Abstract

A method for estimating the optical properties of two-layered media (such as squamous epithelial tissue) over a range of wavelengths in the ultraviolet–visible spectrum is proposed and tested with Monte Carlo modeling. The method first used a fiber-optic probe with angled illumination and the collection fibers placed at a small separation (300  μm) to restrict the transport of detected light to the top layer. A Monte Carlo-based inverse model for a homogeneous medium was employed to estimate the top layer optical properties from the measured diffuse reflectance spectrum. Then a flat-tip probe with a large source-detector separation (1000  μm) was used to detect diffuse reflectance preferentially from the bottom layer. A second Monte Carlo-based inverse model for a two-layered medium was applied to estimate the bottom layer optical properties, as well as the top layer thickness, given that the top layer optical properties have been estimated. The results of Monte Carlo validation show that this method works well for an epithelial tissue model with a top layer thickness ranging from 200  to  500  μm. For most thicknesses within this range, the absorption coefficients were estimated to within 15% of the true values, the reduced scattering coefficients were estimated to within 20% and the top layer thicknesses were estimated to within 20%. The application of a variance reduction technique to the Monte Carlo modeling proved to be effective in improving the accuracy with which the optical properties are estimated.

© 2006 Optical Society of America

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2006

2005

Z. Rong, W. Verkruysse, B. Choi, J. A. Viator, J. Byungjo, L. O. Svaasand, G. Aguilar, and J. S. Nelson, "Determination of human skin optical properties from spectrophotometric measurements based on optimization by genetic algorithms," J. Biomed. Opt. 10, 24030 (2005).
[CrossRef]

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, 1159-1161 (2005).
[CrossRef] [PubMed]

2004

2003

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

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

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

Y. S. Fawzi, A.-B. M. Youssef, M. H. El-Batanony, and Y. M. Kadah, "Determination of the optical properties of a two-layer tissue model by detecting photons migrating at progressively increasing depths," Appl. Opt. 42, 6398-6411 (2003).
[CrossRef] [PubMed]

P. Thueler, I. Charvet, F. Bevilacqua, P. Marquet, P. Meda, B. Vermeulen, C. Depeursinge, M. S. Ghislain, and G. Ory, "In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties," J. Biomed. Opt. 8, 495 (2003).
[CrossRef] [PubMed]

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

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

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, 636-641 (2001).
[CrossRef] [PubMed]

G. Alexandrakis, D. R. Busch, G. W. Faris, and M. S. Patterson, "Determination of the optical properties of two-layer turbid media by use of a frequency-domain hybrid Monte Carlo diffusion model," Appl. Opt. 40, 3810-3821 (2001).
[CrossRef]

D. E. Hyde, T. J. Farrell, M. S. Patterson, and B. C. Wilson, "A diffusion theory model of spatially resolved fluorescence from depth-dependent fluorophore concentrations," Phys. Med. Biol. 46, 369-383 (2001).
[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, 385-396 (2001).
[CrossRef] [PubMed]

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

C. K. Hayakawa, T. Spanier, F. Bevilacqua, A. K. Dunn, J. S. You, B. J. Tromberg, and V. Venugopalan, "Peturbation Monte Carlo methods to solve inverse photon migration problems in heterogeneous tissues," Opt. Lett. 26, 1335-1337 (2001).
[CrossRef]

2000

1999

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, 967-981 (1999).
[CrossRef] [PubMed]

F. Bevilacqua, and C. Depeursinge, "Monte Carlo study of diffuse reflectance at source-detector separations close to one transport mean free path," J. Opt. Soc. Am. A 16, 2935-2945 (1999).
[CrossRef]

A. Kienle and T. Glanzmann, "In vivo determination of the optical properties of muscle with time-resolved reflectance using a layered model," Phys. Med. Biol. 44, 2689-2702 (1999).
[CrossRef] [PubMed]

1998

1997

1996

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, 131-146 (1995).
[CrossRef] [PubMed]

E. Gratton and J. B. Fishkin, "Optical spectroscopy of tissuelike phantoms using photon density waves," Comments Mol. Cell. Biophys. 8, 307 (1995).

A. H. Hielscher, S. L. Jacques, W. Lihong, and F. K. Tittel, "The influence of boundary conditions on the accuracy of diffusion theory in time-resolved reflectance spectroscopy of biological tissues," Phys. Med. Biol. 40, 1957-1975 (1995).
[CrossRef] [PubMed]

I. Saidi, S. Jacques, and F. Tittel, "Mie and Rayleigh modeling of visible-light scattering in neonatal skin," Appl. Opt. 34, 7410-7418 (1995).
[CrossRef] [PubMed]

1993

R. Graaff, M. H. Koelink, F. F. M. de Mul, W. G. Zijlstra, A. C. M. Dassel, and J. G. Aarnoudse, "Condensed Monte Carlo simulations for the description of light transport," Appl. Opt. 32, 426-434 (1993).
[CrossRef] [PubMed]

A. J. Durkin, S. Jaikumar, and R. Richards-Kortum, "Optically dilute, absorbing and turbid phantoms for fluorescence spectrocopy of homogeneous and Inhomogeneous Samples," Appl. Spectros. 47, 2114-2121 (1993).
[CrossRef]

1992

T. J. Farrell, M. S. Patterson, and B. Wilson, "A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo," Med. Phys. 19, 879-888 (1992).
[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, 967-981 (1999).
[CrossRef] [PubMed]

Aarnoudse, J. G.

Aaron, J.

Aguilar, G.

Z. Rong, W. Verkruysse, B. Choi, J. A. Viator, J. Byungjo, L. O. Svaasand, G. Aguilar, and J. S. Nelson, "Determination of human skin optical properties from spectrophotometric measurements based on optimization by genetic algorithms," J. Biomed. Opt. 10, 24030 (2005).
[CrossRef]

Alexandrakis, G.

Andersson-Engels, S.

Antonioli, D. A.

L. Burke, D. A. Antonioli, and B. S. Duatman, Colposcopy: Text and Atlas (Appleton & Large, 1991).

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, 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, 511-522 (2004).
[CrossRef] [PubMed]

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

Bassi, A.

Bevilacqua, F.

Bohren, F. C.

F. C. Bohren and R. D. Huffman, Absorption and Scattering of Light by Small Particles (Wiley, 1983).

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, 636-641 (2001).
[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, 385-396 (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, 636-641 (2001).
[CrossRef] [PubMed]

Burke, L.

L. Burke, D. A. Antonioli, and B. S. Duatman, Colposcopy: Text and Atlas (Appleton & Large, 1991).

Busch, D. R.

Byungjo, J.

Z. Rong, W. Verkruysse, B. Choi, J. A. Viator, J. Byungjo, L. O. Svaasand, G. Aguilar, and J. S. Nelson, "Determination of human skin optical properties from spectrophotometric measurements based on optimization by genetic algorithms," J. Biomed. Opt. 10, 24030 (2005).
[CrossRef]

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, 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, 511-522 (2004).
[CrossRef] [PubMed]

Chapon, P. F.

N. Salas, Jr., F. Manns, P. F. Chapon, P. J. Milne, S. G. Mendoza, D. B. Denham, J.-M. A. Parel, and D. S. Robinson, "Development of a tissue phantom for experimental studies on laser interstitial thermotherapy of breast cancer," in Lasers in Surgery: Advanced Characterization, Therapeutics, and Systems X, R. R. Anderson, K. E. Bartels, L. S. Bass, C. G. Garrett, K. W. Gregory, N. Kollias, H. Lui, R. S. Malek, G. M. Peavy, H.-D. Reidenbach, L. Reinisch, D. S. Robinson, L. P. Tate, E. A. Trowers, and T. A. Woodward, eds. Proc. SPIE 3907, 623-631 (2000).

Charvet, I.

P. Thueler, I. Charvet, F. Bevilacqua, P. Marquet, P. Meda, B. Vermeulen, C. Depeursinge, M. S. Ghislain, and G. Ory, "In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties," J. Biomed. Opt. 8, 495 (2003).
[CrossRef] [PubMed]

Choi, B.

Z. Rong, W. Verkruysse, B. Choi, J. A. Viator, J. Byungjo, L. O. Svaasand, G. Aguilar, and J. S. Nelson, "Determination of human skin optical properties from spectrophotometric measurements based on optimization by genetic algorithms," J. Biomed. Opt. 10, 24030 (2005).
[CrossRef]

Collier, T.

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

Contini, D.

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, 967-981 (1999).
[CrossRef] [PubMed]

Cubeddu, R.

Dam, J. S.

Dassel, A. C. M.

de Mul, F. F. M.

Del Bianco, S.

Denham, D. B.

N. Salas, Jr., F. Manns, P. F. Chapon, P. J. Milne, S. G. Mendoza, D. B. Denham, J.-M. A. Parel, and D. S. Robinson, "Development of a tissue phantom for experimental studies on laser interstitial thermotherapy of breast cancer," in Lasers in Surgery: Advanced Characterization, Therapeutics, and Systems X, R. R. Anderson, K. E. Bartels, L. S. Bass, C. G. Garrett, K. W. Gregory, N. Kollias, H. Lui, R. S. Malek, G. M. Peavy, H.-D. Reidenbach, L. Reinisch, D. S. Robinson, L. P. Tate, E. A. Trowers, and T. A. Woodward, eds. Proc. SPIE 3907, 623-631 (2000).

Depeursinge, C.

P. Thueler, I. Charvet, F. Bevilacqua, P. Marquet, P. Meda, B. Vermeulen, C. Depeursinge, M. S. Ghislain, and G. Ory, "In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties," J. Biomed. Opt. 8, 495 (2003).
[CrossRef] [PubMed]

F. Bevilacqua, and C. Depeursinge, "Monte Carlo study of diffuse reflectance at source-detector separations close to one transport mean free path," J. Opt. Soc. Am. A 16, 2935-2945 (1999).
[CrossRef]

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, 967-981 (1999).
[CrossRef] [PubMed]

Drezek, R.

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N. Ramanujam, R. Richards-Kortum, S. Thomsen, A. Mahadevan-Jansen, and M. Follen, "Low temperature fluorescence imaging of freeze-trapped human cervical tissue," Opt. Express 8, 335-343 (2000).
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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, 385-396 (2001).
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U. Utzinger and R. R. Richards-Kortum, "Fiber optic probes for biomedical optical spectroscopy," J. Biomed. Opt. 8, 121-147 (2003).
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Z. Rong, W. Verkruysse, B. Choi, J. A. Viator, J. Byungjo, L. O. Svaasand, G. Aguilar, and J. S. Nelson, "Determination of human skin optical properties from spectrophotometric measurements based on optimization by genetic algorithms," J. Biomed. Opt. 10, 24030 (2005).
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Z. Rong, W. Verkruysse, B. Choi, J. A. Viator, J. Byungjo, L. O. Svaasand, G. Aguilar, and J. S. Nelson, "Determination of human skin optical properties from spectrophotometric measurements based on optimization by genetic algorithms," J. Biomed. Opt. 10, 24030 (2005).
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Figures (12)

Fig. 1
Fig. 1

Flow chart for sequential estimation of the optical properties of a two-layered medium. Arrows indicate the direction of data flow.

Fig. 2
Fig. 2

Side views of the (a) flat-tip, (b) angled probes, and (c) combination of flat-tip and angled probe designs, and their acceptance cones in a two-layered medium. The arrows indicate light direction. The thick horizontal line is the probe–sample interface, and the thin horizontal line marks the boundary between top and bottom layers of the two-layered model. The dashed lines below the interface define the boundaries of light cones coming out of individual fibers as if in an optically dilute sample. The shaded area is the overlap between the acceptance cones of the illumination and the collection fibers.

Fig. 3
Fig. 3

Absorption and reduced scattering coefficients of the (a) top layer and (b) bottom layer of a theoretical two-layered epithelial tissue model as a function of wavelength that were used as inputs in the Monte Carlo simulations.

Fig. 4
Fig. 4

Flow charts of (a) the forward model and (b) the inverse model for estimation of the top layer optical properties. The figures were adapted from Ref. 34.

Fig. 5
Fig. 5

Longitudinal views of (a) the weighted fluence distribution and (b) the weighted visiting frequency distribution at 420 nm, for the angled probe (source-detector separation of 300 μm), as well as (c) the weighted fluence distribution, and (d) the weighted visiting frequency distribution at 580 nm for the flat-tip probe (source–detector separation of 1500 μm) within the two-layered tissue model. The top layer thickness in the two-layered model is 300 μm. The dashed horizontal lines indicate the boundary between two layers. The arrows indicate the direction of light propagation. The unit of both distributions is cm−3.

Fig. 6
Fig. 6

Distribution of the exiting photons' survival weights for the two-layered tissue model (for a top layer thickness of 300 μm) at (a) 420 nm (smallest absorption coefficient), simulated for the angled probe, and (b) 580 nm (largest absorption coefficient), simulated with the flat-tip probe. Also shown are the exiting photons' survival weights from corresponding homogeneous tissue models with the optical properties of the top (for the angled probe) or bottom layer (for the flat-tip probe) for the purposes of comparison. These are, respectively, marked as “Homogeneous Top” and “Homogeneous Bottom” in the legends. A total of 50 equally spaced weight bins that cover [0, 1] was used to count the number of photons whose weights fall within these bins. The counts were then divided by the total number of incident photons to obtain a probability distribution.

Fig. 7
Fig. 7

Simulated diffuse reflectance spectra of the two-layered tissue model (thickness of the top layer is 300 μm) for (a) the flat-tip probe with a separation of 300 μm, (b) the flat-tip probe with a separation of 1500 μm, (c) the angled probe with a separation of 300 μm, and (d) the angled probe with a separation of 1500 μm. For purposes of comparison, the spectra simulated for corresponding homogeneous media with optical properties equal to those of either the top or bottom layer are also shown, which are, respectively, marked as “Homogeneous Top” and “Homogeneous Bottom” in the legends.

Fig. 8
Fig. 8

Actual and estimated absorption (μ a ) and reduced scattering coefficients (μ s ′) of (a) the top layer, and (b) and (c) the bottom layer in the two-layered tissue model. (The thickness of the top layer is 300 μm.) For the results shown in (b), the exact optical properties of the top layer were assumed as known in the inversion, while in (c), the estimated top layer optical properties shown in (a) were used in the inversion. The optical properties of the phantoms are shown in Fig. 3. Extraction of the top layer optical properties was based on the reflectance spectrum simulated for the angled probe with a source–detector separation of 300 μm while extraction of the bottom layer optical properties was based on the reflectance spectrum simulated for the flat-tip probe with a source–detector separation of 1500 μm.

Fig. 9
Fig. 9

Percent deviation in the estimated top layer thicknesses as a function of the layer thickness for the case in which the exact optical properties of the the layer were assumed as known in the inversion (open circles); and for the case in which the estimated top layer optical properties were used in the inversion (star symbols). The horizontal line indicates zero deviation.

Fig. 10
Fig. 10

Percent deviations of (a) estimated absorption coefficients and (b) estimated reduced scattering coefficients from their actual values. The legend “Regular MC” means that both the baseline simulations for the Monte Carlo database and the simulations of the two-layered tissue model were run with a Monte Carlo code without the geometry splitting variance reduction technique incorporated; the legend “Improved MC” means that these simulations were run with a Monte Carlo code with the geometry splitting technique built in. The category on the x axis, “Bottom layer with known top layer properties,” means that the bottom layer optical properties were estimated with the exact top layer optical properties as known; the category, “Bottom layer with estimated top layer properties,” means that the bottom layer optical properties were estimated in the case where the top layer optical properties estimated in the previous step were used in inversion.

Fig. 11
Fig. 11

Schematic of the trajectory of a photon in a turbid medium. The number 1, . . . , N indicates the index of the collision. The area beneath the horizontal line represents the turbid medium.

Fig. 12
Fig. 12

Schematic of the geometry splitting setup in the improved Monte Carlo code. The arrows indicate the direction of light. The half-circle arcs represent hemispherical volumes with the displayed numbers denoting different importance values. It should be pointed out that the radii of the arcs were not drawn to scale.

Tables (4)

Tables Icon

Table 1 Scattering Coefficients and Thicknesses of the Top and Bottom Layers Used in the Baseline Simulations to Generate the Monte Carlo Database for Two-Layered Media a

Tables Icon

Table 2 Sensitivity of the Angled Probe to the Top Layer a

Tables Icon

Table 3 Percent Deviations of Estimated Optical Properties a

Tables Icon

Table 4 Contribution of a Photon to the Absorption, Fluence, and Visiting Frequency Distribution at Each Collision in Fig. 11

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