Crossref] [PubMed]

Curvers, W.

P. Sharma, R. H. Hawes, A. Bansal, N. Gupta, W. Curvers, A. Rastogi, M. Singh, M. Hall, S. C. Mathur, S. B. Wani, B. Hoffman, S. Gaddam, P. Fockens, and J. J. Bergman, “Standard endoscopy with random biopsies versus narrow band imaging targeted biopsies in Barrett’s oesophagus: a prospective, international, randomised controlled trial,” Gut 62(1), 15–21 (2013).
[Crossref] [PubMed]

Demos, S. G.

B. Lin, S. Urayama, R. M. G. Saroufeem, D. L. Matthews, and S. G. Demos, “Establishment of rules for interpreting ultraviolet autofluorescence microscopy images for noninvasive detection of Barrett’s esophagus and dysplasia,” J. Biomed. Opt. 17(1), 016013 (2012).
[Crossref] [PubMed]

Denk, W.

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[Crossref] [PubMed]

Domingue, S. R.

O. Masihzadeh, T. C. Lei, S. R. Domingue, M. Y. Kahook, R. A. Bartels, and D. A. Ammar, “Third harmonic generation microscopy of a mouse retina,” Mol. Vis. 21, 538–547 (2015).
[PubMed]

Dong, C. Y.

T. L. Sun, Y. Liu, M. C. Sung, H. C. Chen, C. H. Yang, V. Hovhannisyan, W. C. Lin, Y. M. Jeng, W. L. Chen, L. L. Chiou, G. T. Huang, K. H. Kim, P. T. C. So, Y. F. Chen, H. S. Lee, and C. Y. Dong, “Ex vivo imaging and quantification of liver fibrosis using second-harmonic generation microscopy,” J. Biomed. Opt. 15(3), 036002 (2010).
[Crossref] [PubMed]

Drexler, W.

Durr, N.

M. Yildirim, N. Durr, and A. Ben-Yakar, “Tripling the maximum imaging depth with third-harmonic generation microscopy,” J. Biomed. Opt. 20(9), 096013 (2015).
[Crossref] [PubMed]

Edmundowicz, S. A.

N. J. Shaheen, P. Sharma, B. F. Overholt, H. C. Wolfsen, R. E. Sampliner, K. K. Wang, J. A. Galanko, M. P. Bronner, J. R. Goldblum, A. E. Bennett, B. A. Jobe, G. M. Eisen, M. B. Fennerty, J. G. Hunter, D. E. Fleischer, V. K. Sharma, R. H. Hawes, B. J. Hoffman, R. I. Rothstein, S. R. Gordon, H. Mashimo, K. J. Chang, V. R. Muthusamy, S. A. Edmundowicz, S. J. Spechler, A. A. Siddiqui, R. F. Souza, A. Infantolino, G. W. Falk, M. B. Kimmey, R. D. Madanick, A. Chak, and C. J. Lightdale, “Radiofrequency ablation in Barrett’s esophagus with dysplasia,” N. Engl. J. Med. 360(22), 2277–2288 (2009).
[Crossref] [PubMed]

Eickhoff, J. C.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, J. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, “Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues,” Cancer Res. 65(4), 1180–1186 (2005).
[Crossref] [PubMed]

Eisen, G. M.

N. J. Shaheen, P. Sharma, B. F. Overholt, H. C. Wolfsen, R. E. Sampliner, K. K. Wang, J. A. Galanko, M. P. Bronner, J. R. Goldblum, A. E. Bennett, B. A. Jobe, G. M. Eisen, M. B. Fennerty, J. G. Hunter, D. E. Fleischer, V. K. Sharma, R. H. Hawes, B. J. Hoffman, R. I. Rothstein, S. R. Gordon, H. Mashimo, K. J. Chang, V. R. Muthusamy, S. A. Edmundowicz, S. J. Spechler, A. A. Siddiqui, R. F. Souza, A. Infantolino, G. W. Falk, M. B. Kimmey, R. D. Madanick, A. Chak, and C. J. Lightdale, “Radiofrequency ablation in Barrett’s esophagus with dysplasia,” N. Engl. J. Med. 360(22), 2277–2288 (2009).
[Crossref] [PubMed]

Eliceiri, K. W.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, J. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, “Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues,” Cancer Res. 65(4), 1180–1186 (2005).
[Crossref] [PubMed]

Ell, C.

O. Pech, A. May, H. Manner, A. Behrens, J. Pohl, M. Weferling, U. Hartmann, N. Manner, J. Huijsmans, L. Gossner, T. Rabenstein, M. Vieth, M. Stolte, and C. Ell, “Long-term efficacy and safety of endoscopic resection for patients with mucosal adenocarcinoma of the esophagus,” Gastroenterology 146(3), 652–660 (2014).
[Crossref] [PubMed]

Eng, W. S.

E. L. Bird-Lieberman, A. A. Neves, P. Lao-Sirieix, M. O’Donovan, M. Novelli, L. B. Lovat, W. S. Eng, L. K. Mahal, K. M. Brindle, and R. C. Fitzgerald, “Molecular imaging using fluorescent lectins permits rapid endoscopic identification of dysplasia in Barrett’s esophagus,” Nat. Med. 18(2), 315–321 (2012).
[Crossref] [PubMed]

Falk, G. W.

G. W. Falk, “Risk factors for esophageal cancer development,” Surg. Oncol. Clin. N. Am. 18(3), 469–485 (2009).
[Crossref] [PubMed]

N. J. Shaheen, P. Sharma, B. F. Overholt, H. C. Wolfsen, R. E. Sampliner, K. K. Wang, J. A. Galanko, M. P. Bronner, J. R. Goldblum, A. E. Bennett, B. A. Jobe, G. M. Eisen, M. B. Fennerty, J. G. Hunter, D. E. Fleischer, V. K. Sharma, R. H. Hawes, B. J. Hoffman, R. I. Rothstein, S. R. Gordon, H. Mashimo, K. J. Chang, V. R. Muthusamy, S. A. Edmundowicz, S. J. Spechler, A. A. Siddiqui, R. F. Souza, A. Infantolino, G. W. Falk, M. B. Kimmey, R. D. Madanick, A. Chak, and C. J. Lightdale, “Radiofrequency ablation in Barrett’s esophagus with dysplasia,” N. Engl. J. Med. 360(22), 2277–2288 (2009).
[Crossref] [PubMed]

Farrar, M. J.

M. J. Farrar, F. W. Wise, J. R. Fetcho, and C. B. Schaffer, “In vivo imaging of myelin in the vertebrate central nervous system using third harmonic generation microscopy,” Biophys. J. 100, 1362–1371 (2011).

Fennerty, M. B.

N. J. Shaheen, P. Sharma, B. F. Overholt, H. C. Wolfsen, R. E. Sampliner, K. K. Wang, J. A. Galanko, M. P. Bronner, J. R. Goldblum, A. E. Bennett, B. A. Jobe, G. M. Eisen, M. B. Fennerty, J. G. Hunter, D. E. Fleischer, V. K. Sharma, R. H. Hawes, B. J. Hoffman, R. I. Rothstein, S. R. Gordon, H. Mashimo, K. J. Chang, V. R. Muthusamy, S. A. Edmundowicz, S. J. Spechler, A. A. Siddiqui, R. F. Souza, A. Infantolino, G. W. Falk, M. B. Kimmey, R. D. Madanick, A. Chak, and C. J. Lightdale, “Radiofrequency ablation in Barrett’s esophagus with dysplasia,” N. Engl. J. Med. 360(22), 2277–2288 (2009).
[Crossref] [PubMed]

Fetcho, J. R.

M. J. Farrar, F. W. Wise, J. R. Fetcho, and C. B. Schaffer, “In vivo imaging of myelin in the vertebrate central nervous system using third harmonic generation microscopy,” Biophys. J. 100, 1362–1371 (2011).

Filippidis, G.

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Hoffman, B.

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E. L. Bird-Lieberman, A. A. Neves, P. Lao-Sirieix, M. O’Donovan, M. Novelli, L. B. Lovat, W. S. Eng, L. K. Mahal, K. M. Brindle, and R. C. Fitzgerald, “Molecular imaging using fluorescent lectins permits rapid endoscopic identification of dysplasia in Barrett’s esophagus,” Nat. Med. 18(2), 315–321 (2012).
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Lauwers, G. Y.

R. D. Odze and G. Y. Lauwers, “Histopathology of Barrett’s esophagus after ablation and endoscopic mucosal resection therapy,” Endoscopy 40(12), 1008–1015 (2008).
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J. R. Goldblum and G. Y. Lauwers, “Dysplasia arising in barrett’s esophagus: diagnostic pitfalls and natural history,” Semin. Diagn. Pathol. 19(1), 12–19 (2002).
[PubMed]

E. Montgomery, M. P. Bronner, J. R. Goldblum, J. K. Greenson, M. M. Haber, J. Hart, L. W. Lamps, G. Y. Lauwers, A. J. Lazenby, D. N. Lewin, M. E. Robert, A. Y. Toledano, Y. Shyr, and K. Washington, “Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation,” Hum. Pathol. 32(4), 368–378 (2001).
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Lazenby, A. J.

E. Montgomery, M. P. Bronner, J. R. Goldblum, J. K. Greenson, M. M. Haber, J. Hart, L. W. Lamps, G. Y. Lauwers, A. J. Lazenby, D. N. Lewin, M. E. Robert, A. Y. Toledano, Y. Shyr, and K. Washington, “Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation,” Hum. Pathol. 32(4), 368–378 (2001).
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Lee, E. J.

E. J. Lee, B. Kim, H. G. Ahn, S. H. Park, E. Cheong, and S. Lee, “In-vivo and label-free imaging of cellular and tissue structures in mouse ear skin by using second- and third-harmonic generation microscopy,” J Korean Phys Soc, Vol. 66(4), 597–601 (2015).
[Crossref]

Lee, H. C.

D. C. Adler, C. Zhou, T. H. Tsai, H. C. Lee, L. Becker, J. M. Schmitt, Q. Huang, J. G. Fujimoto, and H. Mashimo, “Three-dimensional optical coherence tomography of Barrett’s esophagus and buried glands beneath neosquamous epithelium following radiofrequency ablation,” Endoscopy 41(9), 773–776 (2009).
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Lee, H. S.

T. L. Sun, Y. Liu, M. C. Sung, H. C. Chen, C. H. Yang, V. Hovhannisyan, W. C. Lin, Y. M. Jeng, W. L. Chen, L. L. Chiou, G. T. Huang, K. H. Kim, P. T. C. So, Y. F. Chen, H. S. Lee, and C. Y. Dong, “Ex vivo imaging and quantification of liver fibrosis using second-harmonic generation microscopy,” J. Biomed. Opt. 15(3), 036002 (2010).
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Lee, S.

E. J. Lee, B. Kim, H. G. Ahn, S. H. Park, E. Cheong, and S. Lee, “In-vivo and label-free imaging of cellular and tissue structures in mouse ear skin by using second- and third-harmonic generation microscopy,” J Korean Phys Soc, Vol. 66(4), 597–601 (2015).
[Crossref]

Lee, S. Y.

Lei, T. C.

O. Masihzadeh, T. C. Lei, S. R. Domingue, M. Y. Kahook, R. A. Bartels, and D. A. Ammar, “Third harmonic generation microscopy of a mouse retina,” Mol. Vis. 21, 538–547 (2015).
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Levitte, J. M.

Lewin, D. N.

E. Montgomery, M. P. Bronner, J. R. Goldblum, J. K. Greenson, M. M. Haber, J. Hart, L. W. Lamps, G. Y. Lauwers, A. J. Lazenby, D. N. Lewin, M. E. Robert, A. Y. Toledano, Y. Shyr, and K. Washington, “Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation,” Hum. Pathol. 32(4), 368–378 (2001).
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B. J. Reid, R. C. Haggitt, C. E. Rubin, G. Roth, C. M. Surawicz, G. Van Belle, K. Lewin, W. M. Weinstein, D. A. Antonioli, H. Goldman, W. Macdonald, and D. Owen, “Observer variation in the diagnosis of dysplasia in Barrett’s esophagus,” Hum. Pathol. 19(2), 166–178 (1988).
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N. J. Shaheen, P. Sharma, B. F. Overholt, H. C. Wolfsen, R. E. Sampliner, K. K. Wang, J. A. Galanko, M. P. Bronner, J. R. Goldblum, A. E. Bennett, B. A. Jobe, G. M. Eisen, M. B. Fennerty, J. G. Hunter, D. E. Fleischer, V. K. Sharma, R. H. Hawes, B. J. Hoffman, R. I. Rothstein, S. R. Gordon, H. Mashimo, K. J. Chang, V. R. Muthusamy, S. A. Edmundowicz, S. J. Spechler, A. A. Siddiqui, R. F. Souza, A. Infantolino, G. W. Falk, M. B. Kimmey, R. D. Madanick, A. Chak, and C. J. Lightdale, “Radiofrequency ablation in Barrett’s esophagus with dysplasia,” N. Engl. J. Med. 360(22), 2277–2288 (2009).
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B. Lin, S. Urayama, R. M. G. Saroufeem, D. L. Matthews, and S. G. Demos, “Establishment of rules for interpreting ultraviolet autofluorescence microscopy images for noninvasive detection of Barrett’s esophagus and dysplasia,” J. Biomed. Opt. 17(1), 016013 (2012).
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J. N. Rogart, J. Nagata, C. S. Loeser, R. D. Roorda, H. Aslanian, M. E. Robert, W. R. Zipfel, and M. H. Nathanson, “Multiphoton imaging can be used for microscopic examination of intact human gastrointestinal mucosa ex vivo,” Clin. Gastroenterol. Hepatol. 6(1), 95–101 (2008).
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M. Solaymani-Dodaran, R. F. Logan, J. West, T. Card, and C. Coupland, “Risk of oesophageal cancer in Barrett’s oesophagus and gastro-oesophageal reflux,” Gut 53(8), 1070–1074 (2004).
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E. L. Bird-Lieberman, A. A. Neves, P. Lao-Sirieix, M. O’Donovan, M. Novelli, L. B. Lovat, W. S. Eng, L. K. Mahal, K. M. Brindle, and R. C. Fitzgerald, “Molecular imaging using fluorescent lectins permits rapid endoscopic identification of dysplasia in Barrett’s esophagus,” Nat. Med. 18(2), 315–321 (2012).
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B. J. Reid, R. C. Haggitt, C. E. Rubin, G. Roth, C. M. Surawicz, G. Van Belle, K. Lewin, W. M. Weinstein, D. A. Antonioli, H. Goldman, W. Macdonald, and D. Owen, “Observer variation in the diagnosis of dysplasia in Barrett’s esophagus,” Hum. Pathol. 19(2), 166–178 (1988).
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N. J. Shaheen, P. Sharma, B. F. Overholt, H. C. Wolfsen, R. E. Sampliner, K. K. Wang, J. A. Galanko, M. P. Bronner, J. R. Goldblum, A. E. Bennett, B. A. Jobe, G. M. Eisen, M. B. Fennerty, J. G. Hunter, D. E. Fleischer, V. K. Sharma, R. H. Hawes, B. J. Hoffman, R. I. Rothstein, S. R. Gordon, H. Mashimo, K. J. Chang, V. R. Muthusamy, S. A. Edmundowicz, S. J. Spechler, A. A. Siddiqui, R. F. Souza, A. Infantolino, G. W. Falk, M. B. Kimmey, R. D. Madanick, A. Chak, and C. J. Lightdale, “Radiofrequency ablation in Barrett’s esophagus with dysplasia,” N. Engl. J. Med. 360(22), 2277–2288 (2009).
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E. L. Bird-Lieberman, A. A. Neves, P. Lao-Sirieix, M. O’Donovan, M. Novelli, L. B. Lovat, W. S. Eng, L. K. Mahal, K. M. Brindle, and R. C. Fitzgerald, “Molecular imaging using fluorescent lectins permits rapid endoscopic identification of dysplasia in Barrett’s esophagus,” Nat. Med. 18(2), 315–321 (2012).
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O. Pech, A. May, H. Manner, A. Behrens, J. Pohl, M. Weferling, U. Hartmann, N. Manner, J. Huijsmans, L. Gossner, T. Rabenstein, M. Vieth, M. Stolte, and C. Ell, “Long-term efficacy and safety of endoscopic resection for patients with mucosal adenocarcinoma of the esophagus,” Gastroenterology 146(3), 652–660 (2014).
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Marty, M.

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T. J. Muldoon, S. Anandasabapathy, D. Maru, and R. Richards-Kortum, “High-resolution imaging in Barrett’s esophagus: a novel, low-cost endoscopic microscope,” Gastrointest. Endosc. 68(4), 737–744 (2008).
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N. J. Shaheen, P. Sharma, B. F. Overholt, H. C. Wolfsen, R. E. Sampliner, K. K. Wang, J. A. Galanko, M. P. Bronner, J. R. Goldblum, A. E. Bennett, B. A. Jobe, G. M. Eisen, M. B. Fennerty, J. G. Hunter, D. E. Fleischer, V. K. Sharma, R. H. Hawes, B. J. Hoffman, R. I. Rothstein, S. R. Gordon, H. Mashimo, K. J. Chang, V. R. Muthusamy, S. A. Edmundowicz, S. J. Spechler, A. A. Siddiqui, R. F. Souza, A. Infantolino, G. W. Falk, M. B. Kimmey, R. D. Madanick, A. Chak, and C. J. Lightdale, “Radiofrequency ablation in Barrett’s esophagus with dysplasia,” N. Engl. J. Med. 360(22), 2277–2288 (2009).
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D. C. Adler, C. Zhou, T. H. Tsai, H. C. Lee, L. Becker, J. M. Schmitt, Q. Huang, J. G. Fujimoto, and H. Mashimo, “Three-dimensional optical coherence tomography of Barrett’s esophagus and buried glands beneath neosquamous epithelium following radiofrequency ablation,” Endoscopy 41(9), 773–776 (2009).
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O. Masihzadeh, T. C. Lei, S. R. Domingue, M. Y. Kahook, R. A. Bartels, and D. A. Ammar, “Third harmonic generation microscopy of a mouse retina,” Mol. Vis. 21, 538–547 (2015).
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P. Sharma, R. H. Hawes, A. Bansal, N. Gupta, W. Curvers, A. Rastogi, M. Singh, M. Hall, S. C. Mathur, S. B. Wani, B. Hoffman, S. Gaddam, P. Fockens, and J. J. Bergman, “Standard endoscopy with random biopsies versus narrow band imaging targeted biopsies in Barrett’s oesophagus: a prospective, international, randomised controlled trial,” Gut 62(1), 15–21 (2013).
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B. Lin, S. Urayama, R. M. G. Saroufeem, D. L. Matthews, and S. G. Demos, “Establishment of rules for interpreting ultraviolet autofluorescence microscopy images for noninvasive detection of Barrett’s esophagus and dysplasia,” J. Biomed. Opt. 17(1), 016013 (2012).
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O. Pech, A. May, H. Manner, A. Behrens, J. Pohl, M. Weferling, U. Hartmann, N. Manner, J. Huijsmans, L. Gossner, T. Rabenstein, M. Vieth, M. Stolte, and C. Ell, “Long-term efficacy and safety of endoscopic resection for patients with mucosal adenocarcinoma of the esophagus,” Gastroenterology 146(3), 652–660 (2014).
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D. J. Kearney, C. Crump, C. Maynard, and E. J. Boyko, “A case-control study of endoscopy and mortality from adenocarcinoma of the esophagus or gastric cardia in persons with GERD,” Gastrointest. Endosc. 57(7), 823–829 (2003).
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T. J. Muldoon, S. Anandasabapathy, D. Maru, and R. Richards-Kortum, “High-resolution imaging in Barrett’s esophagus: a novel, low-cost endoscopic microscope,” Gastrointest. Endosc. 68(4), 737–744 (2008).
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N. J. Shaheen, P. Sharma, B. F. Overholt, H. C. Wolfsen, R. E. Sampliner, K. K. Wang, J. A. Galanko, M. P. Bronner, J. R. Goldblum, A. E. Bennett, B. A. Jobe, G. M. Eisen, M. B. Fennerty, J. G. Hunter, D. E. Fleischer, V. K. Sharma, R. H. Hawes, B. J. Hoffman, R. I. Rothstein, S. R. Gordon, H. Mashimo, K. J. Chang, V. R. Muthusamy, S. A. Edmundowicz, S. J. Spechler, A. A. Siddiqui, R. F. Souza, A. Infantolino, G. W. Falk, M. B. Kimmey, R. D. Madanick, A. Chak, and C. J. Lightdale, “Radiofrequency ablation in Barrett’s esophagus with dysplasia,” N. Engl. J. Med. 360(22), 2277–2288 (2009).
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J. N. Rogart, J. Nagata, C. S. Loeser, R. D. Roorda, H. Aslanian, M. E. Robert, W. R. Zipfel, and M. H. Nathanson, “Multiphoton imaging can be used for microscopic examination of intact human gastrointestinal mucosa ex vivo,” Clin. Gastroenterol. Hepatol. 6(1), 95–101 (2008).
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J. Chen, S. Wong, M. H. Nathanson, and D. Jain, “Evaluation of Barrett esophagus by multi-photon microscopy,” Arch Pathol Lab Med. 138(8), 582 (2014).

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E. L. Bird-Lieberman, A. A. Neves, P. Lao-Sirieix, M. O’Donovan, M. Novelli, L. B. Lovat, W. S. Eng, L. K. Mahal, K. M. Brindle, and R. C. Fitzgerald, “Molecular imaging using fluorescent lectins permits rapid endoscopic identification of dysplasia in Barrett’s esophagus,” Nat. Med. 18(2), 315–321 (2012).
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Novelli, M.

E. L. Bird-Lieberman, A. A. Neves, P. Lao-Sirieix, M. O’Donovan, M. Novelli, L. B. Lovat, W. S. Eng, L. K. Mahal, K. M. Brindle, and R. C. Fitzgerald, “Molecular imaging using fluorescent lectins permits rapid endoscopic identification of dysplasia in Barrett’s esophagus,” Nat. Med. 18(2), 315–321 (2012).
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E. L. Bird-Lieberman, A. A. Neves, P. Lao-Sirieix, M. O’Donovan, M. Novelli, L. B. Lovat, W. S. Eng, L. K. Mahal, K. M. Brindle, and R. C. Fitzgerald, “Molecular imaging using fluorescent lectins permits rapid endoscopic identification of dysplasia in Barrett’s esophagus,” Nat. Med. 18(2), 315–321 (2012).
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N. A. Gray, R. D. Odze, and S. J. Spechler, “Buried metaplasia after endoscopic ablation of Barrett’s esophagus: a systematic review,” Am. J. Gastroenterol. 106(11), 1899–1909 (2011).
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R. D. Odze and G. Y. Lauwers, “Histopathology of Barrett’s esophagus after ablation and endoscopic mucosal resection therapy,” Endoscopy 40(12), 1008–1015 (2008).
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Overholt, B. F.

N. J. Shaheen, P. Sharma, B. F. Overholt, H. C. Wolfsen, R. E. Sampliner, K. K. Wang, J. A. Galanko, M. P. Bronner, J. R. Goldblum, A. E. Bennett, B. A. Jobe, G. M. Eisen, M. B. Fennerty, J. G. Hunter, D. E. Fleischer, V. K. Sharma, R. H. Hawes, B. J. Hoffman, R. I. Rothstein, S. R. Gordon, H. Mashimo, K. J. Chang, V. R. Muthusamy, S. A. Edmundowicz, S. J. Spechler, A. A. Siddiqui, R. F. Souza, A. Infantolino, G. W. Falk, M. B. Kimmey, R. D. Madanick, A. Chak, and C. J. Lightdale, “Radiofrequency ablation in Barrett’s esophagus with dysplasia,” N. Engl. J. Med. 360(22), 2277–2288 (2009).
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B. J. Reid, R. C. Haggitt, C. E. Rubin, G. Roth, C. M. Surawicz, G. Van Belle, K. Lewin, W. M. Weinstein, D. A. Antonioli, H. Goldman, W. Macdonald, and D. Owen, “Observer variation in the diagnosis of dysplasia in Barrett’s esophagus,” Hum. Pathol. 19(2), 166–178 (1988).
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B. J. Reid, R. C. Haggitt, C. E. Rubin, G. Roth, C. M. Surawicz, G. Van Belle, K. Lewin, W. M. Weinstein, D. A. Antonioli, H. Goldman, W. Macdonald, and D. Owen, “Observer variation in the diagnosis of dysplasia in Barrett’s esophagus,” Hum. Pathol. 19(2), 166–178 (1988).
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T. J. Muldoon, S. Anandasabapathy, D. Maru, and R. Richards-Kortum, “High-resolution imaging in Barrett’s esophagus: a novel, low-cost endoscopic microscope,” Gastrointest. Endosc. 68(4), 737–744 (2008).
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J. N. Rogart, J. Nagata, C. S. Loeser, R. D. Roorda, H. Aslanian, M. E. Robert, W. R. Zipfel, and M. H. Nathanson, “Multiphoton imaging can be used for microscopic examination of intact human gastrointestinal mucosa ex vivo,” Clin. Gastroenterol. Hepatol. 6(1), 95–101 (2008).
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J. N. Rogart, J. Nagata, C. S. Loeser, R. D. Roorda, H. Aslanian, M. E. Robert, W. R. Zipfel, and M. H. Nathanson, “Multiphoton imaging can be used for microscopic examination of intact human gastrointestinal mucosa ex vivo,” Clin. Gastroenterol. Hepatol. 6(1), 95–101 (2008).
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J. N. Rogart, J. Nagata, C. S. Loeser, R. D. Roorda, H. Aslanian, M. E. Robert, W. R. Zipfel, and M. H. Nathanson, “Multiphoton imaging can be used for microscopic examination of intact human gastrointestinal mucosa ex vivo,” Clin. Gastroenterol. Hepatol. 6(1), 95–101 (2008).
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B. J. Reid, R. C. Haggitt, C. E. Rubin, G. Roth, C. M. Surawicz, G. Van Belle, K. Lewin, W. M. Weinstein, D. A. Antonioli, H. Goldman, W. Macdonald, and D. Owen, “Observer variation in the diagnosis of dysplasia in Barrett’s esophagus,” Hum. Pathol. 19(2), 166–178 (1988).
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Rothstein, R. I.

N. J. Shaheen, P. Sharma, B. F. Overholt, H. C. Wolfsen, R. E. Sampliner, K. K. Wang, J. A. Galanko, M. P. Bronner, J. R. Goldblum, A. E. Bennett, B. A. Jobe, G. M. Eisen, M. B. Fennerty, J. G. Hunter, D. E. Fleischer, V. K. Sharma, R. H. Hawes, B. J. Hoffman, R. I. Rothstein, S. R. Gordon, H. Mashimo, K. J. Chang, V. R. Muthusamy, S. A. Edmundowicz, S. J. Spechler, A. A. Siddiqui, R. F. Souza, A. Infantolino, G. W. Falk, M. B. Kimmey, R. D. Madanick, A. Chak, and C. J. Lightdale, “Radiofrequency ablation in Barrett’s esophagus with dysplasia,” N. Engl. J. Med. 360(22), 2277–2288 (2009).
[Crossref] [PubMed]

Rubin, C. E.

B. J. Reid, R. C. Haggitt, C. E. Rubin, G. Roth, C. M. Surawicz, G. Van Belle, K. Lewin, W. M. Weinstein, D. A. Antonioli, H. Goldman, W. Macdonald, and D. Owen, “Observer variation in the diagnosis of dysplasia in Barrett’s esophagus,” Hum. Pathol. 19(2), 166–178 (1988).
[Crossref] [PubMed]

Saalfeld, S.

S. Preibisch, S. Saalfeld, and P. Tomancak, “Globally optimal stitching of tiled 3D microscopic image acquisitions,” Bioinformatics 25(11), 1463–1465 (2009).
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Sampliner, R. E.

N. J. Shaheen, P. Sharma, B. F. Overholt, H. C. Wolfsen, R. E. Sampliner, K. K. Wang, J. A. Galanko, M. P. Bronner, J. R. Goldblum, A. E. Bennett, B. A. Jobe, G. M. Eisen, M. B. Fennerty, J. G. Hunter, D. E. Fleischer, V. K. Sharma, R. H. Hawes, B. J. Hoffman, R. I. Rothstein, S. R. Gordon, H. Mashimo, K. J. Chang, V. R. Muthusamy, S. A. Edmundowicz, S. J. Spechler, A. A. Siddiqui, R. F. Souza, A. Infantolino, G. W. Falk, M. B. Kimmey, R. D. Madanick, A. Chak, and C. J. Lightdale, “Radiofrequency ablation in Barrett’s esophagus with dysplasia,” N. Engl. J. Med. 360(22), 2277–2288 (2009).
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Saroufeem, R. M. G.

B. Lin, S. Urayama, R. M. G. Saroufeem, D. L. Matthews, and S. G. Demos, “Establishment of rules for interpreting ultraviolet autofluorescence microscopy images for noninvasive detection of Barrett’s esophagus and dysplasia,” J. Biomed. Opt. 17(1), 016013 (2012).
[Crossref] [PubMed]

Schaffer, C. B.

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

M. J. Farrar, F. W. Wise, J. R. Fetcho, and C. B. Schaffer, “In vivo imaging of myelin in the vertebrate central nervous system using third harmonic generation microscopy,” Biophys. J. 100, 1362–1371 (2011).

G. O. Clay, A. C. Millard, C. B. Schaffer, J. Aus-der-Au, P. S. Tsai, J. A. Squier, and D. Kleinfeld, “Spectroscopy of third harmonic generation: Evidence for resonances in model compounds and ligated hemoglobin,” J. Opt. Soc. Am. B 23(5), 932–950 (2006).
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Schmitt, J. M.

D. C. Adler, C. Zhou, T. H. Tsai, H. C. Lee, L. Becker, J. M. Schmitt, Q. Huang, J. G. Fujimoto, and H. Mashimo, “Three-dimensional optical coherence tomography of Barrett’s esophagus and buried glands beneath neosquamous epithelium following radiofrequency ablation,” Endoscopy 41(9), 773–776 (2009).
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Shaheen, N. J.

N. J. Shaheen, P. Sharma, B. F. Overholt, H. C. Wolfsen, R. E. Sampliner, K. K. Wang, J. A. Galanko, M. P. Bronner, J. R. Goldblum, A. E. Bennett, B. A. Jobe, G. M. Eisen, M. B. Fennerty, J. G. Hunter, D. E. Fleischer, V. K. Sharma, R. H. Hawes, B. J. Hoffman, R. I. Rothstein, S. R. Gordon, H. Mashimo, K. J. Chang, V. R. Muthusamy, S. A. Edmundowicz, S. J. Spechler, A. A. Siddiqui, R. F. Souza, A. Infantolino, G. W. Falk, M. B. Kimmey, R. D. Madanick, A. Chak, and C. J. Lightdale, “Radiofrequency ablation in Barrett’s esophagus with dysplasia,” N. Engl. J. Med. 360(22), 2277–2288 (2009).
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Sharma, P.

P. Sharma, R. H. Hawes, A. Bansal, N. Gupta, W. Curvers, A. Rastogi, M. Singh, M. Hall, S. C. Mathur, S. B. Wani, B. Hoffman, S. Gaddam, P. Fockens, and J. J. Bergman, “Standard endoscopy with random biopsies versus narrow band imaging targeted biopsies in Barrett’s oesophagus: a prospective, international, randomised controlled trial,” Gut 62(1), 15–21 (2013).
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N. J. Shaheen, P. Sharma, B. F. Overholt, H. C. Wolfsen, R. E. Sampliner, K. K. Wang, J. A. Galanko, M. P. Bronner, J. R. Goldblum, A. E. Bennett, B. A. Jobe, G. M. Eisen, M. B. Fennerty, J. G. Hunter, D. E. Fleischer, V. K. Sharma, R. H. Hawes, B. J. Hoffman, R. I. Rothstein, S. R. Gordon, H. Mashimo, K. J. Chang, V. R. Muthusamy, S. A. Edmundowicz, S. J. Spechler, A. A. Siddiqui, R. F. Souza, A. Infantolino, G. W. Falk, M. B. Kimmey, R. D. Madanick, A. Chak, and C. J. Lightdale, “Radiofrequency ablation in Barrett’s esophagus with dysplasia,” N. Engl. J. Med. 360(22), 2277–2288 (2009).
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M. J. Connor and P. Sharma, “Chromoendoscopy and magnification endoscopy in Barrett’s esophagus,” Gastrointest. Endosc. Clin. N. Am. 13(2), 269–277 (2003).
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Sharma, V. K.

N. J. Shaheen, P. Sharma, B. F. Overholt, H. C. Wolfsen, R. E. Sampliner, K. K. Wang, J. A. Galanko, M. P. Bronner, J. R. Goldblum, A. E. Bennett, B. A. Jobe, G. M. Eisen, M. B. Fennerty, J. G. Hunter, D. E. Fleischer, V. K. Sharma, R. H. Hawes, B. J. Hoffman, R. I. Rothstein, S. R. Gordon, H. Mashimo, K. J. Chang, V. R. Muthusamy, S. A. Edmundowicz, S. J. Spechler, A. A. Siddiqui, R. F. Souza, A. Infantolino, G. W. Falk, M. B. Kimmey, R. D. Madanick, A. Chak, and C. J. Lightdale, “Radiofrequency ablation in Barrett’s esophagus with dysplasia,” N. Engl. J. Med. 360(22), 2277–2288 (2009).
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Shieh, D. B.

Shyr, Y.

E. Montgomery, M. P. Bronner, J. R. Goldblum, J. K. Greenson, M. M. Haber, J. Hart, L. W. Lamps, G. Y. Lauwers, A. J. Lazenby, D. N. Lewin, M. E. Robert, A. Y. Toledano, Y. Shyr, and K. Washington, “Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation,” Hum. Pathol. 32(4), 368–378 (2001).
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Siddiqui, A. A.

N. J. Shaheen, P. Sharma, B. F. Overholt, H. C. Wolfsen, R. E. Sampliner, K. K. Wang, J. A. Galanko, M. P. Bronner, J. R. Goldblum, A. E. Bennett, B. A. Jobe, G. M. Eisen, M. B. Fennerty, J. G. Hunter, D. E. Fleischer, V. K. Sharma, R. H. Hawes, B. J. Hoffman, R. I. Rothstein, S. R. Gordon, H. Mashimo, K. J. Chang, V. R. Muthusamy, S. A. Edmundowicz, S. J. Spechler, A. A. Siddiqui, R. F. Souza, A. Infantolino, G. W. Falk, M. B. Kimmey, R. D. Madanick, A. Chak, and C. J. Lightdale, “Radiofrequency ablation in Barrett’s esophagus with dysplasia,” N. Engl. J. Med. 360(22), 2277–2288 (2009).
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Silberberg, Y.

Singh, K.

L. Jay, J. M. Bourget, B. Goyer, K. Singh, I. Brunette, T. Ozaki, and S. Proulx, “Characterization of tissue-engineered posterior corneas using second- and third-harmonic generation microscopy,” PLoS One 10(4), e0125564 (2015).
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Singh, M.

P. Sharma, R. H. Hawes, A. Bansal, N. Gupta, W. Curvers, A. Rastogi, M. Singh, M. Hall, S. C. Mathur, S. B. Wani, B. Hoffman, S. Gaddam, P. Fockens, and J. J. Bergman, “Standard endoscopy with random biopsies versus narrow band imaging targeted biopsies in Barrett’s oesophagus: a prospective, international, randomised controlled trial,” Gut 62(1), 15–21 (2013).
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Skala, M. C.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, J. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, “Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues,” Cancer Res. 65(4), 1180–1186 (2005).
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Skordos, I.

E. Gavgiotaki, G. Filippidis, M. Kalognomou, A. A. Tsouko, I. Skordos, C. Fotakis, and I. Athanassakis, “Third harmonic generation microscopy as a reliable diagnostic tool for evaluating lipid body modification during cell activation: the example of BV-2 microglia cells,” J. Struct. Biol. 189(2), 105–113 (2015).
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So, P. T. C.

T. L. Sun, Y. Liu, M. C. Sung, H. C. Chen, C. H. Yang, V. Hovhannisyan, W. C. Lin, Y. M. Jeng, W. L. Chen, L. L. Chiou, G. T. Huang, K. H. Kim, P. T. C. So, Y. F. Chen, H. S. Lee, and C. Y. Dong, “Ex vivo imaging and quantification of liver fibrosis using second-harmonic generation microscopy,” J. Biomed. Opt. 15(3), 036002 (2010).
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Solaymani-Dodaran, M.

M. Solaymani-Dodaran, R. F. Logan, J. West, T. Card, and C. Coupland, “Risk of oesophageal cancer in Barrett’s oesophagus and gastro-oesophageal reflux,” Gut 53(8), 1070–1074 (2004).
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Souza, R. F.

S. J. Spechler and R. F. Souza, “Barrett’s esophagus,” N. Engl. J. Med. 371(9), 836–845 (2014).
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N. J. Shaheen, P. Sharma, B. F. Overholt, H. C. Wolfsen, R. E. Sampliner, K. K. Wang, J. A. Galanko, M. P. Bronner, J. R. Goldblum, A. E. Bennett, B. A. Jobe, G. M. Eisen, M. B. Fennerty, J. G. Hunter, D. E. Fleischer, V. K. Sharma, R. H. Hawes, B. J. Hoffman, R. I. Rothstein, S. R. Gordon, H. Mashimo, K. J. Chang, V. R. Muthusamy, S. A. Edmundowicz, S. J. Spechler, A. A. Siddiqui, R. F. Souza, A. Infantolino, G. W. Falk, M. B. Kimmey, R. D. Madanick, A. Chak, and C. J. Lightdale, “Radiofrequency ablation in Barrett’s esophagus with dysplasia,” N. Engl. J. Med. 360(22), 2277–2288 (2009).
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Spechler, S. J.

S. J. Spechler and R. F. Souza, “Barrett’s esophagus,” N. Engl. J. Med. 371(9), 836–845 (2014).
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N. A. Gray, R. D. Odze, and S. J. Spechler, “Buried metaplasia after endoscopic ablation of Barrett’s esophagus: a systematic review,” Am. J. Gastroenterol. 106(11), 1899–1909 (2011).
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N. J. Shaheen, P. Sharma, B. F. Overholt, H. C. Wolfsen, R. E. Sampliner, K. K. Wang, J. A. Galanko, M. P. Bronner, J. R. Goldblum, A. E. Bennett, B. A. Jobe, G. M. Eisen, M. B. Fennerty, J. G. Hunter, D. E. Fleischer, V. K. Sharma, R. H. Hawes, B. J. Hoffman, R. I. Rothstein, S. R. Gordon, H. Mashimo, K. J. Chang, V. R. Muthusamy, S. A. Edmundowicz, S. J. Spechler, A. A. Siddiqui, R. F. Souza, A. Infantolino, G. W. Falk, M. B. Kimmey, R. D. Madanick, A. Chak, and C. J. Lightdale, “Radiofrequency ablation in Barrett’s esophagus with dysplasia,” N. Engl. J. Med. 360(22), 2277–2288 (2009).
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Squier, J. A.

Squirrell, J. M.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, J. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, “Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues,” Cancer Res. 65(4), 1180–1186 (2005).
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Stolte, M.

O. Pech, A. May, H. Manner, A. Behrens, J. Pohl, M. Weferling, U. Hartmann, N. Manner, J. Huijsmans, L. Gossner, T. Rabenstein, M. Vieth, M. Stolte, and C. Ell, “Long-term efficacy and safety of endoscopic resection for patients with mucosal adenocarcinoma of the esophagus,” Gastroenterology 146(3), 652–660 (2014).
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Strickler, J. H.

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
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Sun, C. K.

Sun, T. L.

T. L. Sun, Y. Liu, M. C. Sung, H. C. Chen, C. H. Yang, V. Hovhannisyan, W. C. Lin, Y. M. Jeng, W. L. Chen, L. L. Chiou, G. T. Huang, K. H. Kim, P. T. C. So, Y. F. Chen, H. S. Lee, and C. Y. Dong, “Ex vivo imaging and quantification of liver fibrosis using second-harmonic generation microscopy,” J. Biomed. Opt. 15(3), 036002 (2010).
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Sun, W.

J. H. Park, W. Sun, and M. Cui, “High-resolution in vivo imaging of mouse brain through the intact skull,” Proc. Natl. Acad. Sci. U.S.A. 112(30), 9236–9241 (2015).
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T. L. Sun, Y. Liu, M. C. Sung, H. C. Chen, C. H. Yang, V. Hovhannisyan, W. C. Lin, Y. M. Jeng, W. L. Chen, L. L. Chiou, G. T. Huang, K. H. Kim, P. T. C. So, Y. F. Chen, H. S. Lee, and C. Y. Dong, “Ex vivo imaging and quantification of liver fibrosis using second-harmonic generation microscopy,” J. Biomed. Opt. 15(3), 036002 (2010).
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Surawicz, C. M.

B. J. Reid, R. C. Haggitt, C. E. Rubin, G. Roth, C. M. Surawicz, G. Van Belle, K. Lewin, W. M. Weinstein, D. A. Antonioli, H. Goldman, W. Macdonald, and D. Owen, “Observer variation in the diagnosis of dysplasia in Barrett’s esophagus,” Hum. Pathol. 19(2), 166–178 (1988).
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Toledano, A. Y.

E. Montgomery, M. P. Bronner, J. R. Goldblum, J. K. Greenson, M. M. Haber, J. Hart, L. W. Lamps, G. Y. Lauwers, A. J. Lazenby, D. N. Lewin, M. E. Robert, A. Y. Toledano, Y. Shyr, and K. Washington, “Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation,” Hum. Pathol. 32(4), 368–378 (2001).
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Tomancak, P.

S. Preibisch, S. Saalfeld, and P. Tomancak, “Globally optimal stitching of tiled 3D microscopic image acquisitions,” Bioinformatics 25(11), 1463–1465 (2009).
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Trägårdh, J.

Travis, C.

Tsai, P. S.

Tsai, T. H.

D. C. Adler, C. Zhou, T. H. Tsai, H. C. Lee, L. Becker, J. M. Schmitt, Q. Huang, J. G. Fujimoto, and H. Mashimo, “Three-dimensional optical coherence tomography of Barrett’s esophagus and buried glands beneath neosquamous epithelium following radiofrequency ablation,” Endoscopy 41(9), 773–776 (2009).
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Tsouko, A. A.

E. Gavgiotaki, G. Filippidis, M. Kalognomou, A. A. Tsouko, I. Skordos, C. Fotakis, and I. Athanassakis, “Third harmonic generation microscopy as a reliable diagnostic tool for evaluating lipid body modification during cell activation: the example of BV-2 microglia cells,” J. Struct. Biol. 189(2), 105–113 (2015).
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Unterhuber, A.

Urayama, S.

B. Lin, S. Urayama, R. M. G. Saroufeem, D. L. Matthews, and S. G. Demos, “Establishment of rules for interpreting ultraviolet autofluorescence microscopy images for noninvasive detection of Barrett’s esophagus and dysplasia,” J. Biomed. Opt. 17(1), 016013 (2012).
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H. Puchtler, F. S. Waldrop, and L. S. Valentine, “Polarization microscopic studies of connective tissue stained with picro-sirius red FBA,” Beitr. Pathol. 150(2), 174–187 (1973).
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B. J. Reid, R. C. Haggitt, C. E. Rubin, G. Roth, C. M. Surawicz, G. Van Belle, K. Lewin, W. M. Weinstein, D. A. Antonioli, H. Goldman, W. Macdonald, and D. Owen, “Observer variation in the diagnosis of dysplasia in Barrett’s esophagus,” Hum. Pathol. 19(2), 166–178 (1988).
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O. Pech, A. May, H. Manner, A. Behrens, J. Pohl, M. Weferling, U. Hartmann, N. Manner, J. Huijsmans, L. Gossner, T. Rabenstein, M. Vieth, M. Stolte, and C. Ell, “Long-term efficacy and safety of endoscopic resection for patients with mucosal adenocarcinoma of the esophagus,” Gastroenterology 146(3), 652–660 (2014).
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Vrotsos, K. M.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, J. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, “Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues,” Cancer Res. 65(4), 1180–1186 (2005).
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H. Puchtler, F. S. Waldrop, and L. S. Valentine, “Polarization microscopic studies of connective tissue stained with picro-sirius red FBA,” Beitr. Pathol. 150(2), 174–187 (1973).
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Wang, K.

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
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N. J. Shaheen, P. Sharma, B. F. Overholt, H. C. Wolfsen, R. E. Sampliner, K. K. Wang, J. A. Galanko, M. P. Bronner, J. R. Goldblum, A. E. Bennett, B. A. Jobe, G. M. Eisen, M. B. Fennerty, J. G. Hunter, D. E. Fleischer, V. K. Sharma, R. H. Hawes, B. J. Hoffman, R. I. Rothstein, S. R. Gordon, H. Mashimo, K. J. Chang, V. R. Muthusamy, S. A. Edmundowicz, S. J. Spechler, A. A. Siddiqui, R. F. Souza, A. Infantolino, G. W. Falk, M. B. Kimmey, R. D. Madanick, A. Chak, and C. J. Lightdale, “Radiofrequency ablation in Barrett’s esophagus with dysplasia,” N. Engl. J. Med. 360(22), 2277–2288 (2009).
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P. Sharma, R. H. Hawes, A. Bansal, N. Gupta, W. Curvers, A. Rastogi, M. Singh, M. Hall, S. C. Mathur, S. B. Wani, B. Hoffman, S. Gaddam, P. Fockens, and J. J. Bergman, “Standard endoscopy with random biopsies versus narrow band imaging targeted biopsies in Barrett’s oesophagus: a prospective, international, randomised controlled trial,” Gut 62(1), 15–21 (2013).
[Crossref] [PubMed]

Washington, K.

E. Montgomery, M. P. Bronner, J. R. Goldblum, J. K. Greenson, M. M. Haber, J. Hart, L. W. Lamps, G. Y. Lauwers, A. J. Lazenby, D. N. Lewin, M. E. Robert, A. Y. Toledano, Y. Shyr, and K. Washington, “Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation,” Hum. Pathol. 32(4), 368–378 (2001).
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Webb, W. W.

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: Multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
[Crossref] [PubMed]

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[Crossref] [PubMed]

Weferling, M.

O. Pech, A. May, H. Manner, A. Behrens, J. Pohl, M. Weferling, U. Hartmann, N. Manner, J. Huijsmans, L. Gossner, T. Rabenstein, M. Vieth, M. Stolte, and C. Ell, “Long-term efficacy and safety of endoscopic resection for patients with mucosal adenocarcinoma of the esophagus,” Gastroenterology 146(3), 652–660 (2014).
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Weinstein, W. M.

B. J. Reid, R. C. Haggitt, C. E. Rubin, G. Roth, C. M. Surawicz, G. Van Belle, K. Lewin, W. M. Weinstein, D. A. Antonioli, H. Goldman, W. Macdonald, and D. Owen, “Observer variation in the diagnosis of dysplasia in Barrett’s esophagus,” Hum. Pathol. 19(2), 166–178 (1988).
[Crossref] [PubMed]

Werkmeister, R.

West, J.

M. Solaymani-Dodaran, R. F. Logan, J. West, T. Card, and C. Coupland, “Risk of oesophageal cancer in Barrett’s oesophagus and gastro-oesophageal reflux,” Gut 53(8), 1070–1074 (2004).
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P. Whittaker, R. A. Kloner, D. R. Boughner, and J. G. Pickering, “Quantitative assessment of myocardial collagen with picrosirius red staining and circularly polarized light,” Basic Res. Cardiol. 89(5), 397–410 (1994).
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Williams, R. M.

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: Multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
[Crossref] [PubMed]

Wise, F. W.

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

M. J. Farrar, F. W. Wise, J. R. Fetcho, and C. B. Schaffer, “In vivo imaging of myelin in the vertebrate central nervous system using third harmonic generation microscopy,” Biophys. J. 100, 1362–1371 (2011).

Wolfsen, H. C.

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Figures (5)

Fig. 1
Fig. 1 Schematic diagram of the in-house MPM system (left) and the multiphoton spectrum of Barrett Esophagus tissue (right). Red: Optical spectrum of the multiphoton generated signal from a normal tissue showing a strong THG signal at ~520nm. Inset: zoom-in SHG spectrum.

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Fig. 2
Fig. 2 Comparison between multi-photon microscopy and conventional light microscopy of BE tissue that is negative for dysplasia. (a) H&E conventional light microscopy image showing intestinal metaplasia with goblet cells. There is surface maturation, low nuclear to cytoplasmic ratio and no dysplasia. (b-d) magnified regions shown in (a). (e) High resolution THG signal from MPM and (f-h) the magnified regions in (e). (i) SHG signal recorded simultaneously with the THG signal showing collagen distribution in the stroma and blood vessels. (j-l) magnified marked regions in the SHG image to show collagen in the basement membrane. The THG signal has a clear correlation to the H&E light-microscope image. The architectural structure of nuclei indicates that the tissue has no dysplastic feature. The yellow arrows show the cells with no evidence of dysplasia. (FOV in (e) and (i): 1000 × 750 µm2, acquisition time: ~2min).

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Fig. 3
Fig. 3 Multi-photon and conventional light microscopy images for low-grade dysplastic BE tissue. (a) Conventional light microscopy image of the tissue stained with H&E; there is intestinal metaplasia with goblet cells, surface luminal cells displaying nuclear stratification, hyperchromasia, and an increased nuclear to cytoplasmic ratio (N: C). (b-d) magnified regions marked in the H&E image. (e-h) High resolution THG images that show features of low-grade dysplasia in the same biopsy. (i-l) corresponding simultaneous SHG signals of the THG images that display the presence of collagen. The spatial distribution of cell nuclei is consistent with low-grade dysplasia. The cells with low-grade dysplasia are marked with arrows. (FOV in (e) and (i): 750 × 1000 um2, acquisition time: ~2min). The vertical white lines in (j)-(l) are the PMT artifacts.

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Fig. 4
Fig. 4 MPM and conventional light microscopy images of high-grade dysplastic tissue. (a) Conventional light microscopy image of the tissue after labeling with H&E. There is a progressive dysplastic change in a background of intestinal metaplasia. Cells have marked hyperchromatic nuclei nuclear stratification, loss of polarity and a markedly increased N:C ratio, considerably more than in low grade dysplasia. (b-d) magnified squared regions marked in (a). (e) High resolution THG and (f-h) corresponding magnified regions. (i) High resolution SHG image and (j-l) the magnified regions marked in to show basement membrane collagen (i). The dense nuclei with variable shapes and sizes as well as the loss of orderly arrangement of the cells are consistent with high-grade dysplasia. Arrows represent the cells with high-grade dysplasia. (FOV in (e) and (i): 500 × 500 um2, acquisition time: <1min).

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Fig. 5
Fig. 5 SHG signal from Barrett’s with non-dysplastic dysplasia (a), low grade dysplasia (b) and high grade dysplasia (c). Corresponding graphs to the right show the thickness of the basement membrane collagen measured at each of the three chosen points per image, which confirm increasing thickness with progression of dysplasia.

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