Evaluation of On- and Off-Line Bioluminescence Tomography System for Focal Irradiation Guidance

Abstract

In response to the limitations of computed tomography (CT) and cone-beam CT (CBCT) in irradiation guidance, especially for soft-tissue targets without the use of contrast agents, our group developed a solution that implemented bioluminescence tomography (BLT) as the image-guidance modality for preclinical radiation research. However, adding such a system to existing small animal irradiators is no small task. A potential solution is to utilize an off-line BLT system in close proximity to the irradiator, with stable and effective animal transport between the two systems. In this study, we investigated the localization accuracy of an off-line BLT system when used for the small animal radiation research platform (SARRP) and compared the results with those of an on-line system. The CBCT was equipped on both the off-line BLT system and the SARRP, with a distance of 5 m between them. To evaluate the setup error during animal transport between the two systems, the mice underwent CBCT imaging on the SARRP and were then transported to the off-line system for a second CBCT imaging session. The normalized intensity difference of the two images and the corresponding histogram and correlation were computed to evaluate if the transport process perturbed animal positioning. Strong correlation (correlation coefficients >0.95) between the SARRP and the off-line mouse CBCT was observed. The offset of the implanted light source center can be maintained within 0.2 mm during transport. To compare the target localization accuracy using the on-line SARRP BLT and the off-line system, a self-illuminated bioluminescent source was implanted in the abdomen of anesthetized mice. In addition to the application for dose calculation, CBCT imaging was also employed to generate the mesh grid of the imaged mouse for BLT reconstruction. Two scenarios were devised and compared, which involved localization of the luminescence source based on either: 1. on-line SARRP bioluminescence image and CBCT; or 2. off-line bioluminescence image and SARRP CBCT. The first scenario is assumed to have the least setup error, because no animal transport was involved. The second scenario examines if an off-line BLT system, with the mesh generated from the SARRP CBCT, can be used to guide SARRP irradiation when there is minimal target contrast in CBCT. Stability during animal transport between the two systems was maintained. The center of mass (CoM) of the light source reconstructed by the off-line BLT had an offset of 1.0 ± 0.4 mm from the true CoM derived from the SARRP CBCT. These results are comparable to the offset of 1.0 ± 0.2 mm using on-line BLT. With CBCT information provided by the SARRP and effective animal immobilization during transport, these findings support the utilization of an off-line BLT-guided system, in close proximity to the SARRP, for accurate soft-tissue target localization. In addition, a dedicated standalone BLT system for our partner site at the University of Pennsylvania was introduced in this study.

Characterization of a commercial bioluminescence tomography‐guided system for pre‐clinical radiation research

“…The design of the mouse bed is innovative as it enables a convenient and fast workflow for users; when the BLI is finished, one can unplug the detachable bed from the bad adaptor and quickly move the bed to another adaptor in the irradiator (Figure 1a). Regarding the potential positioning error caused by animal transportation, as shown in a previous study, 33 the positioning error can be maintained within 0.2 mm as long as the animals are anesthetized with effective immobilization during transportation (Figure S4) and the BLT system is in close proximity (<5 m) to the irradiator. Most importantly, when we mapped the 2D BLIs to the surface of 3D mesh generated from the CBCT image, this positioning error, if present, either rigid or non‐rigid error, will be propagated to the data mapping, and finally to the BLT reconstruction, which can be accounted for in radiation margin design 15 .…”

Quantitative Bioluminescence Tomography-Guided Conformal Irradiation for Preclinical Radiation Research

“…The PTV QBLT was designed to account for the localization uncertainties of the GTV QBLT in target positioning and volume delineation. Regarding the potential positioning error caused by animal transport, from our study, 25 as long as animals are anesthetized with effective immobilization during transport and the off-line optical system is in close proximity (< 5 m) to SARRP, the positioning error can be maintained within 0.2 mm. Most importantly, when we mapped the 2-dimensional bioluminescence images to the surface of 3D mesh generated from SARRP CBCT image, this positioning error, if any, will be propagated to the data mapping and finally to the BLT reconstruction, which had been accounted in PTV QBLT .…”

“…It was operated within 2 m to the SARRP to minimize the effects of transport on the animal position. 25 …”