WO2019213179A1

WO2019213179A1 - Systems and devices for removing obstructive material from an intravascular site

Info

Publication number: WO2019213179A1
Application number: PCT/US2019/030073
Authority: WO
Inventors: Lex Jansen; Ryan KRONE; Tiffany NGO; Cyrus OINEZA; Miranda RAY; Carolyn Stone
Original assignee: Imperative Care, Inc.
Priority date: 2018-05-01
Filing date: 2019-04-30
Publication date: 2019-11-07

Abstract

A system for removing embolic material from an intravascular site is disclosed. The system includes an elongate, flexible tubular body, having a proximal end, a distal end, and a tubular side wall defining at least one lumen extending axially there through; an axial restraint carried by the side wall and exposed to the lumen; a rotatable core wire extendable through the lumen, the core wire having a distal end; a limit carried by the core wire, the limit having a bearing surface for rotatably engaging the restraint; and an agitator tip on the distal end of the core wire. The limit and the restraint are engageable to permit rotation of the core wire but limit distal advance of the tip relative to the tubular body. Kits including a first agitator tip, and a second agitator tip, each configured for one or more types of obstructive material are also disclosed.

Description

SYSTEMS AND DEVICES FOR REMOVING OBSTRUCTIVE MATERIAL FROM AN INTRAVASCULAR SITE

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the priority benefit of U.S. Provisional Patent Application Ser. No. 62/665,369 filed May 1, 2018, the entirety of which is herein incorporated by reference.

[0002] This application also claims the priority benefit of U.S. Provisional Patent Application Ser. No. 62/788,399, filed January 4, 2019, the entirety of which is herein incorporated by reference.

TECHNICAL FIELD

[0003] This disclosure relates generally to the field of pulmonary embolism and stroke treatment, and more specifically to the field of thrombus removal. Described herein are systems and methods for thrombus removal.

BACKGROUND

[0004] Thrombus formation can occur in any blood vessel within the human body with the possibility of the emboli traveling to critical areas including the lungs and brain causing pulmonary embolism (PE) and stroke, respectively. PE and deep vein thrombosis (DVT) occur in more than 600,000 people per year in the United States with a mortality rate of 60,000-100,000 people per year. Within one month of diagnosis of PE/DVT, 10- 30% of the people will die. Furthermore, the 10 year recurrence rate of a PE/DVT in a patient is about 33% meaning novel embolus formation will need to be monitored closely in these patients. Stroke occurs in nearly 800,000 people per year either as a new or recurrent stroke and is the fifth leading cause of death in the United States. Ischemic stroke occurs by a blockage of a blood vessel caused by a thrombus formation that can either form outside of the brain and travel into smaller cerebral blood vessels or form inside of the cerebral arteries leading to inhibition of blood flow to the brain.

[0005] Current treatments of PE/DVT are focused not on breaking up and removing obstructive emboli, but oral medications, intravenous or intramuscular injections of blood thinners/thrombolytics and the placement of filters in the vena cava to prevent PE from traveling clots. [0006] Treatment of ischemic stroke can use either blood thinners/thrombolytics or catheter devices that pull out or break up the clot. Mechanical removal of obstructive emboli in many vasculature sites has been standard of care for many years. These techniques include collecting and extracting the clot, dissolving the clot, creating a channel for blood to flow through the clot, and aspiration of the clot. Briefly, a guide catheter is placed in the femoral artery and threaded up to the internal carotid artery (ICA), a microcatheter topped with a clot retriever is then placed into the guide catheter and deployed to the clot. The clot is captured and the microcatheter/retriever/clot are pulled back out either as a whole clot or pieces of a broken up embolus. There is concern with a clot breaking into multiple pieces and/or one or more pieces escaping the retriever system leading to a novel ischemic event. Aspiration pumps have been used in conjunction with thrombolytics to remove the emboli as it is broken apart.

[0007] Although all of these are promising mechanical manipulation and removal of emboli in the body, new devices and treatment methods for vasculature occlusions in the body are needed to decrease patient morbidity and mortality.

SUMMARY OF THE INVENTION

[0008] There is provided in accordance with one aspect of the present invention, a system for removing embolic material from an intravascular site. The system comprises an elongate, flexible tubular body, having a proximal end, a distal end, and a tubular side wall defining at least one lumen extending axially there through; an axial restraint carried by the side wall and exposed to the lumen; a rotatable core wire extendable through the lumen, the core wire having a proximal end and a distal end; a limit carried by the core wire, the limit having a bearing surface for rotatably engaging the restraint; and an agitator tip on the distal end of the core wire; wherein the limit and the restraint are engageable to permit rotation of the core wire but limit distal advance of the tip relative to the tubular body.

[0009] The axial restraint may comprise a proximally facing bearing surface, which may be carried by a radially inwardly extending projection or an annular flange. The limit may comprise a distally facing bearing surface, which may be carried by a radially outwardly extending projection. The radially outwardly extending projection may comprise at least one spoke which supports a slider configured for sliding contact with an inside surface of the tubular side wall. Some implementations may comprise three spokes each supporting a slider. The bearing surface decouples distal advance of the agitator tip beyond the tubular body in response to positioning the tubular body within tortuous vasculature.

[00010] In some implementations, the limit comprises an annular ring. The annular ring may be spaced radially outwardly apart from the core wire. At least two spokes may be provided, extending between the core wire and the ring. In one implementation, three spokes extend between the core wire and the ring. The limit may be positioned within about the distal most 50% or within the distal most 25 % of the catheter length.

[00011] A flow path is defined between each adjacent pair of spokes and in communication with the central lumen. In one implementation, three flow paths are provided, and the sum of the cross-sectional areas of the three flow paths is at least about 90% or at least about 95% of the cross-sectional area of the lumen within 1 cm proximally of the restraint.

[00012] The core wire may be tapered from a larger diameter at a proximal point to a smaller diameter at the limit that is no more than about 30% of the larger diameter. The core wire may be tapered to a smaller diameter at the limit that is no more than about 18% of the larger diameter. The core wire may be tapered from a diameter of about 0.025 inches at a proximal point to a diameter that is no more than about 0.005 inches at the limit.

[00013] The agitator tip may comprise a helical thread. The helical thread may have a major diameter that is no more than about 90% of the inside diameter of the lumen, leaving an annular flow path between the tip and the inner surface of the side wall. The helical thread may have a blunt outer edge. The helical thread defines a helical flow channel between axially adjacent threads, and the sum of the cross-sectional area of the helical flow channel and the annular flow path may be at least about 10% or 20% or 25% or more of the cross-sectional area of the lumen without the tip present.

[00014] In any of the agitator tip embodiments described herein, the agitator tip may have a major diameter that is no more than about 90% of the inside diameter of the lumen, leaving an annular flow path between the tip and the inner surface of the side wall. In any of the agitator tip embodiments described herein, the agitator tip defines a flow channel between adjacent tip features, and the sum of the cross-sectional area of the flow channel and the annular flow path may be at least about 10% or 20% or 25% or more of the cross-sectional area of the lumen without the tip present.

[00015] At least one helical spring coil may be carried by the core wire, extending proximally from the tip for a length within the range of from about 5 cm to about 60 cm. The spring may extend proximally from the tip for a length within the range of from about 20 cm to about 40 cm.

[00016] The core wire may be permanently positioned within, or be removably positionable within the tubular body.

[00017] In accordance with a further aspect of the present invention, there is provided a method of removing embolic material from a vessel with mechanical and aspiration assistance. The method comprises the steps of providing an aspiration catheter having a central lumen and a distal end; advancing the distal end to obstructive material in a vessel; rotating a tip within the lumen, the tip having an axial length of no more than about 5 mm and a helical thread having a major diameter that is at least about 0.015 inches smaller than an inside diameter of the lumen, to provide an aspiration flow path around the outside of the tip; and applying vacuum to the lumen and rotating the tip to draw material into the lumen.

[00018] The rotating step may comprises manually rotating a core wire which extends through the catheter and rotates the tip. The method may additionally comprise the step of limiting distal advance of the core wire by rotating a limit carried by the core wire in sliding contact with a restraint positioned in the central lumen.

[00019] In accordance with another aspect of the present invention, there is provided a method of aspirating a vascular occlusion from a remote site. The method comprises the steps of advancing an elongate tubular body through a vascular access site and up to a vascular occlusion, the tubular body comprising a proximal end, a distal end, a central lumen, and a stop extending into the lumen from the tubular body; advancing a rotatable core wire distally through the lumen until a limit carried by the core wire slidably engages the stop to provide a rotatable bearing which limits further distal advance of the core wire within the lumen; and applying vacuum to the lumen and rotating the core wire to draw thrombus into the lumen.

[00020] The applying vacuum step may comprise applying pulsatile vacuum. The advancing an elongate tubular body step may be accomplished directly over a guidewire without any intervening tubular bodies. The advancing the tubular body step may be at least as distal as the cavernous segment of the internal carotid artery, or at least as distal as the cerebral segment of the internal carotid artery.

[00021] The advancing a rotatable core wire step may be accomplished after the advancing an elongate tubular body through a vascular access site and up to a vascular occlusion step. Alternatively, the advancing a rotatable core wire step may be accomplished simultaneously with the advancing an elongate tubular body through a vascular access site and up to a vascular occlusion step.

[00022] There is provided in accordance with one aspect of the present invention a neurovascular catheter having an angled, atraumatic navigational tip. The catheter comprises an elongate flexible tubular body, having a proximal end, a distal end and a side wall defining a central lumen. A distal zone of the tubular body comprises a tubular inner liner; a helical coil surrounding the inner liner and having a distal end, and a tubular jacket surrounding the helical coil, and extending distally beyond the helical coil distal end to terminate in a catheter distal face. A tubular radiopaque marker is embedded in the tubular jacket in between the distal end of the coil and the distal face. The distal face resides on a plane which crosses a longitudinal axis of the tubular body at an angle within the range of from about 35 degrees to about 55 degrees; and the marker has a proximal face that is approximately perpendicular to the longitudinal axis and a distal face that resides on a plane which crosses the longitudinal axis at an angle within the range of from about 35 degrees to about 55 degrees. The distal face defines a leading edge of the tubular body which extends distally of a trailing edge of the tubular body, the leading edge and training edge spaced about 180 degrees apart from each other around the longitudinal axis.

[00023] An advance segment of the tubular body extends distally beyond the marker band. The advance segment may have an axial length within the range of from about 1 mm to about 3 mm on the leading edge side of the tubular body. The length of the advance segment on the leading edge side of the tubular body may be greater than the length of the advance segment on the trailing edge side of the tubular body.

[00024] The axial length of the marker band on the leading edge side of the tubular body may be at least about 20% longer than the axial length of the marker band on the trailing edge side of the tubular body. The axial length of the marker band on the leading edge side of the tubular body may be within the range of from about 1 mm to about 5 mm. The marker band comprises at least one axial slit.

[00025] The tubular liner may be formed by dip coating a removable mandrel. The tubular liner may comprises PTFE. The tubular body may further comprise a tie layer between the inner liner and the helical coil. The tie layer may have a wall thickness of no more than about 0.005 inches, and may extend along at least the most distal 20 cm of the flexible body. [00026] The coil may comprise Nitinol, and may comprise an Austenite state at body temperature. The outer jacket may be formed from at least five discrete axially adjacent tubular segments. In some implementations, the outer jacket may be formed from at least nine discrete axially adjacent tubular segments. The difference in durometer between a proximal one of the tubular segments and a distal one of the tubular segments is at least about 20D, and in some implementations the difference in durometer between a proximal one of the tubular segments and a distal one of the tubular segments is at least about 30D.

[00027] The tubular body may additionally comprise a tension support for increasing the tension resistance in the distal zone. The tension support may comprise an axially extending filament. The axially extending filament may be carried between the inner liner and the helical coil. The axially extending filament may increase the tensile strength of the tubular body to at least about 5 pounds before failure.

[00028] In accordance with another aspect of the present invention, there is provided a system for removing embolic material from an intravascular site. The system includes an elongate, flexible tubular body, having a proximal end, a distal end, and a tubular side wall defining at least one lumen extending axially there through; an axial restraint carried by the side wall and exposed to the lumen; a rotatable core wire extendable through the lumen, the core wire having a proximal end and a distal end; a limit carried by the core wire, the limit having a bearing surface for rotatably engaging the restraint; and an agitator tip on the distal end of the core wire. The agitator tip comprises a helical thread comprising: a first section having a distal tip aligned with a center axis of the core wire, the first section comprising at least one revolution having a first pitch, a second section attached to the first section, the second section comprising at least one revolution having a second pitch, and a third straight section attached to the second section and the distal end of the core wire. The limit and the restraint are engageable to permit rotation of the core wire but limit distal advance of the agitator tip relative to the tubular body.

[00029] In some embodiments, the first pitch is 0.02 to 0.06 threads per inch. In some embodiments, the second pitch is 0.1 to 0.25 threads per inch. In some embodiments, the second section comprises 1.25 revolutions.

[00030] In some embodiments, an angle between the first section and the second section is between 0 to 30 degrees. In some embodiments, an angle between the second section and the third section is 30 to 60 degrees.

[00031] In some embodiments, the axial restraint comprises a proximally facing bearing surface. In some embodiments, the axial restraint comprises a radially inwardly extending projection. In some embodiments, the axial restraint comprises an annular flange.

[00032] In some embodiments, the limit comprises a distally facing bearing surface. In some embodiments, the limit comprises a radially outwardly extending projection.

[00033] In some embodiments, the radially outwardly extending projection comprises a spoke which supports a slider configured for sliding contact with an inside surface of the tubular side wall. In some embodiments, the radially outwardly extending projection comprises three spokes each supporting a slider.

[00034] In some embodiments, the limit comprises an annular ring. In some embodiments, the limit comprises an annular ring spaced radially outwardly apart from the core wire. In some embodiments, the limit comprises at least two spokes extending between the core wire and the ring. In some embodiments, the limit comprises three spokes extending between the core wire and the ring.

[00035] In some embodiments, a flow path is defined between each adjacent pair of spokes and in communication with the lumen. In some embodiments, the flow path comprised three flow paths and a sum of the cross-sectional areas of the three flow paths is at least about 75% of the cross-sectional area of the lumen within 1 cm proximally of the restraint. In some embodiments, the sum of the cross-sectional areas of the three flow paths is at least about 90% of the cross-sectional area of the lumen within 1 cm proximally of the restraint.

[00036] In any of the embodiments described herein, the core wire is tapered from a larger diameter at a proximal point to a smaller diameter at the limit that is no more than about 30% of the larger diameter. In any of the embodiments described herein, the core wire is tapered to a smaller diameter at the limit that is no more than about 18% of the larger diameter. In any of the embodiments described herein, the core wire is tapered from a diameter of about 0.025 inches at a proximal point to a diameter that is no more than about 0.005 inches at the limit.

[00037] In some embodiments, a spring is carried by the core wire and extends proximally from the tip for a length within the range of from about 5 cm to about 60 cm. In some embodiments, the spring extends proximally from the tip for a length within the range of from about 20 cm to about 40 cm.

[00038] In some embodiments, the limit is positioned within about the distal most 50% of the catheter length. In some embodiments, the limit is positioned within about the distal most 25% of the catheter length. [00039] In some embodiments, the core wire is removably positionable within the tubular body.

[00040] In some embodiments, the bearing surface decouples distal advance of the agitator tip beyond the tubular body in response to positioning the tubular body within tortuous vasculature.

[00041] In accordance with another aspect of the present invention, there is provided a system for removing embolic material from an intravascular site. In some embodiments, the system comprises: an elongate, flexible tubular body, having a proximal end, a distal end, and a tubular side wall defining at least one lumen extending axially there through; an axial restraint carried by the side wall and exposed to the lumen; a rotatable core wire extendable through the lumen, the core wire having a proximal end and a distal end; a limit carried by the core wire, the limit having a bearing surface for rotatably engaging the restraint; and an agitator tip on the distal end of the core wire. The agitator tip comprises: a first section having a distal tip offset from a center axis of the core wire by 0.02 to 0.03 inches, the first section comprising a first bend opposite the distal tip and having a radius of curvature of 0.01 to 0.02 inches; a second section attached to the first section, the second section comprising a second bend in a first direction opposite the first bend, the second bend having a radius of curvature of 0.01 to 0.015 inches, and a third section attached to the second section and the distal end of the core wire, the third section comprising a third bend in a second direction opposite the second bend and in the same direction as the first bend, the third bend having a radius of curvature of 0.012 to 0.013 inches. A width-wise cross-section of the distal tip, the first bend, the second bend, and the third bend is in the same plane as the core wire. The limit and the restraint are engageable to permit rotation of the core wire but limit distal advance of the agitator tip relative to the tubular body.

[00042] In some embodiments, the tubular side wall further comprises one or more tracks configured to contact one or more of the first bend, the second bend, and the third bend. In some embodiments, a number of tracks matches a number of bends. In some embodiments, one or more of the first bend, the second bend, and the third bend are configured to contact the tubular side wall and maintain the core wire axially centered during rotation.

[00043] In some embodiments, the first bend is offset from the center axis by 0.0.01 to 0.02 inches. In some embodiments, the second bend is offset from the center axis in the first direction by 0.03 to 0.04 inches. In some embodiments, the third bend is offset from the center axis in the second direction by 0.03 to 0.04 inches.

[00044] In some embodiments, the distal tip and second bend extend from a first side of the agitator tip and the first bend and the third bend extend from a second side of the agitator tip, the first side being opposite the second side.

[00045] In accordance with another aspect of the present invention, there is provided a kit for removing embolic material from an intravascular site. The kit comprises: an elongate, flexible tubular body, having a proximal end, a distal end, and a tubular side wall defining at least one lumen extending axially there through; an axial restraint carried by the side wall and exposed to the lumen; a rotatable core wire extendable through the lumen and comprising: a proximal end and a distal end, a limit having a bearing surface for rotatably engaging the restraint, and an agitator tip on the distal end, such that the agitator tip comprises at least one loop joined to the core wire at a junction. The limit and the restraint are engageable to permit rotation of the core wire but limit distal advance of the agitator tip relative to the tubular body.

[00046] In some embodiments, the at least one loop is configured to remove a first type of emboli from the intravascular site. In some embodiments, the first type of emboli comprises predominantly red blood cells.

[00047] In some embodiments, the agitator tip comprises a second loop joined to the core wire at the junction. In some embodiments, the second loop is spaced apart from the at least one loop by 20 to 60 degrees.

[00048] In some embodiments, a length of the at least one loop and the second loop is less than 3 mm.

[00049] In some embodiments, the system further comprises a second rotatable core wire independently extendable through the lumen and comprising: a second proximal end and a second distal end, a second limit having a second bearing surface for rotatably engaging the restraint, and a helical thread agitator tip on the distal end. The second limit and the restraint are engageable to permit rotation of the second core wire but limit distal advance of the helical thread agitator tip relative to the tubular body.

[00050] In some embodiments, the helical thread agitator tip is configured to remove a first type or a second type of emboli from the intravascular site.

[00051] In some embodiments, the first type of emboli comprises predominantly red blood cells and the second type of emboli comprises predominantly one or more of: nucleated cells, fibrin, collagen, and plasma. [00052] In some embodiments, the helical thread agitator tip has a major diameter that is no more than about 90% of the inside diameter of the lumen, leaving an annular flow path between the tip and an inner surface of the side wall. In some embodiments, the helical thread agitator tip has a blunt outer edge. In some embodiments, the helical thread agitator tip defines a helical flow channel between axially adjacent threads, and the sum of the cross-sectional area of the helical flow channel and the annular flow path is at least about 20% of the cross-sectional area of the lumen. In accordance with another aspect of the present invention, there is provided a method of removing embolic material from a vessel with mechanical and aspiration assistance. The method comprises: providing a kit comprising an aspiration catheter having a central lumen and a distal end, a first agitator tip, and a second agitator tip; determining a type of obstructive material in a vessel;

selecting the first agitator tip or the second agitator tip based on the type of obstructive material in the vessel; advancing the selected agitator tip to the obstructive material in the vessel; rotating the selected agitator tip within the central lumen, the selected agitator tip having an axial length of no more than about 5 mm and a major diameter that is at least about 0.015 inches smaller than an inside diameter of the lumen, to provide an aspiration flow path around the outside of the tip; and applying vacuum to the central lumen and rotating the selected agitator tip to draw material into the lumen.

[00053] In some embodiments, rotating comprises manually rotating a core wire which extends through the catheter and rotates the tip.

[00054] In some embodiments, the method additionally comprises limiting distal advance of the core wire by rotating a limit carried by the core wire with respect to a restraint positioned in the central lumen.

[00055] In some embodiments, applying vacuum comprises applying pulsatile vacuum.

[00056] Any feature, structure, or step disclosed herein can be replaced with or combined with any other feature, structure, or step disclosed herein, or omitted. Further, for purposes of summarizing the disclosure, certain aspects, advantages, and features of the embodiments have been described herein. It is to be understood that not necessarily any or all such advantages are achieved in accordance with any particular embodiment disclosed herein. No individual aspects of this disclosure are essential or indispensable. Further features and advantages of the embodiments will become apparent to those of skill in the art in view of the Detailed Description which follows when considered together with the attached drawings and claims. BRIEF DESCRIPTION OF THE DRAWINGS

[00057] FIG. 1 depicts cerebral arterial vasculature including the Circle of Willis, and an access catheter positioned at an occlusion in the left carotid siphon artery.

[00058] FIGS. 2 through 6 show a sequence of steps involved in positioning of the catheter and aspirating obstructive material from the middle cerebral artery.

[00059] FIGS. 7A-7F depict a sequence of steps to access a neurovascular occlusion for aspiration.

[00060] FIGS. 8A-8F depict an alternative sequence of steps in accordance with an aspect of the present invention involved in accessing a neurovascular occlusion for aspiration.

[00061] FIG. 9 illustrates an aspiration system configured to apply pulsatile negative pressure through the aspiration catheter.

[00062] FIG. 10 illustrates an alternative aspiration system configured to apply pulsatile negative pressure through the aspiration catheter.

[00063] FIG. 11 illustrates a further alternative aspiration system configured to apply mechanical vibration through the aspiration catheter.

[00064] FIGS. 12A-12C depict a pulsed aspiration cycle according to an embodiment.

[00065] FIGS. 13 and 14 illustrate a further alternative aspiration system configured to apply mechanical vibration through the aspiration catheter.

[00066] FIG. 15 illustrates an embodiment of a stylet configured to apply mechanical vibration at a vibration zone on the aspiration catheter.

[00067] FIG. 16A shows an embodiment of a navigation aid assembly having an asymmetrically weighted wire used to create translational movement of the aspiration catheter.

[00068] FIG. 16B shows another embodiment of a navigation aid assembly having a polymer coated wire and/or an asymmetric weight used to create translational movement of the aspiration catheter.

[00069] FIG. 17 illustrates a cross-sectional view of a navigation aid assembly in an inner diameter of a catheter according to an embodiment.

[00070] FIG. 18A illustrates an asymmetric weight distribution of a navigation aid assembly, according to an embodiment.

[00071] FIG. 18B illustrates a varied strut pattern of a navigation aid assembly, according to an embodiment. [00072] FIG. 19 depicts an embodiment of an embolism treatment device that incorporates a distal restriction element in an aspiration catheter.

[00073] FIG. 20 depicts an embodiment of an embolism treatment device that incorporates a telescoping aspiration catheter.

[00074] FIGS. 21A-21B show various embodiments of a distal stopper of an embolism treatment device.

[00075] FIG. 22 depicts a perspective view of a rotating hemostasis valve and a proximal drive assembly.

[00076] FIG. 23A depicts a longitudinal cross-sectional elevational view taken along the line 23A-23A in FIG. 22.

[00077] FIG. 23B depicts an enlarged longitudinal cross-sectional elevational view of the proximal drive assembly from FIG. 23 A.

[00078] FIG. 24 depicts a cross-sectional perspective view of the proximal portion of FIG. 22.

[00079] FIG. 25 depicts a perspective view of an agitator driver, a proximal drive assembly, and a rotating hemostasis valve.

[00080] FIG. 26 depicts an embodiment of an actuator as an automatic electric motor at a proximal portion of an embolism treatment device.

[00081] FIG. 27 depicts an embodiment of a battery powered actuator at a proximal portion of an embolism treatment device.

[00082] F1G.28 depicts an embodiment of an actuator having a thumb paddle configuration.

[00083] FIG. 29 depicts an embodiment of an actuator having a manual ratchet configuration.

[00084] FIG. 30 depicts a simplified stylet such as a hypo tube supported wire placed in a catheter to create a vibration zone.

[00085] FIG. 31 depicts an embodiment of an agitator assembly which can be delivered through a telescoping catheter assembly.

[00086] FIGS. 32A-32B depict another embodiment of an aspiration catheter having a lumen in a sidewall of the aspiration catheter. An embolism treatment device with an extendable distal tip translates axially in the lumen.

[00087] FIG. 33 depicts another embodiment of an actuator at a proximal portion of an embolism treatment device, wherein an agitator translates reciprocally in an axial direction a limited distance defined by a proximal stop in the actuator. [00088] FIGS. 34A-34B depict a cross-sectional view and exploded view, respectively, of a proximal assembly for coupling an actuator to an aspiration and vacuum source.

[00089] FIG. 35 depicts an embodiment of a proximal threaded assembly configured to limit axial translation of an agitator assembly.

[00090] FIGS. 36A-36C depict various embodiments of variable diameter coil assemblies that are located on a distal portion of an embolism treatment device to prevent undesirable shortening and lengthening of a rotating coil inside an aspiration catheter.

[00091] FIGS. 37A-37B depict an embodiment of an agitator tip that is contained in an expandable frame to prevent vessel damage as the agitator tip is extended outside of the catheter lumen and rotated to macerate thrombi.

[00092] FIG. 38A depicts a top view of an embodiment of an agitator tip of an embolism treatment device with a corkscrew wire of variable pitch with a distal section acting to macerate the clot.

[00093] FIG. 38B depicts a side view of the agitator tip of FIG. 38 A.

[00094] FIG. 38C depicts a side view of another embodiment of the agitator tip of

FIG. 38 A.

[00095] FIGS. 39A-39B depict another embodiment of an agitator tip of an embolism treatment device with a single loop configuration.

[00096] FIG. 40 depicts another embodiment of an agitator tip of an embolism treatment device with a double loop configuration.

[00097] FIG. 41 depicts another embodiment of an agitator tip of an embolism treatment device with a flat wire double loop configuration.

[00098] FIG. 42 depicts another embodiment of an agitator tip of an embolism treatment device with a two loop configuration.

[00099] FIG. 43 depicts an embodiment of an aspiration catheter comprising a threaded lumen with threads with the same and opposite pitch as the coils of an agitator tip, for example the agitator tip of FIGS. 38A-38C, such that the agitator tip is prevented from translating beyond the coils having the opposite pitch.

[000100] FIG. 44 depicts an embodiment of an agitator tip further comprising an expandable distal funnel to increase embolus engagement.

[000101] FIG. 45 depicts another embodiment of an agitator tip of an embolism treatment device with a double loop configuration that rotates to maintain a tighter clearance between the embolism treatment device and a catheter inner diameter. [000102] FIGS. 46A-46C depict an embodiment of an agitator tip of an embolism treatment device with a multi -bend configuration.

[000103] FIGS. 47A-47D depict various views of an agitator tip of an embolism treatment device having a curved surface tip configuration that interfaces with a catheter wall at a distal end of the catheter, allowing a corked clot to gently slide into an inner diameter of the catheter.

[000104] FIGS. 48A-48C depict various views of an agitator tip of an embolism treatment device having a flat surface configuration that interfaces with a catheter wall at a distal end of the catheter, allowing a corked clot to gently slide into an inner diameter of the catheter.

[000105] FIGS. 49A-49D depict various embodiments of an agitator tip of an embolism treatment device with a ribbon wire configuration that is configured to spiral upon torqueing of the agitator tip to move clot fragments down the lumen of the catheter after clot maceration at the tip.

[000106] FIG. 50 depicts an embodiment of an agitator tip of an embolism treatment device with an auger feature on an outer diameter of a rotational structure (e.g., coil, braided cable, core wire) that moves clot fragments down the lumen of the catheter after clot maceration at the tip.

[000107] FIGS. 51A-51B depict various embodiments of an agitator tip of an embolism treatment device with an expandable macerating wire with sleeve, wherein removal of the sleeve allows the macerating wire to expand.

[000108] FIG. 52 depicts an embodiment of an enlargeable distal end of a catheter, where an internally threaded corkscrew coil translates the torque from a proximal end to a distal tip of an aspiration catheter to enlarge an inner diameter of the aspiration catheter. The enlargeable distal end rotates and draws the clot into the inner diameter of the large distal end via internal threads.

[000109] FIGS. 53A-53B depict a retracted and unfurled distal end of a catheter, respectively, wherein the unfurled distal end is configured to improve aspiration power by increasing a cross-sectional area of the distal tip of the catheter.

[000110] FIGS. 54A-54B depict an unexpanded and expanded agitator tip, respectively, wherein the expanded agitator tip is configured to improve aspiration power by increasing a cross-sectional area of the distal tip of the catheter. [000111] FIGS. 55A-55C depict various embodiments of an aspiration catheter having a distal end cap defining one or more apertures therethrough to increase an aspiration power and efficiency.

[000112] FIGS. 56A-56D depict various views of an agitator tip of an embolism treatment device, where the catheter has an angled distal tip opening. The agitator tip comprises an inner coil that transmits torque that is modified at a distal end by attaching a soft polymer tube with a tapered or angled distal end.

[000113] FIG. 57 depicts an embodiment of a torque coil that has a large pitch outer wire to minimize the forelengthening and foreshortening.

[000114] FIGS. 58A-58B depict various embodiments of an inner lumen of a catheter that has grooves or flutes to process clot fragments as they progress down the lumen of the catheter to prevent these fragments from getting stuck in the lumen during rotation of the agitator tip or wire assemblies.

[000115] FIGS. 59A-59B depict an embodiment of a clot reseating mechanism, where a cuff or telecoping catheter is slidably placed inside the lumen of the aspiration catheter.

[000116] FIG. 60 depicts an embodiment of an agitator tip of an embolism treatment device that comprises a square shaped tip with a proximal ring fixed to the rotating assembly to gently massage the clot and guide it into the catheter.

[000117] FIG. 61 A depicts a side elevational view of a catheter having an internal stop ring.

[000118] FIG. 61B depicts a longitudinal cross-section through the catheter of FIG.

61 A, and detail view of the stop ring.

[000119] FIG. 61C depicts a side elevational view of an agitator having a

complementary limit for engaging the stop ring of FIGS. 61 A and 61B.

[000120] FIG. 61D depicts a side elevational view of a distal portion of the agitator of FIG. 61C.

[000121] FIG. 61E depicts a longitudinal cross-section through the agitator of FIG. 61D.

[000122] FIG. 61F depicts a perspective cut away view of a distal portion of the agitator of FIG. 61C.

[000123] FIG. 61G depicts a transverse cross-section through a distal stopper carried by the agitator.

[000124] FIG. 61H depicts a transverse cross-section through an alternative distal stopper. [000125] FIG. 62 depicts a side elevational cross-section through an angled distal catheter or extension tube tip.

[000126] The illustrated embodiments are merely examples and are not intended to limit the disclosure. The schematics are drawn to illustrate features and concepts and are not necessarily drawn to scale.

DETAILED DESCRIPTION

[000127] The above mentioned aspects, as well as other aspects, features, and advantages of the present technology will now be described in connection with various embodiments. The inclusion of the following embodiments is not intended to limit the disclosure to these embodiments, but rather to enable any person skilled in the art to make and use the contemplated invention(s). Other embodiments may be utilized and modifications may be made without departing from the spirit or scope of the subject matter presented herein. Aspects of the disclosure, as described and illustrated herein, can be arranged, combined, modified, and designed in a variety of different formulations, all of which are explicitly contemplated and form part of this disclosure.

[000128] The embodiments described herein include a vascular catheter device comprising a proximal end actuator and attachments to an aspiration catheter and agitator assembly. The agitator assembly of some embodiments described herein comprises an elongate member that extends through a lumen of an aspiration catheter and functions to guide a particle, clot, or thrombus into the aspiration catheter; break up the particle, clot, or thrombus; massage a particle, clot, or thrombus; and/or reseat the particle, clot, or thrombus on a distal portion of the aspiration catheter; and/or otherwise interact with the particle, clot, or thrombus. In other embodiments, a wall of the aspiration catheter includes a lumen through which the agitator assembly longitudinally extends, retracts, and/or rotates.

[000129] In other embodiments, a telescoping catheter assembly defining a lumen is positionable in a lumen of an aspiration catheter, such that the agitator assembly is axially translatable and/or rotatable in the lumen of the telescoping catheter assembly. The telescoping catheter assembly is manipulatable from a proximal end via a pusher wire or the like. Exemplary telescoping catheter assemblies are described at least with respect to FIG. 20, FIG. 31, and FIGS. 59A-59B. [000130] In general, the embodiments described herein may include radiopaque markings for tracking using fluoroscopy or other methods. For example, one or more markers may be positioned on a distal tip, portion, segment, or region of a catheter, agitator assembly, or other structure. Alternatively, one or more markers may be positioned anywhere along the length of a catheter, agitator assembly, or other structure. For example, in embodiments in which an agitator assembly includes one or more bends, twists, or coils, a marker band may be included on the one or more bends, twists, or coils to track the location or position of the bend, twist, or coil relative to a wall of the catheter or a vessel wall.

[000131] In general, one or more agitator tips or assemblies described herein may be coupled or attached to a distal end of a core wire, torque coil, braided coil, or the like with or without a lumen therethrough for axial translation and/or rotation. Exemplary torque coils are described at least with respect to FIGS. 36A-36C and FIG. 57.

[000132] In general, one or more core wires, torque coils, braided coils, or the like or a distal end of a catheter or an agitator tip may comprise an expandable feature at a distal end. Exemplary expandable features are described at least with respect to FIGS. 37A- 37B, FIG. 44, FIG. 52, FIG. 53A-53B, and FIGS. 54A-54B.

[000133] In general, an inner diameter and/or a lumen of one or more catheters or elongate tubular bodies described herein may include one or more features to promote clot ingestion and/or limit distance advance of an assembly extending through the lumen of the catheter. Exemplary features or limits are described at least with respect to FIG. 19, FIGS. 21A-21B, FIG. 43, FIGS. 46A-46C, FIGS. 58A-58C, and FIGS. 61A-61H.

[000134] In general, any embodiments described herein may include applying vibration to an elongate body, stylet, agitator assembly, agitator tip, torque coil, core wire, braided coil, etc. in a vibration zone or along a length of the elongate body (e.g., catheter) to reduce stiction and promote catheter tracking in the vasculature.

[000135] Turning now to FIG. 1, which depicts cerebral arterial vasculature including the Circle of Willis. Aorta 100 gives rise to right brachiocephalic artery 82, left common carotid artery (CCA) 80, and left subclavian artery 84. The brachiocephalic artery 82 further branches into right common carotid artery 85 and right subclavian artery 83. The left CCA gives rise to left internal carotid artery (ICA) 90 which becomes left middle cerebral artery (MCA) 97 and left anterior cerebral artery (ACA) 99. Anteriorly, the Circle of Willis is formed by the internal carotid arteries, the anterior cerebral arteries, and anterior communicating artery 91 which connects the two ACAs. The right and left ICA also send right posterior communicating artery 72 and left posterior communicating artery 95 to connect, respectively, with right posterior cerebral artery (PCA) 74 and left PCA 94. The two posterior communicating arteries and PCAs, and the origin of the posterior cerebral artery from basilar artery 92 complete the circle posteriorly.

[000136] When an occlusion occurs acutely, for example, in left carotid siphon 70, as depicted in FIG. 5, blood flow in the right cerebral arteries, left external carotid artery 78, right vertebral artery 76 and left vertebral artery 77 increases, resulting in directional change of flow through the Circle of Willis to compensate for the sudden decrease of blood flow in the left carotid siphon. Specifically, blood flow reverses in right posterior communicating artery 72, right PCA 74, left posterior communicating artery 95. Anterior communicating artery 91 opens, reversing flow in left ACA 99, and flow increases in the left external carotid artery, reversing flow along left ophthalmic artery 75, all of which contribute to flow in left ICA 90 distal the occlusion to provide perfusion to the ischemic area distal to the occlusion.

[000137] As illustrated in FIG. 5, the proximal segment of catheter 10 is transluminally navigated along or over the guidewire, to the proximal side of the occlusion.

Transluminal navigation may be accomplished with the distal section 34 of the catheter in the first, proximally retracted configuration. This enables distal advance of the proximal section 33 until further progress is inhibited by small and/or tortuous vasculature.

Alternatively, the distal section 34 is a separate device, and is not inserted into the proximal section 33 until it is determined that the proximal section 33 cannot safely reach the occlusion. In the example illustrated in FIG. 5, the occlusion may be safely reached by the proximal section 33, without the need to insert or distally extend a distal section 34.

[000138] The distal end of the proximal section 33 of aspiration catheter 10 is inserted typically through an incision on a peripheral artery over a guidewire and advanced as far as deemed safe into a more distal carotid or intracranial artery, such as the cervical carotid, terminal ICA, carotid siphon, MCA, or ACA. The occlusion site can be localized with cerebral angiogram or IVUS. In emergency situations, the catheter can be inserted directly into the symptomatic carotid artery after localization of the occlusion with the assistance of IVUS or standard carotid doppler and TCD.

[000139] If it does not appear that sufficient distal navigation of the proximal section 33 to reach the occlusion can be safely accomplished, the distal section 34 is inserted into the proximal port 20 and/or distally extended beyond proximal section 33 until distal tip 38 is positioned in the vicinity of the proximal edge of the obstruction.

[000140] Referring to FIG. 2, an obstruction 70 is lodged in the middle cerebral artery 97. Proximal section 33 is positioned in the ICA and not able to navigate beyond a certain point such as at the branch 96 to the MCA artery 97. The proximal section 33 may be provided with a distal section 34 carried therein. Alternatively, a separate distal section 34 may be introduced into the proximal end of proximal section 33 once the determination has been made that the obstruction 70 cannot be reached directly by proximal section 33 alone. As seen in FIGS. 3 and 4, the distal section 34 may thereafter be transluminally navigated through the distal tortuous vasculature between proximal section 33 and the obstruction 70.

[000141] Referring to FIG. 5, the obstruction 70 may thereafter be drawn into distal section 34 upon application of constant or pulsatile negative pressure with or without the use of jaws or other activation on the distal end of distal section 34. Once the obstruction 70 has either been drawn into distal section 34, or drawn sufficiently into distal section 34 that it may be proximately withdrawn from the body, proximal section 33 and distal section 34 are thereafter proximally withdrawn.

[000142] Aspiration may be applied via lumen 40, either in a constant mode, or in a pulsatile mode. Preferably, pulsatile application of vacuum will cause the distal tip 38 to open and close like a jaw, which facilitates reshaping the thrombus or biting or nibbling the thrombus material into strands or pieces to facilitate proximal withdrawal under negative pressure through lumen 40. Application of aspiration may be accompanied by distal advance of the distal tip 38 into the thrombotic material.

[000143] Pulsatile application of a vacuum may oscillate between positive vacuum and zero vacuum, or between a first lower negative pressure and a second higher negative pressure. Alternatively, a slight positive pressure may be alternated with a negative pressure, with the application of negative pressure dominating to provide a net aspiration through the lumen 40. Pulse cycling is discussed in greater detail in connection with FIGS. 25A-25C.

[000144] The proximal manifold and/or a proximal control unit (not illustrated) connected to the manifold may enable the clinician to adjust any of a variety of pulse parameters including pulse rate, pulse duration, timing between pulses as well as the intensity of the pulsatile vacuum. [000145] The distal section may thereafter be proximally retracted into proximal section 33 and the catheter proximally retracted from the patient. Alternatively, proximal retraction of the catheter 10 may be accomplished with the distal section 34 in the distally extended position. A vasodilator, e.g., nifedipine or nitropmsside, may be injected through a second lumen to inhibit vascular spasm induced as a result of instrumentation.

[000146] Pressure may be monitored by a manometer carried by the catheter or a wire positioned in a lumen of the catheter. A pressure control and display may be included in the proximal control unit or proximal end of the catheter, allowing suction within the vessel to be regulated.

[000147] Focal hypothermia, which has been shown to be neuroprotective, can be administered by perfusing hypothermic oxygenated blood or fluid. Moderate

hypothermia, at approximately 32 to 34°C, can be introduced during the fluid infusion. Perfusion through a port on manifold 18 can be achieved by withdrawing venous blood from a peripheral vein and processing through a pump oxygenator, or by withdrawing oxygenated blood from a peripheral artery, such as a femoral artery, and pumping it back into the carotid artery.

[000148] If continuous and/or intermittent suction fails to dislodge the occlusion, a thrombolytic agent, e.g., t-PA, can be infused through central lumen 40 or a second lumen to lyse any thrombotic material with greater local efficacy and fewer systemic complications. Administration of thrombolytic agent, however, may not be recommended for devices which are inserted directly into the carotid artery due to increased risk of hemorrhage.

[000149] The intensity of intermittent or pulsatile vacuum applied to lumen 40 may be adjusted to cause the distal tip 38 of the catheter 10 to experience an axial reciprocation or water hammer effect, which can further facilitate both translumenal navigation as well as dislodging or breaking up the obstruction. Water hammer, or more generally fluid hammer, is a pressure surge or wave caused when a fluid in motion is forced to stop or change direction suddenly, creating a momentum change. A water hammer commonly occurs when a valve closes suddenly at the end of a pipeline system, and a pressure wave propagates in the pipe. A pressure surge or wave is generated inside the lumen 40 of the aspiration catheter 10 when a solenoid or valve closes and stops the fluid flow suddenly, or other pulse generator is activated. As the pressure wave propagates in the catheter 10, it causes the catheter 10 to axially vibrate. Since vibration can reduce surface friction between the outer diameter of the catheter 10 and the inner diameter of the vessel wall, it enables catheter to track through tortuous anatomies as well as assist capturing thrombus.

[000150] Referring to FIGS. 7A-7F, the cerebral circulation 1100 is simplified for the ease of demonstrating procedural steps. A thrombotic occlusion 1102 is in the right middle cerebral artery (RMCA) 1104. The RMCA 1104 branches from the right internal carotid artery (RICA) 1106. The RICA 1106 branches from the right common carotid artery (RCCA) (not shown). The RICA 1106 comprises cerebral 1108 (most distal from the aorta 100), cavernous 1110, and petrous 1112 (most proximal from the aorta 100) segments. The RCCA branches from the brachiocephalic artery. The brachiocephalic artery branches from the arch 1114 of the aorta 100.

[000151] The procedural steps for aspirating a thrombotic occlusion are described as follows. Referring to FIG. 7A, an introducer sheath 1120 is introduced at the femoral artery 1118. The outer diameter of the introducer sheath 1120 may be equal to or less than about 12F, 11F, 10F, 9F, 8F, 7F, or 6F. Then, a guide sheath 1122 is inserted through the introducer sheath 1120. The outer diameter of the guide sheath 1122 may be equal to or less than about 9F, 8F, 7F, 6F, 5F, 4F, or 3F, and the inner diameter of the introducer sheath 1120 may be greater than the outer diameter of the guide sheath 1122.

[000152] Referring to FIG. 7B, an insert catheter 1124 is inserted through the guide sheath 1122. The outer diameter of the insert catheter 1124 may be equal to or less than about 9F, 8F, 7F, 6F, 5F, 4F, or 3F, and the inner diameter of the guide sheath 1122 may be greater than the outer diameter of the insert catheter 1124. In some cases, a first guidewire 1126 may be introduced through the insert catheter 1124 (not shown in FIG. 11B). Then, the guide sheath 1122, the insert catheter 1124, and optionally the first guidewire 1126 are tracked up to the aortic arch 1114. The insert catheter 1124 is used to engage the origin of a vessel. In FIG. 7B, the insert catheter 1124 engages the origin 1116 of the brachiocephalic artery 82. An angiographic run is performed by injecting contrast media through the insert catheter 1124. In the cases where the first guidewire 1126 is used before the angiographic ran, the first guidewire 1126 is removed prior to injecting the contrast media.

[000153] Referring to FIG. 7C, the first guidewire 1126 is inserted through the lumen of the insert catheter 1124. Then, the first guidewire 1126, the insert catheter 1124, and the guide sheath 1122 are advanced together to the ICA 1106. Referring to FIG. 7D, due to the stiffness of a typical guide sheath 1122 currently available in the market (e.g., Neuron MAX System produced by Penumbra Inc.), the most distal vessel that the guide sheath 1122 could navigate to is the petrous segment 1112 of the ICA 1106. Once the first guidewire 1126, the insert catheter 1124, and the guide sheath 1122 are advanced to the ICA 1106, both the first guidewire 1126 and the insert catheter 1124 are removed.

[000154] Referring to FIG. 7E, a second guidewire 1132 loaded inside the central lumen of a reperfusion catheter 1130 (e.g., 3Max), which is loaded inside the central lumen of an aspiration catheter 1128 (e.g., ACE 68), are introduced through the guide sheath 1122. The diameter of the second guidewire 1132 may be equal to or less than about 0.03", about 0.025", about 0.02", about 0.016", about 0.014", about 0.01", or about 0.005". The inner diameter of the reperfusion catheter 1130 may be greater than the outer diameter of the second guidewire 1132. The inner diameter of the aspiration catheter 1128 may be greater than the outer diameter of the reperfusion catheter 1130. The inner diameter of the guide sheath 1122 may be greater than the outer diameter of the aspiration catheter 1128. Then, the second guidewire 1132 is advanced distally and positioned at the proximal end of the clot 1102 in the MCA 1104.

[000155] Referring to FIG. 7F, the aspiration catheter 1128 is tracked over the reperfusion catheter 1130 and the second guidewire 1132 to the proximal end of the clot 1102 in the MCA 1104. Both the second guidewire 1132 and the reperfusion catheter 1130 are removed. A vacuum pressure is then applied at the proximal end of the aspiration catheter 1128 to aspirate the clot 1102 through the central lumen of the aspiration catheter 1128.

[000156] A preferable, simplified method for aspirating a thrombotic occlusion in accordance with the present invention is described in connection with FIGS. 8A— 8F.

The alternative steps for aspirating a thrombotic occlusion make use of a transitional guidewire and a transitional guide sheath. The transitional guidewire has a soft and trackable distal segment with a smaller diameter so that the transitional guidewire may be advanced deeper than the guidewire 1126 described in FIG. 1C. In addition, the transitional guide sheath has a soft and trackable distal segment such that the transitional guide sheath may be advanced deeper than the guide sheath 1122 described in FIG. 7D. Using a transitional guidewire and a transitional guide sheath that can be advanced to an area near the clot eliminates the need to use a second guidewire or a reperfusion catheter to reach the clot.

[000157] A pulsatile vacuum pressure aspirator may be used in order to improve effectiveness of aspiration for vascular thrombectomy and to improve catheter trackability through tortuous vasculatures. FIG. 9 shows an embodiment of a pulsatile vacuum pressure aspirator 300 that applies intermittent or pulsatile vacuum to lumen 40. In the illustrated embodiment, the pulsatile vacuum pressure aspirator 300 is in fluid connection with the proximal end 12 of the catheter 10, which comprises a vacuum generator 302, vacuum chamber 310, collection canister 312, solenoid valve 314, frequency modulator 316, valve controller 318, and remote controller 320.

[000158] Vacuum generator 302 comprises a vacuum pump 304, a vacuum gauge 306, and a pressure adjustment control 308. The vacuum pump 304 generates suction. The vacuum gauge 306 is in fluid connection with the vacuum pump 304 and indicates the vacuum pressure generated by the pump 304. The pressure adjustment control 308 allows the user to set a specific vacuum pressure. Any of a variety of controls may be utilized, including switches, buttons, levers, rotatable knobs, and others which will be apparent to those of skill in the art in view of the disclosure herein.

[000159] Vacuum chamber 310 is in fluid connection with the vacuum generator 302 and acts as a pressure reservoir and/or damper. Collection canister 312 is in fluid connection with the vacuum chamber 310 and collects debris. The collection canister 312 may be a removable vial that collects debris or tissues, which may be used for pathologic diagnosis. Vacuum chamber 310 and collection canister 312 may be separate components that are in fluid connection with each other or a merged component. In the illustrated embodiment, the vacuum chamber 310 and the collection canister 312 are a merged component and are in fluid connection with the vacuum generator 302.

[000160] Solenoid valve 314 is located in the fluid connection path between a luer or other connector configured to releasably connect to an access port of the catheter 10 and the vacuum chamber 310 / collection canister 312. The solenoid valve 314 controls the fluid flow from the catheter 10 to the vacuum chamber 310 / collection canister 312.

[000161] Pulsatile vacuum pressure aspirator 300 may comprise a frequency modulator 316 for control of the solenoid valve 314. The frequency modulator 316 generates different electrical wave frequencies and forms, which are translated into the movement of the solenoid valve 314 by the valve controller 318. The wave forms generated from the frequency modulator 316 comprise sinusoidal, square, and sawtooth waves. The wave forms generated from the frequency modulator 316 typically have frequencies less than about 500 Hz, in some modes of operation less than about 20 Hz or less than about 5 Hz. The wave forms have duty cycles ranging from 0%, in which the solenoid valve 314 is fully shut, to 100%, in which the solenoid valve 314 is fully open. [000162] Valve controller 318 modulates the solenoid valve 314 on and off. The valve controller 318 may be electrically or mechanically connected to the solenoid valve 314. Any of a variety of controls may be utilized, including electrical controllers, switches, buttons, levers, rotatable knobs, and others which will be apparent to those of skill in the art in view of the disclosure herein. The valve controller 318 may be mechanically controlled by users or may be electrically controlled by the frequency modulator 316. The frequency modulator 316 and the valve controller 318 may be separate components that are electrically or mechanically connected or a merged component.

[000163] Remote control 320 enables physicians to control the frequency modulator 316 and/or the valve controller 318 for various purposes, such as turning the valve on/off, selecting different wave frequencies, and selecting different wave forms, while manipulating the catheter 10 at the patient side. Remote control 320 may be in wired or wireless communication with aspirator 300.

[000164] By tuning frequency, duty cycle, and wave form, one skilled in the art may match or approximate the resonating frequency to the natural frequency of the catheter. This may further enhance the efficacy of aspiration. The natural frequency of the catheter is typically less than about 260 Hz.

[000165] In another embodiment, shown in FIG. 10, the solenoid valve 414 is positioned in and fluidly connects between the air/fluid reservoir 422 at the atmospheric pressure and the aspiration line 424 connecting the catheter 10 to the vacuum chamber 410 / collection canister 412. Unlike the first embodiment in FIG. 9, this system modulates pressure in the catheter 10 by allowing pressure to vary from vacuum to atmospheric pressure. When the solenoid valve 414 is open to the air/fluid reservoir 422 at atmospheric pressure, the vacuum pressure in the aspiration line 424 decreases to the atmospheric pressure. When the solenoid valve 414 is closed, it increases the vacuum pressure in the aspiration line 424.

[000166] In yet another embodiment, shown in FIG. 11, an electro-magnetic actuated diaphragm 522 is attached to the aspiration line 524 connecting the catheter 10 to the vacuum chamber 510 / collection canister 512. The electromagnetic actuated diaphragm 522, which is similar to that of a speaker driver, generates acoustic pressure waves in the catheter 10. The diaphragm 522 typically has a structure similar to a speaker driver and comprises frame 526, cone 528, dust cap 530, surround 532, spider or damper 534, voice coil 536, and magnet 538. Strength of the acoustic pressure waves may be modulated by the strength of the magnet 538. The frequency modulator 516 connected to the remote control 520 is electrically connected to the diaphragm 522 and generates different electrical wave frequencies and forms, which are translated by the diaphragm 522 into acoustic pressure waves in the aspiration line 524 and the catheter 10.

[000167] Referring to FIGS. 12A-12C, experiments showed that an interrupted vacuum can help aspirate a corked clot stuck at the distal end 2512 of the catheter 2510 by loosening the clot and reshaping it to fit into the catheter 2510 after each vacuum and release cycle. Merely stopping the vacuum is not sufficient to loosen the clot.

Completely releasing (venting to atmospheric pressure) the vacuum and allowing the clot to relax before reapplying a vacuum is found to aspirate the corked clot most efficiently. The period of each vacuum and release cycle may be equal to or greater than about 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 seconds. Alternatively or additionally, devices are described elsewhere herein that all the clot to be reseated on a distal end of the aspiration catheter.

[000168] FIGS. 12A-12C show a logical progression of the vacuum and release cycle as applied to the catheter 2510. A release line 2518 and a vacuum line 2520 are connected to or near the proximal end of the catheter 2510. The release line 2518 is in communication with atmospheric pressure on its proximal end and has a release valve 2514 configured to open or close the fluid communication between the catheter 2510 and the vacuum. The vacuum line 2520 is connected to vacuum on its proximal end and has a vacuum valve 2516 configured to open or close the fluid communication between the catheter 2510 and the vacuum.

[000169] In the first step as shown in FIG. 12A, the release valve 2514 is closed, and the vacuum valve 2516 is open such that the vacuum is applied to the catheter 2510 to aspirate the clot. Then, as shown in FIG. 12B, the release valve 2514 is opened while the vacuum valve 2516 stays open. Because the release line 2518 and the vacuum line 2520 are in fluid communication, either directly or via at least a portion of the catheter 2510, the vacuum is applied mainly through the release line 2518, dropping vacuum applied to the catheter. Finally, as shown in FIG. 12C, the vacuum valve 2516 is shut off, allowing the vacuum to be completely released and the clot to relax. Then, another cycle from FIG. 12A to FIG. 12C begins by closing the release valve 2514 and opening the vacuum valve 2516.

[000170] Despite aspiration being an effective first line therapy, tortuous vasculature is a common reason for failure to treat vasculature occlusions in the body due to inability to track the catheter to the location of the disease. Navigating catheters through tortuous anatomy such as neurovasculature can be a challenge. The catheter has to be very soft as not to damage the vessel wall. At the same time, it also has to be able to negotiate multiple tight turns without kinking. In addition, it has to have sufficient column strength to transmit force axially for advancing through the vasculature. All these performance characteristics are competing design requirements. It is difficult to optimize one performance characteristic without sacrificing the others.

[000171] Reducing friction between the inner diameter of the vessel and the outer diameter of the catheter can minimize axial force required to advance the catheter through tortuous vasculature. Therefore, the column strength of the catheter may be traded off for optimizing other performance requirements of the catheter. An example of a method to reduce friction between the inner diameter of the blood vessel and the outer diameter of the catheter is to apply a thin layer of coating, usually hydrophilic in nature, to the outer diameter of the catheter to reduce its surface friction coefficient while in vivo.

[000172] In addition or as an alternative to the water hammer construction discussed above, axial and or rotational mechanical energy such as vibration or shock waves may be propagated to or generated at the distal end of the catheter using a variety of vibration generators, such as spark gap generators, piezoelectric pulse generators, electric solenoids, rotational shaft (wire) having one or more bends or carrying an eccentric weight, or any of a variety of other impulse generating sources well understood for example in the lithotripsy arts. Mechanical shock wave or pulse generators or motors may be built into the proximal manifold, and/or mechanically coupled to the manifold or proximal catheter shaft as desired. For example, controls are provided on the manifold or on a proximal control coupled to the manifold, to enable the clinician to vary the intensity and time parameters of the mechanical pulses. Shock waves may be propagated along the proximal section to assist in transluminal advance and/or distal section by way of pull wire, depending upon the desired clinical performance.

[000173] In an embodiment shown in FIGS. 13 and 14, the distal end 608 of a vibrating device 600 is placed in fluid connection with the proximal end of the catheter and generates transverse and/or longitudinal vibration in the catheter. By inducing transverse vibration in the catheter, it reduces effective contact surface area between the vessel and the catheter, which in turn reduces surface friction force between the inner diameter of the vessel and the outer diameter of the catheter. In addition, by inducing longitudinal vibration in the catheter, the vibrating device 600 breaks static friction between the inner diameter of the vessel and the outer diameter of the catheter, which reduces overall surface friction. By reducing the friction between the inner diameter of the vessel and the outer diameter of the catheter, the vibrating device 600 improves catheter trackability through tortuous vasculatures.

[000174] In the illustrated embodiment, the proximal end 602 of the vibrating device 600 may be connected to a vacuum pressure source such as a vacuum generator. The proximal connector 604 is attached to the housing 606. In at least one embodiment, the proximal connector 604 may be a luer connector. The distal end 608 of the vibrating device 600 is connected to the catheter. The distal connector 610 is held in place by a flexible seal 612 that is attached to the housing 606. In at least one embodiment, the distal connector 610 may be a luer connector. The flexible seal 612 allows the distal connector 610 to move longitudinally as well as transversely. The flexible tubing links the proximal connector 604 and the distal connector 610, creating an aspiration channel 614 for the fluid to travel through.

[000175] The vibrating device has a controller 616 to turn on/off the vibrating action as well as to vary its frequency. In this embodiment, the controller 616 is drawn as a sliding switch. Any of a variety of controls may be utilized, including electrical controllers, switches, buttons, levers, rotatable knobs, and others which will be apparent to those of skill in the art in view of the disclosure herein.

[000176] A vibration generator, such as a motor 618, has an eccentrically mounted inertial weight on its shaft to generate vibration. Any of a variety of motors may be used, including an electric motor, an electro-magnetic actuator, and a piezoelectric transducer. The frequency of the vibration is related to the RPM of the motor 618. A driving circuit 620 is connected to the motor 618 and the controller 616 and drives the motor 618 at different RPMs based on the manipulation of the controller 616. In the illustrated embodiment, the circuit 620 drives the motor 618 at different RPMs based on the position of the sliding switch. A battery 622 is connected to and powers the driving circuit 620 and the motor 618.

[000177] The motor 618 may be mounted perpendicularly to the length of the aspiration channel 614 to create longitudinal vibration. Also, a mechanical cam may be attached to the motor 618 to create larger magnitude longitudinal reciprocating motion. The frequency range generated by the electric motor is typically less than about 85 Hz. To achieve sonic frequencies in the range from about 85 Hz to about 260 Hz, the electric motor with an electro-magnetic actuator may be used. To achieve ultrasonic frequencies in the range of about 20 Hz to about 1.6 MHz, a piezoelectric transducer may be used. [000178] Turning now to FIGS. 15-18B. Rotational and/or axial mechanical motion, vibration or shock waves may be propagated along or generated within the catheter shaft using a rotational shaft (hypotube or wire) extended therethrough. The rotational shaft may have one or more bends or carry an eccentric weight and may be extended into and through a vascular lumen and rotated to generate vibration at preselected positions (e.g., a distal vibration zone) along the catheter shaft as desired. Mechanical energy may be propagated along the catheter shaft to provide dynamic assistance in translumenal advance, by reducing the effects of friction between the catheter and adjacent vessel wall.

[000179] FIGS. 15-18B relate generally to a system which causes an undulating motion of the catheter along its length. The undulation may be in a plane or may rotate such as a corkscrew pattern. The undulation may consist of a wave-like motion where the wave is a standing wave such that any section of the catheter within a wave moves cyclically along a path lateral to the catheter, where the shape of the catheter along its length at any given time is described by a smoothly varying wave such a sinusoid. The catheter may also be distorted into a corkscrew spiral shape such that the corkscrew rotates along its axis.

It is thought that the undulation motion relieves the stiction at a given point and allows the catheter to progress into the vessel when a force is applied proximally at generally the entry point, such that there is no limit to how slowly the shaft can be rotated and still achieve reduced stiction. At high RPM, such as 10,000 RPM, while this mechanism may also be active, it is possible that the catheter is more generally conceived to be vibrating, possibly meaning that the speed at which contact is made and broken between the catheter and the vessel wall is such that the friction is in the realm of kinetic friction which may be significantly less than the static friction.

[000180] For example, shown in FIG. 15, an agitator such as stylet 702 is permanently or removably inserted into a lumen 40 of the catheter 10 and rotated to generate vibration in the catheter 10 and thus improve catheter trackability through tortuous vasculatures. The stylet 702, whose outer diameter is within the range of from about 0.005 inches (about 0.l27mm) to about 0.035 inches (about 0.889mm), may have at least one bend or at least one weight. The peak to peak transverse distance between the bends will be less than the inner diameter of the catheter 10 when positioned within the catheter. The bends or weights of the stylet 702 may be positioned at different locations along the entire length of the catheter 10 or contained within a vibration zone within the distal most 50% or 30% or 10% of the length of the catheter depending upon desired performance, with the purpose to create the most desirable vibration when tracking the catheter 10 through the distal vasculature.

[000181] The proximal end of the stylet is attached to a motor driver 704 capable of generating rotational and/or axially reciprocating motion at various frequencies to form a motor driver-stylet assembly 700. The assembly 700 has a controller 706 to turn on/off the rotating action as well as to vary its frequency. In this embodiment, the controller 706 is drawn as an on/off button. Any of a variety of controls may be utilized, including electrical controllers, switches, buttons, levers, rotatable knobs, and others which will be apparent to those of skill in the art in view of the disclosure herein. The proximal luer 708 or other connector of the catheter 10 reversibly attaches the catheter 10 to the motor driver.

[000182] Once the catheter 10 has reached its intended location, the entire motor driver-stylet assembly 700 may be detached and removed from the catheter 10 leaving a central aspiration lumen.

[000183] Alternatively, as shown in FIG. 16 A, the stylet 802 may include a long tubular or solid body or hypotube that is weighted at various points along the length eccentrically about the center of rotation to cause vibration under rotation. For example, stylet 802, permanently or removably inserted into a lumen 40 of the catheter 10, may have an asymmetric weight 804 such as a bead at a distal vibration zone or at its distal end. Weight 804 may comprise or be formed of a metallic material, such as steel, aluminum, Nitinol, or polymer material, such as thermoplastic polymers, silicone, etc.

The stylet 802 and weights 804 may be formed as a monolithic elongate member, or the weights 804 may be attached to stylet 802 through a secondary process, such as welding, adhesives, soldering, etc. The stylet 802 may comprise a monofilament, braided or woven filaments or wires. Additionally, in some embodiments as shown in FIG. 16B, stylet 802 may further include a polymer 806 of either a monolithic, extruded component or an injection molded component. The polymer 806 may be disposed about stylet 802 and/or weights 804. The polymer 806 on stylet 802 protects an inner wall of catheter 10 during translation/vibration of stylet 802.

[000184] In another alternative, the stylet 702 may have a heater (e.g., an electric coil) at its distal end that facilitates the dissolution of the thrombus or changes the size of the thrombus that is aspirated into the catheter.

[000185] In another embodiment, as shown in FIG. 17, stylet 902 is disposed internal to the catheter 10 such that the stylet 902, when rotated along the axis of the catheter 10, causes the catheter 10 to move laterally. The motion is generally reciprocal or cyclical, where the cycle may be sinusoidal or have sharp jumps in the position, such as a pulse or sawtooth waveform. Stylet 902 has a flexible shaft of diameter less than the internal diameter of the catheter 10 and protrusions 906 at various positions along the length of the shaft. There may be one or more protrusions 906. The protrusions 906 may have a specific or nonspecific pattern in their rotational orientation around the shaft with respect to each other. In one embodiment, the protrusions 906 are generally alternating sides of the shaft such that they are disposed at or in the vicinity of 180 degrees with respect to each other. In another embodiment, the protrusions 906 have an angle with respect to each other, e.g., less than 180 degrees, and each protrusion 906 is spaced at generally the same angle such that the positions of the protrusions form a spiral. In yet another embodiment, the protrusions 906 have an angle of 0 degrees with respect to each other, such that they are generally all on the same side of the shaft when the shaft is in a relaxed state. In yet another embodiment, the angle between the protrusions 906 is random or varied.

[000186] The protrusions 906 may be spaced several mm to several cm apart. For example, the protrusions 906 may be 1-2 mm, 2-3 mm, 3-4, mm, 4-5 mm, 5-6 mm, 6-7 mm, 7-8 mm, 8-9 mm, 9-10 mm, 1-2 cm, 2-3 cm, 3-4 cm, 4-5 cm, 5-6 cm, 6-7 cm, 7-8 cm, 8-9 cm, 9-10 cm, etc. apart. The protrusions may be of a length of 0.5 to 5 mm, for example 0.5-1 mm ,1-2 mm, 2-3 mm, 3-4 mm, 4-5 mm, 0.5-2 mm, 2-4 mm, etc., where other lengths are also conceived.

[000187] The protrusions 906 may be of different cross-sections and shapes, for example rectangular, square, semi-circular, columnar, etc. They may form a ridge of the width of the stylet 902, or they may extend outward, forming a fan or semicircle in cross- section. Along the length of stylet 902, they may taper such that there are no sharp leading or trailing edges.

[000188] The material of the protrusions 906 may be hard or soft or possess low friction with a catheter wall. An advantage of a soft material may be that is has low abrasion on the inside of the catheter 10. The material may also be a composite, with an internal hard region and an external soft region. Exemplary, non- limiting materials include: steel, aluminum, Nitinol, thermoplastic polymers, silicone, etc. The stylet 902 may also be covered in a soft or low-friction material, for example any of the lubricious coatings described elsewhere herein. The shaft and protrusions may be encapsulated in a preferred material, for example a polymer as described in connection with FIG. 16B. The protrusions 906 may further include or consist of a metal fused to the stylet 902. In one embodiment, a section of metal fused to a stylet 902 provides strength to a protrusion 906 and may be combined with a layer of soft and/or low-friction material generally covering the metal protrusion.

[000189] In one exemplary embodiment, adjacent protrusions 906 are spaced 1 cm or less apart and positioned in the same plane on opposing sides of stylet 902. Protrusion 906 height 912 may be substantially the same as a diameter of stylet 902 and have a length 914 of 2 to 4 mm.

[000190] There may be one protrusion or multiple protrusions 906. In one

embodiment, a single protrusion 906 is positioned at the distal end 910 of the shaft. A single protrusion 906 may also be anywhere along the length of the shaft.

[000191] The height of the protrusions 906 above the shaft, or the thickness of the protrusion 906, may be in the range of 0.1 mm to 5mm or more. In one embodiment, the protrusions 906 are of a height such that the combined thickness of the protrusion 906 and stylet 902 is substantially equal to an internal diameter of the catheter 10 in which it is disposed. For example, a combined thickness of the protrusion 906 and stylet 902 may be 1%, 5%, 10%, 1% to 5%, 5% to 10%, 10% to 15%, 15 to 20%, etc. less than an internal diameter of catheter 10.

[000192] In some embodiments, the protrusions 906 alternate sides of the stylet 902 and a combined width of a protrusion and stylet is nearly equal to an internal diameter of a catheter 10. When the shaft and protrusion system 906 are disposed inside the catheter 10, the stylet 902 is of sufficient stiffness to distort the catheter 10 along its length into a wave pattern, where the wave is smooth and cyclical, such as a sinusoidal wave. This embodiment has been found to be effective at reducing stiction of the catheter 10 when it is inserted in a tube or lumen when the stylet 902 is rotated. At a rotation of around 500 RPM, the catheter 10, when inserted, may move forward at a rate determined by the RPM such that the speed of insertion is generally independent of the force applied at the insertion point. At a rotation rate generally above 10,000 RPM, the catheter 10 may glide easily in a lumen in which it would otherwise be stuck, where the speed of insertion is generally solely dependent on the insertion force. The shaft may be rotated at a low revolution per minute (RPM) range of 1 to 500 RPM, or it may be rotated at a high RPM range of 10 to 20,000 RPM.

[000193] The shaft and protrusions 906 are generally disposed inside the catheter 10 such that the distal ends of the stylet 902 and the catheter are generally coincident. It may be preferable in some instances to have the stylet 902 retracted a distance, such as 0.5 mm to 3 mm, from the catheter tip. In other embodiments, it may be preferable to have the stylet 902 extend a distance of 0.5 to 3mm from the catheter tip. The retracted position may minimize impact to the vessel walls 908 of the edge of the moving catheter tip. In the extended position, the moving stylet 902 may aide in navigation by contacting the vessel walls 908 directly preventing such impediments to motion of the catheter 10, such as hooking of the distal catheter tip on the vessel walls 908 of vessel side branches. Further, in such extended position embodiments, a distal end of stylet 902 of catheter may include a frame or cage to protect the vessel walls from the moving stylet or catheter distal end, as described elsewhere herein.

[000194] A method of catheter insertion includes progressing a catheter to a point where it is inside a vessel in which it is closely contained, such that it does not need additional systems to navigate, and the impediment to progress is dominated by stiction generally arising from progressing through multiple bends of the vessel. At that point, the navigational aid system may be inserted such that the tip of the stylet and catheter are coincident, at which point the rotation may be initiated. The rotation may also be initiated as the stylet is inserted thereby easing the shaft insertion. Once the catheter has progressed to its clinically desirable target location, the stylet may be removed by retracting it out of the catheter. Suction may be employed during any or all of the insertion and progression process, possibly to collect particulates that may be generated by contact between the stylet and the inner catheter wall.

[000195] In another method, a navigational aid system may be inserted into a catheter once the catheter has become stuck, rotation turned on, and the catheter progressed, and the stylet removed. The stylet may be inserted to a point where the stiction is thought to be arising. In this method, an embodiment of the stylet 902 may comprise 3, 4 or 5 protrusions 906 at the distal tip 910 of the stylet 902. The stylet 902 may be moved to different positions along the catheter 10, or it may be moved in a reciprocating fashion, noting that with an induced undulating motion of the catheter 10, in certain embodiments, there may be generally stationary portions of the catheter 10 such as a node in a wave.

The reciprocating motion may be a function of the spacing of the protrusions, such as one spacing distance, or a half spacing distance, corresponding generally to a half or quarter wavelength along the catheter, such that the stationary section and maximally moving section alternate over time. [000196] The shaft may comprise or be made of any flexible material that can also rotate while bent around single or multiple turns, such as any embodiments of a torque coil described herein or known to one of skill in the art.

[000197] In an alternative implementation, as shown in FIGS. 18A-18B, an asymmetric weight distribution is integrally formed into a stylet or an agitator wire 1002 such as by laser cutting, electrical discharge machining, or other technique known in the art. An elongate, flexible wire 1002, with or without a central lumen, is provided with a repeating pattern of windows separated by circumferential struts 552 and axial stmts 546.

[000198] In at least one zone at an axial position 546 along the length of the wire 1002 where vibration is desired, the stmt pattern is varied to create a radially asymmetric weight distribution. As illustrated in FIG. 18B, one or two or five or more stmts 546 may be widened in a vibration zone 548 to leave a little more material in the side wall on a first side 514 of axial stmt 546 compared with a second side 516 of axial stmt 546, the first side 514 being opposite the second side 516 of axial strut 546 of wire 1002.

[000199] Alternatively, asymmetric weighting may be accomplished by crimping a radially asymmetric radiopaque marker into a window on the wire sidewall, which additionally enables visualization of the vibration zone 548. Rotation of the wire above a threshold speed causes the weight to induce lateral vibration of the catheter in the vicinity of the vibration zone. The vibration zone may be at least about 2 cm or 5 cm or 10 cm or 20 cm or more in length, and will typically be in the distal most 10 cm or 20 cm or 50 cm of the wire or stylet length, with the wire configured for insertion into the catheter such that the distal end of the wire is positioned within about 5 cm or 2 cm or less from the distal end of the catheter.

[000200] Turning now to FIGS. 19-20. A system for retrieving clots may include an aspiration catheter; an agitator longitudinally extendable inside the lumen of the aspiration catheter (or in a lumen in a wall of a catheter or in a lumen extendable from the lumen of the aspiration catheter); and, optionally, a driver or actuator connectable to the proximal end of the agitator (e.g., via the rotating hemostasis valve or the proximal drive assembly) with or without a synchronization port. A system for retrieving clots may also be manually manipulated, such that the actuator is absent from the system and a physician or a user of the system manipulates the agitator. The system may allow impulse aspiration and/or impulse injection of media. The media may comprise water, saline solution, or media with an effective amount of drug (e.g., drug therapy such as heparin, plavix, tPA). The components may be manipulated individually or in a synchronized manner using predetemiined operating parameters (e.g., for synchronized aspiration, injection, and rotation).

[000201] In patients with vertebral artery occlusions, treatment with angioplasty can result in complications due to embolization of the occlusive lesion downstream to the basilar artery. Emboli small enough to pass through the vertebral arteries into the larger basilar artery are usually arrested at the top of the basilar artery, where it bifurcates into the posterior cerebral arteries. The resulting reduction in blood flow to the ascending reticular formation of the midbrain and thalamus produces immediate loss of

consciousness. The devices described herein can be used to remove thromboembolic material from the vertebral artery or more distally such as in Ml or M2 arteries.

[000202] A method of retrieving a clot may comprise providing the aspiration catheter, the agitator longitudinally extending or positionable inside the lumen of the aspiration catheter; and, optionally, an actuator coupled to the proximal end of the agitator; placing the catheter adjacent to the clot; attempting to aspirate the clot; if not successful, advancing an agitator distally through the catheter; rotating the agitator in the catheter or extending from the catheter to loosen the clot or guide the clot into the catheter;

optionally injecting media through the agitator to lubricate the clot and/or create a media jet from the distal end of the agitator, configured to help aspirate the clot; transporting the clot proximally inside the lumen of the catheter by applying the vacuum at the proximal end of the catheter; and optionally pulsing the vacuum. As pieces of the clot separate, transport may be assisted by the rotating agitator and/or injection media.

[000203] FIG. 19 shows an embolism treatment system 1900 including a distal agitator tip structure 1915 (several embodiments of which are described elsewhere herein), a catheter 1920, a distal restriction element 1930 disposed on an inner diameter of catheter 1920, a core wire 1960, a distal stopper 1940 on core wire 1960, a torque coil 1950, a proximal hypotube 1970, a rotating hemostatic valve 1980, a hub 1990, a motor or actuator 1996, and an aspiration port 1944, each of which will be described in turn.

[000204] A distal agitator tip structure 1915 may comprise or be formed of a round or flat wire, e.g., diameters 0.001 to 0.050 inches. Various distal agitator tip structures are contemplated and described elsewhere herein. The agitator tip may be formed of or comprise nitinol, stainless steel or other metallic material, formed via laser welding, soldering, brazing, adhesive, or other mechanism known in the art into the final shape.

[000205] In some embodiments, an agitator assembly may be added as an ancillary component to an embolism treatment device, from an array of agitator options (i.e., distinct agitators used for different clinical conditions; e.g., a softer agitator used for disrupting smaller clots), or as a single pre-built assembly (i.e., one agitator/assembly combination). The agitator assembly may have a length less than the length of the main catheter, the same length of the main catheter, the main catheter plus the extension catheter, or longer.

[000206] Studies using histological examination and MRI and CT scans have been performed to characterize thrombus composition based on low flow versus high flow arteries, thrombus size, thrombus location in intracranial circulation, stroke etiology, site of occlusion, reperfusion status, etc. (See, e.g., De Meyer et al.“Analyses of thrombi in acute ischemic stroke: A consensus statement on current knowledge and future directions.” Int. J of Stroke. 2017; 12(6): 606-614; Duffy et. al.“Novel methodology to replicate clot analogs with diverse composition in acute ischemic stroke.” J

Neurolnterventional Surg. 2017; 9:486-491; Sing et al.“Clot Composition and treatment approach to acute ischemic stroke: The road so far.” Ann Indian Acad Neurol. 2013 Oct- Dee; 16(4): 494-497, the disclosures of each of which are herein incorporated by reference in their entireties). These studies and additional insights may allow a physician to know, prior to treatment, a composition of the thrombus that will be encountered during the course of treatment. Therefore, in some embodiments, a kit may include a first agitator assembly configured for use with softer and/or smaller thrombi (e.g., thrombi dominated by red blood cells), and a second agitator assembly configured for use with more fibrous and/or larger thrombi (e.g., thrombi dominated by fibrin, collagen, plasma, nucleated cells, etc). The first agitator assembly may include one or more non-limiting embodiments as shown and described in connection with FIGS. 39-A-39B, 40-42. The second agitator assembly may include one or more non-limiting embodiments as shown and described in connection with FIGS. 38A-38C, 43-44, 46A-46C, 50, 61A-61H. In some embodiments, the first and/or second agitator assembly is configured to maximize a space and/or area between the agitator distal tip and an inner diameter of the catheter, as described in connection with FIGS. 61A-61H. Such agitator assemblies are discussed in greater detail elsewhere herein. In other embodiments, an agitator assembly is provided that is configured for use with more fibrous and/or larger thrombi and softer thrombi, which removes the need to identify a thrombus composition before treatment.

[000207] In some embodiments, the agitator assembly transmits rotational and translational energy from a manual actuator or motor-driven actuator inside a lumen of the aspiration catheter to the thrombus. The agitator assembly may comprise an elongate body comprising a stiff proximal tubular section (i.e., hypotube) attached to a tubular distal section of flexible (in bending) construction that may be attached to a torque coil via welding (laser welding), soldering or adhesives, as described elsewhere herein.

[000208] In general, the agitator subassemblies described herein may include one or more active features at the tip to cause a change in the mechanical properties of the clot and promote easier ingestion into the main aspiration catheter. These features may include local heating or cooling of the face or body of the clot, a microwire for resistive heating, radiofrequency ablation to increase local temperatures, injection of chemical mixtures that are exothermic or light-based (e.g., infrared) heating, injection of liquid nitrogen or other endothermic chemical to induce a heat exchanger that draws heat away from the clot. In some embodiments, the agitator subassembly includes a lumen therethrough and one or more ports at the distal end or tip to deliver such liquids or chemicals.

[000209] In general, the agitator subassembly may be in its final expanded form during insertion into the aspiration catheter, or it may expand from a smaller, unexpanded configuration to a larger, expanded configuration, for example by removing a thin covering sheath or extending the agitator from a distal end of the catheter. Such configurations will be described in greater detail elsewhere herein.

[000210] In some embodiments, as shown in FIG. 19, FIGS. 21A-21B, and FIGS. 61, an embolism treatment system 1900 further includes catheter 1920 with a distal restriction element 1930 disposed on an internal surface 1936 of lumen of catheter 1920. For example, the distal restriction element 1930 may be a metallic (e.g., nitinol, stainless steel, aluminum, etc.) circular band or ring or protrusion built into a sidewall of the catheter near the distal tip, the distal restriction element 130 extending into the inner diameter of the catheter. Distal restriction element 130 may be positioned a distance 1932 from a distal end 1942 of catheter 1920, for example distance 1932 may be 1 to 10 mm,

10 to 20 mm, 20 to 30 mm, 25 to 30 mm, etc. Distance 1932 may be measured from a distal end of a marker band or from a shorter end of an angled distal end. Distance 1932 may be optimized for vessel tortuosity, clot size, clot composition, etc. Further, the distal restriction element 1930 may be radiopaque for visibility under fluoroscopy. In some embodiments, the distal restriction element 1930 may also include one or more features, for example circumferential protrusions or a set of protrusions that extend into the inner diameter of the catheter to interface with a distal stopper 1940 (e.g., distal ring) on the agitator assembly, for example core wire 1960 or torque coil 1950 of agitator assembly. For example, the distal stopper 1940 may comprise one or more protrusions or a circular feature on the rotating assembly which interfaces with the distal restriction element 1930 of the catheter to stop the distal advancement and prevent distal tip displacement beyond the catheter distal tip. The distal stopper 1940 may be optionally supported by an annular hub 1948 carried by the torque coil 1950. The distal stopper 1940 may be a wire, e.g., diameter 0.001 to 0.100 inches, which has an outer diameter closely matched (but undersized) relative to the inner diameter of the catheter. The distal stopper 1940 may be attached to the rotating assembly (i.e., torque coil via multiple (e.g., 2 to 50 thin spokes). The distal stopper 1940 may comprise one or more spokes in the absence of a ring. These spokes center the distal stopper 1940 around the rotating assembly but allow clot material to pass through during ingestion. The spokes may be round wires, e.g., diameter 0.001 to 0.025 inches, or thin flat wires of nitinol, stainless steel, aluminum or other metallic material. In some embodiments, the distal stopper includes 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 spokes. In other embodiments, the distal stopper includes 0 to 5 spokes, 5 to 10 spokes, or 10 to 15 spokes. For example, the distal stopper 2414 may include 3 spokes, as shown in FIGS. 61C and 61F. An angle between adjacent spokes may be between 24 degrees and 180 degrees, depending on the number of spokes. An angle between a first and second spoke may be equal to an angle between a second and third spoke; alternatively, an angle between a first and second spoke may be different than an angle between a second and third spoke. Alternatively or additionally, the distal stopper includes a ring connecting the one or more spokes together, for example as shown in FIGS. 21A-21B. The spokes and/or ring act to center the rotating assembly in the inner diameter of the catheter.

[000211] In some embodiments, as shown in FIG. 19, an embolism treatment system 1900 further includes a torque coil 1950. The torque coil is configured to transmit torque from a proximal end to a distal end of the agitator subassembly. The torque coil 1950 may be a single or multiple layer coil that transmits the torque from the proximal end of the device (e.g., actuator 1996 - manual or electric actuation) to the agitator tip 1915. The torque coil 1950 may be formed of or comprise nitinol, stainless or regular steel, or another alloy. The wire diameters of the torque coil are from 0.001 to 0.010 inches, for example. The number of filers (wires for each wrap) are from 1 to 50, for example. The pitch of the one or more coils is from 0.001 to 5.00 inches, for example. There can be two layers of coil for unidirectional torque transmission or three layers for bi-directional torque transmission or any number of layers is contemplated. The torque coil 1950 outer diameter is from 0.010 to 0.100 inches, for example. In some embodiments, the torque coil further includes a core wire 160 that runs down the center lumen of the torque coil 150 and provides bending stiffness support to the outer torque coil 150. The core wire 160 may be formed of ground nitinol or stainless steel wire with a proximal diameter of 0.002 to 0.050 inches, for example, tapered to a proximal diameter of 0.0020 to 0.050 inches. The taper may be placed anywhere along the length of the core wire 160. In some embodiments, the taper is positioned at an anatomical location such as the petrous segment of the internal carotid artery to allow for proximal stiffness and support, but distal flexibility. In some embodiments, material is aspirated through a lumen of the torque coil.

[000212] In some embodiments, as shown in FIGS. 36A-36C, the torque coil 3600 may include variable diameter coil assemblies, wherein there are segments of larger outer diameter coils 3622 (e.g., 0.05 to 0.09 inches) and smaller outer diameter coils 3624 (e.g., 0.006 to 0.046 inches) connected in series with smaller coils used in selected regions along the length to allow for flexibility and navigation and prevent undesirable shortening and lengthening of the rotating coil. In another embodiment, as shown in FIG. 36B, the torque coil assembly 3600 may include a first larger diameter segment 3626 (e.g., 0.05 to 0.09 inches) and a smaller diameter segment 3628 that comprises one layer of coils removed as compared to the larger diameter segment, yielding a diameter, for example, of 0.036 to 0.076 inches. In some embodiments, the smaller outer diameter coils may include a low bending stiffness at a distal end to improve trackability of the torque coil assembly and ultimately agitator subassembly 3620 in aspiration catheter 3610. A length of larger outer diameter coils 3622, 3626 in FIGS. 36A and 36B, respectively, may approximate an average length of the cervical ICA, for example 10 cm to 13 cm, 11 cm to 12 cm, or 11 cm to 11.5 cm, substantially 11.4 cm. A length of smaller outer diameter coils 3624, 3628 in FIGS. 36A and 36B, respectively, may approximate an average length from Petrous through M2, for example 12 cm to 15 cm, 13 cm to 14 cm, or 13.5 cm to 14 cm, substantially 13.8cm.

[000213] In another embodiment of a variable diameter coil assembly, a tapered coil is used to allow for smoother transitions in stiffness. In another embodiment, as shown in FIG. 36C, a smaller outer diameter torque coil 3600 may include a variable diameter jacket 3630 (e.g., PTFE) over the torque coils, any of the embodiments of torque coils described herein, to increase the diameter of the assembly at various locations along the length. [000214] Further, as shown in FIG. 57, any of the embodiments described elsewhere herein may include a nylon wire 5920 wrapped torque coil 5910 to minimize

forelengthening and foreshortening. Further, the nylon wire 5920 may include a large pitch that allows for continuous processing of the clot as the nylon wire 5920 is longitudinally oriented. For example, with a 0.071 inch outer diameter catheter, core wire 5930 is wrapped with a torque coil 5910 having an 0.026 inch outer diameter, which is further wrapped with a 0.022 inch outer diameter nylon wire 5920 having a pitch between 0.050 inches to 0.060 inches, substantially 0.055 inches. In other embodiments, a 0.017 inch outer diameter nylon wire 5920 having a pitch between 0.040 inches to 0.050 inches, substantially 0.045 inches, is wrapped around torque coil 5910. The combined outer diameter of torque coil 5910 and nylon wire 5920 creates a snug fit between the assembly outer diameter and catheter inner diameter. This snug fit allows the agitator assembly to be retracted proximally without rotation to create a distal vacuum and pull the thrombus or corked thrombus proximally. Other embodiments of torque coil nylon wire assemblies will be described elsewhere herein.

[000215] In some embodiments, as shown in FIG. 19, an embolism treatment system 1900 includes a proximal hypotube 1970. The proximal hypotube 1970 provides additional proximal stiffness. For example, there may be a proximal section of the torque coil l950/core wire 1960 assembly, which is joined (e.g., via solder, braze, weld, adhesive) to a nitinol or stainless steel proximal hypotube 1970. The proximal hypotube 1970 may have an inner diameter from 0.005 to 0.100 inches. Further, the proximal hypotube 1970 may also have a pattern of holes or notches around the circumference for a sectional length which can be tailored to give preferential stiffness or flexibility at desired anatomical locations. The pattern may comprise an interrupted spiral, alternating notches, alternating spiral, repeating sections removed, etc. so that hypotube 1979 bends as agitator tip structure 1915 is rotated.

[000216] In some embodiments, an embolism treatment system 1900 includes a rotating hemostatic valve 1980 that allows the proximal hypotube 1970 to exit the lumen of the telescoping catheter 1920 through a seal. The system 1900 may further include a proximal attachment 1990 that allows for the attachment/detachment of the actuator 1996. This allows the system to be discarded after use if the actuator 1996 is reusable. The proximal attachment 1990 may have a simple key/slot design with a mating feature on the actuator 1996 to provide the torque and rotational input to the system 1900. An exemplary proximal attachment is shown and described in connection with FIGS. 34 A- 34B. Various embodiments of actuator 1994 will be described elsewhere herein.

[000217] Alternatively, in some embodiments, as shown in FIGS. 20 and 31, an embolism treatment system 2000 includes a telescoping catheter 2010, an agitator tip 2020, a seal 2030, an outer aspiration catheter 2040 defining lumen 1302, a sheath 2050, a pusher sheath 2060, a torque coil 2070, a rotating hemostatic valve 2080, an actuator 2090 (e.g., manually or electrically actuated), and a push rod 2018 (e.g., hypotube, skive, wire, rod, etc.). For example, the telescoping catheter 2010 may be a single or multi lumen extrusion of soft polymer, PeBax or Tecothane of varying durometers from 35D to 95D, which contains an internal nitinol or stainless-steel coil and/or braid to give structure support along the length to a varying degree. The telescoping catheter 2010 is positionable in outer aspiration catheter 2040 via push rod 2018. Once outer aspiration catheter 2040 is positioned in the vasculature proximate a thrombus, telescoping catheter 2010 is delivered to a distal end of outer aspiration catheter 2040 via push rod 2018.

[000218] In some embodiments, as shown in FIGS. 20 and 31, a proximal end of the telescoping catheter 2010 includes a seal 2030 to mate the outer diameter 2014 of the telescoping catheter 2010 to the inner diameter 2044 of the larger aspiration catheter 2040. The seal 2030 functions to provide a vacuum seal between the lumens. The proximal section may also include a taper on the extruded plastic to provide strain relief in bending. The proximal section is also open to the lumen of the outer aspiration catheter 2040. The telescoping catheter 2010 may also have a marker band, ring, or other elements 2016 for radiopacity.

[000219] In some embodiments, as shown in FIGS. 20 and 31, system 2000 includes an agitator tip 2020. The agitator tip 2020 may include or be formed of round or flat wire, e.g., diameters 0.001 to 0.050 inches, in nitinol, stainless steel or other metallic material, which is formed via laser welding, soldering, brazing, adhesive, or other process known in the art into the final shape. Various embodiments of agitator tips will be described in greater detail elsewhere herein.

[000220] In some embodiments, as shown in FIGS. 20 and 31, system 2000 optionally includes a sheath 2050 that prevents the rotating torque coil 2070 from wrapping around the inner diameter 2012 of the telescoping catheter 2010 under rotation. The sheath 2050 may be a laser-cut steel or nitinol hypotube or a polymer. It may have a variable stiffness where the proximal section is stiffer than the distal section. This can be achieved by having more material removed from the distal section when creating the hole pattern. In some embodiments, sheath 2050 is coupled to the end of a pusher sheath 2060 by either being a continuous piece, where the pusher sheath 2060 has no material removed from the wall, or by adhesive, solder, braze, weld, or other process known in the art as a butt joint. This feature is attached to the inner diameter 2012 of the telescoping catheter 2010 from the proximal most end of the taper for a length of 0.1 to 10 inches, for example. The sheath 2050 is free within the lumen of the telescoping catheter 2010 after the attachment to the wall ends, allowing the rotating agitator tip 2020 to center itself in the lumen of the catheter at the tip.

[000221] In some embodiments, the pusher sheath 2060 is a stiff hypotube or polymer lumen which pushes the telescoping catheter 2010 into place. It also provides a radial constraint for the rotating torque coil 2070 so it doesn’t coil-over and wrap along the inner diameter 2044 of the catheter 2040. This will reduce the unpredictable shortening or lengthening under rotation of the tip of the rotating assembly relative to the tip of the telescoping catheter 2010. The pusher sheath 2060 may be anywhere from 0.010 to 0.200 inches in outer diameter. In some embodiments, the outer diameter of the pusher sheath 2060 is closer to 0.020 to 0.040 inches. The inner diameter may range from 0.005 to 0.150 inches. In some embodiments, the inner diameter of the pusher sheath 2060 is 0.010 to 0.020 inches.

[000222] In some embodiments of the system 2000, the torque coil 2070 is a single or multiple layer coil that transmits the torque from the proximal end of the device to the agitator tip 2020. The torque coil 2070 may be formed of nitinol, stainless or regular steel, or another alloy. The wire diameters of the torque coil range from 0.001 to 0.010 inches, for example. The number of filers (wires for each wrap) are from 1 to 50, for example.

The pitch of the one or more coils is from 0.001 to 5.00 inches, for example. There can be two layers of coil for unidirectional torque transmission, or three layers for bi-directional torque transmission or any number of layers. The torque coil 2070 outer diameter is from 0.005 to 0.100 inches. In some embodiments, the torque coil 2070 outer diameter is 0.010 to 0.020 inches.

[000223] Further, in some embodiments, as shown in FIG. 20, there may be a rotating hemostatic valve 2080 that allows the rotating assembly to exit the lumen of the telescoping catheter 2010 through a seal 2030. System 2000 may further include an aspiration port and an actuator 2090, as described elsewhere herein.

[000224] In another aspect of the invention, as shown in FIGS. 32A-32B, an embolism treatment system 3200 includes a lumen 3270 in a wall of catheter 3210 for axially translating an agitator subassembly 3272 therethrough. Lumen 3270 includes a restriction element 3274 (e.g., groove) that interacts with stop 3276 on the agitator subassembly to limit axial translation of the agitator subassembly 3200. FIG. 32A shows stop 3276 of agitator subassembly 3200 disposed proximally with respect to restriction element 3274 of lumen 3270 so that a distal tip 3220 of agitator subassembly 3200 is undeployed. FIG. 32B shows stop 3276 of agitator subassembly 3200 disposed distally in restriction element 3274 of lumen 3270 so that a distal tip 3220 of agitator subassembly 3200 is deployed and can interact with thrombus in a lumen 3230 of aspiration catheter 3210 or a thrombus external to catheter 3210. Restriction element 3274 has a defined length so as to control a length (e.g., 1 to 5 mm, 5 to 10 mm, 10 to 15 mm, 1 to 10 cm, 10 to 20 cm, etc.) of the agitator subassembly 3200 that is deployed. The agitator subassembly 3200 may be rotated, where the distal tip 3220 acts as an agitator to the thrombus. In some

embodiments, restriction element 3274 has a larger diameter than the rest of the lumen 3270 to accommodate, for example, stop 3276 on the agitator subassembly 3272. In some embodiments, stop 3276 functions as a marker band.

[000225] In some embodiments of an embolism treatment system, as shown in FIGS. 58A-58B, a lumen 6000 of the aspiration catheter 6010 may be a fluted or grooved to prevent clot or thrombus fragments from becoming stuck as they rotate with a rotating agitator subassembly. The flutes or grooves offer resistance to clot rotation and may not compromise the aspiration lumen patency of the catheter. These grooves or flutes may be part of a separate sleeve that is added to the lumen of the aspiration catheter as an accessory to be used with the rotating agitator subassembly or integrated during manufacturing into the inner diameter of the aspiration catheter. For example, the flutes or grooves may be configured as evenly distributed and sized serrations 6020, as shown in FIG. 26A, or angled serrations 6030, as shown in FIG. 26B, angled in the same direction as the direction of rotation of the agitator subassembly. An angle of the serrations may be 10 to 50 degrees, 20 to 45 degrees, 35 to 45 degrees, etc. The serrations may have a depth of 10% to 90%, 10% to 20%, 20% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 80%, 80% to 90%, etc. of a wall thickness of the catheter, for example. The serrations may be distributed on the inner diameter of the catheter, for example 1 to 5 cm from the tip, 1 to 10 cm, 10 to 20 cm, 20 to 40 cm, 40 to 60 cm, etc. or along an entirety of the catheter inner diameter. [000226] Turning now to FIGS. 61A - 61H which depict an embolization treatment system 2401 in accordance with the present invention, having a distal tip with enhanced axial position control.

[000227] Referring to FIGS. 61 A and 61B, any of the aspiration catheters or tubular extension segments disclosed herein may be provided with an axial restraint for cooperating with a complementary stopper on the agitator to permit rotation of the agitator but limit the distal axial range of travel of the agitator. This allows precise positioning of the distal agitator tip with respect to the distal end of the catheter, decoupled from bending of the catheter shaft, and prevent the distal tip from extending beyond a preset position such as the distal end of the catheter.

[000228] As shown, the restraint comprises at least one projection extending radially inwardly from the inside surface of the tubular body, configured to restrict the inside diameter of the aspiration lumen and engage a distal face carried by the agitator. The restraint may comprise one or two or three or four or more projections such as tabs, or, as illustrated, may comprise an annular ring providing a continuous annular proximally facing restraint surface.

[000229] The distal restraint may be a metallic (e.g., nitinol, stainless steel, aluminum, etc.) circular band or ring or protrusion 2402 mounted on or built into a sidewall 2403 of the catheter near the distal tip, the distal restriction element 2402 extending into the inner diameter of the catheter. Further, the distal restriction element 2402 may be radiopaque for visibility under fluoroscopy. The distal restriction element 2402 carries a proximally facing surface 2405 for example an annular circumferential bearing surface that extends into the inner diameter of the catheter to interface with a distal stopper 2414 on the rotating assembly. For example, the distal stopper 2414 may be a circular feature on the rotating assembly, for example any of the agitator subassemblies described elsewhere herein, which interfaces with the distal restriction element 2402 of the catheter to stop the distal advancement and prevent distal tip displacement beyond the catheter distal tip.

[000230] In some embodiments, in its relaxed form prior to securing within the catheter lumen, the ring 2402 is a C-shaped or cylinder shaped with an axially extending slit to form a split ring. The ring 2402 is compressed using a fixture that collapses the ring to a closed circle shape, allowing it to slide inside the (e.g., 0.071”) catheter. When the ring is released from the fixture, the ring expands radially to the largest diameter permitted by the inside diameter of the catheter. The radial force of the ring engages the insider surface of the catheter and resists axial displacement under the intended use applied forces. In another embodiment, the ring is a fully closed, continuous annular structure (like a typical marker band) and its distal end is slightly flared in a radially outwardly direction to create a locking edge. The ring is inserted into the catheter from the distal end. The flared section with the locking edge keeps the ring in place when axial force is applied from the proximal side.

[000231] Referring to FIGS. 61C and 61D, distal segment 2407 of the rotatable core wire comprises a torque coil 2412 surrounding a core wire 2410. Torque coil 2412 comprises an outer coil 2413 concentrically surrounding an inner coil 2415 having windings in opposite directions. Although the coil 2412 is shown as having a constant diameter, this leaves an internal entrapped space between the coil and the core wire, as a result of the tapering core wire. When the area of the aspiration lumen between the coil and the inside wall of the corresponding catheter is optimally maximized, the diameter of the coil 2412 can taper smaller in the distal direction to track the taper of the core wire. This may be accomplished by winding the coil onto the core wire which functions as a tapered mandrel, or using other techniques known in the art. In this execution, the outer diameter of the core wire tapers smaller in the distal direction, while the area of the aspiration lumen tapers larger in the distal direction.

[000232] As illustrated further in FIGS. 61E and 61F, the torque coil 2412 extends between a proximal end 430 and a distal end 432. The proximal end 430 is secured to a tapered portion of the core wire 2410. As illustrated in FIGS. 61E, the core wire 2410 tapers from a larger diameter in a proximal zone to a smaller diameter in a distal zone 434 with a distal transition 436 between the tapered section and the distal zone 434 which may have a substantially constant diameter throughout. The inside diameter of the inner coil 2415 is complementary to (approximately the same as) the outside diameter at the proximal end 430 of the core wire 2410. The tapered section of the core wire 2410 extends proximally from the distal transition 436 to a proximal transition (not illustrated) proximal to which the core wire 2410 has a constant diameter.

[000233] The torque coil 2412 may additionally be provided with a proximal radiopaque marker and / or connector such as a solder joint 438. In some embodiments, the proximal connector 438 is in the form of an annular silver solder band, surrounding the inner coil 415 and abutting a proximal end of the outer coil 2413.

[000234] The axial length of the torque coil 2412 is within the range of from about 10 mm to about 50 mm and in some embodiments within the range of from about 20 mm to about 40 mm. The distal transition 436 may be positioned within the range of from about 5 mm to about 20 mm and in some implementations within the range of from about 8 mm to about 12 mm from the proximal end of the distal cap 2420.

[000235] Referring to FIG. 61E, the distal stopper 414 may be provided with one or two or three or more spokes 440, extending radially outwardly from the outer coil 413, and optionally supported by an annular hub 442 carried by the torque coil 2412. The spoke 440 supports a slider 441 having a peripheral surface 442, configured for a sliding fit within the inside diameter of the delivery catheter lumen. Preferably at least three or four or five or more spokes 440 are provided, spaced apart equidistantly to provide rotational balance. In the illustrated embodiment, three spokes 440 are provided, spaced at approximately 120° intervals around the circumference of the torque coil 2412.

[000236] The distal stopper 2414 carries a plurality of distal surfaces 446, such as on the slider 441. The distal surface 446 is configured to slidably engage a proximal surface of a stop on the inside diameter of the delivery catheter, such as a proximally facing surface 2405 on a radially inwardly extending annular flange or ring 2402. See FIG. 61B discussed previously. This creates an interference fit with a bearing surface so that the distal stopper 2414 can rotate within the delivery catheter, and travel in an axial distal direction no farther than when distal surface 446 slidably engages the proximal surface 2405 on the stop ring 2402.

[000237] Referring to FIG. 61E, the distal end 432 of the torque coil 2412 is provided with a distal cap 2420. Distal cap 2420 may comprise an annular band such as a radiopaque marker band, bonded to the outside surface of the inner coil 2415, and axially distally adjacent or overlapping a distal end of the outer coil 2413. A proximally extending attachment such as an annular flange 2417 may be provided on the agitator tip 2416, for bonding to the distal cap 2420 and in the illustrated embodiment to the outer coil 2413. The distal cap 2420 may also be directly or indirectly bonded to a distal end of the core wire 2410.

[000238] The agitator tip 2416 is provided with a distal end 450, and a proximally extending helical flange 452 that increases in diameter in the proximal direction.

Although as will be appreciated by those of skill in the art, any agitator tip herein described may be provided in association with the embodiments disclosed in FIGS. 61A- 61H or any other embodiments described elsewhere herein. The flange may extend at least about one full revolution and generally less than about five or four or three revolutions about an extension of the longitudinal axis of the core wire 2410. The helical flange is provided with a rounded, blunt edge 454, configured for slidably rotating within the tubular delivery catheter.

[000239] The maximum outer diameter for the tip 2416 is generally at least about .005 inches and preferably at least about 0.01 inches or 0.015 inches or more smaller than the inner diameter of the catheter aspiration lumen through which the embolism treatment system 2401 is intended to advance, measured at the axial operating location of the tip 2416 when the stopper 2414 is engaged with the stop ring. For example, a tip having a maximum outer diameter in the range of from about 0.050 - 0.056 inches will be positioned within a catheter having a distal inner diameter within the range of from about 0.068 to about 0.073 inches, and in one embodiment about 0.071 inches. With the tip centered in the lumen of the delivery (aspiration) catheter, the tip is spaced from the inside wall of the catheter by a distance in all directions of at least about 0.005 inches and in some embodiments at least about 0.007 inches or 0.010 inches or more.

[000240] Thus, an unimpeded flow path is created in the annular space between the maximum outer diameter of the tip, and the inner diameter of the catheter lumen. This annular flow path cooperates with the vacuum and helical tip to grab and pull obstructive material into the catheter under rotation and vacuum. The annular flow path is significantly greater than any flow path created by manufacturing tolerances in a tip configured to shear embolic material between the tip and the catheter wall.

[000241] Additional aspiration volume is obtained as a result of the helical channel defined between each two adjacent threads of the tip. A cross-sectional area of the helical flow path of a tip having a maximum outer diameter in the range of from about 0.050 to about 0.056 inches will generally be at least about 0.0003 square inches, and in some embodiments at least about 0.00035 or at least about 0.000375 inches. The total aspiration flow path across the helical tip is therefore the sum of the helical flow path through the tip and the annular flow path defined between the outer diameter of the tip and the inner diameter of the catheter lumen.

[000242] The combination of a rounded edge 454 on the thread 452 and space between the thread 452 and catheter inside wall enables aspiration both through the helical channel formed between adjacent helical threads as well as around the outside of the tip 2416 such that the assembly is configured for engaging and capturing embolic material but not shearing it between a sharp edge and the inside wall of the catheter. The axial length of the tip 2416 including the attachment sleeve 2417 is generally less than about 6 mm, and preferably less than about 4 mm or 3 mm or 2.5 mm or less depending upon desired performance.

[000243] The pitch of the thread 452 may vary generally within the range of from about 35 degrees to about 80 degrees, depending upon desired performance. Thread pitches within the range of from about 40 - 50 degrees may work best for hard clots, while pitches within the range of from about 50 to 70 degrees may work best for soft clots. For some implementations the pitch will be within the range of from about 40 - 65 degrees or about 40 - 50 degrees. In some embodiments, a kit may include a first agitator tip having a thread pitch within that range of from about 40-50 degrees and a second agitator tip having a thread pitch within the range of from about 50-70 degrees, such that a physician may select an appropriate agitator tip for a type of clot or switch between agitator tips to better engage and remove thrombus.

[000244] The tip 2416 may additionally be provided with a feature for attracting and / or enhancing adhesion of the clot to the tip. For example, a texture such as a

microporous, microparticulate, nanoporous or nanoparticulate surface may be provided on the tip, either by treating the material of the tip or applying a coating. A coating of a clot attracting moiety such as a polymer or drug may be applied to the surface of the tip. For example, a roughened Polyurathane (Tecothane, Tecoflex) coating may be applied to the surface of at least the threads and optionally to the entire tip. The polyurethane may desirably be roughened such as by a solvent treatment after coating, and adhesion of the coating to the tip may be enhanced by roughening the surface of the tip prior to coating. As will be appreciated by one of skill in the art, such coatings may be applied to any agitator tips described elsewhere herein.

[000245] Alternatively, the core wire 2410 may be provided with an insulating coating to allow propagation of a negative electric charge to be delivered to the tip to attract thrombus. Two conductors may extend throughout the length of the body, such as in a coaxial configuration. Energy parameters and considerations are disclosed in US patent no. 10,028,782 to Orion and US patent publication No. 2018/0116717 to Taff et ak, the disclosures of each of which are hereby expressly incorporated by reference in their entireties herein. As a further alternative, the tip 2416 can be cooled to cryogenic temperatures to produce a small frozen adhesion between the tip and the thrombus. Considerations for forming small cryogenic tips for intravascular catheters are disclosed in US patent publication Nos. 2015/0112195 to Berger et a , and 2018/0116704 to Ryba et ak, the disclosures of each of which are hereby expressly incorporated by reference in their entireties herein. As will be appreciated by one of skill in the art, such insulating coatings and/or cryogenic properties may be applied to any agitator tips described elsewhere herein.

[000246] Referring to FIG. 61G, there is illustrated a cross-section through a distal stopper 2414 in which the slider 441 is a continuous circumferential wall having a continuous peripheral bearing surface 442. Three stmts 440 are spaced apart to define three flow passageways 443 extending axially therethrough. The sum of the surface areas of the leading edges of the struts 440 is preferably minimized as a percentage of the sum of the surface areas of the open flow passageways 443. This allows maximum area for aspiration while still providing adequate support axially for the distal surface 446 (see FIG. 61F) to engage the complementary stop surface on the inside wall of the catheter and prevent the tip 2416 from advancing distally beyond a preset relationship with the catheter. The sum of the leading (distal facing) surface area of the struts is generally less than about 45% and typically is less than about 30% or 25% or 20% of the sum of the areas of the flow passageways 443.

[000247] In an embodiment having a torque coil 2412 with an outer diameter of about 0.028 inches, the outer diameter of the stopper 2414 is about 0.068 inches. The wall thickness of the stmts is generally less than about .015 inches and typically less than about 0.010 inches and, in some implementations, less than about 0.008 inches or 0.005 inches or less. The struts 440 have a length in the catheter axial direction that is sufficient to support the assembly against distal travel beyond the catheter stop ring, and may be at least about 50% of the outer diameter of the stopper 2414. In a stopper 2414 having an outer diameter of about 0.68 inches, the struts 2440 have an axial length of at least about 0.75 mm or 0.95 mm.

[000248] Referring to FIG. 61H, there is illustrated a stopper 2414 having three distinct sliders 441 each supported by a unique stmt 440. The sum of the circumference of the three peripheral surfaces is preferably no more than about 75% and, in some

implementations, no more than about 50% or 40% of the full circumference of a continuous circumferential peripheral surface 442 as in FIG. 61G. This further increases the cross-sectional area of the flow paths 443. In a catheter having an inner diameter of no more than about 0.07 inches, an outer diameter of the hub 443 of at least about 0.026 or 0.028 or 0.030 or more, the sum of the flow paths 443 is at least about .0015 inches, and preferably at least about 0.020 or 0.022 inches or more. The area of the leading edges of the struts 440 and sliders 441 is preferably less than about .003 inches, and preferably less than about 0.001 inches or 0.0008 inches or less. In the catheter axial direction, the length of the struts 440 is at least about 0.50 mm or 0.75 mm, and in one embodiment the length of the struts 440 and sliders 441 is about 1 mm.

[000249] Turning now to FIG. 33, which shows a reciprocating mechanism 3300, disposed in proximal actuator 3320, for axially translating the agitator subassembly 3310 in catheter 3340. For example, the rotational energy of the actuator 3320 to the proximal end 3312 of the agitator subassembly 3310 may be translational as vibrational energy at the distal tip 3314 of the agitator subassembly 3310 that may manifest as either small amplitude lateral or longitudinal translational movement. The longitudinal translational movement may be a“pecking” motion to the thrombus using a reciprocating mechanism 3300 that includes one or two restriction elements 3318. In one embodiment, longitudinal movement may comprise one restriction element 3318, such that a stop (e.g., single bar attached with pins to a wheel on the agitator subassembly) on the agitator subassembly 3310 contacts the restriction element 3318 in a repeated sequence resulting in the “pecking” motion. In another embodiment, longitudinal movement may comprise two restriction elements 3318 spaced apart axially in the proximal actuator 3320, as shown in FIG. 33. The restriction elements 3318 may include a ring, protrusion, or the like that extends into an inner diameter of catheter 3340. The restriction elements 3318 restrict translational movement of the agitator subassembly 3310 to a pre-defined range, resulting in the“pecking” motion. For example, a distance between the two restriction elements 3318 may be 1 to 4 mm, 1 to 2 mm, 1 to 3 mm, 2 to 4 mm, etc. Further, agitator subassembly 3310 includes proximal stop 3316 that restricts axially translation, in a reciprocating manner, between the one or two restriction elements 3318.

[000250] In another aspect of the invention, as shown in FIG. 35, translation of the agitator subassembly 3500 in catheter 3510 is controlled by a screw-like mechanism in actuator 3520. For example, the screw-like mechanism comprises an externally threaded feature 3530, of any thread pitch, and an internally threaded feature 3540. Relative rotation between the internally threaded feature 3540 and the externally threaded feature 3530 allows for translation of the agitator subassembly 3500 with respect to the aspiration catheter 3510. The translation of the agitator subassembly 3500 results in a“pecking” motion at the distal end of the agitator subassembly, the“pecking” motion comprising axial translation 1 to 4 mm, 1 to 2 mm, 1 to 3 mm, 2 to 4 mm, etc.

[000251] In another aspect of the invention, FIGS. 34A-34B show a cross-sectional view and exploded view, respectively, of a proximal coupling attachment 3400. Proximal coupling attachment 3400 includes one or more aspiration ports 3450 and a keyed feature 3416 for coupling proximal coupling attachment to actuator 3410. Actuator 3410 includes a complementary surface 3412 for receiving keyed feature 3416 of the proximal coupling attachment 3400. A proximal end 3418 of proximal coupling attachment 3400 is attached to vacuum source 3400 comprising one or more vacuum ports 3446, 3448. Vacuum port 3448 is in fluid communication with a torque coil, hypotube, core wire, or other elongate body 3420 defining a lumen, the torque coil or core wire 3420 having an agitator tip on a distal end.

[000252] Any of the assemblies, systems, or devices described herein may be manipulated or axially translated manually or using a motorized actuator using any mechanisms described elsewhere herein, for example at least those described in connection with FIG. 22, FIGS. 23A-23B, FIG. 24, FIG. 33, FIGS. 34A-34B, FIG. 35, and FIGS. 61A-61H. Various embodiments of motorized actuators will now be discussed in turn.

[000253] Referring to FIG. 22, there is illustrated a proximal drive assembly and/or the rotating hemostasis valve to provide the interface for driving the agitator 2200, providing the port for injecting media, and the aspiration port. Referring to FIGS. 22, 23 A, 23B, and 24, the proximal drive assembly 2602 and the rotating hemostasis valve 2620 may be releasably or permanently coupled to the proximal end of the agitator 2200. The proximal portion of the agitator 2200 passes proximally through a lumen of the rotating hemostasis valve 2620 and then that of the proximal drive assembly 2602. The proximal end of the agitator 2200 may terminate inside the lumen of the proximal drive assembly 2602. The distal portion of the proximal drive assembly 2602 is inserted into the proximal end of the rotating hemostasis valve 2620. In another embodiment, the proximal drive assembly 2602 may be integrated into the rotating hemostasis valve 2620.

[000254] The rotating hemostasis valve (RHV) 2620 comprises a distal connector 2630 at its distal end, which is configured to couple the rotating hemostasis valve to the proximal end of the catheter (not shown). The distal connector 2630 may be a luer connector. The rotating hemostasis valve 2620 comprises a central lumen along its longitudinal length, through which a proximal section of agitator 2200 passes. The rotating hemostasis valve 2620 further comprises an aspiration port 2622, which bifurcates from the central lumen of the rotating hemostasis valve 2620 and provides the aspiration flow path. The rotating hemostasis valve 2620 comprises a RHV seal 2626 and a proximal rotating collar 2628 at its proximal end. The proximal rotating collar 2628 controls the opening and closing of the RHV seal 2626. The user (e.g., physician) can either open or close the RHV seal 2626 by rotating the proximal rotating collar 2628.

The RHV seal 2626, when closed, does not allow fluid communication between the inside lumen distal of the RHV seal 262 and the inside lumen proximal of the RHV seal 262. At the same time, the RHV seal 262 does not hamper the longitudinal movement of the distal portion of the proximal drive assembly 2602 inside the rotating hemostasis valve 2629.

[000255] Experiments showed that as the wire or hypo tube is rotated back and forth (i.e., oscillating), the distal end of the agitator 2200 changes its position relative to the catheter. The distal end of the agitator 2200 was shown to foreshorten/lengthen as the wire or hypo tube 2624 wound/unwound within the catheter due to the rotation of the agitator 2200 or the increase/decrease in media injection pressure. The proximal rotating collar 2628 and the RHV seal 2626 permit the user (e.g., physician) to account for this variance in length and advance/withdraw the agitator 2200 relative to the catheter and fix it in place by simply moving the proximal drive assembly 2602 in/out of the rotating hemostasis valve 2629. If the agitator 2200 is preloaded into the catheter, the distance may be initially set at a nominal position. In another embodiment, the proximal rotating collar 2628 of the rotating hemostasis valve 2620 may be part of the proximal drive assembly 2602.

[000256] The proximal drive assembly 2602 comprises a proximal drive connector 2604, to which the driver is connected, and a media injection port 2610, into which media is injected. The proximal drive assembly also comprises a bearing 2606, which allows free rotation of the proximal drive connector 2604 with respect to the proximal drive assembly 2602. The proximal drive connection 2604 may be coupled to the proximal end of the agitator 2200 such that the rotation of the proximal drive connector 2604 is translated to the rotation of the wire or hypo tube. The proximal drive assembly further comprises a drive tube seal 2608, which prevents fluid communication between the inside lumen (of the proximal drive assembly 2602) distal of the drive tube seal 2608 and the inside lumen proximal of the drive tube seal 2608.

[000257] Referring to FIG. 25, the driver 2950 is removably connected to the proximal end of the proximal drive assembly 2902 via the proximal drive connection 2604. The driver 2950 is configured to drive the agitator 2200. The driver 2950 is a motorized driver that is automatically controlled with respect to one or more factors such as direction (CCW/CW), speed, duration, etc. The driver 2950 comprises a control 2954 such as a button, which executes a pre-programmed series of steps when pushed. The driver 2954 may be under synchronized control, in which the driver 2954 drives the agitator 2200 in synchronization with aspiration and media injection, when the back of the driver 2950 is plugged into the synchronization port 2952.

[000258] Turning now to FIGS. 26-29, which show various actuator embodiments configured to be used with one or more agitator subassemblies described elsewhere herein. An actuator may be positioned on a proximal portion of an aspiration catheter, the proximal portion further including attachments to the aspiration catheter and agitator subassembly. The distal portion of the system includes everything distal from the proximal attachments to the actuator including the aspiration catheter and the agitator assembly that includes the elongate structure and the distal tip that interacts with the thrombus.

[000259] In some embodiments, as shown in FIG. 26, an actuator 2640 comprises an electric motor configured to provide energy to an agitator subassembly via proximal coupling attachments, particularly occlusive emboli treatment devices. The energy provided by the actuator 2640 may be automatic through a rotational mechanism including a motor that may be activated with a switch, button 2642, or other mechanism known in the art. In some embodiments, the motor may continually or intermittently rotate from 50 to 500,000 RPM. The rotation intermittency may include pulsed, short- burst rotations with a 0.5 second to 100 second duration and a 0.5 second to 100 second pause between pulses. The rotations may be clockwise, counterclockwise, or a combination thereof. Such combinations of rotations may be pre-determined in a particular sequence or manipulatable during a procedure to fit the needs of the user.

[000260] In another aspect of the invention, as shown in FIG. 27, actuator 2730 includes a proximal coupling attachment 2732, input element 2734 (e.g., button, switch, etc.), replaceable power source 2736 (e.g., one or more batteries), power source access cover 2738, and indicator 2740 (e.g., visual, haptic, etc.). As described elsewhere herein, proximal coupling attachment 2732 is configured to matingly receive a feature (e.g., hypotube or hub) of an agitator subassembly to effect movement (e.g., translation, rotation, etc.) of the agitator subassembly via a motor in actuator 2730. A motor in actuator 2730 is turned on or off using input element 2734. In some embodiments, input element 2734 further includes a dial, switch or the like that allows a user to manipulate an RPM or pulsing sequence of motor in actuator 2730. Indicator 2740 may include a light- emitting diode (LED) or other visual indicator as a status indicator of the actuator (e.g., indicator 2740 is on to indicate that the actuator is on; indicator 2740 is on to indicate low batteries/power, indicator 2740 is off to indicate no power, etc.)·

[000261] In another aspect of the invention, as shown in FIGS. 28-29, the rotational energy of the actuator to the proximal end of the agitator subassembly may include a manual mechanism that rotates the agitator subassembly a fixed number of rotations in the clockwise, counterclockwise, or both directions. The rotational mechanism may be geared down, such that one rotation equals 5, 10, 15, 20, or more rotations, for example. The rotations may be from 50 to 50,000 RPM and may ramp from low (e.g., 10 RPM) to high (e.g., 50,000 RPM) speeds with actuation or ramp from high to low. In another aspect of the invention, the actuator 2800 may be a thumb-paddle 2810, as shown in FIG. 28, or squeeze handle with a defined paddle stroke that causes rotation in one, and then the opposite direction when the paddle is returned to the starting position using a torsion spring. In some embodiments, the actuator may include a weighted fly-wheel that uses rotational inertia to maintain rotation following application of a mechanical force or the actuator 2900 may be a simple rotational knob 2910 with or without a ratchet to prevent counter rotation of an agitator subassembly 2920 between turns, as shown in FIG. 29.

[000262] In some embodiments, gearing may be included on either the automatic or manual actuator to increase the output torque to the agitator subassembly that multiples the torque by multiples of 1 to 1,000 times.

[000263] In any of the actuator embodiments described herein, the rotational energy of the actuator to the proximal end of the agitator subassembly may be vibrational at either low frequency (e.g., 1 Hz), medium frequency (e.g., up to 20 kHz), or ultrasonic (e.g., over 20 kHz). The vibrational energy may be transmitted proximally from the actuator, distally through the length of the agitator to the distal tip that engages and/or interacts with an intraluminal thrombus. In some embodiments, the vibrational energy may be applied directly at the distal tip of the agitator from electrically exciting a piezoelectric material at the tip of the agitator. The conductive elements may be added to the length of the agitator assembly or housing catheter wall that carries electrical current to the piezoelectric element to cause distal vibration.

[000264] Various distal tip designs of the agitator subassembly will now be described in turn. FIGS. 30, 37A-53B, 60, and 61A-H described below or elsewhere herein illustrate various agitator tip subassemblies. Any of the agitator subassemblies described herein may be used in combination with any of the trackability, actuation, proximal attachments, and/or aspiration/vacuum embodiments described above or elsewhere herein. [000265] Referring to FIG. 30, an agitator 3000 may comprise an elongate, flexible body such as a wire or hypo tube having a proximal, control end and a distal, active zone or end. The hypo tube agitator has an inside lumen extending longitudinally that allows infusion of media. As shown in FIG. 30, agitator 3000 comprises a wire or hypo tube 1904, introduced into the proximal end of a catheter 1902 and advanced to the distal end 1907 of the catheter 1902. The distal tip 1905 of the agitator 3000 may be placed at, beyond, or inside the distal end of the catheter 1902. The agitator 3000 can be either preloaded into the catheter 1902 and inserted into the patient’s body together with the catheter 1902 or added after the catheter 1902 has been placed. When loaded inside the catheter 1902, the agitator 3000 may extend substantially longitudinally along the length of the catheter 1902. The agitator 3000 may further comprise a controller at the proximal end to axially adjust the distal tip position. The controller of the agitator 3000 may be used to axially adjust the position of the distal tip 1905 when the agitator 3000 is introduced into a variable length catheter.

[000266] The agitator 3000 may be rotated manually or via a motor 1906 driven from the catheter 1902 proximal end to rotate or translate the distal end of the agitator 3000. The driver 1906 may be connected to the proximal end of the agitator 3000 either permanently or removably. The driver 1906 may be a manual driver that is manually controlled such as a guide wire torquer. The driver 1906 may be a motorized driver. The motorized driver may be manually controlled with respect to one or more factors such as rotational direction (CCW/CW), speed, duration, etc. The motorized driver may be automatically controlled with respect to one or more factors such as direction

(CCW/CW), speed, duration, etc. In one mode, the rotational direction of the agitator is periodically reversed.

[000267] The automatically controlled driver may comprise an actuator, and actuating the actuator may execute a pre-programmed series of steps. The actuator may be a button, a dial, a knob, a switch, a lever, a valve, a slide, a keypad, or any combinations thereof, as described elsewhere herein. The driver 1906 may also be under synchronized control, in which the driver 1906 drives the agitator 3000 in synchronization with aspiration and media injection. Media may be infused into/around the clot area to help liberate the clot from the vasculature. The agitator 3000 may be configured to promote motion at the distal end to help engage and move the clot.

[000268] The agitator 3000 comprises a distal end 1912, a proximal end 1914, and a distal tip 1905. The proximal end 1914 of the agitator 3000 has a cross-section and/or wall thickness that is large enough to transmit the torque required to rotate the distal end 1912 of the agitator 3000 when placed in the catheter 1902, within the curved vasculature. The outer diameter of the agitator 3000 may be from about 0.25 mm to about 0.65 mm, from about 0.3 mm to about 0.6 mm, from about 0.35 mm to about 0.55 mm, from about 0.4 mm to about 0.5 mm, from about 0.42 mm to about 0.48 mm, or from about 0.44 mm to about 0.46 mm. In case of the hypo tube 1904, the wall thickness of the hypo tube 1904 may be from about 0.01 mm to about 0.29 mm, from about 0.05 mm to about 0.25 mm, from about 0.1 mm to about 0.2 mm, from about 0.12 mm to about 0.18 mm, from about 0.13 mm to about 0.17 mm, or from about 0.14 mm to about 0.16 mm.

[000269] The agitator 3000 may additionally be provided with a guide tube 3010, such as a hypo tube, to allow the agitator to spin, or axially or rotationally reciprocate, while constraining a proximal drive segment of the agitator 3000 against lateral motion. A distal end 1911 of guide tube 3010 may be positioned within about 25 cm or within about 20 cm or 15 cm or less of the distal end of the agitator 3000, depending upon desired performance. The distal section of the agitator 3000, extending beyond distal end 1911 of guide tube 3010, is laterally unconstrained within the inner diameter of distal segment 34 and available to agitate and facilitate aspiration of material into and through the central lumen.

[000270] The diameter of the agitator 3000 may be constant along its longitudinal length. The diameter of the agitator 3000 may increase or decrease along its longitudinal length to coincide with features of the catheter 1902. In one implementation, the diameter of the agitator 3000 decreases in the distal direction along its longitudinal length by at least one step or tapered zone to provide increasing flexibility.

[000271] The distal end 1912 of the agitator 3000 may be straight. Alternatively, the distal end 1912 of the agitator 3000 may be curved or formed into different shapes to interact with the clot, as described in further detail elsewhere herein. FIG. 30 illustrates a bend 1917 spaced apart from the distal tip 1905 by a motion segment 1909 having a length of from about 1 mm to about 15 mm.

[000272] The agitator 3000 may comprise a single, uniform material or multiple materials. The materials of the agitator 3000 may be processed (e.g., heat

treatment/annealing) to give varying properties for the local performance requirements. The agitator 3000 may be structured to provide flexibility while exhibiting high torque transmission. The agitator 3000 may be made of Nitinol, 304 Stainless Steel, 316 LVM Stainless Steel, PTFE, Parylene, or any combinations thereof. At least a portion of the surface of the agitator 3000 may be coated. The entire length of the agitator 3000 may be coated. The coating on the agitator 3000 may provide lubrication between the inner diameter wall of the catheter 1902 and the agitator 3000. In a case that an intermediate hypotube is placed between the wall of the catheter 1902 and the agitator 3000, e.g., constraining tube 1910 or tubular pull wire 42, the coating on the agitator 3000 may provide lubrication between the intermediate hypotube and the proximal drive portion of the agitator 3000. The coating materials of the wire or hypo tube 1904 include PTFE, Parylene, Teflon, or any combinations thereof.

[000273] Any of the inner diameter or outer diameter of any of the catheter shafts or other catheter components disclosed herein may be provided with a lubricious coating or may be made from a lubricious material. For example, a hydrophilic polymer such as Polyacrylamide, PEO, thermoplastic starch, PVP, and/or copolymers of hydrophilic polymer that can be extruded with hydrophobic polymers such as PEO soft segmented polyurethane blended with Tecoflex. The lubricious coating or the lubricious material may include surface modifying additives (SMA) during melt processing. The lubricious coating or the lubricious material contributes to at least ease of navigation, lower inner diameter skin friction, or better clot removal. In some embodiments, post processing wire ebeam, Gamma, UV, etc. additionally may be desirable to expose to moisture, temperature, etc. Catheters may be made from PEO impregnated polyurethanes such as Hydrothane, Tecophilic polyurethane for both outer diameter and inner diameter lubricity and inherent thromboresistant property without requiring a secondary coating process.

[000274] As shown in FIGS. 37A-37B, in another aspect of the invention, an agitator subassembly may comprise an agitator tip 3700 that expands from an unexpanded configuration when it is constrained by a lumen or sidewall of sheath catheter 3710, as shown in FIG. 37A, to an expanded configuration when it is extended distally out of a lumen of sheath catheter 3710, as shown in FIG. 37B. The agitator tip 3700 may comprise Nitinol that comprises an Austenite state at body temperature. The agitator tip 3700 is prevented from damaging a vessel wall 3704 by frame 3720. Frame 3720 may comprise a shape memory alloy, such that when removed from the constraints of internal diameter of sheath catheter 3710, frame 3720 expands to an internal diameter or substantially an internal diameter of vessel 3704. Frame 3720 may comprise or be formed of two or more metallic wires (e.g., 3, 4, 5, 6, etc.) that are soldered, welded, or adhered and defines one or more apertures 3722 to allow for thrombus 3730 to engage the agitator tip 3700. As shown in FIG. 37B, agitator tip 3700 may be affixed to a distal end of a torquable, tubular body, for example torque coil 3740, so that agitator tip 3700 may rotate independently of frame 3720. Further, as shown in FIG. 37B, frame 3720 is coupled, adhered, soldered, etc. to a distal end of the aspiration catheter 3712 such that as aspiration catheter 3712 is extended distally out of sheath catheter 3710, frame 3720 expands to an internal diameter of vessel 3704. In such embodiments, frame 3720 rotates in unison with aspiration catheter 3712 and agitator tip 3700 rotates in response to torque applied to torque coil 3740. In some embodiments, as shown in FIG. 37B, the agitator tip 3700 further comprises or is coated, at least partially, by a membrane or polymer 3750 (e.g., silicone, super elastic material, fine wire mesh, elastomer, etc.) that creates flow arrest and helps guide the clot 3730 into the agitator tip 3700 and into the aspiration catheter 3712.

[000275] In some embodiments, as shown in FIG. 45, frame 4520 is coupled to a distal end of torque coil 4522 in the absence of an agitator tip disposed within frame 4520. Torque coil 4522 functions to minimize foreshortening/lengthening and is substantially the same diameter as inner diameter of catheter 4510. In such embodiments, frame 4520 is rotated in aspiration lumen 4540 to draw thrombus 4530 into aspiration lumen 4540. Further, in some embodiments, frame 4520 may be formed of or comprise radiopaque wire or material.

[000276] In another aspect of the invention, an agitator tip acts to mechanically disrupt the clot via shearing or impact forces and is in physical contact with the thrombus. As shown in FIGS. 38A-38C, agitator tip 3800 include one or more sections 3852, 3858,

3856 of varying or similar pitch. As shown in FIGS. 38B-38C, a first section 3852 is attached to a second section 3858 and comprises one revolution or turn having a pitch of 0.02 to 0.06 threads/inch (TPI), 0.03 to 0.05 TPI, 0.035 to 0.045 TPI, etc. A second section 3850 is attached to a third section 3856 and comprises 1 to 2 revolutions or turns,

1 to 1.5 revolutions, 1.15 to 1.25 revolutions, 1.2 to 1.3 revolutions, substantially 1.25 revolutions, etc. having a pitch of 0.1 to 0.25 TPI, 0.15 to 0.25 TPI, 0.15 to 0.2 TPI, 0.17 to 0.19 TPI, etc. In some embodiments, a third section 3856 is straight as shown in FIG. 38C; in other embodiments, a third section 3858 comprises 0.25 to 0.5 revolutions, 0.25 to 0.75 revolutions, etc. having a pitch of .1 to 0.25 TPI, 0.15 to 0.25 TPI, 0.15 to 0.2 TPI, 0.17 to 0.19 TPI, etc. In some variations, a first section 3852 and a second section 3850 have the same pitch; in other variations, first section 3852 and second section 3850 have a different pitch. Further, as shown in FIG. 38C, an angle 3870 between the first section 3852 and the second section 3850 may be 0 to 50 degrees, 0 to 40 degrees, 0 to 30 degrees, 0 to 20 degrees, 10 to 30 degrees, 20 to 40 degrees, etc. An angle 3860 between the second section 3850 and the third section 3856 may be 0 to 90 degrees, 30 to 60 degrees, 30 to 45 degrees, 40 to 70 degrees, etc. Agitator tip 3800 further includes distal tip 3856. Distal tip 3856 is angled such that the distal tip aligns with a center axis 3880 of agitator tip 3800, shown as line 3880 in FIG. 38B. In other embodiments, distal tip 3856 is off center from a center axis 3880 by 0.0001 to 0.0005 mm, 0.0001 to 0.005 mm, 0.0005 to 0.005 mm, etc. Distal tip 3856 is configured to engage and/or hook into a thrombus. Distal tip 3856 may have a radius of curvature 3892 of 0.01 to 0.02 inches, 0.011 to 0.015 inches, 0.0115 to 0.0125 inches, or substantially 0.012 inches.

[000277] In some embodiments, an annular flow path from a distal tip 3856 to the third section 3856 is optimized to allow thrombus of varying size and density to pass by agitator tip 3800. For example, angle 3866 between the second section 3858 and third section 3856 may be optimized for an annular flow path of thrombus. Angle 3866 may be greater than 90 degrees, 100 to 180 degrees, 100 to 150 degrees, greater than 100 degrees, 130 to 150 degrees, etc. such that the annular flow path comprises 10% to 50%, 20% to 50%, 20% to 70%, 70% to 99%, 80 to 90%, 90 to 99%, etc. of a catheter inner diameter.

[000278] Further, as shown in FIG. 38 A, a width 3890 of agitator tip 3800 is 0.05 to 1 mm, 0.05 to 0.09 mm, 0.05 to 0.08 mm, 0.05 to 0.07 mm, 0.06 to 0.07 mm, 0.065 to 0.07 mm, etc. As shown in FIG. 38C, a length 3898 of agitator tip 3800 is 2 to 10 mm, 3 to 9 mm, 3 to 9 mm, 4 to 8 mm, 4 to 7 mm, 4.5 to 5.5. mm, etc. A length 3894 of a first section 3852 and a second section 3858 is 1 to 5 mm, 1 to 4 mm, 2 to 3 mm, 2 to 2.5 mm, 2.2 to 2.4 mm, etc.

[000279] In some embodiments, agitator tip 3800 is configured for use with a catheter 4310, as shown in FIG. 43. In other embodiments, agitator tip 3800 is configured for use with a system, comprising a limit and distal restriction element, as shown and described in connection with FIGS. 61A-61H or any other embodiments described elsewhere herein. Returning to FIG. 43, catheter 3800 includes at least two rib-like features 4320, 4322 on an inner diameter of catheter 3800 configured to receive agitator tip 3800. The at least two rib-like features 4320, 4322 protrude into the lumen (i.e., inner diameter) of catheter 4310 and match the pitch of the first turn 3858 and/or second turn 3852 of agitator tip 3800. In some embodiments, agitator tip 3800 is advanced to a first rib-like feature 4322 on the inner diameter of catheter 4310 and rotates or screws past until it reaches the second rib-like feature 4320 on the inner diameter of catheter 4310 where it cannot rotate past due to the opposite pitch of rib-like feature 4320, but rather rotates against to cause a pecking motion, as shown in FIG. 43. In some embodiments, as shown in FIG. 44, agitator tip 4400 is coupled to torque coil 4410 for rotation of agitator tip 4400 and positioned in an internal diameter of a second torque coil or aspiration catheter 4420. Expandable funnel tip 4430 is coupled to a distal end of the second torque coil or aspiration catheter 4420 such that is moves from an unexpanded configuration in a retracted position in sheath catheter 4450 to an expanded configuration in an extended position out of a distal end of sheath catheter 4450. Expandable funnel tip 4430 may comprise or be formed of an expandable membrane or polymer (e.g., elastomer, silicone, etc.) to increase a cross-sectional area of the aspiration catheter 4420 that interacts with thrombus 4460. Funnel tip 4430 may comprise or be formed of a thin, medium durometer polymer or a wire mesh, laminated to form a seal. For example, funnel tip 4430 may have a durometer of 10 to 30A, 5 to 20A, 15 to 25 A, etc. Further, as agitator tip 4400 rotates, funnel tip 4430 functions to protect the vessel walls from damage caused by agitator tip 4400 rotation.

[000280] In another embodiment of an agitator tip, as shown in FIGS. 39-42, an agitator tip may comprise one or more loops. As shown in FIGS. 39A-39B, agitator tip 3900 comprises one loop or curved distal end 3910 coupled to a distal end of torque coil 3914 defining lumen 3915 or core wire at junction 3912. In another embodiment in FIG. 40, agitator tip 4000 includes two loops 4010 coupled to a distal end of torque coil 4014 or core wire at junction 4012. In still another embodiment, agitator tip 4200 may comprise two or more loops 4210 comprising or formed of wire, for example, that protrude distally from a common junction 4212, coupled to a distal end of a torque coil 4214 or core wire, for example. The loops 4210 may have a wire diameter of 0.002 to 0.020 inches, 0.002 to 0.04 inches, 0.004 to 0.025 inches, etc., for example, wherein a thicker wire for loops 4210 results in more stiffness, less fatigue, so that loops 4210 do not collapse during rotation. In some embodiments, a loop diameter may vary from 0.010 to 0.068 inches or can be larger or smaller using a wire from 0.005 to 0.025 inches. The loops may have a diameter that is 10% to 75% of the diameter of the wire or torque coil to which the loops are joined via a junction. The loops may have a length of 1 to 6 mm, for example. The angle between the loops can be from 0 to 180 degrees, 0 to 10 degrees, 10 to 20 degrees, 20 to 30 degrees, 10 to 30 degrees, 30 to 40 degrees, 40 to 50 degrees, 50 to 60 degrees, 40 to 45 degrees, 50 to 70 degrees, 45 to 90 degrees, 90 to 180 degrees, 120 to 180 degrees, 150 to 180 degrees, etc. In one embodiment, as shown in FIG. 40, an angle 4020 between loops 4010 is greater than 150 degrees, substantially 180 degrees, etc. In another embodiment, as shown in FIG. 42, angle 4220 between loops 4210 is 10 to 90 degrees, 30 to 50 degrees, 20 to 60 degrees, etc. In some embodiments, the loops may further include a twist feature, where each loop takes a slight helical shape. In some embodiments, agitator tip 4200 is particularly configured for delivery using an embodiment as shown and described in connection with FIG. 31, but can also be delivered with any of the embodiments described elsewhere herein.

[000281] In some embodiments of an agitator tip 4100, as shown in FIG. 41, two or more loops 4110 may intersect at a distal end 4120 of agitator tip 4100 and couple or adhere to torque coil 4114 or core wire at one or more junctions 4130 at a proximal end of agitator tip 4100. The loops 4110 may comprise or be formed of 1 by 4 mm wire, such that a height of the wire is less than a width of the wire, as shown in FIG. 41. In some embodiments, loops 4110 couple to torque coil 4114 or core wire at four junctions 4130, two per loop 4110. In other embodiments, loops 4110 couple to torque coil 4114 at two junctions 4130, one per loop 4110. The loops 4210 may have a wire diameter of 0.002 to 0.020 inches, 0.002 to 0.04 inches, 0.004 to 0.025 inches, etc., for example, wherein a thicker wire for loops 4210 results in more stiffness, less fatigue, so that loops 4210 do not collapse during rotation. In some embodiments, a loop diameter may vary from 0.010 to 0.068 inches or can be larger or smaller using a wire from 0.005 to 0.025 inches. The loops may have a length of 1 to 6 mm, for example. The angle between the loops can be from 0 to 60 degrees, 0 to 10 degrees, 10 to 20 degrees, 20 to 30 degrees, 10 to 30 degrees, 30 to 40 degrees, 40 to 50 degrees, 50 to 60 degrees, 40 to 45 degrees, etc. In some embodiments, the loops may further include a twist feature, where each loop takes a slight helical shape. In some embodiments, agitator tip 4200 is particularly configured for delivery using an embodiment as shown and described in connection with FIG. 31 , but can be delivered using any embodiments described elsewhere herein. Any of the embodiments of FIGS. 39-42 and as shown in FIG. 39B, the one or more loops may include one or more ports, apertures, or holes 3950 fluidly connected to a lumen of a torque coil or core wire or hypotube to which it is attached to deliver saline, contrast, etc. to a site of occlusion.

[000282] In another embodiment, as shown in FIGS. 46A-46C an agitator tip 4600 may comprise a multi -bend shape. The multi-bend shape functions to center agitator tip 4600 in an inner diameter of a catheter. For example, agitator tip 4600 may include two or more bends, preferably three bends 4610, 4620, 4630. Agitator tip 4600 may be coupled to a distal end of a torque coil 4636, as described elsewhere herein, or to a distal end of a core wire 4634 or wire having a corkscrew configuration, for example as shown in FIG. 46B, and as described elsewhere herein. Distal tip 4650 is attached to a first bend 4630, which is attached to a second bend 4620, which is attached to a third bend 4610. Each bend 4610, 4620, 4630 may have a radius of curvature of 0.01 to 0.025 inches or an angle of curvature of 10 degrees to 90 degrees, 10 to 30 degrees, 20 to 45 degrees, 40 to 60 degrees, etc. For example, a first bend 4630 may have a radius of curvature of 0.005 to 0.025 inches, 0.01 to 0.02 inches, 0.0115 to 0.02 inches, 0.0115 to 0.0118 inches, or substantially 0.0117 inches. Further, for example, a second bend 4620 may have a radius of curvature of 0.01 to 0.015 inches, 0.01 to 0.02 inches, 0.005 to 0.02 inches, 0.0101 to 0.0105 inches, or substantially 0.0102 inches. A third bend 4610 may have a radius of curvature of 0.01 to 0.02 inches, 0.0120 to 0.0130 inches, 0.015 to 0.0125 inches, or substantially 0.0124 inches.

[000283] Distal tip 4650 is offset 4637 from a center axis 4612 of agitator tip 4600 by 0.02 to 0.03 inches, 0.02 to 0.025 inches, 0.015 to 0.03 inches, 0.02005 to 0.0205 inches, substantially 0.0202 inches. The first bend 4630 is offset 4631 from a center axis 4612 of agitator tip 4600 by 0.01 to 0.03 inches, 0.015 to 0.02 inches, 0.0185 to 0.0195 inches, or substantially 0.019 inches. The second bend 4620 is offset 4633 from a center axis 4612 of agitator tip 4600 by 0.03 to 0.04 inches, 0.025 to 0.04 inches, 0.03 to 0.0335 inches, or substantially 0.034 inches. The third bend 4620 is offset 4635 from a center axis 4612 of agitator tip 4600 by 0.03 to 0.04 inches, 0.025 to 0.04 inches, 0.03 to 0.0335 inches, or substantially 0.034 inches. Distal tip 4650 and the second bend 4620 are offset from a center axis 4612 of agitator tip 4600 on a first side of the agitator tip 4600 and the first bend 4630 and third bend 4610 are offset from a center axis 4612 of agitator tip 4600 on a second side of the agitator tip 4600, the first side opposite the second side. Further, as shown in FIG. 46C, a width-wise, or latitudinal cross-section of distal tip 4650 and bends 4610, 4620, 4630 are in the same plane as core wire 4634 or torque coil 4636.

[000284] A total width of agitator tip 4600, offset 4635 plus offset 4633, may be optimized so that agitator tip 4600 is substantially centered and/or axially translatable within a catheter lumen. For example, a total width of agitator tip 4600 may be substantially equal to an inner diameter of the catheter in which the agitator tip 4600 is moving. In some embodiments, a total width of the agitator tip 4600 is 0.05 to 0.1 inches, 0.05 to 0.075 inches, 0.06 to 0.07 inches, 0.065 to 0.075 inches, or substantially 0.068 inches.

[000285] Bend 4630 and distal tip 4650 act to pinch, snare, or otherwise capture a clot therein and draw it into a lumen of the catheter. In some embodiments, bends 4610, 4620, 4630 function to break up the clot, and then smaller clot fragments or emboli are ingested further into the catheter via aspiration and/or a screw mechanism, as shown in FIG. 46B. Agitator tip 4600 may comprise or be formed of a wire of diameter of 0.002 to 0.100 mm, 0.05 to 0.1 mm, 0.004 to 0.05 mm, 0.01 to 0.1 mm, etc. One or more bends 4610, 4620, 4630 are configured to contact an inner diameter wall of a catheter to keep agitator tip 4600 axially centered during rotation. As such, a diameter of agitator tip 4600 is substantially the same as or similar to the inner diameter of the lumen of the catheter in which is axially translates. The catheter inner diameter may include grooves, depressions, or tracks for contacting the bends 4610, 4620, 4630. There may be 1 to 5 or more places of contact (e.g., equal to the number of bends) between the agitator tip 4600 and catheter inner diameter with an atraumatic distal tip 4650 that curls into the center lumen of the catheter to allow for safe tracking through the catheter during insertion in tortuosity. Agitator tip 4600 may have an overall length 4680 of 1 to 10 mm, 1 to 9 mm, 1 to 8 mm,

3 to 8 mm, 4 to 6 mm, 4.5 to 5.5 mm, etc. An overall length 4690 of bent sections 4610, 4620, 4630 is 0.5 to 5 mm, 1 to 4 mm, 2 to 5 mm, 2 to 4 mm, 2 to 3 mm, etc. Agitator tip 4600 may comprise or be formed of a solid wire, braided coil, a coil, hypotube, or other structure which can be robust enough to macerate thrombus under rotation but flexible enough to track the catheter in tortuosity.

[000286] In another embodiment, as shown in FIGS. 47A-47D and FIGS. 48A-48C, an agitator tip 4700, 4800 may comprise a circular, oval, elongated circle, or ellipse shaped configuration. In other embodiments, agitator tip 4720 comprises a square, rectangular, trapezoid or the like shaped configuration, as shown in FIG. 47D. Agitator tips 4700, 4800, 4720 function to guide a clot into a lumen of an aspiration catheter and/or sweep the perimeter of the catheter inner diameter to dislodge and macerate the clot stuck at the catheter tip. As shown in FIGS. 47A-47D, agitator tip 4700, 4720 may include a slight twist or curvature 4710 to a surface of agitator tip 4700, 4720 that may optionally include a serrated feature to allow the agitator tip to increase engagement with the clot. Agitator tip 4700, 4720 may be bent or flexed 4710 from a planar axis or central axis of the device 10 to 50 degrees, 15 to 35 degrees, 10 to 35 degrees, 15 to 40 degrees, 18 to 28 degrees, 20 to 30 degrees, 25 to 30 degrees, 25 +/- 10 degrees, or any range or subrange there between. In another embodiment as shown in FIGS. 48A-48C, the agitator tip 4800 may comprise a substantially unbent or flat configuration, such that a degree of curvature is 0 degrees or substantially 0 degrees. A length 4810 of agitator tip 4700, 4720, 4800 may be 0.05 to 0.2 inches, 0.1 +/- 0.01 inches, 0.08 to 0.1 inches, etc. A thickness 4820 of agitator tip 4700, 4720, 4800 may be 0.001 to 0.01 inches, 0.001 to 0.008 inches, 0.004 to 0.006 inches, etc. A width 4830 of agitator tip 4700, 4720, 4800 may be 0.05 to 0.08 inches, 0.055 to 0.075 inches, 0.06 to 0.07 inches, 0.065 +/- 0.002 inches, etc.

[000287] In another embodiment of the agitator tip 5000, as shown in FIGS. 49A-49D, one or more ribbons 5010 may be attached distally to a wire or torque coil 5020, as shown in FIGS. 49 A and 49C. The one or more ribbons transition from a coiled configuration when torque is applied to wire or torque coil 5020, as shown in FIGS. 49B and 49D, to an unraveled or uncoiled configuration when torque is reduced or released on wire or torque coil 5020, as shown in FIGS. 49A and 49C. In some embodiments, the one or more ribbons 5010 are attached to a distal end 5012 of torque coil 5020, such that the one or more ribbons 5010 slip near or proximal to the distal tip 5012. Torqueing of the wire or torque coil 5020 causes the one or more ribbons 5010 to corkscrew, turning it into a transport mechanism (e.g., Archimedes screw), as shown in FIGS. 49BB and 49D. The pitch of the twist may vary based on an amount of friction and/or whether a clot is engaged. In another embodiment, reverse rotation may be applied to unravel the one or more ribbons 5010 to reduce friction between the wire or torque coil 5020 and the clot and shorten the aspiration distance, where continued reversed rotation causes the screw thread to form in the opposite direction (e.g., right hand thread to left hand thread) to work a difficult to aspirate clot from either direction. The one or more ribbons 5010 may be formed of or comprise a soft or low durometer material, for example silicone. In other embodiments, ribbons 5010 are attached to torque coil 5020 along the length of torque coil 5020 such that movement or slip of ribbons 5010 is minimized during torqueing and/or rotation.

[000288] Turning now to FIG.50. An agitator tip or a torque coil, wire, braided cable, or otherwise body 5200 may include one or more corkscrew or auger features 5210. The auger features 5210 be located on an outer diameter of the rotational structure (e.g., torque coil, braided cable, core wire, etc.) that moves clot fragments down the catheter after clot maceration at the tip. The auger features 5210 may have a pitch of 0.001 to 1.0 TPI, 0.05 to 0.5 TPI, 0.005 to 0.08 TPI, etc. and may be formed of or comprise a round wire, flat ribbon, or other shape. Body 5200 may have a wire diameter from 0.002 to 0.050 inches, 0.005 to 0.05 inches, 0.008 to 0.05 inches, etc. or a flat ribbon wire diameter from 0.003 to 0.015 inches and may be sized to fit close or loose to an inner diameter of the catheter. [000289] In some embodiments, an inner diameter of the catheter may include indentations, grooves, or other features that match a pitch of the auger features 5210, such that the auger features 5210 track along these indentations, grooves, or other features. The auger features 5210 may be metallic to add overall bending stiffness to the rotational structure or non-metallic (e.g., nylon, polyurethane, PEEK, etc.) to maintain flexibility of the rotational structure. The auger features 5210 may be optimized to reduce friction against an inner diameter of the catheter wall through hydrophilic or hydrophobic coatings or through soft-lubricious materials like Teflon and may make up the auger features 5210 itself or added as a jacket or coating over the auger features 5210 or the entirety of body 5200. The auger features 5210 can either span the entire length of body 5200 or sub-section of the body 5200, for example the last (most distal) 0.1 to 30 inches of the distal section of the body 5200. The body 5200 may comprise a center core wire or a torque coil with a flexible filament or wire wrapped around its circumference in a loose pitch along the length to allow for maximum flexibility of the assembly but still provide clot movement down the auger features 5210. The flexible auger material may be nylon, or other polymer material and may have a diameter of 0.001 to 0.250 inches or larger dimension.

[000290] In another embodiment, as shown in FIGS. 51A-51B, the agitator tip 5300 may include a macerating wire 5310 with a sleeve 5320. Macerating wire 5310 is configured to be delivered in an unexpanded configuration in sleeve 5320 and then extended from sleeve 5320 into an expanded configuration. The expanded configuration of macerating wire 5310 forms an eyelet or ellipse, as shown in FIG. 51 A. In the expanded configuration, a first side or wire 5312 and a second side or wire 5314 may be spaced apart by 1 to 10 mm at the greatest diameter and 1 to 2 mm or less than 1 mm at its smallest diameter. The proximal end of the agitator tip 5300 may have an outer diameter of 0.005 to 0.05 inches, 0.01 to 0.05 inches, 0.03 to 0.04 inches, etc. and an inner diameter of 0.005 to 0.05 inches, 0.01 to 0.05 inches, 0.01 to 0.03 inches, 0.02 to 0.03 inches, etc. and may be bonded at junction 5330 to the distal end of a similarly sized core wire, torque coil, or hypotube 5340. The distal tip and torque coil outer diameter may be 0.005 to 0.05 inches, 0.005 to 0.005 inches, 0.005 to 0.03 inches, 0.01 to 0.02 inches, 0.015 to 0.02 inches, etc. and may be bonded to the distal end of a guide wire with an outer diameter of 0.011 inches from a 30 cm taper down to the tip of 0.009 inches. In some embodiments, the proximal end of the guidewire has an outer diameter of 0.005 to 0.05 inches, 0.005 to 0.03 inches, 0.005 to 0.02 inches, 0.01 to 0.02 inches, 0.015 to 0.02 inches, etc. There is a proximal guide wire that may be loaded from a distal tip of the tubing to the proximal tip of the hypotube and may be connected to the guide wire assembly in order to rotate the assembly tip to macerate the clot and increase the ability for smooth tracking through the vasculature, while minimizing the foreshortening and forelengthening of the agitator tip 5300. In some embodiments, agitator tip 5300 comprising macerating wire 5310 and sleeve 5320 may be delivered through an assembly as shown and described in connection with FIG. 20 and/or FIG. 31, but can be delivered with any assembly or catheter structure described elsewhere herein.

[000291] In another embodiment, as shown in FIG. 60, an agitator assembly 6100 may be formed of or comprise a square shaped tip 6110 with a ring 6120 fixed to the assembly 6100 to maintain torque coil 6130 positioned in proximity to or substantially against the catheter wall, leaving maximum space for a clot to pass the torque coil 6130 and to orient the square tip 6110 in a catheter distal tip. For example, the square tip 6110 may be positioned inside the aspiration catheter distal tip, modifying it from a substantially round shape to a square shape to massage the clot and guide it into the catheter. As the clot is massaged and aspirated into the catheter, the clot travels through square tip 6100, through opening 6112, and through ring 6120. As such, a flow path through the square tip 6110 through ring 6120 may be optimized, so that the flow path is 10 to 60%, 60 to 99%, 80 to 99%, 80 to 90%, 70 to 90%, etc. of the inner diameter of the lumen of the catheter in which agitator assembly 6100 resides.

[000292] In another aspect of the inventions described herein, as shown in FIGS. 54- 57, an aspiration catheter or an elongate member may include an expandable distal end configured to improve aspiration power, which is proportional to the cross-sectional area of the tip of the catheter. In some embodiments, the distal end of the catheter is expanded by axial translation of a member, for example a series of torque coils therethrough.

[000293] In some embodiments, as shown in FIG. 52, an embolism treatment device 5400 includes catheter 5410 defining lumen 5412 and has a distal end restriction element 5450. A torque coil is axially translatable through lumen 5412. The torque coil comprises a variable diameter inner torque coil 5430 (e.g., diameter of 0.001 to 0.05 inches), wherein a distal portion 5440 of inner torque coil 5430 is wound with a proximal outer torque coil 5420 (e.g., diameter of 0.005 to 0.05 inches). The distal portion 5440 of inner torque coil 5430 has a larger diameter than a more proximal portion 5442 of inner torque coil 5430. The proximal portion 5442 of inner torque coil 5430 is wound with an outer torque coil 5420, which acts to restrict a diameter of inner torque coil 5420. As the series of torque coils are rotated or torqued, the distal portion 5440 of inner torque coil 5430 acts as a spring to interact with, engage, or otherwise grab a clot, which is then aspirated through lumen 5412. Distal end restriction element 5450 on a distal end of catheter 5410 acts to maintain the series of torque coils within an inner diameter of catheter 5410 as the series of torque coils are rotated in lumen 5412 of catheter 5410. The series of torque coils, comprising inner torque coil 5430 and outer torque coil 5420, comprises a flexible tubular structure that has a substantially similar diameter to an inner diameter of the catheter 5410. Following distal pushing of the series of torque coils, the distal portion 5440 of inner torque coil 5430 flares out to form a funnel shape. The distal portion 5440 of inner torque coil 5430 expands to a pre-determined diameter in improve aspiration power. For example, the pre-determined diameter may be substantially equal to a diameter of the inner diameter of lumen 5412 of catheter 5410.

[000294] In another embodiment, as shown in FIG. 53 A, catheter 5510 includes a torque coil or wire 5520 having a flexible sleeve or membrane 5530 (e.g., same extrusion as catheter tip but unsupported by a coil or braid) on its distal end, the flexible sleeve 5530 being coupled or attached to a distal end 5540 of catheter 5510. Axial displacement of the torque coil or wire 5520 towards a distal end 5540 of catheter 5510, as shown in FIG. 53B, causes the sleeve 5530 to flare out and/or be deployed so that a diameter 5560 of the distal end 5540 of the catheter 5510 is substantially equal to a diameter of the vessel 5550.

[000295] In some embodiments, as shown in FIG. 55 A, catheter 5710 or torque coil comprises a distal end cap 5720 having a suction cup configuration or similar configuration. Distal end cap 5720 extends beyond a distal end of catheter 5710 a distance 5730 of approximately 0.01 to 0.05 inches, substantially 0.035 inches. Distal end cap 5720 defines one or more through holes or apertures configured to improve aspiration power and efficiency. Distal end cap 5720 defines, for example an 8 hole or 6 hole configuration. As shown in FIG. 55B, an 8 hole configuration comprises 8 holes 5726 encircling a center hole 5725, such that each hole 5726 on a perimeter of distal end cap 5720 is approximately 45 degrees from an adjacent hole, as shown by angle 5722.

Further, as shown in FIG. 57C, a 6 hole configuration comprises 6 holes 5728 encircling a center hole 5727, such that each hole 5728 on a perimeter of distal end cap 5720 is approximately 60 degrees from an adjacent hole, as shown by angle 5724. A distance between each hole may be 0.005 to 0.02 inches, for example. [000296] In another variation, the embodiment shown in FIGS. 54A-54B is a combination of the embodiments shown and described in connection with FIGS. 53A- 53B and FIGS. 55A-55C. FIGS. 54A-54B illustrate catheter 5610 having a torque coil or wire 5620 with a flexible membrane 5630 disposed on the distal end of torque coil 5620. As shown in FIG. 54B, as torque coil 5620 is translated axially, flexible membrane 5630 is urged out of the distal end 5612 of catheter 5610 and deployed to an expanded configuration to enable a larger cross-sectional area to interface with a clot. For example, flexible membrane 5630 may expand to a diameter substantially similar to a vessel inner diameter. Flexible membrane 5630 may define one or more holes, for example 1 to 8 holes, to allow clot fragments to be aspirated through lumen 5614. Catheter 5610 may further include a distal end restriction element similar to that described in FIG. 52 to limit distal advancement of flexible membrane 5630. Flexible membrane 5630 may also be attached to a distal end of catheter 5610, as described in FIGS. 53A-53B.

[000297] In another embodiment of the agitator tip, as shown in FIGS. 56A-56D, a distal end 5812 of catheter 5810 defining a lumen and including an angled configuration and an elongate body 5814 (e.g., catheter, hypotube, torque coil, etc.) defining a lumen 5816 extending therethrough may also include an angled configuration. The features of an angled tip configuration are shown and described in connection with FIG. 62. As shown in FIG. 56B, rotation of the elongate body 5814 with respect to the distal end 5812 of catheter 5810 results in an angled opening 5820 at the distal end 5812 of catheter 5810 defined by catheter 5810 and elongate body 5814. Angled opening 5820 may be 10 to 120 degrees, 10 to 90 degrees, 10 to 60 degrees, 20 to 60 degrees, 20 to 45 degrees, etc. The interaction of the angled ends of catheter 5810 and elongate body 5813 creates a scissoring, jaws, or chewing effect to aspirate and/or macerate thrombus 5830. As shown in FIG. 56C, elongate body 5814 may be defined by torque coil 5840, for example with an inner diameter of 0.07 inches with an angled distal tip 5842 having an inner diameter of 0.071 inches, although any diameter size is contemplated. Elongate body 5814 is axially translatable and rotatable within lumen of catheter 5810 (e.g., 0.088 outer diameter catheter). As the clot 5830 is macerated, the fragments are aspirated down the center lumen of the elongate body 5814 and catheter 5810 assembly. In one embodiment, the angles of both distal ends (of the aspiration catheter and agitator tip) may be optimized to slip between the clot and the vessel wall to peel or scrape the clot from the wall, as shown in FIG. 56B. Further, as shown in FIG. 56D, elongate body 5814 may extend distally from catheter 5810 to interface with a clot and draw the clot back to catheter 5810. For example, a clot may become corked on a distal end 5842 of elongate body 5814, such that the corked clot is drawn back into catheter 5810 for removal from the vessel.

[000298] In another embodiment of the invention, as shown in FIGS. 59A-59B, clot corking or reseating devices may be incorporated. A distal end 6212 of catheter 6210 defines one or more flush holes 6230 (e.g., 50 to 500 microns in diameter) in various patterns to allow blood flow or flushing with a fluid (e.g, saline, media, contrast, etc.) into catheter 6210 when a clot 6220 is corked on the distal end 6212. For example, a plurality of flush holes 6230 may be distributed circumferentially around distal end 6212, two flush holes 6230 may be disposed on opposing sides of distal end 6212, or any other configuration is contemplated herein. Flush holes 6230 may be opened (FIG. 59B) and closed (FIG. 59A) with an intraluminal assembly 6240, similar to the telescoping catheter 2010 described in FIG. 31 or comprising a circular cuff 6240 or other structure that impedes flow by covering or blocking flush holes 6230. Circular cuff 6240 or telescoping catheter 2010 is attached to a control wire 6250 or pusher wire axially translatable in lumen 6260 of catheter 6210 and is controlled at the proximal end of the assembly. The size of flush holes 6230 may be optimized to maintain a minimum pressure differential on each side of the clot with smaller holes yielding less flow, but higher-pressure differentials.

[000299] In another embodiment of clot reseating, pulsed pressure waves, as described elsewhere herein, up the column of blood inside lumen 6260 of catheter 6210 may be used. These pressure pulses may be created with a function generator, attached to an amplifier and oscillating diaphragm which is in direct contact with catheter 6210.

Longitudinal waves will travel up lumen 6260 of catheter 6210 through circular cuff 6240 to interface with the corked clot 6220 and reseat it on the distal end 6212 of catheter 6210 as the acoustic waves are generated to improve ingestion. Following corking of the clot 6220, the circular cuff 6240 may be pushed with control wire 6250 controllable from a proximal end of the catheter 6210 and force it a small distance away from the distal end 6212 of catheter 6210. The circular cuff 6240 retracts back into catheter 6210 and, under vacuum, the clot 6220 would re-seat against the distal end 6212 of catheter 6210 and help mobilize the catheter 6210 to ingest the clot 6220. In some embodiments, the circular cuff 6240 may be advanced/retracted cyclically to gently poke the face of the clot 6220.

[000300] Any of the aspiration catheters or tubular extension segments disclosed herein, whether or not an axial filament is included, may be provided with an angled distal tip. Referring to FIG. 62, distal catheter tip 3110 comprises a tubular body 3112 which includes an advance segment 3114, a marker band 3116 and a proximal segment 3118. An inner tubular liner 3120 may extend throughout the length of the distal catheter tip 3110, and may comprise dip coated PTFE .

[000301] A reinforcing element 3122 such as a braid or spring coil is embedded in an outer jacket 3124 which may extend the entire length of the distal catheter tip 3110.

[000302] The advance segment 3114 terminates distally in an angled face 3126, to provide a leading side wall portion 3128 having a length measured between the distal end 3130 of the marker band 3116 and a distal tip 3132. A trailing side wall portion 3134 of the advance segment 3114, has an axial length in the illustrated embodiment of approximately equal to the axial length of the leading side wall portion 3128 as measured at approximately 180 degrees around the catheter from the leading side wall portion 3128. The leading side wall portion 3128 may have an axial length within the range of from about 0.1 mm to about 5 mm and generally within the range of from about 1 to 3 mm.

The trailing side wall portion 3134 may be at least about 0.1 or 0.5 or 1 mm or 2 mm or more shorter than the axial length of the leading side wall portion 3128, depending upon the desired performance.

[000303] The angled face 3126 inclines at an angle within the range of from about 10 degrees to about 80 degrees from the longitudinal axis of the catheter. For certain implementations, the angle is within the range of from about 35 degrees to about 55 degrees from the longitudinal axis of the catheter.

[000304] In the illustrated embodiment, the axial length of the advance segment is substantially constant around the circumference of the catheter, so that the angled face 3126 is approximately parallel to the distal surface 3136 of the marker band 3116. The marker band 3116 has a proximal surface approximately transverse to the longitudinal axis of the catheter, producing a marker band 3116 having a right trapezoid configuration in side elevational view. A short sidewall 3138 is rotationally aligned with the trailing side wall portion 3134, and has an axial length within the range of from about 0.2 mm to about 4 mm, and typically from about 0.5 mm to about 2 mm. An opposing long sidewall 3140 is rotationally aligned with the leading side wall portion 3128. Long sidewall 3140 of the marker band 3116 is generally at least about 10% or 20% longer than short sidewall 3138 and may be at least about 50% or 70% or 90% or more longer than short sidewall 3138, depending upon desired performance. Generally, the long sidewall 3140 will have a length of at least about 0.5 mm or 1 mm and less than about 5 mm or 4 mm. [000305] The marker band may have at least one and optionally two or three or more axially extending slits throughout its length to enable radial expansion. The slit may be located on the short sidewall 3138 or the long sidewall 3140 or in between, depending upon desired bending characteristics. The marker band may comprise any of a variety of radiopaque materials, such as a platinum / iridium alloy, with a wall thickness preferably no more than about 0.003 inches and in one implementation is about 0.001 inches.

[000306] The marker band zone of the assembled catheter will have a relatively high bending stiffness and high crush strength, such as at least about 50% or at least about 100% less than proximal segment 18 but generally no more than about 200% less than proximal segment 3118. The high crush strength may provide radial support to the adjacent advance segment 3114 and particularly to the leading side wall portion 3128, to facilitate the functioning of distal tip 3132 as an atraumatic bumper during transluminal advance and to resist collapse under vacuum. The proximal segment 3118 preferably has a lower bending stiffness than the marker band zone, and the advance segment 3114 preferably has even a lower bending stiffness and crush strength than the proximal segment 3118.

[000307] The advance segment 3114 may comprise a distal extension of the outer jacket 3124 and optionally the inner liner 3120, without other internal supporting structures distally of the marker band 3116. Outer jacket may comprise extruded Tecothane. The advance segment 3114 may have a bending stiffness and radial crush stiffness that is no more than about 50%, and in some implementations no more than about 25% or 15% or 5% or less than the corresponding value for the proximal segment 3118.

[000308] A support fiber 3142 as has been discussed elsewhere herein extends through at least a distal portion of the length of the proximal segment 3118. As illustrated, the support fiber 3142 may terminate distally at a proximal surface of the marker band 3116 and extend axially radially outwardly of the tubular liner 3120 and radially inwardly from the support coil 3122. Fiber 3142 may extend substantially parallel to the longitudinal axis, or may be inclined into a mild spiral having no more than 10 or 7 or 3 or 1 or less complete revolutions around the catheter along the length of the spiral. The fiber may comprise a high tensile strength material such as a multifilament yarn spun from liquid crystal polymer such as a Vectran multifilament LCP fiber.

[000309] One or more of the features illustrated in the drawings and/or described herein may be rearranged and/or combined into a single component or embodied in several components. Additional components may also be added. While certain example embodiments have been described and shown in the accompanying drawings, it is to be understood that such embodiments are merely illustrative and not restrictive. Thus, the inventions are not limited to the specific constructions and arrangements shown and described, since various other modifications may occur to those ordinarily skilled in the art based on the present disclosure.

[000310] Various operations of methods described above may be performed by any suitable means capable of performing the operations. Generally, any operations illustrated in the Figures may be performed by corresponding functional means capable of performing the operations.

[000311] The methods disclosed herein comprise one or more steps or actions for achieving the described method. The method steps and/or actions may be interchanged with one another without departing from the scope of the claims. In other words, unless a specific order of steps or actions is specified, the order and/or use of specific steps and/or actions may be modified without departing from the scope of the claims. Method step and/or actions disclosed herein can be performed in conjunction with each other, and steps and/or actions can be further divided into additional steps and/or actions.

[000312] It is to be understood that the claims are not limited to the precise configuration and components illustrated above. Various modifications, changes and variations may be made in the arrangement, operation and details of the methods and apparatus described above.

Claims

CLAIMS WHAT IS CLAIMED IS:

1. A system for removing embolic material from an intravascular site, comprising:

an elongate, flexible tubular body, having a proximal end, a distal end, and a tubular side wall defining at least one lumen extending axially there through; an axial restraint carried by the side wall and exposed to the lumen;

a rotatable core wire extendable through the lumen, the core wire having a proximal end and a distal end;

a limit carried by the core wire, the limit having a bearing surface for rotatably engaging the restraint; and

an agitator tip on the distal end of the core wire, wherein the agitator tip comprises a helical thread comprising:

a first section having a distal tip aligned with a center axis of the core wire, the first section comprising at least one revolution having a first pitch,

a second section attached to the first section, the second section comprising at least one revolution having a second pitch, and a third straight section attached to the second section and the distal end of the core wire,

wherein the limit and the restraint are engageable to permit rotation of the core wire but limit distal advance of the agitator tip relative to the tubular body.

2. A system as in Claim 1, wherein the first pitch is 0.02 to 0.06 threads per inch.

3. A system as in Claim 1, wherein the second pitch is 0.1 to 0.25 threads per inch.

4. A system as in Claim 1, wherein the second section comprises 1.25 revolutions.

5. A system as in Claim 1, wherein an angle between the first section and the second section is between 0 to 30 degrees.

6. A system as in Claim 1, wherein an angle between the second section and the third section is 30 to 60 degrees.

7. A system as in Claim 1, wherein the axial restraint comprises a proximally facing bearing surface.

8. A system as in Claim 7, wherein the axial restraint comprises a radially inwardly extending projection.

9. A system as in Claim 8, wherein the axial restraint comprises an annular flange.

10. A system as in Claim 1, wherein the limit comprises a distally facing bearing surface.

11. A system as in Claim 10, wherein the limit comprises a radially outwardly extending projection.

12. A system as in Claim 11, wherein the radially outwardly extending projection comprises a spoke which supports a slider configured for sliding contact with an inside surface of the tubular side wall.

13. A system as in Claim 12, comprising three spokes each supporting a slider.

14. A system as in Claim 11, wherein the limit comprises an annular ring.

15. A system as in Claim 1, wherein the limit comprises an annular ring spaced radially outwardly apart from the core wire.

16. A system as in Claim 15, further comprising at least two spokes extending between the core wire and the ring.

17. A system as in Claim 16, comprising three spokes extending between the core wire and the ring.

18. A system as in Claim 13, comprising a flow path defined between each adjacent pair of spokes and in communication with the lumen.

19. A system as in Claim 18, comprising three flow paths and a sum of the cross- sectional areas of the three flow paths is at least about 75% of the cross-sectional area of the lumen within 1 cm proximally of the restraint.

20. A system as in Claim 19, wherein the sum of the cross-sectional areas of the three flow paths is at least about 90% of the cross-sectional area of the lumen within 1 cm proximally of the restraint.

21. A system as in Claim 1, wherein the core wire is tapered from a larger diameter at a proximal point to a smaller diameter at the limit that is no more than about 30% of the larger diameter.

22. A system as in Claim 21, wherein the core wire is tapered to a smaller diameter at the limit that is no more than about 18% of the larger diameter.

23. A system as in Claim 22, wherein the core wire is tapered from a diameter of about 0.025 inches at a proximal point to a diameter that is no more than about 0.005 inches at the limit.

24. A system as in Claim 21, further comprising a spring carried by the core wire and extending proximally from the tip for a length within the range of from about 5 cm to about 60 cm.

25. A system as in Claim 24, wherein the spring extends proximally from the tip for a length within the range of from about 20 cm to about 40 cm.

26. A system as in Claim 1, wherein the limit is positioned within about the distal most 50% of the catheter length.

27. A system as in Claim 26, wherein the limit is positioned within about the distal most 25% of the catheter length.

28. A system as in Claim 1, wherein the core wire is removably positionable within the tubular body.

29. A system as in Claim 26, wherein the bearing surface decouples distal advance of the agitator tip beyond the tubular body in response to positioning the tubular body within tortuous vasculature.

30. A system for removing embolic material from an intravascular site, comprising:

an agitator tip on the distal end of the core wire, wherein the agitator tip comprises:

a first section having a distal tip offset from a center axis of the core wire by 0.02 to 0.03 inches, the first section comprising a first bend opposite the distal tip and having a radius of curvature of 0.01 to 0.02 inches; a second section attached to the first section, the second section comprising a second bend in a first direction opposite the first bend, the second bend having a radius of curvature of 0.01 to 0.015 inches, and

a third section attached to the second section and the distal end of the core wire, the third section comprising a third bend in a second direction opposite the second bend and in the same direction as the first bend, the third bend having a radius of curvature of 0.012 to 0.013 inches, wherein a width-wise cross-section of the distal tip, the first bend, the second bend, and the third bend is in the same plane as the core wire,

31. A system as in Claim 30, wherein the tubular side wall further comprises one or more tracks configured to contact one or more of the first bend, the second bend, and the third bend.

32. A system as in Claim 31, wherein a number of tracks matches a number of bends.

33. A system as in Claim 30, wherein one or more of the first bend, the second bend, and the third bend are configured to contact the tubular side wall and maintain the core wire axially centered during rotation.

34. A system as in Claim 30, wherein the first bend is offset from the center axis by 0.0.01 to 0.02 inches.

35. A system as in Claim 30, wherein the second bend is offset from the center axis in the first direction by 0.03 to 0.04 inches.

36. A system as in Claim 30, wherein the third bend is offset from the center axis in the second direction by 0.03 to 0.04 inches.

37. A system as in Claim 30, wherein the distal tip and second bend extend from a first side of the agitator tip and the first bend and the third bend extend from a second side of the agitator tip, the first side being opposite the second side.

38. A kit for removing embolic material from an intravascular site, comprising: an elongate, flexible tubular body, having a proximal end, a distal end, and a tubular side wall defining at least one lumen extending axially there through; an axial restraint carried by the side wall and exposed to the lumen;

a rotatable core wire extendable through the lumen and comprising:

a proximal end and a distal end, a limit having a bearing surface for rotatably engaging the restraint, and

an agitator tip on the distal end, wherein the agitator tip comprises at least one loop joined to the core wire at a junction;

39. A kit as in Claim 38, wherein the at least one loop is configured to remove a first type of emboli from the intravascular site.

40. A kit as in Claim 39, wherein the first type of emboli comprises predominantly red blood cells.

41. A kit as in Claim 38, wherein the agitator tip comprises a second loop joined to the core wire at the junction.

42. A kit as in Claim 41, wherein the second loop is spaced apart from the at least one loop by 20 to 60 degrees.

43. A kit as in Claim 41, wherein a length of the at least one loop and the second loop is less than 3 mm.

44. A kit as in Claim 38, further comprising a second rotatable core wire independently extendable through the lumen and comprising:

a second proximal end and a second distal end,

a second limit having a second bearing surface for rotatably engaging the restraint, and

a helical thread agitator tip on the distal end,

wherein the second limit and the restraint are engageable to permit rotation of the second core wire but limit distal advance of the helical thread agitator tip relative to the tubular body.

45. A kit as in Claim 44, wherein the helical thread agitator tip is configured to remove a first type or a second type of emboli from the intravascular site.

46. A kit as in Claim 45, wherein the first type of emboli comprises predominantly red blood cells and the second type of emboli comprises predominantly one or more of: nucleated cells, fibrin, collagen, and plasma.

47. A kit as in Claim 44, wherein the helical thread agitator tip has a major diameter that is no more than about 90% of the inside diameter of the lumen, leaving an annular flow path between the tip and an inner surface of the side wall.

48. A system as in Claim 44, wherein the helical thread agitator tip has a blunt outer edge.

49. A system as in Claim 44, wherein the helical thread agitator tip defines a helical flow channel between axially adjacent threads, and the sum of the cross-sectional area of the helical flow channel and the annular flow path is at least about 20% of the cross- sectional area of the lumen.

50. A method of removing embolic material from a vessel with mechanical and aspiration assistance, comprising:

providing a kit comprising an aspiration catheter having a central lumen and a distal end, a first agitator tip, and a second agitator tip;

determining a type of obstructive material in a vessel;

selecting the first agitator tip or the second agitator tip based on the type of obstructive material in the vessel;

advancing the selected agitator tip to the obstructive material in the vessel; rotating the selected agitator tip within the central lumen, the selected agitator tip having an axial length of no more than about 5 mm and a major diameter that is at least about 0.015 inches smaller than an inside diameter of the lumen, to provide an aspiration flow path around the outside of the tip; and

applying vacuum to the central lumen and rotating the selected agitator tip to draw material into the lumen.

51. A method as in Claim 50, wherein rotating comprises manually rotating a core wire which extends through the catheter and rotates the tip.

52. A method as in Claim 51, additionally comprising limiting distal advance of the core wire by rotating a limit carried by the core wire with respect to a restraint positioned in the central lumen.

53. A method as in Claim 50, wherein the applying vacuum comprises applying pulsatile vacuum.