Abstract

The reconstruction of internal light sources in bioluminescence tomography (BLT) is a challenging inverse problem because of the limited amount of information available compared with that for other kinds of tomography such as fluorescence tomography in which external illumination sources are used. We demonstrated previously, using phantom experiments, that a target containing luciferases could be detected tomographically when the target was located relatively close to the imaging boundary. Here we describe an improved BLT reconstruction method that can detect luciferase-containing targets located anywhere within an imaging domain. The method is tested with numerical simulations and further confirmed with several phantom experiments.

© 2006 Optical Society of America

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References

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  1. S. Bhaumik and S. Gambhir, "Optical imaging of Renilla luciferase reporter gene express in living mice," Proc. Natl. Acad. Sci. USA 99, 377-382 (2002).
    [CrossRef]
  2. C. Contag and M. Bachmann, "Advances in in vivo bioluminescence imaging of gene express," Annu. Rev. Biomed. Eng. 4, 235-260 (2002).
    [CrossRef] [PubMed]
  3. S. Mandl, C. Schimmelpfennig, M. Edinger, R. Negrin, and C. Contag, "Understanding immune cell trafficking patterns via in vivo bioluminescence imaging," J. Cell. Biochem. Suppl. 39, 239-248 (2002).
    [CrossRef]
  4. V. Ntziachristos, J. Ripoll, L. V Wang, and R. Weissleder, "Looking and listening to light: the evolution of whole-body photonic imaging," Nat. Biotechnol. 23, 313-320 (2005).
    [CrossRef] [PubMed]
  5. H. R. Herschman, "Molecular imaging: looking at problems, seeing solutions," Science 302, 605-608 (2003).
    [CrossRef] [PubMed]
  6. R. Weissleder and V. Ntziachristos, "Shedding light onto live molecular targets," Nat. Med. 9, 123-128 (2003).
    [CrossRef] [PubMed]
  7. G. Wang, Y. Li, and M. Jiang, "Uniqueness theorems in bioluminescence tomography," Med. Phys. 31, 2289-2299 (2004).
    [CrossRef] [PubMed]
  8. X. Gu, Q. Zhang, L. Larcom, and H. Jiang, "Three dimensional bioluminescence tomography with model-based reconstruction," Opt. Express 12, 3996-4000 (2004).
    [CrossRef] [PubMed]

2005

V. Ntziachristos, J. Ripoll, L. V Wang, and R. Weissleder, "Looking and listening to light: the evolution of whole-body photonic imaging," Nat. Biotechnol. 23, 313-320 (2005).
[CrossRef] [PubMed]

2004

2003

H. R. Herschman, "Molecular imaging: looking at problems, seeing solutions," Science 302, 605-608 (2003).
[CrossRef] [PubMed]

R. Weissleder and V. Ntziachristos, "Shedding light onto live molecular targets," Nat. Med. 9, 123-128 (2003).
[CrossRef] [PubMed]

2002

S. Bhaumik and S. Gambhir, "Optical imaging of Renilla luciferase reporter gene express in living mice," Proc. Natl. Acad. Sci. USA 99, 377-382 (2002).
[CrossRef]

C. Contag and M. Bachmann, "Advances in in vivo bioluminescence imaging of gene express," Annu. Rev. Biomed. Eng. 4, 235-260 (2002).
[CrossRef] [PubMed]

S. Mandl, C. Schimmelpfennig, M. Edinger, R. Negrin, and C. Contag, "Understanding immune cell trafficking patterns via in vivo bioluminescence imaging," J. Cell. Biochem. Suppl. 39, 239-248 (2002).
[CrossRef]

Bachmann, M.

C. Contag and M. Bachmann, "Advances in in vivo bioluminescence imaging of gene express," Annu. Rev. Biomed. Eng. 4, 235-260 (2002).
[CrossRef] [PubMed]

Bhaumik, S.

S. Bhaumik and S. Gambhir, "Optical imaging of Renilla luciferase reporter gene express in living mice," Proc. Natl. Acad. Sci. USA 99, 377-382 (2002).
[CrossRef]

Contag, C.

C. Contag and M. Bachmann, "Advances in in vivo bioluminescence imaging of gene express," Annu. Rev. Biomed. Eng. 4, 235-260 (2002).
[CrossRef] [PubMed]

S. Mandl, C. Schimmelpfennig, M. Edinger, R. Negrin, and C. Contag, "Understanding immune cell trafficking patterns via in vivo bioluminescence imaging," J. Cell. Biochem. Suppl. 39, 239-248 (2002).
[CrossRef]

Edinger, M.

S. Mandl, C. Schimmelpfennig, M. Edinger, R. Negrin, and C. Contag, "Understanding immune cell trafficking patterns via in vivo bioluminescence imaging," J. Cell. Biochem. Suppl. 39, 239-248 (2002).
[CrossRef]

Gambhir, S.

S. Bhaumik and S. Gambhir, "Optical imaging of Renilla luciferase reporter gene express in living mice," Proc. Natl. Acad. Sci. USA 99, 377-382 (2002).
[CrossRef]

Gu, X.

Herschman, H. R.

H. R. Herschman, "Molecular imaging: looking at problems, seeing solutions," Science 302, 605-608 (2003).
[CrossRef] [PubMed]

Jiang, H.

Jiang, M.

G. Wang, Y. Li, and M. Jiang, "Uniqueness theorems in bioluminescence tomography," Med. Phys. 31, 2289-2299 (2004).
[CrossRef] [PubMed]

Larcom, L.

Li, Y.

G. Wang, Y. Li, and M. Jiang, "Uniqueness theorems in bioluminescence tomography," Med. Phys. 31, 2289-2299 (2004).
[CrossRef] [PubMed]

Mandl, S.

S. Mandl, C. Schimmelpfennig, M. Edinger, R. Negrin, and C. Contag, "Understanding immune cell trafficking patterns via in vivo bioluminescence imaging," J. Cell. Biochem. Suppl. 39, 239-248 (2002).
[CrossRef]

Negrin, R.

S. Mandl, C. Schimmelpfennig, M. Edinger, R. Negrin, and C. Contag, "Understanding immune cell trafficking patterns via in vivo bioluminescence imaging," J. Cell. Biochem. Suppl. 39, 239-248 (2002).
[CrossRef]

Ntziachristos, V.

V. Ntziachristos, J. Ripoll, L. V Wang, and R. Weissleder, "Looking and listening to light: the evolution of whole-body photonic imaging," Nat. Biotechnol. 23, 313-320 (2005).
[CrossRef] [PubMed]

R. Weissleder and V. Ntziachristos, "Shedding light onto live molecular targets," Nat. Med. 9, 123-128 (2003).
[CrossRef] [PubMed]

Ripoll, J.

V. Ntziachristos, J. Ripoll, L. V Wang, and R. Weissleder, "Looking and listening to light: the evolution of whole-body photonic imaging," Nat. Biotechnol. 23, 313-320 (2005).
[CrossRef] [PubMed]

Schimmelpfennig, C.

S. Mandl, C. Schimmelpfennig, M. Edinger, R. Negrin, and C. Contag, "Understanding immune cell trafficking patterns via in vivo bioluminescence imaging," J. Cell. Biochem. Suppl. 39, 239-248 (2002).
[CrossRef]

Wang, G.

G. Wang, Y. Li, and M. Jiang, "Uniqueness theorems in bioluminescence tomography," Med. Phys. 31, 2289-2299 (2004).
[CrossRef] [PubMed]

Wang, L. V

V. Ntziachristos, J. Ripoll, L. V Wang, and R. Weissleder, "Looking and listening to light: the evolution of whole-body photonic imaging," Nat. Biotechnol. 23, 313-320 (2005).
[CrossRef] [PubMed]

Weissleder, R.

V. Ntziachristos, J. Ripoll, L. V Wang, and R. Weissleder, "Looking and listening to light: the evolution of whole-body photonic imaging," Nat. Biotechnol. 23, 313-320 (2005).
[CrossRef] [PubMed]

R. Weissleder and V. Ntziachristos, "Shedding light onto live molecular targets," Nat. Med. 9, 123-128 (2003).
[CrossRef] [PubMed]

Zhang, Q.

Annu. Rev. Biomed. Eng.

C. Contag and M. Bachmann, "Advances in in vivo bioluminescence imaging of gene express," Annu. Rev. Biomed. Eng. 4, 235-260 (2002).
[CrossRef] [PubMed]

J. Cell. Biochem. Suppl.

S. Mandl, C. Schimmelpfennig, M. Edinger, R. Negrin, and C. Contag, "Understanding immune cell trafficking patterns via in vivo bioluminescence imaging," J. Cell. Biochem. Suppl. 39, 239-248 (2002).
[CrossRef]

Med. Phys.

G. Wang, Y. Li, and M. Jiang, "Uniqueness theorems in bioluminescence tomography," Med. Phys. 31, 2289-2299 (2004).
[CrossRef] [PubMed]

Nat. Biotechnol.

V. Ntziachristos, J. Ripoll, L. V Wang, and R. Weissleder, "Looking and listening to light: the evolution of whole-body photonic imaging," Nat. Biotechnol. 23, 313-320 (2005).
[CrossRef] [PubMed]

Nat. Med.

R. Weissleder and V. Ntziachristos, "Shedding light onto live molecular targets," Nat. Med. 9, 123-128 (2003).
[CrossRef] [PubMed]

Opt. Express

Proc. Natl. Acad. Sci. USA

S. Bhaumik and S. Gambhir, "Optical imaging of Renilla luciferase reporter gene express in living mice," Proc. Natl. Acad. Sci. USA 99, 377-382 (2002).
[CrossRef]

Science

H. R. Herschman, "Molecular imaging: looking at problems, seeing solutions," Science 302, 605-608 (2003).
[CrossRef] [PubMed]

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Figures (6)

Fig. 1
Fig. 1

Meshes used for the circular (top) and square (bottom) boundary models. Open circles, locations of given light sources for the simulation study.

Fig. 2
Fig. 2

(Color online) The experimental setup used in this study.

Fig. 3
Fig. 3

(Color online) Simulated results for the circular boundary model:(a), (c), (e) reconstructed images; (b), (d), (f) plots of light intensity across the center of the target (thinner lines, exact value; thicker curves, reconstructed results). Refer to Fig. 1 for the target locations indicated there by open circles.

Fig. 4
Fig. 4

(Color online) Simulated results for the square boundary model: (a), (c), (e), (g) reconstructed images; (b), (d), (f) plots of light intensity across the center of the target (thinner lines, exact value; thicker curves, reconstructed results). Refer to Fig. 1 for the target locations indicated there by open circles.

Fig. 5
Fig. 5

Test geometry for the phantom experiments.

Fig. 6
Fig. 6

(Color online) Images reconstructed from experimental data. Refer to Fig. 5 for the target locations indicated there by open circles.

Equations (39)

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

S ( x , y )
S ( x , y ) = 0
D Φ ( x , y ) μ a Φ ( x , y ) = S ( x , y )
D Φ i ^ n = α Φ ,
D   and   μ a
i ^ n
Δ S = ( Δ S 1 , Δ S 2 , , Δ S N ) T
( J T J + λ I ) Δ S = J T [ Φ ( m ) Φ ( c ) ] .
Φ / S
λ = 0.1
Φ i     ( m )   and   Φ i     ( c )
i = 1 , 2 , , M
S ( x , y )
Δ S
1 % )
S new = S old + W Δ S ,
d 2 / 50 + 0.1
W = ( d 1     1.5 + d 2     1.5 ) / 40
d 1   and   d 2
( 5   cm
( 3   cm × 3   cm )
1   cm
0.33   mm   and   0.005 mm 1
S k = 1.0
S k = 0
560   nm
10 6
( 350   μl )
( 350   μl )
30   mm × 30   mm × 30   mm
1 %
+ 1 %
D = 0.33   mm
μ a = 0.0023 mm 1
( 30 ° C )
97 %
77 %
98 %
32 %

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