Intravascular tissue reactions induced by various types of bioabsorbable polymeric materials: correlation between the degradation profiles and corresponding tissue reactions.

INTRODUCTION: Several different bioabsorbable polymeric coil materials are currently used with the goal of improving treatment outcomes of endovascular embolization of intracranial aneurysms. However, little is known about the correlation between polymer degradation profiles and concomitant tissue responses in a blood vessel. The authors describe in vitro degradation characteristics of nine different polymeric materials and their corresponding tissue responses induced in rabbit carotid arteries. METHODS: Mass loss and molecular weight loss of nine commercially available bioabsorbable sutures were evaluated in vitro up to16 weeks. The same nine materials, as well as platinum coils, were implanted into blind-end carotid arteries (n = 44) in rabbits, and their tissue reactions were evaluated histologically 14 days after the implantation. RESULTS: Five of the nine polymers elicited moderate to strong tissue reactions relative to the remaining materials. While polymer mass loss did not correlate with their histologic findings, polymers that showed a faster rate of molecular weight loss had a tendency to present more active tissue reactions such as strong fibrocellular response around the implanted material with a moderate inflammatory cell infiltration. Maxon exhibited the fastest rate of molecular weight loss and poly-l-lactic acid the slowest. CONCLUSIONS: The rate of molecular weight loss may be an important factor that is associated with the degree of bioactivity when bioabsorbable polymers are implanted into blood vessels. For further quantitative analysis, additional experiments utilizing established aneurysm models need to be conducted.

Thrombus organization and healing in the swine experimental aneurysm model. Part I. A histological and molecular analysis.

OBJECT: The authors describe the process of thrombus organization in the swine surgical aneurysm model. METHODS: Lateral carotid artery aneurysms with immediately induced thrombosis were created in 31 swine for a time-course study. Aneurysms were evaluated at 1, 3, 7, 14, 30, and 90 days after they were created. Histological analyses included quantitative immunohistochemical studies and evaluation of collagen deposition. Complementary DNA microarray analysis was performed for gene expression profiling. The lists of up- and downregulated genes were cross-matched with lists of genes known to be associated with cytokines or the extracellular matrix. The expression of selected genes was quantified using real-time polymerase chain reaction. Functional clustering was performed with the Expression Analysis Systematic Explorer (EASE) bioinformatics package. RESULTS: Histological analysis demonstrated leukocyte and macrophage infiltration in the thrombus at Day 3, myofibroblast infiltration at Days 7 to 14, and progressive collagen deposition and contraction thereafter. Tissue organization occurred in a centripetal fashion. A previously undescribed reticular network of connective tissue was observed at the periphery of the aneurysm at Day 3. Macrophages appeared critical to this thrombus organization. A total of 1109 genes were significantly changed from reference time zero during the time course: CXCL14, which produces a monocyte-specific chemokine, was upregulated over 100-fold throughout the time course; IGF1 was upregulated fourfold at Day 7, whereas IGFBP2 was downregulated approximately 50% at Days 7 and 14. Osteopontin (SPP1) upregulation increased from 30-fold at Day 30 to 45-fold at Day 14. The EASE analysis yielded eight functional classes of gene expression. CONCLUSIONS: This investigation provides a detailed histological and molecular analysis of thrombus organization in the swine aneurysm model. The companion study will describe the effect of embolic bioabsorbable polymers on this process.

Initial clinical experience with matrix detachable coils for the treatment of intracranial aneurysms.

OBJECT: The Matrix detachable coil is a new bioactive, bioabsorbable coil used in the endovascular embolization of intracranial aneurysms. It has a platinum core covered with a bioactive, bioabsorbable polymer (polyglycolic acid/lactide). The authors report on their initial midterm clinical experience with the first-generation Matrix detachable coil. METHODS: One hundred twelve patients harboring 118 aneurysms were treated using Matrix coils. Forty-nine aneurysms (41.5%) were associated with acute subarachnoid hemorrhage (SAH). Twenty-four lesions (49%) were harbored by patients with Hunt and Hess Grade I, 11 (23.4%) by patients with Grade II, eight (16.3%) by those with Grade III, and six (12.2%) by those with Grade IV. Four aneurysms (3.4%) were harbored by patients who had presented with nonacute SAH. Sixty-five aneurysms (55%) were unruptured. Fifty-seven lesions (48.3%) were small with a small neck, 29 (24.6%) were small with a wide neck, 30 (25.4%) were large, and two (1.7%) were giant. All patients were followed up to obtain angiography and clinical outcome data. Technical complications occurred in six patients: two thromboembolic complications and four aneurysm perforations. Of these six patients, the status of two deteriorated because of aneurysm perforation and another two because of thrombus formation (morbidity 3.6%). There were five deaths--one due to rerupture after embolization. Angiography follow-up studies of 87 aneurysms were obtained. Seventy aneurysms demonstrated progressive occlusion or a stable neck (80.5%), and 17 had some degree of recanalization (19.5%). The aneurysms originally diagnosed as a neck remnant showed a 15% rate of recanalization. CONCLUSIONS: Matrix coils can be delivered into aneurysms with technical complications similar to those encountered using GDCs. Midterm anatomical outcomes to date have shown moderate improvement in the recanalization rate when compared with those realized using the GDC system. Because of the increased friction associated with the first-generation Matrix coil, the packing density in most aneurysms was less than that achieved with GDCs. Prolonged angiography follow-up evaluations are needed to document long-term efficacy.

Treatment of unruptured aneurysms with GDCs: clinical experience with 247 aneurysms.

BACKGROUND AND PURPOSE: The GDC system is a valuable therapeutic alternative to surgical treatment of intracranial aneurysms. We present our clinical experience with the GDC technique used to treat unruptured cerebral aneurysms. METHODS: This is a retrospective review of 217 patients with 247 unruptured intracranial aneurysms who underwent embolization with GDCs between August 1991 and June 2000. One hundred sixty-seven of the 217 were female patients. Patient age ranged from 13 to 83 years. In 118 patients, the aneurysms were found when unrelated non-neurologic conditions indicated angiography, CT angiography, or MR angiography (group 1). Fifty-one patients with mass effect symptoms comprised group 2, 12 patients with aneurysms associated with arteriovenous malformations or tumors of the brain comprised group 3, 17 patients with unruptured aneurysms treated during the chronic phase of subarachnoid hemorrhage (SAH) comprised group 4, and 19 patients treated during the acute phase of SAH due to another ruptured aneurysm comprised group 5. RESULTS: Angiographic results revealed complete occlusion in 138 of 247 aneurysms (55.9%), neck remnants in 92 (37.2%), and incomplete occlusion in three (1.2%). GDC embolization was attempted unsuccessfully in 14 aneurysms (5.7%). Of the 198 patients without acute SAH (groups 1-4), 186 (93.9%) of 198 remained neurologically unchanged. Eleven of the 217 patients (5.1%) experienced neurologic deterioration caused by immediate procedural complications. One patient died (0.5%) as a result of aneurysmal rupture during embolization. For asymptomatic patients and those treated after the chronic period of SAH, the mean hospitalization stay was 2.9 days. CONCLUSION: GDC technology constitutes safe treatment for unruptured aneurysms, with successful anatomic and clinical results and low complication rates achieved.

Guglielmi detachable coil embolization of cerebral aneurysms: 11 years' experience.

OBJECT: The authors report on their 11 years' experience with embolization of cerebral aneurysms using Guglielmi Detachable Coil (GDC) technology and on the attendant anatomical and clinical outcomes. METHODS: Since December 1990, 818 patients harboring 916 aneurysms were treated with GDC embolization at University of California at Los Angeles Medical Center. For comparative purposes, the patients were divided into two groups: Group A included their initial 5 years' experience with 230 patients harboring 251 aneurysms and Group B included the later 6 years' experience with 588 patients harboring 665 aneurysms. Angiographically demonstrated complete occlusion was achieved in 55% of aneurysms and a neck remnant was displayed in 35.4% of lesions. Incomplete embolization was performed in 3.5% of aneurysms, and in 5% occlusion was attempted unsuccessfully. A comparison between the two groups revealed a higher complete embolization rate in patients in Group B compared with that in Group A patients (56.8 and 50.2%, respectively). The overall morbidity/mortality rate was 9.4%. Angiographic follow ups were obtained in 53.4% of cases of aneurysms, and recanalization was exhibited in 26.1% of aneurysms in Group A and 17.2% of those in Group B. The overall recanalization rate was 20.9%. Note that recanalization was related to the size of the dome and neck of the aneurysm. Overall incidence of delayed aneurysm rupture was 1.6%, a rate that improved in the past 5 years to 0.5%. Ten of 12 delayed ruptures occurred in large or giant aneurysms. CONCLUSIONS: The clinical and postembolization outcomes in patients treated with the GDC system have improved in the past 5 years. Aneurysm recanalization, however, is still a major limitation of current GDC therapy. Follow-up angiography is mandatory after GDC embolization of cerebral aneurysms. Further technical and device improvements are mandatory to overcome current GDC limitations.

Intraaneurysmal flow visualization by using phase-contrast magnetic resonance imaging: feasibility study based on a geometrically realistic in vitro aneurysm model.

OBJECT: The aim of this study was to evaluate the feasibility of complex intraaneurysmal flow visualization with the currently available phase-contrast magnetic resonance (MR) imaging modality. METHODS: A geometrically realistic in vitro aneurysm model, in which detailed flow velocity analysis had already been conducted using laser Doppler velocimetry was used for this in vitro hemodynamic simulation, so that the results of phase-contrast velocity measurements could be compared with the previous reliable results. On a 1.5-tesla unit, three orthogonal components of velocity were obtained using a standard two-dimensional fast low-angle shot flow quantification sequence. Three-dimensional (3D) intraaneurysmal flow structures recorded during one cardiac cycle were depicted in one midsagittal and three axial cross-sectional planes with the aid of gray scale phase-contrast velocity maps. Isovelocity contour maps and secondary flow vectors were also created based on the phase-contrast velocity maps by using MATLAB software. The isovelocity contours in those three axial sections could demonstrate the shapes of inward and outward flow areas and their alternation over one cardiac cycle. The secondary flow vectors demonstrated twin vortices within the outward flow area adjacent to the boundary layer of inward and outward flow in all axial planes. CONCLUSIONS: The phase-contrast MR imaging method was able to depict the complex 3D intraaneurysmal flow structures in the in vitro aneurysm model. Detailed 3D intraaneurysmal flow information will be obtainable in vivo after improvements are made in spatial resolution, which is expected in the near future. The capability to visualize intraaneurysmal flow structures directly with the use of noninvasive MR imaging technology will have a positive impact on future clinical practice.

Periprocedural management of acute ischemic stroke intervention.

Periprocedural medical management is an important aspect in optimizing the outcome of patients who undergo endovascular treatment for acute ischemic stroke. Blood pressure, fluid hydration, and antithrombotics are some of the elements that need to be tailored carefully to the patient according to the patency of his or her cerebral vasculature, the extent of his or her infarct, and the potential for hemorrhagic transformation. This article reviews the medical care of acute stroke patients before and after endovascular therapy.

A rabbit model for efficacy evaluation of endovascular coil materials.

BACKGROUND: To investigate biomaterials seeking for their possible use for aneurysm treatment, in vivo screening tests using a number of potential materials are required. However, there is no established animal model that is suitable for such purpose. Some models require special preparation of tested materials for transcatheter delivery and others are inappropriate in view of their cost-effectiveness. The purpose of this study is to establish an animal model that overcomes these limitations and help us select potential materials before the preclinical evaluation. METHODS: Bilateral CCAs in a rabbit were surgically ligated, and a 2-cm segment of either a bare platinum coil or a polymeric coil (a platinum coil coated with PLGA 10/90) was implanted into each blind-ended arterial segment (n = 26). They were harvested at day 1, 7, 10, 14, or 30, respectively. Angiographic and histologic evaluations as well as quantitative analysis on the development of the organized thrombus were performed. RESULTS: One day after the implantation, both platinum and PLGA coils were surrounded by immature thrombus that was induced by blood flow stagnation in the arterial segment. At day 7, minimal thrombus organization was observed around both types of materials. At postimplantation days 10 and 14, fibrocellular responses, the early findings of the thrombus organization process, were observed in both material groups. Such histologic findings were more prominent in the PLGA coil group as compared to the platinum coil group (day 10, P = .051; day 14, P = .011). Well-organized thrombus was observed in both material groups at day 30 without showing statistical difference (P = .12). CONCLUSION: Given the cost-effectiveness, the simple material preparation process, and its feasible histologic evaluation methods, this new animal model can be useful in screening other potential biomaterials for the development of new coil devices.

Cerebral collateral circulation in carotid artery disease.

Carotid artery disease is common and increases the risk of stroke. However, there is wide variability on the severity of clinical manifestations of carotid disease, ranging from asymptomatic to fatal stroke. The collateral circulation has been recognized as an important aspect of cerebral circulation affecting the risk of stroke as well as other features of stroke presentation, such as stroke patterns in patients with carotid artery disease. The cerebral circulation attempts to maintain constant cerebral perfusion despite changes in systemic conditions, due to its ability to autoregulate blood flow. In case that one of the major cerebral arteries is compromised by occlusive disease, the cerebral collateral circulation plays an important role in preserving cerebral perfusion through enhanced recruitment of blood flow. With the advent of techniques that allow rapid evaluation of cerebral perfusion, the collateral circulation of the brain and its effectiveness may also be evaluated, allowing for prompt assessment of patients with acute stroke due to involvement of the carotid artery, and risk stratification of patients with carotid stenosis in chronic stages. Understanding the cerebral collateral circulation provides a basis for the future development of new diagnostic tools, risk stratification, predictive models and new therapeutic modalities. In the present review we discuss basic aspects of the cerebral collateral circulation, diagnostic methods to assess collateral circulation, and implications in occlusive carotid artery disease.

Immediate and midterm outcomes of patients with cerebral aneurysms treated with Matrix1 and Matrix2 coils: a comparative analysis based on a single-center experience in 250 consecutive cases.

OBJECTIVE: Recanalization after coil embolization of cerebral aneurysms remains a limitation of this progressively accepted modality. The Matrix detachable bioabsorbable coil (Boston Scientific Neurovascular, Natick, MA) was developed to overcome this limitation. We report a single-center experience using first- and second-generation Matrix coils. METHODS: Immediate and midterm angiographic outcomes of 235 consecutive patients with 250 aneurysms treated with Matrix coils were reviewed retrospectively. The first 16 aneurysms included in the postmarket Acceleration of Connective Tissue Formation in Endovascular Aneurysm Repair (ACTIVE) study were treated exclusively with the Matrix coil, as per protocol. The next 234 aneurysms were treated in combination with bare platinum coils, stents, and the balloon-assisted technique. First-generation Matrix coils were used in 155 aneurysms (Matrix1 group) and second-generation Matrix coils were used in 79 aneurysms (Matrix2 group). Outcomes of the 3 groups were compared. RESULTS: Immediate complete obliteration was achieved in 12.5% of the ACTIVE group aneurysms, 32.9% of the Matrix1 group, and 43.0% of the Matrix2 group. Overall, 87 (34.8%) aneurysms were completely occluded acutely. Procedure-related morbidity and mortality were 2.4 and 0%, respectively. Follow-up (median, 7.9 months) angiograms were obtained for 186 (74.4%) aneurysms. Complete obliteration of aneurysms was confirmed in 26.7% of the ACTIVE group, 53.4% of the Matrix1 group, and 64.2% of the Matrix2 group. Recanalization was observed in 33.3% of the ACTIVE group, 16.9% of the Matrix1 group, and 9.4% of the Matrix2 group. The overall recanalization rate was 16.1%. CONCLUSION: Use of Matrix2 coils resulted in improved mechanical performance and anatomic outcome compared with Matrix1 coils. However, practitioners must be familiar with the mechanical characteristics of the Matrix coils, which are different from those of bare platinum coils.

Visualization and quantification of flow and velocity fields in intracranial arteriovenous malformations using phase-contrast MR angiography.

OBJECTIVE: The objective of this study was to describe postprocessing tools for MR phase-contrast flow quantification images and apply those tools to cerebral arteriovenous malformations (AVMs) to visualize blood flow dynamics noninvasively. CONCLUSION: Inflow and outflow zones were clearly depicted at different regions in the AVM. The processed images showed flow patterns including vortical flow and variations in velocity over the cardiac cycle. Particle tracking gave an impression of the overall flow state and of the venous drainage system in particular.