Abstract

The instrument development and design of a prototype frequency-domain optical imaging device for breast cancer detection is described in detail. This device employs radio-frequency intensity modulated near-infrared light to image quantitatively both the scattering and absorption coefficients of tissue. The functioning components of the system include a laser diode and a photomultiplier tube, which are multiplexed automatically through 32 large core fiber optic bundles using high precision linear translation stages. Image reconstruction is based on a finite element solution of the diffusion equation. This tool for solving the forward problem of photon migration is coupled to an iterative optical property estimation algorithm, which uses a Levenberg-Marquardt routine with total variation minimization. The result of this development is an automated frequency-domain optical imager for computed tomography which produces quantitatively accurate images of the test phantoms used to date. This paper is a description and characterization of an automated frequency-domain computed tomography scanner, which is more quantitative than earlier systems used in diaphanography because of the combination of intensity modulated signal detection and iterative image reconstruction.

© Optical Society of America

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  1. M. Cutler, "Transillumination as an aid in the diagnosis of breast lesions," Surg. Gyn. Obst. 48, 721-729 (1929).
  2. D. J. Watmough, "Transillumination of breast tissues: factors governing optimal imaging of lesions," Radiol. 147, 89-92 (1982).
  3. R. J. Bartrum, H. C. Crow, "Transillumination light scanning to diagnose breast cancer: a feasibility study," Am. J. Roentgenol. 142, 409-414 (1984).
  4. A. Alveryd, I. Andersson, K. Aspegren, G. Balldin, N. Bjurstam, G. Edstrom, G. Fagerberg, U. Glas, O. Jarlman, S. A. Larsson, et al., "Lightscanning versus mammography for the detection of breast cancer in screening and clinical practice. A Swedish multicenter study," Cancer; Diag. Treat. Res. 65, 1671-1677 (1990).
  5. G. A. Navarro, A. E. Profio, "Contrast in diaphanography of the breast," Med. Phys. 15, 181-187 (1988).
    [CrossRef] [PubMed]
  6. A. E. Profio, G. A. Navarro, "Scientific basis of breast diaphanography," Med. Phys. 16, 60-65 (1989).
    [CrossRef] [PubMed]
  7. P. C. Jackson, P. H. Stevens, J. H. Smith, D. Kear, H. Key, P. N. T. Wells, "The development of a system for transillumination computed tomography," Br. J. Radiol. 60, 375-380 (1987).
    [CrossRef] [PubMed]
  8. J. R. Singer, F. A. Grunbaum, P. D. Kohn, J. P. Zubelli, "Image reconstruction of the interior of bodies that diffuse radiation," Science 24,: 990-993 (1990).
    [CrossRef]
  9. S. R. Arridge,P. van der Zee, M. Cope, D. T. Delpy "Reconstruction methods for infrared absorption imaging," Proc. SPIE 1431, 204-215 (1991).
    [CrossRef]
  10. H. Jiang, K. D. Paulsen, U. L. Osterberg, B. W. Pogue, M. S. Patterson "Optical image reconstruction using frequency-domain data: simulations and experiments," J. Opt. Soc. Am. A. 13, 253-266 (1996).
    [CrossRef]
  11. H. Jiang, K. D. Paulsen, U. L. Osterberg, M. S. Patterson, "Frequency-domain optical image reconstruction for breast imaging: initial evaluation in multi-target tissue-like phantoms," Med. Phys. (in press):, 1997.
    [PubMed]
  12. K. D. Paulsen, H. Jiang "Spatially varying optical property reconstruction using a finite element diffusion equation approximation," Med. Phys. 22, 691-701 (1995).
    [CrossRef] [PubMed]
  13. K. D. Paulsen, H. Jiang "Enhanced frequency-domain optical image reconstruction in tissues through total-variation minimization," Appl. Opt. 35, 3447-3458 (1996).
    [CrossRef] [PubMed]
  14. S.R. Arridge, M. Schweiger, "Image reconstruction in optical tomography," Philos. Trans. R. Soc. London Ser. B. 352, 717-726 (1997).
    [CrossRef]
  15. A. Ishimaru, "Diffusion of light in turbid material," Appl. Opt. 28, 2210-2215 (1989).
    [CrossRef] [PubMed]
  16. S. T. Flock, M. S. Patterson, B. C. Wilson D. R. Wyman "Monte Carlo modeling of light propagation in highly scattering tissues -I: Model predictions and comparison with diffusion theory," IEEE trans. Biomed. Eng. 36, 1162-1168 (1989).
    [CrossRef] [PubMed]
  17. R. F. Bonner, R. Nossal, S. Havlin, "Model for photon migration in turbid biological media," J. Opt. Soc. Am. A. 4, 423-432 (1988).
    [CrossRef]
  18. B. C. Wilson, G. A. Adam, "Monte Carlo model for the absorption and flux distributions of light in tissue," Med. Phys. 10, 824-830 (1983).
    [CrossRef] [PubMed]
  19. M. S. Patterson, B. C. Wilson, D. R. Wyman, "The propagation of optical radiation in tissue: I. Models of radiation transport and their application," Lasers Med. Sci. 6, 155-168 (1992).
    [CrossRef]
  20. M. A. O'Leary, D. A. Boas, B. Chance, A. G. Yodh, "Experimental images of heterogeneous turbid media by frequency-domain diffusing-photon tomography," Opt. Lett. 20, 426-428 (1995).
    [CrossRef] [PubMed]
  21. S. Walker, S. Fantini, E. Gratton, "Image reconstruction by backprojection from frequency-domain optical measurements in highly scattering media," Appl. Opt. 36, 170-179 (1997).
    [CrossRef] [PubMed]
  22. M. S. Patterson, J. D. Moulton, B. C. Wilson, K. W. Berndt, J. R. Lakowicz, "Frequency-domain reflectance for the determination of the scattering and absorption properties of tissue," Appl. Opt. 30, 4474-4476 (1991).
    [CrossRef] [PubMed]
  23. J. Fishkin, E. Gratton, M. J. van de Ven, W. W. Mantulin, "Diffusion of intensity modulated near infrared light in turbid media," Proc. SPIE 1431, 122-135 (1991).
    [CrossRef]
  24. M. A. O'Leary, D. A. Boas, B. Chance, A. G. Yodh, "Refraction of photon diffuse photon density waves in multiple-scattering media," Phys. Rev. Lett. 69, 2658-2661 (1992).
    [CrossRef] [PubMed]
  25. B. J. Tromberg, L. O. Svaasand, T. T. Tsay, R. C. Haskell, "Properties of photon density waves in multiple-scattering media," Appl. Opt. 32, 607-616 (1993).
    [CrossRef] [PubMed]
  26. B. J. Tromberg, O. Coquoz, J. B. Fishkin, T. Pham, E. R. Anderson, J. Butler, M. Cahn, J. D. Gross, V. Venugopalan, D. Pham "Non-invasive measurements of breast tissue optical properties using frequency-domain photon migration," Philos. Trans. R. Soc. London Ser. B. 352, 661-668 (1997).
    [CrossRef]
  27. B. W. Pogue, M. S. Patterson, "Error Assessment of a wavelength tunable frequency-domain system for noninvasive tissue spectroscopy," J. Biomed.. Opt. 1, 311-323 (1996).
    [CrossRef] [PubMed]
  28. J. Hoogenraad, J. M. van der Mark, S. B. Colak, G. W. t'Hooft, E. S. van der Linden, "First results of the Phillips optical mammoscope." Proc. SPIE 3194 (in press).
  29. M. A. Franceschini, K. T. Moesta, S. Fantini, G. Gaida, E. Gratton, H. Jess, W. W. Mantulin, M. Seeber, P. M. Schlag, M. Kaschke, "Frequency-domain techniques enhance optical mammography: initial clinical results." Proc. Nat. Acad. Sci. USA 94(12), 6468-73 (1997).
    [CrossRef] [PubMed]
  30. V. V. Sobolev, A Treatise on Radiative Transfer, (Van Nostrand-Reinhold, Princeton, 1963), pp. 240-244.
  31. A. Ishimaru, Wave Propagation and Scattering in Random Media, (Academic Press, New York, 1978), Vol. 1, pp. 147-167 and pp.175-190.
  32. S. R. Arridge, M. Cope, D. T. Delpy, "The theoretical basis for the determination of optical pathlengths in tissue: temporal and frequency analysis," Phys. Med. Biol. 37, 1531-1560 (1992).
    [CrossRef] [PubMed]
  33. L. Wang, S. L. Jacques, Monte Carlo Modeling of Light Transport in Multi-layered Tissues in Standard C, (University of Texas M. D. Anderson Cancer Center, Houston, 1992-93).
  34. I. V. Yaroslavsky, A. N. Yaroslavsky, V. V. Tuchin, H.-J. Schwarzmaier, "Effect of scattering delay on time-dependent photon migration in turbid media," Appl. Opt. 36, 6529-6538 (1997).
    [CrossRef]
  35. B. W. Pogue, M. S. Patterson, T. Farrell, "Forward and inverse calculations for 3-D frequency-domain diffuse optical tomography," Proc. SPIE 2389, 328-339 (1995)
    [CrossRef]
  36. V. G. Peters, D. R. Wyman, M. S. Patterson, G. L. Frank, "Optical properties of normal and diseased breast tissue in the visible and near infrared," Phys Med. Biol. 35, 1317-1334, (1990).
    [CrossRef] [PubMed]
  37. T. L. Troy, D. L. Page, E. M. Sevick-Muraca, "Optical properties of normal and diseased breast tissues: prognosis for optical mammography," J. Biomed. Opt. 1, 342-355 (1996).
    [CrossRef] [PubMed]
  38. K. Suzuki, Y. Yamashita, K. Ohta, M. Kaneko, M. Yoshida, B. Chance, "Quantitative measurement of optical parameters in normal breasts using time-resolved spectroscopy: In vivo results of 30 Japanese women," J. Biomed. Opt. 1(3), 330-334 (1996).
    [CrossRef] [PubMed]

Other (38)

M. Cutler, "Transillumination as an aid in the diagnosis of breast lesions," Surg. Gyn. Obst. 48, 721-729 (1929).

D. J. Watmough, "Transillumination of breast tissues: factors governing optimal imaging of lesions," Radiol. 147, 89-92 (1982).

R. J. Bartrum, H. C. Crow, "Transillumination light scanning to diagnose breast cancer: a feasibility study," Am. J. Roentgenol. 142, 409-414 (1984).

A. Alveryd, I. Andersson, K. Aspegren, G. Balldin, N. Bjurstam, G. Edstrom, G. Fagerberg, U. Glas, O. Jarlman, S. A. Larsson, et al., "Lightscanning versus mammography for the detection of breast cancer in screening and clinical practice. A Swedish multicenter study," Cancer; Diag. Treat. Res. 65, 1671-1677 (1990).

G. A. Navarro, A. E. Profio, "Contrast in diaphanography of the breast," Med. Phys. 15, 181-187 (1988).
[CrossRef] [PubMed]

A. E. Profio, G. A. Navarro, "Scientific basis of breast diaphanography," Med. Phys. 16, 60-65 (1989).
[CrossRef] [PubMed]

P. C. Jackson, P. H. Stevens, J. H. Smith, D. Kear, H. Key, P. N. T. Wells, "The development of a system for transillumination computed tomography," Br. J. Radiol. 60, 375-380 (1987).
[CrossRef] [PubMed]

J. R. Singer, F. A. Grunbaum, P. D. Kohn, J. P. Zubelli, "Image reconstruction of the interior of bodies that diffuse radiation," Science 24,: 990-993 (1990).
[CrossRef]

S. R. Arridge,P. van der Zee, M. Cope, D. T. Delpy "Reconstruction methods for infrared absorption imaging," Proc. SPIE 1431, 204-215 (1991).
[CrossRef]

H. Jiang, K. D. Paulsen, U. L. Osterberg, B. W. Pogue, M. S. Patterson "Optical image reconstruction using frequency-domain data: simulations and experiments," J. Opt. Soc. Am. A. 13, 253-266 (1996).
[CrossRef]

H. Jiang, K. D. Paulsen, U. L. Osterberg, M. S. Patterson, "Frequency-domain optical image reconstruction for breast imaging: initial evaluation in multi-target tissue-like phantoms," Med. Phys. (in press):, 1997.
[PubMed]

K. D. Paulsen, H. Jiang "Spatially varying optical property reconstruction using a finite element diffusion equation approximation," Med. Phys. 22, 691-701 (1995).
[CrossRef] [PubMed]

K. D. Paulsen, H. Jiang "Enhanced frequency-domain optical image reconstruction in tissues through total-variation minimization," Appl. Opt. 35, 3447-3458 (1996).
[CrossRef] [PubMed]

S.R. Arridge, M. Schweiger, "Image reconstruction in optical tomography," Philos. Trans. R. Soc. London Ser. B. 352, 717-726 (1997).
[CrossRef]

A. Ishimaru, "Diffusion of light in turbid material," Appl. Opt. 28, 2210-2215 (1989).
[CrossRef] [PubMed]

S. T. Flock, M. S. Patterson, B. C. Wilson D. R. Wyman "Monte Carlo modeling of light propagation in highly scattering tissues -I: Model predictions and comparison with diffusion theory," IEEE trans. Biomed. Eng. 36, 1162-1168 (1989).
[CrossRef] [PubMed]

R. F. Bonner, R. Nossal, S. Havlin, "Model for photon migration in turbid biological media," J. Opt. Soc. Am. A. 4, 423-432 (1988).
[CrossRef]

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

M. S. Patterson, B. C. Wilson, D. R. Wyman, "The propagation of optical radiation in tissue: I. Models of radiation transport and their application," Lasers Med. Sci. 6, 155-168 (1992).
[CrossRef]

M. A. O'Leary, D. A. Boas, B. Chance, A. G. Yodh, "Experimental images of heterogeneous turbid media by frequency-domain diffusing-photon tomography," Opt. Lett. 20, 426-428 (1995).
[CrossRef] [PubMed]

S. Walker, S. Fantini, E. Gratton, "Image reconstruction by backprojection from frequency-domain optical measurements in highly scattering media," Appl. Opt. 36, 170-179 (1997).
[CrossRef] [PubMed]

M. S. Patterson, J. D. Moulton, B. C. Wilson, K. W. Berndt, J. R. Lakowicz, "Frequency-domain reflectance for the determination of the scattering and absorption properties of tissue," Appl. Opt. 30, 4474-4476 (1991).
[CrossRef] [PubMed]

J. Fishkin, E. Gratton, M. J. van de Ven, W. W. Mantulin, "Diffusion of intensity modulated near infrared light in turbid media," Proc. SPIE 1431, 122-135 (1991).
[CrossRef]

M. A. O'Leary, D. A. Boas, B. Chance, A. G. Yodh, "Refraction of photon diffuse photon density waves in multiple-scattering media," Phys. Rev. Lett. 69, 2658-2661 (1992).
[CrossRef] [PubMed]

B. J. Tromberg, L. O. Svaasand, T. T. Tsay, R. C. Haskell, "Properties of photon density waves in multiple-scattering media," Appl. Opt. 32, 607-616 (1993).
[CrossRef] [PubMed]

B. J. Tromberg, O. Coquoz, J. B. Fishkin, T. Pham, E. R. Anderson, J. Butler, M. Cahn, J. D. Gross, V. Venugopalan, D. Pham "Non-invasive measurements of breast tissue optical properties using frequency-domain photon migration," Philos. Trans. R. Soc. London Ser. B. 352, 661-668 (1997).
[CrossRef]

B. W. Pogue, M. S. Patterson, "Error Assessment of a wavelength tunable frequency-domain system for noninvasive tissue spectroscopy," J. Biomed.. Opt. 1, 311-323 (1996).
[CrossRef] [PubMed]

J. Hoogenraad, J. M. van der Mark, S. B. Colak, G. W. t'Hooft, E. S. van der Linden, "First results of the Phillips optical mammoscope." Proc. SPIE 3194 (in press).

M. A. Franceschini, K. T. Moesta, S. Fantini, G. Gaida, E. Gratton, H. Jess, W. W. Mantulin, M. Seeber, P. M. Schlag, M. Kaschke, "Frequency-domain techniques enhance optical mammography: initial clinical results." Proc. Nat. Acad. Sci. USA 94(12), 6468-73 (1997).
[CrossRef] [PubMed]

V. V. Sobolev, A Treatise on Radiative Transfer, (Van Nostrand-Reinhold, Princeton, 1963), pp. 240-244.

A. Ishimaru, Wave Propagation and Scattering in Random Media, (Academic Press, New York, 1978), Vol. 1, pp. 147-167 and pp.175-190.

S. R. Arridge, M. Cope, D. T. Delpy, "The theoretical basis for the determination of optical pathlengths in tissue: temporal and frequency analysis," Phys. Med. Biol. 37, 1531-1560 (1992).
[CrossRef] [PubMed]

L. Wang, S. L. Jacques, Monte Carlo Modeling of Light Transport in Multi-layered Tissues in Standard C, (University of Texas M. D. Anderson Cancer Center, Houston, 1992-93).

I. V. Yaroslavsky, A. N. Yaroslavsky, V. V. Tuchin, H.-J. Schwarzmaier, "Effect of scattering delay on time-dependent photon migration in turbid media," Appl. Opt. 36, 6529-6538 (1997).
[CrossRef]

B. W. Pogue, M. S. Patterson, T. Farrell, "Forward and inverse calculations for 3-D frequency-domain diffuse optical tomography," Proc. SPIE 2389, 328-339 (1995)
[CrossRef]

V. G. Peters, D. R. Wyman, M. S. Patterson, G. L. Frank, "Optical properties of normal and diseased breast tissue in the visible and near infrared," Phys Med. Biol. 35, 1317-1334, (1990).
[CrossRef] [PubMed]

T. L. Troy, D. L. Page, E. M. Sevick-Muraca, "Optical properties of normal and diseased breast tissues: prognosis for optical mammography," J. Biomed. Opt. 1, 342-355 (1996).
[CrossRef] [PubMed]

K. Suzuki, Y. Yamashita, K. Ohta, M. Kaneko, M. Yoshida, B. Chance, "Quantitative measurement of optical parameters in normal breasts using time-resolved spectroscopy: In vivo results of 30 Japanese women," J. Biomed. Opt. 1(3), 330-334 (1996).
[CrossRef] [PubMed]

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Figures (7)

Fig. 1.
Fig. 1.

Schematic of the automated imaging instrument including hardware and software processing. Source optical fibers are indicated in red and detector optical fibers in green.

Fig. 2.
Fig. 2.

Photograph of the optical setup. The 32 fiber bundles set up for taking measurements from cylindrical phantoms are connected to two linear translation stages one on each side, which are used for rapid multiplexing of light source and detector.

Fig. 3.
Fig. 3.

(a) Measured standard deviation in the AC intensity signal (in volts) and the phase measurement (in degrees) plotted against the total AC intensity (in volts), here using a constant DC offset intensity of 1 Volt (5 Volt saturation), and 100 MHz AC frequency, and a data acquisition time of 0.2 seconds. (b) Measured modulation ratio out of the diode laser as a function of input frequency, using the same conditions as in (a).

Fig. 4.
Fig. 4.

Cylindrical geometry used for data acquisition: sources and detectors are located at the cylindrical boundary within the same plane, A.

Fig. 5.
Fig. 5.

Comparison between experimental data, Monte Carlo simulation and finite element calculation for a homogeneous cylindrical phantom (absorption μa=0.003mm-1, diffusion coefficient D=0.72mm). AC amplitude (a) and phase (b) of the measurement correspond fairly well to both theoretical models.

Fig. 6.
Fig. 6.

Reconstruction of a 25 mm absorbing object within a tissue simulating phantom (exact optical coefficients of background D = 0.67 mm, μa = 0.0062 mm-1, and object D = 0.67 mm and μa = 0.056 mm-1).

Fig. 7.
Fig. 7.

Reconstruction of a 25 mm diameter scattering object (corresponding to a decrease in diffusion), with the same background optical properties as in Fig. 6 but with inhomogeneity properties of D = 0.2 mm-1, and μa = 0.0062 mm-1.

Equations (3)

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1 c I ( r , s , t ) t = I ( r , s , t ) μ t I ( r , s , t ) + μ t 4 π 4 π p ( s , s ' ) I ( r , s ' , t ) d Ω ' + ε ( r , s , t ) ,
· [ D ϕ ( r , ω ) ] ( μ a + i ω c ) ϕ ( r , ω ) = S ( r , ω )
ϕ = α n ϕ

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