Distinguishing tumor recurrence from radiation necrosis following brain tumor therapy remains a major clinical challenge. Here we demonstrate the ability to distinguish these lesions using the amide proton transfer (APT) MRI signals of endogenous cellular proteins and peptides as an imaging biomarker. When comparing two orthotopic glioma models (SF188/V+ glioma and 9L gliosarcoma) with a radiation necrosis model in rats, viable glioma (hyperintense) and radiation necrosis (hypointense to isointense) could be clearly differentiated using APT MRI. When irradiating rats with U87MG gliomas, the APT signals in the irradiated tumors decreased significantly at 3 days and 6 days post-radiation. The amide protons detected by APT provide a unique and non-invasive MRI biomarker for assessing viable malignancy versus radiation necrosis and predicting tumor response to therapy.

Purpose-To demonstrate the CT imaging, conformal irradiation and treatment planning capabilities of a small animal radiation research platform (SARRP).Methods-The SARRP employs a dual-focal spot, constant voltage x-ray source mounted on a gantry with a source-to-isocenter distance of 35 cm. Gantry rotation is limited to 120° from vertical. Eighty to 100 kVp x-rays from the smaller 0.4 mm focal spot are used for imaging. Both 0.4 mm and 3.0 mm focal spots operate at 225 kVp for irradiation. Robotic translate/rotate stages are used to position the animal. Cone-beam (CB) CT imaging is achieved by rotating the horizontal animal between the stationary x-ray source and a flat-panel detector. Radiation beams range from 0.5 mm in diameter to (60 × 60) mm 2 . Dosimetry is measured with radio-chromic films. Monte Carlo dose calculations are employed for treatment planning. The combination of gantry and robotic stage motions facilitate conformal irradiation.Results-The SARRP spans 3 ft × 4 ft × 6 ft (WxLxH). Depending on filtration, the isocenter dose outputs at 1 cm depth in water range from 22 to 375 cGy/min from the smallest to the largest radiation fields. The 20% to 80% dose fall-off spans 0.16 mm. CBCT with (0.6 × 0.6 × 0.6) mm 3 voxel resolution is acquired with less than 1 cGy. Treatment planning is performed at sub-mm resolution.Conclusions-The capability of the SARRP to deliver highly focal beams to multiple animal model systems provides new research opportunities that more realistically bridge laboratory research and clinical translation.

Advances in conformal radiation therapy and advancements in pre-clinical radiotherapy research have recently stimulated the development of precise micro-irradiators for small animals such as mice and rats. These devices are often kilovolt x-ray radiation sources combined with high-resolution CT imaging equipment for image guidance, as the latter allows precise and accurate beam positioning. This is similar to modern human radiotherapy practice. These devices are considered a major step forward compared to the current standard of animal experimentation in cancer radiobiology research. The availability of this novel equipment enables a wide variety of pre-clinical experiments on the synergy of radiation with other therapies, complex radiation schemes, sub-target boost studies, hypofractionated radiotherapy, contrast-enhanced radiotherapy and studies of relative biological effectiveness, to name just a few examples. In this review we discuss the required irradiation and imaging capabilities of small animal radiation research platforms. We describe the need for improved small animal radiotherapy research and highlight pioneering efforts, some of which led recently to commercially available prototypes. From this, it will be clear that much further development is still needed, on both the irradiation side and imaging side. We discuss at length the need for improved treatment planning tools for small animal platforms, and the current lack of a standard therein. Finally, we mention some recent experimental work using the early animal radiation research platforms, and the potential they offer for advancing radiobiology research.