Abstract

Reflectance spectroscopy is a promising technology for detection of epithelial precancer. Fiber-optic probes that selectively collect scattered light from both the epithelium and the underlying stroma are likely to improve diagnostic performance of in vivo reflectance spectroscopy by revealing diagnostic features unique to each layer. We present Monte Carlo models with which to evaluate fiber-optic probe geometries with respect to sampling depth and depth resolution. We propose a probe design that utilizes half-ball lens coupled source and detector fibers to isolate epithelial scattering from stromal scattering and hence to resolve spectral information from the two layers. The probe is extremely compact and can provide easy access to different organ sites.

© 2005 Optical Society of America

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2005 (1)

2004 (9)

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. M. Harper, L. Burke, S. T. Sum, R. F. Flewelling, R. D. Alvarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of a 604-patient study,” Am. J. Obstet. Gynecol. 190, 1249–1257 (2004).
[CrossRef] [PubMed]

S. K. Chang, D. Arifler, R. Drezek, M. Follen, R. Richards-Kortum, “An analytical model to describe fluorescence spectra of normal and pre-neoplastic epithelial tissue: comparison with Monte Carlo simulations and clinical measurements,” J. Biomed. Opt. 9, 511–522 (2004).
[CrossRef] [PubMed]

M. C. Skala, G. M. Palmer, C. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, N. Ramanujam, “Investigation of fiber-optic probe designs for optical spectroscopic diagnosis of epithelial precancers,” Lasers Surg. Med. 34, 25–38 (2004).
[CrossRef]

J. T. Motz, M. Hunter, L. H. Galindo, J. A. Gardecki, J. R. Kramer, R. R. Dasari, M. S. Feld, “Optical fiber probe for biomedical Raman spectroscopy,” Appl. Opt. 43, 542–554 (2004).
[CrossRef] [PubMed]

L. Nieman, A. Myakov, J. Aaron, K. Sokolov, “Optical sectioning using a fiber probe with an angled illumination-collection geometry: evaluation in engineered tissue phantoms,” Appl. Opt. 43, 1308–1319 (2004).
[CrossRef] [PubMed]

A. Garcia-Uribe, N. Kehtarnavaz, G. Marquez, V. Prieto, M. Duvic, L. V. Wang, “Skin cancer detection by spectroscopic oblique-incidence reflectometry: classification and physiological origins,” Appl. Opt. 43, 2643–2650 (2004).
[CrossRef] [PubMed]

T. Papaioannou, N. W. Preyer, Q. Fang, A. Brightwell, M. Carnohan, G. Cottone, R. Ross, L. R. Jones, L. Marcu, “Effects of fiber-optic probe design and probe-to-target distance on diffuse reflectance measurements of turbid media: an experimental and computational study at 337 nm,” Appl. Opt. 43, 2846–2860 (2004).
[CrossRef] [PubMed]

A. Amelink, H. J. C. M. Sterenborg, “Measurement of the local optical properties of turbid media by differential path-length spectroscopy,” Appl. Opt. 43, 3048–3054 (2004).
[CrossRef] [PubMed]

Y. L. Kim, Y. Liu, V. M. Turzhitsky, H. K. Roy, R. K. Wali, V. Backman, “Coherent backscattering spectroscopy,” Opt. Lett. 29, 1906–1908 (2004).
[CrossRef] [PubMed]

2003 (10)

C. Zhu, Q. Liu, N. Ramanujam, “Effect of fiber optic probe geometry on depth-resolved fluorescence measurements from epithelial tissues: a Monte Carlo simulation,” J. Biomed. Opt. 8, 237–247 (2003).
[CrossRef] [PubMed]

T. Collier, D. Arifler, A. Malpica, M. Follen, R. Richards-Kortum, “Determination of epithelial tissue scattering coefficient using confocal microscopy,” IEEE J. Sel. Top. Quantum Electron. 9, 307–313 (2003).
[CrossRef]

D. C. Walker, B. H. Brown, A. D. Blackett, J. Tidy, R. H. Smallwood, “A study of the morphological parameters of cervical squamous epithelium,” Physiol. Meas. 24, 121–135 (2003).
[CrossRef] [PubMed]

U. Utzinger, R. Richards-Kortum, “Fiber optic probes for biomedical optical spectroscopy,” J. Biomed. Opt. 8, 121–147 (2003).
[CrossRef] [PubMed]

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. MacAulay, M. Follen, R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
[CrossRef] [PubMed]

D. Arifler, M. Guillaud, A. Carraro, A. Malpica, M. Follen, R. Richards-Kortum, “Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition,” J. Biomed. Opt. 8, 484–494 (2003).
[CrossRef] [PubMed]

M. G. Müller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, M. S. Feld, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer 97, 1681–1692 (2003).
[CrossRef] [PubMed]

I. Pavlova, K. Sokolov, R. Drezek, A. Malpica, M. Follen, R. Richards-Kortum, “Microanatomical and biochemical origins of normal and precancerous cervical autofluorescence using laser-scanning fluorescence confocal microscopy,” Photochem. Photobiol. 77, 550–555 (2003).
[CrossRef] [PubMed]

M. Larsson, H. Nilsson, T. Strömberg, “In vivo determination of local skin optical properties and photon path length by use of spatially resolved diffuse reflectance with applications in laser Doppler flowmetry,” Appl. Opt. 42, 124–134 (2003).
[CrossRef] [PubMed]

T. J. Pfefer, L. S. Matchette, A. M. Ross, M. N. Ediger, “Selective detection of fluorophore layers in turbid media: the role of fiber-optic probe design,” Opt. Lett. 28, 120–122 (2003).
[CrossRef] [PubMed]

2002 (5)

J. S. Lee, H. S. Kim, J. J. Jung, M. C. Lee, C. S. Park, “Angiogenesis, cell proliferation and apoptosis in progression of cervical neoplasia,” Anal. Quant. Cytol. Histol. 24, 103–113 (2002).
[PubMed]

M. Larsson, W. Steenbergen, T. Strömberg, “Influence of optical properties and fiber separation on laser Doppler flowmetry,” J. Biomed. Opt. 7, 236–243 (2002).
[CrossRef] [PubMed]

I. Georgakoudi, E. E. Sheets, M. G. Müller, V. Backman, C. P. Crum, K. Badizadegan, R. R. Dasari, M. S. Feld, “Trimodal spectroscopy for the detection and characterization of cervical precancers in vivo,” Am. J. Obstet. Gynecol. 186, 374–382 (2002).
[CrossRef] [PubMed]

Y. N. Mirabal, S. K. Chang, E. N. Atkinson, A. Malpica, M. Follen, R. Richards-Kortum, “Reflectance spectroscopy for in vivo detection of cervical precancer,” J. Biomed. Opt. 7, 587–594 (2002).
[CrossRef] [PubMed]

T. J. Pfefer, K. T. Schomacker, M. N. Ediger, N. S. Nishioka, “Multiple-fiber probe design for fluorescence spectroscopy in tissue,” Appl. Opt. 41, 4712–4721 (2002).
[CrossRef] [PubMed]

2001 (4)

I. V. Meglinskii, S. D. Matcher, “Analysis of the spatial distribution of detector sensitivity in a multilayer randomly inhomogeneous medium with strong light scattering and absorption by the Monte Carlo method,” Opt. Spectrosc. 91, 654–659 (2001).
[CrossRef]

T. P. Moffitt, S. A. Prahl, “Sized-fiber reflectometry for measuring local optical properties,” IEEE J. Sel. Top. Quantum Electron. 7, 952–958 (2001).
[CrossRef]

R. J. Nordstrom, L. Burke, J. M. Niloff, J. F. Myrtle, “Identification of cervical intraepithelial neoplasia (CIN) using UV-excited fluorescence and diffuse-reflectance tissue spectroscopy,” Lasers Surg. Med. 29, 118–127 (2001).
[CrossRef] [PubMed]

T. J. Pfefer, K. T. Schomacker, M. N. Ediger, N. S. Nishioka, “Light propagation in tissue during fluorescence spectroscopy with single-fiber probes,” IEEE J. Sel. Top. Quantum Electron. 7, 1004–1012 (2001).
[CrossRef]

2000 (2)

I. J. Bigio, S. G. Bown, G. Briggs, C. Kelley, S. Lakhani, D. Pickard, P. M. Ripley, I. G. Rose, C. Saunders, “Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results,” J. Biomed. Opt. 5, 221–228 (2000).
[CrossRef] [PubMed]

T. A. Winning, G. C. Townsend, “Oral mucosal embryology and histology,” Clin. Dermatol. 18, 499–511 (2000).
[CrossRef]

1999 (3)

1998 (1)

F. Koenig, R. Larne, H. Enquist, F. J. McGovern, K. T. Schomacker, N. Kollias, T. F. Deutsch, “Spectroscopic measurement of diffuse reflectance for enhanced detection of bladder carcinoma,” Urology 51, 342–345 (1998).
[CrossRef] [PubMed]

1997 (1)

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21, 166–178 (1997).
[CrossRef] [PubMed]

1996 (2)

P. Ravazoula, V. Zolota, O. Hatjicondi, G. Sakellaropoulos, G. Kourounis, M. E. Maragoudakis, “Assessment of angiogenesis in human cervical lesions,” Anticancer Res. 16, 3861–3864 (1996).
[PubMed]

K. J. Heppner, L. M. Matrisian, R. A. Jensen, W. H. Rodgers, “Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response,” Am. J. Pathol. 149, 273–282 (1996).

1995 (3)

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 Surg. Med. 17, 350–357 (1995).
[CrossRef] [PubMed]

L. Wang, S. L. Jacques, L. Zheng, “MCML—Monte Carlo modeling of light transport in multi-layered tissues,” Comput. Methods Programs Biomed. 47, 131–146 (1995).
[CrossRef] [PubMed]

M. S. Patterson, S. Andersson-Engels, B. C. Wilson, E. K. Osei, “Absorption spectroscopy in tissue-simulating materials: a theoretical and experimental study of photon paths,” Appl. Opt. 34, 22–30 (1995).
[CrossRef] [PubMed]

Aaron, J.

Alvarez, R. D.

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. M. Harper, L. Burke, S. T. Sum, R. F. Flewelling, R. D. Alvarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of a 604-patient study,” Am. J. Obstet. Gynecol. 190, 1249–1257 (2004).
[CrossRef] [PubMed]

Amelink, A.

Andersson-Engels, S.

Arifler, D.

R. A. Schwarz, D. Arifler, S. K. Chang, I. Pavlova, I. A. Hussain, V. Mack, B. Knight, A. M. Gillenwater, R. Richards-Kortum, “Ball lens coupled fiber-optic probe for depth-resolved spectroscopy of epithelial tissue,” Opt. Lett. 30, 1159–1161 (2005).

S. K. Chang, D. Arifler, R. Drezek, M. Follen, R. Richards-Kortum, “An analytical model to describe fluorescence spectra of normal and pre-neoplastic epithelial tissue: comparison with Monte Carlo simulations and clinical measurements,” J. Biomed. Opt. 9, 511–522 (2004).
[CrossRef] [PubMed]

D. Arifler, M. Guillaud, A. Carraro, A. Malpica, M. Follen, R. Richards-Kortum, “Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition,” J. Biomed. Opt. 8, 484–494 (2003).
[CrossRef] [PubMed]

T. Collier, D. Arifler, A. Malpica, M. Follen, R. Richards-Kortum, “Determination of epithelial tissue scattering coefficient using confocal microscopy,” IEEE J. Sel. Top. Quantum Electron. 9, 307–313 (2003).
[CrossRef]

Atkinson, E. N.

Y. N. Mirabal, S. K. Chang, E. N. Atkinson, A. Malpica, M. Follen, R. Richards-Kortum, “Reflectance spectroscopy for in vivo detection of cervical precancer,” J. Biomed. Opt. 7, 587–594 (2002).
[CrossRef] [PubMed]

Backman, V.

Y. L. Kim, Y. Liu, V. M. Turzhitsky, H. K. Roy, R. K. Wali, V. Backman, “Coherent backscattering spectroscopy,” Opt. Lett. 29, 1906–1908 (2004).
[CrossRef] [PubMed]

M. G. Müller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, M. S. Feld, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer 97, 1681–1692 (2003).
[CrossRef] [PubMed]

I. Georgakoudi, E. E. Sheets, M. G. Müller, V. Backman, C. P. Crum, K. Badizadegan, R. R. Dasari, M. S. Feld, “Trimodal spectroscopy for the detection and characterization of cervical precancers in vivo,” Am. J. Obstet. Gynecol. 186, 374–382 (2002).
[CrossRef] [PubMed]

G. Zonios, L. T. Perelman, V. Backman, R. Manoharan, M. Fitzmaurice, J. Van Dam, M. S. Feld, “Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo,” Appl. Opt. 38, 6628–6637 (1999).
[CrossRef]

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5, 1019–1026 (1999).
[CrossRef]

Badizadegan, K.

I. Georgakoudi, E. E. Sheets, M. G. Müller, V. Backman, C. P. Crum, K. Badizadegan, R. R. Dasari, M. S. Feld, “Trimodal spectroscopy for the detection and characterization of cervical precancers in vivo,” Am. J. Obstet. Gynecol. 186, 374–382 (2002).
[CrossRef] [PubMed]

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5, 1019–1026 (1999).
[CrossRef]

Bigio, I. J.

I. J. Bigio, S. G. Bown, G. Briggs, C. Kelley, S. Lakhani, D. Pickard, P. M. Ripley, I. G. Rose, C. Saunders, “Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results,” J. Biomed. Opt. 5, 221–228 (2000).
[CrossRef] [PubMed]

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 Surg. Med. 17, 350–357 (1995).
[CrossRef] [PubMed]

Blackett, A. D.

D. C. Walker, B. H. Brown, A. D. Blackett, J. Tidy, R. H. Smallwood, “A study of the morphological parameters of cervical squamous epithelium,” Physiol. Meas. 24, 121–135 (2003).
[CrossRef] [PubMed]

Boiko, I.

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. MacAulay, M. Follen, R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
[CrossRef] [PubMed]

Boone, C. W.

M. G. Müller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, M. S. Feld, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer 97, 1681–1692 (2003).
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R. M. Verdaasdonk, C. Borst, “Optics of fibers and fiber probes,” in Optical-Thermal Response of Laser-Irradiated Tissue, A. J. Welch, M. J. C. van Gemert, eds. (Plenum, 1995).
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I. J. Bigio, S. G. Bown, G. Briggs, C. Kelley, S. Lakhani, D. Pickard, P. M. Ripley, I. G. Rose, C. Saunders, “Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results,” J. Biomed. Opt. 5, 221–228 (2000).
[CrossRef] [PubMed]

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 Surg. Med. 17, 350–357 (1995).
[CrossRef] [PubMed]

Briggs, G.

I. J. Bigio, S. G. Bown, G. Briggs, C. Kelley, S. Lakhani, D. Pickard, P. M. Ripley, I. G. Rose, C. Saunders, “Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results,” J. Biomed. Opt. 5, 221–228 (2000).
[CrossRef] [PubMed]

Brightwell, A.

Brown, B. H.

D. C. Walker, B. H. Brown, A. D. Blackett, J. Tidy, R. H. Smallwood, “A study of the morphological parameters of cervical squamous epithelium,” Physiol. Meas. 24, 121–135 (2003).
[CrossRef] [PubMed]

Burke, L.

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. M. Harper, L. Burke, S. T. Sum, R. F. Flewelling, R. D. Alvarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of a 604-patient study,” Am. J. Obstet. Gynecol. 190, 1249–1257 (2004).
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R. J. Nordstrom, L. Burke, J. M. Niloff, J. F. Myrtle, “Identification of cervical intraepithelial neoplasia (CIN) using UV-excited fluorescence and diffuse-reflectance tissue spectroscopy,” Lasers Surg. Med. 29, 118–127 (2001).
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Carnohan, M.

Carraro, A.

D. Arifler, M. Guillaud, A. Carraro, A. Malpica, M. Follen, R. Richards-Kortum, “Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition,” J. Biomed. Opt. 8, 484–494 (2003).
[CrossRef] [PubMed]

Cestero, R. M.

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. M. Harper, L. Burke, S. T. Sum, R. F. Flewelling, R. D. Alvarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of a 604-patient study,” Am. J. Obstet. Gynecol. 190, 1249–1257 (2004).
[CrossRef] [PubMed]

Chan, E.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21, 166–178 (1997).
[CrossRef] [PubMed]

Chang, S. K.

R. A. Schwarz, D. Arifler, S. K. Chang, I. Pavlova, I. A. Hussain, V. Mack, B. Knight, A. M. Gillenwater, R. Richards-Kortum, “Ball lens coupled fiber-optic probe for depth-resolved spectroscopy of epithelial tissue,” Opt. Lett. 30, 1159–1161 (2005).

S. K. Chang, D. Arifler, R. Drezek, M. Follen, R. Richards-Kortum, “An analytical model to describe fluorescence spectra of normal and pre-neoplastic epithelial tissue: comparison with Monte Carlo simulations and clinical measurements,” J. Biomed. Opt. 9, 511–522 (2004).
[CrossRef] [PubMed]

Y. N. Mirabal, S. K. Chang, E. N. Atkinson, A. Malpica, M. Follen, R. Richards-Kortum, “Reflectance spectroscopy for in vivo detection of cervical precancer,” J. Biomed. Opt. 7, 587–594 (2002).
[CrossRef] [PubMed]

Collier, T.

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. MacAulay, M. Follen, R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
[CrossRef] [PubMed]

T. Collier, D. Arifler, A. Malpica, M. Follen, R. Richards-Kortum, “Determination of epithelial tissue scattering coefficient using confocal microscopy,” IEEE J. Sel. Top. Quantum Electron. 9, 307–313 (2003).
[CrossRef]

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 Surg. Med. 17, 350–357 (1995).
[CrossRef] [PubMed]

Cottone, G.

Criswell, G.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21, 166–178 (1997).
[CrossRef] [PubMed]

Crum, C. P.

I. Georgakoudi, E. E. Sheets, M. G. Müller, V. Backman, C. P. Crum, K. Badizadegan, R. R. Dasari, M. S. Feld, “Trimodal spectroscopy for the detection and characterization of cervical precancers in vivo,” Am. J. Obstet. Gynecol. 186, 374–382 (2002).
[CrossRef] [PubMed]

Dasari, R. R.

J. T. Motz, M. Hunter, L. H. Galindo, J. A. Gardecki, J. R. Kramer, R. R. Dasari, M. S. Feld, “Optical fiber probe for biomedical Raman spectroscopy,” Appl. Opt. 43, 542–554 (2004).
[CrossRef] [PubMed]

M. G. Müller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, M. S. Feld, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer 97, 1681–1692 (2003).
[CrossRef] [PubMed]

I. Georgakoudi, E. E. Sheets, M. G. Müller, V. Backman, C. P. Crum, K. Badizadegan, R. R. Dasari, M. S. Feld, “Trimodal spectroscopy for the detection and characterization of cervical precancers in vivo,” Am. J. Obstet. Gynecol. 186, 374–382 (2002).
[CrossRef] [PubMed]

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5, 1019–1026 (1999).
[CrossRef]

Deutsch, T. F.

F. Koenig, R. Larne, H. Enquist, F. J. McGovern, K. T. Schomacker, N. Kollias, T. F. Deutsch, “Spectroscopic measurement of diffuse reflectance for enhanced detection of bladder carcinoma,” Urology 51, 342–345 (1998).
[CrossRef] [PubMed]

Drezek, R.

S. K. Chang, D. Arifler, R. Drezek, M. Follen, R. Richards-Kortum, “An analytical model to describe fluorescence spectra of normal and pre-neoplastic epithelial tissue: comparison with Monte Carlo simulations and clinical measurements,” J. Biomed. Opt. 9, 511–522 (2004).
[CrossRef] [PubMed]

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. MacAulay, M. Follen, R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
[CrossRef] [PubMed]

I. Pavlova, K. Sokolov, R. Drezek, A. Malpica, M. Follen, R. Richards-Kortum, “Microanatomical and biochemical origins of normal and precancerous cervical autofluorescence using laser-scanning fluorescence confocal microscopy,” Photochem. Photobiol. 77, 550–555 (2003).
[CrossRef] [PubMed]

Drezek, R. A.

Duvic, M.

Ediger, M. N.

Enquist, H.

F. Koenig, R. Larne, H. Enquist, F. J. McGovern, K. T. Schomacker, N. Kollias, T. F. Deutsch, “Spectroscopic measurement of diffuse reflectance for enhanced detection of bladder carcinoma,” Urology 51, 342–345 (1998).
[CrossRef] [PubMed]

Fang, Q.

Feld, M. S.

J. T. Motz, M. Hunter, L. H. Galindo, J. A. Gardecki, J. R. Kramer, R. R. Dasari, M. S. Feld, “Optical fiber probe for biomedical Raman spectroscopy,” Appl. Opt. 43, 542–554 (2004).
[CrossRef] [PubMed]

M. G. Müller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, M. S. Feld, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer 97, 1681–1692 (2003).
[CrossRef] [PubMed]

I. Georgakoudi, E. E. Sheets, M. G. Müller, V. Backman, C. P. Crum, K. Badizadegan, R. R. Dasari, M. S. Feld, “Trimodal spectroscopy for the detection and characterization of cervical precancers in vivo,” Am. J. Obstet. Gynecol. 186, 374–382 (2002).
[CrossRef] [PubMed]

G. Zonios, L. T. Perelman, V. Backman, R. Manoharan, M. Fitzmaurice, J. Van Dam, M. S. Feld, “Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo,” Appl. Opt. 38, 6628–6637 (1999).
[CrossRef]

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5, 1019–1026 (1999).
[CrossRef]

Fitzmaurice, M.

Flewelling, R. F.

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. M. Harper, L. Burke, S. T. Sum, R. F. Flewelling, R. D. Alvarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of a 604-patient study,” Am. J. Obstet. Gynecol. 190, 1249–1257 (2004).
[CrossRef] [PubMed]

Follen, M.

S. K. Chang, D. Arifler, R. Drezek, M. Follen, R. Richards-Kortum, “An analytical model to describe fluorescence spectra of normal and pre-neoplastic epithelial tissue: comparison with Monte Carlo simulations and clinical measurements,” J. Biomed. Opt. 9, 511–522 (2004).
[CrossRef] [PubMed]

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. MacAulay, M. Follen, R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
[CrossRef] [PubMed]

T. Collier, D. Arifler, A. Malpica, M. Follen, R. Richards-Kortum, “Determination of epithelial tissue scattering coefficient using confocal microscopy,” IEEE J. Sel. Top. Quantum Electron. 9, 307–313 (2003).
[CrossRef]

D. Arifler, M. Guillaud, A. Carraro, A. Malpica, M. Follen, R. Richards-Kortum, “Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition,” J. Biomed. Opt. 8, 484–494 (2003).
[CrossRef] [PubMed]

I. Pavlova, K. Sokolov, R. Drezek, A. Malpica, M. Follen, R. Richards-Kortum, “Microanatomical and biochemical origins of normal and precancerous cervical autofluorescence using laser-scanning fluorescence confocal microscopy,” Photochem. Photobiol. 77, 550–555 (2003).
[CrossRef] [PubMed]

Y. N. Mirabal, S. K. Chang, E. N. Atkinson, A. Malpica, M. Follen, R. Richards-Kortum, “Reflectance spectroscopy for in vivo detection of cervical precancer,” J. Biomed. Opt. 7, 587–594 (2002).
[CrossRef] [PubMed]

Fuentes, C.

M. G. Müller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, M. S. Feld, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer 97, 1681–1692 (2003).
[CrossRef] [PubMed]

Galindo, L. H.

Garcia, F. A.

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. M. Harper, L. Burke, S. T. Sum, R. F. Flewelling, R. D. Alvarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of a 604-patient study,” Am. J. Obstet. Gynecol. 190, 1249–1257 (2004).
[CrossRef] [PubMed]

Garcia-Uribe, A.

Gardecki, J. A.

Gardner, C.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21, 166–178 (1997).
[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, N. Ramanujam, “Investigation of fiber-optic probe designs for optical spectroscopic diagnosis of epithelial precancers,” Lasers Surg. Med. 34, 25–38 (2004).
[CrossRef]

Georgakoudi, I.

M. G. Müller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, M. S. Feld, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer 97, 1681–1692 (2003).
[CrossRef] [PubMed]

I. Georgakoudi, E. E. Sheets, M. G. Müller, V. Backman, C. P. Crum, K. Badizadegan, R. R. Dasari, M. S. Feld, “Trimodal spectroscopy for the detection and characterization of cervical precancers in vivo,” Am. J. Obstet. Gynecol. 186, 374–382 (2002).
[CrossRef] [PubMed]

Gillenwater, A. M.

Gold, M. A.

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. M. Harper, L. Burke, S. T. Sum, R. F. Flewelling, R. D. Alvarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of a 604-patient study,” Am. J. Obstet. Gynecol. 190, 1249–1257 (2004).
[CrossRef] [PubMed]

Gossage, K.

Guido, R. S.

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. M. Harper, L. Burke, S. T. Sum, R. F. Flewelling, R. D. Alvarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of a 604-patient study,” Am. J. Obstet. Gynecol. 190, 1249–1257 (2004).
[CrossRef] [PubMed]

Guillaud, M.

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. MacAulay, M. Follen, R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
[CrossRef] [PubMed]

D. Arifler, M. Guillaud, A. Carraro, A. Malpica, M. Follen, R. Richards-Kortum, “Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition,” J. Biomed. Opt. 8, 484–494 (2003).
[CrossRef] [PubMed]

Gurjar, R.

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5, 1019–1026 (1999).
[CrossRef]

Harper, D. M.

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. M. Harper, L. Burke, S. T. Sum, R. F. Flewelling, R. D. Alvarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of a 604-patient study,” Am. J. Obstet. Gynecol. 190, 1249–1257 (2004).
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Hatjicondi, O.

P. Ravazoula, V. Zolota, O. Hatjicondi, G. Sakellaropoulos, G. Kourounis, M. E. Maragoudakis, “Assessment of angiogenesis in human cervical lesions,” Anticancer Res. 16, 3861–3864 (1996).
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Huh, W. K.

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. M. Harper, L. Burke, S. T. Sum, R. F. Flewelling, R. D. Alvarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of a 604-patient study,” Am. J. Obstet. Gynecol. 190, 1249–1257 (2004).
[CrossRef] [PubMed]

Hunter, M.

Hussain, I. A.

Itzkan, I.

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5, 1019–1026 (1999).
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[CrossRef]

Jensen, R. A.

K. J. Heppner, L. M. Matrisian, R. A. Jensen, W. H. Rodgers, “Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response,” Am. J. Pathol. 149, 273–282 (1996).

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 Surg. Med. 17, 350–357 (1995).
[CrossRef] [PubMed]

Jones, L. R.

Jung, J. J.

J. S. Lee, H. S. Kim, J. J. Jung, M. C. Lee, C. S. Park, “Angiogenesis, cell proliferation and apoptosis in progression of cervical neoplasia,” Anal. Quant. Cytol. Histol. 24, 103–113 (2002).
[PubMed]

Kabani, S.

M. G. Müller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, M. S. Feld, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer 97, 1681–1692 (2003).
[CrossRef] [PubMed]

Kehtarnavaz, N.

Kelley, C.

I. J. Bigio, S. G. Bown, G. Briggs, C. Kelley, S. Lakhani, D. Pickard, P. M. Ripley, I. G. Rose, C. Saunders, “Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results,” J. Biomed. Opt. 5, 221–228 (2000).
[CrossRef] [PubMed]

Kim, H. S.

J. S. Lee, H. S. Kim, J. J. Jung, M. C. Lee, C. S. Park, “Angiogenesis, cell proliferation and apoptosis in progression of cervical neoplasia,” Anal. Quant. Cytol. Histol. 24, 103–113 (2002).
[PubMed]

Kim, Y. L.

Knight, B.

Koenig, F.

F. Koenig, R. Larne, H. Enquist, F. J. McGovern, K. T. Schomacker, N. Kollias, T. F. Deutsch, “Spectroscopic measurement of diffuse reflectance for enhanced detection of bladder carcinoma,” Urology 51, 342–345 (1998).
[CrossRef] [PubMed]

Kollias, N.

F. Koenig, R. Larne, H. Enquist, F. J. McGovern, K. T. Schomacker, N. Kollias, T. F. Deutsch, “Spectroscopic measurement of diffuse reflectance for enhanced detection of bladder carcinoma,” Urology 51, 342–345 (1998).
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L. G. Koss, Diagnostic Cytology and Its Histopathologic Bases (Lippincott, 1992).

Kourounis, G.

P. Ravazoula, V. Zolota, O. Hatjicondi, G. Sakellaropoulos, G. Kourounis, M. E. Maragoudakis, “Assessment of angiogenesis in human cervical lesions,” Anticancer Res. 16, 3861–3864 (1996).
[PubMed]

Kramer, J. R.

Lakhani, S.

I. J. Bigio, S. G. Bown, G. Briggs, C. Kelley, S. Lakhani, D. Pickard, P. M. Ripley, I. G. Rose, C. Saunders, “Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results,” J. Biomed. Opt. 5, 221–228 (2000).
[CrossRef] [PubMed]

Larne, R.

F. Koenig, R. Larne, H. Enquist, F. J. McGovern, K. T. Schomacker, N. Kollias, T. F. Deutsch, “Spectroscopic measurement of diffuse reflectance for enhanced detection of bladder carcinoma,” Urology 51, 342–345 (1998).
[CrossRef] [PubMed]

Larsson, M.

Laver, N.

M. G. Müller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, M. S. Feld, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer 97, 1681–1692 (2003).
[CrossRef] [PubMed]

Lee, J. S.

J. S. Lee, H. S. Kim, J. J. Jung, M. C. Lee, C. S. Park, “Angiogenesis, cell proliferation and apoptosis in progression of cervical neoplasia,” Anal. Quant. Cytol. Histol. 24, 103–113 (2002).
[PubMed]

Lee, M. C.

J. S. Lee, H. S. Kim, J. J. Jung, M. C. Lee, C. S. Park, “Angiogenesis, cell proliferation and apoptosis in progression of cervical neoplasia,” Anal. Quant. Cytol. Histol. 24, 103–113 (2002).
[PubMed]

Liu, Q.

M. C. Skala, G. M. Palmer, C. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, N. Ramanujam, “Investigation of fiber-optic probe designs for optical spectroscopic diagnosis of epithelial precancers,” Lasers Surg. Med. 34, 25–38 (2004).
[CrossRef]

C. Zhu, Q. Liu, N. Ramanujam, “Effect of fiber optic probe geometry on depth-resolved fluorescence measurements from epithelial tissues: a Monte Carlo simulation,” J. Biomed. Opt. 8, 237–247 (2003).
[CrossRef] [PubMed]

Liu, Y.

MacAulay, C.

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. MacAulay, M. Follen, R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
[CrossRef] [PubMed]

Mack, V.

Malpica, A.

D. Arifler, M. Guillaud, A. Carraro, A. Malpica, M. Follen, R. Richards-Kortum, “Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition,” J. Biomed. Opt. 8, 484–494 (2003).
[CrossRef] [PubMed]

T. Collier, D. Arifler, A. Malpica, M. Follen, R. Richards-Kortum, “Determination of epithelial tissue scattering coefficient using confocal microscopy,” IEEE J. Sel. Top. Quantum Electron. 9, 307–313 (2003).
[CrossRef]

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. MacAulay, M. Follen, R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
[CrossRef] [PubMed]

I. Pavlova, K. Sokolov, R. Drezek, A. Malpica, M. Follen, R. Richards-Kortum, “Microanatomical and biochemical origins of normal and precancerous cervical autofluorescence using laser-scanning fluorescence confocal microscopy,” Photochem. Photobiol. 77, 550–555 (2003).
[CrossRef] [PubMed]

Y. N. Mirabal, S. K. Chang, E. N. Atkinson, A. Malpica, M. Follen, R. Richards-Kortum, “Reflectance spectroscopy for in vivo detection of cervical precancer,” J. Biomed. Opt. 7, 587–594 (2002).
[CrossRef] [PubMed]

Manoharan, R.

Maragoudakis, M. E.

P. Ravazoula, V. Zolota, O. Hatjicondi, G. Sakellaropoulos, G. Kourounis, M. E. Maragoudakis, “Assessment of angiogenesis in human cervical lesions,” Anticancer Res. 16, 3861–3864 (1996).
[PubMed]

Marcu, L.

Marquez, G.

Marshek-Stone, C. L.

M. C. Skala, G. M. Palmer, C. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, N. Ramanujam, “Investigation of fiber-optic probe designs for optical spectroscopic diagnosis of epithelial precancers,” Lasers Surg. Med. 34, 25–38 (2004).
[CrossRef]

Matcher, S. D.

I. V. Meglinskii, S. D. Matcher, “Analysis of the spatial distribution of detector sensitivity in a multilayer randomly inhomogeneous medium with strong light scattering and absorption by the Monte Carlo method,” Opt. Spectrosc. 91, 654–659 (2001).
[CrossRef]

Matchette, L. S.

Matrisian, L. M.

K. J. Heppner, L. M. Matrisian, R. A. Jensen, W. H. Rodgers, “Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response,” Am. J. Pathol. 149, 273–282 (1996).

McGovern, F. J.

F. Koenig, R. Larne, H. Enquist, F. J. McGovern, K. T. Schomacker, N. Kollias, T. F. Deutsch, “Spectroscopic measurement of diffuse reflectance for enhanced detection of bladder carcinoma,” Urology 51, 342–345 (1998).
[CrossRef] [PubMed]

McIntyre-Seltman, K.

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. M. Harper, L. Burke, S. T. Sum, R. F. Flewelling, R. D. Alvarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of a 604-patient study,” Am. J. Obstet. Gynecol. 190, 1249–1257 (2004).
[CrossRef] [PubMed]

Meglinskii, I. V.

I. V. Meglinskii, S. D. Matcher, “Analysis of the spatial distribution of detector sensitivity in a multilayer randomly inhomogeneous medium with strong light scattering and absorption by the Monte Carlo method,” Opt. Spectrosc. 91, 654–659 (2001).
[CrossRef]

Mirabal, Y. N.

Y. N. Mirabal, S. K. Chang, E. N. Atkinson, A. Malpica, M. Follen, R. Richards-Kortum, “Reflectance spectroscopy for in vivo detection of cervical precancer,” J. Biomed. Opt. 7, 587–594 (2002).
[CrossRef] [PubMed]

Moffitt, T. P.

T. P. Moffitt, S. A. Prahl, “Sized-fiber reflectometry for measuring local optical properties,” IEEE J. Sel. Top. Quantum Electron. 7, 952–958 (2001).
[CrossRef]

Motz, J. T.

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 Surg. Med. 17, 350–357 (1995).
[CrossRef] [PubMed]

Müller, M. G.

M. G. Müller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, M. S. Feld, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer 97, 1681–1692 (2003).
[CrossRef] [PubMed]

I. Georgakoudi, E. E. Sheets, M. G. Müller, V. Backman, C. P. Crum, K. Badizadegan, R. R. Dasari, M. S. Feld, “Trimodal spectroscopy for the detection and characterization of cervical precancers in vivo,” Am. J. Obstet. Gynecol. 186, 374–382 (2002).
[CrossRef] [PubMed]

Myakov, A.

Myrtle, J. F.

R. J. Nordstrom, L. Burke, J. M. Niloff, J. F. Myrtle, “Identification of cervical intraepithelial neoplasia (CIN) using UV-excited fluorescence and diffuse-reflectance tissue spectroscopy,” Lasers Surg. Med. 29, 118–127 (2001).
[CrossRef] [PubMed]

Nieman, L.

Niloff, J. M.

R. J. Nordstrom, L. Burke, J. M. Niloff, J. F. Myrtle, “Identification of cervical intraepithelial neoplasia (CIN) using UV-excited fluorescence and diffuse-reflectance tissue spectroscopy,” Lasers Surg. Med. 29, 118–127 (2001).
[CrossRef] [PubMed]

Nilsson, H.

Nishioka, N. S.

T. J. Pfefer, K. T. Schomacker, M. N. Ediger, N. S. Nishioka, “Multiple-fiber probe design for fluorescence spectroscopy in tissue,” Appl. Opt. 41, 4712–4721 (2002).
[CrossRef] [PubMed]

T. J. Pfefer, K. T. Schomacker, M. N. Ediger, N. S. Nishioka, “Light propagation in tissue during fluorescence spectroscopy with single-fiber probes,” IEEE J. Sel. Top. Quantum Electron. 7, 1004–1012 (2001).
[CrossRef]

Nordstrom, R. J.

R. J. Nordstrom, L. Burke, J. M. Niloff, J. F. Myrtle, “Identification of cervical intraepithelial neoplasia (CIN) using UV-excited fluorescence and diffuse-reflectance tissue spectroscopy,” Lasers Surg. Med. 29, 118–127 (2001).
[CrossRef] [PubMed]

Osei, E. K.

Palmer, G. M.

M. C. Skala, G. M. Palmer, C. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, N. Ramanujam, “Investigation of fiber-optic probe designs for optical spectroscopic diagnosis of epithelial precancers,” Lasers Surg. Med. 34, 25–38 (2004).
[CrossRef]

Papaioannou, T.

Park, C. S.

J. S. Lee, H. S. Kim, J. J. Jung, M. C. Lee, C. S. Park, “Angiogenesis, cell proliferation and apoptosis in progression of cervical neoplasia,” Anal. Quant. Cytol. Histol. 24, 103–113 (2002).
[PubMed]

Parks, W. C.

W. C. Parks, Matrix Metalloproteinases (Academic, 1998).

Patterson, M. S.

Pavlova, I.

R. A. Schwarz, D. Arifler, S. K. Chang, I. Pavlova, I. A. Hussain, V. Mack, B. Knight, A. M. Gillenwater, R. Richards-Kortum, “Ball lens coupled fiber-optic probe for depth-resolved spectroscopy of epithelial tissue,” Opt. Lett. 30, 1159–1161 (2005).

I. Pavlova, K. Sokolov, R. Drezek, A. Malpica, M. Follen, R. Richards-Kortum, “Microanatomical and biochemical origins of normal and precancerous cervical autofluorescence using laser-scanning fluorescence confocal microscopy,” Photochem. Photobiol. 77, 550–555 (2003).
[CrossRef] [PubMed]

Perelman, L. T.

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5, 1019–1026 (1999).
[CrossRef]

G. Zonios, L. T. Perelman, V. Backman, R. Manoharan, M. Fitzmaurice, J. Van Dam, M. S. Feld, “Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo,” Appl. Opt. 38, 6628–6637 (1999).
[CrossRef]

Pfefer, J.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21, 166–178 (1997).
[CrossRef] [PubMed]

Pfefer, T. J.

Pickard, D.

I. J. Bigio, S. G. Bown, G. Briggs, C. Kelley, S. Lakhani, D. Pickard, P. M. Ripley, I. G. Rose, C. Saunders, “Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results,” J. Biomed. Opt. 5, 221–228 (2000).
[CrossRef] [PubMed]

Prahl, S. A.

T. P. Moffitt, S. A. Prahl, “Sized-fiber reflectometry for measuring local optical properties,” IEEE J. Sel. Top. Quantum Electron. 7, 952–958 (2001).
[CrossRef]

Preyer, N. W.

Prieto, V.

Ramanujam, N.

M. C. Skala, G. M. Palmer, C. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, N. Ramanujam, “Investigation of fiber-optic probe designs for optical spectroscopic diagnosis of epithelial precancers,” Lasers Surg. Med. 34, 25–38 (2004).
[CrossRef]

C. Zhu, Q. Liu, N. Ramanujam, “Effect of fiber optic probe geometry on depth-resolved fluorescence measurements from epithelial tissues: a Monte Carlo simulation,” J. Biomed. Opt. 8, 237–247 (2003).
[CrossRef] [PubMed]

Ravazoula, P.

P. Ravazoula, V. Zolota, O. Hatjicondi, G. Sakellaropoulos, G. Kourounis, M. E. Maragoudakis, “Assessment of angiogenesis in human cervical lesions,” Anticancer Res. 16, 3861–3864 (1996).
[PubMed]

Richards-Kortum, R.

R. A. Schwarz, D. Arifler, S. K. Chang, I. Pavlova, I. A. Hussain, V. Mack, B. Knight, A. M. Gillenwater, R. Richards-Kortum, “Ball lens coupled fiber-optic probe for depth-resolved spectroscopy of epithelial tissue,” Opt. Lett. 30, 1159–1161 (2005).

S. K. Chang, D. Arifler, R. Drezek, M. Follen, R. Richards-Kortum, “An analytical model to describe fluorescence spectra of normal and pre-neoplastic epithelial tissue: comparison with Monte Carlo simulations and clinical measurements,” J. Biomed. Opt. 9, 511–522 (2004).
[CrossRef] [PubMed]

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. MacAulay, M. Follen, R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
[CrossRef] [PubMed]

T. Collier, D. Arifler, A. Malpica, M. Follen, R. Richards-Kortum, “Determination of epithelial tissue scattering coefficient using confocal microscopy,” IEEE J. Sel. Top. Quantum Electron. 9, 307–313 (2003).
[CrossRef]

D. Arifler, M. Guillaud, A. Carraro, A. Malpica, M. Follen, R. Richards-Kortum, “Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition,” J. Biomed. Opt. 8, 484–494 (2003).
[CrossRef] [PubMed]

U. Utzinger, R. Richards-Kortum, “Fiber optic probes for biomedical optical spectroscopy,” J. Biomed. Opt. 8, 121–147 (2003).
[CrossRef] [PubMed]

I. Pavlova, K. Sokolov, R. Drezek, A. Malpica, M. Follen, R. Richards-Kortum, “Microanatomical and biochemical origins of normal and precancerous cervical autofluorescence using laser-scanning fluorescence confocal microscopy,” Photochem. Photobiol. 77, 550–555 (2003).
[CrossRef] [PubMed]

Y. N. Mirabal, S. K. Chang, E. N. Atkinson, A. Malpica, M. Follen, R. Richards-Kortum, “Reflectance spectroscopy for in vivo detection of cervical precancer,” J. Biomed. Opt. 7, 587–594 (2002).
[CrossRef] [PubMed]

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21, 166–178 (1997).
[CrossRef] [PubMed]

Richards-Kortum, R. R.

Ripley, P. M.

I. J. Bigio, S. G. Bown, G. Briggs, C. Kelley, S. Lakhani, D. Pickard, P. M. Ripley, I. G. Rose, C. Saunders, “Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results,” J. Biomed. Opt. 5, 221–228 (2000).
[CrossRef] [PubMed]

Rodgers, W. H.

K. J. Heppner, L. M. Matrisian, R. A. Jensen, W. H. Rodgers, “Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response,” Am. J. Pathol. 149, 273–282 (1996).

Rose, I. G.

I. J. Bigio, S. G. Bown, G. Briggs, C. Kelley, S. Lakhani, D. Pickard, P. M. Ripley, I. G. Rose, C. Saunders, “Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results,” J. Biomed. Opt. 5, 221–228 (2000).
[CrossRef] [PubMed]

Ross, A. M.

Ross, R.

Roy, H. K.

Sakellaropoulos, G.

P. Ravazoula, V. Zolota, O. Hatjicondi, G. Sakellaropoulos, G. Kourounis, M. E. Maragoudakis, “Assessment of angiogenesis in human cervical lesions,” Anticancer Res. 16, 3861–3864 (1996).
[PubMed]

Saunders, C.

I. J. Bigio, S. G. Bown, G. Briggs, C. Kelley, S. Lakhani, D. Pickard, P. M. Ripley, I. G. Rose, C. Saunders, “Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results,” J. Biomed. Opt. 5, 221–228 (2000).
[CrossRef] [PubMed]

Schomacker, K. T.

T. J. Pfefer, K. T. Schomacker, M. N. Ediger, N. S. Nishioka, “Multiple-fiber probe design for fluorescence spectroscopy in tissue,” Appl. Opt. 41, 4712–4721 (2002).
[CrossRef] [PubMed]

T. J. Pfefer, K. T. Schomacker, M. N. Ediger, N. S. Nishioka, “Light propagation in tissue during fluorescence spectroscopy with single-fiber probes,” IEEE J. Sel. Top. Quantum Electron. 7, 1004–1012 (2001).
[CrossRef]

F. Koenig, R. Larne, H. Enquist, F. J. McGovern, K. T. Schomacker, N. Kollias, T. F. Deutsch, “Spectroscopic measurement of diffuse reflectance for enhanced detection of bladder carcinoma,” Urology 51, 342–345 (1998).
[CrossRef] [PubMed]

Schwarz, R. A.

Shapshay, S. M.

M. G. Müller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, M. S. Feld, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer 97, 1681–1692 (2003).
[CrossRef] [PubMed]

Sheets, E. E.

I. Georgakoudi, E. E. Sheets, M. G. Müller, V. Backman, C. P. Crum, K. Badizadegan, R. R. Dasari, M. S. Feld, “Trimodal spectroscopy for the detection and characterization of cervical precancers in vivo,” Am. J. Obstet. Gynecol. 186, 374–382 (2002).
[CrossRef] [PubMed]

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 Surg. Med. 17, 350–357 (1995).
[CrossRef] [PubMed]

Skala, M. C.

M. C. Skala, G. M. Palmer, C. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, N. Ramanujam, “Investigation of fiber-optic probe designs for optical spectroscopic diagnosis of epithelial precancers,” Lasers Surg. Med. 34, 25–38 (2004).
[CrossRef]

Smallwood, R. H.

D. C. Walker, B. H. Brown, A. D. Blackett, J. Tidy, R. H. Smallwood, “A study of the morphological parameters of cervical squamous epithelium,” Physiol. Meas. 24, 121–135 (2003).
[CrossRef] [PubMed]

Sokolov, K.

Steenbergen, W.

M. Larsson, W. Steenbergen, T. Strömberg, “Influence of optical properties and fiber separation on laser Doppler flowmetry,” J. Biomed. Opt. 7, 236–243 (2002).
[CrossRef] [PubMed]

Sterenborg, H. J. C. M.

Strömberg, T.

Sum, S. T.

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. M. Harper, L. Burke, S. T. Sum, R. F. Flewelling, R. D. Alvarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of a 604-patient study,” Am. J. Obstet. Gynecol. 190, 1249–1257 (2004).
[CrossRef] [PubMed]

Tidy, J.

D. C. Walker, B. H. Brown, A. D. Blackett, J. Tidy, R. H. Smallwood, “A study of the morphological parameters of cervical squamous epithelium,” Physiol. Meas. 24, 121–135 (2003).
[CrossRef] [PubMed]

Townsend, G. C.

T. A. Winning, G. C. Townsend, “Oral mucosal embryology and histology,” Clin. Dermatol. 18, 499–511 (2000).
[CrossRef]

Turzhitsky, V. M.

Utzinger, U.

U. Utzinger, R. Richards-Kortum, “Fiber optic probes for biomedical optical spectroscopy,” J. Biomed. Opt. 8, 121–147 (2003).
[CrossRef] [PubMed]

Valdez, T. A.

M. G. Müller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, M. S. Feld, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer 97, 1681–1692 (2003).
[CrossRef] [PubMed]

Van Dam, J.

Verdaasdonk, R. M.

R. M. Verdaasdonk, C. Borst, “Optics of fibers and fiber probes,” in Optical-Thermal Response of Laser-Irradiated Tissue, A. J. Welch, M. J. C. van Gemert, eds. (Plenum, 1995).
[CrossRef]

Vrotsos, K. M.

M. C. Skala, G. M. Palmer, C. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, N. Ramanujam, “Investigation of fiber-optic probe designs for optical spectroscopic diagnosis of epithelial precancers,” Lasers Surg. Med. 34, 25–38 (2004).
[CrossRef]

Wali, R. K.

Walker, D. C.

D. C. Walker, B. H. Brown, A. D. Blackett, J. Tidy, R. H. Smallwood, “A study of the morphological parameters of cervical squamous epithelium,” Physiol. Meas. 24, 121–135 (2003).
[CrossRef] [PubMed]

Wang, L.

L. Wang, S. L. Jacques, L. Zheng, “MCML—Monte Carlo modeling of light transport in multi-layered tissues,” Comput. Methods Programs Biomed. 47, 131–146 (1995).
[CrossRef] [PubMed]

S. L. Jacques, L. Wang, “Monte Carlo modeling of light transport in tissues,” in Optical-Thermal Response of Laser-Irradiated Tissue, A. J. Welch, M. J. C. van Gemert, eds. (Plenum, 1995).
[CrossRef]

Wang, L. V.

Wang, Z.

M. G. Müller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, M. S. Feld, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer 97, 1681–1692 (2003).
[CrossRef] [PubMed]

Warren, S.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21, 166–178 (1997).
[CrossRef] [PubMed]

Welch, A. J.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21, 166–178 (1997).
[CrossRef] [PubMed]

Wilson, B. C.

Winning, T. A.

T. A. Winning, G. C. Townsend, “Oral mucosal embryology and histology,” Clin. Dermatol. 18, 499–511 (2000).
[CrossRef]

Zheng, L.

L. Wang, S. L. Jacques, L. Zheng, “MCML—Monte Carlo modeling of light transport in multi-layered tissues,” Comput. Methods Programs Biomed. 47, 131–146 (1995).
[CrossRef] [PubMed]

Zhu, C.

M. C. Skala, G. M. Palmer, C. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, N. Ramanujam, “Investigation of fiber-optic probe designs for optical spectroscopic diagnosis of epithelial precancers,” Lasers Surg. Med. 34, 25–38 (2004).
[CrossRef]

C. Zhu, Q. Liu, N. Ramanujam, “Effect of fiber optic probe geometry on depth-resolved fluorescence measurements from epithelial tissues: a Monte Carlo simulation,” J. Biomed. Opt. 8, 237–247 (2003).
[CrossRef] [PubMed]

Zolota, V.

P. Ravazoula, V. Zolota, O. Hatjicondi, G. Sakellaropoulos, G. Kourounis, M. E. Maragoudakis, “Assessment of angiogenesis in human cervical lesions,” Anticancer Res. 16, 3861–3864 (1996).
[PubMed]

Zonios, G.

Am. J. Obstet. Gynecol. (2)

I. Georgakoudi, E. E. Sheets, M. G. Müller, V. Backman, C. P. Crum, K. Badizadegan, R. R. Dasari, M. S. Feld, “Trimodal spectroscopy for the detection and characterization of cervical precancers in vivo,” Am. J. Obstet. Gynecol. 186, 374–382 (2002).
[CrossRef] [PubMed]

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. M. Harper, L. Burke, S. T. Sum, R. F. Flewelling, R. D. Alvarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of a 604-patient study,” Am. J. Obstet. Gynecol. 190, 1249–1257 (2004).
[CrossRef] [PubMed]

Am. J. Pathol. (1)

K. J. Heppner, L. M. Matrisian, R. A. Jensen, W. H. Rodgers, “Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response,” Am. J. Pathol. 149, 273–282 (1996).

Anal. Quant. Cytol. Histol. (1)

J. S. Lee, H. S. Kim, J. J. Jung, M. C. Lee, C. S. Park, “Angiogenesis, cell proliferation and apoptosis in progression of cervical neoplasia,” Anal. Quant. Cytol. Histol. 24, 103–113 (2002).
[PubMed]

Anticancer Res. (1)

P. Ravazoula, V. Zolota, O. Hatjicondi, G. Sakellaropoulos, G. Kourounis, M. E. Maragoudakis, “Assessment of angiogenesis in human cervical lesions,” Anticancer Res. 16, 3861–3864 (1996).
[PubMed]

Appl. Opt. (9)

M. S. Patterson, S. Andersson-Engels, B. C. Wilson, E. K. Osei, “Absorption spectroscopy in tissue-simulating materials: a theoretical and experimental study of photon paths,” Appl. Opt. 34, 22–30 (1995).
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G. Zonios, L. T. Perelman, V. Backman, R. Manoharan, M. Fitzmaurice, J. Van Dam, M. S. Feld, “Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo,” Appl. Opt. 38, 6628–6637 (1999).
[CrossRef]

J. T. Motz, M. Hunter, L. H. Galindo, J. A. Gardecki, J. R. Kramer, R. R. Dasari, M. S. Feld, “Optical fiber probe for biomedical Raman spectroscopy,” Appl. Opt. 43, 542–554 (2004).
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L. Nieman, A. Myakov, J. Aaron, K. Sokolov, “Optical sectioning using a fiber probe with an angled illumination-collection geometry: evaluation in engineered tissue phantoms,” Appl. Opt. 43, 1308–1319 (2004).
[CrossRef] [PubMed]

A. Garcia-Uribe, N. Kehtarnavaz, G. Marquez, V. Prieto, M. Duvic, L. V. Wang, “Skin cancer detection by spectroscopic oblique-incidence reflectometry: classification and physiological origins,” Appl. Opt. 43, 2643–2650 (2004).
[CrossRef] [PubMed]

T. Papaioannou, N. W. Preyer, Q. Fang, A. Brightwell, M. Carnohan, G. Cottone, R. Ross, L. R. Jones, L. Marcu, “Effects of fiber-optic probe design and probe-to-target distance on diffuse reflectance measurements of turbid media: an experimental and computational study at 337 nm,” Appl. Opt. 43, 2846–2860 (2004).
[CrossRef] [PubMed]

A. Amelink, H. J. C. M. Sterenborg, “Measurement of the local optical properties of turbid media by differential path-length spectroscopy,” Appl. Opt. 43, 3048–3054 (2004).
[CrossRef] [PubMed]

T. J. Pfefer, K. T. Schomacker, M. N. Ediger, N. S. Nishioka, “Multiple-fiber probe design for fluorescence spectroscopy in tissue,” Appl. Opt. 41, 4712–4721 (2002).
[CrossRef] [PubMed]

M. Larsson, H. Nilsson, T. Strömberg, “In vivo determination of local skin optical properties and photon path length by use of spatially resolved diffuse reflectance with applications in laser Doppler flowmetry,” Appl. Opt. 42, 124–134 (2003).
[CrossRef] [PubMed]

Cancer (1)

M. G. Müller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, M. S. Feld, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer 97, 1681–1692 (2003).
[CrossRef] [PubMed]

Clin. Dermatol. (1)

T. A. Winning, G. C. Townsend, “Oral mucosal embryology and histology,” Clin. Dermatol. 18, 499–511 (2000).
[CrossRef]

Comput. Methods Programs Biomed. (1)

L. Wang, S. L. Jacques, L. Zheng, “MCML—Monte Carlo modeling of light transport in multi-layered tissues,” Comput. Methods Programs Biomed. 47, 131–146 (1995).
[CrossRef] [PubMed]

IEEE J. Sel. Top. Quantum Electron. (4)

T. P. Moffitt, S. A. Prahl, “Sized-fiber reflectometry for measuring local optical properties,” IEEE J. Sel. Top. Quantum Electron. 7, 952–958 (2001).
[CrossRef]

T. Collier, D. Arifler, A. Malpica, M. Follen, R. Richards-Kortum, “Determination of epithelial tissue scattering coefficient using confocal microscopy,” IEEE J. Sel. Top. Quantum Electron. 9, 307–313 (2003).
[CrossRef]

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5, 1019–1026 (1999).
[CrossRef]

T. J. Pfefer, K. T. Schomacker, M. N. Ediger, N. S. Nishioka, “Light propagation in tissue during fluorescence spectroscopy with single-fiber probes,” IEEE J. Sel. Top. Quantum Electron. 7, 1004–1012 (2001).
[CrossRef]

J. Biomed. Opt. (8)

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Figures (10)

Fig. 1
Fig. 1

Fiber-optic probe geometry with tilted source and detector fibers. The fiber tips are polished parallel to the tissue surface.

Fig. 2
Fig. 2

Fiber-optic probe geometry with half-ball lens coupled source and detector fibers. The fibers are symmetrically oriented about the central axis of the lens.

Fig. 3
Fig. 3

Modeling light propagation across the spherical lens interface through creation of a simulation geometry with infinitely wide and parallel layers.

Fig. 4
Fig. 4

Situation in which the parallel layer formulation fails to describe accurately the spherical lens boundary. When the photon encounters the spherical boundary for a second time, it should be considered to be incident from a medium with refractive index n2 to a medium with refractive index n1, but the parallel layer geometry assumption incorrectly suggests the contrary.

Fig. 5
Fig. 5

Penetration depth histograms for normal epithelial tissue at (a) λ = 450 nm and (b) λ = 650 nm obtained with tilted source and detector fibers.

Fig. 6
Fig. 6

Penetration depth histograms for dysplastic epithelial tissue at (a) λ = 450 nm and (b) λ = 650 nm obtained with tilted source and detector fibers.

Fig. 7
Fig. 7

Penetration depth histograms for normal epithelial tissue at (a) λ = 450 nm and (b) λ = 650 nm obtained with half-ball lens coupled source and detector fibers (w = 0 µm).

Fig. 8
Fig. 8

Penetration depth histograms for normal epithelial tissue at (a) λ = 450 nm and (b) λ = 650 nm obtained with half-ball lens coupled source and detector fibers (w = 300 µm).

Fig. 9
Fig. 9

Penetration depth histograms for dysplastic epithelial tissue at (a) λ = 450 nm and (b) λ = 650 nm obtained with half-ball lens coupled source and detector fibers (w = 300 µm).

Fig. 10
Fig. 10

Penetration depth histograms for the proposed probe design with two pairs of half-ball lens coupled source and detector fibers and a window with w = 300 µm. The fiber pair with s = 900 µm and β = 0° can selectively target the epithelium at (a) λ = 450 nm and (b) λ = 650 nm, and the fiber pair with s = 500 µm and β = −5° can selectively target the stroma at (c) λ = 450 nm and (d) λ = 650 nm.

Tables (7)

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Table 1 Optical Properties of Normal Epithelial Tissuea

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Table 2 Penetration Depth Statistics for Normal Epithelial Tissue Obtained with Tilted Source and Detector Fibers

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Table 3 Penetration Depth Statistics for Dysplastic Epithelial Tissue Obtained with Tilted Source and Detector Fibers

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Table 4 Penetration Depth Statistics for Normal Epithelial Tissue Obtained with Half-Ball Lens Coupled Source and Detector Fibers (w = 0 µm)

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Table 5 Penetration Depth Statistics for Normal Epithelial Tissue Obtained with Half-Ball Lens Coupled Source and Detector Fibers (w = 300 µm)

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Table 6 Penetration Depth Statistics for Dysplastic Epithelial Tissue Obtained with Half-Ball Lens Coupled Source and Detector Fibers (w = 300 µm)

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Table 7 Penetration Depth Statistics for the Proposed Probe Design

Equations (1)

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M ( β ) = [ cos β 0 sin β 0 1 0 sin β 0 cos β ] .

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