Abstract

Despite the broad impact in medicine that optics can bring, thus far practical approaches are limited to weak scatter or near-surface monitoring. We show a method that utilizes a laser topography scan and a diffusion equation model to describe the photon transport, together with a multiresolution unstructured grid solution to the nonlinear optimization measurement functional, that overcomes these limitations. We conclude that it is possible to achieve whole body optical imaging with a resolution suitable for finding cancer nodules within an organ during surgery, with the aid of a targeted imaging agent.

© 2013 Optical Society of America

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2011 (2)

G. M. van Dam, G. Themelis, L. M. A. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. S. de Jong, H. J. Arts, A. G. van der Zee, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescent imaging in ovarian cancer by folate receptor-α targeting: first in-human results,” Nat. Med. 17, 1315–1319 (2011).
[CrossRef]

Y. Lu, B. Zhu, C. Darne, I.-C. Tan, J. C. Rasmussen, and E. M. Sevick-Muraca, “Improvement of fluorescence-enhanced optical tomography with improved optical filtering and accurate model-based reconstruction algorithms,” J. Biomed. Opt. 16, 126002 (2011).
[CrossRef]

2010 (2)

Q. T. Nguyen, E. S. Olson, T. A. Aguilera, T. Jiang, M. Scadeng, L. G. Ellies, and R. Y. Tsien, “Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival,” Proc. Natl. Acad. Sci. USA 107, 4317–4322 (2010).
[CrossRef]

V. Gaind, S. Kularatne, P. S. Low, and K. J. Webb, “Deep tissue imaging of intramolecular fluorescence resonance energy transfer parameters,” Opt. Lett. 35, 1314–1316 (2010).
[CrossRef]

2009 (4)

V. Gaind, K. J. Webb, S. Kularatne, and C. A. Bouman, “Towards in vivo imaging of intramolecular fluorescence resonance energy transfer parameters,” J. Opt. Soc. Am. A 26, 1805–1813 (2009).
[CrossRef]

T. A. Aguilera, E. S. Olson, M. M. Timmers, T. Jiang, and R. Y. Tsien, “Systemic in vivo distribution of activatable cell penetrating peptides is superior to that of cell penetrating peptides,” Integr. Biol. 1, 371–381 (2009).
[CrossRef]

X. Zhang, C. T. Badea, and G. A. Johnson, “Three-dimensional reconstruction in free-space whole-body fluorescence tomography of mice using optically reconstructed surface and atlas anatomy,” J. Biomed. Opt. 14, 064010 (2009).
[CrossRef]

R. Choe, S. D. Konecky, A. Corlu, K. Lee, T. Durduran, D. R. Busch, S. Pathak, B. J. Czerniecki, J. Tchou, D. L. Fraker, A. DeMichele, B. Chance, S. R. Arridge, M. Schweiger, J. P. Culver, M. D. Schnall, M. E. Putt, M. A. Rosen, and A. G. Yodh, “Differentiation of benign and malignant breast tumors by in-vivo three-dimensional parallel-plate diffuse optical tomography,” J. Biomed. Opt. 14, 024020 (2009).
[CrossRef]

2008 (2)

A. T. Kumar, S. B. Raymond, A. K. Dunn, B. J. Bacskai, and D. A. Boas, “A time domain fluorescence tomography system for small animal imaging,” IEEE Trans. Med. Imaging 27, 1152–1163 (2008).
[CrossRef]

P. S. Low, W. A. Henne, and D. D. Doorneweerd, “Discovery and development of folic-acid-based receptor targeting for imaging and therapy of cancer and inflammatory diseases,” Acc. Chem. Res. 41, 120–129 (2008).
[CrossRef]

2007 (1)

2005 (4)

S. V. Patwardhan, S. R. Bloch, S. Achilefu, and J. P. Culver, “Time-dependent whole-body fluorescence tomography of probe bio-distributions in mice,” Opt. Express 13, 2564–2577 (2005).
[CrossRef]

E. Haas, “The study of protein folding and dynamics by determination of intramolecular distance distributions and their fluctuations using ensemble and single-molecule fret measurement,” Chem. Phys. Chem. 6, 858–870 (2005).
[CrossRef]

S. Oh, A. B. Milstein, C. A. Bouman, and K. J. Webb, “A general framework for nonlinear multigrid inversion,” IEEE Trans. Image Process. 14, 125–140 (2005).
[CrossRef]

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, 4225–4241 (2005).
[CrossRef]

2004 (1)

2003 (3)

2002 (1)

2001 (2)

T. O. McBride, B. W. Pogue, S. Jiang, U. L. Österberg, and K. D. Paulsen, “A parallel-detection frequency-domain near-infrared tomography system for hemoglobin imaging of the breast in vivo,” Rev. Sci. Instrum. 72, 1817–1824 (2001).
[CrossRef]

J. C. Ye, C. A. Bouman, K. J. Webb, and R. P. Millane, “Nonlinear multigrid algorithms for Bayesian optical diffusion tomography,” IEEE Trans. Image Process. 10, 909–922 (2001).
[CrossRef]

2000 (1)

V. Ratner, M. Sinev, and E. Haas, “Determination of intramolecular distance distribution during protein folding on the millisecond timescale,” J. Mol. Biol. 299, 1363–1371 (2000).
[CrossRef]

1999 (2)

1998 (2)

1997 (1)

A. Miyawaki, J. Llopis, R. Heim, J. M. McCaffery, J. A. Adams, M. Ikura, and R. Y. Tsien, “Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin,” Nature 388, 881–887 (1997).

1993 (1)

S. R. Arridge, M. Schweiger, M. Hiraoka, and D. T. Delpy, “A finite element approach for modeling photon transport in tissue,” Med. Phys. 20, 299–309 (1993).
[CrossRef]

1992 (1)

T. J. Farrell, M. S. Patterson, and B. Wilson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19, 879–888 (1992).
[CrossRef]

1991 (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254, 1178–1181 (1991).
[CrossRef]

1990 (1)

W.-F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quantum Electron. 26, 2166–2185 (1990).
[CrossRef]

1948 (1)

T. Förster, “Zwischenmolekulare energiewanderung und fluoreszenze,” Ann. Phys. 437, 55–75 (1948).
[CrossRef]

Achilefu, S.

Adams, J. A.

A. Miyawaki, J. Llopis, R. Heim, J. M. McCaffery, J. A. Adams, M. Ikura, and R. Y. Tsien, “Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin,” Nature 388, 881–887 (1997).

Aguilera, T. A.

Q. T. Nguyen, E. S. Olson, T. A. Aguilera, T. Jiang, M. Scadeng, L. G. Ellies, and R. Y. Tsien, “Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival,” Proc. Natl. Acad. Sci. USA 107, 4317–4322 (2010).
[CrossRef]

T. A. Aguilera, E. S. Olson, M. M. Timmers, T. Jiang, and R. Y. Tsien, “Systemic in vivo distribution of activatable cell penetrating peptides is superior to that of cell penetrating peptides,” Integr. Biol. 1, 371–381 (2009).
[CrossRef]

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, 4225–4241 (2005).
[CrossRef]

Arridge, S. R.

R. Choe, S. D. Konecky, A. Corlu, K. Lee, T. Durduran, D. R. Busch, S. Pathak, B. J. Czerniecki, J. Tchou, D. L. Fraker, A. DeMichele, B. Chance, S. R. Arridge, M. Schweiger, J. P. Culver, M. D. Schnall, M. E. Putt, M. A. Rosen, and A. G. Yodh, “Differentiation of benign and malignant breast tumors by in-vivo three-dimensional parallel-plate diffuse optical tomography,” J. Biomed. Opt. 14, 024020 (2009).
[CrossRef]

S. R. Arridge, “Optical tomography in medical imaging,” Inverse Probl. 15, R41–R93 (1999).
[CrossRef]

S. R. Arridge, M. Schweiger, M. Hiraoka, and D. T. Delpy, “A finite element approach for modeling photon transport in tissue,” Med. Phys. 20, 299–309 (1993).
[CrossRef]

Arts, H. J.

G. M. van Dam, G. Themelis, L. M. A. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. S. de Jong, H. J. Arts, A. G. van der Zee, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescent imaging in ovarian cancer by folate receptor-α targeting: first in-human results,” Nat. Med. 17, 1315–1319 (2011).
[CrossRef]

Bacskai, B. J.

A. T. Kumar, S. B. Raymond, A. K. Dunn, B. J. Bacskai, and D. A. Boas, “A time domain fluorescence tomography system for small animal imaging,” IEEE Trans. Med. Imaging 27, 1152–1163 (2008).
[CrossRef]

Badea, C. T.

X. Zhang, C. T. Badea, and G. A. Johnson, “Three-dimensional reconstruction in free-space whole-body fluorescence tomography of mice using optically reconstructed surface and atlas anatomy,” J. Biomed. Opt. 14, 064010 (2009).
[CrossRef]

Bart, J.

G. M. van Dam, G. Themelis, L. M. A. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. S. de Jong, H. J. Arts, A. G. van der Zee, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescent imaging in ovarian cancer by folate receptor-α targeting: first in-human results,” Nat. Med. 17, 1315–1319 (2011).
[CrossRef]

Bloch, S. R.

Boas, D. A.

Bouman, C. A.

Busch, D. R.

R. Choe, S. D. Konecky, A. Corlu, K. Lee, T. Durduran, D. R. Busch, S. Pathak, B. J. Czerniecki, J. Tchou, D. L. Fraker, A. DeMichele, B. Chance, S. R. Arridge, M. Schweiger, J. P. Culver, M. D. Schnall, M. E. Putt, M. A. Rosen, and A. G. Yodh, “Differentiation of benign and malignant breast tumors by in-vivo three-dimensional parallel-plate diffuse optical tomography,” J. Biomed. Opt. 14, 024020 (2009).
[CrossRef]

Chance, B.

R. Choe, S. D. Konecky, A. Corlu, K. Lee, T. Durduran, D. R. Busch, S. Pathak, B. J. Czerniecki, J. Tchou, D. L. Fraker, A. DeMichele, B. Chance, S. R. Arridge, M. Schweiger, J. P. Culver, M. D. Schnall, M. E. Putt, M. A. Rosen, and A. G. Yodh, “Differentiation of benign and malignant breast tumors by in-vivo three-dimensional parallel-plate diffuse optical tomography,” J. Biomed. Opt. 14, 024020 (2009).
[CrossRef]

Chang, W.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254, 1178–1181 (1991).
[CrossRef]

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, 4225–4241 (2005).
[CrossRef]

Cheong, W.-F.

W.-F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quantum Electron. 26, 2166–2185 (1990).
[CrossRef]

Choe, R.

R. Choe, S. D. Konecky, A. Corlu, K. Lee, T. Durduran, D. R. Busch, S. Pathak, B. J. Czerniecki, J. Tchou, D. L. Fraker, A. DeMichele, B. Chance, S. R. Arridge, M. Schweiger, J. P. Culver, M. D. Schnall, M. E. Putt, M. A. Rosen, and A. G. Yodh, “Differentiation of benign and malignant breast tumors by in-vivo three-dimensional parallel-plate diffuse optical tomography,” J. Biomed. Opt. 14, 024020 (2009).
[CrossRef]

Corlu, A.

R. Choe, S. D. Konecky, A. Corlu, K. Lee, T. Durduran, D. R. Busch, S. Pathak, B. J. Czerniecki, J. Tchou, D. L. Fraker, A. DeMichele, B. Chance, S. R. Arridge, M. Schweiger, J. P. Culver, M. D. Schnall, M. E. Putt, M. A. Rosen, and A. G. Yodh, “Differentiation of benign and malignant breast tumors by in-vivo three-dimensional parallel-plate diffuse optical tomography,” J. Biomed. Opt. 14, 024020 (2009).
[CrossRef]

Crane, L. M. A.

G. M. van Dam, G. Themelis, L. M. A. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. S. de Jong, H. J. Arts, A. G. van der Zee, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescent imaging in ovarian cancer by folate receptor-α targeting: first in-human results,” Nat. Med. 17, 1315–1319 (2011).
[CrossRef]

Culver, J. P.

R. Choe, S. D. Konecky, A. Corlu, K. Lee, T. Durduran, D. R. Busch, S. Pathak, B. J. Czerniecki, J. Tchou, D. L. Fraker, A. DeMichele, B. Chance, S. R. Arridge, M. Schweiger, J. P. Culver, M. D. Schnall, M. E. Putt, M. A. Rosen, and A. G. Yodh, “Differentiation of benign and malignant breast tumors by in-vivo three-dimensional parallel-plate diffuse optical tomography,” J. Biomed. Opt. 14, 024020 (2009).
[CrossRef]

S. V. Patwardhan, S. R. Bloch, S. Achilefu, and J. P. Culver, “Time-dependent whole-body fluorescence tomography of probe bio-distributions in mice,” Opt. Express 13, 2564–2577 (2005).
[CrossRef]

Czerniecki, B. J.

R. Choe, S. D. Konecky, A. Corlu, K. Lee, T. Durduran, D. R. Busch, S. Pathak, B. J. Czerniecki, J. Tchou, D. L. Fraker, A. DeMichele, B. Chance, S. R. Arridge, M. Schweiger, J. P. Culver, M. D. Schnall, M. E. Putt, M. A. Rosen, and A. G. Yodh, “Differentiation of benign and malignant breast tumors by in-vivo three-dimensional parallel-plate diffuse optical tomography,” J. Biomed. Opt. 14, 024020 (2009).
[CrossRef]

Darne, C.

Y. Lu, B. Zhu, C. Darne, I.-C. Tan, J. C. Rasmussen, and E. M. Sevick-Muraca, “Improvement of fluorescence-enhanced optical tomography with improved optical filtering and accurate model-based reconstruction algorithms,” J. Biomed. Opt. 16, 126002 (2011).
[CrossRef]

de Jong, J. S.

G. M. van Dam, G. Themelis, L. M. A. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. S. de Jong, H. J. Arts, A. G. van der Zee, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescent imaging in ovarian cancer by folate receptor-α targeting: first in-human results,” Nat. Med. 17, 1315–1319 (2011).
[CrossRef]

Deliolanis, N.

Delpy, D. T.

S. R. Arridge, M. Schweiger, M. Hiraoka, and D. T. Delpy, “A finite element approach for modeling photon transport in tissue,” Med. Phys. 20, 299–309 (1993).
[CrossRef]

DeMichele, A.

R. Choe, S. D. Konecky, A. Corlu, K. Lee, T. Durduran, D. R. Busch, S. Pathak, B. J. Czerniecki, J. Tchou, D. L. Fraker, A. DeMichele, B. Chance, S. R. Arridge, M. Schweiger, J. P. Culver, M. D. Schnall, M. E. Putt, M. A. Rosen, and A. G. Yodh, “Differentiation of benign and malignant breast tumors by in-vivo three-dimensional parallel-plate diffuse optical tomography,” J. Biomed. Opt. 14, 024020 (2009).
[CrossRef]

Dobson, C. M.

C. M. Dobson, “Protein folding and misfolding,” Nature 426, 884–890 (2003).
[CrossRef]

Doorneweerd, D. D.

P. S. Low, W. A. Henne, and D. D. Doorneweerd, “Discovery and development of folic-acid-based receptor targeting for imaging and therapy of cancer and inflammatory diseases,” Acc. Chem. Res. 41, 120–129 (2008).
[CrossRef]

Dunn, A. K.

A. T. Kumar, S. B. Raymond, A. K. Dunn, B. J. Bacskai, and D. A. Boas, “A time domain fluorescence tomography system for small animal imaging,” IEEE Trans. Med. Imaging 27, 1152–1163 (2008).
[CrossRef]

Durduran, T.

R. Choe, S. D. Konecky, A. Corlu, K. Lee, T. Durduran, D. R. Busch, S. Pathak, B. J. Czerniecki, J. Tchou, D. L. Fraker, A. DeMichele, B. Chance, S. R. Arridge, M. Schweiger, J. P. Culver, M. D. Schnall, M. E. Putt, M. A. Rosen, and A. G. Yodh, “Differentiation of benign and malignant breast tumors by in-vivo three-dimensional parallel-plate diffuse optical tomography,” J. Biomed. Opt. 14, 024020 (2009).
[CrossRef]

Ellies, L. G.

Q. T. Nguyen, E. S. Olson, T. A. Aguilera, T. Jiang, M. Scadeng, L. G. Ellies, and R. Y. Tsien, “Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival,” Proc. Natl. Acad. Sci. USA 107, 4317–4322 (2010).
[CrossRef]

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P. S. Low, W. A. Henne, and D. D. Doorneweerd, “Discovery and development of folic-acid-based receptor targeting for imaging and therapy of cancer and inflammatory diseases,” Acc. Chem. Res. 41, 120–129 (2008).
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T. O. McBride, B. W. Pogue, S. Jiang, U. L. Österberg, and K. D. Paulsen, “A parallel-detection frequency-domain near-infrared tomography system for hemoglobin imaging of the breast in vivo,” Rev. Sci. Instrum. 72, 1817–1824 (2001).
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Q. T. Nguyen, E. S. Olson, T. A. Aguilera, T. Jiang, M. Scadeng, L. G. Ellies, and R. Y. Tsien, “Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival,” Proc. Natl. Acad. Sci. USA 107, 4317–4322 (2010).
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A. Miyawaki, J. Llopis, R. Heim, J. M. McCaffery, J. A. Adams, M. Ikura, and R. Y. Tsien, “Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin,” Nature 388, 881–887 (1997).

Low, P. S.

G. M. van Dam, G. Themelis, L. M. A. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. S. de Jong, H. J. Arts, A. G. van der Zee, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescent imaging in ovarian cancer by folate receptor-α targeting: first in-human results,” Nat. Med. 17, 1315–1319 (2011).
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Y. Lu, B. Zhu, C. Darne, I.-C. Tan, J. C. Rasmussen, and E. M. Sevick-Muraca, “Improvement of fluorescence-enhanced optical tomography with improved optical filtering and accurate model-based reconstruction algorithms,” J. Biomed. Opt. 16, 126002 (2011).
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T. O. McBride, B. W. Pogue, S. Jiang, U. L. Österberg, and K. D. Paulsen, “A parallel-detection frequency-domain near-infrared tomography system for hemoglobin imaging of the breast in vivo,” Rev. Sci. Instrum. 72, 1817–1824 (2001).
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A. Miyawaki, J. Llopis, R. Heim, J. M. McCaffery, J. A. Adams, M. Ikura, and R. Y. Tsien, “Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin,” Nature 388, 881–887 (1997).

Millane, R. P.

Milstein, A. B.

Miyawaki, A.

A. Miyawaki, J. Llopis, R. Heim, J. M. McCaffery, J. A. Adams, M. Ikura, and R. Y. Tsien, “Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin,” Nature 388, 881–887 (1997).

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T. O. McBride, B. W. Pogue, S. Jiang, U. L. Österberg, and K. D. Paulsen, “A parallel-detection frequency-domain near-infrared tomography system for hemoglobin imaging of the breast in vivo,” Rev. Sci. Instrum. 72, 1817–1824 (2001).
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T. J. Farrell, M. S. Patterson, and B. Wilson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19, 879–888 (1992).
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T. O. McBride, B. W. Pogue, S. Jiang, U. L. Österberg, and K. D. Paulsen, “A parallel-detection frequency-domain near-infrared tomography system for hemoglobin imaging of the breast in vivo,” Rev. Sci. Instrum. 72, 1817–1824 (2001).
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T. O. McBride, B. W. Pogue, S. Jiang, U. L. Österberg, and K. D. Paulsen, “A parallel-detection frequency-domain near-infrared tomography system for hemoglobin imaging of the breast in vivo,” Rev. Sci. Instrum. 72, 1817–1824 (2001).
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R. Choe, S. D. Konecky, A. Corlu, K. Lee, T. Durduran, D. R. Busch, S. Pathak, B. J. Czerniecki, J. Tchou, D. L. Fraker, A. DeMichele, B. Chance, S. R. Arridge, M. Schweiger, J. P. Culver, M. D. Schnall, M. E. Putt, M. A. Rosen, and A. G. Yodh, “Differentiation of benign and malignant breast tumors by in-vivo three-dimensional parallel-plate diffuse optical tomography,” J. Biomed. Opt. 14, 024020 (2009).
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V. Ratner, M. Sinev, and E. Haas, “Determination of intramolecular distance distribution during protein folding on the millisecond timescale,” J. Mol. Biol. 299, 1363–1371 (2000).
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A. T. Kumar, S. B. Raymond, A. K. Dunn, B. J. Bacskai, and D. A. Boas, “A time domain fluorescence tomography system for small animal imaging,” IEEE Trans. Med. Imaging 27, 1152–1163 (2008).
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Ripoll, J.

Rosen, M. A.

R. Choe, S. D. Konecky, A. Corlu, K. Lee, T. Durduran, D. R. Busch, S. Pathak, B. J. Czerniecki, J. Tchou, D. L. Fraker, A. DeMichele, B. Chance, S. R. Arridge, M. Schweiger, J. P. Culver, M. D. Schnall, M. E. Putt, M. A. Rosen, and A. G. Yodh, “Differentiation of benign and malignant breast tumors by in-vivo three-dimensional parallel-plate diffuse optical tomography,” J. Biomed. Opt. 14, 024020 (2009).
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G. M. van Dam, G. Themelis, L. M. A. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. S. de Jong, H. J. Arts, A. G. van der Zee, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescent imaging in ovarian cancer by folate receptor-α targeting: first in-human results,” Nat. Med. 17, 1315–1319 (2011).
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Q. T. Nguyen, E. S. Olson, T. A. Aguilera, T. Jiang, M. Scadeng, L. G. Ellies, and R. Y. Tsien, “Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival,” Proc. Natl. Acad. Sci. USA 107, 4317–4322 (2010).
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Schnall, M. D.

R. Choe, S. D. Konecky, A. Corlu, K. Lee, T. Durduran, D. R. Busch, S. Pathak, B. J. Czerniecki, J. Tchou, D. L. Fraker, A. DeMichele, B. Chance, S. R. Arridge, M. Schweiger, J. P. Culver, M. D. Schnall, M. E. Putt, M. A. Rosen, and A. G. Yodh, “Differentiation of benign and malignant breast tumors by in-vivo three-dimensional parallel-plate diffuse optical tomography,” J. Biomed. Opt. 14, 024020 (2009).
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D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254, 1178–1181 (1991).
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R. Choe, S. D. Konecky, A. Corlu, K. Lee, T. Durduran, D. R. Busch, S. Pathak, B. J. Czerniecki, J. Tchou, D. L. Fraker, A. DeMichele, B. Chance, S. R. Arridge, M. Schweiger, J. P. Culver, M. D. Schnall, M. E. Putt, M. A. Rosen, and A. G. Yodh, “Differentiation of benign and malignant breast tumors by in-vivo three-dimensional parallel-plate diffuse optical tomography,” J. Biomed. Opt. 14, 024020 (2009).
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Y. Lu, B. Zhu, C. Darne, I.-C. Tan, J. C. Rasmussen, and E. M. Sevick-Muraca, “Improvement of fluorescence-enhanced optical tomography with improved optical filtering and accurate model-based reconstruction algorithms,” J. Biomed. Opt. 16, 126002 (2011).
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V. Ratner, M. Sinev, and E. Haas, “Determination of intramolecular distance distribution during protein folding on the millisecond timescale,” J. Mol. Biol. 299, 1363–1371 (2000).
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Stinson, W. G.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254, 1178–1181 (1991).
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Stott, J. J.

Swanson, E. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254, 1178–1181 (1991).
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Y. Lu, B. Zhu, C. Darne, I.-C. Tan, J. C. Rasmussen, and E. M. Sevick-Muraca, “Improvement of fluorescence-enhanced optical tomography with improved optical filtering and accurate model-based reconstruction algorithms,” J. Biomed. Opt. 16, 126002 (2011).
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R. Choe, S. D. Konecky, A. Corlu, K. Lee, T. Durduran, D. R. Busch, S. Pathak, B. J. Czerniecki, J. Tchou, D. L. Fraker, A. DeMichele, B. Chance, S. R. Arridge, M. Schweiger, J. P. Culver, M. D. Schnall, M. E. Putt, M. A. Rosen, and A. G. Yodh, “Differentiation of benign and malignant breast tumors by in-vivo three-dimensional parallel-plate diffuse optical tomography,” J. Biomed. Opt. 14, 024020 (2009).
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G. M. van Dam, G. Themelis, L. M. A. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. S. de Jong, H. J. Arts, A. G. van der Zee, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescent imaging in ovarian cancer by folate receptor-α targeting: first in-human results,” Nat. Med. 17, 1315–1319 (2011).
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T. A. Aguilera, E. S. Olson, M. M. Timmers, T. Jiang, and R. Y. Tsien, “Systemic in vivo distribution of activatable cell penetrating peptides is superior to that of cell penetrating peptides,” Integr. Biol. 1, 371–381 (2009).
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Q. T. Nguyen, E. S. Olson, T. A. Aguilera, T. Jiang, M. Scadeng, L. G. Ellies, and R. Y. Tsien, “Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival,” Proc. Natl. Acad. Sci. USA 107, 4317–4322 (2010).
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G. M. van Dam, G. Themelis, L. M. A. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. S. de Jong, H. J. Arts, A. G. van der Zee, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescent imaging in ovarian cancer by folate receptor-α targeting: first in-human results,” Nat. Med. 17, 1315–1319 (2011).
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G. M. van Dam, G. Themelis, L. M. A. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. S. de Jong, H. J. Arts, A. G. van der Zee, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescent imaging in ovarian cancer by folate receptor-α targeting: first in-human results,” Nat. Med. 17, 1315–1319 (2011).
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Wang, X.

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Commercial systems like the SoftScan from Advanced Research Technologies Inc., Canada, immerse the breast in a scattering emulsion.

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Figures (9)

Fig. 1.
Fig. 1.

(a) Schematic of a 3D topography laser scanner and (b) schematic of the ODT measurement system. A mirror scans the laser to various points on the subject surface. The diffusively scattered light is then collected by a camera (each pixel gives a detector location). (c) Photograph of the experimental setup, including the topography scanner (lower left), the 633 nm pulsed laser (top left), the stage on which the imaging subject was placed (middle right), and the CCD camera for detection (top right).

Fig. 2.
Fig. 2.

Illustration of the mapping between the unstructured FEM meshes on which the forward model was calculated and the Cartesian grids on which the reconstructed images were formed.

Fig. 3.
Fig. 3.

(a) Camera image of the phantom (width 41 mm, height 21 mm, and length 80 mm) with the ordinate (y axis) and abscissa (x axis) measured in camera pixels. The image domain was discretized into 33×17×17 grid points for reconstruction. (b) Location of the laser source positions on the bottom of the phantom and the detector positions on the top, curved surface of the phantom, selected by choosing CCD camera pixels from a full-field image. The perspective view is given on the left and the plan view on the right.

Fig. 4.
Fig. 4.

Image reconstructions using measured data for the tissue phantom of Fig. 3. (a) μa=0.25mm1 isosurface image. Note the accuracy in reconstructing the spatial position of the absorbing rod. (b) A slice through the reconstructed μa image at y=230 pixels (dimensions along the xy axes match the camera image, dimensions along the z axis are in millimeters). (c) A slice through the reconstructed D image at pixel plane y=230.

Fig. 5.
Fig. 5.

Comparison of fixed (fine) grid and multigrid image error reduction as a function of computation time for the tissue phantom of Fig. 3.

Fig. 6.
Fig. 6.

(a) General location of the sources (inner blue circle) and detectors (outer red circle). The image domain was discretized into 33×65×33 grid points for reconstruction. (b) Dissected mouse with the imaged kidney. The grid paper beneath the mouse is 0.25cm on a side. (c) Camera image of the fluorescing kidney, with 633 nm laser excitation and measured through a 710 nm filter.

Fig. 7.
Fig. 7.

Optical image reconstruction of a mouse kidney. (a) The reconstructed μa=0.1mm1 isosurface. (b) A cross section of the mouse at pixel y=175 showing the isosurface image of the kidney at μa=0.1mm1. (c) A slice of the reconstructed μa image at z=14.5mm (with z normal to the page). (d) The fluorescence isosurface of the mouse kidney at η˜=1.2×105mm1, where η˜ is proportional to the concentration of the fluorophore. (e) A cross section of the mouse at y=175 pixels showing the fluorescence isosurface image of the kidney at η˜=1.2×105mm1. (f) A slice of the η˜ image at z=14.5mm. The dimensions along the xy axis are in pixels to match the camera image, while the dimensions along the z axis are in millimeters. The grid paper beneath the mouse in the camera is 0.25cm on a side.

Fig. 8.
Fig. 8.

(a) General location of the sources (inner blue circle) and detectors (outer red circle). The image domain was discretized into 33×65×17 grid points for reconstruction. (b) Dissected mouse with the liver. The grid paper beneath the mouse is 0.25cm on a side.

Fig. 9.
Fig. 9.

Optical image reconstruction of a mouse liver. (a) The 3D surface profile of the mouse. (b) The mouse with the reconstructed μa=0.1mm1 isosurface. (c) A cross section of the mouse at y=223 pixels showing an isosurface image at μa=0.1mm1. (d) A slice of the μa image at z=14mm (with z normal to the page). The dimensions along the xy axis are in pixels to match the camera image, while the dimensions along the z axis are in millimeters. The grid paper beneath the mouse in the camera image is 0.25cm on a side.

Equations (11)

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·[Dx(r)ϕx(r,ω)][μax(r)+jω/c]ϕx(r,ω)=βδ(rs),
·[Dx(r)ϕx(r,ω)][μax(r)+jω/c]ϕx(r,ω)=δ(rs),
·[Dm(r)ϕm(r,ω)][μam(r)+jω/c]ϕm(r,ω)=ϕx(r,ω)Sm(r,ω),
x=[μa(r1),,μa(rN),D(r1),,D(rN)]T,
x=[η˜(r1),,η˜(rN),τ(r1),,τ(rN)]T.
f(x)=[f1(x),f2(x),,fP(x)]T,
=[ϕ1(d1,ω),ϕ1(d2,ω),,ϕ1(dM,ω),ϕ2(d1,ω),,ϕK(dM,ω)]T,
x^MAP=argmaxx0{p(y|x)p(x)},
p(y|x)=1(πα)P|Λ|1exp[yf(x)Λ2α],
c˜(q)(x(q))=P2logy(q)f(q)(x(q))Λ2+S(q)(x(q)).
x˜(q)x(q)+I(q+1)(q)(x˜(q+1)I(q)(q+1)x(q)),

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