Experimental Study On Flexibility And Apposition As Well As Endothelialization Of Intracranial Covered Stent

Chapter One IntroductionThe cranial internal carotid artery(CICA)comprising the petrous segment (C2) to the communicating segment (C7) of the segment of ICA (Bouthillier classification), is predisposed to intracranial aneurysm,carotid cavernous fistula,dural arteriovenous fistulas,atherosclerotic stenosis, arterio-venous fistulae and pseudoaneurysm secondary to iatrogenic injuries or laceration including radiotherapy of nasopharyngeal carcinoma and hypophyseoma resection as well as incision of middle ear. It is estimated that the CICA vascular diseases approximately account for 15% of all intracranial vascular diseases. These lesions are associated with a high morbidity and mortality. In the past decade, the dramatic progress in the treatment of these diseases has been made, with the development of neurosurgical and endovascular techniques. However, the treatment of large or giant aneurysm, pseudoaneurysm, small aneurysm with wide-neck, and recurrent aneurysm located in the CICA as well as complex and intractable carotid cavernous fistula remain a formidable challenge in the fields of neurosurgery and neuro-interventional radiology. Therefore, the exploring and developing of the optimal neurovascular devices aimed to anatomically cure these neuro-vascular diseases with a relatively simple endovascular technique on the condition of safety have become urgent and essential. Theoretically, endovascular treatment with covered stent, allowing to immediately exclude aneurysm from circulation and preserve patency of parent artery, close orificium of carotid cavernous fistula(CCFs)and supplying arteries of dural arteriovenous fistula, might be the most promising alternative to established neurosurgical or endovascular options. However, currently there is lack of the dedicated intracranial covered stent, the available covered stents are typically coronary stent grafts, which had a high-profile and lacked longitudinal flexibility, and are difficult to navigate through the tortuous carotid siphon with relatively small diameter. Additionally, the coronary covered stent is also lack of a favorable conformability and is difficult to adapt to the curvature of vesse. Moreover,thus far, Healing characteristics of stent grafts in intracranial artery are undetermined. Thereby, the development of the dedicated intracranial covered stent and the study of healing characteristics of stent grafts in intracranial artery has become the frontier of study in the treatment of the neurovascular diseases.Chapter Two Construction of in vitro model of the individual carotid siphonPurpose To investigate the feasibility and reliability to develop an in vitro carotid siphon model by using the rapid prototype and the lost-wax techniques. Materials and Methods Six patients who were suspected cerebral vascular diseases underwent cerebral angiography and three-dimension rotation angiography. Their 3D angiographic data sets were used to reconstruct the 3D visual carotid siphon model by using the proprietary Materialise's Interactive Medical Image Control System (MIMIC) software. The converted data sets were transferred to 3D printer and the wax copies of the carotid siphon were manufactured. The surface of the wax model was manually coated prosthetic silicone elastomer, and then the wax was removed by lost-wax technique, leaving a replica of the carotid siphon. The frontal and lateral projection of the model was obtained. The morphology of the model was visually evaluated and compared with that of the original patients by two independent neuro-interventionists. The geometric parameters of the model and the prototype were measured and analyzed to evaluate the accuracy of the model. The paired T-test was performed to compare the geometric parameters of the in vitro model and their prototype. Results Six in vitro model of the carotid siphon were successfully created using the rapid prototype and lost-wax technique. The morphology of the model is visually similar to their prototype. There is no significant difference between the geometric parameters(H/B,2S/H×B.K/T) of the model and their prototype (P﹥0.05). Conclusion the construction of the in vitro carotid siphon model by using the rapid prototype and lost-wax technique is feasible. This model has high similarity to the prototype and can be used the experimental platform which assist the development of novel neurovascular devices and techniques as well as construction of the in vivo carotid siphon model.Chapter Three Surgical Construction of a Novel Simulated Carotid Siphon in CaninesPurpose To develop an in vivo carotid siphon models by surgical method using the shaped devices for testing the performance of covered stent specially designed for intracranial vascular diseases. Materials and Methods Six carotid siphon-shaped devices were established using sterolithographic biomodeling and the lost-wax technique. Six canines underwent surgery to expose and isolate bilateral CCA. The right CCA origin was ligated and incised distal to ligation point after the distal right CCA was temporarily closed. The distal left CCA was ligated and incised proximal to ligation point after the left CCA origin was closed. The proximal isolated left CCA was passed through the shaped device. The distal isolated right CCA and the proximal isolated left CCA was anastomosed end-to-end. Finally,the shaped device of carotid siphon was fixed with suture and embedded in the left neck. The intraarterial DSA was performed on postprocedural 7 days, 2 weeks and 1 month. The morphological characteristics of carotid siphon models were visually evaluated by two observers. The patency of siphon model and the stenosis of anastomotic stoma were followed-up. Endovascular interventional simulation in all models was performed to evaluate whether the model provided a practical environment encountered in clinical practice. Results Animals tolerated the surgical procedure well. The mean time for construction of model is 90 minutes. The morphological characteristics and endovascular manuipulation feeling of siphon models were similar to those in human. The stenosis of anastomotic stoma occurred in 2 siphon models, and thrombosis of anastomotic stoma in 1 siphon model, but all models were patent on post-procedural follow-up angiography. Conclusion Surgical construction of an in vivo carotid siphon model in canine with shaped device is practically feasible. This model can be used for testing neurovascular devices. Chapter Four Experimental study on flexibility and apposition of covered stent specially designed for intracranial vasculaturePurpose To evaluate the longitudinal flexibility and apposition to vascular wall of the Willis covered stent specially designed for intracranial vasculature. Materials and Methods 12 in vitro carotid siphon models were established by using the rapid prototype and lost-wax techniques, based on the 3D angiographic data set obtained from four patients who underwent cerebral angiography and three-dimension rotation angiography. Three in vitro models per geometry were established. These models were used as the shaped devices. 12 in vivo carotid siphon models were developed by surgical method using these shaped devices in canines and divided into four group (A,B,C,D) according their geometry. Each group were attempted to implant the Willis covered stent with length selected randomly (7mm,10mm,13mm,16mm)after the diameter of the covered stent was determined. The technique success rate, subjective feelings and support measure, as well as angiographic changes during the procedure were recorded. The morphology of the anterior segment of the carotid siphon model were compared and measured before and after covered stent placement to evaluate straightening effects on vascular curves and the degree of apposition to the wall of vessel. The morphology of the stent after deployment was observed. Results The covered stents were successfully implanted into the anterior segment of the carotid siphon in all models. There are no angiographic changes secondary to the navigation of the covered stent in all models. After deployment of the covered stent, the proximal and distal of the anterior segment of the carotid siphon in all models was revealed a mild straightening by visual evaluation. The opening angle of the anterior segment of the carotid siphon before and after the deployment of covered stent is 104.63°±32.9°and 110.69°±28.2°respectively, there is no statistically significant difference between them (P>0.05). The visual evaluation revealed that the covered stents are lack of complete apposition between covered stent and the wall at the concavity of the anterior segment of carotid siphon in all models. The mean apposition ratio in anterior segment of the carotid siphon is 0.05±0.02. After the placement of the covered stent, the gap between modules of the stent at the lesser curvature of the anterior segment revealed a slight decrease, the neighboring stent strut has a tendency to imbricate and protrude into the lumen of vessel; whereas the gap between modules of the stent at the larger curvature of the anterior segment showed a slight increase, the neighboring stent strut separate one another and partially protrude toward the wall of vessel. Conclusion The Willis covered stent specially designed for intracranial vasculature had an excellent longitudinal flexibility and favorable apposition, which can navigate through the tortuous carotid siphon and had a negliable straightening effect. After the deployment of Willis covered stent with a larger diameter into the anterior segment of carotid siphon, there exists incomplete apposition at between covered stent and the wall at the concavity of the anterior segment of carotid siphon.Chapter Five Experimental study on time course of endothelialization of intracranial covered stentPurpose To investigate time course of endothelialization and the main mechanism of endothelialization of the intracranial covered stent. Materials and Methods 12 carotid siphon model in canines were developed by surgical reconstruction with carotid siphon-shaped device created by rapid prototype and lost-wax techniques. 12 intracranial covered stent were placed in the anterior segment of carotid siphon model. Angiography immediately after covered stent placement and at the end of procedure was performed to assess acute in-stent thrombosis. Angiographic follow-up was performed to evaluate in-stent subacute thrombosis and stenosis on post-procedure 2 weeks, 6 weeks and 12 weeks. At every follow-up time point, 4 animals were sacrificed and the specimen of stenting segment was harvested. The gross pathologic examination and scan electronic microscopy (SEM) were performed to assess the endothelialization at every time point. Results 12 animals were shown complete patency on angiography immediately after the covered stent placement and at the end of procedure. No acute in-stent thrombois was observed in the stenting segment in all animals. At 2 weeks, 2 animals were observed in-stent occlusion of the stenting segment; 10 animals were shown patency, but one animal was found in-stent mural thrombosis on post-procedural angiography. At 6 weeks, the follow-up 8 animal were shown complet patency, no subacute in-stent occlusion and early in-stent stenosis were observed on post-procedural angiography. At 12 weeks, the follow-up 4 animal remained patency, no in-stent occlusion and early in-stent stenosis were observed on post-procedural angiography. In 4 specimens obtained on post-procedural 2 weeks, the stenting segment were observed the filling of dull redness thrombus in 2 specimens; the luminal surface of the stent in one was covered by a thin yellow-white membranes with pink thrombus-like materials deposition in the midgraft; in the remaining one, the luminal surface of the stent was covered by a thin white translucent membranes. In 4 specimens obtained on post-procedural 6 weeks, the luminal surface of the stent was covered by a thin white or gray-white translucent membrane with partial stent strut exposure. In 4 specimens obtained on post-procedural 12 weeks, the luminal surface of the stent was covered by a thin white or gray-white translucent membrane with partial strut exposure in 3 specimens, complete coverage of the luminal surface of the stent with thick glistening white neointima was observed in the remain one. SEM examination of the 2 weeks specimens revealed the surface of the stent and grafts was covered with fibrin, there is associated with adherence of large amount of red cell in one specimen, only one specimen revealed pannus ingrowth of the endothelial cell from the end of the graft. SEM examination of the 6 weeks specimens revealed the surface of the stent and grafts was covered with neointima associated with partial strut exposure. The endothelial cell migrated along the strut and grafts from the proximal and distal of the stent-graft, the midgraft was covered with fibrin without coverage of the endothelial cell. SEM examination of the 12 weeks specimens revealed the endothelial cell migrated along the strut and grafts from the proximal and distal of the stent-graft with approximate 50% of the surface of the graft, there is no coverage of the endothelial cell in the midgraft and partial strut. Conclusion The endothelialization started as early as 2 weeks after implantation of intracranial covered stent into the carotid siphon model in canines, and was incomplete at 3 months, which suggested the prlonged antiplated therapy should be considered beyond 3 months after the intracranial covered was placed in the intracranial internal carotid artery; the migration of the endothelial cell along the strut and graft from the two edges of the stent graft is main mechanism of the covered stent.