MicroCT presents an intriguing platform for the engineering of small animal radiotherapy devices because of the advanced state of development of this technology. We have added hardware and software to an existing scanner in order to produce a hybrid imaging and radiotherapy system. The two-dimensional translation stage and variable aperture collimator needed to introduce radiotherapy capability to this system can be manufactured at a cost of less than $25,000, facilitating commercial development of this system as a low-cost add-on option to existing microCT scanners. The collimator can be permanently installed on the microCT gantry without compromising imaging ability, and can be removed and reinstalled using positioning markers in order to quickly achieve alignment with the x-ray axis. Further development of these mechanical components is ongoing, improving their positioning accuracy and mechanical performance while reducing their travel times so as to move towards potential dynamic adjustment of this hardware during radiation treatments. The conformal radiotherapy capabilities of this hybrid device were demonstrated in phantoms as well as in vivo
in a spontaneous murine tumor model. Treatment of rats with this unit is theoretically possible given the beam depth dose profile reported previously (9
), however given the limited travel distances of the motion stages these larger animals would have to be positioned on the bed such that the desired target was close to the microCT isocenter.
Based on the Monte Carlo dosimetry simulation generated for the lung tumor irradiation, it is apparent that the kilovoltage beams of this system deliver significant doses to bony structures. At present it is unknown whether this dose will limit the application of this system. The mass attenuation coefficient of human bone is an order of magnitude greater at the kilovoltage energies of this system relative to the megavoltage energies of clinical radiotherapy systems, however the elemental composition and density of mouse bone have not been rigorously studied. Recent Monte Carlo material modeling efforts have suggested that more rigorous treatment of bony tissues in Monte Carlo simulations is required, and suggests that the dose to mouse bones may be overestimated when using material properties derived from human bones (14
). Ultimately the problem of bone dose in radiotherapy is not unique to this system, as Monte Carlo simulations have demonstrated elevated dose to bone using x-ray energies from 120 to 300 kVp (data not shown). Evaluation of the biological effects of bone dose in small animal models will be required to assess the significance of these observations.
The increase in temperature in the x-ray generator and its thermal limits provide constraints on the length of radiotherapy treatments and correspondingly the doses that can be delivered. We have measured the temperature rise in the generator during several x-ray delivery sequences, and have found that a six minute x-ray firing (corresponding to a mouse dose of approximately 1 Gy) followed by a four minute cooling period results in a stable peak generator temperature of 60°C over repeated firings. The addition of cooling equipment to the generator could compensate for temperature increases in order to reduce the duration of cooling periods. It is also important to mention that conformal treatment plans using large (more than 10) numbers of beams, in which the dose per beam is less than 1 Gy, will cause smaller temperature increases for each beam and thus require shorter cooling periods.
Heating of the x-ray tube is a second important consideration. Replacement of the x-ray tube with a more robust model, or alternately use of a larger focal spot at the cost of increased beam penumbra, may be required for radiotherapy protocols desiring radiosurgical doses (more than 20 Gy per fraction). Rodriguez et al.
observed a 0.5 mm penumbra when using the current 0.3 mm focal spot of the x-ray tube (9
). The tube has a second focal spot option of 0.9 mm, which would be expected to increase the observed penumbra to 2-3 mm. These two states could be selected on a per-application basis. Scenarios requiring high precision, such as treatment of small (< 2 mm) tumors in sensitive sites such as brain or lung could use the small focal spot at the cost of longer treatment times, while irradiation of larger targets (large tumors, normal tissues) could reduce treatment times through use of the large focal spot, at the cost of spatial accuracy.
This work has shown that it is technically possible to modify a microCT scanner to serve as a small animal conformal radiotherapy system, operating in a fashion analogous to current clinical image-guided radiotherapy devices. Although the spontaneous lung tumor model studied here was treated with only 8 beams, in principle this device can deliver large numbers of beams from multiple angles approaching current arc treatment strategies. We anticipate that the applications of radiation in molecular biology studies of animal tumors using technology such as that demonstrated here will significantly enhance our knowledge of radiobiology and provide a means to study clinically-relevant radiation treatment strategies in a preclinical setting.