A Multi-modality Image-guided Precision Radiation Research Platform: Integrating X-ray, Bioluminescence and Fluorescence Tomography with Radiotherapy.

Abstract Purpose Small animal irradiation is crucial to the investigation of radiobiological mechanisms. The paradigm of clinical radiotherapy is trending to high-precision, stereotactic treatment. However, translating this scheme to small animal irradiation is challenging due to the lack of high-quality image guidance. To overcome this obstacle, we developed a multi-modality image-guided precision radiation platform. Methods and Materials The platform consists of four modules: x-ray computed tomography (CT), bioluminescence tomography (BLT), fluorescence molecular tomography (FMT), and radiotherapy. CT provides animal anatomy and material density for radiation dose calculation, as well as body contour for BLT and FMT reconstruction. BLT and FMT provide tumor localization to guide radiation beams and molecular activity to evaluate treatment outcome. Furthermore, we developed a Monte Carlo based treatment planning system (TPS) for three-dimension dose calculation, calibrated it using radiochromic films sandwiched in a water-equivalent phantom, and validated it using in vivo dosimeters surgically implanted into euthanized mice (n=4). Finally, we performed image-guided irradiation on mice bearing orthotopic breast and prostate tumors, and confirmed radiation delivery using γH2AX histology. Results The Monte Carlo based TPS was successfully calibrated by benchmarking simulation dose against film measurement. For in vivo dosimetry measured in the euthanized mice, the average difference between the TPS calculated dose and measured dose was 3.86±1.12%. Following the TPS-generated treatment plan, we successfully delivered 20 Gy dose to an animal bearing an orthotopic prostate tumor using BLT-guided four radiation beams, and 5 Gy dose to an animal bearing an orthotopic breast tumor using FMT-guided single radiation beam. γH2AX histology presented significantly more DNA damage in irradiated tumors and thus validated the dose delivery accuracy under BLT/FMT guidance. Conclusions Combined with Monte Carlo TPS, this multi-modality CT/BLT/FMT image-guided small animal radiation platform can specifically localize tumors, accurately calculate dose distribution, precisely guide radiation delivery, and molecularly evaluate treatment response. It provides an advanced toolset for radiobiology and translational cancer research.