Abstract

White-light surveillance colonoscopy is the standard of care for the detection and removal of premalignant lesions to prevent colorectal cancer, and the main screening recommendation following treatment for recurrence detection. However, it lacks sufficient diagnostic yield, exhibits unacceptable adenoma miss-rates and is not capable of revealing functional and morphological information of the detected lesions. Fluorescence molecular guidance in the near-infrared (NIR) is expected to have outstanding relevance regarding early lesion detection and heterogeneity characterization within and among lesions in these interventional procedures. Thereby, superficial and sub-surface tissue biomarkers can be optimally visualized due to a minimization of tissue attenuation and autofluorescence by comparison with the visible, which simultaneously enhance tissue penetration and assure minimal background. At present, this potential is challenged by the difficulty associated with the clinical propagation of disease-specific contrast agents and the absence of a commercially available endoscope that is capable of acquiring wide-field, NIR fluorescence at video-rates. We propose two alternative flexible endoscopic fluorescence imaging methods, each based on a CE certified commercial, clinical grade endoscope, and the employment of an approved monoclonal antibody labeled with a clinically applicable NIR fluorophore. Pre-clinical validation of these two strategies that aim at bridging NIR fluorescence molecular guidance to clinical translation is demonstrated in this study.

© 2013 Optical Society of America

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  20. N. Thekkek, M. C. Pierce, M. H. Lee, A. D. Polydorides, R. M. Flores, S. Anandasabapathy, and R. R. Richards-Kortum, “Modular video endoscopy for in vivo cross-polarized and vital-dye fluorescence imaging of Barrett’s-associated neoplasia,” J. Biomed. Opt.18(2), 026007 (2013).
    [CrossRef] [PubMed]
  21. C. M. Lee, C. J. Engelbrecht, T. D. Soper, F. Helmchen, and E. J. Seibel, “Scanning fiber endoscopy with highly flexible, 1 mm catheterscopes for wide-field, full-color imaging,” J. Biophotonics3(5-6), 385–407 (2010).
    [CrossRef] [PubMed]
  22. S. J. Miller, C. M. Lee, B. P. Joshi, A. Gaustad, E. J. Seibel, and T. D. Wang, “Targeted detection of murine colonic dysplasia in vivo with flexible multispectral scanning fiber endoscopy,” J. Biomed. Opt.17(2), 021103 (2012).
    [CrossRef] [PubMed]
  23. J. Glatz, J. Varga, P. B. Garcia-Allende, M. Koch, F. R. Greten, and V. Ntziachristos, “Concurrent video-rate color and near-infrared fluorescence laparoscopy,” J. Biomed. Opt.18(10), 101302 (2013).
    [CrossRef] [PubMed]
  24. G. van Dam, G. Themelis, L. M. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescent imaging in ovarian cancer by folate receptor-α targeting,” Nat. Med.17, 1315–1319 (2011).
    [CrossRef] [PubMed]
  25. J. A. Udovich, N. D. Kirkpatrick, A. Kano, A. Tanbakuchi, U. Utzinger, and A. F. Gmitro, “Spectral background and transmission characteristics of fiber optic imaging bundles,” Appl. Opt.47(25), 4560–4568 (2008).
    [CrossRef] [PubMed]
  26. M. A. Funovics, R. Weissleder, and U. Mahmood, “Catheter-based in vivo imaging of enzyme activity and gene expression: feasibility study in mice,” Radiology231(3), 659–666 (2004).
    [CrossRef] [PubMed]
  27. R. J. Shah, D. G. Adler, J. D. Conway, D. L. Diehl, F. A. Farraye, S. V. Kantsevoy, R. Kwon, P. Mamula, S. Rodriguez, L. M. Wong Kee Song, W. M. Tierney, and ASGE Technology Committee, “Cholangiopancreatoscopy,” Gastrointest. Endosc.68(3), 411–421 (2008).
    [CrossRef] [PubMed]
  28. A. R. Rouse, A. Kano, J. A. Udovich, S. M. Kroto, and A. F. Gmitro, “Design and demonstration of a miniature catheter for a confocal microendoscope,” Appl. Opt.43(31), 5763–5771 (2004).
    [CrossRef] [PubMed]
  29. T. J. Muldoon, M. C. Pierce, D. L. Nida, M. D. Williams, A. Gillenwater, and R. Richards-Kortum, “Subcellular-resolution molecular imaging within living tissue by fiber microendoscopy,” J. Vasc. Res.41, 400–411 (2004).
    [PubMed]
  30. D. P. Noonan, D. S. Elson, G. P. Mylonas, A. Darzi, and G. Z. Yang, “Laser-induced fluorescence and reflected white light imaging for robot-assisted MIS,” IEEE Trans. Biomed. Eng.56(3), 889–892 (2009).
    [CrossRef] [PubMed]
  31. R. S. Bradley and M. S. Thorniley, “A review of attenuation correction techniques for tissue fluorescence,” J. R. Soc. Interface3(6), 1–13 (2006).
    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
  33. M. Raica, A. M. Cimpean, and D. Ribatti, “Angiogenesis in pre-malignant conditions,” Eur. J. Cancer45(11), 1924–1934 (2009).
    [CrossRef] [PubMed]
  34. A. J. McEwan, H. F. Van Brocklin, and C. Divgi, “Action plan for emerging molecular imaging technologies,” J. Nucl. Med.49(2), 37N–40N (2008).
    [PubMed]
  35. International Commission on Non-Ionizing Radiation Protection, “Revision of guidelines on limits of exposure to laser radiation of wavelengths between 400 nm and 1.4 µm,” Health Phys.79(4), 431–440 (2000).
    [CrossRef] [PubMed]
  36. P. B. Garcia-Allende, J. Glatz, M. Koch, and V. Ntziachristos, “Enriching the interventional vision of cancer with fluorescence and optoacoustic imaging,” J. Nucl. Med.54(5), 664–667 (2013).
    [CrossRef] [PubMed]

2013

E. M. Sevick-Muraca, W. J. Akers, B. P. Joshi, G. D. Luker, C. S. Cutler, L. J. Marnett, C. H. Contag, T. D. Wang, and A. Azhdarinia, “Advancing the translation of optical imaging agents for clinical imaging,” Biomed. Opt. Express4(1), 160–170 (2013).
[CrossRef] [PubMed]

Z. Liu, S. J. Miller, B. P. Joshi, and T. D. Wang, “In vivo targeting of colonic dysplasia on fluorescence endoscopy with near-infrared octapeptide,” Gut62(3), 395–403 (2013).
[CrossRef] [PubMed]

N. Thekkek, M. C. Pierce, M. H. Lee, A. D. Polydorides, R. M. Flores, S. Anandasabapathy, and R. R. Richards-Kortum, “Modular video endoscopy for in vivo cross-polarized and vital-dye fluorescence imaging of Barrett’s-associated neoplasia,” J. Biomed. Opt.18(2), 026007 (2013).
[CrossRef] [PubMed]

E. J. Blok, P. J. K. Kuppen, J. E. M. van Leeuwen, and C. F. M. Sier, “Cytoplasmic overexpression of HER2: a key factor in colorectal cancer,” Clin Med Insights Oncol7, 41–51 (2013).
[CrossRef] [PubMed]

M. Goetz, M. S. Hoetker, M. Diken, P. R. Galle, and R. Kiesslich, “In vivo molecular imaging with cetuximab, an anti-EGFR antibody, for prediction of response in xenograft models of human colorectal cancer,” Endoscopy45(6), 469–477 (2013).
[CrossRef] [PubMed]

J. Glatz, J. Varga, P. B. Garcia-Allende, M. Koch, F. R. Greten, and V. Ntziachristos, “Concurrent video-rate color and near-infrared fluorescence laparoscopy,” J. Biomed. Opt.18(10), 101302 (2013).
[CrossRef] [PubMed]

P. B. Garcia-Allende, J. Glatz, M. Koch, and V. Ntziachristos, “Enriching the interventional vision of cancer with fluorescence and optoacoustic imaging,” J. Nucl. Med.54(5), 664–667 (2013).
[CrossRef] [PubMed]

2012

W. Scheuer, G. M. van Dam, M. Dobosz, M. Schwaiger, and V. Ntziachristos, “Drug-based optical agents: Infiltrating clinics at lower risk,” Sci. Transl. Med.4, 134ps11 (2012).

S. J. Miller, C. M. Lee, B. P. Joshi, A. Gaustad, E. J. Seibel, and T. D. Wang, “Targeted detection of murine colonic dysplasia in vivo with flexible multispectral scanning fiber endoscopy,” J. Biomed. Opt.17(2), 021103 (2012).
[CrossRef] [PubMed]

P. A. Valdés, F. Leblond, V. L. Jacobs, B. C. Wilson, K. D. Paulsen, and D. W. Roberts, “Quantitative, spectrally-resolved intraoperative fluorescence imaging,” Sci Rep2, 798 (2012).
[CrossRef] [PubMed]

S. Misale, R. Yaeger, S. Hobor, E. Scala, M. Janakiraman, D. Liska, E. Valtorta, R. Schiavo, M. Buscarino, G. Siravegna, K. Bencardino, A. Cercek, C. T. Chen, S. Veronese, C. Zanon, A. Sartore-Bianchi, M. Gambacorta, M. Gallicchio, E. Vakiani, V. Boscaro, E. Medico, M. Weiser, S. Siena, F. Di Nicolantonio, D. Solit, and A. Bardelli, “Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer,” Nature486(7404), 532–536 (2012).
[PubMed]

R. Banerjee and D. N. Reddy, “Advances in endoscopic imaging: Advantages and limitations,” J. Dig. Endosc.3(5), 7–12 (2012).
[CrossRef]

2011

T. E. Goranova, M. Ohue, Y. Shimoharu, and K. Kato, “Dynamics of cancer cell subpopulations in primary and metastatic colorectal tumors,” Clin. Exp. Metastasis28(5), 427–435 (2011).
[CrossRef] [PubMed]

L. M. W. K. Song, S. Banerjee, D. Desilets, D. L. Diehl, F. A. Farraye, V. Kaul, S. R. Kethu, R. S. Kwon, P. Mamula, M. C. Pedrosa, S. A. Rodriguez, W. M. Tierney, and ASGE Technology Committee, “Autofluorescence imaging,” Gastrointest. Endosc.73(4), 647–650 (2011).
[CrossRef] [PubMed]

A. G. Terwisscha van Scheltinga, G. M. van Dam, W. B. Nagengast, V. Ntziachristos, H. Hollema, J. L. Herek, C. P. Schröder, J. G. Kosterink, M. N. Lub-de Hoog, and E. G. de Vries, “Intraoperative near-infrared fluorescence tumor imaging with vascular endothelial growth factor and human epidermal growth factor receptor 2 targeting antibodies,” J. Nucl. Med.52(11), 1778–1785 (2011).
[CrossRef] [PubMed]

G. van Dam, G. Themelis, L. M. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescent imaging in ovarian cancer by folate receptor-α targeting,” Nat. Med.17, 1315–1319 (2011).
[CrossRef] [PubMed]

2010

M. V. Marshall, D. Draney, E. M. Sevick-Muraca, and D. M. Olive, “Single-dose intravenous toxicity study of IRDye 800CW in Sprague-Dawley rats,” Mol. Imaging Biol.12(6), 583–594 (2010).
[CrossRef] [PubMed]

L. Herszényi and Z. Tulassay, “Epidemiology of gastrointestinal and liver tumors,” Eur. Rev. Med. Pharmacol. Sci.14(4), 249–258 (2010).
[PubMed]

C. M. Lee, C. J. Engelbrecht, T. D. Soper, F. Helmchen, and E. J. Seibel, “Scanning fiber endoscopy with highly flexible, 1 mm catheterscopes for wide-field, full-color imaging,” J. Biophotonics3(5-6), 385–407 (2010).
[CrossRef] [PubMed]

S. E. Baldus, K. L. Schaefer, R. Engers, D. Hartleb, N. H. Stoecklein, and H. E. Gabbert, “Prevalence and heterogeneity of KRAS, BRAF, and PIK3CA mutations in primary colorectal adenocarcinomas and their corresponding metastases,” Clin. Cancer Res.16(3), 790–799 (2010).
[CrossRef] [PubMed]

T. Ahmed, J. Monti, and B. Lashner, “Random versus targeted biopsies for colorectal cancer surveillance in inflammatory bowel disease,” Gastroenterol Hepatol (N Y)6(7), 438–442 (2010).
[PubMed]

S. A. Hilderbrand and R. Weissleder, “Near-infrared fluorescence: application to in vivo molecular imaging,” Curr. Opin. Chem. Biol.14(1), 71–79 (2010).
[CrossRef] [PubMed]

2009

M. Raica, A. M. Cimpean, and D. Ribatti, “Angiogenesis in pre-malignant conditions,” Eur. J. Cancer45(11), 1924–1934 (2009).
[CrossRef] [PubMed]

D. P. Noonan, D. S. Elson, G. P. Mylonas, A. Darzi, and G. Z. Yang, “Laser-induced fluorescence and reflected white light imaging for robot-assisted MIS,” IEEE Trans. Biomed. Eng.56(3), 889–892 (2009).
[CrossRef] [PubMed]

2008

R. J. Shah, D. G. Adler, J. D. Conway, D. L. Diehl, F. A. Farraye, S. V. Kantsevoy, R. Kwon, P. Mamula, S. Rodriguez, L. M. Wong Kee Song, W. M. Tierney, and ASGE Technology Committee, “Cholangiopancreatoscopy,” Gastrointest. Endosc.68(3), 411–421 (2008).
[CrossRef] [PubMed]

A. J. McEwan, H. F. Van Brocklin, and C. Divgi, “Action plan for emerging molecular imaging technologies,” J. Nucl. Med.49(2), 37N–40N (2008).
[PubMed]

J. A. Udovich, N. D. Kirkpatrick, A. Kano, A. Tanbakuchi, U. Utzinger, and A. F. Gmitro, “Spectral background and transmission characteristics of fiber optic imaging bundles,” Appl. Opt.47(25), 4560–4568 (2008).
[CrossRef] [PubMed]

P. L. Hsiung, J. Hardy, S. Friedland, R. Soetikno, C. B. Du, A. P. Wu, P. Sahbaie, J. M. Crawford, A. W. Lowe, C. H. Contag, and T. D. Wang, “Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy,” Nat. Med.14(4), 454–458 (2008).
[CrossRef] [PubMed]

E. M. Stoffel, D. K. Turgeon, D. H. Stockwell, L. Zhao, D. P. Normolle, M. K. Tuck, R. S. Bresalier, N. E. Marcon, J. A. Baron, M. T. Ruffin, D. E. Brenner, S. Syngal, and Great Lakes-New England Clinical Epidemiology and Validation Center of the Early Detection Research Network, “Missed adenomas during colonoscopic surveillance in individuals with Lynch syndrome (hereditary nonpolyposis colorectal cancer),” Cancer Prev. Res. (Phila.)1(6), 470–475 (2008).
[CrossRef] [PubMed]

L. M. W. K. Song, D. G. Adler, J. D. Conway, D. L. Diehl, F. A. Farraye, S. V. Kantsevoy, R. Kwon, P. Mamula, B. Rodriguez, R. J. Shah, W. M. Tierney, and ASGE Technology Committee, “Narrow band imaging and multiband imaging,” Gastrointest. Endosc.67(4), 581–589 (2008).
[CrossRef] [PubMed]

2007

L. M. Wong Kee Song, D. G. Adler, B. Chand, J. D. Conway, J. M. B. Croffie, J. A. Disario, D. S. Mishkin, R. J. Shah, L. Somogyi, W. M. Tierney, B. T. Petersen, and ASGE Technology Committee, “Chromoendoscopy,” Gastrointest. Endosc.66(4), 639–649 (2007).
[CrossRef] [PubMed]

2006

R. S. Bradley and M. S. Thorniley, “A review of attenuation correction techniques for tissue fluorescence,” J. R. Soc. Interface3(6), 1–13 (2006).
[CrossRef] [PubMed]

2004

A. R. Rouse, A. Kano, J. A. Udovich, S. M. Kroto, and A. F. Gmitro, “Design and demonstration of a miniature catheter for a confocal microendoscope,” Appl. Opt.43(31), 5763–5771 (2004).
[CrossRef] [PubMed]

T. J. Muldoon, M. C. Pierce, D. L. Nida, M. D. Williams, A. Gillenwater, and R. Richards-Kortum, “Subcellular-resolution molecular imaging within living tissue by fiber microendoscopy,” J. Vasc. Res.41, 400–411 (2004).
[PubMed]

M. A. Funovics, R. Weissleder, and U. Mahmood, “Catheter-based in vivo imaging of enzyme activity and gene expression: feasibility study in mice,” Radiology231(3), 659–666 (2004).
[CrossRef] [PubMed]

2000

International Commission on Non-Ionizing Radiation Protection, “Revision of guidelines on limits of exposure to laser radiation of wavelengths between 400 nm and 1.4 µm,” Health Phys.79(4), 431–440 (2000).
[CrossRef] [PubMed]

Adler, D. G.

L. M. W. K. Song, D. G. Adler, J. D. Conway, D. L. Diehl, F. A. Farraye, S. V. Kantsevoy, R. Kwon, P. Mamula, B. Rodriguez, R. J. Shah, W. M. Tierney, and ASGE Technology Committee, “Narrow band imaging and multiband imaging,” Gastrointest. Endosc.67(4), 581–589 (2008).
[CrossRef] [PubMed]

R. J. Shah, D. G. Adler, J. D. Conway, D. L. Diehl, F. A. Farraye, S. V. Kantsevoy, R. Kwon, P. Mamula, S. Rodriguez, L. M. Wong Kee Song, W. M. Tierney, and ASGE Technology Committee, “Cholangiopancreatoscopy,” Gastrointest. Endosc.68(3), 411–421 (2008).
[CrossRef] [PubMed]

L. M. Wong Kee Song, D. G. Adler, B. Chand, J. D. Conway, J. M. B. Croffie, J. A. Disario, D. S. Mishkin, R. J. Shah, L. Somogyi, W. M. Tierney, B. T. Petersen, and ASGE Technology Committee, “Chromoendoscopy,” Gastrointest. Endosc.66(4), 639–649 (2007).
[CrossRef] [PubMed]

Ahmed, T.

T. Ahmed, J. Monti, and B. Lashner, “Random versus targeted biopsies for colorectal cancer surveillance in inflammatory bowel disease,” Gastroenterol Hepatol (N Y)6(7), 438–442 (2010).
[PubMed]

Akers, W. J.

Anandasabapathy, S.

N. Thekkek, M. C. Pierce, M. H. Lee, A. D. Polydorides, R. M. Flores, S. Anandasabapathy, and R. R. Richards-Kortum, “Modular video endoscopy for in vivo cross-polarized and vital-dye fluorescence imaging of Barrett’s-associated neoplasia,” J. Biomed. Opt.18(2), 026007 (2013).
[CrossRef] [PubMed]

Azhdarinia, A.

Baldus, S. E.

S. E. Baldus, K. L. Schaefer, R. Engers, D. Hartleb, N. H. Stoecklein, and H. E. Gabbert, “Prevalence and heterogeneity of KRAS, BRAF, and PIK3CA mutations in primary colorectal adenocarcinomas and their corresponding metastases,” Clin. Cancer Res.16(3), 790–799 (2010).
[CrossRef] [PubMed]

Banerjee, R.

R. Banerjee and D. N. Reddy, “Advances in endoscopic imaging: Advantages and limitations,” J. Dig. Endosc.3(5), 7–12 (2012).
[CrossRef]

Banerjee, S.

L. M. W. K. Song, S. Banerjee, D. Desilets, D. L. Diehl, F. A. Farraye, V. Kaul, S. R. Kethu, R. S. Kwon, P. Mamula, M. C. Pedrosa, S. A. Rodriguez, W. M. Tierney, and ASGE Technology Committee, “Autofluorescence imaging,” Gastrointest. Endosc.73(4), 647–650 (2011).
[CrossRef] [PubMed]

Bardelli, A.

S. Misale, R. Yaeger, S. Hobor, E. Scala, M. Janakiraman, D. Liska, E. Valtorta, R. Schiavo, M. Buscarino, G. Siravegna, K. Bencardino, A. Cercek, C. T. Chen, S. Veronese, C. Zanon, A. Sartore-Bianchi, M. Gambacorta, M. Gallicchio, E. Vakiani, V. Boscaro, E. Medico, M. Weiser, S. Siena, F. Di Nicolantonio, D. Solit, and A. Bardelli, “Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer,” Nature486(7404), 532–536 (2012).
[PubMed]

Baron, J. A.

E. M. Stoffel, D. K. Turgeon, D. H. Stockwell, L. Zhao, D. P. Normolle, M. K. Tuck, R. S. Bresalier, N. E. Marcon, J. A. Baron, M. T. Ruffin, D. E. Brenner, S. Syngal, and Great Lakes-New England Clinical Epidemiology and Validation Center of the Early Detection Research Network, “Missed adenomas during colonoscopic surveillance in individuals with Lynch syndrome (hereditary nonpolyposis colorectal cancer),” Cancer Prev. Res. (Phila.)1(6), 470–475 (2008).
[CrossRef] [PubMed]

Bart, J.

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M. Goetz, M. S. Hoetker, M. Diken, P. R. Galle, and R. Kiesslich, “In vivo molecular imaging with cetuximab, an anti-EGFR antibody, for prediction of response in xenograft models of human colorectal cancer,” Endoscopy45(6), 469–477 (2013).
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L. M. W. K. Song, S. Banerjee, D. Desilets, D. L. Diehl, F. A. Farraye, V. Kaul, S. R. Kethu, R. S. Kwon, P. Mamula, M. C. Pedrosa, S. A. Rodriguez, W. M. Tierney, and ASGE Technology Committee, “Autofluorescence imaging,” Gastrointest. Endosc.73(4), 647–650 (2011).
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Z. Liu, S. J. Miller, B. P. Joshi, and T. D. Wang, “In vivo targeting of colonic dysplasia on fluorescence endoscopy with near-infrared octapeptide,” Gut62(3), 395–403 (2013).
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J. Glatz, J. Varga, P. B. Garcia-Allende, M. Koch, F. R. Greten, and V. Ntziachristos, “Concurrent video-rate color and near-infrared fluorescence laparoscopy,” J. Biomed. Opt.18(10), 101302 (2013).
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T. E. Goranova, M. Ohue, Y. Shimoharu, and K. Kato, “Dynamics of cancer cell subpopulations in primary and metastatic colorectal tumors,” Clin. Exp. Metastasis28(5), 427–435 (2011).
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M. V. Marshall, D. Draney, E. M. Sevick-Muraca, and D. M. Olive, “Single-dose intravenous toxicity study of IRDye 800CW in Sprague-Dawley rats,” Mol. Imaging Biol.12(6), 583–594 (2010).
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L. M. W. K. Song, S. Banerjee, D. Desilets, D. L. Diehl, F. A. Farraye, V. Kaul, S. R. Kethu, R. S. Kwon, P. Mamula, M. C. Pedrosa, S. A. Rodriguez, W. M. Tierney, and ASGE Technology Committee, “Autofluorescence imaging,” Gastrointest. Endosc.73(4), 647–650 (2011).
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L. M. Wong Kee Song, D. G. Adler, B. Chand, J. D. Conway, J. M. B. Croffie, J. A. Disario, D. S. Mishkin, R. J. Shah, L. Somogyi, W. M. Tierney, B. T. Petersen, and ASGE Technology Committee, “Chromoendoscopy,” Gastrointest. Endosc.66(4), 639–649 (2007).
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N. Thekkek, M. C. Pierce, M. H. Lee, A. D. Polydorides, R. M. Flores, S. Anandasabapathy, and R. R. Richards-Kortum, “Modular video endoscopy for in vivo cross-polarized and vital-dye fluorescence imaging of Barrett’s-associated neoplasia,” J. Biomed. Opt.18(2), 026007 (2013).
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[PubMed]

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G. van Dam, G. Themelis, L. M. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescent imaging in ovarian cancer by folate receptor-α targeting,” Nat. Med.17, 1315–1319 (2011).
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N. Thekkek, M. C. Pierce, M. H. Lee, A. D. Polydorides, R. M. Flores, S. Anandasabapathy, and R. R. Richards-Kortum, “Modular video endoscopy for in vivo cross-polarized and vital-dye fluorescence imaging of Barrett’s-associated neoplasia,” J. Biomed. Opt.18(2), 026007 (2013).
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T. J. Muldoon, M. C. Pierce, D. L. Nida, M. D. Williams, A. Gillenwater, and R. Richards-Kortum, “Subcellular-resolution molecular imaging within living tissue by fiber microendoscopy,” J. Vasc. Res.41, 400–411 (2004).
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N. Thekkek, M. C. Pierce, M. H. Lee, A. D. Polydorides, R. M. Flores, S. Anandasabapathy, and R. R. Richards-Kortum, “Modular video endoscopy for in vivo cross-polarized and vital-dye fluorescence imaging of Barrett’s-associated neoplasia,” J. Biomed. Opt.18(2), 026007 (2013).
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P. A. Valdés, F. Leblond, V. L. Jacobs, B. C. Wilson, K. D. Paulsen, and D. W. Roberts, “Quantitative, spectrally-resolved intraoperative fluorescence imaging,” Sci Rep2, 798 (2012).
[CrossRef] [PubMed]

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L. M. W. K. Song, D. G. Adler, J. D. Conway, D. L. Diehl, F. A. Farraye, S. V. Kantsevoy, R. Kwon, P. Mamula, B. Rodriguez, R. J. Shah, W. M. Tierney, and ASGE Technology Committee, “Narrow band imaging and multiband imaging,” Gastrointest. Endosc.67(4), 581–589 (2008).
[CrossRef] [PubMed]

Rodriguez, S.

R. J. Shah, D. G. Adler, J. D. Conway, D. L. Diehl, F. A. Farraye, S. V. Kantsevoy, R. Kwon, P. Mamula, S. Rodriguez, L. M. Wong Kee Song, W. M. Tierney, and ASGE Technology Committee, “Cholangiopancreatoscopy,” Gastrointest. Endosc.68(3), 411–421 (2008).
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L. M. W. K. Song, S. Banerjee, D. Desilets, D. L. Diehl, F. A. Farraye, V. Kaul, S. R. Kethu, R. S. Kwon, P. Mamula, M. C. Pedrosa, S. A. Rodriguez, W. M. Tierney, and ASGE Technology Committee, “Autofluorescence imaging,” Gastrointest. Endosc.73(4), 647–650 (2011).
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Ruffin, M. T.

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P. L. Hsiung, J. Hardy, S. Friedland, R. Soetikno, C. B. Du, A. P. Wu, P. Sahbaie, J. M. Crawford, A. W. Lowe, C. H. Contag, and T. D. Wang, “Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy,” Nat. Med.14(4), 454–458 (2008).
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W. Scheuer, G. M. van Dam, M. Dobosz, M. Schwaiger, and V. Ntziachristos, “Drug-based optical agents: Infiltrating clinics at lower risk,” Sci. Transl. Med.4, 134ps11 (2012).

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Figures (5)

Fig. 1
Fig. 1

Schematic of the two imaging platforms proposed for NIR fluorescence guidance in surveillance colonoscopy; (a) shows the adaption of the clinical grade gastrointestinal fiberscope, while the alternative based on the semi-disposable imaging fiber bundle that can be integrated with conventional videocolonoscopes is shown in (b).

Fig. 2
Fig. 2

(a) Detail of the USAF 1951 resolution target image. Contrast transfer functions obtained by determining the specific contrast produced by bar group patterns of various spatial frequencies taken by the endoscopic imaging platforms based on a clinical grade fiberscope (b) and on the miniature cholangioscope (c).

Fig. 3
Fig. 3

Signal-to-noise ratio over concentration measured from the CW800 dilution series by the endoscopic imaging platforms based on a clinical grade fiberscope (a) and on the miniature cholangioscope (b), both under video-rate constraints (100 ms exposure time).

Fig. 4
Fig. 4

Comparison of the visualization of a subcutaneous tumor with the proposed imaging platforms; Color images under white-light illumination, fluorescence and color with superimposed fluorescence acquired with the adapted fiberscope for gastrointestinal endoscopy ((a) to (c)) and the miniature cholangioscope ((d) to (f)); (g) H&E stained tissue slide preserved from the subcutaneous tumor; Scale bar 1 mm (h) Detail of H&E staining (20x); Scale bar 50 µm.

Fig. 5
Fig. 5

Representative images that showcase the characterization of the HER2 expression in the inoculated subcutaneous tumor in 2-6 cm upfront in the bowel with an insufflation-dependent diameter; color images ((a), (d), and (g)), fluorescence ((b), (e), and (h)), and color with superimposed fluorescence ((c), (f), and (i)) were acquired with the adapted fiberscope for gastrointestinal endoscopy at 2, 4 and 6 cm distances, respectively; (j) H&E stained tissue slide preserved from the subcutaneous tumor; Scale bar 1 mm; (k) Detail of H&E staining (20x); Scale bar 50 µm.

Tables (1)

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Table 1 Technical specifications of the two clinical grade scopes employed in the wide-field, concurrent, video-rate color and NIR fluorescence imaging platform for flexible endoscopy

Equations (1)

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