Endovascular treatment of experimentally induced aneurysms in rabbits using stents: a feasibility study

Although Guglielmi detachable coil (GDC) systems have been generally accepted for treatment of intracranial aneurysms, primary stenting of aneurysms using porous stents or implantation of coils after stent placement remains experimental. Testing of these new methods requires an animal model which imitates human aneurysms in size, configuration and neck morphology. We assessed in detail the technical requirements of and steps for transfemoral stent treatment of experimentally induced aneurysms at the top of the brachiocephalic trunk in rabbits. We created aneurysms in ten rabbits by distal ligation and intraluminal digestion of the right common carotid artery with elastase. We treated five animals with porous stents alone, and five with stents plus coiling via the meshes of the stent, which permitted dense packing of coils. No complications related to the procedures occurred. In all animals, even in those treated solely with porous stents, total occlusion of the aneurysm was achieved. Our animal model can be suitable for testing the biocompatibility and occlusion rate of new methods and devices for the treatment of experimental aneurysms.     

Twin-tube endografts for aortic aneurysms: an experimental feasibility study.

PURPOSE: To explore feasibility of twin-tube endografts (TTEGs) for treatment of abdominal aortic aneurysm (AAA). MATERIALS AND METHODS: AAAs were created in six dogs by overdilation of Palmaz stents. TTEGs made of seven 9.5-mm-diameter Gianturco R?sch Z (GRZ) stents and covered with PTFE were deployed simultaneously from both femoral arteries through 10-F sheaths to exclude the AAA. Follow-up aortography was performed immediately and at 2, 4, and 8 weeks. Two dogs were killed at 4 weeks and four were killed at 8 weeks. Gross and histologic examinations were performed. RESULTS: AAA creation and TTEG placement were successful in all six dogs. TTEGs completely excluded AAAs in five dogs. Minor temporary perigraft leak was seen in one dog immediately after stent placement. Four dogs had TTEGs patent to termination at 8 weeks. In two dogs with oversized TTEGs, one of the twin endografts occluded at 2 weeks. At autopsy, TTEGs were formed in semicircular shape and histology did not show any significant inflammatory reaction. CONCLUSION: TTEGs show promise for treatment of AAA, with the potential of reducing the introductory sheath size. Further experimental studies, particularly with TTEGs extended into iliac arteries, are warranted.     

Emergent treatment of a primary aortoenteric fistula with N-butyl 2-cyanoacrylate and endovascular stent

A novel endovascular treatment involving cyanoacrylate injection followed by endovascular stent placement is described in the setting of life-threatening acute exsanguination through a primary aortoenteric fistula. In a patient in unstable condition, N-butyl 2-cyanoacrylate was injected into the fistula tract. Rapid polymerization first provided hemostasis and allowed the patient to be resuscitated and stabilized for several hours, and then an AneuRx endovascular stent-graft was deployed to reinforce the aortic wall and permanently occlude the fistula. This approach can benefit patients whose condition would otherwise be too unstable for open surgery.     

α-氰基丙烯酸正丁酯栓塞治疗肝细胞癌并肝动脉-门静脉瘘的临床价值

目的 探讨α-氰基丙烯酸正丁酯(N-butyl 2-cyanoacrylate,NBCA)在肝细胞癌(HCC)并肝动脉-门静脉瘘(arterio-portal fistural,APF)栓塞治疗中的临床应用价值.方法 回顾性分析分别使用NBCA(NBCA组,26例)和无水酒精(无水酒精组,54例)栓塞治疗HCC合并APF患者的临床资料.治疗方法为常规经导管动脉化疗栓塞(TACE)过程中先使用液体栓塞剂对APF进行治疗.NBCA组根据APF的动静脉循环时间(≤1、1～2和≥2 s)分别使用不同浓度的NBCA(分别为40%～50%、28%～33%和20%～25%)进行栓塞;无水酒精组则根据APF的分流程度用无水酒精加海绵颗粒等栓塞治疗.两组栓塞中的疼痛反应和肝功能受影响程度的比较采用x2检验,1年生存率的比较采用Log-rank检验,一次性栓塞闭塞成功率的比较采用Fisher's精确检验.结果 栓塞过程中NBCA组有4例、无水酒精组有52例患者感到不同程度疼痛,两组差异有统计学意义(x2=58.86,P＜0.01);一次性栓塞闭塞成功率NBCA组92.3%(24/26)、无水酒精组68.5%(37/54),差异有统计学意义(P＜0.05);两组栓塞前后肝功能的变化(x2=0.652)以及1年生存率差异均无统计学意义(P＞0.05).结论 NBCA柃塞治疗HCC合并的APF安全、有效、准确性高,为HCC合并APF的栓塞治疗提供了一种新的可选择的方法.     

Endovascular treatment of experimental canine aneurysms: feasibility with MR imaging guidance

PURPOSE: To evaluate the feasibility of using magnetic resonance (MR) imaging to guide and monitor endovascular therapeutic procedures. MATERIALS AND METHODS: Endovascular therapeutic procedures were performed with MR imaging guidance in eight dogs by using a 1.5-T MR unit with echo-planar imaging capabilities. Carotid arterial aneurysms were surgically created in four dogs. The ability to depict, track, and position catheters, guide wires, and Guglielmi detachable coils was assessed. Catheters were first positioned with fluoroscopic guidance. Tracking and depiction were achieved with MR imaging by using commercially available catheters filled with a gadopentetate dimeglumine solution and a fast, two-dimensional, time-resolved, variable-rate k-space sampling technique. RESULTS: When either a catheter or the coaxial space between a catheter and a guide wire was filled with a solution of gadopentetate dimeglumine, catheter movement was always depicted. In the animals with aneurysms, it was possible to depict movement of a catheter into and out of the aneurysm. This was achieved by superimposing reconstructed images obtained during catheter movement onto a previously acquired MR angiogram ("road map"). Prototype Guglielmi detachable coils were successfully positioned and detached. Aneurysm obliteration was monitored with the acquisition of new road map images. CONCLUSION: The results demonstrate the feasibility of using MR imaging to guide endovascular therapeutic procedures.     

Effect of glacial acetic acid and ethiodized oil concentration on embolization with N-butyl 2-cyanoacrylate: an in vivo investigation

BACKGROUND AND PURPOSE: Precise control of the polymerization dynamics of cyanoacrylate mixtures used in the embolization of cerebral arteriovenous malformations is required to achieve a safe and permanent obliteration of the lesion. In this study, in vivo embolization using mixtures of Histoacryl, Lipiodol Ultra-Fluid, and glacial acetic acid (GAA) was investigated. The present study investigated whether increased ethiodized oil concentration or the addition of GAA increased rate of embolization. METHODS: Using embolic mixtures containing Histoacryl (N-butyl 2-cyanoacrylate [NBCA]), the embolization process in the femoral and subclavian arteries of the rabbit was examined. Various embolic agents composed of ethiodized oil and N-BCA mixtures, either with or without the addition of minute quantities of GAA, were injected. Blood flow through the aforementioned arteries was measured during embolization. The transient decay of blood flow to zero was modeled, and an optimized model parameter, termed the time elapsed to flow arrest (TEFA) factor, was compared with the experimental data related to the embolization process. RESULTS: The TEFA factor was independent of the variation of the ethiodized oil concentration in the mixture (P >.05). In contradistinction, the addition of GAA significantly increased the TEFA factor (P <.05). Moreover, a linear relation between the TEFA factor and the quantity of GAA in the mixture was discerned. CONCLUSION: Predictable control of the embolization process with N-BCA in vivo is attained by varying the amount of GAA in the embolic mixture.     

Transtympanic iontophoresis with a biocompatible paramagnetic solution at MR imaging: experimental feasibility study in rabbits

PURPOSE: To determine the feasibility of transtympanic iontophoresis in experimental animals with a paramagnetic contrast agent at magnetic resonance (MR) imaging. MATERIALS AND METHODS: Optimal MR sequence parameters and appropriate paramagnetic ion concentrations of a water and gadopentetate dimeglumine solution were initially assessed with phantoms. Iontophoresis was performed in left ears of five rabbits after the external auditory canals were filled with a solution of water and gadopentetate dimeglumine of optimal concentration, and right ears were used as controls. Signal-to-structural noise ratio (SSNR) and contrast-to-structural noise ratio (CSNR) were measured by using regions of interest, and the overall image quality was assessed subjectively. RESULTS: Spin-echo (SE) MR sequences were superior to gradient-echo (GRE) MR sequences in terms of SSNR, CSNR, and overall image quality. Highest SSNR and CSNR values were achieved with 2 mmol/L (2 mM) of gadopentetate dimeglumine solution with both SE (repetition time msec/echo time msec, 500/12; flip angle, 90 degrees ) and GRE (300/10; flip angle, 90 degrees ) sequences in both phantoms and animals. The high signal intensity of gadopentetate dimeglumine solution was recognized in middle ears, vestibules, and semicircular canals of all rabbit ears that had undergone iontophoresis and in none of the control ears. CONCLUSION: With the solution of water and gadopentetate dimeglumine, the maximum SSNR and CSNR with both SE and GRE MR imaging sequences were achieved. The solution can be transferred to the middle and inner ear cavities across an intact tympanic membrane by using transtympanic iontophoresis.     

Europium fluorescence to visualize N-butyl 2-cyanoacrylate in embolized vessels of an arteriovenous malformation swine model

BACKGROUND AND PURPOSE: Standard tissue staining using the lipid dye Oil-Red-O has been previously applied to stain vessel specimens, which were embolized with a mixture of n-butyl 2-cyanoacrylate (NBCA) and oil (Lipiodol). That technique, however, results in nonspecific and nonquantitative staining that does not provide the necessary differentiation between NBCA and Lipiodol. We present an innovative staining procedure that quantifies NBCA within treated tissues. METHODS: An arteriovenous malformation (AVM) model in swine was used to evaluate the polymerization characteristics of various ratios of Lipiodol/NBCA/glacial acetic acid (GAA) mixtures. To determine the depth of NBCA penetration within the AVM model and to characterize the polymerization patterns of various mixtures within the vessel, histologic cross- and longitudinal sections were prepared for microscopy. These paraffin-embedded tissue sections were stained with a europium aryl-beta-diketone complex (TEC) to improve differentiation between NBCA and Lipiodol. Quantification of NBCA and Lipiodol within the lumen of rete cross-sections was accomplished using image analysis software to determine percent luminal area occluded by embolization. RESULTS: Upon application of TEC, intense europium fluorescence was seen when the tissue samples were excited by low-power UV light (excitation at 365 nm; emission at 614 nm). The area of europium intensity within the lumen corresponded to NBCA concentration, and addition of GAA aided the NBCA distribution throughout the lumen without affecting fluorescence intensity. It was seen that NBCA could be easily differentiated from Lipiodol and that quantification could be readily performed on these sections because of the improved differentiation. For the case of a 50:50 (vol. %) mixture with an added 20 microL of GAA, luminal area distribution of Lipiodol, NBCA, and blood products was 42.6 +/- 3.5%, 33.8 +/- 5.7%, and 23.7 +/-2.7%, respectively. CONCLUSION: The rare earth metal europium, when added as a fluorescent chelate compound to histologic tissue sections, allowed for differentiation between NBCA and Lipiodol with good detail. These results have facilitated further characterization of NBCA polymerization for the use of AVM embolization.     

α-氰丙烯酸正丁酯治疗肝癌高流量动脉-门静分流的临床研究

目的:评价应用α-氰丙烯酸正丁酯(NBCA)治疗肝癌高流量动脉-门静脉分流(HAPS)的临床疗效.材料和方法:对12例肝癌伴HAPS的患者以NBCA栓塞瘘口并行肝动脉化疗栓塞术.结果:9例患者瘘口闭合,2例患者瘘口部分闭合,1例因不良反应终止瘘口栓塞.结论:应用NBCA治疗高流量HAPS是一种安全有效的方法.     

Elastase-induced saccular aneurysms in rabbits: a dose-escalation study

BACKGROUND AND PURPOSE: Reproducible animal models facilitate preclinical assessment of aneurysm therapies. Our purpose was to determine if increased elastase doses enlarge aneurysms and parent arteries. METHODS: Rabbit right common carotid artery (CCA) aneurysms were created with distal ligation and intraluminal elastase incubation. Groups were 1) sham (no elastase, n = 3), 2) 25% elastase (10 minutes, n = 9), 3) 50% elastase (10 minutes, n = 7), and 4) 50% elastase (20 minutes, n = 41). Angiography was performed after 14 days. Resultant aneurysm width and height and parent artery diameters were measured and compared with the Student t or Mann-Whitney (Wilcoxon rank sum) test. RESULTS: Proximal segments were enlarged in all elastase subjects and no sham subjects. Mean measurements were significantly smaller in the sham group than in other groups. Aneurysm widths and heights, respectively, were 3.8 mm +/- 0.8 and 7.4 mm +/- 2.0 in the low-dose group; 3.9 mm +/- 1.3 and 8.5 mm +/- 3.8, medium-dose group; and 4.1 mm +/- 1.1 and 8.7 mm +/- 2.6, high-dose group. Differences were not significant. Parent artery widths were 3.5 mm +/- 0.7, 3.8 mm +/- 0.7, and 4.3 mm +/- 1.4 in the low-, medium-, and high-dose groups, respectively; the high-dose group had larger arteries (P =.07). CONCLUSION: Aneurysms were reliably created and were sized similar to human intracranial aneurysms. Elastase concentration and incubation duration did not affect resultant size. Relatively short incubation (eg, 10 minutes) and 25% elastase can be used to create rabbit aneurysms, especially if dilatation of adjacent parent arteries is to be avoided.     

Liquid 2-poly-hydroxyethyl-methacrylate embolization of experimental arteriovenous malformations: feasibility study

BACKGROUND AND PURPOSE: We investigated the use of 2-poly-hydroxyethyl-methacrylate (2-P-HEMA) as an embolic agent in swine arteriovenous malformations (AVMs). METHODS: In seven mini swine, experimental AVMs were created surgically. The aim of treatment was complete embolization of the nidus compartment filled by the feeding artery, without brain embolization. Six animals received pure liquid 2-P-HEMA, and one, 50% 2-P-HEMA. For radiopacity, liquid 2-P-HEMA was mixed with tungsten powder. Six animals underwent angiographic follow-up within 5-8 mo (mean, 6.5 mo). Evaluation criteria were controllability, procedural reproducibility, and duration of the nidus occlusion. To detect complications, brain MR imaging and CT were performed. Histopathologic studies were performed to prove occlusion and assess histopathologic responses. RESULTS: 2-P-HEMA was easily injected through microcatheters, with a reproducible technique. Because of the radiopacity of the mixture, deep nidus penetration was controlled with fluoroscopy and confirmed with CT and histopathologic examination. In five AVMs embolized with pure 2-P-HEMA, feeder obliteration was long term. One animal had vasospasm during embolization, and complete obliteration of the main feeder was maintained for 3 mo, but partial recanalization developed 2 mo later. One animal receiving pure 2-P-HEMA had an infarction. In the animal embolized with 50% 2-P-HEMA, angiography and CT revealed embolic material in the circle of Willis; the animal died after embolization. No marked inflammatory reaction in the vessel wall or perivascular tissue was observed in the embolized AVMs. CONCLUSION: Experimental AVM embolization with pure 2-P-HEMA, made radiopaque with tungsten, is technically feasible in swine. Because of its properties, 2-P-HEMA has great potential as a therapeutic embolic agent.     

Endoluminal embolization of bilateral atherosclerotic common iliac aneurysms with fibrin tissue glue (Beriplast)

The standard surgical approach to nonleaking iliac aneurysms found at repair of a leaking abdominal aortic aneurysm is to minimize the operative risk by repairing the abdominal aorta only. This means that the bypassed iliac aneurysms may have to be repaired later. As this population of patients are usually elderly with coexisting medical problems, interventional radiology is being used to embolize these aneurysms, thus avoiding the morbidity and mortality associated with further general anesthesia and surgery. Various materials and stents have been reported to be effective in the treatment of iliac aneurysms. We report the successful use of endoluminal fibrin tissue glue (Beriplast) to treat two large iliac aneurysms in a patient who had had a previous abdominal aortic aneurysm repair. We discuss the technique involved and the reasons why we used tissue glue in this patient.     

兔VX2膀胱癌移植瘤模型实验研究

目的 通过模拟原位膀胱癌发生机制构建兔VX2膀胱癌移植瘤动物模型,研究其生物学特性及影像学表现.方法 采用同轴法穿刺接种VX2细胞株于25只新西兰大白兔膀胱,接种术后14、21、28 d分别作CT平扫及增强扫描,评估肿瘤种植及生长情况.取兔膀胱组织标本作大体解剖学及组织病理学检查,同时观察腹腔淋巴结及肝肺转移情况.结果 22只实验兔建模成功,植瘤成瘤率为88.0％(22/25).植瘤后14、21、28 d瘤体平均长径分别为(1.38±0.20) mm、(2.30±0.08) mm、(3.22±0.24) mm,且瘤体变化差异有显著统计学意义(P＜0.01).VX2移植瘤CT表现为膀胱壁局部不规则增厚或肿块突起,呈均匀强化(14 d)或环型强化(21、28 d),肿瘤腔内呈不同程度充盈缺损.种植瘤大体形态及其影像学特征基本相符,组织病理学表现为血管丰富的低分化鳞状细胞癌,呈浸润性生长,21 d后瘤体中心出现坏死,21、28 d出现肝、肺及腹腔淋巴结转移.结论 本研究成功构建兔VX2膀胱移植瘤模型,基本反映了膀胱癌发生与发展过程,适合CT动态观察及实验研究.     

N-butyl 2-cyanoacrylate embolization of spinal dural arteriovenous fistulae: CT evaluation, technical features, and outcome prognosis in 26 cases

BACKGROUND AND PURPOSE: This study investigated the role of CT as an early predictor of outcome prognosis after glue embolization of spinal dural arteriovenous fistulas (SDAVF). METHODS: Over a 13-year period, 26 patients underwent glue embolization of SDAVF and were retrospectively reviewed. Immediately after embolization, each patient had CT evaluation of cast position. Mean follow-up angiography was 23.4 months (range, 1-87 months; median, 21 months). Both MR images and clinical data (e.g., gait and micturition disabilities according to the Aminoff and Logue disability scale, deep and superficial sensitivity) were analyzed, with a mean follow-up of 37.7 months (range, 12-98 months; median, 28 months). Data were tested by univariate analysis by using Fisher's exact test and the Kruskall Wallis test, depending on the order of the qualitative variables. RESULTS: Glue was found in the dura mater on CT in 19 (73%) patients. None of these patients had a recanalized fistula on angiography, and the clinical status of all of them improved. Glue was observed in or proximal to the foramen on CT in seven (27%) patients. In five of them, the fistula was recanalized within a mean period of 9 months (range, 3-24 months; median, 6 months) and their clinical status worsened. All five required surgical treatment. On angiography, the absence of fistula recanalization was observed in 21 (81%) patients and correlated with improvements in gait (P = .016), sensitivity (P = .030), and micturition (P = .080). It also correlated with a decrease in the extent of the abnormally high intramedullary T2 signal intensity (P = .002), a decrease in spinal cord diameter (P = .017), and the resolution of prominent perimedullary vessels (P < .001). The presence of glue within the dura mater on CT correlated with the absence of fistula recanalization (P = .045) and with overall improvement in clinical status, including gait and/or sensitivity and/or micturition (P = .042). CONCLUSION: CT evaluation of embolization cast position immediately after embolization may constitute an early and reliable tool for predicting permanent fistula occlusion and the prognosis for outcome.     

Combined stent implantation and endosaccular coil placement for treatment of experimental wide-necked aneurysms: a feasibility study in swine.

PURPOSETo assess the feasibility of combining stent implantation in the parent artery with endosaccular coil placement for the treatment of experimentally created wide-necked aneurysms.METHODSWide-necked aneurysms were surgically created on the common carotid artery in 12 swine. A metal stent was endovascularly implanted across each aneurysm neck and its effect documented anigiographically. If the aneurysm remained patent, a microcatheter was introduced into the aneurysm through the stent mesh. Electrically detachable coils were delivered into the aneurysm sac to produce thrombosis.RESULTSAfter stent implantation, one carotid artery thrombosed and two aneurysms spontaneously occluded. In the other 9 cases, coils were deposited through the stent to occlude the aneurysm. Complete aneurysm packing was possible in all 9 cases. The presence of the stent allowed placement of small coils near the aneurysm neck, thus contributing to the safe occlusion of small remnants in the final stages of aneurysm packing.CONCLUSIONThe combination of stent implantation and coil placement is feasible in the treatment of experimental wide-necked saccular aneurysms. The stent maintains patency of the parent artery while allowing aneurysm occlusion by endosaccular coil placement through the stent''s mesh. Occlusion of small aneurysm remnants is possible with no fear of coil hernation or migration into the parent artery. Long-term studies will be necessary before application to treatment of selected intracranial aneurysms.     

兔血管造影的实验研究

目的 改良实验动物兔血管造影的方法,优化血管造影后的止血过程,提高DSA检查的成功率,并且对兔主要的血管的CT三维血管成像和DSA检查进行了初步研究,为兔成像的方法的顺利进行提供了相关经验.方法 新西兰大白兔15只,麻醉后于耳缘静脉置管行CTA检查,测量主要血管的管径并观察相关血管形态和走行方向.解剖腹股沟区,分离股动...     

Technical feasibility of 2D–3D coregistration for visualization of self-expandable microstents to facilitate coil embolization of broad-based intracranial aneurysms: an in vitro study

Introduction  

The use of self-expandable microstents for treatment of broad-based intracranial aneurysms is widely spread. However, poor fluoroscopic visibility of the stents remains disadvantageous during the coiling procedure. Flat detector angiographic computed tomography (ACT) provides high resolution imaging of microstents even though integration of this imaging modality in the neurointerventional workflow has not been widely reported.     

可降解镁合金覆膜支架治疗兔颈总动脉侧壁型动脉瘤可行性研究

目的 评价可降解镁合金覆膜支架治疗兔颈总动脉侧壁型动脉瘤的可行性.方法 20只新西兰大白兔饲养1周后采用间断式外翻缝合法将右侧颈总动脉与静脉囊吻合,构建20枚颈总动脉侧壁型动脉瘤.72 h内分别实施可降解镁合金覆膜支架植入术和Willis覆膜支架植入术.术前、术后即刻、术后3、6、12个月作DSA造影检查,对比动脉瘤闭塞、内漏、血管痉挛、血管损伤、血栓事件、血管闭塞和狭窄等情况.结果 可降解镁合金覆膜支架和Willis覆膜支架各植入10枚,技术成功率为100％.支架植入术后即刻造影显示所有动脉瘤腔完全闭塞,载瘤动脉通畅,可降解镁合金覆膜支架组血管痉挛3例,Willis覆膜支架组血管痉挛1例;术后3、6、12个月复查造影显示动脉瘤完全消失,载瘤动脉通畅.结论 可降解镁合金覆膜支架治疗兔颈总动脉侧壁型动脉瘤是可行的.