Patent Description:
In this specification the non-SI unit 'inch' is used, which may be converted to the SI or metric unit according to the following conversion: <NUM> inch ≈ <NUM>.

A thrombus (also referred to as a blood clot) can block the flow of blood through a vessel, thereby depriving tissues of blood and oxygen and causing damage thereto. Thrombi are the predominant cause of strokes, which require prompt treatment to mitigate the risk of long-term disability and death.

A thrombectomy is a common procedure for treating strokes. In a thrombectomy, a guide catheter is inserted into a patient' s vasculature at the groin and advanced therethrough toward the thrombus. A stent retriever can then be passed through the guide catheter and engage the thrombus to capture it; once the thrombus is captured, the stent retriever and catheter can be removed to restore blood flow to the brain. Alternatively, a small-bore aspiration catheter can be passed through the guide catheter and, when its distal end is at the thrombus, a vacuum can be applied at the catheter's proximal end to draw the thrombus against the aspiration catheter's mouth for removal. Over the past decade, thrombectomies have improved the stroke treatment success rate, with about <NUM>% of the procedures achieving recanalization.

However, the inventor has recognized a number of challenges that have prevented successful recanalization in all thrombectomies. For example, blood flow against a thrombus acts to impede removal. While some have attempted to address this with a balloon guide catheter at the internal carotid artery (ICA) that blocks ICA blood flow to the thrombus, other vessels can continue to supply blood to the neurovasculature and thereby continue to impede thrombus removal.

Additionally, thrombi include (<NUM>) white thrombi that predominantly comprise platelets and (<NUM>) red thrombi that predominantly comprise red blood cells. These different thrombi compositions yield different mechanical properties, with white thrombi tending to have a higher Young's modulus and tensile strength and red thrombi tending to have a lower Young's modulus and tensile strength. Accordingly, stent retrievers can readily achieve mechanical engagement with red thrombi for removal, but may not be able to capture white thrombi, which are harder than red thrombi.

Aspiration catheters can maintain a hold of thrombi at the mouth thereof when the vacuum is applied, even if a stent retriever would not be able to mechanically engage such thrombi. But aspiration catheters face challenges as well. Because aspiration catheters must be able to access the vasculature in which a thrombus is located-commonly the ICA or the middle cerebral artery (MCA) (e.g., the M1 segment thereof), for strokes-they usually are relatively narrow, having a diameter that is less than <NUM>% of the diameter of the blood vessel. Such narrow aspiration catheters may not be able to ingest a stroke-inducing thrombus that spans across the blood vessel. As a result, thrombus removal is often achieved by retracting the aspiration catheter with most of the thrombus disposed outside of its lumen, rather than by allowing the vacuum source to draw the thrombus through the lumen. The exposed thrombus is at risk of detachment during catheter withdrawal, which can result in failed recanalization.

Some have improved aspiration success rates with larger-diameter aspiration catheters whose design allows them to reach the target vasculature despite their size. For example, while aspiration catheters commonly had an internal diameter of <NUM>", MicroVention, Inc. developed the SOFIA™ Plus catheter that has a <NUM>" internal diameter but can reach the MCA, and Perfuze Ltd. is developing the Millipede CIS catheter that has an internal diameter of <NUM>". While these aspiration catheters have larger lumen cross-sectional areas and thus can yield larger suction forces during aspiration, they still may not be able to ingest thrombi, which often have a diameters that are around twice as large (e.g., around <NUM>").

Another approach to aspiration includes advancing a self-expanding stent disposed within a small-diameter sheath to a thrombus and deploying the stent distally out of the sheath such that a distal portion of the stent expands radially to the artery wall. In this manner, the stent can ingest the thrombus through its expanded mouth. One example of such a device is the Anaconda Biomed S. ANCD Advanced Thrombectomy System. While such devices can have an expanded mouth through which a thrombus may readily pass, their stent narrows at a proximal portion thereof to a diameter than is smaller than that of the sheath to which the stent is attached. For example, the stent of the ANCD Advanced Thrombectomy System narrows down to a <NUM>" internal diameter. This constriction can impede ingestion of the thrombus through the sheath during aspiration.

Accordingly, there is a need in the art for thrombectomy systems that can better ingest thrombi to increase the likelihood of successful recanalization.

<CIT> discloses systems and methods for providing early blood flow restoration, maceration of an embolus, lysis of the embolus, and optional retrieval of any non-lysed portions of the embolus.

<CIT> discloses devices intended for removing acute blockages from blood vessels. Acute obstructions may include clot, misplaced devices, migrated devices, large emboli and the like.

<CIT> discloses technology of this disclosure pertains generally to aspiration catheters, and more particularly to aspiration catheters for stent and/or clot retrieval.

<CIT> discloses devices to remove blood clots and specifies a clot suction catheter with a funnel-shaped radially expandable seal.

The present invention is described in the claims. No methods of surgery or treatment are claimed. The present systems address this need in the art with a first tube, a second tube that is slidable within the first tube, and a self-expanding receiver positioned at least partially within the second tube. The first tube can have a relatively large internal transverse dimension (e.g., at least approximately <NUM>") and can be inserted into a patient's vasculature at the groin and advanced to or before the patient's ICA. The receiver and second tube-which is narrower than the first tube-can be passed through the first tube and beyond the distal end thereof to reach a thrombus in the patient's neurovasculature. The receiver can then be pushed distally (e.g., via a pusher wire connected thereto or a pusher coil) and/or the second tube can be pulled proximally such that a distal portion of the receiver advances beyond the second tube's distal end and thereby expands radially to contact the artery wall. In contrast with current systems, the second tube can be withdrawn from the first tube to permit a proximal portion of the receiver to radially expand to the inner wall of the first tube. The receiver's proximal portion, while narrower than the expanded distal portion thereof, can thus have an internal transverse dimension larger than that of self-expandable stents used in current thrombectomy systems (e.g., at least approximately <NUM>").

With a larger throat, the receiver can more readily ingest and pass the thrombus to the first tube when a vacuum is applied at the proximal end thereof, thereby allowing the vacuum source to draw the thrombus through the first tube's lumen for removal. The narrowing transition between the distal and proximal portions of the receiver can facilitate thrombus ingestion into the first tube, which might not otherwise occur with an aspiration catheter like the SOFIA™ Plus or Millipede CIS that does not include a receiver with a distal portion expanded to the artery wall.

To further promote thrombus ingestability, the first tube can have a radially-expandable distal end portion such that the receiver's proximal portion, when expanded to first tube's inner wall, causes the radially-expandable distal end portion to expand. With such expansion, an internal transverse dimension of the receiver's proximal portion can be at least as large as that of the first tube at a location proximal of its distal end portion (e.g., at least approximately <NUM>"), yielding a throat that is even more amenable to thrombus ingestion.

In this manner, the second tube and receiver can have a narrow profile during insertion to facilitate access to a thrombus that is disposed at a location that the larger-diameter first tube may not be able to readily access, and the receiver can expand at both its distal and proximal ends to the larger blood vessel and first tube walls, respectively, for aspiration such that thrombus removal through the first tube can be achieved.

Some of the present systems for use in blood clot removal comprise a first tube, a second tube, and a self-expanding receiver. The second tube, in some systems, is slidable within the first tube. The self-expanding receiver, in some systems, is positioned at least partially within the second tube. In some systems, the receiver is radially expandable. In some of such systems, when the second tube and a proximal portion of the receiver are positioned within a distal end portion of the first tube and the second tube is moved proximally relative to the receiver until a distal end of the second tube is positioned proximally of a proximal end of the receiver, the proximal portion of the receiver radially expands and makes contact with the distal end portion of the first tube and a distal portion of the receiver radially expands such that it has an inner diameter that is larger than an inner diameter of the first tube, optionally as at least <NUM>% larger than an inner diameter of the first tube. In some methods, the receiver includes a transition portion that narrows between the distal portion of the receiver and the proximal portion of the receiver.

Some systems comprise a multi-port adapter having a first port, a second port, and a third port. In some systems, the first tube has a proximal fitting and the first port is configured to be coupled to the proximal fitting of the first tube. The second port, in some systems, is configured to seal around a cylindrical structure positioned therethrough. The third port, in some systems, has a luer lock.

Some systems comprise a vacuum source. In some systems, the vacuum source is coupleable to the luer lock of the third port of the multi-port adapter.

Some systems comprise a guidewire positionable within a lumen of, and movable relative to, the second tube.

Some of the present methods for blood clot removal comprise advancing a first tube through vasculature of a patient and advancing through the first tube a second tube in which a self-expanding receiver is positioned in a constrained orientation until a proximal portion of the receiver is positioned within a distal end portion of the first tube. Some methods comprise moving the second tube proximally relative to the receiver at least until a distal end of the second tube is proximal of a proximal end of the receiver, a distal portion of the receiver expands and makes contact with a blood vessel, and the proximal portion of the receiver contacts the distal end portion of the first tube. In some of such methods, the contact the distal portion of the receiver makes with the blood vessel is sufficient to occlude blood flow in the blood vessel. Some methods comprise applying a vacuum to the first tube. Application of the vacuum, in some methods, aspirates a blood clot into the receiver. Some of such methods comprise aspirating the clot through the receiver and into the first tube and withdrawing the receiver into the first tube. Some methods comprise withdrawing the first tube, the receiver, and the blood clot from the patient.

In some embodiments, the distal end portion of the first tube is radially expandable. In some of such embodiments, the proximal portion of the receiver is capable, when in contact with the radially-expandable distal end portion of the first tube, of causing the radially-expandable distal end portion to radially expand, optionally such that the proximal portion of the self-expanding receiver comprises an inner diameter that is at least as great as an inner diameter of the first tube at a location proximal of the radially-expandable distal end portion. In some methods, the proximal portion of the receiver causes such radial expansion of the distal end portion of the first tube.

In some embodiments, the self-expanding receiver has a membrane. The membrane, in some embodiments, comprises polytetrafluoroethylene. In some embodiments, the membrane comprises urethane. The receiver, in some embodiments comprises struts. In some embodiments, the receiver comprises nitinol. The receiver, in some embodiments, has a radiopaque marker positioned within <NUM> millimeter or less of a distal end of the receiver and/or a radiopaque marker positioned within <NUM> millimeter or less of a proximal end of the receiver.

In some embodiments, the system comprises a pusher. Some methods comprise, during at least some of the moving applying pressure to the receiver through the pusher. The pusher, in some embodiments, comprises a pusher wire connected to the receiver. In some embodiments, the pusher is positionable within the second tube and sized to make contact with the proximal end of the receiver within the second tube. The pusher, in some embodiments, is not connected to the receiver. In some of such embodiments, the method comprises withdrawing the pusher.

The term "coupled" is defined as connected, although not necessarily directly, and not necessarily mechanically; two items that are "coupled" may be unitary with each other. The terms "a" and "an" are defined as one or more unless this disclosure explicitly requires otherwise. The term "substantially" is defined as largely but not necessarily wholly what is specified-and includes what is specified; e.g., substantially <NUM> degrees includes <NUM> degrees and substantially parallel includes parallel-as understood by a person of ordinary skill in the art. In any disclosed embodiment, the terms "substantially" and "approximately" may be substituted with "within [a percentage] of" what is specified, where the percentage includes <NUM>, <NUM>, <NUM>, and <NUM> percent.

The terms "comprise" and any form thereof such as "comprises" and "comprising," "have" and any form thereof such as "has" and "having," and "include" and any form thereof such as "includes" and "including" are open-ended linking verbs. As a result, a product or system that "comprises," "has," or "includes" one or more elements possesses those one or more elements, but is not limited to possessing only those elements. Likewise, a method that "comprises," "has," or "includes" one or more steps possesses those one or more steps, but is not limited to possessing only those one or more steps.

Any embodiment of any of the products, systems, and methods can consist of or consist essentially of-rather than comprise/include/have-any of the described steps, elements, and/or features. Thus, in any of the claims, the term "consisting of' or "consisting essentially of' can be substituted for any of the open-ended linking verbs recited above, in order to change the scope of a given claim from what it would otherwise be using the open-ended linking verb.

The feature or features of one embodiment may be applied to other embodiments, even though not described or illustrated, unless expressly prohibited by this disclosure or the nature of the embodiments.

Some details associated with the embodiments described above and others are described below.

The following drawings illustrate by way of example and not limitation. For the sake of brevity and clarity, every feature of a given structure is not always labeled in every figure in which that structure appears. Identical reference numbers do not necessarily indicate an identical structure. Rather, the same reference number may be used to indicate a similar feature or a feature with similar functionality, as may non-identical reference numbers.

Referring to <FIG> and <FIG>, shown is a first embodiment <NUM> of the present systems for thrombus removal that includes a first tube <NUM>, a second tube <NUM>, and a self-expanding receiver <NUM>. First and second tubes <NUM> and <NUM> can each comprise, for example, a catheter or sheath defining a lumen that extends between the proximal (e.g., 62a, 66a) and distal (e.g., 62b, 66b) ends thereof. As shown in <FIG>, second tube <NUM> is disposable within the lumen of first tube <NUM>. Receiver <NUM> can be compressed from its expanded state (<FIG>) and positioned at least partially within the lumen of second tube <NUM> (<FIG>).

First tube <NUM>, second tube <NUM>, and self-expanding receiver <NUM> can be sized such that system <NUM> can reach and remove a thrombus from a patient's neurovasculature, such as in the ICA or MCA (e.g., in the M1 segment thereof). Referring additionally to <FIG>, first and second tubes <NUM> and <NUM> can each have internal and external transverse dimensions (e.g., diameters) 30a, 34a and 30b, 34b, respectively. First tube <NUM>'s internal transverse dimension 30a can be greater than or equal to any one of, or between any two of, <NUM>", <NUM>", <NUM>", <NUM>", <NUM>", <NUM>", or <NUM>" (e.g., at least <NUM>" or at least approximately <NUM>") and its external transverse dimension 30b can be greater than or equal to any one of, or between any two of, <NUM>", <NUM>", <NUM>",<NUM>", <NUM>", <NUM>", or <NUM>" (e.g., at least <NUM>") (e.g., the first tube can be an 8F catheter or a 6F sheath). Each dimension herein provided in an English unit may be translated to the corresponding metric unit by rounding to the nearest millimeter. With such transverse dimensions, first tube <NUM> can have sufficient flexibility to facilitate access up to the ICA, while having a relatively large internal transverse dimension 30a to facilitate aspiration as described in further detail below. To travel up to the ICA from an insertion point at a patient's groin, a length <NUM> of first tube <NUM> can be greater than or equal to any one of, or between any two of, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, or <NUM> (e.g., at least <NUM>).

External transverse dimension 34b of second tube <NUM> can be smaller than first tube <NUM>'s internal transverse dimension 30a such that the second tube can slide within the first tube and access the narrower vessels of a patient's neurovasculature, such as in the ICA or MCA (e.g., the M1 segment). For example, second tube <NUM>'s external transverse dimension 34b can be less than or equal to any one of, or between any two of, <NUM>", <NUM>", <NUM>", <NUM>", <NUM>", <NUM>", or <NUM>" (e.g., less than <NUM>") and its internal transverse dimension 34a can be less than or equal to an one of, or between any two of, <NUM>", <NUM>", <NUM>", <NUM>", <NUM>", <NUM>", or <NUM>" (e.g., less than <NUM>") (e.g., the second tube can be a 6F catheter or a 4F sheath). Additionally, second tube <NUM>'s length <NUM> can be longer than length <NUM> of first tube <NUM> such that the second tube can be advanced past the first tube's distal end 62b to reach the thrombus. For example, length <NUM> can be greater than or equal to any one of, or between any two of, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, or <NUM> (e.g., at least <NUM>).

As shown in <FIG>, when in its expanded state receiver <NUM> can have internal and external transverse dimensions (e.g., diameters) 38a and 38b that are larger than those of first and second tubes <NUM> and <NUM>. For example, when fully expanded, receiver <NUM>'s internal transverse dimension 38a can be at least <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, or <NUM>% larger than first tube <NUM>'s internal transverse dimension 30a, such as greater than or equal to any one of, or between any two of, <NUM>", <NUM>", <NUM>. <NUM>", <NUM>", <NUM>", <NUM>", or <NUM>" (e.g., at least <NUM>") and its external transverse dimension 38b can be greater than or equal to any one of, or between any two of, <NUM>", <NUM>", <NUM>", <NUM>", <NUM>", or <NUM>" (e.g., at least <NUM>"). As sized, receiver <NUM> can radially expand to contact the vessel walls in a patient's neurovasculature, thereby facilitating thrombus ingestion as described in further detail below.

Referring additionally to <FIG>, while receiver <NUM> is wider than first and second tubes <NUM> and <NUM> when in its expanded state, it can be compressed and positioned at least partially within the second tube such that it can be advanced through the first tube and readily transported to the thrombus using the second tube. When in second tube <NUM>, receiver <NUM> can be in contact with the second tube's inner wall such that the receiver's compressed external transverse dimension is equal to the second tube's internal transverse dimension 34a. Receiver <NUM> can also have a first compressed internal transverse dimension 58a that is smaller than its uncompressed internal transverse dimension 38a, such as a first compressed internal transverse dimension that less than or equal to any one of, or between any two of, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, or <NUM>% of the uncompressed internal transverse dimension.

Receiver <NUM> can have a length <NUM> that, while shorter than lengths <NUM> and <NUM> of first and second tubes <NUM> and <NUM>, permits it to extend from a distal end portion <NUM> of the first tube to a thrombus in the patient's neurovasculature. For example, length <NUM> can be greater than or equal to any one of, or between any two of, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, or <NUM>. To permit manipulation of receiver <NUM> (e.g., for deployment out of second tube <NUM>) while the receiver is disposed within the patient, system <NUM> can comprise a pusher <NUM> that can be connected to a proximal end 70a of the receiver. Lengths <NUM> and <NUM> of receiver <NUM> and pusher <NUM> can together be longer than length <NUM> of first tube <NUM> and length <NUM> of second tube <NUM> such that the pusher extends out of the first and second tubes' proximal ends 62a and 66a while the receiver is disposed at or at least partially beyond the first tube's distal end 62b (<FIG>). For example, pusher <NUM>'s length <NUM> can be greater than or equal to any one of, or between any two of, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, or <NUM>.

Referring to <FIG>, to permit deployment of receiver <NUM> for thrombus ingestion, the receiver can be slidable relative to second tube <NUM>. In this manner, receiver <NUM> can be pushed distally (e.g., by applying pressure with pusher <NUM>) and/or second tube <NUM> can be pulled proximally (e.g., from its proximal end 66a disposed outside of the patient) such that the receiver's distal end 70b is disposed distally of distal ends 62b and 66b of first and second tubes <NUM> and <NUM>. When receiver <NUM> is deployed, its distal portion 74b can radially expand such that the internal transverse dimension thereof increases up to the receiver's maximum uncompressed internal transverse dimension 38a, promoting its ability to ingest a thrombus. The expanded distal portion 74b can engage with a patient's blood vessel wall, thereby arresting flow to the thrombus to facilitate removal thereof. Receiver <NUM>'s proximal end 70a can remain proximal of first tube <NUM>'s distal end 62b such that a proximal portion 74a of the receiver remains compressed, with a transition portion <NUM> of the receiver narrowing from the receiver's expanded distal portion 74b to its compressed proximal portion.

As shown in <FIG>, second tube <NUM> is disposed in first tube <NUM> such that it is in contact with and thus compresses receiver <NUM>'s proximal portion 74a. Proximal portion 74a of receiver <NUM> thus has an internal transverse dimension equal to first compressed internal transverse dimension 58a. However, referring additionally to <FIG>, second tube <NUM> can be pulled proximally relative to receiver <NUM> and thus withdrawn from first tube <NUM> such that the receiver's proximal portion 74a (e.g., including at its proximal end 70a) can radially expand to the inner wall of the first tube's distal end portion. As a result, receiver <NUM>'s proximal portion 74a can have a second compressed internal transverse dimension 58b that is larger than first compressed internal transverse dimension 58a, such as at least <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, or <NUM>% (e.g., at least <NUM>%) larger than the first compressed internal transverse dimension. For example, second compressed internal transverse dimension 58b can be greater than or equal to any one of, or between any two of, <NUM>", <NUM>", <NUM>", <NUM>", <NUM>", <NUM>", or <NUM>" (e.g., at least <NUM>" or at least approximately <NUM>"), optionally where it is at least <NUM>%, <NUM>%, <NUM>%, or <NUM>% of receiver <NUM>'s uncompressed transverse dimension 38a. The expandability of receiver <NUM>'s proximal portion 74a can facilitate thrombus ingestion to first tube <NUM> when a vacuum is applied at the first tube's proximal end, and thus promote higher recanalization success rates than current expandable stent systems whose narrower throats impede ingestion.

According to the invention, receiver <NUM>'s proximal portion 74a can engage and thereby create a seal with first tube <NUM>'s distal end portion <NUM> to impede blood flow into first tube <NUM>'s lumen when a vacuum is applied at the first tube's proximal end 62a. This engagement can also be sufficient to permit withdrawal of receiver <NUM> when first tube <NUM> is withdrawn from a patient's vasculature. Such engagement can be achieved via friction and/or fastening components coupled to receiver <NUM>'s proximal portion 74a and first tube <NUM>'s distal end portion <NUM>. For example, receiver <NUM>'s proximal portion 74a can be configured to exert a pressure on first tube <NUM>'s distal end portion <NUM> that is greater than or equal to any one of, or between any two of, <NUM> kPa, <NUM> kPa, <NUM> kPa, <NUM> kPa, <NUM> kPa, <NUM> kPa, <NUM> kPa, or <NUM> kPa (e.g., between <NUM> and <NUM> kPa); such pressure can yield a seal between the receiver and first tube to impede blood flow at the interface therebetween and enough friction to maintain the connection between the receiver and first tube when they are withdrawn from a patient's vasculature.

Referring additionally to <FIG>, in the embodiment of the invention, the first tube <NUM>'s distal end portion <NUM> is radially expandable. In such embodiments, receiver <NUM>'s proximal portion 74a can cause first tube <NUM>'s distal end portion <NUM> to radially expand when it comes in contact with and thus exerts pressure on the distal end portion. After expanding distal end portion <NUM>, receiver <NUM>'s proximal portion 74a can have a third compressed internal transverse dimension 58c that is larger than second compressed internal transverse dimension 58b. As shown, receiver <NUM>'s proximal portion 74a can exert sufficient force on distal end portion <NUM> such that third compressed internal transverse dimension 58c is at least as large as first tube <NUM>'s internal transverse dimension 30a at a location proximal of the distal end portion, such as greater than or equal to any one of, or between any two of, <NUM>%, <NUM>%, <NUM>%, <NUM>%, or <NUM>% of internal transverse dimension 30a. For example, third compressed internal transverse dimension 58c can be greater than or equal to any one of, or between any two of, <NUM>", <NUM>", <NUM>", <NUM>", <NUM>", <NUM>", or <NUM>" (e.g., at least <NUM>" or at least approximately <NUM>"), and/or can be at least <NUM>%, <NUM>%, <NUM>%, or <NUM>% of receiver <NUM>'s uncompressed transverse dimension 38a. By yielding a larger throat, this additional expandability can further facilitate thrombus ingestion through receiver <NUM> and to first tube <NUM>.

Receiver <NUM> can have any suitable structure that yields the above-described expandability and permits the receiver to occlude flow between portions of a patient's blood vessel that are proximal and distal of the receiver. Referring to <FIG>, for example, receiver <NUM> can comprise a membrane <NUM> that defines an outer surface thereof. Membrane <NUM> can be liquid-impermeable such that receiver <NUM>, when its distal portion 74b expands and contacts the vessel wall, can impede blood flow to a thrombus while allowing fluid communication between the thrombus and first tube <NUM> for aspiration. Suitable materials for membrane <NUM> include polymers such as polytetrafluoroethylene (PTFE) and urethane. PTFE, for example, advantageously exhibits low friction with other surfaces and thus facilitates insertion and deployment of receiver <NUM>.

To promote its expandability, receiver <NUM> can include struts <NUM>. Struts <NUM> can be configured to urge radial expansion of receiver <NUM> when the receiver is radially compressed. For example, struts <NUM> can comprise nitinol (i.e., an alloy comprising nickel and titanium), which is superelastic such that the struts can regain their original shape when a mechanical load exerted thereon is released. Bonding between struts <NUM> and membrane <NUM> can be achieved in a variety of ways. As one example, receiver <NUM> can comprise a second membrane (e.g., comprising the same material as membrane <NUM>, such as PTFE and/or urethane) that defines the receiver's inner wall and is adhered to membrane <NUM> such that struts <NUM> are disposed between the two membranes. Such a membrane configuration can facilitate a stronger membrane-strut connection, particularly when-as is preferred for the strut construction-membrane <NUM> comprises PTFE and struts <NUM> comprise nitinol. This is because the adhesion between the membranes that maintains struts <NUM> therebetween can be stronger than that between PTFE and nitinol. Nevertheless, struts <NUM> can be adhered to the inner wall of membrane <NUM> without a second membrane disposed on the other side thereof; while this configuration may not be as strong as the two-membrane configuration, it can yield adequate strength to withstand the forces exerted on receiver <NUM> during aspiration.

In other embodiments, receiver <NUM> can have a braided construction in which braided wires (e.g., comprising nitinol) are attached to membrane <NUM>. In some of such embodiments, the braided wires can be encapsulated by membrane <NUM>, which preferably comprises urethane for the braided construction.

Receiver <NUM> can also comprise one or more radiopaque markers <NUM>. Radiopaque marker(s) <NUM> can inhibit the passage of X-rays therethrough and thus can be viewed via fluoroscopy when receiver <NUM> is disposed in a patient. For example, each radiopaque marker <NUM> can comprise tantalum or platinum. Radioplaque marker(s) <NUM> can thereby aid a physician in determining the position of receiver <NUM> in a patient's vasculature during insertion and deployment thereof. At least one radiopaque marker <NUM> can be disposed closer to receiver <NUM>'s distal end 70b than to its proximal end 70a, such as within a distance 98b of the distal end that is less than or equal to any one of, or between any two of, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, or <NUM> (e.g., less than or equal to <NUM>). Such distally-positioned radiopaque marker(s) <NUM> can assist a physician in determining receiver <NUM>'s position relative to a thrombus such that the receiver can be positioned adjacent thereto to achieve adequate engagement for aspiration. Additionally or alternatively, at least one radiopaque marker <NUM> can be disposed closer to receiver <NUM>'s proximal end 70a than to its distal end 70b, such as within a distance 98a of the proximal end that is less than or equal to any one of, or between any two of, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, or <NUM> (e.g., less than or equal to <NUM>). Such proximally-positioned radiopaque markers <NUM>, in combination with the distally-positioned radiopaque markers, can allow a physician to determine the length of receiver <NUM> when deployed. In some embodiments, components of receiver <NUM> that span its length <NUM> (e.g., struts <NUM>, collectively) can be radiopaque such that a least a portion thereof is visible along the receiver's length via fluoroscopy.

As described above, a pusher <NUM> can be connected to receiver <NUM> such that the receiver can be advanced toward the thrombus. Such a pusher <NUM> can comprise a pusher wire comprising, for example, stainless steel, such as a wire that is traditionally used in guide wires. One suitable wire for pusher <NUM> is that used in the CHIKAI black18 Neurovascular Guide Wire, available from Asahi Intecc Co. However, turning to <FIG>, in other embodiments the pusher need not be connected to the receiver and can instead be positionable within second tube <NUM> and sized to make contact with receiver <NUM>'s proximal end 70a. For example, rather than a wire, pusher <NUM> can comprise a coil having any of the above-described pusher lengths such that its distal end can reach receiver <NUM> at a distal portion of second tube <NUM> while its proximal end is accessible outside of first and second tubes <NUM> and <NUM>, and can have an external transverse dimension smaller than the second tube's internal transverse dimension 34a but large enough to engage with the receiver's proximal end 70a. Unconnected pusher <NUM> can thus be advanced through second tube <NUM> to push and thereby deploy receiver <NUM> (<FIG>). Once receiver <NUM> is deployed, pusher <NUM> can be withdrawn from the patient (<FIG>) such that the full cross-section of first tube <NUM>'s lumen proximal of receiver <NUM> can be available for thrombus ingestion.

Referring to <FIG>, system <NUM> can comprise a multi-port adapter <NUM> that can facilitate advancement of second tube <NUM> and receiver <NUM> through first tube <NUM> and can be coupled to a vacuum source <NUM> for aspiration. As shown, multi-port adapter <NUM> can comprise at least three ports 106a-106c (<FIG>) to do so. First port 106a can be configured to be coupled to a proximal fitting <NUM> of first tube <NUM> (<FIG>) such that a lumen of multi-port adapter <NUM> is in fluid communication with the first tube's lumen. Second port 106b can be configured to permit second tube <NUM> to pass therethrough into the lumen of multi-port adapter <NUM> and through the lumen of first tube <NUM> when the first tube's proximal fitting <NUM> is coupled to first port 106a (<FIG>). In this manner, second tube <NUM> and receiver <NUM> can be advanced to a thrombus in a patient's neurovasculature as described above. Additionally, second tube <NUM> can be withdrawn from first tube <NUM> through second port 106b during deployment of receiver <NUM>.

For aspiration, multi-port adapter <NUM> can comprise a third port 106c that can be coupleable to a vacuum source <NUM> (<FIG>). Third port 106c can have a luer lock for achieving such a vacuum source connection. When vacuum source <NUM> is coupled to third port 106c, it can be in fluid communication with the lumen of multi-port adapter <NUM> and thus with the lumen of first tube <NUM>. Vacuum source <NUM> can thus apply a vacuum to first tube <NUM> by lowering the pressure at third port 106c, thereby drawing the thrombus into receiver <NUM> and through the first tube. To promote efficient application of the vacuum and mitigate blood leakage out of multi-port adapter <NUM>, second port 106b can be closed during aspiration such that fluid cannot flow therethrough. For example, second port 106b can be configured to seal around a cylindrical structure positioned therethrough (e.g., can comprise a Tuohy-Borst adapter) such that, if pusher <NUM> is connected to receiver <NUM> and remains in first tube <NUM> during aspiration, the second port can form a seal around the pusher after second tube <NUM> is withdrawn.

System <NUM>'s vacuum source <NUM> can comprise any suitable device by which a vacuum can be applied to first tube <NUM>'s proximal end 62a to draw a thrombus into the deployed receiver <NUM> and through the first tube for removal. For example, as shown vacuum source <NUM> can comprise a syringe that, optionally, has a barrel configured to hold greater than or equal to any one of, or between any two of, <NUM>, <NUM>, <NUM>, <NUM>, or <NUM> of fluid. The relatively small negative pressure differential that a syringe can yield between first tube <NUM>'s proximal end 64a and receiver <NUM>'s distal end 70b during aspiration can be sufficient for thrombus ingestion and removal due at least in part to the relatively large cross-sectional areas of receiver <NUM>'s mouth and throat. For example, such a pressure differential can be less than or equal to any one of, or between any two of, <NUM>, <NUM>, <NUM>, <NUM>, or <NUM> Hg.

Referring to <FIG>, in other embodiments vacuum source <NUM> can comprise a vacuum pump, which can include a pumping unit <NUM> (e.g., having a motor) and a container <NUM> in fluid communication with the pumping unit such that the pumping unit can draw a vacuum on the container. Container <NUM> can in turn be coupled to multi-port adapter <NUM>'s third port 106c via a tube <NUM> such that pumping unit <NUM> is in fluid communication with and thus can apply a vacuum at first tube <NUM>'s proximal end 62a via the container, which can receive fluids drawn from a patient's vasculature during aspiration. Pumping unit <NUM> can be configured to control the pressure at first tube <NUM>'s proximal end 62a (e.g., with a regulator <NUM>) to yield a sufficient pressure differential for thrombus removal.

Any of the present systems can be included in a kit. In such a kit, self-expanding receiver <NUM> can already be positioned at least partially within second tube <NUM> such that the receiver is ready for insertion into a patient, thereby allowing prompt treatment.

Turning to <FIG>, some of the present methods of removing a thrombus (e.g., <NUM>) (e.g., a red thrombus or a white thrombus) comprise advancing a first tube (e.g., <NUM>) (e.g., any of those described above) through vasculature (e.g., <NUM>) of a patient (<FIG>). As described above, the first tube can be inserted into the patient's vasculature at the groin and advanced up to the ICA (e.g., <NUM>), such as within <NUM>, <NUM>, <NUM>, or <NUM> of the ICA. System <NUM> optionally comprises a guidewire <NUM>, which can be advanced to the thrombus before the first tube is inserted such that the first tube can pass over the guidewire, facilitating advancement of the first tube through the patient's vasculature.

With the first tube disposed in the patient's vasculature, some methods comprise advancing a second tube (e.g., <NUM>) (e.g., any of those described above) through the first tube (<FIG>). The second tube can be advanced such that a distal end (e.g., 66b) thereof is positioned distally of the first tube's distal end (e.g., 62b) in the ICA or MCA (e.g., the M1 segment thereof). In this manner, the second tube's distal end can be positioned near the thrombus, such as within <NUM>, <NUM>, <NUM>, <NUM>, or <NUM> of the thrombus. When advanced through the first tube, a proximal end (e.g., 66a) of the second tube can remain outside of the patient such that it can be accessed by a physician.

Referring to <FIG>, in some methods a self-expanding receiver (e.g., <NUM>) (e.g., any of those described above) can also be advanced to the thrombus. For example, the self-expanding receiver can be positioned in a constrained orientation in the second tube (e.g., in a distal portion thereof) such that the receiver is advanced with the second tube. In such methods, the second tube can be advanced until a proximal portion (e.g., 74a) of the receiver is positioned within a distal end portion (e.g., <NUM>) of the first tube. Alternatively, after the second tube is advanced through the first tube such that its distal end is in the ICA or MCA, the receiver can be pushed through the second tube (e.g., with pusher <NUM>, which can comprise any of those described above) until its proximal portion is positioned in the first tube's distal portion.

To deploy the receiver, some methods comprise moving the second tube proximally relative to the receiver (<FIG> and <FIG>), such as by pulling a proximal portion of the second tube. During at least some of the moving (e.g., while a portion of the receiver is disposed in the second tube), pressure can be applied to the receiver through the pusher, thereby facilitating unsheathing thereof. The second tube can be moved such that its distal end is positioned proximally of the receiver's distal end, thereby allowing a distal portion (e.g., 74b) of the receiver to radially expand and make contact with the blood vessel. The receiver's maximum uncompressed external transverse dimension can be larger than the vessel's internal transverse dimension (e.g., diameter) such that the expanded distal portion can exert sufficient pressure on the blood vessel to occlude blood flow therein. For example, the receiver's distal portion can exert a pressure that is greater than or equal to any one of, or between any two of, <NUM> kPa, <NUM> kPa, <NUM> kPa, <NUM> kPa, <NUM> kPa, <NUM> kPa, <NUM> kPa, or <NUM> kPa (e.g., between <NUM> and <NUM> kPa) on the vessel wall.

Movement of the second tube can be performed at least until its distal end is proximal of the receiver's proximal end. With the receiver unsheathed from the second tube, the receiver's proximal portion can radially expand and contact the first tube's distal end portion (<FIG>). As explained above, this permits the receiver's throat to have a larger internal transverse dimension to facilitate aspiration. If the first tube's distal end portion is radially expandable as described above, the receiver's proximal portion can cause the radially-expandable distal end portion to radially expand such that the receiver's proximal portion has an internal transverse dimension (e.g., 58c) that is at least as great as that of the first tube at a location proximal of first tube's distal end portion. When deployed, the receiver can include a transition portion (e.g., <NUM>) that narrows between the receiver's expanded distal portion and the receiver's proximal portion disposed within the second tube.

During deployment, the position of the receiver relative to the thrombus can be adjusted with the pusher. For example, application of pressure on the receiver via the pusher can cause the receiver to advance such that the distal end thereof contacts the thrombus, which can facilitate aspiration of the thrombus. As described above, the pusher need not be connected to the receiver; with this configuration, some methods comprise withdrawing the pusher from the patient to render a greater portion of the first tube's cross-section available for aspiration.

Referring to <FIG>, some methods comprise applying a vacuum to the first tube (e.g., in any of the manners described above, such as with a syringe or vacuum pump). As a result, pressure at the first tube's proximal end can be reduced, yielding a negative pressure differential between the receiver's distal end and the first tube's proximal end that can cause the thrombus to aspirate into the receiver (<FIG>). Because the receiver's distal portion is expanded to the vessel wall, such ingestion can readily occur. Additionally, and referring to <FIG>, application of the vacuum can cause the thrombus to aspirate through the receiver and into the first tube. As shown, the receiver's narrowing transition section and radially-expanded proximal portion facilitates deformation and compression of the thrombus such that the thrombus can enter the first tube. This ingestion can occur even if the thrombus is a white thrombus that is more resistant to compression than a red thrombus. The vacuum can continue to draw the ingested thrombus through the first tube and out of its proximal end. If a vacuum pump is used for aspiration, recanalization can be confirmed when a change in pump pressure occurs. In some methods, the receiver can be withdrawn into the first tube (e.g., by pulling on a proximal portion of the pusher disposed outside of the patient, if the pusher is connected to the receiver) and the first tube can be withdrawn from the patient's vasculature.

In some procedures, the thrombus may not aspirate into the first tube when the vacuum is applied, even with the relatively large receiver throat. When this occurs, to remove the thrombus the first tube and receiver can be withdrawn from the patient with the thrombus disposed in the receiver. Alternatively, the receiver can be withdrawn into the first tube (e.g., with the pusher) while the vacuum is applied to the first tube, which may allow thrombus ingestion into the first tube for removal.

The present invention will be described in greater detail by way of specific examples. The following examples are offered for illustrative purposes only and are not intended to limit the present invention in any manner. Those skilled in the art will readily recognize a variety of noncritical parameters that can be changed or modified to yield essentially the same results.

Referring to <FIG>, the ingestability of a model white thrombus into a catheter during aspiration was assessed with and without a narrowing receiver (or funnel). In both experiments, the catheter through which a vacuum was drawn had a <NUM>-mm diameter In the experiment employing a funnel, the funnel narrowed to a <NUM>-mm diameter. As shown in <FIG>, without the funnel the model white thrombus was drawn to the catheter's mouth but could not pass therethrough. However, as shown in <FIG>, the model white thrombus could pass through the funnel and exit its throat even though the throat's <NUM>-mm diameter was smaller than that of the catheter that could not ingest the thrombus. This illustrated how the tapering of the funnel facilitated thrombus ingestion.

Referring to <FIG>, shown is an illustrative receiver (e.g., <NUM>) that comprised struts and a membrane being deployed from a sheath with a pusher (e.g., <NUM>). As shown, when the pusher was advanced forward, the receiver exited the sheath and expanded radially (<FIG>). The pusher was then withdrawn (<FIG>).

Referring to <FIG>, shown is an exemplary system in which the first tube (e.g., <NUM>) was a 6F sheath with an internal diameter of <NUM>", the second tube (e.g., <NUM>) was a 4F sheath with an internal diameter of <NUM>", and the self-expanding receiver (e.g., <NUM>) comprised struts and a membrane. To simulate insertion into the M1 segment of the MCA, the system was inserted into a tube having an internal diameter of <NUM>", with the 4F sheath disposed in and extending past the distal end of the 6F sheath and the receiver compressed and disposed in the 4F sheath. The pusher (e.g., <NUM>) was used to hold the receiver in place while the 4F sheath was retracted (<FIG>). When the 4F sheath was retracted from the 6F sheath, the receiver expanded radially such that its distal portion engaged the inner wall of the <NUM>"-diameter tube and its proximal portion engaged the inner wall of the 6F sheath, with a narrowing transition portion therebetween (<FIG>).

Referring to <FIG>, an aspiration experiment was performed with a self-expanding receiver (e.g., <NUM>) deployed from an 8F catheter such that the catheter's distal portion was expanded radially to the inner wall of a <NUM>-mm-diameter tube and its proximal portion was expanded radially to the inner wall of the 8F catheter. A model thrombus (e.g., <NUM>) was positioned in the <NUM>-mm-dimeter tube distally of the receiver (<FIG>). A vacuum was applied at the 8F catheter's proximal end, drawing the model thrombus toward and into the receiver (<FIG>). The model thrombus was able to pass through the throat of the receiver and through the 8F catheter (<FIG>).

Claim 1:
A system for use in blood clot removal via aspiration, the system comprising:
a first tube (<NUM>);
a second tube (<NUM>) slidable within the first tube (<NUM>); and
a self-expanding receiver (<NUM>) having a membrane (<NUM>) and positioned at least partially within the second tube (<NUM>), wherein
the second tube (<NUM>) is configured to be moved proximally relative to the receiver (<NUM>), wherein
the receiver (<NUM>) is configured to be radially expandable such that in a state when the second tube (<NUM>) and a proximal portion (74a) of the receiver (<NUM>) are positioned within a distal end portion (<NUM>) of the first tube (<NUM>) and a distal end (66b) of the second tube (<NUM>) is positioned proximally of a proximal end (70a) of the receiver (<NUM>):
the proximal portion (74a) of the receiver (<NUM>) radially expands and makes contact with the distal end portion (<NUM>) of the first tube (<NUM>); and
a distal portion (74b) of the receiver (<NUM>) radially expands such that it has an inner diameter that is at least <NUM>% larger than an inner diameter of the first tube (<NUM>),
the proximal portion (74a) of the receiver (<NUM>) is configured to cause the distal end portion (<NUM>) of the first tube (<NUM>) to radially expand when the proximal portion (74a) makes contact with the distal end portion (<NUM>) of the first tube (<NUM>) and thus exerts pressure on the distal end portion (<NUM>), and
the proximal portion (74a) of the receiver (<NUM>) is configured to engage and thereby create a seal with the distal end portion (<NUM>) of the first tube (<NUM>) when a vacuum is applied at a proximal end (62a) of the first tube (<NUM>).