Abstract

Using scanning time-domain instrumentation we recorded fluorescence projection mammograms on few breast cancer patients prior, during and after infusion of indocyanine green (ICG), while monitoring arterial ICG concentration by transcutaneous pulse densitometry. Late-fluorescence mammograms recorded after ICG had been largely cleared from the blood by the liver, showed invasive carcinomas at high contrast over a rather homogeneous background, whereas benign lesions did not produce (focused) fluorescence contrast. During infusion, tissue concentration contrast and hence fluorescence contrast is determined by intravascular contributions, whereas late-fluorescence mammograms are dominated by contributions from protein-bound ICG extravasated into the interstitium, reflecting relative microvascular permeabilities of carcinomas and normal breast tissue. We simulated intravascular and extravascular contributions to ICG tissue concentration contrast within a two-compartment unidirectional pharmacokinetic model.

© 2009 OSA

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    [PubMed]
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2008 (4)

H. Rinneberg, D. Grosenick, K. T. Moesta, H. Wabnitz, J. Mucke, G. Wübbeler, R. Macdonald, and P. Schlag, “Detection and characterization of breast tumours by time-domain scanning optical mammography,” Opto-Electronics Review 16(2), 147–162 (2008).

E. E. Uzgiris, “Tumor microvasculature: endothelial leakiness and endothelial pore size distribution in a breast cancer model,” Breast Cancer: Basic and Clinical Research 1, 83–90 (2008).

B. Alacam, B. Yazici, X. Intes, S. Nioka, and B. Chance, “Pharmacokinetic-rate images of indocyanine green for breast tumors using near-infrared optical methods,” Phys. Med. Biol. 53(4), 837–859 (2008).
[PubMed]

S. A. Carp, J. Selb, Q. Fang, R. Moore, D. B. Kopans, E. Rafferty, and D. A. Boas, “Dynamic functional and mechanical response of breast tissue to compression,” Opt. Express 16(20), 16064–16078 (2008).
[PubMed]

2007 (5)

A. Corlu, R. Choe, T. Durduran, M. A. Rosen, M. Schweiger, S. R. Arridge, M. D. Schnall, and A. G. Yodh, “Three-dimensional in vivo fluorescence diffuse optical tomography of breast cancer in humans,” Opt. Express 15(11), 6696–6716 (2007).
[PubMed]

A. Hagen, O. Steinkellner, D. Grosenick, M. Möller, R. Ziegler, T. Nielsen, K. Lauritsen, R. Macdonald, and H. Rinneberg, “Development of a multi-channel time-domain fluorescence mammograph,” Proc. SPIE 6434, 64340Z (2007).

S. P. Poplack, T. D. Tosteson, W. A. Wells, B. W. Pogue, P. M. Meaney, A. Hartov, C. A. Kogel, S. K. Soho, J. J. Gibson, and K. D. Paulsen, “Electromagnetic breast imaging: results of a pilot study in women with abnormal mammograms,” Radiology 243(2), 350–359 (2007).
[PubMed]

A. Cerussi, D. Hsiang, N. Shah, R. Mehta, A. Durkin, J. Butler, and B. J. Tromberg, “Predicting response to breast cancer neoadjuvant chemotherapy using diffuse optical spectroscopy,” Proc. Natl. Acad. Sci. U.S.A. 104(10), 4014–4019 (2007).
[PubMed]

C. Zhou, R. Choe, N. Shah, T. Durduran, G. Yu, A. Durkin, D. Hsiang, R. Mehta, J. Butler, A. Cerussi, B. J. Tromberg, and A. G. Yodh, “Diffuse optical monitoring of blood flow and oxygenation in human breast cancer during early stages of neoadjuvant chemotherapy,” J. Biomed. Opt. 12(5), 051903 (2007).
[PubMed]

2006 (4)

A. Cerussi, N. Shah, D. Hsiang, A. Durkin, J. Butler, and B. J. Tromberg, “In vivo absorption, scattering, and physiologic properties of 58 malignant breast tumors determined by broadband diffuse optical spectroscopy,” J. Biomed. Opt. 11(4), 044005 (2006).
[PubMed]

B. W. Pogue, S. C. Davis, X. Song, B. A. Brooksby, H. Dehghani, and K. D. Paulsen, “Image analysis methods for diffuse optical tomography,” J. Biomed. Opt. 11(3), 033001 (2006).

R. Duncan, “Polymer conjugates as anticancer nanomedicines,” Nat. Rev. Cancer 6(9), 688–701 (2006).
[PubMed]

M. R. Dreher, W. Liu, C. R. Michelich, M. W. Dewhirst, F. Yuan, and A. Chilkoti, “Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers,” J. Natl. Cancer Inst. 98(5), 335–344 (2006).
[PubMed]

2005 (4)

C. Perlitz, K. Licha, F. D. Scholle, B. Ebert, M. Bahner, P. Hauff, K. T. Moesta, and M. Schirner, “Comparison of two tricarbocyanine-based dyes for fluorescence optical imaging,” J. Fluoresc. 15(3), 443–454 (2005).
[PubMed]

P. Taroni, A. Torricelli, L. Spinelli, A. Pifferi, F. Arpaia, G. Danesini, and R. Cubeddu, “Time-resolved optical mammography between 637 and 985 nm: clinical study on the detection and identification of breast lesions,” Phys. Med. Biol. 50(11), 2469–2488 (2005).
[PubMed]

D. Grosenick, K. Th. Moesta, M. Möller, J. Mucke, H. Wabnitz, B. Gebauer, Ch. Stroszczynski, B. Wassermann, P. M. Schlag, and H. Rinneberg, “Time-domain scanning optical mammography: I. Recording and assessment of mammograms of 154 patients,” Phys. Med. Biol. 50(11), 2429–2449 (2005).
[PubMed]

D. Grosenick, H. Wabnitz, K. Th. Moesta, J. Mucke, P. M. Schlag, and H. Rinneberg, “Time-domain scanning optical mammography: II. Optical properties and tissue parameters of 87 carcinomas,” Phys. Med. Biol. 50(11), 2451–2468 (2005).
[PubMed]

2004 (1)

G. Brix, F. Kiessling, R. Lucht, S. Darai, K. Wasser, S. Delorme, and J. Griebel, “Microcirculation and microvasculature in breast tumors: pharmacokinetic analysis of dynamic MR image series,” Magn. Reson. Med. 52(2), 420–429 (2004).
[PubMed]

2003 (5)

H. E. Daldrup-Link and R. C. Brasch, “Macromolecular contrast agents for MR mammography: current status,” Eur. Radiol. 13(2), 354–365 (2003).
[PubMed]

X. Intes, J. Ripoll, Y. Chen, S. Nioka, A. G. Yodh, and B. Chance, “In vivo continuous-wave optical breast imaging enhanced with Indocyanine Green,” Med. Phys. 30(6), 1039–1047 (2003).
[PubMed]

M. Möller, H. Wabnitz, A. Kummrow, D. Grosenick, A. Liebert, B. Wassermann, R. Macdonald, and H. Rinneberg, “A four-wavelength multi-channel scanning time-resolved optical mammograph,” Proc. SPIE 5138, 290–297 (2003).

H. Dehghani, B. W. Pogue, S. P. Poplack, and K. D. Paulsen, “Multiwavelength three-dimensional near-infrared tomography of the breast: initial simulation, phantom, and clinical results,” Appl. Opt. 42(1), 135–145 (2003).
[PubMed]

D. J. Cuccia, F. Bevilacqua, A. J. Durkin, S. Merritt, B. J. Tromberg, G. Gulsen, H. Yu, J. Wang, and O. Nalcioglu, “In vivo quantification of optical contrast agent dynamics in rat tumors by use of diffuse optical spectroscopy with magnetic resonance imaging coregistration,” Appl. Opt. 42(16), 2940–2950 (2003).
[PubMed]

2002 (1)

D. Feng, J. A. Nagy, H. F. Dvorak, and A. M. Dvorak, “Ultrastructural studies define soluble macromolecular, particulate, and cellular transendothelial cell pathways in venules, lymphatic vessels, and tumor-associated microvessels in man and animals,” Microsc. Res. Tech. 57(5), 289–326 (2002).
[PubMed]

2001 (1)

Z. M. Bhujwalla, D. Artemov, K. Natarajan, E. Ackerstaff, and M. Solaiyappan, “Vascular differences detected by MRI for metastatic versus nonmetastatic breast and prostate cancer xenografts,” Neoplasia 3(2), 143–153 (2001).
[PubMed]

2000 (5)

M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, and E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72(1), 94–102 (2000).
[PubMed]

P. Carmeliet and R. K. Jain, “Angiogenesis in cancer and other diseases,” Nature 407(6801), 249–257 (2000).
[PubMed]

H. Hashizume, P. Baluk, S. Morikawa, J. W. McLean, G. Thurston, S. Roberge, R. K. Jain, and D. M. McDonald, “Openings between defective endothelial cells explain tumor vessel leakiness,” Am. J. Pathol. 156(4), 1363–1380 (2000).
[PubMed]

V. Ntziachristos, A. G. Yodh, M. Schnall, and B. Chance, “Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement,” Proc. Natl. Acad. Sci. U.S.A. 97(6), 2767–2772 (2000).
[PubMed]

P. Vaupel and M. Höckel, “Blood supply, oxygenation status and metabolic micromilieu of breast cancers: characterization and therapeutic relevance,” Int. J. Oncol. 17(5), 869–879 (2000) (review).
[PubMed]

1999 (3)

D. Grosenick, H. Wabnitz, H. H. Rinneberg, K. Th. Moesta, and P. M. Schlag, “Development of a time-domain optical mammograph and first in vivo applications,” Appl. Opt. 38(13), 2927–2943 (1999).

C. C. Michel and F. E. Curry, “Microvascular permeability,” Physiol. Rev. 79(3), 703–761 (1999).
[PubMed]

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(4), 1143–1158 (1999).

1998 (3)

H. Daldrup, D. M. Shames, M. Wendland, Y. Okuhata, T. M. Link, W. Rosenau, Y. Lu, and R. C. Brasch, “Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media,” AJR Am. J. Roentgenol. 171(4), 941–949 (1998).
[PubMed]

S. Yoneya, T. Saito, Y. Komatsu, I. Koyama, K. Takahashi, and J. Duvoll-Young, “Binding properties of indocyanine green in human blood,” Invest. Ophthalmol. Vis. Sci. 39(7), 1286–1290 (1998).
[PubMed]

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).

1997 (2)

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. U.S.A. 94(12), 6468–6473 (1997).
[PubMed]

P. Ott and R. A. Weisiger, “Nontraditional effects of protein binding and hematocrit on uptake of indocyanine green by perfused rat liver,” Am. J. Physiol. 273(1 Pt 1), G227–G238 (1997).
[PubMed]

1996 (1)

P. Ott, L. Bass, and S. Keiding, “The kinetics of continuously infused indocyanine green in the pig,” J. Pharmacokinet. Biopharm. 24(1), 19–44 (1996).
[PubMed]

1994 (1)

P. S. Tofts and B. A. Berkowitz, “Measurement of capillary permeability from the Gd enhancement curve: a comparison of bolus and constant infusion injection methods,” Magn. Reson. Imaging 12(1), 81–91 (1994).
[PubMed]

1993 (1)

S. Keiding, P. Ott, and L. Bass, “Enhancement of unbound clearance of ICG by plasma proteins, demonstrated in human subjects and interpreted without assumption of facilitating structures,” J. Hepatol. 19(3), 327–344 (1993).
[PubMed]

1992 (2)

U. Schilling, E. A. Friedrich, H. Sinn, H. H. Schrenk, J. H. Clorius, and W. Maier-Borst, “Design of compounds having enhanced tumor uptake, using serum albumin as a carrier – Part II. In vivo studies,” Nucl. Med. Biol. 19(6), 685–695 (1992).

C. B. Wilson, A. A. Lammertsma, C. G. McKenzie, K. Sikora, and T. Jones, “Measurements of blood flow and exchanging water space in breast tumors using positron emission tomography: a rapid and noninvasive dynamic method,” Cancer Res. 52(6), 1592–1597 (1992).
[PubMed]

1988 (1)

D. K. F. Meijer, B. Weert, and G. A. Vermeer, “Pharmacokinetics of biliary excretion in man. VI. Indocyanine green,” Eur. J. Clin. Pharmacol. 35(3), 295–303 (1988).
[PubMed]

1986 (2)

K. Sauda, T. Imasaka, and N. Ishibashi, “Determination of protein in human serum by high-performance liquid chromatography with semiconductor laser fluorometric detection,” Anal. Chem. 58(13), 2649–2653 (1986).
[PubMed]

Y. Matsumura and H. Maeda, “A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs,” Cancer Res. 46(12 Pt 1), 6387–6392 (1986).
[PubMed]

1962 (1)

E. Brown, J. Hopper, J. L. Hodges, B. Bradley, R. Wennesland, and H. Yamauchi, “Red cell, plasma, and blood volume in the healthy women measured by radiochromium cell-labeling and hematocrit,” J. Clin. Invest. 41(12), 2182–2190 (1962).
[PubMed]

Ackerstaff, E.

Z. M. Bhujwalla, D. Artemov, K. Natarajan, E. Ackerstaff, and M. Solaiyappan, “Vascular differences detected by MRI for metastatic versus nonmetastatic breast and prostate cancer xenografts,” Neoplasia 3(2), 143–153 (2001).
[PubMed]

Alacam, B.

B. Alacam, B. Yazici, X. Intes, S. Nioka, and B. Chance, “Pharmacokinetic-rate images of indocyanine green for breast tumors using near-infrared optical methods,” Phys. Med. Biol. 53(4), 837–859 (2008).
[PubMed]

Arpaia, F.

P. Taroni, A. Torricelli, L. Spinelli, A. Pifferi, F. Arpaia, G. Danesini, and R. Cubeddu, “Time-resolved optical mammography between 637 and 985 nm: clinical study on the detection and identification of breast lesions,” Phys. Med. Biol. 50(11), 2469–2488 (2005).
[PubMed]

Arridge, S. R.

Artemov, D.

Z. M. Bhujwalla, D. Artemov, K. Natarajan, E. Ackerstaff, and M. Solaiyappan, “Vascular differences detected by MRI for metastatic versus nonmetastatic breast and prostate cancer xenografts,” Neoplasia 3(2), 143–153 (2001).
[PubMed]

Bahner, M.

C. Perlitz, K. Licha, F. D. Scholle, B. Ebert, M. Bahner, P. Hauff, K. T. Moesta, and M. Schirner, “Comparison of two tricarbocyanine-based dyes for fluorescence optical imaging,” J. Fluoresc. 15(3), 443–454 (2005).
[PubMed]

Baluk, P.

H. Hashizume, P. Baluk, S. Morikawa, J. W. McLean, G. Thurston, S. Roberge, R. K. Jain, and D. M. McDonald, “Openings between defective endothelial cells explain tumor vessel leakiness,” Am. J. Pathol. 156(4), 1363–1380 (2000).
[PubMed]

Bass, L.

P. Ott, L. Bass, and S. Keiding, “The kinetics of continuously infused indocyanine green in the pig,” J. Pharmacokinet. Biopharm. 24(1), 19–44 (1996).
[PubMed]

S. Keiding, P. Ott, and L. Bass, “Enhancement of unbound clearance of ICG by plasma proteins, demonstrated in human subjects and interpreted without assumption of facilitating structures,” J. Hepatol. 19(3), 327–344 (1993).
[PubMed]

Berkowitz, B. A.

P. S. Tofts and B. A. Berkowitz, “Measurement of capillary permeability from the Gd enhancement curve: a comparison of bolus and constant infusion injection methods,” Magn. Reson. Imaging 12(1), 81–91 (1994).
[PubMed]

Bevilacqua, F.

Bhujwalla, Z. M.

Z. M. Bhujwalla, D. Artemov, K. Natarajan, E. Ackerstaff, and M. Solaiyappan, “Vascular differences detected by MRI for metastatic versus nonmetastatic breast and prostate cancer xenografts,” Neoplasia 3(2), 143–153 (2001).
[PubMed]

Boas, D. A.

Bradley, B.

E. Brown, J. Hopper, J. L. Hodges, B. Bradley, R. Wennesland, and H. Yamauchi, “Red cell, plasma, and blood volume in the healthy women measured by radiochromium cell-labeling and hematocrit,” J. Clin. Invest. 41(12), 2182–2190 (1962).
[PubMed]

Brasch, R. C.

H. E. Daldrup-Link and R. C. Brasch, “Macromolecular contrast agents for MR mammography: current status,” Eur. Radiol. 13(2), 354–365 (2003).
[PubMed]

H. Daldrup, D. M. Shames, M. Wendland, Y. Okuhata, T. M. Link, W. Rosenau, Y. Lu, and R. C. Brasch, “Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media,” AJR Am. J. Roentgenol. 171(4), 941–949 (1998).
[PubMed]

Brix, G.

G. Brix, F. Kiessling, R. Lucht, S. Darai, K. Wasser, S. Delorme, and J. Griebel, “Microcirculation and microvasculature in breast tumors: pharmacokinetic analysis of dynamic MR image series,” Magn. Reson. Med. 52(2), 420–429 (2004).
[PubMed]

Brooksby, B. A.

B. W. Pogue, S. C. Davis, X. Song, B. A. Brooksby, H. Dehghani, and K. D. Paulsen, “Image analysis methods for diffuse optical tomography,” J. Biomed. Opt. 11(3), 033001 (2006).

Brown, E.

E. Brown, J. Hopper, J. L. Hodges, B. Bradley, R. Wennesland, and H. Yamauchi, “Red cell, plasma, and blood volume in the healthy women measured by radiochromium cell-labeling and hematocrit,” J. Clin. Invest. 41(12), 2182–2190 (1962).
[PubMed]

Butler, J.

A. Cerussi, D. Hsiang, N. Shah, R. Mehta, A. Durkin, J. Butler, and B. J. Tromberg, “Predicting response to breast cancer neoadjuvant chemotherapy using diffuse optical spectroscopy,” Proc. Natl. Acad. Sci. U.S.A. 104(10), 4014–4019 (2007).
[PubMed]

C. Zhou, R. Choe, N. Shah, T. Durduran, G. Yu, A. Durkin, D. Hsiang, R. Mehta, J. Butler, A. Cerussi, B. J. Tromberg, and A. G. Yodh, “Diffuse optical monitoring of blood flow and oxygenation in human breast cancer during early stages of neoadjuvant chemotherapy,” J. Biomed. Opt. 12(5), 051903 (2007).
[PubMed]

A. Cerussi, N. Shah, D. Hsiang, A. Durkin, J. Butler, and B. J. Tromberg, “In vivo absorption, scattering, and physiologic properties of 58 malignant breast tumors determined by broadband diffuse optical spectroscopy,” J. Biomed. Opt. 11(4), 044005 (2006).
[PubMed]

Carmeliet, P.

P. Carmeliet and R. K. Jain, “Angiogenesis in cancer and other diseases,” Nature 407(6801), 249–257 (2000).
[PubMed]

Carp, S. A.

Cerussi, A.

C. Zhou, R. Choe, N. Shah, T. Durduran, G. Yu, A. Durkin, D. Hsiang, R. Mehta, J. Butler, A. Cerussi, B. J. Tromberg, and A. G. Yodh, “Diffuse optical monitoring of blood flow and oxygenation in human breast cancer during early stages of neoadjuvant chemotherapy,” J. Biomed. Opt. 12(5), 051903 (2007).
[PubMed]

A. Cerussi, D. Hsiang, N. Shah, R. Mehta, A. Durkin, J. Butler, and B. J. Tromberg, “Predicting response to breast cancer neoadjuvant chemotherapy using diffuse optical spectroscopy,” Proc. Natl. Acad. Sci. U.S.A. 104(10), 4014–4019 (2007).
[PubMed]

A. Cerussi, N. Shah, D. Hsiang, A. Durkin, J. Butler, and B. J. Tromberg, “In vivo absorption, scattering, and physiologic properties of 58 malignant breast tumors determined by broadband diffuse optical spectroscopy,” J. Biomed. Opt. 11(4), 044005 (2006).
[PubMed]

Chance, B.

B. Alacam, B. Yazici, X. Intes, S. Nioka, and B. Chance, “Pharmacokinetic-rate images of indocyanine green for breast tumors using near-infrared optical methods,” Phys. Med. Biol. 53(4), 837–859 (2008).
[PubMed]

X. Intes, J. Ripoll, Y. Chen, S. Nioka, A. G. Yodh, and B. Chance, “In vivo continuous-wave optical breast imaging enhanced with Indocyanine Green,” Med. Phys. 30(6), 1039–1047 (2003).
[PubMed]

V. Ntziachristos, A. G. Yodh, M. Schnall, and B. Chance, “Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement,” Proc. Natl. Acad. Sci. U.S.A. 97(6), 2767–2772 (2000).
[PubMed]

Chen, Y.

X. Intes, J. Ripoll, Y. Chen, S. Nioka, A. G. Yodh, and B. Chance, “In vivo continuous-wave optical breast imaging enhanced with Indocyanine Green,” Med. Phys. 30(6), 1039–1047 (2003).
[PubMed]

Chilkoti, A.

M. R. Dreher, W. Liu, C. R. Michelich, M. W. Dewhirst, F. Yuan, and A. Chilkoti, “Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers,” J. Natl. Cancer Inst. 98(5), 335–344 (2006).
[PubMed]

Choe, R.

A. Corlu, R. Choe, T. Durduran, M. A. Rosen, M. Schweiger, S. R. Arridge, M. D. Schnall, and A. G. Yodh, “Three-dimensional in vivo fluorescence diffuse optical tomography of breast cancer in humans,” Opt. Express 15(11), 6696–6716 (2007).
[PubMed]

C. Zhou, R. Choe, N. Shah, T. Durduran, G. Yu, A. Durkin, D. Hsiang, R. Mehta, J. Butler, A. Cerussi, B. J. Tromberg, and A. G. Yodh, “Diffuse optical monitoring of blood flow and oxygenation in human breast cancer during early stages of neoadjuvant chemotherapy,” J. Biomed. Opt. 12(5), 051903 (2007).
[PubMed]

Clorius, J. H.

U. Schilling, E. A. Friedrich, H. Sinn, H. H. Schrenk, J. H. Clorius, and W. Maier-Borst, “Design of compounds having enhanced tumor uptake, using serum albumin as a carrier – Part II. In vivo studies,” Nucl. Med. Biol. 19(6), 685–695 (1992).

Colak, S. B.

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(4), 1143–1158 (1999).

Corlu, A.

Cubeddu, R.

P. Taroni, A. Torricelli, L. Spinelli, A. Pifferi, F. Arpaia, G. Danesini, and R. Cubeddu, “Time-resolved optical mammography between 637 and 985 nm: clinical study on the detection and identification of breast lesions,” Phys. Med. Biol. 50(11), 2469–2488 (2005).
[PubMed]

Cuccia, D. J.

Curry, F. E.

C. C. Michel and F. E. Curry, “Microvascular permeability,” Physiol. Rev. 79(3), 703–761 (1999).
[PubMed]

Daldrup, H.

H. Daldrup, D. M. Shames, M. Wendland, Y. Okuhata, T. M. Link, W. Rosenau, Y. Lu, and R. C. Brasch, “Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media,” AJR Am. J. Roentgenol. 171(4), 941–949 (1998).
[PubMed]

Daldrup-Link, H. E.

H. E. Daldrup-Link and R. C. Brasch, “Macromolecular contrast agents for MR mammography: current status,” Eur. Radiol. 13(2), 354–365 (2003).
[PubMed]

Danesini, G.

P. Taroni, A. Torricelli, L. Spinelli, A. Pifferi, F. Arpaia, G. Danesini, and R. Cubeddu, “Time-resolved optical mammography between 637 and 985 nm: clinical study on the detection and identification of breast lesions,” Phys. Med. Biol. 50(11), 2469–2488 (2005).
[PubMed]

Darai, S.

G. Brix, F. Kiessling, R. Lucht, S. Darai, K. Wasser, S. Delorme, and J. Griebel, “Microcirculation and microvasculature in breast tumors: pharmacokinetic analysis of dynamic MR image series,” Magn. Reson. Med. 52(2), 420–429 (2004).
[PubMed]

Davis, S. C.

B. W. Pogue, S. C. Davis, X. Song, B. A. Brooksby, H. Dehghani, and K. D. Paulsen, “Image analysis methods for diffuse optical tomography,” J. Biomed. Opt. 11(3), 033001 (2006).

Dehghani, H.

B. W. Pogue, S. C. Davis, X. Song, B. A. Brooksby, H. Dehghani, and K. D. Paulsen, “Image analysis methods for diffuse optical tomography,” J. Biomed. Opt. 11(3), 033001 (2006).

H. Dehghani, B. W. Pogue, S. P. Poplack, and K. D. Paulsen, “Multiwavelength three-dimensional near-infrared tomography of the breast: initial simulation, phantom, and clinical results,” Appl. Opt. 42(1), 135–145 (2003).
[PubMed]

Delorme, S.

G. Brix, F. Kiessling, R. Lucht, S. Darai, K. Wasser, S. Delorme, and J. Griebel, “Microcirculation and microvasculature in breast tumors: pharmacokinetic analysis of dynamic MR image series,” Magn. Reson. Med. 52(2), 420–429 (2004).
[PubMed]

Dewhirst, M. W.

M. R. Dreher, W. Liu, C. R. Michelich, M. W. Dewhirst, F. Yuan, and A. Chilkoti, “Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers,” J. Natl. Cancer Inst. 98(5), 335–344 (2006).
[PubMed]

Dreher, M. R.

M. R. Dreher, W. Liu, C. R. Michelich, M. W. Dewhirst, F. Yuan, and A. Chilkoti, “Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers,” J. Natl. Cancer Inst. 98(5), 335–344 (2006).
[PubMed]

Duncan, R.

R. Duncan, “Polymer conjugates as anticancer nanomedicines,” Nat. Rev. Cancer 6(9), 688–701 (2006).
[PubMed]

Durduran, T.

A. Corlu, R. Choe, T. Durduran, M. A. Rosen, M. Schweiger, S. R. Arridge, M. D. Schnall, and A. G. Yodh, “Three-dimensional in vivo fluorescence diffuse optical tomography of breast cancer in humans,” Opt. Express 15(11), 6696–6716 (2007).
[PubMed]

C. Zhou, R. Choe, N. Shah, T. Durduran, G. Yu, A. Durkin, D. Hsiang, R. Mehta, J. Butler, A. Cerussi, B. J. Tromberg, and A. G. Yodh, “Diffuse optical monitoring of blood flow and oxygenation in human breast cancer during early stages of neoadjuvant chemotherapy,” J. Biomed. Opt. 12(5), 051903 (2007).
[PubMed]

Durkin, A.

C. Zhou, R. Choe, N. Shah, T. Durduran, G. Yu, A. Durkin, D. Hsiang, R. Mehta, J. Butler, A. Cerussi, B. J. Tromberg, and A. G. Yodh, “Diffuse optical monitoring of blood flow and oxygenation in human breast cancer during early stages of neoadjuvant chemotherapy,” J. Biomed. Opt. 12(5), 051903 (2007).
[PubMed]

A. Cerussi, D. Hsiang, N. Shah, R. Mehta, A. Durkin, J. Butler, and B. J. Tromberg, “Predicting response to breast cancer neoadjuvant chemotherapy using diffuse optical spectroscopy,” Proc. Natl. Acad. Sci. U.S.A. 104(10), 4014–4019 (2007).
[PubMed]

A. Cerussi, N. Shah, D. Hsiang, A. Durkin, J. Butler, and B. J. Tromberg, “In vivo absorption, scattering, and physiologic properties of 58 malignant breast tumors determined by broadband diffuse optical spectroscopy,” J. Biomed. Opt. 11(4), 044005 (2006).
[PubMed]

Durkin, A. J.

Duvoll-Young, J.

S. Yoneya, T. Saito, Y. Komatsu, I. Koyama, K. Takahashi, and J. Duvoll-Young, “Binding properties of indocyanine green in human blood,” Invest. Ophthalmol. Vis. Sci. 39(7), 1286–1290 (1998).
[PubMed]

Dvorak, A. M.

D. Feng, J. A. Nagy, H. F. Dvorak, and A. M. Dvorak, “Ultrastructural studies define soluble macromolecular, particulate, and cellular transendothelial cell pathways in venules, lymphatic vessels, and tumor-associated microvessels in man and animals,” Microsc. Res. Tech. 57(5), 289–326 (2002).
[PubMed]

Dvorak, H. F.

D. Feng, J. A. Nagy, H. F. Dvorak, and A. M. Dvorak, “Ultrastructural studies define soluble macromolecular, particulate, and cellular transendothelial cell pathways in venules, lymphatic vessels, and tumor-associated microvessels in man and animals,” Microsc. Res. Tech. 57(5), 289–326 (2002).
[PubMed]

Ebert, B.

C. Perlitz, K. Licha, F. D. Scholle, B. Ebert, M. Bahner, P. Hauff, K. T. Moesta, and M. Schirner, “Comparison of two tricarbocyanine-based dyes for fluorescence optical imaging,” J. Fluoresc. 15(3), 443–454 (2005).
[PubMed]

Fang, Q.

Fantini, S.

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. U.S.A. 94(12), 6468–6473 (1997).
[PubMed]

Feng, D.

D. Feng, J. A. Nagy, H. F. Dvorak, and A. M. Dvorak, “Ultrastructural studies define soluble macromolecular, particulate, and cellular transendothelial cell pathways in venules, lymphatic vessels, and tumor-associated microvessels in man and animals,” Microsc. Res. Tech. 57(5), 289–326 (2002).
[PubMed]

Franceschini, M. A.

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. U.S.A. 94(12), 6468–6473 (1997).
[PubMed]

Friedrich, E. A.

U. Schilling, E. A. Friedrich, H. Sinn, H. H. Schrenk, J. H. Clorius, and W. Maier-Borst, “Design of compounds having enhanced tumor uptake, using serum albumin as a carrier – Part II. In vivo studies,” Nucl. Med. Biol. 19(6), 685–695 (1992).

Gaida, G.

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. U.S.A. 94(12), 6468–6473 (1997).
[PubMed]

Gebauer, B.

D. Grosenick, K. Th. Moesta, M. Möller, J. Mucke, H. Wabnitz, B. Gebauer, Ch. Stroszczynski, B. Wassermann, P. M. Schlag, and H. Rinneberg, “Time-domain scanning optical mammography: I. Recording and assessment of mammograms of 154 patients,” Phys. Med. Biol. 50(11), 2429–2449 (2005).
[PubMed]

Gibson, J. J.

S. P. Poplack, T. D. Tosteson, W. A. Wells, B. W. Pogue, P. M. Meaney, A. Hartov, C. A. Kogel, S. K. Soho, J. J. Gibson, and K. D. Paulsen, “Electromagnetic breast imaging: results of a pilot study in women with abnormal mammograms,” Radiology 243(2), 350–359 (2007).
[PubMed]

Götz, L.

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).

Gratton, E.

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. U.S.A. 94(12), 6468–6473 (1997).
[PubMed]

Griebel, J.

G. Brix, F. Kiessling, R. Lucht, S. Darai, K. Wasser, S. Delorme, and J. Griebel, “Microcirculation and microvasculature in breast tumors: pharmacokinetic analysis of dynamic MR image series,” Magn. Reson. Med. 52(2), 420–429 (2004).
[PubMed]

Grosenick, D.

H. Rinneberg, D. Grosenick, K. T. Moesta, H. Wabnitz, J. Mucke, G. Wübbeler, R. Macdonald, and P. Schlag, “Detection and characterization of breast tumours by time-domain scanning optical mammography,” Opto-Electronics Review 16(2), 147–162 (2008).

A. Hagen, O. Steinkellner, D. Grosenick, M. Möller, R. Ziegler, T. Nielsen, K. Lauritsen, R. Macdonald, and H. Rinneberg, “Development of a multi-channel time-domain fluorescence mammograph,” Proc. SPIE 6434, 64340Z (2007).

D. Grosenick, K. Th. Moesta, M. Möller, J. Mucke, H. Wabnitz, B. Gebauer, Ch. Stroszczynski, B. Wassermann, P. M. Schlag, and H. Rinneberg, “Time-domain scanning optical mammography: I. Recording and assessment of mammograms of 154 patients,” Phys. Med. Biol. 50(11), 2429–2449 (2005).
[PubMed]

D. Grosenick, H. Wabnitz, K. Th. Moesta, J. Mucke, P. M. Schlag, and H. Rinneberg, “Time-domain scanning optical mammography: II. Optical properties and tissue parameters of 87 carcinomas,” Phys. Med. Biol. 50(11), 2451–2468 (2005).
[PubMed]

M. Möller, H. Wabnitz, A. Kummrow, D. Grosenick, A. Liebert, B. Wassermann, R. Macdonald, and H. Rinneberg, “A four-wavelength multi-channel scanning time-resolved optical mammograph,” Proc. SPIE 5138, 290–297 (2003).

D. Grosenick, H. Wabnitz, H. H. Rinneberg, K. Th. Moesta, and P. M. Schlag, “Development of a time-domain optical mammograph and first in vivo applications,” Appl. Opt. 38(13), 2927–2943 (1999).

Gulsen, G.

Gurfinkel, M.

M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, and E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72(1), 94–102 (2000).
[PubMed]

Gust, J. D.

M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, and E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72(1), 94–102 (2000).
[PubMed]

Hagen, A.

A. Hagen, O. Steinkellner, D. Grosenick, M. Möller, R. Ziegler, T. Nielsen, K. Lauritsen, R. Macdonald, and H. Rinneberg, “Development of a multi-channel time-domain fluorescence mammograph,” Proc. SPIE 6434, 64340Z (2007).

Hartov, A.

S. P. Poplack, T. D. Tosteson, W. A. Wells, B. W. Pogue, P. M. Meaney, A. Hartov, C. A. Kogel, S. K. Soho, J. J. Gibson, and K. D. Paulsen, “Electromagnetic breast imaging: results of a pilot study in women with abnormal mammograms,” Radiology 243(2), 350–359 (2007).
[PubMed]

Hashizume, H.

H. Hashizume, P. Baluk, S. Morikawa, J. W. McLean, G. Thurston, S. Roberge, R. K. Jain, and D. M. McDonald, “Openings between defective endothelial cells explain tumor vessel leakiness,” Am. J. Pathol. 156(4), 1363–1380 (2000).
[PubMed]

Hauff, P.

C. Perlitz, K. Licha, F. D. Scholle, B. Ebert, M. Bahner, P. Hauff, K. T. Moesta, and M. Schirner, “Comparison of two tricarbocyanine-based dyes for fluorescence optical imaging,” J. Fluoresc. 15(3), 443–454 (2005).
[PubMed]

Hawrysz, D. J.

M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, and E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72(1), 94–102 (2000).
[PubMed]

Heywang-Köbrunner, S. H.

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).

Höckel, M.

P. Vaupel and M. Höckel, “Blood supply, oxygenation status and metabolic micromilieu of breast cancers: characterization and therapeutic relevance,” Int. J. Oncol. 17(5), 869–879 (2000) (review).
[PubMed]

Hodges, J. L.

E. Brown, J. Hopper, J. L. Hodges, B. Bradley, R. Wennesland, and H. Yamauchi, “Red cell, plasma, and blood volume in the healthy women measured by radiochromium cell-labeling and hematocrit,” J. Clin. Invest. 41(12), 2182–2190 (1962).
[PubMed]

Hoogenraad, J. H.

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(4), 1143–1158 (1999).

Hopper, J.

E. Brown, J. Hopper, J. L. Hodges, B. Bradley, R. Wennesland, and H. Yamauchi, “Red cell, plasma, and blood volume in the healthy women measured by radiochromium cell-labeling and hematocrit,” J. Clin. Invest. 41(12), 2182–2190 (1962).
[PubMed]

Hsiang, D.

C. Zhou, R. Choe, N. Shah, T. Durduran, G. Yu, A. Durkin, D. Hsiang, R. Mehta, J. Butler, A. Cerussi, B. J. Tromberg, and A. G. Yodh, “Diffuse optical monitoring of blood flow and oxygenation in human breast cancer during early stages of neoadjuvant chemotherapy,” J. Biomed. Opt. 12(5), 051903 (2007).
[PubMed]

A. Cerussi, D. Hsiang, N. Shah, R. Mehta, A. Durkin, J. Butler, and B. J. Tromberg, “Predicting response to breast cancer neoadjuvant chemotherapy using diffuse optical spectroscopy,” Proc. Natl. Acad. Sci. U.S.A. 104(10), 4014–4019 (2007).
[PubMed]

A. Cerussi, N. Shah, D. Hsiang, A. Durkin, J. Butler, and B. J. Tromberg, “In vivo absorption, scattering, and physiologic properties of 58 malignant breast tumors determined by broadband diffuse optical spectroscopy,” J. Biomed. Opt. 11(4), 044005 (2006).
[PubMed]

Imasaka, T.

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M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, and E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72(1), 94–102 (2000).
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M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, and E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72(1), 94–102 (2000).
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H. Dehghani, B. W. Pogue, S. P. Poplack, and K. D. Paulsen, “Multiwavelength three-dimensional near-infrared tomography of the breast: initial simulation, phantom, and clinical results,” Appl. Opt. 42(1), 135–145 (2003).
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C. Perlitz, K. Licha, F. D. Scholle, B. Ebert, M. Bahner, P. Hauff, K. T. Moesta, and M. Schirner, “Comparison of two tricarbocyanine-based dyes for fluorescence optical imaging,” J. Fluoresc. 15(3), 443–454 (2005).
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H. Dehghani, B. W. Pogue, S. P. Poplack, and K. D. Paulsen, “Multiwavelength three-dimensional near-infrared tomography of the breast: initial simulation, phantom, and clinical results,” Appl. Opt. 42(1), 135–145 (2003).
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Ralston, W.

M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, and E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72(1), 94–102 (2000).
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M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, and E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72(1), 94–102 (2000).
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H. Rinneberg, D. Grosenick, K. T. Moesta, H. Wabnitz, J. Mucke, G. Wübbeler, R. Macdonald, and P. Schlag, “Detection and characterization of breast tumours by time-domain scanning optical mammography,” Opto-Electronics Review 16(2), 147–162 (2008).

A. Hagen, O. Steinkellner, D. Grosenick, M. Möller, R. Ziegler, T. Nielsen, K. Lauritsen, R. Macdonald, and H. Rinneberg, “Development of a multi-channel time-domain fluorescence mammograph,” Proc. SPIE 6434, 64340Z (2007).

D. Grosenick, K. Th. Moesta, M. Möller, J. Mucke, H. Wabnitz, B. Gebauer, Ch. Stroszczynski, B. Wassermann, P. M. Schlag, and H. Rinneberg, “Time-domain scanning optical mammography: I. Recording and assessment of mammograms of 154 patients,” Phys. Med. Biol. 50(11), 2429–2449 (2005).
[PubMed]

D. Grosenick, H. Wabnitz, K. Th. Moesta, J. Mucke, P. M. Schlag, and H. Rinneberg, “Time-domain scanning optical mammography: II. Optical properties and tissue parameters of 87 carcinomas,” Phys. Med. Biol. 50(11), 2451–2468 (2005).
[PubMed]

M. Möller, H. Wabnitz, A. Kummrow, D. Grosenick, A. Liebert, B. Wassermann, R. Macdonald, and H. Rinneberg, “A four-wavelength multi-channel scanning time-resolved optical mammograph,” Proc. SPIE 5138, 290–297 (2003).

Rinneberg, H. H.

Ripoll, J.

X. Intes, J. Ripoll, Y. Chen, S. Nioka, A. G. Yodh, and B. Chance, “In vivo continuous-wave optical breast imaging enhanced with Indocyanine Green,” Med. Phys. 30(6), 1039–1047 (2003).
[PubMed]

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H. Hashizume, P. Baluk, S. Morikawa, J. W. McLean, G. Thurston, S. Roberge, R. K. Jain, and D. M. McDonald, “Openings between defective endothelial cells explain tumor vessel leakiness,” Am. J. Pathol. 156(4), 1363–1380 (2000).
[PubMed]

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Rosenau, W.

H. Daldrup, D. M. Shames, M. Wendland, Y. Okuhata, T. M. Link, W. Rosenau, Y. Lu, and R. C. Brasch, “Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media,” AJR Am. J. Roentgenol. 171(4), 941–949 (1998).
[PubMed]

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S. Yoneya, T. Saito, Y. Komatsu, I. Koyama, K. Takahashi, and J. Duvoll-Young, “Binding properties of indocyanine green in human blood,” Invest. Ophthalmol. Vis. Sci. 39(7), 1286–1290 (1998).
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C. Perlitz, K. Licha, F. D. Scholle, B. Ebert, M. Bahner, P. Hauff, K. T. Moesta, and M. Schirner, “Comparison of two tricarbocyanine-based dyes for fluorescence optical imaging,” J. Fluoresc. 15(3), 443–454 (2005).
[PubMed]

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H. Rinneberg, D. Grosenick, K. T. Moesta, H. Wabnitz, J. Mucke, G. Wübbeler, R. Macdonald, and P. Schlag, “Detection and characterization of breast tumours by time-domain scanning optical mammography,” Opto-Electronics Review 16(2), 147–162 (2008).

Schlag, P. M.

D. Grosenick, K. Th. Moesta, M. Möller, J. Mucke, H. Wabnitz, B. Gebauer, Ch. Stroszczynski, B. Wassermann, P. M. Schlag, and H. Rinneberg, “Time-domain scanning optical mammography: I. Recording and assessment of mammograms of 154 patients,” Phys. Med. Biol. 50(11), 2429–2449 (2005).
[PubMed]

D. Grosenick, H. Wabnitz, K. Th. Moesta, J. Mucke, P. M. Schlag, and H. Rinneberg, “Time-domain scanning optical mammography: II. Optical properties and tissue parameters of 87 carcinomas,” Phys. Med. Biol. 50(11), 2451–2468 (2005).
[PubMed]

D. Grosenick, H. Wabnitz, H. H. Rinneberg, K. Th. Moesta, and P. M. Schlag, “Development of a time-domain optical mammograph and first in vivo applications,” Appl. Opt. 38(13), 2927–2943 (1999).

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. U.S.A. 94(12), 6468–6473 (1997).
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V. Ntziachristos, A. G. Yodh, M. Schnall, and B. Chance, “Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement,” Proc. Natl. Acad. Sci. U.S.A. 97(6), 2767–2772 (2000).
[PubMed]

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Scholle, F. D.

C. Perlitz, K. Licha, F. D. Scholle, B. Ebert, M. Bahner, P. Hauff, K. T. Moesta, and M. Schirner, “Comparison of two tricarbocyanine-based dyes for fluorescence optical imaging,” J. Fluoresc. 15(3), 443–454 (2005).
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U. Schilling, E. A. Friedrich, H. Sinn, H. H. Schrenk, J. H. Clorius, and W. Maier-Borst, “Design of compounds having enhanced tumor uptake, using serum albumin as a carrier – Part II. In vivo studies,” Nucl. Med. Biol. 19(6), 685–695 (1992).

Schütz, O.

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).

Schweiger, M.

Seeber, M.

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. U.S.A. 94(12), 6468–6473 (1997).
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Sevick-Muraca, E. M.

M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, and E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72(1), 94–102 (2000).
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A. Cerussi, D. Hsiang, N. Shah, R. Mehta, A. Durkin, J. Butler, and B. J. Tromberg, “Predicting response to breast cancer neoadjuvant chemotherapy using diffuse optical spectroscopy,” Proc. Natl. Acad. Sci. U.S.A. 104(10), 4014–4019 (2007).
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[PubMed]

A. Cerussi, N. Shah, D. Hsiang, A. Durkin, J. Butler, and B. J. Tromberg, “In vivo absorption, scattering, and physiologic properties of 58 malignant breast tumors determined by broadband diffuse optical spectroscopy,” J. Biomed. Opt. 11(4), 044005 (2006).
[PubMed]

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H. Daldrup, D. M. Shames, M. Wendland, Y. Okuhata, T. M. Link, W. Rosenau, Y. Lu, and R. C. Brasch, “Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media,” AJR Am. J. Roentgenol. 171(4), 941–949 (1998).
[PubMed]

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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).

Sikora, K.

C. B. Wilson, A. A. Lammertsma, C. G. McKenzie, K. Sikora, and T. Jones, “Measurements of blood flow and exchanging water space in breast tumors using positron emission tomography: a rapid and noninvasive dynamic method,” Cancer Res. 52(6), 1592–1597 (1992).
[PubMed]

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U. Schilling, E. A. Friedrich, H. Sinn, H. H. Schrenk, J. H. Clorius, and W. Maier-Borst, “Design of compounds having enhanced tumor uptake, using serum albumin as a carrier – Part II. In vivo studies,” Nucl. Med. Biol. 19(6), 685–695 (1992).

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S. P. Poplack, T. D. Tosteson, W. A. Wells, B. W. Pogue, P. M. Meaney, A. Hartov, C. A. Kogel, S. K. Soho, J. J. Gibson, and K. D. Paulsen, “Electromagnetic breast imaging: results of a pilot study in women with abnormal mammograms,” Radiology 243(2), 350–359 (2007).
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Z. M. Bhujwalla, D. Artemov, K. Natarajan, E. Ackerstaff, and M. Solaiyappan, “Vascular differences detected by MRI for metastatic versus nonmetastatic breast and prostate cancer xenografts,” Neoplasia 3(2), 143–153 (2001).
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B. W. Pogue, S. C. Davis, X. Song, B. A. Brooksby, H. Dehghani, and K. D. Paulsen, “Image analysis methods for diffuse optical tomography,” J. Biomed. Opt. 11(3), 033001 (2006).

Spinelli, L.

P. Taroni, A. Torricelli, L. Spinelli, A. Pifferi, F. Arpaia, G. Danesini, and R. Cubeddu, “Time-resolved optical mammography between 637 and 985 nm: clinical study on the detection and identification of breast lesions,” Phys. Med. Biol. 50(11), 2469–2488 (2005).
[PubMed]

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A. Hagen, O. Steinkellner, D. Grosenick, M. Möller, R. Ziegler, T. Nielsen, K. Lauritsen, R. Macdonald, and H. Rinneberg, “Development of a multi-channel time-domain fluorescence mammograph,” Proc. SPIE 6434, 64340Z (2007).

Stroszczynski, Ch.

D. Grosenick, K. Th. Moesta, M. Möller, J. Mucke, H. Wabnitz, B. Gebauer, Ch. Stroszczynski, B. Wassermann, P. M. Schlag, and H. Rinneberg, “Time-domain scanning optical mammography: I. Recording and assessment of mammograms of 154 patients,” Phys. Med. Biol. 50(11), 2429–2449 (2005).
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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(4), 1143–1158 (1999).

Takahashi, K.

S. Yoneya, T. Saito, Y. Komatsu, I. Koyama, K. Takahashi, and J. Duvoll-Young, “Binding properties of indocyanine green in human blood,” Invest. Ophthalmol. Vis. Sci. 39(7), 1286–1290 (1998).
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P. Taroni, A. Torricelli, L. Spinelli, A. Pifferi, F. Arpaia, G. Danesini, and R. Cubeddu, “Time-resolved optical mammography between 637 and 985 nm: clinical study on the detection and identification of breast lesions,” Phys. Med. Biol. 50(11), 2469–2488 (2005).
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M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, and E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72(1), 94–102 (2000).
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M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, and E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72(1), 94–102 (2000).
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H. Hashizume, P. Baluk, S. Morikawa, J. W. McLean, G. Thurston, S. Roberge, R. K. Jain, and D. M. McDonald, “Openings between defective endothelial cells explain tumor vessel leakiness,” Am. J. Pathol. 156(4), 1363–1380 (2000).
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P. Taroni, A. Torricelli, L. Spinelli, A. Pifferi, F. Arpaia, G. Danesini, and R. Cubeddu, “Time-resolved optical mammography between 637 and 985 nm: clinical study on the detection and identification of breast lesions,” Phys. Med. Biol. 50(11), 2469–2488 (2005).
[PubMed]

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S. P. Poplack, T. D. Tosteson, W. A. Wells, B. W. Pogue, P. M. Meaney, A. Hartov, C. A. Kogel, S. K. Soho, J. J. Gibson, and K. D. Paulsen, “Electromagnetic breast imaging: results of a pilot study in women with abnormal mammograms,” Radiology 243(2), 350–359 (2007).
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A. Cerussi, D. Hsiang, N. Shah, R. Mehta, A. Durkin, J. Butler, and B. J. Tromberg, “Predicting response to breast cancer neoadjuvant chemotherapy using diffuse optical spectroscopy,” Proc. Natl. Acad. Sci. U.S.A. 104(10), 4014–4019 (2007).
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C. Zhou, R. Choe, N. Shah, T. Durduran, G. Yu, A. Durkin, D. Hsiang, R. Mehta, J. Butler, A. Cerussi, B. J. Tromberg, and A. G. Yodh, “Diffuse optical monitoring of blood flow and oxygenation in human breast cancer during early stages of neoadjuvant chemotherapy,” J. Biomed. Opt. 12(5), 051903 (2007).
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A. Cerussi, N. Shah, D. Hsiang, A. Durkin, J. Butler, and B. J. Tromberg, “In vivo absorption, scattering, and physiologic properties of 58 malignant breast tumors determined by broadband diffuse optical spectroscopy,” J. Biomed. Opt. 11(4), 044005 (2006).
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M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, and E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72(1), 94–102 (2000).
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van der Mark, M. B.

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(4), 1143–1158 (1999).

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H. Rinneberg, D. Grosenick, K. T. Moesta, H. Wabnitz, J. Mucke, G. Wübbeler, R. Macdonald, and P. Schlag, “Detection and characterization of breast tumours by time-domain scanning optical mammography,” Opto-Electronics Review 16(2), 147–162 (2008).

D. Grosenick, K. Th. Moesta, M. Möller, J. Mucke, H. Wabnitz, B. Gebauer, Ch. Stroszczynski, B. Wassermann, P. M. Schlag, and H. Rinneberg, “Time-domain scanning optical mammography: I. Recording and assessment of mammograms of 154 patients,” Phys. Med. Biol. 50(11), 2429–2449 (2005).
[PubMed]

D. Grosenick, H. Wabnitz, K. Th. Moesta, J. Mucke, P. M. Schlag, and H. Rinneberg, “Time-domain scanning optical mammography: II. Optical properties and tissue parameters of 87 carcinomas,” Phys. Med. Biol. 50(11), 2451–2468 (2005).
[PubMed]

M. Möller, H. Wabnitz, A. Kummrow, D. Grosenick, A. Liebert, B. Wassermann, R. Macdonald, and H. Rinneberg, “A four-wavelength multi-channel scanning time-resolved optical mammograph,” Proc. SPIE 5138, 290–297 (2003).

D. Grosenick, H. Wabnitz, H. H. Rinneberg, K. Th. Moesta, and P. M. Schlag, “Development of a time-domain optical mammograph and first in vivo applications,” Appl. Opt. 38(13), 2927–2943 (1999).

Wang, J.

Wasser, K.

G. Brix, F. Kiessling, R. Lucht, S. Darai, K. Wasser, S. Delorme, and J. Griebel, “Microcirculation and microvasculature in breast tumors: pharmacokinetic analysis of dynamic MR image series,” Magn. Reson. Med. 52(2), 420–429 (2004).
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[PubMed]

M. Möller, H. Wabnitz, A. Kummrow, D. Grosenick, A. Liebert, B. Wassermann, R. Macdonald, and H. Rinneberg, “A four-wavelength multi-channel scanning time-resolved optical mammograph,” Proc. SPIE 5138, 290–297 (2003).

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D. K. F. Meijer, B. Weert, and G. A. Vermeer, “Pharmacokinetics of biliary excretion in man. VI. Indocyanine green,” Eur. J. Clin. Pharmacol. 35(3), 295–303 (1988).
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[PubMed]

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H. Daldrup, D. M. Shames, M. Wendland, Y. Okuhata, T. M. Link, W. Rosenau, Y. Lu, and R. C. Brasch, “Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media,” AJR Am. J. Roentgenol. 171(4), 941–949 (1998).
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C. B. Wilson, A. A. Lammertsma, C. G. McKenzie, K. Sikora, and T. Jones, “Measurements of blood flow and exchanging water space in breast tumors using positron emission tomography: a rapid and noninvasive dynamic method,” Cancer Res. 52(6), 1592–1597 (1992).
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H. Rinneberg, D. Grosenick, K. T. Moesta, H. Wabnitz, J. Mucke, G. Wübbeler, R. Macdonald, and P. Schlag, “Detection and characterization of breast tumours by time-domain scanning optical mammography,” Opto-Electronics Review 16(2), 147–162 (2008).

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E. Brown, J. Hopper, J. L. Hodges, B. Bradley, R. Wennesland, and H. Yamauchi, “Red cell, plasma, and blood volume in the healthy women measured by radiochromium cell-labeling and hematocrit,” J. Clin. Invest. 41(12), 2182–2190 (1962).
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X. Intes, J. Ripoll, Y. Chen, S. Nioka, A. G. Yodh, and B. Chance, “In vivo continuous-wave optical breast imaging enhanced with Indocyanine Green,” Med. Phys. 30(6), 1039–1047 (2003).
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V. Ntziachristos, A. G. Yodh, M. Schnall, and B. Chance, “Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement,” Proc. Natl. Acad. Sci. U.S.A. 97(6), 2767–2772 (2000).
[PubMed]

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S. Yoneya, T. Saito, Y. Komatsu, I. Koyama, K. Takahashi, and J. Duvoll-Young, “Binding properties of indocyanine green in human blood,” Invest. Ophthalmol. Vis. Sci. 39(7), 1286–1290 (1998).
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Yu, G.

C. Zhou, R. Choe, N. Shah, T. Durduran, G. Yu, A. Durkin, D. Hsiang, R. Mehta, J. Butler, A. Cerussi, B. J. Tromberg, and A. G. Yodh, “Diffuse optical monitoring of blood flow and oxygenation in human breast cancer during early stages of neoadjuvant chemotherapy,” J. Biomed. Opt. 12(5), 051903 (2007).
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Yu, H.

Yuan, F.

M. R. Dreher, W. Liu, C. R. Michelich, M. W. Dewhirst, F. Yuan, and A. Chilkoti, “Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers,” J. Natl. Cancer Inst. 98(5), 335–344 (2006).
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C. Zhou, R. Choe, N. Shah, T. Durduran, G. Yu, A. Durkin, D. Hsiang, R. Mehta, J. Butler, A. Cerussi, B. J. Tromberg, and A. G. Yodh, “Diffuse optical monitoring of blood flow and oxygenation in human breast cancer during early stages of neoadjuvant chemotherapy,” J. Biomed. Opt. 12(5), 051903 (2007).
[PubMed]

Ziegler, R.

A. Hagen, O. Steinkellner, D. Grosenick, M. Möller, R. Ziegler, T. Nielsen, K. Lauritsen, R. Macdonald, and H. Rinneberg, “Development of a multi-channel time-domain fluorescence mammograph,” Proc. SPIE 6434, 64340Z (2007).

AJR Am. J. Roentgenol. (1)

H. Daldrup, D. M. Shames, M. Wendland, Y. Okuhata, T. M. Link, W. Rosenau, Y. Lu, and R. C. Brasch, “Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media,” AJR Am. J. Roentgenol. 171(4), 941–949 (1998).
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Figures (10)

Fig. 1
Fig. 1

Time course of molar ICG concentration in plasma of arterial blood, recorded at the finger pad of a 72-year-old patient by transcutaneous pulse densitometry. The entire time course is divided into five periods corresponding to the initial (native) phase, the period during which the ICG bolus is administered (bolus phase), the infusion period (vascular phase), the washout phase after termination of the infusion and the extravascular phase when the ICG arterial plasma concentration has returned to zero. Periods during which absorption and fluorescence mammograms were taken are indicated by vertical bars. The red solid line represents a mono-exponential fit of the ICG decay after the infusion was stopped.

Fig. 2
Fig. 2

Schematic of scanning time-domain laser and fluorescence mammograph.

Fig. 3
Fig. 3

Fluorescence raw mammogram (a) based on diffusely transmitted, time-integrated fluorescence intensity, absorption raw mammogram (b), corresponding to time-integrated transmitted laser intensity and corresponding ratio mammogram of (a) and (b) without edge correction (c) and with edge correction (d). Unlike ratio images, absorption and fluorescence mammograms are dominated by hemoglobin absorption. The carcinoma (arrow) is visible in laser and ratio mammograms but invisible in the fluorescence mammogram due to cancellation effects. Each mammogram is normalized to the center region of the breast.

Fig. 4
Fig. 4

Open unidirectional compartmental model (right hand side, solid lines) for simulating local ICG concentrations. Model consists of local vascular (plasma) compartment and local extravascular-extracellular space (EES), with apparent capillary plasma flow per unit volume of tissue (Fpρ), apparent permeability-surface-area product (PSρ) and (bound) ICG outflow rate (kout) entering as parameters (s. Table 1). Left hand side (dashed lines) illustrates (global) open redistribution compartment model used by Ott et al. [23] to interpret ICG plasma disappearance curve.

Fig. 5
Fig. 5

Fluorescence ratio images taken (a) in the vascular phase, i.e. during ICG infusion (Scan 3, s. Figure 1), and (b) in the extravascular phase, i.e. about 30 min post infusion (Scan 5, Fig. 1), of 72-year-old patient; (c) x-ray mammogram shown for comparison with arrow indicating the position of the invasive ductal carcinoma. In (a) fluorescence originates predominantly from ICG in vasculature, in (b) fluorescence predominantly reflects ICG that extravasated into the interstitium. The higher fluorescence intensity of the carcinoma reveals its higher permeability for ICG bound plasma proteins. Distance between image-ticks is 2 cm.

Fig. 6
Fig. 6

Mammogram showing reciprocal photon counts of a late time window of the TPSF recorded at 660 nm prior to ICG administration (a). The intrinsic absorption contrast reveals structures that can also be seen in the fluorescence ratio image taken during the vascular phase (b). Distance between image-ticks is 2 cm.

Fig. 7
Fig. 7

X-ray-mammogram (cranio-caudal projection) of the left breast of a 51-year-old patient bearing an invasive ductal carcinoma. The tumor is hardly visible due to very dense glandular tissue.

Fig. 8
Fig. 8

Fluorescence ratio images in cranio-caudal projection taken (a) in the vascular phase and (b) in the extravascular phase 54 min after termination of ICG infusion. Axial reconstruction of Gd-DTPA enhanced MR breast scan (c) showing maximum intensity projection. In contrast to x-ray mammogram (s. Figure 7), late-fluorescence ratio mammogram (b) and MR image reveal the ductal carcinoma indicated by arrows in (c). Distance between image-ticks is 2 cm.

Fig. 9
Fig. 9

Fluorescence ratio mammograms in cranio-caudal projection taken (a) in the vascular phase and (b) in the extravascular phase, 26 min after termination of ICG infusion, of a 52-year-old patient with benign fibroadenoma. The lesion does not lead to a focused area with higher fluorescence intensity above background, i.e. is invisible in the ratio images, indicating that ICG extravasated at a rate comparable with normal breast tissue. Distance between image-ticks is 2 cm.

Fig. 10
Fig. 10

(a,b) Simulated time course of concentration corresponding to (a) vascular contribution (vpCp(t)), and (b) extravascular contribution (veCe(t)) to total ICG concentration in carcinoma (), breast parenchyma () and normal breast tissue (fat) () during (0 ≤ t ≤ 25 min) and after ICG infusion, with simulation input parameters listed in Table 1; (c,d) Simulated concentration contrast of (c) intravascular (vpCp(t)) and extravascular (veCe(t)) contributions and (d) of total ICG concentration normalized to total ICG concentration Ct in normal breast tissue (fat) for carcinoma (), breast parenchyma () and fat (). In (c,d) vertical gray bars indicate periods during which optical mammograms of the 72-year-old patient were recorded (case 1, Scan 3, Scan 5, s. Figure 1).

Tables (2)

Tables Icon

Table 1 Simulation input parameters

Tables Icon

Table A1 Coefficients and abbreviations used in analytical solutions of rate equations

Equations (9)

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dCAssdt=kelimCAss+Sinf=0
dCp(t)/dt=kFCA(t)(kF+kpPSρ)Cp(t)
dCe(t)/dt=kePSρCp(t)koutCe(t)
CAbolus(t)=A1exp(m1t)+A2exp(m2t)
CA(t)=Sinfkelim{1qexp(m1t)(1q)exp(m2t)}
Cp(t)=A0Am1(1)exp(m1t)Am2(1)exp(m2t)+AF(1)exp{(kF+kpPSρ)t}
Ce(t)=B0+Bm1(1)exp(m1t)+Bm2(1)exp(m2t)foutAF(1)exp{(kF+kpPSρ)t}Bout(1)exp{koutt}
Cp(t)=Am1(2)exp{m1(tτinf)}+Am2(2)exp{m2(tτinf)}AF(2)exp{(kF+kpPSρ)(tτinf)}
Ce(t)=Bm1(2)exp{m1(tτinf)}Bm2(2)exp{m2(tτinf)}     +foutAF(2)exp{(kF+kpPSρ)(tτinf)}+Bout(2)exp{kout(tτinf)}

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