Abstract

We have designed, fabricated, and tested a compact, transportable, excitation-emission spectrofluorimeter with optical-fiber light delivery and collection for use in rapid analysis of tissues in a clinical setting. This system provides up to eleven different excitation wavelengths, permitting collection of all the corresponding emission spectra in approximately 600 ms. It uses a N2 laser that pumps a sequence of dyes placed in cuvettes on a rotating wheel. A white-light excitation source permits acquisition of the tissue’s diffuse reflectance spectrum on each cycle. Return fluorescence and reflected light are dispersed by a small spectrograph and detected by a photodiode-array detector. The system can collect a single-shot spectrum from biological tissue with a signal-to-noise ratio in excess of 50:1.

© 1996 Optical Society of America

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    [CrossRef] [PubMed]
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  5. Y. Senga, S. Minami, “Excitation-emission matrix scanning spectrofluorometer,” Appl. Spectrosc. 45, 1721–1725 (1991).
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  7. T. A. Taylor, G. B. Jarvis, H. Xu, A. C. Bevilacqua, J. E. Kenny, “Laser-based fluorescence EEM instrument for in situ groundwater monitoring,” Anal. Instrum. 21, 141–162 (1993).
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  8. M. Forrer, T. Glanzmann, J. Mizeret, D. Braichotte, G. Wagnieres, H. van den Bergh, P. Jichlinski, H. J. Leisinger, “Fluorescence excitation and emission spectra of ALA induced protoporphyrin IX in normal and tumoral tissue of the human bladder,” in Optical Biopsy and Fluorescence Spectroscopy and Imaging, R. Cubeddu, R. Marchesini, S. R. Mordon, K. Svanberg, H. H. Rinneberg, G. Wagnieres, eds., Proc. SPIE2324, 84–88 (1995).
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    [CrossRef]
  10. J. A. Zuclich, T. Shimada, T. R. Loree, I. Bigio, K. Strobl, S. Nie, “Rapid noninvasive optical characterization of the human lens,” Lasers Life Sci. 6, 39–53 (1994).
  11. M. Keijzer, R. Richards-Kortum, S. L. Jacques, M. S. Feld, “Fluorescence spectroscopy of turbid media: autofluorescence of human aorta,” Appl. Opt. 28, 4286–4292 (1989).
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    [CrossRef]
  19. R. M. Cothren, G. B. Hayes, J. R. Kramer, B. Sacks, C. Kittrell, M. S. Feld, “A multifiber catheter with an optical shield for laser angiosurgery,” Lasers Life Sci. 1, 1–12 (1986).
  20. R. Richards-Kortum, N. B. Ratliff, J. R. Kramer, M. S. Feld, “Spectral diagnosis of atherosclerosis using an optical fiber catheter,” Am. Heart J. 118, 381–391 (1989).
    [CrossRef] [PubMed]
  21. J. F. Brennan, G. Zonios, T. D. Wang, R. P. Rava, G. B. Hayes, R. R. Dasari, M. S. Feld, “Portable laser spectrofluorimeter system for in vivo human tissue fluorescence studies,” Appl. Spectrosc. 47, 2081–2086 (1993).
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  24. J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, T. Shimada, “Spectroscopic diagnosis of bladder cancer with elastic light scattering,” Lasers Life Sci. 17, 350–357 (1995).
  25. S. R. Utz, Y. P. Sinichkin, I. V. Meglinsky, H. A. Pilienko, “Fluorescence spectroscopy in combination with reflectance measurements in human skin examination: what for and how,” in Optical Biopsy and Fluorescence Spectroscopy and Imaging, R. Cubeddu, R. Marchesini, S. R. Mordon, K. Svanberg, H. H. Rinneberg, G. Wagnieres, eds., Proc. SPIE2324, 125–136 (1994).
  26. M. J. Sorell, J. Tribble, L. Reinisch, J. A. Werkhaven, R. H. Ossof, “Bacteria identification of otitis media with fluorescence spectroscopy,” Lasers Surg. Med. 14, 155–163 (1994).
    [CrossRef]
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1996 (1)

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. Van Dam, J. M. Crawford, R. Manoharan, M. S. Feld, “Morphological model of human colon tissue fluorescence,” IEEE Trans. Biomed. Eng. 43, 113–122 (1996).
[CrossRef] [PubMed]

1995 (1)

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, T. Shimada, “Spectroscopic diagnosis of bladder cancer with elastic light scattering,” Lasers Life Sci. 17, 350–357 (1995).

1994 (2)

M. J. Sorell, J. Tribble, L. Reinisch, J. A. Werkhaven, R. H. Ossof, “Bacteria identification of otitis media with fluorescence spectroscopy,” Lasers Surg. Med. 14, 155–163 (1994).
[CrossRef]

J. A. Zuclich, T. Shimada, T. R. Loree, I. Bigio, K. Strobl, S. Nie, “Rapid noninvasive optical characterization of the human lens,” Lasers Life Sci. 6, 39–53 (1994).

1993 (4)

1992 (1)

Y. Oki, E. Tashiro, M. Maeda, “Automatic wide-range scanning and calibration over 220–740 nm using a dye laser with rapid cell exchanger,” Rev. Sci. Instrum. 63, 2927–2931 (1992).
[CrossRef]

1991 (1)

1989 (2)

R. Richards-Kortum, N. B. Ratliff, J. R. Kramer, M. S. Feld, “Spectral diagnosis of atherosclerosis using an optical fiber catheter,” Am. Heart J. 118, 381–391 (1989).
[CrossRef] [PubMed]

M. Keijzer, R. Richards-Kortum, S. L. Jacques, M. S. Feld, “Fluorescence spectroscopy of turbid media: autofluorescence of human aorta,” Appl. Opt. 28, 4286–4292 (1989).
[CrossRef] [PubMed]

1986 (1)

R. M. Cothren, G. B. Hayes, J. R. Kramer, B. Sacks, C. Kittrell, M. S. Feld, “A multifiber catheter with an optical shield for laser angiosurgery,” Lasers Life Sci. 1, 1–12 (1986).

1979 (1)

I. M. Warner, M. P. Fogarty, D. C. Shelly, “Design considerations for a two-dimensional rapid scanning fluorimeter,” Anal. Chim. Acta 109, 361–372 (1979).
[CrossRef]

1970 (1)

J. A. Myer, C. L. Johnson, E. Kierstead, R. D. Sharma, I. Itzkan, “Dye laser stimulation with a pulsed N2 laser line at 3371 Å,” Appl. Phys. Lett. 16, 3–5 (1970).
[CrossRef]

Arendt, J. T.

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. Van Dam, J. M. Crawford, R. Manoharan, M. S. Feld, “Morphological model of human colon tissue fluorescence,” IEEE Trans. Biomed. Eng. 43, 113–122 (1996).
[CrossRef] [PubMed]

Bevilacqua, A. C.

T. A. Taylor, G. B. Jarvis, H. Xu, A. C. Bevilacqua, J. E. Kenny, “Laser-based fluorescence EEM instrument for in situ groundwater monitoring,” Anal. Instrum. 21, 141–162 (1993).
[CrossRef]

Bigio, I.

J. A. Zuclich, T. Shimada, T. R. Loree, I. Bigio, K. Strobl, S. Nie, “Rapid noninvasive optical characterization of the human lens,” Lasers Life Sci. 6, 39–53 (1994).

Bigio, I. J.

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, T. Shimada, “Spectroscopic diagnosis of bladder cancer with elastic light scattering,” Lasers Life Sci. 17, 350–357 (1995).

I. J. Bigio, J. Boyer, T. M. Johnson, J. Lacey, J. R. Mourant, R. Conn, A. Bohorfousch, “Optical diagnostics based on elastic scattering: an update of clinical demonstrations with the optical biopsy system,” in Optical Biopsy and Fluorescence Spectroscopy and Imaging, R. Cubeddu, R. Marchesini, S. R. Mordon, K. Svanberg, H. H. Rinneberg, G. Wagnieres, eds., Proc. SPIE2324, 46–54 (1994).

Bohorfousch, A.

I. J. Bigio, J. Boyer, T. M. Johnson, J. Lacey, J. R. Mourant, R. Conn, A. Bohorfousch, “Optical diagnostics based on elastic scattering: an update of clinical demonstrations with the optical biopsy system,” in Optical Biopsy and Fluorescence Spectroscopy and Imaging, R. Cubeddu, R. Marchesini, S. R. Mordon, K. Svanberg, H. H. Rinneberg, G. Wagnieres, eds., Proc. SPIE2324, 46–54 (1994).

Boyer, J.

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, T. Shimada, “Spectroscopic diagnosis of bladder cancer with elastic light scattering,” Lasers Life Sci. 17, 350–357 (1995).

I. J. Bigio, J. Boyer, T. M. Johnson, J. Lacey, J. R. Mourant, R. Conn, A. Bohorfousch, “Optical diagnostics based on elastic scattering: an update of clinical demonstrations with the optical biopsy system,” in Optical Biopsy and Fluorescence Spectroscopy and Imaging, R. Cubeddu, R. Marchesini, S. R. Mordon, K. Svanberg, H. H. Rinneberg, G. Wagnieres, eds., Proc. SPIE2324, 46–54 (1994).

Braichotte, D.

M. Forrer, T. Glanzmann, J. Mizeret, D. Braichotte, G. Wagnieres, H. van den Bergh, P. Jichlinski, H. J. Leisinger, “Fluorescence excitation and emission spectra of ALA induced protoporphyrin IX in normal and tumoral tissue of the human bladder,” in Optical Biopsy and Fluorescence Spectroscopy and Imaging, R. Cubeddu, R. Marchesini, S. R. Mordon, K. Svanberg, H. H. Rinneberg, G. Wagnieres, eds., Proc. SPIE2324, 84–88 (1995).

Brennan, J. F.

Conn, R.

I. J. Bigio, J. Boyer, T. M. Johnson, J. Lacey, J. R. Mourant, R. Conn, A. Bohorfousch, “Optical diagnostics based on elastic scattering: an update of clinical demonstrations with the optical biopsy system,” in Optical Biopsy and Fluorescence Spectroscopy and Imaging, R. Cubeddu, R. Marchesini, S. R. Mordon, K. Svanberg, H. H. Rinneberg, G. Wagnieres, eds., Proc. SPIE2324, 46–54 (1994).

Conn, R. L.

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, T. Shimada, “Spectroscopic diagnosis of bladder cancer with elastic light scattering,” Lasers Life Sci. 17, 350–357 (1995).

Cothren, R. M.

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. Van Dam, J. M. Crawford, R. Manoharan, M. S. Feld, “Morphological model of human colon tissue fluorescence,” IEEE Trans. Biomed. Eng. 43, 113–122 (1996).
[CrossRef] [PubMed]

R. M. Cothren, G. B. Hayes, J. R. Kramer, B. Sacks, C. Kittrell, M. S. Feld, “A multifiber catheter with an optical shield for laser angiosurgery,” Lasers Life Sci. 1, 1–12 (1986).

Crawford, J. M.

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. Van Dam, J. M. Crawford, R. Manoharan, M. S. Feld, “Morphological model of human colon tissue fluorescence,” IEEE Trans. Biomed. Eng. 43, 113–122 (1996).
[CrossRef] [PubMed]

Dasari, R. R.

Destrampe, K. A.

Duarte, F. J.

F. J. Duarte, L. W. Hillman, Dye Laser Principles (Academic, San Diego, Calif., 1990), p. 17.

Feld, M. S.

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. Van Dam, J. M. Crawford, R. Manoharan, M. S. Feld, “Morphological model of human colon tissue fluorescence,” IEEE Trans. Biomed. Eng. 43, 113–122 (1996).
[CrossRef] [PubMed]

J. F. Brennan, G. Zonios, T. D. Wang, R. P. Rava, G. B. Hayes, R. R. Dasari, M. S. Feld, “Portable laser spectrofluorimeter system for in vivo human tissue fluorescence studies,” Appl. Spectrosc. 47, 2081–2086 (1993).
[CrossRef]

J. Wu, M. S. Feld, P. Rava, “Analytical model for extracting intrinsic fluorescence in turbid media,” Appl. Opt. 32, 3585–3595 (1993).
[CrossRef] [PubMed]

M. Keijzer, R. Richards-Kortum, S. L. Jacques, M. S. Feld, “Fluorescence spectroscopy of turbid media: autofluorescence of human aorta,” Appl. Opt. 28, 4286–4292 (1989).
[CrossRef] [PubMed]

R. Richards-Kortum, N. B. Ratliff, J. R. Kramer, M. S. Feld, “Spectral diagnosis of atherosclerosis using an optical fiber catheter,” Am. Heart J. 118, 381–391 (1989).
[CrossRef] [PubMed]

R. M. Cothren, G. B. Hayes, J. R. Kramer, B. Sacks, C. Kittrell, M. S. Feld, “A multifiber catheter with an optical shield for laser angiosurgery,” Lasers Life Sci. 1, 1–12 (1986).

Fogarty, M. P.

I. M. Warner, M. P. Fogarty, D. C. Shelly, “Design considerations for a two-dimensional rapid scanning fluorimeter,” Anal. Chim. Acta 109, 361–372 (1979).
[CrossRef]

Forrer, M.

M. Forrer, T. Glanzmann, J. Mizeret, D. Braichotte, G. Wagnieres, H. van den Bergh, P. Jichlinski, H. J. Leisinger, “Fluorescence excitation and emission spectra of ALA induced protoporphyrin IX in normal and tumoral tissue of the human bladder,” in Optical Biopsy and Fluorescence Spectroscopy and Imaging, R. Cubeddu, R. Marchesini, S. R. Mordon, K. Svanberg, H. H. Rinneberg, G. Wagnieres, eds., Proc. SPIE2324, 84–88 (1995).

Glanzmann, T.

M. Forrer, T. Glanzmann, J. Mizeret, D. Braichotte, G. Wagnieres, H. van den Bergh, P. Jichlinski, H. J. Leisinger, “Fluorescence excitation and emission spectra of ALA induced protoporphyrin IX in normal and tumoral tissue of the human bladder,” in Optical Biopsy and Fluorescence Spectroscopy and Imaging, R. Cubeddu, R. Marchesini, S. R. Mordon, K. Svanberg, H. H. Rinneberg, G. Wagnieres, eds., Proc. SPIE2324, 84–88 (1995).

Hayes, G. B.

J. F. Brennan, G. Zonios, T. D. Wang, R. P. Rava, G. B. Hayes, R. R. Dasari, M. S. Feld, “Portable laser spectrofluorimeter system for in vivo human tissue fluorescence studies,” Appl. Spectrosc. 47, 2081–2086 (1993).
[CrossRef]

R. M. Cothren, G. B. Hayes, J. R. Kramer, B. Sacks, C. Kittrell, M. S. Feld, “A multifiber catheter with an optical shield for laser angiosurgery,” Lasers Life Sci. 1, 1–12 (1986).

Hieftje, G. M.

Hillman, L. W.

F. J. Duarte, L. W. Hillman, Dye Laser Principles (Academic, San Diego, Calif., 1990), p. 17.

Itzkan, I.

J. A. Myer, C. L. Johnson, E. Kierstead, R. D. Sharma, I. Itzkan, “Dye laser stimulation with a pulsed N2 laser line at 3371 Å,” Appl. Phys. Lett. 16, 3–5 (1970).
[CrossRef]

Jacques, S. L.

Jarvis, G. B.

T. A. Taylor, G. B. Jarvis, H. Xu, A. C. Bevilacqua, J. E. Kenny, “Laser-based fluorescence EEM instrument for in situ groundwater monitoring,” Anal. Instrum. 21, 141–162 (1993).
[CrossRef]

Jichlinski, P.

M. Forrer, T. Glanzmann, J. Mizeret, D. Braichotte, G. Wagnieres, H. van den Bergh, P. Jichlinski, H. J. Leisinger, “Fluorescence excitation and emission spectra of ALA induced protoporphyrin IX in normal and tumoral tissue of the human bladder,” in Optical Biopsy and Fluorescence Spectroscopy and Imaging, R. Cubeddu, R. Marchesini, S. R. Mordon, K. Svanberg, H. H. Rinneberg, G. Wagnieres, eds., Proc. SPIE2324, 84–88 (1995).

Johnson, C. L.

J. A. Myer, C. L. Johnson, E. Kierstead, R. D. Sharma, I. Itzkan, “Dye laser stimulation with a pulsed N2 laser line at 3371 Å,” Appl. Phys. Lett. 16, 3–5 (1970).
[CrossRef]

Johnson, T.

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, T. Shimada, “Spectroscopic diagnosis of bladder cancer with elastic light scattering,” Lasers Life Sci. 17, 350–357 (1995).

Johnson, T. M.

I. J. Bigio, J. Boyer, T. M. Johnson, J. Lacey, J. R. Mourant, R. Conn, A. Bohorfousch, “Optical diagnostics based on elastic scattering: an update of clinical demonstrations with the optical biopsy system,” in Optical Biopsy and Fluorescence Spectroscopy and Imaging, R. Cubeddu, R. Marchesini, S. R. Mordon, K. Svanberg, H. H. Rinneberg, G. Wagnieres, eds., Proc. SPIE2324, 46–54 (1994).

Keijzer, M.

Kenny, J. E.

T. A. Taylor, G. B. Jarvis, H. Xu, A. C. Bevilacqua, J. E. Kenny, “Laser-based fluorescence EEM instrument for in situ groundwater monitoring,” Anal. Instrum. 21, 141–162 (1993).
[CrossRef]

Kierstead, E.

J. A. Myer, C. L. Johnson, E. Kierstead, R. D. Sharma, I. Itzkan, “Dye laser stimulation with a pulsed N2 laser line at 3371 Å,” Appl. Phys. Lett. 16, 3–5 (1970).
[CrossRef]

Kittrell, C.

R. M. Cothren, G. B. Hayes, J. R. Kramer, B. Sacks, C. Kittrell, M. S. Feld, “A multifiber catheter with an optical shield for laser angiosurgery,” Lasers Life Sci. 1, 1–12 (1986).

Kramer, J. R.

R. Richards-Kortum, N. B. Ratliff, J. R. Kramer, M. S. Feld, “Spectral diagnosis of atherosclerosis using an optical fiber catheter,” Am. Heart J. 118, 381–391 (1989).
[CrossRef] [PubMed]

R. M. Cothren, G. B. Hayes, J. R. Kramer, B. Sacks, C. Kittrell, M. S. Feld, “A multifiber catheter with an optical shield for laser angiosurgery,” Lasers Life Sci. 1, 1–12 (1986).

Lacey, J.

I. J. Bigio, J. Boyer, T. M. Johnson, J. Lacey, J. R. Mourant, R. Conn, A. Bohorfousch, “Optical diagnostics based on elastic scattering: an update of clinical demonstrations with the optical biopsy system,” in Optical Biopsy and Fluorescence Spectroscopy and Imaging, R. Cubeddu, R. Marchesini, S. R. Mordon, K. Svanberg, H. H. Rinneberg, G. Wagnieres, eds., Proc. SPIE2324, 46–54 (1994).

Leisinger, H. J.

M. Forrer, T. Glanzmann, J. Mizeret, D. Braichotte, G. Wagnieres, H. van den Bergh, P. Jichlinski, H. J. Leisinger, “Fluorescence excitation and emission spectra of ALA induced protoporphyrin IX in normal and tumoral tissue of the human bladder,” in Optical Biopsy and Fluorescence Spectroscopy and Imaging, R. Cubeddu, R. Marchesini, S. R. Mordon, K. Svanberg, H. H. Rinneberg, G. Wagnieres, eds., Proc. SPIE2324, 84–88 (1995).

Loree, T. R.

J. A. Zuclich, T. Shimada, T. R. Loree, I. Bigio, K. Strobl, S. Nie, “Rapid noninvasive optical characterization of the human lens,” Lasers Life Sci. 6, 39–53 (1994).

Maeda, M.

Y. Oki, E. Tashiro, M. Maeda, “Automatic wide-range scanning and calibration over 220–740 nm using a dye laser with rapid cell exchanger,” Rev. Sci. Instrum. 63, 2927–2931 (1992).
[CrossRef]

Manoharan, R.

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. Van Dam, J. M. Crawford, R. Manoharan, M. S. Feld, “Morphological model of human colon tissue fluorescence,” IEEE Trans. Biomed. Eng. 43, 113–122 (1996).
[CrossRef] [PubMed]

Meglinsky, I. V.

S. R. Utz, Y. P. Sinichkin, I. V. Meglinsky, H. A. Pilienko, “Fluorescence spectroscopy in combination with reflectance measurements in human skin examination: what for and how,” in Optical Biopsy and Fluorescence Spectroscopy and Imaging, R. Cubeddu, R. Marchesini, S. R. Mordon, K. Svanberg, H. H. Rinneberg, G. Wagnieres, eds., Proc. SPIE2324, 125–136 (1994).

Minami, S.

Mizeret, J.

M. Forrer, T. Glanzmann, J. Mizeret, D. Braichotte, G. Wagnieres, H. van den Bergh, P. Jichlinski, H. J. Leisinger, “Fluorescence excitation and emission spectra of ALA induced protoporphyrin IX in normal and tumoral tissue of the human bladder,” in Optical Biopsy and Fluorescence Spectroscopy and Imaging, R. Cubeddu, R. Marchesini, S. R. Mordon, K. Svanberg, H. H. Rinneberg, G. Wagnieres, eds., Proc. SPIE2324, 84–88 (1995).

Mourant, J. R.

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, T. Shimada, “Spectroscopic diagnosis of bladder cancer with elastic light scattering,” Lasers Life Sci. 17, 350–357 (1995).

I. J. Bigio, J. Boyer, T. M. Johnson, J. Lacey, J. R. Mourant, R. Conn, A. Bohorfousch, “Optical diagnostics based on elastic scattering: an update of clinical demonstrations with the optical biopsy system,” in Optical Biopsy and Fluorescence Spectroscopy and Imaging, R. Cubeddu, R. Marchesini, S. R. Mordon, K. Svanberg, H. H. Rinneberg, G. Wagnieres, eds., Proc. SPIE2324, 46–54 (1994).

Myer, J. A.

J. A. Myer, C. L. Johnson, E. Kierstead, R. D. Sharma, I. Itzkan, “Dye laser stimulation with a pulsed N2 laser line at 3371 Å,” Appl. Phys. Lett. 16, 3–5 (1970).
[CrossRef]

Nelson, W. H.

W. H. Nelson, Instrumental Methods for Rapid Microbiological Analysis (VCH, New York, 1985), Chap. 1, p. 1.

Nie, S.

J. A. Zuclich, T. Shimada, T. R. Loree, I. Bigio, K. Strobl, S. Nie, “Rapid noninvasive optical characterization of the human lens,” Lasers Life Sci. 6, 39–53 (1994).

Oki, Y.

Y. Oki, E. Tashiro, M. Maeda, “Automatic wide-range scanning and calibration over 220–740 nm using a dye laser with rapid cell exchanger,” Rev. Sci. Instrum. 63, 2927–2931 (1992).
[CrossRef]

Ossof, R. H.

M. J. Sorell, J. Tribble, L. Reinisch, J. A. Werkhaven, R. H. Ossof, “Bacteria identification of otitis media with fluorescence spectroscopy,” Lasers Surg. Med. 14, 155–163 (1994).
[CrossRef]

Pilienko, H. A.

S. R. Utz, Y. P. Sinichkin, I. V. Meglinsky, H. A. Pilienko, “Fluorescence spectroscopy in combination with reflectance measurements in human skin examination: what for and how,” in Optical Biopsy and Fluorescence Spectroscopy and Imaging, R. Cubeddu, R. Marchesini, S. R. Mordon, K. Svanberg, H. H. Rinneberg, G. Wagnieres, eds., Proc. SPIE2324, 125–136 (1994).

Ratliff, N. B.

R. Richards-Kortum, N. B. Ratliff, J. R. Kramer, M. S. Feld, “Spectral diagnosis of atherosclerosis using an optical fiber catheter,” Am. Heart J. 118, 381–391 (1989).
[CrossRef] [PubMed]

Rava, P.

Rava, R. P.

Reinisch, L.

M. J. Sorell, J. Tribble, L. Reinisch, J. A. Werkhaven, R. H. Ossof, “Bacteria identification of otitis media with fluorescence spectroscopy,” Lasers Surg. Med. 14, 155–163 (1994).
[CrossRef]

Richards-Kortum, R.

M. Keijzer, R. Richards-Kortum, S. L. Jacques, M. S. Feld, “Fluorescence spectroscopy of turbid media: autofluorescence of human aorta,” Appl. Opt. 28, 4286–4292 (1989).
[CrossRef] [PubMed]

R. Richards-Kortum, N. B. Ratliff, J. R. Kramer, M. S. Feld, “Spectral diagnosis of atherosclerosis using an optical fiber catheter,” Am. Heart J. 118, 381–391 (1989).
[CrossRef] [PubMed]

R. Richards-Kortum, “Fluorescence spectroscopy as a technique for diagnosis of pathologic conditions in human arterial, urinary bladder, and gastro-intestinal tissues,” Ph.D. dissertation (MIT, Cambridge, Mass., 1990).

Sacks, B.

R. M. Cothren, G. B. Hayes, J. R. Kramer, B. Sacks, C. Kittrell, M. S. Feld, “A multifiber catheter with an optical shield for laser angiosurgery,” Lasers Life Sci. 1, 1–12 (1986).

Schafer, F. P.

F. P. Schafer, Dye Lasers, 3rd ed., Vol. 1 of Topics in Applied Physics (Springer-Verlag, Berlin, 1977), p. 31.

Senga, Y.

Sharma, R. D.

J. A. Myer, C. L. Johnson, E. Kierstead, R. D. Sharma, I. Itzkan, “Dye laser stimulation with a pulsed N2 laser line at 3371 Å,” Appl. Phys. Lett. 16, 3–5 (1970).
[CrossRef]

Shelly, D. C.

I. M. Warner, M. P. Fogarty, D. C. Shelly, “Design considerations for a two-dimensional rapid scanning fluorimeter,” Anal. Chim. Acta 109, 361–372 (1979).
[CrossRef]

Shimada, T.

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, T. Shimada, “Spectroscopic diagnosis of bladder cancer with elastic light scattering,” Lasers Life Sci. 17, 350–357 (1995).

J. A. Zuclich, T. Shimada, T. R. Loree, I. Bigio, K. Strobl, S. Nie, “Rapid noninvasive optical characterization of the human lens,” Lasers Life Sci. 6, 39–53 (1994).

Sinichkin, Y. P.

S. R. Utz, Y. P. Sinichkin, I. V. Meglinsky, H. A. Pilienko, “Fluorescence spectroscopy in combination with reflectance measurements in human skin examination: what for and how,” in Optical Biopsy and Fluorescence Spectroscopy and Imaging, R. Cubeddu, R. Marchesini, S. R. Mordon, K. Svanberg, H. H. Rinneberg, G. Wagnieres, eds., Proc. SPIE2324, 125–136 (1994).

Sorell, M. J.

M. J. Sorell, J. Tribble, L. Reinisch, J. A. Werkhaven, R. H. Ossof, “Bacteria identification of otitis media with fluorescence spectroscopy,” Lasers Surg. Med. 14, 155–163 (1994).
[CrossRef]

Strobl, K.

J. A. Zuclich, T. Shimada, T. R. Loree, I. Bigio, K. Strobl, S. Nie, “Rapid noninvasive optical characterization of the human lens,” Lasers Life Sci. 6, 39–53 (1994).

Tashiro, E.

Y. Oki, E. Tashiro, M. Maeda, “Automatic wide-range scanning and calibration over 220–740 nm using a dye laser with rapid cell exchanger,” Rev. Sci. Instrum. 63, 2927–2931 (1992).
[CrossRef]

Taylor, T. A.

T. A. Taylor, G. B. Jarvis, H. Xu, A. C. Bevilacqua, J. E. Kenny, “Laser-based fluorescence EEM instrument for in situ groundwater monitoring,” Anal. Instrum. 21, 141–162 (1993).
[CrossRef]

Tribble, J.

M. J. Sorell, J. Tribble, L. Reinisch, J. A. Werkhaven, R. H. Ossof, “Bacteria identification of otitis media with fluorescence spectroscopy,” Lasers Surg. Med. 14, 155–163 (1994).
[CrossRef]

Utz, S. R.

S. R. Utz, Y. P. Sinichkin, I. V. Meglinsky, H. A. Pilienko, “Fluorescence spectroscopy in combination with reflectance measurements in human skin examination: what for and how,” in Optical Biopsy and Fluorescence Spectroscopy and Imaging, R. Cubeddu, R. Marchesini, S. R. Mordon, K. Svanberg, H. H. Rinneberg, G. Wagnieres, eds., Proc. SPIE2324, 125–136 (1994).

van Assendelft, O. W.

O. W. van Assendelft, Spectrophotometry of Haemoglobin Derivatives (C.C. Thomas, Springfield, Ill., 1970).

Van Dam, J.

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. Van Dam, J. M. Crawford, R. Manoharan, M. S. Feld, “Morphological model of human colon tissue fluorescence,” IEEE Trans. Biomed. Eng. 43, 113–122 (1996).
[CrossRef] [PubMed]

van den Bergh, H.

M. Forrer, T. Glanzmann, J. Mizeret, D. Braichotte, G. Wagnieres, H. van den Bergh, P. Jichlinski, H. J. Leisinger, “Fluorescence excitation and emission spectra of ALA induced protoporphyrin IX in normal and tumoral tissue of the human bladder,” in Optical Biopsy and Fluorescence Spectroscopy and Imaging, R. Cubeddu, R. Marchesini, S. R. Mordon, K. Svanberg, H. H. Rinneberg, G. Wagnieres, eds., Proc. SPIE2324, 84–88 (1995).

Wagnieres, G.

M. Forrer, T. Glanzmann, J. Mizeret, D. Braichotte, G. Wagnieres, H. van den Bergh, P. Jichlinski, H. J. Leisinger, “Fluorescence excitation and emission spectra of ALA induced protoporphyrin IX in normal and tumoral tissue of the human bladder,” in Optical Biopsy and Fluorescence Spectroscopy and Imaging, R. Cubeddu, R. Marchesini, S. R. Mordon, K. Svanberg, H. H. Rinneberg, G. Wagnieres, eds., Proc. SPIE2324, 84–88 (1995).

Wang, T. D.

Warner, I. M.

I. M. Warner, M. P. Fogarty, D. C. Shelly, “Design considerations for a two-dimensional rapid scanning fluorimeter,” Anal. Chim. Acta 109, 361–372 (1979).
[CrossRef]

Werkhaven, J. A.

M. J. Sorell, J. Tribble, L. Reinisch, J. A. Werkhaven, R. H. Ossof, “Bacteria identification of otitis media with fluorescence spectroscopy,” Lasers Surg. Med. 14, 155–163 (1994).
[CrossRef]

Wu, J.

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. Van Dam, J. M. Crawford, R. Manoharan, M. S. Feld, “Morphological model of human colon tissue fluorescence,” IEEE Trans. Biomed. Eng. 43, 113–122 (1996).
[CrossRef] [PubMed]

J. Wu, M. S. Feld, P. Rava, “Analytical model for extracting intrinsic fluorescence in turbid media,” Appl. Opt. 32, 3585–3595 (1993).
[CrossRef] [PubMed]

Xu, H.

T. A. Taylor, G. B. Jarvis, H. Xu, A. C. Bevilacqua, J. E. Kenny, “Laser-based fluorescence EEM instrument for in situ groundwater monitoring,” Anal. Instrum. 21, 141–162 (1993).
[CrossRef]

Zonios, G.

Zonios, G. I.

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. Van Dam, J. M. Crawford, R. Manoharan, M. S. Feld, “Morphological model of human colon tissue fluorescence,” IEEE Trans. Biomed. Eng. 43, 113–122 (1996).
[CrossRef] [PubMed]

Zuclich, J. A.

J. A. Zuclich, T. Shimada, T. R. Loree, I. Bigio, K. Strobl, S. Nie, “Rapid noninvasive optical characterization of the human lens,” Lasers Life Sci. 6, 39–53 (1994).

Am. Heart J. (1)

R. Richards-Kortum, N. B. Ratliff, J. R. Kramer, M. S. Feld, “Spectral diagnosis of atherosclerosis using an optical fiber catheter,” Am. Heart J. 118, 381–391 (1989).
[CrossRef] [PubMed]

Anal. Chim. Acta (1)

I. M. Warner, M. P. Fogarty, D. C. Shelly, “Design considerations for a two-dimensional rapid scanning fluorimeter,” Anal. Chim. Acta 109, 361–372 (1979).
[CrossRef]

Anal. Instrum. (1)

T. A. Taylor, G. B. Jarvis, H. Xu, A. C. Bevilacqua, J. E. Kenny, “Laser-based fluorescence EEM instrument for in situ groundwater monitoring,” Anal. Instrum. 21, 141–162 (1993).
[CrossRef]

Appl. Opt. (2)

Appl. Phys. Lett. (1)

J. A. Myer, C. L. Johnson, E. Kierstead, R. D. Sharma, I. Itzkan, “Dye laser stimulation with a pulsed N2 laser line at 3371 Å,” Appl. Phys. Lett. 16, 3–5 (1970).
[CrossRef]

Appl. Spectrosc. (3)

IEEE Trans. Biomed. Eng. (1)

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. Van Dam, J. M. Crawford, R. Manoharan, M. S. Feld, “Morphological model of human colon tissue fluorescence,” IEEE Trans. Biomed. Eng. 43, 113–122 (1996).
[CrossRef] [PubMed]

Lasers Life Sci. (3)

R. M. Cothren, G. B. Hayes, J. R. Kramer, B. Sacks, C. Kittrell, M. S. Feld, “A multifiber catheter with an optical shield for laser angiosurgery,” Lasers Life Sci. 1, 1–12 (1986).

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, T. Shimada, “Spectroscopic diagnosis of bladder cancer with elastic light scattering,” Lasers Life Sci. 17, 350–357 (1995).

J. A. Zuclich, T. Shimada, T. R. Loree, I. Bigio, K. Strobl, S. Nie, “Rapid noninvasive optical characterization of the human lens,” Lasers Life Sci. 6, 39–53 (1994).

Lasers Surg. Med. (1)

M. J. Sorell, J. Tribble, L. Reinisch, J. A. Werkhaven, R. H. Ossof, “Bacteria identification of otitis media with fluorescence spectroscopy,” Lasers Surg. Med. 14, 155–163 (1994).
[CrossRef]

Rev. Sci. Instrum. (1)

Y. Oki, E. Tashiro, M. Maeda, “Automatic wide-range scanning and calibration over 220–740 nm using a dye laser with rapid cell exchanger,” Rev. Sci. Instrum. 63, 2927–2931 (1992).
[CrossRef]

Other (12)

W. H. Nelson, Instrumental Methods for Rapid Microbiological Analysis (VCH, New York, 1985), Chap. 1, p. 1.

M. Forrer, T. Glanzmann, J. Mizeret, D. Braichotte, G. Wagnieres, H. van den Bergh, P. Jichlinski, H. J. Leisinger, “Fluorescence excitation and emission spectra of ALA induced protoporphyrin IX in normal and tumoral tissue of the human bladder,” in Optical Biopsy and Fluorescence Spectroscopy and Imaging, R. Cubeddu, R. Marchesini, S. R. Mordon, K. Svanberg, H. H. Rinneberg, G. Wagnieres, eds., Proc. SPIE2324, 84–88 (1995).

R. Richards-Kortum, “Fluorescence spectroscopy as a technique for diagnosis of pathologic conditions in human arterial, urinary bladder, and gastro-intestinal tissues,” Ph.D. dissertation (MIT, Cambridge, Mass., 1990).

O. W. van Assendelft, Spectrophotometry of Haemoglobin Derivatives (C.C. Thomas, Springfield, Ill., 1970).

I. J. Bigio, J. Boyer, T. M. Johnson, J. Lacey, J. R. Mourant, R. Conn, A. Bohorfousch, “Optical diagnostics based on elastic scattering: an update of clinical demonstrations with the optical biopsy system,” in Optical Biopsy and Fluorescence Spectroscopy and Imaging, R. Cubeddu, R. Marchesini, S. R. Mordon, K. Svanberg, H. H. Rinneberg, G. Wagnieres, eds., Proc. SPIE2324, 46–54 (1994).

Photomultiplier Tubes, Principles & Applications (Phillips Photonics, Slaterville, R.I., 1994).

Oriel Corp. Catalog, Vol. II (Oriel Corp., Stratford, Conn., 1994).

Exciton Chemical Company Catalog (Exciton Chemical Company, Overlock Station, Dayton, Ohio1995).

F. P. Schafer, Dye Lasers, 3rd ed., Vol. 1 of Topics in Applied Physics (Springer-Verlag, Berlin, 1977), p. 31.

F. J. Duarte, L. W. Hillman, Dye Laser Principles (Academic, San Diego, Calif., 1990), p. 17.

Phosphors Data Sheet (Princeton Applied Research, Princeton, N.J., 1994).

S. R. Utz, Y. P. Sinichkin, I. V. Meglinsky, H. A. Pilienko, “Fluorescence spectroscopy in combination with reflectance measurements in human skin examination: what for and how,” in Optical Biopsy and Fluorescence Spectroscopy and Imaging, R. Cubeddu, R. Marchesini, S. R. Mordon, K. Svanberg, H. H. Rinneberg, G. Wagnieres, eds., Proc. SPIE2324, 125–136 (1994).

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Figures (7)

Fig. 1
Fig. 1

Block diagram of the fast-EEM system. L1, L2, L3, L4, lenses; M1, M2, mirrors; TRIG, trigger source.

Fig. 2
Fig. 2

Geometry of the pumping configuration.

Fig. 3
Fig. 3

Relative output intensities and excitation bandwidth for various dyes used in the fast-EEM system.

Fig. 4
Fig. 4

EEM surface plots for a mixture of dye solutions (Rhodamine B, concentration 100 nM and Coumarin 450, concentration 100 nM, in ethanol). (a) Obtained with the fast-EEM system, 500 ms. (b) Obtained with commercial Spex spectrofluorimeters, 40 min.

Fig. 5
Fig. 5

In vivo EEM fluorescence contour map of a normal human colonic mucosal tissue site, measured during routine colonoscopy.

Fig. 6
Fig. 6

Diffuse reflectance spectrum of an in vivo sample of normal human colonic mucosa taken simultaneously at the same tissue location as the fluorescence data of Fig. 5. Tissue reflectance is normalized to the reflectance of a (20 g/20 m) BaSO4 water suspension (set to unity for all wavelengths).

Fig. 7
Fig. 7

In vivo fluorescence spectra of normal human colon tissue used to construct the EEM shown in Fig. 5. The spectral line shapes for 10 different excitation wavelengths are shown. Fluorescence intensity for various excitation wavelengths is normalized with a reference Rhodamine dye solution as described in the text.

Tables (1)

Tables Icon

Table 1 Characteristics of the Dyes Used in the Fast-EEM System

Equations (3)

Equations on this page are rendered with MathJax. Learn more.

E f = E out ( 1 - R ) 7 ( F 1 / F 2 ) 2 = 15.8 μ J .
E PDA = E f C T F E f G ( 1 - R ) 3 ( F 3 / F 5 ) 2 .
N = ( N S 2 + N R 2 + N D 2 ) 1 / 2 ,

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