Online October 3, 2016 Journal of Neuroendovascular Therapy 2017; 11: 105–108 DOI: 10.5797/jnet.ra-diverter.2016-0027 Basics of the Flow Diverter: Development and Principles Satoshi Tateshima 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. Keywords▶ flow diverter, pipeline, aneurysm Principles of Flow Diversion thrombosis by the placement of a flow diverter.1,2) The prin- ciple that “flow diversionˮ is not “pressure diversionˮ is Therapeutic strategies based on intra-aneurysmal emboliza- knowledge indispensable for the appropriate use of flow tion have limitations for fusiform and giant aneurysms, in diverters. There are two mainstays in the mechanism of aneu- which injury of the parent artery extends circumferentially rysm treatment using flow diverters. One is the effect of inhi- over a wide area. If the permanent cure is the goal in treating bition of the blood flow itself, and the other is reinforcement those aneurysms, either the reconstructive approach, namely and repair of the missing or injured parent artery wall using reinforcement of the parent artery itself, or the deconstructive the stent mesh as the scaffold for intimal generation (scaffold- approach in which occlusion of the parent artery is necessi- ing). The first mechanism alone tends to be focused on, but tated due to severe arterial injury is selected. The flow diverter intractable giant aneurysms cannot be cured completely by is a therapeutic device that makes a sophisticated reconstruc- the blood flow inhibiting effect alone. tive approach possible and is the most reasonable treatment A case that clearly demonstrated the importance of scaf- in consideration of the etiology of large and giant intracranial folding is presented briefly Figs.( 1–5). The patient was a aneurysms. woman in her 40s who was surgically treated in her child- The essence of the flow diversion effect, or the inhibition of hood more than 40 years ago for a giant aneurysm in the the entry of the blood flow into the aneurysm by the flow cavernous portion of the right internal carotid artery. The diverter, is the pressure loss of the fluid.1) However, it does not treatment was ligation of the external carotid artery and need so much pressure loss that is necessary to sufficiently artificial stenosis of the common carotid artery using the stagnate the intra-aneurysmal blood flow for the induction of Selverstone clamp in order to reduce the intra-aneurysmal blood flow Fig.( 1). After the procedure, the aneurysm was Ronald Reagan UCLA Medical Center - Interventional Neurora- thrombosed, and her extraocular muscle paralysis was diology, Los Angeles, CA, United States resolved. However, symptoms recurred after more than Received: February 18, 2016; Accepted: June 15, 2016 40 years, and the persistence of a thrombosed aneurysm at Corresponding author: Satoshi Tateshima. Ronald Reagan UCLA the same site was demonstrated by head CT and angiogra- Medical Center – Interventional Neuroradiology, 757 Westwood phy (Figs 2 and 3). Immediately, treatment by the place- Plaza Ste2129, Los Angeles, CA 90095-7437, United States ment of the Pipeline Flex embolization device was Email: [email protected] ©2017 The Editorial Committee of Journal of Neuroendovascular performed, and complete occlusion of the aneurysm was Therapy. All rights reserved. confirmed after 6 months by cerebral angiography (Fig. 4). Journal of Neuroendovascular Therapy Vol. 11, No. 3 (2017) 105 Tateshima S Fig. 3 Lateral right common carotid arteriogram. A saccular aneu- rysm is observed in the cavernous part. The clinoid segment of the internal carotid artery also shows fusiform dilation (arrow), suggesting advanced degeneration of the parent artery. Small branches of the internal carotid artery to the Fig. 1 Lateral right common carotid arteriogram. Artificial stenosis maxillary artery are delineated due to ligation of the ipsilat- created with the Selverstone clamp is observed. The exter- eral external carotid artery. nal carotid artery is ligated at its origin to prevent the forma- tion of collateral vessels from the external carotid artery. Fig. 4 Complete occlusion of the aneurysm was confirmed by angiography half a year after the Pipeline treatment. History of the Development of Flow Fig. 2 A thrombosed giant aneurysm is observed in the cavernous Diverters part of the right internal carotid artery. The development of the Pipeline embolization device (Pipe- line), which became a byword for flow diverters, dates back Head CT performed simultaneously showed complete more than 10 years. It was initiated by a venture start up disappearance of the thrombosed aneurysm (Fig. 5). Scaf- company, Chestnut Medical Technologies, Inc. based in folding clearly played an important role as a mechanism of North California.3) Pipeline stent, developed with the objec- the complete disappearance of the aneurysm, which had tive of reconstructing tortuous parent arteries in the cavern- not been cured over more than 40 years by blood flow stag- ous segment of internal carotid artery, adopted a braided nation and intra-aneurysmal thrombosis alone. structure. As a result, Pipeline behaved differently from 106 Journal of Neuroendovascular Therapy Vol. 11, No. 3 (2017) Basics of the Flow Diverter: Development and Principles in Japan since its approval. Despite slight differences in the delivery system and placement method, Pipeline 2 and Pipe- line Flex are identical in stent structure. The method for the placement of Pipeline with a flexible braid structure differs compared with conventional laser-cut stents. The stability of the microcatheter during the place- ment procedure is particularly important, and various coax- ial catheters have been used for this purpose. Simultaneously with the approval of Pipeline in the United States in 2011, ReFlex coaxial catheter developed by Reverse Medical Cor- poration, a venture start up in Irvine, California, was intro- duced to the market.6) While it was originally developed as Fig. 5 A Head CT scan half a year after Pipeline treatment. The an aspiration catheter to be used with a stent retriever, it thrombosed aneurysm completely disappeared. began to be used frequently to hold the Marksman microca- theter for the placement of Pipeline. After Reverse Medical Corporation was acquired by Covidien/ev3 Neurovascular conventional laser cut stents and prompted the establish- in early 2012, the product was renamed from ReFlex to ment of the placement technique and development of sup- Navien and is still used today as a support catheter for Pipe- 7) port equipment along with the development of the implant line placement. itself. Intracranial endovascular therapists, such as Peter In the field of flow diverters, which is an innovative Nelson and Pedro Lylyk, played major roles in the treat- treatment, big enterprises other than Covidien/ev3 Neuro- ment of early clinical cases and devised assist equipment, vascular avoided running the risk and have tried to figure such as Marksman 027 microcatheter, which was devel- out the timing of participation by studying the market situ- oped exclusively for Pipeline placement. Pipeline, first used ation and results of scientific validation. Under such cir- as an unapproved device in patients with intractable aneu- cumstances, the second flow diverter was developed by the rysms for humane purposes, was approved as a formal med- group of Ajay Wakhloo on the basis of data of their basic ical device in Europe and South America through the PITA experiments. It is called Surpass Flow Diverter designed to (Pipeline for Intracranial Treatment of Aneurysms) Trial improve the flow diverting effect while maintaining the carried out from 2006 to 2007.4) As Covidien/ev3 Neurovas- porosity at the same level by reducing the absolute diameter 8) cular, a large company, acquired Chestnut Medical Technol- of the stent mesh pores. At the end of 2012, Stryker, a large ogies in 2009 and obtained approval in the United States in enterprise, decided to acquire Surpass, which prompted the 2011 through the PUFs (Pipeline Embolization Device for entry of other big enterprises. As of January 2016, Microven- Uncoilable or Failed Aneurysms), clinical cases treated tion has completed patient registration for a clinical trial in TM with Pipeline have increased markedly.5) the Unites States of FRED , a self-developed flow diverter, In the first-generation Pipeline, the maximum coverage and Codman is also preparing a trial of its self-developed was made 30% (minimum porosity: 70%) in consideration device for intracranial endovascular treatment in the United of the patency rate of the penetrating branch and occlusion States. The circumstances that prompted all the major com- rate of the aneurysm. The first-generation model