Late radiation effects after stereotactic small-volume radiosurgery of therat brain: Measurement of the local cerebral blood flow and histopathologic investigations

Background: The goal of this study was to investigate late effects followin g stereotactic single fraction and small volume irradiation on cerebral blo od flow and histologic alterations in the rat brain parenchyma. Material and Methods: 66 Copenhagen rats, separated into eleven groups of s ix animals each received single doses of 20, 30, 40, 50 and 100 Gy using a 15 MV linear accelerator. Six rats served as controls. Two cylindrical coll imators of 2 mm and 3 mm aperture were used. The diameters of the spherical 80% isodose were 3.7 and 4.7 mm, respectively (Table 1). Irradiation was a pplied to a predefined area in the right frontal lobe. 19 months after irra diation local cerebral blood flow (LCBF) was measured by the autoradiograph ic method in one animal of each dose group between 20 and 50 Gy. 9 and 19 m onths after irradiation, half of the animals of each group were sacrificed for brain histology. All animals irradiated with 100 Gy were sacrificed 7 m onths after irradiation. Results: An increase of Local cerebral blood flow was measured in brain str uctures within the 80% isodose in animals irradiated with 50 Gy (Figure 3) compared to the contralateral hemisphere. Measurements close to necrotic ar eas showed a strong decrease of Local cerebral blood flow (Figure 1). A vol ume increase of the irradiated hemisphere was seen after 19 months (Figure 2). The histologic examination after 19 months showed necrotic areas in the 30-50 Gy groups (Figure 4b) but not in the 20 Gy groups (Figure 4c). The a nimals who received 100 Gy demonstrated brain necrosis within 9 months afte r irradiation (Figure 4a). At both points in time the groups irradiated wit h the 3-mm collimator showed more pronounced histomorphologic and functiona l changes compared to the groups irradiated with the 2-mm collimator. Conclusion: Alterations of the local cerebral blood flow were measured as a Late effect after single dose irradiation. The alterations of the local ce rebral blood flow could be explained by the histomorphologic changes of the blood vessels. Using a semiquantitative classification a dose, time and vo lume dependence for the endpoint radionecrosis was seen.