Differences in tissue proliferation and maturation between Matrix2 and bare platinum coil embolization in experimental swine aneurysms.

BACKGROUND AND PURPOSE: Recanalization of post-embolization cerebral aneurysms remains a serious problem that influences treatment outcomes. Matrix2 is a bioactive, bio-absorbable, detachable coil that was developed to reduce the risk of recanalization. We examined the short-term efficacy of the Matrix2 coil system, and evaluated the temporal profile of tissue proliferation in a swine experimental aneurysm model compared with the bare platinum (BP) coil. MATERIALS AND METHODS: Thirty-six experimental aneurysms were created in 18 swine. All aneurysms were tightly packed with Matrix2 or BP coils. Comparative histologic and morphologic analyses were undertaken 1, 2 and 4 weeks post-embolization. RESULTS: Endothelial-like cells were observed partially lining the aneurysmal opening one week post-embolization with both coil types. At two and four weeks post-embolization, the aneurysms treated with Matrix2 coils had more extensive areas of organized thrombus than those packed with BP coils, but the numbers of functional proliferating endothelial cells identified by immunohistochemistry in the tissue were broadly comparable between the groups. Moreover, morphological analysis suggested there were more mature endothelial cells in aneurysms treated with bare platinum rather than Matrix2 coils. CONCLUSIONS: Our results indicate that aneurysms embolized with Matrix2 coils build thicker scaffolds for endothelialization, but this is not necessarily evidence of earlier tissue proliferation and maturation than those embolized with BP coils. Matrix2 coils may not be superior to BP coils for preventing aneurysmal recanalization after endovascular treatment of cerebral aneurysms.

Intracranial Aneurysm Model for Detachable Coil Testing.

Intracranial aneurysm is major vascular disease which is life-threatening and challenging treatment. Detachable coil is one of the standard treatments. Because of little knowledge about it, the detachable coils were evaluated by various methods. Animal aneurysm models were also used to test this equipment. In the present study, sidewall aneurysms were created on common carotid arteries of Landrace-Yorkshire-Durocswine. External jugular vein grafts were used as aneurysm sac. End-to-side anastomosis was done. Ten aneurysms were created successfully in 5 swine. There is no perioperative death. This animal aneurysm model is appropriated for coil testing especially in the histopathology aspect.

Woven Endo Bridge shape modification contributes to decrease in adequate occlusion rate after Woven Endo Bridge implantation for wide-neck bifurcation intracranial aneurysms.

PURPOSE: Recently, a novel device, the Woven Endo Bridge (WEB), was developed for wide-neck bifurcation intracranial aneurysms (WNBAs). The aim of this study is to investigate factors that contribute to adequate occlusion (AO) after the operation using detailed radiological images. METHODS: The subjects were 29 patients with 29 aneurysms who received WEB implantation for WNBAs between December 2020 and April 2022. We assessed the contributing factors to AO by retrospectively comparing the AO group and non-AO group. RESULTS: The mean age was 64.6 ± 13.1 years, and 18 were female (62.1%). The mean aneurysm dome width, aneurysm height, and aneurysm neck diameter were 4.8 ± 0.6 mm, 5.1 ± 0.6 mm, and 3.7 ± 0.6 mm, respectively. After about 6 months, 22 of 29 patients (75.9%) had AO. Complications were observed in 2 patients (6.9%), renal artery injury in one, and minor cerebral infarction in another, but the modified Rankin scale scores of both patients remained unchanged. Multivariate analysis extracted only WEB shape modification (WSM) as a contributing factor to AO (odds ratio: 0.912, p = 0.0287). CONCLUSION: WEB implantation for WNBAs was a treatment modality with acceptable efficacy and safety. WSM was the only significant factor contributing to non-AO after the treatment. We should clarify the mechanisms or causes of WSM to achieve AO after WEB implantation in future.

It Is Necessary to Pay Attention to Where the Pcom Originate from the Aneurysm to Treat with FD.

Objective With the expansion of indications of flow diverter (FD) for cerebral aneurysms, FD placement for posterior communicating artery (Pcom) aneurysms has been approved. However, it is controversial whether Pcom aneurysms should be treated with FD or not. In this study, we report the outcome of FD treatment for Pcom aneurysms in Japan. Materials and Methods We retrospectively analyzed 36 patients with 38 aneurysms treated with FD placement for Pcom aneurysms between 2015 and 2021 in our hospital. We divided our cases into complete occlusion (CO) and non-CO groups. And we extracted contributing factors to CO using multivariate analysis. We also compared the complications rate among the three types of FDs. Results CO was obtained in 29 cases (79.3%), and complications were observed in 3 cases (7.9%). Multivariate analysis revealed that the type of Pcom branch from the aneurysmal dome was a significant factor contributing to CO (odds ratio: 0.0052, 95% confidence interval 0.000048-0.584, p = 0.029). In terms of complications, complication rate was significantly higher in the Flow-Redirection Endoluminal Device (FRED) group ( p = 0.0491). Conclusion The outcome for Pcom aneurysms treated by FD was acceptable. When treating, we must pay attention to where Pcom originates. Achieving CO with FD is difficult for aneurysms where the Pcom branches from the dome. Furthermore, when treating Pcom aneurysms with FRED, it is necessary to be careful about thromboembolic complications.

Endovascular Treatment of Bifurcation Aneurysms with the Woven EndoBridge: Product Features and Selected Results of Off-Label Use.

Treatment for wide-neck bifurcation cerebral aneurysms (WNBAs) is widely performed by endovascular treatment as well as open surgical clipping. However, due to factors such as the shape and size of the aneurysms, as well as the anatomical features of surrounding branch vessels, there are some cases in which simple coiling or conventional adjunctive techniques, such as balloon-assisted or neck bridge stent-assisted coiling, are not sufficient to achieve a satisfactory cure. Against this backdrop, the device known as the Woven EndoBridge (WEB) (MicroVention, Aliso Viejo, CA, USA) was developed and can be deployed directly into the aneurysm for treatment. Over a decade has passed since its development, and it is now used in many countries worldwide. This review provides insights into the evolution of the WEB device from its development to the date of this writing, highlighting the unique features of the device and its treatment indications. Additionally, it discusses the posttreatment course, perspectives on recurrence and retreatment, imaging assessments, and potential off-label use based on numerous studies primarily conducted in Europe and the USA.

Safety and efficacy of pipeline embolization device treatments for intradural internal carotid artery aneurysms in a single center in a Japanese population.

Background: The pipeline embolization device (PED) is the most common flow diverter device in the world. To date, there have been no reports of treatment outcomes specific to intradural internal carotid artery (ICA) aneurysms. The safety and efficacy of the PED treatments for intradural ICA aneurysms are reported. Methods: 131 patients with 133 aneurysms underwent PED treatments for intradural ICA aneurysms. The mean aneurysm dome size and neck length were 12.7 ± 4.3 mm and 6.1 ± 2.2 mm, respectively. We used adjunctive endosaccular coil embolization for 88 aneurysms (66.2%). A total of 113 aneurysms (85%) were angiographically followed up 6 months following the procedure, and 93 aneurysms (69.9%) were followed up for 1 year. Results: The angiographic outcome at 6 months showed that 94 (83.2%) aneurysms had O'Kelly-Marotta (OKM) grade D, 6 (5.3%) had C, 10 (8.8%) had B, and 3 (2.7%) had A. At 1 year, 82 (88.2%) aneurysms had OKM grade D, 6 (6.5%) had C, 3 (3.2%) had B, and 2 (2.2%) had A. Multivariate analysis showed that aneurysm neck size and adjunctive coiling were statistically significant in aneurysm occlusion status. Major morbidity modified Rankin Scale >2 and mortality rates related to procedures were 3.0% and 0%, respectively. Delayed aneurysm ruptures were not observed. Conclusion: These results reveal that PED treatment of intradural ICA aneurysms is safe and efficacious. The combined use of adjunctive coil embolization not only prevents delayed aneurysm ruptures but also contributes to an increase in the rate of complete occlusion.

Pipeline Flex with Shield Technology Placement for Small- and Medium-sized Aneurysms Achieves Early Complete Occlusion.

The flow diverter has been shown to be a safe and effective device for large cerebral aneurysms in the proximal internal carotid artery (ICA). Recently, its indication has been expanded to small- and medium-sized cerebral aneurysms in the distal segment of the ICA. In this study, we report a single-center, retrospective investigation of the safety and efficacy of the Pipeline Flex device to treat these aneurysms. Of the patients who underwent Pipeline implantation for small- and medium-sized ICA aneurysms (≤12 mm) at our hospital between July 2013 and October 2021, 102 patients with 104 aneurysms were included in this study. The mean age of the patients was 57.7 ± 12.1 years, and 94 (90.4%) were female. The mean aneurysmal dome diameter was 9.2 ± 2.3 mm, the mean neck diameter was 5.3 ± 1.6 mm, and the mean dome-to-neck ratio was 1.8 ± 0.5. Twenty-five patients (24.0%) had incorporated vessels from the aneurysm. Complete occlusion of the aneurysms was obtained in 96 patients (92.3%). There were no cases of parent artery stenosis or major stroke after the procedure. Absence of incorporated vessel from the aneurysm dome and adjunctive coil embolization are statistically significant factors indicating complete occlusion in multivariate analysis. The time to complete occlusion was determined earlier with the use of the Pipeline Shield (p = 0.0386) and with adjunctive coils (p = 0.0025). We showed that Pipeline implantation for small- and medium-sized aneurysms was safe and highly effective.

Evaluation for Vertebral Artery Injury with Cervical Dislocated Fracture and Optimal Treatment before Reduction.

Objective: Cervical dislocated fractures frequently cause vertebral artery injury (VAI), which, in turn, propagates the thrombus at the site of injury. Cerebral embolism due to a thrombus after the reduction of dislocation leads to a poorer neurological outcome. Therefore, we investigated the outcome of treatment for cervical dislocated fractures and the usefulness of parent artery occlusion (PAO) before reduction. Methods: Eight patients with cervical dislocated fractures with a locked facets treated at our hospital between January 2018 and December 2020 were evaluated. We retrospectively examined patient characteristics and clinical outcomes. Results: Among the eight patients, two were injured at C4/5, four at C5/6, and two at C6/7. All patients had locked facets. Four patients had bilateral dislocation, while the others had unilateral dislocation. Two patients with unilateral dislocation had ipsilateral vertebral artery occlusion (VAO), while the other six did not. Both patients with VAO underwent PAO to prevent cerebral embolism before reduction. The six patients who did not have VAI underwent reduction without preprocedural treatment. No cerebral ischemic complications were observed. One patient died due to paralysis of the respiratory muscles caused by spinal cord injury but the remaining seven recovered well. Conclusion: PAO before reduction for cervical dislocated fractures with VAO may be effective in preventing cerebral embolism after reduction.

Long-term outcomes of Y-stent-assisted coil embolization using Low-profile Visualized Intraluminal Support Junior (LVIS Jr) for intracranial bifurcation aneurysms.

OBJECTIVE: Y-stent-assisted coil embolization is indicated for the treatment of complex intracranial bifurcation aneurysms. However, the long-term outcomes associated with this technique remain unclear. The purpose of this study was to evaluate the long-term outcomes of Y-stent-assisted coil embolization using the Low-profile Visualized Intraluminal Support Junior (LVIS Jr) device. METHODS: We retrospectively reviewed our databases to identify patients treated with Y-stent-assisted coiling using LVIS Jr. Digital subtraction angiography, silent magnetic resonance angiography (MRA), and time-of-flight MRA were performed at 1 year after the procedure. Patients also received an annual follow-up using MRA. Aneurysm occlusion status was classified into complete occlusion (CO), neck remnant (NR), and body filling (BF). Clinical outcomes were assessed using the modified Rankin Scale. RESULTS: Twenty-one patients (22 aneurysms) were included in this study. All procedures were performed successfully. Immediate postprocedural angiograms showed CO in 13 aneurysms (59.1%), NR in two aneurysms (9.1%), and BF in seven aneurysms (31.8%). One-year follow-up angiograms revealed CO in 86.4% of patients. Only one patient had a major recurrence and required retreatment. The mean follow-up duration was 43.5 months. The last angiographic studies demonstrated CO in 18 aneurysms (81.8%), NR in three aneurysms (13.6%), and BF in one aneurysm (4.5%). Periprocedural and delayed complications occurred in two patients and one patient, respectively. There was no permanent morbidity or death. The modified Rankin Scale scores at last clinical follow-up were equal to those before the procedures in all patients. CONCLUSION: Y-stent-assisted coil embolization using LVIS Jr for intracranial bifurcation aneurysms has favorable long-term angiographic and clinical outcomes.

Long-term Follow-up Results after Flow Diverter Therapy Using the Pipeline Embolization Device for Large or Giant Unruptured Internal Carotid Artery Aneurysms: Single-center Retrospective Analysis in the Japanese Population.

Flow diverter (FD) therapy using Pipeline embolization device (PED) has become an important alternative to treat internal carotid artery (ICA) aneurysms. Herein, we report the long-term outcome for 3 years after FD therapy using PED for ICA aneurysms in Japan. The patients who underwent angiographical and/or clinical follow-up for 3 years after the FD therapy using PED of large or giant unruptured ICA aneurysms from December 2012 at our university hospital are the subjects of this study. We retrospectively reviewed the in- and outpatients' medical charts, and written operative and radiological records. There were 84 patients with 90 aneurysms who could be clinically and/or angiographically followed up for 3 years. Of these, 7 aneurysms were only available for clinical follow-up. Of the remaining 83 aneurysms, 6 aneurysms had vessel occlusion due to stent thrombosis or parent artery occlusion, and 60 of the remaining 77 (77.9%) had complete occlusion. In multivariate analysis, older age (>70 years), wide neck, and non-adjunctive coiling contributed statistically significantly to incomplete occlusion. Of the 84 patients, 2 patients (2.4%) had delayed complications between 6 months and 3 years after the initial FD placement. Three patients (3.6%) had poor outcome due to postoperative major stroke complications, 2 of which were acute complications. The long-term results after FD therapy are good both angiographically and clinically. Endothelialization of the aneurysmal neck and intra-aneurysmal thrombosis contribute to complete occlusion. The primary reason for the somewhat low complete occlusion in Japan may be the patients are generally older.

Outcomes following aneurysmal coil embolization with intentionally shortened low-profile visible intraluminal support stent deployment.

PURPOSE: Among all stents available for neuroendovascular therapy, the low-profile visible intraluminal support stent bears the highest metal coverage ratio. We deployed a low-profile visible intraluminal support stent with a delivery wire or/and microcatheter system push action to shorten the low-profile visible intraluminal support stent and thus achieve a flow diversion effect. We report our single-institution experience with the use of low-profile visible intraluminal support stents for intentionally shortened deployment (shortening group) and non-shortened deployment (non-shortening group) for unruptured intracranial aneurysms. METHODS: We retrospectively reviewed the medical records of 130 patients with 131 intracranial aneurysms who were treated with low-profile visible intraluminal support stent-assisted coil embolization from February 2016-January 2019. All perioperative complications were noted. Every 6 months, we re-examined the patients with cerebral angiography or magnetic resonance angiography. The outcomes of aneurysm occlusion were evaluated by the modified Raymond-Roy occlusion classification. We used the finite element method and computational fluid dynamics to investigate the hemodynamics after shortened low-profile visible intraluminal support stent deployment. RESULTS: Immediately after treatment, the modified Raymond-Roy occlusion classification was significantly better in the shortening group than in the non-shortening group (p<0.05). The latest angiographic outcomes showed the same tendency. Hemodynamic analysis by computational fluid dynamics suggested an adequate flow diversion effect with the use of our intentional shortening method. CONCLUSIONS: Stent-assisted coil embolization using this technique showed good results of a high complete occlusion rate and low complication rate. These findings suggest that shortened low-profile visible intraluminal support stent deployment yields a flow diversion effect and may lead to early intra-aneurysmal thrombus formation.

Pioglitazone Prevents Hemorrhagic Infarction After Transient Focal Ischemia in Type 2 Diabetes.

Pioglitazone (PGZ), a PPARγ agonist, has been used for diabetic patients as an insulin-sensitizing agent. Recent studies have demonstrated that PGZ increases adiponectin (APN) levels and provides vascular protection in ischemic conditions. This study was designed to assess the neuroprotective effects of PGZ against cerebral ischemia-reperfusion injury via an APN-related mechanism. Type 2 diabetic leptin-deficient mice (db/db) were administered PGZ for 1 week, and plasma insulin and APN levels were measured. These mice received a middle cerebral artery occlusion and reperfusion injury, and they were evaluated for the infarct volume and by immunohistochemistry and western blotting analysis at several time points after ischemia. PGZ-administered db/db mice showed improved insulin sensitivity, and the hemorrhagic rate and infarct volume were decreased (P < 0.05). In the PGZ-administered group, plasma APN levels increased compared with the vehicle group. In the db/db group, PGZ administration significantly suppressed inflammatory reactions and oxidative stress after reperfusion (P < 0.05). PGZ may be applicable for acute cerebral ischemia treatment in metabolic syndrome patients as well as antidiabetic agents.

Histological and Transmission Electron Microscopy Results after Embolization with HydroSoft/HydroFrame Coils in Experimental Swine Aneurysm.

Coiling and clipping are standard treatment strategies for cerebral aneurysms. Regardless of the strategy used, recanalization may affect the patient's prognosis. The aim of this study was to histologically and morphologically compare the tissue proliferation after coil embolization using bare platinum coils versus second-generation hydrogel coils (HydroSoft/HydroFrame; MicroVention, Inc., Aliso Viejo, CA, USA). Endothelial-like cell proliferation was seen in both groups at 2 weeks after surgery. Macroscopic findings showed a tighter layer at 4 weeks in the hydrogel coil group, and histological and immunohistochemical findings revealed endothelial cell proliferation. This layer became much thicker and tighter at 4 weeks after surgery. Aneurysms treated with second-generation hydrogel coils may be more stable and have a lower incidence of recanalization than those treated with bare platinum coils because of the tight endothelial layer proliferation.

Endothelial cell proliferation in swine experimental aneurysm after coil embolization.

After coil embolization, recanalization in cerebral aneurysms adversely influences long-term prognosis. Proliferation of endothelial cells on the coil surface may reduce the incidence of recanalization and further improve outcomes after coil embolization. We aimed to map the expression of proliferating tissue over the aneurysmal orifice and define the temporal profile of tissue growth in a swine experimental aneurysm model. We compared the outcomes after spontaneous thrombosis with those of coil embolization using histological and morphological techniques. In aneurysms that we not coiled, spontaneous thrombosis was observed, and weak, easily detachable proliferating tissue was evident in the aneurysmal neck. In contrast, in the coil embolization group, histological analysis showed endothelial-like cells lining the aneurysmal opening. Moreover, immunohistochemical and morphological analysis suggested that these cells were immature endothelial cells. Our results indicated the existence of endothelial cell proliferation 1 week after coil embolization and showed immature endothelial cells in septal tissue between the systemic circulation and the aneurysm. These findings suggest that endothelial cells are lead to and proliferate in the former aneurysmal orifice. This is the first examination to evaluate the temporal change of proliferating tissue in a swine experimental aneurysm model.

Adrenomedullin deficiency and aging exacerbate ischemic white matter injury after prolonged cerebral hypoperfusion in mice.

Adrenomedullin was originally isolated from pheochromocytoma cells and reduces insulin resistance by decreasing oxidative stress. White matter lesions induced by aging and hyperglycemia play a crucial role in cognitive impairment in poststroke patients. Here, we examine whether adrenomedullin deficiency and aging exacerbate ischemic white matter injury after prolonged cerebral hypoperfusion. Adrenomedullin heterozygous, wild-type young/aged mice were subjected to prolonged hypoperfusion. Prolonged cerebral hypoperfusion followed by immunohistochemical analysis was used to evaluate white matter injury. After prolonged hypoperfusion, white matter damage progressed in a time-dependent manner in AM(+/-) group compared with the wild-type group. The number of oligodendrocyte progenitor cells gradually increased after prolonged hypoperfusion, whereas oligodendrocytes decreased following a transient increase, but the ratio of increase was mild in the AM(+/-) group (P < 0.05). Oxidative stress was detected in oligodendrocytes, with a larger increase in the AM(+/-) group (P < 0.05). Aged mice showed the same tendency, but white matter damage was worse, especially in the aged AM(+/-) group. Our results demonstrated that white matter injury was increased in adrenomedullin deficiency, which induced oxidative stress. White matter injury was more exacerbated because of hyperglycemia in aged AM(+/-) group. Adrenomedullin may be an important target in the control of ischemic white matter injury.

Differences in phosphodiesterase 3A and 3B expression after ischemic insult.

Phosphodiesterase (PDE) exists in the cardiovascular system, adipose tissue and platelets, and its inhibition increases the cellular levels of cAMP, which could activate cAMP-responsive element binding protein (pCREB). The present study was designed to map the expression of PDE3A/B in the forebrain and define the time course of PDE3 expression in the ischemic boundary zone after ischemia. The number of PDE3A-positive cells (neurons and endothelial cells) remained unchanged, while PDE3B-positive cells gradually increased after ischemia/reperfusion. In the corpus callosum, PDE3B was expressed in oligodendrocytes, oligodendrocyte progenitor cells, and astrocytes. PDE3B-expressing astrocytes showed gradual increase after ischemia/reperfusion. In the cortex, the majority of PDE3B-expressing cells before ischemia were neurons, though few were astrocytes. Ischemic insult resulted in gradual increase in PDE3B-expressing astrocytes and neurons, with larger increase in astrocytes. Expression of brain derived neurotrophic factor (BDNF) and B-cell leukemia/lymphoma 2 protein (Bcl-2) was detected in pCREB-positive cells, not in PDE3B-positive cells. Our results demonstrated that ischemic insult increased PDE3B expression, but not PDE3A, and changed the number and type of cells in a time-dependent manner. The variation of PDE3B-expression in the brain might play a crucial pathophysiological role, and regulation of PDE3B production might protect against ischemic brain damage.

New experimental model of terminal aneurysms in Swine: technical note.

BACKGROUND: Animal models of intracranial aneurysms are important for training surgeons and creating innovative endovascular treatment. Swine have physical dimensions close to those of humans and so are widely used in cardiology research. swine used as models for intracranial aneurysms have had difficulty maintaining long-term aneurysm patency. We present a swine model that may allow researchers to follow long-term outcomes after endovascular treatment. MATERIALS AND METHODS: We developed a terminal aneurysm model in swine (n = 3) using a vein pouch of an end-to-side anastomosis of the right carotid artery. We anastomosed the left carotid artery end and the right carotid artery side, designing it so the blood flows into the aneurysmal neck directly from the opposite side. we also anastomosed the ascending cervical artery and the right carotid artery, with flow reversal in the proximal right carotid artery by ligating the more proximal side. At the same time, a side-wall aneurysm was made, and we compared their patency periods. RESULTS: The terminal aneurysms remained patent for 3 months, and there were no major changes in their size or shape. In contrast, the side-wall aneurysms had become occluded at the 1-month follow-up. CONCLUSION: Our swine model displayed long-term patency and has the potential to allow long-term evaluation of new techniques and embolic agents.