The flow diverter enables complete reconstruction of the diseased segment of an intracranial artery harboring a large or giant aneurysm. The introduction of flow diverters induced a major paradigm shift in the treatment of intracranial aneurysms. The two main mechanisms of action for flow diverters are: (1) disruption of the blood flow from the parent artery into the aneurysm which leads to thrombosis and scarring of the aneurysm, and (2) serving as a scaffold over which the native tissue, such as neo-intima and endothelium, can grow. Continuous improvements in flow diverter technology and indisputable clinical results have led to broader acceptance for the use of flow diverters. In-depth understanding on the concept of flow diverter treatment is imperative for those involved in the modern comprehensive management of intracranial aneurysms.
To enrich our understanding of endovascular treatment of cerebral aneurysm in the era of flow diverters (FD), related literature dealing with fluid dynamic engineering is reviewed and elaborated on here.The intra-aneurysmal flow patterns could be classified into shear-driven flow and inertia-driven flow. The flow reduction effects of FD are better anticipated among aneurysms with a shear-driven flow pattern.The FDs with lower porosity reduce more blood flow into aneurysms. Under certain porosity, FDs with thinner filaments reduce more blood flow.The flow reductions of side-branches after FD are estimated as less than 20% by computer simulation. Thus, other factors such as anti-platelet drugs and neo-intimal hyperplasia may also be involved in the ischemic complications in the territory of side-branch after FD placement.Pulsatility of blood flow, which is considerably decreased in the parent artery downstream to large aneurysms, recovers shortly after FD deployment and the peak systolic velocity becomes higher after FD. The peripheral brain circulation might be changed after FD deployment in cases of large aneurysms.Blood flow simulation for FD is not easy but it would provide useful information for selecting the proper cases for FD as well as selecting the proper devices for a certain case.
Flow diverter stents have been used widely for treatment of cerebral aneurysms in the US and EU. Although flow diverter stents are very promising, there are a few clinical concerns such as delayed rupture or incomplete occlusion. Engineers have been addressing these issues using computational fluid dynamics simulations (CFD). Because flow diverter stents have “flow diverting” effects, as the name indicates, we consider that the effects could be predicted by CFD. In this review, I will describe CFD research on clinical aspects of flow diverter stents.
Objective: An outline and the results of clinical trials of flow diverters in Japan are reported.Subjects and Methods: There have been three flow diverters that have been evaluated by clinical trials in Japan: Pipeline, Surpass, and FRED. Since the clinical trials of Surpass and FRED are in progress as of January 2016, this report primarily focuses on Pipeline, which was approved for clinical use in April 2015 for the treatment of unruptured or chronic ruptured large/giant intracranial aneurysms.Results: The Japanese clinical trial of Pipeline was performed at four facilities by registering 22 patients, with 22 aneurysms. The procedure was completed in 21 (95.5%) of the 22 patients. The achievement rate of “complete occlusion of the target intracranial aneurysm and 50% or less stenosis of the parent artery” 180 days after the procedure, which was the primary endpoint, was 61.9%. “Severe ipsilateral stroke or neurologic death” within 180 days after the procedure, which was a major secondary endpoint, occurred in two patients (9.1%), and both events were subarachnoid hemorrhage due to rupture of the target aneurysm.Conclusion: The flow diverter is undoubtedly a revolutionary device in the treatment of large/giant intracranial aneurysms, but the results of the clinical trials in Japan were not satisfactory compared with previous reports. Therefore, the devices should be used carefully by comparing the safety and efficacy with those of existing endovascular treatment techniques including stent-assisted coil embolization and direct surgery in individual patients.
Flow diverters are making a breakthrough for the endovascular treatment of cerebral aneurysms. Of them, Pipeline is the only device approved in Japan. The first generation device, classic type and advanced one, Flex are compared, and the points of difference are discussed. The tip of a Flex is fixed with two protective sleeves instead of the capture coil in the classic type. This structural change simplifies and facilitates the initial deployment. The pusher wire has been replaced by a larger, elongated hypotube to permit better pushability. Flex is almost completely resheathable due to the introduction of resheath pad. The Pipeline Flex embolization device allows more precise and controlled deployment than the classic type.
The indication for a Pipeline Flex in Japan is internal carotid artery aneurysms proximal to the posterior communicating artery with maximum diameter of more than 10 mm and neck of more than 4 mm. Total coverage of neck and wall apposition to the parent artery are both necessary to obtain total occlusion using a Pipeline. Nevertheless, it is not necessarily technically feasible. It becomes more challenging to appropriately deploy a Pipeline particularly if there are multiple tortuous curvatures adjacent to the aneurysm, wide-neck of more than 8 mm, or discrepancy of more than 2 mm in the proximal and distal artery. There are several reports of delayed aneurysmal rupture following flow diverter treatment for intra-dural extra-large or giant aneurysms. Coil embolization immediately after Pipeline placement is the only way to possibly prevent this fatal complication. Physicians are recommended to begin with a straightforward case by skipping these challenging aneurysms.
The flow diverter was developed with great expectations as a therapeutic device for intracranial aneurysms that have been difficult to treat to date. Placed in the parent artery of an intracranial aneurysm, it covers its neck, promotes complete occlusion, and prevents rupture of the aneurysm by reducing the blood flow to the aneurysm, inducing its thrombosation, serving as a scaffold for newly formed intimal tissue covering the neck of the aneurysm, and separating the aneurysm from the circulation of the parent artery.
Objective: There are some reports concerning the effectiveness of flow-diverter (FD) stents for untreatable cerebral aneurysm by conventional surgery and endovascular treatment. Treatment with a Pipeline embolization device, one of the original FD stents, has just started in Japan. We report herewith our initial experience of Flow Re-direction Endoluminal Device (FRED), which is a new FD with unique double layer structures, for wide-neck large or giant cerebral aneurysms.
Materials and Methods: This report is part of a clinical trial for the approval of FRED in Japan with permission of the Institutional Review Board of Toranomon Hospital. Between October 2014 and January 2015, we treated six aneurysms in six patients with FRED including three cavernous and three paraclinoid aneurysms, three asymptomatic and three symptomatic aneurysms, four large and two giant aneurysms.
Results: All patients were treated with single FRED without any coils. There were no transient ischemic attack, no stroke and no death in peri- and post-operative periods. One patient’s preexisting eye symptom temporarily worsened. Follow-up angiography at 6 months showed no filling (O’Kelly Marotta scale: D) in two patients, entry remnant (OKM scale C) in two patients, and subtotal filling (OKM scale B) in two patients.
Conclusion: Treatments using FRED were achieved without any severe complication. Clinical trials will continue to demonstrate its safety and efficacy for complex aneurysms.
The introduction of flow diverters induced a major paradigm shift in the treatment of intracranial aneurysms. Not just large and giant aneurysms, but also some of the aneurysms that are amenable to conventional coil embolization could be better treated with flow diverters because of the high efficacy and treatment durability. As such, there are two ongoing studies, the Flow Diversion in Aneurysms Trial study (FIAT) and Prospective Study on Embolization of Intracranial Aneurysms With Pipeline™ Embolization Device (PREMIER) study, which aim to clarify the true indication of flow diverter treatment. Simultaneously, the next generation of flow diverters is being developed by the industry. After multiple iterations of the design and improvements in the mechanical performance, industry leaders are developing a new coating technology that modifies the biocompatibility of flow diverters. Continuous improvements in the devices and compiling good quality clinical data will increase the role of the flow diverter in the treatment of intracranial aneurysms.
Clinical evidence regarding a new endovascular treatment device, flow diverter (FD), for large/giant cerebral aneurysms is introduced. Currently, three kinds of FD, Pipeline, Surpass, and FRED, are being used in our country.Pipeline: Pipeline was successfully placed in 107/108 patients (99.1%) in PUFS trial. An international study, IntrePED, collected clinical data of 793 patients with 906 aneurysms, and showed favorable clinical results with relatively low neurologic morbidity-mortality (7.4%). However, adverse events were more frequent in large, ruptured, and posterior circulation aneurysms. Ischemic stroke was the majority of complications (4.7%). On the other hand, delayed rupture of the treated aneurysm was rare (0.6%).Surpass: In a prospective, single-armed, multicenter clinical study of Surpass flow diverter, successful placement was observed in 161 of 186 aneurysms (98%), and neurologic death or any stroke within 6 months was seen in 18 patients (12%).FRED: In FRED, clinical reports regarding 29 patients with 34 aneurysms showed 100% successful placement and no complications in 26 cases (89%).A recent meta-analysis reported that FDs were used for unruptured aneurysms, particularly, of the internal carotid or vertebrobasilar artery, and fusiform, dissecting, or wide-necked saccular aneurysms, and progressive occlusion of the aneurysm during follow-up after the procedure and neurologic morbidity in 3.5% and death in 3.4% in 1483 patients with 1704 aneurysms.In conclusion, FDs are shown as relatively safe and useful devices for aneurysms with complex anatomical structures which are not treatable by coiling or clipping. A better clinical result is expected by selecting appropriate patients and careful treatment with FDs in the future.
Flow diverter (FD) is stent-like fine-mesh device for the treatment of intracranial aneurysms, and endovascular therapy with FD has been developed for aneurysms difficult to be cured by standard treatment, and is already widely introduced in other countries. Japanese Society of Neuroendovascular Therapy (JSNET) submitted FD to the government committee as a priority device for the Japanese market in 2011. And, Pipeline Flex (Medtronic Neurovascular, Irvine, CA, USA) was approved in 2015, based on the result of an approving study in Japan and published data of pipeline for uncoilable or failed aneurysms (PUFS) study. At Pipeline Flex approval, three related medical societies, Japan Neurosurgical Society, Japan Stroke Society, and JSNET, established a clinical guideline, including clinical indication of FD, institute criteria, and operator criteria. Furthermore, these societies prepared to operate a clinical database of all cases where FD was used and post-market surveillance will be reported using this database. These activities may work for development of FD in Japan with support of the Ministry of Health, Labour and Welfare, Japan and Pharmaceuticals, and Medical Devices Agency.