Abstract

Diffuse optical methods were used to monitor two different therapies in K1735 malignant mouse melanoma tumor models: anti-vascular therapy and radiation therapy. Anti-vascular therapy induced acute variation in hemodynamic parameters within an hour, and radiation therapy induced longitudinal changes within 2 weeks. During anti-vascular therapy, the drug Combretastatin A-4 3-O-Phosphate (CA4P, 2.5 mg/200 μl PBS/mouse) significantly decreased tissue blood flow (65%) and blood oxygenation (38%) one hour after injection. In the longitudinal study, single-fraction ionizing radiation (12 Gy x 1) induced significant reduction of tissue blood flow (36%) and blood oxygenation (24%) 14 days after radiation. The results correlated well with contrast enhanced ultrasound, tumor histology, and a nitroimidazole hypoxia marker (EF5). The research provides further evidence that noninvasive diffuse optical spectroscopies can be useful tools for monitoring cancer therapy in vivo.

© 2007 Optical Society of America

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2007 (2)

C. Zhou, R. Choe, N. Shah, T. Durduran, G. Q. Yu, A. Durkin, A. Cerussi, D. Hsiang, R. Mehta, 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, 051903 (2007).
[CrossRef] [PubMed]

G. Yu, T. F. Floyd, T. Durduran, C. Zhou, J. J. Wang, J. A. Detre, and A. G. Yodh. "Validation of diffuse correlation spectroscopy for muscle blood flow with concurrent arterial spin labeled perfusion MRI," Opt. Express 15, 1064-1075 (2007).
[CrossRef] [PubMed]

2006 (2)

U. Sunar, H. Quon, T. Durduran, J. Zhang, J. Du, C. Zhou, G. Yu, R. Choe, A. Kilger, R. Lustig, L. Loevner, S. Nioka, B. Chance, and A.G. Yodh. "Noninvasive diffuse optical measurement of blood flow and blood oxygenation for monitoring radiation therapy in patients with head and neck tumors," J. Biomed. Opt. 11, 064021 (2006).
[CrossRef]

C. Zhou, G. Yu, F. Daisuke, J. H. Greenberg, A. G. Yodh, and T. Durduran. "Diffuse optical correlation tomography of cerebral blood flow during cortical spreading depression in rat brain," Opt. Express 14, 1125-1144 (2006).
[CrossRef] [PubMed]

2005 (9)

T. Durduran, R. Choe, G. Yu, C. Zhou, J. C. Tchou, B. J. Czerniecki, and A. G. Yodh. "Diffuse optical measurement of blood flow in breast tumors," Opt. Lett. 30, 2915-2917 (2005).
[CrossRef] [PubMed]

G. Yu, T. Durduran, H. W. Wang, C. Zhou, H. M. Saunders, C. M. Sehgal, T. M. Busch, and A. G. Yodh. "Noninvasive monitoring of hemodynamic responses in RIF tumors during and after PDT," Clin. Cancer Res. 11, 3543-3552 (2005).
[CrossRef] [PubMed]

L. S. Ziemer, W. M. F. Lee, S. A. Vinogradov, C. Sehgal, and D. F. Wilson. "Oxygen distribution in murine tumors: characterization using oxygen-dependent quenching of phosphorence," J. Appl. Physiol. 98, 1503-1510 (2005).
[CrossRef]

R. Choe, A. Corlu, K. Lee, T. Durduran, S. D. Konecky, M. Koptyra, S. R. Arridge, B. J. Czerniecki, D. L. Fraker, A. DeMichele, B. Chance, M. Rosen, and A. G. Yodh. "Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: A case study with comparison to MRI," Med. Phys. 32, 1-11 (2005).
[CrossRef]

Q. Zhu, S. H. Kurtzmany, P. Hegde, S. Tannenbaum, M. Kane, M. Huang, N. G. Chen, B. Jagjivan, and K. Zarfos. "Utilizing optical tomography with ultrasound localization to image heterogeneous hemoglobin distribution in large breast cancers," Neoplasia 7, 263-270 (2005).
[CrossRef] [PubMed]

H.W. Wang, T. C. Zhu, M. E. Putt, M. Solonenko, J. Metz, A. Dimofte, J. Miles, D. L. Fraker, E. Glatstein, S. M. Hahn, and A. G. Yodh. "Broadband reflectance measurement of light penetration, blood oxygenation, hemoglobin concentration, and drug concentration in human intraperitoneal tissues before and after photodynamic therapy," J. Biomed. Opt. 10, 014004 (2005).
[CrossRef]

J.H. Tsai, S. Makonnen, M. Feldman, C.M. Sehgal, A. Maity, and W.M. Lee. "Ionizing radiation inhibits tumor neovascularization by inducing ineffective angiogenesis," Cancer Biol. Ther. 4, 1395-1400 (2005).
[CrossRef] [PubMed]

J. Li, G. Dietsche, D. Iftime, S. E. Skipetrov, G. Maret, T. Elbert, B. Rockstroh, and T. Gisler. "Noninvasive detection of functional brain activity with near-infrared diffusing-wave spectroscopy," J. Biomed. Opt. 10, 44002 (2005).
[CrossRef] [PubMed]

G. Yu, T. Durduran, G. Lech, C. Zhou, B. Chance, E. R. MohlerIII, and A. G. Yodh. "Time-dependent blood flow and oxygenation in human skeletal muscle measured by noninvasive near-infrared diffuse optical spectroscopies," J. Biomed. Opt. 10, 024027 (2005).
[CrossRef] [PubMed]

2004 (3)

H. W. Wang, M. E. Putt, M. J. Emanuele, D. B. Shin, E. Glatstein, A. G. Yodh, and T. M. Busch. "Treatmentinduced changes in tumor oxygenation predict photodynamic therapy outcome," Cancer Res. 64, 7553-7561 (2004).
[CrossRef] [PubMed]

D. B. Jakubowski, A. E. Cerussi, F. Bevilacqua, N. Shah, D. Hsiang, J. Butler, and B. J. Tromberg. "Monitoring neoadjuvant chemotherapy in breast cancer using quantitative diffuse optical spectroscopy: A case study," J. Biomed. Opt. 9, 230-238 (2004).
[CrossRef] [PubMed]

T. Durduran, G. Yu, M. G. Burnett, J. A. Detre, J. H. Greenberg, J. Wang, C. Zhou, and A. G. Yodh. "Diffuse optical measurement of blood flow, blood oxygenation, and metabolism in a human brain during sensorimotor cortex activation," Opt. Lett. 29, 1766-1768 (2004).
[CrossRef] [PubMed]

2003 (5)

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh. "Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia," J. Cereb. Blood Flow Metab. 23, 911-924 (2003).
[CrossRef] [PubMed]

S. M. Galbraith, R. J. Maxwell, M. A. Lodge, G. M. Tozer, J. Wilson, N. J. Taylor, J. J. Stirling, L. Sena, A. R. Padhani, and G. J. S. Rustin. "Combretastatin A4 phosphate has tumor antivascular activity in rat and man as demonstrated by dynamic magnetic resonance imaging," J. Clin. Oncol. 21, 2831-2842 (2003).
[CrossRef] [PubMed]

G. M. Tozer. "Measuring tumour vascular response to antivascular and antiangiogenic drugs," Br. J. Radiol. 76, 23-35 (2003).
[CrossRef]

H. L. Anderson, J. T. Yap, M. P. Miller, A. Robbins, T. Jones and P. M. Price. "Assessment of pharmacodynamic vascular response in a phase I trial of Combretastatin A4 Phosphate," J. Clin. Oncol. 21, 2823-2830 (2003).
[CrossRef] [PubMed]

A. F. DeVries, C. Kremser, P. A. Hein, J. Griebel, A. Krezcy, D. Ofner, K. P. Pfeiffer, P. Lukas, and W. Judmaier. "Tumor microcirculation and diffusion predict therapy outcome for primary rectal carcinoma," Int. J. Radiat. Oncol. Biol. Phys. 56, 958-965 (2003).
[CrossRef] [PubMed]

2002 (3)

R. K. Jain, L. L. Munn, and D. Fukumura. "Dissecting tumour pathophysiology using intravital microscopy," Nat. Rev. Cancer 2, 266-276 (2002).
[CrossRef] [PubMed]

D. E. Goertz, J. L. Yu, R. S. Kerbel, P. N. Burns, and F. S. Foster. "High-frequency Doppler ultrasound monitors the effects of antivascular therapy on tumor blood flow," Cancer Res. 62, 6371-6375 (2002).
[PubMed]

M. Kragh, B. Quistorff, M. R. Horsman, and P. E. G. Kristjansen. "Acute effects of vascular modifying agents in solid tumors assessed by noninvasive laser Doppler flowmetry and near infrared spectroscopy," Neoplasia 4, 263-267 (2002).
[CrossRef] [PubMed]

2001 (4)

R. K. Jain. "Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy," Nat. Med. 7, 987-989 (2001).
[CrossRef] [PubMed]

R. Murata, D.W. Siemann, J. Overgaard, and M. R. Horsman. "Improved tumor response by combining radiation and the vascular-damaging drug 5,6-dimethylxanthenone-4-acetic acid," Radiat. Res. 156, 503-509 (2001).
[CrossRef] [PubMed]

R. Murata, D.W. Siemann, J. Overgaard, and M. R. Horsman. "Interaction between combretastatin A-4 disodium phosphate and radiation in murine tumors," Radiother. Oncol. 60, 155-161 (2001).
[CrossRef] [PubMed]

C. Cheung, J. P. Culver, K. Takahashi, J. H. Greenberg, and A. G. Yodh. "In vivo cerebrovascular measurement combining diffuse near-infrared absorption and correlation spectroscopies," Phys. Med. Biol. 46, 2053-2065 (2001).
[CrossRef] [PubMed]

2000 (3)

D.W. Siemann, K.H. Warrington, and M.R. Horsman. "Ionizing radiation inhibits tumor neovascularization by inducing ineffective angiogenesis," Radiother. Oncol. 57, 5-12 (2000).
[CrossRef] [PubMed]

C. M. Sehgal, P. H. Arger, S. E. Rowling, E. F. Conant, C. Reynolds, and J. A. Patton. "Quantitative vascularity of breast masses by Doppler imaging: Regional variations and diagnostic implications," J. Ultrasound Med. 19, 427-440 (2000).
[PubMed]

S. M. Evans, S. Hahn, D. R. Pook, W. T. Jenkins, A. A Chalian, P. Zhang, C. Stevens, R. Weber, G. Weinstein, I. Benjamin, N. Mirza, M. Morgan, S. Rubin,W. G. McKenna, E. M. Lord, and C. J. Koch. "Detection of hypoxia in human squamous cell carcinoma by EF5 binding," Cancer Res. 60, 2018-2024 (2000).
[PubMed]

1998 (1)

D. A. Beauregard, P. E. Thelwall, D. J. Chaplin, S. A. Hill, G. E. Adams, and K. M. Brindle. "Magnetic resonance imaging and spectroscopy of combretastatin A4 prodrug-induced disruption of tumour perfusion and energetic status," Br. J. Cancer 77, 1761-1767 (1998).
[CrossRef] [PubMed]

1997 (3)

1996 (2)

M. Nordsmark, S.M. Bentzen, and J. Overgaard. "Pretreatment oxygenation predicts radiation response in advanced squamous cell carcinoma of the head & neck," Radiother. Oncol. 41, 31-39 (1996).
[PubMed]

N. A. Mayr, W. T. Yuh, V. A. Magnotta, J. C. Ehrhardt, J. A. Wheeler, J. I. Sorosky, C. S. Davis, B. C. Wen, D. D. Martin, R. E. Pelsang, R. E. Buller, L.W. Oberley, D. E. Mellenberg, and D. H. Hussey. "Tumor perfusion studies using fast magnetic resonance imaging technique in advanced cervical cancer: a new noninvasive predictive assay," Int. J. Radiat. Oncol. Biol. Phys. 36, 623-633 (1996).
[CrossRef] [PubMed]

1995 (1)

D. A. Boas, L. E. Campbell, and A. G. Yodh. "Scattering and imaging with diffusing temporal field correlations," Phys. Rev. Lett. 75, 1855-58 (1995).
[CrossRef] [PubMed]

1990 (1)

B. C. Wilson, T. J. Farrell, and M. S. Patterson. "An optical fiber-based diffuse reflectance spectrometer for non-invasive investigation of photodynamic sensitizers in vivo," Proc. SPIE 6, 219-232 (1990).

1989 (1)

P. Vaupel, F. Kallinowski, and P. Okunieff. "Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: A review," Cancer Res. 49, 6449-6465 (1989).
[PubMed]

1988 (1)

D. J. Pine, D. A. Weitz, P. M. Chaikin, and E. Herbolzheimer. "Diffusing wave spectroscopy," Phys. Rev. Lett. 60, 1134-1137 (1988).
[CrossRef] [PubMed]

1987 (1)

G. Maret and P. E. Wolf. "Multiple light scattering from disordered media. the effect of brownian motion of scatterers," Z. Phys. B 65, 409-413 (1987).
[CrossRef]

1972 (1)

R.F. Kallman. "The phenomenon of reoxygenation and its implications for fractionated radiotherapy," Radiol. 105, 135-142 (1972).Q1

1953 (1)

L.H. Gray, A.D. Conger, M. Ebert, S. Horsney, and O.C.A. Scott. "The concentration of oxygen dissolved in tissue at the time of irradiation as a factor in radiotherapy," Br. J. Radiol. 26, 638-42 (1953).
[CrossRef] [PubMed]

Adams, G. E.

D. A. Beauregard, P. E. Thelwall, D. J. Chaplin, S. A. Hill, G. E. Adams, and K. M. Brindle. "Magnetic resonance imaging and spectroscopy of combretastatin A4 prodrug-induced disruption of tumour perfusion and energetic status," Br. J. Cancer 77, 1761-1767 (1998).
[CrossRef] [PubMed]

Anderson, H. L.

H. L. Anderson, J. T. Yap, M. P. Miller, A. Robbins, T. Jones and P. M. Price. "Assessment of pharmacodynamic vascular response in a phase I trial of Combretastatin A4 Phosphate," J. Clin. Oncol. 21, 2823-2830 (2003).
[CrossRef] [PubMed]

Arger, P. H.

C. M. Sehgal, P. H. Arger, S. E. Rowling, E. F. Conant, C. Reynolds, and J. A. Patton. "Quantitative vascularity of breast masses by Doppler imaging: Regional variations and diagnostic implications," J. Ultrasound Med. 19, 427-440 (2000).
[PubMed]

Arridge, S. R.

R. Choe, A. Corlu, K. Lee, T. Durduran, S. D. Konecky, M. Koptyra, S. R. Arridge, B. J. Czerniecki, D. L. Fraker, A. DeMichele, B. Chance, M. Rosen, and A. G. Yodh. "Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: A case study with comparison to MRI," Med. Phys. 32, 1-11 (2005).
[CrossRef]

Beauregard, D. A.

D. A. Beauregard, P. E. Thelwall, D. J. Chaplin, S. A. Hill, G. E. Adams, and K. M. Brindle. "Magnetic resonance imaging and spectroscopy of combretastatin A4 prodrug-induced disruption of tumour perfusion and energetic status," Br. J. Cancer 77, 1761-1767 (1998).
[CrossRef] [PubMed]

Benjamin, I.

S. M. Evans, S. Hahn, D. R. Pook, W. T. Jenkins, A. A Chalian, P. Zhang, C. Stevens, R. Weber, G. Weinstein, I. Benjamin, N. Mirza, M. Morgan, S. Rubin,W. G. McKenna, E. M. Lord, and C. J. Koch. "Detection of hypoxia in human squamous cell carcinoma by EF5 binding," Cancer Res. 60, 2018-2024 (2000).
[PubMed]

Bentzen, S.M.

M. Nordsmark, S.M. Bentzen, and J. Overgaard. "Pretreatment oxygenation predicts radiation response in advanced squamous cell carcinoma of the head & neck," Radiother. Oncol. 41, 31-39 (1996).
[PubMed]

Bevilacqua, F.

D. B. Jakubowski, A. E. Cerussi, F. Bevilacqua, N. Shah, D. Hsiang, J. Butler, and B. J. Tromberg. "Monitoring neoadjuvant chemotherapy in breast cancer using quantitative diffuse optical spectroscopy: A case study," J. Biomed. Opt. 9, 230-238 (2004).
[CrossRef] [PubMed]

Boas, D. A.

D. A. Boas and A. G. Yodh. "Spatially varying dynamical properties of turbid media probed with diffusing temporal light correlation," J. Opt. Soc. Am. A 14, 192-215 (1997).
[CrossRef]

D. A. Boas, L. E. Campbell, and A. G. Yodh. "Scattering and imaging with diffusing temporal field correlations," Phys. Rev. Lett. 75, 1855-58 (1995).
[CrossRef] [PubMed]

Brindle, K. M.

D. A. Beauregard, P. E. Thelwall, D. J. Chaplin, S. A. Hill, G. E. Adams, and K. M. Brindle. "Magnetic resonance imaging and spectroscopy of combretastatin A4 prodrug-induced disruption of tumour perfusion and energetic status," Br. J. Cancer 77, 1761-1767 (1998).
[CrossRef] [PubMed]

Brizel, D.M.

D.M. Brizel, G.S. Sibley, L.R. Prosnitz, R.L. Scher, and M.W. Dewhirst. "Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck," Int. J. Radiat. Oncol. Biol. Phys. 38, 285-289 (1997).
[CrossRef] [PubMed]

Buller, R. E.

N. A. Mayr, W. T. Yuh, V. A. Magnotta, J. C. Ehrhardt, J. A. Wheeler, J. I. Sorosky, C. S. Davis, B. C. Wen, D. D. Martin, R. E. Pelsang, R. E. Buller, L.W. Oberley, D. E. Mellenberg, and D. H. Hussey. "Tumor perfusion studies using fast magnetic resonance imaging technique in advanced cervical cancer: a new noninvasive predictive assay," Int. J. Radiat. Oncol. Biol. Phys. 36, 623-633 (1996).
[CrossRef] [PubMed]

Burnett, M. G.

Burns, P. N.

D. E. Goertz, J. L. Yu, R. S. Kerbel, P. N. Burns, and F. S. Foster. "High-frequency Doppler ultrasound monitors the effects of antivascular therapy on tumor blood flow," Cancer Res. 62, 6371-6375 (2002).
[PubMed]

Busch, T. M.

G. Yu, T. Durduran, H. W. Wang, C. Zhou, H. M. Saunders, C. M. Sehgal, T. M. Busch, and A. G. Yodh. "Noninvasive monitoring of hemodynamic responses in RIF tumors during and after PDT," Clin. Cancer Res. 11, 3543-3552 (2005).
[CrossRef] [PubMed]

H. W. Wang, M. E. Putt, M. J. Emanuele, D. B. Shin, E. Glatstein, A. G. Yodh, and T. M. Busch. "Treatmentinduced changes in tumor oxygenation predict photodynamic therapy outcome," Cancer Res. 64, 7553-7561 (2004).
[CrossRef] [PubMed]

Butler, J.

D. B. Jakubowski, A. E. Cerussi, F. Bevilacqua, N. Shah, D. Hsiang, J. Butler, and B. J. Tromberg. "Monitoring neoadjuvant chemotherapy in breast cancer using quantitative diffuse optical spectroscopy: A case study," J. Biomed. Opt. 9, 230-238 (2004).
[CrossRef] [PubMed]

Campbell, L. E.

D. A. Boas, L. E. Campbell, and A. G. Yodh. "Scattering and imaging with diffusing temporal field correlations," Phys. Rev. Lett. 75, 1855-58 (1995).
[CrossRef] [PubMed]

Cerussi, A.

C. Zhou, R. Choe, N. Shah, T. Durduran, G. Q. Yu, A. Durkin, A. Cerussi, D. Hsiang, R. Mehta, 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, 051903 (2007).
[CrossRef] [PubMed]

Cerussi, A. E.

D. B. Jakubowski, A. E. Cerussi, F. Bevilacqua, N. Shah, D. Hsiang, J. Butler, and B. J. Tromberg. "Monitoring neoadjuvant chemotherapy in breast cancer using quantitative diffuse optical spectroscopy: A case study," J. Biomed. Opt. 9, 230-238 (2004).
[CrossRef] [PubMed]

Chaikin, P. M.

D. J. Pine, D. A. Weitz, P. M. Chaikin, and E. Herbolzheimer. "Diffusing wave spectroscopy," Phys. Rev. Lett. 60, 1134-1137 (1988).
[CrossRef] [PubMed]

Chalian, A. A

S. M. Evans, S. Hahn, D. R. Pook, W. T. Jenkins, A. A Chalian, P. Zhang, C. Stevens, R. Weber, G. Weinstein, I. Benjamin, N. Mirza, M. Morgan, S. Rubin,W. G. McKenna, E. M. Lord, and C. J. Koch. "Detection of hypoxia in human squamous cell carcinoma by EF5 binding," Cancer Res. 60, 2018-2024 (2000).
[PubMed]

Chance, B.

U. Sunar, H. Quon, T. Durduran, J. Zhang, J. Du, C. Zhou, G. Yu, R. Choe, A. Kilger, R. Lustig, L. Loevner, S. Nioka, B. Chance, and A.G. Yodh. "Noninvasive diffuse optical measurement of blood flow and blood oxygenation for monitoring radiation therapy in patients with head and neck tumors," J. Biomed. Opt. 11, 064021 (2006).
[CrossRef]

G. Yu, T. Durduran, G. Lech, C. Zhou, B. Chance, E. R. MohlerIII, and A. G. Yodh. "Time-dependent blood flow and oxygenation in human skeletal muscle measured by noninvasive near-infrared diffuse optical spectroscopies," J. Biomed. Opt. 10, 024027 (2005).
[CrossRef] [PubMed]

R. Choe, A. Corlu, K. Lee, T. Durduran, S. D. Konecky, M. Koptyra, S. R. Arridge, B. J. Czerniecki, D. L. Fraker, A. DeMichele, B. Chance, M. Rosen, and A. G. Yodh. "Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: A case study with comparison to MRI," Med. Phys. 32, 1-11 (2005).
[CrossRef]

Chaplin, D. J.

D. A. Beauregard, P. E. Thelwall, D. J. Chaplin, S. A. Hill, G. E. Adams, and K. M. Brindle. "Magnetic resonance imaging and spectroscopy of combretastatin A4 prodrug-induced disruption of tumour perfusion and energetic status," Br. J. Cancer 77, 1761-1767 (1998).
[CrossRef] [PubMed]

Chen, N. G.

Q. Zhu, S. H. Kurtzmany, P. Hegde, S. Tannenbaum, M. Kane, M. Huang, N. G. Chen, B. Jagjivan, and K. Zarfos. "Utilizing optical tomography with ultrasound localization to image heterogeneous hemoglobin distribution in large breast cancers," Neoplasia 7, 263-270 (2005).
[CrossRef] [PubMed]

Cheung, C.

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh. "Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia," J. Cereb. Blood Flow Metab. 23, 911-924 (2003).
[CrossRef] [PubMed]

C. Cheung, J. P. Culver, K. Takahashi, J. H. Greenberg, and A. G. Yodh. "In vivo cerebrovascular measurement combining diffuse near-infrared absorption and correlation spectroscopies," Phys. Med. Biol. 46, 2053-2065 (2001).
[CrossRef] [PubMed]

Choe, R.

C. Zhou, R. Choe, N. Shah, T. Durduran, G. Q. Yu, A. Durkin, A. Cerussi, D. Hsiang, R. Mehta, 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, 051903 (2007).
[CrossRef] [PubMed]

U. Sunar, H. Quon, T. Durduran, J. Zhang, J. Du, C. Zhou, G. Yu, R. Choe, A. Kilger, R. Lustig, L. Loevner, S. Nioka, B. Chance, and A.G. Yodh. "Noninvasive diffuse optical measurement of blood flow and blood oxygenation for monitoring radiation therapy in patients with head and neck tumors," J. Biomed. Opt. 11, 064021 (2006).
[CrossRef]

R. Choe, A. Corlu, K. Lee, T. Durduran, S. D. Konecky, M. Koptyra, S. R. Arridge, B. J. Czerniecki, D. L. Fraker, A. DeMichele, B. Chance, M. Rosen, and A. G. Yodh. "Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: A case study with comparison to MRI," Med. Phys. 32, 1-11 (2005).
[CrossRef]

T. Durduran, R. Choe, G. Yu, C. Zhou, J. C. Tchou, B. J. Czerniecki, and A. G. Yodh. "Diffuse optical measurement of blood flow in breast tumors," Opt. Lett. 30, 2915-2917 (2005).
[CrossRef] [PubMed]

Conant, E. F.

C. M. Sehgal, P. H. Arger, S. E. Rowling, E. F. Conant, C. Reynolds, and J. A. Patton. "Quantitative vascularity of breast masses by Doppler imaging: Regional variations and diagnostic implications," J. Ultrasound Med. 19, 427-440 (2000).
[PubMed]

Conger, A.D.

L.H. Gray, A.D. Conger, M. Ebert, S. Horsney, and O.C.A. Scott. "The concentration of oxygen dissolved in tissue at the time of irradiation as a factor in radiotherapy," Br. J. Radiol. 26, 638-42 (1953).
[CrossRef] [PubMed]

Corlu, A.

R. Choe, A. Corlu, K. Lee, T. Durduran, S. D. Konecky, M. Koptyra, S. R. Arridge, B. J. Czerniecki, D. L. Fraker, A. DeMichele, B. Chance, M. Rosen, and A. G. Yodh. "Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: A case study with comparison to MRI," Med. Phys. 32, 1-11 (2005).
[CrossRef]

Culver, J. P.

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh. "Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia," J. Cereb. Blood Flow Metab. 23, 911-924 (2003).
[CrossRef] [PubMed]

C. Cheung, J. P. Culver, K. Takahashi, J. H. Greenberg, and A. G. Yodh. "In vivo cerebrovascular measurement combining diffuse near-infrared absorption and correlation spectroscopies," Phys. Med. Biol. 46, 2053-2065 (2001).
[CrossRef] [PubMed]

Czerniecki, B. J.

T. Durduran, R. Choe, G. Yu, C. Zhou, J. C. Tchou, B. J. Czerniecki, and A. G. Yodh. "Diffuse optical measurement of blood flow in breast tumors," Opt. Lett. 30, 2915-2917 (2005).
[CrossRef] [PubMed]

R. Choe, A. Corlu, K. Lee, T. Durduran, S. D. Konecky, M. Koptyra, S. R. Arridge, B. J. Czerniecki, D. L. Fraker, A. DeMichele, B. Chance, M. Rosen, and A. G. Yodh. "Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: A case study with comparison to MRI," Med. Phys. 32, 1-11 (2005).
[CrossRef]

Daisuke, F.

Davis, C. S.

N. A. Mayr, W. T. Yuh, V. A. Magnotta, J. C. Ehrhardt, J. A. Wheeler, J. I. Sorosky, C. S. Davis, B. C. Wen, D. D. Martin, R. E. Pelsang, R. E. Buller, L.W. Oberley, D. E. Mellenberg, and D. H. Hussey. "Tumor perfusion studies using fast magnetic resonance imaging technique in advanced cervical cancer: a new noninvasive predictive assay," Int. J. Radiat. Oncol. Biol. Phys. 36, 623-633 (1996).
[CrossRef] [PubMed]

DeMichele, A.

R. Choe, A. Corlu, K. Lee, T. Durduran, S. D. Konecky, M. Koptyra, S. R. Arridge, B. J. Czerniecki, D. L. Fraker, A. DeMichele, B. Chance, M. Rosen, and A. G. Yodh. "Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: A case study with comparison to MRI," Med. Phys. 32, 1-11 (2005).
[CrossRef]

Detre, J. A.

DeVries, A. F.

A. F. DeVries, C. Kremser, P. A. Hein, J. Griebel, A. Krezcy, D. Ofner, K. P. Pfeiffer, P. Lukas, and W. Judmaier. "Tumor microcirculation and diffusion predict therapy outcome for primary rectal carcinoma," Int. J. Radiat. Oncol. Biol. Phys. 56, 958-965 (2003).
[CrossRef] [PubMed]

Dewhirst, M.W.

D.M. Brizel, G.S. Sibley, L.R. Prosnitz, R.L. Scher, and M.W. Dewhirst. "Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck," Int. J. Radiat. Oncol. Biol. Phys. 38, 285-289 (1997).
[CrossRef] [PubMed]

Dietsche, G.

J. Li, G. Dietsche, D. Iftime, S. E. Skipetrov, G. Maret, T. Elbert, B. Rockstroh, and T. Gisler. "Noninvasive detection of functional brain activity with near-infrared diffusing-wave spectroscopy," J. Biomed. Opt. 10, 44002 (2005).
[CrossRef] [PubMed]

Dimofte, A.

H.W. Wang, T. C. Zhu, M. E. Putt, M. Solonenko, J. Metz, A. Dimofte, J. Miles, D. L. Fraker, E. Glatstein, S. M. Hahn, and A. G. Yodh. "Broadband reflectance measurement of light penetration, blood oxygenation, hemoglobin concentration, and drug concentration in human intraperitoneal tissues before and after photodynamic therapy," J. Biomed. Opt. 10, 014004 (2005).
[CrossRef]

Du, J.

U. Sunar, H. Quon, T. Durduran, J. Zhang, J. Du, C. Zhou, G. Yu, R. Choe, A. Kilger, R. Lustig, L. Loevner, S. Nioka, B. Chance, and A.G. Yodh. "Noninvasive diffuse optical measurement of blood flow and blood oxygenation for monitoring radiation therapy in patients with head and neck tumors," J. Biomed. Opt. 11, 064021 (2006).
[CrossRef]

Durduran, T.

G. Yu, T. F. Floyd, T. Durduran, C. Zhou, J. J. Wang, J. A. Detre, and A. G. Yodh. "Validation of diffuse correlation spectroscopy for muscle blood flow with concurrent arterial spin labeled perfusion MRI," Opt. Express 15, 1064-1075 (2007).
[CrossRef] [PubMed]

C. Zhou, R. Choe, N. Shah, T. Durduran, G. Q. Yu, A. Durkin, A. Cerussi, D. Hsiang, R. Mehta, 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, 051903 (2007).
[CrossRef] [PubMed]

U. Sunar, H. Quon, T. Durduran, J. Zhang, J. Du, C. Zhou, G. Yu, R. Choe, A. Kilger, R. Lustig, L. Loevner, S. Nioka, B. Chance, and A.G. Yodh. "Noninvasive diffuse optical measurement of blood flow and blood oxygenation for monitoring radiation therapy in patients with head and neck tumors," J. Biomed. Opt. 11, 064021 (2006).
[CrossRef]

C. Zhou, G. Yu, F. Daisuke, J. H. Greenberg, A. G. Yodh, and T. Durduran. "Diffuse optical correlation tomography of cerebral blood flow during cortical spreading depression in rat brain," Opt. Express 14, 1125-1144 (2006).
[CrossRef] [PubMed]

G. Yu, T. Durduran, H. W. Wang, C. Zhou, H. M. Saunders, C. M. Sehgal, T. M. Busch, and A. G. Yodh. "Noninvasive monitoring of hemodynamic responses in RIF tumors during and after PDT," Clin. Cancer Res. 11, 3543-3552 (2005).
[CrossRef] [PubMed]

G. Yu, T. Durduran, G. Lech, C. Zhou, B. Chance, E. R. MohlerIII, and A. G. Yodh. "Time-dependent blood flow and oxygenation in human skeletal muscle measured by noninvasive near-infrared diffuse optical spectroscopies," J. Biomed. Opt. 10, 024027 (2005).
[CrossRef] [PubMed]

R. Choe, A. Corlu, K. Lee, T. Durduran, S. D. Konecky, M. Koptyra, S. R. Arridge, B. J. Czerniecki, D. L. Fraker, A. DeMichele, B. Chance, M. Rosen, and A. G. Yodh. "Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: A case study with comparison to MRI," Med. Phys. 32, 1-11 (2005).
[CrossRef]

T. Durduran, R. Choe, G. Yu, C. Zhou, J. C. Tchou, B. J. Czerniecki, and A. G. Yodh. "Diffuse optical measurement of blood flow in breast tumors," Opt. Lett. 30, 2915-2917 (2005).
[CrossRef] [PubMed]

T. Durduran, G. Yu, M. G. Burnett, J. A. Detre, J. H. Greenberg, J. Wang, C. Zhou, and A. G. Yodh. "Diffuse optical measurement of blood flow, blood oxygenation, and metabolism in a human brain during sensorimotor cortex activation," Opt. Lett. 29, 1766-1768 (2004).
[CrossRef] [PubMed]

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh. "Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia," J. Cereb. Blood Flow Metab. 23, 911-924 (2003).
[CrossRef] [PubMed]

Durkin, A.

C. Zhou, R. Choe, N. Shah, T. Durduran, G. Q. Yu, A. Durkin, A. Cerussi, D. Hsiang, R. Mehta, 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, 051903 (2007).
[CrossRef] [PubMed]

Ebert, M.

L.H. Gray, A.D. Conger, M. Ebert, S. Horsney, and O.C.A. Scott. "The concentration of oxygen dissolved in tissue at the time of irradiation as a factor in radiotherapy," Br. J. Radiol. 26, 638-42 (1953).
[CrossRef] [PubMed]

Ehrhardt, J. C.

N. A. Mayr, W. T. Yuh, V. A. Magnotta, J. C. Ehrhardt, J. A. Wheeler, J. I. Sorosky, C. S. Davis, B. C. Wen, D. D. Martin, R. E. Pelsang, R. E. Buller, L.W. Oberley, D. E. Mellenberg, and D. H. Hussey. "Tumor perfusion studies using fast magnetic resonance imaging technique in advanced cervical cancer: a new noninvasive predictive assay," Int. J. Radiat. Oncol. Biol. Phys. 36, 623-633 (1996).
[CrossRef] [PubMed]

Elbert, T.

J. Li, G. Dietsche, D. Iftime, S. E. Skipetrov, G. Maret, T. Elbert, B. Rockstroh, and T. Gisler. "Noninvasive detection of functional brain activity with near-infrared diffusing-wave spectroscopy," J. Biomed. Opt. 10, 44002 (2005).
[CrossRef] [PubMed]

Emanuele, M. J.

H. W. Wang, M. E. Putt, M. J. Emanuele, D. B. Shin, E. Glatstein, A. G. Yodh, and T. M. Busch. "Treatmentinduced changes in tumor oxygenation predict photodynamic therapy outcome," Cancer Res. 64, 7553-7561 (2004).
[CrossRef] [PubMed]

Evans, S. M.

S. M. Evans, S. Hahn, D. R. Pook, W. T. Jenkins, A. A Chalian, P. Zhang, C. Stevens, R. Weber, G. Weinstein, I. Benjamin, N. Mirza, M. Morgan, S. Rubin,W. G. McKenna, E. M. Lord, and C. J. Koch. "Detection of hypoxia in human squamous cell carcinoma by EF5 binding," Cancer Res. 60, 2018-2024 (2000).
[PubMed]

Farrell, T. J.

B. C. Wilson, T. J. Farrell, and M. S. Patterson. "An optical fiber-based diffuse reflectance spectrometer for non-invasive investigation of photodynamic sensitizers in vivo," Proc. SPIE 6, 219-232 (1990).

Feldman, M.

J.H. Tsai, S. Makonnen, M. Feldman, C.M. Sehgal, A. Maity, and W.M. Lee. "Ionizing radiation inhibits tumor neovascularization by inducing ineffective angiogenesis," Cancer Biol. Ther. 4, 1395-1400 (2005).
[CrossRef] [PubMed]

Floyd, T. F.

Foster, F. S.

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H.W. Wang, T. C. Zhu, M. E. Putt, M. Solonenko, J. Metz, A. Dimofte, J. Miles, D. L. Fraker, E. Glatstein, S. M. Hahn, and A. G. Yodh. "Broadband reflectance measurement of light penetration, blood oxygenation, hemoglobin concentration, and drug concentration in human intraperitoneal tissues before and after photodynamic therapy," J. Biomed. Opt. 10, 014004 (2005).
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J. Li, G. Dietsche, D. Iftime, S. E. Skipetrov, G. Maret, T. Elbert, B. Rockstroh, and T. Gisler. "Noninvasive detection of functional brain activity with near-infrared diffusing-wave spectroscopy," J. Biomed. Opt. 10, 44002 (2005).
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G. Yu, T. Durduran, G. Lech, C. Zhou, B. Chance, E. R. MohlerIII, and A. G. Yodh. "Time-dependent blood flow and oxygenation in human skeletal muscle measured by noninvasive near-infrared diffuse optical spectroscopies," J. Biomed. Opt. 10, 024027 (2005).
[CrossRef] [PubMed]

U. Sunar, H. Quon, T. Durduran, J. Zhang, J. Du, C. Zhou, G. Yu, R. Choe, A. Kilger, R. Lustig, L. Loevner, S. Nioka, B. Chance, and A.G. Yodh. "Noninvasive diffuse optical measurement of blood flow and blood oxygenation for monitoring radiation therapy in patients with head and neck tumors," J. Biomed. Opt. 11, 064021 (2006).
[CrossRef]

C. Zhou, R. Choe, N. Shah, T. Durduran, G. Q. Yu, A. Durkin, A. Cerussi, D. Hsiang, R. Mehta, 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, 051903 (2007).
[CrossRef] [PubMed]

D. B. Jakubowski, A. E. Cerussi, F. Bevilacqua, N. Shah, D. Hsiang, J. Butler, and B. J. Tromberg. "Monitoring neoadjuvant chemotherapy in breast cancer using quantitative diffuse optical spectroscopy: A case study," J. Biomed. Opt. 9, 230-238 (2004).
[CrossRef] [PubMed]

J. Cereb. Blood Flow Metab. (1)

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh. "Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia," J. Cereb. Blood Flow Metab. 23, 911-924 (2003).
[CrossRef] [PubMed]

J. Clin. Oncol. (2)

S. M. Galbraith, R. J. Maxwell, M. A. Lodge, G. M. Tozer, J. Wilson, N. J. Taylor, J. J. Stirling, L. Sena, A. R. Padhani, and G. J. S. Rustin. "Combretastatin A4 phosphate has tumor antivascular activity in rat and man as demonstrated by dynamic magnetic resonance imaging," J. Clin. Oncol. 21, 2831-2842 (2003).
[CrossRef] [PubMed]

H. L. Anderson, J. T. Yap, M. P. Miller, A. Robbins, T. Jones and P. M. Price. "Assessment of pharmacodynamic vascular response in a phase I trial of Combretastatin A4 Phosphate," J. Clin. Oncol. 21, 2823-2830 (2003).
[CrossRef] [PubMed]

J. Opt. Soc. Am. A (2)

J. Ultrasound Med. (1)

C. M. Sehgal, P. H. Arger, S. E. Rowling, E. F. Conant, C. Reynolds, and J. A. Patton. "Quantitative vascularity of breast masses by Doppler imaging: Regional variations and diagnostic implications," J. Ultrasound Med. 19, 427-440 (2000).
[PubMed]

Med. Phys. (1)

R. Choe, A. Corlu, K. Lee, T. Durduran, S. D. Konecky, M. Koptyra, S. R. Arridge, B. J. Czerniecki, D. L. Fraker, A. DeMichele, B. Chance, M. Rosen, and A. G. Yodh. "Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: A case study with comparison to MRI," Med. Phys. 32, 1-11 (2005).
[CrossRef]

Nat. Med. (1)

R. K. Jain. "Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy," Nat. Med. 7, 987-989 (2001).
[CrossRef] [PubMed]

Nat. Rev. Cancer (1)

R. K. Jain, L. L. Munn, and D. Fukumura. "Dissecting tumour pathophysiology using intravital microscopy," Nat. Rev. Cancer 2, 266-276 (2002).
[CrossRef] [PubMed]

Neoplasia (2)

Q. Zhu, S. H. Kurtzmany, P. Hegde, S. Tannenbaum, M. Kane, M. Huang, N. G. Chen, B. Jagjivan, and K. Zarfos. "Utilizing optical tomography with ultrasound localization to image heterogeneous hemoglobin distribution in large breast cancers," Neoplasia 7, 263-270 (2005).
[CrossRef] [PubMed]

M. Kragh, B. Quistorff, M. R. Horsman, and P. E. G. Kristjansen. "Acute effects of vascular modifying agents in solid tumors assessed by noninvasive laser Doppler flowmetry and near infrared spectroscopy," Neoplasia 4, 263-267 (2002).
[CrossRef] [PubMed]

Opt. Express (2)

Opt. Lett. (2)

Phys. Med. Biol. (1)

C. Cheung, J. P. Culver, K. Takahashi, J. H. Greenberg, and A. G. Yodh. "In vivo cerebrovascular measurement combining diffuse near-infrared absorption and correlation spectroscopies," Phys. Med. Biol. 46, 2053-2065 (2001).
[CrossRef] [PubMed]

Phys. Rev. Lett. (2)

D. J. Pine, D. A. Weitz, P. M. Chaikin, and E. Herbolzheimer. "Diffusing wave spectroscopy," Phys. Rev. Lett. 60, 1134-1137 (1988).
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D. A. Boas, L. E. Campbell, and A. G. Yodh. "Scattering and imaging with diffusing temporal field correlations," Phys. Rev. Lett. 75, 1855-58 (1995).
[CrossRef] [PubMed]

Proc. SPIE (1)

B. C. Wilson, T. J. Farrell, and M. S. Patterson. "An optical fiber-based diffuse reflectance spectrometer for non-invasive investigation of photodynamic sensitizers in vivo," Proc. SPIE 6, 219-232 (1990).

Radiat. Res. (1)

R. Murata, D.W. Siemann, J. Overgaard, and M. R. Horsman. "Improved tumor response by combining radiation and the vascular-damaging drug 5,6-dimethylxanthenone-4-acetic acid," Radiat. Res. 156, 503-509 (2001).
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Radiol. (1)

R.F. Kallman. "The phenomenon of reoxygenation and its implications for fractionated radiotherapy," Radiol. 105, 135-142 (1972).Q1

Radiother. Oncol. (3)

D.W. Siemann, K.H. Warrington, and M.R. Horsman. "Ionizing radiation inhibits tumor neovascularization by inducing ineffective angiogenesis," Radiother. Oncol. 57, 5-12 (2000).
[CrossRef] [PubMed]

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R. Murata, D.W. Siemann, J. Overgaard, and M. R. Horsman. "Interaction between combretastatin A-4 disodium phosphate and radiation in murine tumors," Radiother. Oncol. 60, 155-161 (2001).
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[CrossRef]

Other (5)

Turgut Durduran, "Noninvasive measurements of tissue hemodynamics with hybrid diffuse optical methods," Ph.D. Thesis, University of Pennsylvania (2004).

S. Prahl. "Optical properties spectra (webpage http://omlc.ogi.edu/spectra/index.html)," (2001).

A. G. Yodh and D. A. Boas, Biomedical Photonics (CRC Press, 2003). Chapter Functional Imaging with Diffusing Light.

Chao Zhou, "In vivo optical imaging and spectroscopy of cerebral hemodynamics," Ph.D. Thesis, University of Pennsylvania (2007).

B. J. Berne and R. Pecora. "Dynamic Light Scattering," (1976) (New York,Wiley).

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Figures (4)

Fig. 1.
Fig. 1.

(A) A representative DCS recording from a single animal showing the acute effects of the drug (in percent units with 100% implying no change).(B) DCS mean percent change in relative flow for N = 9 mice. (C) Effects of antivascular drug on tumor vasculature, imaged with micro-bubble contrast enhanced power Doppler ultrasound. In ultrasound images, yellow regions occur due to contrast enhancement in perfused blood vessels. Pretreatment tumor is uniformly perfused; (D) post treatment vasculature is destroyed, and blood perfusion is reduced. ٭ denotes p < .05, when compared to baseline value.

Fig. 2.
Fig. 2.

Histology showing untreated (control) and CA4P-treated tumor sections. (A) Untreated tumor, dark blue spots represent tumor cell nuclei. (B) 5 hours post-treatment, red spots represent red blood cells. (C) 10 times magnified version of (B). It is clearly seen that after treatment, vessel occlusion occurs, blood vessels become congested and cells coagulated, forming “blood cell lakes” (B and C).

Fig. 3.
Fig. 3.

(A) Mean percent change in StO 2(N = 5). (B) EF5 immunofluorescence shows no binding for the control mice, but binding (shown in red) in the treated tumors showing hypoxia is induced (C). ٭ denotes p < .05, when compared to baseline value.

Fig. 4.
Fig. 4.

(A) Average values of weekly rBF for both radiation treated mice and control groups (N = 8). Blood flow is normalized to initial (before radiation) value. ٭ denotes p < .05, when compared to baseline value. (B) Average values of weekly StO 2 for both radiation treated mice and control groups (N = 8). ٭ denotes p < .05, when compared to baseline value.

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