Comparing N-hexyl cyanoacrylate (Magic Glue) and N-butyl cyanoacrylate (NBCA) for neurovascular embolization using the pressure cooker technique: An experimental study in swine.

BACKGROUND: The pressure cooker (PC) technique uses a second microcatheter to produce a proximal occlusion to prevent the reflux of liquid embolic agent (LEA) injected through a more distal microcatheter, and can be used to treat arteriovenous malformations and dural arteriovenous fistulae. The liquid embolic Magic Glue (MG) (N-hexyl cyanoacrylate (NHCA)) has been introduced as an alternative to N-butyl cyanoacrylate (NBCA). Our goals were to compare the extent of embolization of rete mirabile with or without the PC technique using NBCA or MG, and to compare the proximal occlusions obtained with MG or NBCA while using the PC technique in a renal arterial model. METHODS: Rete mirabile were embolized with (n = 4) and without (n = 4) the PC technique, using MG (n = 4) or NBCA (n = 4). A renal arterial model was then used to study the characteristics of the MG plug (n = 10) used for the PC technique, and resistance to catheter withdrawal as compared to NBCA (n = 4). Specimens were analyzed macro- and microscopically and compared to angiographic results. RESULTS: Extent of rete embolization with CYA agents was not significantly greater when using the PC technique. Results were similar with both types of cyanoacrylate (p = 0.657). The force necessary to withdraw the microcatheter was less with MG than with NBCA (p = 0.035). CONCLUSION: MG was similar to NBCA in extent of rete embolization. Less traction force was necessary to withdraw trapped non-detachable microcatheters using MG compared to NBCA.

Testing the Medina embolization device in experimental aneurysms.

OBJECTIVE: The Medina embolization device (MED) is a novel, braided self-expanding endovascular device designed to occlude aneurysms by constructing an in situ intrasaccular flow diverter. Although a single device can be positioned at the neck of simple spherical in vitro aneurysms, the best way to occlude more complex in vivo aneurysms (using multiple MEDs or a combination of MEDs and platinum coils) is currently unknown. METHODS: Fifty-two aneurysms of 3 different types were created in 31 canines, yielding 48 patent aneurysms. Treatments were randomly allocated by drawing lots: group 1, MEDs alone (n = 16); group 2, MEDs plus standard platinum coils (n = 16); and group 3, control aneurysms treated with coils alone (n = 16). Angiographic results were scored and compared immediately following treatment completion and at 3 months. Specimens were photographed and the extent of neointimal closure of the aneurysmal neck scored, followed by histopathological analyses. RESULTS: Angiographic scores of 0 or 1 (occlusion or near occlusion) were initially obtained in 2 of 16 (12.5%, 95% CI 1.6%-38.3%) group 1 (MEDs alone), 3 of 16 (18.7%, 95% CI 4%-45.6%) group 2 (MEDs plus coils), and 10 of 16 (62.5%, 95% CI 35.4%-84.8%) group 3 (coils alone) aneurysms (p = 0.005). At 3 months, scores of 0 or 1 were found in 11 of 16 (68.7%, 95% CI 41.3%-89.0%) group 1, 9 of 16 (56.2%, 95% CI 29.9%-80.2%) group 2, and 8 of 16 (50%, 95% CI 24.7%-75.3%) group 3 aneurysms (p = 0.82). Neointimal scores were similar for the 3 treated groups (p = 0.66). CONCLUSION: Endovascular treatment of experimental aneurysms with MEDs or MEDs and coils showed angiographic occlusion and neointimal scores at 3 months that were similar to those achieved with standard platinum coiling.

Shear wave elasticity imaging for residual endoleak and thrombus characterisation after endoleak embolisation following endovascular aneurysm repair: a canine animal study.

BACKGROUND: To evaluate residual endoleak and thrombus organisation with shear wave imaging (SWI) after endoleak embolisation through an animal study. METHODS: This prospective experimental study involved eight dogs with creation of 16 iliac aneurysms and type I endoleak after endovascular aneurysm repair (EVAR). Embolisation agents were injected into the sac to seal endoleak. SWI and colour flow Doppler ultrasound (DUS) were performed at implantation, one week, and one and three months after implantation; for three dogs, SWI and DUS were also performed six months after implantation. Digital subtraction angiography and contrast-enhanced computed tomography were performed at sacrifice. Macroscopic and histopathological analyses were processed to identify regions of interest (ROIs) for endoleak, fresh thrombus, organised thrombus and embolisation agent, where SWI elasticity moduli were compared. RESULTS: At sacrifice, nine aneurysms had residual endoleak, while seven were sealed. Ten had a fresh and 15 had an organised thrombus. SWI was able to detect all endoleaks, including two cases undetected with DUS. Elasticity moduli of 0.2 kPa ± 0.1 kPa (mean ± SD), 9.5 kPa ± 3.3 kPa, 48.1 kPa ± 21.3 kPa and 44.9 kPa ± 23.7 kPa were found in the ROIs positioned in endoleaks, fresh thrombi, organised thrombi and embolisation agent, respectively. Elasticity values of endoleak and fresh thrombus were lower than those of organised thrombi and embolisation agent (p < 0.001). Stiffness of fresh thrombus at one week (8.7 kPa ± 3.6 kPa) increased at three months (30.2 kPa ± 13.8 kPa), indicating thrombus maturation (p < 0.001). CONCLUSIONS: In a dog model of iliac EVAR, SWI was able to identify endoleak, thrombus maturation and embolising agents after endoleak embolisation.

Re-treatment of residual aneurysms after flow diversion: An experimental study.

Aim Flow diverters are increasingly used to treat aneurysms, but treatment is not always effective. The management of aneurysms that fail to occlude following flow diversion is problematic. We aimed to reproduce failures in an animal model and study re-treatment with additional flow diverters alone or with flow diverters and liquid embolic agent. Material and methods Twenty wide-necked aneurysms were created at the carotid-lingual bifurcation in 10 dogs, and were treated with flow diverters 4-6 weeks later. Follow-up angiography was performed at three months. Suitable residual aneurysms were randomly allocated: re-treatment with flow diverters alone ( n = 6), or with the injection of liquid embolic between two layers of flow diverters ( n = 4) or no re-treatment ( n = 2). Angiography was repeated three months later, followed by euthanasia, photography and pathology. Results Patent wide-necked aneurysms were produced in 17/20 attempts (85%); three months after flow diversion there were 15/17 (88%) residual aneurysms. In three cases, re-treatment was not possible because the flow diverter had prolapsed into the aneurysm, leaving 12 aneurysms to study. Re-treated aneurysms showed improved angiographic results at six months (median score of 2; P = 0.03), but residual aneurysms were present in all cases. Parent artery occlusion occurred in two aneurysms treated with flow diverter plus liquid embolic. At pathology, aneurysms were only partially filled with thrombus; leaks through the flow diverters were found in the neointima connecting the arterial lumen to residual aneurysms. Conclusion Re-treatment of residual flow-diverted experimental aneurysms with additional flow diverters did not lead to aneurysm occlusion.

Flow diversion: what can clinicians learn from animal models?

INTRODUCTION: Flow diversion is increasingly used for treating intracranial aneurysms. This article aims to review the evidence obtained from animal models and summarizes the findings that might be of clinical interest. METHODS: From a systematic review of studies published between 2000 and 2016, we extracted the data on the following questions: What roles do aneurysm dimension, morphology, and vascular geometry have on success of flow diversion? What characteristics of a flow diverter can influence aneurysm occlusion? What are the risk factors for jailed branch occlusion? RESULTS: Flow diversion has been shown to be less effective in occluding large aneurysms with wide or undefined necks, as compared to smaller aneurysms with narrower necks. Straight sidewall aneurysms were more likely to occlude after flow diversion than curved sidewall aneurysms or bifurcation aneurysms with branches originating from the neck or the fundus. The main characteristics of devices that may impact on the success of flow diversion are porosity and pore-density, but challenging aneurysm models were not better occluded with devices of lower porosity. Porosity is not uniform when devices deform to adapt to local in vivo anatomy when deployed. Neointima formation on devices correlates with low porosity. Branches are rarely occluded when they are jailed, but persistent branch flow may prevent aneurysm occlusion. CONCLUSION: Experimental models may help anticipate clinical results of flow diversion.

Bipolar radiofrequency ablation of aneurysm remnants after coil embolization can improve endovascular treatment of experimental bifurcation aneurysms.

OBJECTIVE Endovascular treatment of aneurysms may result in incomplete initial occlusion and aneurysm recurrence at angiographic follow-up studies. This study aimed to assess the feasibility and efficacy of bipolar radiofrequency ablation (RFA) of aneurysm remnants after coil embolization. METHODS Bipolar RFA was accomplished using the coil mass as 1 electrode, while the second electrode was a stent placed across the aneurysmal neck. After preliminary experiments and protocol approval from the Animal Care committee, wide-necked bifurcation aneurysms were constructed in 24 animals. Aneurysms were allocated to 1 of 3 groups: partial intraoperative coil embolization, followed by RFA (n = 12; treated group) or without RFA (n = 6; control group 1); or attempted complete endovascular coil embolization 2-4 weeks later (n = 6; control group 2). Angiographic results were compared at baseline, immediately after RFA, and at 12 weeks, using an ordinal scale. Pathological results and neointima formation at the neck were compared using a semiquantitative grading scale. RESULTS Bipolar RFA was able to reliably target the aneurysm neck when the coil mass and stent were used as electrodes. RFA improved angiographic results immediately after partial coiling (p = 0.0024). Two RFA-related complications occurred, involving transient occlusion of 1 carotid artery and 1 hemorrhage from an adventitial arterial blister. At 12 weeks, angiographic results were improved with RFA (median score of 0), when compared with controls (median score of 2; p = 0.0013). Neointimal closure of the aneurysm neck was better with RFA compared with controls (p = 0.0003). CONCLUSIONS Bipolar RFA can improve results of embolization in experimental models by selectively ablating residual lesions after coil embolization.

Abdominal aortic aneurysm follow-up by shear wave elasticity imaging after endovascular repair in a canine model.

OBJECTIVES: To investigate if shear wave imaging (SWI) can detect endoleaks and characterize thrombus organization in abdominal aortic aneurysms (AAAs) after endovascular aneurysm repair. METHODS: Stent grafts (SGs) were implanted in 18 dogs after surgical creation of type I endoleaks (four AAAs), type II endoleaks (13 AAAs) and no endoleaks (one AAA). Color flow Doppler ultrasonography (DUS) and SWI were performed before SG implantation (baseline), on days 7, 30 and 90 after SG implantation, and on the day of the sacrifice (day 180). Angiography, CT scans and macroscopic tissue sections obtained on day 180 were evaluated for the presence, size and type of endoleaks, and thrombi were characterized as fresh or organized. Endoleak areas in aneurysm sacs were identified on SWI by two readers and compared with their appearance on DUS, CT scans and macroscopic examination. Elasticity moduli were calculated in different regions (endoleaks, and fresh and organized thrombi). RESULTS: All 17 endoleaks (100 %) were identified by reader 1, whereas 16 of 17 (94 %) were detected by reader 2. Elasticity moduli in endoleaks, and in areas of organized thrombi and fresh thrombi were 0.2 ± 0.4, 90.0 ± 48.2 and 13.6 ± 4.5 kPa, respectively (P < 0.001 between groups). SWI detected endoleaks while DUS (three endoleaks) and CT (one endoleak) did not. CONCLUSIONS: SWI has the potential to detect endoleaks and evaluate thrombus organization based on the measurement of elasticity. KEY POINTS: • SWI has the potential to detect endoleaks in post-EVAR follow-up. • SWI has the potential to characterize thrombus organization in post-EVAR follow-up. • SWI may be combined with DUS in post-EVAR surveillance of endoleak.

Fatal arterial rupture during angioplasty of a flow diverter in a recurrent, previously Y-stented giant MCA bifurcation aneurysm.

BACKGROUND AND PURPOSE: A patient with a previously Y-stented giant left middle cerebral artery (MCA) bifurcation aneurysm returned with a recurrence. MATERIALS AND METHODS: A flow diverter (FD) was deployed through one limb of the high-porosity Y-stenting construction. The proximal FD failed to expand and an attempt at balloon angioplasty led to fatal rupture of the MCA. RESULTS: Autopsy demonstrated subarachnoid hemorrhage, vessel rupture and fracture of the proximal high-porosity stent. Microscopic photographs showed that the FD had failed to open because the guiding wire had inadvertently exited and re-entered the proximal segment of the high-porosity stent partially incorporated to the wall of the MCA. Balloon dilatation of the FD which had remained collapsed between the stent and the vessel wall caused fracture of the stent and rupture of the artery. CONCLUSION: Angioplasty and flow-diversion of previously Y-stented aneurysms can lead to serious complications.

Testing flow diversion in animal models: a systematic review.

INTRODUCTION: Flow diversion (FD) is increasingly used to treat intracranial aneurysms. We sought to systematically review published studies to assess the quality of reporting and summarize the results of FD in various animal models. METHODS: Databases were searched to retrieve all animal studies on FD from 2000 to 2015. Extracted data included species and aneurysm models, aneurysm and neck dimensions, type of flow diverter, occlusion rates, and complications. Articles were evaluated using a checklist derived from the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. RESULTS: Forty-two articles reporting the results of FD in nine different aneurysm models were included. The rabbit elastase-induced aneurysm model was the most commonly used, with 3-month occlusion rates of 73.5%, (95%CI [61.9-82.6%]). FD of surgical sidewall aneurysms, constructed in rabbits or canines, resulted in high occlusion rates (100% [65.5-100%]). FD resulted in modest occlusion rates (15.4% [8.9-25.1%]) when tested in six complex canine aneurysm models designed to reproduce more difficult clinical contexts (large necks, bifurcation, or fusiform aneurysms). Adverse events, including branch occlusion, were rarely reported. There were no hemorrhagic complications. Articles complied with 20.8 ± 3.9 of 41 ARRIVE items; only a small number used randomization (3/42 articles [7.1%]) or a control group (13/42 articles [30.9%]). CONCLUSION: Preclinical studies on FD have shown various results. Occlusion of elastase-induced aneurysms was common after FD. The model is not challenging but standardized in many laboratories. Failures of FD can be reproduced in less standardized but more challenging surgical canine constructions. The quality of reporting could be improved.

Temporary surgical clipping of flow-diverted arteries in an experimental aneurysm model.

OBJECTIVE Surgical management of recurrent aneurysms following failed flow diversion may pose difficulties in securing vascular control with temporary clips. The authors tested the efficacy and impact of different types of aneurysm clips on flow-diverted arteries. METHODS Six wide-necked experimental aneurysms were created in canines and treated with Pipeline flow diverters. In 4 aneurysms, occlusion of the artery at the level of the proximal and distal landing zones (n = 2 per aneurysm) was attempted, using temporary, fenestrated, single, and double permanent aneurysm clips. Two aneurysms served as unclipped controls. Serial angiography was performed to investigate the efficacy of clip occlusion, flow diverter deformation, and thrombus formation. After the animals were killed, the flow-diverted aneurysm constructs were opened and photographed to determine neointimal or device damage as a result of clip placement. RESULTS Angiography-confirmed clip occlusion was only possible for 4 of 8 of the tested flow-diverted arterial segments. Clip application attempts led to filling defects consistent with thrombus formation in 2 of 4 flow-diverted constructs, and to minor damage of the flow diverter with neointimal fracture in 1 of 4 cases. CONCLUSIONS Aneurysm clips placed on canine parent arteries bearing a Pipeline flow diverter were unable to reliably stop blood flow. Application of aneurysm clips can cause mild damage to the device and neointima, which might translate into thromboembolic risks. If possible, vascular control should be sought beyond the terminal ends of the implanted device.

Endovascular Repair of Abdominal Aortic Aneurysm: Follow-up with Noninvasive Vascular Elastography in a Canine Model.

PURPOSE: To assess the ability of noninvasive vascular elastography (NIVE) to help characterize endoleaks and thrombus organization in a canine model of abdominal aortic aneurysm after endovascular aneurysm repair with stent-grafts, in comparison with computed tomography (CT) and pathologic examination findings. MATERIALS AND METHODS: All protocols were approved by the Animal Care Committee in accordance with the guidelines of the Canadian Council of Animal Care. Stent-grafts were implanted in a group of 18 dogs with aneurysms created in the abdominal aorta. Type I endoleak was created in four aneurysms; type II endoleak, in 13 aneurysms; and no endoleak, in one aneurysm. Doppler ultrasonography and NIVE examinations were performed at baseline and at 1-week, 1-month, 3-month, and 6-month follow-up. Angiography, CT, and macroscopic tissue examination were performed at sacrifice. Strain values were computed by using the Lagrangian speckle model estimator. Areas of endoleak, solid organized thrombus, and fresh thrombus were identified and segmented by comparing the results of CT and macroscopic tissue examination. Strain values were compared by using the Wilcoxon rank-sum and Kruskal-Wallis tests. RESULTS: All stent-grafts were successfully deployed, and endoleaks were clearly depicted in the last follow-up elastography examinations. Maximal axial strains over consecutive heart cycles in endoleak, organized thrombus, and fresh thrombus areas were 0.78% ± 0.22, 0.23% ± 0.02, 0.10% ± 0.04, respectively. Strain values were significantly different between endoleak and organized or fresh thrombus areas (P < .000) and between organized and fresh thrombus areas (P < .0002). No correlation was found between strain values and type of endoleak, sac pressure, endoleak size, and aneurysm size. CONCLUSION: NIVE may be able to help characterize endoleak and thrombus organization, regardless of the size, pressure, and type of endoleak.

Compaction of flow diverters improves occlusion of experimental wide-necked aneurysms.

INTRODUCTION: Flow diverters (FDs) are increasingly used in the treatment of wide-necked aneurysms. OBJECTIVE: To examine the hypothesis that intentional FD compaction might improve aneurysm occlusion rates. METHODS: Bilateral wide-necked carotid aneurysms were created in 12 dogs. Endovascular treatment was performed 1 month later, using Pipeline embolization devices deployed with compaction across the aneurysm neck (n=12). Group 1a consisted of aneurysms treated with a single compacted FD (n=8), while group 1b aneurysms required two compacted FDs (n=4). Control aneurysms were treated with a single non-compacted FD (group 3; n=6), or not treated (group 4; n=4). Angiographic results were compared at 3 months. Pathology specimens were photographed and the neointimal coverage of devices scored using an ordinal grading system. RESULTS: Twenty-two of 24 aneurysms were patent at 1 month. Deployment with compaction was successful in eight cases (group 1a aneurysms). The compaction maneuver led to immediate FD prolapse into the aneurysm in four cases, rescued by deploying a second, telescoping FD (forming group 1b aneurysms). One compacted device later migrated distally, leaving the aneurysm untreated. Angiographic results differed significantly between groups (p=0.0002). At 3 months, aneurysms successfully treated with a single compacted FD were more often occluded at 3 months (7/7) than aneurysms flow-diverted without compaction (2/6; p=0.021). All aneurysms treated with two compacted FDs were occluded, while all untreated aneurysms remained patent. There were no parent vessel stenoses. CONCLUSIONS: Compaction of FDs can improve angiographic occlusion of experimental wide-necked aneurysms.

Fatal avulsion of choroidal or perforating arteries by guidewires. Case reports, ex vivo experiments, potential mechanisms and prevention.

Innovations in endovascular tools have permitted an increasingly broad range of neurovascular lesions to be treated via minimally invasive methods. However, some device modifications may carry additional risks, not immediately apparent to operators. A patient with a symptomatic, partially thrombosed basilar apex aneurysm was allocated balloon-assisted coiling. Attempts were made to place a microwire across the basilar apex through the posterior communicating artery. Overlapping courses of the posterior cerebral and posterior choroidal arteries on the roadmap images were not recognized and a flanged-tip microwire was inadvertently advanced deep into the choroidal artery. Following the wire with a microcatheter led to binding of arterial tissue within the microcatheter. Removing the wire led to an avulsion of the choroidal artery and a severe hemorrhagic complication which proved fatal. Tissue was identified on the tip of the guidewire. Pathology showed layers of vascular tissue within the laser-cut flanges of the distal wire tip. A similar complication, also fatal, occurred during balloon angioplasty of a distal vertebral artery, when an exchange wire was accidently introduced into a perforator from a posterior cerebral artery. Ex vivo catheterization of distal mesenteric arterial branches showed that the wall of small arteries can be entrapped by laser-cut, flanged, but not by smooth guidewire tips. Microwires with a flanged instead of smooth distal tip, when placed into small caliber vessels, may cause hemorrhagic complications from avulsions*.

Flow diversion of giant curved sidewall and bifurcation experimental aneurysms with very-low-porosity devices.

OBJECTIVE: Flow diverters (FDs) are increasingly used to treat difficult intracranial aneurysms. The objective of this study was to test whether treatment challenges posed by giant curved sidewall (cSW) and endwall bifurcation (EwB) aneurysms can be overcome with the use of very-low-porosity devices. METHODS: Large and giant EwB (n = 12) and cSW aneurysms (n = 5) were constructed in 17 dogs. EwB aneurysms were treated with 48 (n = 4), 64 (n = 4), or two overlapping 64-wire low-porosity devices (n = 4), whereas all cSW aneurysms were treated with single 64-wire devices. Angiographic results were recorded immediately and at 12 weeks before euthanasia. Pathologic specimens were photographed and neointimal coverage of devices measured and scored. RESULTS: By 12 weeks, 1 of 12 EwB and 1 of 5 cSW aneurysms were occluded. All other aneurysms were patent. Device-related arterial stenoses occurred in 13 of 17 animals, hemodynamically significant in two. All branches jailed by the FDs remained patent. There was a significant correlation between angiographic scores and the degree of neointima formation on the device (Rho = 0.527; P = 0.04). Failures of aneurysm occlusion could be explained by holes, sometimes barely visible, in the neointima that formed over FDs. CONCLUSION: Low-porosity FDs fail to reliably occlude experimental giant EwB and cSW aneurysms.

In vitro reproduction of device deformation leading to thrombotic complications and failure of flow diversion.

Flow diverters (FDs) are increasingly used for complex intracranial aneurysms. As these self-expanding devices are deployed across an aneurysm neck, they can undergo deformations. The potential clinical consequences of FD deformations remain unclear. We describe an immediate thrombotic complication attributed to a stereotypical stenotic deformation of an FD extremity that can occur when landing zones are of insufficient length. This case is supplemented with in vitro studies showing the relationship between i) the length of the landing zones and ii) discrepancies between the diameter of the device and recipient vessel, and the severity of FD stenosis. In vitro, a shorter landing zone was associated with a progressive stenotic deformation of the terminal ends of all FDs studied. This deformation was more pronounced when the diameter of the device was oversized compared to the size of the recipient tube. In our clinical case, the presence of this deformation led to an immediate thrombotic complication, requiring deployment of a second stent to correct the observed stenosis. In addition, treatment failure ultimately led to a fatal rupture, a failure that can be explained by residual flows through a more porous transition zone, another characteristic FD deformation which occurs when they are oversized as compared to the parent vessel, but free to expand at the level of the aneurysm. Proper selection of device diameter and length of the landing zone is important, and may decrease the incidence of deformation-related complications.

Y-crossing of braided stents with stents and flow diverters does not cause significant stenosis in bench-top studies.

Y-stent placement to treat bifurcation aneurysms requires the second device to cross the confines of the first stent, with concerns regarding the formation of stenosis of the second device at the site of crossing. Various braided stents and flow diverters (FDs) were deployed to cross through a high porosity braided stent, in a Y configuration, with the ends of the devices inserted in plastic tubes of various diameters, leaving the mid-portion free to expand. The ensuing constructs were photographed, paying attention to the degree of stenosis, if any, created where the second device crosses the first stent. Experiments were repeated selecting different zones of the first stent as the site of crossing for the second device, different tube diameters, and changing the angle of the bifurcation. Crossing the first stent did not cause the second stent to become significantly stenosed in any case. Crossing through the transition or expansion zone of the first device had no influence on results. Different bifurcation angles had no influence on the occurrence of stenosis. Y-stent placement to treat arterial bifurcations using braided self-expanding stents and FDs does not lead to significant stenosis in bench-top studies.

Endovascular treatment with flow diverters may fail to occlude experimental bifurcation aneurysms.

INTRODUCTION: Animal models may explain how stents and flow diverters (FDs) may succeed or fail to treat bifurcation aneurysms. METHODS: In vitro studies were designed to anticipate device deformations in bifurcations. Large, wide-necked bifurcation aneurysms were constructed in 21 animals and treated 4-8 weeks later using stents and FDs in various combinations, forming four main groups: parent artery to right branch flow diversion (RBFD, n = 6), parent artery to left branch flow diversion (LBFD, n = 6), Y flow diversion (YFD, n = 4), and compared with high-porosity Y-stenting (YHPS, n = 4). The results include immediate and follow-up angiography at 3 months, followed by grading of the extent of neointimal coverage of devices at pathology. RESULTS: In vitro, all braided devices showed varying porosities according to characteristic zones. FDs can be compacted to decrease porosities, but a limiting factor is the constant presence of a more porous transition zone. In vivo, 3/6 RBFD, 4/6 LBFD, and 2/4 YFD treated aneurysms had decreased in size by 3 months, while those treated with YHPS increased in size (P = 0.15). There was a significant correlation between device porosities and extent of neointimal coverage (r = 0.639, P = 0.002), and between porosities and angiographic evolution (r = -0.655, P = 0.002), but not between neointima formation and angiographic evolution (r = -0.278, P = 0.235). Failures could be explained in all cases by the presence of leaks or holes in the neointima at the level of the transition zones. CONCLUSION: FDs did not successfully treat most bifurcation aneurysms, at least in this animal model.

Flow diversion to treat aneurysms: the free segment of stent.

PURPOSE: Flow diverters (FDs) have led to spectacular results in otherwise untreatable aneurysm cases, but complications can occur. There is a pressing need to study factors that might predict their safety and efficacy. METHODS: The anatomical constraints that may impact on the ability of FDs to redirect blood flow and provide a scaffold for neointima formation across the aneurysm or branch ostia are explored and classified. A nomenclature is needed to identify the key factors that should be taken into account before contemplating the use of FDs in clinical aneurysms, and that should be reproduced in experimental models, if they are to guide safe clinical use. RESULTS: The free stent segment (FSS), the portion of the device that covers an aneurysm or branch origin, dictates whether aneurysms or branches will remain patent. Three levels of increasing complexity must be taken into account to anticipate what will occur at the FSS level. (1) Virtual models can provide basic principles; (2) in vitro studies allow testing FSS deformations that may occur in various anatomical circumstances and impact on efficacy and safety; (3) but only in vivo studies can provide key information on neointimal closure following implantation that will differentiate success from failure. CONCLUSIONS: A nomenclature is necessary to determine the optimal or suboptimal conditions for FDs and to design the virtual, in vitro and in vivo studies that will allow a better understanding of the factors involved in the success or failure of this novel treatment.

Stents and flow diverters in the treatment of aneurysms: device deformation in vivo may alter porosity and impact efficacy.

INTRODUCTION: High-porosity (HP) and flow-diverting (FD) stents are increasingly used to treat intracranial aneurysms. In vivo device deformations and their impact on the porosity of the segment of device lying over the aneurysm neck remain inadequately characterized. METHODS: Porosities of different braided FDs were studied in straight and 90° curved glass tubes. In vivo, 11 experimental lateral wall aneurysms were treated with FD (n = 7) or HP (n = 4) stents. At 3 months, the segment of FDs and HP stents over the aneurysm neck was analyzed, paying attention to changes in device diameter, metallic porosity, and neointimal closure of pores over the aneurysm or branch ostia. Device deformations were reproduced with benchtop experiments. RESULTS: In 90° curved tubes, FD porosity was higher (P = 0.025) and pore density was lower (P = 0.01) on convex compared to concave surfaces, but variations remained within 5-10 %. After in vivo deployment, a spindle-shaped deformation of FDs occurred, with focal expansion at the level of the aneurysm neck (P = 0.004). This deformation translated into an accordion-like distribution of stent struts across the aneurysm neck, where porosity was not uniform. The midsection of the aneurysm ostium had more metal coverage than adjacent ostial areas (P = 0.002). Mean porosity over the aneurysm neck was 78 ± 9.4 and 32.6 ± 12.1 % for HP and FD stents, respectively (P = 0.008), decreasing to 13.0 ± 10.1 and 1.4 ± 0.6 % (P = 0.022) following neointimal coverage, respectively. Spindle-shaped deformations and accordion effects were reproduced with benchtop manipulations; fluctuations in porosity and diameter changes correlated closely (R = 0.81; P = 0.005). CONCLUSION: Alterations in porosity may occur following in vivo implantation.

Flow diverters failing to occlude experimental bifurcation or curved sidewall aneurysms: an in vivo study in canines.

OBJECT: Flow diverters (FDs) are increasingly used to treat complex intracranial aneurysms, but preclinical studies that could guide clinical applications are lacking. The authors designed a modular aneurysm model in canines to address this problem. METHODS: Three variants of one modular aneurysm model were constructed in 21 animals. Sidewall (n=5), curved sidewall (n=5), and end-wall bifurcation (n=7) aneurysms were treated with prototype 36-wire FDs. Four more end-wall bifurcation aneurysms were treated with prototype 48-wire lower-porosity FDs. Angiographic results postimplantation and at 3 months were scored with an ordinal scale. Animals were euthanized at 3 (n=17) or 6 (n=3) months, and the FD covering the aneurysm ostium was photographed to analyze metallic porosity and amount of neointima formation. RESULTS: Straight sidewall aneurysms were better occluded than curved sidewall and end-wall bifurcation aneurysms at the 3-month angiography follow-up (p=0.010). Flow diverters failed to occlude curved sidewall aneurysms (n=0/5) and all but one (n=1/7) end-wall bifurcation aneurysm. Angiographic results were no better (n=0/4) using a 48-wire FD (p=0.788). Branches jailed by the FD (n=16) remained patent in all cases. Metallic porosity was decreased (p=0.014) and neointimal closure of the aneurysm ostium was more complete (p=0.040) in sidewall aneurysms than in curved or bifurcation variants of the model. CONCLUSIONS: Flow diverters may succeed in treating straight sidewall aneurysms, but the same device repeatedly fails to occlude curved sidewall and end-wall bifurcation aneurysms. In vivo studies can be designed to test basic principles that, once validated, may serve to guide clinical use of new devices.