Abstract

Early detection and surveillance of disease progression in epithelial tissue is key to improving long term patient outcomes for colon and esophageal cancers, which account for nearly a quarter of cancer related mortalities worldwide. Spatially resolved diffuse reflectance spectroscopy (SRDRS) is a non-invasive optical technique to sense biological changes at the cellular and sub-cellular level that occur when normal tissue becomes diseased, and has the potential to significantly improve the current standard of care for endoscopic gastrointestinal (GI) screening. Herein the design, fabrication, and characterization of the first custom SRDRS device to enable endoscopic SRDRS GI tissue characterization using a custom silicon (Si) thin film multi-pixel endoscopic optical sensor (MEOS) is described.

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

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References

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2017 (2)

M. F. Byrne, N. Shahidi, and D. K. Rex, “Will computer-aided detection and diagnosis revolutionize colonoscopy?” Gastroenterology 153(6), 1460–1464 (2017).
[Crossref] [PubMed]

D. M. Miller and N. M. Jokerst, “Flexible silicon sensors for diffuse reflectance spectroscopy of tissue,” Biomed. Opt. Express 8(3), 1512–1524 (2017).
[Crossref] [PubMed]

2016 (3)

O. Senlik and N. M. Jokerst, “Concentric Multipixel Silicon Photodiode Array Probes for Spatially Resolved Diffuse Reflectance Spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 22(3), 7–12 (2016).
[Crossref]

O. Senlik, G. Greening, T. J. Muldoon, and N. M. Jokerst, “Spatially resolved diffuse reflectance spectroscopy of two-layer turbid media using a densely packed multi-pixel photodiode probe,” Proc. SPIE 9700, 97000O (2016).
[Crossref]

G. J. Greening, H. M. James, M. K. Dierks, N. Vongkittiargorn, S. M. Osterholm, N. Rajaram, and T. J. Muldoon, “Towards monitoring dysplastic progression in the oral cavity using a hybrid fiber-bundle imaging and spectroscopy probe,” Sci. Rep. 6(1), 26734 (2016).
[Crossref] [PubMed]

2015 (2)

S. Pimenta, E. M. S. Castanheira, and G. Minas, “Optical Microsystem for Analysis of Diffuse Reflectance and Fluorescence Signals Applied to Early Gastrointestinal Cancer Detection,” Sensors (Basel) 15(12), 3138–3153 (2015).
[Crossref] [PubMed]

E. Rodriguez-Diaz, Q. Huang, S. R. Cerda, M. J. O’Brien, I. J. Bigio, and S. K. Singh, “Endoscopic histological assessment of colonic polyps by using elastic scattering spectroscopy,” Gastrointest. Endosc. 81(3), 539–547 (2015).
[Crossref] [PubMed]

2014 (3)

K.-B. Sung, K.-W. Shih, F.-W. Hsu, H.-P. Hsieh, M.-J. Chuang, Y.-H. Hsiao, Y.-H. Su, and G.-H. Tien, “Accurate extraction of optical properties and top layer thickness of two-layered mucosal tissue phantoms from spatially resolved reflectance spectra,” J. Biomed. Opt. 19(7), 77002 (2014).
[Crossref] [PubMed]

S. Dhar, D. M. Miller, and N. M. Jokerst, “High responsivity, low dark current, heterogeneously integrated thin film Si photodetectors on rigid and flexible substrates,” Opt. Express 22(5), 5052–5059 (2014).
[Crossref] [PubMed]

R. Hennessy, W. Goth, M. Sharma, M. K. Markey, and J. W. Tunnell, “Effect of probe geometry and optical properties on the sampling depth for diffuse reflectance spectroscopy,” J. Biomed. Opt. 19(10), 107002 (2014).
[Crossref] [PubMed]

2013 (2)

D. J. Cappon, T. J. Farrell, Q. Fang, and J. E. Hayward, “Fiber-optic probe design and optical property recovery algorithm for optical biopsy of brain tissue,” J. Biomed. Opt. 18(10), 107004 (2013).
[Crossref] [PubMed]

S. L. Jacques, “Optical properties of biological tissues: a review,” Phys. Med. Biol. 58(11), R37–R61 (2013).
[Crossref] [PubMed]

2011 (5)

D. S. Ferreira, V. C. Pinto, J. H. Correia, and G. Minas, “Spectroscopic Detection of Gastrointestinal Dysplasia Using Optical Microsensors,” IEEE Trans. Biomed. Eng. 58(9), 2633–2639 (2011).
[Crossref] [PubMed]

D. K. Rex, C. Kahi, M. O’Brien, T. R. Levin, H. Pohl, A. Rastogi, L. Burgart, T. Imperiale, U. Ladabaum, J. Cohen, and D. A. Lieberman, “The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) on real-time endoscopic assessment of the histology of diminutive colorectal polyps,” Gastrointest. Endosc. 73(3), 419–422 (2011).
[Crossref] [PubMed]

B. Yu, H. L. Fu, and N. Ramanujam, “Instrument independent diffuse reflectance spectroscopy,” J. Biomed. Opt. 16(1), 011010 (2011).
[Crossref] [PubMed]

E. Rodriguez-Diaz, I. J. Bigio, and S. K. Singh, “Integrated optical tools for minimally invasive diagnosis and treatment at gastrointestinal endoscopy,” Robot. Comput.-Integr. Manuf. 27(2), 249–256 (2011).
[Crossref] [PubMed]

Y. Zhu, N. G. Terry, J. T. Woosley, N. J. Shaheen, and A. Wax, “Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology,” J. Biomed. Opt. 16(1), 011003 (2011).
[Crossref] [PubMed]

2010 (2)

N. Rajaram, A. Gopal, X. Zhang, and J. W. Tunnell, “Experimental validation of the effects of microvasculature pigment packaging on in vivo diffuse reflectance spectroscopy,” Lasers Surg. Med. 42(7), 680–688 (2010).
[Crossref] [PubMed]

T. M. Bydlon, S. A. Kennedy, L. M. Richards, J. Q. Brown, B. Yu, M. K. Junker, J. Gallagher, J. Geradts, L. G. Wilke, and N. Ramanujam, “Performance metrics of an optical spectral imaging system for intra-operative assessment of breast tumor margins,” Opt. Express 18(8), 8058–8076 (2010).
[Crossref] [PubMed]

2009 (3)

2007 (1)

2006 (3)

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, “Diagnosis of breast cancer using diffuse reflectance spectroscopy: Comparison of a Monte Carlo versus partial least squares analysis based feature extraction technique,” Lasers Surg. Med. 38(7), 714–724 (2006).
[Crossref] [PubMed]

A. Dhar, K. S. Johnson, M. R. Novelli, S. G. Bown, I. J. Bigio, L. B. Lovat, and S. L. Bloom, “Elastic scattering spectroscopy for the diagnosis of colonic lesions: Initial results of a novel optical biopsy technique,” Gastrointest. Endosc. 63(2), 257–261 (2006).
[Crossref] [PubMed]

G. M. Palmer and N. Ramanujam, “Monte Carlo-based inverse model for calculating tissue optical properties. Part I: Theory and validation on synthetic phantoms,” Appl. Opt. 45(5), 1062–1071 (2006).
[Crossref] [PubMed]

2005 (1)

C. Zhu, G. M. Palmer, T. M. Breslin, F. Xu, and N. Ramanujam, “Use of a multiseparation fiber optic probe for the optical diagnosis of breast cancer,” J. Biomed. Opt. 10(2), 024032 (2005).
[Crossref] [PubMed]

2004 (2)

2003 (2)

P. Thueler, I. Charvet, F. Bevilacqua, M. St Ghislain, G. Ory, P. Marquet, P. Meda, B. Vermeulen, and C. Depeursinge, “In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties,” J. Biomed. Opt. 8(3), 495–503 (2003).
[Crossref] [PubMed]

I. J. Bigio and J. R. Mourant, “Optical biopsy,” Encycl. Opt. Eng. 1577, 1593 (2003).

2001 (2)

I. Georgakoudi, B. C. Jacobson, J. Van Dam, V. Backman, M. B. Wallace, M. G. Müller, Q. Zhang, K. Badizadegan, D. Sun, G. A. Thomas, L. T. Perelman, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett’s esophagus,” Gastroenterology 120(7), 1620–1629 (2001).
[Crossref] [PubMed]

J. S. Dam, C. B. Pedersen, T. Dalgaard, P. E. Fabricius, P. Aruna, and S. Andersson-Engels, “Fiber-optic probe for noninvasive real-time determination of tissue optical properties at multiple wavelengths,” Appl. Opt. 40(7), 1155–1164 (2001).
[Crossref] [PubMed]

1999 (1)

1998 (1)

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]

1996 (2)

A. Kienle, L. Lilge, M. S. Patterson, R. Hibst, R. Steiner, and B. C. Wilson, “Spatially resolved absolute diffuse reflectance measurements for noninvasive determination of the optical scattering and absorption coefficients of biological tissue,” Appl. Opt. 35(13), 2304–2314 (1996).
[Crossref] [PubMed]

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. VanDam, J. M. Crawford, R. Manoharan, and M. S. Feld, “Morphological model of human colon tissue fluorescence (vol 43, pg 113, 1996),” IEEE Trans. Biomed. Eng. 43, 437 (1996).
[Crossref]

1992 (1)

T. J. Farrell, B. C. Wilson, and M. S. Patterson, “The use of a neural network to determine tissue optical properties from spatially resolved diffuse reflectance measurements,” Phys. Med. Biol. 37(12), 2281–2286 (1992).
[Crossref] [PubMed]

Andersson-Engels, S.

Arendt, J. T.

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. VanDam, J. M. Crawford, R. Manoharan, and M. S. Feld, “Morphological model of human colon tissue fluorescence (vol 43, pg 113, 1996),” IEEE Trans. Biomed. Eng. 43, 437 (1996).
[Crossref]

Aruna, P.

Backman, V.

I. Georgakoudi, B. C. Jacobson, J. Van Dam, V. Backman, M. B. Wallace, M. G. Müller, Q. Zhang, K. Badizadegan, D. Sun, G. A. Thomas, L. T. Perelman, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett’s esophagus,” Gastroenterology 120(7), 1620–1629 (2001).
[Crossref] [PubMed]

G. Zonios, L. T. Perelman, V. Backman, R. Manoharan, M. Fitzmaurice, J. Van Dam, and M. S. Feld, “Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo,” Appl. Opt. 38(31), 6628–6637 (1999).
[Crossref] [PubMed]

Badizadegan, K.

I. Georgakoudi, B. C. Jacobson, J. Van Dam, V. Backman, M. B. Wallace, M. G. Müller, Q. Zhang, K. Badizadegan, D. Sun, G. A. Thomas, L. T. Perelman, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett’s esophagus,” Gastroenterology 120(7), 1620–1629 (2001).
[Crossref] [PubMed]

Bender, J. E.

Bevilacqua, F.

P. Thueler, I. Charvet, F. Bevilacqua, M. St Ghislain, G. Ory, P. Marquet, P. Meda, B. Vermeulen, and C. Depeursinge, “In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties,” J. Biomed. Opt. 8(3), 495–503 (2003).
[Crossref] [PubMed]

Bigio, I. J.

E. Rodriguez-Diaz, Q. Huang, S. R. Cerda, M. J. O’Brien, I. J. Bigio, and S. K. Singh, “Endoscopic histological assessment of colonic polyps by using elastic scattering spectroscopy,” Gastrointest. Endosc. 81(3), 539–547 (2015).
[Crossref] [PubMed]

E. Rodriguez-Diaz, I. J. Bigio, and S. K. Singh, “Integrated optical tools for minimally invasive diagnosis and treatment at gastrointestinal endoscopy,” Robot. Comput.-Integr. Manuf. 27(2), 249–256 (2011).
[Crossref] [PubMed]

A. Dhar, K. S. Johnson, M. R. Novelli, S. G. Bown, I. J. Bigio, L. B. Lovat, and S. L. Bloom, “Elastic scattering spectroscopy for the diagnosis of colonic lesions: Initial results of a novel optical biopsy technique,” Gastrointest. Endosc. 63(2), 257–261 (2006).
[Crossref] [PubMed]

I. J. Bigio and J. R. Mourant, “Optical biopsy,” Encycl. Opt. Eng. 1577, 1593 (2003).

Bloom, S. L.

A. Dhar, K. S. Johnson, M. R. Novelli, S. G. Bown, I. J. Bigio, L. B. Lovat, and S. L. Bloom, “Elastic scattering spectroscopy for the diagnosis of colonic lesions: Initial results of a novel optical biopsy technique,” Gastrointest. Endosc. 63(2), 257–261 (2006).
[Crossref] [PubMed]

Boppart, S. A.

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]

Bouma, B. E.

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]

Bown, S. G.

A. Dhar, K. S. Johnson, M. R. Novelli, S. G. Bown, I. J. Bigio, L. B. Lovat, and S. L. Bloom, “Elastic scattering spectroscopy for the diagnosis of colonic lesions: Initial results of a novel optical biopsy technique,” Gastrointest. Endosc. 63(2), 257–261 (2006).
[Crossref] [PubMed]

Breslin, T. M.

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, “Diagnosis of breast cancer using diffuse reflectance spectroscopy: Comparison of a Monte Carlo versus partial least squares analysis based feature extraction technique,” Lasers Surg. Med. 38(7), 714–724 (2006).
[Crossref] [PubMed]

C. Zhu, G. M. Palmer, T. M. Breslin, F. Xu, and N. Ramanujam, “Use of a multiseparation fiber optic probe for the optical diagnosis of breast cancer,” J. Biomed. Opt. 10(2), 024032 (2005).
[Crossref] [PubMed]

Brezinski, M. E.

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]

Brightwell, A.

Brown, J. Q.

Burgart, L.

D. K. Rex, C. Kahi, M. O’Brien, T. R. Levin, H. Pohl, A. Rastogi, L. Burgart, T. Imperiale, U. Ladabaum, J. Cohen, and D. A. Lieberman, “The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) on real-time endoscopic assessment of the histology of diminutive colorectal polyps,” Gastrointest. Endosc. 73(3), 419–422 (2011).
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Bydlon, T. M.

Byrne, M. F.

M. F. Byrne, N. Shahidi, and D. K. Rex, “Will computer-aided detection and diagnosis revolutionize colonoscopy?” Gastroenterology 153(6), 1460–1464 (2017).
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Cappon, D. J.

D. J. Cappon, T. J. Farrell, Q. Fang, and J. E. Hayward, “Fiber-optic probe design and optical property recovery algorithm for optical biopsy of brain tissue,” J. Biomed. Opt. 18(10), 107004 (2013).
[Crossref] [PubMed]

Carnohan, M.

Castanheira, E. M. S.

S. Pimenta, E. M. S. Castanheira, and G. Minas, “Optical Microsystem for Analysis of Diffuse Reflectance and Fluorescence Signals Applied to Early Gastrointestinal Cancer Detection,” Sensors (Basel) 15(12), 3138–3153 (2015).
[Crossref] [PubMed]

Cerda, S. R.

E. Rodriguez-Diaz, Q. Huang, S. R. Cerda, M. J. O’Brien, I. J. Bigio, and S. K. Singh, “Endoscopic histological assessment of colonic polyps by using elastic scattering spectroscopy,” Gastrointest. Endosc. 81(3), 539–547 (2015).
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P. Thueler, I. Charvet, F. Bevilacqua, M. St Ghislain, G. Ory, P. Marquet, P. Meda, B. Vermeulen, and C. Depeursinge, “In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties,” J. Biomed. Opt. 8(3), 495–503 (2003).
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Chuang, M.-J.

K.-B. Sung, K.-W. Shih, F.-W. Hsu, H.-P. Hsieh, M.-J. Chuang, Y.-H. Hsiao, Y.-H. Su, and G.-H. Tien, “Accurate extraction of optical properties and top layer thickness of two-layered mucosal tissue phantoms from spatially resolved reflectance spectra,” J. Biomed. Opt. 19(7), 77002 (2014).
[Crossref] [PubMed]

Cohen, J.

D. K. Rex, C. Kahi, M. O’Brien, T. R. Levin, H. Pohl, A. Rastogi, L. Burgart, T. Imperiale, U. Ladabaum, J. Cohen, and D. A. Lieberman, “The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) on real-time endoscopic assessment of the histology of diminutive colorectal polyps,” Gastrointest. Endosc. 73(3), 419–422 (2011).
[Crossref] [PubMed]

Correia, J. H.

D. S. Ferreira, V. C. Pinto, J. H. Correia, and G. Minas, “Spectroscopic Detection of Gastrointestinal Dysplasia Using Optical Microsensors,” IEEE Trans. Biomed. Eng. 58(9), 2633–2639 (2011).
[Crossref] [PubMed]

Cothren, R. M.

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. VanDam, J. M. Crawford, R. Manoharan, and M. S. Feld, “Morphological model of human colon tissue fluorescence (vol 43, pg 113, 1996),” IEEE Trans. Biomed. Eng. 43, 437 (1996).
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Cottone, G.

Crawford, J. M.

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. VanDam, J. M. Crawford, R. Manoharan, and M. S. Feld, “Morphological model of human colon tissue fluorescence (vol 43, pg 113, 1996),” IEEE Trans. Biomed. Eng. 43, 437 (1996).
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Dalgaard, T.

Dam, J. S.

Davis, M. A.

L. R. Jones, N. W. Preyer, H. C. Wolfsen, D. M. Reynolds, M. A. Davis, and M. B. Wallace, “Monte Carlo model of stricture formation in photodynamic therapy of normal pig esophagus,” Photochem. Photobiol. 85(1), 341–346 (2009).
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P. Thueler, I. Charvet, F. Bevilacqua, M. St Ghislain, G. Ory, P. Marquet, P. Meda, B. Vermeulen, and C. Depeursinge, “In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties,” J. Biomed. Opt. 8(3), 495–503 (2003).
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Dhar, A.

A. Dhar, K. S. Johnson, M. R. Novelli, S. G. Bown, I. J. Bigio, L. B. Lovat, and S. L. Bloom, “Elastic scattering spectroscopy for the diagnosis of colonic lesions: Initial results of a novel optical biopsy technique,” Gastrointest. Endosc. 63(2), 257–261 (2006).
[Crossref] [PubMed]

Dhar, S.

Dierks, M. K.

G. J. Greening, H. M. James, M. K. Dierks, N. Vongkittiargorn, S. M. Osterholm, N. Rajaram, and T. J. Muldoon, “Towards monitoring dysplastic progression in the oral cavity using a hybrid fiber-bundle imaging and spectroscopy probe,” Sci. Rep. 6(1), 26734 (2016).
[Crossref] [PubMed]

Fabricius, P. E.

Fang, Q.

Farrell, T. J.

D. J. Cappon, T. J. Farrell, Q. Fang, and J. E. Hayward, “Fiber-optic probe design and optical property recovery algorithm for optical biopsy of brain tissue,” J. Biomed. Opt. 18(10), 107004 (2013).
[Crossref] [PubMed]

T. J. Farrell, B. C. Wilson, and M. S. Patterson, “The use of a neural network to determine tissue optical properties from spatially resolved diffuse reflectance measurements,” Phys. Med. Biol. 37(12), 2281–2286 (1992).
[Crossref] [PubMed]

Feld, M. S.

I. Georgakoudi, B. C. Jacobson, J. Van Dam, V. Backman, M. B. Wallace, M. G. Müller, Q. Zhang, K. Badizadegan, D. Sun, G. A. Thomas, L. T. Perelman, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett’s esophagus,” Gastroenterology 120(7), 1620–1629 (2001).
[Crossref] [PubMed]

G. Zonios, L. T. Perelman, V. Backman, R. Manoharan, M. Fitzmaurice, J. Van Dam, and M. S. Feld, “Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo,” Appl. Opt. 38(31), 6628–6637 (1999).
[Crossref] [PubMed]

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. VanDam, J. M. Crawford, R. Manoharan, and M. S. Feld, “Morphological model of human colon tissue fluorescence (vol 43, pg 113, 1996),” IEEE Trans. Biomed. Eng. 43, 437 (1996).
[Crossref]

Ferreira, D. S.

D. S. Ferreira, V. C. Pinto, J. H. Correia, and G. Minas, “Spectroscopic Detection of Gastrointestinal Dysplasia Using Optical Microsensors,” IEEE Trans. Biomed. Eng. 58(9), 2633–2639 (2011).
[Crossref] [PubMed]

Fitzmaurice, M.

Fu, H. L.

Fujimoto, J. G.

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]

Gallagher, J.

Ge, Z.

Gendron-Fitzpatrick, A.

Georgakoudi, I.

I. Georgakoudi, B. C. Jacobson, J. Van Dam, V. Backman, M. B. Wallace, M. G. Müller, Q. Zhang, K. Badizadegan, D. Sun, G. A. Thomas, L. T. Perelman, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett’s esophagus,” Gastroenterology 120(7), 1620–1629 (2001).
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Geradts, J.

Gopal, A.

N. Rajaram, A. Gopal, X. Zhang, and J. W. Tunnell, “Experimental validation of the effects of microvasculature pigment packaging on in vivo diffuse reflectance spectroscopy,” Lasers Surg. Med. 42(7), 680–688 (2010).
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Goth, W.

R. Hennessy, W. Goth, M. Sharma, M. K. Markey, and J. W. Tunnell, “Effect of probe geometry and optical properties on the sampling depth for diffuse reflectance spectroscopy,” J. Biomed. Opt. 19(10), 107002 (2014).
[Crossref] [PubMed]

Greening, G.

O. Senlik, G. Greening, T. J. Muldoon, and N. M. Jokerst, “Spatially resolved diffuse reflectance spectroscopy of two-layer turbid media using a densely packed multi-pixel photodiode probe,” Proc. SPIE 9700, 97000O (2016).
[Crossref]

Greening, G. J.

G. J. Greening, H. M. James, M. K. Dierks, N. Vongkittiargorn, S. M. Osterholm, N. Rajaram, and T. J. Muldoon, “Towards monitoring dysplastic progression in the oral cavity using a hybrid fiber-bundle imaging and spectroscopy probe,” Sci. Rep. 6(1), 26734 (2016).
[Crossref] [PubMed]

Harter, J.

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, “Diagnosis of breast cancer using diffuse reflectance spectroscopy: Comparison of a Monte Carlo versus partial least squares analysis based feature extraction technique,” Lasers Surg. Med. 38(7), 714–724 (2006).
[Crossref] [PubMed]

Hayward, J. E.

D. J. Cappon, T. J. Farrell, Q. Fang, and J. E. Hayward, “Fiber-optic probe design and optical property recovery algorithm for optical biopsy of brain tissue,” J. Biomed. Opt. 18(10), 107004 (2013).
[Crossref] [PubMed]

Hennessy, R.

R. Hennessy, W. Goth, M. Sharma, M. K. Markey, and J. W. Tunnell, “Effect of probe geometry and optical properties on the sampling depth for diffuse reflectance spectroscopy,” J. Biomed. Opt. 19(10), 107002 (2014).
[Crossref] [PubMed]

Hibst, R.

Hsiao, Y.-H.

K.-B. Sung, K.-W. Shih, F.-W. Hsu, H.-P. Hsieh, M.-J. Chuang, Y.-H. Hsiao, Y.-H. Su, and G.-H. Tien, “Accurate extraction of optical properties and top layer thickness of two-layered mucosal tissue phantoms from spatially resolved reflectance spectra,” J. Biomed. Opt. 19(7), 77002 (2014).
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Hsieh, H.-P.

K.-B. Sung, K.-W. Shih, F.-W. Hsu, H.-P. Hsieh, M.-J. Chuang, Y.-H. Hsiao, Y.-H. Su, and G.-H. Tien, “Accurate extraction of optical properties and top layer thickness of two-layered mucosal tissue phantoms from spatially resolved reflectance spectra,” J. Biomed. Opt. 19(7), 77002 (2014).
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Hsu, F.-W.

K.-B. Sung, K.-W. Shih, F.-W. Hsu, H.-P. Hsieh, M.-J. Chuang, Y.-H. Hsiao, Y.-H. Su, and G.-H. Tien, “Accurate extraction of optical properties and top layer thickness of two-layered mucosal tissue phantoms from spatially resolved reflectance spectra,” J. Biomed. Opt. 19(7), 77002 (2014).
[Crossref] [PubMed]

Huang, G.-J.

Huang, Q.

E. Rodriguez-Diaz, Q. Huang, S. R. Cerda, M. J. O’Brien, I. J. Bigio, and S. K. Singh, “Endoscopic histological assessment of colonic polyps by using elastic scattering spectroscopy,” Gastrointest. Endosc. 81(3), 539–547 (2015).
[Crossref] [PubMed]

Imperiale, T.

D. K. Rex, C. Kahi, M. O’Brien, T. R. Levin, H. Pohl, A. Rastogi, L. Burgart, T. Imperiale, U. Ladabaum, J. Cohen, and D. A. Lieberman, “The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) on real-time endoscopic assessment of the histology of diminutive colorectal polyps,” Gastrointest. Endosc. 73(3), 419–422 (2011).
[Crossref] [PubMed]

Jacobson, B. C.

I. Georgakoudi, B. C. Jacobson, J. Van Dam, V. Backman, M. B. Wallace, M. G. Müller, Q. Zhang, K. Badizadegan, D. Sun, G. A. Thomas, L. T. Perelman, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett’s esophagus,” Gastroenterology 120(7), 1620–1629 (2001).
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S. L. Jacques, “Optical properties of biological tissues: a review,” Phys. Med. Biol. 58(11), R37–R61 (2013).
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James, H. M.

G. J. Greening, H. M. James, M. K. Dierks, N. Vongkittiargorn, S. M. Osterholm, N. Rajaram, and T. J. Muldoon, “Towards monitoring dysplastic progression in the oral cavity using a hybrid fiber-bundle imaging and spectroscopy probe,” Sci. Rep. 6(1), 26734 (2016).
[Crossref] [PubMed]

Jiang, J.-K.

Johnson, K. S.

A. Dhar, K. S. Johnson, M. R. Novelli, S. G. Bown, I. J. Bigio, L. B. Lovat, and S. L. Bloom, “Elastic scattering spectroscopy for the diagnosis of colonic lesions: Initial results of a novel optical biopsy technique,” Gastrointest. Endosc. 63(2), 257–261 (2006).
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Jokerst, N. M.

D. M. Miller and N. M. Jokerst, “Flexible silicon sensors for diffuse reflectance spectroscopy of tissue,” Biomed. Opt. Express 8(3), 1512–1524 (2017).
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O. Senlik and N. M. Jokerst, “Concentric Multipixel Silicon Photodiode Array Probes for Spatially Resolved Diffuse Reflectance Spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 22(3), 7–12 (2016).
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O. Senlik, G. Greening, T. J. Muldoon, and N. M. Jokerst, “Spatially resolved diffuse reflectance spectroscopy of two-layer turbid media using a densely packed multi-pixel photodiode probe,” Proc. SPIE 9700, 97000O (2016).
[Crossref]

S. Dhar, D. M. Miller, and N. M. Jokerst, “High responsivity, low dark current, heterogeneously integrated thin film Si photodetectors on rigid and flexible substrates,” Opt. Express 22(5), 5052–5059 (2014).
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Jones, L. R.

Junker, M. K.

Kahi, C.

D. K. Rex, C. Kahi, M. O’Brien, T. R. Levin, H. Pohl, A. Rastogi, L. Burgart, T. Imperiale, U. Ladabaum, J. Cohen, and D. A. Lieberman, “The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) on real-time endoscopic assessment of the histology of diminutive colorectal polyps,” Gastrointest. Endosc. 73(3), 419–422 (2011).
[Crossref] [PubMed]

Kennedy, S. A.

Kienle, A.

Kuech, T. F.

Ladabaum, U.

D. K. Rex, C. Kahi, M. O’Brien, T. R. Levin, H. Pohl, A. Rastogi, L. Burgart, T. Imperiale, U. Ladabaum, J. Cohen, and D. A. Lieberman, “The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) on real-time endoscopic assessment of the histology of diminutive colorectal polyps,” Gastrointest. Endosc. 73(3), 419–422 (2011).
[Crossref] [PubMed]

Levin, T. R.

D. K. Rex, C. Kahi, M. O’Brien, T. R. Levin, H. Pohl, A. Rastogi, L. Burgart, T. Imperiale, U. Ladabaum, J. Cohen, and D. A. Lieberman, “The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) on real-time endoscopic assessment of the histology of diminutive colorectal polyps,” Gastrointest. Endosc. 73(3), 419–422 (2011).
[Crossref] [PubMed]

Lieberman, D. A.

D. K. Rex, C. Kahi, M. O’Brien, T. R. Levin, H. Pohl, A. Rastogi, L. Burgart, T. Imperiale, U. Ladabaum, J. Cohen, and D. A. Lieberman, “The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) on real-time endoscopic assessment of the histology of diminutive colorectal polyps,” Gastrointest. Endosc. 73(3), 419–422 (2011).
[Crossref] [PubMed]

Lilge, L.

Lin, C.-H.

Lin, J.-K.

Lo, J. Y.

Lovat, L. B.

A. Dhar, K. S. Johnson, M. R. Novelli, S. G. Bown, I. J. Bigio, L. B. Lovat, and S. L. Bloom, “Elastic scattering spectroscopy for the diagnosis of colonic lesions: Initial results of a novel optical biopsy technique,” Gastrointest. Endosc. 63(2), 257–261 (2006).
[Crossref] [PubMed]

Manoharan, R.

G. Zonios, L. T. Perelman, V. Backman, R. Manoharan, M. Fitzmaurice, J. Van Dam, and M. S. Feld, “Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo,” Appl. Opt. 38(31), 6628–6637 (1999).
[Crossref] [PubMed]

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. VanDam, J. M. Crawford, R. Manoharan, and M. S. Feld, “Morphological model of human colon tissue fluorescence (vol 43, pg 113, 1996),” IEEE Trans. Biomed. Eng. 43, 437 (1996).
[Crossref]

Marcu, L.

Markey, M. K.

R. Hennessy, W. Goth, M. Sharma, M. K. Markey, and J. W. Tunnell, “Effect of probe geometry and optical properties on the sampling depth for diffuse reflectance spectroscopy,” J. Biomed. Opt. 19(10), 107002 (2014).
[Crossref] [PubMed]

Marquet, P.

P. Thueler, I. Charvet, F. Bevilacqua, M. St Ghislain, G. Ory, P. Marquet, P. Meda, B. Vermeulen, and C. Depeursinge, “In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties,” J. Biomed. Opt. 8(3), 495–503 (2003).
[Crossref] [PubMed]

Meda, P.

P. Thueler, I. Charvet, F. Bevilacqua, M. St Ghislain, G. Ory, P. Marquet, P. Meda, B. Vermeulen, and C. Depeursinge, “In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties,” J. Biomed. Opt. 8(3), 495–503 (2003).
[Crossref] [PubMed]

Miller, D. M.

Minas, G.

S. Pimenta, E. M. S. Castanheira, and G. Minas, “Optical Microsystem for Analysis of Diffuse Reflectance and Fluorescence Signals Applied to Early Gastrointestinal Cancer Detection,” Sensors (Basel) 15(12), 3138–3153 (2015).
[Crossref] [PubMed]

D. S. Ferreira, V. C. Pinto, J. H. Correia, and G. Minas, “Spectroscopic Detection of Gastrointestinal Dysplasia Using Optical Microsensors,” IEEE Trans. Biomed. Eng. 58(9), 2633–2639 (2011).
[Crossref] [PubMed]

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I. J. Bigio and J. R. Mourant, “Optical biopsy,” Encycl. Opt. Eng. 1577, 1593 (2003).

Muldoon, T. J.

G. J. Greening, H. M. James, M. K. Dierks, N. Vongkittiargorn, S. M. Osterholm, N. Rajaram, and T. J. Muldoon, “Towards monitoring dysplastic progression in the oral cavity using a hybrid fiber-bundle imaging and spectroscopy probe,” Sci. Rep. 6(1), 26734 (2016).
[Crossref] [PubMed]

O. Senlik, G. Greening, T. J. Muldoon, and N. M. Jokerst, “Spatially resolved diffuse reflectance spectroscopy of two-layer turbid media using a densely packed multi-pixel photodiode probe,” Proc. SPIE 9700, 97000O (2016).
[Crossref]

Müller, M. G.

I. Georgakoudi, B. C. Jacobson, J. Van Dam, V. Backman, M. B. Wallace, M. G. Müller, Q. Zhang, K. Badizadegan, D. Sun, G. A. Thomas, L. T. Perelman, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett’s esophagus,” Gastroenterology 120(7), 1620–1629 (2001).
[Crossref] [PubMed]

Nishioka, N. S.

Novelli, M. R.

A. Dhar, K. S. Johnson, M. R. Novelli, S. G. Bown, I. J. Bigio, L. B. Lovat, and S. L. Bloom, “Elastic scattering spectroscopy for the diagnosis of colonic lesions: Initial results of a novel optical biopsy technique,” Gastrointest. Endosc. 63(2), 257–261 (2006).
[Crossref] [PubMed]

O’Brien, M.

D. K. Rex, C. Kahi, M. O’Brien, T. R. Levin, H. Pohl, A. Rastogi, L. Burgart, T. Imperiale, U. Ladabaum, J. Cohen, and D. A. Lieberman, “The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) on real-time endoscopic assessment of the histology of diminutive colorectal polyps,” Gastrointest. Endosc. 73(3), 419–422 (2011).
[Crossref] [PubMed]

O’Brien, M. J.

E. Rodriguez-Diaz, Q. Huang, S. R. Cerda, M. J. O’Brien, I. J. Bigio, and S. K. Singh, “Endoscopic histological assessment of colonic polyps by using elastic scattering spectroscopy,” Gastrointest. Endosc. 81(3), 539–547 (2015).
[Crossref] [PubMed]

Ory, G.

P. Thueler, I. Charvet, F. Bevilacqua, M. St Ghislain, G. Ory, P. Marquet, P. Meda, B. Vermeulen, and C. Depeursinge, “In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties,” J. Biomed. Opt. 8(3), 495–503 (2003).
[Crossref] [PubMed]

Osterholm, S. M.

G. J. Greening, H. M. James, M. K. Dierks, N. Vongkittiargorn, S. M. Osterholm, N. Rajaram, and T. J. Muldoon, “Towards monitoring dysplastic progression in the oral cavity using a hybrid fiber-bundle imaging and spectroscopy probe,” Sci. Rep. 6(1), 26734 (2016).
[Crossref] [PubMed]

Palmer, G. M.

Papaioannou, T.

Patterson, M. S.

A. Kienle, L. Lilge, M. S. Patterson, R. Hibst, R. Steiner, and B. C. Wilson, “Spatially resolved absolute diffuse reflectance measurements for noninvasive determination of the optical scattering and absorption coefficients of biological tissue,” Appl. Opt. 35(13), 2304–2314 (1996).
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T. J. Farrell, B. C. Wilson, and M. S. Patterson, “The use of a neural network to determine tissue optical properties from spatially resolved diffuse reflectance measurements,” Phys. Med. Biol. 37(12), 2281–2286 (1992).
[Crossref] [PubMed]

Pedersen, C. B.

Perelman, L. T.

I. Georgakoudi, B. C. Jacobson, J. Van Dam, V. Backman, M. B. Wallace, M. G. Müller, Q. Zhang, K. Badizadegan, D. Sun, G. A. Thomas, L. T. Perelman, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett’s esophagus,” Gastroenterology 120(7), 1620–1629 (2001).
[Crossref] [PubMed]

G. Zonios, L. T. Perelman, V. Backman, R. Manoharan, M. Fitzmaurice, J. Van Dam, and M. S. Feld, “Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo,” Appl. Opt. 38(31), 6628–6637 (1999).
[Crossref] [PubMed]

Pimenta, S.

S. Pimenta, E. M. S. Castanheira, and G. Minas, “Optical Microsystem for Analysis of Diffuse Reflectance and Fluorescence Signals Applied to Early Gastrointestinal Cancer Detection,” Sensors (Basel) 15(12), 3138–3153 (2015).
[Crossref] [PubMed]

Pinto, V. C.

D. S. Ferreira, V. C. Pinto, J. H. Correia, and G. Minas, “Spectroscopic Detection of Gastrointestinal Dysplasia Using Optical Microsensors,” IEEE Trans. Biomed. Eng. 58(9), 2633–2639 (2011).
[Crossref] [PubMed]

Pitris, C.

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]

Pohl, H.

D. K. Rex, C. Kahi, M. O’Brien, T. R. Levin, H. Pohl, A. Rastogi, L. Burgart, T. Imperiale, U. Ladabaum, J. Cohen, and D. A. Lieberman, “The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) on real-time endoscopic assessment of the histology of diminutive colorectal polyps,” Gastrointest. Endosc. 73(3), 419–422 (2011).
[Crossref] [PubMed]

Preyer, N. W.

Rajaram, N.

G. J. Greening, H. M. James, M. K. Dierks, N. Vongkittiargorn, S. M. Osterholm, N. Rajaram, and T. J. Muldoon, “Towards monitoring dysplastic progression in the oral cavity using a hybrid fiber-bundle imaging and spectroscopy probe,” Sci. Rep. 6(1), 26734 (2016).
[Crossref] [PubMed]

N. Rajaram, A. Gopal, X. Zhang, and J. W. Tunnell, “Experimental validation of the effects of microvasculature pigment packaging on in vivo diffuse reflectance spectroscopy,” Lasers Surg. Med. 42(7), 680–688 (2010).
[Crossref] [PubMed]

Ramanujam, N.

B. Yu, H. L. Fu, and N. Ramanujam, “Instrument independent diffuse reflectance spectroscopy,” J. Biomed. Opt. 16(1), 011010 (2011).
[Crossref] [PubMed]

T. M. Bydlon, S. A. Kennedy, L. M. Richards, J. Q. Brown, B. Yu, M. K. Junker, J. Gallagher, J. Geradts, L. G. Wilke, and N. Ramanujam, “Performance metrics of an optical spectral imaging system for intra-operative assessment of breast tumor margins,” Opt. Express 18(8), 8058–8076 (2010).
[Crossref] [PubMed]

J. Y. Lo, B. Yu, H. L. Fu, J. E. Bender, G. M. Palmer, T. F. Kuech, and N. Ramanujam, “A strategy for quantitative spectral imaging of tissue absorption and scattering using light emitting diodes and photodiodes,” Opt. Express 17(3), 1372–1384 (2009).
[Crossref] [PubMed]

M. C. Skala, G. M. Palmer, K. M. Vrotsos, A. Gendron-Fitzpatrick, and N. Ramanujam, “Comparison of a physical model and principal component analysis for the diagnosis of epithelial neoplasias in vivo using diffuse reflectance spectroscopy,” Opt. Express 15(12), 7863–7875 (2007).
[Crossref] [PubMed]

G. M. Palmer and N. Ramanujam, “Monte Carlo-based inverse model for calculating tissue optical properties. Part I: Theory and validation on synthetic phantoms,” Appl. Opt. 45(5), 1062–1071 (2006).
[Crossref] [PubMed]

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, “Diagnosis of breast cancer using diffuse reflectance spectroscopy: Comparison of a Monte Carlo versus partial least squares analysis based feature extraction technique,” Lasers Surg. Med. 38(7), 714–724 (2006).
[Crossref] [PubMed]

C. Zhu, G. M. Palmer, T. M. Breslin, F. Xu, and N. Ramanujam, “Use of a multiseparation fiber optic probe for the optical diagnosis of breast cancer,” J. Biomed. Opt. 10(2), 024032 (2005).
[Crossref] [PubMed]

Rastogi, A.

D. K. Rex, C. Kahi, M. O’Brien, T. R. Levin, H. Pohl, A. Rastogi, L. Burgart, T. Imperiale, U. Ladabaum, J. Cohen, and D. A. Lieberman, “The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) on real-time endoscopic assessment of the histology of diminutive colorectal polyps,” Gastrointest. Endosc. 73(3), 419–422 (2011).
[Crossref] [PubMed]

Rex, D. K.

M. F. Byrne, N. Shahidi, and D. K. Rex, “Will computer-aided detection and diagnosis revolutionize colonoscopy?” Gastroenterology 153(6), 1460–1464 (2017).
[Crossref] [PubMed]

D. K. Rex, C. Kahi, M. O’Brien, T. R. Levin, H. Pohl, A. Rastogi, L. Burgart, T. Imperiale, U. Ladabaum, J. Cohen, and D. A. Lieberman, “The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) on real-time endoscopic assessment of the histology of diminutive colorectal polyps,” Gastrointest. Endosc. 73(3), 419–422 (2011).
[Crossref] [PubMed]

Reynolds, D. M.

L. R. Jones, N. W. Preyer, H. C. Wolfsen, D. M. Reynolds, M. A. Davis, and M. B. Wallace, “Monte Carlo model of stricture formation in photodynamic therapy of normal pig esophagus,” Photochem. Photobiol. 85(1), 341–346 (2009).
[Crossref] [PubMed]

Richards, L. M.

Rodriguez-Diaz, E.

E. Rodriguez-Diaz, Q. Huang, S. R. Cerda, M. J. O’Brien, I. J. Bigio, and S. K. Singh, “Endoscopic histological assessment of colonic polyps by using elastic scattering spectroscopy,” Gastrointest. Endosc. 81(3), 539–547 (2015).
[Crossref] [PubMed]

E. Rodriguez-Diaz, I. J. Bigio, and S. K. Singh, “Integrated optical tools for minimally invasive diagnosis and treatment at gastrointestinal endoscopy,” Robot. Comput.-Integr. Manuf. 27(2), 249–256 (2011).
[Crossref] [PubMed]

Ross, R.

Schomacker, K. T.

Senlik, O.

O. Senlik, G. Greening, T. J. Muldoon, and N. M. Jokerst, “Spatially resolved diffuse reflectance spectroscopy of two-layer turbid media using a densely packed multi-pixel photodiode probe,” Proc. SPIE 9700, 97000O (2016).
[Crossref]

O. Senlik and N. M. Jokerst, “Concentric Multipixel Silicon Photodiode Array Probes for Spatially Resolved Diffuse Reflectance Spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 22(3), 7–12 (2016).
[Crossref]

Shaheen, N. J.

Y. Zhu, N. G. Terry, J. T. Woosley, N. J. Shaheen, and A. Wax, “Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology,” J. Biomed. Opt. 16(1), 011003 (2011).
[Crossref] [PubMed]

Shahidi, N.

M. F. Byrne, N. Shahidi, and D. K. Rex, “Will computer-aided detection and diagnosis revolutionize colonoscopy?” Gastroenterology 153(6), 1460–1464 (2017).
[Crossref] [PubMed]

Sharma, M.

R. Hennessy, W. Goth, M. Sharma, M. K. Markey, and J. W. Tunnell, “Effect of probe geometry and optical properties on the sampling depth for diffuse reflectance spectroscopy,” J. Biomed. Opt. 19(10), 107002 (2014).
[Crossref] [PubMed]

Shih, K.-W.

K.-B. Sung, K.-W. Shih, F.-W. Hsu, H.-P. Hsieh, M.-J. Chuang, Y.-H. Hsiao, Y.-H. Su, and G.-H. Tien, “Accurate extraction of optical properties and top layer thickness of two-layered mucosal tissue phantoms from spatially resolved reflectance spectra,” J. Biomed. Opt. 19(7), 77002 (2014).
[Crossref] [PubMed]

Singh, S. K.

E. Rodriguez-Diaz, Q. Huang, S. R. Cerda, M. J. O’Brien, I. J. Bigio, and S. K. Singh, “Endoscopic histological assessment of colonic polyps by using elastic scattering spectroscopy,” Gastrointest. Endosc. 81(3), 539–547 (2015).
[Crossref] [PubMed]

E. Rodriguez-Diaz, I. J. Bigio, and S. K. Singh, “Integrated optical tools for minimally invasive diagnosis and treatment at gastrointestinal endoscopy,” Robot. Comput.-Integr. Manuf. 27(2), 249–256 (2011).
[Crossref] [PubMed]

Skala, M. C.

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]

St Ghislain, M.

P. Thueler, I. Charvet, F. Bevilacqua, M. St Ghislain, G. Ory, P. Marquet, P. Meda, B. Vermeulen, and C. Depeursinge, “In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties,” J. Biomed. Opt. 8(3), 495–503 (2003).
[Crossref] [PubMed]

Steiner, R.

Su, Y.-H.

K.-B. Sung, K.-W. Shih, F.-W. Hsu, H.-P. Hsieh, M.-J. Chuang, Y.-H. Hsiao, Y.-H. Su, and G.-H. Tien, “Accurate extraction of optical properties and top layer thickness of two-layered mucosal tissue phantoms from spatially resolved reflectance spectra,” J. Biomed. Opt. 19(7), 77002 (2014).
[Crossref] [PubMed]

Sun, D.

I. Georgakoudi, B. C. Jacobson, J. Van Dam, V. Backman, M. B. Wallace, M. G. Müller, Q. Zhang, K. Badizadegan, D. Sun, G. A. Thomas, L. T. Perelman, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett’s esophagus,” Gastroenterology 120(7), 1620–1629 (2001).
[Crossref] [PubMed]

Sung, K.-B.

K.-B. Sung, K.-W. Shih, F.-W. Hsu, H.-P. Hsieh, M.-J. Chuang, Y.-H. Hsiao, Y.-H. Su, and G.-H. Tien, “Accurate extraction of optical properties and top layer thickness of two-layered mucosal tissue phantoms from spatially resolved reflectance spectra,” J. Biomed. Opt. 19(7), 77002 (2014).
[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]

Terry, N. G.

Y. Zhu, N. G. Terry, J. T. Woosley, N. J. Shaheen, and A. Wax, “Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology,” J. Biomed. Opt. 16(1), 011003 (2011).
[Crossref] [PubMed]

Thomas, G. A.

I. Georgakoudi, B. C. Jacobson, J. Van Dam, V. Backman, M. B. Wallace, M. G. Müller, Q. Zhang, K. Badizadegan, D. Sun, G. A. Thomas, L. T. Perelman, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett’s esophagus,” Gastroenterology 120(7), 1620–1629 (2001).
[Crossref] [PubMed]

Thueler, P.

P. Thueler, I. Charvet, F. Bevilacqua, M. St Ghislain, G. Ory, P. Marquet, P. Meda, B. Vermeulen, and C. Depeursinge, “In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties,” J. Biomed. Opt. 8(3), 495–503 (2003).
[Crossref] [PubMed]

Tien, G.-H.

K.-B. Sung, K.-W. Shih, F.-W. Hsu, H.-P. Hsieh, M.-J. Chuang, Y.-H. Hsiao, Y.-H. Su, and G.-H. Tien, “Accurate extraction of optical properties and top layer thickness of two-layered mucosal tissue phantoms from spatially resolved reflectance spectra,” J. Biomed. Opt. 19(7), 77002 (2014).
[Crossref] [PubMed]

Tunnell, J. W.

R. Hennessy, W. Goth, M. Sharma, M. K. Markey, and J. W. Tunnell, “Effect of probe geometry and optical properties on the sampling depth for diffuse reflectance spectroscopy,” J. Biomed. Opt. 19(10), 107002 (2014).
[Crossref] [PubMed]

N. Rajaram, A. Gopal, X. Zhang, and J. W. Tunnell, “Experimental validation of the effects of microvasculature pigment packaging on in vivo diffuse reflectance spectroscopy,” Lasers Surg. Med. 42(7), 680–688 (2010).
[Crossref] [PubMed]

Van Dam, J.

T. D. Wang and J. Van Dam, “Optical biopsy: A new frontier in endoscopic detection and diagnosis,” Clin. Gastroenterol. Hepatol. 2(9), 744–753 (2004).
[Crossref] [PubMed]

I. Georgakoudi, B. C. Jacobson, J. Van Dam, V. Backman, M. B. Wallace, M. G. Müller, Q. Zhang, K. Badizadegan, D. Sun, G. A. Thomas, L. T. Perelman, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett’s esophagus,” Gastroenterology 120(7), 1620–1629 (2001).
[Crossref] [PubMed]

G. Zonios, L. T. Perelman, V. Backman, R. Manoharan, M. Fitzmaurice, J. Van Dam, and M. S. Feld, “Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo,” Appl. Opt. 38(31), 6628–6637 (1999).
[Crossref] [PubMed]

VanDam, J.

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. VanDam, J. M. Crawford, R. Manoharan, and M. S. Feld, “Morphological model of human colon tissue fluorescence (vol 43, pg 113, 1996),” IEEE Trans. Biomed. Eng. 43, 437 (1996).
[Crossref]

Vermeulen, B.

P. Thueler, I. Charvet, F. Bevilacqua, M. St Ghislain, G. Ory, P. Marquet, P. Meda, B. Vermeulen, and C. Depeursinge, “In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties,” J. Biomed. Opt. 8(3), 495–503 (2003).
[Crossref] [PubMed]

Vongkittiargorn, N.

G. J. Greening, H. M. James, M. K. Dierks, N. Vongkittiargorn, S. M. Osterholm, N. Rajaram, and T. J. Muldoon, “Towards monitoring dysplastic progression in the oral cavity using a hybrid fiber-bundle imaging and spectroscopy probe,” Sci. Rep. 6(1), 26734 (2016).
[Crossref] [PubMed]

Vrotsos, K. M.

Wallace, M. B.

L. R. Jones, N. W. Preyer, H. C. Wolfsen, D. M. Reynolds, M. A. Davis, and M. B. Wallace, “Monte Carlo model of stricture formation in photodynamic therapy of normal pig esophagus,” Photochem. Photobiol. 85(1), 341–346 (2009).
[Crossref] [PubMed]

I. Georgakoudi, B. C. Jacobson, J. Van Dam, V. Backman, M. B. Wallace, M. G. Müller, Q. Zhang, K. Badizadegan, D. Sun, G. A. Thomas, L. T. Perelman, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett’s esophagus,” Gastroenterology 120(7), 1620–1629 (2001).
[Crossref] [PubMed]

Wang, H.-W.

Wang, T. D.

T. D. Wang and J. Van Dam, “Optical biopsy: A new frontier in endoscopic detection and diagnosis,” Clin. Gastroenterol. Hepatol. 2(9), 744–753 (2004).
[Crossref] [PubMed]

Wax, A.

Y. Zhu, N. G. Terry, J. T. Woosley, N. J. Shaheen, and A. Wax, “Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology,” J. Biomed. Opt. 16(1), 011003 (2011).
[Crossref] [PubMed]

Wilke, L. G.

Wilson, B. C.

A. Kienle, L. Lilge, M. S. Patterson, R. Hibst, R. Steiner, and B. C. Wilson, “Spatially resolved absolute diffuse reflectance measurements for noninvasive determination of the optical scattering and absorption coefficients of biological tissue,” Appl. Opt. 35(13), 2304–2314 (1996).
[Crossref] [PubMed]

T. J. Farrell, B. C. Wilson, and M. S. Patterson, “The use of a neural network to determine tissue optical properties from spatially resolved diffuse reflectance measurements,” Phys. Med. Biol. 37(12), 2281–2286 (1992).
[Crossref] [PubMed]

Wolfsen, H. C.

L. R. Jones, N. W. Preyer, H. C. Wolfsen, D. M. Reynolds, M. A. Davis, and M. B. Wallace, “Monte Carlo model of stricture formation in photodynamic therapy of normal pig esophagus,” Photochem. Photobiol. 85(1), 341–346 (2009).
[Crossref] [PubMed]

Woosley, J. T.

Y. Zhu, N. G. Terry, J. T. Woosley, N. J. Shaheen, and A. Wax, “Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology,” J. Biomed. Opt. 16(1), 011003 (2011).
[Crossref] [PubMed]

Wu, J.

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. VanDam, J. M. Crawford, R. Manoharan, and M. S. Feld, “Morphological model of human colon tissue fluorescence (vol 43, pg 113, 1996),” IEEE Trans. Biomed. Eng. 43, 437 (1996).
[Crossref]

Xu, F.

C. Zhu, G. M. Palmer, T. M. Breslin, F. Xu, and N. Ramanujam, “Use of a multiseparation fiber optic probe for the optical diagnosis of breast cancer,” J. Biomed. Opt. 10(2), 024032 (2005).
[Crossref] [PubMed]

Yu, B.

Yu, J.-S.

Zhang, Q.

I. Georgakoudi, B. C. Jacobson, J. Van Dam, V. Backman, M. B. Wallace, M. G. Müller, Q. Zhang, K. Badizadegan, D. Sun, G. A. Thomas, L. T. Perelman, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett’s esophagus,” Gastroenterology 120(7), 1620–1629 (2001).
[Crossref] [PubMed]

Zhang, X.

N. Rajaram, A. Gopal, X. Zhang, and J. W. Tunnell, “Experimental validation of the effects of microvasculature pigment packaging on in vivo diffuse reflectance spectroscopy,” Lasers Surg. Med. 42(7), 680–688 (2010).
[Crossref] [PubMed]

Zhu, C.

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, “Diagnosis of breast cancer using diffuse reflectance spectroscopy: Comparison of a Monte Carlo versus partial least squares analysis based feature extraction technique,” Lasers Surg. Med. 38(7), 714–724 (2006).
[Crossref] [PubMed]

C. Zhu, G. M. Palmer, T. M. Breslin, F. Xu, and N. Ramanujam, “Use of a multiseparation fiber optic probe for the optical diagnosis of breast cancer,” J. Biomed. Opt. 10(2), 024032 (2005).
[Crossref] [PubMed]

Zhu, Y.

Y. Zhu, N. G. Terry, J. T. Woosley, N. J. Shaheen, and A. Wax, “Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology,” J. Biomed. Opt. 16(1), 011003 (2011).
[Crossref] [PubMed]

Zonios, G.

Zonios, G. I.

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. VanDam, J. M. Crawford, R. Manoharan, and M. S. Feld, “Morphological model of human colon tissue fluorescence (vol 43, pg 113, 1996),” IEEE Trans. Biomed. Eng. 43, 437 (1996).
[Crossref]

Appl. Opt. (5)

Appl. Spectrosc. (1)

Biomed. Opt. Express (1)

Clin. Gastroenterol. Hepatol. (1)

T. D. Wang and J. Van Dam, “Optical biopsy: A new frontier in endoscopic detection and diagnosis,” Clin. Gastroenterol. Hepatol. 2(9), 744–753 (2004).
[Crossref] [PubMed]

Encycl. Opt. Eng. (1)

I. J. Bigio and J. R. Mourant, “Optical biopsy,” Encycl. Opt. Eng. 1577, 1593 (2003).

Gastroenterology (2)

M. F. Byrne, N. Shahidi, and D. K. Rex, “Will computer-aided detection and diagnosis revolutionize colonoscopy?” Gastroenterology 153(6), 1460–1464 (2017).
[Crossref] [PubMed]

I. Georgakoudi, B. C. Jacobson, J. Van Dam, V. Backman, M. B. Wallace, M. G. Müller, Q. Zhang, K. Badizadegan, D. Sun, G. A. Thomas, L. T. Perelman, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett’s esophagus,” Gastroenterology 120(7), 1620–1629 (2001).
[Crossref] [PubMed]

Gastrointest. Endosc. (3)

E. Rodriguez-Diaz, Q. Huang, S. R. Cerda, M. J. O’Brien, I. J. Bigio, and S. K. Singh, “Endoscopic histological assessment of colonic polyps by using elastic scattering spectroscopy,” Gastrointest. Endosc. 81(3), 539–547 (2015).
[Crossref] [PubMed]

D. K. Rex, C. Kahi, M. O’Brien, T. R. Levin, H. Pohl, A. Rastogi, L. Burgart, T. Imperiale, U. Ladabaum, J. Cohen, and D. A. Lieberman, “The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) on real-time endoscopic assessment of the histology of diminutive colorectal polyps,” Gastrointest. Endosc. 73(3), 419–422 (2011).
[Crossref] [PubMed]

A. Dhar, K. S. Johnson, M. R. Novelli, S. G. Bown, I. J. Bigio, L. B. Lovat, and S. L. Bloom, “Elastic scattering spectroscopy for the diagnosis of colonic lesions: Initial results of a novel optical biopsy technique,” Gastrointest. Endosc. 63(2), 257–261 (2006).
[Crossref] [PubMed]

IEEE J. Sel. Top. Quantum Electron. (1)

O. Senlik and N. M. Jokerst, “Concentric Multipixel Silicon Photodiode Array Probes for Spatially Resolved Diffuse Reflectance Spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 22(3), 7–12 (2016).
[Crossref]

IEEE Trans. Biomed. Eng. (2)

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. VanDam, J. M. Crawford, R. Manoharan, and M. S. Feld, “Morphological model of human colon tissue fluorescence (vol 43, pg 113, 1996),” IEEE Trans. Biomed. Eng. 43, 437 (1996).
[Crossref]

D. S. Ferreira, V. C. Pinto, J. H. Correia, and G. Minas, “Spectroscopic Detection of Gastrointestinal Dysplasia Using Optical Microsensors,” IEEE Trans. Biomed. Eng. 58(9), 2633–2639 (2011).
[Crossref] [PubMed]

J. Biomed. Opt. (7)

C. Zhu, G. M. Palmer, T. M. Breslin, F. Xu, and N. Ramanujam, “Use of a multiseparation fiber optic probe for the optical diagnosis of breast cancer,” J. Biomed. Opt. 10(2), 024032 (2005).
[Crossref] [PubMed]

K.-B. Sung, K.-W. Shih, F.-W. Hsu, H.-P. Hsieh, M.-J. Chuang, Y.-H. Hsiao, Y.-H. Su, and G.-H. Tien, “Accurate extraction of optical properties and top layer thickness of two-layered mucosal tissue phantoms from spatially resolved reflectance spectra,” J. Biomed. Opt. 19(7), 77002 (2014).
[Crossref] [PubMed]

D. J. Cappon, T. J. Farrell, Q. Fang, and J. E. Hayward, “Fiber-optic probe design and optical property recovery algorithm for optical biopsy of brain tissue,” J. Biomed. Opt. 18(10), 107004 (2013).
[Crossref] [PubMed]

R. Hennessy, W. Goth, M. Sharma, M. K. Markey, and J. W. Tunnell, “Effect of probe geometry and optical properties on the sampling depth for diffuse reflectance spectroscopy,” J. Biomed. Opt. 19(10), 107002 (2014).
[Crossref] [PubMed]

Y. Zhu, N. G. Terry, J. T. Woosley, N. J. Shaheen, and A. Wax, “Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology,” J. Biomed. Opt. 16(1), 011003 (2011).
[Crossref] [PubMed]

P. Thueler, I. Charvet, F. Bevilacqua, M. St Ghislain, G. Ory, P. Marquet, P. Meda, B. Vermeulen, and C. Depeursinge, “In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties,” J. Biomed. Opt. 8(3), 495–503 (2003).
[Crossref] [PubMed]

B. Yu, H. L. Fu, and N. Ramanujam, “Instrument independent diffuse reflectance spectroscopy,” J. Biomed. Opt. 16(1), 011010 (2011).
[Crossref] [PubMed]

Lasers Surg. Med. (2)

N. Rajaram, A. Gopal, X. Zhang, and J. W. Tunnell, “Experimental validation of the effects of microvasculature pigment packaging on in vivo diffuse reflectance spectroscopy,” Lasers Surg. Med. 42(7), 680–688 (2010).
[Crossref] [PubMed]

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, “Diagnosis of breast cancer using diffuse reflectance spectroscopy: Comparison of a Monte Carlo versus partial least squares analysis based feature extraction technique,” Lasers Surg. Med. 38(7), 714–724 (2006).
[Crossref] [PubMed]

Opt. Express (5)

Photochem. Photobiol. (1)

L. R. Jones, N. W. Preyer, H. C. Wolfsen, D. M. Reynolds, M. A. Davis, and M. B. Wallace, “Monte Carlo model of stricture formation in photodynamic therapy of normal pig esophagus,” Photochem. Photobiol. 85(1), 341–346 (2009).
[Crossref] [PubMed]

Phys. Med. Biol. (2)

S. L. Jacques, “Optical properties of biological tissues: a review,” Phys. Med. Biol. 58(11), R37–R61 (2013).
[Crossref] [PubMed]

T. J. Farrell, B. C. Wilson, and M. S. Patterson, “The use of a neural network to determine tissue optical properties from spatially resolved diffuse reflectance measurements,” Phys. Med. Biol. 37(12), 2281–2286 (1992).
[Crossref] [PubMed]

Proc. SPIE (1)

O. Senlik, G. Greening, T. J. Muldoon, and N. M. Jokerst, “Spatially resolved diffuse reflectance spectroscopy of two-layer turbid media using a densely packed multi-pixel photodiode probe,” Proc. SPIE 9700, 97000O (2016).
[Crossref]

Robot. Comput.-Integr. Manuf. (1)

E. Rodriguez-Diaz, I. J. Bigio, and S. K. Singh, “Integrated optical tools for minimally invasive diagnosis and treatment at gastrointestinal endoscopy,” Robot. Comput.-Integr. Manuf. 27(2), 249–256 (2011).
[Crossref] [PubMed]

Sci. Rep. (1)

G. J. Greening, H. M. James, M. K. Dierks, N. Vongkittiargorn, S. M. Osterholm, N. Rajaram, and T. J. Muldoon, “Towards monitoring dysplastic progression in the oral cavity using a hybrid fiber-bundle imaging and spectroscopy probe,” Sci. Rep. 6(1), 26734 (2016).
[Crossref] [PubMed]

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]

Sensors (Basel) (1)

S. Pimenta, E. M. S. Castanheira, and G. Minas, “Optical Microsystem for Analysis of Diffuse Reflectance and Fluorescence Signals Applied to Early Gastrointestinal Cancer Detection,” Sensors (Basel) 15(12), 3138–3153 (2015).
[Crossref] [PubMed]

Other (9)

S. Dhar, “Development of Custom Imaging Arrays for Biomedical Spectral Imaging Systems,” Duke PhD Diss. (2012).

O. Senlik, “Custom Photodiode Arrays for Diffuse Reflectance Spectroscopic Imaging of Tissues,” Duke PhD Diss. (2016).

T. RadianT Zemax LLC, Zemax 12 EE OpticStudio, www.zemax.com

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Figures (8)

Fig. 1
Fig. 1 Cross-sectional conceptual diagram of the measurement of multiple partially overlapping tissue volumes V1, V2 and V3 by three photodiodes PD1, PD2 and PD3.
Fig. 2
Fig. 2 Dependence of the minimum SNR, contrast FOM, and the minimum signal contours as functions of PD2 and PD3 width for PD1 width fixed at 58 µm. The magenta circle in the center of the plot denotes the PD2 and PD3 widths of 100 µm, and 550 µm, respectively, which satisfy the design criteria.
Fig. 3
Fig. 3 (a) Photomicrograph of the front (tissue facing) side of a fabricated MEOS three PD probe. The scale bar shown is 750 µm, which is also the diameter of the illumination aperture. (b) Surface normal responsivity for a fabricated MEOS probe, with error bars as indicated.
Fig. 4
Fig. 4 Scattering and absorption coefficients for each of the prepared liquid phantoms. The inset legend applies to both graphs. On the left-hand graph, Phantom 1 has absorption coefficients shown in red, and Phantoms 2-6 have absorption coefficients shown in blue.
Fig. 5
Fig. 5 Experimental and MC simulated scaled reflectance spectra from six liquid phantoms for each of the three MEOS PDs. From left to right, data and simulations for PD1 through PD3 are shown. Error bars are included in the plots, but are indistinguishable from the data points.
Fig. 6
Fig. 6 Photograph of a full-thickness porcine esophageal tissue sample in contact with the MEOS probe surface, which is completely covered by the tissue. An optical fiber used for light delivery is coupled to the backside of the MEOS glass substrate through a hole in the yellow printed circuit board shown in the photograph above.
Fig. 7
Fig. 7 Representative spectra for ex-vivo porcine esophagus. (a) normal, (b) min-max normalized normal, (c) denuded porcine, and (d) irregularly keratinized samples for which histology cross sections are shown in Fig. 8.
Fig. 8
Fig. 8 Photomicrographs (4x mag) of H&E stained porcine (a) normal, (b) irregularly keratinized, and (c) denuded esophagus samples. The scale bar in the upper left of (a) is 300 μm long.

Equations (4)

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Γ ( λ , P D i ) = ( 1 I a d e n o m a (   λ , P D i ) I n o r m a l ( λ , P D i ) )
C F O M = Π i = 1 3 m e a n λ ( Γ ( λ , P D i ) )
R ( λ ) = ( I p h a n t o m ( λ ) I b a c k g r o u n d ( λ ) I s t a n d a r d ( λ ) I b a c k g r o u n d ( λ ) ) / A P D
S N R =   20   l o g 10 (   ( I p h a n t o m ¯ I b a c k g r o u n d ¯   ) / ( σ p h a n t o m + σ b a c k g r o u n d ) )

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