Abstract

Using two dimensional synthetic frequency-domain measurements, the inverse imaging problem is solved for absorption and fluorescence lifetime mapping with the truncated Newton’s optimization scheme developed in Part I of this contribution. Herein, we present reconstructed maps of absorption owing to a fluorophore from excitation and emission measurements which detail the presence of tissue heterogeneities characterized by tenfold increase in fluorescent contrast agent. Our results confirm that fluorescence provides superior mapping of heterogeneities over excitation measurements. Using emission measurements we then map fluorescent lifetime under conditions of tenfold uptake of contrast agent in tissue heterogeneities. The ability to map fluorescent quenching and lengthening of contrast agents facilitates the solution of the inverse problem and further improves the ability to reconstruct tissue heterogeneities.

© 1999 Optical Society of America

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  1. R. Roy and E. M. Sevick-Muraca, “Truncated Newton’s optimization scheme for absorption and fluorescence optical tomography: Part I- Theory and formulation,” Opt. Express 4, 353–371 (1999); http://www.opticsexpress.org/oearchive/source/9268.htm.
    [CrossRef] [PubMed]
  2. T. L. Troy, D. L. Page, and E. M. Sevick-Muraca, “Optical properties of normal and diseased breast tissues: prognosis for optical mammography,” J. Biomedical Opt. 1, 342–355 (1996).
    [CrossRef]
  3. E. M. Sevick-Muraca, G. Lopez, T. L. Troy, J. S. Reynolds, and C. L. Hutchinson, “Fluorescence and absorption contrast mechanisms for biomedical optical imaging using frequency-domain techniques,” Photochem. Photobiolo. 66, 55–64 (1997).
    [CrossRef]
  4. R. Cubeddu, G. Canti, A. Pifferi, P. Taroni, and G. Valentini, “Fluorescence lifetime imaging of experimental tumors in hematoporhyrin derivate-sensitized mice,” Photochem. Photobiol. 66, 229–236 (1997).
    [CrossRef] [PubMed]
  5. D. Y. Paithankar, A. U. Chen, B. W. Pogue, M. S. Patterson, and E. M. Sevick-Muraca, “Imaging of fluorescent yield and lifetime from multiply scattered light re-emitted from tissues and other random media,” Appl. Opt. 36, 2260–2272 (1997).
    [CrossRef] [PubMed]
  6. M. A. O’Leary, D. A. Boas, B. Chance, and A. G. Yodh, “Fluorescence lifetime imaging in turbid media,” Opt. Lett. 21, 158–160 (1996).
    [CrossRef]
  7. E. M. Sevick-Muraca, C. L. Hutchinson, and D. Y. Paithankar, “Optical Tissue Biodiagnostics Using Fluorescence Lifetime,” Opt. Photon. News 7, (1996) pp 25–28.
    [CrossRef]
  8. H. Jiang, “Frequency-domain fluorescent diffusion tomography: a finite-element based algorithm and simulations,” Appl. Opt. 37, 5337–5343 (1998).
    [CrossRef]
  9. M. J. Eppstein, D. E. Dougherty, D. J. Hawrysz, and E. M. Sevick-Muraca, “Three-dimensional optical tomography,” Optical Tomography and Spectroscopy of Tissue III, B. Chance, R. R. Alfano, and B. J. Tromberg (eds.). Proc. Soc. Photo-Opt. Instrum. Eng.,  3597: 000–000 (1999).
  10. M. Schweiger and S. R. Arridge, “Comparison of two- and three- dimensional reconstruction methods in optical tomography,” Appl. Opt. 37, 7419–7428 (1998).
    [CrossRef]
  11. J. S. Reynolds, T. L. Troy, and E. M. Sevick-Muraca, “Multi-pixel techniques for frequency-domain photon migration imaging,” Biotech. Prog. 13, 669–680 (1997).
    [CrossRef]
  12. J. S. Reynolds, T. L. Troy, A. Thompson, R. Mayer, A. B. Thompson, D. J. Waters, K. K. Cornell, P. W. Snyder, and E. M. Sevick-Muraca, “Multi-pixel frequency-domain of spontaneous canine breast disease using fluorescent agents,” Optical Tomography and Spectroscopy of Tissue III, B. Chance, R. R. Alfano, and B. J. Tromberg (eds.). Proc. Soc. Photo-Opt. Instrum. Eng.,  3597: 000–000, 1999.

1999 (3)

M. J. Eppstein, D. E. Dougherty, D. J. Hawrysz, and E. M. Sevick-Muraca, “Three-dimensional optical tomography,” Optical Tomography and Spectroscopy of Tissue III, B. Chance, R. R. Alfano, and B. J. Tromberg (eds.). Proc. Soc. Photo-Opt. Instrum. Eng.,  3597: 000–000 (1999).

J. S. Reynolds, T. L. Troy, A. Thompson, R. Mayer, A. B. Thompson, D. J. Waters, K. K. Cornell, P. W. Snyder, and E. M. Sevick-Muraca, “Multi-pixel frequency-domain of spontaneous canine breast disease using fluorescent agents,” Optical Tomography and Spectroscopy of Tissue III, B. Chance, R. R. Alfano, and B. J. Tromberg (eds.). Proc. Soc. Photo-Opt. Instrum. Eng.,  3597: 000–000, 1999.

R. Roy and E. M. Sevick-Muraca, “Truncated Newton’s optimization scheme for absorption and fluorescence optical tomography: Part I- Theory and formulation,” Opt. Express 4, 353–371 (1999); http://www.opticsexpress.org/oearchive/source/9268.htm.
[CrossRef] [PubMed]

1998 (2)

1997 (4)

J. S. Reynolds, T. L. Troy, and E. M. Sevick-Muraca, “Multi-pixel techniques for frequency-domain photon migration imaging,” Biotech. Prog. 13, 669–680 (1997).
[CrossRef]

E. M. Sevick-Muraca, G. Lopez, T. L. Troy, J. S. Reynolds, and C. L. Hutchinson, “Fluorescence and absorption contrast mechanisms for biomedical optical imaging using frequency-domain techniques,” Photochem. Photobiolo. 66, 55–64 (1997).
[CrossRef]

R. Cubeddu, G. Canti, A. Pifferi, P. Taroni, and G. Valentini, “Fluorescence lifetime imaging of experimental tumors in hematoporhyrin derivate-sensitized mice,” Photochem. Photobiol. 66, 229–236 (1997).
[CrossRef] [PubMed]

D. Y. Paithankar, A. U. Chen, B. W. Pogue, M. S. Patterson, and E. M. Sevick-Muraca, “Imaging of fluorescent yield and lifetime from multiply scattered light re-emitted from tissues and other random media,” Appl. Opt. 36, 2260–2272 (1997).
[CrossRef] [PubMed]

1996 (3)

T. L. Troy, D. L. Page, and E. M. Sevick-Muraca, “Optical properties of normal and diseased breast tissues: prognosis for optical mammography,” J. Biomedical Opt. 1, 342–355 (1996).
[CrossRef]

E. M. Sevick-Muraca, C. L. Hutchinson, and D. Y. Paithankar, “Optical Tissue Biodiagnostics Using Fluorescence Lifetime,” Opt. Photon. News 7, (1996) pp 25–28.
[CrossRef]

M. A. O’Leary, D. A. Boas, B. Chance, and A. G. Yodh, “Fluorescence lifetime imaging in turbid media,” Opt. Lett. 21, 158–160 (1996).
[CrossRef]

Arridge, S. R.

Boas, D. A.

Canti, G.

R. Cubeddu, G. Canti, A. Pifferi, P. Taroni, and G. Valentini, “Fluorescence lifetime imaging of experimental tumors in hematoporhyrin derivate-sensitized mice,” Photochem. Photobiol. 66, 229–236 (1997).
[CrossRef] [PubMed]

Chance, B.

Chen, A. U.

Cornell, K. K.

J. S. Reynolds, T. L. Troy, A. Thompson, R. Mayer, A. B. Thompson, D. J. Waters, K. K. Cornell, P. W. Snyder, and E. M. Sevick-Muraca, “Multi-pixel frequency-domain of spontaneous canine breast disease using fluorescent agents,” Optical Tomography and Spectroscopy of Tissue III, B. Chance, R. R. Alfano, and B. J. Tromberg (eds.). Proc. Soc. Photo-Opt. Instrum. Eng.,  3597: 000–000, 1999.

Cubeddu, R.

R. Cubeddu, G. Canti, A. Pifferi, P. Taroni, and G. Valentini, “Fluorescence lifetime imaging of experimental tumors in hematoporhyrin derivate-sensitized mice,” Photochem. Photobiol. 66, 229–236 (1997).
[CrossRef] [PubMed]

Dougherty, D. E.

M. J. Eppstein, D. E. Dougherty, D. J. Hawrysz, and E. M. Sevick-Muraca, “Three-dimensional optical tomography,” Optical Tomography and Spectroscopy of Tissue III, B. Chance, R. R. Alfano, and B. J. Tromberg (eds.). Proc. Soc. Photo-Opt. Instrum. Eng.,  3597: 000–000 (1999).

Eppstein, M. J.

M. J. Eppstein, D. E. Dougherty, D. J. Hawrysz, and E. M. Sevick-Muraca, “Three-dimensional optical tomography,” Optical Tomography and Spectroscopy of Tissue III, B. Chance, R. R. Alfano, and B. J. Tromberg (eds.). Proc. Soc. Photo-Opt. Instrum. Eng.,  3597: 000–000 (1999).

Hawrysz, D. J.

M. J. Eppstein, D. E. Dougherty, D. J. Hawrysz, and E. M. Sevick-Muraca, “Three-dimensional optical tomography,” Optical Tomography and Spectroscopy of Tissue III, B. Chance, R. R. Alfano, and B. J. Tromberg (eds.). Proc. Soc. Photo-Opt. Instrum. Eng.,  3597: 000–000 (1999).

Hutchinson, C. L.

E. M. Sevick-Muraca, G. Lopez, T. L. Troy, J. S. Reynolds, and C. L. Hutchinson, “Fluorescence and absorption contrast mechanisms for biomedical optical imaging using frequency-domain techniques,” Photochem. Photobiolo. 66, 55–64 (1997).
[CrossRef]

E. M. Sevick-Muraca, C. L. Hutchinson, and D. Y. Paithankar, “Optical Tissue Biodiagnostics Using Fluorescence Lifetime,” Opt. Photon. News 7, (1996) pp 25–28.
[CrossRef]

Jiang, H.

Lopez, G.

E. M. Sevick-Muraca, G. Lopez, T. L. Troy, J. S. Reynolds, and C. L. Hutchinson, “Fluorescence and absorption contrast mechanisms for biomedical optical imaging using frequency-domain techniques,” Photochem. Photobiolo. 66, 55–64 (1997).
[CrossRef]

Mayer, R.

J. S. Reynolds, T. L. Troy, A. Thompson, R. Mayer, A. B. Thompson, D. J. Waters, K. K. Cornell, P. W. Snyder, and E. M. Sevick-Muraca, “Multi-pixel frequency-domain of spontaneous canine breast disease using fluorescent agents,” Optical Tomography and Spectroscopy of Tissue III, B. Chance, R. R. Alfano, and B. J. Tromberg (eds.). Proc. Soc. Photo-Opt. Instrum. Eng.,  3597: 000–000, 1999.

O’Leary, M. A.

Page, D. L.

T. L. Troy, D. L. Page, and E. M. Sevick-Muraca, “Optical properties of normal and diseased breast tissues: prognosis for optical mammography,” J. Biomedical Opt. 1, 342–355 (1996).
[CrossRef]

Paithankar, D. Y.

Patterson, M. S.

Pifferi, A.

R. Cubeddu, G. Canti, A. Pifferi, P. Taroni, and G. Valentini, “Fluorescence lifetime imaging of experimental tumors in hematoporhyrin derivate-sensitized mice,” Photochem. Photobiol. 66, 229–236 (1997).
[CrossRef] [PubMed]

Pogue, B. W.

Reynolds, J. S.

J. S. Reynolds, T. L. Troy, A. Thompson, R. Mayer, A. B. Thompson, D. J. Waters, K. K. Cornell, P. W. Snyder, and E. M. Sevick-Muraca, “Multi-pixel frequency-domain of spontaneous canine breast disease using fluorescent agents,” Optical Tomography and Spectroscopy of Tissue III, B. Chance, R. R. Alfano, and B. J. Tromberg (eds.). Proc. Soc. Photo-Opt. Instrum. Eng.,  3597: 000–000, 1999.

J. S. Reynolds, T. L. Troy, and E. M. Sevick-Muraca, “Multi-pixel techniques for frequency-domain photon migration imaging,” Biotech. Prog. 13, 669–680 (1997).
[CrossRef]

E. M. Sevick-Muraca, G. Lopez, T. L. Troy, J. S. Reynolds, and C. L. Hutchinson, “Fluorescence and absorption contrast mechanisms for biomedical optical imaging using frequency-domain techniques,” Photochem. Photobiolo. 66, 55–64 (1997).
[CrossRef]

Roy, R.

Schweiger, M.

Sevick-Muraca, E. M.

M. J. Eppstein, D. E. Dougherty, D. J. Hawrysz, and E. M. Sevick-Muraca, “Three-dimensional optical tomography,” Optical Tomography and Spectroscopy of Tissue III, B. Chance, R. R. Alfano, and B. J. Tromberg (eds.). Proc. Soc. Photo-Opt. Instrum. Eng.,  3597: 000–000 (1999).

J. S. Reynolds, T. L. Troy, A. Thompson, R. Mayer, A. B. Thompson, D. J. Waters, K. K. Cornell, P. W. Snyder, and E. M. Sevick-Muraca, “Multi-pixel frequency-domain of spontaneous canine breast disease using fluorescent agents,” Optical Tomography and Spectroscopy of Tissue III, B. Chance, R. R. Alfano, and B. J. Tromberg (eds.). Proc. Soc. Photo-Opt. Instrum. Eng.,  3597: 000–000, 1999.

R. Roy and E. M. Sevick-Muraca, “Truncated Newton’s optimization scheme for absorption and fluorescence optical tomography: Part I- Theory and formulation,” Opt. Express 4, 353–371 (1999); http://www.opticsexpress.org/oearchive/source/9268.htm.
[CrossRef] [PubMed]

D. Y. Paithankar, A. U. Chen, B. W. Pogue, M. S. Patterson, and E. M. Sevick-Muraca, “Imaging of fluorescent yield and lifetime from multiply scattered light re-emitted from tissues and other random media,” Appl. Opt. 36, 2260–2272 (1997).
[CrossRef] [PubMed]

J. S. Reynolds, T. L. Troy, and E. M. Sevick-Muraca, “Multi-pixel techniques for frequency-domain photon migration imaging,” Biotech. Prog. 13, 669–680 (1997).
[CrossRef]

E. M. Sevick-Muraca, G. Lopez, T. L. Troy, J. S. Reynolds, and C. L. Hutchinson, “Fluorescence and absorption contrast mechanisms for biomedical optical imaging using frequency-domain techniques,” Photochem. Photobiolo. 66, 55–64 (1997).
[CrossRef]

T. L. Troy, D. L. Page, and E. M. Sevick-Muraca, “Optical properties of normal and diseased breast tissues: prognosis for optical mammography,” J. Biomedical Opt. 1, 342–355 (1996).
[CrossRef]

E. M. Sevick-Muraca, C. L. Hutchinson, and D. Y. Paithankar, “Optical Tissue Biodiagnostics Using Fluorescence Lifetime,” Opt. Photon. News 7, (1996) pp 25–28.
[CrossRef]

Snyder, P. W.

J. S. Reynolds, T. L. Troy, A. Thompson, R. Mayer, A. B. Thompson, D. J. Waters, K. K. Cornell, P. W. Snyder, and E. M. Sevick-Muraca, “Multi-pixel frequency-domain of spontaneous canine breast disease using fluorescent agents,” Optical Tomography and Spectroscopy of Tissue III, B. Chance, R. R. Alfano, and B. J. Tromberg (eds.). Proc. Soc. Photo-Opt. Instrum. Eng.,  3597: 000–000, 1999.

Taroni, P.

R. Cubeddu, G. Canti, A. Pifferi, P. Taroni, and G. Valentini, “Fluorescence lifetime imaging of experimental tumors in hematoporhyrin derivate-sensitized mice,” Photochem. Photobiol. 66, 229–236 (1997).
[CrossRef] [PubMed]

Thompson, A.

J. S. Reynolds, T. L. Troy, A. Thompson, R. Mayer, A. B. Thompson, D. J. Waters, K. K. Cornell, P. W. Snyder, and E. M. Sevick-Muraca, “Multi-pixel frequency-domain of spontaneous canine breast disease using fluorescent agents,” Optical Tomography and Spectroscopy of Tissue III, B. Chance, R. R. Alfano, and B. J. Tromberg (eds.). Proc. Soc. Photo-Opt. Instrum. Eng.,  3597: 000–000, 1999.

Thompson, A. B.

J. S. Reynolds, T. L. Troy, A. Thompson, R. Mayer, A. B. Thompson, D. J. Waters, K. K. Cornell, P. W. Snyder, and E. M. Sevick-Muraca, “Multi-pixel frequency-domain of spontaneous canine breast disease using fluorescent agents,” Optical Tomography and Spectroscopy of Tissue III, B. Chance, R. R. Alfano, and B. J. Tromberg (eds.). Proc. Soc. Photo-Opt. Instrum. Eng.,  3597: 000–000, 1999.

Troy, T. L.

J. S. Reynolds, T. L. Troy, A. Thompson, R. Mayer, A. B. Thompson, D. J. Waters, K. K. Cornell, P. W. Snyder, and E. M. Sevick-Muraca, “Multi-pixel frequency-domain of spontaneous canine breast disease using fluorescent agents,” Optical Tomography and Spectroscopy of Tissue III, B. Chance, R. R. Alfano, and B. J. Tromberg (eds.). Proc. Soc. Photo-Opt. Instrum. Eng.,  3597: 000–000, 1999.

J. S. Reynolds, T. L. Troy, and E. M. Sevick-Muraca, “Multi-pixel techniques for frequency-domain photon migration imaging,” Biotech. Prog. 13, 669–680 (1997).
[CrossRef]

E. M. Sevick-Muraca, G. Lopez, T. L. Troy, J. S. Reynolds, and C. L. Hutchinson, “Fluorescence and absorption contrast mechanisms for biomedical optical imaging using frequency-domain techniques,” Photochem. Photobiolo. 66, 55–64 (1997).
[CrossRef]

T. L. Troy, D. L. Page, and E. M. Sevick-Muraca, “Optical properties of normal and diseased breast tissues: prognosis for optical mammography,” J. Biomedical Opt. 1, 342–355 (1996).
[CrossRef]

Valentini, G.

R. Cubeddu, G. Canti, A. Pifferi, P. Taroni, and G. Valentini, “Fluorescence lifetime imaging of experimental tumors in hematoporhyrin derivate-sensitized mice,” Photochem. Photobiol. 66, 229–236 (1997).
[CrossRef] [PubMed]

Waters, D. J.

J. S. Reynolds, T. L. Troy, A. Thompson, R. Mayer, A. B. Thompson, D. J. Waters, K. K. Cornell, P. W. Snyder, and E. M. Sevick-Muraca, “Multi-pixel frequency-domain of spontaneous canine breast disease using fluorescent agents,” Optical Tomography and Spectroscopy of Tissue III, B. Chance, R. R. Alfano, and B. J. Tromberg (eds.). Proc. Soc. Photo-Opt. Instrum. Eng.,  3597: 000–000, 1999.

Yodh, A. G.

Appl. Opt. (3)

Biotech. Prog. (1)

J. S. Reynolds, T. L. Troy, and E. M. Sevick-Muraca, “Multi-pixel techniques for frequency-domain photon migration imaging,” Biotech. Prog. 13, 669–680 (1997).
[CrossRef]

J. Biomedical Opt. (1)

T. L. Troy, D. L. Page, and E. M. Sevick-Muraca, “Optical properties of normal and diseased breast tissues: prognosis for optical mammography,” J. Biomedical Opt. 1, 342–355 (1996).
[CrossRef]

Opt. Express (1)

Opt. Lett. (1)

Opt. Photon. News (1)

E. M. Sevick-Muraca, C. L. Hutchinson, and D. Y. Paithankar, “Optical Tissue Biodiagnostics Using Fluorescence Lifetime,” Opt. Photon. News 7, (1996) pp 25–28.
[CrossRef]

Photochem. Photobiol. (1)

R. Cubeddu, G. Canti, A. Pifferi, P. Taroni, and G. Valentini, “Fluorescence lifetime imaging of experimental tumors in hematoporhyrin derivate-sensitized mice,” Photochem. Photobiol. 66, 229–236 (1997).
[CrossRef] [PubMed]

Photochem. Photobiolo. (1)

E. M. Sevick-Muraca, G. Lopez, T. L. Troy, J. S. Reynolds, and C. L. Hutchinson, “Fluorescence and absorption contrast mechanisms for biomedical optical imaging using frequency-domain techniques,” Photochem. Photobiolo. 66, 55–64 (1997).
[CrossRef]

Proc. Soc. Photo-Opt. Instrum. Eng. (2)

M. J. Eppstein, D. E. Dougherty, D. J. Hawrysz, and E. M. Sevick-Muraca, “Three-dimensional optical tomography,” Optical Tomography and Spectroscopy of Tissue III, B. Chance, R. R. Alfano, and B. J. Tromberg (eds.). Proc. Soc. Photo-Opt. Instrum. Eng.,  3597: 000–000 (1999).

J. S. Reynolds, T. L. Troy, A. Thompson, R. Mayer, A. B. Thompson, D. J. Waters, K. K. Cornell, P. W. Snyder, and E. M. Sevick-Muraca, “Multi-pixel frequency-domain of spontaneous canine breast disease using fluorescent agents,” Optical Tomography and Spectroscopy of Tissue III, B. Chance, R. R. Alfano, and B. J. Tromberg (eds.). Proc. Soc. Photo-Opt. Instrum. Eng.,  3597: 000–000, 1999.

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Figures (6)

Figure 1
Figure 1

(a) Actual ‘true’ distribution of absorption, μaxf [target 1 top, target 2 right, target 3 bottom] (b) reconstructed μaxf from excitation measurement (c) Average value of μaxf as a function of iteration

Figure 2
Figure 2

(a) Reconstructed absorption, μ a xm , from fluorescence measurements and (b) Average value of μ a xm , as a function of iteration.

Figure 3
Figure 3

(a) “True’ distribution of fluorophore lifetime, possessing longer lifetime within three heterogeneities having ten-fold uptake of fluorescent dye; (b) Reconstructed lifetime at 50 MHz; (c) 100 MHz; (d) 150 MHz.

Figure 4
Figure 4

The distribution of fluorophore lifetime, possessing longer fluorescent lifetime within three heterogeneities having ten-fold uptake of fluorescent dye. Average value of heterogeneity lifetime as function of iteration; (b) at 50 MHz; (c) 100 MHz; (d) 150 MHz

Figure 5
Figure 5

(a) ‘True’ distribution of fluorophore lifetime, with fluorophore quenching within three heterogeneities having ten-fold uptake of fluorescent dye; (b) Reconstructed lifetime at 50 MHz; (c) 100MHz; (d) 150 MHz.

Figure 6
Figure 6

The distribution of fluorophore lifetime, quenching fluorescent lifetime within three hetergeneities having ten-fold uptake of fluorescent dye. Average value of heterogeneity lifetime as function of iteration; (b) at 50 MHz; (c) 100 MHz; (d) 150 MHz

Tables (1)

Tables Icon

Table 1. Parameters used in truncated Newton method optimization for absorption and lifetime imaging

Equations (8)

Equations on this page are rendered with MathJax. Learn more.

Φ x = Φ x ( 1.0 + Z * G ( 0,1 ) )
tan ( θ + 0.1 * G ( 0,1 ) ) = img ( Φ x 1 ) re ( Φ x 1 )
tan θ + tan ( 0.1 * G ) 1 tan θ tan ( 0.1 * G ) = img ( Φ x 1 ) re ( Φ x 1 )
img ( Φ x ) re ( Φ x ) + tan ( 0.1 * G ) 1 img ( Φ x ) re ( Φ x ) * tan ( 1.0 * G ) = img ( Φ x 1 ) re ( Φ x 1 )
img ( Φ x ) + re ( Φ x ) * tan ( 0.1 * G ) re ( Φ x ) img ( Φ x ) * tan ( 0.1 * G ) = img ( Φ x 1 ) re ( Φ x 1 )
img ( Φ x 1 ) = img ( Φ x ) re ( Φ x ) * tan ( 0.1 * G )
re ( Φ x 1 ) = re ( Φ x ) img ( Φ x ) * tan ( 0.1 * G )
Now our new fluence is : Φ x = ( re ( Φ x 1 ) , img ( Φ x 1 ) )

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