Abstract

Measurements of Cherenkov emission in tissue during radiation therapy are shown to enable estimation of hemoglobin oxygen saturation non-invasively, through spectral fitting of the spontaneous emissions from the treated tissue. Tissue oxygenation plays a critical role in the efficacy of radiation therapy to kill tumor tissue. Yet in-vivo measurement of this has remained elusive in routine use because of the complexity of oxygen measurement techniques. There is a spectrally broad emission of Cherenkov light that is induced during the time of irradiation, and as this travels through tissue from the point of the radiation deposition, the tissue absorption and scatter impart spectral changes. These changes can be quantified by diffuse spectral fitting of the signal. Thus Cherenkov emission spectroscopy is demonstrated for the first time quantitatively in vitro and qualitatively in vivo, and has potential for real-time online tracking of tissue oxygen during radiation therapy when fully characterized and developed.

© 2012 OSA

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2011 (1)

J. Axelsson, S. C. Davis, D. J. Gladstone, and B. W. Pogue, “Cerenkov emission induced by external beam radiation stimulates molecular fluorescence,” Med. Phys. 38(7), 4127–4132 (2011).
[CrossRef] [PubMed]

2010 (3)

H. Liu, G. Ren, Z. Miao, X. Zhang, X. Tang, P. Han, S. S. Gambhir, and Z. Cheng, “Molecular optical imaging with radioactive probes,” PLoS ONE 5(3), e9470 (2010).
[CrossRef] [PubMed]

A. E. Spinelli, D. D’Ambrosio, L. Calderan, M. Marengo, A. Sbarbati, and F. Boschi, “Cerenkov radiation allows in vivo optical imaging of positron emitting radiotracers,” Phys. Med. Biol. 55(2), 483–495 (2010).
[CrossRef] [PubMed]

M. A. Lewis, V. D. Kodibagkar, O. K. Oz, and R. P. Mason, “On the potential for molecular imaging with Cerenkov luminescence,” Opt. Lett. 35(23), 3889–3891 (2010).
[CrossRef] [PubMed]

2009 (3)

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, “Near infrared optical tomography using NIRFAST: Algorithm for numerical model and image reconstruction,” Commun. Numer. Methods Eng. 25(6), 711–732 (2009).
[CrossRef] [PubMed]

R. Robertson, M. S. Germanos, C. Li, G. S. Mitchell, S. R. Cherry, and M. D. Silva, “Optical imaging of Cerenkov light generation from positron-emitting radiotracers,” Phys. Med. Biol. 54(16), N355–N365 (2009).
[CrossRef] [PubMed]

K. Vishwanath, D. Klein, K. Chang, T. Schroeder, M. W. Dewhirst, and N. Ramanujam, “Quantitative optical spectroscopy can identify long-term local tumor control in irradiated murine head and neck xenografts,” J. Biomed. Opt. 14(5), 054051 (2009).
[CrossRef] [PubMed]

2007 (1)

2006 (1)

K. Newbold, M. Partridge, G. Cook, S. A. Sohaib, E. Charles-Edwards, P. Rhys-Evans, K. Harrington, and C. Nutting, “Advanced imaging applied to radiotherapy planning in head and neck cancer: a clinical review,” Br. J. Radiol. 79(943), 554–561 (2006).
[CrossRef] [PubMed]

2005 (3)

S. Srinivasan, B. W. Pogue, S. D. Jiang, H. Dehghani, and K. D. Paulsen, “Spectrally constrained chromophore and scattering near-infrared tomography provides quantitative and robust reconstruction,” Appl. Opt. 44(10), 1858–1869 (2005).
[CrossRef] [PubMed]

M. Nordsmark, S. M. Bentzen, V. Rudat, D. Brizel, E. Lartigau, P. Stadler, A. Becker, M. Adam, M. Molls, J. Dunst, D. J. Terris, and J. Overgaard, “Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study,” Radiother. Oncol. 77(1), 18–24 (2005).
[CrossRef] [PubMed]

G. Alexandrakis, F. R. Rannou, and A. F. Chatziioannou, “Tomographic bioluminescence imaging by use of a combined optical-PET (OPET) system: a computer simulation feasibility study,” Phys. Med. Biol. 50(17), 4225–4241 (2005).
[CrossRef] [PubMed]

2004 (1)

C. Baudelet and B. Gallez, “Effect of anesthesia on the signal intensity in tumors using BOLD-MRI: comparison with flow measurements by Laser Doppler flowmetry and oxygen measurements by luminescence-based probes,” Magn. Reson. Imaging 22(7), 905–912 (2004).
[CrossRef] [PubMed]

2003 (1)

S. M. Evans and C. J. Koch, “Prognostic significance of tumor oxygenation in humans,” Cancer Lett. 195(1), 1–16 (2003).
[CrossRef] [PubMed]

2001 (1)

K. S. Chao, W. R. Bosch, S. Mutic, J. S. Lewis, F. Dehdashti, M. A. Mintun, J. F. Dempsey, C. A. Perez, J. A. Purdy, and M. J. Welch, “A novel approach to overcome hypoxic tumor resistance: Cu-ATSM-guided intensity-modulated radiation therapy,” Int. J. Radiat. Oncol. Biol. Phys. 49(4), 1171–1182 (2001).
[CrossRef] [PubMed]

1999 (1)

R. A. Cooper, C. M. L. West, J. P. Logue, S. E. Davidson, A. Miller, S. Roberts, I. J. Statford, D. J. Honess, and R. D. Hunter, “Changes in oxygenation during radiotherapy in carcinoma of the cervix,”International Journal of Radiation. Oncology*. Biology*, Physics 45, 119–126 (1999).

1991 (1)

1979 (1)

J. W. Severinghaus, “Simple, accurate equations for human blood O2 dissociation computations,” J. Appl. Physiol. 46(3), 599–602 (1979).
[PubMed]

1973 (1)

1969 (1)

H. H. Ross, “Measurement of b-emitting nuclides using Cherenkov radiation,” Anal. Chem. 41(10), 1260–1265 (1969).
[CrossRef]

1953 (1)

L. H. Gray, A. D. Conger, M. Ebert, S. Hornsey, and O. C. Scott, “The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy,” Br. J. Radiol. 26(312), 638–648 (1953).
[CrossRef] [PubMed]

1937 (1)

I. E. Tamm and I. M. Frank, “Coherent radiation from a fast electron in a medium,” Dokl. Akad. Nauk SSSR 14, 107–112 (1937).

1934 (1)

P. Cherenkov, “Visible Emission of Clean Liquids by Action of $\gamma$ Radiation,” Dokl. Akad. Nauk SSSR 2, 451–454 (1934).

Adam, M.

M. Nordsmark, S. M. Bentzen, V. Rudat, D. Brizel, E. Lartigau, P. Stadler, A. Becker, M. Adam, M. Molls, J. Dunst, D. J. Terris, and J. Overgaard, “Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study,” Radiother. Oncol. 77(1), 18–24 (2005).
[CrossRef] [PubMed]

Alexandrakis, G.

G. Alexandrakis, F. R. Rannou, and A. F. Chatziioannou, “Tomographic bioluminescence imaging by use of a combined optical-PET (OPET) system: a computer simulation feasibility study,” Phys. Med. Biol. 50(17), 4225–4241 (2005).
[CrossRef] [PubMed]

Axelsson, J.

J. Axelsson, S. C. Davis, D. J. Gladstone, and B. W. Pogue, “Cerenkov emission induced by external beam radiation stimulates molecular fluorescence,” Med. Phys. 38(7), 4127–4132 (2011).
[CrossRef] [PubMed]

Baudelet, C.

C. Baudelet and B. Gallez, “Effect of anesthesia on the signal intensity in tumors using BOLD-MRI: comparison with flow measurements by Laser Doppler flowmetry and oxygen measurements by luminescence-based probes,” Magn. Reson. Imaging 22(7), 905–912 (2004).
[CrossRef] [PubMed]

Becker, A.

M. Nordsmark, S. M. Bentzen, V. Rudat, D. Brizel, E. Lartigau, P. Stadler, A. Becker, M. Adam, M. Molls, J. Dunst, D. J. Terris, and J. Overgaard, “Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study,” Radiother. Oncol. 77(1), 18–24 (2005).
[CrossRef] [PubMed]

Bentzen, S. M.

M. Nordsmark, S. M. Bentzen, V. Rudat, D. Brizel, E. Lartigau, P. Stadler, A. Becker, M. Adam, M. Molls, J. Dunst, D. J. Terris, and J. Overgaard, “Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study,” Radiother. Oncol. 77(1), 18–24 (2005).
[CrossRef] [PubMed]

Bosch, W. R.

K. S. Chao, W. R. Bosch, S. Mutic, J. S. Lewis, F. Dehdashti, M. A. Mintun, J. F. Dempsey, C. A. Perez, J. A. Purdy, and M. J. Welch, “A novel approach to overcome hypoxic tumor resistance: Cu-ATSM-guided intensity-modulated radiation therapy,” Int. J. Radiat. Oncol. Biol. Phys. 49(4), 1171–1182 (2001).
[CrossRef] [PubMed]

Boschi, F.

A. E. Spinelli, D. D’Ambrosio, L. Calderan, M. Marengo, A. Sbarbati, and F. Boschi, “Cerenkov radiation allows in vivo optical imaging of positron emitting radiotracers,” Phys. Med. Biol. 55(2), 483–495 (2010).
[CrossRef] [PubMed]

Brizel, D.

M. Nordsmark, S. M. Bentzen, V. Rudat, D. Brizel, E. Lartigau, P. Stadler, A. Becker, M. Adam, M. Molls, J. Dunst, D. J. Terris, and J. Overgaard, “Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study,” Radiother. Oncol. 77(1), 18–24 (2005).
[CrossRef] [PubMed]

Calderan, L.

A. E. Spinelli, D. D’Ambrosio, L. Calderan, M. Marengo, A. Sbarbati, and F. Boschi, “Cerenkov radiation allows in vivo optical imaging of positron emitting radiotracers,” Phys. Med. Biol. 55(2), 483–495 (2010).
[CrossRef] [PubMed]

Carpenter, C. M.

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, “Near infrared optical tomography using NIRFAST: Algorithm for numerical model and image reconstruction,” Commun. Numer. Methods Eng. 25(6), 711–732 (2009).
[CrossRef] [PubMed]

Chang, K.

K. Vishwanath, D. Klein, K. Chang, T. Schroeder, M. W. Dewhirst, and N. Ramanujam, “Quantitative optical spectroscopy can identify long-term local tumor control in irradiated murine head and neck xenografts,” J. Biomed. Opt. 14(5), 054051 (2009).
[CrossRef] [PubMed]

Chao, K. S.

K. S. Chao, W. R. Bosch, S. Mutic, J. S. Lewis, F. Dehdashti, M. A. Mintun, J. F. Dempsey, C. A. Perez, J. A. Purdy, and M. J. Welch, “A novel approach to overcome hypoxic tumor resistance: Cu-ATSM-guided intensity-modulated radiation therapy,” Int. J. Radiat. Oncol. Biol. Phys. 49(4), 1171–1182 (2001).
[CrossRef] [PubMed]

Charles-Edwards, E.

K. Newbold, M. Partridge, G. Cook, S. A. Sohaib, E. Charles-Edwards, P. Rhys-Evans, K. Harrington, and C. Nutting, “Advanced imaging applied to radiotherapy planning in head and neck cancer: a clinical review,” Br. J. Radiol. 79(943), 554–561 (2006).
[CrossRef] [PubMed]

Chatziioannou, A. F.

G. Alexandrakis, F. R. Rannou, and A. F. Chatziioannou, “Tomographic bioluminescence imaging by use of a combined optical-PET (OPET) system: a computer simulation feasibility study,” Phys. Med. Biol. 50(17), 4225–4241 (2005).
[CrossRef] [PubMed]

Cheng, Z.

H. Liu, G. Ren, Z. Miao, X. Zhang, X. Tang, P. Han, S. S. Gambhir, and Z. Cheng, “Molecular optical imaging with radioactive probes,” PLoS ONE 5(3), e9470 (2010).
[CrossRef] [PubMed]

Cherenkov, P.

P. Cherenkov, “Visible Emission of Clean Liquids by Action of $\gamma$ Radiation,” Dokl. Akad. Nauk SSSR 2, 451–454 (1934).

Cherry, S. R.

R. Robertson, M. S. Germanos, C. Li, G. S. Mitchell, S. R. Cherry, and M. D. Silva, “Optical imaging of Cerenkov light generation from positron-emitting radiotracers,” Phys. Med. Biol. 54(16), N355–N365 (2009).
[CrossRef] [PubMed]

Conger, A. D.

L. H. Gray, A. D. Conger, M. Ebert, S. Hornsey, and O. C. Scott, “The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy,” Br. J. Radiol. 26(312), 638–648 (1953).
[CrossRef] [PubMed]

Cook, G.

K. Newbold, M. Partridge, G. Cook, S. A. Sohaib, E. Charles-Edwards, P. Rhys-Evans, K. Harrington, and C. Nutting, “Advanced imaging applied to radiotherapy planning in head and neck cancer: a clinical review,” Br. J. Radiol. 79(943), 554–561 (2006).
[CrossRef] [PubMed]

Cooper, R. A.

R. A. Cooper, C. M. L. West, J. P. Logue, S. E. Davidson, A. Miller, S. Roberts, I. J. Statford, D. J. Honess, and R. D. Hunter, “Changes in oxygenation during radiotherapy in carcinoma of the cervix,”International Journal of Radiation. Oncology*. Biology*, Physics 45, 119–126 (1999).

D’Ambrosio, D.

A. E. Spinelli, D. D’Ambrosio, L. Calderan, M. Marengo, A. Sbarbati, and F. Boschi, “Cerenkov radiation allows in vivo optical imaging of positron emitting radiotracers,” Phys. Med. Biol. 55(2), 483–495 (2010).
[CrossRef] [PubMed]

Davidson, S. E.

R. A. Cooper, C. M. L. West, J. P. Logue, S. E. Davidson, A. Miller, S. Roberts, I. J. Statford, D. J. Honess, and R. D. Hunter, “Changes in oxygenation during radiotherapy in carcinoma of the cervix,”International Journal of Radiation. Oncology*. Biology*, Physics 45, 119–126 (1999).

Davis, S. C.

J. Axelsson, S. C. Davis, D. J. Gladstone, and B. W. Pogue, “Cerenkov emission induced by external beam radiation stimulates molecular fluorescence,” Med. Phys. 38(7), 4127–4132 (2011).
[CrossRef] [PubMed]

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, “Near infrared optical tomography using NIRFAST: Algorithm for numerical model and image reconstruction,” Commun. Numer. Methods Eng. 25(6), 711–732 (2009).
[CrossRef] [PubMed]

Dehdashti, F.

K. S. Chao, W. R. Bosch, S. Mutic, J. S. Lewis, F. Dehdashti, M. A. Mintun, J. F. Dempsey, C. A. Perez, J. A. Purdy, and M. J. Welch, “A novel approach to overcome hypoxic tumor resistance: Cu-ATSM-guided intensity-modulated radiation therapy,” Int. J. Radiat. Oncol. Biol. Phys. 49(4), 1171–1182 (2001).
[CrossRef] [PubMed]

Dehghani, H.

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, “Near infrared optical tomography using NIRFAST: Algorithm for numerical model and image reconstruction,” Commun. Numer. Methods Eng. 25(6), 711–732 (2009).
[CrossRef] [PubMed]

S. Srinivasan, B. W. Pogue, S. D. Jiang, H. Dehghani, and K. D. Paulsen, “Spectrally constrained chromophore and scattering near-infrared tomography provides quantitative and robust reconstruction,” Appl. Opt. 44(10), 1858–1869 (2005).
[CrossRef] [PubMed]

Dempsey, J. F.

K. S. Chao, W. R. Bosch, S. Mutic, J. S. Lewis, F. Dehdashti, M. A. Mintun, J. F. Dempsey, C. A. Perez, J. A. Purdy, and M. J. Welch, “A novel approach to overcome hypoxic tumor resistance: Cu-ATSM-guided intensity-modulated radiation therapy,” Int. J. Radiat. Oncol. Biol. Phys. 49(4), 1171–1182 (2001).
[CrossRef] [PubMed]

Dewhirst, M. W.

K. Vishwanath, D. Klein, K. Chang, T. Schroeder, M. W. Dewhirst, and N. Ramanujam, “Quantitative optical spectroscopy can identify long-term local tumor control in irradiated murine head and neck xenografts,” J. Biomed. Opt. 14(5), 054051 (2009).
[CrossRef] [PubMed]

Dunst, J.

M. Nordsmark, S. M. Bentzen, V. Rudat, D. Brizel, E. Lartigau, P. Stadler, A. Becker, M. Adam, M. Molls, J. Dunst, D. J. Terris, and J. Overgaard, “Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study,” Radiother. Oncol. 77(1), 18–24 (2005).
[CrossRef] [PubMed]

Eames, M. E.

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, “Near infrared optical tomography using NIRFAST: Algorithm for numerical model and image reconstruction,” Commun. Numer. Methods Eng. 25(6), 711–732 (2009).
[CrossRef] [PubMed]

Ebert, M.

L. H. Gray, A. D. Conger, M. Ebert, S. Hornsey, and O. C. Scott, “The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy,” Br. J. Radiol. 26(312), 638–648 (1953).
[CrossRef] [PubMed]

Evans, S. M.

S. M. Evans and C. J. Koch, “Prognostic significance of tumor oxygenation in humans,” Cancer Lett. 195(1), 1–16 (2003).
[CrossRef] [PubMed]

Fleming, S. C.

Frank, I. M.

I. E. Tamm and I. M. Frank, “Coherent radiation from a fast electron in a medium,” Dokl. Akad. Nauk SSSR 14, 107–112 (1937).

Gallez, B.

C. Baudelet and B. Gallez, “Effect of anesthesia on the signal intensity in tumors using BOLD-MRI: comparison with flow measurements by Laser Doppler flowmetry and oxygen measurements by luminescence-based probes,” Magn. Reson. Imaging 22(7), 905–912 (2004).
[CrossRef] [PubMed]

Gambhir, S. S.

H. Liu, G. Ren, Z. Miao, X. Zhang, X. Tang, P. Han, S. S. Gambhir, and Z. Cheng, “Molecular optical imaging with radioactive probes,” PLoS ONE 5(3), e9470 (2010).
[CrossRef] [PubMed]

Germanos, M. S.

R. Robertson, M. S. Germanos, C. Li, G. S. Mitchell, S. R. Cherry, and M. D. Silva, “Optical imaging of Cerenkov light generation from positron-emitting radiotracers,” Phys. Med. Biol. 54(16), N355–N365 (2009).
[CrossRef] [PubMed]

Gladstone, D. J.

J. Axelsson, S. C. Davis, D. J. Gladstone, and B. W. Pogue, “Cerenkov emission induced by external beam radiation stimulates molecular fluorescence,” Med. Phys. 38(7), 4127–4132 (2011).
[CrossRef] [PubMed]

Gray, L. H.

L. H. Gray, A. D. Conger, M. Ebert, S. Hornsey, and O. C. Scott, “The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy,” Br. J. Radiol. 26(312), 638–648 (1953).
[CrossRef] [PubMed]

Hale, G. M.

Han, P.

H. Liu, G. Ren, Z. Miao, X. Zhang, X. Tang, P. Han, S. S. Gambhir, and Z. Cheng, “Molecular optical imaging with radioactive probes,” PLoS ONE 5(3), e9470 (2010).
[CrossRef] [PubMed]

Harrington, K.

K. Newbold, M. Partridge, G. Cook, S. A. Sohaib, E. Charles-Edwards, P. Rhys-Evans, K. Harrington, and C. Nutting, “Advanced imaging applied to radiotherapy planning in head and neck cancer: a clinical review,” Br. J. Radiol. 79(943), 554–561 (2006).
[CrossRef] [PubMed]

Honess, D. J.

R. A. Cooper, C. M. L. West, J. P. Logue, S. E. Davidson, A. Miller, S. Roberts, I. J. Statford, D. J. Honess, and R. D. Hunter, “Changes in oxygenation during radiotherapy in carcinoma of the cervix,”International Journal of Radiation. Oncology*. Biology*, Physics 45, 119–126 (1999).

Hornsey, S.

L. H. Gray, A. D. Conger, M. Ebert, S. Hornsey, and O. C. Scott, “The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy,” Br. J. Radiol. 26(312), 638–648 (1953).
[CrossRef] [PubMed]

Hunter, R. D.

R. A. Cooper, C. M. L. West, J. P. Logue, S. E. Davidson, A. Miller, S. Roberts, I. J. Statford, D. J. Honess, and R. D. Hunter, “Changes in oxygenation during radiotherapy in carcinoma of the cervix,”International Journal of Radiation. Oncology*. Biology*, Physics 45, 119–126 (1999).

Jiang, S. D.

Klein, D.

K. Vishwanath, D. Klein, K. Chang, T. Schroeder, M. W. Dewhirst, and N. Ramanujam, “Quantitative optical spectroscopy can identify long-term local tumor control in irradiated murine head and neck xenografts,” J. Biomed. Opt. 14(5), 054051 (2009).
[CrossRef] [PubMed]

Koch, C. J.

S. M. Evans and C. J. Koch, “Prognostic significance of tumor oxygenation in humans,” Cancer Lett. 195(1), 1–16 (2003).
[CrossRef] [PubMed]

Kodibagkar, V. D.

Lartigau, E.

M. Nordsmark, S. M. Bentzen, V. Rudat, D. Brizel, E. Lartigau, P. Stadler, A. Becker, M. Adam, M. Molls, J. Dunst, D. J. Terris, and J. Overgaard, “Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study,” Radiother. Oncol. 77(1), 18–24 (2005).
[CrossRef] [PubMed]

Law, S. H.

Lewis, J. S.

K. S. Chao, W. R. Bosch, S. Mutic, J. S. Lewis, F. Dehdashti, M. A. Mintun, J. F. Dempsey, C. A. Perez, J. A. Purdy, and M. J. Welch, “A novel approach to overcome hypoxic tumor resistance: Cu-ATSM-guided intensity-modulated radiation therapy,” Int. J. Radiat. Oncol. Biol. Phys. 49(4), 1171–1182 (2001).
[CrossRef] [PubMed]

Lewis, M. A.

Li, C.

R. Robertson, M. S. Germanos, C. Li, G. S. Mitchell, S. R. Cherry, and M. D. Silva, “Optical imaging of Cerenkov light generation from positron-emitting radiotracers,” Phys. Med. Biol. 54(16), N355–N365 (2009).
[CrossRef] [PubMed]

Lin, T.

Liu, H.

H. Liu, G. Ren, Z. Miao, X. Zhang, X. Tang, P. Han, S. S. Gambhir, and Z. Cheng, “Molecular optical imaging with radioactive probes,” PLoS ONE 5(3), e9470 (2010).
[CrossRef] [PubMed]

Logue, J. P.

R. A. Cooper, C. M. L. West, J. P. Logue, S. E. Davidson, A. Miller, S. Roberts, I. J. Statford, D. J. Honess, and R. D. Hunter, “Changes in oxygenation during radiotherapy in carcinoma of the cervix,”International Journal of Radiation. Oncology*. Biology*, Physics 45, 119–126 (1999).

Marengo, M.

A. E. Spinelli, D. D’Ambrosio, L. Calderan, M. Marengo, A. Sbarbati, and F. Boschi, “Cerenkov radiation allows in vivo optical imaging of positron emitting radiotracers,” Phys. Med. Biol. 55(2), 483–495 (2010).
[CrossRef] [PubMed]

Mason, R. P.

McKenzie, D. R.

Miao, Z.

H. Liu, G. Ren, Z. Miao, X. Zhang, X. Tang, P. Han, S. S. Gambhir, and Z. Cheng, “Molecular optical imaging with radioactive probes,” PLoS ONE 5(3), e9470 (2010).
[CrossRef] [PubMed]

Miller, A.

R. A. Cooper, C. M. L. West, J. P. Logue, S. E. Davidson, A. Miller, S. Roberts, I. J. Statford, D. J. Honess, and R. D. Hunter, “Changes in oxygenation during radiotherapy in carcinoma of the cervix,”International Journal of Radiation. Oncology*. Biology*, Physics 45, 119–126 (1999).

Mintun, M. A.

K. S. Chao, W. R. Bosch, S. Mutic, J. S. Lewis, F. Dehdashti, M. A. Mintun, J. F. Dempsey, C. A. Perez, J. A. Purdy, and M. J. Welch, “A novel approach to overcome hypoxic tumor resistance: Cu-ATSM-guided intensity-modulated radiation therapy,” Int. J. Radiat. Oncol. Biol. Phys. 49(4), 1171–1182 (2001).
[CrossRef] [PubMed]

Mitchell, G. S.

R. Robertson, M. S. Germanos, C. Li, G. S. Mitchell, S. R. Cherry, and M. D. Silva, “Optical imaging of Cerenkov light generation from positron-emitting radiotracers,” Phys. Med. Biol. 54(16), N355–N365 (2009).
[CrossRef] [PubMed]

Moes, C. J. M.

Molls, M.

M. Nordsmark, S. M. Bentzen, V. Rudat, D. Brizel, E. Lartigau, P. Stadler, A. Becker, M. Adam, M. Molls, J. Dunst, D. J. Terris, and J. Overgaard, “Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study,” Radiother. Oncol. 77(1), 18–24 (2005).
[CrossRef] [PubMed]

Mutic, S.

K. S. Chao, W. R. Bosch, S. Mutic, J. S. Lewis, F. Dehdashti, M. A. Mintun, J. F. Dempsey, C. A. Perez, J. A. Purdy, and M. J. Welch, “A novel approach to overcome hypoxic tumor resistance: Cu-ATSM-guided intensity-modulated radiation therapy,” Int. J. Radiat. Oncol. Biol. Phys. 49(4), 1171–1182 (2001).
[CrossRef] [PubMed]

Newbold, K.

K. Newbold, M. Partridge, G. Cook, S. A. Sohaib, E. Charles-Edwards, P. Rhys-Evans, K. Harrington, and C. Nutting, “Advanced imaging applied to radiotherapy planning in head and neck cancer: a clinical review,” Br. J. Radiol. 79(943), 554–561 (2006).
[CrossRef] [PubMed]

Nordsmark, M.

M. Nordsmark, S. M. Bentzen, V. Rudat, D. Brizel, E. Lartigau, P. Stadler, A. Becker, M. Adam, M. Molls, J. Dunst, D. J. Terris, and J. Overgaard, “Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study,” Radiother. Oncol. 77(1), 18–24 (2005).
[CrossRef] [PubMed]

Nutting, C.

K. Newbold, M. Partridge, G. Cook, S. A. Sohaib, E. Charles-Edwards, P. Rhys-Evans, K. Harrington, and C. Nutting, “Advanced imaging applied to radiotherapy planning in head and neck cancer: a clinical review,” Br. J. Radiol. 79(943), 554–561 (2006).
[CrossRef] [PubMed]

Overgaard, J.

M. Nordsmark, S. M. Bentzen, V. Rudat, D. Brizel, E. Lartigau, P. Stadler, A. Becker, M. Adam, M. Molls, J. Dunst, D. J. Terris, and J. Overgaard, “Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study,” Radiother. Oncol. 77(1), 18–24 (2005).
[CrossRef] [PubMed]

Oz, O. K.

Partridge, M.

K. Newbold, M. Partridge, G. Cook, S. A. Sohaib, E. Charles-Edwards, P. Rhys-Evans, K. Harrington, and C. Nutting, “Advanced imaging applied to radiotherapy planning in head and neck cancer: a clinical review,” Br. J. Radiol. 79(943), 554–561 (2006).
[CrossRef] [PubMed]

Paulsen, K. D.

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, “Near infrared optical tomography using NIRFAST: Algorithm for numerical model and image reconstruction,” Commun. Numer. Methods Eng. 25(6), 711–732 (2009).
[CrossRef] [PubMed]

S. Srinivasan, B. W. Pogue, S. D. Jiang, H. Dehghani, and K. D. Paulsen, “Spectrally constrained chromophore and scattering near-infrared tomography provides quantitative and robust reconstruction,” Appl. Opt. 44(10), 1858–1869 (2005).
[CrossRef] [PubMed]

Perez, C. A.

K. S. Chao, W. R. Bosch, S. Mutic, J. S. Lewis, F. Dehdashti, M. A. Mintun, J. F. Dempsey, C. A. Perez, J. A. Purdy, and M. J. Welch, “A novel approach to overcome hypoxic tumor resistance: Cu-ATSM-guided intensity-modulated radiation therapy,” Int. J. Radiat. Oncol. Biol. Phys. 49(4), 1171–1182 (2001).
[CrossRef] [PubMed]

Pogue, B. W.

J. Axelsson, S. C. Davis, D. J. Gladstone, and B. W. Pogue, “Cerenkov emission induced by external beam radiation stimulates molecular fluorescence,” Med. Phys. 38(7), 4127–4132 (2011).
[CrossRef] [PubMed]

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, “Near infrared optical tomography using NIRFAST: Algorithm for numerical model and image reconstruction,” Commun. Numer. Methods Eng. 25(6), 711–732 (2009).
[CrossRef] [PubMed]

S. Srinivasan, B. W. Pogue, S. D. Jiang, H. Dehghani, and K. D. Paulsen, “Spectrally constrained chromophore and scattering near-infrared tomography provides quantitative and robust reconstruction,” Appl. Opt. 44(10), 1858–1869 (2005).
[CrossRef] [PubMed]

Prahl, S. A.

Purdy, J. A.

K. S. Chao, W. R. Bosch, S. Mutic, J. S. Lewis, F. Dehdashti, M. A. Mintun, J. F. Dempsey, C. A. Perez, J. A. Purdy, and M. J. Welch, “A novel approach to overcome hypoxic tumor resistance: Cu-ATSM-guided intensity-modulated radiation therapy,” Int. J. Radiat. Oncol. Biol. Phys. 49(4), 1171–1182 (2001).
[CrossRef] [PubMed]

Querry, M. R.

Ramanujam, N.

K. Vishwanath, D. Klein, K. Chang, T. Schroeder, M. W. Dewhirst, and N. Ramanujam, “Quantitative optical spectroscopy can identify long-term local tumor control in irradiated murine head and neck xenografts,” J. Biomed. Opt. 14(5), 054051 (2009).
[CrossRef] [PubMed]

Rannou, F. R.

G. Alexandrakis, F. R. Rannou, and A. F. Chatziioannou, “Tomographic bioluminescence imaging by use of a combined optical-PET (OPET) system: a computer simulation feasibility study,” Phys. Med. Biol. 50(17), 4225–4241 (2005).
[CrossRef] [PubMed]

Ren, G.

H. Liu, G. Ren, Z. Miao, X. Zhang, X. Tang, P. Han, S. S. Gambhir, and Z. Cheng, “Molecular optical imaging with radioactive probes,” PLoS ONE 5(3), e9470 (2010).
[CrossRef] [PubMed]

Rhys-Evans, P.

K. Newbold, M. Partridge, G. Cook, S. A. Sohaib, E. Charles-Edwards, P. Rhys-Evans, K. Harrington, and C. Nutting, “Advanced imaging applied to radiotherapy planning in head and neck cancer: a clinical review,” Br. J. Radiol. 79(943), 554–561 (2006).
[CrossRef] [PubMed]

Roberts, S.

R. A. Cooper, C. M. L. West, J. P. Logue, S. E. Davidson, A. Miller, S. Roberts, I. J. Statford, D. J. Honess, and R. D. Hunter, “Changes in oxygenation during radiotherapy in carcinoma of the cervix,”International Journal of Radiation. Oncology*. Biology*, Physics 45, 119–126 (1999).

Robertson, R.

R. Robertson, M. S. Germanos, C. Li, G. S. Mitchell, S. R. Cherry, and M. D. Silva, “Optical imaging of Cerenkov light generation from positron-emitting radiotracers,” Phys. Med. Biol. 54(16), N355–N365 (2009).
[CrossRef] [PubMed]

Ross, H. H.

H. H. Ross, “Measurement of b-emitting nuclides using Cherenkov radiation,” Anal. Chem. 41(10), 1260–1265 (1969).
[CrossRef]

Rudat, V.

M. Nordsmark, S. M. Bentzen, V. Rudat, D. Brizel, E. Lartigau, P. Stadler, A. Becker, M. Adam, M. Molls, J. Dunst, D. J. Terris, and J. Overgaard, “Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study,” Radiother. Oncol. 77(1), 18–24 (2005).
[CrossRef] [PubMed]

Sbarbati, A.

A. E. Spinelli, D. D’Ambrosio, L. Calderan, M. Marengo, A. Sbarbati, and F. Boschi, “Cerenkov radiation allows in vivo optical imaging of positron emitting radiotracers,” Phys. Med. Biol. 55(2), 483–495 (2010).
[CrossRef] [PubMed]

Schroeder, T.

K. Vishwanath, D. Klein, K. Chang, T. Schroeder, M. W. Dewhirst, and N. Ramanujam, “Quantitative optical spectroscopy can identify long-term local tumor control in irradiated murine head and neck xenografts,” J. Biomed. Opt. 14(5), 054051 (2009).
[CrossRef] [PubMed]

Scott, O. C.

L. H. Gray, A. D. Conger, M. Ebert, S. Hornsey, and O. C. Scott, “The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy,” Br. J. Radiol. 26(312), 638–648 (1953).
[CrossRef] [PubMed]

Severinghaus, J. W.

J. W. Severinghaus, “Simple, accurate equations for human blood O2 dissociation computations,” J. Appl. Physiol. 46(3), 599–602 (1979).
[PubMed]

Silva, M. D.

R. Robertson, M. S. Germanos, C. Li, G. S. Mitchell, S. R. Cherry, and M. D. Silva, “Optical imaging of Cerenkov light generation from positron-emitting radiotracers,” Phys. Med. Biol. 54(16), N355–N365 (2009).
[CrossRef] [PubMed]

Sohaib, S. A.

K. Newbold, M. Partridge, G. Cook, S. A. Sohaib, E. Charles-Edwards, P. Rhys-Evans, K. Harrington, and C. Nutting, “Advanced imaging applied to radiotherapy planning in head and neck cancer: a clinical review,” Br. J. Radiol. 79(943), 554–561 (2006).
[CrossRef] [PubMed]

Spinelli, A. E.

A. E. Spinelli, D. D’Ambrosio, L. Calderan, M. Marengo, A. Sbarbati, and F. Boschi, “Cerenkov radiation allows in vivo optical imaging of positron emitting radiotracers,” Phys. Med. Biol. 55(2), 483–495 (2010).
[CrossRef] [PubMed]

Srinivasan, S.

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, “Near infrared optical tomography using NIRFAST: Algorithm for numerical model and image reconstruction,” Commun. Numer. Methods Eng. 25(6), 711–732 (2009).
[CrossRef] [PubMed]

S. Srinivasan, B. W. Pogue, S. D. Jiang, H. Dehghani, and K. D. Paulsen, “Spectrally constrained chromophore and scattering near-infrared tomography provides quantitative and robust reconstruction,” Appl. Opt. 44(10), 1858–1869 (2005).
[CrossRef] [PubMed]

Stadler, P.

M. Nordsmark, S. M. Bentzen, V. Rudat, D. Brizel, E. Lartigau, P. Stadler, A. Becker, M. Adam, M. Molls, J. Dunst, D. J. Terris, and J. Overgaard, “Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study,” Radiother. Oncol. 77(1), 18–24 (2005).
[CrossRef] [PubMed]

Statford, I. J.

R. A. Cooper, C. M. L. West, J. P. Logue, S. E. Davidson, A. Miller, S. Roberts, I. J. Statford, D. J. Honess, and R. D. Hunter, “Changes in oxygenation during radiotherapy in carcinoma of the cervix,”International Journal of Radiation. Oncology*. Biology*, Physics 45, 119–126 (1999).

Suchowerska, N.

Tamm, I. E.

I. E. Tamm and I. M. Frank, “Coherent radiation from a fast electron in a medium,” Dokl. Akad. Nauk SSSR 14, 107–112 (1937).

Tang, X.

H. Liu, G. Ren, Z. Miao, X. Zhang, X. Tang, P. Han, S. S. Gambhir, and Z. Cheng, “Molecular optical imaging with radioactive probes,” PLoS ONE 5(3), e9470 (2010).
[CrossRef] [PubMed]

Terris, D. J.

M. Nordsmark, S. M. Bentzen, V. Rudat, D. Brizel, E. Lartigau, P. Stadler, A. Becker, M. Adam, M. Molls, J. Dunst, D. J. Terris, and J. Overgaard, “Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study,” Radiother. Oncol. 77(1), 18–24 (2005).
[CrossRef] [PubMed]

van Gemert, M. J. C.

van Marie, J.

van Staveren, H. J.

Vishwanath, K.

K. Vishwanath, D. Klein, K. Chang, T. Schroeder, M. W. Dewhirst, and N. Ramanujam, “Quantitative optical spectroscopy can identify long-term local tumor control in irradiated murine head and neck xenografts,” J. Biomed. Opt. 14(5), 054051 (2009).
[CrossRef] [PubMed]

Welch, M. J.

K. S. Chao, W. R. Bosch, S. Mutic, J. S. Lewis, F. Dehdashti, M. A. Mintun, J. F. Dempsey, C. A. Perez, J. A. Purdy, and M. J. Welch, “A novel approach to overcome hypoxic tumor resistance: Cu-ATSM-guided intensity-modulated radiation therapy,” Int. J. Radiat. Oncol. Biol. Phys. 49(4), 1171–1182 (2001).
[CrossRef] [PubMed]

West, C. M. L.

R. A. Cooper, C. M. L. West, J. P. Logue, S. E. Davidson, A. Miller, S. Roberts, I. J. Statford, D. J. Honess, and R. D. Hunter, “Changes in oxygenation during radiotherapy in carcinoma of the cervix,”International Journal of Radiation. Oncology*. Biology*, Physics 45, 119–126 (1999).

Yalavarthy, P. K.

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, “Near infrared optical tomography using NIRFAST: Algorithm for numerical model and image reconstruction,” Commun. Numer. Methods Eng. 25(6), 711–732 (2009).
[CrossRef] [PubMed]

Zhang, X.

H. Liu, G. Ren, Z. Miao, X. Zhang, X. Tang, P. Han, S. S. Gambhir, and Z. Cheng, “Molecular optical imaging with radioactive probes,” PLoS ONE 5(3), e9470 (2010).
[CrossRef] [PubMed]

Anal. Chem. (1)

H. H. Ross, “Measurement of b-emitting nuclides using Cherenkov radiation,” Anal. Chem. 41(10), 1260–1265 (1969).
[CrossRef]

Appl. Opt. (3)

Br. J. Radiol. (2)

K. Newbold, M. Partridge, G. Cook, S. A. Sohaib, E. Charles-Edwards, P. Rhys-Evans, K. Harrington, and C. Nutting, “Advanced imaging applied to radiotherapy planning in head and neck cancer: a clinical review,” Br. J. Radiol. 79(943), 554–561 (2006).
[CrossRef] [PubMed]

L. H. Gray, A. D. Conger, M. Ebert, S. Hornsey, and O. C. Scott, “The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy,” Br. J. Radiol. 26(312), 638–648 (1953).
[CrossRef] [PubMed]

Cancer Lett. (1)

S. M. Evans and C. J. Koch, “Prognostic significance of tumor oxygenation in humans,” Cancer Lett. 195(1), 1–16 (2003).
[CrossRef] [PubMed]

Commun. Numer. Methods Eng. (1)

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, “Near infrared optical tomography using NIRFAST: Algorithm for numerical model and image reconstruction,” Commun. Numer. Methods Eng. 25(6), 711–732 (2009).
[CrossRef] [PubMed]

Dokl. Akad. Nauk SSSR (2)

P. Cherenkov, “Visible Emission of Clean Liquids by Action of $\gamma$ Radiation,” Dokl. Akad. Nauk SSSR 2, 451–454 (1934).

I. E. Tamm and I. M. Frank, “Coherent radiation from a fast electron in a medium,” Dokl. Akad. Nauk SSSR 14, 107–112 (1937).

Int. J. Radiat. Oncol. Biol. Phys. (1)

K. S. Chao, W. R. Bosch, S. Mutic, J. S. Lewis, F. Dehdashti, M. A. Mintun, J. F. Dempsey, C. A. Perez, J. A. Purdy, and M. J. Welch, “A novel approach to overcome hypoxic tumor resistance: Cu-ATSM-guided intensity-modulated radiation therapy,” Int. J. Radiat. Oncol. Biol. Phys. 49(4), 1171–1182 (2001).
[CrossRef] [PubMed]

International Journal of Radiation. Oncology*. Biology*, Physics (1)

R. A. Cooper, C. M. L. West, J. P. Logue, S. E. Davidson, A. Miller, S. Roberts, I. J. Statford, D. J. Honess, and R. D. Hunter, “Changes in oxygenation during radiotherapy in carcinoma of the cervix,”International Journal of Radiation. Oncology*. Biology*, Physics 45, 119–126 (1999).

J. Appl. Physiol. (1)

J. W. Severinghaus, “Simple, accurate equations for human blood O2 dissociation computations,” J. Appl. Physiol. 46(3), 599–602 (1979).
[PubMed]

J. Biomed. Opt. (1)

K. Vishwanath, D. Klein, K. Chang, T. Schroeder, M. W. Dewhirst, and N. Ramanujam, “Quantitative optical spectroscopy can identify long-term local tumor control in irradiated murine head and neck xenografts,” J. Biomed. Opt. 14(5), 054051 (2009).
[CrossRef] [PubMed]

Magn. Reson. Imaging (1)

C. Baudelet and B. Gallez, “Effect of anesthesia on the signal intensity in tumors using BOLD-MRI: comparison with flow measurements by Laser Doppler flowmetry and oxygen measurements by luminescence-based probes,” Magn. Reson. Imaging 22(7), 905–912 (2004).
[CrossRef] [PubMed]

Med. Phys. (1)

J. Axelsson, S. C. Davis, D. J. Gladstone, and B. W. Pogue, “Cerenkov emission induced by external beam radiation stimulates molecular fluorescence,” Med. Phys. 38(7), 4127–4132 (2011).
[CrossRef] [PubMed]

Opt. Lett. (2)

Phys. Med. Biol. (3)

G. Alexandrakis, F. R. Rannou, and A. F. Chatziioannou, “Tomographic bioluminescence imaging by use of a combined optical-PET (OPET) system: a computer simulation feasibility study,” Phys. Med. Biol. 50(17), 4225–4241 (2005).
[CrossRef] [PubMed]

R. Robertson, M. S. Germanos, C. Li, G. S. Mitchell, S. R. Cherry, and M. D. Silva, “Optical imaging of Cerenkov light generation from positron-emitting radiotracers,” Phys. Med. Biol. 54(16), N355–N365 (2009).
[CrossRef] [PubMed]

A. E. Spinelli, D. D’Ambrosio, L. Calderan, M. Marengo, A. Sbarbati, and F. Boschi, “Cerenkov radiation allows in vivo optical imaging of positron emitting radiotracers,” Phys. Med. Biol. 55(2), 483–495 (2010).
[CrossRef] [PubMed]

PLoS ONE (1)

H. Liu, G. Ren, Z. Miao, X. Zhang, X. Tang, P. Han, S. S. Gambhir, and Z. Cheng, “Molecular optical imaging with radioactive probes,” PLoS ONE 5(3), e9470 (2010).
[CrossRef] [PubMed]

Radiother. Oncol. (1)

M. Nordsmark, S. M. Bentzen, V. Rudat, D. Brizel, E. Lartigau, P. Stadler, A. Becker, M. Adam, M. Molls, J. Dunst, D. J. Terris, and J. Overgaard, “Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study,” Radiother. Oncol. 77(1), 18–24 (2005).
[CrossRef] [PubMed]

Other (5)

P. Vaupel, A. Mayer, and M. Höckel, “Relationship between hemoglobin levels and tumor oxygenation,” in Recombinant Human Erythropoietin (rhEPO) in Clinical Oncology, M. R. Nowrousian, ed. (Springer, 2008), pp. 265–282.

J. V. Jelley, Cerenkov radiation and its applications (Pergamon Press, 1958).

S. A. Prahl, “Optical absorption of hemoglobin,” URL http://omlc.ogi.edu/spectra/hemoglobin/index.html (2009).

E. Podgorsak, Radiation Oncology Physics: A Handbook for Teachers and Students, (IAEA, 2005), http://www. iaea.org/books (2005).

NIST, “ESTAR: Stopping power and range tables for electrons,” URL http://physics.nist.gov/PhysRefData/Star/Text/ESTAR.html (2011).

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Figures (4)

Fig. 1
Fig. 1

Experimental setup. (a) a schematics showing the setup where electron beam irradiates from top of phantom. (b) the Frank-Tamm formula is plotted showing the number of photons generated per mm and electron for varying energy. (c) electron range as a function of energy. (d-f) electron beams at 6, 12 and 18 MeV irradiating a water tank. (g-i) electron beams irradiating a scattering solution of saline and intralipid. (j-l) electron beams irradiating a scattering phantom with added blood. (m) a schematic showing the optical point sources distributed throughout the electron beam.

Fig. 2
Fig. 2

Cherenkov emission spectroscopy of hemoglobin concentration. (a) Cherenkov emission spectra from phantom solutions with varying concentrations of porcine blood, indicated in the legend. (b) fitted values for the total hemoglobin concentration are offset against the true values. The inset shows the retrieved oxygenation values.

Fig. 3
Fig. 3

Cherenkov emission spectroscopy of tissue oxygenation. (a) spectra from a well-oxygenated and a de-oxygenated scattering phantom solution are shown. The photos in (b) and (c) depict the color-change in the well- and de-oxygenated phantoms respectively.

Fig. 4
Fig. 4

Cherenkov emission spectroscopy of tissue oxygenation in vivo. (a) mouse positioned in the target region with the beam profile delineated in red. (b) typical spectra from a mouse pre and post euthanasia. (c) the results from the fitting procedure for both total hemoglobin concentration (left y-axis) and oxygen saturation (right y-axis). The mean of four animals is shown and the error bars indicate the standard deviation of this small population.

Equations (9)

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dN( λ,E )= 2π 137 ( 1 λΔλ 1 λ+Δλ )( 1 1 β ( E ) 2 n 2 )dx
β( E )= [ 1 ( 1 E 0.511 +1 ) 2 ] 1 2
E= E 0 ( 1 z R p ).
R p =4.612× E 0 +3.074.
dN( λ, E 0 ,z )= 2π 137 ( 1 λΔλ 1 λ+Δλ )( 1 1 β ( E 0 ,z ) 2 n 2 )dx
β( E 0 ,z )= [ 1 ( 1 E 0 0.511 ( 1 z R p )+1 ) 2 ] 1 2 .
I( λ )=C i=1 M hc λ N( λ, E 0 ,z ) 4πD R i exp( μ eff R i )
μ s '(λ)=A λ b
μ a (λ)=cH b tot ×[ S O 2 ε Hb O 2 (λ)+( 1S O 2 ) ε Hb (λ) ]+ C w μ H 2 O (λ)

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