Brain aneurysms and arteriovenous malformations: advancements and emerging treatments in endovascular embolization

BACKGROUND AND PURPOSE: Brain aneurysms and vascular malformations can cause cerebral hemorrhages, with devastating consequences for the patients and their families. Since the development of microcatheters and materials used for endovascular embolization, we have witnessed a rapid advancement in the technology and in the number or patients treated with this approach. The aim of this review is to survey recent data relevant to new technologies and emerging treatment strategies in these areas. SUMMARY OF REVIEW: Clinical trials assessing the safety and efficacy of coil embolization for cerebral aneurysms were based on the use of bare platinum, helical coils. Since then, endovascular operators have been testing and using new materials such as bioactive coils, expandable coils, and complex-shaped coils. Based on the data so far obtained, third and fourth generation coil designs are rapidly emerging and will be ready for clinical application in the near future. Balloon- and stent-assisted coil embolization is enabling the treatment of complex, large-neck aneurysms and the vascular reconstruction of lesions previously considered not treatable. New open- and closed-cell designs allow the navigation and deployment of stents in extremely tortuous vessels. With regards to the embolization of vascular malformations, it is possible to safely navigate microcatheters and microwires through very small arteries previously considered not accessible. In addition, embolization materials such as n-butyl cyanoacrylate and ethylene-vinyl alcohol copolymer are now routinely injected to safely reduce or obliterate large and complex arteriovenous malformations and fistulae. CONCLUSIONS: Advancements in technology are rapidly improving the endovascular approach to the treatment of cerebral aneurysms and arteriovenous malformations

Effectiveness of mechanical endovascular thrombectomy in a model system of cerebrovascular occlusion

BACKGROUND AND PURPOSE: A number of thrombectomy devices are currently undergoing clinical evaluation; meanwhile, various novel devices are under investigation. The aims of this study were to quantify flow restoration and the particle size distribution of the effluent pursuant to MET in an in vitro occlusion model. MATERIALS AND METHODS: The model system was composed of 3 elements: an ICA/MCA replica, a clot model with mechanical properties similar to those of thrombi found in patients at risk of stroke, and a pulsatile flow loop. Different thrombectomy mechanisms including mechanical retrieval, aspiration, and waveguide induced cavitation were used. The efficacy end points were recanalization rate and amount of flow restoration. The risk of the embolic shower was assessed to evaluate device safety. RESULTS: The recanalization rates were the following: Merci, 67%; Solitaire, 100%; Penumbra, 83%; Enterprise, 17%; and the waveguide, 0%. In experiments in which recanalization was achieved, the amount of flow restoration for the Merci, Solitaire, and Enterprise devices was 100%, 92%, and 86%, respectively. The mean sizes of generated small and large clot fragments were between 23 and 37 and 215 and 285 mum, respectively, depending on the device used. The Merci device generated the fewest number of large fragments compared with the Penumbra system (P \u3c .05) and Solitaire (not significant). CONCLUSIONS: The risk of embolic shower was influenced by the mechanism of action for the thrombectomy device. Clinically reported recanalization rates for the Solitaire, Penumbra, and Merci devices were nearly identical in this model system, suggesting that this model may provide a predictive tool for preclinical evaluation of MET

Techniques in distal access of wide-necked giant intracranial aneurysms during treatment with flow diversion

BACKGROUND: Accessing the normal distal vessel in treatment of wide-necked giant intracranial aneurysms with flow diversion can be difficult. CASE DESCRIPTION: Through illustrative cases, the authors present several useful techniques in distal access of wide-necked giant aneurysms during flow diversion treatment. Obtaining an optimal projection that separates the outflow limb from the aneurysm is most critical. Each of the three techniques described enabled the distal access to giant intracranial aneurysms during treatment with flow diversion. CONCLUSION: The looped-around technique, balloon-assisted technique, and retrograde access are valuable strategies in crossing the aneurysm if direct distal access cannot be obtained

Risk of distal embolization with stent retriever thrombectomy and ADAPT

BACKGROUND: There is a discrepancy in clinical outcomes and the achieved recanalization rates with stent retrievers in the endovascular treatment of ischemic stroke. It is our hypothesis that procedural release of embolic particulate may be one contributor to poor outcomes and is a modifiable risk. The goal of this study is to assess various treatment strategies that reduce the risk of distal emboli. METHODS: Mechanical thrombectomy was simulated in a vascular phantom with collateral circulation. Hard fragment-prone clots (HFC) and soft elastic clots (SECs) were used to generate middle cerebral artery (MCA) occlusions that were retrieved by the Solitaire FR devices through (1) an 8 Fr balloon guide catheter (BGC), (2) a 5 Fr distal access catheter at the proximal aspect of the clot in the MCA (Solumbra), or (3) a 6 Fr guide catheter with the tip at the cervical internal carotid artery (guide catheter, GC). Results from mechanical thrombectomy were compared with those from direct aspiration using the Penumbra 5MAX catheter. The primary endpoint was the size distribution of emboli to the distribution of the middle and anterior cerebral arteries. RESULTS: Solumbra was the most efficient method for reducing HFC fragments (p \u3c 0.05) while BGC was the best method for preventing SEC fragmentation (p \u3c 0.05). The risk of forming HFC distal emboli ( \u3e 1000 microm) was significantly increased using GC. A non-statistically significant benefit of direct aspiration was observed in several subgroups of emboli with size 50-1000 microm. However, compared with the stent-retriever mechanical thrombectomy techniques, direct aspiration significantly increased the risk of SEC fragmentation (microm) by at least twofold. CONCLUSIONS: The risk of distal embolization is affected by the catheterization technique and clot mechanics

Polyglycolide/polylactide-coated platinum coils for patients with ruptured and unruptured cerebral aneurysms: a single-center experience

BACKGROUND AND PURPOSE: Recanalization of cerebral aneurysm is a limitation of bare platinum coils (BPCs). In a swine aneurysm model, polyglycolide/polylactide (a polymer)-coated platinum coils (Matrix) accelerated clot fibrosis and reduced recanalization rate and aneurysmal volume. We aimed to evaluate the safety of Matrix coils in patients with intracranial aneurysm. METHODS: This is a single-center, prospective study of patients with intracranial aneurysms treated with Matrix alone or in combination with BPCs. Follow-up evaluation included a 1-month clinical evaluation and a 6- and 12-month clinical and angiographic examination. Primary adverse events included death, stroke, and permanent neurological deficits. RESULTS: Between May 2002 and January 2004, 52 patients (range 34 to 79 years of age; 38 females) were treated for 54 aneurysms (size 7.9+/-4.6 mm; neck 3.9+/-1.5 mm; 26 ruptured). Matrix alone was used in 13 aneurysms. In 39, we used a combination of Matrix and BPCs. Twenty-one aneurysms had a 6-month follow-up examination (11 Matrix; 10 Matrix combined with bare platinum), and 11 completed the 12-month follow-up evaluation (Matrix only). Adverse events not related to the procedure were 2 deaths (ruptured basilar aneurysms) and 1 stroke at day 10 postcoiling secondary to vasospasm. Procedure-related adverse events were 2 strokes. At 6-month follow-up (n=21) evaluation, 2 of 3 recanalizations needed retreatment. At 12-month follow-up (n=11), there was no recanalization in patients treated with Matrix alone and no significant reduction in aneurysmal size. CONCLUSIONS: Polyglycolide/polylactide-coated coils had a satisfactory safety profile. Significant aneurysmal size reduction after coiling was not observed

A thromboembolic model for the efficacy and safety evaluation of combined mechanical and pharmacologic revascularization strategies

BACKGROUND AND PURPOSE: Recanalization strategies mediated by intra-arterial fibrinolytic therapy in combination with mechanical clot disruption may be a more effective treatment approach than either therapy used alone. There are few preclinical animal models to evaluate these strategies. Here we report on a model to simultaneously evaluate both of these treatment approaches. METHODS: Allogeneic clot was injected through the 6 F guide catheter after creating \u3e50% luminal stenosis of the common carotid arteries of New Zealand White rabbits. The stenosis was released after 1 h, allowing sufficient time for clot-vessel wall interaction. Occlusion was confirmed and each vessel was assigned to receive either balloon angioplasty alone, intra-arterial tissue plasminogen activator (tPA, Alteplase, Genentech, San Francisco, California, USA), tPA delivery through prototype balloon infusion wire (NIT Therapeutics, Pittsburgh, Pennsylvania, USA), partial stent deployment or partial stent deployment with locally delivered tPA. The negative control received no treatment. RESULTS: In vivo revascularization Thrombolysis in Cerebral Infarction (TICI) score revealed that the balloon infusion wire achieved a stable and higher revascularization score of TICI 2B, with a lower dose of tPA in comparison with other treatment strategies. All treatment strategies resulted in endothelial denudation and exposure of the internal elastic lamina. CONCLUSIONS: The proposed animal model permits reliable and consistent thromboembolic occlusion of the target vasculature and allows for an assessment of both pharmacologic and mechanical revascularization strategies for acute ischemic stroke

Porcine brachial artery tortuosity for in vivo evaluation of neuroendovascular devices

We report a novel model of arterial tortuosity in the porcine brachial artery for testing of endovascular devices in the flexed forelimb position. This provides an ideal vascular territory for an in vivo assessment of guidewires, microcatheters, and endovascular implants because it closely mimics the challenging curvature at the carotid siphon

Closed-cell stent for coil embolization of intracranial aneurysms: clinical and angiographic results

BACKGROUND AND PURPOSE: Recanalization is observed in 20-40% of endovascularly treated intracranial aneurysms. To further reduce the recanalization and expand endovascular treatment, we evaluated the safety and efficacy of closed-cell SACE. MATERIALS AND METHODS: Between 2007 and 2010, 147 consecutive patients (110 women; mean age, 54 years) presenting at 2 centers with 161 wide-neck ruptured and unruptured aneurysms were treated by using SACE. Inclusion criteria were wide-neck aneurysms ( \u3e 4 mm or a dome/neck ratio RESULTS: Eighteen aneurysms (11%) were treated following rupture. Procedure-related mortality and permanent neurologic deficits occurred in 2 (1.4%) and 5 patients (3.4%), respectively. In total, 7 patients (4.8%) died, including 2 with reruptures. Of the 140 surviving patients, 113 (80.7%) patients with 120 aneurysms were available for follow-up neurologic examination at a mean of 11.8 months. An increase in mRS score from admission to follow-up by 1, 2, or 3 points was seen in 7 (6.9%), 1 (1%), and 2 (2%) patients, respectively. Follow-up angiography was performed in 120 aneurysms at a mean of 11.9 months. Recanalization occurred in 12 aneurysms (10%), requiring retreatment in 7 (5.8%). Moderate in-stent stenosis was seen in 1 (0.8%), which remained asymptomatic. CONCLUSIONS: This series adds to the evidence demonstrating the safety and effectiveness of SACE in the treatment of intracranial aneurysms. However, SACE of ruptured aneurysms and premature termination of antiplatelet treatment are associated with increased morbidity and mortality

Aneurysm permeability following coil embolization: packing density and coil distribution

BACKGROUND: Rates of durable aneurysm occlusion following coil embolization vary widely, and a better understanding of coil mass mechanics is desired. The goal of this study is to evaluate the impact of packing density and coil uniformity on aneurysm permeability. METHODS: Aneurysm models were coiled using either Guglielmi detachable coils or Target coils. The permeability was assessed by taking the ratio of microspheres passing through the coil mass to those in the working fluid. Aneurysms containing coil masses were sectioned for image analysis to determine surface area fraction and coil uniformity. RESULTS: All aneurysms were coiled to a packing density of at least 27%. Packing density, surface area fraction of the dome and neck, and uniformity of the dome were significantly correlated (p \u3c 0.05). Hence, multivariate principal components-based partial least squares regression models were used to predict permeability. Similar loading vectors were obtained for packing and uniformity measures. Coil mass permeability was modeled better with the inclusion of packing and uniformity measures of the dome (r(2)=0.73) than with packing density alone (r(2)=0.45). The analysis indicates the importance of including a uniformity measure for coil distribution in the dome along with packing measures. CONCLUSIONS: A densely packed aneurysm with a high degree of coil mass uniformity will reduce permeability

Quantitative analysis of high-resolution, contrast-enhanced, cone-beam CT for the detection of intracranial in-stent hyperplasia

BACKGROUND: Intracranial in-stent hyperplasia is a stroke-associated complication that requires routine surveillance. OBJECTIVE: To compare the results of in vivo experiments to determine the accuracy and precision of in-stent hyperplasia measurements obtained with modified C-arm contrast-enhanced, cone-beam CT (CE-CBCT) imaging with those obtained by \u27gold standard\u27 histomorphometry. Additionally, to carry out clinical analyses comparing this CE-CBCT protocol with digital subtraction angiography (DSA). METHODS: A non-binned CE-CBCT protocol (VasoCT) was used that acquires x-ray images with a small field-of-view and applies a full-scale reconstruction algorithm providing high-resolution three-dimensional (3D) imaging with 100 microm isotropic voxels. In an vivo porcine model, VasoCT cross-sectional area measurements were compared with gold standard vessel histology. VasoCT and DSA were used to calculate in-stent stenosis in 23 imaging studies. RESULTS: Porcine VasoCT cross-sectional stent, lumen, and in-stent hyperplasia areas strongly correlated with histological measurements (r(2)=0.97, 0.93, 0.90; slope=1.14, 1.07, and 0.76, respectively; p\u3c0.0001). Clinical VasoCT percentage stenosis correlated well with DSA percentage stenosis (r(2)=0.84; slope=0.76), and the two techniques were free of consistent bias (Bland-Altman, bias=3.29%; 95% CI -14.75% to 21.33%). An illustrative clinical case demonstrated the advantages of VasoCT, including 3D capability and non-invasive IV contrast administration, for detection of in-stent hyperplasia. CONCLUSIONS: C-arm VasoCT is a high-resolution 3D capable imaging technique that has been validated in an animal model for measurement of in-stent tissue growth. Successful clinical implementation of the protocol was performed in a small case series. already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions