Abstract

Lens based setups have been explored for non-contact diffuse reflectance measurements to reduce the uncertainty due to inconsistent probe-sample pressure in the past years. However, there have been no reports describing the details of Monte Carlo modeling of lens based non-contact setup for depth sensitive diffuse reflectance measurements to the best of our knowledge. In this study, we first presented a flexible Monte Carlo method to model non-contact diffuse reflectance measurements in a lens based setup. Then this method was used to simulate diffuse reflectance measurements from a squamous cell carcinoma (SCC) tissue model in the cone shell, cone and hybrid configurations, in which the cone shell configuration has not been previously proposed in optical spectroscopy. Depth sensitive measurements were achieved by adjusting the following two parameters: (1) the depth of focal point of the imaging lens in the SCC model; and (2) the cone radius in the cone configuration or the ring radius in the cone shell configuration. It was demonstrated that the cone shell and the hybrid configurations in general have better depth sensitivity to the tumor and the stroma than the more commonly used cone configuration for diffuse reflectance measurements in the SCC model.

© 2012 OSA

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2012

M. Mazurenka, A. Jelzow, H. Wabnitz, D. Contini, L. Spinelli, A. Pifferi, R. Cubeddu, A. D. Mora, A. Tosi, F. Zappa, and R. Macdonald, “Non-contact time-resolved diffuse reflectance imaging at null source-detector separation,” Opt. Express20(1), 283–290 (2012).
[CrossRef] [PubMed]

K. B. Sung and H. H. Chen, “Enhancing the sensitivity to scattering coefficient of the epithelium in a two-layered tissue model by oblique optical fibers: Monte Carlo study,” J. Biomed. Opt.17(10), 107003 (2012).
[CrossRef] [PubMed]

2011

C. G. Zhu and Q. Liu, “Validity of the semi-infinite tumor model in diffuse reflectance spectroscopy for epithelial cancer diagnosis: a Monte Carlo study,” Opt. Express19(18), 17799–17812 (2011).
[CrossRef] [PubMed]

A. J. Radosevich, N. N. Mutyal, V. Turzhitsky, J. D. Rogers, J. Yi, A. Taflove, and V. Backman, “Measurement of the spatial backscattering impulse-response at short length scales with polarized enhanced backscattering,” Opt. Lett.36(24), 4737–4739 (2011).
[CrossRef] [PubMed]

S. F. Bish, N. Rajaram, B. Nichols, and J. W. Tunnell, “Development of a noncontact diffuse optical spectroscopy probe for measuring tissue optical properties,” J. Biomed. Opt.16(12), 120505 (2011).
[CrossRef] [PubMed]

E. Vitkin, V. Turzhitsky, L. Qiu, L. Guo, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Photon diffusion near the point-of-entry in anisotropically scattering turbid media,” Nat Commun2, 587 (2011).
[CrossRef] [PubMed]

V. Turzhitsky, N. N. Mutyal, A. J. Radosevich, and V. Backman, “Multiple scattering model for the penetration depth of low-coherence enhanced backscattering,” J. Biomed. Opt.16(9), 097006 (2011).
[CrossRef] [PubMed]

Q. Liu, “Role of optical spectroscopy using endogenous contrasts in clinical cancer diagnosis,” World J Clin Oncol2(1), 50–63 (2011).
[CrossRef] [PubMed]

L. A. Lim, B. Nichols, N. Rajaram, and J. W. Tunnell, “Probe pressure effects on human skin diffuse reflectance and fluorescence spectroscopy measurements,” J. Biomed. Opt.16(1), 011012 (2011).
[CrossRef] [PubMed]

2010

S. Andree, C. Reble, J. Helfmann, I. Gersonde, and G. Illing, “Evaluation of a novel noncontact spectrally and spatially resolved reflectance setup with continuously variable source-detector separation using silicone phantoms,” J. Biomed. Opt.15(6), 067009 (2010).
[CrossRef] [PubMed]

2009

H. W. Wang, J. K. Jiang, C. H. Lin, J. K. Lin, G. J. Huang, and J. S. Yu, “Diffuse reflectance spectroscopy detects increased hemoglobin concentration and decreased oxygenation during colon carcinogenesis from normal to malignant tumors,” Opt. Express17(4), 2805–2817 (2009).
[CrossRef] [PubMed]

J. Delgado Atencio, E. Orozco Guillén, S. Vázquez y Montiel, M. Cunill Rodríguez, J. Castro Ramos, J. Gutiérrez, and F. Martínez, “Influence of probe pressure on human skin diffuse reflectance spectroscopy measurements,” Opt. Mem. Neural. Networks18(1), 6–14 (2009).
[CrossRef]

2008

Y. L. Ti and W. C. Lin, “Effects of probe contact pressure on in vivo optical spectroscopy,” Opt. Express16(6), 4250–4262 (2008).
[CrossRef] [PubMed]

R. Reif, M. S. Amorosino, K. W. Calabro, O. A’Amar, S. K. Singh, and I. J. Bigio, “Analysis of changes in reflectance measurements on biological tissues subjected to different probe pressures,” J. Biomed. Opt.13(1), 010502 (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]

R. A. Schwarz, W. Gao, D. Daye, M. D. Williams, R. Richards-Kortum, and A. M. Gillenwater, “Autofluorescence and diffuse reflectance spectroscopy of oral epithelial tissue using a depth-sensitive fiber-optic probe,” Appl. Opt.47(6), 825–834 (2008).
[CrossRef] [PubMed]

2006

2005

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]

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]

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]

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

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]

U. Utzinger and R. R. Richards-Kortum, “Fiber optic probes for biomedical optical spectroscopy,” J. Biomed. Opt.8(1), 121–147 (2003).
[CrossRef] [PubMed]

2001

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]

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

1997

1995

L. H. Wang, S. L. Jacques, and L. Q. Zheng, “Mcml - Monte-Carlo Modeling of Light Transport in Multilayered Tissues,” Comput Meth Prog Bio47(2), 131–146 (1995).
[CrossRef]

1994

A’Amar, O.

R. Reif, M. S. Amorosino, K. W. Calabro, O. A’Amar, S. K. Singh, and I. J. Bigio, “Analysis of changes in reflectance measurements on biological tissues subjected to different probe pressures,” J. Biomed. Opt.13(1), 010502 (2008).
[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]

Amorosino, M. S.

R. Reif, M. S. Amorosino, K. W. Calabro, O. A’Amar, S. K. Singh, and I. J. Bigio, “Analysis of changes in reflectance measurements on biological tissues subjected to different probe pressures,” J. Biomed. Opt.13(1), 010502 (2008).
[CrossRef] [PubMed]

Andree, S.

S. Andree, C. Reble, J. Helfmann, I. Gersonde, and G. Illing, “Evaluation of a novel noncontact spectrally and spatially resolved reflectance setup with continuously variable source-detector separation using silicone phantoms,” J. Biomed. Opt.15(6), 067009 (2010).
[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, 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]

Backman, V.

V. Turzhitsky, N. N. Mutyal, A. J. Radosevich, and V. Backman, “Multiple scattering model for the penetration depth of low-coherence enhanced backscattering,” J. Biomed. Opt.16(9), 097006 (2011).
[CrossRef] [PubMed]

A. J. Radosevich, N. N. Mutyal, V. Turzhitsky, J. D. Rogers, J. Yi, A. Taflove, and V. Backman, “Measurement of the spatial backscattering impulse-response at short length scales with polarized enhanced backscattering,” Opt. Lett.36(24), 4737–4739 (2011).
[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]

Bigio, I.

Bigio, I. J.

R. Reif, M. S. Amorosino, K. W. Calabro, O. A’Amar, S. K. Singh, and I. J. Bigio, “Analysis of changes in reflectance measurements on biological tissues subjected to different probe pressures,” J. Biomed. Opt.13(1), 010502 (2008).
[CrossRef] [PubMed]

Bish, S. F.

S. F. Bish, N. Rajaram, B. Nichols, and J. W. Tunnell, “Development of a noncontact diffuse optical spectroscopy probe for measuring tissue optical properties,” J. Biomed. Opt.16(12), 120505 (2011).
[CrossRef] [PubMed]

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]

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]

Calabro, K. W.

R. Reif, M. S. Amorosino, K. W. Calabro, O. A’Amar, S. K. Singh, and I. J. Bigio, “Analysis of changes in reflectance measurements on biological tissues subjected to different probe pressures,” J. Biomed. Opt.13(1), 010502 (2008).
[CrossRef] [PubMed]

Castro Ramos, J.

J. Delgado Atencio, E. Orozco Guillén, S. Vázquez y Montiel, M. Cunill Rodríguez, J. Castro Ramos, J. Gutiérrez, and F. Martínez, “Influence of probe pressure on human skin diffuse reflectance spectroscopy measurements,” Opt. Mem. Neural. Networks18(1), 6–14 (2009).
[CrossRef]

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]

Chen, H. H.

K. B. Sung and H. H. Chen, “Enhancing the sensitivity to scattering coefficient of the epithelium in a two-layered tissue model by oblique optical fibers: Monte Carlo study,” J. Biomed. Opt.17(10), 107003 (2012).
[CrossRef] [PubMed]

Contini, D.

Cubeddu, R.

Cunill Rodríguez, M.

J. Delgado Atencio, E. Orozco Guillén, S. Vázquez y Montiel, M. Cunill Rodríguez, J. Castro Ramos, J. Gutiérrez, and F. Martínez, “Influence of probe pressure on human skin diffuse reflectance spectroscopy measurements,” Opt. Mem. Neural. Networks18(1), 6–14 (2009).
[CrossRef]

Daye, D.

Delgado Atencio, J.

J. Delgado Atencio, E. Orozco Guillén, S. Vázquez y Montiel, M. Cunill Rodríguez, J. Castro Ramos, J. Gutiérrez, and F. Martínez, “Influence of probe pressure on human skin diffuse reflectance spectroscopy measurements,” Opt. Mem. Neural. Networks18(1), 6–14 (2009).
[CrossRef]

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.

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]

Eick, A.

Feld, M. S.

Fitzmaurice, M.

Follen, M.

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]

Freyer, J.

Gao, W.

Gersonde, I.

S. Andree, C. Reble, J. Helfmann, I. Gersonde, and G. Illing, “Evaluation of a novel noncontact spectrally and spatially resolved reflectance setup with continuously variable source-detector separation using silicone phantoms,” J. Biomed. Opt.15(6), 067009 (2010).
[CrossRef] [PubMed]

Gillenwater, A. M.

Guo, L.

E. Vitkin, V. Turzhitsky, L. Qiu, L. Guo, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Photon diffusion near the point-of-entry in anisotropically scattering turbid media,” Nat Commun2, 587 (2011).
[CrossRef] [PubMed]

Gutiérrez, J.

J. Delgado Atencio, E. Orozco Guillén, S. Vázquez y Montiel, M. Cunill Rodríguez, J. Castro Ramos, J. Gutiérrez, and F. Martínez, “Influence of probe pressure on human skin diffuse reflectance spectroscopy measurements,” Opt. Mem. Neural. Networks18(1), 6–14 (2009).
[CrossRef]

Hanlon, E. B.

E. Vitkin, V. Turzhitsky, L. Qiu, L. Guo, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Photon diffusion near the point-of-entry in anisotropically scattering turbid media,” Nat Commun2, 587 (2011).
[CrossRef] [PubMed]

Helfmann, J.

S. Andree, C. Reble, J. Helfmann, I. Gersonde, and G. Illing, “Evaluation of a novel noncontact spectrally and spatially resolved reflectance setup with continuously variable source-detector separation using silicone phantoms,” J. Biomed. Opt.15(6), 067009 (2010).
[CrossRef] [PubMed]

Hielscher, A.

Hijazi, Y. R.

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]

Huang, G. J.

Illing, G.

S. Andree, C. Reble, J. Helfmann, I. Gersonde, and G. Illing, “Evaluation of a novel noncontact spectrally and spatially resolved reflectance setup with continuously variable source-detector separation using silicone phantoms,” J. Biomed. Opt.15(6), 067009 (2010).
[CrossRef] [PubMed]

Itzkan, I.

E. Vitkin, V. Turzhitsky, L. Qiu, L. Guo, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Photon diffusion near the point-of-entry in anisotropically scattering turbid media,” Nat Commun2, 587 (2011).
[CrossRef] [PubMed]

Ivarie, C. A. R.

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]

Jacques, S. L.

L. H. Wang, S. L. Jacques, and L. Q. Zheng, “Mcml - Monte-Carlo Modeling of Light Transport in Multilayered Tissues,” Comput Meth Prog Bio47(2), 131–146 (1995).
[CrossRef]

Jelzow, A.

Jiang, J. K.

Kortun, C.

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]

Lam, S.

Liang, G.

Lim, L. A.

L. A. Lim, B. Nichols, N. Rajaram, and J. W. Tunnell, “Probe pressure effects on human skin diffuse reflectance and fluorescence spectroscopy measurements,” J. Biomed. Opt.16(1), 011012 (2011).
[CrossRef] [PubMed]

Lin, C. H.

Lin, J. K.

Lin, W. C.

Liu, Q.

Macaulay, C.

Macdonald, R.

Malpica, A.

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]

Manoharan, R.

Martínez, F.

J. Delgado Atencio, E. Orozco Guillén, S. Vázquez y Montiel, M. Cunill Rodríguez, J. Castro Ramos, J. Gutiérrez, and F. Martínez, “Influence of probe pressure on human skin diffuse reflectance spectroscopy measurements,” Opt. Mem. Neural. Networks18(1), 6–14 (2009).
[CrossRef]

Mazurenka, M.

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).
[CrossRef] [PubMed]

Mora, A. D.

Mourant, J.

Mutyal, N. N.

V. Turzhitsky, N. N. Mutyal, A. J. Radosevich, and V. Backman, “Multiple scattering model for the penetration depth of low-coherence enhanced backscattering,” J. Biomed. Opt.16(9), 097006 (2011).
[CrossRef] [PubMed]

A. J. Radosevich, N. N. Mutyal, V. Turzhitsky, J. D. Rogers, J. Yi, A. Taflove, and V. Backman, “Measurement of the spatial backscattering impulse-response at short length scales with polarized enhanced backscattering,” Opt. Lett.36(24), 4737–4739 (2011).
[CrossRef] [PubMed]

Nichols, B.

S. F. Bish, N. Rajaram, B. Nichols, and J. W. Tunnell, “Development of a noncontact diffuse optical spectroscopy probe for measuring tissue optical properties,” J. Biomed. Opt.16(12), 120505 (2011).
[CrossRef] [PubMed]

L. A. Lim, B. Nichols, N. Rajaram, and J. W. Tunnell, “Probe pressure effects on human skin diffuse reflectance and fluorescence spectroscopy measurements,” J. Biomed. Opt.16(1), 011012 (2011).
[CrossRef] [PubMed]

O’Connor, S. 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]

Orozco Guillén, E.

J. Delgado Atencio, E. Orozco Guillén, S. Vázquez y Montiel, M. Cunill Rodríguez, J. Castro Ramos, J. Gutiérrez, and F. Martínez, “Influence of probe pressure on human skin diffuse reflectance spectroscopy measurements,” Opt. Mem. Neural. Networks18(1), 6–14 (2009).
[CrossRef]

Palcic, B.

Perelman, L. T.

E. Vitkin, V. Turzhitsky, L. Qiu, L. Guo, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Photon diffusion near the point-of-entry in anisotropically scattering turbid media,” Nat Commun2, 587 (2011).
[CrossRef] [PubMed]

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]

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).
[CrossRef] [PubMed]

Pfefer, T. J.

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]

Pifferi, A.

Qiu, L.

E. Vitkin, V. Turzhitsky, L. Qiu, L. Guo, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Photon diffusion near the point-of-entry in anisotropically scattering turbid media,” Nat Commun2, 587 (2011).
[CrossRef] [PubMed]

Qu, J.

Radosevich, A. J.

V. Turzhitsky, N. N. Mutyal, A. J. Radosevich, and V. Backman, “Multiple scattering model for the penetration depth of low-coherence enhanced backscattering,” J. Biomed. Opt.16(9), 097006 (2011).
[CrossRef] [PubMed]

A. J. Radosevich, N. N. Mutyal, V. Turzhitsky, J. D. Rogers, J. Yi, A. Taflove, and V. Backman, “Measurement of the spatial backscattering impulse-response at short length scales with polarized enhanced backscattering,” Opt. Lett.36(24), 4737–4739 (2011).
[CrossRef] [PubMed]

Rajaram, N.

L. A. Lim, B. Nichols, N. Rajaram, and J. W. Tunnell, “Probe pressure effects on human skin diffuse reflectance and fluorescence spectroscopy measurements,” J. Biomed. Opt.16(1), 011012 (2011).
[CrossRef] [PubMed]

S. F. Bish, N. Rajaram, B. Nichols, and J. W. Tunnell, “Development of a noncontact diffuse optical spectroscopy probe for measuring tissue optical properties,” J. Biomed. Opt.16(12), 120505 (2011).
[CrossRef] [PubMed]

Ramanujam, N.

Reble, C.

S. Andree, C. Reble, J. Helfmann, I. Gersonde, and G. Illing, “Evaluation of a novel noncontact spectrally and spatially resolved reflectance setup with continuously variable source-detector separation using silicone phantoms,” J. Biomed. Opt.15(6), 067009 (2010).
[CrossRef] [PubMed]

Reif, R.

R. Reif, M. S. Amorosino, K. W. Calabro, O. A’Amar, S. K. Singh, and I. J. Bigio, “Analysis of changes in reflectance measurements on biological tissues subjected to different probe pressures,” J. Biomed. Opt.13(1), 010502 (2008).
[CrossRef] [PubMed]

Richards-Kortum, R.

R. A. Schwarz, W. Gao, D. Daye, M. D. Williams, R. Richards-Kortum, and A. M. Gillenwater, “Autofluorescence and diffuse reflectance spectroscopy of oral epithelial tissue using a depth-sensitive fiber-optic probe,” Appl. Opt.47(6), 825–834 (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]

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]

Richards-Kortum, R. R.

U. Utzinger and R. R. Richards-Kortum, “Fiber optic probes for biomedical optical spectroscopy,” J. Biomed. Opt.8(1), 121–147 (2003).
[CrossRef] [PubMed]

Rogers, J. D.

Sattler, C. A.

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.

Shen, D.

Singh, S. K.

R. Reif, M. S. Amorosino, K. W. Calabro, O. A’Amar, S. K. Singh, and I. J. Bigio, “Analysis of changes in reflectance measurements on biological tissues subjected to different probe pressures,” J. Biomed. Opt.13(1), 010502 (2008).
[CrossRef] [PubMed]

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]

Spinelli, L.

Sung, K. B.

K. B. Sung and H. H. Chen, “Enhancing the sensitivity to scattering coefficient of the epithelium in a two-layered tissue model by oblique optical fibers: Monte Carlo study,” J. Biomed. Opt.17(10), 107003 (2012).
[CrossRef] [PubMed]

Taflove, A.

Ti, Y. L.

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]

Tosi, A.

Tunnell, J. W.

L. A. Lim, B. Nichols, N. Rajaram, and J. W. Tunnell, “Probe pressure effects on human skin diffuse reflectance and fluorescence spectroscopy measurements,” J. Biomed. Opt.16(1), 011012 (2011).
[CrossRef] [PubMed]

S. F. Bish, N. Rajaram, B. Nichols, and J. W. Tunnell, “Development of a noncontact diffuse optical spectroscopy probe for measuring tissue optical properties,” J. Biomed. Opt.16(12), 120505 (2011).
[CrossRef] [PubMed]

Turzhitsky, V.

A. J. Radosevich, N. N. Mutyal, V. Turzhitsky, J. D. Rogers, J. Yi, A. Taflove, and V. Backman, “Measurement of the spatial backscattering impulse-response at short length scales with polarized enhanced backscattering,” Opt. Lett.36(24), 4737–4739 (2011).
[CrossRef] [PubMed]

E. Vitkin, V. Turzhitsky, L. Qiu, L. Guo, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Photon diffusion near the point-of-entry in anisotropically scattering turbid media,” Nat Commun2, 587 (2011).
[CrossRef] [PubMed]

V. Turzhitsky, N. N. Mutyal, A. J. Radosevich, and V. Backman, “Multiple scattering model for the penetration depth of low-coherence enhanced backscattering,” J. Biomed. Opt.16(9), 097006 (2011).
[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]

U. Utzinger and R. R. Richards-Kortum, “Fiber optic probes for biomedical optical spectroscopy,” J. Biomed. Opt.8(1), 121–147 (2003).
[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]

Van Dam, J.

Vázquez y Montiel, S.

J. Delgado Atencio, E. Orozco Guillén, S. Vázquez y Montiel, M. Cunill Rodríguez, J. Castro Ramos, J. Gutiérrez, and F. Martínez, “Influence of probe pressure on human skin diffuse reflectance spectroscopy measurements,” Opt. Mem. Neural. Networks18(1), 6–14 (2009).
[CrossRef]

Vitkin, E.

E. Vitkin, V. Turzhitsky, L. Qiu, L. Guo, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Photon diffusion near the point-of-entry in anisotropically scattering turbid media,” Nat Commun2, 587 (2011).
[CrossRef] [PubMed]

Wabnitz, H.

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]

Wang, A. M. 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).
[CrossRef] [PubMed]

Wang, H. W.

Wang, L. H.

L. H. Wang, S. L. Jacques, and L. Q. Zheng, “Mcml - Monte-Carlo Modeling of Light Transport in Multilayered Tissues,” Comput Meth Prog Bio47(2), 131–146 (1995).
[CrossRef]

Wang, L. V.

Williams, M. D.

Yi, J.

Yu, J. S.

Zappa, F.

Zheng, L. Q.

L. H. Wang, S. L. Jacques, and L. Q. Zheng, “Mcml - Monte-Carlo Modeling of Light Transport in Multilayered Tissues,” Comput Meth Prog Bio47(2), 131–146 (1995).
[CrossRef]

Zhu, C. G.

Zonios, G.

Appl. Opt.

Comput Meth Prog Bio

L. H. Wang, S. L. Jacques, and L. Q. Zheng, “Mcml - Monte-Carlo Modeling of Light Transport in Multilayered Tissues,” Comput Meth Prog Bio47(2), 131–146 (1995).
[CrossRef]

J. Biomed. Opt.

R. Reif, M. S. Amorosino, K. W. Calabro, O. A’Amar, S. K. Singh, and I. J. Bigio, “Analysis of changes in reflectance measurements on biological tissues subjected to different probe pressures,” J. Biomed. Opt.13(1), 010502 (2008).
[CrossRef] [PubMed]

U. Utzinger and R. R. Richards-Kortum, “Fiber optic probes for biomedical optical spectroscopy,” J. Biomed. Opt.8(1), 121–147 (2003).
[CrossRef] [PubMed]

L. A. Lim, B. Nichols, N. Rajaram, and J. W. Tunnell, “Probe pressure effects on human skin diffuse reflectance and fluorescence spectroscopy measurements,” J. Biomed. Opt.16(1), 011012 (2011).
[CrossRef] [PubMed]

S. Andree, C. Reble, J. Helfmann, I. Gersonde, and G. Illing, “Evaluation of a novel noncontact spectrally and spatially resolved reflectance setup with continuously variable source-detector separation using silicone phantoms,” J. Biomed. Opt.15(6), 067009 (2010).
[CrossRef] [PubMed]

S. F. Bish, N. Rajaram, B. Nichols, and J. W. Tunnell, “Development of a noncontact diffuse optical spectroscopy probe for measuring tissue optical properties,” J. Biomed. Opt.16(12), 120505 (2011).
[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]

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]

V. Turzhitsky, N. N. Mutyal, A. J. Radosevich, and V. Backman, “Multiple scattering model for the penetration depth of low-coherence enhanced backscattering,” J. Biomed. Opt.16(9), 097006 (2011).
[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]

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]

K. B. Sung and H. H. Chen, “Enhancing the sensitivity to scattering coefficient of the epithelium in a two-layered tissue model by oblique optical fibers: Monte Carlo study,” J. Biomed. Opt.17(10), 107003 (2012).
[CrossRef] [PubMed]

J. Invest. Dermatol.

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]

Nat Commun

E. Vitkin, V. Turzhitsky, L. Qiu, L. Guo, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Photon diffusion near the point-of-entry in anisotropically scattering turbid media,” Nat Commun2, 587 (2011).
[CrossRef] [PubMed]

Opt. Express

Opt. Lett.

Opt. Mem. Neural. Networks

J. Delgado Atencio, E. Orozco Guillén, S. Vázquez y Montiel, M. Cunill Rodríguez, J. Castro Ramos, J. Gutiérrez, and F. Martínez, “Influence of probe pressure on human skin diffuse reflectance spectroscopy measurements,” Opt. Mem. Neural. Networks18(1), 6–14 (2009).
[CrossRef]

Physiol. Meas.

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]

World J Clin Oncol

Q. Liu, “Role of optical spectroscopy using endogenous contrasts in clinical cancer diagnosis,” World J Clin Oncol2(1), 50–63 (2011).
[CrossRef] [PubMed]

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Figures (15)

Fig. 1
Fig. 1

(a) Schematic of the lens based set up for non-contact diffuse reflectance measurements; (b) The circular (top) and ring (bottom) shapes of the mask between Lens 2 and the beam splitter in the cone and cone shell configurations. In (b), light can pass through the white area but is blocked in the gray area. The symbols, “r”, “R” and “t” represent the radius of the circle in the cone configuration, and the ring radius and the ring thickness in the cone shell configuration. The cone configuration can be seen as a special case of cone shell configuration in which the ring radius is zero.

Fig. 2
Fig. 2

Cone shell illumination schematic.

Fig. 3
Fig. 3

(a) Schematic of the cone shell detection; (b) Detailed view of the cone shell detection at the interface of Lens 2 and the tissue model.

Fig. 4
Fig. 4

Absorption distribution of detected photons for (a) the depth of focal point in the tissue model was 0.5 mm; and (b) the depth of focal point in the tissue model was 1.0 mm.

Fig. 5
Fig. 5

Cross section view of the squamous cell carcinoma (SCC) tissue model. The tumor width and length were set to 0.5 mm while the tumor thickness was set to 0.3 mm. This model represents a tumor in an early stage.

Fig. 6
Fig. 6

Diffuse reflectance as a function of the ring radius for a range of depths of the focal point in the tissue model in a cone shell configuration. Each line represents the results for a different depth value as indicated in the legends. The ring thickness and the diameter of detection fiber were fixed at 2 mm and 0.2 mm, respectively.

Fig. 7
Fig. 7

Fraction of collisions in (a) the tumor, (b) the epithelium and (c) the stroma layer in the cone shell configuration. Each line represents the results for a different depth value as indicated in the legends. The ring thickness and the diameter of detection fiber were fixed at 2 mm and 0.2 mm, respectively.

Fig. 8
Fig. 8

Fraction of path length in (a) the tumor, (b) the epithelium and (c) the stroma layer in the cone shell configuration. Each line represents the results for a different depth value as indicated in the legends. The ring thickness and the diameter of detection fiber were fixed at 2 mm, and 0.2 mm respectively.

Fig. 9
Fig. 9

Effect of the ring thickness on the fraction of collisions in (a) the tumor and (b) the Stroma for the cone shell configurations. In (a), the depth of focal point in the tissue model, i.e. Zf, is 0.3 mm; while in (b), the depth of focal point in the tissue model, i.e. Zf, is 1.0 mm. Each line represents the results for a different ring thickness as indicated in the legends. The diameter of detection fiber was fixed at 0.2 mm.

Fig. 10
Fig. 10

Effect of the detection fiber size on the fraction of collisions in (a) the tumor and (b) the Stroma for the cone shell configurations. In (a), the depth of focal point in the tissue model, i.e. Zf, is 0.3 mm; while in (b), the depth of focal point in the tissue model, i.e. Zf, is 1.0 mm. Each line represents the results for a different detection fiber size as indicated in the legends. The ring thickness was fixed at 2 mm.

Fig. 11
Fig. 11

Effect of the detection fiber size on the fraction of collisions in (a) the tumor and (b) the Stroma for the cone configurations. In (a), the depth of focal point in the tissue model, i.e. Zf, is 0.3 mm; while in (b), the depth of focal point in the tissue model, i.e. Zf, is 1.0 mm. Each line represents the results for a different detection fiber size as indicated in the legends.

Fig. 12
Fig. 12

Effect of the ring thickness on the fraction of collisions in (a) the tumor and (b) the stroma for the hybrid configuration. In (a), the depth of the focal point in the tissue model, i.e. Zf, is 0.3 mm; while in (b), the depth of the focal point is 1.0 mm. Each line represents the results for a different ring thickness as indicated by the legends. The diameter of the detection fiber was fixed at 0.2 mm. The radius of the cone for detection is equal to the radius of the imaging lens, i.e. 10 mm.

Fig. 13
Fig. 13

Effect of the detection fiber size on the fraction of collisions in (a) the tumor and (b) the stroma for the hybrid configuration. In (a), the depth of the focal point in the tissue model, i.e. Zf, is 0.3 mm; while in (b), the depth of the focal point is 1.0 mm. Each line represents a different size of the detection fiber as indicated by the legends. The ring thickness was fixed at 3 mm. The radius of the cone for detection is equal to the radius of the imaging lens, i.e. 10 mm.

Fig. 14
Fig. 14

Intersection of the cone shell region and the tumor when the depth of the focal point in the tumor model is (a) 0.3 mm and (b) 1.0 mm.

Fig. 15
Fig. 15

Intersection of the cone shell region and the tumor when the ring thickness is different. The symbols “α” and “β” refer to the angles between the light beam and the normal axis for a thin and a thick ring respectively.

Tables (6)

Tables Icon

Table 1 Optical properties of the SCC tissue model at 420nm [22]

Tables Icon

Table 2 Simulations for the cone shell configuration

Tables Icon

Table 3 Simulations for the cone configuration

Tables Icon

Table 4 Simulations for the hybrid configuration*

Tables Icon

Table 5 The best FCT between the cone, the hybrid and the cone shell set up for a depth of focus of 0.3 mm

Tables Icon

Table 6 The best FCS between the cone, the hybrid and the cone shell set up for a depth of focus of 1.0 mm

Equations (14)

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

ρ ring R = Z f f
t new t = Z f f
ρ= [ ( ρ ring + t new ) 2 ρ ring 2 ] ε ρ + ρ ring 2
θ=2π ε θ
x=ρcos(θ)
y=ρsin(θ)
u x = x / ρ 2 + Z f 2
u y = y / ρ 2 + Z f 2
u z = Z f / ρ 2 + Z f 2
NC ¯ = i=1 N W i *N C i i=1 N W i
FCT= N C tumor ¯ N C epithelium ¯ + N C tumor ¯ + N C Stroma ¯
PL ¯ = i=1 N W i *P L i i=1 N W i
FPLT= P L tumor ¯ P L epithelium ¯ + P L tumor ¯ + P L Stroma ¯
TC= | R tumor R control | R control ×100%

Metrics