Abstract

X-ray luminescence computed tomography (XLCT) has the potential to image the biodistribution of nanoparticles inside deep tissues. In XLCT, X-ray excitable nanophosphors emit optical photons for tomographic imaging. The lifetime of the nanophosphor signal, rather than its intensity, could be used to extract biological microenvironment information such as oxygenation in deep tumors. In this study, we propose the design, the forward model, and the reconstruction algorithm of a time domain XLCT for lifetime imaging with high spatial resolution. We have investigated the feasibility of the proposed design with numerical simulations. We found that the reconstructed lifetime images are robust to noise levels up to 5% and to unknown optical properties up to 4 times of absorption and scattering coefficients.

© 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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References

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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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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. P. Favier, L. Amoudry, K. Cassou, K. Dupraz, A. Martens, H. Monard, and F. Zomer, “The compact x-ray source ThomX,” Proc. SPIE 10387, 1038708 (2017).

2017 (4)

M. C. Lun, W. Zhang, and C. Li, “Sensitivity study of x-ray luminescence computed tomography,” Appl. Opt. 56(11), 3010–3019 (2017).
[Crossref] [PubMed]

W. Zhang, D. Zhu, M. Lun, and C. Li, “Collimated superfine x-ray beam based x-ray luminescence computed tomography,” J. XRay Sci. Technol. 25(6), 945–957 (2017).
[Crossref] [PubMed]

W. Zhang, M. C. Lun, A. A. Nguyen, and C. Li, “X-ray luminescence computed tomography using a focused x-ray beam,” J. Biomed. Opt. 22(11), 1–11 (2017).
[Crossref] [PubMed]

P. Favier, L. Amoudry, K. Cassou, K. Dupraz, A. Martens, H. Monard, and F. Zomer, “The compact x-ray source ThomX,” Proc. SPIE 10387, 1038708 (2017).

2016 (3)

2015 (1)

W. Zheng, D. Tu, P. Huang, S. Zhou, Z. Chen, and X. Chen, “Time-resolved luminescent biosensing based on inorganic lanthanide-doped nanoprobes,” Chem. Commun. (Camb.) 51(20), 4129–4143 (2015).
[Crossref] [PubMed]

2014 (4)

L. M. Hirvonen, F. Festy, and K. Suhling, “Wide-field time-correlated single-photon counting (TCSPC) lifetime microscopy with microsecond time resolution,” Opt. Lett. 39(19), 5602–5605 (2014).
[Crossref] [PubMed]

D. Zhu and C. Li, “Nonuniform update for sparse target recovery in fluorescence molecular tomography accelerated by ordered subsets,” Biomed. Opt. Express 5(12), 4249–4259 (2014).
[Crossref] [PubMed]

D. Zhu and C. Li, “Nonconvex regularizations in fluorescence molecular tomography for sparsity enhancement,” Phys. Med. Biol. 59(12), 2901–2912 (2014).
[Crossref] [PubMed]

C. Li, A. Martínez-Dávalos, and S. R. Cherry, “Numerical simulation of x-ray luminescence optical tomography for small-animal imaging,” J. Biomed. Opt. 19(4), 046002 (2014).
[Crossref] [PubMed]

2013 (3)

2010 (3)

G. Pratx, C. M. Carpenter, C. Sun, and L. Xing, “X-ray luminescence computed tomography via selective excitation: a feasibility study,” IEEE Trans. Med. Imaging 29(12), 1992–1999 (2010).
[Crossref] [PubMed]

G. Pratx, C. M. Carpenter, C. Sun, R. P. Rao, and L. Xing, “Tomographic molecular imaging of x-ray-excitable nanoparticles,” Opt. Lett. 35(20), 3345–3347 (2010).
[Crossref] [PubMed]

C. Supnet and I. Bezprozvanny, “The dysregulation of intracellular calcium in Alzheimer disease,” Cell Calcium 47(2), 183–189 (2010).
[Crossref] [PubMed]

2009 (1)

2008 (1)

M. Lazarczyk and M. Favre, “Role of Zn2+ ions in host-virus interactions,” J. Virol. 82(23), 11486–11494 (2008).
[Crossref] [PubMed]

2007 (1)

K. Hanaoka, K. Kikuchi, S. Kobayashi, and T. Nagano, “Time-resolved long-lived luminescence imaging method employing luminescent lanthanide probes with a new microscopy system,” J. Am. Chem. Soc. 129(44), 13502–13509 (2007).
[Crossref] [PubMed]

2006 (1)

2005 (2)

K. Suhling, P. M. French, and D. Phillips, “Time-resolved fluorescence microscopy,” Photochem. Photobiol. Sci. 4(1), 13–22 (2005).
[Crossref] [PubMed]

A. P. Gibson, J. C. Hebden, and S. R. Arridge, “Recent advances in diffuse optical imaging,” Phys. Med. Biol. 50(4), R1–R43 (2005).
[Crossref] [PubMed]

2003 (2)

E. Gratton, S. Breusegem, J. Sutin, Q. Ruan, and N. Barry, “Fluorescence lifetime imaging for the two-photon microscope: time-domain and frequency-domain methods,” J. Biomed. Opt. 8(3), 381–390 (2003).
[Crossref] [PubMed]

H. J. Lin, P. Herman, and J. R. Lakowicz, “Fluorescence lifetime-resolved pH imaging of living cells,” Cytometry A 52(2), 77–89 (2003).
[Crossref] [PubMed]

Amoudry, L.

P. Favier, L. Amoudry, K. Cassou, K. Dupraz, A. Martens, H. Monard, and F. Zomer, “The compact x-ray source ThomX,” Proc. SPIE 10387, 1038708 (2017).

Arridge, S. R.

A. P. Gibson, J. C. Hebden, and S. R. Arridge, “Recent advances in diffuse optical imaging,” Phys. Med. Biol. 50(4), R1–R43 (2005).
[Crossref] [PubMed]

Barry, N.

E. Gratton, S. Breusegem, J. Sutin, Q. Ruan, and N. Barry, “Fluorescence lifetime imaging for the two-photon microscope: time-domain and frequency-domain methods,” J. Biomed. Opt. 8(3), 381–390 (2003).
[Crossref] [PubMed]

Bec, J.

Bezprozvanny, I.

C. Supnet and I. Bezprozvanny, “The dysregulation of intracellular calcium in Alzheimer disease,” Cell Calcium 47(2), 183–189 (2010).
[Crossref] [PubMed]

Breusegem, S.

E. Gratton, S. Breusegem, J. Sutin, Q. Ruan, and N. Barry, “Fluorescence lifetime imaging for the two-photon microscope: time-domain and frequency-domain methods,” J. Biomed. Opt. 8(3), 381–390 (2003).
[Crossref] [PubMed]

Carpenter, C. M.

G. Pratx, C. M. Carpenter, C. Sun, and L. Xing, “X-ray luminescence computed tomography via selective excitation: a feasibility study,” IEEE Trans. Med. Imaging 29(12), 1992–1999 (2010).
[Crossref] [PubMed]

G. Pratx, C. M. Carpenter, C. Sun, R. P. Rao, and L. Xing, “Tomographic molecular imaging of x-ray-excitable nanoparticles,” Opt. Lett. 35(20), 3345–3347 (2010).
[Crossref] [PubMed]

Cassou, K.

P. Favier, L. Amoudry, K. Cassou, K. Dupraz, A. Martens, H. Monard, and F. Zomer, “The compact x-ray source ThomX,” Proc. SPIE 10387, 1038708 (2017).

Chen, D.

D. Chen, S. Zhu, H. Yi, X. Zhang, D. Chen, J. Liang, and J. Tian, “Cone beam x-ray luminescence computed tomography: a feasibility study,” Med. Phys. 40(3), 031111 (2013).
[Crossref] [PubMed]

D. Chen, S. Zhu, H. Yi, X. Zhang, D. Chen, J. Liang, and J. Tian, “Cone beam x-ray luminescence computed tomography: a feasibility study,” Med. Phys. 40(3), 031111 (2013).
[Crossref] [PubMed]

Chen, W.

Chen, X.

W. Zheng, D. Tu, P. Huang, S. Zhou, Z. Chen, and X. Chen, “Time-resolved luminescent biosensing based on inorganic lanthanide-doped nanoprobes,” Chem. Commun. (Camb.) 51(20), 4129–4143 (2015).
[Crossref] [PubMed]

Chen, Z.

S. Liu, Y. Zhang, H. Liang, Z. Chen, Z. Liu, and Q. Zhao, “Time-resolved luminescence imaging of intracellular oxygen levels based on long-lived phosphorescent iridium(III) complex,” Opt. Express 24(14), 15757–15764 (2016).
[Crossref] [PubMed]

W. Zheng, D. Tu, P. Huang, S. Zhou, Z. Chen, and X. Chen, “Time-resolved luminescent biosensing based on inorganic lanthanide-doped nanoprobes,” Chem. Commun. (Camb.) 51(20), 4129–4143 (2015).
[Crossref] [PubMed]

Cherry, S. R.

Di, K.

Dupraz, K.

P. Favier, L. Amoudry, K. Cassou, K. Dupraz, A. Martens, H. Monard, and F. Zomer, “The compact x-ray source ThomX,” Proc. SPIE 10387, 1038708 (2017).

Favier, P.

P. Favier, L. Amoudry, K. Cassou, K. Dupraz, A. Martens, H. Monard, and F. Zomer, “The compact x-ray source ThomX,” Proc. SPIE 10387, 1038708 (2017).

Favre, M.

M. Lazarczyk and M. Favre, “Role of Zn2+ ions in host-virus interactions,” J. Virol. 82(23), 11486–11494 (2008).
[Crossref] [PubMed]

Festy, F.

French, P. M.

K. Suhling, P. M. French, and D. Phillips, “Time-resolved fluorescence microscopy,” Photochem. Photobiol. Sci. 4(1), 13–22 (2005).
[Crossref] [PubMed]

Gao, F.

Gibson, A. P.

A. P. Gibson, J. C. Hebden, and S. R. Arridge, “Recent advances in diffuse optical imaging,” Phys. Med. Biol. 50(4), R1–R43 (2005).
[Crossref] [PubMed]

Gratton, E.

E. Gratton, S. Breusegem, J. Sutin, Q. Ruan, and N. Barry, “Fluorescence lifetime imaging for the two-photon microscope: time-domain and frequency-domain methods,” J. Biomed. Opt. 8(3), 381–390 (2003).
[Crossref] [PubMed]

Hanaoka, K.

K. Hanaoka, K. Kikuchi, S. Kobayashi, and T. Nagano, “Time-resolved long-lived luminescence imaging method employing luminescent lanthanide probes with a new microscopy system,” J. Am. Chem. Soc. 129(44), 13502–13509 (2007).
[Crossref] [PubMed]

Hebden, J. C.

A. P. Gibson, J. C. Hebden, and S. R. Arridge, “Recent advances in diffuse optical imaging,” Phys. Med. Biol. 50(4), R1–R43 (2005).
[Crossref] [PubMed]

Herman, P.

H. J. Lin, P. Herman, and J. R. Lakowicz, “Fluorescence lifetime-resolved pH imaging of living cells,” Cytometry A 52(2), 77–89 (2003).
[Crossref] [PubMed]

Hirvonen, L. M.

Howard, S. S.

Huang, P.

W. Zheng, D. Tu, P. Huang, S. Zhou, Z. Chen, and X. Chen, “Time-resolved luminescent biosensing based on inorganic lanthanide-doped nanoprobes,” Chem. Commun. (Camb.) 51(20), 4129–4143 (2015).
[Crossref] [PubMed]

Khan, A. A.

Kikuchi, K.

K. Hanaoka, K. Kikuchi, S. Kobayashi, and T. Nagano, “Time-resolved long-lived luminescence imaging method employing luminescent lanthanide probes with a new microscopy system,” J. Am. Chem. Soc. 129(44), 13502–13509 (2007).
[Crossref] [PubMed]

Kobayashi, S.

K. Hanaoka, K. Kikuchi, S. Kobayashi, and T. Nagano, “Time-resolved long-lived luminescence imaging method employing luminescent lanthanide probes with a new microscopy system,” J. Am. Chem. Soc. 129(44), 13502–13509 (2007).
[Crossref] [PubMed]

Lakowicz, J. R.

H. J. Lin, P. Herman, and J. R. Lakowicz, “Fluorescence lifetime-resolved pH imaging of living cells,” Cytometry A 52(2), 77–89 (2003).
[Crossref] [PubMed]

Lazarczyk, M.

M. Lazarczyk and M. Favre, “Role of Zn2+ ions in host-virus interactions,” J. Virol. 82(23), 11486–11494 (2008).
[Crossref] [PubMed]

Li, C.

W. Zhang, D. Zhu, M. Lun, and C. Li, “Collimated superfine x-ray beam based x-ray luminescence computed tomography,” J. XRay Sci. Technol. 25(6), 945–957 (2017).
[Crossref] [PubMed]

W. Zhang, M. C. Lun, A. A. Nguyen, and C. Li, “X-ray luminescence computed tomography using a focused x-ray beam,” J. Biomed. Opt. 22(11), 1–11 (2017).
[Crossref] [PubMed]

M. C. Lun, W. Zhang, and C. Li, “Sensitivity study of x-ray luminescence computed tomography,” Appl. Opt. 56(11), 3010–3019 (2017).
[Crossref] [PubMed]

W. Zhang, D. Zhu, M. Lun, and C. Li, “Multiple pinhole collimator based X-ray luminescence computed tomography,” Biomed. Opt. Express 7(7), 2506–2523 (2016).
[Crossref] [PubMed]

D. Zhu and C. Li, “Nonuniform update for sparse target recovery in fluorescence molecular tomography accelerated by ordered subsets,” Biomed. Opt. Express 5(12), 4249–4259 (2014).
[Crossref] [PubMed]

C. Li, A. Martínez-Dávalos, and S. R. Cherry, “Numerical simulation of x-ray luminescence optical tomography for small-animal imaging,” J. Biomed. Opt. 19(4), 046002 (2014).
[Crossref] [PubMed]

D. Zhu and C. Li, “Nonconvex regularizations in fluorescence molecular tomography for sparsity enhancement,” Phys. Med. Biol. 59(12), 2901–2912 (2014).
[Crossref] [PubMed]

C. Li, K. Di, J. Bec, and S. R. Cherry, “X-ray luminescence optical tomography imaging: experimental studies,” Opt. Lett. 38(13), 2339–2341 (2013).
[Crossref] [PubMed]

C. Li, G. Wang, J. Qi, and S. R. Cherry, “Three-dimensional fluorescence optical tomography in small-animal imaging using simultaneous positron-emission-tomography priors,” Opt. Lett. 34(19), 2933–2935 (2009).
[Crossref] [PubMed]

Li, J.

Liang, H.

Liang, J.

D. Chen, S. Zhu, H. Yi, X. Zhang, D. Chen, J. Liang, and J. Tian, “Cone beam x-ray luminescence computed tomography: a feasibility study,” Med. Phys. 40(3), 031111 (2013).
[Crossref] [PubMed]

Lin, H. J.

H. J. Lin, P. Herman, and J. R. Lakowicz, “Fluorescence lifetime-resolved pH imaging of living cells,” Cytometry A 52(2), 77–89 (2003).
[Crossref] [PubMed]

Liu, S.

Liu, Z.

Lu, Y.

Lun, M.

W. Zhang, D. Zhu, M. Lun, and C. Li, “Collimated superfine x-ray beam based x-ray luminescence computed tomography,” J. XRay Sci. Technol. 25(6), 945–957 (2017).
[Crossref] [PubMed]

W. Zhang, D. Zhu, M. Lun, and C. Li, “Multiple pinhole collimator based X-ray luminescence computed tomography,” Biomed. Opt. Express 7(7), 2506–2523 (2016).
[Crossref] [PubMed]

Lun, M. C.

M. C. Lun, W. Zhang, and C. Li, “Sensitivity study of x-ray luminescence computed tomography,” Appl. Opt. 56(11), 3010–3019 (2017).
[Crossref] [PubMed]

W. Zhang, M. C. Lun, A. A. Nguyen, and C. Li, “X-ray luminescence computed tomography using a focused x-ray beam,” J. Biomed. Opt. 22(11), 1–11 (2017).
[Crossref] [PubMed]

Martens, A.

P. Favier, L. Amoudry, K. Cassou, K. Dupraz, A. Martens, H. Monard, and F. Zomer, “The compact x-ray source ThomX,” Proc. SPIE 10387, 1038708 (2017).

Martínez-Dávalos, A.

C. Li, A. Martínez-Dávalos, and S. R. Cherry, “Numerical simulation of x-ray luminescence optical tomography for small-animal imaging,” J. Biomed. Opt. 19(4), 046002 (2014).
[Crossref] [PubMed]

Monard, H.

P. Favier, L. Amoudry, K. Cassou, K. Dupraz, A. Martens, H. Monard, and F. Zomer, “The compact x-ray source ThomX,” Proc. SPIE 10387, 1038708 (2017).

Nagano, T.

K. Hanaoka, K. Kikuchi, S. Kobayashi, and T. Nagano, “Time-resolved long-lived luminescence imaging method employing luminescent lanthanide probes with a new microscopy system,” J. Am. Chem. Soc. 129(44), 13502–13509 (2007).
[Crossref] [PubMed]

Nguyen, A. A.

W. Zhang, M. C. Lun, A. A. Nguyen, and C. Li, “X-ray luminescence computed tomography using a focused x-ray beam,” J. Biomed. Opt. 22(11), 1–11 (2017).
[Crossref] [PubMed]

Phillips, D.

K. Suhling, P. M. French, and D. Phillips, “Time-resolved fluorescence microscopy,” Photochem. Photobiol. Sci. 4(1), 13–22 (2005).
[Crossref] [PubMed]

Pratx, G.

G. Pratx, C. M. Carpenter, C. Sun, and L. Xing, “X-ray luminescence computed tomography via selective excitation: a feasibility study,” IEEE Trans. Med. Imaging 29(12), 1992–1999 (2010).
[Crossref] [PubMed]

G. Pratx, C. M. Carpenter, C. Sun, R. P. Rao, and L. Xing, “Tomographic molecular imaging of x-ray-excitable nanoparticles,” Opt. Lett. 35(20), 3345–3347 (2010).
[Crossref] [PubMed]

Qi, J.

Rao, R. P.

Ruan, Q.

E. Gratton, S. Breusegem, J. Sutin, Q. Ruan, and N. Barry, “Fluorescence lifetime imaging for the two-photon microscope: time-domain and frequency-domain methods,” J. Biomed. Opt. 8(3), 381–390 (2003).
[Crossref] [PubMed]

Suhling, K.

Sun, C.

G. Pratx, C. M. Carpenter, C. Sun, R. P. Rao, and L. Xing, “Tomographic molecular imaging of x-ray-excitable nanoparticles,” Opt. Lett. 35(20), 3345–3347 (2010).
[Crossref] [PubMed]

G. Pratx, C. M. Carpenter, C. Sun, and L. Xing, “X-ray luminescence computed tomography via selective excitation: a feasibility study,” IEEE Trans. Med. Imaging 29(12), 1992–1999 (2010).
[Crossref] [PubMed]

Supnet, C.

C. Supnet and I. Bezprozvanny, “The dysregulation of intracellular calcium in Alzheimer disease,” Cell Calcium 47(2), 183–189 (2010).
[Crossref] [PubMed]

Sutin, J.

E. Gratton, S. Breusegem, J. Sutin, Q. Ruan, and N. Barry, “Fluorescence lifetime imaging for the two-photon microscope: time-domain and frequency-domain methods,” J. Biomed. Opt. 8(3), 381–390 (2003).
[Crossref] [PubMed]

Tanikawa, Y.

Tian, J.

D. Chen, S. Zhu, H. Yi, X. Zhang, D. Chen, J. Liang, and J. Tian, “Cone beam x-ray luminescence computed tomography: a feasibility study,” Med. Phys. 40(3), 031111 (2013).
[Crossref] [PubMed]

Tu, D.

W. Zheng, D. Tu, P. Huang, S. Zhou, Z. Chen, and X. Chen, “Time-resolved luminescent biosensing based on inorganic lanthanide-doped nanoprobes,” Chem. Commun. (Camb.) 51(20), 4129–4143 (2015).
[Crossref] [PubMed]

Vigil, G. D.

Wang, G.

Wang, X.

Wu, L.

Xing, L.

G. Pratx, C. M. Carpenter, C. Sun, R. P. Rao, and L. Xing, “Tomographic molecular imaging of x-ray-excitable nanoparticles,” Opt. Lett. 35(20), 3345–3347 (2010).
[Crossref] [PubMed]

G. Pratx, C. M. Carpenter, C. Sun, and L. Xing, “X-ray luminescence computed tomography via selective excitation: a feasibility study,” IEEE Trans. Med. Imaging 29(12), 1992–1999 (2010).
[Crossref] [PubMed]

Yamada, Y.

Yi, H.

D. Chen, S. Zhu, H. Yi, X. Zhang, D. Chen, J. Liang, and J. Tian, “Cone beam x-ray luminescence computed tomography: a feasibility study,” Med. Phys. 40(3), 031111 (2013).
[Crossref] [PubMed]

Yi, X.

Zhang, L.

Zhang, W.

Zhang, X.

D. Chen, S. Zhu, H. Yi, X. Zhang, D. Chen, J. Liang, and J. Tian, “Cone beam x-ray luminescence computed tomography: a feasibility study,” Med. Phys. 40(3), 031111 (2013).
[Crossref] [PubMed]

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Figures (4)

Fig. 1
Fig. 1 Schematic of the proposed time domain XLCT system.
Fig. 2
Fig. 2 The phantom geometry and fiber bundle position for numerical simulation with three targets.
Fig. 3
Fig. 3 The reconstruction results of phosphorescence yield (top) and lifetime (bottom) for three targets numerical simulation. A: The reconstructed phosphorescence yield and lifetime images, respectively; B: Zoomed in regions of reconstructed targets, the green dotted line indicates the exact target size and position, the blue dotted line indicates the profile location; C: profile plots across target T2 and target T3.
Fig. 4
Fig. 4 The zoomed regions of the reconstructed phosphorescence yield images and lifetime images for three targets numerical simulation with measurements at different projections. The dotted circles indicate the true target position and size. The bottom row shows the profile plots cross the bottom two targets where “1 det” indicates one detector we used in the simulations.

Tables (5)

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Table 1 Optical and phosphorescent parameters of the phantom and targets

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Table 2 Quantitative imaging quality metrics for the numerical simulation with three targets.

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Table 3 Quantitative imaging quality metrics for the numerical simulations with different noise levels

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Table 4 Quantitative imaging quality metrics for the numerical simulations with measurements of different projection numbers

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Table 5 Quantitative imaging quality metrics for the numerical simulations with mismatched optical properties. The first row indicates the true optical properties with µa = 0.0072 mm−1 and µs’ = 0.72 mm−1

Equations (12)

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{ [D(r) μ a (r)cp]Φ(r,p)= S k (r,p),rΩ cΦ(r,p)+2KD(r) e n Φ(r,p)=0,rΩ
S k (r,p)= T k (r) η μ af (r) 1+pτ(r)
T k (r)= T 0 exp( μ x (r)×L(r))
A n d ×I×J,m (p) x m,1 (p)= b n d ×I×J,1 (p)
A n d ×I×J,m (p)=[ [ Φ 1 (p) Φ n d (p) ] Γ 1 T 1 [ Φ 1 (p) Φ n d (p) ] Γ I×J T I×J ]
Γ j (s)={ 1,nodesiswithintheXraybeam 0,otherwise
x(p)= argmin x0 F(x(p)):= 1 2 ||b(p)A(p)x(p)| | 2 2 +α||x(p)| | q q
{ η μ af (r)= ( p 1 p 2 )x(r, p 1 )x(r, p 2 ) p 1 x(r, p 1 ) p 2 x(r, p 2 ) τ(r)= x(r, p 1 )x(r, p 1 ) p 1 x(r, p 1 ) p 2 x(r, p 2 )
p 1,2 =± k (2/ μ a (B) c)+ τ (B) ,(0k1)
T k (r)=exp(0.0214×L(r))
CDE= |Dis t r Dis t t | Dis t r ×100%
DICE= 2×|RO I r RO I t | |RO I r |+|RO I t | ×100%

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