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Yuichi Murayama, Fernando Viñuela, Akira Ishii, Yih-Lin Nien, Ichiro Yuki, Gary Duckwiler, and Reza Jahan

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.

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Ichiro Yuki, Daniel Lee, Yuichi Murayama, Alexander Chiang, Harry V. Vinters, Ichiro Nishimura, Chiachien J. Wang, Akira Ishii, Benjamin M. Wu, and Fernando Viñuela

Object

Bioabsorbable polymeric material coils are being used in the endovascular treatment of aneurysms to achieve better thrombus organization than is possible using bare platinum coils. We used immunohistochemical and molecular biological analysis techniques in experimental aneurysms implanted with three different bioabsorbable polymer coils and platinum coils.

Methods

The degradation kinetics of nine polymer candidates for further analysis were first analyzed in vitro, and three materials with different degradation rates were selected. Seventy-four aneurysms were created in 37 swine using the venous pouch technique. The aneurysms were surgically implanted with one of the materials as follows (time points = 3, 7, and 14 days): Group 1, Guglielmi detachable coils (platinum); Group 2, Polysorb (90:10 polyglycolic acid [PGA]/polylactic acid); Group 3, Maxon (PGA/trimethylene carbonate); and Group 4, poly-l-lactic acid. Histological, immunohistochemical, and cDNA microarray analyses were performed on tissue specimens.

Results

Groups 1 and 4 showed minimal inflammatory response adjacent to the coil mass. In Group 2, Polysorb elicited a unique, firm granulation tissue that accelerated intraaneurysmal thrombus organization. In Group 3 intermediate inflammatory reactions were seen. Microarray analysis with Expression Analysis Sytematic Explorer software showed functional-cluster-gene activation to be increased at Day 7, preceding the histologic manifestation of polymer-induced granulation tissue at Day 14. A profile of expression changes in cytokine-related and extracellular membrane–related genes was compiled.

Conclusions

Degradation speed was not the only factor determining the strength of the biological response. Polysorb induced an early, unique granulation tissue that conferred greater mechanical strength to the intraaneurysmal coil–thrombus complex. Enhancing the formation of this polymer-induced granulation tissue may provide a new direction for improving long-term anatomical outcomes in cases involving aneurysms embolized with detachable coils.

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Daniel Lee, Ichiro Yuki, Yuichi Murayama, Alexander Chiang, Ichiro Nishimura, Harry V. Vinters, Chiachien J. Wang, Yih-Lin Nien, Akira Ishii, Benjamin M. WU, and Fernando Viñuela

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.