Kim Vang Hansen

Introduction: Stereotactic radiosurgery (SRS) has proven an effective tool for treatment of tumors, arterio-venous malformation, acoustic neuroma, and functional conditions, in which cell death is the desired treatment outcome. However, radiation-induced therapeutic effect in the remaining living cells in functional SRS is also suggested. Modulation of the neuronal activity without causing death requires knowledge of radiation dose tolerance at very small tissue volume. The aim of the presented study was to document the thresholds for late-onset cell death when high doses of radiation are delivered to small brain volumes.
Methods: Six female Gottingen minipigs were used. At baseline, the MRI was acquired. Five animals received focal stereotactic radiosurgery in the left primary motor cortex and to the right cortical white matter, and one animal remained as unirradiated control. Follow-up MRI and PET scans were done at three weeks, three and six months after the irradiation, followed by analysis of the histological changes at 6 months post-radiation after euthanization and fixation.
Results: We observed a dose dependent gradient of cellular reaction to the radiation and spreading inflammatory changes along the neural tracts in white matter. Necrotic changes in both MRI and histology were seen at 6 months post-radiation. The threshold of radio-destructive lesions was 100 Gy in cortical gray matter, and 60 Gy in white matter.
Conclusion: The threshold for radiation doses causing necrotic changes were defined in this study. Radiosurgery have both direct dose-dependent effect, and possibly indirect neuromodulatory effects; mediated by endogenous immunoreactive agents. Neuromodulative responses to radiation may be mediated by both vascular changes, as well as neuronal cell changes and glial cell remodeling.