Computational flow dynamics of a novel next-generation flow diverter

IntroductionHistorically, adjunctive stents had different constructions than flow diverters. The former were open- (e.g. Neuroform) or closed-cell (e.g. Enterprise) laser cut nitinol devices, with low metal-to-artery ratios and pore densities....

The introduction of flow diverters (FDs) has represented a paradigm shift in the management of unruptured cerebral aneurysms (UCA). Flow Re-direction Endoluminal Devices (FREDs) and Pipeline Embolization Devices (PEDs) have gained widespread popularity. We aimed to investigate the cumulative incidence of aneurysm occlusion. A total of 195 patients with 199 UCAs were analyzed retrospectively. The outcomes were aneurysmal occlusion during the follow-up, a modified Rankin Scale score of 0-2 at 90days, additional treatment, major stroke, and steno-occlusive events of FD. Propensity score-matched analysis was performed, controlling for age, sex, aneurysmal size, and location of the internal carotid artery (ICA) aneurysm. Non-ICA aneurysms were excluded from matching. During the follow-up period (median, 366days), complete and satisfactory aneurysmal occlusions were observed in 128 (68%) and 148 (78%) of 189 UCAs in the unmatched cohort. The 142 (71 each) propensity score-matched cohort was complied. The FRED group had a higher cumulative incidence of ICA aneurysm occlusion (complete: HR 2.7, 95% CI 1.4-5.1, p = 0.0025; satisfactory: HR 2.4, 95% CI 1.1-5.2, p = 0.025). The proportion of additional treatment was significantly smaller in the FRED group (OR 0.077, 95% CI 0.010-0.57, p = 0.0007). Other outcomes showed no significant differences. Propensity score-matched analysis indicated that FRED might have a higher cumulative incidence of aneurysmal occlusion in the treatment of unruptured ICA aneurysms. Whether a cumulative incidence of aneurysmal occlusion may differ by the type of FDs warrants further investigation.

Analysis of Predictors and Probability of Aneurysm Occlusion in the Internal Carotid Artery After Treatment with Pipeline Embolization Device.

No. 172: Short-term and long-term results after aneurysm treatment with the pipeline embolization device

Objective To evaluate risk factors for acute ischemic stroke following treatment of paraclinoid aneurysms using flow diverters. Methods Between September 2015 and July 2018, 205 consecutive patients with 229 paraclinoid aneurysms were treated with Pipeline embolization device (PED) at Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University. The aneurysm size and parent artery size were measured. According to the length, proximal and distal diameter of the parent artery, appropriate size of PED was deployed with or without coiling. Various potential risk factors associated with acute ischemic stroke following PED treatment were documented. Univariate and multivariate logistic regression analyses were applied to identify risk factors. Results Among the 205 patients with 229 paraclinoid aneurysms, 110 aneurysms were treated by PED and 119 aneurysms received PED with coiling, all PED were delivered and implanted successfully. Eighteen (8.8%) patients with 20 aneurysms had acute ischemic stroke after PED deployment. Univariate analysis suggested that ADP inhibition, high MA-ADP value, clopidogrel non-response, application of complex intraoperative techniques, and long operation time were associated with the acute ischemic stroke following PED treatment (all P<0.05). Further multivariate logistic regression analysis showed the clopidogrel non-response (OR=6.161, 95% CI: 1.480-25.649, P=0.012), application of complex intraoperative techniques (OR=8.405, 95% CI: 1.437-49.146, P=0.018) and operation time (OR=1.011, 95% CI: 1.002-1.020, P=0.022) were independent factors for acute ischemic stroke following PED treatment. Conclusions Clopidogrel non-response, application of complex intraoperative techniques and long operation time may increase the risk of ischemic events. Key words: Intracranial aneurysm; Stroke; Factor analysis, statistical; Flow diverter; Paraclinoid

<h3>Introduction</h3> Utilization of the Pipeline Embolization Device (PED) for treating large and giant aneurysms of the distal internal carotid artery (ICA) is not well characterized. Conclusive evidence does not exist regarding flow diversion consequences related to PED placement into the M1 segment of the middle cerebral artery (MCA). <h3>Methods</h3> A retrospective chart review of patients treated for aneurysms with PEDs that extend into the MCA. All treated at a single medical center between 2011 and the present. Patient demographics, follow-up imaging and bilateral A1 and M1 vessel diameters with pertinent ratios were recorded. <h3>Results</h3> A total of 32 patients were included in the study (9 male, 23 female, ages 51±14 years). Follow-up angiogram was conducted at an average of 6±2 months. Seventeen (53%) patients demonstrated complete patency of the covered A1 segment and 3 (9%) patients showed narrowing of this segment. Twelve (38%) patients demonstrated occlusion of the covered A1 segment. Together, patients who maintained A1 patency and those that only showed vessel narrowing had an average A1 diameter to ipsilateral M1 segment diameter ratio of 0.70 and an average A1 diameter to contralateral A1 diameter ratio of 1.09. These values corresponded to 1.30 and 1.51 times their equivalent ratios in the patients whose A1 did not demonstrate blood flow on follow-up angiogram. Interestingly, none of the patients treated developed anterior cerebral artery (ACA) stroke or worsening of modified Rankin Score on follow-up. Two patients experienced vision loss and one patient's stent was found to be asymptomatically occluded. <h3>Conclusions</h3> The PED can safely be used to treat aneurysms with deployment from the distal ICA into the M1 segment of MCA. Unilateral A1 segment dominance may be predictive of cerebral blood flow into the ACA following deployment at this location. <h3>Learning objectives</h3> Identify opportunities for safe application of the Pipeline Embolization Device (PED) with coverage of the ACA. Discuss flow–related dynamics of the ICA–terminus and how they relate to PED placement and vessel dominance. <h3>Disclosures</h3> <b>A. Pujari:</b> None. <b>B. Howard:</b> None. <b>T. Madaelil:</b> None. <b>C. Cawley:</b> None. <b>J. Grossberg:</b> None.

We report histopathological findings from a human cerebral aneurysm following treatment with a flow diverter. A 75-year-old male underwent flow diversion treatment (Pipeline Embolization Device (PED)) and coil embolization for treatment of an aneurysm at the basilar tip. At four months, angiography showed complete aneurysm occlusion; at 12 months angiography demonstrated that the aneurysm had reopened. The patient expired from brainstem compression. The aneurysm cavity was primarily filled with unorganized thrombus. Thick, interrupted neointima crossed the neck interface indicating blood flow into aneurysm through small channels. Along the parent artery the PED was covered by neointima having a measured thickness of 0.19 ± 0.01 mm; the maximal stenosis of the proximal parent artery was 27%. The perforating arteries that were crossed by the PED remained patent. Findings in this human case are similar to those in the elastase-induced aneurysms in rabbits.

Pipeline embolization device (PED) is thought to induce aneurysmal occlusion through diversion of flow away from the aneurysmal sac with subsequent thrombosis and endothelialization. The impact of different factors especially hypertension (HTN)-a known predisposing factor to hypercoagulability and altered endothelial function-on aneurysmal occlusion after flow diversion has not been studied. We sought to determine predictors of aneurysmal occlusion following PED treatment focusing on impact of blood pressure. Database of patients with cerebral aneurysms treated with PED from 2013 to 2019 at our institution was retrospectively reviewed. Patients were defined as hypertensive if (1) they had a documented history of HTN requiring anti-HTN medications or (2) average systolic blood pressure on three measurements was > 130mmHg. The primary outcome was aneurysm occlusion status at the last imaging follow-up. Multivariable logistic regression model was constructed to assess the effect of HTN on occlusion, controlling for age, smoking, aneurysmal size, fusiform morphology, posterior circulation location, and incorporated branches. A total of 331 aneurysms in 294 patients were identified for this analysis. The mean age was 59years (79.9% female). Fifty-five percent of the cohort were classified as hypertensive. When controlling for other potential confounders, hypertensive patients trended toward higher odds of achieving complete occlusion compared to non-hypertensive patients (OR = 2.05; 95% CI = 0.99-4.25; p = 0.052). Meanwhile, age (OR = 0.91; 95% CI = 0.88-0.95; p < 0.001) and an incorporated branch into an aneurysm (OR = 0.22; 95% CI = 0.08-0.58; p < 0.002) were associated with decreased odds for complete aneurysmal occlusion. Hypertensive patients show a trend toward higher odds of achieving complete occlusion when controlling for potential confounders. The HTN-induced hypercoagulable state, enhanced endothelial activation, and altered extracellular matrix regulation might be the contributing factors. Further research is warranted to explore clinical implications of these findings.

The pipeline embolization device (PED) Flex with Shield technology is a third-generation flow diverter used for intracranial aneurysm treatment designed to decrease thrombogenicity through a phosphorylcholine coating. Herein, we aim to compare the rate of thromboembolic events in PED with Shield technology and PED without it through propensity score matching. We conducted a retrospective analysis of aneurysms treated with PED first-generation/PED Flex and PED with Shield between 2013 and 2023 at a single academic institution. Patients were matched through propensity score by controlling for confounding factors including age, smoking history, diabetes, previous subarachnoid hemorrhage, modified Rankin Scale pretreatment, location, aneurysm size, previous treatment, and clopidogrel or aspirin resistance. After matching, we evaluated for periprocedural and postoperative thromboembolic events. Data analysis was performed using Stata 14. A total of 543 patients with 707 aneurysms treated in 605 procedures were included in the analysis. From these, 156 aneurysms were treated with PED with Shield (22.07%) and 551 (77.93%) without Shield technology. Propensity score matching resulted in 84 matched pairs. The rate of thromboembolic events was 3.57% for PED Shield and 10.71% for PED first-generation/PED Flex ( P = .07), while retreatment rates were 2.38% for PED Shield and 8.32% for PED Flex ( P = .09). Complete occlusion at first ( P = .41) and last imaging follow-up ( P = .71), in-stent stenosis ( P = .95), hemorrhagic complications ( P = .31), and functional outcomes ( P = .66) were comparable for both groups. This is the first study in the literature performing a propensity scored-matched analysis comparing PED with PED with Shield technology. Our study suggests a trend toward lower thromboembolic events for PED Shield, even after controlling for aspirin and clopidogrel resistance, and a trend toward lower aneurysm retreatment rates with PED Shield, without reaching statistical significance.

Comparative Analysis of the Pipeline and the Derivo Flow Diverters for the Treatment of Unruptured Intracranial Aneurysms—A Multicentric Study

Endovascular intervention using traditional neurovascular stents and densely braided flow diverters (FDs) have become the preferred treatment strategies for traditionally challenging intracranial aneurysms. Modeling stent and FD deployment in patient-specific aneurysms and its flow modification results prior to the actual intervention can potentially predict the patient outcome and treatment optimization. We present a clinically focused, streamlined virtual stenting workflow that efficiently simulates stent and FD treatment in patient-specific aneurysms based on expanding a simplex mesh structure. The simplex mesh is generated using an innovative vessel-specific initialization technique, which uses the patient’s parent artery diameter to identify the initial position of the simplex mesh inside the artery. A novel adaptive expansion algorithm enables the acceleration of deployment process by adjusting the expansion forces based on the distance of the simplex mesh from the parent vessel. The virtual stenting workflow was tested by modeling the treatment of two patient-specific aneurysms using the Enterprise stent and the Pipeline Embolization Device (commercial FD). Both devices were deployed in the aneurysm models in a few seconds. Computational fluid dynamics analyses of pre- and post-treatment aneurysmal hemodynamics show flow reduction in the aneurysmal sac in treated aneurysms, with the FD diverting more flow than the Enterprise stent. The test results show that this workflow can rapidly simulate clinical deployment of stents and FDs, hence paving the way for its future clinical implementation.

Objective To evaluate the use of this stent for treatment of fusiform and broad-necked intracranial aneurysms. Method Seventeen fusiform and broad-necked intracranial aneurysms in 15 patients were treated electively. They were located at the internal carotid artery (8), vertebral artery (5), basilar tip(1), middle cerebral artery (1), posterior cerebellar artery (1) and posterior inferior cerebellar artery(1). In all cases,previous attempts with the remodeling technique were technically judged difficult and combined stent placement across the aneurysm neck and subsequent coiling of the sac. Aneurysms diameter size varied from 4 to 30 mm. Results A total of 16 aneurysms in 15 patients were treated with this procedure. In no cases, stent deployment failed. All aneurysms were initially stented, followed by coil placement. Complere or subtotal (>95%) occlusion was achieved in 6 patients, and partial occlusion (<95%) was achieved in 9 patients. The periprocedural rate of any stroke or death was 0%. Angiographic follow-up was obtained in 10 patients. Neurological status remained well in all patients at a mean clinical follow-up of (6.2±3.2)months. Conclusions Primary and recurrence treatment of fusiforra and wide-necked intracranial aneurysms using the Neurofonn stent is feasible and effective. No permanent neurological deficits were associated with stent deployment. Short-term follow-up identified intact parent arteries and stable occlusion rates in the majority of cases. Key words: Intracranial aneurysm; Neuroform stent; Coil

Flow diversion via Pipeline Embolization Device (PED) represents the most recent advancement in endovascular therapy of intracranial aneurysms. This exploratory study aims at a proof of concept for an advanced device-modeling tool in conjunction with computational fluid dynamics (CFD) to evaluate flow modification effects by PED in actual, treated cases. The authors performed computational modeling of 3 PED-treated complex aneurysm cases. The patient in Case 1 had a fusiform vertebral aneurysm treated with a single PED. In Case 2 the patient had a giant internal carotid artery (ICA) aneurysm treated with 2 PEDs. Case 3 consisted of tandem ICA aneurysms (III-a and III-b) treated by a single PED. The authors' recently developed high-fidelity virtual stenting (HiFiVS) technique was used to recapitulate the clinical deployment process of PEDs in silico for these 3 cases. Pretreatment and posttreatment aneurysmal hemodynamics studies performed using CFD simulation were analyzed. Changes in aneurysmal flow velocity, inflow rate, wall shear stress (WSS), and turnover time were calculated and compared with the clinical outcome. In Case 1 (occluded within the first 3 months), the aneurysm had the most drastic flow reduction after PED placement; the aneurysmal average velocity, inflow rate, and average WSS were decreased by 76.3%, 82.5%, and 74.0%, respectively, whereas the turnover time was increased to 572.1% of its pretreatment value. In Case 2 (occluded at 6 months), aneurysmal average velocity, inflow rate, and average WSS were decreased by 39.4%, 38.6%, and 59.1%, respectively, and turnover time increased to 163.0%. In Case 3, Aneurysm III-a (occluded at 6 months) had a decrease by 38.0%, 28.4%, and 50.9% in average velocity, inflow rate, and average WSS, respectively, and turnover time increased to 139.6%, which was quite similar to Aneurysm II. Surprisingly, the adjacent Aneurysm III-b had more substantial flow reduction (a decrease by 77.7%, 53.0%, and 84.4% in average velocity, inflow rate, and average WSS, respectively, and an increase to 213.0% in turnover time) than Aneurysm III-a, which qualitatively agreed with angiographic observation at 3-month follow-up. However, Aneurysm III-b remained patent at both 6 months and 9 months. A closer examination of the vascular anatomy in Case 3 revealed blood draining to the ophthalmic artery off Aneurysm III-b, which may have prevented its complete thrombosis. This proof-of-concept study demonstrates that HiFiVS modeling of flow diverter deployment enables detailed characterization of hemodynamic alteration by PED placement. Posttreatment aneurysmal flow reduction may be correlated with aneurysm occlusion outcome. However, predicting aneurysm treatment outcome by flow diverters also requires consideration of other factors, including vascular anatomy.

Objective To investigate the short-term efficacy of Pipeline embolization device (PED) in the treatment of complex intracranial aneurysms. Methods A retrospective analysis of clinical data was conducted on 37 patients who underwent endovascular treatment with PEDs at Neurosurgery Department of Nanfang Hospital, Southern Medical University from January 2018 to March 2019. There were 45 aneurysms in 37 patients (including 7 cases with tandem wide-necked small aneurysms) which were distributed in internal carotid artery (38 cases), vertebral artery (3 cases), middle cerebral artery (3 cases) and anterior cerebral artery (1 case). The maximum diameter of aneurysm ranged from 2.0 to 34.8 mm. In this series, the diameters in 22 aneurysms were no longer than 10 mm and those in the other 23 aneurysms were larger than 10 mm. The modified Rankin scale (mRS) was used to evaluate the prognosis. Results A total of 37 PEDs were placed for 37 patients with 45 intracranial aneurysms in this study (Pipeline Flex stent-assisted embolization performed in 13 cases and stent-only treatment in 24). Retentions of contrast agent in the aneurysm cavity were detected by immediate postoperative radiography for 37 aneurysms, which showed that the aneurysm-bearing arteries were smooth and had no stenosis. All PEDs were well attached according to DynaCT fusion 3D reconstruction. Perioperative complications occurred in 11 patients, among whom 2 died. There were 35 patients followed-up for 1 month after discharge and no neurological symptoms were observed. Conclusions The treatment of complex intracranial aneurysms with PEDs is relatively safe and effective. Further optimization may still be needed for the perioperative anti-platelet aggregation regimen. Key words: Intracranial aneurysm; Endovascular procedures; Flow diverter; Treatment outcome

Combined intravascular parent artery and ophthalmic artery occlusion for giant aneurysms of the supraclinoid internal carotid artery