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.

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.

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.

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.

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.

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.

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.

Endothelial denudation combined with embolization in the prevention of endoleaks after endovascular aneurysm repair: an animal study.

PURPOSE: To test whether combining embolization with endothelial denudation could reduce endoleak persistence and recurrence after endovascular aneurysm repair (EVAR) in an animal model. METHODS: Type I endoleaks with collateral outflow were created in bilateral iliac aneurysms in 12 dogs. In 6 animals (group 1), endoleaks were treated by thrombin injection, with or without mechanical denudation of the endothelium. In the other 6 animals (group 2), simultaneous occlusion and endothelial denudation was induced in one side by treatment with a gel containing ethanol, ethylcellulose, and lipiodol, whereas the other side was treated with saline control. Follow-up ultrasonography and angiography were performed before necropsy and histology at 3 months. RESULTS: Denudation combined with thrombin injection led to higher aneurysm shrinkage than thrombin alone, as shown by the mean relative aneurysm diameter (89% vs. 124% at baseline, p<0.01) and length (61% vs. 82% at baseline, p<0.01). Denudation did not significantly reduce endoleak occurrence (4/6 vs. 6/6); however, endoleaks in denuded aneurysms were significantly smaller and located in areas inaccessible to denudation. Six of the 10 endoleaks seen at 3 months occurred despite complete initial occlusion (recurrent endoleaks). In the gel-treated group, embolized aneurysms did not shrink significantly, and stent-graft thrombosis developed in 3/6 embolized aneurysms; however, the 3 other aneurysms showed no endoleaks, while all 6 saline-treated controls exhibited persistent endoleaks. CONCLUSION: This study demonstrates the role of recanalization in endoleak recurrence and indicates that combining embolization and endothelial denudation could be a promising strategy to prevent endoleak persistence or recurrence after EVAR. However, the sclerosing gel tested in this study is not appropriate since it is prone to migration with resultant stent-graft thrombosis.

Radiofrequency endothelial ablation prevents recanalization after endovascular coil occlusion: in vitro and in vivo assessment.

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 Omega) 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 < .001, chi(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.

[Functional consequences of eccentric contractions of the diaphragm]. / Consecuencias de las contracciones excéntricas del diafragma sobre su función.

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<.001 in both cases). Tetanic stimulation also demonstrated an early deterioration in contractility, which fell by 29% in the right hemidiaphragm (P<.05) and by 14% in the left hemidiaphragm (P<.001). Functional impairment was persistent, lasting at least 12 hours, and was associated with sarcomeric and sarcolemmal damage. 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.

[Modifications of diaphragmatic activity induced by midline laparotomy and changes in abdominal wall compliance]. / Modificaciones en la actividad del diafragma inducidas por laparotomía media y cambios en la rigidez de la pared abdominal.

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 H(2)O to 6.3 [0.9]cm H(2)O, P<.01; Pdi(tw), from 12.1 [2.0]cm H(2)O to 15.4 [1.8]cm H(2)O, P<.05]), and these values increased even further with the rigid cast (Pga, to 12.6 [1.5]cm H(2)O; Pdi, to 20.2 [2.3]cm H(2)O; P<.01 for both comparisons); this occurred despite smaller degrees of muscle shortening: by 57% [5%] of the initial length at functional residual capacity at baseline, by 49% [5%] with the bandage (P<.05), and by 39% [6%] with the cast (P<.01). With progressive lengthening of the muscle, its contractile efficacy increased up to a certain point (105% of the length at functional residual capacity), after which it began to decline. CONCLUSIONS: Abdominal wall compliance plays an important role in the diaphragmatic response to stimulation. This appears to be due mainly to changes in its length at rest.

[Diaphragmatic response is influenced by previous muscle activity]. / Respuesta diafragmática en función de la actividad previa del músculo.

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 H(2)O to 3.7 (0.3) cm H(2)O, and from 3.5 (0.3) cm H(2)O to 3.9 (0.3) cm H(2)O, 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 H(2)O to 2.5 (0.3) cm H(2)O (P< .05), probably due to fatigue overcoming the effect of potentiation. 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.

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.

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.

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.

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.

Safety and effectiveness of radioactive coil embolization of aneurysms: effects of radiation on recanalization, clot organization, neointima formation, and surrounding nerves in experimental models.

BACKGROUND AND PURPOSE: Recanalization after coil embolization can be prevented by radiation emitted from 32P coils. We wanted to determine the upper limits of 32P activities that could be implanted onto coils with respect to the potential injury to nearby nerves, delay in organization of the clot, and effects on neointima formation and recanalization. METHODS: We studied the effects of various 32P activities on recanalization and organization of thrombus after coil occlusion of canine arteries and on neointima formation at the neck of canine carotid bifurcation aneurysms. We also tested potential injury to nerves in the vicinity of radioactive or nonradioactive coils in 3 models: the brachial plexus (near proximal vertebral arteries) and the lingual nerve in a lingual artery bifurcation aneurysm model, both models being treated by radioactive or standard coil occlusion. Finally, we wrapped lingual nerves with nonradioactive or high-activity coils and studied their effects on lingual nerves and tongues. Results were assessed with a pathological scoring system and compared with Mann-Whitney and Kruskal-Wallis tests. RESULTS: No deleterious effect of radiation on nerves could be detected. Neointima formation was not hampered, scores of aneurysms treated with 32P-coils being significantly better when compared with treatments with standard coils (P=0.002). Arteries treated with high-activity coils (>3.39 microCi) showed absent recanalization but delayed organization of the clot at 3 months compared with low-activity or nonradioactive coils (P<0.05). CONCLUSIONS: beta-Radiation can prevent recanalization after coil occlusion. We could not demonstrate any deleterious effects of radioactivity on nervous structure or on neointima formation. Delayed organization of thrombus provides a rational basis to establish an upper limit for 32P activities to be implanted onto coils.

Production of radioactive particles for endovascular therapeutic interventions.

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.

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 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.