Purpose In pre-clinical radiation research, it is challenging to localize soft tissue targets based on cone beam computed tomography (CBCT)-guidance. As a more effective method to localize soft tissue targets, we developed an online bioluminescence tomography (BLT) system for the small animal radiation research platform (SARRP). We demonstrated BLT-guided radiotherapy and validated targeting accuracy, based on a newly developed reconstruction algorithm. Methods and Materials The BLT system was designed to dock onto the SARRP for image acquisition and to be detached before radiation delivery. A 3-mirror system was devised to reflect the bioluminescence emitted from the subject to a stationary CCD camera. Multispectral BLT and the incomplete variables truncated conjugate gradient method with a permissible region shrinking strategy were employed as the optimization scheme to reconstruct bioluminescent source distributions. To validate BLT targeting accuracy, a small cylindrical light source with high CBCT contrast was placed in a phantom and also in the abdomen of a mouse carcass. The center of mass (CoM) of the source was recovered from BLT and used to guide radiation delivery. The accuracy of the BLT-guided targeting was validated with films and compared with the CBCT-guided delivery. In vivo experiments were conducted to demonstrate the BLT localization capability for various source geometries. Results Online BLT was able to recover the CoM of the imbedded light source with an average accuracy of 1 mm compared to CBCT localization. The difference between the BLT- and CBCT-guided irradiation shown on the films was consistent with the source localization revealed in the BLT and CBCT images. The in vivo results demonstrated that our BLT system could potentially be applied for multiple targets and tumors. Conclusions The online BLT/CBCT/SARRP system provides an effective solution for soft tissue targeting, particularly for small, non-palpable, or orthotopic tumor models.

Non-invasive in vivo imaging of diffuse and wide-spread colonization within the lungs, rather than distinct solid primary tumors, is still a challenging work. In this work, a lung colonization mouse model bearing A549 human lung tumor was simultaneously scanned by a dual-modality fluorescence molecular tomography (FMT) and X-ray computed tomography (CT) system in vivo. A two steps method which incorporates CT structural information into the FMT reconstruction procedure is employed to provide concurrent anatomical and functional information. By using the target-specific fluorescence agent, the fluorescence tomographic results show elevated fluorescence intensity deep within the lungs which is colonized with diffuse and wide-spread tumors. The results were confirmed with ex vivo fluorescence reflectance imaging and histological examination of the lung tissues. With FMT reconstruction combined with the CT information, the dual-modality FMT/micro-CT system is expected to offer sensitive and noninvasive imaging of diffuse tumor colonization within the lungs in vivo.

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