Hypofractionated stereotactic radiotherapy to the rat hippocampus. Determination of dose response and tolerance.
OBJECTIVE
To determine the effect of hypofractionated stereotactic radiotherapy (hfSRT) on adult rat brain tissue (necrosis, impact on blood-brain barrier, signal changes on high-field magnetic resonance imaging [MRI]).


METHODS
Adult male Wistar rats underwent MRI and CT scanning of the brain and respective images were introduced into the Novalis radiosurgery device (BrainLab, Feldkirchen, Germany). All animals (body weight 350 g) were irradiated weekly with doses of 2 x 10 Gy (n = 3 animals), 3 x 10 Gy (n = 3 animals) and 4 x 10 Gy (n = 3 animals), targeted to the left hippocampus after image-guided positioning. 4.7-T T2-weighted MRI scanning was performed in each animal. Animals were sacrificed 8, 12, and 16 weeks after hfSRT and brains were immersion-fixed in 4% paraformaldehyde for subsequent histopathologic analysis.


RESULTS
In concordance with isodose distributions, pathologic signal hyperintensities in MRI were recorded from 4 x 10 Gy after 8 weeks, 3 x 10 Gy after 12 weeks, while 2 x 10 Gy induced slight detectable alterations only after 16 weeks. Subsequent histopathologic analysis revealed hippocampal cell necrosis with significantly earlier and stronger occurrence for higher doses (40 Gy > 30 Gy > 20 Gy). Pial microvessel permeability also increased after 40 Gy, whereas 30 Gy induced moderate changes.


CONCLUSIONS
Partial-brain irradiation with hfSRT (Novalis System) was successfully adopted for small animals and histopathologic analysis confirmed its repositioning accuracy. The neuropathologic effects correlated with dose and observation time. The approach will be further developed for quality assurance in hfSRT of normal brain tissue, as well as novel treatment modalities in epileptic rats and orthotopic tumor models.
Department of Radiation Therapy and Novalis Shaped Beam Surgery Center, Friedrich Alexander University of Erlangen-Nuremberg, Erlangen, Germany. antje.fahrig@strahlen.imed.uni-erlangen.de
Antje
A
Ernst-Stecken
Ina
I
Jeske
Andreas
A
Hess
Franz
F
Rödel
Oliver
O
Ganslandt
Gerhard
G
Grabenbauer
Rolf
R
Sauer
Kai
K
Brune
Ingmar
I
Blümcke
D000818:Animals; D001930:Brain Injuries / Q000209:etiology / Q000473:pathology*; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D006624:Hippocampus / Q000473:pathology* / Q000528:radiation effects*; D011832:Radiation Injuries / Q000209:etiology / Q000473:pathology*; D011836:Radiation Tolerance; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods*; D051381:Rats; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors