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OBJECTIVEThe 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.METHODSFifty-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.RESULTSAngiographic 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).CONCLUSIONEndovascular 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.

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.

OBJECTIVEEndovascular 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.METHODSBipolar 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.RESULTSBipolar 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).CONCLUSIONSBipolar RFA can improve results of embolization in experimental models by selectively ablating residual lesions after coil embolization.

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. 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? 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. Experimental models may help anticipate clinical results of flow diversion.

BackgroundFlow diverters (FDs) are increasingly used for bifurcation aneurysms. Failure of aneurysm occlusion may be caused by residual flow maintaining patency of the jailed branch along with the aneurysm. Our aim was to test whether endovascular occlusion of the jailed branch could improve efficacy of flow diversion of bifurcation aneurysms.Materials and methodsSixteen wide-necked lingual–carotid artery bifurcation aneurysms were created in eight canines. Patent aneurysms were randomly allocated 4 weeks later to flow diversion combined with jailed branch occlusion using coils and/or Onyx (n=6) or flow diversion alone (n=8). Angiographic results of aneurysm occlusion at 3 months were scored using an ordinal scale. Pathology specimens were photographed and neointimal coverage estimated using a semiquantitative scoring system.ResultsFourteen aneurysms were patent at 1 month. FD deployment was successful in all cases but, at 3-month follow-up, three devices had prolapsed into the aneurysm. None of the bifurcation aneurysms treated with FD alone were occluded at 3 months. Endovascular branch occlusion combined with flow diversion significantly improved aneurysm occlusion rates compared with flow diversion alone (median angiographic scores 2 vs 0: p=0.0137). Flow-limiting parent vessel stenosis was not observed in any arteries. Devices were covered with thick neointima in most cases, but patent aneurysms were associated with leaks or holes in the neointima covering the aneurysm neck.ConclusionsTreatment failures following flow diversion of bifurcation aneurysms can be caused by persistent flow to the jailed branch. Branch occlusion combined with flow diversion may improve angiographic occlusion scores of a canine bifurcation aneurysm model.

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. 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. 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 %]). 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.

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

BACKGROUND AND PURPOSE: Liquid embolic agents are increasingly used to treat vascular malformations. We sought to assess embolization with these agents by using a dual-lumen balloon catheter in an experimental setting. MATERIALS AND METHODS: Eighteen injections of liquid embolic agents were performed in the rete mirabile of swine. We used 3 methods to control liquid embolic agent reflux: 1) dual-lumen balloon-catheter (group A, n = 8); 2) injection of liquid embolic agent after proximal n-BCA plug formation through a second microcatheter (group B, n = 4); and 3) standard liquid embolic agent injection (group C, controls, n = 6). The following outcomes were graded by using ordinal scales by angiography, macrophotography, and radiography of retia after euthanasia: 1) angiographic and pathologic extent of liquid embolic agent embolization of the rete, 2) reflux of liquid embolic agents in the parent artery, and 3) density of liquid embolic agents in the proximal rete. Technical complications were also recorded. A successful injection was defined as an embolization that reached the contralateral rete without reflux into proximal external branches. Exact logistic regression analyses were performed to compare groups. RESULTS: There were significant differences among groups for reflux (P = .029) and liquid embolic agent density in the proximal rete (P = .014), while extension to the contralateral rete did not reach statistical significance (P = .07). Injections differed among groups (P = .004), with dual-lumen balloon-catheter injections more frequently successful compared with control injections (P = .019). CONCLUSIONS: Dual-lumen balloon catheters allowed better liquid embolic agent injections than standard injections.

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.

BACKGROUND AND PURPOSE: Rabbit elastase-induced saccular aneurysms have been commonly used for preclinical testing of endovascular devices, including flow diverters. However, all tested devices have been shown to be capable of aneurysm occlusion with this model. We aimed to create a more challenging model to test and discriminate among neurovascular devices of varying efficacies. MATERIALS AND METHODS: With a surgical approach that included elastase infusion and balloon dilation, we attempted the creation of complex fusiform aneurysms in 16 rabbits, with standard saccular carotid aneurysms created in 15 other animals. Aneurysms were randomly allocated to one of the following treatments: flow diversion (n = 8), high-porosity stent (n = 6), double high-porosity stent (n = 5), and control (n = 6). Angiographic assessment and pathologic analyses were performed at 3 months. RESULTS: Creation of complex fusiform and standard saccular aneurysms was successful in 12/16 and 13/15 attempts, respectively. All saccular (n = 4) or complex fusiform (n = 4) aneurysms treated with flow diverters were successfully occluded. Three of 3 saccular compared with 0/2 complex fusiform aneurysms were occluded by double high-porosity stents. One of 3 saccular and 0/3 complex fusiform aneurysms were occluded by a single high-porosity stent. Both aneurysm types shared the same pathologic findings when untreated: The aneurysm wall lacked an elastic layer and smooth muscle cells, while the lumen was lined with neointima of varying thickness. Neointimal coverage of the devices was complete when aneurysms were occluded, while leaks were always associated with aneurysm remnants. CONCLUSIONS: Challenging fusiform aneurysms can be created in rabbits by using a surgical modification of the elastase method.

BACKGROUND AND PURPOSE: Flow diverters are designed to occlude aneurysms while preserving flow to jailed arterial branches. We postulated that treatment success depended on the size of the aneurysm ostium or defect in the parent artery. MATERIALS AND METHODS: Flow diverter expansion and deformation were studied in silicone tubes with wall apertures of various sizes. Large and giant canine sidewall aneurysms, featuring a branch located immediately opposite the aneurysm, and a smaller 6- to 8-mm (group A, n = 6) or a larger 10- to 16-mm (group B, n = 6) ostium were created to study the effects of ostium size on aneurysm or branch occlusion by flow diverters. Angiographic results after deployment and at 3 months were scored by using an ordinal scale. The amount of neointima formation on the segment of the device overlying the aneurysm or the branch ostia was determined by specimen photography. RESULTS: The fusiform deformation of flow diverters was maximal with larger defects in silicone tubes. At 3 months, group B aneurysms showed worse angiographic results than group A aneurysms, with larger residual aneurysm volumes ( P = .002). Neointimal coverage of the aneurysm ostia was more complete in group A compared with group B ( P = .002). CONCLUSIONS: The effects of flow diversion may vary with the size of the aneurysm ostium.

Introduction et objectifs La « Pressure Cooker technique (PC) » est une technique endovasculaire avec 2 microcatheters qui reduit le reflux des agents emboliques au moyen d’un bouchon proximal. En utilisant un modele porcin et plusieurs cyanoacrylates, nous avons effectue une technique PC et une injection reguliere sans bouchon proximal afin de comparer la penetration des agents emboliques liquides dans le rete mirabile. Nous avons evalue egalement, en injectant dans les arteres des reins a l’aide de PC, la force necessaire pour retirer les microcatethers a la fin de la injection. Materiaux et methodes Huit porcs ont ete utilises pour les injections dans la Rete mirabile. Nous avons utilise les cyanoacrylates et PC technique en 4 injections et une injection conventionnelle dans 4 autres (groupe temoin). Nous avons utilise deux types de cyanoacrylates, le NBCA et un cyanoacrylate non adhesif (n = 4), l’alpha-hexil-cyanoacrylate (Magic Glue MG, n = 4). La penetration dans le rete a ete evaluee par radiographie a l’aide d’echelles ordinales apres euthanasie. Dans les arteres renales segmentaires, 14 injections utilisant PC ont ete realisees utilisant MG pour le plug (n = 10) et utilisant NBCA pour le plug (n = 4). La force necessaire pour retirer les microcatheters a ete evaluee avec une echelle numerique. Resultats Aucune difference significative n’a ete trouvee pour la penetration du cyanoacrylate dans le Rete Mirabile pour les groupes PC et non-PC (p = 0,657) et concernant la penetration entre MG et NBCA (p = 0,657). En ce qui concerne les forces necessaires pour retirer le catheter distal, elles etaient moins importantes lorsque MG etait utilise proximalement que NBCA (p = 0,035). La variation de longueur du bouchon proximal etait significative avec MG (p = 0,005) mais non avec NBCA (p = 0,066). Aucune difference n’a ete trouvee concernant les mouvements des bobines (p = 0,517) Conclusions La PC technique utilisant un bouchon proximal et des injections distales de cyanoacrylates n’a pas ameliore l’embolisation du Rete Mirabile dans cette etude. L’utilisation d’alpha-hexil-cyanoacrylate (MG) peut reduire les forces de traction lors du retrait du microcatheter, mais la longueur du bouchon proximal initial a tendance a augmenter.

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.

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.

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.

BACKGROUND AND PURPOSE: Braided self-expandable stents and flow diverters of uniform construction may develop zones of heterogeneous porosity in vivo. Unwanted stenoses may also occur at the extremities of the device. We studied these phenomena in dedicated benchtop experiments. MATERIALS AND METHODS: Five braided devices of decreasing porosity were studied. To simulate discrepancies in diameters between the landing zones of the parent vessel and the aneurysm neck area, device extremities were inserted into silicone tubes of various diameters (2–3 mm), leaving the midportion free to react to experimental manipulations, which included axial approximation of the tubes (0–7 mm), and curvature (0–135°), with or without axial compression (0–2 mm). The length of the landing zone was sequentially decreased to study terminal device stenosis. RESULTS: All devices adopted a conformation characterized by 3 different zones: bilateral landing zones, a middle compaction zone, and 2 transition zones. It is possible, during deployment, to compact stents and FDs to decrease porosity, but a limiting factor was the transition zone, which remained relatively unchanged and of higher porosity than the expansion zone. Length of the transition zone increased when devices were constrained in smaller tubes. Heterogeneities in porosity with compaction and curvatures were predictable and followed simple geometric rules. Extremity stenoses occurred increasingly with decreasing length of the landing zone. CONCLUSIONS: Braided self-expandable devices show predictable changes in porosity according to device size, vessel diameter, and curvature. Adequate landing zones are required to prevent terminal device stenosis. FD : flow diverter FSS : free segment of stent HPS : high-porosity stent P : porosity SF : strut frequency

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.

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.

BACKGROUND AND PURPOSE: FDs are new intracranial stents designed to occlude aneurysms while preserving flow to jailed arterial branches. We tested this fundamental principle in a new aneurysm model. MATERIALS AND METHODS: Canine lateral wall aneurysms, featuring a branch located immediately opposite the aneurysm, were created in 16 animals to study the effects on aneurysm or branch occlusion using single HP stents ( n = 4), 2 overlapping HP stents ( n = 4), or an FD ( n = 8). Two other animals, in which an efferent arterial branch was anastomosed to the aneurysm fundus, were also treated with FDs. Angiographic results after deployment, at 2 weeks, and at 3 months were scored using an ordinal scale. The metal porosity of the FSS and the amount of FSS neointima formation was determined by postmortem photography. RESULTS: FDs led to better angiographic occlusion scores compared with HP stents ( P = .026). FDs were significantly more likely to occlude the aneurysm than the branch ( P = .01). When the branch was switched to originate from the aneurysm fundus, the FDs became ineffective (0/2). Neointimal closure of the aneurysm ostium was significantly better with FDs than with single or double HP stents ( P = .039). Angiographic occlusion correlated with metallic porosity and neointimal tissue coverage (Spearman ρ = −0.81; P = .001). CONCLUSIONS: In this study, flow diverters occluded lateral wall aneurysms more readily than branches. Metal device porosity strongly influenced the occlusion rate. ASA : aspirin CCA : common carotid artery CFD : computational fluid dynamics FD : flow diverters FSS : free segment of stent HP : high- porosity

To investigate if shear wave imaging (SWI) can detect endoleaks and characterize thrombus organization in abdominal aortic aneurysms (AAAs) after endovascular aneurysm repair. 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). 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

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.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.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.NIVE may be able to help characterize endoleak and thrombus organization, regardless of the size, pressure, and type of endoleak.

Purpose Coil embolization of intracranial aneurysms may be followed by recurrences. Radiofrequency (RF) ablation of the endothelium may prevent recanalization after coil embolization. Materials and Methods The authors performed in vitro experiments in chicken meat and egg white models to investigate the thermal distribution and geometry of lesions created with RF applied through standard coils alone or by using a prototype RF electrode inserted in a coil or a mass of coils. A mathematic model was designed to predict perianeurysmal isotherm lesions by using the bio-heat equation. In an in vivo coil arterial occlusion model (six dogs), the authors compared angiographic and pathologic results of coil embolization ( n = 8) with those of coil embolization preceded by RF ablation ( n = 7) by using a cardiac electrode at 1 month. Results Current coils offer high impedance (400 Ω) at high current frequencies and are damaged by RF transmission. A dedicated electrode generated reproducible lesions, but contact with coils interferes with lesion reproducibility. When the coil mass was used, a uniform RF lesion that conformed to the coil mass shape was produced. The mathematic model predicted a uniform heat distribution within 1 mm from the coil mass periphery. Arterial coil embolization led to occlusion followed by recanalization ( n = 8), whereas RF ablation (20–30 W for 60 seconds) prevented recanalization in all coil-occluded arteries ( P 2 test). Pathologic findings helped confirm complete arterial occlusion with RF ablation. One animal developed brachial plexus injury with excessive levels of RF ablation. Conclusions RF ablation can prevent recanalization after coil occlusion—at least in the arterial model. Modifications of coils, dedicated neurovascular electrodes, and technique optimization remain necessary before considering a clinical application.

Resumen Introduccion y objetivos las contracciones excentricas (CC.EE.) se caracterizan por producirse previa elongacion muscular, lo que facilita la lesion. La mayoria de los estudios precedentes se han desarrollado en musculos de las extremidades, por lo que se desconoce la relevancia potencial de las CC.EE. en los musculos respiratorios. El objetivo del presente trabajo ha sido evaluar los efectos funcionales de series repetidas de CC.EE. sobre el diafragma. Metodo se provoco la elongacion del diafragma mediante presion externa abdominal en 6 perros y se indujeron CC.EE. mediante series consecutivas de pulsos supramaximos bilaterales. El efecto se valoro mediante la posterior respuesta del musculo ante estimulacion frenica bilateral tanto de pulso unico como tetanica, en terminos de presion y acortamiento (sonomicrometria) de los hemidiafragmas derecho e izquierdo. En 4 casos se realizo estudio estructural. Resultados se consiguio inducir CC.EE. en todos los casos. Las presiones diafragmaticas inducidas por estimulacion disminuyeron inmediatamente despues de la actividad excentrica (pulso unico: 53%; tetanica: 67%; p Conclusion con el modelo propuesto, que permite estudiar el efecto de las CC.EE. en el diafragma, se demuestra una perdida funcional mantenida durante horas, que en parte parece debida a una lesion estructural. Clinicamente se deberia ser cauto con las maniobras fisiologicas o terapeuticas que impliquen la elongacion basal del diafragma.

Introduction and Objectives Eccentric contractions are those that occur after a muscle has been stretched, and they can predispose the muscle to damage. Most previous studies have been performed on limb muscles, and the potential consequences of eccentric contractions on the respiratory muscles are therefore unknown. The aim of this study was to evaluate the effects of repeated eccentric contractions on diaphragmatic function. Methods In 6 dogs, the diaphragm was stretched by applying pressure on the abdominal wall, and consecutive series of eccentric contractions were induced by bilateral supramaximal stimulation. The effect of these contractions on the diaphragm was then evaluated by applying bilateral twitch and tetanic stimulation of the phrenic nerves and measuring the changes in abdominal pressure and the shortening of the right and left hemidiaphragms (by sonomicrometry). Structural study of the muscle was also performed in 4 animals. Results Eccentric contractions were successfully achieved in all cases. Stimulation-induced diaphragmatic pressures became lower immediately after these contractions: twitch pressure fell by 53% and tetanic pressure by 67% after the first 10 eccentric contractions (P Conclusions This experimental model, which enabled the effects of eccentric contractions to be studied in the diaphragm, revealed a deterioration of muscle function that persisted for hours and that appeared to be partly due to structural damage. In the clinical setting, physiologic or therapeutic maneuvers that increase the resting length of the diaphragm should be used with caution.

a b s t r a c t Introduction and Objective. Diaphragmatic activity varies with the initial length of the muscle. Our objective was to evaluate the influence of surgery and changes in abdominal wall compliance on diaphragmatic activity. Methods. Both phrenic nerves in 7 mongrel dogs were stimulated electrically with single supramaximal pulses (twitch). The gastric (Pga) and transdiaphragmatic (Pdi) pressures generated and muscle shortening (sonomicrometry) were used to evaluate diaphragmatic activity, which was determined at baseline, after midline laparotomy, with an elastic abdominal bandage, and with a rigid circular cast. Abdominal pressure was then gradually increased in order to induce progressive lengthening of the diaphragm. Results. After laparotomy, the pressures were somewhat lower (by 12%) than at baseline. The elastic bandage produced a slight increase in the pressure generated by the diaphragm (mean (SE) values: Pga, from 4.2 (0.3) cm H2O to 6.3 (0.9) cm H2O, P

Resumen Introduccion y objetivos la actividad del diafragma puede verse modificada por su longitud inicial. Nuestro objetivo ha sido evaluar la influencia de la cirugia y los cambios en la rigidez de la pared abdominal sobre la actividad del musculo. Metodo en 7 perros mestizos se estimularon electricamente ambos nervios frenicos con pulsos unicos supramaximos ( twitch ). Para evaluar la actividad del diafragma se determinaron las presiones generadas —gastrica (Pga tw ) y transdiafragmatica (Pdi tw )— y el acortamiento muscular (sonomicrometria). La respuesta diafragmatica se obtuvo en situacion basal, tras laparotomia media, con venda abdominal elastica y con protesis rigida circular. A continuacion se incremento ligera y progresivamente la presion abdominal para conseguir el alargamiento sucesivo del diafragma. Resultados tras la laparotomia, las presiones fueron algo inferiores a las basales (12%). La banda elastica provoco un leve aumento de la presion generada por el diafragma (valores medios±error estandar. Pga tw : 4,2±0,3 a 6,3±0,9 cmH 2 O, p tw : 12,1±2,0 a 15,4±1,8 cmH 2 O, p tw : 12,6±1,5 cmH 2 O; Pdi tw : 20,2±2,3 cmH 2 O; p Conclusion la rigidez de la pared abdominal desempena un papel importante en la respuesta del diafragma a la estimulacion. Esto parece deberse fundamentalmente a cambios en su longitud de reposo.

Objetivo La actividad previa puede modificar la contractilidad muscular, lo que puede conducir a la infra o supraestimacion de la fuerza en las determinaciones funcionales. El presente trabajo se ha propuesto como objetivo valorar cambios en la presion maxima generada por el diafragma tras diferentes series de contracciones isometricas espontaneas y cuasi maximas. Metodos Se estudiaron por duplicado 6 perros con un peso medio ± desviacion estandar de 26 ± 7 kg. Se obtuvo la respuesta supramaxima del diafragma –presiones gastrica (Pgatw) y esofagica (Pestw) inducidas por estimulacion frenica bilateral, y acortamiento muscular (sonomicrometria)— por estimulacion simultanea supramaxima de ambos nervios frenicos, tanto en situacion basal como tras series cortas (5), medianas (10) y largas (20) de esfuerzos inspiratorios espontaneos contra la via aerea ocluida, antes y despues de administrar anestesia subaracnoidea (elimina la contribucion ventilatoria de los musculos intercostales). Resultados La serie corta y, sobre todo, la serie mediana provocaron la potenciacion de la respuesta contractil (Pgatw de 3,2 ± 0,4 a 3,7 ± 0,3, y de 3,5 ± 0,3 a 3,9 ± 0,3 cmH2O, respectivamente; p < 0,05 ambas). La potenciacion fue algo superior con anestesia subaracnoidea (un 21 frente al 11% sin anestesia, para la Pgatw tras las series medianas). La serie larga provoco, sin embargo, una disminucion de la respuesta (Pgatw: 3,2 ± 0,4 a 2,5 ± 0,3 cmH2O; p < 0,05), probablemente por predominio de la fatiga sobre la potenciacion. Conclusiones Los esfuerzos previos determinan la capacidad contractil del diafragma y resulta dificil predecir el predominio de fatiga o de potenciacion en la respuesta. Este factor deberia tenerse en cuenta al determinar las presiones respiratorias maximas en la clinica diaria.

BACKGROUND AND PURPOSE: Endovascular treatment of aneurysms may result in complete or incomplete occlusions or may be followed by recurrences. The goal of the present study was to better define pathologic features associated with so-called healing or recurrences after coiling and to propose an alternative concept to the currently accepted view. MATERIALS AND METHODS: Experimental canine venous pouch aneurysms were created by using a T-type (group A, N = 29) or a Y-type constructed bifurcation (group B, N = 37) between the carotid arteries. Coil embolization was performed 2 weeks later; and angiography, immediately after and at 12 weeks. Angiographic results, neointima formation at the neck, endothelialization, and organization of thrombus were compared between groups by using qualitative scores and immunohistochemistry. RESULTS: Angiographic results at 3 months were significantly better in group A than in group B ( P = .001). Macroscopic neointimal scores were also better ( P = .012). Only 10/32 aneurysms with satisfactory results at angiography were completely sealed by neointima formation. Animals with residual or recurrent aneurysms had significantly worse neointimal scores than those with completely occluded ones ( P = .0003). On histologic sections, the neointima was constantly present in “healed” and in recurrent aneurysms. This neointima was a multicellular layer of α-actin+ cells in a collagenous matrix, covered with a single layer of nitric oxide synthetase (NOS+) endothelial cells, whether it completely occluded the neck of the aneurysm or dived into the recurring or residual space between the aneurysm wall and the coil mass embedded in organizing thrombus. CONCLUSION: Complete angiographic occlusions at 3 months can be associated with incomplete neointimal closure of the neck at pathology. Thrombus organization, endothelialization, and neointima formation can occur concurrently with recurrences.

Objective Previous muscle activity can alter muscle contractility and lead to strength underestimation or overestimation in functional measurements. The objective of this study was to evaluate changes in the maximum pressure produced by the diaphragm after different series of spontaneous near-to-maximal isometric contractions. Methods Duplicate studies were performed on 6 dogs with a mean (SD) weight of 26 (7) kg. The supramaximal response of the diaphragm was achieved by simultaneous supramaximal stimulation of both phrenic nerves, both under basal conditions and after series of 5, 10, and 20 spontaneous inspiratory efforts against the occluded airway, performed before and after spinal anesthesia (which eliminates the ventilatory contribution of the intercostal muscles). The response was measured using the twitch gastric pressure (Pga) and twitch esophageal pressure (Pes) and by muscle shortening (sonomicrometry). Results The short series of 5 inspiratory efforts and, in particular, the medium series of 10 efforts produced potentiation of the contractile response, with a rise in the Pga from 3.2 (0.4) cm H2O to 3.7 (0.3) cm H2O, and from 3.5 (0.3) cm H2O to 3.9 (0.3) cm H2O, respectively (P=.05 in both cases). The potentiation was somewhat greater after subarachnoid anesthesia (an increase in the Pga of 21% after the medium series of 10 efforts with anesthesia vs 11% without anesthesia). However, the long series of 20 efforts produced a fall in the response, with a decrease in the Pga from 3.2 (0.4) cm H2O to 2.5 (0.3) cm H2O (P Conclusions Previous effort affects the contractile capacity of the diaphragm and it is difficult to predict the predominance of fatigue or potentiation in the response. This factor must be taken into account when determining the maximum respiratory pressures in daily clinical practice.

Despite the increasing use of embolic protection systems (EPS) for carotid stenting, their intrinsic in vivo thrombogenicity remains unknown. We studied three different types of EPS (n = 24) deployed in the carotid arteries of pigs in which pools of platelets and fibrinogen were labelled with 111In and 125I. The amount of clot deposition seen on photography was also scored using a qualitative scale. EPS made of fabric nets under normal flow conditions were 5–6 and 15–16 times more thrombogenic (for both platelet (P=.04) and fibrin (P=.007)) than Nitinol mesh nets. Clot deposition on Nitinol mesh nets was more abundant under flow arrest than under normal flow conditions (P=.018). EPS differ in intrinsic thrombogenicity, a characteristic of the material that could be investigated in pre-clinical studies designed to optimize devices.

Purpose: To examine in a canine model the feasibility of antegrade fenestration of abdominal aortic stent-grafts to preserve the patency of the renal arteries. Methods: Two large dogs underwent antegrade fenestration of stent-grafts in the perirenal aorta. Before fenestration, bare stents were inserted in both renal arteries as fluoroscopic landmarks. A 12-mm iliac extension served as the canine aortic endograft. The first procedure was done under ultrasound and fluoroscopic guidance, using an intravascular ultrasound (IVUS) probe inserted in the vena cava and a Pioneer IVUS catheter. The second was performed exclusively under fluoroscopic guidance with a Brockenbrough needle. Angiograms and duplex ultrasound were planned for 1 month, after which the dogs would be sacrificed for autopsy. The explanted endograft was subjected to biomaterials analysis, with a focus on fabric tear. Results: Perforation of the aortic graft and catheterization of the renal arteries with a floppy guidewire were possible in both animals. In dog 1, aortic graft dilation and subsequent fenestration were not possible, and the experiment was terminated. However, the procedure was successful in both renal arteries of dog 2. At 1-month follow-up in this dog, both renal arteries were patent. Stent fractures were observed bilaterally. There was no extension of the damage to the fabric beyond the area of fenestration. Conclusion: In vivo antegrade fenestration of aortic endografts is technically feasible. However, improvements in technique, instrumentation, and materials are required to make it a reliable and reproducible way of allowing stent-graft vascularization of aortic side branches.

PURPOSE Endovascular embolization with platinum coils is sometimes followed by recanalization. The present study was undertaken to assess whether cryoablation of the endothelial lining could prevent recanalization after coil occlusion. MATERIALS AND METHODS Recanalization rates of canine maxillary and vertebral arteries ( n = 20) occluded with platinum coils with or without previous cryoablation (with temperatures of −40°C to −45°C for 90 seconds) were analyzed by angiography immediately and at 1 and 3 months in five animals. Pathologic recanalization and fibrosis was assessed at 3 months with use of a qualitative scoring system. Findings were compared with Mann-Whitney tests. RESULTS Recanalization after coil occlusion occurred in 50% and 60% of cases with cryoablation at 1 and 3 months, respectively, compared with 100% without ablation ( P = .012 and P = .029). There was no significant difference in pathologic scores ( P = .348). The brachial plexus in the vicinity of vertebral arteries was injured by cryotherapy in three animals in which an ipsilateral neurologic deficit developed. CONCLUSIONS Cryotherapy was moderately effective in the prevention of recanalization after coil occlusion. Deep nerve injury was excessive with the protocol used in the present study.

Recanalization after coil occlusion is a concern for long-term results of endovascular treatment. Knowledge of molecular events following coil occlusion and recanalization could help design specific strategies to promote permanent occlusion. Platinum coils were implanted into canine maxillary, vertebral or lingual arteries. Coil occlusion (treatment 1), routinely followed by recanalization was compared with two strategies to prevent recanalization: beta radiation using 32P coils (treatment 2) and endothelial denudation, using an endovascular device, followed by coil occlusion (treatment 3). The evolution of initial complete occlusions was followed by angiography and pathology at three months. Levels of messenger RNA of vWF (von Willebrand factor), SMA (smooth muscle actin), CD14, CD31 (or PECAM-1: Platelet Endothelial Cell Adhesion Molecule-1), PDGFBB (platelet-derived growth factor), TGF-b1 (transforming growth factor), MCP-1 (macrophage chemoattractant protein), Angiopoietins, Metalloproteinases-9, 14 and inhibitors (TIMP-2, 4) were followed by Reverse Transcription and Polymerase Chain Reaction (RT-PCR). Analyses were performed one, four, seven and 14 days after coiling, and levels of expression after the three treatments were compared using ANOVA s. Intact arteries treated with platinum coils routinely recanalize (100%), but arteries treated by denudation and coiling or with radioactive coils recanalize in only 17% and 4% respectively (P Recanalization is associated with early vWF expression, perhaps reflecting the development of endothelialized channels through thrombus formed after coil occlusion.

Recanalization is a common phenomenon that decreases the efficacy of embolization procedures. It can be inhibited by beta-radiation. Two novel ways of producing radioactive particles are described, by neutron beam irradiation of gold-containing microspheres, or by using the 32P binding capacity of zirconium-containing microspheres. Particles were tested in vivo, to assess their ability to deliver radioactivity locally, using canine renal artery, porcine rete mirabile, and rabbit ear embolization models. Both radioactive microspheres (198Au and 32P) showed no detectable activity outside the target territory. 32P microspheres demonstrated typical radiation changes in a porcine rete mirabile arteriovenous malformation model.

Objective We developed an animal model to evaluate vascular trauma induced by endovascular devices that are proposed for the treatment of cerebrovascular diseases. Methods The model was constructed in six domestic swine by elongating the common carotid artery using interpositional grafts. Balloon catheters (n = 3), stents (n = 2), and a snare were tested 9 to 13 days after surgery. Device performance was evaluated by angiography, macroscopic photography, and histopathological examination. Results Animals tolerated the surgical procedure well, and artificial siphons were thought to provide realistic conditions for device testing. Balloon catheters induced minimal trauma, whereas coronary stents caused severe spasm or thrombosis and extensive macroscopic changes. Conclusion Construction of an in vivo siphon model is feasible and potentially useful for testing neurovascular devices.

Endovascular treatment of cerebral aneurysm is safe and effective, but recurrence of disease is frequent compared with results with surgery. The purpose of this study was to determine the effects of recombinant transforming growth factor beta(1) (rTGFbeta(1)) secreted by transplanted autologous vascular smooth muscle cells (VSMC) on results of endovascular treatment.VSMC from canine femoral arteries were infected with adenovirus vector encoding rTGFbeta(1)/green fluorescent protein (rTGFbeta(1)/GFP) or GFP only. rTGFbeta(1) production was measured with an enzyme-linked immunosorbent assay, and autocrine and paracrine effects of rTGFbeta(1) on cell functions were quantified with a proliferation assay and collagen synthesis. A bilateral carotid aneurysm model was used to compare angiographic and pathologic results after embolization with sponges seeded (n = 14) or not seeded (n = 34) with VSMC expressing TGFbeta(1) or GFP (n = 7 each). Transgene retention was confirmed with Western blot analysis.In vitro, TGFbeta(1) production varied from 0.9 to 180 ng/mL/d with increasing multiplicity of infection (MOI). Collagen synthesis was doubled at low (300) MOI and increased by one and a half times at high (or=300) MOI. rTGFbeta(1) was biologically active, as shown with the mink lung epithelial cell proliferation assay. VSMC grafts showed effective GFP expression up to 3 weeks after transplantation. Angiographic results were improved and neointima thickness was increased with cellular grafts, as compared with controls, but there was no significant difference between aneurysms treated with VSMC encoding rTGFbeta(1)/GFP or GFP vectors.Cellular grafts can promote healing of aneurysms, but overexpression of rTGFbeta(1)/GFP did not demonstrate added benefits in this model.

Background and Purpose— Beta radiation prevents recanalization after coil embolization. We sought to determine the effects of varying coil caliber, length, activity of 32 P per centimeter of coil or per volume, and spatial distribution of coils on recanalization. Methods— We studied the angiographic evolution of 81 canine maxillary, cervical, and vertebral arteries implanted with a variety of nonradioactive (n=29 arteries) or radioactive (n=52) devices. We compared 1- or 2-caliber 0.015 or 0.010 coils ion-implanted or not with 3 different activity levels (0.05 to 0.08, 0.06 to 0.12, 0.18 to 0.32 μCi/cm) of 32 P and totaling 4, 8, and 16 cm in length for the same arterial volume. We also compared inhibition of recanalization by beta radiation delivered by stents, after coil occlusion proximal to or within the stent, with that delivered by coils placed within nonradioactive stents. We finally studied the angiographic evolution of canine lateral wall carotid aneurysms treated with 1 or 2 stents of various activity levels positioned inside the parent artery across the neck. Animals were killed at 4 and 12 weeks for macroscopic photography and pathological examination. Results— All arteries (29 of 29) occluded with nonradioactive devices were recanalized, while 49 of 52 arteries (94%) implanted with 32 P devices were occluded at 4 weeks. All aneurysms treated with stents, radioactive or not, demonstrated residual filling of the sac or of channels leading to the aneurysms at follow-up angiography at 4 weeks. Conclusions— The recanalization process found in the canine arterial occlusion model is minimally affected by coil caliber, number, and length or packing density. Beta radiation reliably inhibits this process, but thrombosis is an essential condition for the efficacy of a radioactive coil strategy.

Cold hibernated elastic memory (CHEM) polyurethane-based foam is a new shape memory polymeric self-deployable structure. Standard cytotoxicity and mutagenicity tests were conducted on CHEM in vitro, to ensure biocompatibility before studying potential medical applications. In vivo, lateral wall aneurysms were constructed on both carotid arteries of eight dogs. Aneurysms were occluded per-operatively with CHEM blocks. In two dogs, CHEM embolization was compared with gelatin sponge fragment embolization. Internal maxillary arteries (Imax) were also occluded with CHEM using a 6F transcatheter technique. Angiography and pathology were used to study the evolution of aneurysms and Imax at 3 and 12 weeks. Imax embolized with CHEM foam remained occluded at 3 weeks. Most aneurysms embolized with CHEM showed a small residual crescent of opacification at initial angiography, but angiographic scores were significantly better at 3 weeks. Thick neointima formation over the CHEM at the neck of aneurysms was demonstrated at pathology. The foamy nature of CHEM favours the ingrowth of cells involved in neointima formation. New devices for endovascular interventions could be designed using CHEM's unique physical properties.

Background and Purpose — We sought to investigate the role of the endothelial lining in aneurysmal persistence and recurrence after endovascular treatment of aneurysms. Methods — Bilateral venous pouch canine carotid aneurysms were studied by angiography and pathology 1, 2, and 3 weeks after intraoperative collagen sponge embolization, coated or not coated with fibrinogen (n=15). In 12 dogs the endothelial lining of one aneurysm was removed before embolization, and results were compared with a control aneurysm after bilateral sponge embolization. In 4 animals embolization with a sponge covered with endothelium was compared with treatment with a sponge covered with adventitia. In 4 animals an inverted venous pouch aneurysm embolized with an adventitia-covered sponge was compared with a normal aneurysm embolized with an endothelialized sponge. In 3 animals inverted venous pouch aneurysms were embolized with a sponge covered or not covered with endothelium. Control aneurysms (n=3 or 4 each) included untreated normal, inverted, and de-endothelialized venous pouch aneurysms. Angiographic results at 3 weeks were compared by Wilcoxon’s test. Results — Endothelialization of the clot that forms on the sponge was complete at 1 week, forming clefts that developed into recurrences. Reversed or de-endothelialized aneurysms spontaneously thrombosed, while normal venous pouch aneurysms remained patent for at least 3 weeks. The addition of fibrinogen, endothelium, or adventitia to the sponges did not prevent recurrences, which occurred routinely after embolization of endothelialized aneurysm. De-endothelialization of the aneurysmal wall improved angiographic results at 3 weeks ( P =0.02), while reversing the venous pouch before embolization led to complete healing ( P =0.003). Conclusions — The endothelial lining is essential to the persistence of residual lesions. Early endothelial invasion of the clot leads to recanalization and recurrences after embolization of aneurysms. This observation provides new opportunities to improve results of endovascular treatment of aneurysms.

Background and Purpose — Endovascular treatment of cerebral aneurysms, a minimally invasive alternative to surgery, is too often followed by recanalization and recurrences. The purpose of this work was to assess if in situ beta radiation can inhibit recanalization after coil embolization. Methods — Radioactive platinum coils ( 32 P-coils) were produced by ion implantation of 32 P. A single-coil arterial occlusion model was used to compare angiographic and pathological results at 1 to 12 weeks after nonradioactive and 32 P-coil embolization of maxillary, cervical, and vertebral arteries in 26 dogs. Coils of varying activities were used and results compared to define the minimal activity required to inhibit recanalization. Similar experiments were performed in 16 porcine maxillary and lingual and 8 rabbit axillary arteries. Results of 32 P-coil embolization of bifurcation aneurysms were then compared with embolization with nonradioactive coils in 12 dogs at 3 months. Results — Nonradioactive coil embolization of canine arteries led to occlusion at 1 week, followed by recanalization at 2 weeks, which persisted at 3 months in all cases. 32 P-coils, ion-implanted with activities above 0.13 μCi/cm, led to persistent occlusion at 3 months in 80% of arteries. 32 P-coils ion-implanted with the same activity inhibited recanalization in porcine and rabbit arteries. Bifurcation aneurysms treated with 32 P-coils had better angiographic results at 3 months ( P =0.006) than aneurysms treated with nonradioactive coils. Arteries occluded were filled with fibrous tissue at 3 months. Aneurysms embolized with 32 P-coils showed more complete neointimal coverage of the neck, without recanalization, as compared with aneurysms treated with nonradioactive coils. Conclusion — In situ low-dose beta radiation inhibits recanalization after coil embolization and may improve long-term results of endovascular treatment of aneurysms.

Porosity and pore density (PD) are important characteristics of flow diverters (FDs), because they may influence device efficacy and safety. Reliable measurement of these parameters would seem to be required for comparisons between devices, device selection at the time of clinical usage, as well as for research purposes. Because there is no standard method of measurement, our aim was to assess the intra-rater and inter-rater reliability of PD measurements and of three different ways of measuring porosity.Six microphotographs of two fully deployed FDs were taken overlying two different millimetric reference grids: one flat and the other corrected to match the cylindrical stent. Standardized protocols for independently measuring PD and porosity according to three different methods were used by three trained observers and by the same observer twice. Bland-Altman plots and intra-class correlation coefficients (ICC) were used to study the reliability of the measurements.For porosity, satisfactory agreement occurred only when the same method of measurement was performed by the same observer. Intra-observer and inter-observer agreement were poor for measures of porosity when different methods were used (with differences in the range of 5-10%, ICC0.6 for all methods). Measurement of PD was more reliable within (ICC 0.991 (0.946 to 0.999)) and between (ICC 0.945 (0.781 to 0.991)) observers.Without standardization, the porosity of different devices cannot reliably be compared because use of different methods or different observers substantially changes results. Pore density seems to be more reliably measured than porosity.

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.

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.

Animal models may explain how stents and flow diverters (FDs) may succeed or fail to treat bifurcation aneurysms. 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. 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. FDs did not successfully treat most bifurcation aneurysms, at least in this animal model.

Haemorrhagic complications can occur following aneurysm treatment with flow diverters (FD), but the underlying mechanism remains unknown. We describe a case where deformation of the device may have contributed to the complication. A patient with a giant, previously unruptured cavernous aneurysm that extended intracranially to cause oedema of the internal capsule was treated with flow diversion. Treatment was followed by multiple episodes of peri-aneurysmal haemorrhages within eight days. A deformation of the device which occurred where it curved to cross the aneurysm neck created residual flows which, in the presence of a stent stenosis immediately beyond the neck, may have contributed to the observed ruptures. Following multiple haemorrhages the patient subsequently died. Autopsy demonstrated early red thrombus partially bridging the struts of the flow diverter, and intra-aneurysmal thrombus of various ages. Microscopic pathology showed an aneurysm wall consisting of collagen infiltrated with neutrophils, but the wall was absent near the cerebral peduncle, adjacent to the brain haemorrhage. Radiographs of the extracted specimen confirmed deformation of the FD construct, located at the transition zone of the stent, leading to increased pore size and porosity. The site of the deformation correlated with the angiographic presence of a continued blood inflow jet into the aneurysm. Stent deformation at the transition zone may promote persistent blood entry into the aneurysm, and in turn potentially contribute to haemorrhagic complications.

BACKGROUND AND PURPOSE: Endovascular treatment of wide-neck bifurcation aneurysms often results in incomplete occlusion or aneurysm recurrence. The goals of this study were to compare results of coil embolization with or without the assistance of self-expandable stents and to examine how stents may influence neointima formation. MATERIALS AND METHODS: Wide-neck bifurcation aneurysms were constructed in 24 animals and, after 4–6 weeks, were randomly allocated to 1 of 5 groups: 1) coil embolization using the assistance of 1 braided stent ( n = 5); 2) coil embolization using the assistance of 2 braided stents in a Y configuration ( n = 5); 3) coil embolization without stent assistance ( n = 6); 4) Y-stenting alone ( n = 4); and 5) untreated controls ( n = 4). Angiographic results were compared at baseline and at 12 weeks, by using an ordinal scale. Neointima formation at the neck at 12 weeks was compared among groups by using a semiquantitative grading scale. Bench studies were performed to assess stent porosities. RESULTS: Initial angiographic results were improved with single stent–assisted coiling compared with simple coiling ( P = .013). Angiographic results at 12 weeks were improved with any stent assistance ( P = .014). Neointimal closure of the aneurysm neck was similar with or without stent assistance ( P = .908), with neointima covering coil loops but rarely stent struts. Y-stent placement alone had no therapeutic effect. Bench studies showed that porosities can be decreased with stent compaction, but a relatively stable porous transition zone was a limiting factor. CONCLUSIONS: Stent-assisted coiling may improve results of embolization by allowing more complete initial coiling, but these high-porosity stents did not provide a scaffold for more complete neointimal closure of aneurysms.

BACKGROUND AND PURPOSE: The relationship between aneurysm dimensions, flow, thrombosis, and rupture remains poorly understood. We attempted to clarify this relationship by exploring various swine aneurysm models. MATERIALS AND METHODS: Bilateral carotid aneurysms were constructed according to 3 protocols in 24 animals: small aneurysms with wide necks (group 1; n = 6 animals); small aneurysms with small necks (group 2; n = 4 animals), and giant aneurysms with large necks (group 3; n = 14 animals). Group 3 included 3 subgroups, related to testing the model in various experimental conditions: The neck was clipped in 3 animals; venous pouches lacked an endothelial lining in 4 animals; and 7 were control animals. Animals were followed until rupture, or for 1–4 weeks. Angiography was performed postoperatively and before euthanasia. We studied lesion pathology, paying attention to thrombosis, recanalization, wall composition, and perianeurysmal hemorrhage. RESULTS: Groups differed significantly in aneurysm dimensions and aspect ratio (P = .002). Ruptures occurred more frequently in animals with untreated giant aneurysms (7/7) than in animals with small wide-neck (0/6) or small-neck (2/4) aneurysms (P = .002). Ruptures occurred only in animals with thrombosed aneurysms. Lesions lacking an endothelial lining and 5 of 6 clipped venous pouches thrombosed but did not rupture. One giant lesion ruptured despite complete clipping. The wall was deficient in α-actin and was infiltrated with inflammatory cells and erythrocytes in all thrombosed cases, ruptured or not. Ruptures were associated with recanalizing channels in 9 of 10 cases. CONCLUSIONS: Thrombosis, inflammation, and recanalization may precipitate aneurysmal ruptures in a swine model

Recanalization after coil occlusion is a concern for long-term results of endovascular treatment. Knowledge of molecular events following coil occlusion and recanalization could help design specific strategies to promote permanent occlusion. Platinum coils were implanted into canine maxillary, vertebral or lingual arteries. Coil occlusion (treatment 1), routinely followed by recanalization was compared with two strategies to prevent recanalization: beta radiation using 32P coils (treatment 2) and endothelial denudation, using an endovascular device, followed by coil occlusion (treatment 3). The evolution of initial complete occlusions was followed by angiography and pathology at three months. Levels of messenger RNA of vWF (von Willebrand factor), SMA (smooth muscle actin), CD14, CD31 (or PECAM-1: Platelet Endothelial Cell Adhesion Molecule-1), PDGF-BB (platelet-derived growth factor), TGF-b1 (transforming growth factor), MCP-1 (macrophage chemoattractant protein), Angiopoietins, Metalloproteinases-9,14 and inhibitors (TIMP-2, 4) were followed by Reverse Transcription and Polymerase Chain Reaction (RT-PCR). Analyses were performed one, four, seven and 14 days after coiling, and levels of expression after the three treatments were compared using ANOVAs. Intact arteries treated with platinum coils routinely recanalize (100%), but arteries treated by denudation and coiling or with radioactive coils recanalize in only 17% and 4% respectively (P