title: Dose-response relationship for late functional changes in the rat brain after radiosurgery evaluated by magnetic resonance imaging.
abstract: OBJECTIVE
  Only few quantitative data are available on late effects in the healthy brain after radiosurgery. An animal model can contribute to systematically investigate such late effects. Therefore, a model applying radiosurgery at the rat brain was established. A long-term (19 months) follow up study with 66 animals after radiosurgery was carried out.
  
  
  METHODS
  In 60 animals, an area in the frontal lobe of the brain was irradiated stereotactically with a 15 MV linac. Different doses of 20, 30, 40, 50, and 100 Gy with two field sizes (3.9 and 5.9 mm collimator) were selected, using the integrated logistic formula with input parameters from human brain. The induced alteration of the blood-brain barrier permeability was investigated by means of contrast enhanced magnetic resonance imaging.
  
  
  RESULTS
  A first intracranial signal enhancement was observed in one animal 160 days after irradiation with 100 Gy. Beginning at 5 months all animals in the two 100 Gy groups homogeneously showed contrast enhancement, but none of the other groups. This remained until 13 months after irradiation. The volume of contrast enhancement as well as the increase of signal intensity were different between the two 100 Gy groups. After 19 months, the animals irradiated with lower doses also showed contrast enhancements, although not uniformly throughout one group. A maximum likelihood fit of the logistic formula P(D) = 1/[1 + (D50/D)k] to the incidence of late effects for the 5.9 mm collimator at 19 months after irradiation results in the parameters D50 = 37.4(-5.2,+6.1) Gy and k = 4.7 +/- 2.4.
  
  
  CONCLUSIONS
  An animal model was established to study late normal brain tissue response. The observed late effects appeared very similar to the estimation of the integrated logistic formula for human brain. Based on these radiosurgery techniques, future experiments will focus on modifications in the irradiation modalities, i.e., irregular volumes, radiation quality or fractionation.
authors.affiliation: German Cancer Research Center, Department of Biophysics and Medical Radiation Physics, Heidelberg.
authors.forename: C P
authors.initials: CP
authors.lastname: Karger
authors.forename: G H
authors.initials: GH
authors.lastname: Hartmann
authors.forename: P
authors.initials: P
authors.lastname: Peschke
authors.forename: J
authors.initials: J
authors.lastname: Debus
authors.forename: U
authors.initials: U
authors.lastname: Hoffmann
authors.forename: G
authors.initials: G
authors.lastname: Brix
authors.forename: E W
authors.initials: EW
authors.lastname: Hahn
authors.forename: W J
authors.initials: WJ
authors.lastname: Lorenz
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000528:radiation effects*; D001812:Blood-Brain Barrier / Q000528:radiation effects; D001921:Brain / Q000528:radiation effects* / Q000601:surgery*; D004307:Dose-Response Relationship, Radiation; D008279:Magnetic Resonance Imaging; D008297:Male; D016634:Radiosurgery / Q000009:adverse effects*; D051381:Rats