Abstract

Radiation treatment of cancer induces an optical Čerenkov emission throughout the treated volume, which could be used to excite molecular reporters in vivo, allowing molecular sensing of tissue response during fractionated therapy. In this Letter, the idea that spatial mapping of this signal can be achieved with tomographic recovery of the fluorophore distribution is tested for the first time using 6 MV photons from a linear accelerator in a heterogeneous tissue phantom. Čerenkov light excited fluorophores throughout the tissue phantom, and diffuse tomography was used to recover images. Measurements from 13 locations were used, with spectrometer detection and spectral fitting, to separate the fluorophore emission from the Čerenkov continuum. Fluorescent diffuse tomographic images showed a linear response between the concentration and the reconstructed values. The potential to apply this molecular imaging in treatment with molecular reporters appears promising.

© 2013 Optical Society of America

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  1. S. E. Noda, T. Lautenschlaeger, M. R. Siedow, D. R. Patel, A. El-Jawahri, Y. Suzuki, J. S. Loeffler, M. R. Bussiere, and A. Chakravarti, Seminars Rad. Onc. 19, 179 (2009).
    [CrossRef]
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    [CrossRef]
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    [CrossRef]
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    [CrossRef]
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2012

2011

J. Axelsson, S. C. Davis, D. J. Gladstone, and B. W. Pogue, Med. Phys. 38, 4127 (2011).
[CrossRef]

2010

C. Li, G. S. Mitchell, and S. R. Cherry, Opt. Lett. 35, 1109 (2010).
[CrossRef]

R. S. Dothager, R. J. Goiffon, E. Jackson, S. Harpstrite, and D. Piwnica-Worms, PLoS ONE 5, e13300 (2010).
[CrossRef]

S. C. Davis, K. S. Samkoe, J. A. O’Hara, S. L. Gibbs-Strauss, K. D. Paulsen, and B. W. Pogue, J. Biomed. Opt. 15, 051602 (2010).
[CrossRef]

2009

S. E. Noda, T. Lautenschlaeger, M. R. Siedow, D. R. Patel, A. El-Jawahri, Y. Suzuki, J. S. Loeffler, M. R. Bussiere, and A. Chakravarti, Seminars Rad. Onc. 19, 179 (2009).
[CrossRef]

S. C. Davis, B. W. Pogue, S. B. Tuttle, H. Dehghani, and K. D. Paulsen, J. Appl. Phys. 105, 102024 (2009).
[CrossRef]

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, Commun. Numer. Methods Eng. 25, 711 (2009).
[CrossRef]

N. C. Deliolanis, J. Dunham, T. Wurdinger, J. L. Figueiredo, B. A. Tannous, and V. Ntziachristos, J. Biomed. Opt. 14, 030509 (2009).
[CrossRef]

Y. Lu, X. Zhang, A. Douraghy, D. Stout, J. Tian, T. F. Chan, and A. F. Chatziioannou, Opt. Express 17, 8062 (2009).
[CrossRef]

2007

D. Razansky and V. Ntziachristos, Med. Phys. 34, 4293 (2007).
[CrossRef]

2006

2005

2003

S. Agostinelli, J. Allison, K. Amako, J. Apostolakis, H. Araujo, P. Arce, M. Asai, D. Axen, S. Banerjee, and G. Barrand, Nucl. Instrum. Methods Phys. Res. A 506, 250 (2003).
[CrossRef]

1937

P. A. Čerenkov, Phys. Rev. 52, 0378 (1937).
[CrossRef]

Agostinelli, S.

S. Agostinelli, J. Allison, K. Amako, J. Apostolakis, H. Araujo, P. Arce, M. Asai, D. Axen, S. Banerjee, and G. Barrand, Nucl. Instrum. Methods Phys. Res. A 506, 250 (2003).
[CrossRef]

Allison, J.

S. Agostinelli, J. Allison, K. Amako, J. Apostolakis, H. Araujo, P. Arce, M. Asai, D. Axen, S. Banerjee, and G. Barrand, Nucl. Instrum. Methods Phys. Res. A 506, 250 (2003).
[CrossRef]

Amako, K.

S. Agostinelli, J. Allison, K. Amako, J. Apostolakis, H. Araujo, P. Arce, M. Asai, D. Axen, S. Banerjee, and G. Barrand, Nucl. Instrum. Methods Phys. Res. A 506, 250 (2003).
[CrossRef]

Apostolakis, J.

S. Agostinelli, J. Allison, K. Amako, J. Apostolakis, H. Araujo, P. Arce, M. Asai, D. Axen, S. Banerjee, and G. Barrand, Nucl. Instrum. Methods Phys. Res. A 506, 250 (2003).
[CrossRef]

Araujo, H.

S. Agostinelli, J. Allison, K. Amako, J. Apostolakis, H. Araujo, P. Arce, M. Asai, D. Axen, S. Banerjee, and G. Barrand, Nucl. Instrum. Methods Phys. Res. A 506, 250 (2003).
[CrossRef]

Arce, P.

S. Agostinelli, J. Allison, K. Amako, J. Apostolakis, H. Araujo, P. Arce, M. Asai, D. Axen, S. Banerjee, and G. Barrand, Nucl. Instrum. Methods Phys. Res. A 506, 250 (2003).
[CrossRef]

P. Arce, P. Rato, M. Cañadas, and J. Lagares, in 2008 Nuclear Science Symposium, Medical Imaging Conference and 16th Room Temperature Semiconductor Detector Workshop, Dresden, Germany (IEEE, 2008), pp. 19–25.

Asai, M.

S. Agostinelli, J. Allison, K. Amako, J. Apostolakis, H. Araujo, P. Arce, M. Asai, D. Axen, S. Banerjee, and G. Barrand, Nucl. Instrum. Methods Phys. Res. A 506, 250 (2003).
[CrossRef]

Axelsson, J.

J. Axelsson, S. C. Davis, D. J. Gladstone, and B. W. Pogue, Med. Phys. 38, 4127 (2011).
[CrossRef]

Axen, D.

S. Agostinelli, J. Allison, K. Amako, J. Apostolakis, H. Araujo, P. Arce, M. Asai, D. Axen, S. Banerjee, and G. Barrand, Nucl. Instrum. Methods Phys. Res. A 506, 250 (2003).
[CrossRef]

Banerjee, S.

S. Agostinelli, J. Allison, K. Amako, J. Apostolakis, H. Araujo, P. Arce, M. Asai, D. Axen, S. Banerjee, and G. Barrand, Nucl. Instrum. Methods Phys. Res. A 506, 250 (2003).
[CrossRef]

Barrand, G.

S. Agostinelli, J. Allison, K. Amako, J. Apostolakis, H. Araujo, P. Arce, M. Asai, D. Axen, S. Banerjee, and G. Barrand, Nucl. Instrum. Methods Phys. Res. A 506, 250 (2003).
[CrossRef]

Bussiere, M. R.

S. E. Noda, T. Lautenschlaeger, M. R. Siedow, D. R. Patel, A. El-Jawahri, Y. Suzuki, J. S. Loeffler, M. R. Bussiere, and A. Chakravarti, Seminars Rad. Onc. 19, 179 (2009).
[CrossRef]

Cañadas, M.

P. Arce, P. Rato, M. Cañadas, and J. Lagares, in 2008 Nuclear Science Symposium, Medical Imaging Conference and 16th Room Temperature Semiconductor Detector Workshop, Dresden, Germany (IEEE, 2008), pp. 19–25.

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, Commun. Numer. Methods Eng. 25, 711 (2009).
[CrossRef]

Cerenkov, P. A.

P. A. Čerenkov, Phys. Rev. 52, 0378 (1937).
[CrossRef]

Chakravarti, A.

S. E. Noda, T. Lautenschlaeger, M. R. Siedow, D. R. Patel, A. El-Jawahri, Y. Suzuki, J. S. Loeffler, M. R. Bussiere, and A. Chakravarti, Seminars Rad. Onc. 19, 179 (2009).
[CrossRef]

Chan, T. F.

Chatziioannou, A. F.

Cherry, S. R.

Cong, W.

Davis, S. C.

A. K. Glaser, R. Zhang, S. C. Davis, D. J. Gladstone, and B. W. Pogue, Opt. Lett. 37, 1193 (2012).
[CrossRef]

R. X. Zhang, A. Glaser, T. V. Esipova, S. C. Kanick, S. C. Davis, S. Vinogradov, D. Gladstone, and B. W. Pogue, Biomed. Opt. Express 3, 2381 (2012).
[CrossRef]

J. Axelsson, S. C. Davis, D. J. Gladstone, and B. W. Pogue, Med. Phys. 38, 4127 (2011).
[CrossRef]

S. C. Davis, K. S. Samkoe, J. A. O’Hara, S. L. Gibbs-Strauss, K. D. Paulsen, and B. W. Pogue, J. Biomed. Opt. 15, 051602 (2010).
[CrossRef]

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, Commun. Numer. Methods Eng. 25, 711 (2009).
[CrossRef]

S. C. Davis, B. W. Pogue, S. B. Tuttle, H. Dehghani, and K. D. Paulsen, J. Appl. Phys. 105, 102024 (2009).
[CrossRef]

H. Dehghani, S. C. Davis, S. D. Jiang, B. W. Pogue, K. D. Paulsen, and M. S. Patterson, Opt. Lett. 31, 365 (2006).
[CrossRef]

Dehghani, H.

S. C. Davis, B. W. Pogue, S. B. Tuttle, H. Dehghani, and K. D. Paulsen, J. Appl. Phys. 105, 102024 (2009).
[CrossRef]

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, Commun. Numer. Methods Eng. 25, 711 (2009).
[CrossRef]

H. Dehghani, S. C. Davis, S. D. Jiang, B. W. Pogue, K. D. Paulsen, and M. S. Patterson, Opt. Lett. 31, 365 (2006).
[CrossRef]

Deliolanis, N. C.

N. C. Deliolanis, J. Dunham, T. Wurdinger, J. L. Figueiredo, B. A. Tannous, and V. Ntziachristos, J. Biomed. Opt. 14, 030509 (2009).
[CrossRef]

Dothager, R. S.

R. S. Dothager, R. J. Goiffon, E. Jackson, S. Harpstrite, and D. Piwnica-Worms, PLoS ONE 5, e13300 (2010).
[CrossRef]

Douraghy, A.

Dunham, J.

N. C. Deliolanis, J. Dunham, T. Wurdinger, J. L. Figueiredo, B. A. Tannous, and V. Ntziachristos, J. Biomed. Opt. 14, 030509 (2009).
[CrossRef]

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, Commun. Numer. Methods Eng. 25, 711 (2009).
[CrossRef]

El-Jawahri, A.

S. E. Noda, T. Lautenschlaeger, M. R. Siedow, D. R. Patel, A. El-Jawahri, Y. Suzuki, J. S. Loeffler, M. R. Bussiere, and A. Chakravarti, Seminars Rad. Onc. 19, 179 (2009).
[CrossRef]

Esipova, T. V.

Figueiredo, J. L.

N. C. Deliolanis, J. Dunham, T. Wurdinger, J. L. Figueiredo, B. A. Tannous, and V. Ntziachristos, J. Biomed. Opt. 14, 030509 (2009).
[CrossRef]

Gibbs-Strauss, S. L.

S. C. Davis, K. S. Samkoe, J. A. O’Hara, S. L. Gibbs-Strauss, K. D. Paulsen, and B. W. Pogue, J. Biomed. Opt. 15, 051602 (2010).
[CrossRef]

Gladstone, D.

Gladstone, D. J.

A. K. Glaser, R. Zhang, S. C. Davis, D. J. Gladstone, and B. W. Pogue, Opt. Lett. 37, 1193 (2012).
[CrossRef]

J. Axelsson, S. C. Davis, D. J. Gladstone, and B. W. Pogue, Med. Phys. 38, 4127 (2011).
[CrossRef]

Glaser, A.

Glaser, A. K.

Goiffon, R. J.

R. S. Dothager, R. J. Goiffon, E. Jackson, S. Harpstrite, and D. Piwnica-Worms, PLoS ONE 5, e13300 (2010).
[CrossRef]

Harpstrite, S.

R. S. Dothager, R. J. Goiffon, E. Jackson, S. Harpstrite, and D. Piwnica-Worms, PLoS ONE 5, e13300 (2010).
[CrossRef]

Hoffman, E. A.

Jackson, E.

R. S. Dothager, R. J. Goiffon, E. Jackson, S. Harpstrite, and D. Piwnica-Worms, PLoS ONE 5, e13300 (2010).
[CrossRef]

Jiang, M.

Jiang, S. D.

Kanick, S. C.

Kumar, D.

Lagares, J.

P. Arce, P. Rato, M. Cañadas, and J. Lagares, in 2008 Nuclear Science Symposium, Medical Imaging Conference and 16th Room Temperature Semiconductor Detector Workshop, Dresden, Germany (IEEE, 2008), pp. 19–25.

Lautenschlaeger, T.

S. E. Noda, T. Lautenschlaeger, M. R. Siedow, D. R. Patel, A. El-Jawahri, Y. Suzuki, J. S. Loeffler, M. R. Bussiere, and A. Chakravarti, Seminars Rad. Onc. 19, 179 (2009).
[CrossRef]

Li, C.

Liu, Y.

Loeffler, J. S.

S. E. Noda, T. Lautenschlaeger, M. R. Siedow, D. R. Patel, A. El-Jawahri, Y. Suzuki, J. S. Loeffler, M. R. Bussiere, and A. Chakravarti, Seminars Rad. Onc. 19, 179 (2009).
[CrossRef]

Lu, Y.

McCray, P. B.

McLennan, G.

Mitchell, G. S.

Noda, S. E.

S. E. Noda, T. Lautenschlaeger, M. R. Siedow, D. R. Patel, A. El-Jawahri, Y. Suzuki, J. S. Loeffler, M. R. Bussiere, and A. Chakravarti, Seminars Rad. Onc. 19, 179 (2009).
[CrossRef]

Ntziachristos, V.

N. C. Deliolanis, J. Dunham, T. Wurdinger, J. L. Figueiredo, B. A. Tannous, and V. Ntziachristos, J. Biomed. Opt. 14, 030509 (2009).
[CrossRef]

D. Razansky and V. Ntziachristos, Med. Phys. 34, 4293 (2007).
[CrossRef]

O’Hara, J. A.

S. C. Davis, K. S. Samkoe, J. A. O’Hara, S. L. Gibbs-Strauss, K. D. Paulsen, and B. W. Pogue, J. Biomed. Opt. 15, 051602 (2010).
[CrossRef]

Patel, D. R.

S. E. Noda, T. Lautenschlaeger, M. R. Siedow, D. R. Patel, A. El-Jawahri, Y. Suzuki, J. S. Loeffler, M. R. Bussiere, and A. Chakravarti, Seminars Rad. Onc. 19, 179 (2009).
[CrossRef]

Patterson, M. S.

Paulsen, K. D.

S. C. Davis, K. S. Samkoe, J. A. O’Hara, S. L. Gibbs-Strauss, K. D. Paulsen, and B. W. Pogue, J. Biomed. Opt. 15, 051602 (2010).
[CrossRef]

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, Commun. Numer. Methods Eng. 25, 711 (2009).
[CrossRef]

S. C. Davis, B. W. Pogue, S. B. Tuttle, H. Dehghani, and K. D. Paulsen, J. Appl. Phys. 105, 102024 (2009).
[CrossRef]

H. Dehghani, S. C. Davis, S. D. Jiang, B. W. Pogue, K. D. Paulsen, and M. S. Patterson, Opt. Lett. 31, 365 (2006).
[CrossRef]

Piwnica-Worms, D.

R. S. Dothager, R. J. Goiffon, E. Jackson, S. Harpstrite, and D. Piwnica-Worms, PLoS ONE 5, e13300 (2010).
[CrossRef]

Pogue, B. W.

R. X. Zhang, A. Glaser, T. V. Esipova, S. C. Kanick, S. C. Davis, S. Vinogradov, D. Gladstone, and B. W. Pogue, Biomed. Opt. Express 3, 2381 (2012).
[CrossRef]

A. K. Glaser, R. Zhang, S. C. Davis, D. J. Gladstone, and B. W. Pogue, Opt. Lett. 37, 1193 (2012).
[CrossRef]

J. Axelsson, S. C. Davis, D. J. Gladstone, and B. W. Pogue, Med. Phys. 38, 4127 (2011).
[CrossRef]

S. C. Davis, K. S. Samkoe, J. A. O’Hara, S. L. Gibbs-Strauss, K. D. Paulsen, and B. W. Pogue, J. Biomed. Opt. 15, 051602 (2010).
[CrossRef]

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, Commun. Numer. Methods Eng. 25, 711 (2009).
[CrossRef]

S. C. Davis, B. W. Pogue, S. B. Tuttle, H. Dehghani, and K. D. Paulsen, J. Appl. Phys. 105, 102024 (2009).
[CrossRef]

H. Dehghani, S. C. Davis, S. D. Jiang, B. W. Pogue, K. D. Paulsen, and M. S. Patterson, Opt. Lett. 31, 365 (2006).
[CrossRef]

Rato, P.

P. Arce, P. Rato, M. Cañadas, and J. Lagares, in 2008 Nuclear Science Symposium, Medical Imaging Conference and 16th Room Temperature Semiconductor Detector Workshop, Dresden, Germany (IEEE, 2008), pp. 19–25.

Razansky, D.

D. Razansky and V. Ntziachristos, Med. Phys. 34, 4293 (2007).
[CrossRef]

Samkoe, K. S.

S. C. Davis, K. S. Samkoe, J. A. O’Hara, S. L. Gibbs-Strauss, K. D. Paulsen, and B. W. Pogue, J. Biomed. Opt. 15, 051602 (2010).
[CrossRef]

Siedow, M. R.

S. E. Noda, T. Lautenschlaeger, M. R. Siedow, D. R. Patel, A. El-Jawahri, Y. Suzuki, J. S. Loeffler, M. R. Bussiere, and A. Chakravarti, Seminars Rad. Onc. 19, 179 (2009).
[CrossRef]

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, Commun. Numer. Methods Eng. 25, 711 (2009).
[CrossRef]

Stout, D.

Suzuki, Y.

S. E. Noda, T. Lautenschlaeger, M. R. Siedow, D. R. Patel, A. El-Jawahri, Y. Suzuki, J. S. Loeffler, M. R. Bussiere, and A. Chakravarti, Seminars Rad. Onc. 19, 179 (2009).
[CrossRef]

Tannous, B. A.

N. C. Deliolanis, J. Dunham, T. Wurdinger, J. L. Figueiredo, B. A. Tannous, and V. Ntziachristos, J. Biomed. Opt. 14, 030509 (2009).
[CrossRef]

Tian, J.

Tuttle, S. B.

S. C. Davis, B. W. Pogue, S. B. Tuttle, H. Dehghani, and K. D. Paulsen, J. Appl. Phys. 105, 102024 (2009).
[CrossRef]

Vinogradov, S.

Wang, G.

Wang, L. V.

Wurdinger, T.

N. C. Deliolanis, J. Dunham, T. Wurdinger, J. L. Figueiredo, B. A. Tannous, and V. Ntziachristos, J. Biomed. Opt. 14, 030509 (2009).
[CrossRef]

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, Commun. Numer. Methods Eng. 25, 711 (2009).
[CrossRef]

Zabner, J.

Zhang, R.

Zhang, R. X.

Zhang, X.

Biomed. Opt. Express

Commun. Numer. Methods Eng.

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, Commun. Numer. Methods Eng. 25, 711 (2009).
[CrossRef]

J. Appl. Phys.

S. C. Davis, B. W. Pogue, S. B. Tuttle, H. Dehghani, and K. D. Paulsen, J. Appl. Phys. 105, 102024 (2009).
[CrossRef]

J. Biomed. Opt.

N. C. Deliolanis, J. Dunham, T. Wurdinger, J. L. Figueiredo, B. A. Tannous, and V. Ntziachristos, J. Biomed. Opt. 14, 030509 (2009).
[CrossRef]

S. C. Davis, K. S. Samkoe, J. A. O’Hara, S. L. Gibbs-Strauss, K. D. Paulsen, and B. W. Pogue, J. Biomed. Opt. 15, 051602 (2010).
[CrossRef]

Med. Phys.

J. Axelsson, S. C. Davis, D. J. Gladstone, and B. W. Pogue, Med. Phys. 38, 4127 (2011).
[CrossRef]

D. Razansky and V. Ntziachristos, Med. Phys. 34, 4293 (2007).
[CrossRef]

Nucl. Instrum. Methods Phys. Res. A

S. Agostinelli, J. Allison, K. Amako, J. Apostolakis, H. Araujo, P. Arce, M. Asai, D. Axen, S. Banerjee, and G. Barrand, Nucl. Instrum. Methods Phys. Res. A 506, 250 (2003).
[CrossRef]

Opt. Express

Opt. Lett.

Phys. Rev.

P. A. Čerenkov, Phys. Rev. 52, 0378 (1937).
[CrossRef]

PLoS ONE

R. S. Dothager, R. J. Goiffon, E. Jackson, S. Harpstrite, and D. Piwnica-Worms, PLoS ONE 5, e13300 (2010).
[CrossRef]

Seminars Rad. Onc.

S. E. Noda, T. Lautenschlaeger, M. R. Siedow, D. R. Patel, A. El-Jawahri, Y. Suzuki, J. S. Loeffler, M. R. Bussiere, and A. Chakravarti, Seminars Rad. Onc. 19, 179 (2009).
[CrossRef]

Other

P. Arce, P. Rato, M. Cañadas, and J. Lagares, in 2008 Nuclear Science Symposium, Medical Imaging Conference and 16th Room Temperature Semiconductor Detector Workshop, Dresden, Germany (IEEE, 2008), pp. 19–25.

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Figures (3)

Fig. 1.
Fig. 1.

(a) Schematic of the experimental setup shows the location of the phantom and measurement devices. (b) The phantom schematic shows the region of the phantom where Čerenkov light would be generated in a three-dimensional volume. (c) The top view of the phantom has a white-light image of the experimental setup with the phantom exterior highlighted with red.

Fig. 2.
Fig. 2.

LS fitting of the background Čerenkov radiation and the fluorophore emission spectrum were done for each detector location shown in (c). (a) Example of 0.1mg/mL concentration fitting. (b) Example of 0.8mg/mL concentration fitting. (d) Integrated intensity of the signal measured in each detector for increasing concentrations of fluorophore in the anomaly.

Fig. 3.
Fig. 3.

(a) Calculated field of Čerenkov radiation is shown in the plane of the detection fibers. (b) The reconstructed images are shown when using no spatial information for each of the concentrations marked. (c) The linear relationship between the concentration of the anomaly and the reconstructed values are shown in the graph.

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