Abstract

The advent of specific molecular markers and probes employing optical reporters has encouraged the application of in vivo diffuse tomographic imaging at greater spatial resolutions and hence data-set volumes. This study applied singular-value analysis (SVA) of the fluorescence tomographic problem to determine optimal source and detector distributions that result in data sets that are balanced between information content and size. Weight matrices describing the tomographic forward problem were constructed for a range of source and detector distributions and fields of view and were decomposed into their associated singular values. These singular-value spectra were then compared so that we could observe the effects of each parameter on imaging performance. The findings of the SVA were then confirmed by examining reconstructions of simulated and experimental data acquired with the same optode distributions as examined by SVA. It was seen that for a 20-mm target width, which is relevant to the small-animal imaging situation, the source and detector fields of view should be set at approximately 30 mm. Equal numbers of sources and detectors result in the best imaging performance in the parallel-plate geometry and should be employed when logistically feasible. These data provide guidelines for the design of small-animal diffuse optical tomographic imaging systems and demonstrate the utility of SVA as a simple and efficient means of optimizing experimental parameters in problems for which a forward model of the data collection process is available.

© 2004 Optical Society of America

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    [CrossRef]
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    [CrossRef] [PubMed]

2003 (3)

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

H. Xu, H. Dehghani, B. W. Pogue, “Near-infrared imaging in the small animal brain: optimization of fiber positions,” J. Biomed. Opt. 8, 102–110 (2003).
[CrossRef] [PubMed]

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, 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, 235–247 (2003).
[CrossRef] [PubMed]

2002 (3)

E. Shives, Y. Xu, H. Jiang, “Fluorescence lifetime tomography of turbid media based on an oxygen-sensitive dye,” Opt. Express 10, 1557–1562 (2002); www.opticsexpress.org .
[CrossRef] [PubMed]

V. Ntziachristos, C. Tung, C. Bremer, R. Weissleder, “Fluorescence-mediated tomography resolves protease activity in vivo,” Nat. Med. 8, 757–760 (2002).
[CrossRef] [PubMed]

V. Ntziachristos, R. Weissleder, “CCD-based scanner for tomography of fluorescent near-infrared probes in turbid media,” Med. Phys. 29, 803–809 (2002).
[CrossRef] [PubMed]

2001 (9)

J. P. Culver, V. Ntziachristos, M. J. Holboke, A. G. Yodh, “Optimization of optode arrangements for diffuse optical tomography: a singular-value analysis,” Opt. Lett. 26, 701–703 (2001).
[CrossRef]

A. Becker, C. Hessenius, K. Licha, B. Ebert, U. Sukowski, W. Semmler, B. Wiedenmann, C. Grotzinger, “Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands,” Nat. Biotechnol. 19, 327–331 (2001).
[CrossRef] [PubMed]

F. S. Wouters, “Imaging biochemistry inside cells,” Trends Cell Biol. 11, 203–211 (2001).
[CrossRef] [PubMed]

J. E. Bugaj, S. Achilefu, R. B. Dorshow, R. Rajagopalan, “Novel fluorescent contrast agents for optical imaging of in vivo tumors based on a receptor-targeted dye-peptide conjugate platform,” J. Biomed. Opt. 6, 122–133 (2001).
[CrossRef] [PubMed]

V. Ntziachristos, B. Chance, “Probing physiology and molecular function using optical imaging: applications to breast cancer,” Breast Cancer Res. 3, 41–46 (2001).
[CrossRef] [PubMed]

D. A. Boas, D. H. Brooks, E. L. Miller, C. A. DiMarzio, M. Kilmer, R. J. Gaudette, Q. Zhang, “Imaging the body with diffuse optical tomography,” IEEE Signal Process. Mag. 18, 57–75 (2001).
[CrossRef]

A. Y. Bluestone, G. Abdoulaev, C. H. Schmitz, R. L. Barbour, A. H. Hielscher, “Three-dimensional optical tomography of hemodynamics in the human head,” Opt. Express 9, 272–286 (2001); www.opticsexpress.org .
[CrossRef] [PubMed]

B. Pogue, S. P. Poplack, T. McBride, W. Wells, K. Osterman, U. Osterberg, K. D. Paulsen, “Quantitative hemoglobin tomography with diffuse near-infrared spectroscopy: pilot results in the breast,” Radiology 218, 261–266 (2001).
[CrossRef] [PubMed]

V. Ntziachristos, R. Weissleder, “Experimental three-dimensional fluorescence reconstruction of diffuse media using a normalized Born approximation,” Opt. Lett. 26, 893–895 (2001).
[CrossRef]

2000 (4)

V. Ntziachristos, A. G. Yodh, M. Schnall, B. Chance, “Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement,” Proc. Natl. Acad. Sci. USA 97, 2767–2772 (2000).
[CrossRef] [PubMed]

D. A. Benaron, S. R. Hintz, A. Villringer, D. Boas, A. Kleinschmidt, J. Frahm, C. Hirth, H. Obrig, J. C. van Houten, E. L. Kermit, W. F. Cheong, D. K. Stevenson, “Noninvasive functional imaging of human brain using light,” J. Cereb. Blood Flow Metab. 20, 469–477 (2000).
[CrossRef] [PubMed]

D. J. Hawrysz, E. M. Sevick-Muraca, “Developments toward diagnostic breast cancer imaging using near-infrared optical measurements and fluorescent contrast agents,” Neoplasia 2, 388–417 (2000).
[CrossRef]

S. Achilefu, R. B. Dorshow, J. E. Bugaj, R. Rajagopalan, “Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging,” Invest. Radiol. 35, 479–485 (2000).
[CrossRef] [PubMed]

1999 (3)

U. Mahmood, C. H. Tung, A. Bogdanov, R. Weissleder, “Near infrared optical imaging system to detect tumor protease activity,” Radiology 213, 866–870 (1999).
[CrossRef] [PubMed]

R. Weissleder, C. H. Tung, U. Mahmood, A. Bogdanov, “In vivo imaging of tumors with protease-activated near-infrared fluorescent probes,” Nat. Biotechnol. 17, 375–378 (1999).
[CrossRef] [PubMed]

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

1997 (3)

R. Pierri, A. Tamburrino, “On the local minima problem in conductivity imaging via a quadratic approach,” Inverse Probl. 13, 1547–1568 (1997).
[CrossRef]

J. H. Chang, H. L. Graber, R. L. Barbour, “Imaging of fluorescence in highly scattering media,” IEEE Trans. Biomed. Eng. 44, 810–822 (1997).
[CrossRef] [PubMed]

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

1996 (2)

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

S. Tyagi, F. R. Kramer, “Molecular beacons: probes that fluoresce upon hybridization,” Nat. Biotechnol. 14, 303–308 (1996).
[CrossRef] [PubMed]

Abdoulaev, G.

Achilefu, S.

J. E. Bugaj, S. Achilefu, R. B. Dorshow, R. Rajagopalan, “Novel fluorescent contrast agents for optical imaging of in vivo tumors based on a receptor-targeted dye-peptide conjugate platform,” J. Biomed. Opt. 6, 122–133 (2001).
[CrossRef] [PubMed]

S. Achilefu, R. B. Dorshow, J. E. Bugaj, R. Rajagopalan, “Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging,” Invest. Radiol. 35, 479–485 (2000).
[CrossRef] [PubMed]

Arridge, S. R.

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

Barbour, R. L.

Becker, A.

A. Becker, C. Hessenius, K. Licha, B. Ebert, U. Sukowski, W. Semmler, B. Wiedenmann, C. Grotzinger, “Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands,” Nat. Biotechnol. 19, 327–331 (2001).
[CrossRef] [PubMed]

Benaron, D. A.

D. A. Benaron, S. R. Hintz, A. Villringer, D. Boas, A. Kleinschmidt, J. Frahm, C. Hirth, H. Obrig, J. C. van Houten, E. L. Kermit, W. F. Cheong, D. K. Stevenson, “Noninvasive functional imaging of human brain using light,” J. Cereb. Blood Flow Metab. 20, 469–477 (2000).
[CrossRef] [PubMed]

Bertero, M.

M. Bertero, P. Boccacci, Introduction to Inverse Problems in Imaging (Institute of Physics, Bristol, UK, 1998).

Bluestone, A. Y.

Boas, D.

D. A. Benaron, S. R. Hintz, A. Villringer, D. Boas, A. Kleinschmidt, J. Frahm, C. Hirth, H. Obrig, J. C. van Houten, E. L. Kermit, W. F. Cheong, D. K. Stevenson, “Noninvasive functional imaging of human brain using light,” J. Cereb. Blood Flow Metab. 20, 469–477 (2000).
[CrossRef] [PubMed]

Boas, D. A.

D. A. Boas, D. H. Brooks, E. L. Miller, C. A. DiMarzio, M. Kilmer, R. J. Gaudette, Q. Zhang, “Imaging the body with diffuse optical tomography,” IEEE Signal Process. Mag. 18, 57–75 (2001).
[CrossRef]

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

Boccacci, P.

M. Bertero, P. Boccacci, Introduction to Inverse Problems in Imaging (Institute of Physics, Bristol, UK, 1998).

Bogdanov, A.

U. Mahmood, C. H. Tung, A. Bogdanov, R. Weissleder, “Near infrared optical imaging system to detect tumor protease activity,” Radiology 213, 866–870 (1999).
[CrossRef] [PubMed]

R. Weissleder, C. H. Tung, U. Mahmood, A. Bogdanov, “In vivo imaging of tumors with protease-activated near-infrared fluorescent probes,” Nat. Biotechnol. 17, 375–378 (1999).
[CrossRef] [PubMed]

Bremer, C.

V. Ntziachristos, C. Tung, C. Bremer, R. Weissleder, “Fluorescence-mediated tomography resolves protease activity in vivo,” Nat. Med. 8, 757–760 (2002).
[CrossRef] [PubMed]

Brooks, D. H.

D. A. Boas, D. H. Brooks, E. L. Miller, C. A. DiMarzio, M. Kilmer, R. J. Gaudette, Q. Zhang, “Imaging the body with diffuse optical tomography,” IEEE Signal Process. Mag. 18, 57–75 (2001).
[CrossRef]

Bugaj, J. E.

J. E. Bugaj, S. Achilefu, R. B. Dorshow, R. Rajagopalan, “Novel fluorescent contrast agents for optical imaging of in vivo tumors based on a receptor-targeted dye-peptide conjugate platform,” J. Biomed. Opt. 6, 122–133 (2001).
[CrossRef] [PubMed]

S. Achilefu, R. B. Dorshow, J. E. Bugaj, R. Rajagopalan, “Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging,” Invest. Radiol. 35, 479–485 (2000).
[CrossRef] [PubMed]

Chance, B.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, 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, 235–247 (2003).
[CrossRef] [PubMed]

V. Ntziachristos, B. Chance, “Probing physiology and molecular function using optical imaging: applications to breast cancer,” Breast Cancer Res. 3, 41–46 (2001).
[CrossRef] [PubMed]

V. Ntziachristos, A. G. Yodh, M. Schnall, B. Chance, “Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement,” Proc. Natl. Acad. Sci. USA 97, 2767–2772 (2000).
[CrossRef] [PubMed]

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

Chang, J. H.

J. H. Chang, H. L. Graber, R. L. Barbour, “Imaging of fluorescence in highly scattering media,” IEEE Trans. Biomed. Eng. 44, 810–822 (1997).
[CrossRef] [PubMed]

Chen, A. U.

Cheong, W. F.

D. A. Benaron, S. R. Hintz, A. Villringer, D. Boas, A. Kleinschmidt, J. Frahm, C. Hirth, H. Obrig, J. C. van Houten, E. L. Kermit, W. F. Cheong, D. K. Stevenson, “Noninvasive functional imaging of human brain using light,” J. Cereb. Blood Flow Metab. 20, 469–477 (2000).
[CrossRef] [PubMed]

Choe, R.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, 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, 235–247 (2003).
[CrossRef] [PubMed]

Culver, J. P.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, 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, 235–247 (2003).
[CrossRef] [PubMed]

J. P. Culver, V. Ntziachristos, M. J. Holboke, A. G. Yodh, “Optimization of optode arrangements for diffuse optical tomography: a singular-value analysis,” Opt. Lett. 26, 701–703 (2001).
[CrossRef]

Dehghani, H.

H. Xu, H. Dehghani, B. W. Pogue, “Near-infrared imaging in the small animal brain: optimization of fiber positions,” J. Biomed. Opt. 8, 102–110 (2003).
[CrossRef] [PubMed]

DiMarzio, C. A.

D. A. Boas, D. H. Brooks, E. L. Miller, C. A. DiMarzio, M. Kilmer, R. J. Gaudette, Q. Zhang, “Imaging the body with diffuse optical tomography,” IEEE Signal Process. Mag. 18, 57–75 (2001).
[CrossRef]

Dorshow, R. B.

J. E. Bugaj, S. Achilefu, R. B. Dorshow, R. Rajagopalan, “Novel fluorescent contrast agents for optical imaging of in vivo tumors based on a receptor-targeted dye-peptide conjugate platform,” J. Biomed. Opt. 6, 122–133 (2001).
[CrossRef] [PubMed]

S. Achilefu, R. B. Dorshow, J. E. Bugaj, R. Rajagopalan, “Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging,” Invest. Radiol. 35, 479–485 (2000).
[CrossRef] [PubMed]

Durduran, T.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, 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, 235–247 (2003).
[CrossRef] [PubMed]

Ebert, B.

A. Becker, C. Hessenius, K. Licha, B. Ebert, U. Sukowski, W. Semmler, B. Wiedenmann, C. Grotzinger, “Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands,” Nat. Biotechnol. 19, 327–331 (2001).
[CrossRef] [PubMed]

Engl, H. W.

H. W. Engl, M. Hanke, A. Neubauer, Regularization of Inverse Problems (Kluwer Academic, Dordrecht, The Netherlands, 1996).

Frahm, J.

D. A. Benaron, S. R. Hintz, A. Villringer, D. Boas, A. Kleinschmidt, J. Frahm, C. Hirth, H. Obrig, J. C. van Houten, E. L. Kermit, W. F. Cheong, D. K. Stevenson, “Noninvasive functional imaging of human brain using light,” J. Cereb. Blood Flow Metab. 20, 469–477 (2000).
[CrossRef] [PubMed]

Gaudette, R. J.

D. A. Boas, D. H. Brooks, E. L. Miller, C. A. DiMarzio, M. Kilmer, R. J. Gaudette, Q. Zhang, “Imaging the body with diffuse optical tomography,” IEEE Signal Process. Mag. 18, 57–75 (2001).
[CrossRef]

Graber, H. L.

J. H. Chang, H. L. Graber, R. L. Barbour, “Imaging of fluorescence in highly scattering media,” IEEE Trans. Biomed. Eng. 44, 810–822 (1997).
[CrossRef] [PubMed]

Graves, E. E.

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

Grotzinger, C.

A. Becker, C. Hessenius, K. Licha, B. Ebert, U. Sukowski, W. Semmler, B. Wiedenmann, C. Grotzinger, “Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands,” Nat. Biotechnol. 19, 327–331 (2001).
[CrossRef] [PubMed]

Hanke, M.

H. W. Engl, M. Hanke, A. Neubauer, Regularization of Inverse Problems (Kluwer Academic, Dordrecht, The Netherlands, 1996).

Hawrysz, D. J.

D. J. Hawrysz, E. M. Sevick-Muraca, “Developments toward diagnostic breast cancer imaging using near-infrared optical measurements and fluorescent contrast agents,” Neoplasia 2, 388–417 (2000).
[CrossRef]

Hessenius, C.

A. Becker, C. Hessenius, K. Licha, B. Ebert, U. Sukowski, W. Semmler, B. Wiedenmann, C. Grotzinger, “Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands,” Nat. Biotechnol. 19, 327–331 (2001).
[CrossRef] [PubMed]

Hielscher, A. H.

Hintz, S. R.

D. A. Benaron, S. R. Hintz, A. Villringer, D. Boas, A. Kleinschmidt, J. Frahm, C. Hirth, H. Obrig, J. C. van Houten, E. L. Kermit, W. F. Cheong, D. K. Stevenson, “Noninvasive functional imaging of human brain using light,” J. Cereb. Blood Flow Metab. 20, 469–477 (2000).
[CrossRef] [PubMed]

Hirth, C.

D. A. Benaron, S. R. Hintz, A. Villringer, D. Boas, A. Kleinschmidt, J. Frahm, C. Hirth, H. Obrig, J. C. van Houten, E. L. Kermit, W. F. Cheong, D. K. Stevenson, “Noninvasive functional imaging of human brain using light,” J. Cereb. Blood Flow Metab. 20, 469–477 (2000).
[CrossRef] [PubMed]

Holboke, M. J.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, 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, 235–247 (2003).
[CrossRef] [PubMed]

J. P. Culver, V. Ntziachristos, M. J. Holboke, A. G. Yodh, “Optimization of optode arrangements for diffuse optical tomography: a singular-value analysis,” Opt. Lett. 26, 701–703 (2001).
[CrossRef]

Jiang, H.

Kak, A. C.

A. C. Kak, M. Slaney, Principles of Computerized Tomographic Imaging (IEEE Press, Piscataway, N.J., 1988).

Kermit, E. L.

D. A. Benaron, S. R. Hintz, A. Villringer, D. Boas, A. Kleinschmidt, J. Frahm, C. Hirth, H. Obrig, J. C. van Houten, E. L. Kermit, W. F. Cheong, D. K. Stevenson, “Noninvasive functional imaging of human brain using light,” J. Cereb. Blood Flow Metab. 20, 469–477 (2000).
[CrossRef] [PubMed]

Kilmer, M.

D. A. Boas, D. H. Brooks, E. L. Miller, C. A. DiMarzio, M. Kilmer, R. J. Gaudette, Q. Zhang, “Imaging the body with diffuse optical tomography,” IEEE Signal Process. Mag. 18, 57–75 (2001).
[CrossRef]

Kleinschmidt, A.

D. A. Benaron, S. R. Hintz, A. Villringer, D. Boas, A. Kleinschmidt, J. Frahm, C. Hirth, H. Obrig, J. C. van Houten, E. L. Kermit, W. F. Cheong, D. K. Stevenson, “Noninvasive functional imaging of human brain using light,” J. Cereb. Blood Flow Metab. 20, 469–477 (2000).
[CrossRef] [PubMed]

Kramer, F. R.

S. Tyagi, F. R. Kramer, “Molecular beacons: probes that fluoresce upon hybridization,” Nat. Biotechnol. 14, 303–308 (1996).
[CrossRef] [PubMed]

Li, X. D.

Licha, K.

A. Becker, C. Hessenius, K. Licha, B. Ebert, U. Sukowski, W. Semmler, B. Wiedenmann, C. Grotzinger, “Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands,” Nat. Biotechnol. 19, 327–331 (2001).
[CrossRef] [PubMed]

Mahmood, U.

U. Mahmood, C. H. Tung, A. Bogdanov, R. Weissleder, “Near infrared optical imaging system to detect tumor protease activity,” Radiology 213, 866–870 (1999).
[CrossRef] [PubMed]

R. Weissleder, C. H. Tung, U. Mahmood, A. Bogdanov, “In vivo imaging of tumors with protease-activated near-infrared fluorescent probes,” Nat. Biotechnol. 17, 375–378 (1999).
[CrossRef] [PubMed]

McBride, T.

B. Pogue, S. P. Poplack, T. McBride, W. Wells, K. Osterman, U. Osterberg, K. D. Paulsen, “Quantitative hemoglobin tomography with diffuse near-infrared spectroscopy: pilot results in the breast,” Radiology 218, 261–266 (2001).
[CrossRef] [PubMed]

Miller, E. L.

D. A. Boas, D. H. Brooks, E. L. Miller, C. A. DiMarzio, M. Kilmer, R. J. Gaudette, Q. Zhang, “Imaging the body with diffuse optical tomography,” IEEE Signal Process. Mag. 18, 57–75 (2001).
[CrossRef]

Neubauer, A.

H. W. Engl, M. Hanke, A. Neubauer, Regularization of Inverse Problems (Kluwer Academic, Dordrecht, The Netherlands, 1996).

Ntziachristos, V.

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

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, 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, 235–247 (2003).
[CrossRef] [PubMed]

V. Ntziachristos, C. Tung, C. Bremer, R. Weissleder, “Fluorescence-mediated tomography resolves protease activity in vivo,” Nat. Med. 8, 757–760 (2002).
[CrossRef] [PubMed]

V. Ntziachristos, R. Weissleder, “CCD-based scanner for tomography of fluorescent near-infrared probes in turbid media,” Med. Phys. 29, 803–809 (2002).
[CrossRef] [PubMed]

V. Ntziachristos, B. Chance, “Probing physiology and molecular function using optical imaging: applications to breast cancer,” Breast Cancer Res. 3, 41–46 (2001).
[CrossRef] [PubMed]

J. P. Culver, V. Ntziachristos, M. J. Holboke, A. G. Yodh, “Optimization of optode arrangements for diffuse optical tomography: a singular-value analysis,” Opt. Lett. 26, 701–703 (2001).
[CrossRef]

V. Ntziachristos, R. Weissleder, “Experimental three-dimensional fluorescence reconstruction of diffuse media using a normalized Born approximation,” Opt. Lett. 26, 893–895 (2001).
[CrossRef]

V. Ntziachristos, A. G. Yodh, M. Schnall, B. Chance, “Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement,” Proc. Natl. Acad. Sci. USA 97, 2767–2772 (2000).
[CrossRef] [PubMed]

Obrig, H.

D. A. Benaron, S. R. Hintz, A. Villringer, D. Boas, A. Kleinschmidt, J. Frahm, C. Hirth, H. Obrig, J. C. van Houten, E. L. Kermit, W. F. Cheong, D. K. Stevenson, “Noninvasive functional imaging of human brain using light,” J. Cereb. Blood Flow Metab. 20, 469–477 (2000).
[CrossRef] [PubMed]

Oleary, M. A.

Osterberg, U.

B. Pogue, S. P. Poplack, T. McBride, W. Wells, K. Osterman, U. Osterberg, K. D. Paulsen, “Quantitative hemoglobin tomography with diffuse near-infrared spectroscopy: pilot results in the breast,” Radiology 218, 261–266 (2001).
[CrossRef] [PubMed]

Osterman, K.

B. Pogue, S. P. Poplack, T. McBride, W. Wells, K. Osterman, U. Osterberg, K. D. Paulsen, “Quantitative hemoglobin tomography with diffuse near-infrared spectroscopy: pilot results in the breast,” Radiology 218, 261–266 (2001).
[CrossRef] [PubMed]

Paithankar, D. Y.

Patterson, M. S.

Paulsen, K. D.

B. Pogue, S. P. Poplack, T. McBride, W. Wells, K. Osterman, U. Osterberg, K. D. Paulsen, “Quantitative hemoglobin tomography with diffuse near-infrared spectroscopy: pilot results in the breast,” Radiology 218, 261–266 (2001).
[CrossRef] [PubMed]

Pierri, R.

R. Pierri, A. Tamburrino, “On the local minima problem in conductivity imaging via a quadratic approach,” Inverse Probl. 13, 1547–1568 (1997).
[CrossRef]

Pogue, B.

B. Pogue, S. P. Poplack, T. McBride, W. Wells, K. Osterman, U. Osterberg, K. D. Paulsen, “Quantitative hemoglobin tomography with diffuse near-infrared spectroscopy: pilot results in the breast,” Radiology 218, 261–266 (2001).
[CrossRef] [PubMed]

Pogue, B. W.

Poplack, S. P.

B. Pogue, S. P. Poplack, T. McBride, W. Wells, K. Osterman, U. Osterberg, K. D. Paulsen, “Quantitative hemoglobin tomography with diffuse near-infrared spectroscopy: pilot results in the breast,” Radiology 218, 261–266 (2001).
[CrossRef] [PubMed]

Rajagopalan, R.

J. E. Bugaj, S. Achilefu, R. B. Dorshow, R. Rajagopalan, “Novel fluorescent contrast agents for optical imaging of in vivo tumors based on a receptor-targeted dye-peptide conjugate platform,” J. Biomed. Opt. 6, 122–133 (2001).
[CrossRef] [PubMed]

S. Achilefu, R. B. Dorshow, J. E. Bugaj, R. Rajagopalan, “Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging,” Invest. Radiol. 35, 479–485 (2000).
[CrossRef] [PubMed]

Ripoll, J.

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

Schmitz, C. H.

Schnall, M.

V. Ntziachristos, A. G. Yodh, M. Schnall, B. Chance, “Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement,” Proc. Natl. Acad. Sci. USA 97, 2767–2772 (2000).
[CrossRef] [PubMed]

Semmler, W.

A. Becker, C. Hessenius, K. Licha, B. Ebert, U. Sukowski, W. Semmler, B. Wiedenmann, C. Grotzinger, “Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands,” Nat. Biotechnol. 19, 327–331 (2001).
[CrossRef] [PubMed]

Sevick-Muraca, E. M.

D. J. Hawrysz, E. M. Sevick-Muraca, “Developments toward diagnostic breast cancer imaging using near-infrared optical measurements and fluorescent contrast agents,” Neoplasia 2, 388–417 (2000).
[CrossRef]

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

Shives, E.

Slaney, M.

A. C. Kak, M. Slaney, Principles of Computerized Tomographic Imaging (IEEE Press, Piscataway, N.J., 1988).

Slemp, A.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, 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, 235–247 (2003).
[CrossRef] [PubMed]

Stevenson, D. K.

D. A. Benaron, S. R. Hintz, A. Villringer, D. Boas, A. Kleinschmidt, J. Frahm, C. Hirth, H. Obrig, J. C. van Houten, E. L. Kermit, W. F. Cheong, D. K. Stevenson, “Noninvasive functional imaging of human brain using light,” J. Cereb. Blood Flow Metab. 20, 469–477 (2000).
[CrossRef] [PubMed]

Sukowski, U.

A. Becker, C. Hessenius, K. Licha, B. Ebert, U. Sukowski, W. Semmler, B. Wiedenmann, C. Grotzinger, “Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands,” Nat. Biotechnol. 19, 327–331 (2001).
[CrossRef] [PubMed]

Tamburrino, A.

R. Pierri, A. Tamburrino, “On the local minima problem in conductivity imaging via a quadratic approach,” Inverse Probl. 13, 1547–1568 (1997).
[CrossRef]

Tung, C.

V. Ntziachristos, C. Tung, C. Bremer, R. Weissleder, “Fluorescence-mediated tomography resolves protease activity in vivo,” Nat. Med. 8, 757–760 (2002).
[CrossRef] [PubMed]

Tung, C. H.

U. Mahmood, C. H. Tung, A. Bogdanov, R. Weissleder, “Near infrared optical imaging system to detect tumor protease activity,” Radiology 213, 866–870 (1999).
[CrossRef] [PubMed]

R. Weissleder, C. H. Tung, U. Mahmood, A. Bogdanov, “In vivo imaging of tumors with protease-activated near-infrared fluorescent probes,” Nat. Biotechnol. 17, 375–378 (1999).
[CrossRef] [PubMed]

Tyagi, S.

S. Tyagi, F. R. Kramer, “Molecular beacons: probes that fluoresce upon hybridization,” Nat. Biotechnol. 14, 303–308 (1996).
[CrossRef] [PubMed]

van Houten, J. C.

D. A. Benaron, S. R. Hintz, A. Villringer, D. Boas, A. Kleinschmidt, J. Frahm, C. Hirth, H. Obrig, J. C. van Houten, E. L. Kermit, W. F. Cheong, D. K. Stevenson, “Noninvasive functional imaging of human brain using light,” J. Cereb. Blood Flow Metab. 20, 469–477 (2000).
[CrossRef] [PubMed]

Villringer, A.

D. A. Benaron, S. R. Hintz, A. Villringer, D. Boas, A. Kleinschmidt, J. Frahm, C. Hirth, H. Obrig, J. C. van Houten, E. L. Kermit, W. F. Cheong, D. K. Stevenson, “Noninvasive functional imaging of human brain using light,” J. Cereb. Blood Flow Metab. 20, 469–477 (2000).
[CrossRef] [PubMed]

Weissleder, R.

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

V. Ntziachristos, C. Tung, C. Bremer, R. Weissleder, “Fluorescence-mediated tomography resolves protease activity in vivo,” Nat. Med. 8, 757–760 (2002).
[CrossRef] [PubMed]

V. Ntziachristos, R. Weissleder, “CCD-based scanner for tomography of fluorescent near-infrared probes in turbid media,” Med. Phys. 29, 803–809 (2002).
[CrossRef] [PubMed]

V. Ntziachristos, R. Weissleder, “Experimental three-dimensional fluorescence reconstruction of diffuse media using a normalized Born approximation,” Opt. Lett. 26, 893–895 (2001).
[CrossRef]

R. Weissleder, C. H. Tung, U. Mahmood, A. Bogdanov, “In vivo imaging of tumors with protease-activated near-infrared fluorescent probes,” Nat. Biotechnol. 17, 375–378 (1999).
[CrossRef] [PubMed]

U. Mahmood, C. H. Tung, A. Bogdanov, R. Weissleder, “Near infrared optical imaging system to detect tumor protease activity,” Radiology 213, 866–870 (1999).
[CrossRef] [PubMed]

Wells, W.

B. Pogue, S. P. Poplack, T. McBride, W. Wells, K. Osterman, U. Osterberg, K. D. Paulsen, “Quantitative hemoglobin tomography with diffuse near-infrared spectroscopy: pilot results in the breast,” Radiology 218, 261–266 (2001).
[CrossRef] [PubMed]

Wiedenmann, B.

A. Becker, C. Hessenius, K. Licha, B. Ebert, U. Sukowski, W. Semmler, B. Wiedenmann, C. Grotzinger, “Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands,” Nat. Biotechnol. 19, 327–331 (2001).
[CrossRef] [PubMed]

Wouters, F. S.

F. S. Wouters, “Imaging biochemistry inside cells,” Trends Cell Biol. 11, 203–211 (2001).
[CrossRef] [PubMed]

Xu, H.

H. Xu, H. Dehghani, B. W. Pogue, “Near-infrared imaging in the small animal brain: optimization of fiber positions,” J. Biomed. Opt. 8, 102–110 (2003).
[CrossRef] [PubMed]

Xu, Y.

Yodh, A. G.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, 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, 235–247 (2003).
[CrossRef] [PubMed]

J. P. Culver, V. Ntziachristos, M. J. Holboke, A. G. Yodh, “Optimization of optode arrangements for diffuse optical tomography: a singular-value analysis,” Opt. Lett. 26, 701–703 (2001).
[CrossRef]

V. Ntziachristos, A. G. Yodh, M. Schnall, B. Chance, “Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement,” Proc. Natl. Acad. Sci. USA 97, 2767–2772 (2000).
[CrossRef] [PubMed]

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

Zhang, Q.

D. A. Boas, D. H. Brooks, E. L. Miller, C. A. DiMarzio, M. Kilmer, R. J. Gaudette, Q. Zhang, “Imaging the body with diffuse optical tomography,” IEEE Signal Process. Mag. 18, 57–75 (2001).
[CrossRef]

Zubkov, L.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, 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, 235–247 (2003).
[CrossRef] [PubMed]

Appl. Opt. (1)

Breast Cancer Res. (1)

V. Ntziachristos, B. Chance, “Probing physiology and molecular function using optical imaging: applications to breast cancer,” Breast Cancer Res. 3, 41–46 (2001).
[CrossRef] [PubMed]

IEEE Signal Process. Mag. (1)

D. A. Boas, D. H. Brooks, E. L. Miller, C. A. DiMarzio, M. Kilmer, R. J. Gaudette, Q. Zhang, “Imaging the body with diffuse optical tomography,” IEEE Signal Process. Mag. 18, 57–75 (2001).
[CrossRef]

IEEE Trans. Biomed. Eng. (1)

J. H. Chang, H. L. Graber, R. L. Barbour, “Imaging of fluorescence in highly scattering media,” IEEE Trans. Biomed. Eng. 44, 810–822 (1997).
[CrossRef] [PubMed]

Inverse Probl. (2)

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

R. Pierri, A. Tamburrino, “On the local minima problem in conductivity imaging via a quadratic approach,” Inverse Probl. 13, 1547–1568 (1997).
[CrossRef]

Invest. Radiol. (1)

S. Achilefu, R. B. Dorshow, J. E. Bugaj, R. Rajagopalan, “Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging,” Invest. Radiol. 35, 479–485 (2000).
[CrossRef] [PubMed]

J. Biomed. Opt. (2)

J. E. Bugaj, S. Achilefu, R. B. Dorshow, R. Rajagopalan, “Novel fluorescent contrast agents for optical imaging of in vivo tumors based on a receptor-targeted dye-peptide conjugate platform,” J. Biomed. Opt. 6, 122–133 (2001).
[CrossRef] [PubMed]

H. Xu, H. Dehghani, B. W. Pogue, “Near-infrared imaging in the small animal brain: optimization of fiber positions,” J. Biomed. Opt. 8, 102–110 (2003).
[CrossRef] [PubMed]

J. Cereb. Blood Flow Metab. (1)

D. A. Benaron, S. R. Hintz, A. Villringer, D. Boas, A. Kleinschmidt, J. Frahm, C. Hirth, H. Obrig, J. C. van Houten, E. L. Kermit, W. F. Cheong, D. K. Stevenson, “Noninvasive functional imaging of human brain using light,” J. Cereb. Blood Flow Metab. 20, 469–477 (2000).
[CrossRef] [PubMed]

Med. Phys. (3)

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, 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, 235–247 (2003).
[CrossRef] [PubMed]

V. Ntziachristos, R. Weissleder, “CCD-based scanner for tomography of fluorescent near-infrared probes in turbid media,” Med. Phys. 29, 803–809 (2002).
[CrossRef] [PubMed]

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

Nat. Biotechnol. (3)

S. Tyagi, F. R. Kramer, “Molecular beacons: probes that fluoresce upon hybridization,” Nat. Biotechnol. 14, 303–308 (1996).
[CrossRef] [PubMed]

R. Weissleder, C. H. Tung, U. Mahmood, A. Bogdanov, “In vivo imaging of tumors with protease-activated near-infrared fluorescent probes,” Nat. Biotechnol. 17, 375–378 (1999).
[CrossRef] [PubMed]

A. Becker, C. Hessenius, K. Licha, B. Ebert, U. Sukowski, W. Semmler, B. Wiedenmann, C. Grotzinger, “Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands,” Nat. Biotechnol. 19, 327–331 (2001).
[CrossRef] [PubMed]

Nat. Med. (1)

V. Ntziachristos, C. Tung, C. Bremer, R. Weissleder, “Fluorescence-mediated tomography resolves protease activity in vivo,” Nat. Med. 8, 757–760 (2002).
[CrossRef] [PubMed]

Neoplasia (1)

D. J. Hawrysz, E. M. Sevick-Muraca, “Developments toward diagnostic breast cancer imaging using near-infrared optical measurements and fluorescent contrast agents,” Neoplasia 2, 388–417 (2000).
[CrossRef]

Opt. Express (2)

Opt. Lett. (3)

Proc. Natl. Acad. Sci. USA (1)

V. Ntziachristos, A. G. Yodh, M. Schnall, B. Chance, “Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement,” Proc. Natl. Acad. Sci. USA 97, 2767–2772 (2000).
[CrossRef] [PubMed]

Radiology (2)

B. Pogue, S. P. Poplack, T. McBride, W. Wells, K. Osterman, U. Osterberg, K. D. Paulsen, “Quantitative hemoglobin tomography with diffuse near-infrared spectroscopy: pilot results in the breast,” Radiology 218, 261–266 (2001).
[CrossRef] [PubMed]

U. Mahmood, C. H. Tung, A. Bogdanov, R. Weissleder, “Near infrared optical imaging system to detect tumor protease activity,” Radiology 213, 866–870 (1999).
[CrossRef] [PubMed]

Trends Cell Biol. (1)

F. S. Wouters, “Imaging biochemistry inside cells,” Trends Cell Biol. 11, 203–211 (2001).
[CrossRef] [PubMed]

Other (3)

H. W. Engl, M. Hanke, A. Neubauer, Regularization of Inverse Problems (Kluwer Academic, Dordrecht, The Netherlands, 1996).

M. Bertero, P. Boccacci, Introduction to Inverse Problems in Imaging (Institute of Physics, Bristol, UK, 1998).

A. C. Kak, M. Slaney, Principles of Computerized Tomographic Imaging (IEEE Press, Piscataway, N.J., 1988).

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Figures (9)

Fig. 1
Fig. 1

Diagram of the fluorescence molecular tomography experimental setup used in the FMT analysis. A two-dimensional mesh distribution was studied by use of linear source and detector arrays in a parallel-plate configuration. The fields of view and number of sources, detectors, and mesh points in X and Y were varied to characterize system performance as a function of these parameters.

Fig. 2
Fig. 2

Test fluorochrome distribution used to assess the experimental trends predicted by SVA. (a) For simulated reconstructions, three-point fluorochromes equivalent to 1000 nM of Cy 5.5 dye were aligned in a diagonal line from sources to detectors with center-to-center separations of 5.7 mm. (b) Experimental data were acquired and reconstructed for a resolution phantom consisting of two parallel tubes, shown in relation to the source and detector arrays.

Fig. 3
Fig. 3

Singular-value analysis of the effects of detector and source FOV and number for symmetric source and detector arrays. Singular-value spectra for weight matrices representing setups with 21 sources and 21 detectors over a 10-mm (squares), 20-mm (crosses), and 30-mm (triangles) FOV are shown. The intersections of each spectrum with an empirically determined noise threshold (10-4) yielded the number of nonnoise, or useful, singular values for that experimental setup.

Fig. 4
Fig. 4

Singular-value analysis of the effects of detector and source FOV and number for symmetric source and detector arrays. (a) Plots of the number of useful singular values, extracted as shown in Fig. 3, versus source and detector FOV for setups with 6 (squares), 11 (crosses), 21 (triangles), and 31 (circles) sources and detectors. (b) Plots for setups involving 21 sources and detectors interrogating media with diffusion lengths of 2.2 mm (circles), 4.3 mm (triangles), and 8.6 mm (crosses).

Fig. 5
Fig. 5

Singular-value analysis of the effects of detector and source FOV and number for asymmetric source and detector arrays. (a) Plots of the number of useful singular values versus detector FOV for 11 (squares), 21 (crosses), 41 (triangles), and 81 (circles) detectors for 6 sources over a 15-mm FOV. (b) Number of useful singular values plotted against detector FOV, in this case for source fields of view of 10 (squares), 20 (crosses), 30 (triangles), and 40 (circles) mm. These plots were generated for 9 sources and 49 detectors.

Fig. 6
Fig. 6

Singular-value analysis of the effects of mesh FOV and number of elements for symmetric and asymmetric source and detector arrays. Circles show the number of useful singular values versus mesh X FOV for 21 sources and 21 detectors over a 20-mm FOV. Triangles are plotted for the corresponding analysis of mesh X FOV and number of points for 9 sources and 49 detectors over a 20-mm FOV.

Fig. 7
Fig. 7

Analysis of the effects of detector and source FOV and number for symmetric source and detector arrays, using reconstructions of simulated data. Reconstructions of the fluorochrome distribution shown in Fig. 2 over a 41×29 element mesh with FOV 20×14 mm are given for varying source and detector number and FOV. These reconstructions were performed for an optical medium with diffusion length 4.3 mm.

Fig. 8
Fig. 8

Image error for reconstructions of simulated data with symmetric source and detector arrays. The reconstruction error, in terms of deviation from the test fluorochrome distribution shown in Fig. 2, for the reconstructions in Fig. 7 (diffusion length 4.3 mm) is plotted as a function of source/detector FOV, with separate traces for reconstructions with different numbers of sources and detectors.

Fig. 9
Fig. 9

Analysis of the effects of detector FOV and number, using reconstructions of experimental data. FMT data were acquired for two tubes filled with 1000 nM Cy 5.5 fluorescent dye, separated by a gap of 1 mm, immersed in a medium with diffusion length 4.3 mm. Reconstructions are shown for a range of detector fields of view and numbers, which were sampled from the acquired high-resolution images. The mesh used contained 41×29 elements with a FOV of 20×14 mm.

Equations (5)

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

UnB(rs, rd)=S0U(rs, rd, kλ1)·U(rs, r, kλ1)·n(r)Dλ2·G(rd-r, kλ2)d3r,
UnB(rs1, rd1)=S0U(rs1, r1, kλ1)G(rd1-r1, kλ2)U(rs1, rd1, kλ1)Dλ2S0U(rs1, rN, kλ1)G(rd1-rN, kλ2)U(rs1, rd1, kλ1)Dλ2·n(r1)n(rN).
UnB(rs1, rd1)UnB(rsM, rdM)=W11W1NWM1WMN·n(r1)n(rN),
Uo(rs, rd)=U(rd-rs, kλ1),
Ufl(rs1, rd1)=[U(rs1, r1, kλ1)G(rd1-r1, kλ2)U(rs1, rN, kλ1)×G(rd1-rN, kλ2)]·n(r1)n(rN).

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