Yuichi Murayama

Matrix and Bioabsorbable Polymeric Coils Accelerate Healing of Intracranial Aneurysms Long-Term Experimental Study

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.

Endovascular treatment of basilar tip aneurysms using Guglielmi detachable coils: anatomic and clinical outcomes in 73 patients from a single institution.

OBJECTIVESeventy-three consecutive patients with 75 basilar tip aneurysms were treated with Guglielmi detachable coil (GDC) technology. Their anatomic and clinical outcomes are discussed. METHODSSeventy-five basilar tip aneurysms were treated with the GDC system at the University of California, Los Angeles Medical Center from 1990 to 1999. The average age of the population was 48.3 years (range, 28–82 yr). Forty-two patients (57.5%) presented with acute subarachnoid hemorrhage, 8 patients (10.9%) had unruptured aneurysms with mass effect, and 23 patients (31.5%) had incidental aneurysms. Thirty-one aneurysms (41.3%) were small with a small neck, 18 (24%) were small with a wide neck, 16 (21.3%) were large, and 10 (13.3%) were giant aneurysms. RESULTSImmediate anatomic outcomes demonstrated complete or near-complete occlusion in 64 aneurysms (85.3%) and incomplete occlusion in 7 aneurysms (9.3%). Four aneurysms (5.3%) could not be embolized because of anatomic difficulties. Of the 69 patients treated with GDCs, 63 patients (91.3%) remained neurologically intact or unchanged from their initial clinical status. Procedure-related morbidity and mortality were 4.1% and 1.4%, respectively. Long-term follow-up angiograms were obtained in 41 patients with 42 aneurysms. Thirty aneurysms (71.4%) demonstrated complete or near-complete occlusion. One incompletely embolized giant aneurysm ruptured during the follow-up period. CONCLUSIONIn contrast to surgical clipping of basilar tip aneurysms, the main technical challenge of the Guglielmi detachable coiling procedure depends on the shape of the aneurysm, not its location. The results of this study indicate that endovascular GDC technology is an appropriate therapeutic alternative in ruptured or unruptured basilar tip aneurysms regardless of patient age, clinical presentation, clinical status, or timing of treatment.

In Vitro Measurement of Fluid-Induced Wall Shear Stress in Unruptured Cerebral Aneurysms Harboring Blebs

Background and Purpose— Little attention has been focused on the role of fluid-induced wall shear stress in fully developed cerebral aneurysms. The purpose of this study is to evaluate the alternation and distribution of wall shear stress over 1 cardiac cycle in patients’ aneurysms. Methods— A middle cerebral artery aneurysm and a basilar tip aneurysm with localized outpouching (blebs) in their domes were selected for this study. With the use of a stereo lithography machine, geometrically realistic aneurysm models were created on the basis of 3-dimensional CT angiograms. In vitro shearing velocity measurement was conducted with the use of laser-Doppler velocimetry at multiple points on the aneurysmal wall to calculate the value of wall shear stress. The wall shear stress was documented at multiple points in the aneurysm inflow zone, dome, and outflow zone. Results— Distribution of wall shear stress was not uniform in the aneurysm walls, and particular regions were exposed to relatively high wall shear stress. The wall shear stress changed dynamically throughout 1 cardiac cycle at the point where a high value of wall shear stress was noted. The blebs of both aneurysms were exposed to high wall shear stress. Unlike previous reports in which an ideal spherical aneurysm model was used, the aneurysm inflow zone was not exposed to high shear stress. Conclusions— In vitro aneurysm models based on the patients’ angiograms allowed us to conduct a more realistic evaluation of wall shear stress in the aneurysms harboring blebs. These results provide us with further indications of the correlation of wall shear stress with the natural history of cerebral aneurysms.

Ion implantation and protein coating of detachable coils for endovascular treatment of cerebral aneurysms: Concepts and preliminary results in swine models

OBJECTIVE Complete anatomic obliteration remains difficult to achieve with endovascular treatment of wide-necked aneurysms using Guglielmi detachable platinum coils (GDCs). Ion implantation is a physicochemical surface modification process resulting from the impingement of a high-energy ion beam. Ion implantation and protein coating were used to alter the surface properties (thrombogenicity, endothelial cellular migration, and adhesion) of GDCs. These modified coils were compared with standard GDCs in the treatment of experimental swine aneurysms. METHODS In an initial study, straight platinum coils were used to compare the acute thrombogenicity of standard and modified coils. Modified coils were coated with albumin, fibronectin, or collagen and underwent Ne+ ion implantation at a dose of 1 x 10(15) ions/cm2 and an energy of 150 keV. Coils were placed in common iliac arteries of 17 swine for 1 hour, to evaluate their acute interactions with circulating blood. In a second study, GDCs were used to treat 34 aneurysms in an additional 17 swine. GDCs were coated with fibronectin, albumin, collagen, laminin, fibrinogen, or vitronectin and then implanted with ions as described above. Bilateral experimental swine aneurysms were embolized with standard GDCs on one side and with ion-implanted, protein-coated GDCs on the other side. The necks of aneurysms were evaluated macroscopically at autopsy, by using post-treatment Day 14 specimens. The dimensions of the orifice and the white fibrous membrane that covered the orifice were measured as the fibrous membrane to orifice proportion. Histopathological evaluation of the neck region was performed by light microscopy and scanning electron microscopy. RESULTS Fibronectin-coated, ion-implanted coils showed the greatest acute thrombogenicity (average thrombus weight for standard coils, 1.9 +/- 1.5 mg; weight for fibronectin-coated coils, 8.6 +/- 6.2 mg; P < 0.0001). By using scanning electron microscopy, an intensive blood cellular response was observed on ion-implanted coil surfaces, whereas this was rare with standard coils. At Day 14, greater fibrous coverage of the necks of aneurysms was observed in the ion-implanted coil group (mean fibrous membrane to orifice proportion of 69.8 +/- 6.2% for the ion-implanted coil group, compared with 46.8 +/- 15.9% for the standard coil group; P = 0.0143). CONCLUSION The results of this preliminary experimental study indicate that ion implantation combined with protein coating of GDCs improved cellular adhesion and proliferation. Future application of this technology may provide early wound healing at the necks of embolized, wide-necked, cerebral aneurysms.

Cellular Responses of Bioabsorbable Polymeric Material and Guglielmi Detachable Coil in Experimental Aneurysms

Background and Purpose— Acceleration of healing mechanisms is a promising approach to improve current limitations of endovascular aneurysm therapy with the use of platinum coils. We evaluated a new endovascular therapeutic, bioabsorbable polymeric material (BPM), which may promote cellular reaction in the aneurysms. Methods— Four different concentrations of lactide/glycolic acid copolymer [poly(d-l-lactic-co-glycolic acid)] (PLGA), 85/15, 75/25, 65/35, and 50/50, were used as BPMs. Sixteen experimental aneurysms were created in 8 swine. Eight-millimeter-long spiral-shaped BPMs were surgically implanted in the aneurysms without tight packing (n=3 for each BPM). Guglielmi detachable coils (GDCs) were used as control (n=4). The animals were killed 14 days after embolization, and angiographic, histological, and immunohistochemical analyses were performed. Results— Despite loose packing of aneurysms with BPMs, faster BPMs such as 50/50 or 65/35 PLGA demonstrated more mature collagen formation and fibrosis in the sac and neck of the aneurysm. One aneurysm treated with 65/35 PLGA, 1 treated with 75/25 PLGA, and all 3 treated with 85/15 PLGA showed a neck remnant on angiography. There was a linear relationship between collagen levels and polymer degradation properties (r =−0.9513). Conclusions— This preliminary animal study indicates that acceleration of aneurysm healing with the use of BPM is feasible. This concept can be applied to decrease and perhaps prevent aneurysmal recanalization after endovascular treatment of cerebral aneurysms.

Challenges in the endovascular treatment of giant intracranial aneurysms.

OBJECTIVE:Giant intracranial aneurysms present unique therapeutic intricacies. The purpose of this study was to evaluate the anatomic and hemodynamic characteristics of these lesions and the current endovascular and combined surgical and endovascular techniques available for their treatment. METHODS:A review of the literature and the personal experiences of the authors with endovascular treatment of giant aneurysms are presented. This review included anatomic and hemodynamic features and analysis of the diverse endovascular techniques that have been reported for the management of these aneurysms. RESULTS:Anatomic features that create particular challenges in the therapeutic approach of giant aneurysms include size, shape (saccular, fusiform, serpentine), neck dimensions, branch involvement, intraluminal thrombosis, and location. Hemodynamic characteristics that affect endovascular treatment are lateral or terminal aneurysm type of flow and embolic material placement (inflow versus outflow aneurysmal region). The current endovascular therapeutic approaches include parent artery occlusion, trapping, endosaccular embolization with or without adjunctive techniques such as balloon-assisted or stent placement, and combined surgical and endovascular approaches, mainly with surgical revascularization and endovascular occlusion. CONCLUSION:Although there are a wide variety of endovascular therapeutic options for the treatment of giant intracranial aneurysms, none of the current techniques is completely successful and free of complications in the management of these complex lesions. A detailed and individualized analysis of each case in conjunction with sufficient understanding of the anatomy and hemodynamics of a particular aneurysm should guide the therapeutic decision. Further research advances will assist in elucidating the factors predisposing to genesis, progression, and aggressive clinical manifestations of these giant lesions.

Endovascular treatment of middle cerebral artery aneurysms with detachable coils: angiographic and clinical outcomes in 115 consecutive patients.

OBJECTIVEBecause of their anatomic configuration, middle cerebral artery (MCA) aneurysms are most often treated with surgical clipping. However, endovascular coil embolization of these aneurysms is an increasingly used alternative. We retrospectively reviewed the anatomic and clinical outcomes of patients with MCA aneurysms who underwent endovascular treatment at our institution. METHODSOne hundred fifteen MCA aneurysms in 115 patients (mean age, 55.1 years) were treated by an endovascular technique from April 1990 to March 2007. Forty-eight patients (42%) presented with acute subarachnoid hemorrhage, and 67 patients (58%) had unruptured aneurysms. Fifty-three aneurysms (46%) were small with a small neck, 28 (24%) were small with a wide neck, 22 (19%) were large, and 12 (11%) were giant. RESULTSAngiographic results immediately after embolization showed complete occlusion in 53 aneurysms (46%), a neck remnant in 51 (44%), and incomplete occlusion in 3 (3%). Because of anatomic difficulties, we could not embolize 8 aneurysms (7%). Thirteen patients underwent combined treatment that included endovascular and extracranial-intracranial bypass surgery. Morbidity and mortality rates were 6.9% (8 patients) and 3% (3 patients), respectively. Procedure-related complications were encountered in 10 patients (9%). Seventy patients had long-term follow-up angiograms. Seven aneurysms (10%) were recanalized; all were large or giant. One partially embolized large aneurysm ruptured 13 months after embolization. CONCLUSIONIn this series, endovascular coil embolization of MCA aneurysms has morbidity and mortality rates comparable to those of conventional surgical clipping. Combined treatment of endovascular and bypass surgery can successfully treat large or giant complex fusiform MCA aneurysms.

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.

Hemodynamic Changes in Arterial Feeders and Draining Veins during Embolotherapy of Arteriovenous Malformations: An Experimental Study in a Swine Model

OBJECTIVE Transcatheter assessment of changes in draining vein (DV) flow velocity has been proposed recently as a potentially useful procedure for hemodynamic monitoring of the progression of embolotherapy in cerebral arteriovenous malformations (AVMs). We compared and contrasted changes in hemodynamic parameters of arterial feeders (AFs) and DVs during experimental AVM embolotherapy. METHODS Carotid-jugular fistula-type AVM models were surgically created in eight swine. Pre- and postembolization transcatheter mean AF and DV pressures, DV-time average spectral peak velocity, and AF and DV pulsatility indices were assessed. An expression, the peak systolic velocity minus end-diastolic velocity (Vs - Ved), was also used in evaluating the transvenous Doppler spectra. Pre- and postembolization hemodynamic parameters were compared statistically. RESULTS Pre-embolization DV flow was pulsatile (Vs - Ved, 12 +/- 4.8 cm/s), with a mean DV velocity of 39.3 +/- 11.4 cm per second. Postembolization, this changed to a less/nonpulsatile pattern (Vs - Ved, 5.4 +/- 2.7 cm/s; P = 0.0035) with a lower mean DV-average spectral peak velocity of 7.0 +/- 3.1 cm per second (P = 0.0001). The mean DV pressure was also reduced from 52.0 +/- 8.2 to 45.5 +/- 8.7 mm Hg (P = 0.0023). The mean AF pressure increased from a mean of 79.5 +/- 15.5 to 96.8 +/- 16.2 mm Hg (P = 0.0004). The DV pulsatility index values also increased from a mean of 0.3 +/- 0.2 to 1.1 +/- 0.5 (P = 0.0003). Periembolization objective hemodynamic changes were detected in the DVs earlier than were the visually subjective angiographic changes observed within the nidus. CONCLUSION This preliminary study indicates that transvenous assessment of average spectral peak velocity and wave pattern (Vs - Ved) may be useful in the hemodynamic evaluation of AVM shunting. The convergence of these two parameters to a range less than 10 cm per second after nidus embolization may afford a theoretical advantage over AF pressure measurements when used for objective and quantitative monitoring of endovascular embolotherapy.

Transvenous Hemodynamic Assessment of Experimental Arteriovenous Malformations Doppler Guidewire Monitoring of Embolotherapy in a Swine Model

BACKGROUND AND PURPOSE A Doppler guidewire was used to monitor progressive changes in draining vein flow parameters during experimental embolotherapy in a swine arteriovenous malformation (AVM) model. METHODS A microcatheter was positioned superselectively in the main arterial feeder and main draining vein in each of 10 AVM models in swine. With use of the Doppler guidewire, preembolization arterial and venous average peak velocities (APVs) and pulsatility indices were recorded. The device was left in the draining vein during transarterial particulate (in 8 swine) or liquid adhesive (in 2 swine) embolization, and continuous transvenous flow during and after treatment was monitored. Periembolization Doppler flow parameters were correlated qualitatively with angiographic changes in the nidus. RESULTS Preembolization draining vein flow was pulsatile, with a mean APV of 38.9 +/- 13.7 cm/s. After embolization, this changed significantly to a less pulsatile or nonpulsatile pattern, with a lower mean APV of 9.2 +/- 4.9 cm/s (P = .0001). A novel expression, the maximum minus the minimum peak velocity (MxPV-MnPV), was used in evaluating the transvenous Doppler spectra. This was reduced significantly after embolization from a mean of 11.1 +/- 3.5 cm/s to 6.7 +/- 2.5 cm/s (P = .0025). Objective periembolization hemodynamic changes were detected in the draining veins earlier than the visually subjective angiographic changes within the nidus. CONCLUSIONS Transvenous Doppler guidewire assessment of two parameters, APV and MxPV-MnPV, is useful in the hemodynamic evaluation of experimental arteriovenous shunting and may be used for future objective and quantitative monitoring during endovascular AVM embolotherapy.