Leksell gamma knife perfexion

Female Balb/c mice were anesthetized using 1.5 L/min oxygen containing isoflurane (3% for induction, 2% for maintenance) and positioned on a custom-designed stereotactic bed [62 (link)] compatible with the Leksell Gamma Knife Perfexion (Elekta AB, Stockholm, Sweden). A maximum dose of 45 Gy (23.1 Gy at the 50% isodose) was delivered through 4 mm collimators in the right hemisphere of the brain. Mouse and human brains have different sensitivities to radiation. This dose was selected because it allows the development and slow progression of radiation necrosis (approximatively appearing at 17 months post-irradiation in T2-weighted MRI; Figure 4), similar to what may be observed in brain cancer patients who received radiotherapy [63 (link)]. After irradiation, mice were placed on a heating pad to recover, and were then returned to their cages.

The Leksell G stereotactic frame (Elekta instruments AB, Stockholm, Sweden) was fixed under local anesthesia and mild sedation, with specific attention given to avoiding the area of the previous posterior fossa craniotomy. All patients underwent stereotactic MRI (1.5 Tesla, Siemens, Erlangen, Germany) and computed tomography (CT) with bone windows. The MR sequences used are T1-weighted with and without gadolinium contrast medium and T2 CISS, without contrast medium (in small remnants) and/or with contrast medium (in larger remnants); T2 CISS with contrast medium helps to differentiate between the nerves and the tumor [24 (link)]. Target definition and treatment dosimetry were performed using Leksell GammaPlan® planning software version 10 or 11. The modiolus of the cochlea was defined on bone CT images and the dose received was further calculated (as the dose received by the first 1% of the volume, and as the maximum dose). If this dose was more than 4 Gy in patients with useful hearing, additional sector blocking was used to ensure that optimal dosimetry results are obtained, as we routinely perform in patients undergoing upfront GKRS for smaller tumors [41 (link), 60 (link)]. The stereotactic irradiation was delivered using the Leksell Gamma Knife® Perfexion™ (Elekta Instruments AB, Stockholm, Sweden). The procedure was performed on an ambulatory basis.

All experiments involving animals were approved by the Macquarie University Animal Care and Ethics Committee (Sydney, Australia) under approval numbers 2014/013 (1 April 2014) and 2014/053 (1 January 2015). Animal experiments were performed in accordance with committee guidelines and the Australian Code of Practice for the Care and Use of Animals for Scientific Purposes. The rat AVM model is formed in Sprague–Dawley rats by surgically anastomosing the rostral end of the left jugular vein to the center of the left common carotid artery, as has been described in detail previously [5 (link),15 (link),16 (link)]. The arteriovenous fistula and the arterialized veins (of the model AVM) are irradiated six weeks after creation in anesthetized animals using a single-fraction stereotactic radiosurgical dose, which delivers a minimum of 20 Gy to the margin of the defined AVM, to a peak value of 40 Gy at the center. This was administered using a Leksell Gamma Knife Perfexion (Elekta Instruments, Stockholm, Sweden) at Macquarie University Hospital (Sydney, Australia), as described previously [5 (link),15 (link)]. Sham-irradiated animals were treated identically but did not receive any radiation.