Small animal irradiators for stereotactic radiation therapy

Characterization of the radiobiology to high fractional dose treatments remains highly controversial because of the difficulty of studying it using an animal model strictly adhering to human treatment protocols, which typically include four important elements: 3-D CT simulation, tumor and organs-atrisk delineation, treatment planning, and accurate dose delivery. Conventional small animal irradiation techniques are generally not targeted and inaccurate in dosimetry. These techniques are applicable under the assumption that tumor responses and normal tissue toxicities can be studied separately, and approximate point doses suffice to characterize the treatment. On the other hand, they are inadequate when both the exact dose and volume of irradiation to the tumor and surrounding normal tissue are important to the outcome. For instance, to study the response of an orthotopic tumor to radiation, it was not possible to focally irradiate the tumor to the expected dose without an animal irradiation system compatible with the aforementioned four basic elements in human treatments. To treat the inoculated tumor using conventional techniques, extensively irradiating surrounding normal tissue to a very high dose produces a disproportional amount of injury to normal tissue compared with human treatment, which, in turn, generates a disproportional amount of injury responses that can potentially alter the response of tumor cells (Barcellos-Hoff, Park, and Wright 2005). Moreover, the tissue attenuation to kV x-rays results in substantial dose heterogeneity from the beam entrance to the beam exit of the animal. Subsequently, evaluation of radiation injury can only be performed qualitatively on a traditional small animal irradiator without the knowledge of the dose volume histogram of the normal tissue. Further limitation from conventional small animal irradiation stems from the lack of reproducibility to reposition the animals for treatments. Multiple fractions of treatments are often needed in human SRT, but it is nearly impossible to irradiate a small target reproducibly without x-ray imaging guidance for animal setup (Armour et al. 2010).