Abstract

A near-infrared Raman system was developed to collect real-time in vivo human lung spectra. The excitation light and the emission were guided to and from the tissue surface by a reusable fiber catheter passed down the instrument channel of a bronchoscope. Two-stage filtering was used to reduce laser noise, fluorescence, and Raman emissions from the fibers. A second fiber bundle guided the emission to a spectrometer where the fibers, in a round packing geometry, were spread out to form a parabolic arc that improved the signal-to-noise ratio 20-fold, facilitating real-time spectral measurements. Preliminary clinical tests show that clear and reliable Raman spectra can be obtained.

© 2008 Optical Society of America

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  1. S. Lam, C. MacAulay, J. Hung, J. C. LeRiche, A. E. Profio, and B. Palcic, J. Thorac. Cardiovasc. Surg. 105, 1035 (1993).
    [PubMed]
  2. M. Zellweger, P. Grosjean, D. Goujon, P. Monnier, H. van den Bergh, and G. Wagnieres, J. Biomed. Opt. 6, 41 (2001).
    [CrossRef] [PubMed]
  3. E. B. Hanlon, R. Manoharan, T.-W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Med. Biol. 45, R1 (2000).
    [CrossRef] [PubMed]
  4. Z. Huang, A. McWilliams, H. Lui, D. I. McLean, S. Lam, and H. Zeng, Int. J. Cancer 107, 1047 (2003).
    [CrossRef] [PubMed]
  5. A. Nijssen, K. Marquelin, L. F. Santos, P. J. Caspers, T. C. Bakker Schut, J. C. den Hollander, M. H. A. Neumann, and G. J. Puppels, J. Biomed. Opt. 12, 0340041 (2007).
    [CrossRef]
  6. Z. Huang, H. Zeng, I. Hamzavi, D. I. McLean, and H. Lui, Opt. Lett. 26, 1782 (2001).
    [CrossRef]
  7. J. Zhao, H. Lui, D. I. McLean, and H. Zeng, “Integrated real-time Raman system for clinical in vivo skin analysis,” Skin Res. Technol. (to be published).
    [PubMed]
  8. S. Koljenovic, T. C. Bakker Schut, J. P. van Meerbeeck, A. P. Maat, S. A. Burgers, P. E. Zondervan, J. M. Kros, and G. J. Puppels, J. Biomed. Opt. 9, 1187 (2004).
    [CrossRef] [PubMed]
  9. M. Chaplin, “Water structure and science,” http://www.lsbu.ac.uk/water/vibrat.html.
  10. Z. Movasaghi, S. Rehman, and I. U. Rehman, Appl. Spectrosc. Rev. 42, 493 (2007).
    [CrossRef]

2007

A. Nijssen, K. Marquelin, L. F. Santos, P. J. Caspers, T. C. Bakker Schut, J. C. den Hollander, M. H. A. Neumann, and G. J. Puppels, J. Biomed. Opt. 12, 0340041 (2007).
[CrossRef]

Z. Movasaghi, S. Rehman, and I. U. Rehman, Appl. Spectrosc. Rev. 42, 493 (2007).
[CrossRef]

2004

S. Koljenovic, T. C. Bakker Schut, J. P. van Meerbeeck, A. P. Maat, S. A. Burgers, P. E. Zondervan, J. M. Kros, and G. J. Puppels, J. Biomed. Opt. 9, 1187 (2004).
[CrossRef] [PubMed]

2003

Z. Huang, A. McWilliams, H. Lui, D. I. McLean, S. Lam, and H. Zeng, Int. J. Cancer 107, 1047 (2003).
[CrossRef] [PubMed]

2001

M. Zellweger, P. Grosjean, D. Goujon, P. Monnier, H. van den Bergh, and G. Wagnieres, J. Biomed. Opt. 6, 41 (2001).
[CrossRef] [PubMed]

Z. Huang, H. Zeng, I. Hamzavi, D. I. McLean, and H. Lui, Opt. Lett. 26, 1782 (2001).
[CrossRef]

2000

E. B. Hanlon, R. Manoharan, T.-W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Med. Biol. 45, R1 (2000).
[CrossRef] [PubMed]

1993

S. Lam, C. MacAulay, J. Hung, J. C. LeRiche, A. E. Profio, and B. Palcic, J. Thorac. Cardiovasc. Surg. 105, 1035 (1993).
[PubMed]

Bakker Schut, T. C.

A. Nijssen, K. Marquelin, L. F. Santos, P. J. Caspers, T. C. Bakker Schut, J. C. den Hollander, M. H. A. Neumann, and G. J. Puppels, J. Biomed. Opt. 12, 0340041 (2007).
[CrossRef]

S. Koljenovic, T. C. Bakker Schut, J. P. van Meerbeeck, A. P. Maat, S. A. Burgers, P. E. Zondervan, J. M. Kros, and G. J. Puppels, J. Biomed. Opt. 9, 1187 (2004).
[CrossRef] [PubMed]

Burgers, S. A.

S. Koljenovic, T. C. Bakker Schut, J. P. van Meerbeeck, A. P. Maat, S. A. Burgers, P. E. Zondervan, J. M. Kros, and G. J. Puppels, J. Biomed. Opt. 9, 1187 (2004).
[CrossRef] [PubMed]

Caspers, P. J.

A. Nijssen, K. Marquelin, L. F. Santos, P. J. Caspers, T. C. Bakker Schut, J. C. den Hollander, M. H. A. Neumann, and G. J. Puppels, J. Biomed. Opt. 12, 0340041 (2007).
[CrossRef]

Chaplin, M.

M. Chaplin, “Water structure and science,” http://www.lsbu.ac.uk/water/vibrat.html.

Dasari, R. R.

E. B. Hanlon, R. Manoharan, T.-W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Med. Biol. 45, R1 (2000).
[CrossRef] [PubMed]

den Hollander, J. C.

A. Nijssen, K. Marquelin, L. F. Santos, P. J. Caspers, T. C. Bakker Schut, J. C. den Hollander, M. H. A. Neumann, and G. J. Puppels, J. Biomed. Opt. 12, 0340041 (2007).
[CrossRef]

Feld, M. S.

E. B. Hanlon, R. Manoharan, T.-W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Med. Biol. 45, R1 (2000).
[CrossRef] [PubMed]

Fitzmaurice, M.

E. B. Hanlon, R. Manoharan, T.-W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Med. Biol. 45, R1 (2000).
[CrossRef] [PubMed]

Goujon, D.

M. Zellweger, P. Grosjean, D. Goujon, P. Monnier, H. van den Bergh, and G. Wagnieres, J. Biomed. Opt. 6, 41 (2001).
[CrossRef] [PubMed]

Grosjean, P.

M. Zellweger, P. Grosjean, D. Goujon, P. Monnier, H. van den Bergh, and G. Wagnieres, J. Biomed. Opt. 6, 41 (2001).
[CrossRef] [PubMed]

Hamzavi, I.

Hanlon, E. B.

E. B. Hanlon, R. Manoharan, T.-W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Med. Biol. 45, R1 (2000).
[CrossRef] [PubMed]

Huang, Z.

Z. Huang, A. McWilliams, H. Lui, D. I. McLean, S. Lam, and H. Zeng, Int. J. Cancer 107, 1047 (2003).
[CrossRef] [PubMed]

Z. Huang, H. Zeng, I. Hamzavi, D. I. McLean, and H. Lui, Opt. Lett. 26, 1782 (2001).
[CrossRef]

Hung, J.

S. Lam, C. MacAulay, J. Hung, J. C. LeRiche, A. E. Profio, and B. Palcic, J. Thorac. Cardiovasc. Surg. 105, 1035 (1993).
[PubMed]

Itzkan, I.

E. B. Hanlon, R. Manoharan, T.-W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Med. Biol. 45, R1 (2000).
[CrossRef] [PubMed]

Koljenovic, S.

S. Koljenovic, T. C. Bakker Schut, J. P. van Meerbeeck, A. P. Maat, S. A. Burgers, P. E. Zondervan, J. M. Kros, and G. J. Puppels, J. Biomed. Opt. 9, 1187 (2004).
[CrossRef] [PubMed]

Koo, T.-W.

E. B. Hanlon, R. Manoharan, T.-W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Med. Biol. 45, R1 (2000).
[CrossRef] [PubMed]

Kramer, J. R.

E. B. Hanlon, R. Manoharan, T.-W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Med. Biol. 45, R1 (2000).
[CrossRef] [PubMed]

Kros, J. M.

S. Koljenovic, T. C. Bakker Schut, J. P. van Meerbeeck, A. P. Maat, S. A. Burgers, P. E. Zondervan, J. M. Kros, and G. J. Puppels, J. Biomed. Opt. 9, 1187 (2004).
[CrossRef] [PubMed]

Lam, S.

Z. Huang, A. McWilliams, H. Lui, D. I. McLean, S. Lam, and H. Zeng, Int. J. Cancer 107, 1047 (2003).
[CrossRef] [PubMed]

S. Lam, C. MacAulay, J. Hung, J. C. LeRiche, A. E. Profio, and B. Palcic, J. Thorac. Cardiovasc. Surg. 105, 1035 (1993).
[PubMed]

LeRiche, J. C.

S. Lam, C. MacAulay, J. Hung, J. C. LeRiche, A. E. Profio, and B. Palcic, J. Thorac. Cardiovasc. Surg. 105, 1035 (1993).
[PubMed]

Lui, H.

Z. Huang, A. McWilliams, H. Lui, D. I. McLean, S. Lam, and H. Zeng, Int. J. Cancer 107, 1047 (2003).
[CrossRef] [PubMed]

Z. Huang, H. Zeng, I. Hamzavi, D. I. McLean, and H. Lui, Opt. Lett. 26, 1782 (2001).
[CrossRef]

J. Zhao, H. Lui, D. I. McLean, and H. Zeng, “Integrated real-time Raman system for clinical in vivo skin analysis,” Skin Res. Technol. (to be published).
[PubMed]

Maat, A. P.

S. Koljenovic, T. C. Bakker Schut, J. P. van Meerbeeck, A. P. Maat, S. A. Burgers, P. E. Zondervan, J. M. Kros, and G. J. Puppels, J. Biomed. Opt. 9, 1187 (2004).
[CrossRef] [PubMed]

MacAulay, C.

S. Lam, C. MacAulay, J. Hung, J. C. LeRiche, A. E. Profio, and B. Palcic, J. Thorac. Cardiovasc. Surg. 105, 1035 (1993).
[PubMed]

Manoharan, R.

E. B. Hanlon, R. Manoharan, T.-W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Med. Biol. 45, R1 (2000).
[CrossRef] [PubMed]

Marquelin, K.

A. Nijssen, K. Marquelin, L. F. Santos, P. J. Caspers, T. C. Bakker Schut, J. C. den Hollander, M. H. A. Neumann, and G. J. Puppels, J. Biomed. Opt. 12, 0340041 (2007).
[CrossRef]

McLean, D. I.

Z. Huang, A. McWilliams, H. Lui, D. I. McLean, S. Lam, and H. Zeng, Int. J. Cancer 107, 1047 (2003).
[CrossRef] [PubMed]

Z. Huang, H. Zeng, I. Hamzavi, D. I. McLean, and H. Lui, Opt. Lett. 26, 1782 (2001).
[CrossRef]

J. Zhao, H. Lui, D. I. McLean, and H. Zeng, “Integrated real-time Raman system for clinical in vivo skin analysis,” Skin Res. Technol. (to be published).
[PubMed]

McWilliams, A.

Z. Huang, A. McWilliams, H. Lui, D. I. McLean, S. Lam, and H. Zeng, Int. J. Cancer 107, 1047 (2003).
[CrossRef] [PubMed]

Monnier, P.

M. Zellweger, P. Grosjean, D. Goujon, P. Monnier, H. van den Bergh, and G. Wagnieres, J. Biomed. Opt. 6, 41 (2001).
[CrossRef] [PubMed]

Motz, J. T.

E. B. Hanlon, R. Manoharan, T.-W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Med. Biol. 45, R1 (2000).
[CrossRef] [PubMed]

Movasaghi, Z.

Z. Movasaghi, S. Rehman, and I. U. Rehman, Appl. Spectrosc. Rev. 42, 493 (2007).
[CrossRef]

Neumann, M. H. A.

A. Nijssen, K. Marquelin, L. F. Santos, P. J. Caspers, T. C. Bakker Schut, J. C. den Hollander, M. H. A. Neumann, and G. J. Puppels, J. Biomed. Opt. 12, 0340041 (2007).
[CrossRef]

Nijssen, A.

A. Nijssen, K. Marquelin, L. F. Santos, P. J. Caspers, T. C. Bakker Schut, J. C. den Hollander, M. H. A. Neumann, and G. J. Puppels, J. Biomed. Opt. 12, 0340041 (2007).
[CrossRef]

Palcic, B.

S. Lam, C. MacAulay, J. Hung, J. C. LeRiche, A. E. Profio, and B. Palcic, J. Thorac. Cardiovasc. Surg. 105, 1035 (1993).
[PubMed]

Profio, A. E.

S. Lam, C. MacAulay, J. Hung, J. C. LeRiche, A. E. Profio, and B. Palcic, J. Thorac. Cardiovasc. Surg. 105, 1035 (1993).
[PubMed]

Puppels, G. J.

A. Nijssen, K. Marquelin, L. F. Santos, P. J. Caspers, T. C. Bakker Schut, J. C. den Hollander, M. H. A. Neumann, and G. J. Puppels, J. Biomed. Opt. 12, 0340041 (2007).
[CrossRef]

S. Koljenovic, T. C. Bakker Schut, J. P. van Meerbeeck, A. P. Maat, S. A. Burgers, P. E. Zondervan, J. M. Kros, and G. J. Puppels, J. Biomed. Opt. 9, 1187 (2004).
[CrossRef] [PubMed]

Rehman, I. U.

Z. Movasaghi, S. Rehman, and I. U. Rehman, Appl. Spectrosc. Rev. 42, 493 (2007).
[CrossRef]

Rehman, S.

Z. Movasaghi, S. Rehman, and I. U. Rehman, Appl. Spectrosc. Rev. 42, 493 (2007).
[CrossRef]

Santos, L. F.

A. Nijssen, K. Marquelin, L. F. Santos, P. J. Caspers, T. C. Bakker Schut, J. C. den Hollander, M. H. A. Neumann, and G. J. Puppels, J. Biomed. Opt. 12, 0340041 (2007).
[CrossRef]

Shafer, K. E.

E. B. Hanlon, R. Manoharan, T.-W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Med. Biol. 45, R1 (2000).
[CrossRef] [PubMed]

van den Bergh, H.

M. Zellweger, P. Grosjean, D. Goujon, P. Monnier, H. van den Bergh, and G. Wagnieres, J. Biomed. Opt. 6, 41 (2001).
[CrossRef] [PubMed]

van Meerbeeck, J. P.

S. Koljenovic, T. C. Bakker Schut, J. P. van Meerbeeck, A. P. Maat, S. A. Burgers, P. E. Zondervan, J. M. Kros, and G. J. Puppels, J. Biomed. Opt. 9, 1187 (2004).
[CrossRef] [PubMed]

Wagnieres, G.

M. Zellweger, P. Grosjean, D. Goujon, P. Monnier, H. van den Bergh, and G. Wagnieres, J. Biomed. Opt. 6, 41 (2001).
[CrossRef] [PubMed]

Zellweger, M.

M. Zellweger, P. Grosjean, D. Goujon, P. Monnier, H. van den Bergh, and G. Wagnieres, J. Biomed. Opt. 6, 41 (2001).
[CrossRef] [PubMed]

Zeng, H.

Z. Huang, A. McWilliams, H. Lui, D. I. McLean, S. Lam, and H. Zeng, Int. J. Cancer 107, 1047 (2003).
[CrossRef] [PubMed]

Z. Huang, H. Zeng, I. Hamzavi, D. I. McLean, and H. Lui, Opt. Lett. 26, 1782 (2001).
[CrossRef]

J. Zhao, H. Lui, D. I. McLean, and H. Zeng, “Integrated real-time Raman system for clinical in vivo skin analysis,” Skin Res. Technol. (to be published).
[PubMed]

Zhao, J.

J. Zhao, H. Lui, D. I. McLean, and H. Zeng, “Integrated real-time Raman system for clinical in vivo skin analysis,” Skin Res. Technol. (to be published).
[PubMed]

Zondervan, P. E.

S. Koljenovic, T. C. Bakker Schut, J. P. van Meerbeeck, A. P. Maat, S. A. Burgers, P. E. Zondervan, J. M. Kros, and G. J. Puppels, J. Biomed. Opt. 9, 1187 (2004).
[CrossRef] [PubMed]

Appl. Spectrosc. Rev.

Z. Movasaghi, S. Rehman, and I. U. Rehman, Appl. Spectrosc. Rev. 42, 493 (2007).
[CrossRef]

Int. J. Cancer

Z. Huang, A. McWilliams, H. Lui, D. I. McLean, S. Lam, and H. Zeng, Int. J. Cancer 107, 1047 (2003).
[CrossRef] [PubMed]

J. Biomed. Opt.

A. Nijssen, K. Marquelin, L. F. Santos, P. J. Caspers, T. C. Bakker Schut, J. C. den Hollander, M. H. A. Neumann, and G. J. Puppels, J. Biomed. Opt. 12, 0340041 (2007).
[CrossRef]

M. Zellweger, P. Grosjean, D. Goujon, P. Monnier, H. van den Bergh, and G. Wagnieres, J. Biomed. Opt. 6, 41 (2001).
[CrossRef] [PubMed]

S. Koljenovic, T. C. Bakker Schut, J. P. van Meerbeeck, A. P. Maat, S. A. Burgers, P. E. Zondervan, J. M. Kros, and G. J. Puppels, J. Biomed. Opt. 9, 1187 (2004).
[CrossRef] [PubMed]

J. Thorac. Cardiovasc. Surg.

S. Lam, C. MacAulay, J. Hung, J. C. LeRiche, A. E. Profio, and B. Palcic, J. Thorac. Cardiovasc. Surg. 105, 1035 (1993).
[PubMed]

Opt. Lett.

Phys. Med. Biol.

E. B. Hanlon, R. Manoharan, T.-W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Med. Biol. 45, R1 (2000).
[CrossRef] [PubMed]

Skin Res. Technol.

J. Zhao, H. Lui, D. I. McLean, and H. Zeng, “Integrated real-time Raman system for clinical in vivo skin analysis,” Skin Res. Technol. (to be published).
[PubMed]

Other

M. Chaplin, “Water structure and science,” http://www.lsbu.ac.uk/water/vibrat.html.

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Figures (2)

Fig. 1
Fig. 1

Schematic showing the Raman system (not to scale) with magnified views of the fiber tips. ⋆ indicates the location of 50 μ m diameter fiber used to calibrate the spectrometer.

Fig. 2
Fig. 2

In vivo spectra of human lung tissue with different pathologies taken with the HF grating ( 2 s integration). A (main graph), smoothed raw data (shifted along y axis for clarity). Top to bottom order: SCC, CIS, moderate dysplasia, and normal tissue. A (inset), unprocessed raw data. B, extracted Raman spectra (intensity calibrated, normalized, and shifted along y axis for clarity) in same top to bottom order as A (main graph). The data above 3100 cm 1 have been scaled by 0.25.

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