Abstract

Pancreatic adenocarcinoma has a five-year survival rate of less than 6%. This low survival rate is attributed to the lack of accurate detection methods, which limits diagnosis to late-stage disease. Here, an in vivo pilot study assesses the feasibility of optical spectroscopy to improve clinical detection of pancreatic adenocarcinoma. During surgery on 6 patients, we collected spectrally-resolved reflectance and fluorescence in vivo. Site-matched in vivo and ex vivo data agreed qualitatively and quantitatively. Quantified differences between adenocarcinoma and normal tissues in vivo were consistent with previous results from a large ex vivo data set. Thus, optical spectroscopy is a promising method for the improved diagnosis of pancreatic cancer in vivo.

© 2013 Optical Society of America

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2013 (2)

2012 (2)

V. J. Konda, A. Meining, L. H. Jamil, M. Giovannini, K. J. Chang, J. H. Hwang, M. B. Wallace, U. D. Siddiqui, H. R. Aslanian, and S. K. Lo, “An International, Multi-Center Trial on Needle-Based Confocal Laser Endomicroscopy (nCLE): Results From the In Vivo CLE Study in the Pancreas With Endosonography of Cystic Tumors (INSPECT),” Gastroenterology142, S620–S621 (2012).

W. Y. Hu, G. Zhao, C. Y. Wang, J. G. Zhang, and L. Fu, “Nonlinear Optical Microscopy for Histology of Fresh Normal and Cancerous Pancreatic Tissues,” PLoS ONE7(5), e37962 (2012).
[CrossRef] [PubMed]

2010 (3)

S. C. Kanick, C. van der Leest, J. G. J. V. Aerts, H. C. Hoogsteden, S. Kascáková, H. J. C. M. Sterenborg, and A. Amelink, “Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes,” J. Biomed. Opt.15(1), 017004 (2010).
[CrossRef] [PubMed]

M. Chandra, J. Scheiman, D. Simeone, B. McKenna, J. Purdy, and M.-A. Mycek, “Spectral areas and ratios classifier algorithm for pancreatic tissue classification using optical spectroscopy,” J. Biomed. Opt.15(1), 010514 (2010).
[CrossRef] [PubMed]

R. H. Wilson, M. Chandra, L.-C. Chen, W. R. Lloyd, J. Scheiman, D. Simeone, J. Purdy, B. McKenna, and M.-A. Mycek, “Photon-tissue interaction model enables quantitative optical analysis of human pancreatic tissues,” Opt. Express18(21), 21612–21621 (2010).
[CrossRef] [PubMed]

2009 (3)

2008 (2)

V. Turzhitsky, Y. Liu, N. Hasabou, M. Goldberg, H. K. Roy, V. Backman, and R. Brand, “Investigating population risk factors of pancreatic cancer by evaluation of optical markers in the duodenal mucosa,” Dis. Markers25(6), 313–321 (2008).
[CrossRef] [PubMed]

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt.13(2), 024012 (2008).
[CrossRef] [PubMed]

2007 (4)

P. A. Testoni, A. Mariani, B. Mangiavillano, P. G. Arcidiacono, S. Di Pietro, and E. Masci, “Intraductal optical coherence tomography for investigating main pancreatic duct strictures,” Am. J. Gastroenterol.102(2), 269–274 (2007).
[CrossRef] [PubMed]

M. Chandra, J. Scheiman, D. Heidt, D. Simeone, B. McKenna, and M.-A. Mycek, “Probing pancreatic disease using tissue optical spectroscopy,” J. Biomed. Opt.12(6), 060501 (2007).
[CrossRef] [PubMed]

Y. Liu, R. E. Brand, V. Turzhitsky, Y. L. Kim, H. K. Roy, N. Hasabou, C. Sturgis, D. Shah, C. Hall, and V. Backman, “Optical markers in duodenal mucosa predict the presence of pancreatic cancer,” Clin. Cancer Res.13(15), 4392–4399 (2007).
[CrossRef] [PubMed]

R. Reif, O. A’Amar, and I. J. Bigio, “Analytical model of light reflectance for extraction of the optical properties in small volumes of turbid media,” Appl. Opt.46(29), 7317–7328 (2007).
[CrossRef] [PubMed]

2006 (2)

M. Chandra, K. Vishwanath, G. D. Fichter, E. Liao, S. J. Hollister, and M.-A. Mycek, “Quantitative molecular sensing in biological tissues: an approach to non-invasive optical characterization,” Opt. Express14(13), 6157–6171 (2006).
[CrossRef] [PubMed]

S. K. Chang, N. Marin, M. Follen, and R. Richards-Kortum, “Model-based analysis of clinical fluorescence spectroscopy for in vivo detection of cervical intraepithelial dysplasia,” J. Biomed. Opt.11(2), 024008 (2006).
[CrossRef] [PubMed]

2005 (2)

P. A. Testoni, B. Mangiavillano, L. Albarello, P. G. Arcidiacono, A. Mariani, E. Masci, and C. Doglioni, “Optical coherence tomography to detect epithelial lesions of the main pancreatic duct: an ex vivo study,” Am. J. Gastroenterol.100(12), 2777–2783 (2005).
[CrossRef] [PubMed]

V. R. Kondepati, J. Zimmermann, M. Keese, J. Sturm, B. C. Manegold, and J. Backhaus, “Near-infrared fiber optic spectroscopy as a novel diagnostic tool for the detection of pancreatic cancer,” J. Biomed. Opt.10(5), 054016 (2005).
[CrossRef] [PubMed]

2003 (1)

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

2002 (2)

T. P. Yeo, R. H. Hruban, S. D. Leach, R. E. Wilentz, T. A. Sohn, S. E. Kern, C. A. Iacobuzio-Donahue, A. Maitra, M. Goggins, M. I. Canto, R. A. Abrams, D. Laheru, E. M. Jaffee, M. Hidalgo, and C. J. Yeo, “Pancreatic cancer,” Curr. Probl. Cancer26(4), 176–275 (2002).
[CrossRef] [PubMed]

A. Fritscher-Ravens, L. Brand, W. T. Knöfel, C. Bobrowski, T. Topalidis, F. Thonke, A. de Werth, and N. Soehendra, “Comparison of endoscopic ultrasound-guided fine needle aspiration for focal pancreatic lesions in patients with normal parenchyma and chronic pancreatitis,” Am. J. Gastroenterol.97(11), 2768–2775 (2002).
[CrossRef] [PubMed]

1998 (1)

M.-A. Mycek, K. T. Schomacker, and N. S. Nishioka, “Colonic polyp differentiation using time-resolved autofluorescence spectroscopy,” Gastrointest. Endosc.48(4), 390–394 (1998).
[CrossRef] [PubMed]

A’Amar, O.

Abrams, R. A.

T. P. Yeo, R. H. Hruban, S. D. Leach, R. E. Wilentz, T. A. Sohn, S. E. Kern, C. A. Iacobuzio-Donahue, A. Maitra, M. Goggins, M. I. Canto, R. A. Abrams, D. Laheru, E. M. Jaffee, M. Hidalgo, and C. J. Yeo, “Pancreatic cancer,” Curr. Probl. Cancer26(4), 176–275 (2002).
[CrossRef] [PubMed]

Aerts, J. G. J. V.

S. C. Kanick, C. van der Leest, J. G. J. V. Aerts, H. C. Hoogsteden, S. Kascáková, H. J. C. M. Sterenborg, and A. Amelink, “Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes,” J. Biomed. Opt.15(1), 017004 (2010).
[CrossRef] [PubMed]

Albarello, L.

P. A. Testoni, B. Mangiavillano, L. Albarello, P. G. Arcidiacono, A. Mariani, E. Masci, and C. Doglioni, “Optical coherence tomography to detect epithelial lesions of the main pancreatic duct: an ex vivo study,” Am. J. Gastroenterol.100(12), 2777–2783 (2005).
[CrossRef] [PubMed]

Amelink, A.

S. C. Kanick, C. van der Leest, J. G. J. V. Aerts, H. C. Hoogsteden, S. Kascáková, H. J. C. M. Sterenborg, and A. Amelink, “Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes,” J. Biomed. Opt.15(1), 017004 (2010).
[CrossRef] [PubMed]

Arcidiacono, P. G.

P. A. Testoni, A. Mariani, B. Mangiavillano, P. G. Arcidiacono, S. Di Pietro, and E. Masci, “Intraductal optical coherence tomography for investigating main pancreatic duct strictures,” Am. J. Gastroenterol.102(2), 269–274 (2007).
[CrossRef] [PubMed]

P. A. Testoni, B. Mangiavillano, L. Albarello, P. G. Arcidiacono, A. Mariani, E. Masci, and C. Doglioni, “Optical coherence tomography to detect epithelial lesions of the main pancreatic duct: an ex vivo study,” Am. J. Gastroenterol.100(12), 2777–2783 (2005).
[CrossRef] [PubMed]

Aslanian, H. R.

V. J. Konda, A. Meining, L. H. Jamil, M. Giovannini, K. J. Chang, J. H. Hwang, M. B. Wallace, U. D. Siddiqui, H. R. Aslanian, and S. K. Lo, “An International, Multi-Center Trial on Needle-Based Confocal Laser Endomicroscopy (nCLE): Results From the In Vivo CLE Study in the Pancreas With Endosonography of Cystic Tumors (INSPECT),” Gastroenterology142, S620–S621 (2012).

Backhaus, J.

V. R. Kondepati, J. Zimmermann, M. Keese, J. Sturm, B. C. Manegold, and J. Backhaus, “Near-infrared fiber optic spectroscopy as a novel diagnostic tool for the detection of pancreatic cancer,” J. Biomed. Opt.10(5), 054016 (2005).
[CrossRef] [PubMed]

Backman, V.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, J. D. Rogers, H. K. Roy, R. E. Brand, and V. Backman, “Partial-wave microscopic spectroscopy detects subwavelength refractive index fluctuations: an application to cancer diagnosis,” Opt. Lett.34(4), 518–520 (2009).
[CrossRef] [PubMed]

V. Turzhitsky, Y. Liu, N. Hasabou, M. Goldberg, H. K. Roy, V. Backman, and R. Brand, “Investigating population risk factors of pancreatic cancer by evaluation of optical markers in the duodenal mucosa,” Dis. Markers25(6), 313–321 (2008).
[CrossRef] [PubMed]

Y. Liu, R. E. Brand, V. Turzhitsky, Y. L. Kim, H. K. Roy, N. Hasabou, C. Sturgis, D. Shah, C. Hall, and V. Backman, “Optical markers in duodenal mucosa predict the presence of pancreatic cancer,” Clin. Cancer Res.13(15), 4392–4399 (2007).
[CrossRef] [PubMed]

Bartels, K. E.

Bechtel, K. L.

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt.13(2), 024012 (2008).
[CrossRef] [PubMed]

Bigio, I. J.

Bobrowski, C.

A. Fritscher-Ravens, L. Brand, W. T. Knöfel, C. Bobrowski, T. Topalidis, F. Thonke, A. de Werth, and N. Soehendra, “Comparison of endoscopic ultrasound-guided fine needle aspiration for focal pancreatic lesions in patients with normal parenchyma and chronic pancreatitis,” Am. J. Gastroenterol.97(11), 2768–2775 (2002).
[CrossRef] [PubMed]

Brand, L.

A. Fritscher-Ravens, L. Brand, W. T. Knöfel, C. Bobrowski, T. Topalidis, F. Thonke, A. de Werth, and N. Soehendra, “Comparison of endoscopic ultrasound-guided fine needle aspiration for focal pancreatic lesions in patients with normal parenchyma and chronic pancreatitis,” Am. J. Gastroenterol.97(11), 2768–2775 (2002).
[CrossRef] [PubMed]

Brand, R.

V. Turzhitsky, Y. Liu, N. Hasabou, M. Goldberg, H. K. Roy, V. Backman, and R. Brand, “Investigating population risk factors of pancreatic cancer by evaluation of optical markers in the duodenal mucosa,” Dis. Markers25(6), 313–321 (2008).
[CrossRef] [PubMed]

Brand, R. E.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, J. D. Rogers, H. K. Roy, R. E. Brand, and V. Backman, “Partial-wave microscopic spectroscopy detects subwavelength refractive index fluctuations: an application to cancer diagnosis,” Opt. Lett.34(4), 518–520 (2009).
[CrossRef] [PubMed]

Y. Liu, R. E. Brand, V. Turzhitsky, Y. L. Kim, H. K. Roy, N. Hasabou, C. Sturgis, D. Shah, C. Hall, and V. Backman, “Optical markers in duodenal mucosa predict the presence of pancreatic cancer,” Clin. Cancer Res.13(15), 4392–4399 (2007).
[CrossRef] [PubMed]

Brentnall, T. A.

E. J. Seibel, T. A. Brentnall, and J. A. Dominitz, “New endoscopic and cytologic tools for cancer surveillance in the digestive tract,” Gastrointest. Endosc. Clin. N. Am.19(2), 299–307 (2009).
[CrossRef] [PubMed]

Canto, M. I.

T. P. Yeo, R. H. Hruban, S. D. Leach, R. E. Wilentz, T. A. Sohn, S. E. Kern, C. A. Iacobuzio-Donahue, A. Maitra, M. Goggins, M. I. Canto, R. A. Abrams, D. Laheru, E. M. Jaffee, M. Hidalgo, and C. J. Yeo, “Pancreatic cancer,” Curr. Probl. Cancer26(4), 176–275 (2002).
[CrossRef] [PubMed]

Capoglu, I. R.

Chandra, M.

Chang, K. J.

V. J. Konda, A. Meining, L. H. Jamil, M. Giovannini, K. J. Chang, J. H. Hwang, M. B. Wallace, U. D. Siddiqui, H. R. Aslanian, and S. K. Lo, “An International, Multi-Center Trial on Needle-Based Confocal Laser Endomicroscopy (nCLE): Results From the In Vivo CLE Study in the Pancreas With Endosonography of Cystic Tumors (INSPECT),” Gastroenterology142, S620–S621 (2012).

Chang, S. K.

S. K. Chang, N. Marin, M. Follen, and R. Richards-Kortum, “Model-based analysis of clinical fluorescence spectroscopy for in vivo detection of cervical intraepithelial dysplasia,” J. Biomed. Opt.11(2), 024008 (2006).
[CrossRef] [PubMed]

Chen, L.-C.

Dasari, R. R.

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt.13(2), 024012 (2008).
[CrossRef] [PubMed]

de Werth, A.

A. Fritscher-Ravens, L. Brand, W. T. Knöfel, C. Bobrowski, T. Topalidis, F. Thonke, A. de Werth, and N. Soehendra, “Comparison of endoscopic ultrasound-guided fine needle aspiration for focal pancreatic lesions in patients with normal parenchyma and chronic pancreatitis,” Am. J. Gastroenterol.97(11), 2768–2775 (2002).
[CrossRef] [PubMed]

Di Pietro, S.

P. A. Testoni, A. Mariani, B. Mangiavillano, P. G. Arcidiacono, S. Di Pietro, and E. Masci, “Intraductal optical coherence tomography for investigating main pancreatic duct strictures,” Am. J. Gastroenterol.102(2), 269–274 (2007).
[CrossRef] [PubMed]

Doglioni, C.

P. A. Testoni, B. Mangiavillano, L. Albarello, P. G. Arcidiacono, A. Mariani, E. Masci, and C. Doglioni, “Optical coherence tomography to detect epithelial lesions of the main pancreatic duct: an ex vivo study,” Am. J. Gastroenterol.100(12), 2777–2783 (2005).
[CrossRef] [PubMed]

Dominitz, J. A.

E. J. Seibel, T. A. Brentnall, and J. A. Dominitz, “New endoscopic and cytologic tools for cancer surveillance in the digestive tract,” Gastrointest. Endosc. Clin. N. Am.19(2), 299–307 (2009).
[CrossRef] [PubMed]

Feld, M. S.

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt.13(2), 024012 (2008).
[CrossRef] [PubMed]

Fichter, G. D.

Fitzmaurice, M.

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt.13(2), 024012 (2008).
[CrossRef] [PubMed]

Follen, M.

S. K. Chang, N. Marin, M. Follen, and R. Richards-Kortum, “Model-based analysis of clinical fluorescence spectroscopy for in vivo detection of cervical intraepithelial dysplasia,” J. Biomed. Opt.11(2), 024008 (2006).
[CrossRef] [PubMed]

Fritscher-Ravens, A.

A. Fritscher-Ravens, L. Brand, W. T. Knöfel, C. Bobrowski, T. Topalidis, F. Thonke, A. de Werth, and N. Soehendra, “Comparison of endoscopic ultrasound-guided fine needle aspiration for focal pancreatic lesions in patients with normal parenchyma and chronic pancreatitis,” Am. J. Gastroenterol.97(11), 2768–2775 (2002).
[CrossRef] [PubMed]

Fu, L.

W. Y. Hu, G. Zhao, C. Y. Wang, J. G. Zhang, and L. Fu, “Nonlinear Optical Microscopy for Histology of Fresh Normal and Cancerous Pancreatic Tissues,” PLoS ONE7(5), e37962 (2012).
[CrossRef] [PubMed]

Giovannini, M.

V. J. Konda, A. Meining, L. H. Jamil, M. Giovannini, K. J. Chang, J. H. Hwang, M. B. Wallace, U. D. Siddiqui, H. R. Aslanian, and S. K. Lo, “An International, Multi-Center Trial on Needle-Based Confocal Laser Endomicroscopy (nCLE): Results From the In Vivo CLE Study in the Pancreas With Endosonography of Cystic Tumors (INSPECT),” Gastroenterology142, S620–S621 (2012).

Goggins, M.

T. P. Yeo, R. H. Hruban, S. D. Leach, R. E. Wilentz, T. A. Sohn, S. E. Kern, C. A. Iacobuzio-Donahue, A. Maitra, M. Goggins, M. I. Canto, R. A. Abrams, D. Laheru, E. M. Jaffee, M. Hidalgo, and C. J. Yeo, “Pancreatic cancer,” Curr. Probl. Cancer26(4), 176–275 (2002).
[CrossRef] [PubMed]

Goldberg, M.

V. Turzhitsky, Y. Liu, N. Hasabou, M. Goldberg, H. K. Roy, V. Backman, and R. Brand, “Investigating population risk factors of pancreatic cancer by evaluation of optical markers in the duodenal mucosa,” Dis. Markers25(6), 313–321 (2008).
[CrossRef] [PubMed]

Haka, A. S.

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt.13(2), 024012 (2008).
[CrossRef] [PubMed]

Hall, C.

Y. Liu, R. E. Brand, V. Turzhitsky, Y. L. Kim, H. K. Roy, N. Hasabou, C. Sturgis, D. Shah, C. Hall, and V. Backman, “Optical markers in duodenal mucosa predict the presence of pancreatic cancer,” Clin. Cancer Res.13(15), 4392–4399 (2007).
[CrossRef] [PubMed]

Hasabou, N.

V. Turzhitsky, Y. Liu, N. Hasabou, M. Goldberg, H. K. Roy, V. Backman, and R. Brand, “Investigating population risk factors of pancreatic cancer by evaluation of optical markers in the duodenal mucosa,” Dis. Markers25(6), 313–321 (2008).
[CrossRef] [PubMed]

Y. Liu, R. E. Brand, V. Turzhitsky, Y. L. Kim, H. K. Roy, N. Hasabou, C. Sturgis, D. Shah, C. Hall, and V. Backman, “Optical markers in duodenal mucosa predict the presence of pancreatic cancer,” Clin. Cancer Res.13(15), 4392–4399 (2007).
[CrossRef] [PubMed]

Heidt, D.

M. Chandra, J. Scheiman, D. Heidt, D. Simeone, B. McKenna, and M.-A. Mycek, “Probing pancreatic disease using tissue optical spectroscopy,” J. Biomed. Opt.12(6), 060501 (2007).
[CrossRef] [PubMed]

Hidalgo, M.

T. P. Yeo, R. H. Hruban, S. D. Leach, R. E. Wilentz, T. A. Sohn, S. E. Kern, C. A. Iacobuzio-Donahue, A. Maitra, M. Goggins, M. I. Canto, R. A. Abrams, D. Laheru, E. M. Jaffee, M. Hidalgo, and C. J. Yeo, “Pancreatic cancer,” Curr. Probl. Cancer26(4), 176–275 (2002).
[CrossRef] [PubMed]

Hollister, S. J.

Hoogsteden, H. C.

S. C. Kanick, C. van der Leest, J. G. J. V. Aerts, H. C. Hoogsteden, S. Kascáková, H. J. C. M. Sterenborg, and A. Amelink, “Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes,” J. Biomed. Opt.15(1), 017004 (2010).
[CrossRef] [PubMed]

Hruban, R. H.

T. P. Yeo, R. H. Hruban, S. D. Leach, R. E. Wilentz, T. A. Sohn, S. E. Kern, C. A. Iacobuzio-Donahue, A. Maitra, M. Goggins, M. I. Canto, R. A. Abrams, D. Laheru, E. M. Jaffee, M. Hidalgo, and C. J. Yeo, “Pancreatic cancer,” Curr. Probl. Cancer26(4), 176–275 (2002).
[CrossRef] [PubMed]

Hu, W. Y.

W. Y. Hu, G. Zhao, C. Y. Wang, J. G. Zhang, and L. Fu, “Nonlinear Optical Microscopy for Histology of Fresh Normal and Cancerous Pancreatic Tissues,” PLoS ONE7(5), e37962 (2012).
[CrossRef] [PubMed]

Hwang, J. H.

V. J. Konda, A. Meining, L. H. Jamil, M. Giovannini, K. J. Chang, J. H. Hwang, M. B. Wallace, U. D. Siddiqui, H. R. Aslanian, and S. K. Lo, “An International, Multi-Center Trial on Needle-Based Confocal Laser Endomicroscopy (nCLE): Results From the In Vivo CLE Study in the Pancreas With Endosonography of Cystic Tumors (INSPECT),” Gastroenterology142, S620–S621 (2012).

Iacobuzio-Donahue, C. A.

T. P. Yeo, R. H. Hruban, S. D. Leach, R. E. Wilentz, T. A. Sohn, S. E. Kern, C. A. Iacobuzio-Donahue, A. Maitra, M. Goggins, M. I. Canto, R. A. Abrams, D. Laheru, E. M. Jaffee, M. Hidalgo, and C. J. Yeo, “Pancreatic cancer,” Curr. Probl. Cancer26(4), 176–275 (2002).
[CrossRef] [PubMed]

Jaffee, E. M.

T. P. Yeo, R. H. Hruban, S. D. Leach, R. E. Wilentz, T. A. Sohn, S. E. Kern, C. A. Iacobuzio-Donahue, A. Maitra, M. Goggins, M. I. Canto, R. A. Abrams, D. Laheru, E. M. Jaffee, M. Hidalgo, and C. J. Yeo, “Pancreatic cancer,” Curr. Probl. Cancer26(4), 176–275 (2002).
[CrossRef] [PubMed]

Jamil, L. H.

V. J. Konda, A. Meining, L. H. Jamil, M. Giovannini, K. J. Chang, J. H. Hwang, M. B. Wallace, U. D. Siddiqui, H. R. Aslanian, and S. K. Lo, “An International, Multi-Center Trial on Needle-Based Confocal Laser Endomicroscopy (nCLE): Results From the In Vivo CLE Study in the Pancreas With Endosonography of Cystic Tumors (INSPECT),” Gastroenterology142, S620–S621 (2012).

Kanick, S. C.

S. C. Kanick, C. van der Leest, J. G. J. V. Aerts, H. C. Hoogsteden, S. Kascáková, H. J. C. M. Sterenborg, and A. Amelink, “Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes,” J. Biomed. Opt.15(1), 017004 (2010).
[CrossRef] [PubMed]

Kascáková, S.

S. C. Kanick, C. van der Leest, J. G. J. V. Aerts, H. C. Hoogsteden, S. Kascáková, H. J. C. M. Sterenborg, and A. Amelink, “Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes,” J. Biomed. Opt.15(1), 017004 (2010).
[CrossRef] [PubMed]

Keese, M.

V. R. Kondepati, J. Zimmermann, M. Keese, J. Sturm, B. C. Manegold, and J. Backhaus, “Near-infrared fiber optic spectroscopy as a novel diagnostic tool for the detection of pancreatic cancer,” J. Biomed. Opt.10(5), 054016 (2005).
[CrossRef] [PubMed]

Kern, S. E.

T. P. Yeo, R. H. Hruban, S. D. Leach, R. E. Wilentz, T. A. Sohn, S. E. Kern, C. A. Iacobuzio-Donahue, A. Maitra, M. Goggins, M. I. Canto, R. A. Abrams, D. Laheru, E. M. Jaffee, M. Hidalgo, and C. J. Yeo, “Pancreatic cancer,” Curr. Probl. Cancer26(4), 176–275 (2002).
[CrossRef] [PubMed]

Kim, Y. L.

Y. Liu, R. E. Brand, V. Turzhitsky, Y. L. Kim, H. K. Roy, N. Hasabou, C. Sturgis, D. Shah, C. Hall, and V. Backman, “Optical markers in duodenal mucosa predict the presence of pancreatic cancer,” Clin. Cancer Res.13(15), 4392–4399 (2007).
[CrossRef] [PubMed]

Knöfel, W. T.

A. Fritscher-Ravens, L. Brand, W. T. Knöfel, C. Bobrowski, T. Topalidis, F. Thonke, A. de Werth, and N. Soehendra, “Comparison of endoscopic ultrasound-guided fine needle aspiration for focal pancreatic lesions in patients with normal parenchyma and chronic pancreatitis,” Am. J. Gastroenterol.97(11), 2768–2775 (2002).
[CrossRef] [PubMed]

Konda, V. J.

V. J. Konda, A. Meining, L. H. Jamil, M. Giovannini, K. J. Chang, J. H. Hwang, M. B. Wallace, U. D. Siddiqui, H. R. Aslanian, and S. K. Lo, “An International, Multi-Center Trial on Needle-Based Confocal Laser Endomicroscopy (nCLE): Results From the In Vivo CLE Study in the Pancreas With Endosonography of Cystic Tumors (INSPECT),” Gastroenterology142, S620–S621 (2012).

Kondepati, V. R.

V. R. Kondepati, J. Zimmermann, M. Keese, J. Sturm, B. C. Manegold, and J. Backhaus, “Near-infrared fiber optic spectroscopy as a novel diagnostic tool for the detection of pancreatic cancer,” J. Biomed. Opt.10(5), 054016 (2005).
[CrossRef] [PubMed]

Laheru, D.

T. P. Yeo, R. H. Hruban, S. D. Leach, R. E. Wilentz, T. A. Sohn, S. E. Kern, C. A. Iacobuzio-Donahue, A. Maitra, M. Goggins, M. I. Canto, R. A. Abrams, D. Laheru, E. M. Jaffee, M. Hidalgo, and C. J. Yeo, “Pancreatic cancer,” Curr. Probl. Cancer26(4), 176–275 (2002).
[CrossRef] [PubMed]

Leach, S. D.

T. P. Yeo, R. H. Hruban, S. D. Leach, R. E. Wilentz, T. A. Sohn, S. E. Kern, C. A. Iacobuzio-Donahue, A. Maitra, M. Goggins, M. I. Canto, R. A. Abrams, D. Laheru, E. M. Jaffee, M. Hidalgo, and C. J. Yeo, “Pancreatic cancer,” Curr. Probl. Cancer26(4), 176–275 (2002).
[CrossRef] [PubMed]

Lee, S. Y.

Liao, E.

Liu, Y.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, J. D. Rogers, H. K. Roy, R. E. Brand, and V. Backman, “Partial-wave microscopic spectroscopy detects subwavelength refractive index fluctuations: an application to cancer diagnosis,” Opt. Lett.34(4), 518–520 (2009).
[CrossRef] [PubMed]

V. Turzhitsky, Y. Liu, N. Hasabou, M. Goldberg, H. K. Roy, V. Backman, and R. Brand, “Investigating population risk factors of pancreatic cancer by evaluation of optical markers in the duodenal mucosa,” Dis. Markers25(6), 313–321 (2008).
[CrossRef] [PubMed]

Y. Liu, R. E. Brand, V. Turzhitsky, Y. L. Kim, H. K. Roy, N. Hasabou, C. Sturgis, D. Shah, C. Hall, and V. Backman, “Optical markers in duodenal mucosa predict the presence of pancreatic cancer,” Clin. Cancer Res.13(15), 4392–4399 (2007).
[CrossRef] [PubMed]

Lloyd, W. R.

Lo, S. K.

V. J. Konda, A. Meining, L. H. Jamil, M. Giovannini, K. J. Chang, J. H. Hwang, M. B. Wallace, U. D. Siddiqui, H. R. Aslanian, and S. K. Lo, “An International, Multi-Center Trial on Needle-Based Confocal Laser Endomicroscopy (nCLE): Results From the In Vivo CLE Study in the Pancreas With Endosonography of Cystic Tumors (INSPECT),” Gastroenterology142, S620–S621 (2012).

Maitra, A.

T. P. Yeo, R. H. Hruban, S. D. Leach, R. E. Wilentz, T. A. Sohn, S. E. Kern, C. A. Iacobuzio-Donahue, A. Maitra, M. Goggins, M. I. Canto, R. A. Abrams, D. Laheru, E. M. Jaffee, M. Hidalgo, and C. J. Yeo, “Pancreatic cancer,” Curr. Probl. Cancer26(4), 176–275 (2002).
[CrossRef] [PubMed]

Manegold, B. C.

V. R. Kondepati, J. Zimmermann, M. Keese, J. Sturm, B. C. Manegold, and J. Backhaus, “Near-infrared fiber optic spectroscopy as a novel diagnostic tool for the detection of pancreatic cancer,” J. Biomed. Opt.10(5), 054016 (2005).
[CrossRef] [PubMed]

Mangiavillano, B.

P. A. Testoni, A. Mariani, B. Mangiavillano, P. G. Arcidiacono, S. Di Pietro, and E. Masci, “Intraductal optical coherence tomography for investigating main pancreatic duct strictures,” Am. J. Gastroenterol.102(2), 269–274 (2007).
[CrossRef] [PubMed]

P. A. Testoni, B. Mangiavillano, L. Albarello, P. G. Arcidiacono, A. Mariani, E. Masci, and C. Doglioni, “Optical coherence tomography to detect epithelial lesions of the main pancreatic duct: an ex vivo study,” Am. J. Gastroenterol.100(12), 2777–2783 (2005).
[CrossRef] [PubMed]

Mariani, A.

P. A. Testoni, A. Mariani, B. Mangiavillano, P. G. Arcidiacono, S. Di Pietro, and E. Masci, “Intraductal optical coherence tomography for investigating main pancreatic duct strictures,” Am. J. Gastroenterol.102(2), 269–274 (2007).
[CrossRef] [PubMed]

P. A. Testoni, B. Mangiavillano, L. Albarello, P. G. Arcidiacono, A. Mariani, E. Masci, and C. Doglioni, “Optical coherence tomography to detect epithelial lesions of the main pancreatic duct: an ex vivo study,” Am. J. Gastroenterol.100(12), 2777–2783 (2005).
[CrossRef] [PubMed]

Marin, N.

S. K. Chang, N. Marin, M. Follen, and R. Richards-Kortum, “Model-based analysis of clinical fluorescence spectroscopy for in vivo detection of cervical intraepithelial dysplasia,” J. Biomed. Opt.11(2), 024008 (2006).
[CrossRef] [PubMed]

Masci, E.

P. A. Testoni, A. Mariani, B. Mangiavillano, P. G. Arcidiacono, S. Di Pietro, and E. Masci, “Intraductal optical coherence tomography for investigating main pancreatic duct strictures,” Am. J. Gastroenterol.102(2), 269–274 (2007).
[CrossRef] [PubMed]

P. A. Testoni, B. Mangiavillano, L. Albarello, P. G. Arcidiacono, A. Mariani, E. Masci, and C. Doglioni, “Optical coherence tomography to detect epithelial lesions of the main pancreatic duct: an ex vivo study,” Am. J. Gastroenterol.100(12), 2777–2783 (2005).
[CrossRef] [PubMed]

McKenna, B.

Meining, A.

V. J. Konda, A. Meining, L. H. Jamil, M. Giovannini, K. J. Chang, J. H. Hwang, M. B. Wallace, U. D. Siddiqui, H. R. Aslanian, and S. K. Lo, “An International, Multi-Center Trial on Needle-Based Confocal Laser Endomicroscopy (nCLE): Results From the In Vivo CLE Study in the Pancreas With Endosonography of Cystic Tumors (INSPECT),” Gastroenterology142, S620–S621 (2012).

Mycek, M.-A.

S. Y. Lee, W. R. Lloyd, M. Chandra, R. H. Wilson, B. McKenna, D. Simeone, J. Scheiman, and M.-A. Mycek, “Characterizing human pancreatic cancer precursor using quantitative tissue optical spectroscopy,” Biomed. Opt. Express4, 2828–2834 (2013).

M. Chandra, J. Scheiman, D. Simeone, B. McKenna, J. Purdy, and M.-A. Mycek, “Spectral areas and ratios classifier algorithm for pancreatic tissue classification using optical spectroscopy,” J. Biomed. Opt.15(1), 010514 (2010).
[CrossRef] [PubMed]

R. H. Wilson, M. Chandra, L.-C. Chen, W. R. Lloyd, J. Scheiman, D. Simeone, J. Purdy, B. McKenna, and M.-A. Mycek, “Photon-tissue interaction model enables quantitative optical analysis of human pancreatic tissues,” Opt. Express18(21), 21612–21621 (2010).
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R. H. Wilson, M. Chandra, J. Scheiman, D. Simeone, B. McKenna, J. Purdy, and M.-A. Mycek, “Optical spectroscopy detects histological hallmarks of pancreatic cancer,” Opt. Express17(20), 17502–17516 (2009).
[CrossRef] [PubMed]

M. Chandra, J. Scheiman, D. Heidt, D. Simeone, B. McKenna, and M.-A. Mycek, “Probing pancreatic disease using tissue optical spectroscopy,” J. Biomed. Opt.12(6), 060501 (2007).
[CrossRef] [PubMed]

M. Chandra, K. Vishwanath, G. D. Fichter, E. Liao, S. J. Hollister, and M.-A. Mycek, “Quantitative molecular sensing in biological tissues: an approach to non-invasive optical characterization,” Opt. Express14(13), 6157–6171 (2006).
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M.-A. Mycek, K. T. Schomacker, and N. S. Nishioka, “Colonic polyp differentiation using time-resolved autofluorescence spectroscopy,” Gastrointest. Endosc.48(4), 390–394 (1998).
[CrossRef] [PubMed]

Nazemi, J.

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt.13(2), 024012 (2008).
[CrossRef] [PubMed]

Nishioka, N. S.

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

M.-A. Mycek, K. T. Schomacker, and N. S. Nishioka, “Colonic polyp differentiation using time-resolved autofluorescence spectroscopy,” Gastrointest. Endosc.48(4), 390–394 (1998).
[CrossRef] [PubMed]

Paithankar, D. Y.

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

Pfefer, T. J.

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

Piao, D.

Poneros, J. M.

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

Postier, R. G.

Pradhan, P.

Purdy, J.

Reed Holyoak, G.

Reif, R.

Richards-Kortum, R.

S. K. Chang, N. Marin, M. Follen, and R. Richards-Kortum, “Model-based analysis of clinical fluorescence spectroscopy for in vivo detection of cervical intraepithelial dysplasia,” J. Biomed. Opt.11(2), 024008 (2006).
[CrossRef] [PubMed]

Ritchey, J. W.

Rogers, J. D.

Roy, H. K.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, J. D. Rogers, H. K. Roy, R. E. Brand, and V. Backman, “Partial-wave microscopic spectroscopy detects subwavelength refractive index fluctuations: an application to cancer diagnosis,” Opt. Lett.34(4), 518–520 (2009).
[CrossRef] [PubMed]

V. Turzhitsky, Y. Liu, N. Hasabou, M. Goldberg, H. K. Roy, V. Backman, and R. Brand, “Investigating population risk factors of pancreatic cancer by evaluation of optical markers in the duodenal mucosa,” Dis. Markers25(6), 313–321 (2008).
[CrossRef] [PubMed]

Y. Liu, R. E. Brand, V. Turzhitsky, Y. L. Kim, H. K. Roy, N. Hasabou, C. Sturgis, D. Shah, C. Hall, and V. Backman, “Optical markers in duodenal mucosa predict the presence of pancreatic cancer,” Clin. Cancer Res.13(15), 4392–4399 (2007).
[CrossRef] [PubMed]

Scheiman, J.

Schomacker, K. T.

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

M.-A. Mycek, K. T. Schomacker, and N. S. Nishioka, “Colonic polyp differentiation using time-resolved autofluorescence spectroscopy,” Gastrointest. Endosc.48(4), 390–394 (1998).
[CrossRef] [PubMed]

Seibel, E. J.

E. J. Seibel, T. A. Brentnall, and J. A. Dominitz, “New endoscopic and cytologic tools for cancer surveillance in the digestive tract,” Gastrointest. Endosc. Clin. N. Am.19(2), 299–307 (2009).
[CrossRef] [PubMed]

Shah, D.

Y. Liu, R. E. Brand, V. Turzhitsky, Y. L. Kim, H. K. Roy, N. Hasabou, C. Sturgis, D. Shah, C. Hall, and V. Backman, “Optical markers in duodenal mucosa predict the presence of pancreatic cancer,” Clin. Cancer Res.13(15), 4392–4399 (2007).
[CrossRef] [PubMed]

Shenk, R.

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt.13(2), 024012 (2008).
[CrossRef] [PubMed]

Siddiqui, U. D.

V. J. Konda, A. Meining, L. H. Jamil, M. Giovannini, K. J. Chang, J. H. Hwang, M. B. Wallace, U. D. Siddiqui, H. R. Aslanian, and S. K. Lo, “An International, Multi-Center Trial on Needle-Based Confocal Laser Endomicroscopy (nCLE): Results From the In Vivo CLE Study in the Pancreas With Endosonography of Cystic Tumors (INSPECT),” Gastroenterology142, S620–S621 (2012).

Simeone, D.

Soehendra, N.

A. Fritscher-Ravens, L. Brand, W. T. Knöfel, C. Bobrowski, T. Topalidis, F. Thonke, A. de Werth, and N. Soehendra, “Comparison of endoscopic ultrasound-guided fine needle aspiration for focal pancreatic lesions in patients with normal parenchyma and chronic pancreatitis,” Am. J. Gastroenterol.97(11), 2768–2775 (2002).
[CrossRef] [PubMed]

Sohn, T. A.

T. P. Yeo, R. H. Hruban, S. D. Leach, R. E. Wilentz, T. A. Sohn, S. E. Kern, C. A. Iacobuzio-Donahue, A. Maitra, M. Goggins, M. I. Canto, R. A. Abrams, D. Laheru, E. M. Jaffee, M. Hidalgo, and C. J. Yeo, “Pancreatic cancer,” Curr. Probl. Cancer26(4), 176–275 (2002).
[CrossRef] [PubMed]

Sterenborg, H. J. C. M.

S. C. Kanick, C. van der Leest, J. G. J. V. Aerts, H. C. Hoogsteden, S. Kascáková, H. J. C. M. Sterenborg, and A. Amelink, “Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes,” J. Biomed. Opt.15(1), 017004 (2010).
[CrossRef] [PubMed]

Sturgis, C.

Y. Liu, R. E. Brand, V. Turzhitsky, Y. L. Kim, H. K. Roy, N. Hasabou, C. Sturgis, D. Shah, C. Hall, and V. Backman, “Optical markers in duodenal mucosa predict the presence of pancreatic cancer,” Clin. Cancer Res.13(15), 4392–4399 (2007).
[CrossRef] [PubMed]

Sturm, J.

V. R. Kondepati, J. Zimmermann, M. Keese, J. Sturm, B. C. Manegold, and J. Backhaus, “Near-infrared fiber optic spectroscopy as a novel diagnostic tool for the detection of pancreatic cancer,” J. Biomed. Opt.10(5), 054016 (2005).
[CrossRef] [PubMed]

Subramanian, H.

Testoni, P. A.

P. A. Testoni, A. Mariani, B. Mangiavillano, P. G. Arcidiacono, S. Di Pietro, and E. Masci, “Intraductal optical coherence tomography for investigating main pancreatic duct strictures,” Am. J. Gastroenterol.102(2), 269–274 (2007).
[CrossRef] [PubMed]

P. A. Testoni, B. Mangiavillano, L. Albarello, P. G. Arcidiacono, A. Mariani, E. Masci, and C. Doglioni, “Optical coherence tomography to detect epithelial lesions of the main pancreatic duct: an ex vivo study,” Am. J. Gastroenterol.100(12), 2777–2783 (2005).
[CrossRef] [PubMed]

Thonke, F.

A. Fritscher-Ravens, L. Brand, W. T. Knöfel, C. Bobrowski, T. Topalidis, F. Thonke, A. de Werth, and N. Soehendra, “Comparison of endoscopic ultrasound-guided fine needle aspiration for focal pancreatic lesions in patients with normal parenchyma and chronic pancreatitis,” Am. J. Gastroenterol.97(11), 2768–2775 (2002).
[CrossRef] [PubMed]

Topalidis, T.

A. Fritscher-Ravens, L. Brand, W. T. Knöfel, C. Bobrowski, T. Topalidis, F. Thonke, A. de Werth, and N. Soehendra, “Comparison of endoscopic ultrasound-guided fine needle aspiration for focal pancreatic lesions in patients with normal parenchyma and chronic pancreatitis,” Am. J. Gastroenterol.97(11), 2768–2775 (2002).
[CrossRef] [PubMed]

Turzhitsky, V.

V. Turzhitsky, Y. Liu, N. Hasabou, M. Goldberg, H. K. Roy, V. Backman, and R. Brand, “Investigating population risk factors of pancreatic cancer by evaluation of optical markers in the duodenal mucosa,” Dis. Markers25(6), 313–321 (2008).
[CrossRef] [PubMed]

Y. Liu, R. E. Brand, V. Turzhitsky, Y. L. Kim, H. K. Roy, N. Hasabou, C. Sturgis, D. Shah, C. Hall, and V. Backman, “Optical markers in duodenal mucosa predict the presence of pancreatic cancer,” Clin. Cancer Res.13(15), 4392–4399 (2007).
[CrossRef] [PubMed]

van der Leest, C.

S. C. Kanick, C. van der Leest, J. G. J. V. Aerts, H. C. Hoogsteden, S. Kascáková, H. J. C. M. Sterenborg, and A. Amelink, “Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes,” J. Biomed. Opt.15(1), 017004 (2010).
[CrossRef] [PubMed]

Vishwanath, K.

Volynskaya, Z.

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt.13(2), 024012 (2008).
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Wallace, M. B.

V. J. Konda, A. Meining, L. H. Jamil, M. Giovannini, K. J. Chang, J. H. Hwang, M. B. Wallace, U. D. Siddiqui, H. R. Aslanian, and S. K. Lo, “An International, Multi-Center Trial on Needle-Based Confocal Laser Endomicroscopy (nCLE): Results From the In Vivo CLE Study in the Pancreas With Endosonography of Cystic Tumors (INSPECT),” Gastroenterology142, S620–S621 (2012).

Wang, C. Y.

W. Y. Hu, G. Zhao, C. Y. Wang, J. G. Zhang, and L. Fu, “Nonlinear Optical Microscopy for Histology of Fresh Normal and Cancerous Pancreatic Tissues,” PLoS ONE7(5), e37962 (2012).
[CrossRef] [PubMed]

Wang, N.

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt.13(2), 024012 (2008).
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Wilentz, R. E.

T. P. Yeo, R. H. Hruban, S. D. Leach, R. E. Wilentz, T. A. Sohn, S. E. Kern, C. A. Iacobuzio-Donahue, A. Maitra, M. Goggins, M. I. Canto, R. A. Abrams, D. Laheru, E. M. Jaffee, M. Hidalgo, and C. J. Yeo, “Pancreatic cancer,” Curr. Probl. Cancer26(4), 176–275 (2002).
[CrossRef] [PubMed]

Wilson, R. H.

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[CrossRef] [PubMed]

Yeo, T. P.

T. P. Yeo, R. H. Hruban, S. D. Leach, R. E. Wilentz, T. A. Sohn, S. E. Kern, C. A. Iacobuzio-Donahue, A. Maitra, M. Goggins, M. I. Canto, R. A. Abrams, D. Laheru, E. M. Jaffee, M. Hidalgo, and C. J. Yeo, “Pancreatic cancer,” Curr. Probl. Cancer26(4), 176–275 (2002).
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Zhang, J. G.

W. Y. Hu, G. Zhao, C. Y. Wang, J. G. Zhang, and L. Fu, “Nonlinear Optical Microscopy for Histology of Fresh Normal and Cancerous Pancreatic Tissues,” PLoS ONE7(5), e37962 (2012).
[CrossRef] [PubMed]

Zhao, G.

W. Y. Hu, G. Zhao, C. Y. Wang, J. G. Zhang, and L. Fu, “Nonlinear Optical Microscopy for Histology of Fresh Normal and Cancerous Pancreatic Tissues,” PLoS ONE7(5), e37962 (2012).
[CrossRef] [PubMed]

Zimmermann, J.

V. R. Kondepati, J. Zimmermann, M. Keese, J. Sturm, B. C. Manegold, and J. Backhaus, “Near-infrared fiber optic spectroscopy as a novel diagnostic tool for the detection of pancreatic cancer,” J. Biomed. Opt.10(5), 054016 (2005).
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Am. J. Gastroenterol. (3)

A. Fritscher-Ravens, L. Brand, W. T. Knöfel, C. Bobrowski, T. Topalidis, F. Thonke, A. de Werth, and N. Soehendra, “Comparison of endoscopic ultrasound-guided fine needle aspiration for focal pancreatic lesions in patients with normal parenchyma and chronic pancreatitis,” Am. J. Gastroenterol.97(11), 2768–2775 (2002).
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P. A. Testoni, A. Mariani, B. Mangiavillano, P. G. Arcidiacono, S. Di Pietro, and E. Masci, “Intraductal optical coherence tomography for investigating main pancreatic duct strictures,” Am. J. Gastroenterol.102(2), 269–274 (2007).
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Appl. Opt. (1)

Biomed. Opt. Express (1)

Clin. Cancer Res. (1)

Y. Liu, R. E. Brand, V. Turzhitsky, Y. L. Kim, H. K. Roy, N. Hasabou, C. Sturgis, D. Shah, C. Hall, and V. Backman, “Optical markers in duodenal mucosa predict the presence of pancreatic cancer,” Clin. Cancer Res.13(15), 4392–4399 (2007).
[CrossRef] [PubMed]

Curr. Probl. Cancer (1)

T. P. Yeo, R. H. Hruban, S. D. Leach, R. E. Wilentz, T. A. Sohn, S. E. Kern, C. A. Iacobuzio-Donahue, A. Maitra, M. Goggins, M. I. Canto, R. A. Abrams, D. Laheru, E. M. Jaffee, M. Hidalgo, and C. J. Yeo, “Pancreatic cancer,” Curr. Probl. Cancer26(4), 176–275 (2002).
[CrossRef] [PubMed]

Dis. Markers (1)

V. Turzhitsky, Y. Liu, N. Hasabou, M. Goldberg, H. K. Roy, V. Backman, and R. Brand, “Investigating population risk factors of pancreatic cancer by evaluation of optical markers in the duodenal mucosa,” Dis. Markers25(6), 313–321 (2008).
[CrossRef] [PubMed]

Gastroenterology (1)

V. J. Konda, A. Meining, L. H. Jamil, M. Giovannini, K. J. Chang, J. H. Hwang, M. B. Wallace, U. D. Siddiqui, H. R. Aslanian, and S. K. Lo, “An International, Multi-Center Trial on Needle-Based Confocal Laser Endomicroscopy (nCLE): Results From the In Vivo CLE Study in the Pancreas With Endosonography of Cystic Tumors (INSPECT),” Gastroenterology142, S620–S621 (2012).

Gastrointest. Endosc. (1)

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J. Biomed. Opt. (6)

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt.13(2), 024012 (2008).
[CrossRef] [PubMed]

S. K. Chang, N. Marin, M. Follen, and R. Richards-Kortum, “Model-based analysis of clinical fluorescence spectroscopy for in vivo detection of cervical intraepithelial dysplasia,” J. Biomed. Opt.11(2), 024008 (2006).
[CrossRef] [PubMed]

V. R. Kondepati, J. Zimmermann, M. Keese, J. Sturm, B. C. Manegold, and J. Backhaus, “Near-infrared fiber optic spectroscopy as a novel diagnostic tool for the detection of pancreatic cancer,” J. Biomed. Opt.10(5), 054016 (2005).
[CrossRef] [PubMed]

M. Chandra, J. Scheiman, D. Heidt, D. Simeone, B. McKenna, and M.-A. Mycek, “Probing pancreatic disease using tissue optical spectroscopy,” J. Biomed. Opt.12(6), 060501 (2007).
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M. Chandra, J. Scheiman, D. Simeone, B. McKenna, J. Purdy, and M.-A. Mycek, “Spectral areas and ratios classifier algorithm for pancreatic tissue classification using optical spectroscopy,” J. Biomed. Opt.15(1), 010514 (2010).
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S. C. Kanick, C. van der Leest, J. G. J. V. Aerts, H. C. Hoogsteden, S. Kascáková, H. J. C. M. Sterenborg, and A. Amelink, “Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes,” J. Biomed. Opt.15(1), 017004 (2010).
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Lasers Surg. Med. (1)

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

Opt. Express (3)

Opt. Lett. (2)

PLoS ONE (1)

W. Y. Hu, G. Zhao, C. Y. Wang, J. G. Zhang, and L. Fu, “Nonlinear Optical Microscopy for Histology of Fresh Normal and Cancerous Pancreatic Tissues,” PLoS ONE7(5), e37962 (2012).
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W. R. Lloyd, L.-C. Chen, R. H. Wilson, and M.-A. Mycek, “Biophotonics: Clinical Fluorescence Spectroscopy and Imaging,” in Biomedical Technology and Devices Handbook, Second Edition, J. E. Moore, and D. J. Maitland, eds. (2013).

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Figures (4)

Fig. 1
Fig. 1

Pancreatic tissue optical measurement protocol, designed to mimic fine-needle aspiration (FNA) procedures by introducing the optical probe via a hollow angiocatheter. (1) In vivo: at this stage of surgery, tissue was still perfused with some blood and was near body temperature. The sterilized fiber-optic probe (6 m length) extended from the RFLS in the non-sterile field to the patient in the sterile field. At each selected site, the surgeon inserted a 14 gauge angiocatheter (B Braun Medical) ~1 cm into the tissue, removed the stylet from the angiocatheter, and inserted the fiber-optic probe. Data acquisition for each site was < 45 s, with each modality acquired in < 1 s. (2) In vivo and ex vivo measurements were acquired at the same tissue site by marking the site prior to resection. (2, right) Each optical measurement was estimated to interrogate ~1 mm3 of tissue. Repeatability was tested by collecting two successive optical measurements at each site, with up to two tissue sites measured per patient. Tissue sites were biopsied for histopathologic analysis.

Fig. 2
Fig. 2

Optical measurements from a tissue site in vivo and ex vivo for (A) steady-state reflectance and (B) steady-state fluorescence. Measurements of the same tissue site contained similar features, attributed to similar tissue composition and morphology [22], and differed only slightly between 400 and 475 nm due to the anticipated blood content variations. The site was histopathologically confirmed to be adenocarcinoma.

Fig. 3
Fig. 3

Representative in vivo reflectance measurements from human pancreatic adenocarcinoma (blue solid: A, B), (A) normal human tissue (green dashed), and (B) human pancreatic cancer tumor xenograft in a non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mouse (red dashed) [20]. In the diagnostically important wavelength range between 455 and 525 nm (shaded), adenocarcinoma tissues have greater relative reflectance than normal tissues, consistent with extensive ex vivo studies [2024].

Fig. 4
Fig. 4

Quantitative analysis of in vivo reflectance data is consistent with ex vivo results and can distinguish between normal human pancreas and pancreatic adenocarcinoma. (A) The R470 nm/R650 nm ratio for in vivo data (gray box plot) analyzed the pronounced spectral feature at 470 nm which clearly distinguished adenocarcinoma from normal tissues. The blue and green overlays show the analysis for an extensive ex vivo data set [22], which shows the same trend as that observed in vivo. Minor differences between ex vivo and in vivo results were attributed to the limited experimental control of local blood content during in vivo measurements. (B) PTI model best fit (red, dotted) to the in vivo adenocarcinoma data in Fig. 2 (blue) (4% fit error between 450 – 530 nm). (C) A PTI-extracted morphological parameter (L/L0, related to changes in cellular nuclear size and shape) from in vivo measurements clearly distinguished adenocarcinoma from normal pancreas, consistent with results from an extensive ex vivo data set [22]. In vivo measurements from adenocarcinoma tissues modeled with an ex vivo “canonical normal” (from [22]) showed comparable results to employing an in vivo “canonical normal.” Error bars represent standard error.

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