Abstract

The accurate understanding of optical properties of human tissues plays an important role in the optical diagnosis of early epithelial cancer. Many inverse models used to determine the optical properties of a tumor have assumed that the tumor was semi-infinite, which infers infinite width and length but finite thickness. However, this simplified assumption could lead to large errors for small tumor, especially at the early stages. We used a modified Monte Carlo code, which is able to simulate light transport in a layered tissue model with buried tumor-like targets, to investigate the validity of the semi-infinite tumor assumption in two common epithelial tissue models: a squamous cell carcinoma (SCC) tissue model and a basal cell carcinoma (BCC) tissue model. The SCC tissue model consisted of three layers, i.e. the top epithelium, the middle tumor and the bottom stroma. The BCC tissue model also consisted of three layers, i.e. the top epidermis, the middle tumor and the bottom dermis. Diffuse reflectance was simulated for two common fiber-optic probes. In one probe, both source and detector fibers were perpendicular to the tissue surface; while in the other, both fibers were tilted at 45 degrees relative to the normal axis of the tissue surface. It was demonstrated that the validity of the semi-infinite tumor model depends on both the fiber-optic probe configuration and the tumor dimensions. Two look-up tables, which relate the validity of the semi-infinite tumor model to the tumor width in terms of the source-detector separation, were derived to guide the selection of appropriate tumor models and fiber optic probe configuration for the optical diagnosis of early epithelial cancers.

© 2011 OSA

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S. Prestin, C. Betz, and M. Kraft, “Measurement of epithelial thickness within the oral cavity using optical coherence tomography (OCT),” Proc. SPIE 7548, 75482F, 75482F-9 (2010).
[CrossRef]

R. Sharma, “Gadolinium toxicity: epidermis thickness measurement by magnetic resonance imaging at 500 MHz,” Skin Res. Technol. 16(3), 339–353 (2010).
[PubMed]

2009

E. Drakaki, E. Kaselouris, M. Makropoulou, A. A. Serafetinides, A. Tsenga, A. J. Stratigos, A. D. Katsambas, and C. Antoniou, “Laser-induced fluorescence and reflectance spectroscopy for the discrimination of basal cell carcinoma from the surrounding normal skin tissue,” Skin Pharmacol. Physiol. 22(3), 158–165 (2009).
[CrossRef] [PubMed]

2008

I. Pavlova, C. R. Weber, R. A. Schwarz, M. Williams, A. El-Naggar, A. Gillenwater, and R. Richards-Kortum, “Monte Carlo model to describe depth selective fluorescence spectra of epithelial tissue: applications for diagnosis of oral precancer,” J. Biomed. Opt. 13(6), 064012 (2008).
[CrossRef] [PubMed]

C. Kortun, Y. R. Hijazi, and D. Arifler, “Combined Monte Carlo and finite-difference time-domain modeling for biophotonic analysis: implications on reflectance-based diagnosis of epithelial precancer,” J. Biomed. Opt. 13(3), 034014 (2008).
[CrossRef] [PubMed]

2007

2006

2005

J. Choi, J. Choo, H. Chung, D. G. Gweon, J. Park, H. J. Kim, S. Park, and C. H. Oh, “Direct observation of spectral differences between normal and basal cell carcinoma (BCC) tissues using confocal Raman microscopy,” Biopolymers 77(5), 264–272 (2005).
[CrossRef] [PubMed]

T. J. Pfefer, A. Agrawal, and R. A. Drezek, “Oblique-incidence illumination and collection for depth-selective fluorescence spectroscopy,” J. Biomed. Opt. 10(4), 044016 (2005).
[CrossRef] [PubMed]

A. M. J. Wang, J. E. Bender, J. Pfefer, U. Utzinger, and R. A. Drezek, “Depth-sensitive reflectance measurements using obliquely oriented fiber probes,” J. Biomed. Opt. 10(4), 044017 (2005).
[CrossRef] [PubMed]

D. Arifler, R. A. Schwarz, S. K. Chang, and R. Richards-Kortum, “Reflectance spectroscopy for diagnosis of epithelial precancer: model-based analysis of fiber-optic probe designs to resolve spectral information from epithelium and stroma,” Appl. Opt. 44(20), 4291–4305 (2005).
[CrossRef] [PubMed]

W. Verkruysse, R. Zhang, B. Choi, G. Lucassen, L. O. Svaasand, and J. S. Nelson, “A library based fitting method for visual reflectance spectroscopy of human skin,” Phys. Med. Biol. 50(1), 57–70 (2005).
[CrossRef] [PubMed]

2004

Q. Liu and N. Ramanujam, “Experimental proof of the feasibility of using an angled fiber-optic probe for depth-sensitive fluorescence spectroscopy of turbid media,” Opt. Lett. 29(17), 2034–2036 (2004).
[CrossRef] [PubMed]

S. K. Chang, D. Arifler, R. Drezek, M. Follen, and R. Richards-Kortum, “Analytical model to describe fluorescence spectra of normal and preneoplastic epithelial tissue: comparison with Monte Carlo simulations and clinical measurements,” J. Biomed. Opt. 9(3), 511–522 (2004).
[CrossRef] [PubMed]

2003

Q. Liu, C. F. Zhu, and N. Ramanujam, “Experimental validation of Monte Carlo modeling of fluorescence in tissues in the UV-visible spectrum,” J. Biomed. Opt. 8(2), 223–236 (2003).
[CrossRef] [PubMed]

D. C. Walker, B. H. Brown, A. D. Blackett, J. Tidy, and R. H. Smallwood, “A study of the morphological parameters of cervical squamous epithelium,” Physiol. Meas. 24(1), 121–135 (2003).
[CrossRef] [PubMed]

S. Merritt, F. Bevilacqua, A. J. Durkin, D. J. Cuccia, R. Lanning, B. J. Tromberg, G. Gulsen, H. Yu, J. Wang, and O. Nalcioglu, “Coregistration of diffuse optical spectroscopy and magnetic resonance imaging in a rat tumor model,” Appl. Opt. 42(16), 2951–2959 (2003).
[CrossRef] [PubMed]

2002

S. K. Chang, M. Y. Dawood, G. Staerkel, U. Utzinger, E. N. Atkinson, R. R. Richards-Kortum, and M. Follen, “Fluorescence spectroscopy for cervical precancer detection: Is there variance across the menstrual cycle?” J. Biomed. Opt. 7(4), 595–602 (2002).
[CrossRef] [PubMed]

Y. Lee and K. Hwang, “Skin thickness of Korean adults,” Surg. Radiol. Anat. 24(3-4), 183–189 (2002).
[CrossRef] [PubMed]

L. Quan and N. Ramanujam, “Relationship between depth of a target in a turbid medium and fluorescence measured by a variable-aperture method,” Opt. Lett. 27(2), 104–106 (2002).
[CrossRef] [PubMed]

2001

2000

B. L. Allen-Hoffmann, S. J. Schlosser, C. A. R. Ivarie, C. A. Sattler, L. F. Meisner, and S. L. O’Connor, “Normal growth and differentiation in a spontaneously immortalized near-diploid human keratinocyte cell line, NIKS,” J. Invest. Dermatol. 114(3), 444–455 (2000).
[CrossRef] [PubMed]

1999

G. Zonios, L. T. Perelman, V. M. Backman, R. Manoharan, M. Fitzmaurice, J. Van Dam, and M. S. Feld, “Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo,” Appl. Opt. 38(31), 6628–6637 (1999).
[CrossRef] [PubMed]

R. M. P. Doornbos, R. Lang, M. C. Aalders, F. W. Cross, and H. J. C. M. Sterenborg, “The determination of in vivo human tissue optical properties and absolute chromophore concentrations using spatially resolved steady-state diffuse reflectance spectroscopy,” Phys. Med. Biol. 44(4), 967–981 (1999).
[CrossRef] [PubMed]

1995

L. H. Wang, S. L. Jacques, and L. Q. Zheng, “MCML--Monte Carlo modeling of light transport in multi-layered tissues,” Comput. Methods Programs Biomed. 47(2), 131–146 (1995).
[CrossRef] [PubMed]

1994

1989

S. T. Flock, M. S. Patterson, B. C. Wilson, and D. R. Wyman, “Monte-Carlo modeling of light-propagation in highly scattering tissues. 1. Model predictions and comparison with diffusion-theory,” IEEE Trans. Bio-Med. Eng. 36(12), 1162–1168 (1989).
[CrossRef]

1983

B. C. Wilson and G. Adam, “A Monte Carlo model for the absorption and flux distributions of light in tissue,” Med. Phys. 10(6), 824–830 (1983).
[CrossRef] [PubMed]

Aalders, M. C.

R. M. P. Doornbos, R. Lang, M. C. Aalders, F. W. Cross, and H. J. C. M. Sterenborg, “The determination of in vivo human tissue optical properties and absolute chromophore concentrations using spatially resolved steady-state diffuse reflectance spectroscopy,” Phys. Med. Biol. 44(4), 967–981 (1999).
[CrossRef] [PubMed]

Adam, G.

B. C. Wilson and G. Adam, “A Monte Carlo model for the absorption and flux distributions of light in tissue,” Med. Phys. 10(6), 824–830 (1983).
[CrossRef] [PubMed]

Agrawal, A.

T. J. Pfefer, A. Agrawal, and R. A. Drezek, “Oblique-incidence illumination and collection for depth-selective fluorescence spectroscopy,” J. Biomed. Opt. 10(4), 044016 (2005).
[CrossRef] [PubMed]

Allen-Hoffmann, B. L.

B. L. Allen-Hoffmann, S. J. Schlosser, C. A. R. Ivarie, C. A. Sattler, L. F. Meisner, and S. L. O’Connor, “Normal growth and differentiation in a spontaneously immortalized near-diploid human keratinocyte cell line, NIKS,” J. Invest. Dermatol. 114(3), 444–455 (2000).
[CrossRef] [PubMed]

Antoniou, C.

E. Drakaki, E. Kaselouris, M. Makropoulou, A. A. Serafetinides, A. Tsenga, A. J. Stratigos, A. D. Katsambas, and C. Antoniou, “Laser-induced fluorescence and reflectance spectroscopy for the discrimination of basal cell carcinoma from the surrounding normal skin tissue,” Skin Pharmacol. Physiol. 22(3), 158–165 (2009).
[CrossRef] [PubMed]

Arifler, D.

C. Kortun, Y. R. Hijazi, and D. Arifler, “Combined Monte Carlo and finite-difference time-domain modeling for biophotonic analysis: implications on reflectance-based diagnosis of epithelial precancer,” J. Biomed. Opt. 13(3), 034014 (2008).
[CrossRef] [PubMed]

D. Arifler, C. MacAulay, M. Follen, and R. Richards-Kortum, “Spatially resolved reflectance spectroscopy for diagnosis of cervical precancer: Monte Carlo modeling and comparison to clinical measurements,” J. Biomed. Opt. 11(6), 064027 (2006).
[CrossRef] [PubMed]

D. Arifler, R. A. Schwarz, S. K. Chang, and R. Richards-Kortum, “Reflectance spectroscopy for diagnosis of epithelial precancer: model-based analysis of fiber-optic probe designs to resolve spectral information from epithelium and stroma,” Appl. Opt. 44(20), 4291–4305 (2005).
[CrossRef] [PubMed]

S. K. Chang, D. Arifler, R. Drezek, M. Follen, and R. Richards-Kortum, “Analytical model to describe fluorescence spectra of normal and preneoplastic epithelial tissue: comparison with Monte Carlo simulations and clinical measurements,” J. Biomed. Opt. 9(3), 511–522 (2004).
[CrossRef] [PubMed]

Atkinson, E. N.

S. K. Chang, M. Y. Dawood, G. Staerkel, U. Utzinger, E. N. Atkinson, R. R. Richards-Kortum, and M. Follen, “Fluorescence spectroscopy for cervical precancer detection: Is there variance across the menstrual cycle?” J. Biomed. Opt. 7(4), 595–602 (2002).
[CrossRef] [PubMed]

Backman, V. M.

Bender, J. E.

A. M. J. Wang, J. E. Bender, J. Pfefer, U. Utzinger, and R. A. Drezek, “Depth-sensitive reflectance measurements using obliquely oriented fiber probes,” J. Biomed. Opt. 10(4), 044017 (2005).
[CrossRef] [PubMed]

Betz, C.

S. Prestin, C. Betz, and M. Kraft, “Measurement of epithelial thickness within the oral cavity using optical coherence tomography (OCT),” Proc. SPIE 7548, 75482F, 75482F-9 (2010).
[CrossRef]

Bevilacqua, F.

Blackett, A. D.

D. C. Walker, B. H. Brown, A. D. Blackett, J. Tidy, and R. H. Smallwood, “A study of the morphological parameters of cervical squamous epithelium,” Physiol. Meas. 24(1), 121–135 (2003).
[CrossRef] [PubMed]

Boiko, I.

R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, “Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: modeling, measurements, and implications,” J. Biomed. Opt. 6(4), 385–396 (2001).
[CrossRef] [PubMed]

Breslin, T. M.

Brown, B. H.

D. C. Walker, B. H. Brown, A. D. Blackett, J. Tidy, and R. H. Smallwood, “A study of the morphological parameters of cervical squamous epithelium,” Physiol. Meas. 24(1), 121–135 (2003).
[CrossRef] [PubMed]

Chang, S. K.

D. Arifler, R. A. Schwarz, S. K. Chang, and R. Richards-Kortum, “Reflectance spectroscopy for diagnosis of epithelial precancer: model-based analysis of fiber-optic probe designs to resolve spectral information from epithelium and stroma,” Appl. Opt. 44(20), 4291–4305 (2005).
[CrossRef] [PubMed]

S. K. Chang, D. Arifler, R. Drezek, M. Follen, and R. Richards-Kortum, “Analytical model to describe fluorescence spectra of normal and preneoplastic epithelial tissue: comparison with Monte Carlo simulations and clinical measurements,” J. Biomed. Opt. 9(3), 511–522 (2004).
[CrossRef] [PubMed]

S. K. Chang, M. Y. Dawood, G. Staerkel, U. Utzinger, E. N. Atkinson, R. R. Richards-Kortum, and M. Follen, “Fluorescence spectroscopy for cervical precancer detection: Is there variance across the menstrual cycle?” J. Biomed. Opt. 7(4), 595–602 (2002).
[CrossRef] [PubMed]

Choi, B.

W. Verkruysse, R. Zhang, B. Choi, G. Lucassen, L. O. Svaasand, and J. S. Nelson, “A library based fitting method for visual reflectance spectroscopy of human skin,” Phys. Med. Biol. 50(1), 57–70 (2005).
[CrossRef] [PubMed]

Choi, J.

J. Choi, J. Choo, H. Chung, D. G. Gweon, J. Park, H. J. Kim, S. Park, and C. H. Oh, “Direct observation of spectral differences between normal and basal cell carcinoma (BCC) tissues using confocal Raman microscopy,” Biopolymers 77(5), 264–272 (2005).
[CrossRef] [PubMed]

Choo, J.

J. Choi, J. Choo, H. Chung, D. G. Gweon, J. Park, H. J. Kim, S. Park, and C. H. Oh, “Direct observation of spectral differences between normal and basal cell carcinoma (BCC) tissues using confocal Raman microscopy,” Biopolymers 77(5), 264–272 (2005).
[CrossRef] [PubMed]

Chung, H.

J. Choi, J. Choo, H. Chung, D. G. Gweon, J. Park, H. J. Kim, S. Park, and C. H. Oh, “Direct observation of spectral differences between normal and basal cell carcinoma (BCC) tissues using confocal Raman microscopy,” Biopolymers 77(5), 264–272 (2005).
[CrossRef] [PubMed]

Cross, F. W.

R. M. P. Doornbos, R. Lang, M. C. Aalders, F. W. Cross, and H. J. C. M. Sterenborg, “The determination of in vivo human tissue optical properties and absolute chromophore concentrations using spatially resolved steady-state diffuse reflectance spectroscopy,” Phys. Med. Biol. 44(4), 967–981 (1999).
[CrossRef] [PubMed]

Cuccia, D. J.

Dawood, M. Y.

S. K. Chang, M. Y. Dawood, G. Staerkel, U. Utzinger, E. N. Atkinson, R. R. Richards-Kortum, and M. Follen, “Fluorescence spectroscopy for cervical precancer detection: Is there variance across the menstrual cycle?” J. Biomed. Opt. 7(4), 595–602 (2002).
[CrossRef] [PubMed]

Doornbos, R. M. P.

R. M. P. Doornbos, R. Lang, M. C. Aalders, F. W. Cross, and H. J. C. M. Sterenborg, “The determination of in vivo human tissue optical properties and absolute chromophore concentrations using spatially resolved steady-state diffuse reflectance spectroscopy,” Phys. Med. Biol. 44(4), 967–981 (1999).
[CrossRef] [PubMed]

Drakaki, E.

E. Drakaki, E. Kaselouris, M. Makropoulou, A. A. Serafetinides, A. Tsenga, A. J. Stratigos, A. D. Katsambas, and C. Antoniou, “Laser-induced fluorescence and reflectance spectroscopy for the discrimination of basal cell carcinoma from the surrounding normal skin tissue,” Skin Pharmacol. Physiol. 22(3), 158–165 (2009).
[CrossRef] [PubMed]

Drezek, R.

S. K. Chang, D. Arifler, R. Drezek, M. Follen, and R. Richards-Kortum, “Analytical model to describe fluorescence spectra of normal and preneoplastic epithelial tissue: comparison with Monte Carlo simulations and clinical measurements,” J. Biomed. Opt. 9(3), 511–522 (2004).
[CrossRef] [PubMed]

R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, “Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: modeling, measurements, and implications,” J. Biomed. Opt. 6(4), 385–396 (2001).
[CrossRef] [PubMed]

Drezek, R. A.

A. M. J. Wang, J. E. Bender, J. Pfefer, U. Utzinger, and R. A. Drezek, “Depth-sensitive reflectance measurements using obliquely oriented fiber probes,” J. Biomed. Opt. 10(4), 044017 (2005).
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T. J. Pfefer, A. Agrawal, and R. A. Drezek, “Oblique-incidence illumination and collection for depth-selective fluorescence spectroscopy,” J. Biomed. Opt. 10(4), 044016 (2005).
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I. Pavlova, C. R. Weber, R. A. Schwarz, M. Williams, A. El-Naggar, A. Gillenwater, and R. Richards-Kortum, “Monte Carlo model to describe depth selective fluorescence spectra of epithelial tissue: applications for diagnosis of oral precancer,” J. Biomed. Opt. 13(6), 064012 (2008).
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S. T. Flock, M. S. Patterson, B. C. Wilson, and D. R. Wyman, “Monte-Carlo modeling of light-propagation in highly scattering tissues. 1. Model predictions and comparison with diffusion-theory,” IEEE Trans. Bio-Med. Eng. 36(12), 1162–1168 (1989).
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D. Arifler, C. MacAulay, M. Follen, and R. Richards-Kortum, “Spatially resolved reflectance spectroscopy for diagnosis of cervical precancer: Monte Carlo modeling and comparison to clinical measurements,” J. Biomed. Opt. 11(6), 064027 (2006).
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S. K. Chang, D. Arifler, R. Drezek, M. Follen, and R. Richards-Kortum, “Analytical model to describe fluorescence spectra of normal and preneoplastic epithelial tissue: comparison with Monte Carlo simulations and clinical measurements,” J. Biomed. Opt. 9(3), 511–522 (2004).
[CrossRef] [PubMed]

S. K. Chang, M. Y. Dawood, G. Staerkel, U. Utzinger, E. N. Atkinson, R. R. Richards-Kortum, and M. Follen, “Fluorescence spectroscopy for cervical precancer detection: Is there variance across the menstrual cycle?” J. Biomed. Opt. 7(4), 595–602 (2002).
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U. Utzinger, D. L. Heintzelman, A. Mahadevan-Jansen, A. Malpica, M. Follen, and R. Richards-Kortum, “Near-infrared Raman spectroscopy for in vivo detection of cervical precancers,” Appl. Spectrosc. 55(8), 955–959 (2001).
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R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, “Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: modeling, measurements, and implications,” J. Biomed. Opt. 6(4), 385–396 (2001).
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Gendron-Fitzpatrick, A.

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I. Pavlova, C. R. Weber, R. A. Schwarz, M. Williams, A. El-Naggar, A. Gillenwater, and R. Richards-Kortum, “Monte Carlo model to describe depth selective fluorescence spectra of epithelial tissue: applications for diagnosis of oral precancer,” J. Biomed. Opt. 13(6), 064012 (2008).
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Gweon, D. G.

J. Choi, J. Choo, H. Chung, D. G. Gweon, J. Park, H. J. Kim, S. Park, and C. H. Oh, “Direct observation of spectral differences between normal and basal cell carcinoma (BCC) tissues using confocal Raman microscopy,” Biopolymers 77(5), 264–272 (2005).
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C. Kortun, Y. R. Hijazi, and D. Arifler, “Combined Monte Carlo and finite-difference time-domain modeling for biophotonic analysis: implications on reflectance-based diagnosis of epithelial precancer,” J. Biomed. Opt. 13(3), 034014 (2008).
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B. L. Allen-Hoffmann, S. J. Schlosser, C. A. R. Ivarie, C. A. Sattler, L. F. Meisner, and S. L. O’Connor, “Normal growth and differentiation in a spontaneously immortalized near-diploid human keratinocyte cell line, NIKS,” J. Invest. Dermatol. 114(3), 444–455 (2000).
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L. H. Wang, S. L. Jacques, and L. Q. Zheng, “MCML--Monte Carlo modeling of light transport in multi-layered tissues,” Comput. Methods Programs Biomed. 47(2), 131–146 (1995).
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E. Salomatina, B. Jiang, J. Novak, and A. N. Yaroslavsky, “Optical properties of normal and cancerous human skin in the visible and near-infrared spectral range,” J. Biomed. Opt. 11(6), 064026 (2006).
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E. Drakaki, E. Kaselouris, M. Makropoulou, A. A. Serafetinides, A. Tsenga, A. J. Stratigos, A. D. Katsambas, and C. Antoniou, “Laser-induced fluorescence and reflectance spectroscopy for the discrimination of basal cell carcinoma from the surrounding normal skin tissue,” Skin Pharmacol. Physiol. 22(3), 158–165 (2009).
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E. Drakaki, E. Kaselouris, M. Makropoulou, A. A. Serafetinides, A. Tsenga, A. J. Stratigos, A. D. Katsambas, and C. Antoniou, “Laser-induced fluorescence and reflectance spectroscopy for the discrimination of basal cell carcinoma from the surrounding normal skin tissue,” Skin Pharmacol. Physiol. 22(3), 158–165 (2009).
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J. Choi, J. Choo, H. Chung, D. G. Gweon, J. Park, H. J. Kim, S. Park, and C. H. Oh, “Direct observation of spectral differences between normal and basal cell carcinoma (BCC) tissues using confocal Raman microscopy,” Biopolymers 77(5), 264–272 (2005).
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C. Kortun, Y. R. Hijazi, and D. Arifler, “Combined Monte Carlo and finite-difference time-domain modeling for biophotonic analysis: implications on reflectance-based diagnosis of epithelial precancer,” J. Biomed. Opt. 13(3), 034014 (2008).
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Lee, Y.

Y. Lee and K. Hwang, “Skin thickness of Korean adults,” Surg. Radiol. Anat. 24(3-4), 183–189 (2002).
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Lucassen, G.

W. Verkruysse, R. Zhang, B. Choi, G. Lucassen, L. O. Svaasand, and J. S. Nelson, “A library based fitting method for visual reflectance spectroscopy of human skin,” Phys. Med. Biol. 50(1), 57–70 (2005).
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D. Arifler, C. MacAulay, M. Follen, and R. Richards-Kortum, “Spatially resolved reflectance spectroscopy for diagnosis of cervical precancer: Monte Carlo modeling and comparison to clinical measurements,” J. Biomed. Opt. 11(6), 064027 (2006).
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Makropoulou, M.

E. Drakaki, E. Kaselouris, M. Makropoulou, A. A. Serafetinides, A. Tsenga, A. J. Stratigos, A. D. Katsambas, and C. Antoniou, “Laser-induced fluorescence and reflectance spectroscopy for the discrimination of basal cell carcinoma from the surrounding normal skin tissue,” Skin Pharmacol. Physiol. 22(3), 158–165 (2009).
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Malpica, A.

U. Utzinger, D. L. Heintzelman, A. Mahadevan-Jansen, A. Malpica, M. Follen, and R. Richards-Kortum, “Near-infrared Raman spectroscopy for in vivo detection of cervical precancers,” Appl. Spectrosc. 55(8), 955–959 (2001).
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R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, “Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: modeling, measurements, and implications,” J. Biomed. Opt. 6(4), 385–396 (2001).
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Meisner, L. F.

B. L. Allen-Hoffmann, S. J. Schlosser, C. A. R. Ivarie, C. A. Sattler, L. F. Meisner, and S. L. O’Connor, “Normal growth and differentiation in a spontaneously immortalized near-diploid human keratinocyte cell line, NIKS,” J. Invest. Dermatol. 114(3), 444–455 (2000).
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Nalcioglu, O.

Nelson, J. S.

W. Verkruysse, R. Zhang, B. Choi, G. Lucassen, L. O. Svaasand, and J. S. Nelson, “A library based fitting method for visual reflectance spectroscopy of human skin,” Phys. Med. Biol. 50(1), 57–70 (2005).
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E. Salomatina, B. Jiang, J. Novak, and A. N. Yaroslavsky, “Optical properties of normal and cancerous human skin in the visible and near-infrared spectral range,” J. Biomed. Opt. 11(6), 064026 (2006).
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B. L. Allen-Hoffmann, S. J. Schlosser, C. A. R. Ivarie, C. A. Sattler, L. F. Meisner, and S. L. O’Connor, “Normal growth and differentiation in a spontaneously immortalized near-diploid human keratinocyte cell line, NIKS,” J. Invest. Dermatol. 114(3), 444–455 (2000).
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J. Choi, J. Choo, H. Chung, D. G. Gweon, J. Park, H. J. Kim, S. Park, and C. H. Oh, “Direct observation of spectral differences between normal and basal cell carcinoma (BCC) tissues using confocal Raman microscopy,” Biopolymers 77(5), 264–272 (2005).
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Palcic, B.

Palmer, G. M.

Park, J.

J. Choi, J. Choo, H. Chung, D. G. Gweon, J. Park, H. J. Kim, S. Park, and C. H. Oh, “Direct observation of spectral differences between normal and basal cell carcinoma (BCC) tissues using confocal Raman microscopy,” Biopolymers 77(5), 264–272 (2005).
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J. Choi, J. Choo, H. Chung, D. G. Gweon, J. Park, H. J. Kim, S. Park, and C. H. Oh, “Direct observation of spectral differences between normal and basal cell carcinoma (BCC) tissues using confocal Raman microscopy,” Biopolymers 77(5), 264–272 (2005).
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S. T. Flock, M. S. Patterson, B. C. Wilson, and D. R. Wyman, “Monte-Carlo modeling of light-propagation in highly scattering tissues. 1. Model predictions and comparison with diffusion-theory,” IEEE Trans. Bio-Med. Eng. 36(12), 1162–1168 (1989).
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I. Pavlova, C. R. Weber, R. A. Schwarz, M. Williams, A. El-Naggar, A. Gillenwater, and R. Richards-Kortum, “Monte Carlo model to describe depth selective fluorescence spectra of epithelial tissue: applications for diagnosis of oral precancer,” J. Biomed. Opt. 13(6), 064012 (2008).
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Pfefer, J.

A. M. J. Wang, J. E. Bender, J. Pfefer, U. Utzinger, and R. A. Drezek, “Depth-sensitive reflectance measurements using obliquely oriented fiber probes,” J. Biomed. Opt. 10(4), 044017 (2005).
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T. J. Pfefer, A. Agrawal, and R. A. Drezek, “Oblique-incidence illumination and collection for depth-selective fluorescence spectroscopy,” J. Biomed. Opt. 10(4), 044016 (2005).
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S. Prestin, C. Betz, and M. Kraft, “Measurement of epithelial thickness within the oral cavity using optical coherence tomography (OCT),” Proc. SPIE 7548, 75482F, 75482F-9 (2010).
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G. M. Palmer and N. Ramanujam, “Monte Carlo-based inverse model for calculating tissue optical properties. Part I: Theory and validation on synthetic phantoms,” Appl. Opt. 45(5), 1062–1071 (2006).
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I. Pavlova, C. R. Weber, R. A. Schwarz, M. Williams, A. El-Naggar, A. Gillenwater, and R. Richards-Kortum, “Monte Carlo model to describe depth selective fluorescence spectra of epithelial tissue: applications for diagnosis of oral precancer,” J. Biomed. Opt. 13(6), 064012 (2008).
[CrossRef] [PubMed]

D. Arifler, C. MacAulay, M. Follen, and R. Richards-Kortum, “Spatially resolved reflectance spectroscopy for diagnosis of cervical precancer: Monte Carlo modeling and comparison to clinical measurements,” J. Biomed. Opt. 11(6), 064027 (2006).
[CrossRef] [PubMed]

D. Arifler, R. A. Schwarz, S. K. Chang, and R. Richards-Kortum, “Reflectance spectroscopy for diagnosis of epithelial precancer: model-based analysis of fiber-optic probe designs to resolve spectral information from epithelium and stroma,” Appl. Opt. 44(20), 4291–4305 (2005).
[CrossRef] [PubMed]

S. K. Chang, D. Arifler, R. Drezek, M. Follen, and R. Richards-Kortum, “Analytical model to describe fluorescence spectra of normal and preneoplastic epithelial tissue: comparison with Monte Carlo simulations and clinical measurements,” J. Biomed. Opt. 9(3), 511–522 (2004).
[CrossRef] [PubMed]

U. Utzinger, D. L. Heintzelman, A. Mahadevan-Jansen, A. Malpica, M. Follen, and R. Richards-Kortum, “Near-infrared Raman spectroscopy for in vivo detection of cervical precancers,” Appl. Spectrosc. 55(8), 955–959 (2001).
[CrossRef]

R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, “Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: modeling, measurements, and implications,” J. Biomed. Opt. 6(4), 385–396 (2001).
[CrossRef] [PubMed]

Richards-Kortum, R. R.

S. K. Chang, M. Y. Dawood, G. Staerkel, U. Utzinger, E. N. Atkinson, R. R. Richards-Kortum, and M. Follen, “Fluorescence spectroscopy for cervical precancer detection: Is there variance across the menstrual cycle?” J. Biomed. Opt. 7(4), 595–602 (2002).
[CrossRef] [PubMed]

Salomatina, E.

E. Salomatina, B. Jiang, J. Novak, and A. N. Yaroslavsky, “Optical properties of normal and cancerous human skin in the visible and near-infrared spectral range,” J. Biomed. Opt. 11(6), 064026 (2006).
[CrossRef] [PubMed]

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B. L. Allen-Hoffmann, S. J. Schlosser, C. A. R. Ivarie, C. A. Sattler, L. F. Meisner, and S. L. O’Connor, “Normal growth and differentiation in a spontaneously immortalized near-diploid human keratinocyte cell line, NIKS,” J. Invest. Dermatol. 114(3), 444–455 (2000).
[CrossRef] [PubMed]

Schlosser, S. J.

B. L. Allen-Hoffmann, S. J. Schlosser, C. A. R. Ivarie, C. A. Sattler, L. F. Meisner, and S. L. O’Connor, “Normal growth and differentiation in a spontaneously immortalized near-diploid human keratinocyte cell line, NIKS,” J. Invest. Dermatol. 114(3), 444–455 (2000).
[CrossRef] [PubMed]

Schwarz, R. A.

I. Pavlova, C. R. Weber, R. A. Schwarz, M. Williams, A. El-Naggar, A. Gillenwater, and R. Richards-Kortum, “Monte Carlo model to describe depth selective fluorescence spectra of epithelial tissue: applications for diagnosis of oral precancer,” J. Biomed. Opt. 13(6), 064012 (2008).
[CrossRef] [PubMed]

D. Arifler, R. A. Schwarz, S. K. Chang, and R. Richards-Kortum, “Reflectance spectroscopy for diagnosis of epithelial precancer: model-based analysis of fiber-optic probe designs to resolve spectral information from epithelium and stroma,” Appl. Opt. 44(20), 4291–4305 (2005).
[CrossRef] [PubMed]

Serafetinides, A. A.

E. Drakaki, E. Kaselouris, M. Makropoulou, A. A. Serafetinides, A. Tsenga, A. J. Stratigos, A. D. Katsambas, and C. Antoniou, “Laser-induced fluorescence and reflectance spectroscopy for the discrimination of basal cell carcinoma from the surrounding normal skin tissue,” Skin Pharmacol. Physiol. 22(3), 158–165 (2009).
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Smallwood, R. H.

D. C. Walker, B. H. Brown, A. D. Blackett, J. Tidy, and R. H. Smallwood, “A study of the morphological parameters of cervical squamous epithelium,” Physiol. Meas. 24(1), 121–135 (2003).
[CrossRef] [PubMed]

Sokolov, K.

R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, “Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: modeling, measurements, and implications,” J. Biomed. Opt. 6(4), 385–396 (2001).
[CrossRef] [PubMed]

Spanier, J.

Staerkel, G.

S. K. Chang, M. Y. Dawood, G. Staerkel, U. Utzinger, E. N. Atkinson, R. R. Richards-Kortum, and M. Follen, “Fluorescence spectroscopy for cervical precancer detection: Is there variance across the menstrual cycle?” J. Biomed. Opt. 7(4), 595–602 (2002).
[CrossRef] [PubMed]

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R. M. P. Doornbos, R. Lang, M. C. Aalders, F. W. Cross, and H. J. C. M. Sterenborg, “The determination of in vivo human tissue optical properties and absolute chromophore concentrations using spatially resolved steady-state diffuse reflectance spectroscopy,” Phys. Med. Biol. 44(4), 967–981 (1999).
[CrossRef] [PubMed]

Stratigos, A. J.

E. Drakaki, E. Kaselouris, M. Makropoulou, A. A. Serafetinides, A. Tsenga, A. J. Stratigos, A. D. Katsambas, and C. Antoniou, “Laser-induced fluorescence and reflectance spectroscopy for the discrimination of basal cell carcinoma from the surrounding normal skin tissue,” Skin Pharmacol. Physiol. 22(3), 158–165 (2009).
[CrossRef] [PubMed]

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W. Verkruysse, R. Zhang, B. Choi, G. Lucassen, L. O. Svaasand, and J. S. Nelson, “A library based fitting method for visual reflectance spectroscopy of human skin,” Phys. Med. Biol. 50(1), 57–70 (2005).
[CrossRef] [PubMed]

Tidy, J.

D. C. Walker, B. H. Brown, A. D. Blackett, J. Tidy, and R. H. Smallwood, “A study of the morphological parameters of cervical squamous epithelium,” Physiol. Meas. 24(1), 121–135 (2003).
[CrossRef] [PubMed]

Tromberg, B. J.

Tsenga, A.

E. Drakaki, E. Kaselouris, M. Makropoulou, A. A. Serafetinides, A. Tsenga, A. J. Stratigos, A. D. Katsambas, and C. Antoniou, “Laser-induced fluorescence and reflectance spectroscopy for the discrimination of basal cell carcinoma from the surrounding normal skin tissue,” Skin Pharmacol. Physiol. 22(3), 158–165 (2009).
[CrossRef] [PubMed]

Utzinger, U.

A. M. J. Wang, J. E. Bender, J. Pfefer, U. Utzinger, and R. A. Drezek, “Depth-sensitive reflectance measurements using obliquely oriented fiber probes,” J. Biomed. Opt. 10(4), 044017 (2005).
[CrossRef] [PubMed]

S. K. Chang, M. Y. Dawood, G. Staerkel, U. Utzinger, E. N. Atkinson, R. R. Richards-Kortum, and M. Follen, “Fluorescence spectroscopy for cervical precancer detection: Is there variance across the menstrual cycle?” J. Biomed. Opt. 7(4), 595–602 (2002).
[CrossRef] [PubMed]

U. Utzinger, D. L. Heintzelman, A. Mahadevan-Jansen, A. Malpica, M. Follen, and R. Richards-Kortum, “Near-infrared Raman spectroscopy for in vivo detection of cervical precancers,” Appl. Spectrosc. 55(8), 955–959 (2001).
[CrossRef]

R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, “Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: modeling, measurements, and implications,” J. Biomed. Opt. 6(4), 385–396 (2001).
[CrossRef] [PubMed]

Van Dam, J.

Venugopalan, V.

Verkruysse, W.

W. Verkruysse, R. Zhang, B. Choi, G. Lucassen, L. O. Svaasand, and J. S. Nelson, “A library based fitting method for visual reflectance spectroscopy of human skin,” Phys. Med. Biol. 50(1), 57–70 (2005).
[CrossRef] [PubMed]

Vrotsos, K. M.

Walker, D. C.

D. C. Walker, B. H. Brown, A. D. Blackett, J. Tidy, and R. H. Smallwood, “A study of the morphological parameters of cervical squamous epithelium,” Physiol. Meas. 24(1), 121–135 (2003).
[CrossRef] [PubMed]

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A. M. J. Wang, J. E. Bender, J. Pfefer, U. Utzinger, and R. A. Drezek, “Depth-sensitive reflectance measurements using obliquely oriented fiber probes,” J. Biomed. Opt. 10(4), 044017 (2005).
[CrossRef] [PubMed]

Wang, J.

Wang, L. H.

L. H. Wang, S. L. Jacques, and L. Q. Zheng, “MCML--Monte Carlo modeling of light transport in multi-layered tissues,” Comput. Methods Programs Biomed. 47(2), 131–146 (1995).
[CrossRef] [PubMed]

Weber, C. R.

I. Pavlova, C. R. Weber, R. A. Schwarz, M. Williams, A. El-Naggar, A. Gillenwater, and R. Richards-Kortum, “Monte Carlo model to describe depth selective fluorescence spectra of epithelial tissue: applications for diagnosis of oral precancer,” J. Biomed. Opt. 13(6), 064012 (2008).
[CrossRef] [PubMed]

Welch, A. J.

Williams, M.

I. Pavlova, C. R. Weber, R. A. Schwarz, M. Williams, A. El-Naggar, A. Gillenwater, and R. Richards-Kortum, “Monte Carlo model to describe depth selective fluorescence spectra of epithelial tissue: applications for diagnosis of oral precancer,” J. Biomed. Opt. 13(6), 064012 (2008).
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S. T. Flock, M. S. Patterson, B. C. Wilson, and D. R. Wyman, “Monte-Carlo modeling of light-propagation in highly scattering tissues. 1. Model predictions and comparison with diffusion-theory,” IEEE Trans. Bio-Med. Eng. 36(12), 1162–1168 (1989).
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S. T. Flock, M. S. Patterson, B. C. Wilson, and D. R. Wyman, “Monte-Carlo modeling of light-propagation in highly scattering tissues. 1. Model predictions and comparison with diffusion-theory,” IEEE Trans. Bio-Med. Eng. 36(12), 1162–1168 (1989).
[CrossRef]

Xu, F. S.

Yaroslavsky, A. N.

E. Salomatina, B. Jiang, J. Novak, and A. N. Yaroslavsky, “Optical properties of normal and cancerous human skin in the visible and near-infrared spectral range,” J. Biomed. Opt. 11(6), 064026 (2006).
[CrossRef] [PubMed]

You, J. S.

Yu, H.

Zhang, R.

W. Verkruysse, R. Zhang, B. Choi, G. Lucassen, L. O. Svaasand, and J. S. Nelson, “A library based fitting method for visual reflectance spectroscopy of human skin,” Phys. Med. Biol. 50(1), 57–70 (2005).
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Figures (8)

Fig. 1
Fig. 1

Probe configurations with tilt angles of both fibers at (a) 0 degree and (b) 45 degrees, relative to the normal axis of the tissue surface. The two cylinders in both sets represent the source and detector fibers and the arrows indicate the direction of light propagation. The acronym S-D represents the center-to-center distance between source and detector fibers.

Fig. 2
Fig. 2

Cross section schematics of the squamous cell carcinoma (SCC) tissue models (a) with a semi-infinite tumor and (b) with a finite-width tumor. The central dashed lines in both (a) and (b) give the central axes of the tissue model used in the simulations, which bisects the source and detector fibers in Fig. 1 and the tumor in Fig. 2 on the cross section view. In the finite-width model, the tumor has a specified finite thickness (h) and width (w).

Fig. 3
Fig. 3

Cross section of the basal cell carcinoma (BCC) tissue model (a) with a semi-infinite tumor and (b) with a finite-width tumor. The central dashed lines in both (a) and (b) represent the central axes of the coordinate systems used in the simulations, bisects the source and detector fibers as in Fig. 1 and the tumors in Fig. 3 on the cross section view. In finite-width tumor model, the tumor has a specified finite thickness (h) and width (w).

Fig. 4
Fig. 4

Simulated diffuse reflectance as a function of the tumor width in terms of the source-detector separation (S-D) when the tumor thickness was fixed at (a) 100 μm and (b) 200 μm in a squamous cell carcinoma (SCC) tissue model. The tilt angles of all fibers were fixed at 0 degree and the S-D was varied from 200 μm to 800 μm with an increment of 200 μm. Each curve is divided into four segments according to the increment of the tumor width on the horizontal axis. The error bars at initial data points and the last data point represent the standard deviation of the data. The label “Inf” on the horizontal axis stands for “Infinity.”

Fig. 7
Fig. 7

Simulated diffuse reflectance as a function of the tumor width in terms of the source-detector separation (S-D) when the tumor thickness was fixed at (a) 200 μm and (b) 400 μm in a basal cell carcinoma (BCC) tissue model. The tilt angles of all fibers were fixed at 45 degrees and the S-D was varied from 400 μm to 800 μm with an increment of 200 μm. Each curve is divided into four segments according to the increment of the tumor width on the horizontal axis. The error bars at initial data points and the last data point represent the standard deviation of the data. Among these data points, the circled ones are statistically different from that for the BCC tissue model with a semi-infinite tumor, which corresponds to the last data point in each subplot. The label “Inf” on the horizontal axis stands for “Infinity.”

Fig. 5
Fig. 5

Simulated diffuse reflectance as a function of the tumor width in terms of the source-detector separation (S-D) when the tumor thickness was fixed at (a) 100 μm and (b) 200 μm in a squamous cell carcinoma (SCC) tissue model. The tilt angles of all fibers were fixed at 45 degrees and the S-D was varied from 400 μm to 800 μm with an increment of 200 μm. Each curve is divided into four segments according to the increment of the tumor width on the horizontal axis. The error bars at initial data points and the last data point represent the standard deviation of the data. Among these data points, the circled ones are statistically different from that for the SCC tissue model with a semi-infinite tumor, which corresponds to the last data point in each subplot. The label “Inf” on the horizontal axis stands for “Infinity.”

Fig. 6
Fig. 6

Simulated diffuse reflectance as a function of the tumor width in terms of the source-detector separation (S-D) when the thickness of tumor was fixed at (a) 200 μm and (b) 400 μm in a basal cell carcinoma (BCC) tissue model. The tilt angles of all fibers were fixed at 0 degree and the S-D was varied from 200 μm to 800 μm with an increment of 200 μm. Each curve is divided into four segments according to the increment of the tumor width on the horizontal axis. The error bars at initial data points and the last data point represent the standard deviation of the data. Among these data points, the circled ones are statistically different from that for the BCC tissue model with a semi-infinite tumor, which corresponds to the last data point in each subplot. The label “Inf” on the horizontal axis stands for “Infinity.”

Fig. 8
Fig. 8

Schematic of the SCC tumor (light gray color) relative to the detection region (black color) with an increasing epithelial thickness for (a) the probe configuration with a zero-degree tilt angle and (b) the probe configuration with a 45-degree tilt angle. It is assumed that the tumor thickness was fixed to be 100 μm when the epithelial thickness was increased from 300 μm to 500 μm in both (a) and (b).

Tables (4)

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Table 1 Optical properties of the SCC tissue model at 500nm [ 26 ]

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Table 2 Optical properties of BCC tissue model at 500nm [ 31 ]

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Table 3 Threshold value of tumor width for the valid semi-infinite SCC tumor model

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Table 4 Threshold value of tumor width for the valid semi-infinite BCC tumor model

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