Preoperative radiosurgery for brain metastases (PREOP-1): A feasibility trial.

Purpose: Preoperative radiosurgery (SRS) of brain metastases (BM) aims to achieve cavity local control with a reduction in leptomeningeal relapse (LMD) and without additional radionecrosis compared to postoperative SRS. We present the final results of a prospective feasibility trial of linac-based stereotactic radiosurgery (SRS) prior to neurosurgical resection of a brain metastasis (PREOP-1). Methods: Eligibility criteria included a BM up to 4 cm in diameter for elective resection. The primary endpoint was the feasibility of delivering linac-based preoperative SRS in all patients prior to anticipated gross tumour resection. Secondary endpoints included rates of LMD, local control and overall survival. Exploratory endpoints were the level of expression of immunological and proliferative markers. Results: Thirteen patients of median age 65 years (range 41-77) were recruited. Twelve patients (92 %) received preoperative radiosurgery and metastasectomy and one patient went directly to surgery and received postoperative SRS, thus the primary endpoint was not met. The median time between referral and preoperative SRS was 6.5 working days (1-10) and from SRS to neurosurgery was 1 day (0-5). The median prescribed dose was 16 Gy (14-19) to a median planning target volume of 12.7 cm3 (5.9-26.1). Five patients completed 12-month follow-up after preoperative SRS without local recurrence or leptomeningeal disease. The patient who received postoperative FSRT developed LMD after six months. There was one transient toxicity (grade 2 alopecia) and nine patients have died from extracranial causes. Patients reported significant improvement in motor weakness at 6 months (P = 0.04). No pattern in changes of marker expression was observed. Conclusion: In patients with large brain metastasis without raised intracranial pressure, linac-based preoperative SRS was feasible in 12/13 patients and safe in 12/12 patients without any surgical delay or intracranial complications.

3D computerized occlusion rating of embolized experimental aneurysms using noninvasive 1.5T MR imaging.

BACKGROUND AND PURPOSE: For embolized cerebral aneurysms, the initial occlusion rate is the most powerful parameter to predict aneurysm rerupture and recanalization. However, the occlusion rate is only estimated subjectively in clinical routine. To minimize subjective bias, computer occlusion-rating (COR) was successfully validated for 2D images. To minimize the remaining inaccuracy of 2D-COR, COR was applied to 1.5T 3D MR imaging. MATERIALS AND METHODS: Twelve experimental rabbit aneurysms were subjected to stent-assisted coil embolization followed by 2D DSA and 3D MR imaging. Subjective occlusion-rate (SOR) was estimated. Linear parameters (aneurysm length, neck width, parent vessel diameter) were measured on 2D DSA and 3D MR imaging. The occlusion rate was measured by contrast medium-based identification of the nonoccluded 2D area/3D volume in relation to the total aneurysm 2D area/3D volume. 2D and 3D parameters were statistically compared. RESULTS: There were no limiting metallic artifacts by using 3D MR imaging. Linear parameters (millimeters) were nearly identical on 2D DSA and 3D MR imaging (aneurysm length: 7.5 ± 2.6 versus 7.4 ± 2.5, P = .2334; neck width: 3.8 ± 1.0 versus 3.7 ± 1.1, P = .6377; parent vessel diameter: 2.7 ± 0.6 versus 2.7 ± 0.5, P = .8438), proving the high accuracy of 3D MR imaging. COR measured on 3D MR imaging was considerably lower (61.8% ± 26.6%) compared with the following: 1) 2D-COR (65.6% ± 27.1%, P = .0537) and 2) 2D-SOR estimations (69.2% ± 27.4%, P = .002). These findings demonstrate unacceptable bias in the current clinical standard SOR estimations. CONCLUSIONS: 3D-COR of embolized aneurysms is easily feasible. Its accuracy is superior to that of the clinical standard 2D-SOR. The difference between 3D-COR and 2D-COR approached statistical significance. 3D-COR may add objectivity to the ability to stratify the risk of rerupture in embolized cerebral aneurysms.

Improved microsurgical creation of venous pouch arterial bifurcation aneurysms in rabbits.

BACKGROUND AND PURPOSE: The choice of the experimental aneurysm model is essential for valid embolization-device evaluations. So far, the use of the rabbit venous pouch arterial bifurcation aneurysm model has been limited by demanding microsurgery, low aneurysm patency rates, and high mortality. This study aimed to facilitate microsurgery and to reduce mortality by optimized peri-/postoperative management. MATERIALS AND METHODS: Aneurysms were created in 16 New Zealand white rabbits under general intravenous anesthesia. Using modified microsurgical techniques, we sutured a jugular vein pouch into a bifurcation created between both CCAs. Aggressive anticoagulation (intraoperative intravenous: 1000-IU heparin, 10-mg acetylsalicylic acid/kg; postoperative subcutaneous: 14 days, 250-IU/kg /day heparin) and prolonged postoperative anesthesia (fentanyl patches: 12.5 µg/h for 72 hours) were applied. Angiographic characteristics of created experimental aneurysms were assessed. RESULTS: The reduced number of interrupted sutures and aggressive anticoagulation caused no intra-/postoperative bleeding, resulting in 0% mortality. Four weeks postoperation, angiography showed patency in 14 of 16 aneurysms (87.5%) and Ohshima type B bifurcation geometry. Mean values of parent-artery diameters (2.3 mm), aneurysm lengths (7.9 mm), and neck widths (4.1 mm) resulted in a mean 1.9 aspect ratio. CONCLUSIONS: Compared with historical controls, the use of modified microsurgical techniques, aggressive anticoagulation, and anesthesia resulted in higher aneurysm patency rates and lower mortality rates in the venous pouch arterial bifurcation aneurysm model. Gross morphologic features of these aneurysms were similar to those of most human intracranial aneurysms.

Complex bilobular, bisaccular, and broad-neck microsurgical aneurysm formation in the rabbit bifurcation model for the study of upcoming endovascular techniques.

BACKGROUND AND PURPOSE: Despite rapid advances in the development of materials and techniques for endovascular intracranial aneurysm treatment, occlusion of large broad-neck aneurysms remains a challenge. Animal models featuring complex aneurysm architecture are needed to test endovascular innovations and train interventionalists. MATERIALS AND METHODS: Eleven adult female New Zealand rabbits were assigned to 3 experimental groups. Complex bilobular, bisaccular, and broad-neck venous pouch aneurysms were surgically formed at an artificially created bifurcation of both CCAs. Three and 5 weeks postoperatively, the rabbits underwent 2D-DSA and CE-3D-MRA, respectively. RESULTS: Mortality was 0%. We observed no neurologic, respiratory, or gastrointestinal complications. The aneurysm patency rate was 91% (1 aneurysm thrombosis). There was 1 postoperative aneurysm hemorrhage (9% morbidity). The mean aneurysm volumes were 176.9 ± 63.6 mm(3), 298.6 ± 75.2 mm(3), and 183.4 ± 72.4 mm(3) in bilobular, bisaccular, and broad-neck aneurysms, respectively. The mean operation time was 245 minutes (range, 175-290 minutes). An average of 27 ± 4 interrupted sutures (range, 21-32) were needed to create the aneurysms. CONCLUSIONS: This study demonstrates the feasibility of creating complex venous pouch bifurcation aneurysms in the rabbit with low morbidity, mortality, and high short-term aneurysm patency. The necks, domes, and volumes of the bilobular, bisaccular, and broad-neck aneurysms created are larger than those previously described. These new complex aneurysm formations are a promising tool for in vivo animal testing of new endovascular devices.