Real-time MR properties of particulate embolic agents tested in a dynamic flow model

PURPOSE: Interventional magnetic resonance (MR)-guided transcatheter embolization could potentially limit radiation exposure and improve visualization of target organs. The feasibility of monitoring injection and distribution of embolic agents was assessed in a dynamic flow model with real-time MR imaging. MATERIALS AND METHODS: MR-compatible flow models were constructed with use of clear plastic chambers containing 170-microm polyethylene tubular filters. Gadolinium (Gd)-impregnated polyvinyl alcohol (PVA) particles (355-500 and 500-710 microm in size) and Gd-impregnated microspheres (Embospheres, 300-500 and 500-700 microm in size) were injected into the flow circuit under real-time dynamic T1-weighted fast field echo guidance at four images per second. A dynamic steady-state free precession sequence at four images per second was used to monitor the injection of unmodified Embo-Gold 700-900- microm particles. High-resolution scans were obtained before and after each particle injection. RESULTS: MR signal enhancement on the dynamic T1-weighted fast field echo sequence was visible during the injection of Gd-impregnated microspheres. Gd-impregnated PVA particles were not detected by this sequence. After injection, microsphere and PVA localization to the filter chambers was confirmed by the high-resolution scans. On the high-resolution sequences, relative MR signal enhancement of the microspheres was higher than that of the PVA particles. The Embo-Gold particles were minimally detectable on the dynamic sequence and undetectable by the high-resolution scan. After particle injection, direct inspection of the filter chamber showed trapping of all particle types and sizes. CONCLUSION: Real-time MR tracking of Gd-impregnated embolic agents is possible in vitro.     

The porous, guidewire-directed, detachable aneurysm liner: a new concept in the endovascular treatment of intracranial aneurysms.

A new device for the endovascular treatment of aneurysms is described. It consists of a guidewire-directed porous liner or bag, detachably mounted on a microcatheter and designed to be inserted into an aneurysm and to be filled with detachable coils or other embolic agents. Several prototypes have been made. Preliminary in vitro and in vivo experiments have demonstrated its behavior in relatively wide-necked aneurysms.     

原发性肝癌介入治疗的药代动力学研究现状

近年来,栓塞剂成为TACE治疗肝癌的讨论热点之一.各种各样的栓塞剂用来提高TACE的疗效,从不规则型到微球,再到载药微球,目的 在于提高肿瘤局部化疗药浓度,降低外周血药浓度,增加抗肿瘤的疗效,降低化疗药的毒性.本文就肝癌不同介入治疗方法的药代动力学变化特性进行回顾.     

不同栓塞剂治疗大咯血的对比研究

目的:观察不同栓塞剂对复发率的影响,探讨并比较不同栓塞剂在支气管动脉栓塞治疗大咯血中的疗效.方法:129例经选择性或超选择性支气管动脉栓塞治疗的大咯血患者,单纯明胶海绵栓塞63例,PVA颗粒联合明胶海绵栓塞组37例,KMG微球联合明胶海绵栓塞组38例.随访16个月,复发病例经再次栓塞.结果:即刻止血率99.2%,复发31例.GS组复发21例,含PvA组复发3例,含KMG组复发5例;1年中总复发率为24.0%;3组复发率差异有显著性意义.结论:合理的选用栓塞物质可有效的降低咯血患者的复发率,PVA颗粒及KMG微球在支气管动脉栓塞治疗大咯血中安全、高效,能有效的减免复发率,值得临床推荐.     

温敏型液体栓塞材料的实验研究

目的合成一种新型温度敏感性液体栓塞材料并探讨其栓塞脑动静脉畸形(arteriovenous malformation,AVM)的可能性。方法应用氮-异丙基丙烯酰胺(N-isopropylacry lamide,NIPAM)和氮-正丙基丙烯酰胺(N-n-propylacrylamide,NNPAM)合成共聚物,进行物理性质测定和体外AVM模型栓塞试验。结果共聚物具有低临界溶解温度(lowercritical solubletem perature,LCST),具有水溶性和非粘附性特点,能成功栓塞体外AVM模型。结论共聚物为一种脑AVM血管内栓塞治疗的新型液体栓塞材料,可用于进一步动物实验。     

Thrombin-soaked embolization coils: the effect on whole blood clotting time.

Embolization coils are well established as embolic agents for the treatment of various conditions. Several authors have commented on the increased 'thrombogenicity' of coils following soaking in thrombin solutions. We have carried out an in vitro study, carefully measuring the effect on whole blood clotting time (WBCT), of soaking coils in thrombin solutions of different concentrations (100, 200, 400, 1000 U/ml). Untreated steel coils are shown to have clot promoting activity (CPA) in vitro, reducing WBCT from 14.85 min to 5.53 min. Passing the coils down a saline-filled catheter slightly reduces their CPA, but not significantly (p = 0.21). With thrombin concentrations above 100 U/ml, a significant reduction in WBCT is recorded, but although there is a trend of increasing CPA with increasing thrombin concentration from 200-1000 U/ml, a plateau in WBCT is seen, and the difference is not significant. It therefore appears that the clot promoting activity of embolic coils is significantly increased by soaking them in a relatively weak thrombin solution. The use of such a solution (e.g. 200 U/ml) in vivo would have obvious value in limiting the potential systemic effects of thrombin.     

新型温度敏感性液体栓塞材料的实验研究

目的探讨一种新型温度敏感性液体栓塞材料的合成及其栓塞脑动静脉畸形(AVM)的可行性。方法应用氮异丙基丙烯酰胺(N isoprophlacrylamide ,NIPAM)和氮正丙基丙烯酰胺(N n propylacrylamide ,NNPAM)合成共聚物,进行物理性质分析和体外AVM模型栓塞试验。结果共聚物具有低临界溶解温度及水溶性和非粘附性的特点,能成功栓塞体外AVM模型。结论共聚物为一种新型液体栓塞材料,可用于进一步动物实验     

Lingual artery bifurcation aneurysms for training and evaluation of neurovascular devices

We present a canine lingual artery bifurcation aneurysm and assess its value for training in endovascular techniques and testing new embolic agents. The experimental aneurysm described herein mirrors human bifurcation aneurysms, and with this model, we sought to reproduce endovascular technical difficulties. However, the lesions created in this canine model did not show angiographic or histologic evidence of aneurysmal recurrence. We conclude that this model may be useful for training in endovascular techniques, but because of the lack of sufficient aneurysmal recurrence, it is not suitable for evaluating new embolic agents.     

New Alcohol and Onyx Mixture for Embolization: Feasibility and Proof of Concept in Both In Vitro and In Vivo Models

Onyx and ethanol are well-known embolic and sclerotic agents that are frequently used in embolization. These agents present advantages and disadvantages regarding visibility, injection control and penetration depth. Mixing both products might yield a new product with different characteristics. The aim of this study is to evaluate the injectability, radiopacity, and mechanical and occlusive properties of different mixtures of Onyx 18 and ethanol in vitro and in vivo (in a swine model). Various Onyx 18 and ethanol formulations were prepared and tested in vitro for their injectability, solidification rate and shrinkage, cohesion and occlusive properties. In vivo tests were performed using 3 swine. Ease of injection, radiopacity, cohesiveness and penetration were analyzed using fluoroscopy and high-resolution CT. All mixtures were easy to inject through a microcatheter with no resistance or blockage in vitro and in vivo. The 50%-ethanol mixture showed delayed copolymerization with fragmentation and proximal occlusion. The 75%-ethanol mixture showed poor radiopacity in vivo and was not tested in vitro. The 25%-ethanol mixture showed good occlusive properties and accepted penetration and radiopacity. Mixing Onyx and ethanol is feasible. The mixture of 25% of ethanol and 75% of Onyx 18 could be a new sclero-embolic agent. Further research is needed to study the chemical changes of the mixture, to confirm the significance of the added sclerotic effect and to find out the ideal mixture percentages.     

经导管肾动脉节段性栓塞治疗肾动静脉畸形

目的：探讨经导管肾动脉节段性栓塞治疗肾动静脉畸形的栓塞材料及其效果。方法：9例因肾动静脉畸形（先天性者8例，获得性者1例）引起大量血尿患者，施行经导管肾动脉节段性栓塞治疗10次，栓塞材料为无水乙醇、聚乙烯醇颗粒、异丁基-2-氰基丙烯酸酯和弹簧圈。9例患者术后随访观察10-56个月。结果：9例患者栓塞术后肾动脉造影显示畸形血管完全闭塞，3d内血尿消失。随访期间，9例患者中，只有1例单纯应用弹簧圈栓塞患者术后6个月血尿复发，血管造影证实为侧支血管形成导致畸形血管再通，改行无水乙醇及弹簧圈栓塞，术后18个月血尿未再复发。9例患者均无严重并发症发生。结论：经导管肾动脉节段性栓塞是治疗肾动静脉畸形的安全有效的方法，栓塞材料以无水乙醇和弹簧 圈联合栓塞为最佳。     

Principles and techniques of transcatheter embolotherapy for peripheral vascular lesions

Transcatheter embolotherapy (TCE), a common procedure for interventional radiologists, comprises transcatheter delivery of embolic agents into target vessels in order to eliminate lesions or lesion-associated symptoms. Good knowledge of delivery catheters and embolic agents is essential to optimize embolization techniques and to obtain the desired therapeutic outcomes. In this review, we describe the principles and techniques of TCE for peripheral arterial and venous lesions featuring visceral aneurysms, peripheral and pulmonary arteriovenous malformations (AVMs), and varicoceles. This work was presented as an educational lecture at the 64^th JRS meeting (April 2005) in Yokohama.     

Initial Clinical Experience Using the Amplatzer Vascular Plug

Background and purpose The Amplatzer Vascular Plug (AVP) is a self-expanding nitinol wire mesh vascular embolization device derived from the Amplatz septal occluder. We assessed the results of vascular embolization obtained using the AVP. Methods A retrospective review was carried out of 23 consecutive cases of vascular embolization using the AVP in a variety of different clinical settings. The AVP was chosen to have a diameter approximately 30–50% greater than the target vessel. The device was delivered via an appropriately sized guide catheter and was released when satisfactorily positioned. Additional embolic agents were used in some cases. Results All target vessels were successfully occluded with no device malpositioning or malfunction. In 14 (61%) patients the AVP was the sole embolic material. In the remaining patients additional agents were used, particularly in preoperative embolization of highly vascular renal tumors. The AVP does not cause instantaneous thrombosis and in high-flow situations thrombosis typically takes up to 15 min. Conclusion The AVP is a safe, effective embolization device that provides a useful adjunct to the therapeutic armamentarium. It is particularly suited to the treatment of short high-flow vessels where coil migration and catheter dislodgment might occur. In the majority of cases no additional embolic agents are necessary but it may take up to 15 min for complete thrombosis to occur.     

Evaluation of three embolic agents in pig rete

In ongoing research into potential embolic agents, three substances were evaluated for their effectiveness in occluding the pig rete. Selective injection of these agents produced varying degrees of occlusion, with the most effective a microfibrillar collagen hemostat in a 33% ethanol solution. Angiostat, a collagen particulate, did not produce rete occlusion, and all pigs injected with it developed adverse effects, including coma and apnea. Tisseel, a tissue sealant, produced partial rete occlusion, but was uniformly difficult to manage through long catheters, and its use was discontinued. Microfibrillar collagen hemostat with ethanol appears to have the greatest potential as an embolic agent in low-flow structures.     

n-Butyl 2-cyanoacrylate--substitute for IBCA in interventional neuroradiology: histopathologic and polymerization time studies

Despite the development of new alternative embolic agents, the endovascular treatment of brain arteriovenous malformations continues to frequently require the use of cyanoacrylic glue, especially in situations where particulate or sclerosing agents are ineffective, such as when flow is very rapid or fistulous. Because isobutyl 2-cyanoacrylate (IBCA), the most commonly used embolic glue, is no longer available or manufactured, a real need exists for an alternative fast polymerizing agent. In vivo and in vitro studies were performed to compare IBCA with n-butyl 2-cyanoacrylate (NBCA, supplied as Histoacryl Blue), a tissue adhesive approved for surgical use in some countries. Polymerization times in static plasma were compared, and the effect of the addition of iophendylate oil or glacial acetic acid on polymerization was assessed. Polymerization times in vivo were compared after intraarterial injection into the internal carotid artery in pigs using a standardized technique. The histopathologic reactions to each glue in the embolized pig rete were assessed and compared over a period of 0-60 days after embolization. Our results show that while NBCA polymerization is demonstrably faster than IBCA in vitro, intraarterial injections of each glue show no significant difference in polymerization times. Like IBCA, NBCA polymerization can be predictably prolonged by the addition of oil or glacial acetic acid, though the effect is less for NBCA. Histopathologic reactions were similar, with acute vasculitis observed, becoming chronic and granulomatous after about 1 month. Both glues showed frequent foci of extravascular extrusion through the embolized rete and recanalization of previously occluded embolized vessels. We conclude that NBCA has clinical and biologic behaviors similar to IBCA, and therefore should be an acceptable alternative to IBCA for intravascular use.     

Middle Meningeal Artery Embolization with Liquid Embolic Agents for Chronic Subdural Hematoma: A Systematic Review and Meta-analysis

PurposeTo assess the efficacy and safety of middle meningeal artery (MMA) embolization with liquid embolic agents and the outcomes of patients following this procedure.Materials and MethodsA review of the literature was conducted to identify studies investigating the efficacy and safety of MMA embolization with liquid embolic agents in patients with chronic subdural hematoma (cSDH) in PubMed, Scopus, Embase, and Web of Science. The keywords “liquid embolic agent,” “middle meningeal artery,” “cSDH,” and “embolization” as well as their synonyms were used to build up the search strategy. The R statistical software and random-effects model were used for analysis. Heterogeneity was reported as I², and publication bias was calculated using the Egger test.ResultsOf 628 articles retrieved, 14 studies were eligible to be included in this study. Data of 276 patients were analyzed. n-Butyl cyanoacrylate and ethylene vinyl alcohol copolymer were the most commonly used embolic agents. This study revealed a pooled mortality rate of 0% (95% confidence interval [CI], 0.00%–100%), recurrence and failure rate of 3% (95% CI, 1%–10%), reoperation/reintervention rate of 4% (95% CI, 2%–12%), rate of size decrease of 94% (95% CI, 79%–98%), technical success rate of 100% (95% CI, 76%–100%), and adverse event rate of 1% (95% CI, 0.00%–4%).ConclusionsWith low mortality, recurrence, reoperation, and adverse event rates and a remarkable decrease in the size of hematomas, MMA embolization with liquid embolic agents may be considered a safe and effective treatment option in patients in whom surgical intervention has previously failed and as an alternative to conventional treatments.     

Functional MR of the kidney.

A bolus injection of Gadopentetate Dimeglumine with dynamic gradient echo MR imaging has allowed for the visualization of normal and abnormal renal function. Following an injection of gadopentetate dimeglumine, NMR T1 relaxation times obtained on serial collections of serum and urine at timed intervals were used to derive the glomerular filtration rate. The merger of dynamic contrast-enhanced MRI with an in vitro NMR-derived GFR provides for assessment of renal function without the use of radioactive agents.     

Biocompatibility and Recanalization Characteristics of Hydrogel Microspheres with Polyzene-F as Polymer Coating

The objective of this study was to evaluate inflammatory response and recanalization after embolization with a new spherical embolic agent based on a core and shell design with a hydrogel core of polymethylmethacrylate (PMMA) and a Polyzene-F nanoscale coating in a porcine kidney model. Thirty-six minipigs were enrolled for superselective renal embolization. Polyzene-F-coated PMMA particles and uncoated PMMA particles with a diameter of 300-600 mum were used. Either 4 or 12 weeks post-embolization, arteriography of the embolized kidneys was performed and then compared with pre- and immediate post-embolization arteriograms using a specific recanalization score to determine the extent of recanalization. Using a microscopic inflammation score (Banff classification), the embolized organs were examined for local inflammatory effects which occurred in response to the embolic agent. In Polyzene-F-coated particles, the Banff classification showed an average inflammation score of 0.26 +/- 0.58 at 4 weeks and of 0.08 +/- 0.28 at 12 weeks. In uncoated particles, the Banff score measured 0.37 +/- 0.6 at 4 weeks, which was higher, but without a statistically significant difference. According to the recanalization score used in this study, mild angiographic recanalization was evident in all groups, without statistically significant differences (3.0 +/- 0.71 in coated particles, 3.09 +/- 0.81 in uncoated particles; p = 0.74). We conclude that both uncoated hydrogel particles and Polyzene-F-coated embolic agents triggered virtually no inflammatory response and effectively occluded target arteries. This study demonstrates good biocompatibility of the new embolic material. As in other spherical embolic agents, recanalization can occur to some degree.     

Identifying the Ideal Target Vessel Size for Bariatric Embolization: Histologic Analysis of Swine and Human Gastric Fundi

This study aimed to identify the ideal arteriole size to target in bariatric embolization, with the goal of maximizing weight loss efficacy while maintaining patient safety. Although all published clinical trials of bariatric embolization have used embolic microspheres that were at least 300 μm in diameter, optimal weight loss outcomes have been achieved safely in swine using 50-μm embolics. Human fundal remnants from bariatric surgery were compared with swine fundal sections after bariatric embolization with 50-μm embolic microspheres to assess the ideal fundal vessel size for bariatric embolization. In swine, the 50-μm embolic microspheres deposited in the luminal half of the submucosa with a mean arteriole size of 49 μm ± 30. The mean arteriole diameter in the corresponding submucosal layer of the human gastric fundi was 40 μm ± 30. These measurements may inform future clinical trials and direct the development of embolic agents for bariatric embolization.     

Comparison of Embolic Agents Used in Uterine Artery Embolisation: A Systematic Review and Meta-Analysis

Purpose

This study was designed to undertake systematic review and meta-analysis of published comparative trials comparing embolic agents used in uterine artery embolisation (UAE) for uterine leiomyomata.

Methods

Systematic literature searches were performed in MEDLINE, Embase, PubMed, and Cochrane Central databases from database inception to July 2012. Randomised and nonrandomised trials comparing two or more embolic agents used in UAE were included. Assessment included five widely used embolic agents: nonspherical polyvinyl alcohol (PVA) (Contour PVA, Boston Scientific or PVA Cook Medical); spherical PVA (Contour SE, Boston Scientific); acrylamido PVA (Beadblock, Biocompatibles, Terumo); tris-acryl gelatin microspheres (TAGM) (Embospheres, Merit Medical Inc); and polyzene-F hydrogel microspheres (Embozenes, CeloNova Biosciences). Outcomes assessed included: quality of life (QOL), assessment, magnetic resonance imaging (MRI), uterine and fibroid volumes and degrees of MRI fibroid enhancement and devascularisation. A total of 262 citations were reviewed with 5 randomised, controlled trials involving 295 women and 5 non-RCTs involving 617 women included.

Results

No evidence of superiority of any embolic agent was demonstrated. Meta-analysis was performed between TAGM (Embospheres) and spherical PVA microspheres. Two RCTs found a trend toward greater uterine and dominant fibroid volume reductions with Embospheres but the combined differences were not statistically significant (p = 0.78 and p = 0.94 respectively). Embospheres demonstrated greater percentage fibroid devascularisation than spherical PVA (p = 0.039).

Conclusions

This study confirms that the current evidence demonstrates superiority of Embospheres over spherical PVA but no reported differences in outcomes between any of the other agents. Comparison of embolic agents was limited by lack of RCT data and further research is warranted.     

Endovascular treatment of scalp arteriovenous fistulas associated with a large varix

Ten patients with scalp arteriovenous fistulas associated with a large varix (cirsoid aneurysms) were treated with a combination of interventional neuroradiologic procedures. These procedures included transarterial embolization, transarterial embolization followed by surgical excision, and two new methods of treatment of cirsoid aneurysms: transvenous embolization and direct puncture of the fistula for embolization. The embolic materials included liquid adhesive agents, particulate agents, detachable balloons, and wire coils. The embolization was performed to lodge the embolic agents in the fistula or proximal draining vein, not just the feeding vessels. Surgery was performed in two cases to remove a small residual nidus of fistula that could not be completely treated with intravascular embolization. With the use of these forms of treatment, cures were obtained in seven patients, and clinical and angiographic improvement was achieved in three patients. No major morbidity, blood loss, or mortality occurred during the treatment of these patients. The follow-up period ranged from 1 month to 8 years.