Abstract

We report on the development of a beveled fiber-optic confocal Raman probe coupled with a ball lens for enhancing in vivo epithelial tissue Raman measurements at endoscopy. Our Monte Carlo simulations show that by selecting a proper fiber-ball lens distance and beveled angle of collection fibers, the confocal Raman probe design can be optimized for maximizing shallower tissue Raman measurements in epithelial tissue; in addition, the ratio of epithelium to stromal Raman photons collected using an optimized confocal Raman probe is approximately 19-fold higher than that using a volume-type Raman probe. Further experiments confirm that the confocal Raman endoscopic probe developed is in favor of probing superficial tissue Raman signals from a two-layer tissue phantom as well as esophagus tissue in vivo during endoscopy. This work suggests the great potential of applying the beveled fiber-optic confocal Raman probe for improving in vivo diagnosis of precancer occurring in epithelial tissue at endoscopy.

© 2013 Optical Society of America

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  1. M. S. Bergholt, W. Zheng, K. Lin, K. Y. Ho, M. Teh, K. G. Yeoh, and Z. Huang, J. Biomed. Opt. 16, 037003 (2011).
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    [CrossRef]
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    [CrossRef]
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2011 (1)

M. S. Bergholt, W. Zheng, K. Lin, K. Y. Ho, M. Teh, K. G. Yeoh, and Z. Huang, J. Biomed. Opt. 16, 037003 (2011).
[CrossRef]

2010 (3)

R. O. P. Draga, M. C. M. Grimbergen, P. L. M. Vijverberg, C. F. P. van Swol, T. G. N. Jonges, J. A. Kummer, and J. L. H. Ruud Bosch, Anal. Chem. 82, 5993 (2010).
[CrossRef]

Z. Huang, M. S. Bergholt, W. Zheng, K. Lin, K. Y. Ho, M. Teh, and K. G. Yeoh, J. Biomed. Opt. 15, 0370171 (2010).

J. Mo, W. Zheng, and Z. Huang, Biomed. Opt. Express 1, 17 (2010).
[CrossRef]

2009 (1)

2008 (2)

M. A. Short, S. Lam, A. McWilliams, J. Zhao, H. Lui, and H. Zeng, Opt. Lett. 33, 711 (2008).
[CrossRef]

I. Pavlova, C. Redden-Weber, R. A. Schwarz, M. Williams, A. El-Naggar, A. Gillenwater, and R. Richards-Kortum, J. Biomed. Opt. 13, 064012 (2008).
[CrossRef]

2007 (1)

C. Holmer, K. S. Lehmann, J. Wanken, C. Reissfelder, A. R. G. Mueller, H. J. Buhr, and P. Ritz, J. Biomed. Opt. 12, 014025 (2007).
[CrossRef]

2003 (1)

U. Utzinger and R. Richards-Kortum, J. Biomed. Opt. 8, 121 (2003).
[CrossRef]

1999 (1)

Bergholt, M. S.

M. S. Bergholt, W. Zheng, K. Lin, K. Y. Ho, M. Teh, K. G. Yeoh, and Z. Huang, J. Biomed. Opt. 16, 037003 (2011).
[CrossRef]

Z. Huang, M. S. Bergholt, W. Zheng, K. Lin, K. Y. Ho, M. Teh, and K. G. Yeoh, J. Biomed. Opt. 15, 0370171 (2010).

Buhr, H. J.

C. Holmer, K. S. Lehmann, J. Wanken, C. Reissfelder, A. R. G. Mueller, H. J. Buhr, and P. Ritz, J. Biomed. Opt. 12, 014025 (2007).
[CrossRef]

Draga, R. O. P.

R. O. P. Draga, M. C. M. Grimbergen, P. L. M. Vijverberg, C. F. P. van Swol, T. G. N. Jonges, J. A. Kummer, and J. L. H. Ruud Bosch, Anal. Chem. 82, 5993 (2010).
[CrossRef]

El-Naggar, A.

I. Pavlova, C. Redden-Weber, R. A. Schwarz, M. Williams, A. El-Naggar, A. Gillenwater, and R. Richards-Kortum, J. Biomed. Opt. 13, 064012 (2008).
[CrossRef]

Gillenwater, A.

I. Pavlova, C. Redden-Weber, R. A. Schwarz, M. Williams, A. El-Naggar, A. Gillenwater, and R. Richards-Kortum, J. Biomed. Opt. 13, 064012 (2008).
[CrossRef]

Grimbergen, M. C. M.

R. O. P. Draga, M. C. M. Grimbergen, P. L. M. Vijverberg, C. F. P. van Swol, T. G. N. Jonges, J. A. Kummer, and J. L. H. Ruud Bosch, Anal. Chem. 82, 5993 (2010).
[CrossRef]

Ho, K. Y.

M. S. Bergholt, W. Zheng, K. Lin, K. Y. Ho, M. Teh, K. G. Yeoh, and Z. Huang, J. Biomed. Opt. 16, 037003 (2011).
[CrossRef]

Z. Huang, M. S. Bergholt, W. Zheng, K. Lin, K. Y. Ho, M. Teh, and K. G. Yeoh, J. Biomed. Opt. 15, 0370171 (2010).

Z. Huang, S. K. Teh, W. Zheng, J. Mo, K. Lin, X. Shao, K. Y. Ho, M. Teh, and K. G. Yeoh, Opt. Lett. 34, 758 (2009).
[CrossRef]

Holmer, C.

C. Holmer, K. S. Lehmann, J. Wanken, C. Reissfelder, A. R. G. Mueller, H. J. Buhr, and P. Ritz, J. Biomed. Opt. 12, 014025 (2007).
[CrossRef]

Huang, Z.

M. S. Bergholt, W. Zheng, K. Lin, K. Y. Ho, M. Teh, K. G. Yeoh, and Z. Huang, J. Biomed. Opt. 16, 037003 (2011).
[CrossRef]

Z. Huang, M. S. Bergholt, W. Zheng, K. Lin, K. Y. Ho, M. Teh, and K. G. Yeoh, J. Biomed. Opt. 15, 0370171 (2010).

J. Mo, W. Zheng, and Z. Huang, Biomed. Opt. Express 1, 17 (2010).
[CrossRef]

Z. Huang, S. K. Teh, W. Zheng, J. Mo, K. Lin, X. Shao, K. Y. Ho, M. Teh, and K. G. Yeoh, Opt. Lett. 34, 758 (2009).
[CrossRef]

Jonges, T. G. N.

R. O. P. Draga, M. C. M. Grimbergen, P. L. M. Vijverberg, C. F. P. van Swol, T. G. N. Jonges, J. A. Kummer, and J. L. H. Ruud Bosch, Anal. Chem. 82, 5993 (2010).
[CrossRef]

Kummer, J. A.

R. O. P. Draga, M. C. M. Grimbergen, P. L. M. Vijverberg, C. F. P. van Swol, T. G. N. Jonges, J. A. Kummer, and J. L. H. Ruud Bosch, Anal. Chem. 82, 5993 (2010).
[CrossRef]

Lam, S.

Lehmann, K. S.

C. Holmer, K. S. Lehmann, J. Wanken, C. Reissfelder, A. R. G. Mueller, H. J. Buhr, and P. Ritz, J. Biomed. Opt. 12, 014025 (2007).
[CrossRef]

Lin, K.

M. S. Bergholt, W. Zheng, K. Lin, K. Y. Ho, M. Teh, K. G. Yeoh, and Z. Huang, J. Biomed. Opt. 16, 037003 (2011).
[CrossRef]

Z. Huang, M. S. Bergholt, W. Zheng, K. Lin, K. Y. Ho, M. Teh, and K. G. Yeoh, J. Biomed. Opt. 15, 0370171 (2010).

Z. Huang, S. K. Teh, W. Zheng, J. Mo, K. Lin, X. Shao, K. Y. Ho, M. Teh, and K. G. Yeoh, Opt. Lett. 34, 758 (2009).
[CrossRef]

Lui, H.

Marple, E.

McWilliams, A.

Mo, J.

Mueller, A. R. G.

C. Holmer, K. S. Lehmann, J. Wanken, C. Reissfelder, A. R. G. Mueller, H. J. Buhr, and P. Ritz, J. Biomed. Opt. 12, 014025 (2007).
[CrossRef]

Pavlova, I.

I. Pavlova, C. Redden-Weber, R. A. Schwarz, M. Williams, A. El-Naggar, A. Gillenwater, and R. Richards-Kortum, J. Biomed. Opt. 13, 064012 (2008).
[CrossRef]

Redden-Weber, C.

I. Pavlova, C. Redden-Weber, R. A. Schwarz, M. Williams, A. El-Naggar, A. Gillenwater, and R. Richards-Kortum, J. Biomed. Opt. 13, 064012 (2008).
[CrossRef]

Reissfelder, C.

C. Holmer, K. S. Lehmann, J. Wanken, C. Reissfelder, A. R. G. Mueller, H. J. Buhr, and P. Ritz, J. Biomed. Opt. 12, 014025 (2007).
[CrossRef]

Richards-Kortum, R.

I. Pavlova, C. Redden-Weber, R. A. Schwarz, M. Williams, A. El-Naggar, A. Gillenwater, and R. Richards-Kortum, J. Biomed. Opt. 13, 064012 (2008).
[CrossRef]

U. Utzinger and R. Richards-Kortum, J. Biomed. Opt. 8, 121 (2003).
[CrossRef]

Ritz, P.

C. Holmer, K. S. Lehmann, J. Wanken, C. Reissfelder, A. R. G. Mueller, H. J. Buhr, and P. Ritz, J. Biomed. Opt. 12, 014025 (2007).
[CrossRef]

Ruud Bosch, J. L. H.

R. O. P. Draga, M. C. M. Grimbergen, P. L. M. Vijverberg, C. F. P. van Swol, T. G. N. Jonges, J. A. Kummer, and J. L. H. Ruud Bosch, Anal. Chem. 82, 5993 (2010).
[CrossRef]

Schwarz, R. A.

I. Pavlova, C. Redden-Weber, R. A. Schwarz, M. Williams, A. El-Naggar, A. Gillenwater, and R. Richards-Kortum, J. Biomed. Opt. 13, 064012 (2008).
[CrossRef]

Shao, X.

Shim, M. G.

Short, M. A.

Teh, M.

M. S. Bergholt, W. Zheng, K. Lin, K. Y. Ho, M. Teh, K. G. Yeoh, and Z. Huang, J. Biomed. Opt. 16, 037003 (2011).
[CrossRef]

Z. Huang, M. S. Bergholt, W. Zheng, K. Lin, K. Y. Ho, M. Teh, and K. G. Yeoh, J. Biomed. Opt. 15, 0370171 (2010).

Z. Huang, S. K. Teh, W. Zheng, J. Mo, K. Lin, X. Shao, K. Y. Ho, M. Teh, and K. G. Yeoh, Opt. Lett. 34, 758 (2009).
[CrossRef]

Teh, S. K.

Utzinger, U.

U. Utzinger and R. Richards-Kortum, J. Biomed. Opt. 8, 121 (2003).
[CrossRef]

van Swol, C. F. P.

R. O. P. Draga, M. C. M. Grimbergen, P. L. M. Vijverberg, C. F. P. van Swol, T. G. N. Jonges, J. A. Kummer, and J. L. H. Ruud Bosch, Anal. Chem. 82, 5993 (2010).
[CrossRef]

Vijverberg, P. L. M.

R. O. P. Draga, M. C. M. Grimbergen, P. L. M. Vijverberg, C. F. P. van Swol, T. G. N. Jonges, J. A. Kummer, and J. L. H. Ruud Bosch, Anal. Chem. 82, 5993 (2010).
[CrossRef]

Wach, M.

Wanken, J.

C. Holmer, K. S. Lehmann, J. Wanken, C. Reissfelder, A. R. G. Mueller, H. J. Buhr, and P. Ritz, J. Biomed. Opt. 12, 014025 (2007).
[CrossRef]

Williams, M.

I. Pavlova, C. Redden-Weber, R. A. Schwarz, M. Williams, A. El-Naggar, A. Gillenwater, and R. Richards-Kortum, J. Biomed. Opt. 13, 064012 (2008).
[CrossRef]

Wilson, B. C.

Yeoh, K. G.

M. S. Bergholt, W. Zheng, K. Lin, K. Y. Ho, M. Teh, K. G. Yeoh, and Z. Huang, J. Biomed. Opt. 16, 037003 (2011).
[CrossRef]

Z. Huang, M. S. Bergholt, W. Zheng, K. Lin, K. Y. Ho, M. Teh, and K. G. Yeoh, J. Biomed. Opt. 15, 0370171 (2010).

Z. Huang, S. K. Teh, W. Zheng, J. Mo, K. Lin, X. Shao, K. Y. Ho, M. Teh, and K. G. Yeoh, Opt. Lett. 34, 758 (2009).
[CrossRef]

Zeng, H.

Zhao, J.

Zheng, W.

M. S. Bergholt, W. Zheng, K. Lin, K. Y. Ho, M. Teh, K. G. Yeoh, and Z. Huang, J. Biomed. Opt. 16, 037003 (2011).
[CrossRef]

Z. Huang, M. S. Bergholt, W. Zheng, K. Lin, K. Y. Ho, M. Teh, and K. G. Yeoh, J. Biomed. Opt. 15, 0370171 (2010).

J. Mo, W. Zheng, and Z. Huang, Biomed. Opt. Express 1, 17 (2010).
[CrossRef]

Z. Huang, S. K. Teh, W. Zheng, J. Mo, K. Lin, X. Shao, K. Y. Ho, M. Teh, and K. G. Yeoh, Opt. Lett. 34, 758 (2009).
[CrossRef]

Anal. Chem. (1)

R. O. P. Draga, M. C. M. Grimbergen, P. L. M. Vijverberg, C. F. P. van Swol, T. G. N. Jonges, J. A. Kummer, and J. L. H. Ruud Bosch, Anal. Chem. 82, 5993 (2010).
[CrossRef]

Appl. Spectrosc. (1)

Biomed. Opt. Express (1)

J. Biomed. Opt. (5)

C. Holmer, K. S. Lehmann, J. Wanken, C. Reissfelder, A. R. G. Mueller, H. J. Buhr, and P. Ritz, J. Biomed. Opt. 12, 014025 (2007).
[CrossRef]

I. Pavlova, C. Redden-Weber, R. A. Schwarz, M. Williams, A. El-Naggar, A. Gillenwater, and R. Richards-Kortum, J. Biomed. Opt. 13, 064012 (2008).
[CrossRef]

M. S. Bergholt, W. Zheng, K. Lin, K. Y. Ho, M. Teh, K. G. Yeoh, and Z. Huang, J. Biomed. Opt. 16, 037003 (2011).
[CrossRef]

Z. Huang, M. S. Bergholt, W. Zheng, K. Lin, K. Y. Ho, M. Teh, and K. G. Yeoh, J. Biomed. Opt. 15, 0370171 (2010).

U. Utzinger and R. Richards-Kortum, J. Biomed. Opt. 8, 121 (2003).
[CrossRef]

Opt. Lett. (2)

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Figures (5)

Fig. 1.
Fig. 1.

(a) Schematic of a beveled fiber-optic confocal Raman endoscopic probe coupled with a ball lens. d: air gap between the fiber and the ball lens; β: beveled angle. (b) A volume-type fiber-optic Raman endoscopic probe. Note that the light rays for illumination are shown in dotted red lines, while the scattered tissue Raman photons collected are in black lines.

Fig. 2.
Fig. 2.

(a) Comparison of tissue Raman photons collected as a function of beveled angles of the confocal Raman probes at different fiber-ball lens gaps (d=0, 300, and 600 μm). (b) Comparison of ratios of the epithelium to stromal Raman photons collected in regard to different beveled angles at different fiber-ball lens gaps.

Fig. 3.
Fig. 3.

Normalized Raman photons collected as a function of tissue depths using different beveled fiber confocal Raman probes (β=0°, 10°, and 20°; gap d=0μm) as well as the Raman photons collected using a volume-type Raman probe in a two-layer tissue model.

Fig. 4.
Fig. 4.

(a) Comparison of Raman spectra acquired from a two-layer tissue phantom using a confocal Raman probe and a volume Raman probe, respectively. (b) Representative Raman spectra of the chicken muscle tissue (top layer) and the chicken fat tissue (bottom layer) in the tissue phantom.

Fig. 5.
Fig. 5.

Comparison of in vivo mean Raman spectra (n=20) of normal esophagus tissue acquired using a beveled fiber-optic confocal Raman probe developed and a volume-type Raman probe during clinical endoscopy. Each Raman spectrum is acquired within 0.5 s.

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