Tomographic bioluminescence imaging by use of a combined optical-PET (OPET) system: a computer simulation feasibility study

Abstract

The feasibility and limits in performing tomographic bioluminescence imaging with a combined optical-PET (OPET) system were explored by simulating its image formation process. A micro-MRI based virtual mouse phantom was assigned appropriate tissue optical properties to each of its segmented internal organs at wavelengths spanning the emission spectrum of the firefly luciferase at 37 degrees C. The TOAST finite-element code was employed to simulate the diffuse transport of photons emitted from bioluminescence sources in the mouse. OPET measurements were simulated for single-point, two-point and distributed bioluminescence sources located in different organs such as the liver, the kidneys and the gut. An expectation maximization code was employed to recover the intensity and location of these simulated sources. It was found that spectrally resolved measurements were necessary in order to perform tomographic bioluminescence imaging. The true location of emission sources could be recovered if the mouse background optical properties were known a priori. The assumption of a homogeneous optical property background proved inadequate for describing photon transport in optically heterogeneous tissues and led to inaccurate source localization in the reconstructed images. The simulation results pointed out specific methodological challenges that need to be addressed before a practical implementation of OPET-based bioluminescence tomography is achieved.

Figure 1

A schematic of the proposed OPET system. Its gantry size is only slightly larger than the mouse torso diameter.

Figure 2

(a) Sagittal view of the MOBY mouse. (b) Corresponding sagittal view for the modified mouse torso phantom. Different colours correspond to different tissue types (dark blue: adipose tissue, light blue: liver, turquoise: lungs, yellow: bone, red: whole blood, orange: heart wall, light green: gut, and purple: skin).

Figure 3

Comparison between MC and TOAST boundary flux predictions for a 3 mm deep point source in the mouse gut emitting at 650 nm. Results are shown for a single ring of HiResOPET detectors centred on the axial plane containing the point source.

Figure 4

(a) Transverse view of the mouse torso gut area with a point source located at its centre (star). (b) Noise-free and spectrally blind OPET detector measurements for the point source described in (a), emitting at wavelengths and spectral intensities defined by the luciferase spectrum. (c) As in (b) but with the point source emitting at an intensity that is three times higher than the standard deviation of background noise as measured at the mouse torso surface. The six OPET detector blocks can be discerned.

Figure 5

(a) Reconstructed source distribution based on noiseless boundary flux data generated by the point source in figure 4(a) emitting at 650 nm. (b) As in (a) but for spectrally distinct detection of photons emitted simultaneously at 625 nm and 650 nm. (c) Reconstructed source distribution for spectrally distinct detection of noise-added boundary flux data generated by the point source in figure 4(a) emitting at 625 nm and 650 nm. (d) As in (c) but with the source emitting at 600, 625 and 650 nm. (e) As in (c) but with the source emitting at 600, 625, 650, 675 and 700 nm.

Figure 6

(a) Transverse view of the homogeneous mouse torso with three individually simulated point sources sequentially placed at its centre, at half-radius and at 1 mm from the surface. (b) Reconstructed source distribution based on noiseless boundary flux data generated by the point source at the torso centre emitting at all five wavelengths. (c) As in (a) but for a source located at half-radius; the red cross indicates the correct position of the point source. (d) As in (a) but for a source located at 1 mm from the surface.

Figure 7

Line profiles through the two source peak intensities in reconstructed images of source pairs in different anatomical locations. (a) Equal intensity sources separated by 4 mm in the gut (solid curve) and the liver (short dashed curve). (b) As in (a) but with the two sources located symmetrically around the torso half-radius. The two sources could be resolved in the liver for a relative intensity ratio of 2:1 (grey long dashed curve). (c) As in (a) but with the two sources located at 1 mm and 5 mm from the torso surface. (d) Two equal intensity point sources, 6.3 mm apart, when the true tissue optical properties (solid curve) and a uniform optical property background (short dashed curve) were utilized in the image reconstructions.

Figure 8

(a) Coronal view of the mouse torso phantom with two equal intensity point sources (red stars) located on either side of the torso centre in the gut. The artefactual source (orange oval) was located at the liver centre and near the OPET FOV (red dashed lines) edge. (b) Reconstructed image of the two point sources based on the OPET detector measurements at SNR = 5. (c) As in (b) but for noiseless detector data. (d) Reconstructed image based on the virtual HiResOPET detector measurements at SNR = 5.

Figure 9

(a) Transverse view of the mouse torso for an axial slice through the kidneys (encircled green voxels). (b) Transverse view of the kidneys reconstructed as a uniform distributed source. The red crosses indicate the peak intensity value in each kidney. (c) As in (b) but assuming a uniform optical property background. The red crosses indicate a shift in the reconstructed kidney source locations. (d) Transverse view of the mouse torso for an axial slice through the gut (yellow–green voxels). (e) Transverse view of the gut reconstructed as a uniform distributed source. (f ) As in (e) but assuming a uniform optical property background.