Abstract

To date, the assessment of fluorescence-enhanced optical imaging has not been performed owing to (i) the lack of tools necessary for objective assessment of image quality (OAIQ), and (ii) the difficulty to test an untested diagnostic contrast agent in patient studies. Herein, we focus upon the development of a framework for OAIQ which includes a model to simulate both natural tissue heterogeneity as well as heterogeneous distribution of a molecularly targeted fluorophore. Specifically, we use a novel tomographic algorithm previously developed and validated in our laboratory (Roy and Sevick-Muraca, IEEE Trans. Med. Imaging, 2005). Our results show that image generation is (i) unaffected by normal anatomical heterogeneity manifested in endogenous tissue optical properties of absorption and scattering, and (ii) restricted by heterogeneous distribution of fluorophore in the background as the contrast is decreased.

© 2005 Optical Society of America

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References

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  1. P. M. Smithjones, B. Stolz, C. Bruns, R. Albert, H. W. Reist, R. Fridrich, and H. R. Macke, "Gallium- 67/Gallium-68-[DFO]-Octreotide- A potential radiopharmaceutical for PET imaging of somatostatin receptor-positive tumors-synthesis and rediolabeling in vitro and preliminary in vivo studies," J. Nucl. Med. 35, 317-325 (1994).
  2. D. L. Bailey, B. F. Hutton, and P. J. Walker, "Improved SPECT using simultaneous emission and transmission tomography," J. Nucl. Med. 28, 844-851 (1987).
    [PubMed]
  3. J. P. Houston, S. Ke, W. Wang, C. Li, and E. M. Sevick-Muraca, "Quality analysis of in vivo NIR fluorescence and conventional gamma images acquired using a dual-labeled tumor-targeting probe," J. Biomed. Opt. (to be published in September/October 2005).
    [CrossRef] [PubMed]
  4. E. M. Sevick-Muraca and D. Y. Paithankar, "Fluorescent imaging system and measurement," U.S. patent 5,865,754, (2 February 1999).
  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. A. Godavarty, M. J. Eppstein, C. Zhang, S. Theru, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, "Fluorescence-enhanced optical imaging in large tissue volumes using a gain modulated ICCD camera," Phys. Med. Biol. 48, 1701-1720 (2003).
    [CrossRef] [PubMed]
  7. A. Godavarty, M. J. Eppstein, C. Zhang, and E. M. Sevick-Muraca, "Detection of multiple targets in breast phantoms using fluorescence enhanced optical imaging," Radiology 235, 148-154 (2005).
    [CrossRef] [PubMed]
  8. A. D. Klose, and A. H. Hielscher, "Iterative scheme for the optical tomography based on the equation of the radiative transfer," Med. Phys. 26, 1698-1707 (1999).
    [CrossRef] [PubMed]
  9. V. Ntziachristos, and B. Chance, "Accuracy limits in the determination of absolute optical properties using time-resolved NIR spectroscopy," Med. Phys. 28, 1115-1124 (2001).
    [CrossRef] [PubMed]
  10. R. Roy, A. B. Thompson, A. Godavarty, and E. M. Sevick-Muraca, "Tomographic fluorescence imaging in tissue Phantoms: a novel reconstruction algorithm and imaging geometry," IEEE Trans. Med. Imaging 24, 137-154 (2005).
    [CrossRef] [PubMed]
  11. A. B. Thompson, D. J. Hawrysz, and E. M. Sevick-Muraca, "Near-infrared contrast-enhanced imaging with area illumination and area detection: the forward imaging problem," Appl. Opt. 42, 4125-4136 (2003).
    [CrossRef] [PubMed]
  12. A. Godavarty, "Fluorescence enhanced optical tomography on breast phantoms with measurements using a gain modulated intensified CCD imaging system," Ph.D. Dissertation, (Texas A&M University, 2003).
  13. R. Marchesini, A. Bertoni, S. Andreola, E. Melloni, and A. E. Sichirollo, "Extinction and absorption coefficients and scattering phase functions of human tissues in vitro," Appl. Opt. 28, 2318-2324 (1989).
    [CrossRef] [PubMed]
  14. V. G. Peters, D. R. Wymant, M. S. Patterson, and G. L. Frank, "Optical properties of normal and diseased human breast tissues in the visible and near infrared," Phys. Med. Biol. 35, 1317-1334 (1990).
    [CrossRef] [PubMed]
  15. K. A. Kang, B. Chance, S. Zhao, S. Srinivasan, E. Patterson, and R. Troupin, "Breast tumor characterization using near-infrared spectroscopy," Proc. photon migration and imaging in random media and tissues 1888, 487-499 (1993).
  16. K. Suzuki, Y. Yamashita, K. Ohta, M. Kaneko, M. Yoshida, and B. Chance, "Quantitative measurements of optical parameters in normal breasts using time resolved spectroscopy: in vivo results of 30 Japanese women," J. Biomed. Opt. 1, 330-334 (1996).
    [CrossRef]
  17. T. L. Troy, D. L. Page, and E. M. Sevick-Muraca, "Optical properties of normal and diseased breast tissues: prognosis for optical mammography" J. Biomed. Opt. 1, 342-355 (1996).
    [CrossRef]
  18. B. J. Tromberg, O. Coquoz, J. B. Fishkin, T. Pham, E. R. Anderson, J. Butler, M. Cahn, J. D. Gross, V. Venugopalan, and D. Pham, "Non-invasive measurement of breast tissue optical properties using frequency-domain photon migration," Philos. Trans. Biol. Sciences, 353, 661-668 (1997).
    [CrossRef]
  19. D. Grosenick, H. Wabnitz, H. H. Rinneberg, K. T. Moesta, and P. M. Schlag, "Development of a time-domain optical mammography and first in vivo applications," Appl. Opt. 38, 2927-1943 (1999).
    [CrossRef]
  20. N. Shah, A. Cerussi, C. Eker, J. Espinoza, J. Butler, J. Fishkin, R. Hornung, and B. J. Tromberg, "Noninvasive functional optical spectroscopy of human breast tissue," Proc. Natl. Acad. Sci. USA 98, 4420-4425 (2001).
    [CrossRef] [PubMed]
  21. T. Durduran, R. Choe, J. P. Culver, L. Zubkov, M. J. Holboke, J. Giammarco, B. Chance, and A. G. Yodh, "Bulk optical properties of healthy female breast tissue," Phys. Med. Biol. 47, 2847-2861 (2002).
    [CrossRef] [PubMed]
  22. 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]
  23. N. Shah, A. E. Cerussi, D. Jakubowski, D. Hsiang, J. Butler, B. J. Tromberg, "Spatial variations in optical and physiological properties of healthy breast tissue," J. Biomed. Opt. 9, 534-540 (2004).
    [CrossRef] [PubMed]
  24. 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," J. Biomed. Opt. 9, 488-496 (2004).
    [CrossRef] [PubMed]
  25. J. P. Rolland, and H. H. Barrett, "Effect of random background inhomogeneity on observer detection performance," J. Opt. Soc. Am. A. 9, 649-658 (1992).
    [CrossRef] [PubMed]
  26. A. R. P. Fortin, "Detection-theoretic evaluation in digital radiography and optical tomography," PhD Thesis, (University of Arizona, 2002).
  27. H. Barrett, and K. J. Myers, Foundations of Image Science, 1st ed. (John Wiley & Sons, Inc., New Jersey, 2004).
  28. R. Roy, A. Godavarty, and E. M. Sevick-Muraca, "Fluorecense-enhanced optical tomography using referenced measurements of heterogeneous media," IEEE Trans. Med. Imaging 22, 824-836 (2003).
    [CrossRef] [PubMed]
  29. M. G. Breitfeld, and D. F. Shanno, "Preliminary computational experience with modified log-barrier function for large-scale nonlinear programming," in Large Scale Optimization: State of the art, W. W. Hager, D. W. Hearn, and P. M. Pardalos, eds. (Kluwer Academic, Dordrecht, The Netherlands: 1994), pp. 45-67.
  30. M. J. Eppstein, D. E. Dougherty, D. J. Hawrysz, and E. M. Sevick-Muraca, "3-D Bayesian optical imaging reconstruction with domain decomposition," IEEE Trans. Med. Imaging 20, 147-161 (2001).
    [CrossRef] [PubMed]

. Biomed. Opt. (1)

J. P. Houston, S. Ke, W. Wang, C. Li, and E. M. Sevick-Muraca, "Quality analysis of in vivo NIR fluorescence and conventional gamma images acquired using a dual-labeled tumor-targeting probe," J. Biomed. Opt. (to be published in September/October 2005).
[CrossRef] [PubMed]

Appl. Opt. (4)

IEEE Trans. Med. Imaging (3)

R. Roy, A. Godavarty, and E. M. Sevick-Muraca, "Fluorecense-enhanced optical tomography using referenced measurements of heterogeneous media," IEEE Trans. Med. Imaging 22, 824-836 (2003).
[CrossRef] [PubMed]

M. J. Eppstein, D. E. Dougherty, D. J. Hawrysz, and E. M. Sevick-Muraca, "3-D Bayesian optical imaging reconstruction with domain decomposition," IEEE Trans. Med. Imaging 20, 147-161 (2001).
[CrossRef] [PubMed]

R. Roy, A. B. Thompson, A. Godavarty, and E. M. Sevick-Muraca, "Tomographic fluorescence imaging in tissue Phantoms: a novel reconstruction algorithm and imaging geometry," IEEE Trans. Med. Imaging 24, 137-154 (2005).
[CrossRef] [PubMed]

J. Biomed. Opt. (4)

N. Shah, A. E. Cerussi, D. Jakubowski, D. Hsiang, J. Butler, B. J. Tromberg, "Spatial variations in optical and physiological properties of healthy breast tissue," J. Biomed. Opt. 9, 534-540 (2004).
[CrossRef] [PubMed]

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," J. Biomed. Opt. 9, 488-496 (2004).
[CrossRef] [PubMed]

K. Suzuki, Y. Yamashita, K. Ohta, M. Kaneko, M. Yoshida, and B. Chance, "Quantitative measurements of optical parameters in normal breasts using time resolved spectroscopy: in vivo results of 30 Japanese women," J. Biomed. Opt. 1, 330-334 (1996).
[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. Biomed. Opt. 1, 342-355 (1996).
[CrossRef]

J. Nucl. Med. (2)

P. M. Smithjones, B. Stolz, C. Bruns, R. Albert, H. W. Reist, R. Fridrich, and H. R. Macke, "Gallium- 67/Gallium-68-[DFO]-Octreotide- A potential radiopharmaceutical for PET imaging of somatostatin receptor-positive tumors-synthesis and rediolabeling in vitro and preliminary in vivo studies," J. Nucl. Med. 35, 317-325 (1994).

D. L. Bailey, B. F. Hutton, and P. J. Walker, "Improved SPECT using simultaneous emission and transmission tomography," J. Nucl. Med. 28, 844-851 (1987).
[PubMed]

J. Opt. Soc. Am. A. (1)

J. P. Rolland, and H. H. Barrett, "Effect of random background inhomogeneity on observer detection performance," J. Opt. Soc. Am. A. 9, 649-658 (1992).
[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]

A. D. Klose, and A. H. Hielscher, "Iterative scheme for the optical tomography based on the equation of the radiative transfer," Med. Phys. 26, 1698-1707 (1999).
[CrossRef] [PubMed]

V. Ntziachristos, and B. Chance, "Accuracy limits in the determination of absolute optical properties using time-resolved NIR spectroscopy," Med. Phys. 28, 1115-1124 (2001).
[CrossRef] [PubMed]

Philos. Trans. Biol. Sciences (1)

B. J. Tromberg, O. Coquoz, J. B. Fishkin, T. Pham, E. R. Anderson, J. Butler, M. Cahn, J. D. Gross, V. Venugopalan, and D. Pham, "Non-invasive measurement of breast tissue optical properties using frequency-domain photon migration," Philos. Trans. Biol. Sciences, 353, 661-668 (1997).
[CrossRef]

Phys. Med. Biol. (3)

V. G. Peters, D. R. Wymant, M. S. Patterson, and G. L. Frank, "Optical properties of normal and diseased human breast tissues in the visible and near infrared," Phys. Med. Biol. 35, 1317-1334 (1990).
[CrossRef] [PubMed]

A. Godavarty, M. J. Eppstein, C. Zhang, S. Theru, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, "Fluorescence-enhanced optical imaging in large tissue volumes using a gain modulated ICCD camera," Phys. Med. Biol. 48, 1701-1720 (2003).
[CrossRef] [PubMed]

T. Durduran, R. Choe, J. P. Culver, L. Zubkov, M. J. Holboke, J. Giammarco, B. Chance, and A. G. Yodh, "Bulk optical properties of healthy female breast tissue," Phys. Med. Biol. 47, 2847-2861 (2002).
[CrossRef] [PubMed]

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

N. Shah, A. Cerussi, C. Eker, J. Espinoza, J. Butler, J. Fishkin, R. Hornung, and B. J. Tromberg, "Noninvasive functional optical spectroscopy of human breast tissue," Proc. Natl. Acad. Sci. USA 98, 4420-4425 (2001).
[CrossRef] [PubMed]

Proc. SPIE (1)

K. A. Kang, B. Chance, S. Zhao, S. Srinivasan, E. Patterson, and R. Troupin, "Breast tumor characterization using near-infrared spectroscopy," Proc. photon migration and imaging in random media and tissues 1888, 487-499 (1993).

Radiology (1)

A. Godavarty, M. J. Eppstein, C. Zhang, and E. M. Sevick-Muraca, "Detection of multiple targets in breast phantoms using fluorescence enhanced optical imaging," Radiology 235, 148-154 (2005).
[CrossRef] [PubMed]

Other (5)

E. M. Sevick-Muraca and D. Y. Paithankar, "Fluorescent imaging system and measurement," U.S. patent 5,865,754, (2 February 1999).

A. R. P. Fortin, "Detection-theoretic evaluation in digital radiography and optical tomography," PhD Thesis, (University of Arizona, 2002).

H. Barrett, and K. J. Myers, Foundations of Image Science, 1st ed. (John Wiley & Sons, Inc., New Jersey, 2004).

M. G. Breitfeld, and D. F. Shanno, "Preliminary computational experience with modified log-barrier function for large-scale nonlinear programming," in Large Scale Optimization: State of the art, W. W. Hager, D. W. Hearn, and P. M. Pardalos, eds. (Kluwer Academic, Dordrecht, The Netherlands: 1994), pp. 45-67.

A. Godavarty, "Fluorescence enhanced optical tomography on breast phantoms with measurements using a gain modulated intensified CCD imaging system," Ph.D. Dissertation, (Texas A&M University, 2003).

Supplementary Material (7)

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Figures (8)

Fig. 1.
Fig. 1.

The geometry of the breast-shaped phantom. The dimensions are in centimeters. The bigger cylindrical volume has a circular base of diameter 20 cm. The hemisphere has a radius of 5 cm.

Fig. 2.
Fig. 2.

The positions of laser sources and detectors on the breast phantom. The stars are the positions of the sources and the circles are the positions of the detectors.

Fig. 3.
Fig. 3.

Movies of the lumps in endogenous and exogenous optical properties using Lumpy object model. The lumps in μaxi (1.08 MB) (a), μsx (1.07 MB) (b), and μaxf (1.10 MB) (c) are shown as the cutplanes to the breast geometry (Fig. 1) parallel to yz-plane. The snapshots shown above are cutplanes passing through x=0.20 cm. The spread of the lumps are 5mm and there are 100 lumps uniformly generated in the hemispherical volume. The lumps have the strength values of 25% of the average background values of μaxi , μsx , and μaxf given in Table 3.

Fig. 4.
Fig. 4.

Actual distribution of exogenous optical property of the target inside the breast phantom. The colorbar shows the values of μaxf in cm-1. The target has μaxf value 100 times more than that of the background. The Fig. shown is a cut plane parallel to yz-plane and passing through point x=0.5. The lumps in the background are not shown here.

Fig. 5.
Fig. 5.

(1.06 MB) Movie of the recovered distribution of exogenous optical property in the presence of 1% lumps in endogenous optical properties using the PMBF/CONTN inverse algorithm. The colorbar shows the values of μaxf in cm-1. The movie shows cut planes parallel to xz-plane. The black spherical mesh represents the actual target.

Fig. 6.
Fig. 6.

The root mean square error (RMSE) values of the reconstructed images in the presence of endogenous lumps in the background. The target-to-background ratio (TBR) is 100:1 and the RMSE is calculated with respect to the actual distribution of the fluorophore shown in Fig. 4.

Fig. 7.
Fig. 7.

Movies of the recovered distribution of exogenous optical property in the presence of 1% lumps in endogenous as well as exogenous optical properties using the PMBF/CONTN inverse algorithm. Figs. (a) (1.25 MB), (b) (1.26 MB), and (c) (1.27 MB) are respectively for TBR values of 100:1, 50:1, and 25:1. The colorbar shows the values of μaxf in cm-1. The movies shown are cut planes parallel to xz-plane. The black spherical mesh represents the actual target.

Fig. 8.
Fig. 8.

The root mean square error (RMSE) values of the reconstructed images in the presence of endogenous as well as exogenous lumps in the background. The plots for all the three cases of TBR values are shown and the RMSE is calculated with respect to the actual distribution of the fluorophore including the target distribution shown in Fig. 4 and the exogenous lumps in the background. The values for 100% are not shown here since we could not reconstruct the target for the TBR values of 50 and 25.

Tables (5)

Tables Icon

Table 1. Experimental breast optical property values reported in literature

Tables Icon

Table 2. Constant factors to obtain lumps at emission wavelength from the generated lumps at excitation wavelength.

Tables Icon

Table 3. Average background optical properties. Also given are the parameters used in equations (2), (3), and (4). The optical properties used in the simulations are similar to breast tissue optical properties reported in literature (see Table 1).

Tables Icon

Table 4. Centroid of the reconstructed targets with varying lump intensities. The coordinate dimensions are in centimeters.

Tables Icon

Table 5. The mean displacement of the reconstructed targets with respect to the actual target’s centroid. The dimension is in centimeters.

Equations (14)

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c Φ ( r , ω ) [ D ( r ) Φ ( r , ω ) ] + μ a ( r ) Φ ( r , ω ) = S ( r , ω )
[ D x ( r ) Φ x ( r , ω ) ] + [ c + μ axi ( r ) + μ axf ( r ) ] Φ x ( r , ω ) = S ( r , ω )
[ D m ( r ) Φ m ( r , ω ) ] + [ c + μ ami ( r ) + μ amf ( r ) ] Φ m ( r , ω ) = ϕ μ axf ( r ) 1 + iωτ 1 + [ ωτ ] 2 Φ x ( r , ω )
D x , m = 1 3 ( μ a x , m i + μ a x , m f + μ s x , m ( 1 g ) )
2 D x , m Φ x , m n + γ Φ x , m = 0
Φ x , m ( r , ω ) = I A C x , m exp ( i θ x , m ( r , ω ) )
b ( r ) = b 0 + n = 1 N p lump ( r r n )
lump ( r r n ) = l 0 exp ( r r n 2 2 w 2 ) 1 V ( Ω ) Ω l 0 exp ( r r n 2 2 w 2 ) d 3 r
E ( μ axf ) = 1 2 p = 1 N B [ ( log ( Z p ) cal log ( Z p ) mea ) ( log ( Z p ) cal * log ( Z p ) mea * ) ]
Z p = I A C ref p exp ( i θ ref p )
( Φ m ) p ( Φ x ) p p = 1 , , N B
min μ axf M ( μ axf , λ , η ) = E ( μ axf ) η i = 1 N { λ i l f ( μ axf i l ) + λ i l f ( u μ axf i ) }
r C = i = 1 N T μ axf i r i i = 1 N T μ axf i
RMSE = i = 1 N { 1 N ( μ axf calc μ axf actual ) i 2 }

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