NZ763908B2

NZ763908B2 - An embolisation device

Info

Publication number: NZ763908B2
Application number: NZ763908A
Authority: NZ
Inventors: Wayne Allen; Colin Forde; Paul Gilson; Liam Mullins; William Sheridan
Original assignee: Embo Medical Limited
Priority date: 2014-09-15
Filing date: 2015-09-15
Publication date: 2022-06-28

Abstract

There is provided herein an embolisation device for promoting clot formation in a lumen. The embolisation device comprises a proximal segment and a distal segment. Each segment comprises a stem and a plurality of flexible bristles extending outwardly from the stem. The bristles have a contracted delivery configuration and a deployed configuration in which the bristles extend generally radially outwardly from the stem to anchor the device in a lumen. In the deployed configuration, bristles of the proximal segment extend partially in a first longitudinal direction and the bristles of the distal segment extend partially in a second longitudinal direction which is opposite to the first longitudinal direction. The distal segment includes more bristles than the proximal segment. delivery configuration and a deployed configuration in which the bristles extend generally radially outwardly from the stem to anchor the device in a lumen. In the deployed configuration, bristles of the proximal segment extend partially in a first longitudinal direction and the bristles of the distal segment extend partially in a second longitudinal direction which is opposite to the first longitudinal direction. The distal segment includes more bristles than the proximal segment.

Description

AN EMBOLISATION DEVICE RELATED APPLICATIONS The present ation is a divisional application of New Zealand patent application no. , which is a divisional application of New Zealand application no. 746276, which is a divisional application of New Zealand application no. 729857, which is a national phase entry of PCT application no. , which claims priority from the EP application nos. 14184807.7, 15151922.0 and 15175292.0, the contents of each of which are included herein by reference.

INTRODUCTION This invention relates to an embolisation device.

Migration of conventional embolisation coils occurs 4-14% of transcatheter embolisations [1,2].

Non-target embolisation is an outcome of coils migration, the impact of which depends on the final on of the coils. In the venous system, the uences can be catastrophic with literature ting that coils can migrate into the renal vein, right atrium of the heart, lung (pulmonary artery). Percutaneous retrieval of the coils is technically very challenging and frequently cannot be attempted as the coils are often entrapped within the organs and tissue.

Coil ion occurs for s reasons: • Technical error: release of a coil or coil pack too distal or proximal to an adjoining larger vessel or plexus [3,4] • High blood flow areas can cause the coil to migrate.

• Coil: vessel mismatch. The coils are undersized, hence will not injure the vessel wall, will not induce thrombosis, and are likely to migrate. Or the coils are oversized and will act like a guide-wire and pass further distally into the vessel [5,6].

• Vessel dilation: coil migration can occur due to a disparity in the size of coils and dilated vessels, which can change in their ers depending on vessel hemodynamics [7].

• Coils impart a very low radial (anchor) force on the lumen, once a clot forms within the coil, blood flow can force it to migrate.

The profile of the embolisation device and delivery system is a critical success factor in successfully accessing target embolisation locations e.g. the iliac arteries are ntly tortuous in the presence of abdominal aortic aneurysms [5]. To combat this issue today, microcatheters are 18517197_1 (GHMatters) P42741NZ05 often employed in difficult or tortuous anatomy where use of standard catheters may induce spasm and lead to a failed embolisation procedure [5]. onally different stages in a procedure may require catheters with different mechanical ties e.g. accessing a visceral vessel, particularly in the presence of diseased or us arteries, may require a er with a high degree of stiffness and torque control. In l, the lower the profile of the device and delivery system, the greater the accessibility of the device into tortuous and higher order vessels. A lower profile device reduces the diameter of catheter required for delivery and lowers the risks of access site infections, hematomas and lumen spasm.

Dependent on the clinical application of the device, variable anchor forces may be required to prevent migration of the prosthesis e.g. arterial and venous applications have variable blood flow rates and forces. This in turn, will lead to a compromise in terms of profile since in order to anchor the device stiffer, and consequently larger elements may be required. For example in the case of a bristle device larger diameter fibres may be required.

The technique generally used to embolise vessels today is to insert a metallic scaffold (coil, plug) into the target vessel, to cause a thrombus that adheres to the scaffold, relying on the thrombus to induce blood cessation and eventually occlude the vessel. In general, available embolisation technology does not interfere with or interact with blood flow densely enough across the vessel cross section to induce rapid, permanent vessel occlusion.

Using technology available today, the physician will often have to prolong a specific duration of time for the technology to induce occlusion. In one ch the physician inserts coils and then waits 20 minutes for the coils to expand and cause vessel occlusion [8].

The restoration of the lumen of a blood vessel following thrombotic occlusion by restoration of the channel or by the formation of new channels, is termed recanalisation. Recanalisation can occur due to, coil migration, fragmentation of the embolisation material, and ion of a new vessel lumen that circumvents the ion [6]. Recanalization rates vary by procedure and c agent, ranging from 10% in portal vein embolisation to 15% for pulmonary arteriovenous malformations to 30% for splenic artery sation [9,10,11]. 97_1 (GHMatters) P42741NZ05 SUMMARY An aspect of the present invention provides an embolisation device for promoting clot formation in a lumen comprising a proximal segment and a distal segment, each segment comprising a stem and a plurality of le bristles extending outwardly from the stem, the bristles having a contracted delivery configuration and a deployed configuration in which the bristles extend generally ly outwardly from the stem to anchor the device in a lumen n, in the deployed configuration bristles of the proximal segment extend partially in a first longitudinal direction and the bristles of the distal segment extend partially in a second longitudinal direction which is opposite to the first longitudinal direction, wherein the distal segment includes more bristles than the proximal segment.

According to embodiments, in the contracted delivery configuration, the bristles of the proximal segment extend lly in a first udinal direction and the bristles of the distal segment extend partially in a second longitudinal direction which is te to the first longitudinal ion.

According to ments, the device r comprises a flow restrictor, optionally wherein the flow restrictor has a contracted delivery configuration and an expanded deployed uration.

According to embodiments, the flow restrictor is located adjacent to a proximal end of the device, optionally wherein the flow restrictor is located within or adjacent to the most proximal segment, optionally wherein the flow restrictor is located on the proximal segment.

According to embodiments, the flow restrictor is located adjacent to a distal end of the device, optionally wherein: the flow restrictor is located within or adjacent to a most distal segment, or the flow restrictor is located on the distal segment.

According to embodiments, the flow restrictor comprises a ne or film. Optionally, in an unconstrained configuration, the bristles extend to a radial extent which is greater than the radial extent of the ne in the constrained configuration. Optionally, in the ained configuration, the membrane has a longitudinal extent, and optionally wherein, in the unconstrained configuration, the membrane has a conical or cup-like shape. 18517197_1 (GHMatters) P42741NZ05 According to embodiments, the flow restrictor is of a flexible al. Optionally, the flow restrictor is of a polymeric material, an elastomeric material or a shape memory material such as Nitinol.

According to embodiments, the flow restrictor is located longitudinally within the bristles of the proximal segment and/or the flow restrictor is located longitudinally within the bristles of the distal segment.

According to embodiments, the flow restrictor extends from the stem. Optionally, the flow restrictor has an outer ion which is less than an outer dimension of the plurality of anchoring bristles. Op tionally, the flow restrictor is ted to the stem According to embodiments, the flow restrictor is not attached to the plurality of bristles. According to embodiments, the flow ctor is more flexible than the bristles adjacent to it.

According to embodiments, a diameter of the bristles in the distal segment is greater than a er of the bristles in the proximal segment.

According to ments, the device further comprises a connector n adjacent segments.

Optionally, a proximal connection between the proximal segment and the t adjacent to the proximal segment is relatively stiff. ing to ments, the stem of the proximal segment is mounted to the stem of the distal segment. O ptionally, the stem of the al segment is substantially rigidly mounted to the stem of the distal segment.

According to embodiments, the device further comprises at least one of the following: - a distal radiopaque marker which is located on a distal side adjacent to a most distal segment; - a proximal radiopaque marker which is located on a proximal side adjacent to a most proximal segment; and/or - a radiopaque marker intermediate the proximal segment and the distal segment. 18517197_1 (GHMatters) P42741NZ05 According to embodiments, the stem of the proximal segment and the stem of the distal segment form parts of the same continuous stem.

According to embodiments, the device further comprises one or more further segments between the distal segment and the proximal segment. Optionally, connections between at least some of the further segments comprise a hinge to facilitate relative movement between the segments.

Optionally, a connection between some of the ts intermediate the proximal segment and the distal segment is relatively rigid.

According to embodiments, a proximal end of the device is adapted for releasable connection with a delivery means such as a delivery wire or tube.

According to embodiments, the device further comprises a proximal connector for able connection to a delivery element. O ptionally, the proximal connector comprises a connector stem.

Optionally, the connector stem is d to a proximal segment stem. Optionally, the connector stem is hingedly mounted to the proximal segment stem.

According to embodiments, the connector stem has a connector mounting feature for engagement with a mounting feature of a delivery element, ally wherein the tor mounting feature comprises a screw thread.

There is further described herein an embolisation device, comprising: a proximal segment; a distal segment, each of the proximal and distal ts including a stem, and a plurality of anchoring bristles ing outwardly from the stem, wherein the distal segments includes more bristles than the proximal segment; and a flow restricting membrane.

There is further bed herein an embolisation , comprising: a proximal segment; a distal segment, each of the proximal and distal segments including a stem, and a ity of anchoring es extending outwardly from the stem; and a flow restricting membrane located on the proximal segment.

There is further described herein an embolisation device, comprising: a proximal t; a distal segment, each of the proximal and distal segments including a stem, and a plurality of anchoring 18517197_1 (GHMatters) P42741NZ05 bristles extending outwardly from the stem; and a flow restricting membrane located longitudinally within the bristles of one of said segments.

There is further described herein an embolisation device, comprising: a al segment; a distal segment, each of the proximal and distal segments including a stem, and a plurality of anchoring es extending outwardly and circumferentially from the stem; and a flow restricting membrane extending from the stem and having an outer dimension less than an outer dimension of the ity of anchoring bristles of the proximal segment.

There is further bed herein an embolisation system, comprising: a delivery catheter; and an embolisation device having a loaded configuration when the device is loaded in the delivery catheter, and a delivered configuration when the device is urged out from the catheter, the embolisation device further including a proximal segment; a distal segment, each of the proximal and distal segments including a stem, and a plurality of anchoring bristles extending outwardly from the stem, the bristles of the proximal segment being deflected in a first direction in the loaded configuration, and the bristles of the distal segment being deflected in a second direction in the loaded configuration, the first direction being opposite the second ion; and a flow restricting membrane deflected in the first direction in the loaded configuration.

There is further described herein an embolisation device for promoting clot formation in a lumen comprising at least two segments, each segment comprising a stem and a plurality of le bristles extending outwardly from the stem, the bristles having a contracted delivery configuration and a deployed configuration in which the bristles extend generally ly outwardly from the stem to anchor the device in a lumen wherein, in the deployed configuration bristles of one segment extend partially in a first longitudinal direction and the bristles of another segment extend partially in a second longitudinal direction which is te to the first longitudinal direction.

In one embodiment in the contracted delivery configuration the es of one segment extend partially in a first longitudinal direction and the bristles of another segment extend partially in a second longitudinal direction which is te to the first longitudinal direction.

In one case the device includes a flow restrictor having a contracted ry uration and an expanded deployed configuration. The flow ctor may be located adjacent to a proximal end 18517197_1 (GHMatters) P42741NZ05 of the . The flow restrictor may be located within or adjacent to the most proximal segment. atively or additionally the flow restrictor is located adjacent to the distal end of the device.

The flow restrictor may be located within or adjacent to the most distal t.

In one embodiment the flow restrictor comprises a membrane.

In one case a flow restricting membrane is located longitudinally within the bristles of the proximal t and/or the distal segment. The flow cting membrane may extend from the stem.

The flow restricting membrane may have an outer dimension which is less than an outer dimension of the plurality of ing bristles. The flow restricting membrane may be connected to the stem. In some cases the flow restricting membrane may have a central hole. The central hole in the ne is ably smaller than the stem on which it is mounted. The central hole in the membrane may have a diameter which is smaller than the diameter of the stem.

The central hole may adapt its shape and dimension at least in part to the shape and dimensions of a cross section of the stem. The central hole may be stretched during mounting in order to fit the stem.

In one case there is an interference fit between the central hole and the stem.

In one case the bristles in an unconstrained configuration extend to a radial extent which is greater than the radial extent of the membrane in the unconstrained configuration. In the constrained configuration, the ne may have a longitudinal extent. In the deployed configuration, the membrane may have a conical or cup-like shape.

In one embodiment the flow restrictor is of a flexible material. The flow restrictor may be of a polymeric material. The flow restrictor may be of an elastomeric material. The flow restrictor may comprise a film.

In one embodiment the flow restrictor comprises a shape memory material such as l. 18517197_1 (GHMatters) P42741NZ05 In one case the device comprises connectors between the segments. A proximal connection between the most proximal segment and the segment adjacent to the proximal segment may be vely stiff. The proximal connection may orate or comprise a marker band.

In one embodiment the embolisation device comprises only a single proximal segment and a single distal segment. The proximal segment and the distal segment in one case are mounted on a single common stem.

In one ment the stem of the al segment and the stem of the distal segment form parts of the same continuous stem.

In one embodiment the device comprises a distal marker which is located on the distal side adjacent to the most distal segment.

In one case the device comprises a proximal marker which is located on the al side adjacent to the most proximal marker.

In one embodiment the device comprises at least one further segment between a distal segment and a proximal segment. There may be a plurality of further segment between a distal segment and a proximal t. The connections between at least some of the further segments may comprise hinges to facilitate relative movement between the further segments.

In one embodiment a al end of the device is adapted for releasable connection with a delivery means such as a delivery wire or tube. There may be a connector for connection to the ry wire. The connector may be ly moveable relative to the most proximal t.

There is further described herein an embolisation device for promoting clot formation in a lumen comprising at least two segments, each segment comprising a stem and a plurality of flexible bristles extending outwardly from the stem, the bristles having a contracted delivery configuration and a deployed configuration in which the bristles extend lly radially outwardly from the stem to anchor the device in a lumen, wherein the device es a flow restrictor having a contracted delivery configuration and an expanded unrestrained configuration. 18517197_1 (GHMatters) P42741NZ05 In one case the flow restrictor is located adjacent to a proximal end of the device. The flow restrictor may be located within or adjacent to the most proximal segment. Alternatively or additionally the flow restrictor is located adjacent to the distal end of the device. The flow restrictor may be located within or adjacent to the most distal segment.

In one embodiment the flow restrictor comprises a membrane. The bristles in an trained configuration may extend to a radial extent which is greater than the radial extent of the membrane in the unconstrained configuration. In the constrained configuration, the membrane may have a udinal extent. In the deployed configuration, the membrane may have a conical or cup-like shape.

In one case the flow restrictor may be of a flexible al. The flow restrictor may be of a polymeric material. The flow restrictor may be of an elastomeric material.

In one embodiment the flow restrictor comprises a film. The flow restrictor may comprise a shape memory material such as Nitinol.

There is r described herein an sation device for promoting clot formation in a lumen comprising at least two segments, each segment comprising a stem and a plurality of flexible bristles extending outwardly from the stem, the bristles having a contracted delivery configuration and a deployed configuration in which the bristles extend generally ly outwardly from the stem to anchor the device in a lumen, comprising a proximal bristle segment and at least one distal bristle segment, a proximal marker proximal the most proximal segment, a distal marker distal of the most distal t and an intermediate marker between the most proximal segment and the t which is adjacent to the most al segment.

There is further described herein an embolisation device for promoting clot formation in a lumen comprising at least two segments, each segment comprising a stem and a plurality of le bristles which extend radially outwardly of the stem, the bristles having a contracted ry configuration and a deployed configuration in which the es extend generally radially outwardly of the stem, the bristles comprising distal bristles in a distal e segment and proximal bristles in a proximal segment and wherein there are differences between at least some of the distal bristles and at least some of the proximal bristles. 18517197_1 (GHMatters) P42741NZ05 In one case the device comprises at least one intermediate t between the proximal t and the distal segment, the intermediate segment sing intermediate bristles and n there are differences between the intermediate bristles and either or both of the proximal bristles and the distal bristles.

In one embodiment the differences comprise a difference in radial extent.

At least some of the bristles in the proximal segment may be tapered proximally or distally.

Alternatively or additionally, at least some of the bristles in the distal segment are tapered proximally or distally. Alternatively or additionally, the device comprises at least one intermediate t and at least some of the bristles in the ediate section are tapered proximally or directly.

In some ments at least some adjacent bristle segments are longitudinally spaced-apart.

In one case the differences comprise differences in properties such as flexibility.

The number of distal es may be different from the number of proximal bristles.

In some embodiments at least some of the bristle segments are of non-circular e in the deployed configuration.

There is further described herein an embolisation device of the invention and a delivery catheter.

In one case the delivery catheter is a microcatheter.

There is further described herein an embolisation system sing:- an embolisation device having a plurality of bristle segments having a cted delivery configuration and an expanded deployed configuration; a connector at a proximal end of the embolisation device; and a delivery element which is releasable connected to the connector for delivery of the embolisation device into the expanded deployed configuration. 18517197_1 (GHMatters) P42741NZ05 The connector may be configured to facilitate movement between the delivery element and the embolisation device. The connector may be hingedly mounted to the embolisation device.

In one case the system further comprises a delivery catheter in which the embolisation device is retained in the retracted configuration.

There is further described herein an sation device comprising:- a proximal segment; a distal segment; and a flow restricting member, each of the al and distal segments including a stem and a plurality of ing bristles extending outwardly from the stem.

The flow restrictor may comprise a membrane. The flow restricting membrane may be located on the proximal segment. The flow restricting membrane may be located on the distal segment.

In one case a flow restricting membrane is located longitudinally within the bristles of the proximal segment and/or the distal segment. The flow restricting membrane may extend from the stem.

The flow restricting ne may have an outer dimension which is less than an outer ion of the plurality of anchoring es. The flow restricting membrane may be connected to the stem. In some cases the flow restricting membrane may have a central hole. The central hole in the ne is preferably smaller than the stem on which it is mounted. The central hole in the membrane may have a diameter which is r than the er of the stem.

In one case the central hole adapts its shape and dimension at least in part to the shape and dimensions of a cross section of the stem. The central hole may be stretched during mounting in order to fit the stem.

In one case there is an interference fit between the central hole and the stem.

In one case the flow restricting membrane is not attached to the plurality of bristles.

The flow restricting membrane may be substantially impermeable.

The flow restricting membrane may have a contracted ry configuration and an expanded deployed configuration. In the constrained configuration, the flow cting membrane may have 18517197_1 (GHMatters) P42741NZ05 a longitudinal extent. In the deployed configuration the flow cting membrane may have a conical or cup-like shape.

The flow restrictor may be of a flexible material. The flow restrictor may be of a polymeric material. The flow restrictor may be of an elastomeric material. The flow restrictor may comprise a film.

In one case the flow restricting membrane is more flexible than the bristles adjacent to it.

In one embodiment the distal segment includes more bristles than the proximal segment.

The diameter of the bristles in the distal segment may be r than the diameter of the bristles in the proximal segment.

In one case the stem of the al segment is mounted to the stem of the distal segment. The stem of the proximal segment may be substantially rigidly mounted to the stem of the distal The embolisation device in some cases further comprises at least one radiopaque marker. There may be a radiopaque marker adjacent to a distal segment and/or a radiopaque marker nt to the al segment and/or a radiopaque marker intermediate the proximal and distal segments.

In one embodiment the device comprises a proximal connector for releasable connection to a delivery element. The proximal tor may comprise a stem portion. The connector stem may be coupled to the proximal segment stem. The connector stem may be hingedly mounted to the proximal segment stem. The connector stem may have a mounting feature for engagement with a mounting feature of a delivery element. The connector mounting feature may comprise a screw In one embodiment the embolisation device comprises only a single al segment and a single distal segment. The proximal segment and the distal t in one case are mounted on a single common stem. 18517197_1 (GHMatters) P42741NZ05 In one embodiment the stem of the proximal t and the stem of the distal t form parts of the same continuous stem.

The embolisation device may comprise at least one further segment between the distal segment and the proximal t. There may be a plurality of r segment between a distal segment and a proximal segment. The connections between at least some of the further segments may comprise a hinge to facilitate relative movement between the further segments. The connection between some of the segments intermediate the proximal segment and the distal segment may be relatively rigid.

In one case the proximal segment comprises from 40 to 150 es, in one case 60 to 150, optionally 70 to 110, optionally about 90, in another case 50 to 110, optionally 70 to 90, optionally about 80, in another case 40 to 100, optionally 40 to 75, optionally 40 to 60.

In one case the distal segment comprises from 40 to 180 bristles, in one case 70 to 180, optionally 100 to 150, optionally about 125, in another case 50 to 130, optionally 80 to 100, optionally about 90, in another case 40 to 80, optionally 40 to 60.

There is further described herein a method for manufacturing an embolisation device comprising the steps of:- ing a bristle segment having a plurality of bristles extending outwardly of the stem; providing a bristle manipulating tool; manipulating at least some of the bristles so that the bristles are aligned with the stem; mounting a flow restrictor membrane between the bristles; and releasing the es from the manipulating tool.

The method may comprise the step of mounting the membrane on the stem of the bristle segment.

In one case the membrane comprises a central hole which is smaller than the diameter of the bristle stem and the method ses engaging the stem in the hole of the membrane. 97_1 (GHMatters) P42741NZ05 In one case the l hole adapts its shape and dimension at least in part to the shape and dimensions of a cross section of the stem. The central hole may be stretched during mounting in order to fit the stem.

In one case there is an interference fit between the central hole and the stem.

BRIEF DESCRIPTION OF THE DRAWINGS The invention will be more y tood from the ing description of an embodiment thereof, given by way of example only, with reference to the accompanying drawings, in which: Fig. 1 is a side view of two connected segments of an embolisation device, in an unconstrained state, according to the invention; Fig. 2 is an oblique view of proximal segment of the device of Fig. 1; Fig. 3 illustrates the collapsed configuration of two segments in a catheter, one pointing distally and the other proximally; Fig. 4 shows the deployed configuration of a device with a proximally pointing proximal segment, a membrane, and a distally pointing distal segment; Fig. 5 is a schematic of the flow ion d arrows) entering a membrane in the deployed configuration and its effect which facilitates the seal against the vessel wall; Fig. 6 shows the configuration of two distally pointing segments (proximal and distal segments) in the collapsed state; Fig. 7 shows the configuration of two distally pointing segments (proximal and distal segments) in the deployed state; Fig. 8 illustrates an unstable device, with poor earity with the vessel centre line which may allow flow to pass through; 97_1 (GHMatters) P42741NZ05 Fig. 9 shows the dimensions of the device in the undeployed state (a) and the vessel diameter definition (b); Fig. 10 illustrates a device with two bristle segments pointing in opposing directions on the same stem; Fig. 11 illustrates a device with two bristle ts in opposing directions, sharing the same stem and without a gap in between; Fig. 12 (a) to (c) illustrates a marking system and the on of markers during different stages of delivery and deployment; Fig. 13 (a) and (b) shows a tion comprising a thread mechanism ing a twisted wire stem as a natural male thread - in this schematic a formed hypotube is used as the female thread; Fig. 14 shows a connection comprising a thread mechanism in which a hypotube is attached to a delivery wire and detachable from the twisted wire mechanism by a thread mechanism on the hypotube; Figs. 15 (a) illustrates an embolisation device in a fully expanded unrestrained configuration and (b) in a deployed configuration; Fig. 15 (c) is an exploded view of an embolisation device; Figs. 16 (a) and (b) are views similar to Fig. 15 of another embolisation device; Figs. 17 (a) and (b) are views similar to Fig. 15 of a further embolisation device; Figs. 18 (a) and (b) are views similar to Fig. 15 of a still r sation device; Fig. 19 is a view of a device of the ion in a packaged configuration ready for use; 18517197_1 (GHMatters) P42741NZ05 Fig. 20 is an enlarged view of a loading tube of Fig. 19; Fig. 20 (a) is an enlarged view of a distal end of r g tube; Fig. 21 is an isometric view of an embolisation device according to the ion; Fig. 22 is an elevational view of an embolisation device of the ion; Fig. 23 is an isometric view of the device of Fig. 22; Figs. 24 (a) to (d) illustrate the delivery and deployment of the device of Figs. 22 and 23; Fig. 25 is an isometric view of a further embolisation device according to the invention; Figs. 26 (a) and (b) illustrate configurations of another sation device; Fig. 27 is an elevational view of portion of a further embolisation device; Figs. 28 (a) to (c) illustrate the deployment of an embolisation device; Fig. 29 is an enlarged view of portion of an embolisation device in a deployed configuration; Fig. 30 a to r illustrates a range of geometries for embolisation devices according to the invention; Figs. 31 illustrate an embolisation device with a low profile; Figs. 32 illustrate another embolisation device according to the invention; Figs. 33 illustrate another embolisation device according to the invention; 18517197_1 (GHMatters) P42741NZ05 Fig. 34 illustrates a further embolisation device including a flow blocking member; Fig. 35 illustrates further embolisation devices according to the invention; Fig. 36 is a diagram of a two segment embolisation device bridging an aneurysm; Fig. 37 is a diagram of a multi segment embolisation device bridging a large aneurysm; Fig. 38 is a diagram of an embolisation device; DETAILED PTION Referring to the drawings there is illustrated an embolisation device 1 according to the invention which comprises a plurality of flexible bristles having deployed and contracted configurations.

The device comprises a series of segments wherein at least one segment 3 points distally and one segment 4 points proximally. In some cases there is only a proximal segment 4 and distal segment The bristles of the proximal segment 4 point ally and the bristles of the distal segment 3 point distally.

A proximally pointing segment is defined as a segment in which the bristles point proximally and the membrane (if present) cone is open at the proximal end. A ly pointing segment is defined as a segment in which the bristles point distally and the membrane (if present) cone is open at the distal end.

At least one t in this case the proximal segment 3, incorporates a flow restrictor which in this case is a thin film flexible ne 5.

In some cases a series of radiopaque markers divides the proximally pointing t 4 and the ly pointing t 3. There may be a proximal marker 6, a distal marker 7 and an intermediate marker 8. 18517197_1 (GHMatters) P42741NZ05 In one case the embolisation device comprises only a single proximal segment 4 and a single distal segment 3. The proximal segment 4 and the distal segment 3 in one case are mounted on a single common stem. The stem of the proximal segment 4 and the stem of the distal segment 3 may form parts of the same continuous stem.

In the case where the device comprises more than two segments, the connection between the two most proximal segments is more stiff than the distal connections. The distal connections generally comprise a hinge.

In one embodiment, a le membrane 5 is present in at least one of the segments. The membrane 5 may comprise a disc of thin film material. The flexibility of the membrane 5 means its orientation is controlled by the orientation of the adjacent bristles – i.e. if the nt bristles are forced to point distally the membrane 5 will adjust its configuration accordingly. Thus, if the membrane 5 is deployed from a collapsed condition, such as from within a er, the bristles will cause it to open up to an expanded configuration. The membrane 5 may also be placed al or distal to the segment.

In one case, the implant device comprises at least two segments. In one configuration the membrane 5 is in the most proximal segment. This is shown, in an unconstrained state schematically in Figs. 1, 2, 21, 22 and 23. In the configuration shown the membrane 5 is located within the proximal segment 4 with bristles both proximal and distal to the membrane 5. In some cases there may be a distal membrane 5’.

In one case a flow restricting ne is located longitudinally within the bristles of the al segment and/or the distal segment. The flow restricting membrane may extend from the stem.

The flow restricting membrane may have an outer dimension which is less than an outer dimension of the plurality of anchoring es. The flow restricting ne may be connected to the stem. In some cases the flow restricting membrane may have a central hole that is an interference fit on the stem. The central hole in the membrane is preferably smaller than the stem on which it is mounted. The central hole in the membrane may have a diameter which is smaller than the diameter of the stem. 97_1 (GHMatters) P42741NZ05 The implant has a collapsed configuration to facilitate delivery through a catheter. By placing the membrane 5 within the t 4, i.e. with bristles proximal and distal to it, it is protected from damage while the implant is being collapsed, or pushed through a catheter. Furthermore, any friction between the er and the ne 5 is reduced.

In one configuration, the implant is collapsed such that, the bristles of the most proximal segment 4 point proximally, while the bristles of the distal segment 3 or segments point distally. Since the membrane orientation is controlled by the orientation of the bristles, if the membrane 5 is within the proximal segment, it will also point proximally. This is shown schematically in Fig. 3.

Fig. 3 shows a collapsed configuration of two segments 3,4 in a catheter 10, one pointing distally and the other ally. It will be noted that the outer periphery of the membrane 5, shown in the proximal segment 4, is pointing proximally.

When deployed from this configuration, into a vessel a similar but partially ed configuration to the collapsed configuration is achieved. This means that the bristles of the proximal segment 4 point ally, and the bristles of the distal segment 3 point distally. This is shown tically in Fig. 4. In this configuration the implant will be anchored from moving in either direction. This is because the ends of the bristle act in a brake-like fashion increasing friction between the implant and the wall. On the ry, if all es point distally, the force required to push the implant distally will be greater than that required to push the implant proximally. Thus a device migration may be more likely to occur in the proximal direction.

In one embodiment the membrane 5, when measured in the unconstrained configuration, has a er which is less than that of the bristle segment, but greater than that of the vessel for which the device is intended. Thus the membrane is sufficiently large in diameter to contact the circumference of the . A larger membrane would increase the profile of the implant when in the collapsed condition necessitating a larger catheter for delivery.

As illustrated in Fig. 4 when the device is ed into a vessel, with a smaller diameter than the implant, the membrane 5 assumes a conical or cup-like shape - the open end of the cone proximal to the closed end. In one uration the deployed implant comprises a membrane 5 with a conical shape, the open end of the cone proximal to the distal end. In es blood from the heart 18517197_1 (GHMatters) P42741NZ05 towards the distal arterial tree, that is from al to distal. The configuration ensures that the blood flows into the cone’s volume, i.e. the opening of the cone opposes flow. Thus the blood will act to expand the cone further enhancing the seal between the membrane and the vessel wall (Fig. 5). In this way occlusion will be facilitated. Thus the greater the force ure) of the flow into the cone, the greater the improvement of the seal t the vessel wall.

Fig. 5 shows a tic of the flow direction (closed arrows) entering a membrane 5 in the deployed configuration and its effect on the seal against the vessel wall.

In another embodiment the implant may be collapsed such that all segments point distally. Fig s. 6 and 7 show the configuration of two distally pointing segments 3,4 (proximal and distal segments) in the collapsed state. When deployed, both the proximal and distal segments will point distally. Similarly, all segments may be sed such that all point proximally. This may be advantageous when ting to occlude a lumen in which flow is from distal to proximal, such as a healthy vein. Figs. 6 and 7 show the configuration of two distally pointing segments (proximal and distal segments) in the collapsed and deployed state.

A different degree of under sizing of the membrane with respect the segment er may be preferable for devices intended for arteries and veins. For example veins are known to distend more than arteries during manoeuvres such as Valsalva. Typically arteries distend by 5 to 15% while veins can distend 20-60%.

To ensure an adequate seal between the membrane 5 and the vessel wall it is preferable that the segment centreline is co-linear with that of the . Use of at least two segments in the device ng in opposite directions helps to remedy this problem, i.e. the bristles of the proximal t pointing proximally, and the bristles of the distal segment pointing distally. This facilitates a m seal of the cone against the vessel wall about its circumference. As can be seen in Fig. 8, if the segment is not ear with the vessel, the membrane may be unstable. This instability may enable flow to open or alter the membrane geometry from a cone-like shape (for example by flipping the direction of the cone). Fig. 8 illustrates an unstable device, with poor co- linearity with the vessel centre line which may allow flow to pass through.

The device may include es to improve co-linearity of the device with the vessel centreline.

In one embodiment, the diameter of the segment is significantly larger than that of the target vessel. 18517197_1 (GHMatters) P42741NZ05 This improves the stability of the device within the vessel facilitating co-linearity of the segment and the vessel centreline. Thus the implant is icantly oversized compared to the target vessel.

Preferable dimensions are outlined in Table 1 and Table 2 for devices rable through 0.0385 to 0.041 inch 9mm to 1.0414mm) and 0.056-0.056 inch (1.4224-1.4224mm) inner diameter catheters respectively. The dimensions are shown schematically in Fig. 9. Fig. 9 shows the dimensions of the device in the undeployed state (a) and the vessel diameter definition (b).

The oversizing (calculated as the percentage difference in diameter between t er and the vessel er) is preferably at least 20%, more preferably 50% of the vessel diameter and more preferably at least 100% of the vessel diameter in which the device is implanted. For example for a target vessel which is 6 mm in diameter, the device er may be at least 7.6mm, preferably at least 9mm, more ably at least 12mm.

To ensure co-linearity in veins, the degree of oversizing may be increased compared to that used in arteries. This is e veins are known to distend icantly (for example during Valsalva).

In one configuration the minimum over-sizing is 100%.

In one uration the connection between two segments has some flexibility to enable tracking through tortuous anatomy or to accommodate vessel movement during waking etc. It is preferable that the flexibility of this connection is limited so as to ensure good co-linearity of the segment with the membrane and the vessel ensuring good vessel occlusion. This prevents the device from deploying in a buckled configuration as it exits the catheter tip.

In one embodiment, the bristle segments are on the same stem 20 and there is a gap 23 between the segments 21, 22 as illustrated in Fig. 10. In another embodiment, two segments 24, 25 on two different stems may be connected. In one configuration this connection comprises a crimped or welded hypotube. Fig. 10 shows a device with two bristles segments 21, 22 pointing in opposing directions on the same stem 20.

In yet another embodiment, the same segment may be configured in the sed and deployed configuration so as to have some bristles (and the membrane) pointing proximally and some bristles pointing distally (Fig. 11). Fig. 11 shows a device with two bristle segments 24, 25 in opposing ions, sharing the same stem and without a gap in between. 18517197_1 (GHMatters) P42741NZ05 In some instances the physician may wish to deploy at least a portion of the device and reposition it if he or she is not satisfied.

In one case the device incorporates at least one proximally pointing proximal segment, and at least one distally pointing distal segment. If the ian deploys the device completely and then wishes to ve and redeploy the device, the action of retrieving the implant by advancing the guide catheter over it will cause the direction of the proximal segment or segments to flip upon passing through the catheter tip. Thus if the implant is re-deployed all segments will point distally.

This will cause the ne to be open distally. Thus flow may be able to flow past the outside of the membrane. It may be preferable to avoid this situation.

To mitigate this, a radiopaque marking system may be utilised to alert the physician of whether the proximally pointing segment or segments have been deployed from the catheter. Thus the physician can deploy the distally pointing segments, and assess their position without deploying the ally ng segment or segments. If the physician is unhappy with the position of the ly pointing segments, they may resheath and redeploy them without altering the direction of the proximally pointing ts.

In one configuration a radiopaque marker, distal marker 7, is t at the most distal point of the most distal segment. A second marker, medial marker 8, is present between the distally ng segment(s) and proximally pointing segment(s). A third marker, proximal marker 6, is present at the most proximal point of the proximally facing segment. In this configuration the section between the distal and medial marker 7,8 defines the distally facing ts which may be deployed, retrieved/repositioned without any effect on their pointing direction, and the section n the medial and third proximal 6,8 defines the proximally facing segment which should not be deployed until the physician is happy with position of the device.

The deployment of the device using this g system is shown schematically in Figs. 12(a) to (c) which show the marking system and their ons during different stages of delivery and deployment.

In one case, a section of tube of a radiopaque material known as a marker band may be crimped onto the connection between the segments. In the case in which a hypotube is used to connect the 18517197_1 (GHMatters) P42741NZ05 segments, the marker may be placed on one or both of the stems of the segments before the hypotube is crimped in place. In another embodiment the marker band may be placed onto the hypotube connection. In yet another embodiment the radiopaque marker band may be used to connect two adjacent segments. Attachment may be facilitated by crimping or welding, soldering, use of an adhesive or other means. In another configuration a marker band may be placed on the stem distal or proximal to the connection between the two segments.

In one embodiment the membrane is made from a thin film of PTFE. In one embodiment the membrane is made from a thin film elastomer such as polyurethane. In one case the membrane is of a plastic polyurethane, such as a poly-ether urethane, for e an aromatic her urethane. In one embodiment the membrane incorporates a small hole at its centre. To facilitate placement of the membrane on the bristle segment, the adjacent bristles are sed by some means. The ne can then be threaded over the collapsed bristles into the desired position.

Manipulating the membrane over the collapsed bristles into position may e that the hole is stretched to a larger diameter. The use of an elastomer which can accommodate larger deformations without permanently deforming tates this step in manufacture facilitates this.

The ability of this al to stretch facilitates placement of the membrane within the t during manufacture.

Because a material such as polyurethane is less lubricious than others ensuring that the membrane is adequately held against the bristles of the segment in the collapsed configuration and cannot be pulled off during loading and delivery h a catheter.

In one embodiment the membrane is made from thin film Nitinol. In this instance the bristles are not required to collapse, expand and support the ne.

Preferably the membrane has a low stiffness. This ensures that its behaviour is dominated by the bristles by the adjacent bristles, and that it can easily flex to ensure a good seal at the vessel wall. rmore a stiff membrane may have channels longitudinally. Another problem with a stiff membrane is that cannot fold and m to a low profile when in the collapsed configuration.

Considering the situation where a polymer membrane such as polyurethane is used, the stiffness of the membrane may be reduced by reducing its thickness to that of thin film. Dimensions for 18517197_1 (GHMatters) P42741NZ05 the membrane are outlined in Table 1 and Table 2. The membrane may also be of PTFE, PET, or Nylon. PTFE is particularly le as it will enhance ity enabling the device to be delivered through the catheter without high force.

It is preferable that the device profile when in the collapsed configuration is as low as possible in order to enable delivery through a small bore catheter. This reduces complications such as hematoma and infection at the site of luminal access for the catheters. It is also able that the implant be detachable from the delivery wire at the discretion of the ian.

In one uration, the implant has a detachment mechanism on its proximal end. This ensures that the physician can readjust its position until he or she is happy, remove the device, or detach the implant at will. For some designs the diameter of the ment mechanism may exceed that of the stem, or even fill the majority of the space within catheter or sheath used to deliver the implant to the target vessel. Accordingly, when in the collapsed state, if the bristles or membrane overlap the detachment mechanism an increased or excessive profile may occur.

Another solution to this problem is to use a low profile detachment mechanism. In one embodiment, a twisted wire stem may be used wherein the geometry of the twisted wire naturally provides a male screw thread as shown in Fig. 13 A female screw thread may then be threaded onto this male screw thread. In one embodiment the female screw thread mechanism comprises a formed hypotube in which the threads on the inside of the hypotube intended to mate with the threads of the d wire stem are formed in place. Preferably the pitch of the twisted wire brush is the pitch of the thread. A relatively low number of threads may be used with success. A minimum of two female threads is used preferably.

Fig. 13 shows a thread mechanism utilising the twisted wire stem 30 as a l male thread. In this schematic a formed be 31 is used as the female thread.

In another embodiment the female screw thread is machined or tapped onto the inside of a tube.

In another uration the female screw thread comprises a coil with a pitch to match that of the male thread providing a reliable screw detachment mechanism. 18517197_1 (GHMatters) P42741NZ05 In one embodiment the male screw thread 30 is a section of the twisted wire stem of the most proximal segment. In a further embodiment, the female thread or hypotube 31 is ed at its proximal end to a delivery wire 35. This tates delivery and detachment of the bustle segment through a catheter. This is illustrated schematically in Fig. 14 which shows a thread ism in which a hypotube 31 is attached to a delivery wire 35 and detachable from the twisted wire stem by a thread mechanism. A thread mechanism which does not utilise the twisted wire stem may also be utilised.

Referring in particular to Figs. 22 and 23 in one case a flexible section 40 is provided between the screw detachment mechanism 41 and the most proximal segment 4 of the implant. In one embodiment this le section 40 is a hinge. This flexible section 40 enables delivery and detachment of the implant in us anatomies. This flexible section 40 also serves to ensure that the proximal end of the implant is atraumatic.

In one embodiment the membrane and es do not overlap the detachment mechanism. In this case the detachment mechanism is located a m distance from the most proximal point of the segment such that the bristles and membrane do not, or at least minimally overlap the detachment mechanism.

A number of potential device configurations are shown in Figs. 15 to 18. In Figs. 15(a) and (b) there are two segments – one proximal containing the membrane 4 and one distal. Marker bands 6,7,8 are oned as described above.

Referring to figs 16(a) and (b) in this case there are onal distal segments 60 and hinge connections 61 are provided between the distal segments to odate movement between the segments.

Referring to Figs. 17(a) and (b), in this case the most distal segment also includes a membrane 5’ which has an opening which faces distally in the deployed configuration. A relatively stiff connection 62 is ed between the most distal segment and the adjacent segment.

Figs. 18(a) and (b) illustrate a device similar to Fig. 17 and again for increased stability when deployed, there is a relatively stiff connection 62 between the most distal segment and the adjacent segment. The connection in this case may be reinforced by or provided by a section of be. 18517197_1 ters) P42741NZ05 Figs, 19 and 20 show the complete device configuration. In the packaged configuration, when ready for use, the implant is stored within a loading tube 50. This loading tube 50 comprises a tube with a haemostasis valve 52 and side arm 51 for flushing. The delivery wire 55 is attached to the al end of the t and passes through the haemostasis valve. The t can be pushed from the loading tube 50 into a catheter for ry to the target site. In one embodiment the loading tube has a taper at its distal end to enable it to easily fit into the luer of the catheter used for delivery of the device to the target vessel.

As usly bed the implant is pushed from a loader into a catheter to be pushed to the site of treatment. An example of the loader is shown in Fig. 20. In one embodiment the loading tube is made from a lubricious material such as PTFE with an outer diameter of approximately 2.9mm and an inner diameter of approximately 1.65mm. This loading tube is compatible with both 0.056- 0.057" (1.4224mm to 1.4478mm) 5F delivery catheters and 0.035"-0.038" (0.889mm to 0.9652mm) 4Fr delivery catheters..

In another embodiment the loading tube has a taper at its distal end to enable it to be compatible with multiple ers of differing hub ries used for delivery of the device to the target vessel. A taper 56 on the loading tube 55 functions by funnelling the bristles 58 of the distal segment of the implant into a conical shape. On exit from the loader, the bristles funnel to a profile less than that of the inner diameter of the catheter hub ensuring that the implant can be pushed freely from the loading tube without snagging. This allows smooth transition across the tube/catheter interface and within the delivery catheter.

In one preferred embodiment the outer diameter of the loading tube is 2.9mm and the inner diameter is 1.65mm. The distal taper comprises an inner diameter from 0.8mm – 1.3mm tapered over a length of 1 – 6 mm.

Various configurations of segments, membranes and connections are illustrated in Figs. 25 to 29.

In some instances, it may be preferable due to space restrictions within the delivery catheter, to incorporate a ent number of bristles within the proximal and distal bristle segment. This enables he number of bristles which encourage thrombus formation and prevent device migration 18517197_1 (GHMatters) P42741NZ05 to be maximised, while preventing excessive friction within the catheter during delivery and ment. This is particularly important in the case in which one bristle segment of the implant incorporates a membrane since the membrane itself will take up space. It is also preferable to minimise the diameter of the stem to further enable addition of more bristles. The stem wire preferably has sufficient er to ensure that when twisted the bristles are securely held via plastic deformation of the stem wire. The following tables contain able combinations of materials and dimensions for the implant.

Attribute Materials Range Preferably More Preferably Bristle Any shape memory metal or polymer - Nitinol, y, Material Nitinol Stem Wire Stainless Steel, Cobalth Chromium, Cobalt Elgiloy, L605 or Material Platinum, Tantalum um MP35N Titanium or Nickel Alloy Membrane PTFE, PEEK, Polyurethane, Polyether - Polyether urethane Material ne, Polyester urethane, 80A Polycarbonate urethane Stem Wire - - ed Material Table 1 Attribute 0.035-0.040in (0.889-1.016mm) ID Catheter Preferably ≥ 0.038in (0.9652mm) Implant for short vessel treatment Range Preferably More Preferably Length of Implant (cm) 1-20 1-6 1.5-2.5 Suitable Artery Diameter (mm) 2-13 3-10 3-7 Suitable Vein Diameter (mm) 2-10 3-8 3-8 Bristle Diameter (in) 0.001-0.002 0.0015- 5 (0.0254 - 0.0018 (0.04445mm) 0.0508mm) (0.0381- 0.04572mm) Number of Segments 2-15 2-15 2 Number of Bristles in Proximal 50-130 70-90 80 Segment Length of Proximal Bristle 2.5-4.0 2.9-3.5 3.5 Segment (mm) Number of Bristles in Distal 60-140 90-110 100 Segment (no. per mm) Length of Distal Bristle t 3.0-5.0 3.7-4.5 (mm) 4.4 18517197_1 ters) P42741NZ05 Membrane Diameter (mm) 6-14 6-10 8 Membrane thickness (µm) < 25 < 18 8-16 Membrane Location Proximal Proximal al segment and distal and distal segment segment Stem Wire Diameter (in) 0.004-0.010 0.005-0.008 0.006 (0.1016- (0.127- (0.1524mm) 0.254mm) 0.2032mm) Distal and Proximal t 7-20 10-18 15 Diameter (mm) Gap n segments (mm) 0.5-10 2-5 3-4 Direction of fibres in most Proximally Proximally Proximally pointing proximal segment pointing pointing ion of fibres in most distal Distally Distally Distally pointing segment, or segments pointing pointing Table 2a Attribute Implant for Treatment of Short Vessel Segments 0.054-0.060in (1.3716 – 1.524mm) ID er Preferably 0.056in (1.4224mm) Range ably More Preferably Length of Implant (cm) 1-30 1.5-9 2.0-3.5 Suitable Vein Diameter (mm) 2-14 3-13 5-11 Suitable Artery Diameter 3-10 4-9 5-8 Number of Bristle Segments 1-30 1-25 2 Number of Bristles in Proximal 60-150 70-110 90 Segment Length of Proximal Bristle Segment 2-6 4-5 4.10± 0.5mm Number of Bristles in Distal 70-180 0 125 Segment Length of Distal Bristle Segment 2-10 5-7 5.75± 0.5mm Membrane Diameter (mm) 11-20 13-15 14 Membrane thickness (µm) < 25 < 18 810-16 97_1 (GHMatters) P42741NZ05 Membrane Location Proximal and Proximal Proximal t or distal and distal segment segment Stem Wire Diameter (in) 0.004-0.010 0.005- 0.006 (0.1016- 0.008 (0.1524mm) m) (0.127- 0.2032mm) e Diameter (in) 0.001-0.0025 0.00175- 0.002 4- 0.002 (0.0508mm) 0.0635mm) (0.04445- 0.0508mm) Segment er (mm) 14-38 18-30 25 Gap Between Segments 0.5-10 2-5 3-4 Direction of fibres in most proximal Proximally Proximally Proximally pointing segment pointing ng Direction of fibres in most distal Distally Distally Distally pointing segment, or segments pointing pointing Table 2b In some instances it may be preferable to use a much longer device for vessel occlusion. For example, in the case of gonadal veins, devices from 5cm to 15cm, or even 25cm may be required to treat the entire vessel length. For such a vessel, a lower bristle diameter may be riate even in a large vessel (e.g. 10mm diameter) since the increased number of bristles, due to the increased length and number of segments, means a ient anchor force can be achieved. A reduced bristle diameter in combination with a larger number of bristles enables a lower force for advancement through a catheter, and deployment from a catheter. The following table outlines some able combinations.

Attribute 0.054-0.060in (1.3716-1.524mm) ID Catheter Preferably 0.056in (1.4224mm) Range Preferably More Preferably Length of Implant (cm) 1-30 1.5-9 5 Suitable Vein Diameter (mm) 2-14 3-13 3-12 Number of Bristle Segments 2-30 4-25 2 Number of Bristles in Proximal 60-150 70-110 90 Segment Length of Proximal Bristle Segment 2-6 4-5 4.5 18517197_1 (GHMatters) P42741NZ05 Number of es in Distal 70-180 100-150 125 Segment Length of Distal Bristle Segment 2-10 5-7 6.2 Membrane Diameter (mm) 11-20 13-15 14 Membrane thickness (µm) < 25 < 18 8-16 ne Location Proximal Proximal and Proximal segment and distal distal segment segment Stem Wire er (in) 0.004- 0.005-0.008 0.006 0.010 (0.0127- (0.1524mm) (0.1016- 0.2032mm) 0.254mm) e Diameter (in) 0.001- 0.00175- 0.002 0.0025 0.002 (0.0508mm) (0.0254- 45- 0.0635mm) 0.0508mm) Segment Diameter (mm) 14-38 18-30 25 Gap Between Segments 0.5-10 2-5 3-4 Direction of fibres in most proximal Proximally Proximally Proximally segment pointing pointing pointing Direction of fibres in most distal Distally Distally Distally pointing segment, or segments pointing pointing Table 3a Attribute 0.054-0.060in (1.3716-1.524mm) ID Catheter Preferably 0.056in (1.4224mm) t for long vessel segment treatment Range Preferably More Preferably Length of Implant (cm) 2-30 4-25 10-20 Suitable Vessel Diameter (mm) 2-20 3-15 3-12 Number of Bristle Segments 2-30 4-25 9-22, or imately 1 segment per cm of implant length Number of Bristles in al 50-110 70-90 80 Segment Length of Proximal Bristle 2-6 2.8-4.2 3.5 Segment (mm) Number of Bristles in Distal 50-130 80-100 90 Segments Length of Distal Bristle 2.5-5 5 3.9 Segment (mm) Membrane Location Proximal and Proximal and Proximal distal segment distal segment segment Membrane Diameter (mm) 11-20 13-15 14 Membrane Thickness (µm) < 25 < 18 9-15 18517197_1 (GHMatters) P42741NZ05 Stem Wire Diameter (in) 0.004-0.010 0.008 0.006-0.008 6- (0.127- (0.1524- 0.254mm) 0.2032mm) mm) Bristle Diameter (in) 0.001-0.002 - 0.0175 (0.0254- (0.4445mm) 0.0508mm) Segment Diameter (mm) 14-38 18-30 25 Gap Between Segments (mm) 0.5-10 2-5 3-7 Direction of fibres in most Proximally Proximally Proximally proximal segment pointing pointing pointing Direction of fibres in most Distally pointing ly Distally distal segment, or segments pointing pointing Table 3b Attribute Implant for long vessel segment treatment 0.054-0.060in (1.3716-1.524mm) ID Catheter Preferably 0.056in (1.4224mm) Range Preferably More Preferably Length of Implant (cm) 2-30 4-25 5-20 le Vein Diameter (mm) 2-15 3-15 3-112 Suitable Artery Diameter 2-15 4-9 5-7 Number of Bristle Segments 2-30 4-25 9-22, or approximately 1 segment per cm of implant length Number of Bristles in Proximal 50-110 70-90 80 Length of Proximal Bristle 2-6 2.8-4.2 3.40 ± 0.5mm Segment (mm) Number of Bristles in Distal 50-130 80-100 90 Segments Length of Distal Bristle 2.5-5 3.5-4.5 3.70± 0.5mm Segment (mm) 18517197_1 (GHMatters) P42741NZ05 Membrane Location Proximal and / al and al or distal segment distal segment segment Membrane Diameter (mm) 11-20 13-15 14 Membrane Thickness (µm) < 25 < 18 10-16 Stem Wire Diameter (in) 0.004-0.010 0.005-0.008 0.006-0.008 6- (0.127- (0.1524- 0.254mm) 0.2032mm) 0.2032mm) Bristle Diameter (in) 0.001-0.002 - 0.0175 (0.0254- (0.4445mm) 0.0508mm) Segment Diameter (mm) 14-38 18-30 25 Gap Between Proximal 0.5-10 2-7 3-4 Segments (mm) Gap Between Distal Segments 0.5-10 2-7 6-6.5 Direction of fibres in most Proximally Proximally Proximally proximal segment ng pointing pointing ion of fibres in most Distally pointing Distally Distally pointing distal segment, or segments ng Table 3c In some instances, it is not le to access a target vessel using a rd catheter or sheath (which usually has an inner diameter of 0.035-0.038 inches (0.889mm - 0.9652mm)). For these instances a range of catheters have been developed known as microcatheters. These catheters exhibit excellent flexibility, and have an outer diameter typically less than 3.3 French. The internal er of these catheters ranges from 0.012 to 0.029 inches (0.3048mm to 0.7366mm). Standard internal diameters are 0.021, 0.024 and 0.027 inches (0.5334, 0.6096 and 0.6858mm). For compatibility with such catheters devices of the ion with the following utes are preferred.

Attribute 0.021-0.029in (0.5334-0.7366mm) ID Catheter Preferably 0.027in (0.6858mm) Range Preferably More Preferably Suitable Vessel Diameter (mm) 1.0-6.0 - 1.5 Bristle Diameter (in) 0.0005-0.002 0.0007-0.0015 0.001 (0.0127-0.0508mm) (0.0254mm) 18517197_1 (GHMatters) P42741NZ05 (0.01778- 0.0381mm) Number of Segments 1-4 1-2 1 Number of Bristles in Segment 100-500 200-450 300-400 Length of Proximal Bristle 2-10 3.5-9 7 Segment (mm) Diameter of Proximal End of 2-12 3-7 3 Segment (mm) Diameter of Distal End of 4-14 4-10 8 Segment (mm) Stem Wire Diameter (in) 0.010 0.003-0.006 0.004-0.005 (0.0762-0.254mm) (0.0762- (0.1016-0.127mm) Stem Diameter (in) 0.005-0.020 0.015 0.007 (0.127-0.508mm) (0.127- (0.1778mm) 0.381mm) Gap between segments (mm) None, or 1-5 None, or 1-3 Not Applicable Direction of fibres in most Proximally pointing Proximally Proximally proximal segment pointing pointing ion of fibres in most distal Distally pointing Distally Distally pointing segment, or segments pointing Table 4a Attribute 0.030 in (0.635-0.762mm) ID Catheter Preferably ≥0.027in (0.6858mm) Implant for short vessel treatment Range Preferably More Preferably Length of Implant (cm) 1.0-2.5 ≤2.0 ≤15 Suitable Artery Diameter 1.5-7 1.5-5 1.5-4.5 Number of Bristle Segments 1-3 - 2 Number of Bristles in Proximal 100-200 115-135 125 Segment Length of Proximal Bristle 2-5 2.5-3.5 3 Segment (mm) Number of Bristles in Distal 50-120 70-90 80 Segments Length of Distal Bristle 2-5 2.5-3.5 3 Segment (mm) ne Location Proximal and Proximal and al distal segment distal segment segment Membrane er (mm) 3-8 4-6 5 Membrane Thickness (µm) < 25 < 18 9-15 Stem Wire Diameter (in) 0.002-0.006 0.003-0.004 0.004 (0.0508- (0.0762- (0.1016mm) mm) 0.1016mm) Diameter of Bristle in 0.00075-0.002 - 0.001 Proximal Segment (in) (0.01905- 4mm) 0.508mm) 18517197_1 (GHMatters) P42741NZ05 Diameter of Bristle in Distal 0.001-0.002 - 0.0015 Segment (in) (0.0254- (0.0381mm) 0.0508mm) Segment er (mm) 6-20 -12 10 Gap n Segments (mm) 0.5-4 1-2 1 Table 4b Attribute 0.025-0.030 in (0.635-0.762mm) ID Catheter ably 0.027in (0.6858mm) Implant for short vessel treatment Range Preferably More Preferably Length of Implant (cm) 1.0-2.5 ≤2.0 ≤1.5 le Artery Diameter 1.5-7 1.5-5 1.5-4.5 Number of Bristle Segments 1-3 - 2 Number of Bristles in al 40-100 40-75 40-60 Segment Length of Proximal Bristle 2-5 2.5-3.5 2 ± 0.5mm Segment (mm) Number of Bristles in Distal 40-80 40-60 40-60 Segments Length of Distal Bristle 2-5 2.5-3.5 2± 0.5mm Segment (mm) Membrane on Proximal and/or Proximal and Proximal distal segment distal segment segment Membrane Diameter (mm) 3-8 4-7 6 Membrane Thickness (µm) < 25 < 18 7-13 Stem Wire Diameter (in) 0.001-0.005 0.002-0.004 0.003 (0.0254- (0.0508- (0.0762mm) 0.127mm) 0.1016mm) Diameter of Bristle in 0.00075-0.002 0.001- 0.0015 0.0015 Proximal Segment (in) (0.01905- (0.0254- (0.0381mm) 0.0508mm) 0.0381mm) 18517197_1 (GHMatters) P42741NZ05 er of Bristle in Distal 0.001-0.002 0.0015 0.0015 Segment (in) 4- (0.254- (0.0381mm) 0.0508mm) 0.0381mm) Segment Diameter (mm) 6-20 -12 10 Gap Between Segments (mm) 0.5-4 1-2 1 Table 4c A range of geometries, incorporating gaps between segments may be used. In one embodiment a bristle segment of uniform diameter may be used (Fig. 30 (a)).

A lower profile collapsed configuration can be achieved for ry through a microcatheter by using a taper in which the proximal diameter of the bristle t is lower than the distal diameter of the bristle segment. This is shown schematically in Fig. 30 (b). This is achievable since the distal es do not need to se onto any stem distally, while the proximal bristles lie on all bristles which are present distally.

In order to ensure adequate anchoring of the implant in the vessel to prevent migration, a specific portion of the bristle segment may be designed such that a minimum degree of oversizing with respect to the vessel diameter is incorporated. The degree of taper uced may be driven by this. In one configuration the lowest diameter of the bristle segment is at least that of the target vessel diameter. For example in Fig. 30 (f), the lower diameter proximal portion of the implant may be at least that of the target vessel, while the larger diameter may be substantially larger than the target vessel. In one ment the lower er portion of the segment may be 2-4 mm, while the larger diameter portion of the bristle segment may be 4-8 mm. In another embodiment the er of the bristle segment may be approximately the same as the target vessel.

In another configuration, a double tapered segment may be used (Fig. 30 (c)), or a number of individual tapered segments may be used (Fig. 30 (d)).

The use of a gap can further improve the efficiency (increase in the number of bristles) with which bristles can be placed within a catheter while maintaining a low profile implant in the collapsed condition. More fibres ensures better anchor force and increased interference with blood flow resulting in better thrombogenicity and shorter time to occlusion. Some examples are shown in 18517197_1 (GHMatters) P42741NZ05 Fig. 30 (m-r) and (d). Any combination of these features (gaps and tapers) can further increase the effectives of the implant in anchoring within the vessel and causing vessel occlusion.

Another means to enable a profile sufficiently low to fit through a microcatheter is the use of bristles of differing types i.e. with different properties. For example, as illustrated in Fig. 31 a large number of fibres of a low diameter may be incorporated in one area of a t to induce rapid thrombus formation and vessel occlusion. Similarly a lower number of fibres of a higher diameter may be incorporated. In one ment a group of fibres of diameter 0.0007 inches (0.01778mm), and a group of fibres of 0.001 inches (0.0254mm) is used. In another ce a group of fibres of 0.0254mm) and 0.0015 inches (0.0381mm) are used.

When the implant is placed into a catheter it is in a collapsed condition. If all bristles of a segment are collapsed such that they all point one direction, the bristles will lie on top of one another. This increases the profile of the segment in the sed condition. A longer segment with more bristles means a larger e in the collapsed condition. One means to reduce the profile in the collapsed condition is to collapse some of the fibres such that they point distally, and others such that they point proximally. This is shown schematically in Fig. 32.

Following deployment the bristle segment may be resheathed. This will force all fibres which al pointed proximally to be flipped such that they point distally. In one embodiment there is sufficient space within the microcatheter to enable all bristles to enter the microcatheter. In another configuration a most distal portion of the segment may not fully enter the microcatheter due to insufficient space for the bristles i.e. the profile is too high when all fibres of the segment point distally.

In yet another embodiment, the amount and configurations of the bristle segment may be tuned such that while not all fibres can enter the catheter, due to icient space, the bristles which remain outside the catheter are aligned roughly parallel to the catheter centreline and thus do not contact the vessel wall. This ensures that if the physician wishes to remove the implant or alter its position he or she will cause damage or tion of the vessel wall.

In yet another embodiment, an extendable connection exists between a distal and proximal segment. This will be advantageous particularly where the sed e is too large to be 97_1 (GHMatters) P42741NZ05 resheathed due to proximal segment bristles overlapping the distal segment bristles. As the physician pulls the proximal segment into the catheter and as the distal segment begins to enter the catheter causing resistance the extendable connection will h increasing or enabling a gap to emerge between segments. The increase in the gap size can enable the collapse of more or all of the segments into the catheter. Fig. 35 (a) shows such a uration with an extendable connection in the unloaded state. Fig. 35 (b) displays the same configuration in the loaded state with the extendable connection elongated. Fig. 35 (c) shows the resheathing step wherein the catheter collapses the proximal segment bristles. This action also causes an elongation of the extendable connection alleviating the degree of overlap of the proximal bristles onto the distal bristles. The extendable connection may comprise a spring or elastic element which can return to its original length upon unloading. The extendable connection may comprise non-elastic type element.

Another means to reduce the profile of the bristle segment is to trim the segment such that it has a rcular cross n. This is shown schematically in Fig. 33. (a) shows a conventional bristle t which has not been trimmed. Fig. 33 (b) shows a segment which has been d such that there is a lower diameter region. In this way the longer fibres will serve to ensure the implant is well anchored in the vessel, while the shorter fibres will support us formation. Other noncircular geometries such as a square Fig. 33 (c), triangular or others may be used.

In some implants, a membrane or flow blocking member may be incorporated. A number of urations are shown schematically in Fig. 34 which deal with the problem of space constraints within a microcatheter. Since the membrane will contribute significantly to the profile of the implant in the collapsed uration, it may be advantageous to place the membrane in an area of the segment which is generally of low profile in the collapsed configuration. This low e area of the segment may be achieved by any of the means described above (including reduced segment diameter, use of lower diameter bristles, use of tapers and the like).

As described previously, the implant may be detached via a screw mechanism. In one embodiment the female or male portion of the detachment ism is comprised of a radiopaque material.

This is to facilitate visibility of detachment during use. In yet r embodiment both female and male portions of the screw detachment mechanism are radiopaque enabling the physician to distinctively see the male detach from the female. 18517197_1 (GHMatters) P42741NZ05 In one embodiment a male portion of a screw detachment mechanism is attached to the t, and the female to the delivery wire. In another embodiment the female n of the screw detachment mechanism is attached to the implant and the male portion to the ry wire.

A gap between segments as shown in Fig 9(a) can facilitate a low profile during delivery and retrieval. During retrieval, via re-sheathing of the implant into a catheter, the gap facilitates a low profile when the fibres of the proximal t which may include a membrane are altered from a proximally ng configuration to a distally pointing ion. In a situation wherein retrieval of the implant is not a desirable attribute the gap between the segments may be as low as 1 mm. In another embodiment there may be no gap between the distally and proximal segments.

A further embodiment of the device, rable through a microcatheter, is described in Table 5.

The design is similar to that shown in Fig. 24. In one configuration a larger bristle diameter is used in the distal segment than the proximal segment. This is to ensure maximum outward radial force from the distal segment helping to anchor the device. A lower bristle diameter may be utilised in the proximal segment in order to facilitate a membrane in the proximal segment while also being deliverable h a microcatheter.

As discussed previously, the oversizing of the device diameter compared to the vessel (calculated as the percentage difference in diameter n t diameter and the vessel diameter) is preferably at least 20%, more preferably 50% of the vessel diameter and more preferably at least 100% of the vessel diameter in which the device is implanted. Even more preferably, 150% oversizing should be employed. sation Procedures Embolisation procedures may be undertaken by a range of physicians, primarily interventional radiologists, endovascular surgeons, and interventional cardiologists. There are a number of indications for sation. Frequently performed procedures, and the associate d physician are summarised in the table below.

In embolisation in general the flow direction is from proximal to the distal (prograde, or away from the . This is the natural flow ion in arteries. In healthy veins, the flow direction will 18517197_1 (GHMatters) P42741NZ05 lly be the opposite (retrograde, towards the heart). However in general, embolisation is performed in ts with reflux meaning flow will also be prograde.

Because the flow will generally be from proximal to distal it is able to have a membrane on the proximal end of the device open proximally, with the bristles also pointing proximally. This tes any potential for flow to pass around the outside of the membrane.

Indication Primary Target Access Site ion Notes Physician Vessel for of Flow Occlusion Assisted Endovascular Accessory Radial Prograde The accessory veins are Maturation of Surgeon, Veins in Artery draining the venous Dialysis Access Interventional AVF outflow, therefore flow Fistulas Radiologist is the opposite of a normal accessory vein.

Catheter tip points in direction of flow during device delivery.

Accessory Venous Prograde The accessory veins are Veins in Outflow draining the venous AVF outflow, therefore flow is the opposite of a normal accessory vein.

Catheter tip points in direction of flow during device delivery. ysis Interventional Bronchial l / Prograde Catheter tip points in Radiologist Artery Radial direction of flow during Artery device delivery Pre Op Y-90 Interventional Gastroduode Femoral / Prograde Catheter tip points in (prevent non- Radiologist nal, Gastric, Radial direction of flow during target Cystic Artery device delivery embolisation) Artery 97_1 (GHMatters) P42741NZ05 Varicocele Vascular Gonadal/ Jugular Prograde Refluxing/diseased Surgeon, Ovarian Vein / vessel, so flow is away Interventional Vein Femoral from heart. Catheter tip Radiologist points in ion of flow during device delivery. Membrane may be used to control sclerosant to treat collateral vessels.

Liver Interventional Hepatic Femoral/ Prograde Catheter tip points in ases Radiologist Artery Radial direction of flow during Artery device ry Type II Vascular Inferior Femoral/ Prograde Catheter tip points in Endoleaks Surgeon Mesenteric Radial direction of flow during Artery, Artery device delivery Internal Iliac Arteries Pelvic Vascular Ovarian Jugular Prograde ing/diseased Congestion Surgeon, Vein, Vein/ vessel, so flow is away Syndrome Interventional Internal or Femoral from heart. Catheter tip Radiologist Pudendal points in direction of Vein flow during device ry. Membrane may be used to control sclerosant to treat collateral vessels.

Hemorrhoids Vascular Internal Iliac Jugular Prograde Refluxing/diseased Surgeon, or Pudendal Vein/ vessel meaning Interventional Vein Femoral rhoidal plexus is Radiologist not ng ly.

Flow is away from heart into the plexus. Catheter tip points in direction of flow during device delivery 18517197_1 (GHMatters) P42741NZ05 Hemorroidal Femoral/ Prograde Catheter tip points in Arteries Radial direction of flow during Artery device delivery Liver Cancer: Interventional Portal Vein Trans- Prograde Catheter tip points in Promotion of Radiologist hepatic direction of flow during future remnant entry via device delivery hypertrophy contralateral approach entional Portal Vein Trans- Prograde Depending on ogist hepatic orientation of entry via er/tip, could be ipsilateral retrograde flow.

Interventional Portal Vein Jugular Prograde Catheter tip points in Radiologist Vein direction of flow during device delivery sms Interventional Splenic, Femoral or Prograde er tip points in Radiologist hepatic Radial direction of flow during artery Artery device delivery rhage Vascular Any artery Radial or Prograde Catheter tip points in Surgeon, Femoral direction of flow during entional Artery device delivery Radiologist Treatment of an aneurysm with a membrane at distal and proximal ends Normally blood flows from proximal to distal in the parent , past an aneurysm, with some filling of the aneurysm sac. It may therefore seem intuitive that occlusion of the proximal inflow towards the aneurysm should prevent flow into the sac. However, in some scenarios occlusion of the proximal vessel can alter the hemodynamics of the vessels y, meaning flow can travel from distal to the aneurysm causing further filling and pressurising of the aneurysm sac. In this scenario the physician aims to occlude the parent vessel proximal and distal to the aneurysm. This is known as front-door backdoor treatment of the aneurysm. 18517197_1 (GHMatters) P42741NZ05 In one embodiment the device may be configured such that there is both a proximal and distal ne on the device, enabling rapid occlusion of the parent vessel both proximal and distal to the aneurysm. ingly the proximal membrane is configured to be proximal the aneurysm sac, while the distal membrane is distal to the membrane sac. In a preferable configuration the ne on the proximal bristle t is open proximally, and the membrane on the distal segment is open distally.

One arrangement with two bristle segments 100, 101 each containing a membrane 102, 103 is illustrated in Fig. 36. Another arrangement with several onal segments 105 to bridge a larger aneurysm is illustrated in Fig. 37.

Use of a Stiff and Flexible Interconnects Between Distal Segments in Longer Device In some instances the properties of the segments may be such that no flexible connections in required. For short devices flexible tions may not be required. However for longer devices some ility may be required. It is preferable that at least one flexible connection per 5cm of the implant length be present.

In one configuration, a device has many distal bristle ts in which the distal segments are connected via both flexible and stiff connections. This may be required when flexible connections between all distal segments mean that the pushability of the implant when being delivered through a catheter is compromised due to too much flexibility. This may be the case in particular where very flexible connections incorporating a hinge are used. The replacement of at least one flexible connection with a stiff or stiffer connection will improve the column stiffness of the t and hence its ility. This will reduce the force required to push the implant through the ry catheter. It may be preferable to place the stiff connections intermittently between the flexible sections to ensure good flexibility along the length while also maintaining good pushability along the length.

One such device is illustrated in Fig. 38. This device has proximal and distal segment 110, 111 and a plurality of intermediate segments 112. Some of the connections between the segments are hinged 113 and others are relatively stiff 114. 18517197_1 (GHMatters) P42741NZ05 It is preferable that the membrane is within the bristle segment. A bristle lating tool may be used and some of the es may be manipulated so that the es are aligned with the stem.

A flow restrictor membrane is mounted between the es and thereafter the bristles are released from the tool or vice versa.

When the bristles recover the membrane will be between and protected and secured by bristles both proximally and distally.

To ensure that the membrane is controlled by the adjacent bristles, some bristles should be present both distal and proximal to the membrane. In one mation the ne 130 is placed such that 50% of bristles are proximal to the membrane while 50% are distal to the membrane. To prevent overlap of the membrane onto structures proximal to the segment (such as a detach mechanism, or ry wire), the membrane may be placed more distally within the segment. In one configuration 60% of fibres are proximal to the membrane while 40% are distal to the membrane. In another configuration 70% of fibres are proximal to the membrane while 30% are distal to the membrane. In another configuration 80% of fibres are proximal to the membrane while 20% are distal to the membrane.

Membrane Hole Diameter and Interference Fit Placement of the membrane within the bristle segments ensures that bristles inhibit the membrane from translating proximally or distally along the segment while in use or when deployed. The ty of the membrane may be further ed via an interference fit between a hole in the membrane and of the segment stem. To e this, the hole in the membrane should be smaller than the stem of the segment. Once placed onto the stem the ch of the diameter of the stem and the hole in the membrane will cause friction between the two surfaces and an interference fit.

To e an interference fit the hole in the membrane should be less the stem diameter.

Preferably the hole diameter in the membrane should be at least 0.001in (0.0254mm) less than the diameter of the stem. More preferably the hole diameter in the membrane should be at least 0.002in (0.508mm) less than the diameter of the stem.

It will be iated that if the hole in the membrane is too small, excessive stretching may be required to apply the membrane to the segment causing irrecoverable deformation of the hole such 18517197_1 (GHMatters) P42741NZ05 that no interference may be present or a gap could exist between the stem and the hole in the membrane. In this instance some flow may pass h this gap inhibiting the device mance in terms of occlusion. The hole of the membrane should be no more than 40% less than the diameter of the stem.

Ideally the hole diameter is ied such that the ratio between the initial hole diameter and stretched hole diameter should be less than the ultimate elongation of the membrane material such that the membrane hole diameter will recover to its lower diameter causing interference fit with the stem.

The device disclosed may also be used in fields beyond embolisation. For example, these embodiments may be particularly useful in the field of contraception wherein the fallopian tubes are occluded. Furthermore the device disclosed may be used in the field of bronchiopulmonary occlusion. For e, in the case where a physician wishes to exclude a portion of the lung by occluding a bronchus.

Modifications and additions can be made to the embodiments of the invention described herein without departing from the scope of the ion. For example, while the embodiments described herein refer to particular features, the invention includes embodiments having different combinations of features. The invention also es embodiments that do not include all of the specific features bed.

The invention is not limited to the embodiments hereinbefore described, with reference to the accompanying drawings, which may be varied in construction and detail. 18517197_1 ters) P42741NZ05 [Link] http://www.terumois.com/products/embolics/AZUR.aspx 1. Ekeh et al., Complications arising from splenic artery embolisation: a review of an 11-year experience. The American Journal of Surgery, 205, 250-254, 2013 2. Ryer et al. 2013, Comparison of outcomes with coils versus vascular plug embolisation of the internal iliac artery for endovascular liac aneurysm repair. Journal of Vascular Surgery, Volume 56, Issue 5, November 2012, Pages 1239–1245. 3. Beddy et al., Testicular celes. Clinical Radiology (2005) 60, 1248–1255 4. Beecroft etal., Percutaneous varicocele embolisation. Canadian ical Association Journal. September 2007, Volume 1, Issue 3 5. Kessel et al., Transcatheter sation and Therapy. Springer ISBN 97884800 0. Published 2010 6. Balian et al. Pelviperineal venous iciency and varicose veins of the lower limbs.

Phlebolymphology. 2008; 17-26. 7. Marsh et al., Coil Protruding into the Common Femoral Vein Following Pelvic Venous Embolisation. Cardiovascular Interventional Radiology (2008) 31:435–438 8. The Technology of Expansion. Terumo Interventional Systems. Downloaded on February 21, 2013 from http://www.terumois.com/products/embolics/AZUR.aspx 9. Letourneau-Guillon et al., Embolisation of Pulmonary Arteriovenous Malformations with Amplatzer Vascular Plugs: Safety and Midterm Effectiveness. Journal of Vascular and Interventional Radiology, Volume 21, Issue 5, Pages 649-656, May 2010.

. Yoo et al., Preoperative portal vein embolisation using an amplatzer vascular plug. an Radiology (2009) 19: 1054-1061. 11. Pelage et al. What is Azur Hydrocoil and How Does it Work? Presented at Society of Interventional Radiology, 2011. 18517197_1 (GHMatters) P42741NZ05

Claims

1. An embolisation device for promoting clot formation in a lumen sing a al segment and a distal segment, each segment comprising a stem and a ity of flexible 5 bristles extending outwardly from the stem, the bristles having a contracted delivery configuration and a deployed uration in which the bristles extend generally radially outwardly from the stem to anchor the device in a lumen wherein, in the deployed configuration bristles of the proximal segment extend partially in a first longitudinal direction and the bristles of the distal segment extend lly in a second longitudinal 10 direction which is opposite to the first longitudinal direction, wherein the distal t includes more bristles than the al segment.

2. The device as claimed in claim 1 wherein in the contracted delivery configuration the bristles of the proximal segment extend lly in a first longitudinal direction and the 15 bristles of the distal segment extend partially in a second longitudinal direction which is opposite to the first longitudinal direction.

3. The device as claimed in claim 1 or 2, further comprising a flow restrictor. 20

4. The device as d in claim 3, wherein the flow restrictor has a contracted delivery configuration and an expanded deployed configuration.

5. The device as claimed in claim 3 or claim 4, wherein the flow restrictor is located adjacent to a proximal end of the device.

6. The device as claimed in any one of claims 3 to 5 wherein the flow restrictor is located within or adjacent to the most proximal segment, optionally

7. The device as claimed in any one of claims 3 to 6 wherein the flow restrictor is located on 30 the proximal segment.

8. The device as claimed in any one of claims 3 to 7, wherein the flow restrictor is located adjacent to a distal end of the . 18517197_1 (GHMatters) P42741NZ05

9. The device as claimed in claim 8, wherein: the flow restrictor is located within or adjacent to a most distal segment, or the flow restrictor is located on the distal segment.

10. The device as claimed in any one of claims 3 to 9, wherein the flow restrictor comprises a 5 membrane or film.

11. The device as claimed in any one of claims 3 to 10, wherein the bristles in an unconstrained configuration extend to a radial extent which is greater than the radial extent of the membrane in a constrained configuration.

12. The device as claimed in any one of claims 3 to 11, wherein, in the ained configuration, the ne has a longitudinal extent.

13. The device as claimed in any one of claims 3 to 12, wherein, in the ed configuration, 15 the membrane has a conical or cup-like shape.

14. The device as d in any one of claims 3 to 13, wherein the flow restrictor is of a flexible material. 20

15. The device as claimed in any one of claims 3 to 14, wherein the flow ctor is of a polymeric material, an elastomeric material or a shape memory material such as Nitinol.

16. The device as claimed in any one of claims 3 to 15, wherein the flow restrictor is located longitudinally within the bristles of the proximal segment and/or the flow ctor is 25 located longitudinally within the bristles of the distal segment.

17. The device as claimed in any one of claims 3 to 16, wherein the flow restrictor extends from the stem. 30

18. The device as claimed in any one of claims 3 to 17, wherein the flow restrictor has an outer dimension which is less than an outer dimension of the plurality of anchoring bristles, and/or wherein the flow restrictor is connected to the stem. 18517197_1 (GHMatters) P42741NZ05

19. The device as claimed in any one of claims 3 to 18, wherein the flow restrictor is not attached to the plurality of bristles.

20. The device as claimed in any one of claims 3 to 19, wherein the flow restrictor is more 5 flexible than the bristles adjacent to it.

21. The device as claimed in any one of the preceding claims, wherein a diameter of the bristles in the distal segment is greater than a diameter of the es in the proximal segment. 10

22. The device as claimed in any one of the preceding claims, further comprising a connector between adjacent ts, optionally wherein a proximal connection between the proximal segment and the t adjacent to the proximal segment is relatively stiff.

23. The device as claimed in any one of the preceding claims, wherein the stem of the proximal 15 t is mounted to the stem of the distal segment, optionally wherein the stem of the proximal segment is ntially rigidly mounted to the stem of the distal segment.

24. The device as d in any one of the preceding claims, r comprising one or more of the following: 20 - a distal radiopaque marker which is located on a distal side adjacent to a most distal segment; - a proximal radiopaque marker which is located on a proximal side adjacent to a most proximal t; and/or - a radiopaque marker intermediate the proximal segment and the distal segment.

25. The device as claimed in any one of the preceding claims, wherein the stem of the proximal segment and the stem of the distal segment form parts of the same continuous stem.

26. The device as claimed in any one of the preceding claims, further comprising one or more 30 further segments between the distal segment and the proximal t, optionally wherein connections between at least some of the further segments comprise a hinge to facilitate relative movement n the segments, and/or optionally wherein a connection between some of the segments intermediate the proximal segment and the distal segment is relatively rigid. 18517197_1 (GHMatters) P42741NZ05

27. The device as claimed in any one of the preceding , wherein a al end of the device is adapted for releasable connection with a delivery means such as a ry wire or tube.

28. The device as claimed in any one of the preceding claims, further comprising a proximal connector for releasable connection to a delivery element, optionally wherein the proximal connector comprises a connector stem, optionally wherein the connector stem is coupled to a proximal segment stem, optionally wherein the tor stem is hingedly mounted to 10 the proximal segment stem.

29. The device as d in claim 28, wherein the connector stem has a connector mounting feature for engagement with a mounting feature of a delivery element, optionally wherein the tor mounting feature comprises a screw thread. 18517197_1 (GHMatters) P42741NZ05 tnun- Ann-a-::tnu $lnnnnnnuxa