Tracking White Matter Changes After Stereotaxic Radiosurgery inMiniature Pigs Using structural MRI, DTI, and FDG-PET

Abstract

Stereotaxic radiosurgery (SRS) non-invasively and precisely ablates brain tumors or glioma located in the location where is surgically inaccessible with the aid of three- dimensional coordination system. This technique can also treat functional or psychiatric disorders, yet its dosimetry and curative mechanism remain to be elucidated. In this study, a miniature pig model was utilized to verify the effect of stereotaxic radiosurgery on a white matter tract with various doses delivered by CyberKnife. As porcine brain bears high resemblance to that of human in size and structure, the potential irradiation- induced change in structures and metabolism was monitored by conventional tools in clinical, including anatomical magnetic resonance image (MRI), diffusion tensor image (DTI) and 18F-Fluoro-D-Glucose positron emission tomography (FDG-PET). The right internal capsule was selected as the surgical target, and a one-year longitudinal study was conducted with whole brain images obtained once per three months. The results indicate that a dose equal to or higher than 60 Gy led to a late-onset radionecrosis which took a period close to 180 d to develop edema and breakage in the blood-brain barrier. In the meanwhile, DTI indices and differential tractography further illustrate a dose- and distance-dependent white matter injury along the tract of internal capsule. In contrast, doses of 40 Gy and below did not result in any discernible harm to the brain structure, but a sustained local inhibition in brain metabolism was observed in some pigs. The modulatory effect of low dose radiation awaits a comprehensive assessment throughout the whole brain in combination with behavioral or cognitive tasks built on pigs. This study showing the dose- and time-dependent changes will improve the understanding of the SRS dosimetry on the white matter and help investigators to decide an optimal window for brain imaging or behavioral assessment to take place on patients.