Abstract

In this study, we present a fiber-optic ball lens Raman probe design for improving depth-selected Raman measurements of epithelial tissue. The Monte Carlo simulation results show that tissue Raman collection efficiency can be improved by properly selecting the refractive index and the diameter of the ball lens for the Raman probe design and the depth-selectivity of Raman measurements can also be improved by either increasing the refractive index or reducing the diameter of the ball lens. An appropriate arrangement of the Raman probe-tissue distance can also optimize the collection efficiency for depth-resolved Raman measurements. Experimental evaluation of a ball lens Raman probe design on a two-layer tissue phantom confirms the potential of the ball lens Raman probe design for efficient depth-selected measurement on epithelial tissue. This work suggests that the fiber-optic Raman probe coupled with a ball lens can facilitate the depth-selected Raman measurements of epithelial tissue, which may improve the diagnosis of epithelial precancer and early cancer at the molecular level.

© 2010 OSA

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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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  20. W. C. Shih, K. L. Bechtel, and M. S. Feld, “Intrinsic Raman spectroscopy for quantitative biological spectroscopy part I: theory and simulations,” Opt. Express 16(17), 12726–12736 (2008).
    [PubMed]
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    [CrossRef] [PubMed]

2009

2008

2005

2004

2003

Z. Huang, A. McWilliams, H. Lui, D. I. McLean, S. Lam, and H. Zeng, “Near-infrared Raman spectroscopy for optical diagnosis of lung cancer,” Int. J. Cancer 107(6), 1047–1052 (2003).
[CrossRef] [PubMed]

2002

N. Stone, C. Kendall, N. Shepherd, P. Crow, and H. Barr, “Near-infrared Raman spectroscopy for the classification of epithelial pre-cancers and cancers,” J. Raman Spectrosc. 33(7), 564–573 (2002).
[CrossRef]

T. J. Pfefer, K. T. Schomacker, M. N. Ediger, and N. S. Nishioka, “Multiple-fiber probe design for fluorescence spectroscopy in tissue,” Appl. Opt. 41(22), 4712–4721 (2002).
[CrossRef] [PubMed]

2001

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, “Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia,” Photochem. Photobiol. 73(6), 636–641 (2001).
[CrossRef] [PubMed]

T. J. Pfefer, K. T. Schomacker, M. N. Ediger, and N. S. Nishioka, “Light propagation in tissue during fluorescence spectroscopy with single-fiber probes,” IEEE Sel. Top. Quantum Electron. 7(6), 1004–1012 (2001).
[CrossRef]

Z. Huang, H. Zeng, I. Hamzavi, D. I. McLean, and H. Lui, “Rapid near-infrared Raman spectroscopy system for real-time in vivo skin measurements,” Opt. Lett. 26(22), 1782–1784 (2001).
[CrossRef] [PubMed]

1999

1997

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21(2), 166–178 (1997).
[CrossRef] [PubMed]

1995

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

1982

F. W. Abdul-Karim, Y. S. Fu, J. W. Reagan, and W. B. Wentz, “Morphometric study of intraepithelial neoplasia of the uterine cervix,” Obstet. Gynecol. 60(2), 210–214 (1982).
[PubMed]

1941

L. G. Henyey and J. L. Greenstein, “Diffuse radiation in galaxy,” Astrophys. J. 93, 70–83 (1941).
[CrossRef]

Aaron, J.

Abdul-Karim, F. W.

F. W. Abdul-Karim, Y. S. Fu, J. W. Reagan, and W. B. Wentz, “Morphometric study of intraepithelial neoplasia of the uterine cervix,” Obstet. Gynecol. 60(2), 210–214 (1982).
[PubMed]

Arifler, D.

R. A. Schwarz, D. Arifler, S. K. Chang, I. Pavlova, I. A. Hussain, V. Mack, B. Knight, R. Richards-Kortum, and A. M. Gillenwater, “Ball lens coupled fiber-optic probe for depth-resolved spectroscopy of epithelial tissue,” Opt. Lett. 30(10), 1159–1161 (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]

Barr, H.

N. Stone, C. Kendall, N. Shepherd, P. Crow, and H. Barr, “Near-infrared Raman spectroscopy for the classification of epithelial pre-cancers and cancers,” J. Raman Spectrosc. 33(7), 564–573 (2002).
[CrossRef]

Bechtel, K. L.

Boiko, I.

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, “Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia,” Photochem. Photobiol. 73(6), 636–641 (2001).
[CrossRef] [PubMed]

Brookner, C.

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, “Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia,” Photochem. Photobiol. 73(6), 636–641 (2001).
[CrossRef] [PubMed]

Chan, E.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21(2), 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, R. Richards-Kortum, and A. M. Gillenwater, “Ball lens coupled fiber-optic probe for depth-resolved spectroscopy of epithelial tissue,” Opt. Lett. 30(10), 1159–1161 (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]

Criswell, G.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21(2), 166–178 (1997).
[CrossRef] [PubMed]

Crow, P.

N. Stone, C. Kendall, N. Shepherd, P. Crow, and H. Barr, “Near-infrared Raman spectroscopy for the classification of epithelial pre-cancers and cancers,” J. Raman Spectrosc. 33(7), 564–573 (2002).
[CrossRef]

Dasari, R. R.

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, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, “Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia,” Photochem. Photobiol. 73(6), 636–641 (2001).
[CrossRef] [PubMed]

Ediger, M. N.

T. J. Pfefer, K. T. Schomacker, M. N. Ediger, and N. S. Nishioka, “Multiple-fiber probe design for fluorescence spectroscopy in tissue,” Appl. Opt. 41(22), 4712–4721 (2002).
[CrossRef] [PubMed]

T. J. Pfefer, K. T. Schomacker, M. N. Ediger, and N. S. Nishioka, “Light propagation in tissue during fluorescence spectroscopy with single-fiber probes,” IEEE Sel. Top. Quantum Electron. 7(6), 1004–1012 (2001).
[CrossRef]

Feld, M. S.

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, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, “Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia,” Photochem. Photobiol. 73(6), 636–641 (2001).
[CrossRef] [PubMed]

Fu, Y. S.

F. W. Abdul-Karim, Y. S. Fu, J. W. Reagan, and W. B. Wentz, “Morphometric study of intraepithelial neoplasia of the uterine cervix,” Obstet. Gynecol. 60(2), 210–214 (1982).
[PubMed]

Galindo, L. H.

Gardecki, J. A.

Gardner, C.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21(2), 166–178 (1997).
[CrossRef] [PubMed]

Gillenwater, A. M.

Greenstein, J. L.

L. G. Henyey and J. L. Greenstein, “Diffuse radiation in galaxy,” Astrophys. J. 93, 70–83 (1941).
[CrossRef]

Hamzavi, I.

Henyey, L. G.

L. G. Henyey and J. L. Greenstein, “Diffuse radiation in galaxy,” Astrophys. J. 93, 70–83 (1941).
[CrossRef]

Ho, K. Y.

Huang, Z.

Z. Huang, S. K. Teh, W. Zheng, J. Mo, K. Lin, X. Shao, K. Y. Ho, M. Teh, and K. G. Yeoh, “Integrated Raman spectroscopy and trimodal wide-field imaging techniques for real-time in vivo tissue Raman measurements at endoscopy,” Opt. Lett. 34(6), 758–760 (2009).
[CrossRef] [PubMed]

J. Mo, W. Zheng, J. J. H. Low, J. Ng, A. Ilancheran, and Z. Huang, “High wavenumber Raman spectroscopy for in vivo detection of cervical dysplasia,” Anal. Chem. 81(21), 8908–8915 (2009).
[CrossRef] [PubMed]

F. Jaillon, W. Zheng, and Z. Huang, “Beveled fiber-optic probe couples a ball lens for improving depth-resolved fluorescence measurements of layered tissue: Monte Carlo simulations,” Phys. Med. Biol. 53(4), 937–951 (2008).
[CrossRef] [PubMed]

F. Jaillon, W. Zheng, and Z. Huang, “Half-ball lens couples a beveled fiber probe for depth-resolved spectroscopy: Monte Carlo simulations,” Appl. Opt. 47(17), 3152–3157 (2008).
[CrossRef] [PubMed]

Z. Huang, A. McWilliams, H. Lui, D. I. McLean, S. Lam, and H. Zeng, “Near-infrared Raman spectroscopy for optical diagnosis of lung cancer,” Int. J. Cancer 107(6), 1047–1052 (2003).
[CrossRef] [PubMed]

Z. Huang, H. Zeng, I. Hamzavi, D. I. McLean, and H. Lui, “Rapid near-infrared Raman spectroscopy system for real-time in vivo skin measurements,” Opt. Lett. 26(22), 1782–1784 (2001).
[CrossRef] [PubMed]

Hunter, M.

Hussain, I. A.

Ilancheran, A.

J. Mo, W. Zheng, J. J. H. Low, J. Ng, A. Ilancheran, and Z. Huang, “High wavenumber Raman spectroscopy for in vivo detection of cervical dysplasia,” Anal. Chem. 81(21), 8908–8915 (2009).
[CrossRef] [PubMed]

Jacques, S. L.

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

Jaillon, F.

F. Jaillon, W. Zheng, and Z. Huang, “Beveled fiber-optic probe couples a ball lens for improving depth-resolved fluorescence measurements of layered tissue: Monte Carlo simulations,” Phys. Med. Biol. 53(4), 937–951 (2008).
[CrossRef] [PubMed]

F. Jaillon, W. Zheng, and Z. Huang, “Half-ball lens couples a beveled fiber probe for depth-resolved spectroscopy: Monte Carlo simulations,” Appl. Opt. 47(17), 3152–3157 (2008).
[CrossRef] [PubMed]

Kendall, C.

N. Stone, C. Kendall, N. Shepherd, P. Crow, and H. Barr, “Near-infrared Raman spectroscopy for the classification of epithelial pre-cancers and cancers,” J. Raman Spectrosc. 33(7), 564–573 (2002).
[CrossRef]

Knight, B.

Kramer, J. R.

Lam, S.

Z. Huang, A. McWilliams, H. Lui, D. I. McLean, S. Lam, and H. Zeng, “Near-infrared Raman spectroscopy for optical diagnosis of lung cancer,” Int. J. Cancer 107(6), 1047–1052 (2003).
[CrossRef] [PubMed]

Lin, K.

Lotan, R.

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, “Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia,” Photochem. Photobiol. 73(6), 636–641 (2001).
[CrossRef] [PubMed]

Low, J. J. H.

J. Mo, W. Zheng, J. J. H. Low, J. Ng, A. Ilancheran, and Z. Huang, “High wavenumber Raman spectroscopy for in vivo detection of cervical dysplasia,” Anal. Chem. 81(21), 8908–8915 (2009).
[CrossRef] [PubMed]

Lui, H.

Z. Huang, A. McWilliams, H. Lui, D. I. McLean, S. Lam, and H. Zeng, “Near-infrared Raman spectroscopy for optical diagnosis of lung cancer,” Int. J. Cancer 107(6), 1047–1052 (2003).
[CrossRef] [PubMed]

Z. Huang, H. Zeng, I. Hamzavi, D. I. McLean, and H. Lui, “Rapid near-infrared Raman spectroscopy system for real-time in vivo skin measurements,” Opt. Lett. 26(22), 1782–1784 (2001).
[CrossRef] [PubMed]

Mack, V.

Malpica, A.

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, “Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia,” Photochem. Photobiol. 73(6), 636–641 (2001).
[CrossRef] [PubMed]

Marple, E.

McLean, D. I.

Z. Huang, A. McWilliams, H. Lui, D. I. McLean, S. Lam, and H. Zeng, “Near-infrared Raman spectroscopy for optical diagnosis of lung cancer,” Int. J. Cancer 107(6), 1047–1052 (2003).
[CrossRef] [PubMed]

Z. Huang, H. Zeng, I. Hamzavi, D. I. McLean, and H. Lui, “Rapid near-infrared Raman spectroscopy system for real-time in vivo skin measurements,” Opt. Lett. 26(22), 1782–1784 (2001).
[CrossRef] [PubMed]

McWilliams, A.

Z. Huang, A. McWilliams, H. Lui, D. I. McLean, S. Lam, and H. Zeng, “Near-infrared Raman spectroscopy for optical diagnosis of lung cancer,” Int. J. Cancer 107(6), 1047–1052 (2003).
[CrossRef] [PubMed]

Mo, J.

Motz, J. T.

Myakov, A.

Ng, J.

J. Mo, W. Zheng, J. J. H. Low, J. Ng, A. Ilancheran, and Z. Huang, “High wavenumber Raman spectroscopy for in vivo detection of cervical dysplasia,” Anal. Chem. 81(21), 8908–8915 (2009).
[CrossRef] [PubMed]

Nieman, L.

Nishioka, N. S.

T. J. Pfefer, K. T. Schomacker, M. N. Ediger, and N. S. Nishioka, “Multiple-fiber probe design for fluorescence spectroscopy in tissue,” Appl. Opt. 41(22), 4712–4721 (2002).
[CrossRef] [PubMed]

T. J. Pfefer, K. T. Schomacker, M. N. Ediger, and N. S. Nishioka, “Light propagation in tissue during fluorescence spectroscopy with single-fiber probes,” IEEE Sel. Top. Quantum Electron. 7(6), 1004–1012 (2001).
[CrossRef]

Palmer, G. M.

G. M. Palmer and N. Ramanujam, “Monte-Carlo-based model for the extraction of intrinsic fluorescence from turbid media,” J. Biomed. Opt. 13(2), 024017–024019 (2008).
[CrossRef] [PubMed]

Pavlova, I.

R. A. Schwarz, D. Arifler, S. K. Chang, I. Pavlova, I. A. Hussain, V. Mack, B. Knight, R. Richards-Kortum, and A. M. Gillenwater, “Ball lens coupled fiber-optic probe for depth-resolved spectroscopy of epithelial tissue,” Opt. Lett. 30(10), 1159–1161 (2005).
[CrossRef] [PubMed]

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, “Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia,” Photochem. Photobiol. 73(6), 636–641 (2001).
[CrossRef] [PubMed]

Pfefer, J.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21(2), 166–178 (1997).
[CrossRef] [PubMed]

Pfefer, T. J.

T. J. Pfefer, K. T. Schomacker, M. N. Ediger, and N. S. Nishioka, “Multiple-fiber probe design for fluorescence spectroscopy in tissue,” Appl. Opt. 41(22), 4712–4721 (2002).
[CrossRef] [PubMed]

T. J. Pfefer, K. T. Schomacker, M. N. Ediger, and N. S. Nishioka, “Light propagation in tissue during fluorescence spectroscopy with single-fiber probes,” IEEE Sel. Top. Quantum Electron. 7(6), 1004–1012 (2001).
[CrossRef]

Ramanujam, N.

G. M. Palmer and N. Ramanujam, “Monte-Carlo-based model for the extraction of intrinsic fluorescence from turbid media,” J. Biomed. Opt. 13(2), 024017–024019 (2008).
[CrossRef] [PubMed]

Reagan, J. W.

F. W. Abdul-Karim, Y. S. Fu, J. W. Reagan, and W. B. Wentz, “Morphometric study of intraepithelial neoplasia of the uterine cervix,” Obstet. Gynecol. 60(2), 210–214 (1982).
[PubMed]

Richards-Kortum, R.

R. A. Schwarz, D. Arifler, S. K. Chang, I. Pavlova, I. A. Hussain, V. Mack, B. Knight, R. Richards-Kortum, and A. M. Gillenwater, “Ball lens coupled fiber-optic probe for depth-resolved spectroscopy of epithelial tissue,” Opt. Lett. 30(10), 1159–1161 (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, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, “Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia,” Photochem. Photobiol. 73(6), 636–641 (2001).
[CrossRef] [PubMed]

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21(2), 166–178 (1997).
[CrossRef] [PubMed]

Schomacker, K. T.

T. J. Pfefer, K. T. Schomacker, M. N. Ediger, and N. S. Nishioka, “Multiple-fiber probe design for fluorescence spectroscopy in tissue,” Appl. Opt. 41(22), 4712–4721 (2002).
[CrossRef] [PubMed]

T. J. Pfefer, K. T. Schomacker, M. N. Ediger, and N. S. Nishioka, “Light propagation in tissue during fluorescence spectroscopy with single-fiber probes,” IEEE Sel. Top. Quantum Electron. 7(6), 1004–1012 (2001).
[CrossRef]

Schwarz, R. A.

Shao, X.

Shepherd, N.

N. Stone, C. Kendall, N. Shepherd, P. Crow, and H. Barr, “Near-infrared Raman spectroscopy for the classification of epithelial pre-cancers and cancers,” J. Raman Spectrosc. 33(7), 564–573 (2002).
[CrossRef]

Shih, W. C.

Shim, M. G.

Sokolov, K.

Stone, N.

N. Stone, C. Kendall, N. Shepherd, P. Crow, and H. Barr, “Near-infrared Raman spectroscopy for the classification of epithelial pre-cancers and cancers,” J. Raman Spectrosc. 33(7), 564–573 (2002).
[CrossRef]

Teh, M.

Teh, S. K.

Wach, M.

Wang, L.

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

Warren, S.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21(2), 166–178 (1997).
[CrossRef] [PubMed]

Welch, A. J.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21(2), 166–178 (1997).
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F. Jaillon, W. Zheng, and Z. Huang, “Half-ball lens couples a beveled fiber probe for depth-resolved spectroscopy: Monte Carlo simulations,” Appl. Opt. 47(17), 3152–3157 (2008).
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Anal. Chem.

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[CrossRef]

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Int. J. Cancer

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[CrossRef] [PubMed]

Obstet. Gynecol.

F. W. Abdul-Karim, Y. S. Fu, J. W. Reagan, and W. B. Wentz, “Morphometric study of intraepithelial neoplasia of the uterine cervix,” Obstet. Gynecol. 60(2), 210–214 (1982).
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Figures (14)

Fig. 1
Fig. 1

Schematic of the Raman probe design and two-layer epithelial tissue model for Monte Carlo (MC) simulations. CL: collimating Lens; FL: Focusing Lens; BPF: Band Pass Filter; LPF: Long Pass Filter; DM: Dichroic Mirror; RM: Reflection Mirror; BL: Ball Lens; EP: Epithelium; ST: Stroma.

Fig. 2
Fig. 2

The 785-nm illumination light distributions along the tissue depth and radial directions in tissue using the Raman probe designs with different refractive indices of the ball lenses (n = 1.46, 1.51, 1.63, 1.76 and 1.83).

Fig. 3
Fig. 3

The 785-nm illumination light distributions along the tissue depth using the Raman probe designs with different refractive indices of the ball lenses (n = 1.46, 1.51, 1.63, 1.76 and 1.83).

Fig. 4
Fig. 4

Distributions of the Raman photons collected from different tissue depths using the Raman probe designs with different refractive indices of the ball lens (n = 1.46, 1.51, 1.63, 1.76 and 1.83).

Fig. 5
Fig. 5

Depth-resolved Raman photons collected from different tissue depths using the Raman probe designs with different refractive indices of the ball lens (n = 1.46, 1.51, 1.63, 1.76 and 1.83). Note that for comparison purpose, the depth-resolved Raman intensity profiles with different refractive indices of the ball lens have been vertically shifted to different intensity levels.

Fig. 6
Fig. 6

Collection efficiency of the Raman probe as a function of the refractive index of the ball lens.

Fig. 7
Fig. 7

The 785-nm illumination light distributions in tissue using the Raman probe designs with different diameters of the ball lens (Φ = 1, 2, 3, 5, 8 and 10 mm).

Fig. 8
Fig. 8

The 785-nm illumination light distribution along the tissue depth using the Raman probe designs with different diameters of the ball lens (Φ = 1, 2, 3, 5, 8 and 10 mm).

Fig. 9
Fig. 9

Distributions of the origins of the Raman photons collected from tissue using the Raman probe designs with different diameters of ball lenses (Φ = 1, 2, 3, 5, 8 and 10 mm).

Fig. 10
Fig. 10

Depth distribution of the origins of the Raman photons collected from tissue using the Raman probe designs with different diameters of the ball lens (Φ = 1, 2, 3, 5, 8 and 10 mm).

Fig. 11
Fig. 11

The simulated performance of the probe design based on various combinations of ball lens diameters (i.e., 1, 2, 3, 5, 8 and 10 mm) and refractive indices (i.e., 1.46, 1.51, 1.63, 1.76 and 1.83): (a) collection efficiency; (b) Proportion of the Raman photons from the epithelium to the total collected Raman photons from the tissue surface.

Fig. 12
Fig. 12

(a) Collection efficiency of the Raman probe as a function of probe-tissue distances; (b) Percentage of the Raman signal collected from the epithelium layer to the overall Raman signal from the entire epithelial tissue. The refractive index and the diameter of the ball lens are 1.83, and 3 mm, respectively, in Raman probe design.

Fig. 13
Fig. 13

Raman spectra acquired from chicken muscle and fat tissue, as well as from the two-layer tissue phantoms with the muscle tissue thickness of 0.3, 1.2, 2.1, 3 and 3.9 mm, respectively. Spectra: (a) fat tissue; (b)-(f): two-layer tissue phantoms with the muscle tissue layer of thickness of 0.3, 1.2, 2.1, 3.0 and 3.9 mm, respectively, overlaying on a fat tissue layer (thickness of 5 mm); (g) muscle tissue. Note that all tissue Raman spectra are acquired with an integration of 1 s under the 785-nm illumination power of 1.5 W/cm2. The dotted and solid vertical lines indicated in Raman spectra stand for the distinctive Raman peaks originating from the muscle and fat chicken tissue, respectively.

Fig. 14
Fig. 14

Raman peaks intensities at 1004 and 1745 cm−1 as a function of thickness ratios of the muscle tissue layer to the fat tissue in a two-layer tissue phantom.

Tables (1)

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Table 1 Optical properties of the two-layer epithelial tissue model for MC simulations [14,15,24]

Equations (5)

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R = 1 2 [ sin 2 ( α i α t ) sin 2 ( α i + α t ) + tan 2 ( α i α t ) tan 2 ( α i + α t ) ]
p = μ s μ a + μ s × R Y
cos β = { 1 2 g { 1 + g 2 [ 1 g 2 1 g + 2 g ξ ] 2 } i f g > 0 2 ξ 1 i f g = 0
θ = sin 1 ( 2 ( n b 1 ) n b n t )
B F L = E F L D 2 ; E F L = n b D 4 ( n b 1 )

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