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Practical reconstruction method for bioluminescence tomography

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Abstract

Bioluminescence tomography (BLT) is used to localize and quantify bioluminescent sources in a small living animal. By advancing bioluminescent imaging to a tomographic framework, it helps to diagnose diseases, monitor therapies and facilitate drug development. In this paper, we establish a direct linear relationship between measured surface photon density and an unknown bioluminescence source distribution by using a finite-element method based on the diffusion approximation to the photon propagation in biological tissue. We develop a novel reconstruction algorithm to recover the source distribution. This algorithm incorporates a priori knowledge to define the permissible source region in order to enhance numerical stability and efficiency. Simulations with a numerical mouse chest phantom demonstrate the feasibility of the proposed BLT algorithm and reveal its performance in terms of source location, density, and robustness against noise. Lastly, BLT experiments are performed to identify the location and power of two light sources in a physical mouse chest phantom.

©2005 Optical Society of America

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Figures (14)

Fig. 1.
Fig. 1. Numerical simulation for BLT reconstruction of one source. (a) The true source distribution in the left lung consisting of 6 volume elements and having a homogeneous density of 200.0pico-Watts/mm3, and (b) the counterpart reconstructed from the surface data corrupted by 10% Gaussian noise. The average density error is 0.5%.
Fig. 2.
Fig. 2. Numerical simulation for BLT reconstruction of two sources in the left and right lungs, respectively. (a) The true source distribution with a density of 200.0pico-Watts/mm3 for each source, and (b) the counterparts reconstructed from the surface data corrupted by 10% Gaussian noise. The average density error is 3%.
Fig. 3.
Fig. 3. Numerical simulation for BLT reconstruction of two sources in the left lung. (a) The true source distribution with density 200.0pico-Watts/mm3 for both the sources, and (b) the counterparts reconstructed from the surface data corrupted by 10% Gaussian noise. The average density error is 5%.
Fig. 4.
Fig. 4. Numerical simulation for BLT reconstruction of three sources: two in the left lung and one in the right lung. (a) The true source distribution in which each source consists of several volume elements and has density 200.0pico-Watts/mm3, and (b) the counterparts reconstructed from the surface data corrupted by 10% Gaussian noise. The average density error is 3%.
Fig. 5.
Fig. 5. Numerical simulation for BLT reconstruction of four sources. (a) Four bioluminescent source separations of 1mm between first and second, 2mm between second and third, and 3mm between third and fourth source with the density of 200.0 pico-Watts/mm3 for each source, and (b) the counterparts reconstructed from the surface data corrupted by 10% Gaussian noise. The source positions are accurately identified with their density being recovered to 196.1 pico-Watts/mm3, 184.7 pico-Watts/mm3, 175.1 pico-Watts/mm3 and 181.5 pico-Watts/mm3, respectively.
Fig. 6.
Fig. 6. (a), (b) and (c) are the reconstructed source distributions (with unit pico-Watts/mm3) from the surface noise-free data subject to permissible source regions Ω s 1 , Ω s 2 and Ω s 3 , respectively. They are identical to the actual source in position and strength.
Fig. 7.
Fig. 7. (a), (b) and (c) are the reconstructed source distribution (with unit pico-Watts/mm3) from the surface data corrupted by 5% Gaussian noise subject to permissible source regions Ω s 1 , Ω s 2 and Ω s 3 , respectively.
Fig. 8.
Fig. 8. (a), (b) and (c) are the reconstructed source distributions (with unit pico-Watts/mm3) from the surface data corrupted by 10% Gaussian noise subject to permissible source regions Ω s 1 , Ω s 2 and Ω s 3 , respectively.
Fig. 9.
Fig. 9. (a), (b) and (c) are the reconstructed source distribution (with unit pico-Watts/mm3), subject to permissible source regions Ω s 1 , Ω s 2 and Ω s 3 , respectively. The measured surface data are corrupted by 15% Gaussian noise.
Fig. 10.
Fig. 10. Mouse Chest phantom. (a) A heterogeneous mouse phantom consisting of bone (B), heart (H), lungs (L), and muscle (M); (b) a middle cross-section through two hollow cylinders for hosting luminescent sources in the left lung. The four arrows show the direction of the CCD camera during data acquisition.
Fig. 11.
Fig. 11. Comparison of experimental and computational photon density profiles for determination of the optical parameters of the phantom materials: (a) Muscle (M), (b) Lung (L), (c) Heart (H), and (d) Bone (B).
Fig. 12.
Fig. 12. Luminescent views of the side surface covering cylindrical phantom taken using a CCD camera in four directions 90 degrees apart. (a) Front view, (b) Right view, (c) Back view, and (d) Left view.
Fig. 13.
Fig. 13. (a) Finite element model for a middle portion of the mouse chest phantom. (b) Physical experiment on BLT reconstruction of two sources in the left lung of the mouse chest phantom. The difference between the reconstructed and real source centers was less than 1mm for both the sources at height 15.0mm. The maximum error of source power was about 18.5%.
Fig. 14.
Fig. 14. Comparison between measured and computational photon density profiles along the detection circle on the phantom surface at heights (a) 10.6mm, (b) 15.9mm, and (c) 21.1mm, from the top surface of the model.

Tables (3)

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Table 1. Optical parameters for the numerical phantom

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Table 2. Relative error (%) with BLT results of total source power

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Table 3. Optical parameters of the mouse chest phantom.

Equations (19)

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{ · ( D ( x ) ∇Φ ( x ) ) + μ a ( x ) Φ ( x ) = S ( x ) ( x Ω ) D ( x ) = ( 3 ( μ a ( x ) + ( 1 g ) μ s ( x ) ) ) 1
Φ ( x ) + 2 A ( x ; n , n′ ) D ( x ) ( v ( x ) · ∇Φ ( x ) ) = 0 ( x Ω )
A ( x ; n , n′ ) ( 1 + R ( x ) ) ( 1 R ( x ) )
Q ( x ) = D ( x ) ( v · ∇Φ ( x ) ) = Φ ( x ) ( 2 A ( x ; n , n′ ) ) ( x Ω ) .
Ω ( D ( x ) ( Φ ( x ) ) · ( Ψ ( x ) ) + μ a ( x ) Φ ( x ) Ψ ( x ) ) d x
+ Ω Φ ( x ) Ψ ( x ) ( 2 A ( x ; n , n ) ) d x = Ω S ( x ) Ψ ( x ) d x
Φ ( x ) Φ h ( x ) = k = 1 T ϕ k φ k ( x ) when x Ω ,
S ( x ) S h ( x ) = k = 1 N s S k γ k ( x ) when x Ω
( [ K ] + [ C ] + [ B ] ) { Φ } = [ M ] { Φ } = [ F ] { S } ,
{ k ij = Ω ( D ( x ) ( φ i ( x ) ) · ( φ i ( x ) ) d x c ij = Ω μ a ( x ) φ i ( x ) φ j ( x ) d x f ij = Ω φ i ( x ) γ j ( x ) d x b ij = Ω φ i ( x ) φ j ( x ) ( 2 A ( x : n , n ) ) d x
[ M 11 M 12 M 12 T M 22 ] { Φ m Φ * } = [ F 11 F 12 F 21 F 22 ] { S p S * } ,
( M 11 M 12 M 22 1 M 12 T ) Φ m = ( F 11 M 12 M 22 1 F 21 ) S p .
Φ m = ( M 11 M 12 M 22 1 M 12 T ) 1 ( F 11 M 12 M 22 1 F 21 ) S p ,
p k = ( 1 2 π Φ k meas ) 1 2 exp [ ( Φ k m Φ k meas ) 2 2 Φ k meas ]
p ( S p ) = ( det ( W ) π M ) 1 2 exp [ k = 1 M ( Φ k m Φ k meas ) 2 2 Φ k meas ] ,
Θ ( S p ) = ( Φ m Φ meas ) T W ( Φ m Φ meas ) .
min U i s i 0 Θ ( S p ) .
Ω s 1 = ( x , y , z ) x < 0 , 5.6 < z < 7.0 , ( x , y , z ) L ,
Ω s 2 = ( x , y , z ) x < 0 , 5.6 < z < 8.0 , ( x , y , z ) L
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