Mammograms of 35 patients suspected of breast cancer were taken along craniocaudal and mediolateral projections with a dual-wavelength scanning laser pulse mammograph measuring time-resolved transmittance. Among 26 tumors known from routine clinical diagnostics, 17 tumors were detected retrospectively in optical mammograms. Effective tumor optical properties derived from a homogeneous model were used to deduce physiological information. All tumors exhibited increased total hemoglobin concentration and decreased or unchanged blood oxygen saturation compared with surrounding healthy tissue. Scatter plots based on a pixelwise analysis of individual mammograms were introduced and applied to represent correlations between characteristic quantities derived from measured distributions of times of flight of photons.

© 2003 Optical Society of America

[Optical Society of America ]

1. B. J. Tromberg, N. Shah, R. Lanning, A. Cerussi, J. Espinoza, T. Pham, L. Svaasand, and J. Butler, “Non-invasive in vivo characterization of breast tumors using photon migration spectroscopy,” Neoplasia 2, 26–40 (2000).
2. R. Cubeddu, C. D’Andrea, A. Pifferi, P. Taroni, A. Torricelli, and G. Valentini, “Effects of the menstrual cycle on the red and near-infrared optical properties of the human breast,” Photochem. Photobiol. 72, 383–391 (2000).
3. A. E. Cerussi, D. Jakubowski, N. Shah, F. Bevilacqua, R. Lanning, A. J. Berger, D. Hsiang, J. Butler, R. F. Holcombe, and B. J. Tromberg, “Spectroscopy enhances the information content of optical mammography,” J. Biomed. Opt. 7, 60–71 (2002).
4. V. Quaresima, S. J. Matcher, and M. Ferrari, “Identification and quantification of intrinsic optical contrast for near-infrared mammography,” Photochem. Photobiol. 67, 4–14 (1998).
5. M. A. Franceschini, K. T. Moesta, S. Fantini, G. Gaida, E. Gratton, H. Jess, W. W. Mantulin, M. Seeber, P. M. Schlag, and M. Kaschke, “Frequency-domain techniques enhance optical mammography: initial clinical results,” Proc. Natl. Acad. Sci. USA 94, 6468–6473 (1997).
6. L. Götz, S. H. Heywang-Köbrunner, O. Schütz, and H. Siebold, “Optical mammography on preoperative patients (Optische Mammographie an präoperativen Patientinnen),” Akt. Radiol. 8, 31–33 (1998).
7. K. T. Moesta, S. Fantini, H. Jess, S. Totkas, M. A. Franceschini, M. Kaschke, and P. M. Schlag, “Contrast features of breast cancer in frequency-domain laser scanning mammography,” J. Biomed. Opt. 3, 129–136 (1998)
8. D. Grosenick, H. Wabnitz, H. Rinneberg, K. T. Moesta, and P. Schlag, “Development of a time-domain optical mammograph and first in vivo applications,” Appl. Opt. 38, 2927–2943 (1999).
9. R. Cubeddu, G. M. Danesini, E. Giambattistelli, F. Messina, L. Pallaro, A. Pifferi, P. Taroni, and A. Torricelli, “Time-resolved optical mammograph for clinical studies beyond 900 nm,” in OSA Biomedical Topical Meetings: Technical Digest Vol. 71 of OSA Trends in Optics and Photonics Series (Optical Society of America, Washington, D.C., 2002), pp. 674–676.
10. H. Rinneberg, D. Grosenick, H. Wabnitz, K. T. Moesta, and P. M. Schlag, “Detection and Characterization of breast tumors by a laser-pulse mammograph,” in Inter-Institute Workshop on In Vivo Optical Imaging at the NIH, A. H. Gandjbakhche, ed. (Optical Society of America, Washington, D.C., 2000), pp. 105–110.
11. S. B. Colak, M. B. van der Mark, G. W. ‘t Hooft J. H. Hoogenraad, E. S. van der Linden, and F. A. Kuijpers, “Clinical optical tomography and NIR spectroscopy for breast cancer detection,” IEEE J. Sel. Top. Quantum Electron. 5, 1143–1158 (1999).
12. T. O. McBride, B. W. Pogue, S. Poplack, S. Soho, W. A. Wells, S. Jiang, U. L. Österberg, and K. D. Paulsen, “Multispectral near-infrared tomography: a case study in compensating for water and lipid content in hemoglobin imaging of the breast,” J. Biomed. Opt. 7, 72–79 (2002).
13. J. C. Hebden, H. Veenstra, H. Dehghani, E. M. Hillman, M. Schweiger, S. R. Arridge, and D. T. Delpy, “Three-dimensional time-resolved optical tomography of a conical breast phantom,” Appl. Opt. 40, 3278–3287 (2001).
14. V. Ntziachristos, A. G. Yodh, M. Schnall, and B. Chance, “Concurrent MRI and diffuse optical tomography of breast cancer after indocyanine green enhancement,” Proc. Natl. Acad. Sci. USA 97, 2767–2772 (2000).
15. R. L. Barbour, H. L. Graber, Y. Pei, S. Zhong, and C. H. Schmitz, “Optical tomographic imaging of dynamic features of dense-scattering media,” J. Opt. Soc. Am. A 18, 3018–3036 (2001).
16. A. H. Gandjbakhche, V. Chernomordik, J. C. Hebden, and R. Nossal, “Time-dependent contrast functions for quantitative imaging in time-resolved transillumination experiments,” Appl. Opt. 37, 1973–1981 (1998).
17. D. J. Hall, J. C. Hebden, and D. T. Delpy, “Imaging very-low-contrast objects in breastlike scattering media with a time-resolved method,” Appl. Opt. 36, 7270–7276 (1997).
18. M. S. Patterson, B. Chance, and B. C. Wilson, “Time-resolved reflectance and transmittance for the noninvasive measurement of tissue optical properties,” Appl. Opt. 28, 2331–2336 (1989).
19. D. Contini, F. Martelli, and G. Zaccanti, “Photon migration through a turbid slab described by a model based on diffusion approximation. I. Theory,” Appl. Opt. 36, 4587–4599 (1997).
20. R. C. Haskell, L. O. Svaasand, T.-T. Tsay, T.-C. Feng, M. S. McAdams, and B. J. Tromberg, “Boundary conditions for the diffusion equation in radiative transfer,” J. Opt. Soc. Am. A 11, 2727–2741 (1994).
21. N. Shah, A. Cerussi, C. Eker, J. Espinoza, J. Butler, J. Fishkin, R. Hornung, and B. Tromberg, “Noninvasive functional optical spectroscopy of human breast tissue,” Proc. Natl. Acad. Sci. USA 98, 4420–4425 (2001).
22. H. Q. Woodard and D. R. White, “The composition of body tissues,” Br. J. Radiol. 59, 1209–1218 (1986).
23. M. Cope, “The development of a near infrared spectroscopy system and its application for noninvasive monitoring of cerebral blood and tissue oxygenation in the newborn infant,” Ph.D. thesis (University College, London, 1991).
24. G. M. Hale and M. R. Querry, “Optical constants of water in the 200-nm to 200-μm wavelength region,” Appl. Opt. 12, 555–563 (1973).
25. S. Thomsen and D. Tatman, “Physiological and pathological factors of human breast disease that can influence optical diagnosis,” in Advances in Optical Biopsy and Optical Mammography, Ann. N.Y. Acad. Sci. 838, 171–193 (1998).
26. J. R. Mourant, T. Fuselier, J. Boyer, T. M. Johnson and I. J. Bigio, “Predictions and measurements of scattering and absorption over broad wavelength ranges in tissue phantoms,” Appl. Opt. 36, 949–957 (1997).
27. A. E. Cerussi, A. J. Berger, F. Bevilacqua, N. Shah, D. Jakubowski, J. Butler, R. F. Holcombe and B. J. Tromberg, “Sources of absorption and scattering contrast for near-infrared optical mammography,” Acad. Radiol. 8, 211–218 (2001).
28. T. Durduran, R. Choe, J. P. Culver, L. Zubkov, M. J. Holboke, J. Giammarco, B. Chance, and A. G. Yodh, “Bulk optical properties of healthy female breast tissue,” Phys. Med. Biol. 47, 2847–2861 (2002).
29. D. A. Boas, M. A. O’Leary, B. Chance, and A. G. Yodh, “Scattering of diffuse photon density waves by spherical inhomogeneities within turbid media: analytic solution and applications,” Proc. Natl. Acad. Sci. USA 91, 4887–4891 (1994).
30. S. Fantini, S. A. Walker, M. A. Franceschini, M. Kaschke, P. M. Schlag and K. T. Moesta, “Assessment of the size, position, and optical properties of breast tumors in vivo by noninvasive optical methods,” Appl. Opt. 37, 1982–1989 (1998).
31. V. G. Peters, D. R. Wyman, M. S. Patterson, and G. L. Frank, “Optical properties of normal and diseased human breast tissues in the visible and near infrared,” Phys. Med. Biol. 35, 1317–1334 (1990).
32. K. Suzuki, Y. Yamashita, K. Ohta, M. Kaneko, M. Yoshida, and B. Chance, “Quantitative measurements of optical parameters in normal breasts using time-resolved spectroscopy: in vivo results of 30 Japanese women,” J. Biomed. Opt. 1, 330–334 (1996).
33. T. L. Troy, D. L. Page, and E. M. Sevick-Muraca, “Optical properties of normal and diseased breast tissue: prognosis for optical mammography,” J. Biomed. Opt. 1, 342–355 (1996).
34. H. Heusmann, J. Kölzer, and G. Mitic, “Characterization of female breasts in vivo by time resolved and spectroscopic measurements in near infrared spectroscopy,” J. Biomed. Opt. 1, 425–434 (1996).
35. V. Chernomordik, D. W. Hattery, D. Grosenick, H. Wabnitz, H. Rinneberg, K. T. Moesta, P. M. Schlag, and A. Gandjbakhche, “Quantification of optical properties of a breast tumor using random walk theory,” J. Biomed. Opt. 7, 80–87 (2002).

Acad. Radiol.

• A. E. Cerussi, A. J. Berger, F. Bevilacqua, N. Shah, D. Jakubowski, J. Butler, R. F. Holcombe and B. J. Tromberg, “Sources of absorption and scattering contrast for near-infrared optical mammography,” Acad. Radiol. 8, 211–218 (2001).

Akt. Radiol.

• L. Götz, S. H. Heywang-Köbrunner, O. Schütz, and H. Siebold, “Optical mammography on preoperative patients (Optische Mammographie an präoperativen Patientinnen),” Akt. Radiol. 8, 31–33 (1998).

Ann. N.Y. Acad. Sci.

• S. Thomsen and D. Tatman, “Physiological and pathological factors of human breast disease that can influence optical diagnosis,” in Advances in Optical Biopsy and Optical Mammography, Ann. N.Y. Acad. Sci. 838, 171–193 (1998).

Appl. Opt.

• J. R. Mourant, T. Fuselier, J. Boyer, T. M. Johnson and I. J. Bigio, “Predictions and measurements of scattering and absorption over broad wavelength ranges in tissue phantoms,” Appl. Opt. 36, 949–957 (1997).
• G. M. Hale and M. R. Querry, “Optical constants of water in the 200-nm to 200-μm wavelength region,” Appl. Opt. 12, 555–563 (1973).
• S. Fantini, S. A. Walker, M. A. Franceschini, M. Kaschke, P. M. Schlag and K. T. Moesta, “Assessment of the size, position, and optical properties of breast tumors in vivo by noninvasive optical methods,” Appl. Opt. 37, 1982–1989 (1998).
• D. Grosenick, H. Wabnitz, H. Rinneberg, K. T. Moesta, and P. Schlag, “Development of a time-domain optical mammograph and first in vivo applications,” Appl. Opt. 38, 2927–2943 (1999).
• J. C. Hebden, H. Veenstra, H. Dehghani, E. M. Hillman, M. Schweiger, S. R. Arridge, and D. T. Delpy, “Three-dimensional time-resolved optical tomography of a conical breast phantom,” Appl. Opt. 40, 3278–3287 (2001).
• A. H. Gandjbakhche, V. Chernomordik, J. C. Hebden, and R. Nossal, “Time-dependent contrast functions for quantitative imaging in time-resolved transillumination experiments,” Appl. Opt. 37, 1973–1981 (1998).
• D. J. Hall, J. C. Hebden, and D. T. Delpy, “Imaging very-low-contrast objects in breastlike scattering media with a time-resolved method,” Appl. Opt. 36, 7270–7276 (1997).
• M. S. Patterson, B. Chance, and B. C. Wilson, “Time-resolved reflectance and transmittance for the noninvasive measurement of tissue optical properties,” Appl. Opt. 28, 2331–2336 (1989).
• D. Contini, F. Martelli, and G. Zaccanti, “Photon migration through a turbid slab described by a model based on diffusion approximation. I. Theory,” Appl. Opt. 36, 4587–4599 (1997).

Br. J. Radiol.

• H. Q. Woodard and D. R. White, “The composition of body tissues,” Br. J. Radiol. 59, 1209–1218 (1986).

IEEE J. Sel. Top. Quantum Electron.

• S. B. Colak, M. B. van der Mark, G. W. ‘t Hooft J. H. Hoogenraad, E. S. van der Linden, and F. A. Kuijpers, “Clinical optical tomography and NIR spectroscopy for breast cancer detection,” IEEE J. Sel. Top. Quantum Electron. 5, 1143–1158 (1999).

J. Biomed. Opt.

• T. O. McBride, B. W. Pogue, S. Poplack, S. Soho, W. A. Wells, S. Jiang, U. L. Österberg, and K. D. Paulsen, “Multispectral near-infrared tomography: a case study in compensating for water and lipid content in hemoglobin imaging of the breast,” J. Biomed. Opt. 7, 72–79 (2002).
• K. T. Moesta, S. Fantini, H. Jess, S. Totkas, M. A. Franceschini, M. Kaschke, and P. M. Schlag, “Contrast features of breast cancer in frequency-domain laser scanning mammography,” J. Biomed. Opt. 3, 129–136 (1998)
• A. E. Cerussi, D. Jakubowski, N. Shah, F. Bevilacqua, R. Lanning, A. J. Berger, D. Hsiang, J. Butler, R. F. Holcombe, and B. J. Tromberg, “Spectroscopy enhances the information content of optical mammography,” J. Biomed. Opt. 7, 60–71 (2002).
• K. Suzuki, Y. Yamashita, K. Ohta, M. Kaneko, M. Yoshida, and B. Chance, “Quantitative measurements of optical parameters in normal breasts using time-resolved spectroscopy: in vivo results of 30 Japanese women,” J. Biomed. Opt. 1, 330–334 (1996).
• T. L. Troy, D. L. Page, and E. M. Sevick-Muraca, “Optical properties of normal and diseased breast tissue: prognosis for optical mammography,” J. Biomed. Opt. 1, 342–355 (1996).
• H. Heusmann, J. Kölzer, and G. Mitic, “Characterization of female breasts in vivo by time resolved and spectroscopic measurements in near infrared spectroscopy,” J. Biomed. Opt. 1, 425–434 (1996).
• V. Chernomordik, D. W. Hattery, D. Grosenick, H. Wabnitz, H. Rinneberg, K. T. Moesta, P. M. Schlag, and A. Gandjbakhche, “Quantification of optical properties of a breast tumor using random walk theory,” J. Biomed. Opt. 7, 80–87 (2002).

J. Opt. Soc. Am. A

• R. L. Barbour, H. L. Graber, Y. Pei, S. Zhong, and C. H. Schmitz, “Optical tomographic imaging of dynamic features of dense-scattering media,” J. Opt. Soc. Am. A 18, 3018–3036 (2001).
• R. C. Haskell, L. O. Svaasand, T.-T. Tsay, T.-C. Feng, M. S. McAdams, and B. J. Tromberg, “Boundary conditions for the diffusion equation in radiative transfer,” J. Opt. Soc. Am. A 11, 2727–2741 (1994).

Neoplasia

• B. J. Tromberg, N. Shah, R. Lanning, A. Cerussi, J. Espinoza, T. Pham, L. Svaasand, and J. Butler, “Non-invasive in vivo characterization of breast tumors using photon migration spectroscopy,” Neoplasia 2, 26–40 (2000).

Photochem. Photobiol.

• R. Cubeddu, C. D’Andrea, A. Pifferi, P. Taroni, A. Torricelli, and G. Valentini, “Effects of the menstrual cycle on the red and near-infrared optical properties of the human breast,” Photochem. Photobiol. 72, 383–391 (2000).
• V. Quaresima, S. J. Matcher, and M. Ferrari, “Identification and quantification of intrinsic optical contrast for near-infrared mammography,” Photochem. Photobiol. 67, 4–14 (1998).

Phys. Med. Biol.

• T. Durduran, R. Choe, J. P. Culver, L. Zubkov, M. J. Holboke, J. Giammarco, B. Chance, and A. G. Yodh, “Bulk optical properties of healthy female breast tissue,” Phys. Med. Biol. 47, 2847–2861 (2002).
• V. G. Peters, D. R. Wyman, M. S. Patterson, and G. L. Frank, “Optical properties of normal and diseased human breast tissues in the visible and near infrared,” Phys. Med. Biol. 35, 1317–1334 (1990).

Proc. Natl. Acad. Sci. USA

• D. A. Boas, M. A. O’Leary, B. Chance, and A. G. Yodh, “Scattering of diffuse photon density waves by spherical inhomogeneities within turbid media: analytic solution and applications,” Proc. Natl. Acad. Sci. USA 91, 4887–4891 (1994).
• M. A. Franceschini, K. T. Moesta, S. Fantini, G. Gaida, E. Gratton, H. Jess, W. W. Mantulin, M. Seeber, P. M. Schlag, and M. Kaschke, “Frequency-domain techniques enhance optical mammography: initial clinical results,” Proc. Natl. Acad. Sci. USA 94, 6468–6473 (1997).
• N. Shah, A. Cerussi, C. Eker, J. Espinoza, J. Butler, J. Fishkin, R. Hornung, and B. Tromberg, “Noninvasive functional optical spectroscopy of human breast tissue,” Proc. Natl. Acad. Sci. USA 98, 4420–4425 (2001).
• V. Ntziachristos, A. G. Yodh, M. Schnall, and B. Chance, “Concurrent MRI and diffuse optical tomography of breast cancer after indocyanine green enhancement,” Proc. Natl. Acad. Sci. USA 97, 2767–2772 (2000).

Other

• R. Cubeddu, G. M. Danesini, E. Giambattistelli, F. Messina, L. Pallaro, A. Pifferi, P. Taroni, and A. Torricelli, “Time-resolved optical mammograph for clinical studies beyond 900 nm,” in OSA Biomedical Topical Meetings: Technical Digest Vol. 71 of OSA Trends in Optics and Photonics Series (Optical Society of America, Washington, D.C., 2002), pp. 674–676.
• H. Rinneberg, D. Grosenick, H. Wabnitz, K. T. Moesta, and P. M. Schlag, “Detection and Characterization of breast tumors by a laser-pulse mammograph,” in Inter-Institute Workshop on In Vivo Optical Imaging at the NIH, A. H. Gandjbakhche, ed. (Optical Society of America, Washington, D.C., 2000), pp. 105–110.
• M. Cope, “The development of a near infrared spectroscopy system and its application for noninvasive monitoring of cerebral blood and tissue oxygenation in the newborn infant,” Ph.D. thesis (University College, London, 1991).

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