Carotid artery vein-pouch bifurcation aneurysm in rats: An experimental model for microneurosurgical training.

BACKGROUND: In the era of endovascular treatment of intracranial aneurysms, surgical clipping is still a relevant treatment method in some cases. However, it has become harder to teach this skill, as the number of surgical cases has decreased over the past years. We therefore decided to use a previously described experimental aneurysm model for surgical training. MATERIAL AND METHODS: We operated on 8 rats and constructed a vein-pouch aneurysm at a surgically created carotid bifurcation. Survivors were kept alive for 1 month and operated on to clip the aneurysm. RESULTS: Only 3 rats had survived at 1 month. All the carotid arteries were permeable. Only 2 aneurysms were circulating at 1 month, as 1 had thrombosed. They were successfully clipped at 1 month. CONCLUSIONS: These preliminary results enabled our junior surgeon to clip two circulating aneurysms, under an operative microscope reproducing surgical conditions. Although the efficacy of the model could be improved, we believe it could be used as a first step in training neurosurgical residents in the basics of aneurysm clipping and microsurgical techniques in a realistic setting.

Testing the Medina embolization device in experimental aneurysms.

OBJECTIVE: The Medina embolization device (MED) is a novel, braided self-expanding endovascular device designed to occlude aneurysms by constructing an in situ intrasaccular flow diverter. Although a single device can be positioned at the neck of simple spherical in vitro aneurysms, the best way to occlude more complex in vivo aneurysms (using multiple MEDs or a combination of MEDs and platinum coils) is currently unknown. METHODS: Fifty-two aneurysms of 3 different types were created in 31 canines, yielding 48 patent aneurysms. Treatments were randomly allocated by drawing lots: group 1, MEDs alone (n = 16); group 2, MEDs plus standard platinum coils (n = 16); and group 3, control aneurysms treated with coils alone (n = 16). Angiographic results were scored and compared immediately following treatment completion and at 3 months. Specimens were photographed and the extent of neointimal closure of the aneurysmal neck scored, followed by histopathological analyses. RESULTS: Angiographic scores of 0 or 1 (occlusion or near occlusion) were initially obtained in 2 of 16 (12.5%, 95% CI 1.6%-38.3%) group 1 (MEDs alone), 3 of 16 (18.7%, 95% CI 4%-45.6%) group 2 (MEDs plus coils), and 10 of 16 (62.5%, 95% CI 35.4%-84.8%) group 3 (coils alone) aneurysms (p = 0.005). At 3 months, scores of 0 or 1 were found in 11 of 16 (68.7%, 95% CI 41.3%-89.0%) group 1, 9 of 16 (56.2%, 95% CI 29.9%-80.2%) group 2, and 8 of 16 (50%, 95% CI 24.7%-75.3%) group 3 aneurysms (p = 0.82). Neointimal scores were similar for the 3 treated groups (p = 0.66). CONCLUSION: Endovascular treatment of experimental aneurysms with MEDs or MEDs and coils showed angiographic occlusion and neointimal scores at 3 months that were similar to those achieved with standard platinum coiling.

Re-treatment of residual aneurysms after flow diversion: An experimental study.

Aim Flow diverters are increasingly used to treat aneurysms, but treatment is not always effective. The management of aneurysms that fail to occlude following flow diversion is problematic. We aimed to reproduce failures in an animal model and study re-treatment with additional flow diverters alone or with flow diverters and liquid embolic agent. Material and methods Twenty wide-necked aneurysms were created at the carotid-lingual bifurcation in 10 dogs, and were treated with flow diverters 4-6 weeks later. Follow-up angiography was performed at three months. Suitable residual aneurysms were randomly allocated: re-treatment with flow diverters alone ( n = 6), or with the injection of liquid embolic between two layers of flow diverters ( n = 4) or no re-treatment ( n = 2). Angiography was repeated three months later, followed by euthanasia, photography and pathology. Results Patent wide-necked aneurysms were produced in 17/20 attempts (85%); three months after flow diversion there were 15/17 (88%) residual aneurysms. In three cases, re-treatment was not possible because the flow diverter had prolapsed into the aneurysm, leaving 12 aneurysms to study. Re-treated aneurysms showed improved angiographic results at six months (median score of 2; P = 0.03), but residual aneurysms were present in all cases. Parent artery occlusion occurred in two aneurysms treated with flow diverter plus liquid embolic. At pathology, aneurysms were only partially filled with thrombus; leaks through the flow diverters were found in the neointima connecting the arterial lumen to residual aneurysms. Conclusion Re-treatment of residual flow-diverted experimental aneurysms with additional flow diverters did not lead to aneurysm occlusion.

Testing flow diversion in animal models: a systematic review.

INTRODUCTION: Flow diversion (FD) is increasingly used to treat intracranial aneurysms. We sought to systematically review published studies to assess the quality of reporting and summarize the results of FD in various animal models. METHODS: Databases were searched to retrieve all animal studies on FD from 2000 to 2015. Extracted data included species and aneurysm models, aneurysm and neck dimensions, type of flow diverter, occlusion rates, and complications. Articles were evaluated using a checklist derived from the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. RESULTS: Forty-two articles reporting the results of FD in nine different aneurysm models were included. The rabbit elastase-induced aneurysm model was the most commonly used, with 3-month occlusion rates of 73.5%, (95%CI [61.9-82.6%]). FD of surgical sidewall aneurysms, constructed in rabbits or canines, resulted in high occlusion rates (100% [65.5-100%]). FD resulted in modest occlusion rates (15.4% [8.9-25.1%]) when tested in six complex canine aneurysm models designed to reproduce more difficult clinical contexts (large necks, bifurcation, or fusiform aneurysms). Adverse events, including branch occlusion, were rarely reported. There were no hemorrhagic complications. Articles complied with 20.8 ± 3.9 of 41 ARRIVE items; only a small number used randomization (3/42 articles [7.1%]) or a control group (13/42 articles [30.9%]). CONCLUSION: Preclinical studies on FD have shown various results. Occlusion of elastase-induced aneurysms was common after FD. The model is not challenging but standardized in many laboratories. Failures of FD can be reproduced in less standardized but more challenging surgical canine constructions. The quality of reporting could be improved.

Differences in tissue proliferation and maturation between Matrix2 and bare platinum coil embolization in experimental swine aneurysms.

BACKGROUND AND PURPOSE: Recanalization of post-embolization cerebral aneurysms remains a serious problem that influences treatment outcomes. Matrix2 is a bioactive, bio-absorbable, detachable coil that was developed to reduce the risk of recanalization. We examined the short-term efficacy of the Matrix2 coil system, and evaluated the temporal profile of tissue proliferation in a swine experimental aneurysm model compared with the bare platinum (BP) coil. MATERIALS AND METHODS: Thirty-six experimental aneurysms were created in 18 swine. All aneurysms were tightly packed with Matrix2 or BP coils. Comparative histologic and morphologic analyses were undertaken 1, 2 and 4 weeks post-embolization. RESULTS: Endothelial-like cells were observed partially lining the aneurysmal opening one week post-embolization with both coil types. At two and four weeks post-embolization, the aneurysms treated with Matrix2 coils had more extensive areas of organized thrombus than those packed with BP coils, but the numbers of functional proliferating endothelial cells identified by immunohistochemistry in the tissue were broadly comparable between the groups. Moreover, morphological analysis suggested there were more mature endothelial cells in aneurysms treated with bare platinum rather than Matrix2 coils. CONCLUSIONS: Our results indicate that aneurysms embolized with Matrix2 coils build thicker scaffolds for endothelialization, but this is not necessarily evidence of earlier tissue proliferation and maturation than those embolized with BP coils. Matrix2 coils may not be superior to BP coils for preventing aneurysmal recanalization after endovascular treatment of cerebral aneurysms.

Comparison between routine cylindrical cerebral aneurysm volume approximation and three-dimensional volume measurements in experimental aneurysms.

OBJECTIVES: Aneurysm volume is routinely approximated calculating cylindrical volumes. Exact aneurysm volume assessment is crucial for liquid polymer embolization. The aim of this study was to compare simple cylindrical volume approximations with direct multiplanar reconstruction (MPR) segmentational volumetry in a saccular/complex experimental rabbit bifurcation aneurysm model. METHODS: In 12 female New Zealand white rabbits, saccular, broad-based, bilobular, and bisaccular aneurysms (three of each) were created using the rabbit venous pouch bifurcation model. Contrast-enhanced magnetic resonance angiography (CE-MRA) was performed, and maximal intensity projection (MIP) reconstructions as well as an MPR dataset were acquired. Aneurysm width and length were measured in MIP images, and the volume was approximated calculating cylindrical volumes. Three-dimensional (3D) segmentational volumetry using the MPR dataset was performed in a semi-automated manner. RESULTS: Maximal intensity projection cylindrical volumes ranged from 53·6 to 503·5 mm(3) (mean 186·5±118 mm(3)). Multiplanar reconstruction segmentation-based volumes ranged from 74·7 to 581·0 mm(3) (mean 202·2±133 mm(3)). The mean relative difference between MIP cylindrical and MPR segmentation volume calculation was 24·7% (range -77·5 to +50·8%). Only 4 of 12 MPR segmentational volumes were within a 10% range of results calculated for MIP cylindrical volume, and 3 of those were in broad-based aneurysms. CONCLUSION: This descriptive study demonstrates that estimated MIP cylindrical volumes differ from those measured by MPR segmentation volumetry. With the increasing acquisition of 3D data as 3D-MRA and the increasing need for exact volume determination, studies on the accuracy of computational segmentational volumetry of CE-MRA are necessary.

Flow diversion of giant curved sidewall and bifurcation experimental aneurysms with very-low-porosity devices.

OBJECTIVE: Flow diverters (FDs) are increasingly used to treat difficult intracranial aneurysms. The objective of this study was to test whether treatment challenges posed by giant curved sidewall (cSW) and endwall bifurcation (EwB) aneurysms can be overcome with the use of very-low-porosity devices. METHODS: Large and giant EwB (n = 12) and cSW aneurysms (n = 5) were constructed in 17 dogs. EwB aneurysms were treated with 48 (n = 4), 64 (n = 4), or two overlapping 64-wire low-porosity devices (n = 4), whereas all cSW aneurysms were treated with single 64-wire devices. Angiographic results were recorded immediately and at 12 weeks before euthanasia. Pathologic specimens were photographed and neointimal coverage of devices measured and scored. RESULTS: By 12 weeks, 1 of 12 EwB and 1 of 5 cSW aneurysms were occluded. All other aneurysms were patent. Device-related arterial stenoses occurred in 13 of 17 animals, hemodynamically significant in two. All branches jailed by the FDs remained patent. There was a significant correlation between angiographic scores and the degree of neointima formation on the device (Rho = 0.527; P = 0.04). Failures of aneurysm occlusion could be explained by holes, sometimes barely visible, in the neointima that formed over FDs. CONCLUSION: Low-porosity FDs fail to reliably occlude experimental giant EwB and cSW aneurysms.

Aneurismas experimentales en ratas / Experimental aneurysms in rats

Objective. 1. The creation of an aneurysm model in an arterial bifurcation for microsurgical training in rats. 2. To verify angiographically the aneurysms patency performing endovascular maneuvers. Material and method. 10 Wistar rats weighted 400-600g were used. Ten aneurysms were performed, 9 in the final aortic bifurcation and one in the origin of the renal artery. The aneurismal sac derived from the external iliac vein. Angiography in each animal was done to examine aneurysm patency. At the same time we tried to manipulate microcateter and microguidewire in the aortic lumen. After that the aneurysm was microscopically inspected in order to verify the angiographic findings. Results. The aneurysms and the angiographic study could be performed in every animal. Four aortic and the renal artery aneurysms were not visualized in the angiography (totally thrombosed). The other five were partially thrombosed. Under microscopic aneurismal inspection could be found thrombus into the sac. The endovascular navigation was difficult due to the animal size. Conclusion. The bifurcation aneurysm model is a good microsurgical training. In our hands the aneurysms created had a high rate of spontaneous thrombosis. Because of animal size it is not a good model for endovascular training.

Aneurismas experimentales en cerdos con la técnica de Varsos / Varsos technique for experimental aneurysms in pigs

Objective. To achieve an aneurysm model in swine with a low rate of sponatneous thrombosis. Material and method. Five swines were operated using a two stages technique (Varsos technique). In the first step ten carotidjugular fistulas in the neck (4 internal and 6 external jugular vein) were performed. The two vessels formed a 45° angle after the anastomosis. After a week the venous component of the fistula was occluded in order to create an aneurysm. The aneurysms patency was angiographically studied fifteen days later. At this time several types of stents and coils could be released. Results . The fistula and the aneuysms could be performed without complications. Seven of 10 aneurysm were angiogaphically patent. Three were thrombosed, all of them were created with the internal jugular vein. A carotid stenosis was observed at the anastomosis site in a thrombosed aneurysm. Conclusions. The Varsos technique in swines, specially when performed with the external yugular vein has a low rate of spontaneous aneurysm thrombosis.

Aneurismas experimentales en ratas / Experimental aneurysms in rats

Objective. 1. The creation of an aneurysm model in an arterial bifurcation for microsurgical training in rats. 2. To verify angiographically the aneurysms patency performing endovascular maneuvers. Material and method. 10 Wistar rats weighted 400-600g were used. Ten aneurysms were performed, 9 in the final aortic bifurcation and one in the origin of the renal artery. The aneurismal sac derived from the external iliac vein. Angiography in each animal was done to examine aneurysm patency. At the same time we tried to manipulate microcateter and microguidewire in the aortic lumen. After that the aneurysm was microscopically inspected in order to verify the angiographic findings. Results. The aneurysms and the angiographic study could be performed in every animal. Four aortic and the renal artery aneurysms were not visualized in the angiography (totally thrombosed). The other five were partially thrombosed. Under microscopic aneurismal inspection could be found thrombus into the sac. The endovascular navigation was difficult due to the animal size. Conclusion. The bifurcation aneurysm model is a good microsurgical training. In our hands the aneurysms created had a high rate of spontaneous thrombosis. Because of animal size it is not a good model for endovascular training.(AU)

Aneurismas experimentales en cerdos con la técnica de Varsos / Varsos technique for experimental aneurysms in pigs

Objective. To achieve an aneurysm model in swine with a low rate of sponatneous thrombosis. Material and method. Five swines were operated using a two stages technique (Varsos technique). In the first step ten carotidjugular fistulas in the neck (4 internal and 6 external jugular vein) were performed. The two vessels formed a 45º angle after the anastomosis. After a week the venous component of the fistula was occluded in order to create an aneurysm. The aneurysms patency was angiographically studied fifteen days later. At this time several types of stents and coils could be rele

Treatment of experimental saccular aneurysms of carotid arteries with three kinds of covered stents in canine models / 介入放射学杂志

Objective To assess the effectiveness and safety and biocompatibility of balloon-expanding stainless steel stents (SSS) covered with polyurethane membrane (PUM), expanding poly teflon ester membrane(ePTFEM)and biomembrane (BM) in the treatment of experimental saccular aneurysms of carotid arteries in canine models.Methods 36 experimental saccular aneurysms of carotid arteries in 20 canines were created successfully by sugery. Experimental aneurysms were treated with covered stents including twelve PUM-SSS, twelve ePTFEM-SSS and twelve BM-SSS for each twelve canines repectively. They were placed endovascularly in the common carotid arteries covering the orifice of aneurysms. Follow up angiography was performed immediately after the procedure and 2, 4 and 12 weeks afterwards under the control of conventional anticoagulation. The animals were then sacrificed for histopathologic and statistical investigation. Results 36 stents were placed successfully in the target arteries. The complete patency rates of PUM-SSS, ePTFEM-SSS and BM-SSS were 25.0%, 41.7% and 91.7% respectively. Histological analysis indicated that all treated aneurysmal pouches were filled with thrombus. Stent wires were found to be located deep within the vessel wall and encased by extension of the tunica intima. Endothelialization of BM-SSS groups already began at the 2nd week which was earlier than that of PUM-SSS and ePTFEM-SSS. Various degrees of degenerative cells were seen under the transmission electron microscopy without surface erosion of stents. Conclusion Placement of covered stent endovascularly is expedient, safe, and effective. BM-SSS provides the best mechanical behavior, physiochemical stability, anticoagulative ability and biocompatibility.

Microsurgical Creation of Aneurysms in the Carotid Artery of Rats

To investigate the role of internal elastic lamina in the formation of an aneurysm and the pathological progression of the aneurysmal wall and neck area, in a series of 32 adult rats, a small discrete mechanical lesion was made following an arteriotomy on the common carotid artery. Through the arteriotomy site, the lesion was made in the intima of the opposite side of the arterial wall by microsurgical technique at the proximal site to the bifurcation of the common carotid artery. Surgical sites of vessels were inspected grossly and light microscopically at intervals of 1, 4, 8 and 12 weeks(each group : 8 animals). Among the 32 animals, well defined aneurysms were seen in 15. In histological examination of the aneurysms, the internal elastic lamina almost disappeared or fragmented at the level of the aneurysmal neck. The aneurysmal wall was composed of only collagen fibers without evidence of elastic fibers. The aneurysmal wall and neck thickened progressively with collagen deposits. These aneurysms were similar to the human aneurysm histologically. This technique provides an experimental surgical formation of aneurysm and lends support to the important role of internal elastic lamina in the formation of an aneurysm. This experiment also showed progressiv thickening of the aneurysmal wall with collagen deposits.