Abstract

Differentiation among malignant tumors, benign tumors, and normal tissue is highly important in the diagnosis and treatment of many malignancies. We have proposed a dynamic schema for noninvasive characterization of pressure-induced changes in solid tumors. Our hypothesis has been that the altered neovascularization processes within cancer-bearing tissues may significantly increase vascular resistance and cause a much slower response of hemoglobin concentration during a dynamic compression stimulus. This hypothesis was tested by the evaluation of data generated from human tumor clinical testing and from animal tumor model testing. In the human tumor clinical testing, a unified diagnostic criterion was derived that integrated the relative characteristics of tumor oxygen, hemoglobin, and hemoglobin dynamics. By applying such a unified criterion, we were able to differentiate benign breast lesions and malignant breast tumors with high sensitivity and specificity within a subset of 14 suspicious breast lesions with similar size and depth characteristics. In the animal testing, a stepped compression load was applied to the subcutaneous tumor deposit on an athymic NU/NU nude mouse model with subcutaneous xenograft BxPC-3 cancer. Characteristic differences were observed between the premortem tumor and the postmortem tumor in terms of pressure-induced tumor structural and functional changes.

© 2008 Optical Society of America

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2007

B. Dome, M. J. Hendrix, S. Paku, J. Tovari, and J. Timar, “Alternative vascularization mechanisms in cancer: pathology and therapeutic implications,” Am. J. Pathol. 170, 1-15 (2007).
[CrossRef] [PubMed]

R. X. Xu and S. P. Povoski, “Diffuse optical imaging and spectroscopy for cancer,” Exp. Rev. Med. Dev. 4, 83-95 (2007).
[CrossRef]

R. X. Xu, B. Qiang, J. J. Mao, and S. P. Povoski, “Development of a handheld near infrared imager for dynamic characterization of in vivo biological tissue systems,” Appl. Opt. 46, 7442-7451 (2007).
[CrossRef] [PubMed]

R. Xu, D. Young, J. Mao, and S. Povoski, “A prospective pilot clinical trial evaluating the utility of a dynamic near infrared imaging device for characterizing suspicious breast lesions,” Breast Cancer Res. 9, R88 (2007).
[CrossRef] [PubMed]

A. L. Darling, P. K. Yalavarthy, M. M. Doyley, H. Dehghani, and B. W. Pogue, “Interstitial fluid pressure in soft tissue as a result of an externally applied contact pressure,” Phys. Med. Biol. 52, 4121-4136 (2007).
[CrossRef] [PubMed]

S. E. Lee, S. K. Hong, B. K. Han, J. H. Yu, J. H. Han, S. J. Jeong, S. S. Byun, Y. H. Park, and G. Choe, “Prognostic significance of tumor necrosis in primary transitional cell carcinoma of upper urinary tract,” Jpn. J. Clin. Oncol. 37, 49-55 (2007).
[CrossRef] [PubMed]

2006

S. A. Carp, T. Kauffman, Q. Fang, E. A. Rafferty, R. H. Moore, D. B. Kopans, and D. A. Boas, “Compression-induced changes in the physiological state of the breast as observed through frequency domain photon migration measurements,” J. Biomed. Opt. 11, 064016 (2006).
[CrossRef]

C. Jackowski, M. Thali, E. Aghayev, K. Yen, M. Sonnenschein, K. Zwygart, R. Dirnhofer, and P. Vock, “Postmortem imaging of blood and its characteristics using MSCT and MRI,” Int. J. Legal Med. 120, 233-240 (2006).
[CrossRef]

R. X. Xu, S. P. Povoski, L. D. Yee, J. O. Olsen, B. Qiang, and J. M. Mao, “Near infrared/ultrasound dual modal imaging for breast cancer detection,” Proc. SPIE 6081, 44-53 (2006).

2005

C. H. Schmitz, D. P. Klemer, R. Hardin, M. S. Katz, Y. Pei, H. L. Graber, M. B. Levin, R. D. Levina, N. A. Franco, W. B. Solomon, and R. L. Barbour, “Design and implementation of dynamic near-infrared optical tomographic imaging instrumentation for simultaneous dual-breast measurements,” Appl. Opt. 44, 2140-2153 (2005).
[CrossRef] [PubMed]

C. Verschraegen, V. Vinh-Hung, G. Cserni, R. Gordon, M. E. Royce, G. Vlastos, P. Tai, and G. Storme, “Modeling the effect of tumor size in early breast cancer,” Ann. Surg. 241, 309-318 (2005).
[CrossRef] [PubMed]

B. Chance, S. Nioka, J. Zhang, E. F. Conant, E. Hwang, S. Briest, S. G. Orel, M. D. Schnall, and B. J. Czerniecki, “Breast cancer detection based on incremental biochemical and physiological properties of breast cancers: a six-year, two-site study,” Acad. Radiol. 12, 925-933 (2005).
[CrossRef] [PubMed]

A. P. Gibson, J. C. Hebden, and S. R. Arridge, “Recent advances in diffuse optical imaging,” Phys. Med. Biol. 50, R1-R43 (2005).
[CrossRef] [PubMed]

2004

N. Shah, A. E. Cerussi, D. Jakubowski, D. Hsiang, J. Butler, and B. J. Tromberg, “Spatial variations in optical and physiological properties of healthy breast tissue,” J Biomed. Opt. 9, 534-540 (2004).
[CrossRef] [PubMed]

B. W. Pogue, S. Jiang, H. Dehghani, C. Kogel, S. Soho, S. Srinivasan, X. Song, T. D. Tosteson, S. P. Poplack, and K. D. Paulsen, “Characterization of hemoglobin, water, and NIR scattering in breast tissue: analysis of intersubject variability and menstrual cycle changes,” J Biomed. Opt. 9, 541-552 (2004).
[CrossRef] [PubMed]

B. Gallez, C. Baudelet, and B. F. Jordan, “Assessment of tumor oxygenation by electron paramagnetic resonance: principles and applications,” NMR Biomed. 17, 240-262 (2004).
[CrossRef] [PubMed]

2003

S. Srinivasan, B. W. Pogue, S. Jiang, H. Dehghani, C. Kogel, S. Soho, J. J. Gibson, T. D. Tosteson, S. P. Poplack, and K. D. Paulsen, “Interpreting hemoglobin and water concentration, oxygen saturation, and scattering measured in vivo by near-infrared breast tomography,” Proc. Natl. Acad. Sci. U.S.A. 100, 12349 (2003).
[CrossRef] [PubMed]

S. Fantini, E. Heffer, H. Siebold, and O. Schutz, “Using near-infrared light to detect breast cancer,” Opt. Photon. News 14(11), 24-29 (2003).
[CrossRef]

Y. Gu, V. A. Bourke, J. G. Kim, A. Constantinescu, R. P. Mason, and H. Liu, “Dynamic response of breast tumor oxygenation to hyperoxic respiratory challenge monitored with three oxygen-sensitive parameters,” Appl. Opt. 42, 2960-2967 (2003).
[CrossRef] [PubMed]

X. Cheng and X. Xu, “Study of the pressure effect in near infrared spectroscopy,” Proc. SPIE 4955, 397-406 (2003).
[CrossRef]

S. Jiang, B. W. Pogue, K. D. Paulsen, C. Kogel, and S. Poplack, “In vivo near-infrared spectral detection of pressure-induced changes in breast tissue,” Opt. Lett. 28, 1212-1214 (2003).
[CrossRef] [PubMed]

C. Pozrikidis and D. A. Farrow, “A model of fluid flow in solid tumors,” Ann. Biomed. Eng. 31, 181-194 (2003).
[CrossRef] [PubMed]

N. Shah, A. E. Cerussi, D. Jakubowski, D. Hsiang, J. Butler, and B. J. Tromberg, “The role of diffuse optical spectroscopy in the clinical management of breast cancer,” Dis. Markers 19, 95-105 (2003).

2002

S. R. McDougall, A. R. Anderson, M. A. Chaplain, and J. A. Sherratt, “Mathematical modelling of flow through vascular networks: implications for tumour-induced angiogenesis and chemotherapy strategies,” Bull. Math. Biol. 64, 673-702(2002).
[CrossRef] [PubMed]

V. Ntziachristos, A. G. Yodh, M. D. Schnall, and B. Chance, “MRI-guided diffuse optical spectroscopy of malignant and benign breast lesions,” Neoplasia 4, 347-354 (2002).
[CrossRef] [PubMed]

D. M. McDonald and P. Baluk, “Significance of blood vessel leakiness in cancer,” Cancer Res. 62, 5381-5385 (2002).
[PubMed]

2001

M. Hockel and P. Vaupel, “Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects,” J. Natl. Cancer Inst. 93, 266-276 (2001).
[CrossRef] [PubMed]

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. U.S.A. 98, 4420-4425 (2001).
[CrossRef] [PubMed]

2000

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).
[CrossRef] [PubMed]

Q. Zhu, E. Conant, and B. Chance, “Optical imaging as an adjunct to sonograph in differentiating benign from malignant breast lesions,” J Biomed. Opt. 5, 229-236 (2000).
[CrossRef] [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, 1363-1380 (2000).
[CrossRef] [PubMed]

1999

M. J. Leahy, F. F. de Mul, G. E. Nilsson, and R. Maniewski, “Principles and practice of the laser-Doppler perfusion technique,” Technol. Health Care 7, 143-162 (1999).
[PubMed]

1998

H. Shangguan, S. Prahl, S. Jacques, L. Casperson, and K. Gregory, “Pressure effects on soft tissues monitored by changes in tissue optical properties,” Proc. SPIE 3254, 366-371 (1998).
[CrossRef]

P. Vaupel, D. K. Kelleher, and O. Thews, “Modulation of tumor oxygenation,” Int. J. Radiat. Oncol. Biol. Phys. 42, 843-848(1998).
[CrossRef] [PubMed]

1996

Y. Boucher, M. Leunig, and R. K. Jain, “Tumor angiogenesis and interstitial hypertension,” Cancer Res. 56, 4264-4266(1996).
[PubMed]

E. K. Chan, B. Sorg, D. Protsenko, M. O'Neil, M. Motamedi, and A. J. Welch, “Effects of compression on soft tissue optical properties,” IEEE J. Sel. Top. Quantum Electron. 2, 943-950(1996).
[CrossRef]

1995

A. Yodh and B. Chance, “Spectroscopy and imaging with diffusing light,” Phys. Today 48(3), 34-40 (1995).
[CrossRef]

Aghayev, E.

C. Jackowski, M. Thali, E. Aghayev, K. Yen, M. Sonnenschein, K. Zwygart, R. Dirnhofer, and P. Vock, “Postmortem imaging of blood and its characteristics using MSCT and MRI,” Int. J. Legal Med. 120, 233-240 (2006).
[CrossRef]

Anderson, A. R.

S. R. McDougall, A. R. Anderson, M. A. Chaplain, and J. A. Sherratt, “Mathematical modelling of flow through vascular networks: implications for tumour-induced angiogenesis and chemotherapy strategies,” Bull. Math. Biol. 64, 673-702(2002).
[CrossRef] [PubMed]

Arridge, S. R.

A. P. Gibson, J. C. Hebden, and S. R. Arridge, “Recent advances in diffuse optical imaging,” Phys. Med. Biol. 50, R1-R43 (2005).
[CrossRef] [PubMed]

Baluk, P.

D. M. McDonald and P. Baluk, “Significance of blood vessel leakiness in cancer,” Cancer Res. 62, 5381-5385 (2002).
[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, 1363-1380 (2000).
[CrossRef] [PubMed]

Barbour, R. L.

Baudelet, C.

B. Gallez, C. Baudelet, and B. F. Jordan, “Assessment of tumor oxygenation by electron paramagnetic resonance: principles and applications,” NMR Biomed. 17, 240-262 (2004).
[CrossRef] [PubMed]

Boas, D. A.

S. A. Carp, T. Kauffman, Q. Fang, E. A. Rafferty, R. H. Moore, D. B. Kopans, and D. A. Boas, “Compression-induced changes in the physiological state of the breast as observed through frequency domain photon migration measurements,” J. Biomed. Opt. 11, 064016 (2006).
[CrossRef]

Boucher, Y.

Y. Boucher, M. Leunig, and R. K. Jain, “Tumor angiogenesis and interstitial hypertension,” Cancer Res. 56, 4264-4266(1996).
[PubMed]

Bourke, V. A.

Briest, S.

B. Chance, S. Nioka, J. Zhang, E. F. Conant, E. Hwang, S. Briest, S. G. Orel, M. D. Schnall, and B. J. Czerniecki, “Breast cancer detection based on incremental biochemical and physiological properties of breast cancers: a six-year, two-site study,” Acad. Radiol. 12, 925-933 (2005).
[CrossRef] [PubMed]

Butler, J.

N. Shah, A. E. Cerussi, D. Jakubowski, D. Hsiang, J. Butler, and B. J. Tromberg, “Spatial variations in optical and physiological properties of healthy breast tissue,” J Biomed. Opt. 9, 534-540 (2004).
[CrossRef] [PubMed]

N. Shah, A. E. Cerussi, D. Jakubowski, D. Hsiang, J. Butler, and B. J. Tromberg, “The role of diffuse optical spectroscopy in the clinical management of breast cancer,” Dis. Markers 19, 95-105 (2003).

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. U.S.A. 98, 4420-4425 (2001).
[CrossRef] [PubMed]

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).
[CrossRef] [PubMed]

Byun, S. S.

S. E. Lee, S. K. Hong, B. K. Han, J. H. Yu, J. H. Han, S. J. Jeong, S. S. Byun, Y. H. Park, and G. Choe, “Prognostic significance of tumor necrosis in primary transitional cell carcinoma of upper urinary tract,” Jpn. J. Clin. Oncol. 37, 49-55 (2007).
[CrossRef] [PubMed]

Carp, S. A.

S. A. Carp, T. Kauffman, Q. Fang, E. A. Rafferty, R. H. Moore, D. B. Kopans, and D. A. Boas, “Compression-induced changes in the physiological state of the breast as observed through frequency domain photon migration measurements,” J. Biomed. Opt. 11, 064016 (2006).
[CrossRef]

Casperson, L.

H. Shangguan, S. Prahl, S. Jacques, L. Casperson, and K. Gregory, “Pressure effects on soft tissues monitored by changes in tissue optical properties,” Proc. SPIE 3254, 366-371 (1998).
[CrossRef]

Cerussi, A.

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. U.S.A. 98, 4420-4425 (2001).
[CrossRef] [PubMed]

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).
[CrossRef] [PubMed]

Cerussi, A. E.

N. Shah, A. E. Cerussi, D. Jakubowski, D. Hsiang, J. Butler, and B. J. Tromberg, “Spatial variations in optical and physiological properties of healthy breast tissue,” J Biomed. Opt. 9, 534-540 (2004).
[CrossRef] [PubMed]

N. Shah, A. E. Cerussi, D. Jakubowski, D. Hsiang, J. Butler, and B. J. Tromberg, “The role of diffuse optical spectroscopy in the clinical management of breast cancer,” Dis. Markers 19, 95-105 (2003).

Chan, E. K.

E. K. Chan, B. Sorg, D. Protsenko, M. O'Neil, M. Motamedi, and A. J. Welch, “Effects of compression on soft tissue optical properties,” IEEE J. Sel. Top. Quantum Electron. 2, 943-950(1996).
[CrossRef]

Chance, B.

B. Chance, S. Nioka, J. Zhang, E. F. Conant, E. Hwang, S. Briest, S. G. Orel, M. D. Schnall, and B. J. Czerniecki, “Breast cancer detection based on incremental biochemical and physiological properties of breast cancers: a six-year, two-site study,” Acad. Radiol. 12, 925-933 (2005).
[CrossRef] [PubMed]

V. Ntziachristos, A. G. Yodh, M. D. Schnall, and B. Chance, “MRI-guided diffuse optical spectroscopy of malignant and benign breast lesions,” Neoplasia 4, 347-354 (2002).
[CrossRef] [PubMed]

Q. Zhu, E. Conant, and B. Chance, “Optical imaging as an adjunct to sonograph in differentiating benign from malignant breast lesions,” J Biomed. Opt. 5, 229-236 (2000).
[CrossRef] [PubMed]

A. Yodh and B. Chance, “Spectroscopy and imaging with diffusing light,” Phys. Today 48(3), 34-40 (1995).
[CrossRef]

Chaplain, M. A.

S. R. McDougall, A. R. Anderson, M. A. Chaplain, and J. A. Sherratt, “Mathematical modelling of flow through vascular networks: implications for tumour-induced angiogenesis and chemotherapy strategies,” Bull. Math. Biol. 64, 673-702(2002).
[CrossRef] [PubMed]

Cheng, X.

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M. J. Leahy, F. F. de Mul, G. E. Nilsson, and R. Maniewski, “Principles and practice of the laser-Doppler perfusion technique,” Technol. Health Care 7, 143-162 (1999).
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S. Srinivasan, B. W. Pogue, S. Jiang, H. Dehghani, C. Kogel, S. Soho, J. J. Gibson, T. D. Tosteson, S. P. Poplack, and K. D. Paulsen, “Interpreting hemoglobin and water concentration, oxygen saturation, and scattering measured in vivo by near-infrared breast tomography,” Proc. Natl. Acad. Sci. U.S.A. 100, 12349 (2003).
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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. U.S.A. 98, 4420-4425 (2001).
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C. Verschraegen, V. Vinh-Hung, G. Cserni, R. Gordon, M. E. Royce, G. Vlastos, P. Tai, and G. Storme, “Modeling the effect of tumor size in early breast cancer,” Ann. Surg. 241, 309-318 (2005).
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Gregory, K.

H. Shangguan, S. Prahl, S. Jacques, L. Casperson, and K. Gregory, “Pressure effects on soft tissues monitored by changes in tissue optical properties,” Proc. SPIE 3254, 366-371 (1998).
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S. E. Lee, S. K. Hong, B. K. Han, J. H. Yu, J. H. Han, S. J. Jeong, S. S. Byun, Y. H. Park, and G. Choe, “Prognostic significance of tumor necrosis in primary transitional cell carcinoma of upper urinary tract,” Jpn. J. Clin. Oncol. 37, 49-55 (2007).
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S. Fantini, E. Heffer, H. Siebold, and O. Schutz, “Using near-infrared light to detect breast cancer,” Opt. Photon. News 14(11), 24-29 (2003).
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B. Dome, M. J. Hendrix, S. Paku, J. Tovari, and J. Timar, “Alternative vascularization mechanisms in cancer: pathology and therapeutic implications,” Am. J. Pathol. 170, 1-15 (2007).
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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. U.S.A. 98, 4420-4425 (2001).
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P. Wellman, R. Howe, E. Dalton, and K. A. Kern, “Breast tissue stiffness in compression is correlated to histological diagnosis,” Tech. Rep. (Harvard BioRobotics Laboratory, 1999).

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N. Shah, A. E. Cerussi, D. Jakubowski, D. Hsiang, J. Butler, and B. J. Tromberg, “Spatial variations in optical and physiological properties of healthy breast tissue,” J Biomed. Opt. 9, 534-540 (2004).
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Hwang, E.

B. Chance, S. Nioka, J. Zhang, E. F. Conant, E. Hwang, S. Briest, S. G. Orel, M. D. Schnall, and B. J. Czerniecki, “Breast cancer detection based on incremental biochemical and physiological properties of breast cancers: a six-year, two-site study,” Acad. Radiol. 12, 925-933 (2005).
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C. Jackowski, M. Thali, E. Aghayev, K. Yen, M. Sonnenschein, K. Zwygart, R. Dirnhofer, and P. Vock, “Postmortem imaging of blood and its characteristics using MSCT and MRI,” Int. J. Legal Med. 120, 233-240 (2006).
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H. Shangguan, S. Prahl, S. Jacques, L. Casperson, and K. Gregory, “Pressure effects on soft tissues monitored by changes in tissue optical properties,” Proc. SPIE 3254, 366-371 (1998).
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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, 1363-1380 (2000).
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N. Shah, A. E. Cerussi, D. Jakubowski, D. Hsiang, J. Butler, and B. J. Tromberg, “Spatial variations in optical and physiological properties of healthy breast tissue,” J Biomed. Opt. 9, 534-540 (2004).
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N. Shah, A. E. Cerussi, D. Jakubowski, D. Hsiang, J. Butler, and B. J. Tromberg, “The role of diffuse optical spectroscopy in the clinical management of breast cancer,” Dis. Markers 19, 95-105 (2003).

Jeong, S. J.

S. E. Lee, S. K. Hong, B. K. Han, J. H. Yu, J. H. Han, S. J. Jeong, S. S. Byun, Y. H. Park, and G. Choe, “Prognostic significance of tumor necrosis in primary transitional cell carcinoma of upper urinary tract,” Jpn. J. Clin. Oncol. 37, 49-55 (2007).
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B. W. Pogue, S. Jiang, H. Dehghani, C. Kogel, S. Soho, S. Srinivasan, X. Song, T. D. Tosteson, S. P. Poplack, and K. D. Paulsen, “Characterization of hemoglobin, water, and NIR scattering in breast tissue: analysis of intersubject variability and menstrual cycle changes,” J Biomed. Opt. 9, 541-552 (2004).
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S. Jiang, B. W. Pogue, K. D. Paulsen, C. Kogel, and S. Poplack, “In vivo near-infrared spectral detection of pressure-induced changes in breast tissue,” Opt. Lett. 28, 1212-1214 (2003).
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B. Gallez, C. Baudelet, and B. F. Jordan, “Assessment of tumor oxygenation by electron paramagnetic resonance: principles and applications,” NMR Biomed. 17, 240-262 (2004).
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S. A. Carp, T. Kauffman, Q. Fang, E. A. Rafferty, R. H. Moore, D. B. Kopans, and D. A. Boas, “Compression-induced changes in the physiological state of the breast as observed through frequency domain photon migration measurements,” J. Biomed. Opt. 11, 064016 (2006).
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Klemer, D. P.

Kogel, C.

B. W. Pogue, S. Jiang, H. Dehghani, C. Kogel, S. Soho, S. Srinivasan, X. Song, T. D. Tosteson, S. P. Poplack, and K. D. Paulsen, “Characterization of hemoglobin, water, and NIR scattering in breast tissue: analysis of intersubject variability and menstrual cycle changes,” J Biomed. Opt. 9, 541-552 (2004).
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S. Jiang, B. W. Pogue, K. D. Paulsen, C. Kogel, and S. Poplack, “In vivo near-infrared spectral detection of pressure-induced changes in breast tissue,” Opt. Lett. 28, 1212-1214 (2003).
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S. Srinivasan, B. W. Pogue, S. Jiang, H. Dehghani, C. Kogel, S. Soho, J. J. Gibson, T. D. Tosteson, S. P. Poplack, and K. D. Paulsen, “Interpreting hemoglobin and water concentration, oxygen saturation, and scattering measured in vivo by near-infrared breast tomography,” Proc. Natl. Acad. Sci. U.S.A. 100, 12349 (2003).
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S. A. Carp, T. Kauffman, Q. Fang, E. A. Rafferty, R. H. Moore, D. B. Kopans, and D. A. Boas, “Compression-induced changes in the physiological state of the breast as observed through frequency domain photon migration measurements,” J. Biomed. Opt. 11, 064016 (2006).
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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).
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M. J. Leahy, F. F. de Mul, G. E. Nilsson, and R. Maniewski, “Principles and practice of the laser-Doppler perfusion technique,” Technol. Health Care 7, 143-162 (1999).
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S. E. Lee, S. K. Hong, B. K. Han, J. H. Yu, J. H. Han, S. J. Jeong, S. S. Byun, Y. H. Park, and G. Choe, “Prognostic significance of tumor necrosis in primary transitional cell carcinoma of upper urinary tract,” Jpn. J. Clin. Oncol. 37, 49-55 (2007).
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Y. Boucher, M. Leunig, and R. K. Jain, “Tumor angiogenesis and interstitial hypertension,” Cancer Res. 56, 4264-4266(1996).
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Levina, R. D.

Liu, H.

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M. J. Leahy, F. F. de Mul, G. E. Nilsson, and R. Maniewski, “Principles and practice of the laser-Doppler perfusion technique,” Technol. Health Care 7, 143-162 (1999).
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S. A. Carp, T. Kauffman, Q. Fang, E. A. Rafferty, R. H. Moore, D. B. Kopans, and D. A. Boas, “Compression-induced changes in the physiological state of the breast as observed through frequency domain photon migration measurements,” J. Biomed. Opt. 11, 064016 (2006).
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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, 1363-1380 (2000).
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M. J. Leahy, F. F. de Mul, G. E. Nilsson, and R. Maniewski, “Principles and practice of the laser-Doppler perfusion technique,” Technol. Health Care 7, 143-162 (1999).
[PubMed]

Nioka, S.

B. Chance, S. Nioka, J. Zhang, E. F. Conant, E. Hwang, S. Briest, S. G. Orel, M. D. Schnall, and B. J. Czerniecki, “Breast cancer detection based on incremental biochemical and physiological properties of breast cancers: a six-year, two-site study,” Acad. Radiol. 12, 925-933 (2005).
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V. Ntziachristos, A. G. Yodh, M. D. Schnall, and B. Chance, “MRI-guided diffuse optical spectroscopy of malignant and benign breast lesions,” Neoplasia 4, 347-354 (2002).
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R. X. Xu, S. P. Povoski, L. D. Yee, J. O. Olsen, B. Qiang, and J. M. Mao, “Near infrared/ultrasound dual modal imaging for breast cancer detection,” Proc. SPIE 6081, 44-53 (2006).

O'Neil, M.

E. K. Chan, B. Sorg, D. Protsenko, M. O'Neil, M. Motamedi, and A. J. Welch, “Effects of compression on soft tissue optical properties,” IEEE J. Sel. Top. Quantum Electron. 2, 943-950(1996).
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B. Chance, S. Nioka, J. Zhang, E. F. Conant, E. Hwang, S. Briest, S. G. Orel, M. D. Schnall, and B. J. Czerniecki, “Breast cancer detection based on incremental biochemical and physiological properties of breast cancers: a six-year, two-site study,” Acad. Radiol. 12, 925-933 (2005).
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Paku, S.

B. Dome, M. J. Hendrix, S. Paku, J. Tovari, and J. Timar, “Alternative vascularization mechanisms in cancer: pathology and therapeutic implications,” Am. J. Pathol. 170, 1-15 (2007).
[CrossRef] [PubMed]

Park, Y. H.

S. E. Lee, S. K. Hong, B. K. Han, J. H. Yu, J. H. Han, S. J. Jeong, S. S. Byun, Y. H. Park, and G. Choe, “Prognostic significance of tumor necrosis in primary transitional cell carcinoma of upper urinary tract,” Jpn. J. Clin. Oncol. 37, 49-55 (2007).
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B. W. Pogue, S. Jiang, H. Dehghani, C. Kogel, S. Soho, S. Srinivasan, X. Song, T. D. Tosteson, S. P. Poplack, and K. D. Paulsen, “Characterization of hemoglobin, water, and NIR scattering in breast tissue: analysis of intersubject variability and menstrual cycle changes,” J Biomed. Opt. 9, 541-552 (2004).
[CrossRef] [PubMed]

S. Jiang, B. W. Pogue, K. D. Paulsen, C. Kogel, and S. Poplack, “In vivo near-infrared spectral detection of pressure-induced changes in breast tissue,” Opt. Lett. 28, 1212-1214 (2003).
[CrossRef] [PubMed]

S. Srinivasan, B. W. Pogue, S. Jiang, H. Dehghani, C. Kogel, S. Soho, J. J. Gibson, T. D. Tosteson, S. P. Poplack, and K. D. Paulsen, “Interpreting hemoglobin and water concentration, oxygen saturation, and scattering measured in vivo by near-infrared breast tomography,” Proc. Natl. Acad. Sci. U.S.A. 100, 12349 (2003).
[CrossRef] [PubMed]

Pei, Y.

Pham, T.

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).
[CrossRef] [PubMed]

Pogue, B. W.

A. L. Darling, P. K. Yalavarthy, M. M. Doyley, H. Dehghani, and B. W. Pogue, “Interstitial fluid pressure in soft tissue as a result of an externally applied contact pressure,” Phys. Med. Biol. 52, 4121-4136 (2007).
[CrossRef] [PubMed]

B. W. Pogue, S. Jiang, H. Dehghani, C. Kogel, S. Soho, S. Srinivasan, X. Song, T. D. Tosteson, S. P. Poplack, and K. D. Paulsen, “Characterization of hemoglobin, water, and NIR scattering in breast tissue: analysis of intersubject variability and menstrual cycle changes,” J Biomed. Opt. 9, 541-552 (2004).
[CrossRef] [PubMed]

S. Jiang, B. W. Pogue, K. D. Paulsen, C. Kogel, and S. Poplack, “In vivo near-infrared spectral detection of pressure-induced changes in breast tissue,” Opt. Lett. 28, 1212-1214 (2003).
[CrossRef] [PubMed]

S. Srinivasan, B. W. Pogue, S. Jiang, H. Dehghani, C. Kogel, S. Soho, J. J. Gibson, T. D. Tosteson, S. P. Poplack, and K. D. Paulsen, “Interpreting hemoglobin and water concentration, oxygen saturation, and scattering measured in vivo by near-infrared breast tomography,” Proc. Natl. Acad. Sci. U.S.A. 100, 12349 (2003).
[CrossRef] [PubMed]

Poplack, S.

Poplack, S. P.

B. W. Pogue, S. Jiang, H. Dehghani, C. Kogel, S. Soho, S. Srinivasan, X. Song, T. D. Tosteson, S. P. Poplack, and K. D. Paulsen, “Characterization of hemoglobin, water, and NIR scattering in breast tissue: analysis of intersubject variability and menstrual cycle changes,” J Biomed. Opt. 9, 541-552 (2004).
[CrossRef] [PubMed]

S. Srinivasan, B. W. Pogue, S. Jiang, H. Dehghani, C. Kogel, S. Soho, J. J. Gibson, T. D. Tosteson, S. P. Poplack, and K. D. Paulsen, “Interpreting hemoglobin and water concentration, oxygen saturation, and scattering measured in vivo by near-infrared breast tomography,” Proc. Natl. Acad. Sci. U.S.A. 100, 12349 (2003).
[CrossRef] [PubMed]

Povoski, S.

R. Xu, D. Young, J. Mao, and S. Povoski, “A prospective pilot clinical trial evaluating the utility of a dynamic near infrared imaging device for characterizing suspicious breast lesions,” Breast Cancer Res. 9, R88 (2007).
[CrossRef] [PubMed]

Povoski, S. P.

R. X. Xu, B. Qiang, J. J. Mao, and S. P. Povoski, “Development of a handheld near infrared imager for dynamic characterization of in vivo biological tissue systems,” Appl. Opt. 46, 7442-7451 (2007).
[CrossRef] [PubMed]

R. X. Xu and S. P. Povoski, “Diffuse optical imaging and spectroscopy for cancer,” Exp. Rev. Med. Dev. 4, 83-95 (2007).
[CrossRef]

R. X. Xu, S. P. Povoski, L. D. Yee, J. O. Olsen, B. Qiang, and J. M. Mao, “Near infrared/ultrasound dual modal imaging for breast cancer detection,” Proc. SPIE 6081, 44-53 (2006).

Pozrikidis, C.

C. Pozrikidis and D. A. Farrow, “A model of fluid flow in solid tumors,” Ann. Biomed. Eng. 31, 181-194 (2003).
[CrossRef] [PubMed]

Prahl, S.

H. Shangguan, S. Prahl, S. Jacques, L. Casperson, and K. Gregory, “Pressure effects on soft tissues monitored by changes in tissue optical properties,” Proc. SPIE 3254, 366-371 (1998).
[CrossRef]

Protsenko, D.

E. K. Chan, B. Sorg, D. Protsenko, M. O'Neil, M. Motamedi, and A. J. Welch, “Effects of compression on soft tissue optical properties,” IEEE J. Sel. Top. Quantum Electron. 2, 943-950(1996).
[CrossRef]

Qiang, B.

R. X. Xu, B. Qiang, J. J. Mao, and S. P. Povoski, “Development of a handheld near infrared imager for dynamic characterization of in vivo biological tissue systems,” Appl. Opt. 46, 7442-7451 (2007).
[CrossRef] [PubMed]

R. X. Xu, S. P. Povoski, L. D. Yee, J. O. Olsen, B. Qiang, and J. M. Mao, “Near infrared/ultrasound dual modal imaging for breast cancer detection,” Proc. SPIE 6081, 44-53 (2006).

Rafferty, E. A.

S. A. Carp, T. Kauffman, Q. Fang, E. A. Rafferty, R. H. Moore, D. B. Kopans, and D. A. Boas, “Compression-induced changes in the physiological state of the breast as observed through frequency domain photon migration measurements,” J. Biomed. Opt. 11, 064016 (2006).
[CrossRef]

Roberge, S.

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, 1363-1380 (2000).
[CrossRef] [PubMed]

Royce, M. E.

C. Verschraegen, V. Vinh-Hung, G. Cserni, R. Gordon, M. E. Royce, G. Vlastos, P. Tai, and G. Storme, “Modeling the effect of tumor size in early breast cancer,” Ann. Surg. 241, 309-318 (2005).
[CrossRef] [PubMed]

Schmitz, C. H.

Schnall, M. D.

B. Chance, S. Nioka, J. Zhang, E. F. Conant, E. Hwang, S. Briest, S. G. Orel, M. D. Schnall, and B. J. Czerniecki, “Breast cancer detection based on incremental biochemical and physiological properties of breast cancers: a six-year, two-site study,” Acad. Radiol. 12, 925-933 (2005).
[CrossRef] [PubMed]

V. Ntziachristos, A. G. Yodh, M. D. Schnall, and B. Chance, “MRI-guided diffuse optical spectroscopy of malignant and benign breast lesions,” Neoplasia 4, 347-354 (2002).
[CrossRef] [PubMed]

Schutz, O.

S. Fantini, E. Heffer, H. Siebold, and O. Schutz, “Using near-infrared light to detect breast cancer,” Opt. Photon. News 14(11), 24-29 (2003).
[CrossRef]

Shah, N.

N. Shah, A. E. Cerussi, D. Jakubowski, D. Hsiang, J. Butler, and B. J. Tromberg, “Spatial variations in optical and physiological properties of healthy breast tissue,” J Biomed. Opt. 9, 534-540 (2004).
[CrossRef] [PubMed]

N. Shah, A. E. Cerussi, D. Jakubowski, D. Hsiang, J. Butler, and B. J. Tromberg, “The role of diffuse optical spectroscopy in the clinical management of breast cancer,” Dis. Markers 19, 95-105 (2003).

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. U.S.A. 98, 4420-4425 (2001).
[CrossRef] [PubMed]

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).
[CrossRef] [PubMed]

Shangguan, H.

H. Shangguan, S. Prahl, S. Jacques, L. Casperson, and K. Gregory, “Pressure effects on soft tissues monitored by changes in tissue optical properties,” Proc. SPIE 3254, 366-371 (1998).
[CrossRef]

Sherratt, J. A.

S. R. McDougall, A. R. Anderson, M. A. Chaplain, and J. A. Sherratt, “Mathematical modelling of flow through vascular networks: implications for tumour-induced angiogenesis and chemotherapy strategies,” Bull. Math. Biol. 64, 673-702(2002).
[CrossRef] [PubMed]

Siebold, H.

S. Fantini, E. Heffer, H. Siebold, and O. Schutz, “Using near-infrared light to detect breast cancer,” Opt. Photon. News 14(11), 24-29 (2003).
[CrossRef]

Soho, S.

B. W. Pogue, S. Jiang, H. Dehghani, C. Kogel, S. Soho, S. Srinivasan, X. Song, T. D. Tosteson, S. P. Poplack, and K. D. Paulsen, “Characterization of hemoglobin, water, and NIR scattering in breast tissue: analysis of intersubject variability and menstrual cycle changes,” J Biomed. Opt. 9, 541-552 (2004).
[CrossRef] [PubMed]

S. Srinivasan, B. W. Pogue, S. Jiang, H. Dehghani, C. Kogel, S. Soho, J. J. Gibson, T. D. Tosteson, S. P. Poplack, and K. D. Paulsen, “Interpreting hemoglobin and water concentration, oxygen saturation, and scattering measured in vivo by near-infrared breast tomography,” Proc. Natl. Acad. Sci. U.S.A. 100, 12349 (2003).
[CrossRef] [PubMed]

Solomon, W. B.

Song, X.

B. W. Pogue, S. Jiang, H. Dehghani, C. Kogel, S. Soho, S. Srinivasan, X. Song, T. D. Tosteson, S. P. Poplack, and K. D. Paulsen, “Characterization of hemoglobin, water, and NIR scattering in breast tissue: analysis of intersubject variability and menstrual cycle changes,” J Biomed. Opt. 9, 541-552 (2004).
[CrossRef] [PubMed]

Sonnenschein, M.

C. Jackowski, M. Thali, E. Aghayev, K. Yen, M. Sonnenschein, K. Zwygart, R. Dirnhofer, and P. Vock, “Postmortem imaging of blood and its characteristics using MSCT and MRI,” Int. J. Legal Med. 120, 233-240 (2006).
[CrossRef]

Sorg, B.

E. K. Chan, B. Sorg, D. Protsenko, M. O'Neil, M. Motamedi, and A. J. Welch, “Effects of compression on soft tissue optical properties,” IEEE J. Sel. Top. Quantum Electron. 2, 943-950(1996).
[CrossRef]

Srinivasan, S.

B. W. Pogue, S. Jiang, H. Dehghani, C. Kogel, S. Soho, S. Srinivasan, X. Song, T. D. Tosteson, S. P. Poplack, and K. D. Paulsen, “Characterization of hemoglobin, water, and NIR scattering in breast tissue: analysis of intersubject variability and menstrual cycle changes,” J Biomed. Opt. 9, 541-552 (2004).
[CrossRef] [PubMed]

S. Srinivasan, B. W. Pogue, S. Jiang, H. Dehghani, C. Kogel, S. Soho, J. J. Gibson, T. D. Tosteson, S. P. Poplack, and K. D. Paulsen, “Interpreting hemoglobin and water concentration, oxygen saturation, and scattering measured in vivo by near-infrared breast tomography,” Proc. Natl. Acad. Sci. U.S.A. 100, 12349 (2003).
[CrossRef] [PubMed]

Storme, G.

C. Verschraegen, V. Vinh-Hung, G. Cserni, R. Gordon, M. E. Royce, G. Vlastos, P. Tai, and G. Storme, “Modeling the effect of tumor size in early breast cancer,” Ann. Surg. 241, 309-318 (2005).
[CrossRef] [PubMed]

Svaasand, L.

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).
[CrossRef] [PubMed]

Tai, P.

C. Verschraegen, V. Vinh-Hung, G. Cserni, R. Gordon, M. E. Royce, G. Vlastos, P. Tai, and G. Storme, “Modeling the effect of tumor size in early breast cancer,” Ann. Surg. 241, 309-318 (2005).
[CrossRef] [PubMed]

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C. Jackowski, M. Thali, E. Aghayev, K. Yen, M. Sonnenschein, K. Zwygart, R. Dirnhofer, and P. Vock, “Postmortem imaging of blood and its characteristics using MSCT and MRI,” Int. J. Legal Med. 120, 233-240 (2006).
[CrossRef]

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P. Vaupel, D. K. Kelleher, and O. Thews, “Modulation of tumor oxygenation,” Int. J. Radiat. Oncol. Biol. Phys. 42, 843-848(1998).
[CrossRef] [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, 1363-1380 (2000).
[CrossRef] [PubMed]

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B. Dome, M. J. Hendrix, S. Paku, J. Tovari, and J. Timar, “Alternative vascularization mechanisms in cancer: pathology and therapeutic implications,” Am. J. Pathol. 170, 1-15 (2007).
[CrossRef] [PubMed]

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B. W. Pogue, S. Jiang, H. Dehghani, C. Kogel, S. Soho, S. Srinivasan, X. Song, T. D. Tosteson, S. P. Poplack, and K. D. Paulsen, “Characterization of hemoglobin, water, and NIR scattering in breast tissue: analysis of intersubject variability and menstrual cycle changes,” J Biomed. Opt. 9, 541-552 (2004).
[CrossRef] [PubMed]

S. Srinivasan, B. W. Pogue, S. Jiang, H. Dehghani, C. Kogel, S. Soho, J. J. Gibson, T. D. Tosteson, S. P. Poplack, and K. D. Paulsen, “Interpreting hemoglobin and water concentration, oxygen saturation, and scattering measured in vivo by near-infrared breast tomography,” Proc. Natl. Acad. Sci. U.S.A. 100, 12349 (2003).
[CrossRef] [PubMed]

Tovari, J.

B. Dome, M. J. Hendrix, S. Paku, J. Tovari, and J. Timar, “Alternative vascularization mechanisms in cancer: pathology and therapeutic implications,” Am. J. Pathol. 170, 1-15 (2007).
[CrossRef] [PubMed]

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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. U.S.A. 98, 4420-4425 (2001).
[CrossRef] [PubMed]

Tromberg, B. J.

N. Shah, A. E. Cerussi, D. Jakubowski, D. Hsiang, J. Butler, and B. J. Tromberg, “Spatial variations in optical and physiological properties of healthy breast tissue,” J Biomed. Opt. 9, 534-540 (2004).
[CrossRef] [PubMed]

N. Shah, A. E. Cerussi, D. Jakubowski, D. Hsiang, J. Butler, and B. J. Tromberg, “The role of diffuse optical spectroscopy in the clinical management of breast cancer,” Dis. Markers 19, 95-105 (2003).

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).
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M. Hockel and P. Vaupel, “Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects,” J. Natl. Cancer Inst. 93, 266-276 (2001).
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P. Vaupel, D. K. Kelleher, and O. Thews, “Modulation of tumor oxygenation,” Int. J. Radiat. Oncol. Biol. Phys. 42, 843-848(1998).
[CrossRef] [PubMed]

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C. Verschraegen, V. Vinh-Hung, G. Cserni, R. Gordon, M. E. Royce, G. Vlastos, P. Tai, and G. Storme, “Modeling the effect of tumor size in early breast cancer,” Ann. Surg. 241, 309-318 (2005).
[CrossRef] [PubMed]

Vinh-Hung, V.

C. Verschraegen, V. Vinh-Hung, G. Cserni, R. Gordon, M. E. Royce, G. Vlastos, P. Tai, and G. Storme, “Modeling the effect of tumor size in early breast cancer,” Ann. Surg. 241, 309-318 (2005).
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Vlastos, G.

C. Verschraegen, V. Vinh-Hung, G. Cserni, R. Gordon, M. E. Royce, G. Vlastos, P. Tai, and G. Storme, “Modeling the effect of tumor size in early breast cancer,” Ann. Surg. 241, 309-318 (2005).
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C. Jackowski, M. Thali, E. Aghayev, K. Yen, M. Sonnenschein, K. Zwygart, R. Dirnhofer, and P. Vock, “Postmortem imaging of blood and its characteristics using MSCT and MRI,” Int. J. Legal Med. 120, 233-240 (2006).
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E. E. Voest and P. A. D'Amore, Tumor Angiogenesis and Microcirculation (Marcel-Dekker, 2001).

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E. K. Chan, B. Sorg, D. Protsenko, M. O'Neil, M. Motamedi, and A. J. Welch, “Effects of compression on soft tissue optical properties,” IEEE J. Sel. Top. Quantum Electron. 2, 943-950(1996).
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P. Wellman, R. Howe, E. Dalton, and K. A. Kern, “Breast tissue stiffness in compression is correlated to histological diagnosis,” Tech. Rep. (Harvard BioRobotics Laboratory, 1999).

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R. Xu, D. Young, J. Mao, and S. Povoski, “A prospective pilot clinical trial evaluating the utility of a dynamic near infrared imaging device for characterizing suspicious breast lesions,” Breast Cancer Res. 9, R88 (2007).
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Xu, R. X.

R. X. Xu, B. Qiang, J. J. Mao, and S. P. Povoski, “Development of a handheld near infrared imager for dynamic characterization of in vivo biological tissue systems,” Appl. Opt. 46, 7442-7451 (2007).
[CrossRef] [PubMed]

R. X. Xu and S. P. Povoski, “Diffuse optical imaging and spectroscopy for cancer,” Exp. Rev. Med. Dev. 4, 83-95 (2007).
[CrossRef]

R. X. Xu, S. P. Povoski, L. D. Yee, J. O. Olsen, B. Qiang, and J. M. Mao, “Near infrared/ultrasound dual modal imaging for breast cancer detection,” Proc. SPIE 6081, 44-53 (2006).

Xu, X.

X. Cheng and X. Xu, “Study of the pressure effect in near infrared spectroscopy,” Proc. SPIE 4955, 397-406 (2003).
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A. L. Darling, P. K. Yalavarthy, M. M. Doyley, H. Dehghani, and B. W. Pogue, “Interstitial fluid pressure in soft tissue as a result of an externally applied contact pressure,” Phys. Med. Biol. 52, 4121-4136 (2007).
[CrossRef] [PubMed]

Yee, L. D.

R. X. Xu, S. P. Povoski, L. D. Yee, J. O. Olsen, B. Qiang, and J. M. Mao, “Near infrared/ultrasound dual modal imaging for breast cancer detection,” Proc. SPIE 6081, 44-53 (2006).

Yen, K.

C. Jackowski, M. Thali, E. Aghayev, K. Yen, M. Sonnenschein, K. Zwygart, R. Dirnhofer, and P. Vock, “Postmortem imaging of blood and its characteristics using MSCT and MRI,” Int. J. Legal Med. 120, 233-240 (2006).
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A. Yodh and B. Chance, “Spectroscopy and imaging with diffusing light,” Phys. Today 48(3), 34-40 (1995).
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Yodh, A. G.

V. Ntziachristos, A. G. Yodh, M. D. Schnall, and B. Chance, “MRI-guided diffuse optical spectroscopy of malignant and benign breast lesions,” Neoplasia 4, 347-354 (2002).
[CrossRef] [PubMed]

Young, D.

R. Xu, D. Young, J. Mao, and S. Povoski, “A prospective pilot clinical trial evaluating the utility of a dynamic near infrared imaging device for characterizing suspicious breast lesions,” Breast Cancer Res. 9, R88 (2007).
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Yu, J. H.

S. E. Lee, S. K. Hong, B. K. Han, J. H. Yu, J. H. Han, S. J. Jeong, S. S. Byun, Y. H. Park, and G. Choe, “Prognostic significance of tumor necrosis in primary transitional cell carcinoma of upper urinary tract,” Jpn. J. Clin. Oncol. 37, 49-55 (2007).
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B. Chance, S. Nioka, J. Zhang, E. F. Conant, E. Hwang, S. Briest, S. G. Orel, M. D. Schnall, and B. J. Czerniecki, “Breast cancer detection based on incremental biochemical and physiological properties of breast cancers: a six-year, two-site study,” Acad. Radiol. 12, 925-933 (2005).
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Zhu, Q.

Q. Zhu, E. Conant, and B. Chance, “Optical imaging as an adjunct to sonograph in differentiating benign from malignant breast lesions,” J Biomed. Opt. 5, 229-236 (2000).
[CrossRef] [PubMed]

Zwygart, K.

C. Jackowski, M. Thali, E. Aghayev, K. Yen, M. Sonnenschein, K. Zwygart, R. Dirnhofer, and P. Vock, “Postmortem imaging of blood and its characteristics using MSCT and MRI,” Int. J. Legal Med. 120, 233-240 (2006).
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Acad. Radiol.

B. Chance, S. Nioka, J. Zhang, E. F. Conant, E. Hwang, S. Briest, S. G. Orel, M. D. Schnall, and B. J. Czerniecki, “Breast cancer detection based on incremental biochemical and physiological properties of breast cancers: a six-year, two-site study,” Acad. Radiol. 12, 925-933 (2005).
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Am. J. Pathol.

B. Dome, M. J. Hendrix, S. Paku, J. Tovari, and J. Timar, “Alternative vascularization mechanisms in cancer: pathology and therapeutic implications,” Am. J. Pathol. 170, 1-15 (2007).
[CrossRef] [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, 1363-1380 (2000).
[CrossRef] [PubMed]

Ann. Biomed. Eng.

C. Pozrikidis and D. A. Farrow, “A model of fluid flow in solid tumors,” Ann. Biomed. Eng. 31, 181-194 (2003).
[CrossRef] [PubMed]

Ann. Surg.

C. Verschraegen, V. Vinh-Hung, G. Cserni, R. Gordon, M. E. Royce, G. Vlastos, P. Tai, and G. Storme, “Modeling the effect of tumor size in early breast cancer,” Ann. Surg. 241, 309-318 (2005).
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Appl. Opt.

Breast Cancer Res.

R. Xu, D. Young, J. Mao, and S. Povoski, “A prospective pilot clinical trial evaluating the utility of a dynamic near infrared imaging device for characterizing suspicious breast lesions,” Breast Cancer Res. 9, R88 (2007).
[CrossRef] [PubMed]

Bull. Math. Biol.

S. R. McDougall, A. R. Anderson, M. A. Chaplain, and J. A. Sherratt, “Mathematical modelling of flow through vascular networks: implications for tumour-induced angiogenesis and chemotherapy strategies,” Bull. Math. Biol. 64, 673-702(2002).
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Cancer Res.

D. M. McDonald and P. Baluk, “Significance of blood vessel leakiness in cancer,” Cancer Res. 62, 5381-5385 (2002).
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Y. Boucher, M. Leunig, and R. K. Jain, “Tumor angiogenesis and interstitial hypertension,” Cancer Res. 56, 4264-4266(1996).
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Dis. Markers

N. Shah, A. E. Cerussi, D. Jakubowski, D. Hsiang, J. Butler, and B. J. Tromberg, “The role of diffuse optical spectroscopy in the clinical management of breast cancer,” Dis. Markers 19, 95-105 (2003).

Exp. Rev. Med. Dev.

R. X. Xu and S. P. Povoski, “Diffuse optical imaging and spectroscopy for cancer,” Exp. Rev. Med. Dev. 4, 83-95 (2007).
[CrossRef]

IEEE J. Sel. Top. Quantum Electron.

E. K. Chan, B. Sorg, D. Protsenko, M. O'Neil, M. Motamedi, and A. J. Welch, “Effects of compression on soft tissue optical properties,” IEEE J. Sel. Top. Quantum Electron. 2, 943-950(1996).
[CrossRef]

Int. J. Legal Med.

C. Jackowski, M. Thali, E. Aghayev, K. Yen, M. Sonnenschein, K. Zwygart, R. Dirnhofer, and P. Vock, “Postmortem imaging of blood and its characteristics using MSCT and MRI,” Int. J. Legal Med. 120, 233-240 (2006).
[CrossRef]

Int. J. Radiat. Oncol. Biol. Phys.

P. Vaupel, D. K. Kelleher, and O. Thews, “Modulation of tumor oxygenation,” Int. J. Radiat. Oncol. Biol. Phys. 42, 843-848(1998).
[CrossRef] [PubMed]

J Biomed. Opt.

N. Shah, A. E. Cerussi, D. Jakubowski, D. Hsiang, J. Butler, and B. J. Tromberg, “Spatial variations in optical and physiological properties of healthy breast tissue,” J Biomed. Opt. 9, 534-540 (2004).
[CrossRef] [PubMed]

B. W. Pogue, S. Jiang, H. Dehghani, C. Kogel, S. Soho, S. Srinivasan, X. Song, T. D. Tosteson, S. P. Poplack, and K. D. Paulsen, “Characterization of hemoglobin, water, and NIR scattering in breast tissue: analysis of intersubject variability and menstrual cycle changes,” J Biomed. Opt. 9, 541-552 (2004).
[CrossRef] [PubMed]

Q. Zhu, E. Conant, and B. Chance, “Optical imaging as an adjunct to sonograph in differentiating benign from malignant breast lesions,” J Biomed. Opt. 5, 229-236 (2000).
[CrossRef] [PubMed]

J. Biomed. Opt.

S. A. Carp, T. Kauffman, Q. Fang, E. A. Rafferty, R. H. Moore, D. B. Kopans, and D. A. Boas, “Compression-induced changes in the physiological state of the breast as observed through frequency domain photon migration measurements,” J. Biomed. Opt. 11, 064016 (2006).
[CrossRef]

J. Natl. Cancer Inst.

M. Hockel and P. Vaupel, “Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects,” J. Natl. Cancer Inst. 93, 266-276 (2001).
[CrossRef] [PubMed]

Jpn. J. Clin. Oncol.

S. E. Lee, S. K. Hong, B. K. Han, J. H. Yu, J. H. Han, S. J. Jeong, S. S. Byun, Y. H. Park, and G. Choe, “Prognostic significance of tumor necrosis in primary transitional cell carcinoma of upper urinary tract,” Jpn. J. Clin. Oncol. 37, 49-55 (2007).
[CrossRef] [PubMed]

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).
[CrossRef] [PubMed]

V. Ntziachristos, A. G. Yodh, M. D. Schnall, and B. Chance, “MRI-guided diffuse optical spectroscopy of malignant and benign breast lesions,” Neoplasia 4, 347-354 (2002).
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NMR Biomed.

B. Gallez, C. Baudelet, and B. F. Jordan, “Assessment of tumor oxygenation by electron paramagnetic resonance: principles and applications,” NMR Biomed. 17, 240-262 (2004).
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Opt. Lett.

Opt. Photon. News

S. Fantini, E. Heffer, H. Siebold, and O. Schutz, “Using near-infrared light to detect breast cancer,” Opt. Photon. News 14(11), 24-29 (2003).
[CrossRef]

Phys. Med. Biol.

A. P. Gibson, J. C. Hebden, and S. R. Arridge, “Recent advances in diffuse optical imaging,” Phys. Med. Biol. 50, R1-R43 (2005).
[CrossRef] [PubMed]

A. L. Darling, P. K. Yalavarthy, M. M. Doyley, H. Dehghani, and B. W. Pogue, “Interstitial fluid pressure in soft tissue as a result of an externally applied contact pressure,” Phys. Med. Biol. 52, 4121-4136 (2007).
[CrossRef] [PubMed]

Phys. Today

A. Yodh and B. Chance, “Spectroscopy and imaging with diffusing light,” Phys. Today 48(3), 34-40 (1995).
[CrossRef]

Proc. Natl. Acad. Sci. U.S.A.

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. U.S.A. 98, 4420-4425 (2001).
[CrossRef] [PubMed]

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[CrossRef]

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Figures (8)

Fig. 1
Fig. 1

Typical compression profile and the corresponding HbT and St O 2 dynamics in our previously reported clinical trial.

Fig. 2
Fig. 2

Oxygen dynamics for benign breast lesions and malignant breast tumors in the prospective clinical trial. (a) For a benign tumor (squares), the rate of the pressure- induced St O 2 changes is similar to that of the normal reference tissue located remotely elsewhere within the ipsilateral breast (diamonds). (b) For a malignant tumor (squares), the rate of pressure-induced St O 2 changes is much greater than that of the normal reference tissue located remotely elsewhere within the ipsilateral breast (diamonds).

Fig. 3
Fig. 3

Hemoglobin dynamics for benign breast lesions and malignant breast tumors in our prospective clinical trial. (a) For a benign tumor (squares), the rate of the pressure- induced HbT changes is much greater than that of the normal reference tissue located remotely elsewhere within the ipsilateral breast (diamonds). (b) For a malignant tumor (squares), the rate of pressure-induced HbT changes is much less than that of the normal reference tissue located remotely elsewhere within the ipsilateral breast (diamonds).

Fig. 4
Fig. 4

Malignancy indexes for 14 suspicious breast lesions included in the dynamic analysis.

Fig. 5
Fig. 5

Benchtop setup for animal model validation testing of the dynamic schema.

Fig. 6
Fig. 6

A stepped compression profile applied in the animal validation test and the corresponding responses in tumor deformation, superficial tissue blood flow, and tumor hemoglobin concentration.

Fig. 7
Fig. 7

Stress–strain curves captured at stage II of the dynamic schema for the tumor premortem and postmortem.

Fig. 8
Fig. 8

HbT changes at stage III of the dynamic schema (right after the stepped compression load was applied).

Tables (2)

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Table 1 Histopathology Findings for the 36 Suspicious Breast Lesions

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Table 2 Results of Independent Samples T Test for Malignant and Benign Tumors

Equations (4)

Equations on this page are rendered with MathJax. Learn more.

α SO 2 = ( [ St O 2 ] ¯ T [ St O 2 ] ¯ R ) / [ St O 2 ] ¯ T ,
α HbT = ( [ HbT ] ¯ T [ HbT ] ¯ R ) / [ HbT ] ¯ T ,
α VAS = [ HbT ] ¯ T / P [ HbT ] ¯ R / P ,
M . I . = [ sgn ( α SO 2 c 1 ) · sgn ( α VAS c 3 ) + sgn ( α SO 2 c 1 ) + sgn ( α VAS c 3 ) ] · e α SO 2 c 1 e α VAS c 3 + [ sgn ( α HbT c 2 ) · sgn ( α VAS c 3 ) + sgn ( α HbT c 2 ) + sgn ( α VAS c 3 ) ] · e α HbT c 2 e α VAS c 3 ,

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