Patent Description:
Migration of conventional embolisation coils occurs <NUM>-<NUM>% of transcatheter embolisations [<NUM>,<NUM>]. Non-target embolisation is an outcome of coils migration, the impact of which depends on the final location of the coils. In the venous system, the consequences can be catastrophic with literature indicating 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 migration occurs for various reasons:.

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 frequently tortuous in the presence of abdominal aortic aneurysms [<NUM>]. To combat this issue today, microcatheters are often employed in difficult or tortuous anatomy where use of standard catheters may induce spasm and lead to a failed embolisation procedure [<NUM>]. Additionally different stages in a procedure may require catheters with different mechanical properties e.g. accessing a visceral vessel, particularly in the presence of diseased or tortuous arteries, may require a catheter with a high degree of stiffness and torque control. In general, 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 approach the physician inserts coils and then waits <NUM> minutes for the coils to expand and cause vessel occlusion [<NUM>]. <CIT> forms prior art under Article <NUM>(<NUM>) EPC and discloses an embolisation device for promoting clot formation in a lumen 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 radially outwardly from the stem to anchor the device in a lumen, the device comprising a plurality of segments, each of which comprises a plurality of bristles and wherein the device comprises flexible sections between at least some of the bristle segments.

<CIT> discloses an occluding member for a patient's reproductive lumen having at least one segment with a first contracted configuration and a second expanded configuration, comprising a first expansive element having a first end secured to a central location in the occluding member and a non-traumatic end radially spaced from the first end when in an expanded configuration; and at least one additional expansive element having a first end secured to the central location in the occluding member and a non-traumatic end radially spaced from the central location in the expanded configuration.

<CIT> discloses a device for fixing a tissue to a bone, comprising; a brush including first and second ends; said brush further including a stem and a plurality of elongated bristles attached to said stem in a spaced apart manner over at least a portion of a length thereof.

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 formation of a new vessel lumen that circumvents the occlusion [<NUM>]. Recanalization rates vary by procedure and embolic agent, ranging from <NUM>% in portal vein embolisation to <NUM>% for pulmonary arteriovenous malformations to <NUM>% for splenic artery embolisation [<NUM>,<NUM>,<NUM>].

The unit "inch" used in the following description is defined as <NUM> inch = <NUM>.

According to the invention, there is provided an embolisation device according to claim <NUM>.

According to one aspect not falling within the scope of the appended claims, there is provided an embolization device, comprising:.

In another aspect not falling within the scope of the appended claims there is provided an embolization device, comprising:.

In a further aspect not falling within the scope of the appended claims there is provided an embolization device, comprising:.

a flow restricting membrane extending from the stem and having an outer dimension less than an outer dimension of the plurality of anchoring bristles of the proximal segment.

In a further aspect not falling within the scope of the appended claims there is provided an embolization system, comprising:.

According to one example not falling within the scope of the appended claims there is also provided 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 generally radially 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 opposite to the first longitudinal direction.

According to the invention the 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 opposite to the first longitudinal direction.

In one case the device includes a flow restrictor having a contracted delivery configuration and an expanded deployed configuration. The flow restrictor may be 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.

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 membrane may have an outer dimension which is less than an outer dimension of the plurality of anchoring 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 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.

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 membrane 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 Nitinol.

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 relatively stiff. The proximal connection may incorporate or comprise a marker band.

In one embodiment the embolization 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 embodiment the stem of the proximal 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 proximal 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 segment. 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 proximal 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 delivery wire. The connector may be hingedly moveable relative to the most proximal segment.

In another aspect not falling within the scope of the appended claims, there is provided 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 generally radially outwardly from the stem to anchor the device in a lumen, wherein the device includes a flow restrictor having a contracted delivery configuration and an expanded unrestrained configuration.

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 unconstrained 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 longitudinal 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 material. 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.

In a further aspect not falling within the scope of the appended claims there is provided 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 generally radially 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 segment and an intermediate marker between the most proximal segment and the segment which is adjacent to the most proximal segment.

An aspect not falling within the scope of the appended claims provides 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 which extend radially outwardly of the stem, the bristles having a contracted delivery configuration and a deployed configuration in which the bristles extend generally radially outwardly of the stem, the bristles comprising distal bristles in a distal bristle 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.

In one case the device comprises at least one intermediate segment between the proximal segment and the distal segment, the intermediate segment comprising intermediate bristles and wherein 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 segment and at least some of the bristles in the intermediate section are tapered proximally or directly.

In some embodiments 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 bristles may be different from the number of proximal bristles.

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

The invention also provides an embolization device according to the invention and a delivery catheter. In one case the delivery catheter is a microcatheter.

According to an aspect not falling within the scope of the appended claims there is provided an embolisation system comprising:-.

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.

According to an aspect not falling within the scope of the appended claims there is also provided an embolization device comprising:-.

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 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 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 delivery configuration and an expanded deployed configuration. In the constrained configuration, the flow restricting membrane may have a longitudinal extent. In the deployed configuration the flow restricting 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 greater than the diameter of the bristles in the proximal segment.

In one case the stem of the proximal 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 segment.

The embolization device further comprises at least one radiopaque marker. There may be a radiopaque marker adjacent to a distal segment and/or a radiopaque marker adjacent to the proximal segment. There is provided 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 connector 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 thread.

The embolization device may comprise at least one further segment between the distal segment and the proximal segment. There may be a plurality of further 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 <NUM> to <NUM> bristles, in one case <NUM> to <NUM>, optionally <NUM> to <NUM>, optionally about <NUM>, in another case <NUM> to <NUM>, optionally <NUM> to <NUM>, optionally about <NUM>, in another case <NUM> to <NUM>, optionally <NUM> to <NUM>, optionally <NUM> to <NUM>.

In one case the distal segment comprises from <NUM> to <NUM> bristles, in one case <NUM> to <NUM>, optionally <NUM> to <NUM>, optionally about <NUM>, in another case <NUM> to <NUM>, optionally <NUM> to <NUM>, optionally about <NUM>, in another case <NUM> to <NUM>, optionally <NUM> to <NUM>.

According to an aspect not falling within the scope of the appended claims there is provided a method for manufacturing an embolization device comprising the steps of:-.

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 comprises engaging the stem in the hole of the membrane.

The invention will be more clearly understood from the following description given by way of example only, with reference to the accompanying drawings, in which:.

Referring to the drawings there is illustrated an embolisation device <NUM> which comprises a plurality of flexible bristles having deployed and contracted configurations. The device comprises a series of segments wherein at least one segment <NUM> points distally and one segment <NUM> points proximally. In some cases there is only a proximal segment <NUM> and distal segment <NUM>.

The bristles of the proximal segment <NUM> point proximally and the bristles of the distal segment <NUM> 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 distally 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 segment in this case the proximal segment <NUM>, incorporates a flow restrictor which in this case is a thin film flexible membrane <NUM>.

In some cases a series of radiopaque markers divides the proximally pointing segment <NUM> and the distally pointing segment <NUM>. There may be a proximal marker <NUM> and/or a distal marker <NUM>. According to the invention of the appended claims there is provided an intermediate marker <NUM>.

In one case the embolization device comprises only a single proximal segment <NUM> and a single distal segment <NUM>. The proximal segment <NUM> and the distal segment <NUM> in one case are mounted on a single common stem. The stem of the proximal segment <NUM> and the stem of the distal segment <NUM> 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 flexible membrane <NUM> is present in at least one of the segments. The membrane <NUM> may comprise a disc of thin film material. The flexibility of the membrane <NUM> means its orientation is controlled by the orientation of the adjacent bristles - i.e. if the adjacent bristles are forced to point distally the membrane <NUM> will adjust its configuration accordingly. Thus, if the membrane <NUM> is deployed from a collapsed condition, such as from within a catheter, the bristles will cause it to open up to an expanded configuration. The membrane <NUM> may also be placed proximal or distal to the segment.

The implant device comprises at least two segments. In one configuration the membrane <NUM> is in the most proximal segment. This is shown, in an unconstrained state schematically in <FIG>, <FIG> and <FIG>. In the configuration shown the membrane <NUM> is located within the proximal segment <NUM> with bristles both proximal and distal to the membrane <NUM>. In some cases there may be a distal membrane <NUM>'.

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 membrane may have an outer dimension which is less than an outer dimension of the plurality of anchoring bristles. The flow restricting membrane 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.

The implant has a collapsed configuration to facilitate delivery through a catheter. By placing the membrane <NUM> within the segment <NUM>, 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 catheter and the membrane <NUM> is reduced.

In a contracted delivery configuration according to the invention of the appended claims, the implant is collapsed such that, the bristles of the most proximal segment <NUM> point proximally, while the bristles of the distal segment <NUM> or segments point distally. Since the membrane orientation is controlled by the orientation of the bristles, if the membrane <NUM> is within the proximal segment, it will also point proximally. This is shown schematically in <FIG>.

<FIG> shows a collapsed configuration of two segments <NUM>,<NUM> in a catheter <NUM>, one pointing distally and the other proximally. It will be noted that the outer periphery of the membrane <NUM>, shown in the proximal segment <NUM>, is pointing proximally.

When deployed from this configuration, into a vessel a similar but partially expanded configuration to the collapsed configuration is achieved. This means that the bristles of the proximal segment <NUM> point proximally, and the bristles of the distal segment <NUM> point distally. This is shown schematically in <FIG>. 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 contrary, if all bristles 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 <NUM>, when measured in the unconstrained configuration, has a diameter 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 vessel. 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> when the device is deployed into a vessel, with a smaller diameter than the implant, the membrane <NUM> assumes a conical or cup-like shape - the open end of the cone proximal to the closed end. In one configuration the deployed implant comprises a membrane <NUM> with a conical shape, the open end of the cone proximal to the distal end. In arteries blood from the heart towards the distal arterial tree, that is from proximal 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>). In this way occlusion will be facilitated. Thus the greater the force (pressure) of the flow into the cone, the greater the improvement of the seal against the vessel wall.

<FIG> shows a schematic of the flow direction (closed arrows) entering a membrane <NUM> in the deployed configuration and its effect on the seal against the vessel wall.

In another configuration the implant may be collapsed such that all segments point distally. <FIG> show the configuration of two distally pointing segments <NUM>,<NUM> (proximal and distal segments) in the collapsed state. When deployed, both the proximal and distal segments will point distally. Similarly, all segments may be collapsed such that all point proximally. This may be advantageous when attempting to occlude a lumen in which flow is from distal to proximal, such as a healthy vein. <FIG> 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 diameter 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 <NUM> to <NUM>% while veins can distend <NUM>-<NUM>%.

To ensure an adequate seal between the membrane <NUM> and the vessel wall it is preferable that the segment centreline is co-linear with that of the vessel. Use of at least two segments in the device pointing in opposite directions helps to remedy this problem, i.e. the bristles of the proximal segment pointing proximally, and the bristles of the distal segment pointing distally. This facilitates a uniform seal of the cone against the vessel wall about its circumference. As can be seen in <FIG>, if the segment is not co-linear 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> illustrates an unstable device, with poor co-linearity with the vessel centre line which may allow flow to pass through.

The device may include features 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. This improves the stability of the device within the vessel facilitating co-linearity of the segment and the vessel centreline. Thus the implant is significantly oversized compared to the target vessel. Preferable dimensions are outlined in Table <NUM> and Table <NUM> for devices deliverable through <NUM> to <NUM> inch, and <NUM>-<NUM> inch inner diameter catheters respectively. The dimensions are shown schematically in <FIG> 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 segment diameter and the vessel diameter) is preferably at least <NUM>%, more preferably <NUM>% of the vessel diameter and more preferably at least <NUM>% of the vessel diameter in which the device is implanted. For example for a target vessel which is <NUM> in diameter, the device diameter may be at least <NUM>, preferably at least <NUM>, more preferably at least <NUM>.

To ensure co-linearity in veins, the degree of oversizing may be increased compared to that used in arteries. This is because veins are known to distend significantly (for example during Valsalva). In one configuration the minimum over-sizing is <NUM>%.

In one configuration 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 <NUM> and there is a gap <NUM> between the segments <NUM>, <NUM> as illustrated in <FIG> which does not fall under the scope of the appended claims. In another embodiment, two segments <NUM>, <NUM> on two different stems may be connected. In one configuration this connection comprises a crimped or welded hypotube. <FIG> shows a device with two bristles segments <NUM>, <NUM> pointing in opposing directions on the same stem <NUM>.

In yet another embodiment, the same segment may be configured in the collapsed and deployed configuration so as to have some bristles (and the membrane) pointing proximally and some bristles pointing distally (<FIG> shows a device not falling within the scope of the appended claims with two bristle segments <NUM>, <NUM> in opposing directions, sharing the same stem and without a gap in between.

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.

The device incorporates at least one proximally pointing proximal segment, and at least one distally pointing distal segment. If the physician deploys the device completely and then wishes to retrieve 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 membrane 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 is 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 proximally pointing segment or segments. If the physician is unhappy with the position of the distally pointing segments, they may resheath and redeploy them without altering the direction of the proximally pointing segments.

All embodiments according to the invention comprise an intermediate radiopaque marker band between two segments. In one configuration a radiopaque marker, distal marker <NUM>, is present at the most distal point of the most distal segment. According to the invention of the appended claims a second marker, medial marker <NUM>, is present between the distally pointing segment(s) and proximally pointing segment(s). A third marker, proximal marker <NUM>, is present at the most proximal point of the proximally facing segment. In this configuration the section between the distal and medial marker <NUM>,<NUM> defines the distally facing segments which may be deployed, retrieved/repositioned without any effect on their pointing direction, and the section between the medial and third proximal <NUM>,<NUM> 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 marking system is shown schematically in <FIG> which show the marking system and their locations 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 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 thermoplastic polyurethane, such as a poly-ether urethane, for example an aromatic polyether 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 collapsed by some means. The membrane can then be threaded over the collapsed bristles into the desired position.

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

The ability of this material to stretch facilitates placement of the membrane within the segment 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 through 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 membrane.

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. Furthermore a stiff membrane may have channels longitudinally. Another problem with a stiff membrane is that cannot fold and conform 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 the membrane are outlined in Table <NUM> and Table <NUM>. The membrane may also be of PTFE, PET, or Nylon. PTFE is particularly suitable as it will enhance lubricity 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 preferable that the implant be detachable from the delivery wire at the discretion of the physician.

In one configuration, 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 detachment 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> 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 twisted 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> shows a thread mechanism utilising the twisted wire stem <NUM> as a natural male thread. In this schematic a formed hypotube <NUM> 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 configuration the female screw thread comprises a coil with a pitch to match that of the male thread providing a reliable screw detachment mechanism.

In one embodiment the male screw thread <NUM> is a section of the twisted wire stem of the most proximal segment. In a further embodiment, the female thread or hypotube <NUM> is attached at its proximal end to a delivery wire <NUM>. This facilitates delivery and detachment of the bustle segment through a catheter. This is illustrated schematically in <FIG> which shows a thread mechanism in which a hypotube <NUM> is attached to a delivery wire <NUM> and detachable from the twisted wire stem <NUM> by a thread mechanism. A thread mechanism which does not utilise the twisted wire stem may also be utilised.

Referring in particular to <FIG> and <FIG> in one case a flexible section <NUM> is provided between the screw detachment mechanism <NUM> and the most proximal segment <NUM> of the implant. In one embodiment this flexible section <NUM> is a hinge. This flexible section <NUM> enables delivery and detachment of the implant in tortuous anatomies. This flexible section <NUM> also serves to ensure that the proximal end of the implant is atraumatic.

In one embodiment the membrane and bristles do not overlap the detachment mechanism. In this case the detachment mechanism is located a minimum 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 <FIG>. In <FIG>there are two segments - one proximal containing the membrane <NUM> and one distal. Marker bands <NUM>,<NUM>,<NUM> are positioned as described above.

Referring to <FIG> in this case there are additional distal segments <NUM> and hinge connections <NUM> are provided between the distal segments to accommodate movement between the segments.

Referring to <FIG>, in this case the most distal segment also includes a membrane <NUM>' which has an opening which faces distally in the deployed configuration. A relatively stiff connection <NUM> is provided between the most distal segment and the adjacent segment.

<FIG> illustrate a device similar to <FIG> and again for increased stability when deployed, there is a relatively stiff connection <NUM> between the most distal segment and the adjacent segment. The connection in this case may be reinforced by or provided by a section of hypotube.

<FIG> show the complete device configuration. In the packaged configuration, when ready for use, the implant is stored within a loading tube <NUM>. This loading tube <NUM> comprises a tube with a haemostasis valve <NUM> and side arm <NUM> for flushing. The delivery wire <NUM> is attached to the proximal end of the implant and passes through the haemostasis valve. The implant can be pushed from the loading tube <NUM> into a catheter for delivery 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 previously described 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>. In one embodiment the loading tube is made from a lubricious material such as PTFE with an outer diameter of approximately <NUM> and an inner diameter of approximately <NUM>. This loading tube is compatible with both <NUM>-<NUM>" 5F delivery catheters and <NUM>"-<NUM>" 4Fr delivery catheters.

In another embodiment the loading tube has a taper at its distal end to enable it to be compatible with multiple catheters of differing hub geometries used for delivery of the device to the target vessel. A taper <NUM> on the loading tube <NUM> functions by funnelling the bristles <NUM> 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 <NUM> and the inner diameter is <NUM>. The distal taper comprises an inner diameter from <NUM> - <NUM> tapered over a length of <NUM> - <NUM>.

Various configurations of segments, membranes and connections are illustrated in <FIG>.

In some instances, it may be preferable due to space restrictions within the delivery catheter, to incorporate a different number of bristles within the proximal and distal bristle segment. This enables he number of bristles which encourage thrombus formation and prevent device migration to be maximised, while preventing excessive friction within the catheter during delivery and deployment. 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 diameter to ensure that when twisted the bristles are securely held via plastic deformation of the stem wire. The following tables contain preferable combinations of materials and dimensions for the implant.

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 <NUM> to <NUM>, or even <NUM> may be required to treat the entire vessel length. For such a vessel, a lower bristle diameter may be appropriate even in a large vessel (e.g. <NUM> diameter) since the increased number of bristles, due to the increased length and number of segments, means a sufficient 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 preferable combinations.

In some instances, it is not possible to access a target vessel using a standard catheter or sheath (which usually has an inner diameter of <NUM>-<NUM> inches). 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 <NUM> French. The internal diameter of these catheters ranges from <NUM> to <NUM> inches. Standard internal diameters are <NUM>, <NUM> and <NUM> inches. For compatibility with such catheters devices of the invention with the following attributes are preferred.

A range of geometries, incorporating gaps between segments may be used. In one embodiment a bristle segment of uniform diameter may be used (<FIG>, not falling within the scope of the appended claims).

A lower profile collapsed configuration can be achieved for delivery through a microcatheter by using a taper in which the proximal diameter of the bristle segment is lower than the distal diameter of the bristle segment. This is shown schematically in <FIG>. This is achievable since the distal bristles do not need to collapse 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 introduced 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>, 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 embodiment the lower diameter portion of the segment may be <NUM>-<NUM>, while the larger diameter portion of the bristle segment may be <NUM>-<NUM>. In another embodiment the diameter of the bristle segment may be approximately the same as the target vessel.

In another configuration, a double tapered segment may be used (<FIG>), or a number of individual tapered segments may be used (<FIG>).

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 <FIG> (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> a large number of fibres of a low diameter may be incorporated in one area of a segment to induce rapid thrombus formation and vessel occlusion. Similarly a lower number of fibres of a higher diameter may be incorporated. In one embodiment a group of fibres of diameter <NUM> inches, and a group of fibres of <NUM> inches is used. In another instance a group of fibres of <NUM> and <NUM> inches 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 collapsed condition. A longer segment with more bristles means a larger profile 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>.

Following deployment the bristle segment may be resheathed. This will force all fibres which original 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 insufficient 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 denudation 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 collapsed profile is too large to be 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 stretch 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. <NUM> (a) shows such a configuration with an extendable connection in the unloaded state. Fig. <NUM> (b) displays the same configuration in the loaded state with the extendable connection elongated. Fig. <NUM> (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 non-circular cross section. This is shown schematically in <FIG>. (a) shows a conventional bristle segment which has not been trimmed. <FIG> shows a segment which has been trimmed 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 thrombus formation. Other non-circular geometries such as a square <FIG>, triangular or others may be used.

In some implants, a membrane or flow blocking member may be incorporated. A number of configurations are shown schematically in <FIG> 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 configuration, 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 profile 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 mechanism is comprised of a radiopaque material. This is to facilitate visibility of detachment during use. In yet another 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.

In one embodiment a male portion of a screw detachment mechanism is attached to the implant, and the female to the delivery wire. In another embodiment the female portion of the screw detachment mechanism is attached to the implant and the male portion to the delivery wire.

A gap between segments as shown in <FIG> 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 segment which may include a membrane are altered from a proximally pointing configuration to a distally pointing direction. In a situation wherein retrieval of the implant is not a desirable attribute the gap between the segments may be as low as <NUM>. In another embodiment there may be no gap between the distally and proximal segments.

A further embodiment of the device, deliverable through a microcatheter, is described in Table <NUM>. The design is similar to that shown in <FIG>. 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 through a microcatheter.

As discussed previously, the oversizing of the device diameter compared to the vessel (calculated as the percentage difference in diameter between segment diameter and the vessel diameter) is preferably at least <NUM>%, more preferably <NUM>% of the vessel diameter and more preferably at least <NUM>% of the vessel diameter in which the device is implanted. Even more preferably, <NUM>% oversizing should be employed.

Embolization procedures may be undertaken by a range of physicians, primarily interventional radiologists, endovascular surgeons, and interventional cardiologists. There are a number of indications for embolization. Frequently performed procedures, and the associated physician are summarised in the table below.

In embolization in general the flow direction is from proximal to the distal (prograde, or away from the heart). This is the natural flow direction in arteries. In healthy veins, the flow direction will generally be the opposite (retrograde, towards the heart). However in general, embolization is performed in patients with reflux meaning flow will also be prograde.

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

Normally blood flows from proximal to distal in the parent vessel, 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 locally, 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.

In one embodiment the device may be configured such that there is both a proximal and distal membrane on the device, enabling rapid occlusion of the parent vessel both proximal and distal to the aneurysm. Accordingly 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 membrane on the proximal bristle segment is open proximally, and the membrane on the distal segment is open distally.

One arrangement with two bristle segments <NUM>, <NUM> each containing a membrane <NUM>, <NUM> is illustrated in <FIG>. Another arrangement with several additional segments <NUM> to bridge a larger aneurysm is illustrated in <FIG>.

In some instances the properties of the segments may be such that no flexible connections in required. For short devices flexible connections may not be required. However for longer devices some flexibility may be required. It is preferable that at least one flexible connection per <NUM> of the implant length be present.

In one configuration, a device has many distal bristle segments 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 implant and hence its pushability. This will reduce the force required to push the implant through the delivery 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>. This device has proximal and distal segment <NUM>, <NUM> and a plurality of intermediate segments <NUM>. Some of the connections between the segments are hinged <NUM> and others are relatively stiff <NUM>.

It is preferable that the membrane is within the bristle segment. A bristle manipulating tool may be used and some of the bristles may be manipulated so that the bristles are aligned with the stem. A flow restrictor membrane is mounted between the bristles 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 confirmation the membrane <NUM> is placed such that <NUM>% of bristles are proximal to the membrane while <NUM>% are distal to the membrane. To prevent overlap of the membrane onto structures proximal to the segment (such as a detach mechanism, or delivery wire), the membrane may be placed more distally within the segment. In one configuration <NUM>% of fibres are proximal to the membrane while <NUM>% are distal to the membrane. In another configuration <NUM>% of fibres are proximal to the membrane while <NUM>% are distal to the membrane. In another configuration <NUM>% of fibres are proximal to the membrane while <NUM>% are distal to the membrane.

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 security of the membrane may be further improved via an interference fit between a hole in the membrane and of the segment stem. To achieve this, the hole in the membrane should be smaller than the stem of the segment. Once placed onto the stem the mismatch of the diameter of the stem and the hole in the membrane will cause friction between the two surfaces and an interference fit.

To achieve 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 <NUM>. 001in less than the diameter of the stem. More preferably the hole diameter in the membrane should be at least <NUM>. 002in less than the diameter of the stem.

It will be appreciated 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 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 through this gap inhibiting the device performance in terms of occlusion. The hole of the membrane should be no more than <NUM>% less than the diameter of the stem.

Ideally the hole diameter is specified 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 embolization. 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 example, 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 invention, as long as their results still fall within the scope of the appended claims. For example, while the embodiments described herein refer to particular features, the invention includes embodiments having different combinations of features and that do not include all of the specific features described.

Claim 1:
An embolisation device (<NUM>) for promoting clot formation in a lumen, the embolisation device 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 when placed in a delivery catheter, and a deployed configuration in which the bristles extend generally radially outwardly from the stem to anchor the device in a lumen, comprising a proximal bristle segment (<NUM>) and at least one distal bristle segment (<NUM>), wherein in the deployed configuration, bristles of the proximal segment extend partially in a proximal longitudinal direction and bristles of the at least one distal segment extend partially in a distal longitudinal direction; the device further comprising an intermediate radiopaque marker band (<NUM>) between two segments.