Treating Saccular Wide-necked Aneurysm With Low Porosity Flow Diversion Stent In A Rabbit Model

Although intravascular coil embolization for aneurysms is widely applied, and has evolved substantially over the past 2 decades, some important limitations remain, particularly in the treatment of wide- necked, large and giant, or "nonsaccular" fusiform aneurysms. These lesions can frequently be difficult to reconstruct with coils, even when they are used with the commercially available self- expanding intracranial stents. New endoluminal flow diversion device offers substantial advances over endosaccular therapies, including the avoidance of aneurysm perforation. This novel device changed the treatment of intracranial aneurysms from embolism by coils to blood-flow diversion. However, the effects remain unknown of this even more highly metallic surfacing stent on aneurysms and small or even minimal perforating artery of parent vessel, and the real metal coverage of stent after implantation in vivo is remain indefinite. In this study, we used flow diversion stent aimed at aneurysm occlusion through flow disruption at the aneurysm neck. We analyzed the real metal coverage of stent in vivo after performance of flow diversion stents in aneurysm parent vessel and normal abdominal aorta and approached their effects on aneurysms, parent vessel, branches and even minimal visualized perforating arteries.PartⅠ:The Establishment and Angiography of Porcine Pancreatic Elastase-induced Aneurysm ModelsOBJECTIVE:To create an animal model to simulate human aneurysm, we modified the porcine pancreatic elastase-induced aneurysm model by a simple surgical technique in rabbits. METHODS:60 New Zealand white rabbits were processed; using sterile techniques, a middle skin incision was made at neck, the origin of the right common carotid artery (RCCA) and part of right subclavian artery (RSCA) were dissected carefully; the RCCA was ligatured 2.5 cm distally from the origin; a temporary arcuated aneurysm clip was placed at the origin of the RCCA and part of RSCA; 75 U porcine pancreatic elastase was incubated for 20 mins within the vessel lumen at the residual of RCCA; then the temporary arcuated aneurysm clip was released. Intravenous digital subtraction angiography (IVDSA) was performed after 3 weeks in all animals and one animal was procedure for intra artery digital subtraction angiography. Aneurysm sizes were measured by angiography. RESULTS:54 of 60 rabbits that underwent the aneurysm creation procedures showed saccular aneurysms on IVDSA 3 weeks after the procedure (93% successful outcome), whereas the other 4 animals showed residual dog-ear remnant at the RCCA stump with diameter of less than 2mm, which we did not define as an aneurysm. Daughter cysts in aneurysm mural and aneurismal dilation in parent vessel were shown in some cases. The mean aneurysms length, width, diameter of neck and diameter of parent artery were 5.93±1.60mm,3.81±0.83mm,3.75±0.84mm, and 3.78±0.61mm respectively. CONCLUSION:The elastase- induced aneurysm model we have developed by surgical method resembled human aneurysm in morphous. These aneurysms are easier to perform and highly reproducible. They can be ideal model for testing endovascular therapies.PartⅡ:Effects of Low Porosity Flow Diversion Stents on Rabbits'Aneurysms, Parent Vessels and BranchesOBJECTIVE:To observe the effects of low porosity flow diversion stents on rabbits' wide necked aneurysms, parent vessels and branches and evaluate the feasibility, safety and effect of the stents to aneurysm models. METHODS:30 New Zealand white rabbits with wide necked aneurysm were randomly divided into three groups:group A, B and C. In group A (n=10) and B (n=10), flow diversion devices were implanted into parent vessel and abdominal arota with metal coverage 30%-35% and 45%-50%, respectively; angiography was performed at 4 weeks after stent implantation; at 3 months all animals were euthanized for Micro-CT scan and pathology after angiography. In group C (n=10), animals were only performed for angiography without any stent implanted after grouped and at 3 months, and then animals were euthanized for pathology after angiography. Aneurysm and parent vessel sizes at different time points, new intima and local metal coverage were measured. Data were analyzed by SPSS 13.0 statistics soft ware. RESULTS:Immediately after stents placement, 90% and 70% aneurysms' necks covered by stents successful in group A and B, respectively, and the contrast retention in aneurysms were 88.7% and 100%, respectively; Intravenous digital subtraction angiography showed 77.8% and 85.7% aneurysms were completely occluded at 4 weeks follow up, respectively; artery digital subtraction angiography showed 71.4% and 85.7% aneurysms were greater than 95% angiographic aneurysm occlusion at 3 months follow up, respectively; all of branches covered by stents were patency at angiography follow up. Mean metal coverage of local stent at aneurysms' neck scanned by Micro-CT in group A and B were 32.6±11.7% and 37.5±12.8%, respectively, and there was no significant difference in two groups (P= 0.432). Mean metal coverage scanned by Micro-CT and measured by DSA in stenting group were 34.7%±12.1% and 35.4%±9.2%, respectively, which was no significant difference (P= 0.53). Aneurysm occlusion was positively correlated with local metal coverage of stent at neck (rs=0.486; P= 0.026). Metal coverage with 35% predicted aneurysm occlusion over a period of 4 weeks with a specificity of 100% and sensitivity of 53.8%. Pathologic analysis showed that the dome of embolized aneurysms were full filled with unorganized or partly organized thrombus and neointimas at neck and parent vessel were composed predominantly of smooth muscle cells, collagen fibers and occasional macrophages. In group C, mean aneurysm dimensions were not significantly changed in angiography after grouped and before sacrificed at 3 months (P>0.05); the mural of aneurysms were partly thin or thicken with absence of elastin, partly parent vessel were aneurismal dilation, and the hyperplastic neointimas at dome and parent vessel were composed predominantly of smooth muscle cells and collagen fibers. CONCLUSIONS:The flow diversion stents with 35% metal coverage can cure aneurysms with preservation of the parent artery and adjacent branch vessels in angiography and without thrombosis in stent. The metal coverage of stent can be measured by angiography.PartⅢ:Effects of Low Porosity Flow Diversion Stents on Rabbits' Abdominal Aorta, Branches and Minimal BranchesOBJECTIVE:To analyze the response of abdominal aorta, ostia of branches and minimal branches by low porosity flow diversion stent. METHODS:30 New Zealand white rabbits were divided into experimental group (n=20) and control group (n=10). In the former group, flow diversion stent with 30%-50% metal coverage was implanted in abdominal aorta across the lumbar artery, angiography was performed at 4 weeks after procedure. Animals in control group only underwent angiography without stent implanted. All animals were sacrificed for pathology after angiography at 3 months. The neointima caused by the stent and the porosity of local stent in abdominal aorta and ostia were calculated. Data were analyzed by SPSS 13.0 statistics soft ware. RESULTS:In experimental group, angiography revealed no stenosis or occlusion in abdominal aorta or branch arteries, either immediately after stent implantation, or 4 weeks or 3 months' follow-up. 9 and 10 minimal branches were confirmed in control and experimental groups, respectively. Neointimal coverage score in ostium of branch was positively correlated with metal coverage of stent (rs=0.507; P= 0.005). Local metal coverage of 30%-40% caused neointimal coverage score in ostium of branch was not significantly greater than that caused by 20%-30% metal coverage (P= 0.792), but significantly less than that caused by 40%-50% metal coverage (P= 0.021). Neointimal thickness in abdominal aorta was positively correlated with metal coverage of stent (r=0.523; P=0.001). These neointimas were composed predominantly of smooth muscle cells, collagen fibers and occasional macrophages. CONCLUSIONS:Flow diversion devices cause neointima covering the struts and meshes at ostium of brach artery, although the branch was patency by angiography, and the local metal coverage of device less than 40% do not cause severe neointimal coverage in ostium at 3 months post operation. Flow diversion devices cause neointima covering the struts and meshes at ostium of brach artery, although the branch was patency by angiography, and the local metal coverage of device less than 40% do not cause severe neointimal coverage in ostium at 3 months post operation.