Published online before print July 17, 2003, doi: 10.1161/01.STR.0000083394.33633.C2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Stroke. 2003;34:2031.)
© 2003 American Heart Association, Inc.
Original Contributions |
Matrix and Bioabsorbable Polymeric Coils Accelerate Healing of Intracranial Aneurysms
Long-Term Experimental Study
From the Division of Interventional Neuroradiology and Leo G. Rigler Radiological Research Center, University of California, Los Angeles.
Correspondence to Yuichi Murayama, MD, Division of Interventional Neuroradiology, Department of Radiological Sciences, David Geffen School of Medicine at UCLA and UCLA Medical Center, 10833 Le Conte Avenue, Los Angeles, CA 90095-1721. E-mail ymurayama{at}jikei.ac.jp
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionConclusionsReferences |
|---|
Background and Purpose— Acceleration of intra-aneurysmal clot organization and fibrosis may be a solution to preventing aneurysm recanalization after endovascular treatment. The purpose of this study was to evaluate the short-term efficacy and long-term safety of the new Matrix coil system.
Methods— Matrix coils consist of thin platinum coils covered with a bioabsorbable, polymeric material (polyglycolic acid/lactide). Fifty-two experimental aneurysms were created in 26 swine. All of the aneurysms were tightly packed with Matrix or Guglielmi detachable coils (GDC). Comparative angiographic and histopathologic data were analyzed at 2 weeks (n=14), 3 months (n=6), and 6 months (n=6) after embolization.
Results— Three aneurysms treated with GDC ruptured despite tight packing. No recanalization or rupturing was observed in the aneurysms embolized with Matrix coils. At 14 days after embolization, the aneurysms treated with Matrix coils exhibited a more extensive area of organized thrombus when compared with the aneurysms treated with GDC (87% versus 75%, P=0.008, n=11). At 3 months, both Matrix and GDC-treated aneurysms demonstrated complete clot organization. Neck tissue thickness was higher in Matrix-treated aneurysms at 14 days and 3 months, but not at 6 months. No untoward parent artery stenosis was observed in aneurysms treated with Matrix during follow-up. The angiographic cross-sectional area of the Matrix-treated aneurysms was smaller than those treated with GDC at the 3 months.
Conclusion— Matrix accelerated aneurysm fibrosis and neointima formation without parent artery stenosis. The Matrix system might prevent aneurysmal recanalization after endovascular treatment of cerebral aneurysms.
Key Words: animal models • endovascular therapy • intracranial aneurysm • polymers • swine
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionsReferences |
|---|
In the past decade, endovascular therapy using Guglielmi detachable coils (GDC) has proven to be a successful alternative for the treatment of intracranial aneurysms.1–11 The most important limitation of the GDC system is the possibility of aneurysm recanalization, particularly in wide-necked or large or giant aneurysms.3,6
Platinum coils are biologically inert and produce a limited and delayed inflammatory response.12 The utilization of "bioactive" material as an embolic agent may be a promising approach to overcome the current limitations of the GDC system.12–24
Recently we applied the concept of tissue engineering to aneurysm therapy using bioabsorbable polymeric material (BPM).25,26 BPMs have been used in biocompatible devices such as sutures and implants and, more recently, as drug delivery vehicles or scaffolds for tissue engineering. BPMs can stimulate cells to regenerate tissue and act as scaffolds for cell transplantation both in vitro and in vivo.
This cellular reaction is necessary to promote scar formation in the aneurysm and can be controlled by the composition of the copolymers. Brain aneurysms can be considered a defect of the normal arterial wall and they can be repaired by applying the concept of tissue engineering. This experimental study was designed to evaluate the acute phase of tissue reaction and long-term safety of Matrix detachable coils in experimental aneurysms.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionsReferences |
|---|
The study was conducted according to the standard operating procedures of our animal research committee. Twenty-six Yorkshire swine of both sexes were acclimated to laboratory conditions for at least 7 days before aneurysm creation and embolization. The swine were approximately 3 to 4 months old and weighed 25 to 40 kg.
Coil Preparation
Matrix detachable coils are platinum coils covered with a bioabsorbable polymer (90% polyglycolide, 10% polylactide) and attached to a stainless steel delivery wire. The details of the coil characteristics were previously described and the detachment system was the same as the one used with GDC.25 Coil diameters ranged from 2 to 12 mm and coil lengths ranged from 4 to 30 cm with both GDC and Matrix detachable coils. Both coil groups were sterilized twice with ethylene oxide prior to use.
Anesthesia
Ketamine 150 mg and xylazine 150 mg were administered intramuscularly. The animals were then intubated and maintained on halothane, 1% to 4% inhaled, administered to effect, in 100% oxygen at 4 to 5 L/min. Monitoring during anesthesia included heart rate, respiratory rate, and temperature.
Aneurysm Construction
Fifty-two lateral wall experimental aneurysms were constructed microsurgically in both common carotid arteries of 26 swine. The details of aneurysm construction have been previously reported.18 Aneurysm sacs (8 to 12 mm) and necks (7 mm) were created of equal size, bilaterally. Aneurysm dimensions were recorded (height, width, length) at the time of creation and used in aneurysm volume and packing density estimation.
Aneurysm volumes were estimated using the formula Va=(4/3)
(a/2)(b/2)(c/2) mm3, where Va equals aneurysm volume, equals height, b equals width, and c equals length; dimensions were obtained at time of aneurysm creation.
The volume of coils was estimated using the formula Vc=(OD/2)2xL, where Vc equals coil volume, OD equals the average outer coil diameter (GDC-18, 0.381 mm; GDC-10, 0.254 mm; Matrix, 0.32 mm), and L equals the total length of coils deployed in the aneurysm. The packing density (PD) for each aneurysm was calculated using the formula PD=(Vc/Va)x100%.
Aneurysm Embolization
All endovascular procedures were performed immediately after aneurysm creation (Figure 1). A total of 52 experimental aneurysms were embolized with standard platinum GDC (n=26) or Matrix coils (n=26). For each swine, the type of coil used to occlude the first aneurysm was randomly chosen.
|
A 6-F sheath was placed in the right femoral artery and selective angiography was performed using a 6-F Fasguide guiding catheter. An intravenous bolus of 3000 U of heparin was injected to prevent thromboembolic complications.
Both GDC and Matrix coils were immersed in sterile saline before embolization. Prior to the embolization procedure, a 2-tipped microcatheter was positioned in the carotid artery to measure the angiographic size of the aneurysm and the parent artery (distance between 2 markers is 3 cm). An Excel 14-microcatheter/Mizzen 10 microguide wire system (Boston Scientific/Target) was advanced through the guiding catheter and the tip of the microcatheter was positioned in the center of the aneurysm. All aneurysms were densely packed using either GDC or Matrix coils.
Postembolization angiograms were performed with the 2-marker microcatheter positioned in the parent artery adjacent to the aneurysm.
Follow-Up Angiogram
At 14 days, follow-up angiograms were performed in all cases, and 14 of 28 animals were then euthanized using standard approved procedures. The remaining 12 animals were kept alive for 3 months (n=6) and 6 months (n=6).
The thickness of the radiolucent tissue gap between the flowing contrast media in the parent artery and the coil mass in the aneurysm (angiographic evidence of neointima) was measured. The measurements were made in 3 points along the neck of the aneurysm corresponding to the center of the coil mass and ±2 mm beyond the center.
Histopathological Analysis
The parent arteries were cut longitudinally, rinsed with saline and photographed (Figure 2). The specimen was placed in 10% buffered formaldehyde. The harvested specimens were sent to an independent pathology laboratory (Wasatch Histology Consultants, Inc, Winnemucca, Nev, and Pathology Associates International, Frederick, Md), and pathology reports were prepared by an independent pathologist. Aneurysms were embedded in methylmethacrylate (MMA). MMA blocks were cut using a diamond band saw blade (EXAKT). At least 3 serial cross-sections (proximal, middle, and distal portions of the aneurysm) were taken across the neck of the aneurysm and aneurysms perpendicular to the parent artery. Sections were grounded to a thickness of approximately100 µm. The percentage of nonorganized clot versus organized thrombus and the tissue thickness across the neck of the aneurysm were evaluated from digital images using NIH Image Software. The neck tissue thickness was determined by drawing a line between the sutures used to create the aneurysm. They were located at the base of the artery and evident on both sides of the aneurysm neck. The distance between the lumen of the artery and this demarcation line was measured as an average between maximum and minimum measurements. If coils were crossed by this line, the demarcation line was moved parallel to its original position, toward the lumen, and redrawn so as to exclude the coil.
|
Statistical Evaluations
Statistical significance of the differences between control and test groups was evaluated using Excel (Microsoft Corp, Inc), or JMP (SAS Statistical Software, Piscataway, NJ). Both the paired t test and the fixed factor analysis of variance (ANOVA) were used primarily as control for different sources of variation. The paired t test was used as control in animal-to-animal variation. The ANOVA, in this case, was a 3-factor nonreplicated analysis.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionsReferences |
|---|
Packing Densities
The packing densities were similar between GDC and Matrix-treated aneurysms (Table 1).
|
Clinical Outcome and Complications
A total of 23 swine survived the surgical and endovascular procedures. Three deaths occurred due to rupturing of aneurysms embolized with GDC (2 at 5 days and 1 at 12 days postimplantation). In these 3 cases, the aneurysms embolized with Matrix were completely occluded. One aneurysm embolized with Matrix developed a parent artery occlusion due to initial damage of the parent artery (first case). The Matrix coil broke before it had been completely deposited in the aneurysm. The coil was retrieved using a coil retriever. The procedure of coil retrieval damaged the parent artery with concomitant arterial occlusion. This manufacturing failure was technically fixed and it was not observed in subsequent embolizations with Matrix.
Neck Tissue Thickness Measured on Angiography
At day 14, the angiographic measurement of neointimal thickness at aneurysmal neck level showed significant differences between Matrix- and GDC-treated aneurysms (average 0.41±0.2 mm for Matrix versus 0.25±0.2 mm for GDC; P=0.009, n=11).
At 3 months, the neck tissue thickness for Matrix was 0.15±0.22 mm and 0 mm for GDC (P=0.0036, n=5). The apparent loss in neck tissue thickness could be related to the increased size of the parent artery due to normal growth of the animal. At 6 months postembolization, the tissue thickness at aneurysmal neck level could not be obtained due to poor radiographic documentation related to the increased thickness of skull bones. No progressive parent artery stenosis was observed in either GDC- or Matrix-treated aneurysms at 3 and 6 months.
Macroscopic Findings
The 2 animals that died 5 days after implantation exhibited unorganized clot in the sac of the aneurysm treated with GDC. The animal that died 12 days after implantation showed almost complete neointimal coverage of the neck of the aneurysm embolized with Matrix, whereas the aneurysm embolized with GDC showed rupturing and a large neck hematoma.
At day 14, the necks of all Matrix-treated aneurysms were completely covered with a fibrous membrane (n=11). The necks of 7 out of 11 GDC-treated aneurysms were completely covered with fibrous tissue. In 4 aneurysms the necks were partially covered with neointima.
All 3- and 6-month aneurysm specimens exhibited fibrous tissue covering the neck of the aneurysms except for 1 GDC-treated aneurysm that had a hole in the orifice. No excessive tissue reaction at the neck was observed with Matrix- and GDC-treated aneurysms. These observations were confirmed by microscopy.
Histological Findings
Thrombus Organization in the Aneurysmal Sac
At day 14, Matrix-treated aneurysms exhibited a more extensive area of organized thrombus when compared with aneurysms embolized with GDC (Figure 3). Matrix-treated aneurysms showed an average of 87% of their area as organized thrombus. GDC-treated aneurysms averaged 75% (P=0.008, n=11). In specimens recovered after 3 and 6 months, both GDC- and Matrix-treated aneurysms were completely occluded with fibrous connective tissue.
|
Tissue Thickness of the Neck of the Aneurysm
At day 14, Matrix-treated aneurysms had a thick and mature neointimal tissue covering the neck of the aneurysm. Cells with morphology consistent with endothelium were present at the luminal surface.
It was found that the average neck tissue thickness was 0.29 mm±0.30 for Matrix versus 0.13 mm±0.17 for GDC (P<0.0001, n=11) at 14 days postimplantation. In month 3, Matrix specimens showed a 71% increase in neck tissue with a thickness of 0.24 mm±0.20 versus 0.14 mm±0.18 for GDC observed in GDC specimens (P=0.0027; ANOVA; n=5). In aneurysm specimens at month 6, the difference was not significant; 0.19 mm±0.29 for Matrix versus 0.15 mm±0.20 for GDC (P=0.09; n=6).
Tissue Reaction to the Coils
At 14 days, the coils of both GDC and Matrix were observed to be surrounded by either leukocytes or well-organized granulation tissue, depending on the location of the coils (Figure 4). The latter surrounded coils in the neck region whereas the former characterized coils in the aneurysm center. The leukocytic infiltrate around the extracellular matrix was subjectively greater for the Matrix coils. The difference in the leukocyte infiltrate was apparent at 14 days, but not at 3 or 6 months postimplantation. At 3 and 6 months postimplantation, for both Matrix and GDC, thrombus was no longer present in the aneurysms. No chronic inflammatory reaction was seen with Matrix and GDC.
|
The absorbable polymer on the Matrix coils was visible at the 14-day stage and was essentially gone at the 3-month stage. Detachment or migration of absorbable polymer away from the coils was not seen and no voids were left by its disappearance.
Angiographic Aneurysm Cross-Sectional Area
The cross sectional area of aneurysms was measured from angiographic images at time zero, and directly from sections for the various end point times. Consistent with baseline aneurysm volume measurements, baseline aneurysm area measurements (measured from angiograms) were equivalent between GDC and Matrix (Table 2).
|
Area measurements taken from 14-day angiograms revealed that both Matrix and GDC groups grew in area over this time period. Three-month angiograms revealed that aneurysms treated with Matrix were 18% smaller than baseline (P=0.03). In contrast, GDC-treated aneurysms remained essentially unchanged (4% increase in area, P=0.55). It was not possible to collect end point data on aneurysm cross-sectional area for the 6-month group because of poor radiographic quality due to growth of skull bone.
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionsReferences |
|---|
The original concept of the GDC system was that the electric current produced thrombus formation in the aneurysm (electrothrombosis).4,5 However, it was noted that the most important mechanism of acute aneurysm occlusion was the mechanical disruption of intra-aneurysmal flow and thrombosis. From histopathologic reports on human aneurysms embolized with GDC, it appears that the intra-aneurysmal clot undergoes a slow organization.12,27–38 It may therefore be advantageous to modify the biological behavior of the coils to accelerate the biological mechanisms that induce clot maturation and fibrosis.
Bioactive Embolic Agents
It is known that platinum coils elicit a mild biological response when deployed into an aneurysm. Tamatani et al reported no endothelial proliferation on the bare-platinum coil surface in an in vitro study.12
Some investigators have modified the surface of GDC by coating them with extracellular matrix proteins such as collagen.14,23 However, protein coatings on a platinum surface are usually weak, and they may be easily removed during standard microcatheter coil delivery. Ion implantation technology in combination with a protein coating has been used to modify the surface of GDC.18–20 Several investigators evaluated a modified GDC using growth factors or genetically modified cells.13,15,16,21,24,39
Tissue Engineering and Bioabsorbable Polymeric Materials for Aneurysm Embolization
Tissue engineering is a new scientific field that studies tissue repair and replacement using bioactive materials.40–44 Bioabsorbable polymeric materials (BPM) are being used in 3-dimensional scaffolds to which cells attach and grow to reconstitute tissues. Synthetic polymers such as polylactide (PLA), polyglycolic acid (PGA), and polyglycolic/poly-L-lactic acid copolymer (PLGA) are widely used in the field of tissue engineering.
We recently reported that aneurysm healing could be controlled by the composition of the polymer ratio. PGLA 50/50 (50% PGA/50% PLA) is a fast, absorbable copolymer and it demonstrated strongest tissue reaction. PGLA 85/15 demonstrated the weakest reaction. There was a linear relationship between polymer absorption time and collagen expression in the aneurysm.27
Based on these findings, we developed a newly designed hybrid platinum/BPM coil (Matrix). Polyglycolic/poly-L-lactic acid copolymers were used for the coating of Matrix. PGLA 90/10 polymer degrades and is absorbed relatively slowly, producing a mild inflammatory reaction.
Histologic results in animal models show that the molecular and histologic responses elicited by these materials accelerate clot maturation. Thicker neointima and neoendothelial coverage of the neck of experimental aneurysms in swine was also noted within 14 days. Another important finding with Matrix is the progressive reduction of aneurysm size within the Matrix test aneurysms. No GDC-treated aneurysms showed such size reduction in long-term angiographic follow-up. Because Matrix consists of 70% BPM and only 30% platinum, the bioabsorbed polymer seemed to be replaced by mature connective tissue. Mature scar tissue also retracts by the process of wound healing. This size reduction may be clinically important, especially in unruptured aneurysm presenting with mass effect.
One major question elicited from the preliminary study was the potential risk of untoward parent artery stenosis or occlusion related to the intra-aneurysmal clot organization and fibrosis. We observed no aggressive parent artery stenosis with the exception of 1 case that required intense arterial manipulation with a clot retrieval system to retrieve a Matrix coil from the parent artery.
There were 3 aneurysm ruptures; all of them had been embolized with GDC coils. Autopsy findings revealed that the rupture point was at the dome of the venous pouch. Although the reason of these ruptures is unknown, we believe that they are related to the high flow created in the wide-neck aneurysms. Some potential limitations of this study should be considered. The samples were not completely interpreted in a blinded manner. Although all specimens were evaluated by an independent pathologist, 14-day specimens clearly identified polymer material under the microscope. Biomechanical properties other than polymer coating (such as coil stiffness) might contribute to therapeutic differences between Matrix and conventional coils. The swine model variables of increased thickness of tissue at aneurysm neck, increased clot organization at 2 weeks, and decreased size of aneurysm at 3 months have not yet been validated as predictors of decreased rate of aneurysm recurrence in humans.
|
Conclusions |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionsReferences |
|---|
Treatment with Matrix exhibits an improved tissue-filling behavior of the aneurysmal space when compared with the standard GDC treatment. Matrix also demonstrated a greater inflammatory cell reaction around the coils at 14 days, but inflammatory reaction was similar to that of GDC at the 3- and 6-month end points. Long-term evaluation indicated that the Matrix was histologically similar to GDC, that the absorbable polymer was no longer visible microscopically, and that the aneurysms packed with Matrix had decreased in size. If the latter observation is confirmed in humans, this may be a beneficial outcome given that reduction in mass effect is held to be a desired result.
|
|
|
|
|
Acknowledgments |
|---|
This project was supported by Boston Scientific/Target Therapeutics. This study was conducted in accordance with the GLP regulations as described in Food and Drug Administration 21 CFR Part 58, Good Laboratory Practice for Nonclinical Laboratory Studies. We gratefully acknowledge the assistance of Yih-Lin Nien, MD, John Robert, Shawn McGill, and Fernando Viñuela, Jr, of the Leo G. Rigler Radiological Research Center, and Janlee Jansen, DVM, and Jerry Werk, Laboratory Animal Medicine at the University of California, Los Angeles. We thank Serge Rousselle, DVM, for histopathologic evaluation. We also thank Paul Siefert, Mike Wallace, Joe Eder, Gulie Grinde, Like Que, Tom Witzel, and Dave Barry from Boston Scientific/Target Therapeutics.
|
Footnotes |
|---|
This article contains supplementary figures that can be viewed online at http://stroke.ahajournals.org.
Received March 26, 2002; revision received October 22, 2002; accepted November 22, 2002.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionsReferences |
|---|
1. Byrne JV, Sohn MJ, Molyneux AJ, Chir B. Five-year experience in using coil embolization for ruptured intracranial aneurysms: outcomes and incidence of late rebleeding. J Neurosurg. 1999; 90: 656–663.[Medline] [Order article via Infotrieve]
2. Debrun GM, Aletich VA, Kehrli P, Misra M, Ausman JI, Charbel F. Selection of cerebral aneurysms for treatment using Guglielmi detachable coils: the preliminary University of Illinois at Chicago experience. Neurosurgery. 1998; 43: 1281–1297.[CrossRef][Medline] [Order article via Infotrieve]
3. Fernandez Zubillaga A, Guglielmi G, Vinuela F, Duckwiler GR. Endovascular occlusion of intracranial aneurysms with electrically detachable coils: correlation of aneurysm neck size and treatment results. AJNR Am J Neuroradiol. 1994; 15: 815–820.[Abstract]
4. Guglielmi G, Vinuela F, Dion J, Duckwiler G. Electrothrombosis of saccular aneurysms via endovascular approach, II: preliminary clinical experience. J Neurosurg. 1991; 75: 8–14.[Medline] [Order article via Infotrieve]
5. Guglielmi G, Vinuela F, Sepetka I, Macellari V. Electrothrombosis of saccular aneurysms via endovascular approach, I: electrochemical basis, technique, and experimental results. J Neurosurg. 1991; 75: 1–7.[Medline] [Order article via Infotrieve]
6. Hayakawa M, Murayama Y, Duckwiler GR, Gobin YP, Guglielmi G, Vinuela F. Natural history of the neck remnant of a cerebral aneurysm treated with the Guglielmi detachable coil system. J Neurosurg. 2000; 93: 561–568.[Medline] [Order article via Infotrieve]
7. Murayama Y, Vinuela F, Duckwiler GR, Gobin YP, Guglielmi G. Embolization of incidental cerebral aneurysms by using the Guglielmi detachable coil system. J Neurosurg. 1999; 90: 207–214.[Medline] [Order article via Infotrieve]
8. Roy D, Milot G, Raymond J. Endovascular treatment of unruptured aneurysms. Stroke. 2001; 32: 1998–2004.
9. Tateshima S, Murayama Y, Gobin YP, Duckwiler GR, Guglielmi G, Vinuela F. Endovascular treatment of basilar tip aneurysms using Guglielmi detachable coils: anatomic and clinical outcomes in 73 patients from a single institution. Neurosurgery. 2000; 47: 1332–1342.[CrossRef][Medline] [Order article via Infotrieve]
10. Uda K, Murayama Y, Gobin YP, Duckwiler GR, Vinuela F. Endovascular treatment of basilar artery trunk aneurysms with Guglielmi detachable coils: clinical experience with 41 aneurysms in 39 patients. J Neurosurg. 2001; 95: 624–632.[Medline] [Order article via Infotrieve]
11. Vinuela F, Duckwiler G, Mawad M. Guglielmi detachable coil embolization of acute intracranial aneurysm: perioperative anatomical and clinical outcome in 403 patients. J Neurosurg. 1997; 86: 475–482.[Medline] [Order article via Infotrieve]
12. Tamatani S, Ozawa T, Minakawa T, Takeuchi S, Koike T, Tanaka R. Histological interaction of cultured endothelial cells and endovascular embolic materials coated with extracellular matrix. J Neurosurg. 1997; 86: 109–112.[Medline] [Order article via Infotrieve]
13. Abrahams JM, Forman MS, Grady MS, Diamond SL. Delivery of human vascular endothelial growth factor with platinum coils enhances wall thickening and coil impregnation in a rat aneurysm model. AJNR Am J Neuroradiol. 2001; 22: 1410–1417.
14. Dawson RC3rd, Shengelaia GG, Krisht AF, Bonner GD. Histologic effects of collagen-filled interlocking detachable coils in the ablation of experimental aneurysms in swine. AJNR Am J Neuroradiol. 1996; 17: 853–858.[Abstract]
15. Kallmes DF, Borland MK, Cloft HJ, Altes TA, Dion JE, Jensen ME, Hankins GR, Helm GA. In vitro proliferation and adhesion of basic fibroblast growth factor-producing fibroblasts on platinum coils. Radiology. 1998; 206: 237–243.
16. Kallmes DF, Williams AD, Cloft HJ, Lopez MB, Hankins GR, Helm GA. Platinum coil-mediated implantation of growth factor-secreting endovascular tissue grafts: an in vivo study. Radiology. 1998; 207: 519–523.
17. Marx WE, Cloft HJ, Helm GA, Short JG, Do HM, Jensen ME, Kallmes DE. Endovascular treatment of experimental aneurysms by use of biologically modified embolic devices: coil-mediated intraaneurysmal delivery of fibroblast tissue allografts. AJNR Am J Neuroradiol. 2001; 22: 323–333.
18. Murayama Y, Vinuela F, Suzuki Y, Do HM, Massoud TF, Guglielmi G, Ji C, Iwaki M, Kusakabe M, Kamio M, Abe T. Ion implantation and protein coating of detachable coils for endovascular treatment of cerebral aneurysms: concepts and preliminary results in swine models. Neurosurgery. 1997; 40: 1233–1244.[CrossRef][Medline] [Order article via Infotrieve]
19. Murayama Y, Vinuela F, Suzuki Y, Akiba Y, Ulihoa A, Duckwiler GR, Gobin YP, Vinters HV, Iwaki M, Abe T. Development of the biologically active Guglielmi detachable coil for the treatment of cerebral aneurysms, II: an experimental study in a swine aneurysm model. AJNR Am J Neuroradiol. 1999; 20: 1992–1999.
20. Murayama Y, Suzuki Y, Vinuela F, Kaibara M, Kurotobi K, Iwaki M, Abe T. Development of a biologically active Guglielmi detachable coil for the treatment of cerebral aneurysms, I: in vitro study. AJNR Am J Neuroradiol. 1999; 20: 1986–1991.
21. Raymond J, Desfaits AC, Roy D. Fibrinogen and vascular smooth muscle cell grafts promote healing of experimental aneurysms treated by embolization. Stroke. 1999; 30: 1657–1664.
22. Raymond J, Venne D, Allas S, Roy D, Oliva VL, Denbow N, Salazkin I, Leclerc G. Healing mechanisms in experimental aneurysms, I: vascular smooth muscle cells and neointima formation. J Neuroradiol. 1999; 26: 7–20.[Medline] [Order article via Infotrieve]
23. Szikora I, Wakhloo AK, Guterman LR, Chavis TD, Dawson RC3rd, Hergenrother RW, Twyford RH, Hopkins LN. Initial experience with collagen-filled Guglielmi detachable coils for endovascular treatment of experimental aneurysms. AJNR Am J Neuroradiol. 1997; 18: 667–672.
24. Venne D, Raymond J, Allas S, Roy D, Leclerc G, Boushira M, Brazeau P. Healing of experimental aneurysms, II: platelet extracts can increase the thickness of the neointima at the neck of treated aneurysms. J Neuroradiol. 1999; 26: 92–100.[Medline] [Order article via Infotrieve]
25. Murayama Y, Vinuela F, Tateshima S, Song JK, Gonzalez NR, Wallace MP. Bioabsorbable polymeric material coils for embolization of intracranial aneurysms: a preliminary experimental study. J Neurosurg. 2001; 94: 454–463.[CrossRef][Medline] [Order article via Infotrieve]
26. Murayama Y, Vinuela F, Tateshima S, Gonzalez NR, Song JK, Mahdavieh H, Iruela-Arispe L. Cellular responses of bioabsorbable polymeric material and Guglielmi detachable coil in experimental aneurysms. Stroke. 2002; 33: 1120–1128.
27. Bavinzski G, Talazoglu V, Killer M, Richling B, Gruber A, Gross CE, Plenk H Jr. Gross and microscopic histopathological findings in aneurysms of the human brain treated with Guglielmi detachable coils. J Neurosurg. 1999; 91: 284–293.[Medline] [Order article via Infotrieve]
28. Castro E, Fortea F, Villoria F, Lacruz C, Ferreras B, Carrillo R. Long-term histopathologic findings in two cerebral aneurysms embolized with Guglielmi detachable coils. AJNR Am J Neuroradiol. 1999; 20: 549–552.
29. Horowitz MB, Purdy PD, Burns D, Bellotto D. Scanning electron microscopic findings in a basilar tip aneurysm embolized with Guglielmi detachable coils. AJNR Am J Neuroradiol. 1997; 18: 688–690.
30. Koizumi T, Kawano T, Kazekawa K, Kawaguchi T, Honma T, Kaneko Y, Dosaka A, Tabuchi K. [Histological findings in aneurysm treated with IDC: scanning electron microscopical study.] No Shinkei Geka. 1997; 25: 1027–1031.[Medline] [Order article via Infotrieve]
31. Mawad ME, Mawad JK, Cartwright J Jr, Gokaslan Z. Long-term histopathologic changes in canine aneurysms embolized with Guglielmi detachable coils. AJNR Am J Neuroradiol. 1995; 16: 7–13.[Abstract]
32. Mizoi K, Yoshimoto T, Takahashi A, Nagamine Y. A pitfall in the surgery of a recurrent aneurysm after coil embolization and its histological observation: technical case report. Neurosurgery. 1996; 39: 165–169.[CrossRef][Medline] [Order article via Infotrieve]
33. Molyneux AJ, Ellison DW, Morris J, Byrne JV. Histological findings in giant aneurysms treated with Guglielmi detachable coils: report of two cases with autopsy correlation. J Neurosurg. 1995; 83: 129–132.[Medline] [Order article via Infotrieve]
34. Spetzger U, Reul J, Weis J, Bertalanffy H, Thron A, Gilsbach JM. Microsurgically produced bifurcation aneurysms in a rabbit model for endovascular coil embolization. J Neurosurg. 1996; 85: 488–495.[Medline] [Order article via Infotrieve]
35. Stiver SI, Porter PJ, Willinsky RA, Wallace MC. Acute human histopathology of an intracranial aneurysm treated using Guglielmi detachable coils: case report and review of the literature. Neurosurgery. 1998; 43: 1203–1208.[CrossRef][Medline] [Order article via Infotrieve]
36. Tenjin H, Fushiki S, Nakahara Y, Masaki H, Matsuo T, Johnson CM, Ueda S. Effect of Guglielmi detachable coils on experimental carotid artery aneurysms in primates. Stroke. 1995; 26: 2075–2080.
37. de Gast AN, Altes TA, Marx WF, Do HM, Helm GA, Kallmes DF. Transforming growth factor beta-coated platinum coils for endovascular treatment of aneurysms: an animal study. Neurosurgery. 2001; 49: 690–696.[CrossRef][Medline] [Order article via Infotrieve]
38. Freed LE, Vunjak-Novakovic G, Biron RJ, Eagles DB, Lesnoy DC, Barlow SK, Langer R. Biodegradable polymer scaffolds for tissue engineering. Biotechnology (N Y). 1994; 12: 689–693.[CrossRef][Medline] [Order article via Infotrieve]
39. Isobe M, Yamazaki Y, Oida S, Ishihara K, Nakabayashi N, Amagasa T. Bone morphogenetic protein encapsulated with a biodegradable and biocompatible polymer. J Biomed Mater Res. 1996; 32: 433–438.[CrossRef][Medline] [Order article via Infotrieve]
40. Langer R. New methods of drug delivery. Science. 1990; 249: 1527–1533.
41. Langer R, Vacanti JP. Tissue engineering. Science. 1993; 260: 920–926.
42. Langer R. Drug delivery and targeting. Nature. 1998; 392: 5–10.[Medline] [Order article via Infotrieve]
43. Middleton JC, Tripton AJ. Synthetic biodegradable polymers as medical devices. Med Plastics Biomater. 1998; 2: 30–39.
44. Miller RA, Brady JM, Cutright DE. Degradation rates of oral resorbable implants (polylactates and polyglycolates): rate modification with changes in PLA/PGA copolymer ratios. J Biomed Mater Res. 1977; 11: 711–719.[CrossRef][Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  C.T. Whitlow, C.P. Geer, C.W.T. Mattern, B.J. Mussat-Whitlow, S.K. Yazdani, J.L. Berry, J.H. Lalli, R.O. Claus, V.R. Challa, and P.P. Morris Endovascular Histologic Effects of Ultrathin Gold- or Vitronectin-Coated Platinum Aneurysm Coils in a Rodent Arterial Occlusion Model: A Preliminary Investigation AJNR Am. J. Neuroradiol., January 1, 2009; 30(1): 85 - 90. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Piotin, L. Spelle, C. Mounayer, C. Loureiros, A. Ghorbani, and J. Moret Intracranial Aneurysms Coiling With Matrix: Immediate Results in 152 Patients and Midterm Anatomic Follow-Up From 115 Patients Stroke, January 1, 2009; 40(1): 321 - 323. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-S. Guan and M.-Q. Wang Endovascular Embolization of Intracranial Aneurysms Angiology, July 1, 2008; 59(3): 342 - 351. [Abstract] [PDF]
|
|
|
|
|
|
W.J. van Rooij, A.N. de Gast, and M. Sluzewski Results of 101 Aneurysms Treated with Polyglycolic/Polylactic Acid Microfilament Nexus Coils Compared with Historical Controls Treated with Standard Coils AJNR Am. J. Neuroradiol., May 1, 2008; 29(5): 991 - 996. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Dai, Y.H. Ding, M.A. Danielson, R. Kadirvel, G.A. Helm, D.A. Lewis, H.J. Cloft, and D.F. Kallmes Endovascular Treatment of Experimental Aneurysms with Use of Fibroblast Transfected with Replication-Deficient Adenovirus Containing Bone Morphogenetic Protein-13 Gene AJNR Am. J. Neuroradiol., April 1, 2008; 29(4): 739 - 744. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Butteriss, A. Gholkar, D. Mitra, D. Birchall, and V. Jayakrishnan Single-Center Experience of Cerecyte Coils in the Treatment of Intracranial Aneurysms: Initial Experience and Early Follow-Up Results AJNR Am. J. Neuroradiol., January 1, 2008; 29(1): 53 - 56. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Pierot, X. Leclerc, A. Bonafe, S. Bracard, and for the French Matrix Registry Investigators Endovascular Treatment of Intracranial Aneurysms with Matrix Detachable Coils: Midterm Anatomic Follow-Up from a Prospective Multicenter Registry AJNR Am. J. Neuroradiol., January 1, 2008; 29(1): 57 - 61. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Johnston, C. F. Dowd, R. T. Higashida, M. T. Lawton, G. R. Duckwiler, D. R. Gress, and for the CARAT Investigators Predictors of Rehemorrhage After Treatment of Ruptured Intracranial Aneurysms: The Cerebral Aneurysm Rerupture After Treatment (CARAT) Study Stroke, January 1, 2008; 39(1): 120 - 125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.J. Rivet, C.J. Moran, A. Mazumdar, T.K. Pilgram, C.P. Derdeyn, and D.T. Cross Single-Institution Experience with Matrix Coils in the Treatment of Intracranial Aneurysms: Comparison with Same-Center Outcomes with the Use of Platinum Coils AJNR Am. J. Neuroradiol., October 1, 2007; 28(9): 1736 - 1742. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ries, S. Siemonsen, G. Thomalla, U. Grzyska, H. Zeumer, and J. Fiehler Long-Term Follow-Up of Cerebral Aneurysms after Endovascular Therapy Prediction and Outcome of Retreatment AJNR Am. J. Neuroradiol., October 1, 2007; 28(9): 1755 - 1761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-J. Priebe Aneurysmal subarachnoid haemorrhage and the anaesthetist Br. J. Anaesth., July 1, 2007; 99(1): 102 - 118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Kadirvel, D. Dai, Y.H. Ding, M.A. Danielson, D.A. Lewis, H.J. Cloft, and D.F. Kallmes Endovascular Treatment of Aneurysms: Healing Mechanisms in a Swine Model Are Associated with Increased Expression of Matrix Metalloproteinases, Vascular Cell Adhesion Molecule-1, and Vascular Endothelial Growth Factor, and Decreased Expression of Tissue Inhibitors of Matrix Metalloproteinases AJNR Am. J. Neuroradiol., May 1, 2007; 28(5): 849 - 856. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Linfante and A. K. Wakhloo Brain Aneurysms and Arteriovenous Malformations: Advancements and Emerging Treatments in Endovascular Embolization Stroke, April 1, 2007; 38(4): 1411 - 1417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Raymond, I. Salazkin, G. Gevry, and T.N. Nguyen Interventional Neuroradiology: The Role of Experimental Models in Scientific Progress AJNR Am. J. Neuroradiol., March 1, 2007; 28(3): 401 - 405. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-H. Im, M.H. Han, B.J. Kwon, C. Jung, J.E. Kim, and D.H. Han Aseptic Meningitis after Embolization of Cerebral Aneurysms Using Hydrogel-Coated Coils: Report of Three Cases AJNR Am. J. Neuroradiol., March 1, 2007; 28(3): 511 - 512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Mitra, A. Herwadkar, C. Soh, and A. Gholkar Follow-Up of Intracranial Aneurysms Treated with Matrix Detachable Coils: A Single-Center Experience AJNR Am. J. Neuroradiol., February 1, 2007; 28(2): 362 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Bendszus and L. Solymosi Cerecyte Coils in the Treatment of Intracranial Aneurysms: A Preliminary Clinical Study AJNR Am. J. Neuroradiol., November 1, 2006; 27(10): 2053 - 2057. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Katsaridis, C. Papagiannaki, and C. Violaris Guglielmi Detachable Coils versus Matrix Coils: A Comparison of the Immediate Posttreatment Results of the Embolization of 364 Cerebral Aneurysms in 307 Patients: A Single-Center, Single-Surgeon Experience. AJNR Am. J. Neuroradiol., October 1, 2006; 27(9): 1841 - 1848. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Pierot, A. Bonafe, S. Bracard, X. Leclerc, and for the French Matrix Registry Investigators Endovascular treatment of intracranial aneurysms with matrix detachable coils: immediate posttreatment results from a prospective multicenter registry. AJNR Am. J. Neuroradiol., September 1, 2006; 27(8): 1693 - 1699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Brisman, J. K. Song, and D. W. Newell Cerebral aneurysms. N. Engl. J. Med., August 31, 2006; 355(9): 928 - 939. [Full Text] [PDF]
|
|
|
|
|
|
D. Dai, Y.H. Ding, R. Kadirvel, M.A. Danielson, D.A. Lewis, H.J. Cloft, and D.F Kallmes A longitudinal immunohistochemical study of the healing of experimental aneurysms after embolization with platinum coils. AJNR Am. J. Neuroradiol., April 1, 2006; 27(4): 736 - 741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Niimi, J. Song, M. Madrid, and A. Berenstein Endosaccular Treatment of Intracranial Aneurysms Using Matrix Coils: Early Experience and Midterm Follow-Up Stroke, April 1, 2006; 37(4): 1028 - 1032. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J. Cloft Have you been smoking something that is biologically active? AJNR Am. J. Neuroradiol., February 1, 2006; 27(2): 240 - 242. [Full Text] [PDF]
|
|
|
|
|
|
I. Szikora, P. Seifert, Z. Hanzely, Z. Kulcsar, Z. Berentei, M. Marosfoi, S. Czirjak, J. Vajda, and I. Nyary Histopathologic evaluation of aneurysms treated with guglielmi detachable coils or matrix detachable microcoils. AJNR Am. J. Neuroradiol., February 1, 2006; 27(2): 283 - 288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Dai, Y.H. Ding, D.A. Lewis, and D.F. Kallmes A Proposed Ordinal Scale for Grading Histology in Elastase-Induced, Saccular Aneurysms AJNR Am. J. Neuroradiol., January 1, 2006; 27(1): 132 - 138. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Dai, Y. H. Ding, M. A. Danielson, R. Kadirvel, D. A. Lewis, H. J. Cloft, and D. F. Kallmes Histopathologic and Immunohistochemical Comparison of Human, Rabbit, and Swine Aneurysms Embolized with Platinum Coils AJNR Am. J. Neuroradiol., November 1, 2005; 26(10): 2560 - 2568. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Oka and P. Gailloud Re: Angiographic Evidence of Aneurysm Neck Healing Following Endovascular Treatment with Bioactive Coils AJNR Am. J. Neuroradiol., October 1, 2005; 26(9): 2435 - 2436. [Full Text] [PDF]
|
|
|
|
|
|
C. A. Taschner, X. Leclerc, H. Rachdi, A. M. Barros, and J.-P. Pruvo Matrix Detachable Coils for the Endovascular Treatment of Intracranial Aneurysms: Analysis of Early Angiographic and Clinical Outcomes Stroke, October 1, 2005; 36(10): 2176 - 2180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-S. Kang, M. H. Han, B. J. Kwon, O-K. Kwon, S. H. Kim, S. H. Choi, and K.-H. Chang Short-Term Outcome of Intracranial Aneurysms Treated with Polyglycolic Acid/Lactide Copolymer-Coated Coils Compared to Historical Controls Treated with Bare Platinum Coils: A Single-Center Experience AJNR Am. J. Neuroradiol., September 1, 2005; 26(8): 1921 - 1928. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Dai, Y. H. Ding, M. A. Danielson, R. Kadirvel, D. A. Lewis, H. J. Cloft, and D. F. Kallmes Modified Histologic Technique for Processing Metallic Coil-Bearing Tissue AJNR Am. J. Neuroradiol., September 1, 2005; 26(8): 1932 - 1936. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sluzewski and W. J. van Rooij Questionable Interpretation of Results of ACTIVE Study on Matrix Coils by Boston Scientific AJNR Am. J. Neuroradiol., September 1, 2005; 26(8): 2163 - 2164. [Full Text] [PDF]
|
|
|
|
|
|
I. Linfante, N. M. Akkawi, A. Perlow, V. Andreone, and A. K. Wakhloo Polyglycolide/Polylactide-Coated Platinum Coils for Patients With Ruptured and Unruptured Cerebral Aneurysms: A Single-Center Experience Stroke, September 1, 2005; 36(9): 1948 - 1953. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. H. Ding, D. Dai, D. A. Lewis, H. J. Cloft, and D. F. Kallmes Angiographic and Histologic Analysis of Experimental Aneurysms Embolized with Platinum Coils, Matrix, and HydroCoil AJNR Am. J. Neuroradiol., August 1, 2005; 26(7): 1757 - 1763. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sluzewski and W. J. van Rooij Questionable Interpretation of Results of ACTIVE Study on Matrix Coils by Boston Scientific AJNR Am. J. Neuroradiol., August 1, 2005; 26(7): 1882 - 1883. [Full Text] [PDF]
|
|
|
|
|
|
B. Lubicz, X. Leclerc, J.-Y. Gauvrit, J.-P. Lejeune, and J.-P. Pruvo Three-Dimensional Packing with Complex Orbit Coils for the Endovascular Treatment of Intracranial Aneurysms AJNR Am. J. Neuroradiol., June 1, 2005; 26(6): 1342 - 1348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Slob, W. J. van Rooij, and M. Sluzewski Coil Thickness and Packing of Cerebral Aneurysms: A Comparative Study of Two Types of Coils AJNR Am. J. Neuroradiol., April 1, 2005; 26(4): 901 - 903. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. R. Gonzalez, A. B. Patel, Y. Murayama, and F. Vinuela Angiographic Evidence of Aneurysm Neck Healing Following Endovascular Treatment with Bioactive Coils AJNR Am. J. Neuroradiol., April 1, 2005; 26(4): 912 - 914. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. F. M. Wijdicks, D. F. Kallmes, E. M. Manno, J. R. Fulgham, and D. G. Piepgras Subarachnoid Hemorrhage: Neurointensive Care and Aneurysm Repair Mayo Clin. Proc., April 1, 2005; 80(4): 550 - 559. [Abstract] [PDF]
|
|
|
|
|
|
B. Lubicz, X. Leclerc, J.-Y. Gauvrit, J.-P. Lejeune, and J.-P. Pruvo Endovascular Treatment of Intracranial Aneurysms with Matrix Coils: A Preliminary Study of Immediate Post-treatment Results AJNR Am. J. Neuroradiol., February 1, 2005; 26(2): 373 - 375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Frosen, A. Piippo, A. Paetau, M. Kangasniemi, M. Niemela, J. Hernesniemi, and J. Jaaskelainen Remodeling of Saccular Cerebral Artery Aneurysm Wall Is Associated With Rupture: Histological Analysis of 24 Unruptured and 42 Ruptured Cases Stroke, October 1, 2004; 35(10): 2287 - 2293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Mounayer, M. Piotin, J. Moret, and J. Raymond Radioactive Coil Embolization of Intracranial Aneurysms: Minimal Inventory to Reach Target Activities in a Virtual Series of 154 patients AJNR Am. J. Neuroradiol., September 1, 2004; 25(8): 1377 - 1380. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Pelz, P. Lylyk, and M. Negoro Interventional Neuroradiology Stroke, February 1, 2004; 35(2): 381 - 382. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||