Abstract

Endocytoscopy is an optical biopsy technique which uses a miniaturized camera to capture white light microscopy images through an endoscope. We have developed an alternative design that instead relays images to an external camera via a coherent fiber bundle. In this paper we characterize the device and demonstrate microscopy of porcine tissue ex vivo. One advantage of our approach is the ease with which other bundle-compatible imaging modalities can be deployed simultaneously. We show this by acquiring quasi-simultaneous endocytoscopy and fluorescence confocal endomicroscopy images through a single fiber bundle. This opens up possibilities for multi-modal endomicroscopy, combining white light and fluorescence imaging.

© 2013 Optical Society of America

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  1. O. Riedl, F. Fitzal, N. Mader, P. Dubsky, M. Rudas, M. Mittlboeck, M. Gnant, and R. Jakesz, “Intraoperative frozen section analysis for breast-conserving therapy in 1016 patients with breast cancer,” Eur. J. Surg. Oncol. 35(3), 264–270 (2009).
    [Crossref] [PubMed]
  2. R. Shukla, W. M. Abidi, R. Richards-Kortum, and S. Anandasabapathy, “Endoscopic imaging: How far are we from real-time histology?” World J Gastrointest Endosc 3(10), 183–194 (2011).
    [Crossref] [PubMed]
  3. J. T. C. Liu, N. O. Loewke, M. J. Mandella, R. M. Levenson, and C. Group, “Review article: Modern trends in imaging ii point-of-care pathology with miniature microscopes,” Pathology 34, 81–98 (2011).
  4. R. C. Newton, S. V. Kemp, P. L. Shah, D. Elson, A. Darzi, K. Shibuya, S. Mulgrew, and G.-Z. Yang, “Progress toward optical biopsy: Bringing the microscope to the patient,” Lung 189(2), 111–119 (2011).
    [Crossref] [PubMed]
  5. G. L. Goualher, A. Perchant, M. Genet, C. Cav, B. Viellerobe, B. Abrat, and N. Ayache, “Towards optical biopsies with an integrated fibered confocal fluorescence microscope,” MICCAI 2004, 761–768 (2004).
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  7. J. M. Jabbour, M. A. Saldua, J. N. Bixler, and K. C. Maitland, “Confocal endomicroscopy: Instrumentation and medical applications,” Ann. Biomed. Eng. 40(2), 378–397 (2012).
    [PubMed]
  8. A. L. Polglase, W. J. McLaren, S. A. Skinner, R. Kiesslich, M. F. Neurath, and P. M. Delaney, “A fluorescence confocal endomicroscope for in vivo microscopy of the upper- and the lower-gi tract,” Gastrointest. Endosc. 62(5), 686–695 (2005).
    [Crossref] [PubMed]
  9. N. Bozinovic, C. Ventalon, T. Ford, and J. Mertz, “Fluorescence endomicroscopy with structured illumination,” Opt. Express 16(11), 8016–8025 (2008).
    [Crossref] [PubMed]
  10. T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence hilo endomicroscopy,” J. Biomed. Opt. 17(2), 021105 (2012).
    [Crossref] [PubMed]
  11. 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]
  12. F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, “A miniature head-mounted two-photon microscope. High-resolution brain imaging in freely moving animals,” Neuron 31(6), 903–912 (2001).
    [Crossref] [PubMed]
  13. W. Göbel, J. N. D. Kerr, A. Nimmerjahn, and F. Helmchen, “Miniaturized two-photon microscope based on a flexible coherent fiber bundle and a gradient-index lens objective,” Opt. Lett. 29(21), 2521–2523 (2004).
    [Crossref] [PubMed]
  14. G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppart, C. Pitris, J. F. Southern, and J. G. Fujimoto, “In vivo endoscopic optical biopsy with optical coherence tomography,” Science 276(5321), 2037–2039 (1997).
    [Crossref] [PubMed]
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    [Crossref] [PubMed]
  16. A. Osdoit, F. Lacombe, C. Cavé, S. Loiseau, and E. Peltier, “To see the unseeable: Confocal miniprobes for routine microscopic imaging during endoscopy,” Proc. SPIE 6432, 64320F (2007).
    [Crossref]
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  19. N. Hasegawa, “Magnifying image pickup unit for an endoscope, an endoscope for in vivo cellular observation that uses it, and endoscopic, in vivo cellular observation methods,” US Patent 7267648 (2007).
  20. H. Inoue, S. E. Kudo, and A. Shiokawa, “Technology insight: Laser-scanning confocal microscopy and endocytoscopy for cellular observation of the gastrointestinal tract,” Nat. Clin. Pract. Gastroenterol. Hepatol. 2(1), 31–37 (2005).
    [Crossref] [PubMed]
  21. C. Szeto, B. Wehrli, F. Whelan, J. Franklin, A. Nichols, J. Yoo, and K. Fung, “Contact endoscopy as a novel technique in the detection and diagnosis of mucosal lesions in the head and neck: A brief review,” J. Oncol. 2011, 196302 (2011).
    [Crossref] [PubMed]
  22. J. Hamou, “Microhysteroscopy — A new technique in endoscopy and its applications,” Acta Endoscopica 10(5-6), 415–422 (1980).
    [Crossref]
  23. M. Tada, S. Nishimura, and Y. Watanabe, “A new method for the ultra-magnifying observation of the colon mucosa,” Kyoto Pref. Univ. Med. 91, 349–354 (1982).
  24. E. Dekker, M. Kara, J. Offerhaus, and P. Fockens, “Endocytoscopy in the colon: Early experience with a new real-time contact microscopy system,” Gastrointest. Endosc. 61(5), AB224 (2005).
    [Crossref]
  25. H. Pohl, M. Koch, A. Khalifa, I. S. Papanikolaou, B. Wiedenmann, and T. Roesch, “Evaluation of an endocytoscopy system in the surveillance of patients with barrett esophagus,” Gastrointest. Endosc. 63(5), AB239 (2006).
    [Crossref]
  26. H. Neumann, M. Vieth, M. F. Neurath, and F. S. Fuchs, “In vivo diagnosis of small-cell lung cancer by endocytoscopy,” J. Clin. Oncol. 29(6), e131–e132 (2011).
    [Crossref] [PubMed]
  27. T. Ohigashi, N. Kozakai, R. Mizuno, A. Miyajima, and M. Murai, “Endocytoscopy: Novel endoscopic imaging technology for in-situ observation of bladder cancer cells,” J. Endourol. 20(9), 698–701 (2006).
    [Crossref] [PubMed]
  28. G. V. Rao, R. Pradeep, M. J. Mansard, C. Ramji, R. Banerjee, and D. Nageshwar Reddy, “Endocytoscopy assists in the intraoperative diagnosis of carcinoma in a patient with chronic pancreatitis,” Endoscopy 39(S1Suppl 1), E317–E318 (2007).
    [Crossref] [PubMed]
  29. H. Neumann, R. Atreya, M. Vieth, and M. F. Neurath, “Toluidine blue is as effective as methylene blue for endocytoscopy,” Gastrointest. Endosc. 75(4), 479 (2012).
    [Crossref]
  30. H. Inoue, A. Yokoyama, and S. E. Kudo, “Ultrahigh magnifying endoscopy: Development of cm double staining for endocytoscopy and its safety,” Nippon Rinsho 68(7), 1247–1252 (2010).
    [PubMed]
  31. T. Ohigashi, N. Kozakai, R. Mizuno, A. Miyajima, and M. Murai, “Endocytoscopy: Novel endoscopic imaging technology for in-situ observation of bladder cancer cells,” J. Endourol. 20(9), 698–701 (2006).
    [Crossref] [PubMed]
  32. H. Minami, H. Inoue, A. Yokoyama, H. Ikeda, H. Satodate, S. Hamatani, A. Haji, and S. Kudo, “Recent advancement of observing living cells in the esophagus using cm double staining: Endocytoscopic atypia classification,” Dis. Esophagus 25(3), 235–241 (2012).
    [Crossref] [PubMed]
  33. K. Chang, “Eus-guided needle-based confocal laser induced endomicroscopy (ncle): A correlation study of “through the needle” imaging with normal histology in a porcine model,” Endoscopy 43(S 03), A14 (2011).
    [Crossref]
  34. G. Sridharan and A. A. Shankar, “Toluidine blue: A review of its chemistry and clinical utility,” J Oral Maxillofac Pathol 16(2), 251–255 (2012).
    [Crossref] [PubMed]
  35. S. Kodashima, M. Fujishiro, K. Takubo, M. Kammori, S. Nomura, N. Kakushima, Y. Muraki, A. Tateishi, M. Kaminishi, and M. Omata, “Ex-vivo study of high-magnification chromoendoscopy in the gastrointestinal tract to determine the optimal staining conditions for endocytoscopy,” Endoscopy 38(11), 1115–1121 (2006).
    [Crossref] [PubMed]
  36. M. Goetz, T. Toermer, M. Vieth, K. Dunbar, A. Hoffman, P. R. Galle, M. F. Neurath, P. Delaney, and R. Kiesslich, “Simultaneous confocal laser endomicroscopy and chromoendoscopy with topical cresyl violet,” Gastrointest. Endosc. 70(5), 959–968 (2009).
    [Crossref] [PubMed]
  37. M. Kyrish and T. S. Tkaczyk, “Achromatized endomicroscope objective for optical biopsy,” Biomed. Opt. Express 4(2), 287–297 (2013).
    [Crossref] [PubMed]
  38. T. Vercauteren, F. Doussoux, M. Cazaux, G. Schmid, N. Linard, M.-A. Durin, H. Gharbi, and F. Lacombe, “Multicolor probe-based confocal laser endomicroscopy: A new world for in vivo and real-time cellular imaging,” Proc. SPIE 8575, 857504 (2013).
    [Crossref]
  39. J.-H. Han, J. Lee, and J. U. Kang, “Pixelation effect removal from fiber bundle probe based optical coherence tomography imaging,” Opt. Express 18(7), 7427–7439 (2010).
    [Crossref] [PubMed]
  40. R. Singh, S. L. Chen Yi Mei, W. Tam, D. Raju, and A. Ruszkiewicz, “Real-time histology with the endocytoscope,” World J. Gastroenterol. 16(40), 5016–5019 (2010).
    [Crossref] [PubMed]
  41. G. L. Goualher, A. Perchant, M. Genet, C. Cav, B. Viellerobe, B. Abrat, and N. Ayache, “Towards optical biopsies with an integrated fibered confocal fluorescence microscope,” in MICCAI (2004), pp. 761–768.
  42. C. Liang, M. R. Descour, K. B. Sung, and R. Richards-Kortum, “Fiber confocal reflectance microscope (fcrm) for in-vivo imaging,” Opt. Express 9(13), 821–830 (2001).
    [Crossref] [PubMed]
  43. X. Liu, Y. Huang, and J. U. Kang, “Dark-field illuminated reflectance fiber bundle endoscopic microscope,” J. Biomed. Opt. 16(4), 046003 (2011).
    [Crossref] [PubMed]
  44. H. Makhlouf, A. F. Gmitro, A. A. Tanbakuchi, J. A. Udovich, and A. R. Rouse, “Multispectral confocal microendoscope for in vivo and in situ imaging,” J. Biomed. Opt. 13(4), 044016 (2008).
    [Crossref] [PubMed]
  45. M. C. Pierce, P. M. Vila, A. D. Polydorides, R. Richards-Kortum, and S. Anandasabapathy, “Low-cost endomicroscopy in the esophagus and colon,” Am. J. Gastroenterol. 106(9), 1722–1724 (2011).
    [Crossref] [PubMed]
  46. R. Regunathan, J. Woo, M. C. Pierce, A. D. Polydorides, M. Raoufi, S. Roayaie, M. Schwartz, D. Labow, D. Shin, R. Suzuki, M. S. Bhutani, L. G. Coghlan, R. Richards-Kortum, S. Anandasabapathy, and M. K. Kim, “Feasibility and preliminary accuracy of high-resolution imaging of the liver and pancreas using fna compatible microendoscopy (with video),” Gastrointest. Endosc. 76(2), 293–300 (2012).
    [Crossref] [PubMed]

2013 (2)

T. Vercauteren, F. Doussoux, M. Cazaux, G. Schmid, N. Linard, M.-A. Durin, H. Gharbi, and F. Lacombe, “Multicolor probe-based confocal laser endomicroscopy: A new world for in vivo and real-time cellular imaging,” Proc. SPIE 8575, 857504 (2013).
[Crossref]

M. Kyrish and T. S. Tkaczyk, “Achromatized endomicroscope objective for optical biopsy,” Biomed. Opt. Express 4(2), 287–297 (2013).
[Crossref] [PubMed]

2012 (6)

R. Regunathan, J. Woo, M. C. Pierce, A. D. Polydorides, M. Raoufi, S. Roayaie, M. Schwartz, D. Labow, D. Shin, R. Suzuki, M. S. Bhutani, L. G. Coghlan, R. Richards-Kortum, S. Anandasabapathy, and M. K. Kim, “Feasibility and preliminary accuracy of high-resolution imaging of the liver and pancreas using fna compatible microendoscopy (with video),” Gastrointest. Endosc. 76(2), 293–300 (2012).
[Crossref] [PubMed]

T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence hilo endomicroscopy,” J. Biomed. Opt. 17(2), 021105 (2012).
[Crossref] [PubMed]

J. M. Jabbour, M. A. Saldua, J. N. Bixler, and K. C. Maitland, “Confocal endomicroscopy: Instrumentation and medical applications,” Ann. Biomed. Eng. 40(2), 378–397 (2012).
[PubMed]

G. Sridharan and A. A. Shankar, “Toluidine blue: A review of its chemistry and clinical utility,” J Oral Maxillofac Pathol 16(2), 251–255 (2012).
[Crossref] [PubMed]

H. Neumann, R. Atreya, M. Vieth, and M. F. Neurath, “Toluidine blue is as effective as methylene blue for endocytoscopy,” Gastrointest. Endosc. 75(4), 479 (2012).
[Crossref]

H. Minami, H. Inoue, A. Yokoyama, H. Ikeda, H. Satodate, S. Hamatani, A. Haji, and S. Kudo, “Recent advancement of observing living cells in the esophagus using cm double staining: Endocytoscopic atypia classification,” Dis. Esophagus 25(3), 235–241 (2012).
[Crossref] [PubMed]

2011 (9)

K. Chang, “Eus-guided needle-based confocal laser induced endomicroscopy (ncle): A correlation study of “through the needle” imaging with normal histology in a porcine model,” Endoscopy 43(S 03), A14 (2011).
[Crossref]

H. Neumann, M. Vieth, M. F. Neurath, and F. S. Fuchs, “In vivo diagnosis of small-cell lung cancer by endocytoscopy,” J. Clin. Oncol. 29(6), e131–e132 (2011).
[Crossref] [PubMed]

H. Neumann, F. S. Fuchs, M. Vieth, R. Atreya, J. Siebler, R. Kiesslich, and M. F. Neurath, “Review article: In vivo imaging by endocytoscopy,” Aliment. Pharmacol. Ther. 33(11), 1183–1193 (2011).
[Crossref] [PubMed]

C. Szeto, B. Wehrli, F. Whelan, J. Franklin, A. Nichols, J. Yoo, and K. Fung, “Contact endoscopy as a novel technique in the detection and diagnosis of mucosal lesions in the head and neck: A brief review,” J. Oncol. 2011, 196302 (2011).
[Crossref] [PubMed]

R. Shukla, W. M. Abidi, R. Richards-Kortum, and S. Anandasabapathy, “Endoscopic imaging: How far are we from real-time histology?” World J Gastrointest Endosc 3(10), 183–194 (2011).
[Crossref] [PubMed]

J. T. C. Liu, N. O. Loewke, M. J. Mandella, R. M. Levenson, and C. Group, “Review article: Modern trends in imaging ii point-of-care pathology with miniature microscopes,” Pathology 34, 81–98 (2011).

R. C. Newton, S. V. Kemp, P. L. Shah, D. Elson, A. Darzi, K. Shibuya, S. Mulgrew, and G.-Z. Yang, “Progress toward optical biopsy: Bringing the microscope to the patient,” Lung 189(2), 111–119 (2011).
[Crossref] [PubMed]

X. Liu, Y. Huang, and J. U. Kang, “Dark-field illuminated reflectance fiber bundle endoscopic microscope,” J. Biomed. Opt. 16(4), 046003 (2011).
[Crossref] [PubMed]

M. C. Pierce, P. M. Vila, A. D. Polydorides, R. Richards-Kortum, and S. Anandasabapathy, “Low-cost endomicroscopy in the esophagus and colon,” Am. J. Gastroenterol. 106(9), 1722–1724 (2011).
[Crossref] [PubMed]

2010 (3)

H. Inoue, A. Yokoyama, and S. E. Kudo, “Ultrahigh magnifying endoscopy: Development of cm double staining for endocytoscopy and its safety,” Nippon Rinsho 68(7), 1247–1252 (2010).
[PubMed]

R. Singh, S. L. Chen Yi Mei, W. Tam, D. Raju, and A. Ruszkiewicz, “Real-time histology with the endocytoscope,” World J. Gastroenterol. 16(40), 5016–5019 (2010).
[Crossref] [PubMed]

J.-H. Han, J. Lee, and J. U. Kang, “Pixelation effect removal from fiber bundle probe based optical coherence tomography imaging,” Opt. Express 18(7), 7427–7439 (2010).
[Crossref] [PubMed]

2009 (2)

M. Goetz, T. Toermer, M. Vieth, K. Dunbar, A. Hoffman, P. R. Galle, M. F. Neurath, P. Delaney, and R. Kiesslich, “Simultaneous confocal laser endomicroscopy and chromoendoscopy with topical cresyl violet,” Gastrointest. Endosc. 70(5), 959–968 (2009).
[Crossref] [PubMed]

O. Riedl, F. Fitzal, N. Mader, P. Dubsky, M. Rudas, M. Mittlboeck, M. Gnant, and R. Jakesz, “Intraoperative frozen section analysis for breast-conserving therapy in 1016 patients with breast cancer,” Eur. J. Surg. Oncol. 35(3), 264–270 (2009).
[Crossref] [PubMed]

2008 (3)

H. Makhlouf, A. F. Gmitro, A. A. Tanbakuchi, J. A. Udovich, and A. R. Rouse, “Multispectral confocal microendoscope for in vivo and in situ imaging,” J. Biomed. Opt. 13(4), 044016 (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]

N. Bozinovic, C. Ventalon, T. Ford, and J. Mertz, “Fluorescence endomicroscopy with structured illumination,” Opt. Express 16(11), 8016–8025 (2008).
[Crossref] [PubMed]

2007 (3)

G. V. Rao, R. Pradeep, M. J. Mansard, C. Ramji, R. Banerjee, and D. Nageshwar Reddy, “Endocytoscopy assists in the intraoperative diagnosis of carcinoma in a patient with chronic pancreatitis,” Endoscopy 39(S1Suppl 1), E317–E318 (2007).
[Crossref] [PubMed]

A. M. Zysk, F. T. Nguyen, A. L. Oldenburg, D. L. Marks, and S. A. Boppart, “Optical coherence tomography: A review of clinical development from bench to bedside,” J. Biomed. Opt. 12(5), 051403 (2007).
[Crossref] [PubMed]

A. Osdoit, F. Lacombe, C. Cavé, S. Loiseau, and E. Peltier, “To see the unseeable: Confocal miniprobes for routine microscopic imaging during endoscopy,” Proc. SPIE 6432, 64320F (2007).
[Crossref]

2006 (4)

T. Ohigashi, N. Kozakai, R. Mizuno, A. Miyajima, and M. Murai, “Endocytoscopy: Novel endoscopic imaging technology for in-situ observation of bladder cancer cells,” J. Endourol. 20(9), 698–701 (2006).
[Crossref] [PubMed]

T. Ohigashi, N. Kozakai, R. Mizuno, A. Miyajima, and M. Murai, “Endocytoscopy: Novel endoscopic imaging technology for in-situ observation of bladder cancer cells,” J. Endourol. 20(9), 698–701 (2006).
[Crossref] [PubMed]

H. Pohl, M. Koch, A. Khalifa, I. S. Papanikolaou, B. Wiedenmann, and T. Roesch, “Evaluation of an endocytoscopy system in the surveillance of patients with barrett esophagus,” Gastrointest. Endosc. 63(5), AB239 (2006).
[Crossref]

S. Kodashima, M. Fujishiro, K. Takubo, M. Kammori, S. Nomura, N. Kakushima, Y. Muraki, A. Tateishi, M. Kaminishi, and M. Omata, “Ex-vivo study of high-magnification chromoendoscopy in the gastrointestinal tract to determine the optimal staining conditions for endocytoscopy,” Endoscopy 38(11), 1115–1121 (2006).
[Crossref] [PubMed]

2005 (3)

A. L. Polglase, W. J. McLaren, S. A. Skinner, R. Kiesslich, M. F. Neurath, and P. M. Delaney, “A fluorescence confocal endomicroscope for in vivo microscopy of the upper- and the lower-gi tract,” Gastrointest. Endosc. 62(5), 686–695 (2005).
[Crossref] [PubMed]

E. Dekker, M. Kara, J. Offerhaus, and P. Fockens, “Endocytoscopy in the colon: Early experience with a new real-time contact microscopy system,” Gastrointest. Endosc. 61(5), AB224 (2005).
[Crossref]

H. Inoue, S. E. Kudo, and A. Shiokawa, “Technology insight: Laser-scanning confocal microscopy and endocytoscopy for cellular observation of the gastrointestinal tract,” Nat. Clin. Pract. Gastroenterol. Hepatol. 2(1), 31–37 (2005).
[Crossref] [PubMed]

2004 (2)

G. L. Goualher, A. Perchant, M. Genet, C. Cav, B. Viellerobe, B. Abrat, and N. Ayache, “Towards optical biopsies with an integrated fibered confocal fluorescence microscope,” MICCAI 2004, 761–768 (2004).

W. Göbel, J. N. D. Kerr, A. Nimmerjahn, and F. Helmchen, “Miniaturized two-photon microscope based on a flexible coherent fiber bundle and a gradient-index lens objective,” Opt. Lett. 29(21), 2521–2523 (2004).
[Crossref] [PubMed]

2001 (2)

C. Liang, M. R. Descour, K. B. Sung, and R. Richards-Kortum, “Fiber confocal reflectance microscope (fcrm) for in-vivo imaging,” Opt. Express 9(13), 821–830 (2001).
[Crossref] [PubMed]

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, “A miniature head-mounted two-photon microscope. High-resolution brain imaging in freely moving animals,” Neuron 31(6), 903–912 (2001).
[Crossref] [PubMed]

1997 (1)

G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppart, C. Pitris, J. F. Southern, and J. G. Fujimoto, “In vivo endoscopic optical biopsy with optical coherence tomography,” Science 276(5321), 2037–2039 (1997).
[Crossref] [PubMed]

1993 (1)

1982 (1)

M. Tada, S. Nishimura, and Y. Watanabe, “A new method for the ultra-magnifying observation of the colon mucosa,” Kyoto Pref. Univ. Med. 91, 349–354 (1982).

1980 (1)

J. Hamou, “Microhysteroscopy — A new technique in endoscopy and its applications,” Acta Endoscopica 10(5-6), 415–422 (1980).
[Crossref]

Abidi, W. M.

R. Shukla, W. M. Abidi, R. Richards-Kortum, and S. Anandasabapathy, “Endoscopic imaging: How far are we from real-time histology?” World J Gastrointest Endosc 3(10), 183–194 (2011).
[Crossref] [PubMed]

Abrat, B.

G. L. Goualher, A. Perchant, M. Genet, C. Cav, B. Viellerobe, B. Abrat, and N. Ayache, “Towards optical biopsies with an integrated fibered confocal fluorescence microscope,” MICCAI 2004, 761–768 (2004).

Anandasabapathy, S.

R. Regunathan, J. Woo, M. C. Pierce, A. D. Polydorides, M. Raoufi, S. Roayaie, M. Schwartz, D. Labow, D. Shin, R. Suzuki, M. S. Bhutani, L. G. Coghlan, R. Richards-Kortum, S. Anandasabapathy, and M. K. Kim, “Feasibility and preliminary accuracy of high-resolution imaging of the liver and pancreas using fna compatible microendoscopy (with video),” Gastrointest. Endosc. 76(2), 293–300 (2012).
[Crossref] [PubMed]

M. C. Pierce, P. M. Vila, A. D. Polydorides, R. Richards-Kortum, and S. Anandasabapathy, “Low-cost endomicroscopy in the esophagus and colon,” Am. J. Gastroenterol. 106(9), 1722–1724 (2011).
[Crossref] [PubMed]

R. Shukla, W. M. Abidi, R. Richards-Kortum, and S. Anandasabapathy, “Endoscopic imaging: How far are we from real-time histology?” World J Gastrointest Endosc 3(10), 183–194 (2011).
[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).
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F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, “A miniature head-mounted two-photon microscope. High-resolution brain imaging in freely moving animals,” Neuron 31(6), 903–912 (2001).
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Doussoux, F.

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O. Riedl, F. Fitzal, N. Mader, P. Dubsky, M. Rudas, M. Mittlboeck, M. Gnant, and R. Jakesz, “Intraoperative frozen section analysis for breast-conserving therapy in 1016 patients with breast cancer,” Eur. J. Surg. Oncol. 35(3), 264–270 (2009).
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M. Goetz, T. Toermer, M. Vieth, K. Dunbar, A. Hoffman, P. R. Galle, M. F. Neurath, P. Delaney, and R. Kiesslich, “Simultaneous confocal laser endomicroscopy and chromoendoscopy with topical cresyl violet,” Gastrointest. Endosc. 70(5), 959–968 (2009).
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T. Vercauteren, F. Doussoux, M. Cazaux, G. Schmid, N. Linard, M.-A. Durin, H. Gharbi, and F. Lacombe, “Multicolor probe-based confocal laser endomicroscopy: A new world for in vivo and real-time cellular imaging,” Proc. SPIE 8575, 857504 (2013).
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F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, “A miniature head-mounted two-photon microscope. High-resolution brain imaging in freely moving animals,” Neuron 31(6), 903–912 (2001).
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O. Riedl, F. Fitzal, N. Mader, P. Dubsky, M. Rudas, M. Mittlboeck, M. Gnant, and R. Jakesz, “Intraoperative frozen section analysis for breast-conserving therapy in 1016 patients with breast cancer,” Eur. J. Surg. Oncol. 35(3), 264–270 (2009).
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E. Dekker, M. Kara, J. Offerhaus, and P. Fockens, “Endocytoscopy in the colon: Early experience with a new real-time contact microscopy system,” Gastrointest. Endosc. 61(5), AB224 (2005).
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Ford, T. N.

T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence hilo endomicroscopy,” J. Biomed. Opt. 17(2), 021105 (2012).
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H. Neumann, F. S. Fuchs, M. Vieth, R. Atreya, J. Siebler, R. Kiesslich, and M. F. Neurath, “Review article: In vivo imaging by endocytoscopy,” Aliment. Pharmacol. Ther. 33(11), 1183–1193 (2011).
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H. Neumann, M. Vieth, M. F. Neurath, and F. S. Fuchs, “In vivo diagnosis of small-cell lung cancer by endocytoscopy,” J. Clin. Oncol. 29(6), e131–e132 (2011).
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G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppart, C. Pitris, J. F. Southern, and J. G. Fujimoto, “In vivo endoscopic optical biopsy with optical coherence tomography,” Science 276(5321), 2037–2039 (1997).
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Fujishiro, M.

S. Kodashima, M. Fujishiro, K. Takubo, M. Kammori, S. Nomura, N. Kakushima, Y. Muraki, A. Tateishi, M. Kaminishi, and M. Omata, “Ex-vivo study of high-magnification chromoendoscopy in the gastrointestinal tract to determine the optimal staining conditions for endocytoscopy,” Endoscopy 38(11), 1115–1121 (2006).
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C. Szeto, B. Wehrli, F. Whelan, J. Franklin, A. Nichols, J. Yoo, and K. Fung, “Contact endoscopy as a novel technique in the detection and diagnosis of mucosal lesions in the head and neck: A brief review,” J. Oncol. 2011, 196302 (2011).
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Galle, P. R.

M. Goetz, T. Toermer, M. Vieth, K. Dunbar, A. Hoffman, P. R. Galle, M. F. Neurath, P. Delaney, and R. Kiesslich, “Simultaneous confocal laser endomicroscopy and chromoendoscopy with topical cresyl violet,” Gastrointest. Endosc. 70(5), 959–968 (2009).
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Genet, M.

G. L. Goualher, A. Perchant, M. Genet, C. Cav, B. Viellerobe, B. Abrat, and N. Ayache, “Towards optical biopsies with an integrated fibered confocal fluorescence microscope,” MICCAI 2004, 761–768 (2004).

Gharbi, H.

T. Vercauteren, F. Doussoux, M. Cazaux, G. Schmid, N. Linard, M.-A. Durin, H. Gharbi, and F. Lacombe, “Multicolor probe-based confocal laser endomicroscopy: A new world for in vivo and real-time cellular imaging,” Proc. SPIE 8575, 857504 (2013).
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H. Makhlouf, A. F. Gmitro, A. A. Tanbakuchi, J. A. Udovich, and A. R. Rouse, “Multispectral confocal microendoscope for in vivo and in situ imaging,” J. Biomed. Opt. 13(4), 044016 (2008).
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O. Riedl, F. Fitzal, N. Mader, P. Dubsky, M. Rudas, M. Mittlboeck, M. Gnant, and R. Jakesz, “Intraoperative frozen section analysis for breast-conserving therapy in 1016 patients with breast cancer,” Eur. J. Surg. Oncol. 35(3), 264–270 (2009).
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Goetz, M.

M. Goetz, T. Toermer, M. Vieth, K. Dunbar, A. Hoffman, P. R. Galle, M. F. Neurath, P. Delaney, and R. Kiesslich, “Simultaneous confocal laser endomicroscopy and chromoendoscopy with topical cresyl violet,” Gastrointest. Endosc. 70(5), 959–968 (2009).
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G. L. Goualher, A. Perchant, M. Genet, C. Cav, B. Viellerobe, B. Abrat, and N. Ayache, “Towards optical biopsies with an integrated fibered confocal fluorescence microscope,” MICCAI 2004, 761–768 (2004).

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H. Minami, H. Inoue, A. Yokoyama, H. Ikeda, H. Satodate, S. Hamatani, A. Haji, and S. Kudo, “Recent advancement of observing living cells in the esophagus using cm double staining: Endocytoscopic atypia classification,” Dis. Esophagus 25(3), 235–241 (2012).
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F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, “A miniature head-mounted two-photon microscope. High-resolution brain imaging in freely moving animals,” Neuron 31(6), 903–912 (2001).
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Hoffman, A.

M. Goetz, T. Toermer, M. Vieth, K. Dunbar, A. Hoffman, P. R. Galle, M. F. Neurath, P. Delaney, and R. Kiesslich, “Simultaneous confocal laser endomicroscopy and chromoendoscopy with topical cresyl violet,” Gastrointest. Endosc. 70(5), 959–968 (2009).
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X. Liu, Y. Huang, and J. U. Kang, “Dark-field illuminated reflectance fiber bundle endoscopic microscope,” J. Biomed. Opt. 16(4), 046003 (2011).
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H. Minami, H. Inoue, A. Yokoyama, H. Ikeda, H. Satodate, S. Hamatani, A. Haji, and S. Kudo, “Recent advancement of observing living cells in the esophagus using cm double staining: Endocytoscopic atypia classification,” Dis. Esophagus 25(3), 235–241 (2012).
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H. Minami, H. Inoue, A. Yokoyama, H. Ikeda, H. Satodate, S. Hamatani, A. Haji, and S. Kudo, “Recent advancement of observing living cells in the esophagus using cm double staining: Endocytoscopic atypia classification,” Dis. Esophagus 25(3), 235–241 (2012).
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H. Inoue, A. Yokoyama, and S. E. Kudo, “Ultrahigh magnifying endoscopy: Development of cm double staining for endocytoscopy and its safety,” Nippon Rinsho 68(7), 1247–1252 (2010).
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H. Inoue, S. E. Kudo, and A. Shiokawa, “Technology insight: Laser-scanning confocal microscopy and endocytoscopy for cellular observation of the gastrointestinal tract,” Nat. Clin. Pract. Gastroenterol. Hepatol. 2(1), 31–37 (2005).
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Jabbour, J. M.

J. M. Jabbour, M. A. Saldua, J. N. Bixler, and K. C. Maitland, “Confocal endomicroscopy: Instrumentation and medical applications,” Ann. Biomed. Eng. 40(2), 378–397 (2012).
[PubMed]

Jakesz, R.

O. Riedl, F. Fitzal, N. Mader, P. Dubsky, M. Rudas, M. Mittlboeck, M. Gnant, and R. Jakesz, “Intraoperative frozen section analysis for breast-conserving therapy in 1016 patients with breast cancer,” Eur. J. Surg. Oncol. 35(3), 264–270 (2009).
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S. Kodashima, M. Fujishiro, K. Takubo, M. Kammori, S. Nomura, N. Kakushima, Y. Muraki, A. Tateishi, M. Kaminishi, and M. Omata, “Ex-vivo study of high-magnification chromoendoscopy in the gastrointestinal tract to determine the optimal staining conditions for endocytoscopy,” Endoscopy 38(11), 1115–1121 (2006).
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S. Kodashima, M. Fujishiro, K. Takubo, M. Kammori, S. Nomura, N. Kakushima, Y. Muraki, A. Tateishi, M. Kaminishi, and M. Omata, “Ex-vivo study of high-magnification chromoendoscopy in the gastrointestinal tract to determine the optimal staining conditions for endocytoscopy,” Endoscopy 38(11), 1115–1121 (2006).
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S. Kodashima, M. Fujishiro, K. Takubo, M. Kammori, S. Nomura, N. Kakushima, Y. Muraki, A. Tateishi, M. Kaminishi, and M. Omata, “Ex-vivo study of high-magnification chromoendoscopy in the gastrointestinal tract to determine the optimal staining conditions for endocytoscopy,” Endoscopy 38(11), 1115–1121 (2006).
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Kang, J. U.

X. Liu, Y. Huang, and J. U. Kang, “Dark-field illuminated reflectance fiber bundle endoscopic microscope,” J. Biomed. Opt. 16(4), 046003 (2011).
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J.-H. Han, J. Lee, and J. U. Kang, “Pixelation effect removal from fiber bundle probe based optical coherence tomography imaging,” Opt. Express 18(7), 7427–7439 (2010).
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E. Dekker, M. Kara, J. Offerhaus, and P. Fockens, “Endocytoscopy in the colon: Early experience with a new real-time contact microscopy system,” Gastrointest. Endosc. 61(5), AB224 (2005).
[Crossref]

Kemp, S. V.

R. C. Newton, S. V. Kemp, P. L. Shah, D. Elson, A. Darzi, K. Shibuya, S. Mulgrew, and G.-Z. Yang, “Progress toward optical biopsy: Bringing the microscope to the patient,” Lung 189(2), 111–119 (2011).
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Kerr, J. N. D.

Khalifa, A.

H. Pohl, M. Koch, A. Khalifa, I. S. Papanikolaou, B. Wiedenmann, and T. Roesch, “Evaluation of an endocytoscopy system in the surveillance of patients with barrett esophagus,” Gastrointest. Endosc. 63(5), AB239 (2006).
[Crossref]

Kiesslich, R.

H. Neumann, F. S. Fuchs, M. Vieth, R. Atreya, J. Siebler, R. Kiesslich, and M. F. Neurath, “Review article: In vivo imaging by endocytoscopy,” Aliment. Pharmacol. Ther. 33(11), 1183–1193 (2011).
[Crossref] [PubMed]

M. Goetz, T. Toermer, M. Vieth, K. Dunbar, A. Hoffman, P. R. Galle, M. F. Neurath, P. Delaney, and R. Kiesslich, “Simultaneous confocal laser endomicroscopy and chromoendoscopy with topical cresyl violet,” Gastrointest. Endosc. 70(5), 959–968 (2009).
[Crossref] [PubMed]

A. L. Polglase, W. J. McLaren, S. A. Skinner, R. Kiesslich, M. F. Neurath, and P. M. Delaney, “A fluorescence confocal endomicroscope for in vivo microscopy of the upper- and the lower-gi tract,” Gastrointest. Endosc. 62(5), 686–695 (2005).
[Crossref] [PubMed]

Kim, M. K.

R. Regunathan, J. Woo, M. C. Pierce, A. D. Polydorides, M. Raoufi, S. Roayaie, M. Schwartz, D. Labow, D. Shin, R. Suzuki, M. S. Bhutani, L. G. Coghlan, R. Richards-Kortum, S. Anandasabapathy, and M. K. Kim, “Feasibility and preliminary accuracy of high-resolution imaging of the liver and pancreas using fna compatible microendoscopy (with video),” Gastrointest. Endosc. 76(2), 293–300 (2012).
[Crossref] [PubMed]

Koch, M.

H. Pohl, M. Koch, A. Khalifa, I. S. Papanikolaou, B. Wiedenmann, and T. Roesch, “Evaluation of an endocytoscopy system in the surveillance of patients with barrett esophagus,” Gastrointest. Endosc. 63(5), AB239 (2006).
[Crossref]

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S. Kodashima, M. Fujishiro, K. Takubo, M. Kammori, S. Nomura, N. Kakushima, Y. Muraki, A. Tateishi, M. Kaminishi, and M. Omata, “Ex-vivo study of high-magnification chromoendoscopy in the gastrointestinal tract to determine the optimal staining conditions for endocytoscopy,” Endoscopy 38(11), 1115–1121 (2006).
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T. Ohigashi, N. Kozakai, R. Mizuno, A. Miyajima, and M. Murai, “Endocytoscopy: Novel endoscopic imaging technology for in-situ observation of bladder cancer cells,” J. Endourol. 20(9), 698–701 (2006).
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H. Minami, H. Inoue, A. Yokoyama, H. Ikeda, H. Satodate, S. Hamatani, A. Haji, and S. Kudo, “Recent advancement of observing living cells in the esophagus using cm double staining: Endocytoscopic atypia classification,” Dis. Esophagus 25(3), 235–241 (2012).
[Crossref] [PubMed]

Kudo, S. E.

H. Inoue, A. Yokoyama, and S. E. Kudo, “Ultrahigh magnifying endoscopy: Development of cm double staining for endocytoscopy and its safety,” Nippon Rinsho 68(7), 1247–1252 (2010).
[PubMed]

H. Inoue, S. E. Kudo, and A. Shiokawa, “Technology insight: Laser-scanning confocal microscopy and endocytoscopy for cellular observation of the gastrointestinal tract,” Nat. Clin. Pract. Gastroenterol. Hepatol. 2(1), 31–37 (2005).
[Crossref] [PubMed]

Kyrish, M.

Labow, D.

R. Regunathan, J. Woo, M. C. Pierce, A. D. Polydorides, M. Raoufi, S. Roayaie, M. Schwartz, D. Labow, D. Shin, R. Suzuki, M. S. Bhutani, L. G. Coghlan, R. Richards-Kortum, S. Anandasabapathy, and M. K. Kim, “Feasibility and preliminary accuracy of high-resolution imaging of the liver and pancreas using fna compatible microendoscopy (with video),” Gastrointest. Endosc. 76(2), 293–300 (2012).
[Crossref] [PubMed]

Lacombe, F.

T. Vercauteren, F. Doussoux, M. Cazaux, G. Schmid, N. Linard, M.-A. Durin, H. Gharbi, and F. Lacombe, “Multicolor probe-based confocal laser endomicroscopy: A new world for in vivo and real-time cellular imaging,” Proc. SPIE 8575, 857504 (2013).
[Crossref]

A. Osdoit, F. Lacombe, C. Cavé, S. Loiseau, and E. Peltier, “To see the unseeable: Confocal miniprobes for routine microscopic imaging during endoscopy,” Proc. SPIE 6432, 64320F (2007).
[Crossref]

Lee, J.

Levenson, R. M.

J. T. C. Liu, N. O. Loewke, M. J. Mandella, R. M. Levenson, and C. Group, “Review article: Modern trends in imaging ii point-of-care pathology with miniature microscopes,” Pathology 34, 81–98 (2011).

Liang, C.

Lim, D.

T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence hilo endomicroscopy,” J. Biomed. Opt. 17(2), 021105 (2012).
[Crossref] [PubMed]

Linard, N.

T. Vercauteren, F. Doussoux, M. Cazaux, G. Schmid, N. Linard, M.-A. Durin, H. Gharbi, and F. Lacombe, “Multicolor probe-based confocal laser endomicroscopy: A new world for in vivo and real-time cellular imaging,” Proc. SPIE 8575, 857504 (2013).
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H. Makhlouf, A. F. Gmitro, A. A. Tanbakuchi, J. A. Udovich, and A. R. Rouse, “Multispectral confocal microendoscope for in vivo and in situ imaging,” J. Biomed. Opt. 13(4), 044016 (2008).
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R. Singh, S. L. Chen Yi Mei, W. Tam, D. Raju, and A. Ruszkiewicz, “Real-time histology with the endocytoscope,” World J. Gastroenterol. 16(40), 5016–5019 (2010).
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J. M. Jabbour, M. A. Saldua, J. N. Bixler, and K. C. Maitland, “Confocal endomicroscopy: Instrumentation and medical applications,” Ann. Biomed. Eng. 40(2), 378–397 (2012).
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H. Neumann, F. S. Fuchs, M. Vieth, R. Atreya, J. Siebler, R. Kiesslich, and M. F. Neurath, “Review article: In vivo imaging by endocytoscopy,” Aliment. Pharmacol. Ther. 33(11), 1183–1193 (2011).
[Crossref] [PubMed]

Singh, R.

R. Singh, S. L. Chen Yi Mei, W. Tam, D. Raju, and A. Ruszkiewicz, “Real-time histology with the endocytoscope,” World J. Gastroenterol. 16(40), 5016–5019 (2010).
[Crossref] [PubMed]

Skinner, S. A.

A. L. Polglase, W. J. McLaren, S. A. Skinner, R. Kiesslich, M. F. Neurath, and P. M. Delaney, “A fluorescence confocal endomicroscope for in vivo microscopy of the upper- and the lower-gi tract,” Gastrointest. Endosc. 62(5), 686–695 (2005).
[Crossref] [PubMed]

Southern, J. F.

G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppart, C. Pitris, J. F. Southern, and J. G. Fujimoto, “In vivo endoscopic optical biopsy with optical coherence tomography,” Science 276(5321), 2037–2039 (1997).
[Crossref] [PubMed]

Sridharan, G.

G. Sridharan and A. A. Shankar, “Toluidine blue: A review of its chemistry and clinical utility,” J Oral Maxillofac Pathol 16(2), 251–255 (2012).
[Crossref] [PubMed]

Sung, K. B.

Suzuki, R.

R. Regunathan, J. Woo, M. C. Pierce, A. D. Polydorides, M. Raoufi, S. Roayaie, M. Schwartz, D. Labow, D. Shin, R. Suzuki, M. S. Bhutani, L. G. Coghlan, R. Richards-Kortum, S. Anandasabapathy, and M. K. Kim, “Feasibility and preliminary accuracy of high-resolution imaging of the liver and pancreas using fna compatible microendoscopy (with video),” Gastrointest. Endosc. 76(2), 293–300 (2012).
[Crossref] [PubMed]

Szeto, C.

C. Szeto, B. Wehrli, F. Whelan, J. Franklin, A. Nichols, J. Yoo, and K. Fung, “Contact endoscopy as a novel technique in the detection and diagnosis of mucosal lesions in the head and neck: A brief review,” J. Oncol. 2011, 196302 (2011).
[Crossref] [PubMed]

Tada, M.

M. Tada, S. Nishimura, and Y. Watanabe, “A new method for the ultra-magnifying observation of the colon mucosa,” Kyoto Pref. Univ. Med. 91, 349–354 (1982).

Takubo, K.

S. Kodashima, M. Fujishiro, K. Takubo, M. Kammori, S. Nomura, N. Kakushima, Y. Muraki, A. Tateishi, M. Kaminishi, and M. Omata, “Ex-vivo study of high-magnification chromoendoscopy in the gastrointestinal tract to determine the optimal staining conditions for endocytoscopy,” Endoscopy 38(11), 1115–1121 (2006).
[Crossref] [PubMed]

Tam, W.

R. Singh, S. L. Chen Yi Mei, W. Tam, D. Raju, and A. Ruszkiewicz, “Real-time histology with the endocytoscope,” World J. Gastroenterol. 16(40), 5016–5019 (2010).
[Crossref] [PubMed]

Tanbakuchi, A. A.

H. Makhlouf, A. F. Gmitro, A. A. Tanbakuchi, J. A. Udovich, and A. R. Rouse, “Multispectral confocal microendoscope for in vivo and in situ imaging,” J. Biomed. Opt. 13(4), 044016 (2008).
[Crossref] [PubMed]

Tank, D. W.

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, “A miniature head-mounted two-photon microscope. High-resolution brain imaging in freely moving animals,” Neuron 31(6), 903–912 (2001).
[Crossref] [PubMed]

Tateishi, A.

S. Kodashima, M. Fujishiro, K. Takubo, M. Kammori, S. Nomura, N. Kakushima, Y. Muraki, A. Tateishi, M. Kaminishi, and M. Omata, “Ex-vivo study of high-magnification chromoendoscopy in the gastrointestinal tract to determine the optimal staining conditions for endocytoscopy,” Endoscopy 38(11), 1115–1121 (2006).
[Crossref] [PubMed]

Tearney, G. J.

G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppart, C. Pitris, J. F. Southern, and J. G. Fujimoto, “In vivo endoscopic optical biopsy with optical coherence tomography,” Science 276(5321), 2037–2039 (1997).
[Crossref] [PubMed]

Tkaczyk, T. S.

Toermer, T.

M. Goetz, T. Toermer, M. Vieth, K. Dunbar, A. Hoffman, P. R. Galle, M. F. Neurath, P. Delaney, and R. Kiesslich, “Simultaneous confocal laser endomicroscopy and chromoendoscopy with topical cresyl violet,” Gastrointest. Endosc. 70(5), 959–968 (2009).
[Crossref] [PubMed]

Udovich, J. A.

H. Makhlouf, A. F. Gmitro, A. A. Tanbakuchi, J. A. Udovich, and A. R. Rouse, “Multispectral confocal microendoscope for in vivo and in situ imaging,” J. Biomed. Opt. 13(4), 044016 (2008).
[Crossref] [PubMed]

Ventalon, C.

Vercauteren, T.

T. Vercauteren, F. Doussoux, M. Cazaux, G. Schmid, N. Linard, M.-A. Durin, H. Gharbi, and F. Lacombe, “Multicolor probe-based confocal laser endomicroscopy: A new world for in vivo and real-time cellular imaging,” Proc. SPIE 8575, 857504 (2013).
[Crossref]

Viellerobe, B.

G. L. Goualher, A. Perchant, M. Genet, C. Cav, B. Viellerobe, B. Abrat, and N. Ayache, “Towards optical biopsies with an integrated fibered confocal fluorescence microscope,” MICCAI 2004, 761–768 (2004).

Vieth, M.

H. Neumann, R. Atreya, M. Vieth, and M. F. Neurath, “Toluidine blue is as effective as methylene blue for endocytoscopy,” Gastrointest. Endosc. 75(4), 479 (2012).
[Crossref]

H. Neumann, M. Vieth, M. F. Neurath, and F. S. Fuchs, “In vivo diagnosis of small-cell lung cancer by endocytoscopy,” J. Clin. Oncol. 29(6), e131–e132 (2011).
[Crossref] [PubMed]

H. Neumann, F. S. Fuchs, M. Vieth, R. Atreya, J. Siebler, R. Kiesslich, and M. F. Neurath, “Review article: In vivo imaging by endocytoscopy,” Aliment. Pharmacol. Ther. 33(11), 1183–1193 (2011).
[Crossref] [PubMed]

M. Goetz, T. Toermer, M. Vieth, K. Dunbar, A. Hoffman, P. R. Galle, M. F. Neurath, P. Delaney, and R. Kiesslich, “Simultaneous confocal laser endomicroscopy and chromoendoscopy with topical cresyl violet,” Gastrointest. Endosc. 70(5), 959–968 (2009).
[Crossref] [PubMed]

Vila, P. M.

M. C. Pierce, P. M. Vila, A. D. Polydorides, R. Richards-Kortum, and S. Anandasabapathy, “Low-cost endomicroscopy in the esophagus and colon,” Am. J. Gastroenterol. 106(9), 1722–1724 (2011).
[Crossref] [PubMed]

Watanabe, Y.

M. Tada, S. Nishimura, and Y. Watanabe, “A new method for the ultra-magnifying observation of the colon mucosa,” Kyoto Pref. Univ. Med. 91, 349–354 (1982).

Wehrli, B.

C. Szeto, B. Wehrli, F. Whelan, J. Franklin, A. Nichols, J. Yoo, and K. Fung, “Contact endoscopy as a novel technique in the detection and diagnosis of mucosal lesions in the head and neck: A brief review,” J. Oncol. 2011, 196302 (2011).
[Crossref] [PubMed]

Whelan, F.

C. Szeto, B. Wehrli, F. Whelan, J. Franklin, A. Nichols, J. Yoo, and K. Fung, “Contact endoscopy as a novel technique in the detection and diagnosis of mucosal lesions in the head and neck: A brief review,” J. Oncol. 2011, 196302 (2011).
[Crossref] [PubMed]

Wiedenmann, B.

H. Pohl, M. Koch, A. Khalifa, I. S. Papanikolaou, B. Wiedenmann, and T. Roesch, “Evaluation of an endocytoscopy system in the surveillance of patients with barrett esophagus,” Gastrointest. Endosc. 63(5), AB239 (2006).
[Crossref]

Woo, J.

R. Regunathan, J. Woo, M. C. Pierce, A. D. Polydorides, M. Raoufi, S. Roayaie, M. Schwartz, D. Labow, D. Shin, R. Suzuki, M. S. Bhutani, L. G. Coghlan, R. Richards-Kortum, S. Anandasabapathy, and M. K. Kim, “Feasibility and preliminary accuracy of high-resolution imaging of the liver and pancreas using fna compatible microendoscopy (with video),” Gastrointest. Endosc. 76(2), 293–300 (2012).
[Crossref] [PubMed]

Yang, G.-Z.

R. C. Newton, S. V. Kemp, P. L. Shah, D. Elson, A. Darzi, K. Shibuya, S. Mulgrew, and G.-Z. Yang, “Progress toward optical biopsy: Bringing the microscope to the patient,” Lung 189(2), 111–119 (2011).
[Crossref] [PubMed]

Yokoyama, A.

H. Minami, H. Inoue, A. Yokoyama, H. Ikeda, H. Satodate, S. Hamatani, A. Haji, and S. Kudo, “Recent advancement of observing living cells in the esophagus using cm double staining: Endocytoscopic atypia classification,” Dis. Esophagus 25(3), 235–241 (2012).
[Crossref] [PubMed]

H. Inoue, A. Yokoyama, and S. E. Kudo, “Ultrahigh magnifying endoscopy: Development of cm double staining for endocytoscopy and its safety,” Nippon Rinsho 68(7), 1247–1252 (2010).
[PubMed]

Yoo, J.

C. Szeto, B. Wehrli, F. Whelan, J. Franklin, A. Nichols, J. Yoo, and K. Fung, “Contact endoscopy as a novel technique in the detection and diagnosis of mucosal lesions in the head and neck: A brief review,” J. Oncol. 2011, 196302 (2011).
[Crossref] [PubMed]

Zysk, A. M.

A. M. Zysk, F. T. Nguyen, A. L. Oldenburg, D. L. Marks, and S. A. Boppart, “Optical coherence tomography: A review of clinical development from bench to bedside,” J. Biomed. Opt. 12(5), 051403 (2007).
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Acta Endoscopica (1)

J. Hamou, “Microhysteroscopy — A new technique in endoscopy and its applications,” Acta Endoscopica 10(5-6), 415–422 (1980).
[Crossref]

Aliment. Pharmacol. Ther. (1)

H. Neumann, F. S. Fuchs, M. Vieth, R. Atreya, J. Siebler, R. Kiesslich, and M. F. Neurath, “Review article: In vivo imaging by endocytoscopy,” Aliment. Pharmacol. Ther. 33(11), 1183–1193 (2011).
[Crossref] [PubMed]

Am. J. Gastroenterol. (1)

M. C. Pierce, P. M. Vila, A. D. Polydorides, R. Richards-Kortum, and S. Anandasabapathy, “Low-cost endomicroscopy in the esophagus and colon,” Am. J. Gastroenterol. 106(9), 1722–1724 (2011).
[Crossref] [PubMed]

Ann. Biomed. Eng. (1)

J. M. Jabbour, M. A. Saldua, J. N. Bixler, and K. C. Maitland, “Confocal endomicroscopy: Instrumentation and medical applications,” Ann. Biomed. Eng. 40(2), 378–397 (2012).
[PubMed]

Biomed. Opt. Express (1)

Dis. Esophagus (1)

H. Minami, H. Inoue, A. Yokoyama, H. Ikeda, H. Satodate, S. Hamatani, A. Haji, and S. Kudo, “Recent advancement of observing living cells in the esophagus using cm double staining: Endocytoscopic atypia classification,” Dis. Esophagus 25(3), 235–241 (2012).
[Crossref] [PubMed]

Endoscopy (3)

K. Chang, “Eus-guided needle-based confocal laser induced endomicroscopy (ncle): A correlation study of “through the needle” imaging with normal histology in a porcine model,” Endoscopy 43(S 03), A14 (2011).
[Crossref]

G. V. Rao, R. Pradeep, M. J. Mansard, C. Ramji, R. Banerjee, and D. Nageshwar Reddy, “Endocytoscopy assists in the intraoperative diagnosis of carcinoma in a patient with chronic pancreatitis,” Endoscopy 39(S1Suppl 1), E317–E318 (2007).
[Crossref] [PubMed]

S. Kodashima, M. Fujishiro, K. Takubo, M. Kammori, S. Nomura, N. Kakushima, Y. Muraki, A. Tateishi, M. Kaminishi, and M. Omata, “Ex-vivo study of high-magnification chromoendoscopy in the gastrointestinal tract to determine the optimal staining conditions for endocytoscopy,” Endoscopy 38(11), 1115–1121 (2006).
[Crossref] [PubMed]

Eur. J. Surg. Oncol. (1)

O. Riedl, F. Fitzal, N. Mader, P. Dubsky, M. Rudas, M. Mittlboeck, M. Gnant, and R. Jakesz, “Intraoperative frozen section analysis for breast-conserving therapy in 1016 patients with breast cancer,” Eur. J. Surg. Oncol. 35(3), 264–270 (2009).
[Crossref] [PubMed]

Gastrointest. Endosc. (7)

A. L. Polglase, W. J. McLaren, S. A. Skinner, R. Kiesslich, M. F. Neurath, and P. M. Delaney, “A fluorescence confocal endomicroscope for in vivo microscopy of the upper- and the lower-gi tract,” Gastrointest. Endosc. 62(5), 686–695 (2005).
[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]

M. Goetz, T. Toermer, M. Vieth, K. Dunbar, A. Hoffman, P. R. Galle, M. F. Neurath, P. Delaney, and R. Kiesslich, “Simultaneous confocal laser endomicroscopy and chromoendoscopy with topical cresyl violet,” Gastrointest. Endosc. 70(5), 959–968 (2009).
[Crossref] [PubMed]

H. Neumann, R. Atreya, M. Vieth, and M. F. Neurath, “Toluidine blue is as effective as methylene blue for endocytoscopy,” Gastrointest. Endosc. 75(4), 479 (2012).
[Crossref]

E. Dekker, M. Kara, J. Offerhaus, and P. Fockens, “Endocytoscopy in the colon: Early experience with a new real-time contact microscopy system,” Gastrointest. Endosc. 61(5), AB224 (2005).
[Crossref]

H. Pohl, M. Koch, A. Khalifa, I. S. Papanikolaou, B. Wiedenmann, and T. Roesch, “Evaluation of an endocytoscopy system in the surveillance of patients with barrett esophagus,” Gastrointest. Endosc. 63(5), AB239 (2006).
[Crossref]

R. Regunathan, J. Woo, M. C. Pierce, A. D. Polydorides, M. Raoufi, S. Roayaie, M. Schwartz, D. Labow, D. Shin, R. Suzuki, M. S. Bhutani, L. G. Coghlan, R. Richards-Kortum, S. Anandasabapathy, and M. K. Kim, “Feasibility and preliminary accuracy of high-resolution imaging of the liver and pancreas using fna compatible microendoscopy (with video),” Gastrointest. Endosc. 76(2), 293–300 (2012).
[Crossref] [PubMed]

J Oral Maxillofac Pathol (1)

G. Sridharan and A. A. Shankar, “Toluidine blue: A review of its chemistry and clinical utility,” J Oral Maxillofac Pathol 16(2), 251–255 (2012).
[Crossref] [PubMed]

J. Biomed. Opt. (4)

A. M. Zysk, F. T. Nguyen, A. L. Oldenburg, D. L. Marks, and S. A. Boppart, “Optical coherence tomography: A review of clinical development from bench to bedside,” J. Biomed. Opt. 12(5), 051403 (2007).
[Crossref] [PubMed]

T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence hilo endomicroscopy,” J. Biomed. Opt. 17(2), 021105 (2012).
[Crossref] [PubMed]

X. Liu, Y. Huang, and J. U. Kang, “Dark-field illuminated reflectance fiber bundle endoscopic microscope,” J. Biomed. Opt. 16(4), 046003 (2011).
[Crossref] [PubMed]

H. Makhlouf, A. F. Gmitro, A. A. Tanbakuchi, J. A. Udovich, and A. R. Rouse, “Multispectral confocal microendoscope for in vivo and in situ imaging,” J. Biomed. Opt. 13(4), 044016 (2008).
[Crossref] [PubMed]

J. Clin. Oncol. (1)

H. Neumann, M. Vieth, M. F. Neurath, and F. S. Fuchs, “In vivo diagnosis of small-cell lung cancer by endocytoscopy,” J. Clin. Oncol. 29(6), e131–e132 (2011).
[Crossref] [PubMed]

J. Endourol. (2)

T. Ohigashi, N. Kozakai, R. Mizuno, A. Miyajima, and M. Murai, “Endocytoscopy: Novel endoscopic imaging technology for in-situ observation of bladder cancer cells,” J. Endourol. 20(9), 698–701 (2006).
[Crossref] [PubMed]

T. Ohigashi, N. Kozakai, R. Mizuno, A. Miyajima, and M. Murai, “Endocytoscopy: Novel endoscopic imaging technology for in-situ observation of bladder cancer cells,” J. Endourol. 20(9), 698–701 (2006).
[Crossref] [PubMed]

J. Oncol. (1)

C. Szeto, B. Wehrli, F. Whelan, J. Franklin, A. Nichols, J. Yoo, and K. Fung, “Contact endoscopy as a novel technique in the detection and diagnosis of mucosal lesions in the head and neck: A brief review,” J. Oncol. 2011, 196302 (2011).
[Crossref] [PubMed]

Kyoto Pref. Univ. Med. (1)

M. Tada, S. Nishimura, and Y. Watanabe, “A new method for the ultra-magnifying observation of the colon mucosa,” Kyoto Pref. Univ. Med. 91, 349–354 (1982).

Lung (1)

R. C. Newton, S. V. Kemp, P. L. Shah, D. Elson, A. Darzi, K. Shibuya, S. Mulgrew, and G.-Z. Yang, “Progress toward optical biopsy: Bringing the microscope to the patient,” Lung 189(2), 111–119 (2011).
[Crossref] [PubMed]

MICCAI (1)

G. L. Goualher, A. Perchant, M. Genet, C. Cav, B. Viellerobe, B. Abrat, and N. Ayache, “Towards optical biopsies with an integrated fibered confocal fluorescence microscope,” MICCAI 2004, 761–768 (2004).

Nat. Clin. Pract. Gastroenterol. Hepatol. (1)

H. Inoue, S. E. Kudo, and A. Shiokawa, “Technology insight: Laser-scanning confocal microscopy and endocytoscopy for cellular observation of the gastrointestinal tract,” Nat. Clin. Pract. Gastroenterol. Hepatol. 2(1), 31–37 (2005).
[Crossref] [PubMed]

Neuron (1)

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, “A miniature head-mounted two-photon microscope. High-resolution brain imaging in freely moving animals,” Neuron 31(6), 903–912 (2001).
[Crossref] [PubMed]

Nippon Rinsho (1)

H. Inoue, A. Yokoyama, and S. E. Kudo, “Ultrahigh magnifying endoscopy: Development of cm double staining for endocytoscopy and its safety,” Nippon Rinsho 68(7), 1247–1252 (2010).
[PubMed]

Opt. Express (3)

Opt. Lett. (2)

Pathology (1)

J. T. C. Liu, N. O. Loewke, M. J. Mandella, R. M. Levenson, and C. Group, “Review article: Modern trends in imaging ii point-of-care pathology with miniature microscopes,” Pathology 34, 81–98 (2011).

Proc. SPIE (2)

A. Osdoit, F. Lacombe, C. Cavé, S. Loiseau, and E. Peltier, “To see the unseeable: Confocal miniprobes for routine microscopic imaging during endoscopy,” Proc. SPIE 6432, 64320F (2007).
[Crossref]

T. Vercauteren, F. Doussoux, M. Cazaux, G. Schmid, N. Linard, M.-A. Durin, H. Gharbi, and F. Lacombe, “Multicolor probe-based confocal laser endomicroscopy: A new world for in vivo and real-time cellular imaging,” Proc. SPIE 8575, 857504 (2013).
[Crossref]

Science (1)

G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppart, C. Pitris, J. F. Southern, and J. G. Fujimoto, “In vivo endoscopic optical biopsy with optical coherence tomography,” Science 276(5321), 2037–2039 (1997).
[Crossref] [PubMed]

World J Gastrointest Endosc (1)

R. Shukla, W. M. Abidi, R. Richards-Kortum, and S. Anandasabapathy, “Endoscopic imaging: How far are we from real-time histology?” World J Gastrointest Endosc 3(10), 183–194 (2011).
[Crossref] [PubMed]

World J. Gastroenterol. (1)

R. Singh, S. L. Chen Yi Mei, W. Tam, D. Raju, and A. Ruszkiewicz, “Real-time histology with the endocytoscope,” World J. Gastroenterol. 16(40), 5016–5019 (2010).
[Crossref] [PubMed]

Other (3)

G. L. Goualher, A. Perchant, M. Genet, C. Cav, B. Viellerobe, B. Abrat, and N. Ayache, “Towards optical biopsies with an integrated fibered confocal fluorescence microscope,” in MICCAI (2004), pp. 761–768.

P. Barlis and J. M. Schmitt, “Current and future developments in intracoronary optical coherence tomography imaging,” EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 4, 529 (2009).

N. Hasegawa, “Magnifying image pickup unit for an endoscope, an endoscope for in vivo cellular observation that uses it, and endoscopic, in vivo cellular observation methods,” US Patent 7267648 (2007).

Supplementary Material (1)

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Figures (9)

Fig. 1
Fig. 1

Stand-alone fiber-bundle endomicroscopy system. (a) Schematic of optics; (b) photograph of system and close-up view of high resolution probe. Abbreviations: MO: 4X microscope objective, LED: light emitting diode (warm white), MM: multimode.

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Fig. 2
Fig. 2

Hybrid endocytoscopy and endomicroscopy system. (a) Schematic of optical system; (b) timing diagram showing synchronization of galvanometer voltage (slow axis scan), laser modulation, camera trigger TTL and acquisition of endomicroscope and endocytoscope image frames. Note that that pulse lengths are illustrative and not precisely to scale, and that the pulse heights are arbitrary. Abbreviations: MM: multimode, Pol.: polarizing, LED: light emitting diode, MO: microscope objective, APD: avalanche photodiode, LPF: long pass wavelength filter, L1 & L3: achromatic doublet, f = 50 mm, L2: achromatic doublet, f = 75 mm.

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Fig. 3
Fig. 3

Lateral resolution and field-of-view of (a) high resolution and (b) low resolution probes, evaluated by imaging a USAF resolution target. The three color channels (red, green and blue) of the camera are shown individually and combined (white).

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Fig. 4
Fig. 4

Non uniformity of (a) low resolution and (b) high resolution probes. The scale shows the relative image intensity averaged across 400 frames when imaging porcine large bowel mucosa. The non-uniformity for the low resolution probe arises because of the location of the illumination fiber.

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Fig. 5
Fig. 5

Removal of fiber bundle core pattern. (a) Raw image of sponge stained with toluidine blue 0.25%, using the high resolution probe; (b) zoom on raw image showing honeycomb pattern of cores; (c,d,e) red, green and blue channels of image in (b), showing that cores can be resolved in each; (f) processed image following application of Gaussian filter; (g) zoom on processed image showing core pattern is no longer visible. Note that the brightness of the color channel images was adjusted for easier viewing. For presentation, the zoomed images were interpolated from 100x100 to 300x300 pixels by cubic interpolation.

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Fig. 6
Fig. 6

Ex vivo porcine tissue imaging results showing using high resolution probe (a,b) and low resolution probe (c,d). showing (a,c) large bowel mucosa, and (b,d) stomach mucosa. All samples were stained with toluidine blue 0.25% for approximately 2 minutes and washed before imaging. A selection of videos from the two tissue types are shown in Media 1. Scale bars are 50 µm.

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Fig. 7
Fig. 7

Axial sensitivity profile measurements for confocal channel. (a) Cross-sectional image of mirror using high resolution probe; (b) cross-sectional image of mirror using low resolution probe; (c) axial sensitivity profiles for high (blue) and low (red) resolution probes.

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Fig. 8
Fig. 8

Ex vivo porcine large bowel mucosa imaged using the combined endocytoscopy and fluorescence confocal endomicroscopy system, using the high resolution probe. The tissue was first stained with acriflavine hydrochloride 0.05% and imaged with the fluorescence channel (a) and subsequently stained with toluidine blue 0.25% and imaged with the endocytoscopy channel (b). Scale bars are 50 µm.

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Fig. 9
Fig. 9

Simultaneous fluorescence confocal endomicroscopy (a,c) and endocytoscopy (b,d). (a,b) Lens tissue paper stained with acriflavine hydrochloride 0.05%, imaged with high resolution probe; (b,d) porcine large bowel mucosa ex vivo stained with acriflavine hydrochloride 0.05% and toluidine blue 0.1%, imaged with high resolution probe; (e) merged fluorescence endomicroscopy and endocytoscopy images of large bowel mucosa with fluorescence shown in green. Scale bar is 50 µm

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