METHOD AMD DEVICES USEFUL FOR THE TREATMENT OF ANEURYSMS

RELATED PATENT APPLICATION The present application gains priority from U.S. Provisional Patent Application

No. 60/963,671 filed 7 August 2007 which is included by reference as if fully set forth herein.

Some aspects of the present application are related to the teachings of PCT

Patent Application No. PCT/IL2007/000140 filed 4 February 2007 and published as WO 2007/088549, U.S. Provisional Patent Application No. 60/929,724 filed 11 July ] 1

2007 and PCT Patent Application No. PCT/IB200S/052799 filed 11 July 2008, all which are included by reference as if fully set forth herein.

FIELD AND BACKGROUND QF THE INVENTION The invention relates to the field of vascular medicine, and especially to methods and device for the treatments of aneurysms, especially cerebral aneurysms.

An aneurysm is a localized ballooning of a blood vessel Aneurysms can occur in any blood vessel although they are most common in arteries, particularly in the arteries at the base of the brain (the Circle of Willis) and in the aorta. Once formed, an aneurysm generally continues to grow until the wall of the aneurysm ruptures. Rupture of an aneurysm causes severe pain, internal hemorrhage, and, without prompt treatment, may result in death. Additionally, aneurysms may release potentially dangerous embolic material into the blood stream.

A stent is a substantially tubular radially-expandable device configured for deployment inside the lumen of a bodily vessel or other structure. For deployment, a stent is mounted on a deployment catheter, inserted through an incision in the skin and percutaneously guided in an unexpanded state with a small radial dimension through the body to the deployment location. At the deployment location, the stent is expanded to an appropriately-sized expanded state with a larger radial dimension, to engage the inner walls of the vessel, acting as a supporting structure to prevent collapse and maintain patency of the vessel lumen.

A first type of stent is the self-expanding stent. When a self-expanding stent is at the deployment location, the stent is released from the deployment catheter and allowed to expand to an expanded state, in a manner analogous to that of a compressed spring.

A second type of stent is expanded from the unexpanded state to an expanded state using an expansion device, typically a catheter-borne balloon. When the stent is at the deployment location, the expansion device is activated inside the bore of the unexpanded stent to exert an outwards radial force to the luminal walls of the stent, causing the stent to expand to an expanded state of a desired radial dimension.

Stents are generally of open-walled construction (e.g., slotted or otherwise cut- out tubes, bent wires), allowing materials such as fluids to pass through the openings between the structural elements that define the stent frame.

Covered stents are stent assemblies comprising a stent with a stent cover (also called a jacket or graft), a sheet of material (synthetic materials or biological tissues) associated with a tubular surface of the stent, whether the inner (luminal) surface, the outer surface or both. When the stent frame is in a non-expanded state (e.g., when associated with a deployment catheter) the cover is usually folded, bunched-up, unstretched or otherwise loosely associated with the frame. When the stent frame is in an expanded state (e.g., when deployed), the cover is held relatively taut and follows the contour of a surface of the frame, e.g., the luminal surface of the frame for internal covers and the outer surface for external covers.

Although stent covers are often tubular and cover substantially the entire surface area of a stent, partial stent covers that leave a portion of the surface area uncovered are known. For example, in WO 2007/088549 and in PCT/ϊB2008/052799, both of the Inventor, are disclosed stent assemblies that are partially-covered stents. One method of treatment of aneurysms is to deploy a covered stent across the ostium of the aneurysm, as taught, inter alia, in WO 2007/088549 and in PCT/IB2008/052799. The stent cover seals the ostium of the aneurysm, preventing entry of blood and consequent further growth of the thus-sealed aneurysm, as well as preventing the release of embolic material from the aneurysm. The use of a covered stent is exceptionally useful for the treatment of aneurysms situated on large blood vessels such as aortic aneurysms. Covered stents are less useful for treating cerebral aneurysms due to the fact that there is a fear that the stent cover will obstruct branching vessels and since covered stents generally have a relatively large

delivery profile and are relatively less flexible due to the presence of the stent cover, all factors that limit the possibility of maneuvering a stent through the small lumen and exceptional tortuousness of the cerebral vascular system to the ostium of a cerebral aneurysm. Endovascular coiling of aneurysms (esepcially cerebral aneurysms) is a minimally invasive surgical procedure which typically involves deploying a catheter from outside the body (e.g., entering through the femoral artery) to the ostium of the aneurysm, see for example US No. 6,344,041 or US 6,984,240. Flexible coils, for example of platinum, are threaded through the catheter and deployed inside the aneurysm to block blood flow into the aneurysm, thereby preventing rupture of the aneurysm. Once in place, blood clots around the coil, reducing pressure in the aneurysm and reducing the risk of rupture even further.

As the coils must be trapped inside an aneurysm during endovascular coiling, endovascular coiling is generally limited to small-necked berry aneurysms having a hollow neck. Endovascular coiling may also be effective for some saccular aneurysms, but is not usually considered for the treatments of fusiform, wide-necked and giant aneurysms. Locations characterized by high-flow conditions are also considered less suitable for treatment with endovascular coiling.

There are also additional disadvantages of endovascular coiling. Endovascular coiling is a complex and time consuming procedure, especially for large aneurysms that may require the use of several individual coils. Embolic material can escape from the aneurysm. There is a risk of perforation of the aneurysm wall by the coils during coil deployment that may lead to catastrophic rupture of the aneurysm wail. There is a risk of coil migration out of the aneurysm and a long-range risk of coil compaction leading to recanalization of the aneurysm.

An alternative treatment related to endovascular coiling, particularly for large and giant cerebral aneurysms, involves filling the aneurysm with a liquid embolic material (e.g., cellulose acetate polymer) through a catheter, see for example WO 1999/020326 (which is included by reference as if fully set forth herein), US 5,667,767, US 5,580,568, and European patent EP 1207791. The liquid embolic material solidifies to occlude the aneurysm. A disadvantage of this method is that the embolic material may leak into the arterial lumen. Further, liquid embolic material is not generally applicable for treating fusiform aneurysms.

In the treatment of wide-neck aneurysms, endovascular coiling may require the use of a stent to retain the coils inside the aneurysm. For example, the use of intracranial stent-assisted coil placement in the treatment of unruptured, wide-necked cerebral aneurysms has been disclosed. Jabbour et al. Neurosurg. Focus 17(5): 1-4, 2004; and Sani et al., Neurosurg. Focus 18(2): 1-5, 2005, using the Neuroform microstent™, which is an uncovered self-expanding nitinol stent. In a first stage, the stent is deployed across the ostium of the aneurysm using a first microcatheter up to 1 mm (3 Fr) outer diameter. A second microcathether is navigated between the struts of the stent into the aneurysm, and used as a conduit to introduce endovascular coils into the aneurysm. The stent acts to partially block the aneurysm neck, reducing the chance of migration of the coils migrating out of the aneurysm through the ostium.

The prior use of stents together with endovascular coils does not effectively prevent the escape of small embolic fragments and only improves the retention of the coils. Such a procedure is also inefficient To effectively trap the coils in the aneurysm, the stent must be "dense walled", that is to say having walls made of relatively much materia! and having relatively few gaps. However, "dense walled" stents are less flexible, have a higher delivery profile, it is difficult to thread a second microcatheter therethrough and cause greater obstruction of branching vessels, so are therefore less suitable for use for treating cerebral aneurysms. However, stents with "spare" walls and more gaps provide an ineffective barrier to the escape of the coils or other embolic material from the aneurysm.

It would be desirable to treat aneurysms, especially cerebral aneurysms, by filling these as is known in the art, for example with endovascualr coils or fluid embolic material in a relatively simple procedure that is more efficient than the methods known in the art.

SUMMARY QF THE INVENTION

Some embodiments of the invention successfully address at least some of the shortcomings of the prior art by providing methods, device and kits useful for the treatement of aneurysms, especially cerebral aneurysms. Some embodiments allow for the treatment of berry, saccular, wide-necked, giant and even fusiform aneurysms by filling the aneurysm with aneurysm-filler. Some embodiments of the invention allow for the filling of an aneurysm with an aneurysm-filler as known in the art but prevent or

reduce the chance of delayed regrowth and/or recanalization and/or dislodgement and/or entry of the aneurysm-filler into the blood stream during or subsequent to the introduction of the aneurysm-filler into the aneurysm. Some embodiments reduce the chance of puncture of the aneurysm. Some embodiments of the invention allow for the removal of some of the contents of an aneurysm, reducing the size of the aneurysm.

Specifically, according to some aspects of the invention, a sheet of material supported by a substantially tubular expandable frame (such as a cover of a partially of fully covered stent) is deployed so that the sheet of material at least partially block/seals the ostium of the aneurysm, and subsequently aneurysm-filler is introduced into the aneurysm or contents of the aneurysm are removed.

According to an aspect of some embodiments of the invention there is provided a method of treating an aneurysm in fluid communication with a blood vessel through the ostium of the aneurysm, comprising: a) deploying an implantable assembly, comprising a sheet of material secured to a radially expandable substantially tubular frame wherein the sheet covers at least a portion of the surface area of the frame, in the blood vessel so that the sheet of material at least partially blocks fluid communication between the blood vessel and the aneurysm through the ostium of the aneurysm; and b) subsequent to a, introducing at least one aneurysm-filler into the aneurysm through an aneurysm-filler introducer tube (e.g., a microcatheter), the aneurysm- filler introducer tube having a proximal end and a distal end, where the distal end of the aneurysm-filler introducer tube accesses the aneurysm through the ostium of the aneurysm.

According to some embodiments, during the deploying of the implantable assembly, the implantable assembly is radially oriented with the help of an elongated radia! orientation guide having a proximal end and a distal end, where the distal end of the elongated radial orientation guide passes into the ostium of the aneurysm. According to some embodiments, the elongated radial orientation guide comprises a guide wire.

According to some embodiments, the elongated radial orientation guide comprises the aneurysm- filler introducer tube.

According to some embodiments, during the introduction of the aneurysm-filler, the aneurysm-filler introducer tube passes on the outside surface of the implantable assembly and to the ostium of the aneurysm.

According to some embodiments, the sheet of material comprises a hole passing through the sheet of material; during the deploying, the implantable assembly is oriented so that the hole passing through the sheet of material is in fluid communication with the aneurysm through the ostium of the aneurysm; and the introducing of at least one aneurysm-filler into the aneurysm is through the aneurysm-filler introducer tube (e.g., a microcatheter) and through the hole in the sheet of material.

According to some embodiments, the distal end of the aneurysm-filler introducer tube is passed through the hole in the sheet of material prior to the introducing of the aneurysm-filler. According to some embodiments, the method further comprises removing at least some of the contents of the aneurysm through the ostium of the aneurysm. According to some embodiments, the removing of contents of the aneurysm is by suction applied through the aneurysm-filler introducer tube. According to some embodiments, the contents are removed through a hole in the sheet of material. According to some embodiments, the deploying of the implantable assembly comprises radially expanding the frame of the implantable assembly so that the sheet of material is brought towards the walls of the blood vessel and the ostium of the aneurysm. According to some embodiments, the radial expansion of the frame is such that an outer surface of the portion of the surface area of the frame covered by the sheet of material presses against walls of the blood vessel surrounding the ostium of the aneurysm, thereby substantially blocking fluid communication between the blood vessel and the aneurysm through the ostium of the aneurysm.

According to some embodiments, the frame of the implantable assembly is self- expanding and the deploying comprises releasing the frame from constraints (e.g., of the delivery device, for example a delivery catheter) to allow the frame to expand radially outwards towards the walls of the blood vessel.

According to some embodiments, the deploying comprises activation of an expansion component of a delivery device (e.g., the balloon of a balloon catheter) to apply an outwards radial force to the frame, radially expanding the frame towards the walls of the blood vessel.

According to an aspect of some embodiments of the invention there is provided a method of treating an aneurysm in fluid communication with a blood vessel through an ostium of an aneurysm, comprising:

a) deploying an implantable assembly, comprising a sheet of material supported by a radially expandable substantially tubular frame wherein the sheet covers at least a portion of the surface area of the frame, in the blood vessel so that the sheet of material substantially blocks fluid communication between the blood vessel and the aneurysm through the ostium of the aneurysm; and b) subsequent to a, removing at least some of the contents of the aneurysm through the ostium of the aneurysm by suction applied through an aneurysm- contents removal tube (e.g., a microcatheter) with a proximal end and a distal end, where the distal end of the aneurysm-contents removal tube accesses the aneurysm through the ostium of the aneurysm.

According to some embodiments, during the deploying of the implantable assembly, the implantable assembly is radially oriented with the help of an elongated radial orientation guide having a proximal end and a distal end, where the distal end of the elongated radial orientation guide passes into the ostium of the aneurysm. According to some embodiments, the elongated radial orientation guide is a guide wire. According to some embodiments, the elongated radial orientation guide is the aneurysm-contents removal tube.

According to some embodiments, during the removing of contents of the aneurysm, the aneurysm-contents removal tube passes on the outside surface of the implantable assembly and to the ostium of the aneurysm.

According to some embodiments, the sheet of material comprises a hole passing through the sheet of material; during the deploying the implantable assembly is oriented so that the hole is in fluid communication with the aneurysm through the ostium of the aneurysm; and the removing of at least some of the contents of the aneurysm is through the aneurysm-contents removal tube (e.g., a microcatheter) and through the hole in the sheet of material.

According to some embodiments, the distal end of the aneurysm-contents removal tube is passed through the hole in the sheet of material prior to the removal of contents of the aneurysm therethrough. According to some embodiments, the deploying comprises radially expanding the frame of the implantable assembly so that an outer surface of the portion of the surface area of the frame covered by the sheet of material presses against walls of the blood vessel surrounding the ostium of the aneurysm, thereby substantially blocking

fluid communication between the blood vessel and the aneurysm through the ostium of the aneurysm.

According to some embodiments, the frame of the implantable assembly is self- expanding and the deploying comprises releasing the frame from constraints (e.g., of the delivery device, for example a delivery catheter) to allow the frame to expand radially outwards towards the walls of the blood vessel.

According to some embodiments, the deploying comprises activation of an expansion component of a delivery device (e.g., the balloon of a balloon catheter) to apply an outwards radial force to the frame, radially expanding the frame towards the walls of the blood vessel.

According to some some embodiments of any of the methods of the invention, the blood vessel is bifurcated. Preferably, during deployment a portion of the frame that is free of the sheet of material is positioned at a bifurcation of the blood vessel so as not to obstruct the flow (e.g., of blood) between the trunk and branch vessels of the bifurcated vessel. In some embodiments, the aneurysm is a cerebral aneurysm, In some embodiments, the aneurysm is a saccular, fusiform or berry aneurysm.

According to an aspect of some embodiments of the invention there is provided a kit for treating an aneurysm, comprising: a) an implantable assembly comprising a sheet of material supported by a radially expandable substantially tubular frame wherein the sheet covers at least a portion of the surface area of the frame; b) a delivery system for deploying the implantable assembly within a blood vessel, the delivery system including a tube having at least one lumen (e.g., a microcatheter) with a proximal end and a distal end, wherein the tube is suitable for use as an aneurysm-filler introducer tube to serve as a conduit to introduce aneurysm-filler into an aneurysm through the distal end; and/or the tube is suitable for use as an aneurysm-contents removal tube to serve as a conduit for removing contents of an aneurysm through the distal end.

According to some embodiments, the delivery system further comprises a delivery catheter with a proximal end and a distal end, the delivery catheter including:a region near the distal end of the delivery catheter where the implantable assembly is positionable for deployment of the implantable deployment in a blood vessel; a lumen for accepting a guide wire passing from the proximal end of the delivery catheter to a

port near a distal tip of the delivery catheter; and a lumen for accepting the tube passing from the proximal end of the delivery catheter to a port in the side of the delivery catheter proximal to the region where the implantable assembly is positionable.

According to some embodiments, the kit is provided where the tube at least partially passes in the lumen for accepting the tube of the delivery catheter.

According to some embodiments, one lumen of the delivery catheter is both the lumen for engaging the guide wire and the lumen for engaging the tube.

According to some embodiments, the lumen of the delivery catheter for engaging the guide wire is distinct from the lumen of the delivery catheter for engaging the tube.

According to some embodiments, the sheet of material comprises a hole passing through the sheet of material and the tube is configured to introduce aneurysm-fiϊler and/or to remove contents of an aneurysm through the hole in the sheet of material.

According to some embodiments, the kit is provided where the implantable assembly is mounted on the region near the distal end of the delivery catheter so that the hole in the sheet of material of the implantable assembly and the port in the side of the delivery catheter are aligned.

According to some embodiments, the distal end of the tube is configured to pass through the hole in the sheet of material. According to some embodiments, the frame of the implantable assembly is self- expanding and the delivery device is configured to constrain the frame to remain in unexpanded state until deployed.

According to some embodiments, the delivery system comprises an expansion component (e.g., a balloon of a balloon catheter) configured to apply an outwards radial force to the frame to radially expanding the frame.

According to some embodiments, the tube comprises at least two distinct lumina, a first of the at least two lurnina configured for the introduction of an aneurysm- fϊϊler therethrough. According to some embodiments, the second of the at least two lumina is configured for removal of contents of an aneurysm therethrough. In some embodiments, the kit further comprises a suction-generator, configured to engage the proximal end of the tube and provide suction from the distal end of the tube through a lumen of the tube.

In some embodiments, the kit further comprises an aneurysm-filler dispenser, configured to engage the proximal end of the tube and force aneurysm-filler into the proximal end, through a lumen of the tube and out of the distal end of the tube.

In some embodiments, the kit further comprises at least one aneurysm-fiiler. In some embodiments, the aneurysm-fillcr is provided in a reservoir. In some embodiments, the reservoir is configured to function as an aneurysm dispenser, as described above.

Unless otherwise defined, all technical and scientific teπns used herein have Hie same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. In case of conflict, the patent specification, including definitions, will control.

As used herein, the terms "comprising", "including", "having" and grammatical variants thereof are to be taken as specifying the stated features, integers, steps or components but do not preclude the addition of one or more additional features, integers, steps, components or groups thereof. These terms encompass the terms

"consisting of and "consisting essentially of.

The phrase "consisting essentially of or grammatical variants thereof when used herein are to be taken as specifying the stated features, integers, steps or components but do not preclude the addition of one or more additional features, integers, steps, components or groups thereof but only if the additional features, integers, steps, components or groups thereof do not materially alter the basic and novel characteristics of the claimed composition, device or method.

Herein the term "proximal" generally refers to the side or end of an elongated medical device such as a catheter that is intended to be closer to the performing medical personnel, further from the location of the intervention and is generally located outside the body of the patient. The term "distal" generally refers to the side or end of an elongated medical device such as a catheter that is intended to be closer to or at the location of the intervention, for example the aneurysm. Herein the terms "jacket", "graft", and "cover" may, in some instances, be used interchangeably and generally (as is made clear by the context) refer to the sheet of a material that is a component of the implantable assembly used in implementing embodiments of the invention.

Herein the terms "radial orientation guide", "orientation guide" and "aneurysm guide" may, in some instances, be used interchangeably.

The teachings of the invention are applicable to the treatment of a wide variety of aneurysms. For clarity, the term "ostium of the aneurysm" has been used to refer to the entrance from a blood vessel into the aneurysm. For berry aneurysms, ball-shaped aneurysms in fluid communication with the blood vessel through a clearly-defined neck, the term ostium generally refers to the ostium of the neck at the blood vessel. For saccular aneurysms, ball-shaped aneurysms in direct fluid communication to the blood vessel without a well-defined neck, the term ostium generally refers to the roughly ring- shaped opening on the blood vessel that leads to the aneurysm. For aneurysms have a broader and less clearly defined opening (e.g., fusiform aneurysms), the term ostium generally refers to the imaginary cylindrical section (and in the case of true fusiform aneurysms, the imaginary cylinder) that would define the luminal surface of the blood vessel in the absence of the aneurysm.

BRIEF DESCRIPTION OF THE FIGURES

Some embodiments of the invention are herein described, by way of example only, with reference to the accompanying figures. The description, together with the figures, makes apparent how embodiments of the invention may be practiced to a person having ordinary skill in the art. The figures are for the purpose of illustrative discussion of embodiments of the invention and no attempt is made to show structural details of an embodiment in more detail than is necessaiy for a fundamental understanding of the invention. For the sake of clarity, objects depicted in the figures are not to scale. In the figures: FIGS. IA-I H depict an embodiment of a method of the invention where an implantable assembly that comprises a sheet of material supported by and covering a part of the surface area of a self-expanding stent is deployed to block the ostium of an aneurysm, followed by the introduction of coils as aneurysm-fillers into the aneurysm;

FIGS 2A-2E depict an embodiment of a method of the invention where an implantable assembly that comprises a sheet of material that is supported by and fully covers the surface area of a stent is deployed to block the ostium of an aneurysm, followed by removal of some of the contents of the aneurysm and the introduction of an embolic fluid as an aneurysm-filler into the aneurysm; and

FIGS 3 A-3C depict an embodiment of the a method of the invention where an implantable assembly that comprises a sheet of material rolled into a tube supported by a radially expandable substantially tubular frame made up of two terminal expandable rings mutually connected by four longitudinal struts is deployed to block the ostium of an aneurysm, in preparation for the removal of some of the contents of the aneurysm and/or the introduction of an aneurysm-filler into the aneurysm.

DESCRIPTION OF SOME EMBODIMENTS OF THE INVENTION

Aspects of the invention relate to methods, devices and kits useful in the treatment of aneurysms, especially cerebral aneurysms. Some embodiments of the invention allow for the filling of an aneurysm with an aneurysm-filler as known in the art but in some embodiments, preventing or reducing the chance of delayed regrowth, recanalization and/or dislodgement and/or entry of the aneurysm-filler into the blood stream during or subsequent to the introduction of the aneurysm-filler into the aneurysm. Some embodiments of the invention allow for the removal of some of the contents of an aneurysm, in some embodiments reducing the size of the aneurysm.

Specifically, according to some aspects of the invention, a sheet of material supported by a substantially tubular expandable frame (such as a cover of a partially of fully covered stent) is deployed so that the sheet of material at least partially blocks or seals the ostium of the aneurysm. Subsequently aneurysm-filler is introduced into the aneurysm or contents of the aneurysm are removed.

The principles, uses and implementations of the teachings of the invention may be better understood with reference to the accompanying description and figures. Upon perusal of the description and figures present herein, one skilled in the art is able to implement the teachings of the invention without undue effort or experimentation. In the figures, like reference numerals refer to like parts throughout.

Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details set forth herein. The invention can be implemented with other embodiments and can be practiced or carried out in various ways. It is also understood that the phraseology and terminology employed herein is for descriptive purpose and should not be regarded as limiting.

As noted above, according to some aspects of methods of the invention, an implantable assembly comprising a sheet of material supported by a substantially tubular expandable frame is deployed so that the sheet of material at least partially blocks or seals the ostium of an aneurysm followed by introduction of an aneurysm- filler through an aneurysm-filler tube or removal of contents of the aneurysm with an aneurysm-contents removal tube.

Deployment of an implantable assembly comprising a sheet of material supported by a substantially tubular frame (such as a completely or partially covered stent) is performed in the usual way with which one skilled in the art is familiar, for example as taught in WO 2007/088549.

Generally, deployment comprises radially expanding the expandable frame of the implantable assembly so that the sheet of material is brought towards the walls of the blood vessel and the ostium of the aneurysm. In some embodiments, the expansion is partial expansion and the blocking of the ostium of the aneurysm is incomplete. In such embodiments, subsequent to the removal of contents of the aneurysm and/or of introduction of the aneurysm-iϊHer into the aneurysm, the exapndable frame is fully expanded. In contrast, in some embodiments the radial expansion of the expandable frame is such that the outer surface of the portion of the surface area of the frame that is covered by the sheet of material presses against walls of the blood vessel surrounding the ostium of the aneurysm, thereby substantially blocking fluid communication between the blood vessel and the aneurysm through the ostium of the aneurysm.

In some embodiments, the tubular frame is a self-expanding tubular frame. As is known in to one skilled in the art, deployment of self-expanding frames generally involves releasing the frame from constraints (such as of a tubular delivery sheath of a delivery catheter), allowing the frame to expand towards the walls of the blood vessel. In such cases, partial deployment generally refers to a situation where a part of the frame has been released from the constraints while a part remains constrained.

In some embodiments, the tubular frame is not self-expanding and is configured to be expanded by activation of the deployment device (e.g., a balloon catheter) to apply an outwards radial force to the luminal surface of the frame, radially expanding the frame towards the walls of the blood vessel. In some such embdoiments, partial deployment generally refers to a situation where the deployment device is activated to

radially expand the frame to a larger diameter that is less than the finally desired diameter.

In some embodiments, the sheet of material covers substantially the entire surface area of the expandable frame of the implantable assembly, for example, as a result of a medical decision, for convenience, for a greater degree of sealing of the aneurysm or to treat a fusiform aneurysm. In some embodiments, the sheet of material covers only part of the surface area of the expandable frame of the implantable assembly (e.g., implantable assemblies taught in PCT/1B2008/052799), for example, when it is desired to have a reduced delivery profile and increased flexibility or when it is desired to treat a bifurcated blood vessel and to avoid obstructing branching vessels.

Deploymentof the implantable assembly is done in a manner that allows subsequent introduction of aneurysm-fiUer into the aneurysm or removal of contents of the aneurysm, through a tube (an aneurysm-filler introducer tube and/or aneurysm- contents removal tube, e.g., a microcatheter) that passes through the vasculature in the usual way and accesses the aneurysm through the ostium of the aneurysm. Generally, the distal end, and specifically the distal tip of the tube is located at the ostium of the aneurysm, or is pushed further, inside the aneurysm neck (if such exists) or inside the aneurysm itself. The exact location where the distal tip is located is dependent on factors, most importantly clinical factors as determined by the performing medical professional and the instructions for use of the aneurysm-filler. That said, in some embodiments when the aneurysm-filler comprises endovascular coils, it is advantageous to position the distal tip of the tube as close as possible to the plane of the ostium of the aneurysm.

In some embodiments, the distal end of the tube passes on the outer surface of the implantable assembly to access the aneurysm, generally between the outer surface of the implantable assembly and the luminal surface of the blood vessel.

In some embodiments, the distal end and distal tip of the tube pass through the sheet of material to access the aneurysm, typically through a hole passing through the sheet of material. In some embodiments, the distal tip just passes through the sheet of material or is flush with the aneurysm-side of the sheet of material. In some embodiments, the distal tip of the tube passes clear through the hole and is found within the volume of the aneurysm.

In some embodiments it is necessary to properly radially orient the implantable assembly. For example, in some embodiments where the sheet of material covers only a portion of the surface area of the expandable frame, it is necessary that the assembly be radially oriented to adequately cover the ostium of the aneurysm. For example, in some embodiments where the distal end of the tube accesses the aneurysm through a hole in the sheet of material, it is necessary that the assembly be radially oriented so that the hole be aligned with the ostium of the aneurysm so that the hole is in fluid communication with the aneurysm through the ostium.

In some embodiments, radial orientation of the implantable assembly is performed substantially as taught in WO 2007/088549 and in PCT/IB2008/052799, where the implantable assembly is radially oriented with reference to an elongated radial orientation guide which distal tip is positioned in the aneurysm. In some embodiments, the elongated radial orientation guide is a guide wire, as taught in WO

2007/088549. In some embodiments, the elongated radial orientation guide is the tube (the aneurysm-filler introducer tube and/or the aneurysm-contents removal tube).

As noted above, subsequent to deploying of the implantable assembly, the aneurysm is treated through the tube.

In some embodiments, at least some of the contents of the aneurysm are removed, for example by suction applied through the distal end of the tube. In such embodiments, the tube constitutes an aneurysm-contents removal tube. In some embodiments, a clot dissolving material (e.g., streptokinase) is introduced into the aneurysm to facilitate removal of contents of the aneurysm.

In some embodiments, one or more aneurysm-fillers are introduced into the aneurysm through the tube. In such embodiments, the tube constitutes an aneurysm- filler introducer tube.

In some embodiments, contents are removed from the aneurysm and at least one aneurysm-filler is introduced into the aneurysm. In some embodiments, the content removal is performed using the same tube as is used to introduce the aneurysm-filler. In such embodiments, the same tube constitutes both an aneurysm-filler introducer tube and an aneurysm-contents removal tube. In some embodiments, a tube having at least two lumina is used, for example, in some embodiments a first lumen is used to introduce aneurysm-filler into the aneurysm and the second lumen is used to remove the contents of the aneurysm.

Embodiments of the invention effectively reduce the chance that an aneurysm- filler, fragments of the aneurysm-filler or other materials be released, dislodged or embolized into the blood stream, even when the potentially released material is very small or when the ostium of the aneurysm is relatively wide. Thus, the teachings of the invention allow for the effective use of aneurysm-fillers, including known aneurysm- fillers for treating many different shapes and sizes of aneurysms, including the treatments of berry, saccular, fusiform, wide-necked and giant aneurysm with endovascular coiling and/or liquid embolic materials.

In some embodiments, the teachings of the invention allow for methods of treatment of wide-necked, fusiform, giant and saccular aneurysms with endovascular coils where the sheet of material prevents the escape of the coils from the aneurysms. Thus, some embodiments provide for the use of endovascular coils in the treatment of wide-necked, fusiform, giant and saccular aneurysms.

In some embodiments, the teachings of the invention allow for methods of treatment of fusiform aneurysms with aneurysm-fillers where the sheet of material prevents the escape of the aneurysm-filler from the aneurysms. Thus, some embodiments provide for the use of aneurysm-fillers in the treatment of fusiform aneurysms.

Embodiments of the invention expand the utility of prior-art methods. Embodiments of the invention have advantages over the prior art during deployment of the aneurysm-filler.

One of the dangers during the prior art deployment of endovascular coils is that the coil will perforate the aneurysm wall, potentially rupturing the aneurysm with catastropic results. In some embodiments of the invention, the dangers of aneurysm rupture are reduced, even if the aneurysm ruptures during (or after) deployment of an aneurysm-filler. In some embodiments, the sheet of material acts as a barrier, isolating the aneurysm from the bood flow. In such cases, even if there is a rupture the resulting leakage is substantially not more than the contents of the aneurysm. Further, the fact that any bleeding is minor provides the performing medical professional with time to decide what steps to take, for example, if surgical intervention is required.

In the deployment of endovascular coils in an aneurysm as known in the art, it is usually preferred to place the distal tip of the deploy ment-microcatheter from which the coils exit deep within the aneurysm to reduce the chance that the loose end of the coil

will escape through the ostium into the blood stream upon release from the microcatheter. However, this reduces the distance between the distal end of the deployment microcatheter and the aneurysm wall, increasing the chance that the coil will perforate the aneurysm wall. In some embodiments of the invention, the distal tip of an ancurysm-filler deployment tube is located close to the aneurysm side of the sheet of material (the outer side) and therefore as far as possible from the aneurysm wall, reducing the chance of aneurysm-wall perforation.

As discussed above, the use of uncovered stents as a partial barrier to retain endovascular coils in an aneurysm is ineffective due to the need to use dense-walled stent, yet dense-walJed stents are difficult to deploy and block branching blood vessels. Embodiments of the invention allow for the use of implantable assemblies with spare- walled expandable frames such as the ring and strut implantable assemblies taught in WO 2001/066027 of the Inventor or spare-walled stents having a low delivery profile and greater maneuverability than comparable dense-walled stents. In some embodiments, such spare- walled implantable assemblies when provided with sheets of material that cover only part of the surface area of the expandable frame, block branching blood vessels to a lesser degree, a critical property when treating cerebral aneurysms. Thus, some embodiments of the invention are exceptionally useful and provide methods for the treatment of bifurcated and side-branched vessels. In embodiments where a fluid aneurysm-filler is introduced into the aeurysm, the sheet of material deployed in accordance with the teachings of the invention constitutes a barrier that efficiently contains the aneurysm-filler inside the aneurysm, helps define a smooth vessel lumen, prevents leakage of unsoldified (uncured) aneurysm-filler into the blood stream and prevents post-procedure erosion of the solidified aneurysm-filler by blood flow.

Embodiments of the invention also have advantages over the prior art subsequent to the filling of the aneurysm with aneurysm-filler when the procedure is complete. For example, in some embodiments, the sheet of material deployed in accordance with the teachings of the invention constitutes a barrier that prevents entry of new blood or other fluids into the aneurysm following post-procedure coiϊ compaction, recanalization or erosion of the aneurysm-filler. Additionally, in some embodiments the sheet of material functions as a lining prosthesis, providing for less turbulent flow through the treated blood vessel past the aneurysm.

Embodiments of the invention also provide the heretofore impossible effective removal and even partial draining, of an aneurysm.

An embodiment of a method of the invention is discussed with reference to Figures lA to IH.

In Figure IA is depicted an implantable assembly 10 comprising a substantially tubular expandable frame 12 and a sheet of material 14 supported by and covering a portion of the surface area of frame 12, similar to implantable assemblies taught in WO 2007/088549 and PCT/IB2008/052799. Frame 12, is a self-expanding stent laser cut from a single tube of Nitinol having

0.1 mm thick walls, is similar to stents known in the art where six individual expandable rings mutually associated with longitudinal struts constitute a radially expandable substantially tubular frame. Each expandable ring is made up of a sinusoidal Iy undulated elongated element. In a typical embodiment, frame 12 is 12 mm long and has a 6.7 mm diameter in an expanded state.

Sheet 14 is a substantially flat oval sheet of 0.1 mm thick crosslinked pericardium (thinned in accordance with the teachings of US 6,468,300 of the Inventor). Sheet 14 is substantially as long as frame 12, but covers only a partial circumferential section of frame 12 and therefore only covers a portion of frame 12. A hole 18 with a diameter of 0.6 mm passes through the center of sheet 14. Sheet 14 is supported by frame 12 with the help of sutures 16 that pass through sheet 14 and around maxima of the rings making up expandable frame 12.

In Figure IB, implantable assembly 10 is depicted in a non-expanded state loaded inside a distal end 20 of a sheath 22, substantially a delivery catheter that is a component of the delivery device of implantable assembly 10 as known in the art of self-expanding stent delivery. Apparent at distal end 20 of sheath 22 is slot 24.

Implantable assembly 10 is loaded inside sheath 22 so that hole 18 is aligned with slot

24. As is discussed below, a free axial lumen 26 of sheath 22 acts as a lumen for accepting guide wires and tubes necessary for implementing the teachings of the invention,

A patient with an unruptured cerebral aneurysm is prepared in the usual way for prior art aneurysm treatment (e.g., for endovascular coiling). Two guide wires are

advanced to proximity of an aneurysm to be treated, one passing the aneurysm and one entering the aneurysm.

In Figure 1C, is depicted a cranial artery 28 with a smaller artery 30 branching off at bifurcation 32. Across from bifurcation 32 is an aneurysm 34 in fluid communication with artery 28 through the ostium of neck 36. Two 0.20 mm (0.008") thick guide wires (Mirage from ev3 Endovascular, Inc, Plymouth, MN, USA) are shown deployed in artery 28. A first guide wire 38 is deployed in the usual way to guide a catheter past aneurysm 34. The distal end of a second guide wire 40 is placed inside aneurysm 34 to serve as an elongated radial orientation guide to ensure that implantable assembly 10 is properly radially oriented, as discussed below.

Sheath 22 with implantable assembly 10 is loaded onto guide wires 38 and 40. Guide wire 38 enters sheath 22 directly into axial lumen 26 at the distal tip of sheath 22 while guide wire 40 enters slot 24 of sheath 22 and passes through hole 18 in sheet 14 of implantable assembly 10 before entering axial lumen 26. In Figure ID, is depicted sheath 22 (in cross section) that has been advanced to proximity with aneurysm 34. The six expandable rings making up expandable frame 12 are seen as six pairs of black rectangles on opposing sides of axial lumen 26 of sheath 22. In accordance with the teachings of WO 2007/088549, guide wire 40 acts as a radial orientation guide, acting as a reference so as to radially orient sheath 22 so that sheet 14 and hole 18 are oriented across from neck 36 of aneurysm 34.

Apparent in Figure 1 D is a delivery pusher/stabilizer/stopper 42, a component of the delivery device used for deploying implantable assemble 10. For deployment of implantable assembly 10, delivery pusher 42 is held in place while sheath 22 is pulled back, outwards from the patient. As depicted in Figure IE, as a result of sheath 22 being pulled back, implantable assembly 10 is released from the constraints of sheath 22, distal end first, and expands outwardly to contact the luminal walls of artery 28. Due to the proper orientation achieved with the help of guide wire 40, frame 12 holds sheet 14 against the luminal walls of artery 28 surrounding the ostium of neck 36 of aneurysm 34, increasingly blocking and sealing-off aneurysm 34 from fluid communication with artery 28.

Once implantable assembly 10 is entirely deployed, delivery pusher 42 is withdrawn from sheath 22 and a tube 44, a microcatheler having a 0.43 mm (0.017")

luminal diameter and a distal outer diameter of 0.57 mm (1.7 Fr) (Echelon™- 10 from ev3 Endovascular, Inc, Plymouth, MN, USA) is advanced along second guide wire 40.

In Figure 1 F, tube 44 is advanced into hole 18 in sheet 14 so that the distal tip 46 of tube 44 is flush with sheet 14 so that the lumen of tube 44 is in fluid communication with the volume of aneurysm 34.

Second guide wire 40 is withdrawn and tube 44 is used as an aneurysm-filler introducer tube.

In Figure IG, aneurysm-filler 48, endovascular coil (e.g., 0.010" coil size NXT™ embolizarion coils from ev3 Endovascular, Inc, Plymouth, 3VIN, USA) are deployed inside aneurysm 34 in accordance with the instructions of the manufacturer.

Subsequently the procedure is ended in the usual way, with the dangers of untreated aneurysm 34 largely neutralized. In Figure IH, is seen how aneurysm 34 has been treated with aneurysm-fillers 48 and how the ostium of neck 36 of aneurysm 34 is substantially sealed-off from fluid communication with artery 28, in accordance with embodiments of the teachings of the invention. Due to the presence of sheet 14, there is practically no chance that embolic material or aneurysm-lϊllers 48 will exit aneurysm 34 and enter artery 28.

An additional embodiment of the method of the invention is discussed with reference to Figures 2A to 2E, where an implantable assembly 50 (depicted in side cross section in Figure 2B) is used in implementing the teachings of the invention.

Frame 12 is similar in size, shape and construction to frame 12 of assembly 10 depicted in Figure IA. However, frame 12 of assembly 50 is not self-expandable, but is configured to expand by the application of an outwards radial force to the luminal surface of frame 12, for example by a balloon of a balloon catheter.

Sheet of material 14 is a rectangular sheet of 0.15 mm thick crosslinked pleura thinned by removal of some of the basal layer in accordance with the teachings of US 6,468,300 which is rolled into a tube with abutting edges. Ro!led-up sheet 14 is secured to the inside (luminal) surface of frame 12 and is supported by frame 12 with the help of sutures that pass through sheet 14 and around maxima of the rings making up expandable frame 12, thereby constituting a complete internal stent cover. A hole 18 with a 0.4 mm diameter passes midway along the length of sheet 14 through one side of sheet 14.

~ 2\ ~ A patient with an unruptured aneurysm is prepared in the usual way for aneurysm treatment (e.g., for injection of a liquid embolic material). Two guide wires are advanced to proximity of an aneurysm to be treated as discussed above and as depicted in Figure IC A tube (a microcatheter) is advanced along lhe second guide wire 40.

In Figure 2A, is depicted a cranial artery 28 with an aneurysm 34 in fluid communication with artery 28 through the ostium of neck 36. Two 0.20 mm (0.008") thick guide wires (Mirage™ from ev3 Endovascular, Inc, Plymouth, MN, USA) are shown deployed in artery 28, as described above with reference to Figure IC A second guide wire 40 is deployed to guide the distal end 46 of tube 44 into aneurysm 34. Tube 44, a microcatheter having a 0.33 mm (0.013") luminal diameter and a distal outer diameter of 0.50 mm (1.5 Fr) (Marathon™ from ev3 Endovascular, Inc, Plymouth, MN, USA) is shown advanced along guide wire 40 so that distal tip 46 of tube 44 opens up in the neck 36 of aneurysm 34. In Figure 2B implantable assembly 50 is mounted on a balloon 52 at the distal end 20 of a delivery device (a modified balloon catheter 54) is advanced along guide wire 38 and tube 44, with tube 44 serving as an elongated radial orientation guide (as discussed below) to proximity of aneurysm 34.

In Figure 2B is depicted distal end 20 of balloon catheter 54, a component of the device for the delivery of implantable assembly 50. Balloon catheter 54 is substantially a standard balloon catheter with expandable balloon 52 configured to be expanded to apply an outwardly radially force to open a stenosed blood vessel and to expand a stent or similar radially expandable frame to an expanded state. Through the center of catheter 54 passes an axial guide wire lumen 26 for accepting a guide wire such as guide wire 38.

Balloon catheter 54 is also provided with an radial orientation guide tube 56, parallel with the main shaft of balloon catheter 54 used for controlling the radial orientation of catheter 54 in accordance with the teachings of WO 2007/088549. Radial orientation guide tube 56 has a proximal end (not depicted) that remains outside the body of the patient during use and a distal end with a distal port 58. The length of radial orientation guide tube 56 is such that distal port 58 is located approximately midway along the length of baϊloon 52. Implantable assembly 50 is crimped onto balloon 52 and

over radial orientation guide 56 in the usual way so that distal port 58 of radial orientation guide tube 56 is accessible through hole 18 in sheet 14.

As is apparent from Figure 2B, for guiding implantable assembly 50 to proximity with aneurysm 34, guide wire 38 is placed from the distal end of catheter 54 into axial lumen 26 while tube 44 is placed through hole 18 in sheet 14 of implantable assembly 50, threaded into distal port 58 and into the lumen of radial orientation guide tube 56. Analgously to described above with reference to Figures 1 and in accordance with the teachings of WO 2007/088549, tube 44 thereby serves as an elongated radial orientation guide, ensuring that hole 18 in sheet of material 14 is oriented across from neck 36 of aneurysm 34.

Once implantable assembly is properly oriented in relation to aneurysm 34, as depicted in Figure 2B, balloon 52 is expanded in the usual way, applying an outwards radial force to expandable frame 12. Expandable frame 12 expands outwards, unfolding and slightly stretching sheet of material 14. As is depicted in Figure 2C, expandable frame 12 is expanded to an extent that sheet of material 14 is substantially flush with the luminal wall of artery 28, Such expansion substantially seals the ostium of neck 36 of aneurysm 34 from fluid communication with artery 28.

A suction generator (e.g., a syringe) is functionally associated with the proximal end of tube 44 so as to apply suction through distal tip 46 of tube 44.

As is depicted in Figure 2D, the applied suction removes some of the contents of aneurysm 34 so that tube 44 serves as an aneurysm-contents removal tube. The removal of contents of aneurysm 44 reduces the size and the internal pressure of aneurysm 34, thereby reducing the chance of rupture. The suction generator is dissociated from the proximal end of tube 44 and a liquid aneurysm-filler dispenser is associated with the proximal end of tube 44. The liquid aneurysm-filler dispenser is used to introduce a liquid aneurysm-filler (e.g., OnyxR™ HD-500 from ev3 Endovascular, Inc, Plymouth, MN, USA) inside aneurysm 34 in accordance with the instructions of the manufacturer. As depicted in Figure 2E, liquid aneurysm-filler 48 embolizes inside aneurysm

34. The procedure is ended in the usual way with the dangers of the untreated aneurysm 34 largly neutralized.

97 _

An additional embodiment of the method of the invention is discussed with reference to Figures 3A to 3C, where an implantable assembly 60 (depicted in side cross section in Figures 3B and 3C) is used in implementing the teachings of the invention.

A substantially tubular expandable frame 12 of implantable assembly 60 is a self-expanding frame similar to frames taught in WO 2001/066037 which comprises two terminal self-expanding rings (similar to the expandable rings of frame 12 of implantable assembly 10) mutually connected with four longitudinal struts. Sheet of material 14 of implantable assembly 60 is a rectangular sheet of 0.10 mm thick crosslinked equine pericardium thinned by removal of some of the basal layer in accordance with the teachings of US 6,468,300 of the Inventor and wrapped around the outside surface of the terminal rings and the struts of expandable frame 12 and is secured to frame 12 with sutures. Sheet 14 constitutes a complete external cover for frame 12 and is supported by frame 12 to have a tubular shape.

In Figure 3 A, implantable assembly 60 is depicted in a non-expanded state loaded inside a distal end 20 of a sheath 22, substantially a delivery catheter that is a component of the delivery device of implantable assembly 60 as known in the art of self-expanding stent delivery. A free axial lumen 26 of sheath 22 acts as a lumen for accepting guide wires and tubes necessary for implementing the teachings of the invention. Functionally associated with sheath 22 is radial orientation guide tube 56, substantially a tube having a proximal end (not depicted), a distal end with a distal port 58, and a lumen between the two ends for accepting an radial orientation guide such as a guide wire.

A patient with an unruptured aneurysm is prepared in the usual way for aneurysm treatment (e.g., for endovascular coiling). In Figure 3B Two guide wires are advanced to proximity of an aneurysm to be treated, one, 38, passing the aneurysm and one, 40, entering the aneurysm as described above and as depicted in Figure 1C. Subsequently, a tube 44, a microcatheter having a 0.53 mm (0.021") luminal diameter and a distal outer diameter of 0.77 mm (2.3 Fr) (Rebar™ from ev3 Endovascular, Inc, Plymouth, MN, USA) is advanced along guide wire 40 so that distal tip 46 of tube 44 opens up just at the ostium of neck 36 of aneurysm 34, as described above and depicted in Figure 2A.

Guide wire 38 is threaded into axial lumen 26 of sheath 22 and tube 44 is threaded into the lumen of radial orientation guide tube 56. With tube 44 serving as an

elongated radial orientation guide, the delivery device comprising sheath 22 and radial orientation guide tube 56 is advanced along guide wire 38 and tube 44 until distal end 20 of sheath 22 is close to aneurysm 34.

As depicted in Figure 3B, a delivery pusher/stabilizer/stopper 42 is used to help deploy implantable assembly 60, so that implantable assembly partially blocks and seals the ostium of neck 36 of aneurysm 34.

As depicted in Figure 3C, implantable assembly 60 is fully deployed, almost completely blocking and sealing the ostium of neck 36 of aneurysm 34 while tube 44 passes on the outside surface of implantable assembly 60 and past the ostium of neck 36 of aneurysm 34.

From the situation depicted in Figure 3C, tube 44 can be used as an aneurysm- contents-removal tube, for example by being functionally associated with a suction- generator, to remove contents of aneurysm 34 substantially as discussed with reference Figures 2. Alternatively or additionally, from the situation depicted in Figure 3C ₅ tube 44 can be used as an aneurysm-filler introducer tube, for example to introduce an aneurysm-filler such as endovascular coils (as discussed with reference to Figures 1 and as known in the art), liquid aneurysm-fillers such as liquid embolic materials (as discussed with reference to Figures 2 and as known in the art) or other aneurysm-fillers, Once the procedure is complete and the presence of tube 44 in neck 36 of aneurysm 34 is not needed, tube 44 is carefully retracted, preventing any recoil or trauma and allowing frame 12 of implantable assembly 60 to completely seal the ostium of neck 36 of aneurysm 34.

The procedure is ended with the dangers of the untreated aneurysm 54 largly neutralized.

In the embodiments of the method of the invention described above, a single aneurysm-fiUer was introduced into an aneurysm. In some embodiments two or more different aneurysms-filiers are introduced into an aneurysm. In the embodiment of a method of the invention depicted in Figures 1 an aneurysm was treated by the introduction of an aneurysm-fϊϋer thereinto while in the embodiment of the method of the invention depicted in Figures 2 an aneurysm was treated by removal of contents of the aneurysm followed by introduction of aneurysm-

fiiler thereinto. In some embodiments, an aneurysm is treated only by removal of contents of the aneurysm. In some embodiments, introduction of an aneurysm-filler is prior to removal of the contents of the aneurysm.

In the embodiments of the method of the invention described above, the expandable frames of the implantable assemblies are folly deployed before aneurysm- filler is introduced or contents of the aneurysm are removed. In some embodiments, an expandable frame is partially deployed, aneurysm-filler is introduced or contents of the aneurysm are removed, and then the deployment of the frame is completed. For example, in embodiments analogous to the embodiment depicted in Figures 3 where the expandable frame of the implantable assembly is not self-expanding, it may be advantageous to complete deployment of the implantable assembly by expanding the expandable frame to a final radial size only after the tube 44 is withdrawn from the aneurysm. It is important to note that in embodiments where the expandable frame is only partially deployed, it is preferred that the partial deployment lead to substantial obstruction or blocking of the fluid communication between the aneurysm and the blood vessel on which the aneurysm is found.

Some embodiments of the methods of the invention may be practiced with devices known in the art and commonly found in a catheterization theater. Suitable implantable assemblies, suitable delivery devices and the like are taught in WO 2007/088549 and in PCT/IB2008/052799 and are available from ITGI Medical (Or Akiva, Israel). Guidewires suitable as elongated radial orientation guide are commercially available from a number of sources, see below, Microcatheters suitable for use as aneurysm-filler introducer tubes, aneurysm-contents removal tubes or elongated radial orientation guide are commercially available from a number of sources, see below. Many types of aneurysm-fillers as well as associated kits, materials and devices are commercially available from a number of sources, see below.

That said, it is preferable to implement the methods of the present using a kit of the invention for treating an aneurysm. Embodiments of a kit of the invention provide some or all of the components or devices required for performing an embodiment of the method of the invention.

In some embodiments, a kit of the invention comprises a) an implantable assembly, b) a delivery system for deploying the implantable assembly within a blood

vessel, the delivery system including a tube having at least one lumen (e.g., a microcatheter) with a proximal end and a distal end, wherein the tube is suitable for use as an aneurysm-filler introducer tube to serve as a conduit to introduce aneurysm-fϊϋer into an aneurysm through the distal end; and/or the tube is suitable for use as an aneurysm-contents removal tube to serve as a conduit for removing contents of an aneurysm through the distal end.

According to some embodiments, the delivery system further comprises a delivery catheter with a proximal end and a distal end, the delivery catheter including:a region near the distal end of the delivery catheter where the implantable assembly is positionable for deployment of the implantable deployment in a blood vessel; a lumen for accepting a guide wire passing from the proximal end of the delivery catheter to a port near a distal tip of the delivery catheter; and a lumen for accepting the tube passing from the proximal end of the delivery catheter to a port in the side of the delivery catheter proximaϊ to the region where the implantable assembly is positionable. According to some embodiments, one lumen of the delivery catheter is both the lumen for engaging the guide wire and the lumen for engaging the tube.

According to some embodiments, the lumen of the delivery catheter for engaging the guide wire is distinct from the lumen of the delivery catheter for engaging the tube. According to some embodiments, the kit is provided where the tube at least partially passes in the lumen for accepting the tube of the delivery catheter, that is to say the tube is preloaded in the delivery catheter for ease of use.

According to some embodiments, the sheet of material comprises a hole passing through the sheet of material and the tube is configured to introduce aneurysm-filler and/or to remove contents of an aneurysm through the hole in the sheet of material, as described above. According to some embodiments, the kit is provided where the implantable assembly is mounted on the region near the distal end of the delivery catheter so that the hole in the sheet of material of the implantable assembly and the port in the side of the delivery catheter are aligned, that is to say the kit is provided where the implantable assembly is preloaded on the delivery catheter.

According to some embodiments, the distal end of the tube is configured to pass through the hole in the sheet of material.

According to some embodiments, the kit is provided where the tube at least partially passes through the hole in the sheet of material, that is to say the kit is provided where the tube is preloaded in the hole of the sheet of material.

According to some embodiments, the frame of the implantable assembly is self- expanding and the delivery device is configured to constrain the frame to remain in unexpanded state until deployed.

According to some embodiments, the delivery system comprises an expansion component (e.g., a balloon of a balloon catheter) configured to apply an outwards radial force to the frame to radially expanding the frame. According to some embodiments, the tube comprises at least two distinct lumina, a first of the at least two lumina configured for the introduction of an aneurysm- filler therethrough. According to some embodiments, the second of the at least two lumina is configured for removal of contents of an aneurysm therethrough.

In some embodiments, the kit further comprises a suction-generator, configured to engage the proximal end of the tube and provide suction from the distal end of the tube through a lumen of the tube. For example, in some embodiments a suction generator is a syringe, e.g., a 10 ml syringe, provided with a first part of a connector and the kit is provided with an aneurysm-contents removal tube having the second part of the connector associated with the proximal end of the tube. For use it is a simple matter to mate the first and second parts of the connectors so as to functionally associate the suction generator to the aneurysm-contents removal tube. When the suction generator is activated, contents of an aneurysm are removed from the aneurysm through the distal tip of the aneurysm-contents removal tube found in the aneurysm.

In some embodiments, the kit further comprises an aneurysm-filler dispenser, configured to engage the proximal end of the tube and force aneurysm-filler into the proximal end, through a lumen of the tube and out of the distal end of the tube. Suitable such aneurysm-filler dispensers are well known and are commercially available form a variety of sources, see below.

In some embodiments, the kit further comprises at least one aneurysm-filler, in some embodiments, the aneurysm-filler is provided in a reservoir. In some embodiments, the reservoir is configured to function as an aneurysm dispenser, as described above.

As noted above, suitable expandable assemblies for implementing the teachings of the invention include expandable assemblies taught in WO 2007/088549 and in PCT/1B2008/052799 as well as appropriately modified assemblies taught in US 6,699,277 of the Inventor. Generally, any suitable expandable frame 12 may be used in implementing the teachings of the invention. For example, in Figures 3, frame 12 comprises two radially expandable terminal rings mutually associated with longitudinal struts. For example, In Figures 1 and 2, frames 12 comprises six radially expandable rings associated with longitudinal struts together constituting a stent. In some embodiments (e.g., assembly 10 of Figures 1 or assembly 60 of Figures

3) the expandable frame 12 is self-expanding. In some embodiments (e.g., assembly 50 of Figures 2), the expandable frame 12 is non self-expanding and is configured to radially expand by application of an outwards force applied to an inner surface of the frame 12 (e.g., analogous to balloon expandable stents known in the art), for example as applied by a standard catheter-mounted balloon.

For non-self expanding frames 12 such as frame 12 of assembly 50, the outwards force applied by the expansion device on the luminal walls of the blood vessel may be quite significant which may be necessary for clearing and dilating the lumen of a stenosed vessel. Thus, in some embodiments where there is a need for dilating the lumen of a stenosed vessel, frames configured to be expanded by application of an outwards force may be preferred.

The fact that the deployment process of self-expanding stents generally leads to the application of a lesser outwards force to the luminal walls of the blood vessel leads many medical professionals to believe that self-expanding frames 12 are safer, especially for the tortuous and delicate vasculature of the brain as not much radial force is needed since no obstructive disease is treated in this cases. Thus, in some embodiments especially some embodiments where the aneurysm is a cerebral aneurysm, it is preferred that a frame 12 be a self-expanding frame.

Two important parameters used when selecting or designing an expandable frame for use as the frame 12 of an implantable assembly are the expanded diameter and the delivery profile of the frame. The expanded diameter of a frame 12 of an implantable assembly is selected based in medical criteria, so that when the implantable assembly is deployed the frame 12 is well anchored in the blood vessel and is expanded

sufficiently to ensure that the associated sheet 14 of material is held sufficiently taut.

Generally, the delivery profile should be as small as possible to increase maneuverability and reduce the chance of damage to the vasculature.

In some embodiments for deployment in the intracranial vasculature, the exapndable frame 12 of an implantable assembly generally has a delivery profile that is no greater than about 2 mm and even no greater than about 1 mm. Suitable such tubular frames 12 generally have a maximal expanded diameter of approximately twice to six times, or even more the delivery profile.

In some embodiments an expandable frame 12 of an implantable assembly is substantially a stent (e.g., assembly 10 in Figures 1 or assembly 50 in Figures 2) which provide substantial support for the walls of a blood vessel in which deployed along the entire length of the frame 12 due to the presence of sufficient radial structural elements, for assemblies 10 and 50 the six expandable rings.

For use in vessels other than those of the brain, generally any type of stent known in the art is useful as a frame 12 of an implantable assembly of the invention. Such stents include but are not limited to stents marketed by affiliates (e.g., Cordis) of Johnson & Johnson, Guidant (Indianapolis, Indiana, USA ₃ now an affiliate of Boston Scientific Corp. and Abbott Laboratories), Medtronic (Minneapolis, Minnesota, USA), Medinol (Tel Aviv, Israel), Cook Inc. (Bloomiπgton, Indiana, USA) and ITGI Medical (Or Akiva, Israel).

For deployment within intracranial blood vessels thin and flexible frames are preferred such as BiodivYsio™ AS (evYsio Medical Devices ULC, Vancouver, Canada), Neuroform stent (Boston Scientific Corp. Natick, MA, USA), Neurolink stent (Guidant, Indianapolis, Indiana, USA, now an affiliate of Boston Scientific Corp. and Abbott Laboratories) or Boa stent (Bait, Montmorency, France). Particularly preferred is the frame used with the Over and Under™ stent (ITGI Medical, Or Akiva, Israel) which is a low-pressure balloon-expandable stent constructed from an electro-polished stainless steel laser-cut tube.

In some embodiments an expandable frame 12 of an implantable assembly does not provide substantial support for a blood vessel in which deployed, for example the expandable frame 12 of assembly 60 which is a self-expanding frame 12 similar to frames 12 taught in WO 2001/066037, which comprises two terminal self-expanding rings mutually connected with four longitudinal struts. Thus, in some embodiments, the

subslantiaOy tubular frame 12 comprises two radially-expandable ring sections mutually connected with at least two longitudinally arrayed struts arrayed about a cirumference of each ring section, where the distance between the ring sections is at least 50% of the length of the frame 12. Such frames are not generally considered proper stents as, due to the lack of radial support elements between the two terminal rings, such frames provide little support to a blood vessel in which deployed in the area between the terminal rings.

Such frames and other similar frames, although not providing substantial support to a blood vessel are highly flexible for delivery, provide sufficient support for an associated sheet of material, and when used together with a sheet of material that only partially covers the surface area of the frame 12, cause relatively little interference to blood flow into branching vessels.

Generally, a sheet of material 14 of an implantable assembly of the invention is substantially a sheet of material that is suitable for deployment in a body. In some embodiments, a sheet 14 is inherently flat and adopts a curved shape when supported by an expandable frame 12. In some embodiments, a sheet 14 is inherently curved, e.g., lias a cylindrical or elliptical cross-section. As discussed above, in some embodiments, the length of a sheet 14 is substantially equal to, or shorter than, that of a supporting frame 12.

In some embodiments, a sheet 14 contacts an inner surface of a frame 12. In some embodiments, a sheet 14 contacts an outer surface if a frame 12. In some embodiments, a sheet 14 contacts both and inner and an outer surface of a frame 12, for example as taught in US 6,699,277. In some embodiments, a sheet 14 encapsulates or sandwiches at least a portion of a frame 12.

In some embodiments, a sheet 14 is of a collapsible material, allowing folding of the sheet 14 for deployment. In some embodiments, a sheet 14 is of a stretchable material. In some embodiments, a sheet 14 is tear-resistant.

In some embodiments, a sheet 14 constitutes a lining prosthesis that ultimately repairs the blood vessel in which deployed.

It is generally preferred that a sheet of material 14 is of a material that is substantially impermeable to fluids so as to effectively seal the ostium to prevent the

flow of blood and fluids into the aneurysm as well as to prevent the flow of fluid aneurysm- filler from the aneurysm to the blood vessel.

In some embodiments, a sheet 14 is of a material allowing proliferation of cells therethrough. In some embodiments, it is preferred that a sheet 14 be impervious to cell growth therethrough (to prevent build up and the migration of smooth muscle cells).

To reduce the delivery profile and to increase axial flexibility of an implantable assembly it is preferred that a sheet 14 be as thin as possible. Generally a sheet 14 used in implementing the invention is less than 1 mm thick and even less than 0.45 mm thick, so long as the strength and other mechanical properties are remain sufficient. In some embodiments . the thickness of a sheet 14 is up to about 0.45 mm, up to about 0.2 mm and even up to about 0.1 mm.

In some embodiments, a sheet 14 is fashioned from a synthetic or polymeric material. Suitable such materials include, but are not limited to, polyfluorohydrocarbon polymers (e.g., polytetrafluorethylene), polyurethanes, elastomers, polyamides (e.g., Nylon), polyesters (e.g., Dacron) and silicone.

In some embodiments, a sheet 14 is fashioned from a biological tissue including but not limited to autologous tissue or heterologous tissue such as venous tissue, arterial tissue, serous tissues, serous membranes, pleura, peritoneum, pericardium, dura mater and aortic leaflet. Generally suitable tissue types include but are not limited to equine, porcine, bovine or human tissue. In order to increase the toughness of the tissue, it is often advantageous to treat the tissue, for example with a glutaraldehyde or a phosphate solution, in order to cross-link collagen in the tissue. To reduce the bulk of the implantable assembly, it is often preferred that the tissue be thinned, that is after harvesting one or more layers of the harvested tissue are removed, e.g. by scraping, shaving, slicing or skiving (see US 6,468,300 of the Inventor).

One type of tissue suitable for implementing the teachings is serous tissue, including serous membranes, pericardium, pleura, peritoneum, dura mater, especially porcine, bovine, equine and human serous tissue.

Serous tissue is made of two strata. The serous stratum (serous membrane) of serous tissue is a very smooth single layer of flattened, nucleated mesothelial cells united at their edges by cement. The serous stratum rests on a tough, fibrous basement layer.

For some embodiments, natural serous tissue comprising both the serous stratum and the basement layer is impermeable to fluids, strong, elastic, tear-resistant and thin enough to be useful in fashioning a sheet 14.

In some embodiments, a preferred material from which to fashion a sheet 14 is serous tissue where at least a portion, and in some embodiments all of the basement layer, has been removed (and is therefore thinned), for example by methods including peeling, shaving as taught in US 6,468,300. In embodiments where all the basement layer is removed, a sheet 14 is thinned serous tissue that is substantially the serous stratum of the serous tissue devoid of a basement layer. Thinned serous tissue is sufficiently impermeable to fluids, strong, elastic, tear resistant and even thinner than serous tissue. In some embodiments (especially for deployment within cranial vessels), sheet 14 comprises serous tissue, especially serous membrane, devoid of at least a portion of associated basement tissue, and even devoid of all the associated basement tissue to substantially comprise only a serous stratum. Serous tissue, including thinned serous tissue, resists suture line bleeding, requires no pre-clotting, supports endothelialization and has an excellent host-tissue response. Serous tissue, depending on the type, the source and whether thinned or not, is available in thicknesses of less than 1 mm, less than 0.45 mm, less than 0.2 mm and even less than about 0.1 mm. In some such embodiments, a sheet 14 has a thickness of between about 0.05 mm and about 0.20 mm.

Generally, a sheet 14 of an implantable assembly is secured to a respective frame 12 with securing components such as sutures, hooks, piercing members, clamps, adhesives, staples, tacks, pins and bending members, or other applicable mechanical mean or combinations thereof. In some embodiments, the securing components are components distinct from the tubular frame 12, such as sutures. In some embodiments, the securing components are components attached to the frame 12 as taught in US 6,929,658 of the Inventor for example piercing members attached to the frame 12 by welding or securing components integrally formed with the frame 12, for example piercing members integrally formed with the frame 12 by a laser cutting process. In some embodiments, the securing components are clamps, for example as described in the WO 2007/088549.

In some embodiments, the tubular frame 12 of an implantable assembly is provided with features (e.g., eyelets, loops, the shape of components of the frame 12)

that together with securing components assist in securing a sheet 14 to the tubular frame 12, as discussed above.

In some embodiments, there is a hole 18 passing through the sheet 14 of material. Preferably, such a hole 18 is positioned at or near the center of the sheet 14 of material The hole is optionally reinforced by a grommet, made, for example, of a material such as biological tissue, muscle tissue, polymer, silicon rubber, metal, gold and titanium.

In some embodiments, the diameter of a hole 18 is about the same or slightly larger than the corresponding tube used as an ancurysm-filler introducer tube or as an aneurysm-contents removal tube. For example, in some embodiments the diameter of the hole is no more than 30%, no more than 20% or even no more than 10% larger than the diameter of the corresponding tube. In some embodiments, especially where the material is elastic and/or tear resistant (such as serous tissue), the hole has a diameter less than that of the corresponding tube. In some embodiments, the diameter of the hole (for allowing passage of a tube therethrough) is dependent on the expanded size of the expandable frame.

In some embodiments, the diameter of the hole is no more than about 50%, no more than about 40% and even no more than about 30% of the expanded diameter of the expandable frame. In some embodiments directed to the treatment of aneurysms on the aorta where the expandable frame has an expanded diameter of between about 10 mm and about 25 mm, the diameter of the hole is typically no more than about 4 mm, no more than about 3 mm and even no more than about 2 mm in diameter.

In some embodiments directed to the treatment of cerebral aneurysms where the expandable frame has an expanded diameter of between about 2 mm and about 4 mm, the diameter of the hole is typically no more than about 1 mm.

In some embodiments, especially those directed to the treatment of cerebral aneurysms, the diameter of the hole (for allowing passage of a tube therethrough) is no more than about 1 mm, no more than about 0.93 mm (2.8 Fr), in some embodiments no more than about 0.83 mm (2.5 Fr), in some embodiments no more than about 0.77 mm (2.2 Fr), in some embodiments no more than about 0.73 mm (2.2 Fr), in some embodiments no more than about 0.67 mm (2.0 Fr), in some embodiments no more than about 0.63 mm (1.9 Fr), in some embodiments no more than about 0.57 mm (1.7 Fr) and

in some embodiments even no more than about 0.50 mm (1.5 Fr). In some embodiments, especially where the material is elastic and/or tear resistant (such as serous tissue), the hole is a puncture in the material through which a corresponding tube may be pushed. Generally, deployment of aneurysm-fillers and of expandable frames 12 is performed under guidance of an imaging modality such as ultrasound or X-ray based imaging modality. Usually, a frame 12 of an implantable assembly is sufficiently visible in such imaging modalities. That said, in some embodiments an implantable assembly is provided with one or more markers detectable in the appropriate imaging modality, for example markers delineating the periphery of a sheet of material 14, markers that allow the orientation and position of sheet 14 to be ascertained, and markers that allow the location of a hole 18 to be determined.

Some embodiments of a implantable assembly are configured to release an active agent when deployed. In some such embodiments, one or more suitable active agents are releasably associated with the sheet 14 and/or the frame 12. Suitable active agents may by associated with a implantable assembly during the manufacturing process, for example as a coating or by impregnating one of the components with an active agent or immediately before deployment of the implantable assembly. For example, in some embodiments, the implantable assembly is immersed for a period of time in an active agent containing solution so as to absorb or adsorb the active agent into the sheet 14 and/or frame 12. Typical active agents include, for example, anti- thrombogenic agents, anti-angiogenic agents, anti inflammatory agents, anti-coagulant agents and other active agents.

Generally, any suitable tube 44 may be used as aneurysm-fϊller introducer tube or aneurysm-contents removal tube for implementing the teachings of the invention. In some embodiments, a tube has a single lumen. In some embodiments, a tube has two (or more) parallel lumina. In some such embodiments, one lumen is configured for introduction of aneurysm-filler into an aneurysm. In some such embodiments, one lumen is configured for removal of contents of an aneurysm. Suitable tubes having two lumina are taught, for example, in US 6,964,657.

The selection of which tube to use to implement the teachings of the invention is dependent on the discretion of the medical professional and is usually based on medical criteria and availability.

That said, it is generally preferred that the outer diameter of the tube be as small as possible but that the luminal diameter be sufficient to allow introduction of aneurysm- filler or removal of aneurysm contents.

In some embodiments, the outer diameter of the tube is dependent on the expanded size of the expandable frame.

In some embodiments, the outer diameter of the tube is no more than about 50%, no more than about 40% and even no more than about 30% of the expanded diameter of the expandable frame.

In some embodiments directed to the treatment of aneurysms on the aorta where the expandable frame has an expanded diameter of between about 10 mm and about 25 mm, the outer diameter of the tube is typically no more than about 4 mm, no more than about 3 mm and even no more than about 2 mm in diameter.

In some embodiments directed to the treatment of cerebral aneurysms where the expandable frame has an expanded diameter of between about 2 mm and about 4 mm, the outer diameter of the tube is typically no more than about 1 mm.

In to some embodiments, especially embodiments directed to the treatment of cerebral aneurysms, the outer diameter of the tube (for introduction of aneurysm-filler or for removal of contents of an aneurysm) is no more than about 1 mm, in some embodiments no more than about 0.93 mm (2.8 Fr), in some embodiments no more than about 0.83 mm (2.5 Fr), in some embodiments no more than about 0.77 mm (2.2 Fr), in some embodiments no more than about 0.73 mm (2.2 Fr), in some embodiments no more than about 0.67 mm (2.0 Fr), in some embodiments no more than about 0.63 mm

(1.9 Fr), in some embodiments no more than about 0.57 mm (1.7 Fr) and in some embodiments even no more than about 0.50 mm (1.5 Fr).

In to some embodiments, the luminal diameter of the tube (for introduction of aneurysm-filler or for removal of contents of an aneurysm) is no more than about 0.69 mm (0.0270"), in some embodiments no more than about 0.53 mm (0.0210"), in some embodiments no more than about 0.48 mm (0.0190"), in some embodiments no more than about 0.46 mm (0.0180"), in some embodiments no more than about 0.43 mm (0.0170"), in some embodiments no more than about 0.42 mm (0.0165"), in some

embodiraents no more than about 0.38 mm (0.0150") and in some embodiments even no more than about 0.33 mm (0.0130").

Suitable tubes are microcatheters available from a variety of suppliers. For example, from ev3 Endovascular, Inc (Plymouth, MN, USA) suitable microcatheters include Marathon™ (ID 0.013", distal OD 1.5 Fr); Rebar™ (ID 0.021" or 0.027", distal OD 2.3 or 2.8 Fr); Echelon™-10 (ID 0.017", distal OD 1.7 Fr); Echelon™~14 (ID 0.017", distal OD 1.9 Fr); and Nautica™ (ID 0.018", distal OD 2.2 Fr).

From Cordis Endovascular Systems (Miami Lakes, FL, USA) suitable microcatheters include Prowler®-10 (ID 0.015", distal OD 1.7 Fr); Prowler®-14 (ID 0.0165", distal OD 1.9 Fr); Prowler® Select™ LP ES (ID 0.021", distal OD 2.3 Fr); Prowler® Select™ Plus (ID 0.021", distal OD 2.3Fr); Prowler® Plus (ID 0.021", distal OD 2.3 Fr); Rapidtransil® (ID 0.021", distal OD 2.3 Fr); Transit® (ID 0.021", distal OD 2.5 Fr) and Masstransit® (ID 0.027", distal OD 2.8 Fr). From Boston Scientific (Natick, MA, USA) suitable microcatheters include

Excelsior SL-IO (ID 0.0165", distal OD 1.7 Fr); Excelsior SL-IOlS (ID 0.019", distal OD 2.0 Fr) and Tracker® ExcelTM-14 (ID 0.017", distal OD 1.9 Fr).

Generally, any suitable guide wire may be used in implementing the teachings of the invention. The selection of which guide wire to use to implement the teachings of the invention is dependent on the discretion of the medical professional and is usually based on medical criteria and availability. Suitable guide wires include commercially available guidewires available from a number of suppliers.

From ev3 Endovascular, Inc (Plymouth, MN, USA) suitable guidewires include Mirage™ (0.008"); SilverSpeed™ (0.010" or 0.014"); X~Celerator™ (0.010" or 0.014") and X-Pedion™ (0.010" or 0.012").

From Cordis Endovascular Systems (Miami Lakes, FL, USA) suitable guidewires include Agility® (0.010" - 0.016") and Essence® (0.012" - 0.018").

Generally, any suitable aneurysm-filler may be used in implementing the teachings of the invention.

In some embodiments, an aneurysm- filler comprises a solid material and the introduction of the aneurysm-filler includes pushing the aneurysm-filler into the

- 31 - aneurysm. Suitable solid materials include known solid aneurysm-fillers such as hairs, hog hairs, metal particles and coils (endovascular coils).

When endovascular coils are used as aneursym-fillers to implement the teachings of the invention, the selection of which endovascualr coil to use is dependent on the discretion of the medical professional and is usually based on medical criteria and availability. Suitable endovascular coils are made of any suitable material, and include but are not limited to platinum, platinum/tungsten and Nitinol.

Suitable commericially available coils include, but are not limited to Axium™, Nexus™ and NXT™ (ev3 Endovascular, Inc, Plymouth, MN, USA), Tπifill® and Trufill DCS Orbit™detachable coils (Cordis Endovascular Systems, Miami Lakes, FL,

USA) and GDC® detachable coils and Matrix® (Boston Scientific, Natick, MA, USA).

In some embodiments, an aneurysm-fiiler comprises a fluid, and the introduction of the aneurysm-fiiler includes injecting the fluid into the aneurysm. The selection of which fluid aneurysm-fϊiler to use is dependent on the discretion of the medical professional and is usually based on medical criteria and availability.

In some embodiments, the fluid comprises a solution and/or a suspension. In some embodiments, the fluid increases in viscosity and/or solidifies and/or polymerizes when inside an aneurysm. In embodiments, the aneurysm-fiiler is thrombogenic.

Suitable fluid aneurysm-fillers for implementing include but are not limited to known suitable materials, for example such as mentioned in US 5,667,767, US 5,580,568, WO/09920326 (which is included by reference as if fully set forth herein) and European patent EP 1207791. Such materials include polymers and prepolymers such as non-biodegradable polymers such as cellulose acetates (including cellulose diacetate and cellulose acetate), ethylene vinyl alcohol copolymers, hydrogels (e.g., acrylics), poly aery lonitrile, polyvinylacetate, cellulose acetate butyrate, nitrocellulose, copolymers of urethanelcarbonate, copolymers of styrene/maleic acid, and mixtures thereof as well as biodegradable polymers such as linear- chain polymers such as polylactides, polyglycolides, polycaprolactones, polyanhydrides, polyamides, polyurethanes, polyesteramides, polyorthoesters, polydioxanones, polyacetals, polyketals, polycarbonates, polyorthocarbonates, polyhydroxybulyrates, polyhydroxyvalerates, polyalkylene oxalates, polyalkylene succinates, poly(malic acid), poly(amino acids), poly hydroxy cellulose, chitin, chitosan, and copolymers, terpolymers and combinations thereof. Also suitable are poly(HEMA) and other poly aery lates,

cyanoacrylates (e.g., n-butyl cyanoacrylate), urethanes and silicones polymers). Additional aneurysm-filling materials include, but are not limited to particulates, gelatin, and sclerosing agents (see WO99/203261).

Suitable commercially available liquid embolic materials include but are not limited to OnyxR™ LES and OnyxR™ HD-500 (ethylene vinyl alcohoVDMSO solutions available from ev3 Endovascular, Inc., Plymouth, MN, USA) and Trafili® n- BCA (n-Buty] Cyanoacrylate / Ethiodized Oil available from from Cordis Endovascular Systems, Miami Lakes, FL, USA).

It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination or as suitable in any other described embodiment of the invention. Certain features described in the context of various embodiments are not to be considered essential features of those embodiments, unless the embodiment is inoperative without those elements.

Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims.

Citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the invention.

Section headings are used herein to ease understanding of the specification and should not be construed as necessarily limiting.