title: Angiographic, hemodynamic, and histological changes in an animal model of brain arteriovenous malformations treated with Gamma Knife radiosurgery.
abstract: OBJECTIVE
  Brain arteriovenous malformations (AVMs) are a major cause of stroke. Many AVMs are effectively obliterated by stereotactic radiosurgery, but such treatment for lesions larger than 3 cm is not as effective. Understanding the responses to radiosurgery may lead to new biological enhancements to this treatment modality. The aim of the present study was to investigate the hemodynamic, morphological, and histological effects of Gamma Knife surgery (GKS) in an animal model of brain AVM.
  
  
  METHODS
  An arteriovenous fistula was created by anastomosing the left external jugular vein to the side of the common carotid artery in 64 male Sprague-Dawley rats (weight 345 ± 8.8 g). Six weeks after AVM creation, 32 rats were treated with a single dose of GKS (20 Gy); 32 animals received sham radiation. Eight irradiated and 8 control animals were studied at each specified time point (1, 3, 6, and 12 weeks) for hemodynamic, morphological, and histological characterization.
  
  
  RESULTS
  Two AVMs showed partial angiographic obliteration at 6 weeks. Angiography revealed complete obliteration in 3 irradiated rats at 12 weeks. Blood flow in the ipsilateral proximal carotid artery (p < 0.001) and arterialized jugular vein (p < 0.05) was significantly lower in the irradiated group than in the control group. The arterialized vein's external diameter was significantly smaller in GKS-treated animals at 6 (p < 0.05) and 12 (p < 0.001) weeks. Histological changes included subendothelial cellular proliferation and luminal narrowing in GKS-treated animals. Neither luminal obliteration nor thrombus formation was identified at any of the time points in either irradiated or nonirradiated animals.
  
  
  CONCLUSIONS
  GKS produced morphological, angiographic, and histological changes in the model of AVM as early as 6 weeks after treatment. These results support the use of this model for studying methods to enhance radiation response in AVMs.
authors.affiliation: Australian School of Advanced Medicine, Macquarie University; and.
authors.forename: Saleh R
authors.initials: SR
authors.lastname: Kashba
authors.affiliation: Australian School of Advanced Medicine, Macquarie University; and.
authors.forename: Nirav J
authors.initials: NJ
authors.lastname: Patel
authors.affiliation: Genesis Cancer Care, Macquarie University Hospital, Sydney, New South Wales, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Grace
authors.affiliation: Australian School of Advanced Medicine, Macquarie University; and.
authors.forename: Vivienne S
authors.initials: VS
authors.lastname: Lee
authors.affiliation: Australian School of Advanced Medicine, Macquarie University; and.
authors.forename: Newsha
authors.initials: N
authors.lastname: Raoufi-Rad
authors.affiliation: Australian School of Advanced Medicine, Macquarie University; and.
authors.forename: Jude V Amal
authors.initials: JV
authors.lastname: Raj
authors.affiliation: Australian School of Advanced Medicine, Macquarie University; and.
authors.forename: Thi Thuy Hong
authors.initials: TT
authors.lastname: Duong
authors.affiliation: Australian School of Advanced Medicine, Macquarie University; and.
authors.forename: Marcus
authors.initials: M
authors.lastname: Stoodley
mesh_terms: D000792:Angiography; D000818:Animals; D004195:Disease Models, Animal; D006439:Hemodynamics; D002538:Intracranial Arteriovenous Malformations / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D008297:Male; D016634:Radiosurgery; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: AVM = arteriovenous malformation; GKS = Gamma Knife surgery; Gamma Knife; LCCA = left common carotid artery; LEJV = left external jugular vein; LINAC = linear accelerator; animal model; arteriovenous malformation; stereotactic radiosurgery