Abstract

An angled fiber-optic probe that facilitates depth-sensitive fluorescence measurements was developed for enhancing detection of epithelial precancers. The probe was tested on solid, two-layered phantoms and proved to be effective in selectively detecting fluorescence from different layers. Specifically, a larger illumination angle provides greater sensitivity to fluorescence from the top layer as well as yielding an overall higher fluorescence signal. Monte Carlo simulations of a theoretical model of the phantoms demonstrate that increasing the illumination angle results in an increased excitation photon density and, thus, in increased fluorescence generated in the top layer.

© 2004 Optical Society of America

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  1. E. M. Gill, A. Malpica, R. E. Alford, A. R. Nath, M. Follen, R. R. Richards-Kortum, and N. Ramanujam, Photochem. Photobiol. 77, 653 (2003).
    [CrossRef] [PubMed]
  2. C. Brookner, U. Utzinger, M. Follen, R. Richards-Kortum, D. Cox, and E. N. Atkinson, J. Biomed. Opt. 8, 479 (2003).
    [CrossRef] [PubMed]
  3. I. Pavlova, K. Sokolov, R. Drezek, A. Malpica, M. Follen, and R. Richards-Kortum, Photochem. Photobiol. 77, 550 (2003).
    [CrossRef] [PubMed]
  4. R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, Photochem. Photobiol. 73, 636 (2001).
    [CrossRef] [PubMed]
  5. T. J. Pfefer, L. S. Matchette, A. M. Ross, and M. N. Ediger, Opt. Lett. 28, 120 (2003).
    [CrossRef] [PubMed]
  6. C. Zhu, Q. Liu, and N. Ramanujam, J. Biomed. Opt. 8, 237 (2003).
    [CrossRef] [PubMed]
  7. M. C. Skala, G. M. Palmer, C. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, and N. Ramanujam, Lasers Surg. Med. 34, 25 (2004).
    [CrossRef]
  8. R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, J. Biomed. Opt. 6, 385 (2001).
    [CrossRef] [PubMed]
  9. S. L. Jacques and L. Wang, in Optical–Thermal Response of Laser-Irradiated Tissue, A. J. Welch and M. J. C. van Gemert, eds. (Plenum, New York, 1995), pp. 73–100.
    [CrossRef]

2004

M. C. Skala, G. M. Palmer, C. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, and N. Ramanujam, Lasers Surg. Med. 34, 25 (2004).
[CrossRef]

2003

C. Zhu, Q. Liu, and N. Ramanujam, J. Biomed. Opt. 8, 237 (2003).
[CrossRef] [PubMed]

T. J. Pfefer, L. S. Matchette, A. M. Ross, and M. N. Ediger, Opt. Lett. 28, 120 (2003).
[CrossRef] [PubMed]

E. M. Gill, A. Malpica, R. E. Alford, A. R. Nath, M. Follen, R. R. Richards-Kortum, and N. Ramanujam, Photochem. Photobiol. 77, 653 (2003).
[CrossRef] [PubMed]

C. Brookner, U. Utzinger, M. Follen, R. Richards-Kortum, D. Cox, and E. N. Atkinson, J. Biomed. Opt. 8, 479 (2003).
[CrossRef] [PubMed]

I. Pavlova, K. Sokolov, R. Drezek, A. Malpica, M. Follen, and R. Richards-Kortum, Photochem. Photobiol. 77, 550 (2003).
[CrossRef] [PubMed]

2001

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, Photochem. Photobiol. 73, 636 (2001).
[CrossRef] [PubMed]

R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, J. Biomed. Opt. 6, 385 (2001).
[CrossRef] [PubMed]

1995

S. L. Jacques and L. Wang, in Optical–Thermal Response of Laser-Irradiated Tissue, A. J. Welch and M. J. C. van Gemert, eds. (Plenum, New York, 1995), pp. 73–100.
[CrossRef]

Alford, R. E.

E. M. Gill, A. Malpica, R. E. Alford, A. R. Nath, M. Follen, R. R. Richards-Kortum, and N. Ramanujam, Photochem. Photobiol. 77, 653 (2003).
[CrossRef] [PubMed]

Atkinson, E. N.

C. Brookner, U. Utzinger, M. Follen, R. Richards-Kortum, D. Cox, and E. N. Atkinson, J. Biomed. Opt. 8, 479 (2003).
[CrossRef] [PubMed]

Boiko, I.

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, Photochem. Photobiol. 73, 636 (2001).
[CrossRef] [PubMed]

R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, J. Biomed. Opt. 6, 385 (2001).
[CrossRef] [PubMed]

Brookner, C.

C. Brookner, U. Utzinger, M. Follen, R. Richards-Kortum, D. Cox, and E. N. Atkinson, J. Biomed. Opt. 8, 479 (2003).
[CrossRef] [PubMed]

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, Photochem. Photobiol. 73, 636 (2001).
[CrossRef] [PubMed]

Cox, D.

C. Brookner, U. Utzinger, M. Follen, R. Richards-Kortum, D. Cox, and E. N. Atkinson, J. Biomed. Opt. 8, 479 (2003).
[CrossRef] [PubMed]

Drezek, R.

I. Pavlova, K. Sokolov, R. Drezek, A. Malpica, M. Follen, and R. Richards-Kortum, Photochem. Photobiol. 77, 550 (2003).
[CrossRef] [PubMed]

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, Photochem. Photobiol. 73, 636 (2001).
[CrossRef] [PubMed]

R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, J. Biomed. Opt. 6, 385 (2001).
[CrossRef] [PubMed]

Ediger, M. N.

Follen, M.

I. Pavlova, K. Sokolov, R. Drezek, A. Malpica, M. Follen, and R. Richards-Kortum, Photochem. Photobiol. 77, 550 (2003).
[CrossRef] [PubMed]

E. M. Gill, A. Malpica, R. E. Alford, A. R. Nath, M. Follen, R. R. Richards-Kortum, and N. Ramanujam, Photochem. Photobiol. 77, 653 (2003).
[CrossRef] [PubMed]

C. Brookner, U. Utzinger, M. Follen, R. Richards-Kortum, D. Cox, and E. N. Atkinson, J. Biomed. Opt. 8, 479 (2003).
[CrossRef] [PubMed]

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, Photochem. Photobiol. 73, 636 (2001).
[CrossRef] [PubMed]

R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, J. Biomed. Opt. 6, 385 (2001).
[CrossRef] [PubMed]

Gendron-Fitzpatrick, A.

M. C. Skala, G. M. Palmer, C. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, and N. Ramanujam, Lasers Surg. Med. 34, 25 (2004).
[CrossRef]

Gill, E. M.

E. M. Gill, A. Malpica, R. E. Alford, A. R. Nath, M. Follen, R. R. Richards-Kortum, and N. Ramanujam, Photochem. Photobiol. 77, 653 (2003).
[CrossRef] [PubMed]

Jacques, S. L.

S. L. Jacques and L. Wang, in Optical–Thermal Response of Laser-Irradiated Tissue, A. J. Welch and M. J. C. van Gemert, eds. (Plenum, New York, 1995), pp. 73–100.
[CrossRef]

Liu, Q.

M. C. Skala, G. M. Palmer, C. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, and N. Ramanujam, Lasers Surg. Med. 34, 25 (2004).
[CrossRef]

C. Zhu, Q. Liu, and N. Ramanujam, J. Biomed. Opt. 8, 237 (2003).
[CrossRef] [PubMed]

Lotan, R.

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, Photochem. Photobiol. 73, 636 (2001).
[CrossRef] [PubMed]

Malpica, A.

E. M. Gill, A. Malpica, R. E. Alford, A. R. Nath, M. Follen, R. R. Richards-Kortum, and N. Ramanujam, Photochem. Photobiol. 77, 653 (2003).
[CrossRef] [PubMed]

I. Pavlova, K. Sokolov, R. Drezek, A. Malpica, M. Follen, and R. Richards-Kortum, Photochem. Photobiol. 77, 550 (2003).
[CrossRef] [PubMed]

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, Photochem. Photobiol. 73, 636 (2001).
[CrossRef] [PubMed]

R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, J. Biomed. Opt. 6, 385 (2001).
[CrossRef] [PubMed]

Marshek-Stone, C. L.

M. C. Skala, G. M. Palmer, C. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, and N. Ramanujam, Lasers Surg. Med. 34, 25 (2004).
[CrossRef]

Matchette, L. S.

Nath, A. R.

E. M. Gill, A. Malpica, R. E. Alford, A. R. Nath, M. Follen, R. R. Richards-Kortum, and N. Ramanujam, Photochem. Photobiol. 77, 653 (2003).
[CrossRef] [PubMed]

Palmer, G. M.

M. C. Skala, G. M. Palmer, C. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, and N. Ramanujam, Lasers Surg. Med. 34, 25 (2004).
[CrossRef]

Pavlova, I.

I. Pavlova, K. Sokolov, R. Drezek, A. Malpica, M. Follen, and R. Richards-Kortum, Photochem. Photobiol. 77, 550 (2003).
[CrossRef] [PubMed]

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, Photochem. Photobiol. 73, 636 (2001).
[CrossRef] [PubMed]

Pfefer, T. J.

Ramanujam, N.

M. C. Skala, G. M. Palmer, C. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, and N. Ramanujam, Lasers Surg. Med. 34, 25 (2004).
[CrossRef]

E. M. Gill, A. Malpica, R. E. Alford, A. R. Nath, M. Follen, R. R. Richards-Kortum, and N. Ramanujam, Photochem. Photobiol. 77, 653 (2003).
[CrossRef] [PubMed]

C. Zhu, Q. Liu, and N. Ramanujam, J. Biomed. Opt. 8, 237 (2003).
[CrossRef] [PubMed]

Richards-Kortum, R.

I. Pavlova, K. Sokolov, R. Drezek, A. Malpica, M. Follen, and R. Richards-Kortum, Photochem. Photobiol. 77, 550 (2003).
[CrossRef] [PubMed]

C. Brookner, U. Utzinger, M. Follen, R. Richards-Kortum, D. Cox, and E. N. Atkinson, J. Biomed. Opt. 8, 479 (2003).
[CrossRef] [PubMed]

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, Photochem. Photobiol. 73, 636 (2001).
[CrossRef] [PubMed]

R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, J. Biomed. Opt. 6, 385 (2001).
[CrossRef] [PubMed]

Richards-Kortum, R. R.

E. M. Gill, A. Malpica, R. E. Alford, A. R. Nath, M. Follen, R. R. Richards-Kortum, and N. Ramanujam, Photochem. Photobiol. 77, 653 (2003).
[CrossRef] [PubMed]

Ross, A. M.

Skala, M. C.

M. C. Skala, G. M. Palmer, C. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, and N. Ramanujam, Lasers Surg. Med. 34, 25 (2004).
[CrossRef]

Sokolov, K.

I. Pavlova, K. Sokolov, R. Drezek, A. Malpica, M. Follen, and R. Richards-Kortum, Photochem. Photobiol. 77, 550 (2003).
[CrossRef] [PubMed]

R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, J. Biomed. Opt. 6, 385 (2001).
[CrossRef] [PubMed]

Utzinger, U.

C. Brookner, U. Utzinger, M. Follen, R. Richards-Kortum, D. Cox, and E. N. Atkinson, J. Biomed. Opt. 8, 479 (2003).
[CrossRef] [PubMed]

R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, J. Biomed. Opt. 6, 385 (2001).
[CrossRef] [PubMed]

Vrotsos, K. M.

M. C. Skala, G. M. Palmer, C. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, and N. Ramanujam, Lasers Surg. Med. 34, 25 (2004).
[CrossRef]

Wang, L.

S. L. Jacques and L. Wang, in Optical–Thermal Response of Laser-Irradiated Tissue, A. J. Welch and M. J. C. van Gemert, eds. (Plenum, New York, 1995), pp. 73–100.
[CrossRef]

Zhu, C.

M. C. Skala, G. M. Palmer, C. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, and N. Ramanujam, Lasers Surg. Med. 34, 25 (2004).
[CrossRef]

C. Zhu, Q. Liu, and N. Ramanujam, J. Biomed. Opt. 8, 237 (2003).
[CrossRef] [PubMed]

J. Biomed. Opt.

C. Brookner, U. Utzinger, M. Follen, R. Richards-Kortum, D. Cox, and E. N. Atkinson, J. Biomed. Opt. 8, 479 (2003).
[CrossRef] [PubMed]

C. Zhu, Q. Liu, and N. Ramanujam, J. Biomed. Opt. 8, 237 (2003).
[CrossRef] [PubMed]

R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, J. Biomed. Opt. 6, 385 (2001).
[CrossRef] [PubMed]

Lasers Surg. Med.

M. C. Skala, G. M. Palmer, C. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, and N. Ramanujam, Lasers Surg. Med. 34, 25 (2004).
[CrossRef]

Opt. Lett.

Photochem. Photobiol.

E. M. Gill, A. Malpica, R. E. Alford, A. R. Nath, M. Follen, R. R. Richards-Kortum, and N. Ramanujam, Photochem. Photobiol. 77, 653 (2003).
[CrossRef] [PubMed]

I. Pavlova, K. Sokolov, R. Drezek, A. Malpica, M. Follen, and R. Richards-Kortum, Photochem. Photobiol. 77, 550 (2003).
[CrossRef] [PubMed]

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, Photochem. Photobiol. 73, 636 (2001).
[CrossRef] [PubMed]

Other

S. L. Jacques and L. Wang, in Optical–Thermal Response of Laser-Irradiated Tissue, A. J. Welch and M. J. C. van Gemert, eds. (Plenum, New York, 1995), pp. 73–100.
[CrossRef]

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Figures (3)

Fig. 1
Fig. 1

Fluorescence spectra measured from two-layered phantoms with top layer thicknesses of 300, 600, and 900 µm; c.u., calibrated units.

Fig. 2
Fig. 2

Ratio between peak intensities at 467 nm (NADH fluorescence in the top layer) and 580 nm (Rhodamine B fluorescence in the bottom layer) for top layer thicknesses of 300, 600, and 900 µm. Results are shown for two phantoms made according to the same recipe.

Fig. 3
Fig. 3

Simulated excitation fluence as a function of depth for top layer thicknesses of 300, 600, and 900 µm in a theoretical model of the two-layered phantom. Dashed lines indicate the interface between top and bottom layers.

Tables (1)

Tables Icon

Table 1 Values of μa [cm-1], μs [cm-1], and g (left to right) for the Top and Bottom Layers of the Two-Layered Phantom at the Excitation Wavelength and at the Peak Emission Wavelengths of NADH and Rhodamine B

Metrics