Radiosurgery performed with the aid of a 3-mm collimator in the subthalamic nucleus and substantia nigra of the vervet monkey

Object. Radiosurgery for functional neurosurgery performed using a linear a ccelerator (LINAC), has not been, extensively characterized in preclinical studies. In the. present study, the properties of a newly designed 3-mm-dia meter collimator were evaluated in a dedicated LINAC, which produced lesion s in the basal ganglia of vervet monkeys. Lesion formation was determined i n vivo in three animals by examining magnetic resonance (MR) images to show the dose-delivery precision of targeting and the geometry and extent of th e lesions. Postmortem immunohistochemical studies were conducted to determi ne the extent of lesion-induced radiobiological effects. Methods. In three male vervet monkeys, the subthalamic nucleus (STN; one an imal) and the pars compacta of-the lateral substantia nigra (SN; two animal s) were targeted by a Novalis Shaped Beam Surgery System that included a 3- mm collimator and delivered a maximum dose of 150 Gy. Magnetic resonance im ages obtained 4, 5, and 9 months posttreatment were reviewed. and the anima ls were killed so that immunohistological characterizations could be made. Conclusions. The generation of precise radiosurgical lesions by a 3-mm coll imator was validated in studies that targeted the basal ganglia of the verv et monkey. The extent of the lesions created in all animals remained restri cted in diameter (< 3 mm) throughout the duration of the studies, as assess ed by reviewing MR images. Histological studies showed that the lesions wer e contained within the STN and SN target areas and that there were persiste nt increases in glial fibrillary acidic protein immunoreactivity. Increases in immunoreactivity for tyrosine hydroxylase, the serotonin transporter, a nd the GluR1 subunit of the alpha -amino-3-hydroxy-5-methyl-4-isoxazole pro pionate glutamate receptor mi penumbral regions of the lesion were suggesti ve of compensatory neuronal adaptations. This radiosurgical approach may be of particular interest for the induction of lesions of the STN and SN in s tudies of experimental parkinsonism, as well as for the development of pote ntial radiosurgical treatments for Parkinson disease.