Occlusion device

RELATED APPLICATIONS All documents and references cited herein and in the above-referenced applications are hereby incorporated by reference.

The occlusion devices disclosed herein relate generally to the field of occlusion devices and/or occlusion device systems and/or implantable occlusion devices and the use of occlusion devices and/or occlusion device systems and/or implantable occlusion devices for the treatment and/or amelioration of vascular occlusion and/or aneurysms and/or for peripheral vascular embolization (a process well known in the art and known to involve the cessation of blood flow distal to a particular vascular site) in the treatment and/or amelioration of peripheral arterial or venous pathology and/or any related pathology requiring vascular occlusion for treatment.

There is a great need for the development of improved occlusion devices and/or systems for the treatment and/or amelioration of aneurysms. This view is supported by the abundance and breadth of current occlusion devices and/or systems in the current field of aneurysm peripheral embolization treatment. However, there remains an unmet need to provide aneurysm treatment and/or amelioration, particularly of neurovascular aneurysms, with occlusion devices that include deployable materials designed to achieve greater blood flow arrest and compartmentalization for induction of hemostasis and/or designed to occlude larger and/or more irregularly shaped aneurysms.

It is well known that aneurysms form when dilated sections of an artery are stretched thin by blood pressure. The weakened section of the artery forms a bulging or bulbous area that is at risk of leaking and/or rupturing. When a neurovascular aneurysm ruptures, it can cause bleeding into the subarachnoid space, the space that surrounds the brain, resulting in a subarachnoid hemorrhage. Subarachnoid hemorrhage from a ruptured neurovascular aneurysm can lead to hemorrhagic stroke, brain damage, and death. Approximately 25 percent of all patients with a neurovascular aneurysm will suffer from a subarachnoid hemorrhage. Neurovascular aneurysms affect 2-5 percent of the population and are more common in women than men. It is estimated that as many as 18 million people currently living in the United States will develop a neurovascular aneurysm in their lifetime. Each year, there are more than 30,000 cases of subarachnoid hemorrhage in the United States. 10-15 percent of these patients die before reaching the hospital, and more than 50 percent die within the first 30 days after the rupture. Of those who survive, about half suffer some kind of permanent neurological damage.

Smoking, high blood pressure, traumatic head injury, alcohol abuse, use of hormonal sterilization methods, a family history of cerebral aneurysms, and other genetic disorders such as Ehlers-Danlos syndrome (EDS), polycystic kidney disease, and Marfan syndrome may contribute to neurovascular aneurysms.

Most unruptured aneurysms are asymptomatic. Some people with unruptured aneurysms experience some or all of the following symptoms: impaired peripheral vision, impaired thinking or processing, difficulty speaking, impaired perception, sudden changes in attitude, loss of balance and coordination, poor concentration, short-term memory difficulties, and fatigue. Symptoms of a ruptured neurovascular aneurysm include nausea and vomiting, neck stiffness or pain, blurred or double vision, pain above and behind the eye, dilated pupils, sensitivity to light, and loss of sensation. Patients sometimes experience one of the symptoms of a ruptured neurovascular aneurysm, describing it as "the worst headache of my life."

Most aneurysms remain undetected until rupture occurs. However, aneurysms may be discovered during a routine physical exam or diagnostic procedures for other health problems. A ruptured brain aneurysm is typically diagnosed by finding signs of subarachnoid hemorrhage on a CT scan (computed tomography). If the CT scan is negative but a ruptured aneurysm is still suspected, a lumbar puncture is performed to detect blood in the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord.

Neuroradiologists use either cerebral angiography or tomographic angiography to identify the exact location, size and shape of the aneurysm. The traditional method of cerebral angiography involves introducing a catheter into an artery (usually in the leg) and advancing it through the body's vasculature to the artery involved in the aneurysm. A special dye called a contrast agent is injected into the patient's artery, and its distribution is shown on an x-ray projection. This method may not detect some aneurysms due to overlying structures or spasm.

Computed tomography angiography (CTA) is an alternative to traditional methods and can be performed without the need for arterial catheterization. The test combines a regular CT scan with the injection of a contrast dye into a vein. Once the dye is injected into the vein, it travels to the cerebral arteries, where images are formed using a CT scan. These images show exactly how blood flows into the cerebral arteries. New diagnostic modalities promise to complement both traditional and conventional diagnostic studies with minimally invasive imaging, potentially providing more precise three-dimensional anatomical information about aneurysmal pathology. Better imaging, in combination with the development of improved minimally invasive treatments, will allow physicians to increasingly detect and treat more silent aneurysms before they cause problems.

Several methods of treating aneurysms have been attempted with varying degrees of success. For example, craniotomy is a procedure in which an aneurysm is identified and treated extravascularly. This type of procedure has significant drawbacks, including the fact that the patient experiences significant trauma in the area of the aneurysm due to the surgeon having to cut through various tissues to reach the aneurysm. To treat a cerebral aneurysm extravascularly, for example, the surgeon must generally remove part of the patient's skull and must also damage brain tissue to reach the aneurysm. This can cause the patient to develop epilepsy as a result of the surgery.

Other procedures used to treat aneurysms are performed endovascularly. Such procedures generally involve attempting to create a mass within the aneurysm sac. A microcatheter is generally used to access the aneurysm. The distal tip of the microcatheter is placed within the aneurysm sac and the microcatheter is used to inject embolic material into the aneurysm sac. Embolic materials include, for example, detachable coils or embolic agents such as liquid polymers. There are drawbacks to injecting these types of embolic materials, most of which are related to the escape of the embolic material from the aneurysm into the parent artery. This can cause permanent and irreversible occlusion of the parent artery.

For example, when detachable coils are used to occlude an aneurysm that does not have a well-defined neck region, the detachable coils may escape from the aneurysm sac into the parent artery. Additionally, it may be difficult to gauge exactly how full the aneurysm sac is when the detachable coil is deployed. This creates a risk of overfilling the aneurysm, which again will result in the detachable coils spilling out into the parent artery.

Another drawback of detachable coils includes compaction of the coils over time. After filling of the aneurysm, spaces remain between the coils. The ongoing hemodynamic forces of the circulation act to compact the coil mass, creating a cavity at the aneurysm neck. This can lead to recanalization of the aneurysm.

Dislodgement of the embolic agent is also an issue. For example, if a liquid polymer is injected into the aneurysm sac, the hemodynamics of the system can cause the liquid polymer to dislodge from the aneurysm sac. This can also lead to irreversible occlusion of the parent vessel.

Approaches have been attempted to address the shortcomings associated with the escape of embolic material into the parent vessel. Such approaches include, but are not limited to, temporary blood flow arrest and parent vessel occlusion, which generally involves temporarily occluding the parent vessel proximal to the aneurysm such that blood flow to the parent vessel does not occur until a thrombus mass forms within the aneurysm sac. In theory, this reduces the tendency for embolic material to escape from the aneurysm sac. However, it has been found that the thrombus mass may dissolve with normal dissolution of blood. Also, in some cases, from a patient risk/benefit perspective, it is highly undesirable to even temporarily occlude the parent vessel. Thus, this approach may not be available as a treatment option. In addition, it is now known that occlusion of the parent vessel does not prevent the escape of all embolic material into the parent vessel.

Another endovascular approach to treating aneurysms involves inserting a detachable balloon into the aneurysm sac using a microcatheter. The detachable balloon is then inflated with saline and/or contrast fluid. The balloon is then detached from the microcatheter and left in the aneurysm sac to attempt to fill the aneurysm sac. However, detachable balloons also have drawbacks, and this approach has been largely replaced by the current approach of coil placement or other types of occlusion devices. For example, detachable balloons, when inflated, generally do not conform to the internal configuration of the aneurysm sac. Instead, detachable balloons require the aneurysm sac to conform to the exterior surface of the detachable balloon. This increases the risk that the detachable balloon will rupture the aneurysm sac. Furthermore, the detachable balloon may rupture and dislodge from the aneurysm.

Another endovascular approach to treating aneurysms involves an occlusion device having two expandable lobes and a waist, or an expandable body portion, a neck and a base.

Yet another endovascular approach for treating aneurysms involves an occlusion device for intrasaccular implantation having a body portion designed to fill and/or radially expand within the intrasaccular space of the aneurysm.

Yet another endovascular approach is disclosed in commonly owned, pending US patent application Ser. No. 14/699,188, which is incorporated herein by reference in its entirety.

Many of the current occlusion devices are not designed for the treatment of large aneurysms or aneurysms of irregular shapes and sizes, including, for example, wide and narrow neck aneurysms, sidewall and bifurcation aneurysms. Many of the current occlusion devices are constructed with a braided or woven mesh design, which, when reconfigured for large and irregular shaped aneurysms, generally use too much material. This makes them difficult to collapse into a confined, low-profile delivery configuration that is small enough to be delivered and placed without excessive friction on the walls of a delivery catheter or other delivery lumen. The sheer bulk of these devices makes them inconvenient or unsuitable for intracranial delivery.

Thus, the occlusion device disclosed herein provides an innovative improvement and several advantages in the field of vascular occlusion devices, as it provides aneurysm and/or body cavity treatment and/or improvement, particularly for larger and more irregularly sized neurovascular aneurysms, through the use of a super-compactable continuous mesh-based fully retrievable deployable material. The occlusion device disclosed herein includes a mesh-based deployable continuous structure that is configured end-to-end with a compressible axial mesh carriage that defines a clamping point at either end of the continuous mesh structure. This novel design provides greater blood flow obstruction and compartmentalization within the aneurysm or body cavity, resulting in increased hemostasis, particularly for occluding larger and more irregularly shaped aneurysms.

All documents and references cited herein and in the referenced patents are hereby incorporated by reference.

<p>The inventors have designed an intra-aneurysmal occlusion device for placement within the aneurysmal sac to provide aneurysm treatment and/or amelioration by creating blood flow arrest and eventual hemostasis. The occlusion device uniquely comprises a series of compressible mesh carriages with distinct clamping points at each end that define the carriage and provide a continuous three-dimensional mesh network within the aneurysm for blood flow arrest, thrombus formation and/or a framework for cell growth. Such implantable occlusion devices are also used for the treatment of vascular occlusion and/or peripheral vascular embolization.</p><p>Disclosed herein is an occlusion device for implantation within a body cavity or aneurysm, the occlusion device including a continuous compressible mesh structure including axial mesh carriages configured end-to-end, each end of each carriage being a clamping point for the continuous mesh structure.</p><p>In one embodiment, the marker surrounds and covers at least one pinch point of the continuous mesh structure, hi a further embodiment, the marker is radiopaque.</p><p>In another embodiment, at least one mesh carriage of the continuous mesh structure includes an inner coaxial mesh carriage or a plurality of inner coaxial mesh carriages. In a further embodiment, the inner coaxial mesh carriage or the plurality of carriages is a different material than the outer mesh carriage. In a further embodiment, the plurality of inner coaxial mesh carriages is two or three inner coaxial mesh carriages. In another further embodiment, the inner coaxial mesh carriage or the plurality of carriages is a different mesh density than the outer mesh carriage.</p><p>In another embodiment, the continuous mesh structure expands into a deployed configuration and fills the body cavity or aneurysm.</p><p>In another embodiment, the number (n) of axial mesh carriages is 2, 3, 4 or 5 axial mesh carriages.</p><p>Also disclosed herein is a kit for the treatment and/or amelioration of a body cavity or aneurysm. The kit includes an occlusion device for implantation within a body cavity or aneurysm, the occlusion device including a continuous compressible mesh structure including axial mesh carriages configured end-to-end, each end of each carriage being a clamping point for the continuous mesh structure, and a delivery or detachment system corresponding to the occlusion device. In one embodiment, the delivery system of the kit is a microcatheter, catheter, guidewire, or pusher wire. In another embodiment, the detachment system of the kit is an electrolytic detachment system.</p><p>Also disclosed herein is a method for treating or ameliorating a body cavity or aneurysm in a patient, the method including delivering an occlusion device to a body cavity or aneurysm including a continuous compressible mesh structure including axial mesh carriages configured end-to-end, each end of each carriage being a clamping point of the continuous mesh structure, and placing the occlusion device within the aneurysm, thereby treating or ameliorating the aneurysm in the patient.</p><p>In another embodiment, disclosed herein is an occlusion device for implantation within a body cavity or aneurysm, the occlusion device including a compressible continuous mesh structure including an axial mesh carriage, each end of the carriage being a pinch point for the continuous mesh structure, the carriage including an inner coaxial mesh carriage.</p><p>Further disclosed herein are methods for making and/or delivering and/or deploying the occlusion devices disclosed herein.</p><p>In other embodiments, the occlusion device of the preceding paragraph may incorporate any of the embodiments disclosed previously or subsequently.</p><p>This Summary is not intended to define the claims or to limit the scope of the invention in any way.</p><p>Other features and advantages of the invention will become apparent from the following drawings, detailed description, and claims.</p>

<figref num="1A">1A-1D show perspective views of one embodiment of an occlusion device as disclosed herein: FIG 1A shows a mesh carriage embodiment of an occlusion device as disclosed herein;</figref><figref num="1B">1A-1C show perspective views of one embodiment of an occlusion device as disclosed herein.FIG 1B shows a series of mesh carriages of an occlusion device as disclosed herein.</figref><figref num="2">1 illustrates a perspective view of one embodiment of a series of variable mesh carriages of an occlusion device disclosed herein.</figref><figref num="3">1 shows a perspective view of one embodiment of a delivery and/or placement of an occlusion device disclosed herein having a series of mesh carriages.</figref><figref num="4">1 shows a perspective view of one embodiment of an occlusion device disclosed herein having a series of mesh carriages placed within an aneurysm.</figref><figref num="5">1 shows a perspective view of one embodiment of an occlusion device disclosed herein having a mesh carriage that includes an inner coaxial mesh carriage.</figref><figref num="6">1 shows a perspective view of one embodiment of an occlusion device disclosed herein having a mesh carriage that includes an inner coaxial mesh carriage.</figref><figref num="7">FIG. 1 shows a perspective view of one embodiment of electrolytic delivery and/or placement and/or detachment of an occlusion device disclosed herein, illustrating delivery via a catheter lumen and/or pusher wire having a mesh carriage and an electrolytic means of an occlusion device disclosed herein having an internal mesh carriage.</figref><figref num="8">FIG. 1 shows a perspective view of one embodiment of electrolytic delivery and/or placement and/or detachment of an occlusion device disclosed herein, illustrating placement of the device and electrolytic detachment of a pusher wire from an occlusion device disclosed herein having a series of mesh carriages and an inner coaxial mesh carriage.</figref><figref num="9">FIG. 1 shows a perspective view of one embodiment of an occlusion device disclosed herein having a series of two variable-sized mesh carriages.</figref><figref num="10">1 shows a perspective view of one embodiment of an occlusion device disclosed herein having a series of two variable-sized mesh carriages placed within an aneurysm.</figref>

The occlusion devices disclosed herein are shown in the drawings and specification, in which like elements are assigned like reference numbers. However, although specific embodiments are shown in the drawings, there is no intention to limit the occlusion devices disclosed herein to the specific embodiment or embodiments disclosed. Rather, the occlusion devices disclosed herein are intended to encompass all modifications, alternative constructions, and equivalents that are within the scope and spirit of the invention. Thus, the drawings are illustrative and not intended to be limiting.

Unless otherwise defined, all technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this technology belongs.

Exemplary embodiments of the occlusion devices disclosed herein are shown in FIGS.

For purposes of the occlusion devices disclosed herein, the term "corresponds to" means that there is a functional and/or mechanical relationship between objects that correspond to one another. For example, an occlusion device delivery system corresponds to (or is compatible with) an occlusion device for its placement.

For purposes of the occlusion devices disclosed herein, the term "occlusion device" may refer to and/or be interchangeable with terms such as, but not limited to, "device" or "occlusion device system" or "occlusion system" or "system" or "occlusion device implant" or "implant" or "intrasaccular implant" or "intraaneurysmal implant", etc.

Occlusion device delivery systems are well known in the art and are readily available. For example, such delivery techniques may be described, but are not limited to, in U.S. Pat. Nos. 4,991,602, 5,067,489, 6,833,003, U.S. Patent Application Publication No. 2006/0167494, and 2007/0288083. Each of these teachings is incorporated herein by reference. For the purposes of the occlusion devices disclosed herein, any type of occlusion device delivery means and/or delivery systems and/or delivery techniques and/or delivery mechanisms and/or detachment (and/or attachment) means and/or detachment systems and/or detachment techniques and/or detachment mechanisms may be used and/or modified in a manner compatible with the occlusion devices disclosed herein. Exemplary occlusion device delivery mechanisms and/or systems include, but are not limited to, guidewires, pusher wires, catheters, microcatheters, and the like. Exemplary occlusion device detachment mechanisms include, but are not limited to, fluid pressure, electrolytic mechanisms, hydraulic mechanisms, interlock mechanisms, and the like. In one embodiment, the occlusion devices disclosed herein are used in a method of electrolytic detachment. Electrolytic detachment is well known in the art and can be described, for example, in U.S. Pat. Nos. 5,122,136, 5,423,829, 5,624,449, 5,891,128, 6,123,714, 6,589,230, and 6,620,152.

The occlusion devices disclosed herein include a series of compressible mesh carriages 20 with a separate pinch point 10 at each end of each carriage 20. In this regard, the occlusion device design is one continuous three-dimensional mesh network that, when placed within an aneurysm 90 or body cavity, provides blood flow arrest, thrombus formation, a framework for cell growth and/or eventual hemostasis. For purposes of the claimed invention, a "carriage" 20 is each pinch point 10 or an axial section of mesh between pinch points 10 that are surrounded and covered by each marker 50. A "pinch point" 10 is located at and defines the end of an axial section of mesh. Such segmented mesh carriages 20 and pinch points 10 are often within a continuous mesh structure or network. The "pinch points" function as constrained, grouped locations of the mesh structure to limit movement of adjacent carriages at a distance, thereby stabilizing the carriages relative to one another. The number (n) of these carriages 20 is as large as clinically and practically possible, and is predetermined by the clinician according to known diagnostic techniques for treating large and/or irregular sized aneurysms 90, and for delivery through a catheter 70 (or microcatheter) of about 150 centimeters (cm). The length (x) 30 of each carriage 20 can vary depending on the number (n) of carriages 20 deemed appropriate to occlude a given size aneurysm 90, so long as the length (x) 30 is sufficient to expand the carriage 20 to dimension y (width 40) in "free gas". As accepted in the art, the diameter of such an occlusion device is measured in free gas. The width (y) 40 of each carriage 20 ranges from about 2 millimeters (mm) to about 50 mm (in free gas) to be clinically feasible. When deployed, the carriages 20 compress in such a way that the diameter or width (y) 40 increases or expands by approximately two such that a carriage 20 of dimension y40 can increase to approximately twice (or 2y) y40. In other words, each carriage 20 compresses like a marshmallow, causing a decrease in x30 and an increase in y40. In one embodiment, in free gas, each carriage 20 can be designed such that x30 is greater than or equal to y40, but in the deployed (compressed) configuration, y40 is greater than x30. Such an occlusion device including a series of compressible carriages 20 can be adjustable and configured to select the number (n) of carriages 20 and the length (x) 30 and width (y) 40 of each carriage 20 to accommodate a wide range of sizes and shapes of aneurysms 90 or body cavities to be treated. Thus, in another embodiment, in free gas, each carriage 20 can be designed such that x30 is less than or equal to y40, and in the parked (compressed) configuration, y40 remains greater than x30.

In one embodiment, the device is made of metal braids of readily available materials, such as, but not limited to, Nitinol (NiTi), cobalt chromium (CoCr) alloy, stainless steel, tungsten iridium alloy, or combinations thereof. For example, the mesh carriage 20 is woven with the most clinically appropriate and practical braided mesh, ranging from as few as 36 braids to as many as 144 braids. In another embodiment, the softest compressible mesh design is created by the weave angle of the metal braid construction. For example, the mesh is braided with wires with diameters of about 0.0075 inches to about 0.005 inches. Thus, the occlusion device disclosed herein is a series of ultra-soft, axially compressible mesh carriages 20, where n is the number of mesh carriages 20 in a single occlusion device. Prior to using such an occlusion device with "n" carriages, the clinician or physician uses readily available diagnostic techniques to identify the size and shape of the aneurysm or body cavity to be treated. The physician or clinician can then optimally select an occlusion device having a desired number (n) of carriages and various sizes of carriages to be used to optimally treat a given aneurysm or body cavity.

FIG. 1A shows an exemplary embodiment of a single mesh carriage 20 having an axial length (x) 30 greater than its width (y) 40 in free gas, with each end of the carriage 20 being a pinch point 10. In another embodiment, the axial carriage 20 may have an axial length (x) 30 equal to its width (y) 40 in free gas. In yet another embodiment, the axial carriage 20 may have an axial length (x) 30 less than its width (y) 40 in free gas. FIG. 1B shows one embodiment of a series of axial mesh segmented carriages 20 that are continuous compressible mesh structures, n=3 axial mesh carriages 20, with each pinch point 10 surrounded and covered by a marker 50. "Markers" are well known and readily available in the medical device art. In some embodiments, the markers are made of a metallic material, often a radiopaque material, and take shapes such as band-shaped markers, ring-shaped markers, tube-shaped, etc. to surround and cover the pinch points of the occlusion device. Alternatively, the markers may consist of wire strands wrapped around and thus surrounding a given pinch point. In one embodiment, the markers 50 surrounding and covering each pinch point 10 provide a positional reference under x-ray as to where the device is within the catheter 70 (or microcatheter) and where it will be after placement within the aneurysm 90 or body cavity. Figure 2 shows an exemplary embodiment of a series of variable sized (varying sizes and/or diameters) segmented axial mesh carriages 20 that are continuous compressible mesh structures, n=3 axial mesh carriages 20, each carriage 20 differing in terms of dimensions x30 and y40, and each pinch point 10 surrounded and covered by a marker 50. 2, the first carriage 20 (on the right) to enter the aneurysm 90 has a diameter or width (y) 40 that is slightly larger than the maximum measured diameter of the aneurysm 90 being treated, so that the continuous mesh structure of the device does not contact the dome of the aneurysm 90, which is often the thinnest and most sensitive area of the aneurysm 90 wall. Additionally, in this configuration shown in FIG. 2, the diameter or width (y) 40 of the last carriage 20 (on the left) to enter the aneurysm 90 is larger than the aneurysm neck 100, so that this last carriage 20 remains firmly anchored (and anchored) within the aneurysm 90.

3 shows one embodiment of an occlusion device disclosed herein with the constrained mesh carriage 20 of the device loaded within the lumen of a catheter 70. The device is advanced by an electrolytic pusher wire 60 having an electrolytic detachment region 80, and once deployed, the carriage 20 expands upon exiting the tip of the catheter 70 to occupy the volume of the aneurysm 90 or body cavity. As the next axial carriage 20 is deployed within the aneurysm 90, the axial carriages 20 compress against each other, filling the aneurysm 90 and forming a series of layers and/or compartments within the aneurysm 90 or body cavity to impede blood flow and ultimately result in hemostasis.

4 shows one embodiment of an occlusion device disclosed herein deployed within an aneurysm 90 to be treated. The compressible mesh carriage 20 forms multiple compartmentalized layers within the aneurysm 90 sac. In this deployed configuration, the axial carriage 20 fills the aneurysm 90 or body cavity in layers or compartments, thereby changing the deployed axial length (x) 30 relative to its ratio of the axial length 30 in free gas. For example, the deployed axial length (x) 30 is about 5% to about 50% of the axial length 30 in free gas.

9 and 10 show an embodiment of the occlusion device disclosed herein. In such an embodiment, the distal carriage 20 (top carriage 20 in Figs. 9 and 10) expands into the aneurysm 90 to provide a stable structure for the next carriage 20 of variable size to push against, thereby stabilizing the device as it is positioned across (or within) the aneurysm neck 100. In such a configuration and in one embodiment, the hourglass-like shape 130 of the distal carriage 20 following the pinch points 10 and/or markers 50 between the carriages 20 contributes to the overall stability of the device. In another embodiment, the hourglass-like shape 130 of the distal carriage 20 is defined by a protrusion pointing outward toward the next carriage 20, rather than recessing inward on itself. Figs. 9 and 10 show the force distribution by arrows. The force (F) distributes a force or pressure to the distal carriage 20, which stably implants and secures the device in place within the aneurysm 90. As with the other variable configurations of the series of carriages 20 shown in Figure 2, Figure 10 shows that the diameter or width (y) 40 of the last carriage 20 to enter the aneurysm 90 is larger than the aneurysm neck 100, keeping this last carriage 20 firmly anchored (and lodged) within the aneurysm 90 to impede blood flow and ultimately provide hemostasis.

Without wishing to be bound by theory, this configuration of a continuous compressible mesh structure divided into segments of the axial carriage 20 gives rise to a mechanism of action believed to contribute to the enhanced acute thrombogenicity of the device in animal studies. It is also believed to promote the aggregation and stabilization of thrombus within the aneurysm 90 by localizing small volumes of clots between the successive carriage 20 layers and segments, where the wire strands contribute a large amount of surface area. The compartmentalization of this occlusion device in its deployed configuration is an effective stabilizing or fixation function of the deployed device, as blood exerts pressure on the mesh structure distributed across or within the aneurysm neck 100. Such a configuration also provides sufficient apposition of the compressible device against the aneurysm 90 wall or vessel wall for peripheral arterial or venous occlusion. The devices disclosed herein provide sufficient mesh density to acutely provide hemostasis, and the distribution of the wire mesh/braids remains relatively uniform upon deployment.

In another embodiment of the occlusion devices disclosed herein, the compressible axial mesh carriage 20 includes a relatively uniform distribution of wire mesh strands or braids, such as, but not limited to, a 72 NiTi wire mesh strand braid configuration or a combination of 72 NiTi and CoCr wire mesh strand braid configurations. In other embodiments, the occlusion device includes wire mesh strands or braids in a range of 36-144 NiTi strand braid configurations.

FIG. 5 shows a single compressible axial mesh carriage 20 including one coaxial inner mesh carriage 120. FIG. 6 shows a single axial mesh carriage 20 including multiple coaxial inner mesh carriages 120. Such a coaxial mesh inner 120 or coaxial mesh inner 120 creates greater hemostatic and compartmentalization than an axial mesh carriage 20 without a coaxial mesh inner carriage 120, thereby resulting in hemostasis and thrombus stabilization. In another embodiment, the axial carriage 20 and one coaxial carriage 120 (or carriages) are composed of dissimilar metal meshes. In a further embodiment, the dissimilar metal meshes create a galvanic effect that can further enhance the development of thrombus. In another further embodiment, the dissimilar metal meshes can include one metal in one carriage 20 that has radiopaque properties relative to the metals of the other carriages 20, 120, thereby improving visualization of the device. In such an embodiment, the braid mesh density may be the same or different between the axial outer carriage 20 and the coaxial inner carriage 120, and the wires of the inner mesh and the wires of the outer mesh may have different numbers of strands and wire diameters. Such a coaxial carriage or carriages 120 may vary in size compared to the outer axial carriage 20. For example, in one embodiment, the coaxial carriage or carriages 120 may range from about 5% to about 95% of the size of the outer axial carriage 20 that contains the coaxial carriage or carriages 120. FIG. 7 shows the axial carriage 20 and the coaxial carriage 120 loaded within the lumen of the catheter 70, and FIG. 8 shows the electrolytic device placement by the electrolytic detachable pusher wire 60 and the extension of the carriages 20, 120 (external and internal) out of the tip of the catheter 70.

In one embodiment, a marker 50, such as a ring, surrounds and covers the pinch points 10 that define each end of each carriage 20, 120 of the continuous mesh structure. Thus, the marker 50 of the occlusion device disclosed herein is a substantially solid collar or rigid member, such as, but not limited to, a solid ring or band, including materials such as, but not limited to, gold, platinum, stainless steel, and/or combinations thereof. In another embodiment, radiopaque materials may be used, such as, but not limited to, gold, platinum, platinum/iridium alloys, and/or combinations thereof. Such markers 50 provide visualization of the device's location during delivery and deployment. The markers 50 are positioned on the occlusion device to surround and cover the pinch points 10 at each end of each carriage 20, 120. In this manner, the marker 50 at the proximal end of the proximal carriage 20, 120 can be placed above or within the neck 100 of the aneurysm 90. The solid nature of the marker 50 provides stability for the device within the aneurysm 90 and prevents misplacement or accidental migration of the device by preventing the movement or transmission of forces through the compressible mesh carriage 20, 120. The marker 50 is also configured with a joint for coupling with and releasing/attaching to a corresponding delivery means, such as, but not limited to, a delivery catheter 70 or guidewire 60 and/or pusher wire technology. The marker 50 also advantageously provides full retrievability of the devices disclosed herein.

In another embodiment, the substantially solid marker 50 comprises a radiopaque material (such as, but not limited to, platinum, gold, platinum/iridium alloys, and/or combinations thereof) to facilitate visualization of the occlusion device under fluoroscopy during delivery, placement, and/or deployment. The marker 50 includes a proximal end and a distal end. The occlusion devices disclosed herein may be configured to incorporate the use of markers to affect the shape, diameter, and/or curvature of the compressible carriage 20, 120 as it expands during deployment. Additionally, the marker 50 may be designed with various shapes to affect the overall profile of the occlusion device having a series of mesh carriages 20, 120 to ensure proper fit of the expanded/deployed occlusion device within the aneurysm 90 sac.

3, 7 and 8 show exemplary means for electrolytic delivery and/or placement and/or detachment of the occlusion device disclosed herein through an artery and/or vessel 110 adjacent to an aneurysm 90 or body cavity. Electrolytic detachment means and methods are known in the art, such as U.S. Pat. No. 5,122,136. In one embodiment, the distal-most end of the coiled core wire 60 (or guidewire or pusher wire) of a catheter 70 (or microcatheter) is attached to the occlusion device disclosed herein (as shown in FIGS. 3, 7 and 8) within a marker 50. The coiled turns maintain a constant diameter (φ) so as not to affect the flexibility or stiffness of the delivery catheter 70 or microcatheter or guidewire 60. In one embodiment, FEP (fluorinated ethylene propylene) heat shrink tubing covers the coiled portion of the core wire. Many readily available and well-known attachment techniques in the medical device art can be used to attach the distal end of the core wire within the marker and to the occlusion device or implant. Such attachment techniques include, but are not limited to, adhesives, laser melting, laser gluing, spot welding, and/or continuous welding. In one embodiment, an adhesive is used to attach the distal end of the core wire inside the marker. In a further embodiment, the adhesive is an epoxy material that is cured or hardened by application of heat or UV (ultraviolet) radiation. In yet another embodiment, the epoxy is a thermally cured two-part epoxy, such as EPO-TEK® 353ND-4, available from Epoxy Technology, Inc., 14 Fortune Drive, Billerica, Mass. Such an adhesive or epoxy material coats the joint of the core wire inside the marker 50 and increases its mechanical stability.

In another embodiment, during and/or after deployment of the device, the coiled core wire 60 automatically detaches the occlusion device disclosed herein at the electrolytic detachment location 80 (or region) of the core wire 60 such that the core wire 60 is cut and/or dissolved by electrolytic action at the base of the marker 50. Such action then releases and/or places the occlusion device within the aneurysm 90 or blood vessel being treated.

In some embodiments, the compressible mesh structure of the occlusion devices disclosed herein may be filled with an embolic material to promote clotting and closure of the aneurysm 90 .

In other embodiments, the occlusion devices disclosed herein may further incorporate additional elements and/or components such as coiling techniques, framing coils, embolic materials, additional markers, polymers, absorbent polymers, and/or combinations thereof.

Elastic and compressible mesh materials for designing and/or manufacturing occlusion devices are readily available and well known to those skilled in the art. Thus, elastic and compressible mesh materials span a wide range of available materials, such as, but not limited to, nickel titanium (Nitinol or otherwise known as NiTi), stainless steel, polymers, and/or combinations thereof. Exemplary known biomedical polymers include, but are not limited to, polymers such as polyphosphazenes, polyanhydrides, polyacetals, poly(orthoesters), polyphosphoesters, polycaprolactones, polyurethanes, polylactides, polycarbonates, polyamides, and/or combinations thereof. (See, e.g., J Polym Sci B Polym Phys.Author manuscript; available in PMC 2012 June 15.)

In one exemplary embodiment, the elastic and compressible mesh material is formed of woven strands of polymeric material, such as, but not limited to, nylon, polypropylene, or polyester. The polymeric strands can be filled with a radiopaque material to allow the physician treating the aneurysm to view the location of the device within the vasculature under fluoroscopy. The radiopaque filler preferably includes bismuth trioxide, tungsten, titanium dioxide, or barium sulfate, or a radiopaque dye such as iodine. The elastic and compressible mesh material can be formed by strands of radiopaque material. The radiopaque strands allow the physician and/or radiologist to view the location of the mesh under fluoroscopy without the use of a filled polymeric material. Such radiopaque strands may be formed of materials such as, but not limited to, gold, platinum, platinum/iridium alloys, and/or combinations thereof. In one embodiment, the elastic mesh material is comprised of 10%-45% platinum core NiTi. In another embodiment, the elastic mesh material is comprised of 10% platinum core NiTi, 15% platinum core NiTi, 20% platinum core NiTi, or 45% platinum core NiTi, with the 10% platinum core NiTi construction being sufficient to provide a ghost image of the occlusion device under x-ray.

Combinations of wires or composite wires with a radiopaque core and a non-radiopaque outer layer or casing constructed in this manner are readily available and are known in medical device and metallurgy as DFT® (stretched filled tube) wires, cables, or ribbons. DFT® wires are metal-metal composites constructed to combine the desired physical and mechanical properties of two or more materials in one wire. By placing a more radiopaque but more ductile material in the core of the wire, the NiTi outer layer can give the resulting composite wire similar mechanical properties to a 100% NiTi wire. DFT® wires are available from Fort Wayne Metals Corp., Fort Wayne, Ind., USA. See also, for example, the article entitled Biocompatible Wire by Schaffer in Advanced Materials &amp; Processes, Oct 2002, pages 51-54, which is incorporated herein by reference.

If the compressible mesh structure is formed of radiopaque metal strands, the strands may be coated with a polymer coating or extrusion. A coating or extrusion over the radiopaque wire strands provides fluoroscopic visualization, but may also increase the resistance of the strands to bending fatigue and may also increase the lubricity of the strands. In one embodiment, the polymer coating or extrusion is coated or treated with an agent that has anticoagulant tendencies, such as heparin. Such anticoagulant coatings are generally known. The polymer coating or extrusion may be any suitable extrudable polymer, or any polymer that can be applied in a thin coating, such as Teflon® or polyurethane.

In yet another embodiment, the strands of the compressible mesh structure are formed using both metallic braided strands and polymeric braided strands. Combining metallic strands with polymeric strands to form a braid changes the flexibility properties of the mesh. The force required to deploy and/or collapse such a mesh section is significantly reduced compared to the force required for a mesh section that includes only metallic mesh strands. However, the radiopaque properties of the mesh for fluoroscopic visualization are maintained. Metallic strands forming such devices include, but are not limited to, stainless steel, gold, platinum, platinum/iridium, nitinol, and/or combinations thereof. Polymeric strands forming the devices may include nylon, polypropylene, polyester, Teflon®, and/or combinations thereof. Additionally, the polymeric strands of the mesh material can be chemically modified to render them radiopaque by well-known techniques, such as, but not limited to, using gold deposition on the polymeric strands, or using ion beam plasma deposition of appropriate metal ions on the polymeric strands.

The compressible mesh structure may also be formed with filaments or strands of various diameters and/or various flexibility. For example, wire diameters for use in the occlusion devices disclosed herein range from about 0.0075 inches to about 0.005 inches. By varying the size or flexibility of the polymer strands, the flexibility characteristics of the mesh during deployment can also be varied. By varying the flexibility characteristics, both the deployed (compressed) and delivery (restrained) configurations of the elastic and compressible mesh structure can be altered or varied to virtually any desired shape.

The mesh can be formed with both polymeric and metallic strands or filaments, as well as using filaments of different polymeric materials. For example, different polymeric materials having different flexibility properties can be used to form the mesh, thereby altering the flexibility properties and resulting configuration of the mesh structure in both the deployed and collapsed states. Such biomedical polymers are known and available in the art and can be derived from polymers such as, but not limited to, polyphosphazenes, polyanhydrides, polyacetals, poly(orthoesters), polyphosphoesters, polycaprolactones, polyurethanes, polylactides, polycarbonates, polyamides, and/or combinations thereof.

Compressible mesh materials suitable for use in the mesh carriage may take the form of flat woven sheets, knitted sheets, or laser cut wire mesh. Generally, the material should include two or more sets of substantially parallel strands, with one set of parallel strands at a pitch of 45 degrees to 135 degrees relative to the other set of parallel strands. In some embodiments, the two sets of parallel strands forming the mesh material are substantially perpendicular to each other. The pitch and overall structure of the mesh material may be optimized to meet the performance requirements of the occlusion device.

The wire strands of the metal fabric used in the occlusion device disclosed herein should be made of a material that is both elastic and compressible and can be heat treated to substantially set the desired shape. Materials that may be suitable for this purpose include a cobalt-based low thermal expansion alloy known in the occlusion device field as Elgiloy®, a nickel-based high temperature, high strength "superalloy" sold by Haynes International under the trade name Hastelloy®, a nickel-based heat treatable alloy sold by International Nickel under the name Incoloy®, and several different grades of stainless steel. An important factor in selecting a suitable material for the wire is that it maintains the appropriate amount of deformation induced by the forming surface (or shape memory, as described below) when exposed to a given heat treatment.

One class of materials that meets these conditions are so-called shape memory alloys. Such alloys tend to have a temperature induced phase change whereby the material has a preferred configuration that can be fixed by heating the material above a particular transition temperature and inducing a change in the material's phase. When the alloy cools, it "remembers" the shape it had at the time of heat treatment and will tend to assume this same and/or similar configuration unless restrained from doing so.

One particular shape memory alloy for use in the occlusion devices disclosed herein is Nitinol, which is a near stoichiometric alloy of nickel and titanium, and may also contain other trace amounts of other metals to obtain desired properties. NiTi alloys such as Nitinol, including the appropriate composition and handling requirements, are well known in the art, and such alloys need not be described in detail herein. For example, U.S. Pat. Nos. 5,067,489 and 4,991,602, the teachings of which are incorporated herein by reference, discuss the use of shape memory NiTi alloys in guidewire-based technology. Such NiTi alloys are preferred, at least in part, because they are commercially available and the handling of such alloys is more well known than other known shape memory alloys. NiTi alloys are also highly elastic. In fact, NiTi alloys are said to be known as "superelastic" or "pseudoelastic". This elasticity allows the occlusion devices disclosed herein to return to their previous expanded configuration for deployment.

The wire strands may comprise standard monofilaments of the selected material, i.e., standard wire stock may be used. In some embodiments, 72 wire strands and/or 72 strand braid configurations are used. In other embodiments, the occlusion device comprises wire mesh strands or braids ranging from 36 to 144 NiTi strand braid configurations. However, if desired, the individual wire strands may be formed from a "cable" comprised of multiple individual wires. For example, cables made of metal wires with several wires helically wound around a central wire are commercially available, and NiTi cables having an outside diameter of 0.003 inches or less can be purchased. One advantage of some cables is that they tend to be "softer" than monofilament wires of the same diameter and made of the same material. In addition, the use of cables can increase the effective surface area of the wire strands, which tends to promote thrombus formation.

The occlusion devices disclosed herein are comprised of a continuous mesh structure with a series of compressible axial carriages 20 (defined by pinch points 10) that have sufficient mesh density to act like an endothelial cell scaffold layer or section, filling a vessel or body cavity or aneurysm 90 and reducing blood flow by about 60%, resulting in clot formation and/or healing and/or eventual hemostasis of the aneurysm 90. For the purposes of the occlusion devices disclosed herein, the term "mesh density" refers to the level of porosity or the ratio of metal to open area of the mesh structure. Mesh density relates to the number and size of the mesh openings or holes, as well as the degree to which the holes are open or closed in situations where the opening or hole openness changes between delivery and deployment. Generally, high mesh density regions of elastic mesh materials have a metal area of about 40% or more and an open area of about 60% or less.

In some embodiments, the compressible mesh structure may be uniformly formed of the same material, however, such material may have different knitted, sewn, braided and/or cut structures.

In other embodiments, the implantable occlusion devices disclosed herein may be used in the process of peripheral vascular embolization (a process well known in the art and known to involve the cessation of blood flow distal to a particular vascular site), for example, in the treatment and/or amelioration of peripheral arterial or venous pathology and/or any related pathology that requires vascular occlusion for treatment.

The occlusion devices disclosed herein may incorporate reasonable design parameters, features, modifications, advantages and variations that would be apparent to one of ordinary skill in the art of occlusion devices.

<p>The research protocol and animal use justification for the occlusion devices disclosed herein were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of ISIS Services, and procedures were performed under veterinary supervision.</p><p>The rabbit elastase aneurysm model is a widely accepted and art-recognized model for testing novel neurointerventional devices and has been the subject of many clinical publications for efficacy and similarity to human responses. (See, e.g., Altes et al. Creation of Saccular Aneurysms in the Rabbit: A Model Suitable for Testing Endovascular Devices. AJR 2000;174:349-354.) Thus, this model is readily accepted by regulatory agencies as a suitable testing model. The coagulation system of this model closely resembles that of the human. In addition, this model has favorable anatomical aspects in that the diameter of the rabbit extracranial carotid artery closely resembles that of the human extracranial carotid artery. Furthermore, elastase-induced aneurysms have been shown to behave histologically similar to human aneurysms.</p><p>Several embodiments of the present invention have been described. Reasonable features, modifications, advantages and design variations of the claimed apparatus will be readily apparent to those skilled in the art by following the guidelines set forth in the preceding detailed description and embodiments without departing from the scope and spirit of the occlusion device disclosed herein. Accordingly, other embodiments are within the scope of the following claims.</p>