Comparison of experimental aneurysms embolized with second-generation embolic devices and platinum coils

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Acta Neurochir (2009) 151:497–505 DOI 10.1007/s00701-009-0237-1

NEUROVASCULAR OBSERVATIONS

Comparison of experimental aneurysms embolized with second-generation embolic devices and platinum coils Monika Killer & Thomas Hauser & Andrea Wenger & Bernd Richling & Gunther Ladurner

Received: 17 August 2008 / Accepted: 6 February 2009 / Published online: 17 March 2009 # Springer-Verlag 2009

Abstract Purpose The purpose of the study was to compare the performance of second-generation embolic devices with that of platinum coils in experimental aneurysms. Methods Microsurgically constructed bifurcation aneurysms in rabbits were embolized with platinum coils (n= 7), HydroCoils 10 (n=10), HydroSoft (n=14) or Cerecyte (n=6) devices. After 1 month, angiographic occlusion was scored and the aneurysms were histologically evaluated by light microscopy. Continuous and ordinal results were compared using ANOVA/Tukey–Kramer HSD and χ2 tests respectively. Results Angiographic occlusion at follow-up was increased in the HydroCoil and HydroSoft groups and decreased in the platinum coil and Cerecyte groups. Fibrovascular tissue was observed in the sac of the Cerecyte group, while mixtures of fibrovascular tissue and fibrinous thrombus were observed in the other three groups. The inflammatory response and endothelialization of the neck were similar in all groups. Conclusions Expansile hydrogel devices have led to increased progressive occlusion, while degradable polymer M. Killer (*) : G. Ladurner Neuroscience Institut Salzburg/Department of Neurology, Christian Doppler Clinic/Paracelsus Medical University, Salzburg, Austria e-mail: [email protected] T. Hauser : B. Richling Department of Neurosurgery, Christian Doppler Clinic/Paracelsus Medical University, Salzburg, Austria A. Wenger Neuroscience Institut Salzburg, Paracelsus Medical University, Salzburg, Austria

devices led to an increased rate of thrombus organization compared with platinum coils. Keywords Aneurysm . Coiling . Vascular disease . Animal model

Introduction The endovascular treatment of cerebral aneurysms with platinum coils has become a widely accepted alternative to surgical clipping [12]. Moreover, in many neurovascular centers, it has become the method of choice for many of these lesions. However, evidence showing equivalent stability of endovascular and surgical treatments does not exist. Problems of recanalization, recurrence, and coil compaction can occur in aneurysms treated with platinum coils, particularly in large and wide-necked aneurysms [15]. In an effort to overcome these limitations, secondgeneration embolic devices were developed. In a first approach, degradable polymers were added to platinum coils. As the polymers hydrolyze, the degradation products elicit a larger inflammatory response compared with platinum coils alone and may increase the rate of conversion of thrombus to fibrous tissue [3, 11]. In a second approach, an expansile hydrogel was added to a platinum coil. Inside the aneurysm sac, the hydrogel expands to increase the volumetric filling of the aneurysm compared with platinum coils alone and may provide greater mechanical stability for thrombus organization [5]. Clinical results from the second-generation devices have been mixed. Some centers have reported better angiographic results, while others report worse, compared with platinum coils [10, 14]. Confounding interpretation of the clinical results, the literature is not complete, with preclin-

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ical evaluations of the different second-generation devices. Where preclinical results are published, different models of experimental aneurysms are often utilized [1, 7, 13, 21]. In an effort to understand the effect of the second-generation devices on angiographic and histological outcomes, we compared platinum coils, HydroCoil® 10 (MicroVention Terumo, Aliso Viejo, CA, USA), HydroSoft® (MicroVention Terumo), and Cerecyte® (Micrus, San Jose, CA, USA) devices in rabbit bifurcation aneurysms.

Materials and methods This study was carried out in accordance with the Austrian regulations governing animal experiments and was approved by the committee for animal experiments from Land Salzburg, Austria. Experimental bifurcation aneurysms were surgically created in 37 New Zealand white rabbits (mixed gender, 2.5–3.5 kg). At least 21 days after aneurysm creation, embolization was performed with platinum coil (n= 7), HydroCoil 10 (n=10), HydroSoft (n=14), and Cerecyte (n=6) devices. All aneurysms underwent angiographic follow-up and harvest at 1 month post-embolization. Microsurgical aneurysm construction The microsurgical construction of the carotid bifurcation aneurysms was performed according to the method described by Forrest and O’Reilly [8]. For all operative procedures, the animals were anesthetized using intramuscular injection of 20–30 mg/kg of ketamine and 0.2 mL of 2% xylazine, followed by maintenance anesthesia by intravenous injection of a saline solution of ketamine and xylazine (5:1:5; 0.5– 1 mL/h/kg). Both common carotid arteries (CCA) were exposed and a permanent ligature was placed proximal to the left CCA bifurcation and transsected. Using single-knot sutures with 10–0 Prolene, an end-to-side anastomosis of the left to the right CCA was performed and the aneurysm sack constructed with a venous graft pouch from the left external jugular vein. Aneurysm embolization and follow-up Under anesthesia and sterile conditions, the right femoral artery was surgically exposed and a 5F vascular sheath was placed. After intravenous heparin (100 U/kg) administration, a 5F guiding catheter was advanced into the right CCA. The aneurysm dimensions were measured using digital subtraction angiography (DSA) with a radiopaque ball bearing (∅ 7.9 mm) as a sizing reference. A microcatheter was advanced into the aneurysm sac.

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Embolization was performed with platinum coil (MicroPlex Coiling System®, MicroVention Terumo or Guglielmi Detachable Coils®, Boston Scientific), HydroCoil 10, HydroSoft, or Cerecyte devices under fluoroscopic guidance. The aneurysms of the HydroCoil 10 and HydroSoft groups were framed with 1–3 platinum coils before filling with hydrogel-containing devices. Embolization was concluded when greater than 85% of the aneurysm sac was occluded. After performing the final DSA, all catheters and the sheath were removed. The proximal aspect of the femoral artery was ligated with 6–0 silk suture. One month post-treatment (32±3 days), the rabbits were anesthetized and a 5Fr sheath was placed in the left femoral artery. Follow-up angiography was performed using a 5Fr guiding catheter positioned in the right CCA. The rabbits were sacrificed by an overdose of the anesthetic agents and 2 mL of T61® euthanasia solution (Veterinaria AG, Zurich, Switzerland). Histological processing After sacrifice, the CCA–aneurysm complex was first rinsed in situ with saline and then perfusion-fixed with 10% neutral buffered formalin. After surgical excision, the specimen was placed in fresh fixative. The fixed specimens were then dehydrated in a graded series of ethanol and embedded in methyl methacrylate. After polymerization, longitudinal sections of the aneurysms were ground to a thickness of 30–40 μm using a circular diamond saw (ISOMET®, Buehler, Lake Bluff, IL, USA) and the EXAKT® system (EXAKT Technologies, Oklahoma City, OK, USA). The ground sections were surface stained with toluidine blue/basic fuchsin or Sanderson Rapid Bone Stain (Surgipath Medical, Richmond, VA, USA). Evaluation criteria Procedural Using the pre-embolization angiogram with the ball bearing calibration tool, the aneurysm dome, length, and neck were determined. The volume of the aneurysm was calculated from the dome and length assuming cylindrical geometry. Additionally, the number of devices and the total device length were recorded. The volumetric filling of the aneurysm was calculated by dividing the volume of all implanted devices by the volume of the aneurysm. Angiographic Aneurysm occlusion post-treatment and at follow-up was scored by one of the authors (M.K.) in accordance with the

Comparison of experimental aneurysms embolized with second-generation

Raymond scale [18]. Complete occlusion, near complete occlusion, and incomplete occlusion were scored 1, 2, and 3 respectively. Histological The ground sections were evaluated using light microscopy. The evaluation focused on the nature of the contents of the aneurysm sac (blood, unorganized thrombus, fibrinous thrombus, and fibrovascular tissue), aneurysm neck (fibrin coverage, neointima coverage, endothelialization, and parent artery protrusions), and inflammation (nature and number of inflammatory cells at the device interface and within the sac). Statistical analysis Statistical analyses were performed using JMP 7.0 (SAS Institute, Cary, NC, USA). Differences in continuous data were assessed using ANOVA. If a difference was identified in the overall test, individual differences were assessed and compared using the Tukey–Kramer HSD test. Differences in discrete data were assessed using a χ2 test. Statistical significance was accepted at α≤0.05.

Results Procedural results All 37 aneurysms were successfully embolized. All rabbits were in good health without any observable neurological deficit over the course of the experiment. The procedural results are summarized in Table 1. Altogether, 25 platinum coil devices were used to embolize the 7 aneurysms of the platinum coil group. Devices with a variety of diameters (2–9 mm) and lengths (4–30 cm) were used to frame and fill the aneurysm sac.

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In the HydroCoil group, 8 of the 10 aneurysms were framed with 1–3 platinum coils (14 in total) and then filled with HydroCoil 10 devices. The other 2 aneurysms were exclusively filled with HydroCoil 10 devices. Sixty-two HydroCoil 10 devices in a variety of diameters (2–6 mm) and lengths (2–12 cm) were used to fill the aneurysm sac. HydroCoil devices comprised 80±15% (range 50–100%) of the devices and 65 ±23% (range 24–100%) of the coil length utilized to embolize the individual aneurysms. The aneurysm dome (p=0.006) and volume (p=0.0006) of the HydroCoil group was significantly larger than in the other three groups. The aneurysm length (p=0.01) was significantly larger in the HydroCoil group than in the Cerecyte group. In the HydroSoft group, 12 out of 14 aneurysms were framed with one platinum coil (12 in total) and then filled with prototype and commercially available HydroSoft devices. The other 2 aneurysms were small and were exclusively filled with HydroSoft devices. Seventy-two HydroSoft devices in a variety of diameters (2–6 mm) and lengths (2–15 cm) were used to fill the aneurysm sac. HydroSoft devices comprised 89±9% (range 67-100%) of the devices and 76±19% (range 40–100%) of the coil length utilized to embolize the individual aneurysms. All 6 aneurysms in the Cerecyte group were filled exclusively with Cerecyte coils. Forty-two commercially available 2D and 3D Cerecyte devices were utilized. Devices with a variety of diameters (2–8 mm) and lengths (2–16 cm) were used to frame and fill the aneurysm sac. Angiographic results The scoring of the post-treatment and follow-up angiograms according to the Raymond scale is shown in Table 2. The choice of embolic device did not affect the posttreatment scores, as complete or near complete occlusion was observed in 36 of the 37 (97%) aneurysms. Statistically significant differences in the post-treatment Raymond scores

Table 1 Procedural results

Dome (mm) Length (mm) Neck (mm) Volume (cm3) Number of devices Device length (cm) Volumetric filling (%)

Platinum coil (n=7)

HydroCoil 10 (n=10)

HydroSoft (n=14)

Cerecyte (n=6)

4.7±0.6a 8.6±2.2a,b 3.2±0.8 0.15±0.06a 2.9±2.0 42±22 22±14

6.7±1.9b 10.9±3.4a 4.6±1.1 0.42±0.27b 8.0±4.6 79±54 41±19

5.0±1.2a 7.8±2.8a,b 3.9±0.9 0.17±0.09a 6.0±2.7 51±26 30±14

4.4±1.2a 6.8±2.2b 4.2±1.3 0.12±0.10a 7.0±2.4 51±26 27±7

Results without superscript labeling do not exhibit statistically significant differences. Statistically significant differences are present in results without common superscript letters

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Table 2 Raymond scoring of angiograms Group

Platinum coil HydroCoil HydroSoft Cerecyte

Post-treatment

One-month follow-up

Complete (%)

Near complete (%)

Incomplete (%)

Complete (%)

Near complete (%)

Incomplete (%)

2 2 5 2

5 8 8 4

0 0 1 0

3 7 9 3

2 3 4 2

2 0 1 1

(29) (20) (36) (33)

(71) (80) (57) (67)

(0) (0) (7) (0)

(43) (70) (64) (50)

(29) (30) (29) (33)

(29) (0) (7) (17)

were not observed (p=0.60). Due to the wide-necked aneurysms treated without neck protection, protrusions of the embolic devices into the parent artery were present in 6, 1, 9, and 6 aneurysms post-treatment in the platinum coil, HydroCoil, HydroSoft, and Cerecyte groups respectively, using angiography. At follow-up, a greater percentage of the aneurysms were scored as complete or near complete occlusion in the HydroCoil (10 out of 10 aneurysms, 100%) and HydroSoft (13 out of 14 aneurysms, 93%) groups compared with the platinum coil (5 out of 7 aneurysms, 71%) and Cerecyte group (5 out of 6 aneurysms, 83%), although the differences were not statistically significant (p=0.41). Angio-

graphically, protrusions of the embolic devices into the parent artery were present in 6, 2, 9, and 6 aneurysms at follow-up in the platinum coil, HydroCoil, HydroSoft, and Cerecyte groups respectively. Representative angiographic results for the platinum coil, HydroCoil, HydroSoft, and Cerecyte groups are shown in the upper panels of Figs. 1, 2, 3, and 4 respectively.

Fig. 1 Aneurysm treated with platinum coils. a Pre-embolization DSA, 5.0×11.6 mm (dome × length). b Post-treatment DSA with device protrusion into the parent artery. c Follow-up DSA. Note the increased neck contrast filling and device protrusion into the parent artery. d–f Ground section, basic fuchsin-toluidine blue surface staining. d Aneurysm overview, showing less coil filling in the center,

neointima-covered concave neck extension over the orifice plane (double arrow), and coil protrusion into the parent artery (PA). e Enlarged upper rectangle from d. Fibrovascular tissue between coils, and multinucleated foreign body giant cells (FBGC) at the inner coil interface. f Enlarged lower rectangle from d, showing FBGC-covered coils underneath a thick neointima

Histological results In the platinum coil group, 4 aneurysms were filled with vascularized fibrovascular tissue between the coil loops (Fig. 1d, e). The other 3 aneurysms had unorganized

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Fig. 2 Aneurysm treated with HydroCoil devices. a Pre-embolization DSA, 4.8×9.5 mm (dome × length). b Post-treatment DSA, showing a single loop protruding into the parent artery. c Follow-up DSA, showing reduced neck contrast filling and no parent artery protrusion. d–f Ground section, Rapid Bone Stain surface staining. d Aneurysm overview, showing platinum coil (MC) framing, and HydroCoil 10 (HC10) filling in the sac center. Note organized red thrombus (orgThr)

trapped in the dome and fibrin remnants (Fi) in the center. In this section no coils protruding through the flat neck surface into the parent arteries (PA) are visible. Enlarged upper rectangle from d showing the foreign body response (FBGC) to the MC and HC10. f Enlarged lower rectangle from d showing the thick neointima covering of the HC10

thrombus and/or fibrinous thrombus remains, predominantly in the center of the sac. Inflammation consisted of single and multiple layers of predominantly multinucleated giant cells lining the inner and outer interfaces of the platinum coils (Fig. 1e, f). The necks were covered with endothelialized neointima resembling a new vessel wall (Fig. 1f) in 5 cases. In the remaining case, the neck was approximately 75% endothelialized. In 3 cases, recanalization was evident due to the concave shape of the neck surface. Platinum coil loops protruding into the parent artery and covered with neointima were present in all 7 aneurysms. In the HydroCoil group, platinum coils were located in the dome and along the aneurysm walls, while the HydroCoil devices were located toward the center of the sac (Fig. 2d). In 8 of the 10 aneurysms, the center of the aneurysm sac had fewer devices than the periphery. Two aneurysms were filled with fibrovascular tissue between the coil loops. The other 8 aneurysms had fibrovascular tissue with fibrin clot remains, predominantly in the center of the sac. In 9 aneurysms, inflammation consisted of macrophages and single multinucleated giant cells in layers around the device interfaces (Fig. 2e). In the tenth

aneurysm, inflammation consisted of macrophages, lymphocytes, and giant cells. Greater numbers of inflammatory cells were associated with increasing amounts of unorganized/fibrinous thrombus. The necks had flat or concave surfaces and were traversed with neointima of varying thicknesses, completely endothelialized in 6 cases and partially endothelialized in 4 (Fig. 2f). Single or multiple platinum coil and/or HydroCoil loops protruding into the parent artery and partially covered with neointima were present in all 10 aneurysms. In the HydroSoft group, 11 aneurysms were filled with fibrovascular tissue between the coil loops (Fig. 3d). The other 3 aneurysms had fibrovascular tissue with fibrin clot remains, predominantly in the center of the sac. In 11 aneurysms, inflammation consisted of macrophages and single multinucleated giant cells in layers around the device interfaces. The inflammatory cells were found mainly around the platinum coil component of the HydroSoft devices (Fig. 3e, f). In 3 aneurysms, inflammation consisted of macrophages, lymphocytes, and giant cells. Increased inflammation was associated with increasing amounts of unorganized/fibrinous thrombus. The necks

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Fig. 3 Aneurysm treated with HydroSoft devices. a Pre-embolization DSA, 5.0×8.5 mm (dome × length). b Post-treatment DSA. c Followup DSA, showing stable neck contrast filling. d–f Ground section, Rapid Bone Stain surface staining. d Aneurysm overview, showing platinum coil (MC) framing, and HydroSoft (HySo) filling in the sac center. Flat neck surface at the orifice plane, but neointima-covered

coils protruding into the parent artery (PA). e Enlarged upper rectangle from d showing a pronounced foreign body response (FBGC) to the platinum overcoil and the polymer filament (asterisk), but less to the hydrogel of the HydroSoft device (HySo). f Enlarged lower rectangle from d showing an HySo with FBGC underneath the neointima

had flat or concave surfaces and were traversed with neointima of varying thicknesses, completely endothelialized in 4 cases and only partially endothelialized in 10 (Fig. 3f). Fibrin deposition was observed where endothelialization was incomplete. Single or multiple platinum coil and/or HydroSoft loops protruding into the parent artery and covered with fibrinous thrombus or neointima were present in 12 aneurysms. In the Cerecyte group, all 6 aneurysms were filled with fibrovascular tissue between the coil loops (Fig. 4d). Remnants of the degradable polymer filaments were observed within the platinum coils (Fig. 4e). In 5 aneurysms, inflammation consisted of macrophages and multinucleated giant cells in layers around the device interfaces (Fig. 4e, f). In one aneurysm, inflammation consisted of macrophages, lymphocytes, and giant cells. Increased inflammation was associated with increasing amounts of unorganized/fibrinous thrombus. In 5 aneurysms, the necks were traversed with endothelialized neointima. The concave neck surface of the sixth aneurysm was covered with fibrin and minimal endothelialization. Single or multiple Cerecyte loops protruding into the parent artery and covered with organizing thrombus or neointima were present in all 6 aneurysms.

Discussion In this study, we evaluated biodegradable and expansile second-generation embolic devices in comparison to platinum coils in experimental rabbit bifurcation aneurysms. Since most human aneurysms are located in or close to bifurcations, we considered the hemodynamics of this model to be ideally suited. Furthermore, the rabbit coagulation profile has been reported to be similar to that of humans [16]. Ideally, an endovascular treatment would provide durable occlusion, as evidenced by angiography, and induce thrombus organization with connective tissue formation inside the aneurysm sac, as evidenced by histology. Until the formation of connective tissue inside the aneurysm sac, it is presumed that an aneurysm can undergo recurrence, recanalization, and/or coil compaction. As such, the coil embolus is required to solely resist these processes until thrombus organization is complete. In preclinical experiments, such as this one, thrombus organization is relatively rapid and largely completed in a month. Despite this rapid organization, recurrence was observed in 33%, 29%, 10%, and 0% of the Cerecyte, platinum coil, HydroCoil, and

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Fig. 4 Aneurysm treated with Cerecyte devices. a Pre-embolization DSA 4.3×7.5 mm (dome × length). b Post-treatment DSA, showing protruding coils in the parent artery and contrast filling in the sac. c Follow-up DSA, showing complete occlusion of the sac and reduced protrusion of coils into the parent artery. d–f Ground section, basic fuchsin-toluidine blue surface staining. d Aneurysm overview show-

ing no coils protruding the flat neck surface in the orifice plane (double arrow) into the parent artery (PA). e Enlarged lower rectangle from d with coils underneath the neointima, showing a foreign body response (FBGC) and resorbable polymer filament remnants (arrows). f Enlarged upper rectangle from d showing dense fibrovascular tissue between the coils with interfacial FBGC

HydroSoft groups respectively. In the limited number of histological analyses of human intracranial aneurysm explants treated with platinum coils, thrombus organization is delayed several months or even years [2, 20]. With the slower rate of thrombus organization in humans, the embolus must resist recanalization, recurrence, and coil compaction much longer than in experimental aneurysm models. In our experiment, platinum coils demonstrated expected performance compared with previous reports [1, 7, 9]. Stable or progressive angiographic occlusion was observed in 5 of the 7 cases. Histologically, these aneurysm sacs were largely filled with fibrovascular tissue with some unorganized thrombus and/or fibrinous thrombus remnants in the center. This residual unorganized thrombus may be prone to recanalization. In the Cerecyte group, thrombus organization was increased relative to platinum coils. The entire aneurysm sac was filled with connective tissue, without unorganized thrombus or fibrinous thrombus remnants. However, stable or progressive aneurysm occlusion was observed in only 4 out of 6 cases. These results are similar to those previously published in the rabbit elastase model

with Matrix devices [7]. Although the degradable polymer amplified thrombus organization, the Cerecyte embolic mass was not resistant enough to withstand the hemodynamic forces of the bifurcation aneurysm. As in previous studies, the aneurysms treated with expansile devices, HydroCoil or HydroSoft, had excellent angiographic results [7]. Nine out of ten aneurysms treated with HydroCoil devices and all 14 aneurysms treated with HydroSoft devices had stable or progressive angiographic occlusion. The HydroCoil and HydroSoft aneurysms were largely filled with fibrovascular tissue with some unorganized thrombus and/or fibrinous thrombus remnants in the center of the sacs, similar to platinum coils. More unorganized thrombus and/or fibrinous thrombus were present in the HydroCoil-treated aneurysms compared with the other groups, although these results may be confounded by the statistically significantly increased volume of the aneurysms in this group. The expansile devices provided a durable embolic mass over a 1-month period, but did not increase the rate of thrombus organization. Using platinum coils as a baseline, Cerecyte-treated aneurysms had decreased durability and an increased rate of thrombus

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organization, while the expansile device-treated aneurysms had increased durability and no change in the rate of thrombus organization. It can be speculated that the combination of a degradable polymer to increase thrombus organization with the expansion of the hydrogel to increase durability may improve upon the results of either mechanism alone. The inflammation observed histologically in the aneurysms was similar regardless of the embolic device utilized. In most aneurysms, the aneurysm sac was largely filled with fibrovascular tissue. The foreign body response was prevalent in the vicinity of platinum coils, less so surrounding the hydrogels. In each embolic device group, 1–3 aneurysms were largely filled with unorganized or fibrinous thrombus. In these cases, the inflammation observed inside the aneurysm sac was greater than in those aneurysms filled with fibrovascular tissue. It is unclear why thrombus organization was largely complete in most, but not all cases, after 1 month in this model. However, this variability in the experimental setting may be reflective of the variability observed with embolic devices in patients. Although this study offers a meaningful comparison of two approaches to second-generation embolic devices with platinum coils, it has limitations. In accordance with clinical practice, the aneurysms in the HydroCoil and HydroSoft groups were framed with 1–3 platinum coils before being filled with the expansile devices. Framing aneurysms with platinum coils before filling with HydroCoil devices is typically done due to the lack of commercially available, three-dimensional secondary shapes and the limitations on repositioning time of the HydroCoil devices. In the Cerecyte group, 3D and 2D devices were used to frame and fill the aneurysms respectively. We do not believe that these variations in the embolization protocol influenced the outcome of the results. The lack of widely accepted, quantifiable techniques for the angiographic and histological evaluation of embolized aneurysms affects all clinical and experimental studies [4, 17–19]. In conjunction with convention, we chose the Raymond scale to analyze the angiography. Additionally, the correlation of angiographic, and particularly histological, results of experimental aneurysms to human intracranial aneurysms is low. The hemodynamics of aneurysms near the heart in the necks of animals probably are not fully reflective of the hemodynamics in more distal locations, such as intracranial arterial bifurcations. Furthermore, the aneurysms in this study varied in volume and neck size. The average aneurysm volume of the HydroCoil group was 2.5- to 3.5-fold larger than the other three groups and this difference was statistically significant. Aneurysm volume is a known factor in the performance of endovascular embolization in experimental aneurysms [6]. Finally, the sample sizes in this experiment were small and only one

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short-term follow-up time point was evaluated; however, these limitations may not be significant due to the congruent results within the groups. From this comparison in a single experimental aneurysm model, both the expansile and degradable polymer approaches to second-generation embolic devices showed improvements compared with platinum coils. However, the improvements did not lead to statistically significant differences in angiographic occlusion scoring compared with platinum coils, due in part to the low number of aneurysms evaluated in each group. While these results are encouraging, they also highlight the unmet need for embolic devices that result in occlusion durability and thrombus organization rates greater than those obtained by platinum coils and the second-generation embolic devices.

Conclusions The use of the expansile devices resulted in increased angiographic occlusion at 1 month compared with platinum coils and biodegradable polymer devices. The rate of thrombus organization was increased in the degradable polymer-treated aneurysms compared with aneurysms treated with expansile devices. The nature and number of inflammatory cells were similar, regardless of embolic device utilized. Both the expansile hydrogel and degradable polymer approaches to second-generation embolic devices showed improvements in the rabbit bifurcation model compared with platinum coils. Acknowledgements This study was supported by MicroVention Terumo, Aliso Viejo, CA, USA. We gratefully acknowledge the surgical assistance of Drs. R. Agic, M. Kral, and L. Ritter.

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Comment The authors compare different embolic devices to fill up brain aneurysms In an experimental rat model. They demonstrated minor differences between the various devices tested, but the standard platinum coils compared with expansile hydrogels and degradable polymers surrounding platinum coils are less efficient. Thus, for neurosurgeons the hydrogel and degradable devices might become the devices of the future. The weak point in the paper seems to be the histological analysis of the data. The authors stain two-dimensional sections only at the surface and try to deduce the histological composition of the whole tridimensional aneurysm. This is only valuable if the content in the filled aneurysm is homogeneous, which is rather doubtful. Leo De Ridder Ghent University, Belgium

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