Abstract

Measurement of early-photons (EPs) from a pulsed laser source has been shown to improve imaging resolution versus continuous wave (CW) systems in diffuse optical tomography (DOT) and fluorescence mediated tomography (FMT). However, EP systems also have reduced noise performance versus CW systems since EP measurements require temporal rejection of large numbers of transmitted photons. In this work, we describe a ‘hybrid data set’ (HDS) image reconstruction approach, the goal of which was to produce a final image that retained the resolution and noise advantages of EP and CW data sets, respectively. Here, CW data was first reconstructed to produce a quantitatively accurate ‘initial guess’ intermediate image, and then this was refined with EP data to yield a higher resolution final image. We performed a series of studies with simulated data to test the resolution, quantitative accuracy and detection sensitivity of the approach. We showed that in principle it was possible to produce final images that retained the bulk of the resolution and quantitative accuracy of EP and CW images, respectively, but the HDS approach did not improve the instrument sensitivity compared to EP data alone.

© 2011 OSA

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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
  26. A. H. Hielscher, A. D. Klose, and K. M. Hanson, “Gradient-based iterative image reconstruction scheme for time-resolved optical tomography,” IEEE Trans. Med. Imaging 18(3), 262–271 (1999).
    [CrossRef] [PubMed]
  27. X. Intes, V. Ntziachristos, J. P. Culver, A. Yodh, and B. Chance, “Projection access order in algebraic reconstruction technique for diffuse optical tomography,” Phys. Med. Biol. 47(1), N1 (2002).
    [CrossRef] [PubMed]
  28. R. J. Gaudette, D. H. Brooks, C. A. DiMarzio, M. E. Kilmer, E. L. Miller, T. Gaudette, and D. A. Boas, “A comparison study of linear reconstruction techniques for diffuse optical tomographic imaging of absorption coefficient,” Phys. Med. Biol. 45(4), 1051–1070 (2000).
    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [PubMed]
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    [CrossRef] [PubMed]
  34. A. Soubret, J. Ripoll, and V. Ntziachristos, “Accuracy of fluorescent tomography in the presence of heterogeneities: study of the normalized Born ratio,” IEEE Trans. Med. Imaging 24(10), 1377–1386 (2005).
    [CrossRef] [PubMed]

2010 (4)

2009 (5)

V. Y. Soloviev, C. D’Andrea, G. Valentini, R. Cubeddu, and S. R. Arridge, “Combined reconstruction of fluorescent and optical parameters using time-resolved data,” Appl. Opt. 48(1), 28–36 (2009).
[CrossRef] [PubMed]

F. Leblond, H. Dehghani, D. Kepshire, and B. W. Pogue, “Early-photon fluorescence tomography: spatial resolution improvements and noise stability considerations,” J. Opt. Soc. Am. A 26(6), 1444–1457 (2009).
[CrossRef] [PubMed]

J. Chen and X. Intes, “Time-gated perturbation Monte Carlo for whole body functional imaging in small animals,” Opt. Express 17(22), 19566–19579 (2009).
[CrossRef] [PubMed]

M. Chu, K. Vishwanath, A. D. Klose, and H. Dehghani, “Light transport in biological tissue using three-dimensional frequency-domain simplified spherical harmonics equations,” Phys. Med. Biol. 54(8), 2493–2509 (2009).
[CrossRef] [PubMed]

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, “A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging,” Rev. Sci. Instrum. 80(4), 043701 (2009).
[CrossRef] [PubMed]

2008 (5)

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(8), 1152–1163 (2008).
[CrossRef] [PubMed]

B. J. Tromberg, B. W. Pogue, K. D. Paulsen, A. G. Yodh, D. A. Boas, and A. E. Cerussi, “Assessing the future of diffuse optical imaging technologies for breast cancer management,” Med. Phys. 35(6), 2443–2451 (2008).
[CrossRef] [PubMed]

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, “Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo,” Proc. Natl. Acad. Sci. U.S.A. 105(49), 19126–19131 (2008).
[CrossRef] [PubMed]

S. L. Jacques and B. W. Pogue, “Tutorial on diffuse light transport,” J. Biomed. Opt. 13(4), 041302 (2008).
[CrossRef] [PubMed]

A. T. Kumar, S. B. Raymond, B. J. Bacskai, and D. A. Boas, “Comparison of frequency-domain and time-domain fluorescence lifetime tomography,” Opt. Lett. 33(5), 470–472 (2008).
[CrossRef] [PubMed]

2007 (1)

G. M. Turner, A. Soubret, and V. Ntziachristos, “Inversion with early photons,” Med. Phys. 34(4), 1405–1411 (2007).
[CrossRef] [PubMed]

2006 (2)

M. A. Franceschini, D. K. Joseph, T. J. Huppert, S. G. Diamond, and D. A. Boas, “Diffuse optical imaging of the whole head,” J. Biomed. Opt. 11(5), 054007 (2006).
[CrossRef] [PubMed]

D. Piao, H. Xie, W. Zhang, J. S. Krasinski, G. Zhang, H. Dehghani, and B. W. Pogue, “Endoscopic, rapid near-infrared optical tomography,” Opt. Lett. 31(19), 2876–2878 (2006).
[CrossRef] [PubMed]

2005 (3)

A. T. Kumar, J. Skoch, B. J. Bacskai, D. A. Boas, and A. K. Dunn, “Fluorescence-lifetime-based tomography for turbid media,” Opt. Lett. 30(24), 3347–3349 (2005).
[CrossRef] [PubMed]

A. Soubret, J. Ripoll, and V. Ntziachristos, “Accuracy of fluorescent tomography in the presence of heterogeneities: study of the normalized Born ratio,” IEEE Trans. Med. Imaging 24(10), 1377–1386 (2005).
[CrossRef] [PubMed]

A. H. Hielscher, “Optical tomographic imaging of small animals,” Curr. Opin. Biotechnol. 16(1), 79–88 (2005).
[CrossRef] [PubMed]

2004 (1)

A. Godavarty, A. B. Thompson, R. Roy, M. Gurfinkel, M. J. Eppstein, C. Zhang, and E. M. Sevick-Muraca, “Diagnostic imaging of breast cancer using fluorescence-enhanced optical tomography: phantom studies,” J. Biomed. Opt. 9(3), 488–496 (2004).
[CrossRef] [PubMed]

2003 (2)

E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, “A submillimeter resolution fluorescence molecular imaging system for small animal imaging,” Med. Phys. 30(5), 901–911 (2003).
[CrossRef] [PubMed]

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, and A. G. Yodh, “Three-dimensional diffuse optical tomography in the parallel plane transmission geometry: evaluation of a hybrid frequency domain/continuous wave clinical system for breast imaging,” Med. Phys. 30(2), 235–247 (2003).
[CrossRef] [PubMed]

2002 (4)

V. Ntziachristos, C. H. Tung, C. Bremer, and R. Weissleder, “Fluorescence molecular tomography resolves protease activity in vivo,” Nat. Med. 8(7), 757–761 (2002).
[CrossRef] [PubMed]

A. H. Hielscher, A. Y. Bluestone, G. S. Abdoulaev, A. D. Klose, J. Lasker, M. Stewart, U. Netz, and J. Beuthan, “Near-infrared diffuse optical tomography,” Dis. Markers 18(5-6), 313–337 (2002).
[PubMed]

X. Intes, V. Ntziachristos, J. P. Culver, A. Yodh, and B. Chance, “Projection access order in algebraic reconstruction technique for diffuse optical tomography,” Phys. Med. Biol. 47(1), N1 (2002).
[CrossRef] [PubMed]

F. Gao, H. Zhao, and Y. Yamada, “Improvement of image quality in diffuse optical tomography by use of full time-resolved data,” Appl. Opt. 41(4), 778–791 (2002).
[CrossRef] [PubMed]

2001 (2)

W. Cai, M. Lax, and R. R. Alfano, “Analytical solution of the polarized photon transport equation in an infinite uniform medium using cumulant expansion,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 63(1 Pt 2), 016606 (2001).
[PubMed]

E. M. Hillman, J. C. Hebden, M. Schweiger, H. Dehghani, F. E. Schmidt, D. T. Delpy, and S. R. Arridge, “Time resolved optical tomography of the human forearm,” Phys. Med. Biol. 46(4), 1117–1130 (2001).
[CrossRef] [PubMed]

2000 (2)

R. J. Gaudette, D. H. Brooks, C. A. DiMarzio, M. E. Kilmer, E. L. Miller, T. Gaudette, and D. A. Boas, “A comparison study of linear reconstruction techniques for diffuse optical tomographic imaging of absorption coefficient,” Phys. Med. Biol. 45(4), 1051–1070 (2000).
[CrossRef] [PubMed]

K. Chen, L. T. Perelman, Q. Zhang, R. R. Dasari, and M. S. Feld, “Optical computed tomography in a turbid medium using early arriving photons,” J. Biomed. Opt. 5(2), 144–154 (2000).
[CrossRef] [PubMed]

1999 (1)

A. H. Hielscher, A. D. Klose, and K. M. Hanson, “Gradient-based iterative image reconstruction scheme for time-resolved optical tomography,” IEEE Trans. Med. Imaging 18(3), 262–271 (1999).
[CrossRef] [PubMed]

1997 (2)

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, “Fluorescence tomographic imaging in turbid media using early-arriving photons and Laplace transforms,” Proc. Natl. Acad. Sci. U.S.A. 94(16), 8783–8788 (1997).
[CrossRef] [PubMed]

A. Kienle and M. S. Patterson, “Improved solutions of the steady-state and the time-resolved diffusion equations for reflectance from a semi-infinite turbid medium,” J. Opt. Soc. Am. A 14(1), 246–254 (1997).
[CrossRef] [PubMed]

Abdoulaev, G. S.

A. H. Hielscher, A. Y. Bluestone, G. S. Abdoulaev, A. D. Klose, J. Lasker, M. Stewart, U. Netz, and J. Beuthan, “Near-infrared diffuse optical tomography,” Dis. Markers 18(5-6), 313–337 (2002).
[PubMed]

Aikawa, E.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, “Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo,” Proc. Natl. Acad. Sci. U.S.A. 105(49), 19126–19131 (2008).
[CrossRef] [PubMed]

Alfano, R. R.

W. Cai, M. Lax, and R. R. Alfano, “Analytical solution of the polarized photon transport equation in an infinite uniform medium using cumulant expansion,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 63(1 Pt 2), 016606 (2001).
[PubMed]

Arridge, S. R.

V. Y. Soloviev, C. D’Andrea, G. Valentini, R. Cubeddu, and S. R. Arridge, “Combined reconstruction of fluorescent and optical parameters using time-resolved data,” Appl. Opt. 48(1), 28–36 (2009).
[CrossRef] [PubMed]

E. M. Hillman, J. C. Hebden, M. Schweiger, H. Dehghani, F. E. Schmidt, D. T. Delpy, and S. R. Arridge, “Time resolved optical tomography of the human forearm,” Phys. Med. Biol. 46(4), 1117–1130 (2001).
[CrossRef] [PubMed]

Bacskai, B. J.

Bassi, A.

Bérubé-Lauzière, Y.

Beuthan, J.

A. H. Hielscher, A. Y. Bluestone, G. S. Abdoulaev, A. D. Klose, J. Lasker, M. Stewart, U. Netz, and J. Beuthan, “Near-infrared diffuse optical tomography,” Dis. Markers 18(5-6), 313–337 (2002).
[PubMed]

Bluestone, A. Y.

A. H. Hielscher, A. Y. Bluestone, G. S. Abdoulaev, A. D. Klose, J. Lasker, M. Stewart, U. Netz, and J. Beuthan, “Near-infrared diffuse optical tomography,” Dis. Markers 18(5-6), 313–337 (2002).
[PubMed]

Boas, D. A.

B. J. Tromberg, B. W. Pogue, K. D. Paulsen, A. G. Yodh, D. A. Boas, and A. E. Cerussi, “Assessing the future of diffuse optical imaging technologies for breast cancer management,” Med. Phys. 35(6), 2443–2451 (2008).
[CrossRef] [PubMed]

A. T. Kumar, S. B. Raymond, B. J. Bacskai, and D. A. Boas, “Comparison of frequency-domain and time-domain fluorescence lifetime tomography,” Opt. Lett. 33(5), 470–472 (2008).
[CrossRef] [PubMed]

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(8), 1152–1163 (2008).
[CrossRef] [PubMed]

M. A. Franceschini, D. K. Joseph, T. J. Huppert, S. G. Diamond, and D. A. Boas, “Diffuse optical imaging of the whole head,” J. Biomed. Opt. 11(5), 054007 (2006).
[CrossRef] [PubMed]

A. T. Kumar, J. Skoch, B. J. Bacskai, D. A. Boas, and A. K. Dunn, “Fluorescence-lifetime-based tomography for turbid media,” Opt. Lett. 30(24), 3347–3349 (2005).
[CrossRef] [PubMed]

R. J. Gaudette, D. H. Brooks, C. A. DiMarzio, M. E. Kilmer, E. L. Miller, T. Gaudette, and D. A. Boas, “A comparison study of linear reconstruction techniques for diffuse optical tomographic imaging of absorption coefficient,” Phys. Med. Biol. 45(4), 1051–1070 (2000).
[CrossRef] [PubMed]

Bouza Domínguez, J.

Bremer, C.

V. Ntziachristos, C. H. Tung, C. Bremer, and R. Weissleder, “Fluorescence molecular tomography resolves protease activity in vivo,” Nat. Med. 8(7), 757–761 (2002).
[CrossRef] [PubMed]

Brida, D.

Brock, J. L.

N. Valim, J. L. Brock, and M. J. Niedre, “Experimental measurement of time-dependent photon scatter for diffuse optical tomography,” J. Biomed. Opt. 15(6), 065006 (2010).
[CrossRef] [PubMed]

Brooks, D. H.

R. J. Gaudette, D. H. Brooks, C. A. DiMarzio, M. E. Kilmer, E. L. Miller, T. Gaudette, and D. A. Boas, “A comparison study of linear reconstruction techniques for diffuse optical tomographic imaging of absorption coefficient,” Phys. Med. Biol. 45(4), 1051–1070 (2000).
[CrossRef] [PubMed]

Cai, W.

W. Cai, M. Lax, and R. R. Alfano, “Analytical solution of the polarized photon transport equation in an infinite uniform medium using cumulant expansion,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 63(1 Pt 2), 016606 (2001).
[PubMed]

Cerullo, G.

Cerussi, A. E.

B. J. Tromberg, B. W. Pogue, K. D. Paulsen, A. G. Yodh, D. A. Boas, and A. E. Cerussi, “Assessing the future of diffuse optical imaging technologies for breast cancer management,” Med. Phys. 35(6), 2443–2451 (2008).
[CrossRef] [PubMed]

Chance, B.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, and A. G. Yodh, “Three-dimensional diffuse optical tomography in the parallel plane transmission geometry: evaluation of a hybrid frequency domain/continuous wave clinical system for breast imaging,” Med. Phys. 30(2), 235–247 (2003).
[CrossRef] [PubMed]

X. Intes, V. Ntziachristos, J. P. Culver, A. Yodh, and B. Chance, “Projection access order in algebraic reconstruction technique for diffuse optical tomography,” Phys. Med. Biol. 47(1), N1 (2002).
[CrossRef] [PubMed]

Chen, J.

Chen, K.

K. Chen, L. T. Perelman, Q. Zhang, R. R. Dasari, and M. S. Feld, “Optical computed tomography in a turbid medium using early arriving photons,” J. Biomed. Opt. 5(2), 144–154 (2000).
[CrossRef] [PubMed]

Choe, R.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, and A. G. Yodh, “Three-dimensional diffuse optical tomography in the parallel plane transmission geometry: evaluation of a hybrid frequency domain/continuous wave clinical system for breast imaging,” Med. Phys. 30(2), 235–247 (2003).
[CrossRef] [PubMed]

Chu, M.

M. Chu, K. Vishwanath, A. D. Klose, and H. Dehghani, “Light transport in biological tissue using three-dimensional frequency-domain simplified spherical harmonics equations,” Phys. Med. Biol. 54(8), 2493–2509 (2009).
[CrossRef] [PubMed]

Cubeddu, R.

Culver, J. P.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, and A. G. Yodh, “Three-dimensional diffuse optical tomography in the parallel plane transmission geometry: evaluation of a hybrid frequency domain/continuous wave clinical system for breast imaging,” Med. Phys. 30(2), 235–247 (2003).
[CrossRef] [PubMed]

X. Intes, V. Ntziachristos, J. P. Culver, A. Yodh, and B. Chance, “Projection access order in algebraic reconstruction technique for diffuse optical tomography,” Phys. Med. Biol. 47(1), N1 (2002).
[CrossRef] [PubMed]

D’Andrea, C.

Dasari, R. R.

K. Chen, L. T. Perelman, Q. Zhang, R. R. Dasari, and M. S. Feld, “Optical computed tomography in a turbid medium using early arriving photons,” J. Biomed. Opt. 5(2), 144–154 (2000).
[CrossRef] [PubMed]

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, “Fluorescence tomographic imaging in turbid media using early-arriving photons and Laplace transforms,” Proc. Natl. Acad. Sci. U.S.A. 94(16), 8783–8788 (1997).
[CrossRef] [PubMed]

de Kleine, R. H.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, “Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo,” Proc. Natl. Acad. Sci. U.S.A. 105(49), 19126–19131 (2008).
[CrossRef] [PubMed]

De Silvestri, S.

Dehghani, H.

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, “A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging,” Rev. Sci. Instrum. 80(4), 043701 (2009).
[CrossRef] [PubMed]

F. Leblond, H. Dehghani, D. Kepshire, and B. W. Pogue, “Early-photon fluorescence tomography: spatial resolution improvements and noise stability considerations,” J. Opt. Soc. Am. A 26(6), 1444–1457 (2009).
[CrossRef] [PubMed]

M. Chu, K. Vishwanath, A. D. Klose, and H. Dehghani, “Light transport in biological tissue using three-dimensional frequency-domain simplified spherical harmonics equations,” Phys. Med. Biol. 54(8), 2493–2509 (2009).
[CrossRef] [PubMed]

D. Piao, H. Xie, W. Zhang, J. S. Krasinski, G. Zhang, H. Dehghani, and B. W. Pogue, “Endoscopic, rapid near-infrared optical tomography,” Opt. Lett. 31(19), 2876–2878 (2006).
[CrossRef] [PubMed]

E. M. Hillman, J. C. Hebden, M. Schweiger, H. Dehghani, F. E. Schmidt, D. T. Delpy, and S. R. Arridge, “Time resolved optical tomography of the human forearm,” Phys. Med. Biol. 46(4), 1117–1130 (2001).
[CrossRef] [PubMed]

Delpy, D. T.

E. M. Hillman, J. C. Hebden, M. Schweiger, H. Dehghani, F. E. Schmidt, D. T. Delpy, and S. R. Arridge, “Time resolved optical tomography of the human forearm,” Phys. Med. Biol. 46(4), 1117–1130 (2001).
[CrossRef] [PubMed]

Diamond, S. G.

M. A. Franceschini, D. K. Joseph, T. J. Huppert, S. G. Diamond, and D. A. Boas, “Diffuse optical imaging of the whole head,” J. Biomed. Opt. 11(5), 054007 (2006).
[CrossRef] [PubMed]

DiMarzio, C. A.

R. J. Gaudette, D. H. Brooks, C. A. DiMarzio, M. E. Kilmer, E. L. Miller, T. Gaudette, and D. A. Boas, “A comparison study of linear reconstruction techniques for diffuse optical tomographic imaging of absorption coefficient,” Phys. Med. Biol. 45(4), 1051–1070 (2000).
[CrossRef] [PubMed]

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(8), 1152–1163 (2008).
[CrossRef] [PubMed]

A. T. Kumar, J. Skoch, B. J. Bacskai, D. A. Boas, and A. K. Dunn, “Fluorescence-lifetime-based tomography for turbid media,” Opt. Lett. 30(24), 3347–3349 (2005).
[CrossRef] [PubMed]

Durduran, T.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, and A. G. Yodh, “Three-dimensional diffuse optical tomography in the parallel plane transmission geometry: evaluation of a hybrid frequency domain/continuous wave clinical system for breast imaging,” Med. Phys. 30(2), 235–247 (2003).
[CrossRef] [PubMed]

Eppstein, M. J.

A. Godavarty, A. B. Thompson, R. Roy, M. Gurfinkel, M. J. Eppstein, C. Zhang, and E. M. Sevick-Muraca, “Diagnostic imaging of breast cancer using fluorescence-enhanced optical tomography: phantom studies,” J. Biomed. Opt. 9(3), 488–496 (2004).
[CrossRef] [PubMed]

Feld, M. S.

K. Chen, L. T. Perelman, Q. Zhang, R. R. Dasari, and M. S. Feld, “Optical computed tomography in a turbid medium using early arriving photons,” J. Biomed. Opt. 5(2), 144–154 (2000).
[CrossRef] [PubMed]

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, “Fluorescence tomographic imaging in turbid media using early-arriving photons and Laplace transforms,” Proc. Natl. Acad. Sci. U.S.A. 94(16), 8783–8788 (1997).
[CrossRef] [PubMed]

Franceschini, M. A.

M. A. Franceschini, D. K. Joseph, T. J. Huppert, S. G. Diamond, and D. A. Boas, “Diffuse optical imaging of the whole head,” J. Biomed. Opt. 11(5), 054007 (2006).
[CrossRef] [PubMed]

Gao, F.

Gaudette, R. J.

R. J. Gaudette, D. H. Brooks, C. A. DiMarzio, M. E. Kilmer, E. L. Miller, T. Gaudette, and D. A. Boas, “A comparison study of linear reconstruction techniques for diffuse optical tomographic imaging of absorption coefficient,” Phys. Med. Biol. 45(4), 1051–1070 (2000).
[CrossRef] [PubMed]

Gaudette, T.

R. J. Gaudette, D. H. Brooks, C. A. DiMarzio, M. E. Kilmer, E. L. Miller, T. Gaudette, and D. A. Boas, “A comparison study of linear reconstruction techniques for diffuse optical tomographic imaging of absorption coefficient,” Phys. Med. Biol. 45(4), 1051–1070 (2000).
[CrossRef] [PubMed]

Godavarty, A.

A. Godavarty, A. B. Thompson, R. Roy, M. Gurfinkel, M. J. Eppstein, C. Zhang, and E. M. Sevick-Muraca, “Diagnostic imaging of breast cancer using fluorescence-enhanced optical tomography: phantom studies,” J. Biomed. Opt. 9(3), 488–496 (2004).
[CrossRef] [PubMed]

Graves, E. E.

E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, “A submillimeter resolution fluorescence molecular imaging system for small animal imaging,” Med. Phys. 30(5), 901–911 (2003).
[CrossRef] [PubMed]

Gruber, J.

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, “A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging,” Rev. Sci. Instrum. 80(4), 043701 (2009).
[CrossRef] [PubMed]

Gurfinkel, M.

A. Godavarty, A. B. Thompson, R. Roy, M. Gurfinkel, M. J. Eppstein, C. Zhang, and E. M. Sevick-Muraca, “Diagnostic imaging of breast cancer using fluorescence-enhanced optical tomography: phantom studies,” J. Biomed. Opt. 9(3), 488–496 (2004).
[CrossRef] [PubMed]

Hanson, K. M.

A. H. Hielscher, A. D. Klose, and K. M. Hanson, “Gradient-based iterative image reconstruction scheme for time-resolved optical tomography,” IEEE Trans. Med. Imaging 18(3), 262–271 (1999).
[CrossRef] [PubMed]

Hebden, J. C.

E. M. Hillman, J. C. Hebden, M. Schweiger, H. Dehghani, F. E. Schmidt, D. T. Delpy, and S. R. Arridge, “Time resolved optical tomography of the human forearm,” Phys. Med. Biol. 46(4), 1117–1130 (2001).
[CrossRef] [PubMed]

Hielscher, A. H.

A. H. Hielscher, “Optical tomographic imaging of small animals,” Curr. Opin. Biotechnol. 16(1), 79–88 (2005).
[CrossRef] [PubMed]

A. H. Hielscher, A. Y. Bluestone, G. S. Abdoulaev, A. D. Klose, J. Lasker, M. Stewart, U. Netz, and J. Beuthan, “Near-infrared diffuse optical tomography,” Dis. Markers 18(5-6), 313–337 (2002).
[PubMed]

A. H. Hielscher, A. D. Klose, and K. M. Hanson, “Gradient-based iterative image reconstruction scheme for time-resolved optical tomography,” IEEE Trans. Med. Imaging 18(3), 262–271 (1999).
[CrossRef] [PubMed]

Hillman, E. M.

E. M. Hillman, J. C. Hebden, M. Schweiger, H. Dehghani, F. E. Schmidt, D. T. Delpy, and S. R. Arridge, “Time resolved optical tomography of the human forearm,” Phys. Med. Biol. 46(4), 1117–1130 (2001).
[CrossRef] [PubMed]

Holboke, M. J.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, and A. G. Yodh, “Three-dimensional diffuse optical tomography in the parallel plane transmission geometry: evaluation of a hybrid frequency domain/continuous wave clinical system for breast imaging,” Med. Phys. 30(2), 235–247 (2003).
[CrossRef] [PubMed]

Huppert, T. J.

M. A. Franceschini, D. K. Joseph, T. J. Huppert, S. G. Diamond, and D. A. Boas, “Diffuse optical imaging of the whole head,” J. Biomed. Opt. 11(5), 054007 (2006).
[CrossRef] [PubMed]

Hutchins, M.

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, “A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging,” Rev. Sci. Instrum. 80(4), 043701 (2009).
[CrossRef] [PubMed]

Hypnarowski, J.

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, “A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging,” Rev. Sci. Instrum. 80(4), 043701 (2009).
[CrossRef] [PubMed]

Intes, X.

J. Chen and X. Intes, “Time-gated perturbation Monte Carlo for whole body functional imaging in small animals,” Opt. Express 17(22), 19566–19579 (2009).
[CrossRef] [PubMed]

X. Intes, V. Ntziachristos, J. P. Culver, A. Yodh, and B. Chance, “Projection access order in algebraic reconstruction technique for diffuse optical tomography,” Phys. Med. Biol. 47(1), N1 (2002).
[CrossRef] [PubMed]

Jacques, S. L.

S. L. Jacques and B. W. Pogue, “Tutorial on diffuse light transport,” J. Biomed. Opt. 13(4), 041302 (2008).
[CrossRef] [PubMed]

Joseph, D. K.

M. A. Franceschini, D. K. Joseph, T. J. Huppert, S. G. Diamond, and D. A. Boas, “Diffuse optical imaging of the whole head,” J. Biomed. Opt. 11(5), 054007 (2006).
[CrossRef] [PubMed]

Kepshire, D.

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, “A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging,” Rev. Sci. Instrum. 80(4), 043701 (2009).
[CrossRef] [PubMed]

F. Leblond, H. Dehghani, D. Kepshire, and B. W. Pogue, “Early-photon fluorescence tomography: spatial resolution improvements and noise stability considerations,” J. Opt. Soc. Am. A 26(6), 1444–1457 (2009).
[CrossRef] [PubMed]

Khayat, M.

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, “A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging,” Rev. Sci. Instrum. 80(4), 043701 (2009).
[CrossRef] [PubMed]

Kienle, A.

Kilmer, M. E.

R. J. Gaudette, D. H. Brooks, C. A. DiMarzio, M. E. Kilmer, E. L. Miller, T. Gaudette, and D. A. Boas, “A comparison study of linear reconstruction techniques for diffuse optical tomographic imaging of absorption coefficient,” Phys. Med. Biol. 45(4), 1051–1070 (2000).
[CrossRef] [PubMed]

Kirsch, D. G.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, “Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo,” Proc. Natl. Acad. Sci. U.S.A. 105(49), 19126–19131 (2008).
[CrossRef] [PubMed]

Klose, A. D.

M. Chu, K. Vishwanath, A. D. Klose, and H. Dehghani, “Light transport in biological tissue using three-dimensional frequency-domain simplified spherical harmonics equations,” Phys. Med. Biol. 54(8), 2493–2509 (2009).
[CrossRef] [PubMed]

A. H. Hielscher, A. Y. Bluestone, G. S. Abdoulaev, A. D. Klose, J. Lasker, M. Stewart, U. Netz, and J. Beuthan, “Near-infrared diffuse optical tomography,” Dis. Markers 18(5-6), 313–337 (2002).
[PubMed]

A. H. Hielscher, A. D. Klose, and K. M. Hanson, “Gradient-based iterative image reconstruction scheme for time-resolved optical tomography,” IEEE Trans. Med. Imaging 18(3), 262–271 (1999).
[CrossRef] [PubMed]

Krasinski, J. S.

Kumar, A. T.

Lasker, J.

A. H. Hielscher, A. Y. Bluestone, G. S. Abdoulaev, A. D. Klose, J. Lasker, M. Stewart, U. Netz, and J. Beuthan, “Near-infrared diffuse optical tomography,” Dis. Markers 18(5-6), 313–337 (2002).
[PubMed]

Lax, M.

W. Cai, M. Lax, and R. R. Alfano, “Analytical solution of the polarized photon transport equation in an infinite uniform medium using cumulant expansion,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 63(1 Pt 2), 016606 (2001).
[PubMed]

Leblond, F.

F. Leblond, H. Dehghani, D. Kepshire, and B. W. Pogue, “Early-photon fluorescence tomography: spatial resolution improvements and noise stability considerations,” J. Opt. Soc. Am. A 26(6), 1444–1457 (2009).
[CrossRef] [PubMed]

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, “A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging,” Rev. Sci. Instrum. 80(4), 043701 (2009).
[CrossRef] [PubMed]

Miller, E. L.

R. J. Gaudette, D. H. Brooks, C. A. DiMarzio, M. E. Kilmer, E. L. Miller, T. Gaudette, and D. A. Boas, “A comparison study of linear reconstruction techniques for diffuse optical tomographic imaging of absorption coefficient,” Phys. Med. Biol. 45(4), 1051–1070 (2000).
[CrossRef] [PubMed]

Mincu, N.

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, “A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging,” Rev. Sci. Instrum. 80(4), 043701 (2009).
[CrossRef] [PubMed]

Netz, U.

A. H. Hielscher, A. Y. Bluestone, G. S. Abdoulaev, A. D. Klose, J. Lasker, M. Stewart, U. Netz, and J. Beuthan, “Near-infrared diffuse optical tomography,” Dis. Markers 18(5-6), 313–337 (2002).
[PubMed]

Niedre, M. J.

N. Valim, J. L. Brock, and M. J. Niedre, “Experimental measurement of time-dependent photon scatter for diffuse optical tomography,” J. Biomed. Opt. 15(6), 065006 (2010).
[CrossRef] [PubMed]

M. J. Niedre and V. Ntziachristos, “Comparison of fluorescence tomographic imaging in mice with early-arriving and quasi-continuous-wave photons,” Opt. Lett. 35(3), 369–371 (2010).
[CrossRef] [PubMed]

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, “Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo,” Proc. Natl. Acad. Sci. U.S.A. 105(49), 19126–19131 (2008).
[CrossRef] [PubMed]

Ntziachristos, V.

M. J. Niedre and V. Ntziachristos, “Comparison of fluorescence tomographic imaging in mice with early-arriving and quasi-continuous-wave photons,” Opt. Lett. 35(3), 369–371 (2010).
[CrossRef] [PubMed]

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, “Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo,” Proc. Natl. Acad. Sci. U.S.A. 105(49), 19126–19131 (2008).
[CrossRef] [PubMed]

G. M. Turner, A. Soubret, and V. Ntziachristos, “Inversion with early photons,” Med. Phys. 34(4), 1405–1411 (2007).
[CrossRef] [PubMed]

A. Soubret, J. Ripoll, and V. Ntziachristos, “Accuracy of fluorescent tomography in the presence of heterogeneities: study of the normalized Born ratio,” IEEE Trans. Med. Imaging 24(10), 1377–1386 (2005).
[CrossRef] [PubMed]

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, and A. G. Yodh, “Three-dimensional diffuse optical tomography in the parallel plane transmission geometry: evaluation of a hybrid frequency domain/continuous wave clinical system for breast imaging,” Med. Phys. 30(2), 235–247 (2003).
[CrossRef] [PubMed]

E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, “A submillimeter resolution fluorescence molecular imaging system for small animal imaging,” Med. Phys. 30(5), 901–911 (2003).
[CrossRef] [PubMed]

V. Ntziachristos, C. H. Tung, C. Bremer, and R. Weissleder, “Fluorescence molecular tomography resolves protease activity in vivo,” Nat. Med. 8(7), 757–761 (2002).
[CrossRef] [PubMed]

X. Intes, V. Ntziachristos, J. P. Culver, A. Yodh, and B. Chance, “Projection access order in algebraic reconstruction technique for diffuse optical tomography,” Phys. Med. Biol. 47(1), N1 (2002).
[CrossRef] [PubMed]

Patterson, M. S.

Paulsen, K. D.

B. J. Tromberg, B. W. Pogue, K. D. Paulsen, A. G. Yodh, D. A. Boas, and A. E. Cerussi, “Assessing the future of diffuse optical imaging technologies for breast cancer management,” Med. Phys. 35(6), 2443–2451 (2008).
[CrossRef] [PubMed]

Perelman, L.

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, “Fluorescence tomographic imaging in turbid media using early-arriving photons and Laplace transforms,” Proc. Natl. Acad. Sci. U.S.A. 94(16), 8783–8788 (1997).
[CrossRef] [PubMed]

Perelman, L. T.

K. Chen, L. T. Perelman, Q. Zhang, R. R. Dasari, and M. S. Feld, “Optical computed tomography in a turbid medium using early arriving photons,” J. Biomed. Opt. 5(2), 144–154 (2000).
[CrossRef] [PubMed]

Piao, D.

Pogue, B. W.

F. Leblond, H. Dehghani, D. Kepshire, and B. W. Pogue, “Early-photon fluorescence tomography: spatial resolution improvements and noise stability considerations,” J. Opt. Soc. Am. A 26(6), 1444–1457 (2009).
[CrossRef] [PubMed]

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, “A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging,” Rev. Sci. Instrum. 80(4), 043701 (2009).
[CrossRef] [PubMed]

B. J. Tromberg, B. W. Pogue, K. D. Paulsen, A. G. Yodh, D. A. Boas, and A. E. Cerussi, “Assessing the future of diffuse optical imaging technologies for breast cancer management,” Med. Phys. 35(6), 2443–2451 (2008).
[CrossRef] [PubMed]

S. L. Jacques and B. W. Pogue, “Tutorial on diffuse light transport,” J. Biomed. Opt. 13(4), 041302 (2008).
[CrossRef] [PubMed]

D. Piao, H. Xie, W. Zhang, J. S. Krasinski, G. Zhang, H. Dehghani, and B. W. Pogue, “Endoscopic, rapid near-infrared optical tomography,” Opt. Lett. 31(19), 2876–2878 (2006).
[CrossRef] [PubMed]

Raymond, S. B.

A. T. Kumar, S. B. Raymond, B. J. Bacskai, and D. A. Boas, “Comparison of frequency-domain and time-domain fluorescence lifetime tomography,” Opt. Lett. 33(5), 470–472 (2008).
[CrossRef] [PubMed]

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(8), 1152–1163 (2008).
[CrossRef] [PubMed]

Ripoll, J.

A. Soubret, J. Ripoll, and V. Ntziachristos, “Accuracy of fluorescent tomography in the presence of heterogeneities: study of the normalized Born ratio,” IEEE Trans. Med. Imaging 24(10), 1377–1386 (2005).
[CrossRef] [PubMed]

E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, “A submillimeter resolution fluorescence molecular imaging system for small animal imaging,” Med. Phys. 30(5), 901–911 (2003).
[CrossRef] [PubMed]

Roy, R.

A. Godavarty, A. B. Thompson, R. Roy, M. Gurfinkel, M. J. Eppstein, C. Zhang, and E. M. Sevick-Muraca, “Diagnostic imaging of breast cancer using fluorescence-enhanced optical tomography: phantom studies,” J. Biomed. Opt. 9(3), 488–496 (2004).
[CrossRef] [PubMed]

Schmidt, F. E.

E. M. Hillman, J. C. Hebden, M. Schweiger, H. Dehghani, F. E. Schmidt, D. T. Delpy, and S. R. Arridge, “Time resolved optical tomography of the human forearm,” Phys. Med. Biol. 46(4), 1117–1130 (2001).
[CrossRef] [PubMed]

Schweiger, M.

E. M. Hillman, J. C. Hebden, M. Schweiger, H. Dehghani, F. E. Schmidt, D. T. Delpy, and S. R. Arridge, “Time resolved optical tomography of the human forearm,” Phys. Med. Biol. 46(4), 1117–1130 (2001).
[CrossRef] [PubMed]

Sevick-Muraca, E. M.

A. Godavarty, A. B. Thompson, R. Roy, M. Gurfinkel, M. J. Eppstein, C. Zhang, and E. M. Sevick-Muraca, “Diagnostic imaging of breast cancer using fluorescence-enhanced optical tomography: phantom studies,” J. Biomed. Opt. 9(3), 488–496 (2004).
[CrossRef] [PubMed]

Skoch, J.

Slemp, A.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, and A. G. Yodh, “Three-dimensional diffuse optical tomography in the parallel plane transmission geometry: evaluation of a hybrid frequency domain/continuous wave clinical system for breast imaging,” Med. Phys. 30(2), 235–247 (2003).
[CrossRef] [PubMed]

Soloviev, V. Y.

Soubret, A.

G. M. Turner, A. Soubret, and V. Ntziachristos, “Inversion with early photons,” Med. Phys. 34(4), 1405–1411 (2007).
[CrossRef] [PubMed]

A. Soubret, J. Ripoll, and V. Ntziachristos, “Accuracy of fluorescent tomography in the presence of heterogeneities: study of the normalized Born ratio,” IEEE Trans. Med. Imaging 24(10), 1377–1386 (2005).
[CrossRef] [PubMed]

Stewart, M.

A. H. Hielscher, A. Y. Bluestone, G. S. Abdoulaev, A. D. Klose, J. Lasker, M. Stewart, U. Netz, and J. Beuthan, “Near-infrared diffuse optical tomography,” Dis. Markers 18(5-6), 313–337 (2002).
[PubMed]

Thompson, A. B.

A. Godavarty, A. B. Thompson, R. Roy, M. Gurfinkel, M. J. Eppstein, C. Zhang, and E. M. Sevick-Muraca, “Diagnostic imaging of breast cancer using fluorescence-enhanced optical tomography: phantom studies,” J. Biomed. Opt. 9(3), 488–496 (2004).
[CrossRef] [PubMed]

Tromberg, B. J.

B. J. Tromberg, B. W. Pogue, K. D. Paulsen, A. G. Yodh, D. A. Boas, and A. E. Cerussi, “Assessing the future of diffuse optical imaging technologies for breast cancer management,” Med. Phys. 35(6), 2443–2451 (2008).
[CrossRef] [PubMed]

Tung, C. H.

V. Ntziachristos, C. H. Tung, C. Bremer, and R. Weissleder, “Fluorescence molecular tomography resolves protease activity in vivo,” Nat. Med. 8(7), 757–761 (2002).
[CrossRef] [PubMed]

Turner, G. M.

G. M. Turner, A. Soubret, and V. Ntziachristos, “Inversion with early photons,” Med. Phys. 34(4), 1405–1411 (2007).
[CrossRef] [PubMed]

Valentini, G.

Valim, N.

N. Valim, J. L. Brock, and M. J. Niedre, “Experimental measurement of time-dependent photon scatter for diffuse optical tomography,” J. Biomed. Opt. 15(6), 065006 (2010).
[CrossRef] [PubMed]

Vishwanath, K.

M. Chu, K. Vishwanath, A. D. Klose, and H. Dehghani, “Light transport in biological tissue using three-dimensional frequency-domain simplified spherical harmonics equations,” Phys. Med. Biol. 54(8), 2493–2509 (2009).
[CrossRef] [PubMed]

Weissleder, R.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, “Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo,” Proc. Natl. Acad. Sci. U.S.A. 105(49), 19126–19131 (2008).
[CrossRef] [PubMed]

E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, “A submillimeter resolution fluorescence molecular imaging system for small animal imaging,” Med. Phys. 30(5), 901–911 (2003).
[CrossRef] [PubMed]

V. Ntziachristos, C. H. Tung, C. Bremer, and R. Weissleder, “Fluorescence molecular tomography resolves protease activity in vivo,” Nat. Med. 8(7), 757–761 (2002).
[CrossRef] [PubMed]

Wu, J.

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, “Fluorescence tomographic imaging in turbid media using early-arriving photons and Laplace transforms,” Proc. Natl. Acad. Sci. U.S.A. 94(16), 8783–8788 (1997).
[CrossRef] [PubMed]

Xie, H.

Yamada, Y.

Yodh, A.

X. Intes, V. Ntziachristos, J. P. Culver, A. Yodh, and B. Chance, “Projection access order in algebraic reconstruction technique for diffuse optical tomography,” Phys. Med. Biol. 47(1), N1 (2002).
[CrossRef] [PubMed]

Yodh, A. G.

B. J. Tromberg, B. W. Pogue, K. D. Paulsen, A. G. Yodh, D. A. Boas, and A. E. Cerussi, “Assessing the future of diffuse optical imaging technologies for breast cancer management,” Med. Phys. 35(6), 2443–2451 (2008).
[CrossRef] [PubMed]

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Figures (10)

Fig. 1
Fig. 1

Overview of the hybrid data set image reconstruction approach.

Fig. 2
Fig. 2

(a) Schematic of the simulated time-resolved fluorescence tomographic instrument used in these studies. (b) An example normalized Alexafluor-680 time-resolved fluorescence curve through diffusive media. The shaded area (arrow) indicates the location of the early-photon time gate, whereas quasi-CW data is equivalent to the area under the full TR curve. Calculated instrument PDSFs are also shown for (c) early and (d) quasi-CW time gates.

Fig. 3
Fig. 3

Numerical phantoms with simulated fluorescent inclusions with varying edge-to-edge separations (a-c) were used to test the resolution properties of the HDS approach. Here, the infinite (10:0) object-to-background contrast was assumed. Purely CW data (d-f) yielded worse imaging resolution than purely EP data (g-i). Images produced with the HDS reconstruction approach with 80CW:20EP (j-l) and 40CW:60EP (m-o) data mixes are shown.

Fig. 4
Fig. 4

Example numerical phantoms with varying edge-to-edge separations (a-c) and an experimentally realistic object-to-background autofluorescence ratio of 5:1. Purely CW data (d-f) yielded worse imaging resolution than purely EP data (g-i). Images produced with the HDS reconstruction approach with 80CW:20EP (j-l) and 40CW:60EP (m-o) data mixes are shown.

Fig. 5
Fig. 5

The minimum edge-to-edge separation distance between fluorescent inclusions for which two distinct objects could be reconstructed for different data mixes, defined by either (a) the full width half maximum intensity separation of both objects or (b) empirical observation of two distinct foci.

Fig. 6
Fig. 6

The area of the imaging point spread function for a 1 pixel by 1 pixel object placed at either the center or a left-edge position in the object for different HDS data mixes, normalized to the PSF area obtained for EPs (unitless).

Fig. 7
Fig. 7

A series of objects with three fluorescent inclusions of varying concentration (a-d) are shown along with the reconstructed images for pure quasi-CW data (e-h) and pure EP data (i-l). Images produced with the HDS reconstruction approach with 80CW:20EP (m-p) and 40CW:60EP (q-t) data mixes are shown.

Fig. 8
Fig. 8

A series of objects with three fluorescent inclusions of varying concentration (a-d) with background autofluorescence are shown along with the reconstructed images for pure quasi-CW data (e-h) and pure EP data (i-l). Images produced with the HDS reconstruction approach with 80CW:20EP (m-p) and 40CW:60EP (q-t) data mixes are shown.

Fig. 9
Fig. 9

The use of more CW data in the HDS data mix resulted in worse resolution but better quantitative accuracy. Example calibrated reconstructed intensities for a dilution series of experiments (no simulated autofluorescence) for the (a) 100CW:0EP HDS data mix, and (b) 0CW:100EP data mix is shown. The mean normalized error (Eq. (9) in the reconstructed intensity for different HDS reconstruction data mixes is shown for the case (c) without background autofluorescence, and (d) with background autofluorescence.

Fig. 10
Fig. 10

The minimum fluorescence concentration for which an object could be reconstructed for different HDS reconstruction approaches.

Equations (9)

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W ( r s , r d ) = U 0 ( r , r s ) G ( r d , r ) d 3 r
Φ ( r ) = 1 4 π D r exp ( μ a D r )
W ( r s , r d , t ) = 0 t U 0 ( r , r s , τ ) G ( r d , r , t τ ) d 3 r d τ
Φ ( r , t ) = 1 ( 4 π D c t ) 3 / 2 exp ( r 2 4 D c t ) exp ( μ a t )
W f l ( r s , r d , t ) = 0 t 0 t U 0 ( r s , r , t ) G ( r d , r , t t ) d 3 r d t 1 τ e t t τ d t
U f l ( r s , r d ) = U 0 ( r , r s ) G ( r d , r ) η ( r ) d 3 r
U f l ( r s , r d , t ) = 0 t 0 t U 0 ( r s , r , t ) G ( r d , r , t t ) η ( r ) τ e t t τ d 3 r d t d t
U f l n o i s e = U f l + a b σ .
M . E . = 1 N i = 1 N ( C r ( i ) C t ( i ) ) 2 C t ( i ) ,

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