Patent Publication Number: US-11395665-B2

Title: Devices and methods for removing obstructive material, from an intravascular site

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation-in-part of U.S. patent application Ser. No. 16/398,626, filed Apr. 30, 2019, which claims the benefit of U.S. Provisional Application No. 62/665,369, filed May 1, 2018, the entirety of each of which is hereby incorporated by reference herein. 
     This application claims the benefit of U.S. Provisional Application No. 62/740,018, filed Oct. 2, 2018, the entirety of this application is hereby incorporated by reference herein. 
     This application claims the benefit of U.S. Provisional Application No. 62/777,955, filed Dec. 11, 2018, the entirety of this application is hereby incorporated by reference herein. 
    
    
     BACKGROUND 
     Stroke is the third most common cause of death in the United States and the most disabling neurologic disorder. Approximately 700,000 patients suffer from stroke annually. Stroke is a syndrome characterized by the acute onset of a neurological deficit that persists for at least 24 hours, reflecting focal involvement of the central nervous system, and is the result of a disturbance of the cerebral circulation. Its incidence increases with age. Risk factors for stroke include systolic or diastolic hypertension, hypercholesterolemia, cigarette smoking, heavy alcohol consumption, and oral contraceptive use. 
     Hemorrhagic stroke accounts for 20% of the annual stroke population. Hemorrhagic stroke often occurs due to rupture of an aneurysm or arteriovenous malformation bleeding into the brain tissue, resulting in cerebral infarction. The remaining 80% of the stroke population are ischemic strokes and are caused by occluded vessels that deprive the brain of oxygen-carrying blood. Ischemic strokes are often caused by emboli or pieces of thrombotic tissue that have dislodged from other body sites or from the cerebral vessels themselves to occlude in the narrow cerebral arteries more distally. When a patient presents with neurological symptoms and signs which resolve completely within 1 hour, the term transient ischemic attack (TIA) is used. Etiologically, TIA and stroke share the same pathophysiologic mechanisms and thus represent a continuum based on persistence of symptoms and extent of ischemic insult. 
     Emboli occasionally form around the valves of the heart or in the left atrial appendage during periods of irregular heart rhythm and then are dislodged and follow the blood flow into the distal regions of the body. Those emboli can pass to the brain and cause an embolic stroke. As will be discussed below, many such occlusions occur in the middle cerebral artery (MCA), although such is not the only site where emboli come to rest. 
     When a patient presents with neurological deficit, a diagnostic hypothesis for the cause of stroke can be generated based on the patient&#39;s history, a review of stroke risk factors, and a neurologic examination. If an ischemic event is suspected, a clinician can tentatively assess whether the patient has a cardiogenic source of emboli, large artery extracranial or intracranial disease, small artery intraparenchymal disease, or a hematologic or other systemic disorder. A head CT scan is often performed to determine whether the patient has suffered an ischemic or hemorrhagic insult. Blood would be present on the CT scan in subarachnoid hemorrhage, intraparenchymal hematoma, or intraventricular hemorrhage. 
     Traditionally, emergent management of acute ischemic stroke consisted mainly of general supportive care, e.g. hydration, monitoring neurological status, blood pressure control, and/or anti-platelet or anti-coagulation therapy. In 1996, the Food and Drug Administration approved the use of Genentech Inc.&#39;s thrombolytic drug, tissue plasminogen activator (t-PA) or Activase®, for treating acute stroke. A randomized, double-blind trial, the National Institute of Neurological Disorders and t-PA Stroke Study, revealed a statistically significant improvement in stoke scale scores at 24 hours in the group of patients receiving intravenous t-PA within 3 hours of the onset of an ischemic stroke. Since the approval of t-PA, an emergency room physician could, for the first time, offer a stroke patient an effective treatment besides supportive care. 
     However, treatment with systemic t-PA is associated with increased risk of intracerebral hemorrhage and other hemorrhagic complications. Patients treated with t-PA were more likely to sustain a symptomatic intracerebral hemorrhage during the first 36 hours of treatment. The frequency of symptomatic hemorrhage increases when t-PA is administered beyond 3 hours from the onset of a stroke. Besides the time constraint in using t-PA in acute ischemic stroke, other contraindications include the following: if the patient has had a previous stroke or serious head trauma in the preceding 3 months, if the patient has a systolic blood pressure above 185 mm Hg or diastolic blood pressure above 110 mmHg, if the patient requires aggressive treatment to reduce the blood pressure to the specified limits, if the patient is taking anticoagulants or has a propensity to hemorrhage, and/or if the patient has had a recent invasive surgical procedure. Therefore, only a small percentage of selected stroke patients are qualified to receive t-PA. 
     Obstructive emboli have also been mechanically removed from various sites in the vasculature for years. Mechanical therapies have involved capturing and removing the clot, dissolving the clot, disrupting and suctioning the clot, and/or creating a flow channel through the clot. One of the first mechanical devices developed for stroke treatment is the MERCI Retriever System (Concentric Medical, Redwood City, Calif.). A balloon-tipped guide catheter is used to access the internal carotid artery (ICA) from the femoral artery. A microcatheter is placed through the guide catheter and used to deliver the coil-tipped retriever across the clot and is then pulled back to deploy the retriever around the clot. The microcatheter and retriever are then pulled back, with the goal of pulling the clot, into the balloon guide catheter while the balloon is inflated and a syringe is connected to the balloon guide catheter to aspirate the guide catheter during clot retrieval. This device has had initially positive results as compared to thrombolytic therapy alone. 
     Other thrombectomy devices utilize expandable cages, baskets, or snares to capture and retrieve clot. Temporary stents, sometimes referred to as stentrievers or revascularization devices, are utilized to remove or retrieve clot as well as restore flow to the vessel. A series of devices using active laser or ultrasound energy to break up the clot have also been utilized. Other active energy devices have been used in conjunction with intra-arterial thrombolytic infusion to accelerate the dissolution of the thrombus. Many of these devices are used in conjunction with aspiration to aid in the removal of the clot and reduce the risk of emboli. Suctioning of the clot has also been used with single-lumen catheters and syringes or aspiration pumps, with or without adjunct disruption of the clot. Devices which apply powered fluid vortices in combination with suction have been utilized to improve the efficacy of this method of thrombectomy. Finally, balloons or stents have been used to create a patent lumen through the clot when clot removal or dissolution was not possible. 
     Notwithstanding the foregoing, there remains a need for new devices and methods for treating vasculature occlusions in the body, including acute ischemic stroke and occlusive cerebrovascular disease. 
     SUMMARY 
     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. 
     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. 
     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. 
     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 95%?] of the cross sectional area of the lumen within 1 cm proximally of the restraint. 
     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. 
     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. 
     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. 
     The core wire may be permanently positioned within, or be removably positionable within the tubular body. 
     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. 
     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. 
     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. 
     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. 
     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. 
     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 
         FIG. 1  is a side elevational schematic view of an intracranial aspiration catheter in accordance with the present invention, with a distal segment in a proximally retracted configuration. 
         FIG. 2  is a side elevational view as in  FIG. 1 , with the distal segment in a distally extended configuration. 
         FIGS. 3A-3B  are cross-sectional elevational views of a distal end of catheter  10 , with the distal section  34  fully extended. 
         FIGS. 4A-4C  schematically illustrate different cutting tip configurations. 
         FIGS. 4D-4E and 4J-4K  schematically illustrate a distal dynamic funnel tip configuration. 
         FIGS. 4F-4G  illustrate a dynamic flared tip having a first restraint system. 
         FIGS. 4H-4I  illustrate a dynamic flared tip having an alternative restraint system. 
         FIG. 5  depicts cerebral arterial vasculature including the Circle of Willis, and an access catheter positioned at an occlusion in the left carotid siphon artery. 
         FIGS. 6 through 9  show a sequence of steps involved in positioning of the catheter and aspirating obstructive material from the middle cerebral artery. 
         FIG. 10  illustrates removal of the catheter following aspiration of obstructive material. 
         FIGS. 11A-11F  depict a sequence of steps to access a neurovascular occlusion for aspiration. 
         FIGS. 12A-12F  depict an alternative sequence of steps in accordance with an aspect of the present invention involved in accessing a neurovascular occlusion for aspiration. 
         FIG. 13  illustrates an aspiration system configured to apply pulsatile negative pressure through the aspiration catheter. 
         FIG. 14  illustrates an alternative aspiration system configured to apply pulsatile negative pressure through the aspiration catheter. 
         FIG. 15  illustrates a further alternative aspiration system configured to apply mechanical vibration through the aspiration catheter. 
         FIGS. 16 and 17  illustrate a further alternative aspiration system configured to apply mechanical vibration through the aspiration catheter. 
         FIG. 18  illustrates a further alternative aspiration system having an agitator configured to apply mechanical vibration at a vibration zone on the aspiration catheter. 
         FIG. 19  depicts a simplified agitator such as a hypo tube supported wire placed in a catheter to create a vibration zone. 
         FIGS. 20A-20C  depict agitators with various distal tip configurations. 
         FIGS. 20D-20E  depict an agitator positioned within a swellable polymer distal funnel tip. 
         FIGS. 21A-21B  illustrate a moving or wiggling distal tip of a catheter in response to activating the agitator. 
         FIGS. 22A-22B  illustrate media injection from a moving or wiggling distal tip of an agitator. 
         FIGS. 23A-23B  illustrate media injection from a distal tip of an agitator to assist aspiration. 
         FIG. 23C  depicts a proximal aspiration port carried by a catheter. 
         FIG. 24A  is a side elevational view of a catheter having an internal stop ring. 
         FIG. 24B  is a longitudinal cross section through the catheter of  FIG. 24A , and detail view of the stop ring. 
         FIG. 24C  is a side elevational view of an agitator having a complementary limit for engaging the stop ring of  FIGS. 24A and 24B . 
         FIG. 24D  is a side elevational view of a distal portion of the agitator of  FIG. 24C . 
         FIG. 24E  is a longitudinal cross section through the agitator of  FIG. 24D . 
         FIG. 24F  is a perspective cut away view of a distal portion of the agitator of  FIG. 24C . 
         FIG. 24G  is a transverse cross section through a distal stopper carried by the agitator. 
         FIG. 24H  is a transverse cross section through an alternative distal stopper. 
         FIGS. 25A-25C  depict a pulsed aspiration cycle according to an embodiment. 
         FIG. 26  depicts a perspective view of a rotating hemostasis valve and a proximal drive assembly. 
         FIG. 27A  illustrates a longitudinal cross-sectional elevational view taken along the line  27 A- 27 A in  FIG. 26 . 
         FIG. 27B  illustrates an enlarged longitudinal cross-sectional elevational view of the proximal drive assembly  2602  from  FIG. 27A . 
         FIG. 28  depicts a cross-sectional perspective view of the proximal portion of  FIG. 26 . 
         FIG. 29  depicts a perspective view of an agitator driver, a proximal drive assembly, and a rotating hemostasis valve. 
         FIG. 30  illustrates a cross-sectional elevational view of a catheter wall according to an embodiment. 
         FIG. 31A  illustrates a cross-sectional elevational view of a catheter wall according to another embodiment, showing one or more axially extending filaments. 
         FIG. 31B  describes a side elevational view of the catheter of  FIG. 31A   
         FIG. 31C  illustrates a cross-sectional view taken along the line C-C of  FIG. 31B , showing one or more axially extending filaments. 
         FIG. 31D  is a side elevational cross section through an angled distal catheter or extension tube tip. 
         FIG. 32A  depicts a side elevational view of a catheter according to one embodiment. 
         FIG. 32B  describes a cross-sectional elevational view taken along the line A-A of  FIG. 32A . 
         FIG. 32C  illustrates a cross-sectional view taken along the line B-B of  FIG. 32A . 
         FIG. 33A  depicts a side elevational view of a catheter according to another embodiment. 
         FIG. 33B  describes a cross-sectional elevational view taken along the line A-A of  FIG. 33A , showing one or more axially extending filaments. 
         FIG. 33C  illustrates a cross-sectional view taken along the line B-B of  FIG. 33A , showing one or more axially extending filaments. 
         FIG. 34A  illustrates a side elevational view of a progressively enhanced flexibility catheter according to an embodiment. 
         FIG. 34B  is a proximal end view of the enhanced flexibility catheter of  FIG. 34A . 
         FIG. 35  illustrates back-up support of the catheter in accordance with the present invention. 
         FIG. 36  depicts a graph of modulus or durometer of the catheter along the length of the catheter, from the proximal end to the distal end. 
         FIG. 37  depicts a graph of flexure test profiles of catheters in accordance with the present invention compared with conventional catheters. 
         FIG. 38  is a side elevational schematic view of a transformable catheter in accordance with the present invention. 
         FIG. 39  is a cross-sectional view taken along the lines  18 - 18  of  FIG. 38 , showing heating elements within the catheter sidewall. 
         FIGS. 40A-40B  are a side elevational cross section through a blunted, angled distal catheter or extension tube tip. 
         FIG. 41A  is a side elevational cross section through a sinusoidal shaped distal catheter or extension tube tip. 
         FIG. 41B  is a perspective view of a sinusoidal shaped distal catheter or extension tube tip. 
         FIG. 42  shows a schematic of a computational fluid dynamics (CFD) velocity field model. 
         FIG. 43A  shows an image of a numerical simulation of clot aspiration using the model of  FIG. 42 , illustrating an initial state after some aspiration has occurred. 
         FIG. 43B  shows an image of a numerical simulation of clot aspiration using the model of  FIG. 42 , illustrating active aspiration. 
         FIG. 44  shows a graphical representation of a percent increase in aspirated material for the catheter distal tip shapes shown in  FIGS. 31D, 40, and 41A-41B , as a percent improvement over the flat or planar catheter distal tip shape shown in  FIG. 18 . 
         FIG. 45A  depicts a CFD velocity field profile for a flat or planar catheter distal tip. 
         FIG. 45B  depicts a CFD velocity field profile for a catheter distal tip having an angle of 30°. 
         FIG. 45C  depicts a CFD velocity field profile for a catheter distal tip having an angle of 60°. 
         FIG. 46A  shows an ingestion length for an angled distal catheter tip. 
         FIG. 46B  shows an ingestion length for a blunted, angled distal catheter tip. 
         FIG. 47  shows a graphical representation of a percent increase in aspirated material for the catheter distal tip shapes shown in  FIGS. 31D, 40, and 41A-41B , as a percent improvement over the flat or planar catheter distal tip shape shown in  FIG. 18 . 
         FIGS. 48A-48B  show various distal cap embodiments for coupling the core wire to an annular flange of the agitator tip. 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
     Referring to  FIG. 1 , there is disclosed a catheter  10  in accordance with one aspect of the present invention. Although primarily described in the context of an axially extendable distal segment aspiration catheter with a single central lumen, catheters of the present invention can readily be modified to incorporate additional structures, such as permanent or removable column strength enhancing mandrels, two or more lumen such as to permit drug, contrast or irrigant infusion or to supply inflation media to an inflatable balloon carried by the catheter, or combinations of these features, as will be readily apparent to one of skill in the art in view of the disclosure herein. In addition, the present invention will be described primarily in the context of removing obstructive material from remote vasculature in the brain, but has applicability as an access catheter for delivery and removal of any of a variety of diagnostics or therapeutic devices with or without aspiration. 
     The catheters disclosed herein may readily be adapted for use throughout the body wherever it may be desirable to distally advance a low profile distal catheter segment from a larger diameter proximal segment. For example, axially extendable catheter shafts in accordance with the present invention may be dimensioned for use throughout the coronary and peripheral vasculature, the gastrointestinal tract, the urethra, ureters, Fallopian tubes and other lumens and potential lumens, as well. The telescoping structure of the present invention may also be used to provide minimally invasive percutaneous tissue access, such as for diagnostic or therapeutic access to a solid tissue target (e.g., breast or liver or brain biopsy or tissue excision), delivery of laparoscopic tools or access to bones such as the spine for delivery of screws, bone cement or other tools or implants. 
     The catheter  10  generally comprises an elongate tubular body  16  extending between a proximal end  12  and a distal functional end  14 . The length of the tubular body  16  depends upon the desired application. For example, lengths in the area of from about 120 cm to about 140 cm or more are typical for use in femoral access percutaneous transluminal coronary applications. Intracranial or other applications may call for a different catheter shaft length depending upon the vascular access site, as will be understood in the art. 
     In the illustrated embodiment, the tubular body  16  is divided into at least a fixed proximal section  33  and an axially extendable and retractable distal section  34  separated at a transition  32 .  FIG. 2  is a side elevational view of the catheter  10  shown in  FIG. 1 , with the distal segment in a distally extended configuration. 
     Referring to  FIGS. 3A and 3B , there is illustrated a cross-sectional view of the distal segment  34  shown extended distally from the proximal segment  33  in accordance with the present invention. Distal segment  34  extends between a proximal end  36  and a distal end  38  and defines at least one elongate central lumen  40  extending axially therethrough. Distal end  38  may be provided with one or more movable side walls or jaws  39 , which move laterally in the direction of an opposing side wall or jaw  41  under the influence of aspiration, to enable the distal end  38  to bite or break thrombus or other material into smaller particles, to facilitate aspiration through lumen  40 . Both walls  39  and  41  may be movable towards and away from each other to break up thrombus as is discussed further below. For certain applications, the proximal section  33  may also or alternatively be provided with one or two opposing jaws, also responsive to vacuum or mechanical actuation to break up thrombus. 
     The inner diameter of the distal section  34  may be between about 0.030 inches and about 0.112 inches, between about 0.040 inches and about 0.102 inches, between about 0.045 inches and about 0.097 inches, between about 0.050 inches and about 0.092 inches, between about 0.055 inches and about 0.087 inches, between about 0.060 inches and about 0.082 inches, between about 0.062 inches and about 0.080 inches, between about 0.064 inches and about 0.078 inches, between about 0.066 inches and about 0.076 inches, between about 0.068 inches and about 0.074 inches, or between about 0.070 inches and about 0.072 inches. 
     The inner diameter and the outer diameter of the distal section  34  may be constant or substantially constant along its longitudinal length. Alternatively, the distal section  34  may be tapered near its distal end. The distal section  34  may be tapered at less than or equal to about 5 cm, about 10 cm, about 15 cm, about 20 cm, about 23 cm, about 25 cm, about 30 cm, about 31 cm, about 35 cm, about 40 cm, about 45 cm, about 50 cm, about 60 cm, or about 70 cm from its distal end. In some embodiments, the taper may be positioned between about 25 cm and about 35 cm from the distal end of the distal section  34 . 
     The inner diameter of the distal section  34  may be tapered or decreased in the distal direction near the distal end to an internal diameter that is less than or equal to about 95%, about 90%, about 85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%, or about 50% of the adjacent, untampered internal diameter. In some embodiments, the internal diameter of the tapered distal section  34  may be between about 50% and about 70% of the adjacent, untampered internal diameter. For example, the untampered internal diameter at the proximal end of the distal section  34  may be about 0.071 inches and the tapered internal diameter at the distal end of the distal section  34  may be about 0.035 inches, 0.045 inches, or 0.055 inches. The inner diameter of the distal section  34  may be tapered or increased near the distal end by greater than or equal to about 102%, 104%, 106%, 108%, or more of the internal diameter just proximal to a transition into the taper. The tapered inner diameter of the distal section  34  may be less than or equal to about 0.11 inches, about 0.1 inches, about 0.090 inches, about 0.080 inches, about 0.070 inches, about 0.065 inches, about 0.060 inches, about 0.055 inches, about 0.050 inches, about 0.045 inches, about 0.040 inches, about 0.035 inches, about 0.030 inches, about 0.025 inches, about 0.020 inches, about 0.015 inches, or about 0.010 inches. In some embodiments, the length of the distal tapered portion of the distal section  34  may be between about 25 cm and about 35 cm, between about 25 cm and about 30 cm, between about 30 cm and 35 cm, or approximately 30 cm. 
     The length of the distal section  34  may be between about 13 cm and about 53 cm, between about 18 cm and about 48 cm, between about 23 cm and about 43 cm, between about 28 cm and about 38 cm, between about 29 cm and about 39 cm, between about 30 cm and about 40 cm, between about 31 cm and about 41 cm, or between about 32 cm and about 42 cm. The length of the distal section  34  may be less than or equal to about 20 cm, about 25 cm, about 30 cm, about 33 cm, about 35 cm, about 40 cm, about 41 cm, about 45 cm, about 50 cm, about 55 cm, about 60 cm, about 70 cm, or about 80 cm. The length of the distal section  34  may depend on the degree of tapering of the internal diameter of the distal section  34 . 
     The proximal end  36  of distal section  34  is provided with a proximally extending pull wire  42 . Pull wire  42  extends proximally throughout the length of the tubular body  16 , to control  24  which may be carried by manifold  18 . Axial movement of control  24  produces a corresponding axial movement of distal section  34  with respect to proximal section  33  as has been discussed. Alternatively, the proximal end of pull wire  42  may exit through a port on manifold  18 , such that it may be manually grasped and pulled or pushed by the clinician to extend or retract the distal section  34 . The length of the pull wire  42  may be between about 700 mm and about 1556 mm, between about 800 mm and about 1456 mm, between about 850 mm and about 1406 mm, between about 900 mm and about 1356 mm, between about 950 mm and about 1306 mm, between about 1000 mm and about 1256 mm, between about 1020 mm and about 1236 mm, between about 1040 mm and about 1216 mm, between about 1060 mm and about 1196 mm, between about 1080 mm and about 1176 mm, between about 1100 mm and about 1156 mm, between about 1110 mm and about 1146 mm, or between about 1120 mm and about 1136 mm. 
     Upon distal advance of pull wire  42  to its limit of travel, an overlap  44  remains between the proximal end  36  of distal section  34  and the proximal section  33 . This overlap  44  is configured to provide a seal to enable efficient transmission of vacuum from proximal section  33  to distal section  34 . Overlap  44  may be provided with any of a variety of additional features to facilitate a seal, such as a gasket, coating or tightly toleranced sliding fit, as described elsewhere herein. Preferably the clearance between the OD of the distal section  34  and ID of the proximal section  33 , at least in the vicinity of transition  32 , will be no more than about 0.005 inches and preferably no more than about 0.003 inches to provide an effective seal in a blood environment. A larger clearance may be more feasible in embodiments comprising a sealing feature as described elsewhere herein. 
     Following positioning of the distal end of proximal section  33  within the vasculature, such as within the cervical carotid artery, the control  24  is manipulated to distally advance distal section  34  deeper into the vasculature. For this purpose, the pull wire  42  will be provided with sufficient column strength to enable distal advance of the distal tip  38  as will be discussed below. 
     The pull wire  42  and distal section  34  may be integrated into a catheter as illustrated in  FIGS. 1 and 2 . Alternatively, distal section  34  and pull wire  42  may be configured as a stand-alone catheter extension device as is discussed in greater detail below. The catheter extension device may be introduced into the proximal end of proximal section  33  after placement of proximal section  33  and advanced distally there through as illustrated in  FIG. 3A , to telescopically extend the reach of the aspiration system. 
     Referring to  FIG. 3B , the pull wire  42  may comprise a tubular wall having an axially extending central lumen  45 . The central lumen  45  permits introduction of media such as lubricants, drugs, contrast agents or others into the distal section  34 . In addition, the central lumen  45  extending through pull wire  42  permits introduction of an agitator as is discussed in greater detail below. As shown in  FIG. 3B , the central lumen  45  may open into the lumen  40 . The distal opening of the central lumen  45  may be positioned at a point along the length of the distal section  34  such that the central lumen  45  terminates where the lumen  40  begins (the distal opening of central lumen  45  may be longitudinally aligned with the proximal opening of lumen  40 ). The proximal opening of lumen  40  may be angled or slanted as shown in  FIG. 3B . In some embodiments, the opening of lumen  40  may be flat. The distal opening of central lumen  45  may be flat as shown in  FIG. 3B . In some embodiments, the opening may be angled or slanted, similar to the opening of lumen  40  in  FIG. 3B . 
     In some embodiments, the central lumen  45  may terminate proximal to the opening of the lumen  40 . In some embodiments, the central lumen  45  may terminate distal to the opening of the lumen  40  and/or the proximal end of the distal section  34  (e.g., at a point within the lumen  40 ). For example, the central lumen  45  may terminate at the distal end of the distal section or just short of the distal end (e.g., no more than approximately 1 cm from the distal end). In some implementations, the portion of the pull wire  42 , with or without a central lumen  45 , which extends beyond the proximal end of the distal section  34  (e.g., into lumen  40 ) may decrease in stiffness (durometer) in a distal direction. The pull wire  42  may be relatively stiff along the portion proximal to the proximal end of the distal section  34  in order to provide sufficient pushability of the extension catheter. The stiffness of the portion of the pull wire  42  distal of the proximal end of the distal section  34  may substantially match or be less than the stiffness of the distal section  34  along the length of the distal section  34 . The portion of the pull wire  42  distal of the proximal end of the distal section  34  may have a uniform stiffness less than the stiffness of the portion proximal of the proximal end of the distal section  34  or it may have a gradated or gradually decreasing stiffness in the distal direction, decreasing from the stiffness of the portion proximal of the proximal end of the distal section  34 . For example, the pull wire  42  may comprise metal along the portion proximal to the proximal end of the distal section  34  and may comprise a polymer, softer than the metal, along the portion distal to the proximal end of the distal section  34 . The portion distal to the proximal end, in some embodiments, may be extruded with decreasing stiffness in the distal direction. 
     Referring to  FIGS. 4A through 4C , the distal tip  38  may be provided any of a variety of structures which produce an active movement such as a biting action in response to the application of an activation force such as a vacuum in lumen  40 . Alternatively, an axially movable control wire may be connected with respect to a side wall of the distal tip  38 , to enable cutting action under positive mechanical force.  FIG. 4A  illustrates a distal tip  38  in an open configuration, while  FIG. 4B  illustrates distal tip  38  with opposing side walls  39  and  41  drawn together by the negative pressure in aspiration lumen  40 . This may be accomplished by providing a tapered thickness in side walls  39  and  41 , or a groove or living hinge which facilitates lateral movement of at least one of side wall  39  or  41 . 
     Alternatively, referring to  FIG. 4C , a pivot point or hinge  43  may be provided to enable lateral movement of side wall  39  to operate as a jaw. Two opposing side walls may be moveable medially and laterally with bilateral symmetry like a duck bill valve. Three or more jaws may be provided, such as three triangular jaws separated at about 120° spacing which under an aspiration pulse close to form a pyramid closed tip. 
     In some implementations of the present invention, the distal tip  14  is preferably provided with the capability to dilate beyond the nominal diameter of distal section  34 . This provides a conical funnel like tip with an enlarged distal opening, to facilitate introduction of thrombotic material into the lumen  40 . See  FIGS. 4D-4K . The diameter at the distal opening of the fully opened funnel exceeds the diameter of a cylindrical extension of the adjacent tubular body by at least about 10%, preferably at least about 25% or 45% or more. This may be accomplished by providing the distal end  14  with an expandable material, or a plurality of laterally movable jaws or petals such as at least about three or five or six or more petals that are advanceable radially inwardly into a coaptive orientation, and radially outwardly to provide a flared inside diameter of aspiration lumen  40  which increases in the distal direction. 
     The flexible petals may be retained in a radially inwardly inclined configuration such as by application of negative pressure via lumen  40  during transluminal navigation of the distal section  34 . Upon removal of the negative pressure, the panels may incline radially outwardly in response to a preset bias. Application of pulsatile vacuum may thereafter cause the panels to close radially inwardly to perform the biting function described previously. 
     The distal funnel opening may be actuated in a variety of other ways as will be apparent to those of skill in the art, such as by providing a pull wire or axially slideable outer or inner sleeve to open and close the funnel in response to mechanical movement of the wire or sleeve. Alternatively the funnel opening may be controlled by rotation of a control wire or tubular sleeve relative to the distal section  34 , to activate an iris or spiral mechanism such as a helical ribbon or wire carried by the distal tip. 
     The normal state of the distal funnel may be a cylindrical configuration, and a mechanical, thermal or electrical actuator may be utilized to enlarge the distal funnel opening. Alternatively, the normal state of the funnel may be conical, and a mechanical, thermal or electrical actuator may be utilized to reduce the diameter such as for transluminal navigation. The petals or other wall of the funnel or elements disposed within the wall of the funnel may comprise a shape memory material such as a shape memory polymer or metal alloy such as nitinol, which may be laser cut from tube stock or woven into a fine mesh. The geometry of the funnel may be transformed by application of heat, such as body heat, or heat from a heat source carried by the catheter such as an electrical resistance wire within the wall or adjacent the catheter tip. Heat may alternatively be applied from a heat source introduced by way of central lumen  40 , such as a heated fluid, or a removable heater such as an elongate flexible body carrying a resistance coil. Transformation of the funnel from one configuration to the other may alternatively be accomplished by reducing the temperature of the funnel below body temperature such as by introducing a cooled fluid into thermal communication with the funnel tip or providing the catheter or a removable cooling catheter with a Joule-Thomson expansion chamber located near the distal end. 
     In an alternate configuration, the sidewall of the funnel is provided with an inflatable balloon in the form of a ring or hoop, in communication with an inflation lumen extending throughout the length of the catheter. Introduction of inflation media inflates the annular balloon, transforming the configuration of the funnel tip from a reduced diameter to an enlarged diameter. 
     In an alternate configuration, the distal tip is biased into the funnel configuration, and restrained into a cylindrical configuration such as for transluminal navigation. When the funnel tip is desired to be enlarged, the restraint can be removed. The restraint may comprise an outer tubular covering membrane or loop configured to be removed by pulling a pull wire in a proximal direction. Alternatively, the restraint may be a bioabsorbable material, which dissolves following a preset amount of time that exceeds the anticipated time from vascular access to reach the final intravascular position. 
     Referring to  FIGS. 4J-4K , the distal flared tip may comprise embedded elastic elements (e.g., a coil, struts or cage) such as spring steel, Nitinol or others known in the art that bias the tip into the flared configuration. The elastic elements such as in the form of a Nitinol cage may alternatively reside on the ID of the catheter. The polymer tip restrains the elastic elements to provide a cylindrical exterior configuration for transluminal navigation as seen in  FIG. 4J . Softening the polymer (e.g., a hydrophilic blend) such as by body heat or moisture allows the elastic elements to transform the tip into the funnel configuration as seen in  FIG. 4K . Alternatively, a conical NiTi cage at the tip is coated with a double hydrophilic non-cross linked glue. As the catheter advances the glue dissolves and gradually flares the tip into a funnel. The polymer tip may be formed without embedded elastic components and instead comprise a coextrusion with multiple layers, varying thickness in multiple layers, blending hydrophilic components at different ratios to control flaring. Multiple axially extending pull wires may be embedded through extruded lumen extending axially throughout the catheter wall. The wires are pushed or pulled to open/close the catheter distal end to flare or collapse. Funnel-shaped, underexpanded NiTi stent can be deployed at the tip area straddling between high and low durometer regions but greater length into high durometer region. Once ready to engage a clot, the stent can be pushed distally further into the low durometer tip. After complete clot retrieval the stent is pulled back into high durometer region, collapsing the funnel. This is an example of an active on-demand funneling tip. 
     Referring to  FIG. 4F , there is illustrated a cross-sectional view of a distal end of a tubular catheter body such as distal section  34 . The tubular body is provided with a distal tip  38  in the form of a self expandable (e.g., NiTinol) mesh  50 , constrained by an outer tubular restraint  52 . Restraint  52  may comprise a proximately retractable tubular body extending proximally to a control on the proximal manifold; a peel away sheath carried by an elongate proximally retractable pull wire, or other mechanism disclosed elsewhere herein. As shown in  FIG. 4G , proximal retraction of tubular restraint  52  with respect to tubular body  34 , or distal advance of tubular body  34  with respect to restraint  52  exposes and releases the mesh  50  to self expand to a funnel shape to facilitate capture and removal of intravascular debris. 
     Referring to  FIGS. 4H and 4I , the self expandable conical mesh  50  is restrained by interweaving an internal restraint wire  54 . Restraint wire  54  may be a procedure guide wire, or a dedicated restraint wire. Proximal retraction of the restraint wire  54  releases the mesh  50 , to self expanded to a final, funnel configuration. Release of the mesh  50  may be accomplished in a variety of alternative ways, such as bio absorbable materials, and electrolytic detachment. 
     The proximal end  12  of catheter  10  is additionally provided with a manifold  18  having one or more access ports as is known in the art. Generally, manifold  18  is provided with a proximal port such as a guidewire port  20  in an over-the-wire construction, and at least one side port such as aspiration port  22 . Alternatively, the aspiration port  22  may be omitted if the procedure involves removal of the guidewire proximally from the guidewire port  20  following placement of the aspiration catheter, and aspiration through the guidewire port. Additional access ports and lumen may be provided as needed, depending upon the functional capabilities of the catheter. Manifold  18  may be injection molded from any of a variety of medical grade plastics, or formed in accordance with other techniques known in the art. 
     Manifold  18  may additionally be provided with a control  24 , for controlling the axial position of the distal segment  34  of the catheter. Control  24  may take any of a variety of forms depending upon the mechanical structure and desired axial range of travel of the distal segment  34 . In the illustrated embodiment, control  24  comprises a slider switch which is mechanically axially movably linked to the distal segment such that proximal retraction of the slider switch  24  produces a proximal movement of the distal segment  34 . This retracts the distal segment  34  into the proximal section  33  as illustrated in  FIG. 1 . Distal axial advancement of the slider switch  24  produces a distal axial advance of the distal segment  34 , as illustrated in  FIGS. 2 and 3 . 
     Any of a variety of controls may be utilized, including switches, buttons, levers, rotatable knobs, pull/push wires, and others which will be apparent to those of skill in the art in view of the disclosure herein. The control will generally be linked to the distal segment by a control wire  42 . 
     Alternatively, the proximal section  33  and distal section  34  maybe provided as separate devices, in which construction the proximal control may be omitted. The distal end of proximal section  33  may be provided with one or more jaws as has been discussed previously herein, for morcellating or otherwise breaking thrombus or other obstruction into pieces or otherwise facilitating aspiration. The proximal section  33  may additionally be mechanically coupled to or adapted for coupling to a source of vibrational or rotational movement, such as to provide the intermittent or pulsatile movement discussed elsewhere herein to facilitate navigation into the vasculature. 
     Using axial reciprocation, and/or rotation, and/or biting action of the distal jaws, the clinician may be able to reach the obstruction using proximal section  33 . See, for example,  FIG. 5  in which proximal section  33  is able to reach an obstruction in the left carotid siphon. If, however, the proximal section  33  is not able to advance sufficiently close to the obstruction, a separate telescoping distal section  34  may be introduced into the proximal section  33  and advanced therethrough and beyond, as illustrated in  FIGS. 2 and 6-10 , to reach the obstruction. 
     The cerebral circulation is regulated in such a way that a constant total cerebral blood flow (CBF) is generally maintained under varying conditions. For example, a reduction in flow to one part of the brain, such as in acute ischemic stroke, may be compensated by an increase in flow to another part, so that CBF to any one region of the brain remains unchanged. More importantly, when one part of the brain becomes ischemic due to a vascular occlusion, the brain compensates by increasing blood flow to the ischemic area through its collateral circulation. 
       FIG. 5  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. 
     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. 
     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 . 
     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. 
     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. 
     Referring to  FIG. 6 , 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 there in. 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. 7 and 8 , the distal section  34  may thereafter be transluminally navigated through the distal tortuous vasculature between proximal section  33  and the obstruction  70 . 
     Referring to  FIG. 9 , 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  as discussed elsewhere herein. 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. 
     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. 
     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  FIG. 25 . 
     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. 
     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 nitroprusside, may be injected through a second lumen to inhibit vascular spasm induced as a result of instrumentation. 
     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. 
     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. 
     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. 
     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. 
     Referring to  FIGS. 11A-11F , 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 . 
     The procedural steps for aspirating a thrombotic occlusion are described as follows. Referring to  FIG. 11A , 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 12 F, 11 F, 10 F, 9 F, 8 F, 7 F, or 6 F. 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 9 F, 8 F, 7 F, 6 F, 5 F, 4 F, or 3 F, and the inner diameter of the introducer sheath  1120  may be greater than the outer diameter of the guide sheath  1122 . 
     Referring to  FIG. 11B , 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 9 F, 8 F, 7 F, 6 F, 5 F, 4 F, or 3 F, 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. 11B , 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 run, the first guidewire  1126  is removed prior to injecting the contrast media. 
     Referring to  FIG. 11C , 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. 11D , 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. 
     Referring to  FIG. 11E , 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 . 
     Referring to  FIG. 11F , 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 . 
     A preferable, simplified method for aspirating a thrombotic occlusion in accordance with the present invention is described in connection with  FIGS. 12A-12F . 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. 11C . 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. 11D . 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. 
     Referring to  FIG. 12A , an introducer sheath  1220  is introduced at the femoral artery  1218 . The outer diameter of the introducer sheath  1220  may be equal to or less than about 12 F, 11 F, 10 F, 9 F, 8 F, 7 F, or 6 F. Then, a transitional guide sheath  1222  such as the combination access and aspiration catheter discussed in greater detail below is inserted through the introducer sheath  1120  at the femoral artery  1218 . The outer diameter of the guide sheath  1222  may be equal to or less than about 9 F, 8 F, 7 F, 6 F, 5 F, 4 F, or 3 F. Referring to  FIG. 12B , an insert catheter  1224  is inserted through the transitional guide sheath  1222 . The outer diameter of the insert catheter  1224  may be less than about 9 F, 8 F, 7 F, 6 F, 5 F, 4 F, or 3 F, and the inner diameter of the transitional guide sheath  1222  may be greater than the outer diameter of the insert catheter  1224 . In some cases, a first guidewire may be introduced through the insert catheter  1224  (not shown in  FIG. 12B ). The diameter of the proximal section of the first guidewire may be equal to or less than about 0.079″, about 0.066″, about 0.053″, about 0.038″, about 0.035″, about 0.030″, or about 0.013″. 
     The transitional guide sheath  1222 , the insert catheter  1224 , and optionally the first guidewire are tracked up to the aortic arch  1214 . See  FIG. 12B . The insert catheter  1224  may be used to select the origin of a vessel. In  FIG. 12B , the insert catheter  1224  engages the origin  1216  of the brachiocephalic artery  82 . An angiographic run may be performed by injecting contrast media through the insert catheter  1224 . In the cases where the first guidewire is used before the angiographic run, the first guidewire is preferably removed prior to injecting the contrast media. 
     Referring to  FIG. 12C , the transitional guidewire  1226  is inserted through the lumen of the insert catheter  1224  or guide sheath  1222 . The diameter of at least a portion of the transitional guidewire  1226  (e.g., proximal diameter) is substantially similar to that of the first guidewire  1126 . The diameter of at least a portion of the transitional guidewire  1226  (e.g., distal diameter) may be smaller than that of the first guidewire  1126  and may have a diameter along a proximal segment of at least about 0.030″ and in one implementation about 0.038″. A transition begins within the range of from about 15 cm-30 cm from the distal end, and typically no more than about 20 cm or 25 cm from the distal end, distally of which the diameter tapers down to no more than about 0.018″ and in one implementation about 0.016″. Referring to  FIG. 12D , if utilized, the insert catheter  1224  may be removed because it is too stiff to be advanced to the MCA  1204 . In certain implementations of the invention, the transitional guidewire  1226  provides sufficient back up support that the combination access and aspiration catheter  1224  may be advanced directly over the transitional guidewire without any intervening devices. Then, the transitional guidewire  1226  is advanced to the MCA  1204 . The transitional guidewire  1226  has a distal segment that has a smaller diameter than that of the first guidewire  1126  described in  FIG. 11C . The distal segment of the transitional guidewire  1226  comprises a soft and atraumatic tip and can be tracked to the remote neurovasculature such as the MCA  1204 , which is distal to the petrous segment  1212  of the ICA  1206 . 
     Referring to  FIG. 12E , the transitional guide sheath  1222  is advanced to or beyond the cavernous segment  1210  or the cerebral  1208  segment of the ICA  1206 . Unlike the guide sheath  1122  described in  FIG. 11D , the transitional guide sheath  1222  may be advanced to the cavernous segment  1210  or the cerebral  1208  segment of the ICA  1206  beyond the petrous segment  1212  because the transitional guide sheath  1222  has a soft yet trackable distal segment described in further detail below, for example in connection with  FIG. 30 . The larger proximal diameter and stiffer body of the transitional guidewire  1226  may provide better support for the transitional guide sheath  1222  to track through the vasculature. 
     Referring to  FIG. 12F , after the transitional guide sheath  1222  is advanced to the cerebral segment  1208  of the ICA  1206 , the transitional guidewire  1226  is removed. Then, a vacuum pressure is applied at the proximal end of the transitional guide sheath  1222  to aspirate the clot  1202  through the central lumen of the transitional guide sheath  1222 . The inner diameter of the transitional guide sheath  1222  may be equal to about or greater than about 0.100″, about 0.088″, about 0.080″, about 0.070″, or about 0.060″. The inner diameter of the transitional guide sheath  1222  is larger than the aspiration catheter  1128  described in  FIG. 11E , which translates to more effective aspiration. The cross-sectional area of the central lumen of the transitional guide sheath  1222  may be almost twice as large as that of the largest aspiration catheter  1128  currently available. 
     If the guide sheath  1222  is not able to track deep enough into the distal vasculature to reach the clot or other desired target site, a telescopic extension segment as discussed elsewhere herein may be introduced into the proximal end of sheath  1222  and advanced distally to extend beyond the distal end of the sheath  1222  and thereby extend the reach of the aspiration system. In one implementation of the invention, the extension segment has an ID of about 0.070″. 
     If thrombotic material is not able to be drawn into the sheath  1222  or extension segment under constant vacuum, pulsatile vacuum may be applied as discussed below. If pulsatile vacuum does not satisfactorily capture the clot, an agitator may be advanced through the sheath  1222  and extension segment to facilitate drawing the clot into the central lumen. Additional details of the agitator and its use are disclosed below. 
     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. 13  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  and comprises vacuum generator  302 , vacuum chamber  310 , collection canister  312 , solenoid valve  314 , frequency modulator  316 , valve controller  318 , and remote controller  320 . 
     Vacuum generator  302  comprises a vacuum pump  304 , a vacuum gauge  306 , and a pressure adjustment control  308 . The vacuum pump  304  generates vacuum. 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 to 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. 
     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  is a merged component and is in fluid connection with the vacuum generator  302 . 
     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 . 
     Pulsatile vacuum pressure aspirator  300  may comprise 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. 
     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. 
     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 . 
     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. 
     In another embodiment, shown in  FIG. 14 , 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. 13 , 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 the 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 . 
     In yet another embodiment, shown in  FIG. 15 , 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 . 
     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. 
     Reducing friction between the inner diameter of the vessel and the outer diameter of the catheter can minimize axial force required to advance 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. 
     In addition or as an alternative to the water hammer construction discussed above, axial mechanical 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 may be built into the proximal manifold  18 , and or mechanically coupled to the manifold or proximal catheter shaft as desired. Preferably, 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  33  to assist in translumenal advance, and/or distal section  34  by way of pull wire  42 , depending upon the desired clinical performance. 
     In an embodiment shown in  FIGS. 16 and 17 , the distal end  608  of a vibrating device  600  is placed in fluid connection with the proximal end  12  of the catheter  10  (not illustrated) and generates transverse and/or longitudinal vibration in the catheter  10 . By inducing transverse vibration in the catheter  10 , it reduces effective contact surface area between the vessel and the catheter  10 , 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  10 , the vibrating device  600  breaks static friction between the inner diameter of the vessel and the outer diameter of the catheter  10 , which reduces overall surface friction. By reducing the friction between the inner diameter of the vessel and the outer diameter of the catheter  10 , the vibrating device  600  improves catheter trackability through tortuous vasculatures. 
     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  10 . 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. 
     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. 
     A vibration generator such as a motor  618  has an eccentrically mounted inertial weight on its shaft generating 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 , and in some embodiments, is less than 1,000 RPM, less than 900 RPM, less than 800 RPM, less than 700 RPM, between 400-700 RPM, 500-750 RPM, 700-800 RPM, etc. 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 . For manual vibration/rotation, an RPM of less than 40 RPM, less than 30 RPM, less than 25 RPM, less than 20 RPM, 20-30 RPM, 15-30 RPM, etc. may be used. 
     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, one might replace the electric motor with an electro-magnetic actuator. To achieve ultrasonic frequencies in the range of about 20 Hz to about 1.6 MHz, one might employ a piezoelectric transducer. 
     In yet another embodiment, shown in  FIG. 18 , 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 0.127 mm) to about 0.035 inches (about 0.889 mm), 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. As shown in  FIG. 18 , the distal tip  11  of catheter  10  is a flat tip where distal tip  11  is a planar-surface orthogonal to the axis of the catheter  10  and parallel to an axial plane of the catheter  10 . The design is the simplest of catheter openings and offers no tip features that are designed to be beneficial for clot ingestion. 
     Alternatively, the stylet  702  may have an asymmetric weight such as a bead at a distal vibration zone or at its distal end. The stylet  702  may comprise a monofilament or braided or woven filaments or wires. 
     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. 
     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  804 . 
     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. 
     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 M1, M2, or M3 arteries. 
     Agitators for providing vibratory assistance for navigation and/or assisting in the capture and aspiration of debris are described further in connection with  FIGS. 19-24 . Referring to  FIG. 19 , an agitator  1900  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. Referring to  FIG. 19 , an agitator  1900  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  1900  may be placed at, beyond, or inside the distal end of the catheter  1902 . The agitator  1900  can be either preloaded into the catheter  1902  and inserted into the patient&#39;s body together with the catheter  1902  or added after the catheter  1902  has been placed. When loaded inside the catheter  1902 , the agitator  1900  may extend substantially longitudinally along the length of the catheter  1902 . The agitator  1900  may further comprise a controller at the proximal end to axially adjust the distal tip position. The controller of the agitator  1900  may be used to axially adjust the position of the distal tip  1905  when the agitator  1900  is introduced into a variable length catheter such as that discussed in connection with  FIG. 3 . 
     In one implementation of the invention, the agitator and drive system are configured as a stand-alone device. Once the distal section  34  ( FIG. 3B ) has been positioned within a few (e.g., no more than about 3 or 2) centimeters of the obstruction, the distal end of agitator  1900  maybe introduced into the proximal end of central lumen  45  of pull wire  42 . Agitator  1900  may thereafter be distally advanced so that a distal segment of agitator  1900  extends beyond the distal end of pull wire  42 , and into the distal section  34 . The portion of the agitator  1900  contained within lumen  45  of pull wire  42  is restrained from any significant lateral motion. However, the distal portion of agitator  1900  which extends beyond the distal end of pull wire  42  is relatively laterally unconstrained and is able to agitate thrombus to facilitate drawing the thrombus into and through the distal section  34 . Once the thrombus has been drawn proximally under vacuum and with activation of the agitator as needed, to reach the step up in ID at the proximal end of distal section  34 , the risk of clogging is greatly reduced. 
     The agitator  1900  may be rotated manually or via a motor  1906  driven from the catheter  1902 &#39;s proximal end to rotate or translate the distal end of the agitator  1900 . The driver  1906  may be connected to the proximal end of the agitator  1900  either permanently or removably. The driver  1906  may be a manual driver that is manually controlled such as a guidewire 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. 
     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. The driver  1906  may also be under synchronized control, in which the driver  1906  drives the agitator  1900  in synchronization with aspiration and media injection. The agitator  1900  may be configured to promote motion at the distal end to help engage and move the clot. 
     Media may be infused into/around the clot area to help liberate the clot from the vasculature. 
     The agitator  1900  comprises a distal end  1912 , a proximal end  1914  and a distal tip  1905 . The proximal end  1914  of the agitator  1900  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  1900  when placed in the catheter  1902 , within the curved vasculature. The outer diameter of the agitator  1900  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. 
     The agitator  1900  may additionally be provided with a guide tube  1910 , 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  1900  against lateral motion. A distal end  1911  of guide tube  1910  may be positioned within about 25 cm or within about 20 cm or 15 cm or less of the distal end of the agitator  1900 , depending upon desired performance. The distal section of the agitator  1900 , extending beyond distal end  1911  of guide tube  1910 , is laterally unconstrained within the ID of distal segment  34  and available to agitate and facilitate aspiration of material into and through the central lumen. 
     The diameter of the agitator  1900  may be constant along its longitudinal length. The diameter of the agitator  1900  may increase or decrease along its longitudinal length to coincide with features of the catheter  1902 . In one implementation, the diameter of the agitator  1900  decreases in the distal direction along its longitudinal length by at least one step or tapered zone to provide increasing flexibility. 
     The distal end  1912  of the agitator  1900  may be straight. Alternatively, the distal end  1912  of the agitator  1900  may be curved or formed into different shapes to interact with the clot.  FIG. 19  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.  FIGS. 20A-20C  depict more complex exemplary shapes of the motion segment  1909  of the agitator  1900 .  FIGS. 20D-20E  depict an agitator positioned within a swellable polymer distal funnel tip. 
     The agitator  1900  may be comprise a single, uniform material or multiple materials. The materials of the agitator  1900  may be processed (e.g., heat treatment/annealing) to give varying properties for the local performance requirements. The agitator  1900  may be structured to provide flexibility while exhibiting high torque transmission. The agitator  1900  may 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  1900  may be coated. The entire length of the agitator  1900  may be coated. The coating on the agitator  1900  may provide lubrication between the ID wall of the catheter  1902  and the agitator  1900 . In a case that an intermediate hypotube is placed between the wall of the catheter  1902  and the agitator  1900 , e.g., constraining tube  1910  or tubular pull wire  42 , the coating on the agitator  1900  may provide lubrication between the intermediate hypotube and the proximal drive portion of the agitator  1900 . The coating materials of the wire or hypo tube  1904  include PTFE, Parylene, Teflon, or any combinations thereof. 
     Any of the ID or OD 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, copolymers of hydrophilic polymer 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 additive (SMA) during melt processing. The lubricious coating or the lubricious material contributes to at least ease of navigation, lower ID 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 OD and ID lubricity and inherent thromboresistant property without requiring a secondary coating process. 
     Referring to  FIG. 20A , the distal end  2012  of the agitator  1900  may comprise a coil  2020  to grip a corked clot and wiggle the distal end  2010  of the catheter  2002  and the clot during rotation  2006 . The coil  2020  may be a tight, offset coil, and may comprise at least one and optionally two or three or more complete revolutions. 
     Referring to  FIG. 20B , the distal end  2012  of the agitator  1900  may comprise a hook  2022  to grip and emulsify a clot. The hook  2022  may be concave proximally, or may extend transversely to the axis of the agitator body, extending in a circumferential orientation. Referring to  FIG. 20C , the distal end  2012  of the agitator  1900  may comprise a loose coil or spring  2024 . The loose coil or spring  2024  may expand (lengthen) and contract (shorten) with a change in direction of rotation. 
     Referring to  FIGS. 20D-20E , the distal end  2012  of the agitator  2000  may comprise a coil  2026  to grip a corked clot and wiggle the distal end  2010  of the catheter  2002  and the clot during rotation. In addition, the distal end  2010  of the catheter  2002  may include a polymer sidewall that reforms by hydration. The coil  2026  maintains a guide wire lumen during placement of the catheter. The polymer enables the distal end  2010  of the catheter  2002  to expand to a funnel shape after absorption of serum from blood. See  FIG. 20E . 
     Referring to  FIGS. 21A-21B , the distal tip  2110  of the catheter  2102  may move or wiggle by interacting with the agitator  1900 . When the distal end of the agitator  1900  rotates (e.g., via a driver  2106 ), the motion segment  1909  and distal tip  1905  of the agitator interact with the side wall of the catheter  2102  which wiggles as shown by broken lines  2112 . The length of the motion segment, stiffness of the agitator  1900  and rotational velocity determines the interaction with the wall of the catheter  2102  and the amount of wiggle transmitted to the catheter  2101  with rotation of the agitator  1900 . 
     Alternatively, the distal tip  2110  of the catheter  2102  may move or wiggle by pulsed media jets existing one or more holes near the distal end of the hypo tube  2124 . The hypo tube  2124  has an inside lumen extending along the longitudinal length of the hypo tube  2124 . One or more side holes  2128  may be placed near the distal end of the hypo tube  2124  and allow fluid communication between the lumen of the hypo tube  2124  and the outside of the hypo tube  2124  (i.e., the lumen of the catheter  2102 ). Media (e.g. saline) may be introduced under pressure into the proximal end of the hypo tube  2124 , through the lumen of the hypo tube  2124 , and then through the one or more holes of the hypo tube  2124 . When media is injected into the hypo tube  2124  in a pulsed manner, pulsed media jets eject from the holes of the hypo tube  2124  and transmit forces on the wall of the catheter  2102 , resulting in a wiggle motion of the catheter  2102 . The hypo tube  2124  may additionally rotate (e.g., via a driver  2106 ) to facilitate a wiggle motion of the catheter  2102 . 
     Referring to  FIGS. 22A-22B , the hypo tube  2204  may have one or more holes  2210  and is bent near its distal portion to provide a motion segment  1909 . Media (e.g. saline, a drug, a lubricant such as polyethylene glycol) is injected from the proximal end  2200 , through the inside lumen, and out of the holes  2210  of the hypo tube  2204  (direction of media ejection shown as  2208 ). Vacuum is applied to the central lumen at the proximal end  2200  of the catheter  2202  such that media ejecting from the holes  2210  of the hypo tube  2204  is drawn proximally along the central lumen of the catheter  2202  toward its proximal end  2200 . 
     As the hypo tube  2204  rotates, the hypo tube  2204  ejects media and simultaneously makes the distal tip of the catheter  2202  wriggle. When the distal tip of the catheter  2202  wriggles by the rotation of the hypo tube  2204 , the wriggle of the catheter  2202  may push the clot  2214  from side to side, and the hypo tube  2204  simultaneously ejects media at the interface between the clot  2214  and the catheter  2202 , providing a lubricious avenue for the clot  2214  to release and flow into the catheter  2202 . 
     With or without injection of media, rotation of the motion segment  1909  helps to break up or reshape the thrombus and facilitate entry into the aspiration lumen. In certain situations, the clot can be aspirated completely within the central lumen. In other situations, the clot may only be able to be partially drawn into the central lumen, such as illustrated in  FIG. 22B . In this situation, rotation of the agitator may be stopped with application of vacuum remaining on to retain the clot on the distal end of the catheter. The catheter may then be proximally withdrawn, pulling the clot along with it, into the access sheath and out of the proximal vascular access point. 
     Referring to  FIGS. 23A-23B , the hypo tube  2304  may have one or more holes along its surface more proximal from the distal end to facilitate the movement or flow of the clot  2314  inside the catheter  2302  toward its proximal end  2300 . Vacuum  2316  is applied at the proximal end  2300  of the catheter  2302  to move the removed clot  2314  from the distal end to the proximal end  2300  of the catheter  2302 . As shown in  FIG. 23A , the holes may provide a thin film  2312  around the inside of the wall of the catheter  2302  to facilitate the flow of media and/or the clot  2314  and minimize any clogging of the clot  2314 . As shown in  FIG. 23B , the hypo tube  2304  may have one or more holes to provide media jets ejecting radially from the hypo tube  2304  to grab, pull, and/or emulsify the clot  2314  as the clot  2314  passes by the one or more holes on the surface of the hypo tube  2304 . 
     Referring to  FIG. 23C , a vacuum port  2416  may be provided near the proximal end  2400  of the catheter  2402  such as on the manifold for releasable connection to a vacuum source to aspirate the clot from the vasculature. This allows the vacuum port  2416  to be distinct from the proximal port  2417  for receiving the agitator  1900 . This can minimize the risk that the movement or control of the wire or hypo tube  2404  at its proximal end may be adversely affected by vacuum, aspirated clot, and/or media. The vacuum port may be connected to the catheter  2400  via a rotating hemostasis valve, discussed below. 
     Referring to  FIGS. 24A-24H  there is illustrated an embolization system  2401  in accordance with the present invention, having a distal tip with enhanced axial position control. 
     Referring to  FIGS. 24A and 24B , any of the aspiration catheters or tubular extension segments disclosed herein may be provided with a distal 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. 
     In the illustrated implementation, the distal restraint or restriction element 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 provide an interference surface to 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. The proximal bearing surface of the axial restraint may be located within about 50 cm or 30 cm or 15 cm from the distal end of the tubular body. In order to optimize alignment of the distal rotatable tip  450  with the distal port of the catheter, and decouple that axial alignment from the tortuosity of the vascular path which otherwise changes the relative axial positions of the catheter exit port and the tip, the proximal bearing surface of the axial restraint is often within the range of from about 3 mm to about 50 mm, in some implementations about 5 mm to about 20 mm and in one implementation from about 6 mm to about 14 mm from the distal port on the catheter. 
     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 ID 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 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. A diameter or outer perimeter of the distal stopper  2414  may be between 0.001 to 0.003 inches less than the ID of the catheter. A diameter or outer perimeter of the distal stopper  2414  may be 0.003 inches less than the ID of the catheter. A diameter or outer perimeter of the distal stopper  2414  may be 0.001 inches less than the ID of the catheter. 
     In one implementation, 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 implementation, 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. 
     Referring to  FIGS. 24C and 24D , 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 OD of the core wire tapers smaller in the distal direction, while the area of the aspiration lumen tapers larger in the distal direction. 
     As illustrated further in  FIGS. 24E and 24F , 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  FIG. 24E , 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. 
     The torque coil  2412  may additionally be provided with a proximal radiopaque marker and/or connector such as a solder joint  438 . In the illustrated implementation, 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 . 
     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  and the distal stopper  2414  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 . An axial length of torque coil  2412  may elongate during use. In such embodiments, core wire  2410  acts to restrict an axial length of torque coil  2412  to prevent a distal end  450  of agitator tip  2416  from extending beyond a distal tip of the catheter and into the vessel. 
     Turning to  FIGS. 48A-48B , core wire  4810  terminates in a distal ball  4822  and cup  4824  joint, as shown in  FIG. 48A , or a distal ribbon section  4832  in joint  4834 . Cup  4824  and joint  4834  function to allow for torque coil  4812  wind-up that can occur during rotation. Cup  4824  and joint  4834  allow the core wire  4810  to move or rotate differentially proximally and distally relative to torque coil  4812  to reduce torque stress on the proximal solder joints  4814  between core wire  4810  and torque coil  4812  and distal solder joints  4826 ,  4830  between torque coil  4812  and cup  4824  or joint  4834 , respectively, while maintaining tensile strength. In some embodiments, cup  4824  and/or joint  4834  form part of the distal cap  2420  (shown in  FIG. 24E ) bonded to an annular flange  2417  (shown in  FIG. 24D ) of agitator tip  4850 . Core wire  4810  may include a consistent diameter along its length, tapered section  4836  from proximal to distal, as shown in  FIG. 48B , or include a smaller diameter section  4838  proximal to cup  4824 , as shown in  FIG. 48A . 
     Referring to  FIG. 24E , the distal stopper  2414  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 . 
     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. 24B  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  slideably engages the proximal surface  2405  on the stop ring  2402 . 
     Referring to  FIG. 24E , 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 . 
     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. 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. The helical flange  452  functions, at least in part, to improve tracking of the agitator tip  2416  through an ID of the catheter and performance of the agitator tip  2415  in an ID of the catheter during use. 
     The maximum OD for the tip  2416  is generally at least about 0.005 inches and preferably at least about 0.01 inches or 0.015 inches or more smaller than the ID 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 OD in the range of from about 0.050-0.056 inches will be positioned within a catheter having a distal ID 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. 
     Thus an unimpeded flow path is created in the annular space between the maximum OD of the tip, and the ID 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. 
     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 OD 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 OD of the tip and the ID of the catheter lumen. 
     The combination of a rounded edge  454  on the thread  452 , slow, manual rotation of the tip through less than about 20 or 10 or 5 or less rotations, 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. Once engaged, additional rotation draws the aspiration catheter distally over the clot to ensconce a proximal portion of the clot to facilitate proximal retraction and removal. 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. 
     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. 
     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. 
     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 U.S. Pat. No. 10,028,782 to Orion and US patent publication No. 2018/0116717 to Taff et al., 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 al., and 2018/0116704 to Ryba et al., the disclosures of each of which are hereby expressly incorporated by reference in their entireties herein. 
     Referring to  FIG. 24G , 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 struts  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. 24F ) 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 . 
     In an embodiment having a torque coil  2412  with an OD of about 0.028 inches, the OD of the stopper  2414  is about 0.068 inches. The wall thickness of the struts is generally less than about 0.015 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 OD of the stopper  2414 . In a stopper  2414  having an OD of about 0.68 inches, the struts  2440  have an axial length of at least about 0.75 mm or 0.95 mm. 
     Referring to  FIG. 24H , there is illustrated a stopper  2414  having three distinct sliders  441  each supported by a unique strut  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. 24G . This further increases the cross sectional area of the flow paths  443 . In a catheter having an ID of no more than about 0.07 inches, an OD 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 0.0015 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 0.003 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. 
     One method for using the system described above is described below. An 0.088 LDP guide catheter is introduces and if possible, advanced until catheter tip is slightly proximal to occlusion site. An 0.071 aspiration catheter of  FIGS. 24A  and B is introduced through the 088 LDP and advanced until the catheter tip reaches the clot face. Any intermediate catheters or guide wires, if applicable, are removed. The rotatable core wire is introduced so that its distal tip is flush with the 0.071 aspiration catheter&#39;s distal end. Seal the proximal RHV and apply vacuum to the 0.071 aspiration catheter using an aspiration pump. The core wire is manually rotated between about 2 and 10 times, generally no more than 20 times to engage the clot without cutting, and to draw the catheter distally partially over the clot and rotation of the core wire is discontinued. 
     The aspiration catheter is at this point anchored to the clot. The 0.088 LDP catheter is then advanced over the aspiration catheter which functions like a guidewire, until the 0.088 catheter reaches the face of the clot. Vacuum is applied to the 088 LDP guide catheter using a vacuum source such as a VacLok syringe. The aspiration catheter with clot secured on its tip, is proximally retracted through the 088 LDP guide, while maintaining position of the 088 LDP at the occlusion site. 
     If flow has not been restored through the 088 LDP, the core wire may be removed from the aspiration catheter. If necessary, the helical tip of the core wire may be wiped to remove residual clot, and the core wire and aspiration catheter returned to the occlusion site to repeat the clot retrieval sequence until flow is restored. Once flow is restored, remove the 0.088 LDP guide catheter. 
     Referring to  FIGS. 25A-25C , experiments showed that an interrupted vacuum can help aspirating 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. 
       FIGS. 25A-25C  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. 
     In the first step as shown in  FIG. 25A , 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. 25B , 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. 25C , the vacuum valve  2516  is shut off, allowing the vacuum to be completely released and the clot to relax. Then, another cycle from  FIG. 25A  to  FIG. 25C  begins by closing the release valve  2514  and opening the vacuum valve  2516 . 
     Referring to  FIG. 26 , there is illustrated a proximal drive assembly and/or the rotating hemostasis valve to provide the interface for driving the agitator  1900 , providing the port for injecting media, and the aspiration port. Referring to  FIGS. 26, 27A, 27B, and 28 , the proximal drive assembly  2602  and the rotating hemostasis valve  2620  may be releasably or permanently coupled to the proximal end of the agitator  1900 . The proximal portion of the agitator  1900  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  1900  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 . 
     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  1900  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 . 
     Experiments showed that as the wire or hypo tube  1900  is rotated back and forth (i.e., oscillating), the distal end of the agitator  1900  changes its position relative to the catheter. The distal end of the agitator  1900  was shown to foreshorten/lengthen as the wire or hypo tube  2624  wound/unwound within the catheter due to the rotation of the agitator  1900  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  1900  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  1900  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 . 
     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  1900  such that the rotation of the proximal drive connector  2604  is translated to the rotation of the wire or hypo tube  1900 . 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 . 
     Referring to  FIG. 29 , 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  1900 . 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  1900  in synchronization with aspiration and media injection, when the back of the driver  2950  is plugged into the synchronization port  2952 . 
     The system for retrieving clots comprises the aspiration catheter; the agitator  1900  longitudinally extendable inside the lumen of the aspiration catheter; and the driver connectable to the proximal end of the agitator  1900  (e.g., via the rotating hemostasis valve or the proximal drive assembly) with or without a synchronization port. 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 predetermined operating parameters (e.g., for synchronized aspiration, injection, and rotation). 
     The 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 the driver coupled to the proximal end of the agitator; placing the catheter adjacent to the clot; attempting to aspirate clot; if not successful, advancing an agitator distally through the catheter; activating the driver to rotate the agitator and loosen the clot; 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. 
     In order to detach a more stubborn clot, aspiration, media injection, and/or rotation of the wire or hypo tube may be timed. Building up a surplus of media around the clot will form a plug. When aspiration is activated and/or pulsed, the vacuum can draw the “plug” proximally inside the lumen of the wire or hypo tube like a syringe plunger. A higher local vacuum around the clot is maintained, and more momentum is added to the “plug” as more media is added. Timing the rotation of the wire or hypo tube with aspiration and media injection may help wiggle or fatigue the clot and detach it out of the vasculature. 
     Any of the catheter shaft or sections of the catheter shaft or telescoping extensions in accordance with the present invention may comprise a multi-layer construct having a high degree of flexibility and sufficient push ability to reach deep into the cerebral vasculature, such as at least as deep as the petrous, cavernous, or cerebral segment of the internal carotid artery (ICA). 
     In one example, referring to  FIG. 30 , the catheter  3000  may have an effective length from the manifold to distal tip from about 70 cm to about 150 cm, from about 80 cm to about 140 cm, from about 90 cm to about 130 cm, from about 100 cm to about 120 cm, or from about 105 cm to about 115 cm. The outer diameter of the catheter  3000  may be from about 0.07 inches to about 0.15 inches, from about 0.08 inches to about 0.14 inches, from about 0.09 inches to about 0.13 inches, from about 0.1 inches to about 0.12 inches, or from about 0.105 inches to about 0.115 inches, and may be lower in a distal segment than in a proximal segment. The inner diameter  3108  of the catheter  3000  in a single central lumen embodiment may be greater than or equal to about 0.11 inches, greater than or equal to about 0.1 inches, greater than or equal to about 0.09 inches, greater than or equal to about 0.088 inches, greater than or equal to about 0.08 inches, greater than or equal to about 0.07 inches, greater than or equal to about 0.06 inches, or greater than or equal to about 0.05 inches. The inner diameter  3108  of the catheter  3000  in a single central lumen embodiment may be less than or equal to about 0.11 inches, less than or equal to about 0.1 inches, less than or equal to about 0.09 inches, less than or equal to about 0.088 inches, less than or equal to about 0.08 inches, less than or equal to about 0.07 inches, less than or equal to about 0.06 inches, or less than or equal to about 0.05 inches. Referring to  FIG. 30 , an inner liner  3014  may be formed by dip coating a mandrel (not shown) to provide a thin walled tubular inside layer of the catheter body  3000 . The dip coating may be produced by coating a wire such as a silver coated copper wire in PTFE. The mandrel may thereafter be axially elongated to reduce diameter, and removed to leave the tubular inner liner. The outside surface of the tubular inner liner  3014  may thereafter be coated with a soft tie layer  3012  such as polyurethane (e.g., Tecoflex™), to produce a layer having a thickness of no more than about 0.005 inches, and in some implementations approximately 0.001 inches. The tie layer  3012  will generally extend along at least about the most distal 10 cm or 20 cm of the catheter shaft  3000  generally less than about 50 cm and may in one implementation extend approximately the distal 30 cm of the catheter shaft  3000 ,  3100 . 
     A braid such as a 75 ppi stainless steel braid  3010  may thereafter be wrapped around the inner liner  3014  through a proximal zone up to a distal transition  3011 . From the distal transition  3011  to the distal end of the catheter  3000 , a coil  3024  comprising a shape memory material such as a Nitinol alloy may thereafter be wrapped around the inner liner  3014 . In one implementation, the Nitinol coil has a transition temperature below body temperature so that the Nitinol resides in the austinite (springy) state at body temperature. Adjacent loops or filars of the coil  3024  may be closely tightly wound in a proximal zone with a distal section having looser spacing between adjacent loops. In an embodiment having a coil section  3024  with an axial length of at least between about 20% and 30% of the overall catheter length, (e.g., 28 cm coil length in a 110 cm catheter shaft  3000 ), at least the distal 1 or 2 or 3 or 4 cm of the coil will have a spacing that is at least about 130%, and in some implementations at least about 150% or more than the spacing in the proximal coil section. In a 110 cm catheter shaft  3000  having a Nitinol coil the spacing in the proximal coil may be about 0.004 inches and in the distal section may be at least about 0.006 inches or 0.007 inches or more. In embodiments comprising an extension catheter, the distal extendable section of the catheter may be constructed according to the foregoing. The length of the coil  3024  may be proportioned to the length of the extendable catheter segment or the total (e.g., extended) length of the catheter  3000 . The coil  3024  may extend from a distal end of the extendable segment over at least about 50%, 60%, 70%, 80%, or 90% of the length of the extendable segment. In some embodiments, the catheter  3000  or the extendable segment may not comprise a braid and the coil  3024  may extend to the proximal end of the extendable segment (100% of the length). 
     The distal end of the coil  3024  can be spaced proximally from the distal end of the inner liner  3014 , for example, to provide room for an annular radiopaque marker  3040 . A distal tip of any of the agitator tips described elsewhere herein may terminate before marker  3040  (on a proximal side of marker  3040 ) or within a length of marker  3040 . The coil  3024  may be set back proximally from the distal end, in some embodiments, by approximately no more than 1 cm, 2 cm, or 3 cm. In one embodiment, the distal end of the catheter  3000  is provided with a beveled distal surface  3006  residing on a plane having an angle of at least about 10° or 20° and in one embodiment about 30° with respect to a longitudinal axis of the catheter  3000 . The radiopaque marker  3040  may reside in a plane that is transverse to the longitudinal axis. Alternatively, at least the distally facing edge of the annular radiopaque marker  3040  may be an ellipse, residing on a plane which is inclined with respect to the longitudinal axis to complement the bevel angle of the distal surface  3006 . Additional details are described in connection with  FIG. 31D  below. 
     After applying the proximal braid  3010 , the distal coil  3024  and the RO marker  3040  an outer Jacket  3020  maybe applied such as a shrink wrap tube to enclose the catheter body  3000 . The outer shrink-wrapped sleeve  3020  may comprise any of a variety of materials, such as polyethylene, polyurethane, polyether block amide (e.g., PEBAX™), nylon or others known in the art. Sufficient heat is applied to cause the polymer to flow into and embed the proximal braid and distal coil. 
     In one implementation, the outer shrink wrap jacket  3020  is formed by sequentially advancing a plurality of short tubular segments  3022 ,  3026 ,  3028 ,  3030 ,  3032 ,  3034 ,  3036 ,  3038  concentrically over the catheter shaft subassembly, and applying heat to shrink the sections on to the catheter  3000  and provide a smooth continuous outer tubular body. The foregoing construction may extend along at least the most distal 10 cm, and preferably at least about the most distal 20 cm, 25 cm, 30 cm, 35 cm, 40 cm, or more than 40 cm of the catheter body  3000 . The entire length of the outer shrink wrap jacket  3020  may be formed from tubular segments and the length of the distal tubular segments (e.g.,  3022 ,  3026 ,  3028 ,  3030 ,  3032 ,  3034 ,  3036 ,  3038 ) may be shorter than the one or more tubular segments forming the proximal portion of the outer shrink wrap jacket  3020  in order to provide steeper transitions in flexibility toward the distal end of the catheter  3000 . 
     The durometer of the outer wall segments may decrease in a distal direction. For example, proximal segments such as  3022  and  3026 , may have a durometer of at least about 60 or 70D, with gradual decrease in durometer of successive segments in a distal direction to a durometer of no more than about 35D or 25D or lower. A 25 cm section may have at least about 3 or 5 or 7 or more segments and the catheter  3000  overall may have at least about 6 or 8 or 10 or more distinct flexibility zones. The distal 1 or 2 or 4 or more segments  3036 ,  3038 , may have a smaller OD following shrinking than the more proximal segments  3022 - 3034  to produce a step down in OD for the finished catheter body  3000 . The length of the lower OD section  3004  may be within the range of from about 3 cm to about 15 cm and in some embodiments is within the range of from about 5 cm to about 10 cm such as about 7 or 8 cm, and may be accomplished by providing the distal segments  3036 ,  3038  with a lower wall thickness. 
     Referring to  FIGS. 31A-31C , the catheter may further comprise a tension support for increasing the tension resistance in the distal zone. The tension support may comprise a filament and, more specifically, may comprise one or more axially extending filaments  3042 . The one or more axially extending filaments  3042  may be axially placed inside the catheter wall near the distal end of the catheter. The one or more axially extending filaments  3042  serve as a tension support and resist elongation of the catheter wall under tension (e.g., when the catheter is being proximally retracted through tortuous vasculature). 
     At least one of the one or more axially extending filaments  3042  may proximally extend along the length of the catheter wall from within about 1.0 cm from the distal end of the catheter to less than about 5 cm from the distal end of the catheter, less than about 10 cm from the distal end of the catheter, less than about 15 cm from the distal end of the catheter, less than about 20 cm from the distal end of the catheter, less than about 25 cm from the distal end of the catheter, less than about 30 cm from the distal end of the catheter, less than about 35 cm from the distal end of the catheter, less than about 40 cm from the distal end of the catheter, or less than about 50 cm from the distal end of the catheter. 
     The one or more axially extending filaments  3042  may have a length greater than or equal to about 50 cm, greater than or equal to about 40 cm, greater than or equal to about 35 cm, greater than or equal to about 30 cm, greater than or equal to about 25 cm, greater than or equal to about 20 cm, greater than or equal to about 15 cm, greater than or equal to about 10 cm, or greater than or equal to about 5 cm. 
     At least one of the one or more axially extending filaments  3042  may have a length less than or equal to about 50 cm, less than or equal to about 40 cm, less than or equal to about 35 cm, less than or equal to about 30 cm, less than or equal to about 25 cm, less than or equal to about 20 cm, less than or equal to about 15 cm, less than or equal to about 10 cm, or less than or equal to about 5 cm. At least one of the one or more axially extending filaments  3042  may extend at least about the most distal 50 cm of the length of the catheter, at least about the most distal 40 cm of the length of the catheter, at least about the most distal 35 cm of the length of the catheter, at least about the most distal 30 cm of the length of the catheter, at least about the most distal 25 cm of the length of the catheter, at least about the most distal 20 cm of the length of the catheter, at least about the most distal 15 cm of the length of the catheter, at least about the most distal 10 cm of the length of the catheter, or at least about the most distal 5 cm of the length of the catheter. 
     In some implementations, the filament extends proximally from the distal end of the catheter along the length of the coil  24  and ends proximally within about 5 cm or 2 cm or less either side of the transition  3011  between the coil  3024  and the braid  3010 . The filament may end at the transition  3011 , without overlapping with the braid  3010 . 
     In another embodiment, the most distal portion of the catheter  3000  may comprise a durometer of less than approximately 35D (e.g., 25D) to form a highly flexible distal portion of the catheter and have a length between approximately 25 cm and approximately 35 cm. The distal portion may comprise one or more tubular segments of the same durometer (e.g., segment  3038 ). A series of proximally adjacent tubular segments may form a transition region between a proximal stiffer portion of the catheter  3000  and the distal highly flexible portion of the catheter. The series of tubular segments forming the transition region may have the same or substantially similar lengths, such as approximately 1 cm. 
     The relatively short length of the series of tubular segments may provide a steep drop in durometer over the transition region. For example, the transition region may have a proximal tubular segment  3036  (proximally adjacent the distal portion) having a durometer of approximately 35D. An adjacent proximal segment  3034  may have a durometer of approximately 55D. An adjacent proximal segment  3032  may have a durometer of approximately 63D. An adjacent proximal segment  3030  may have a durometer of approximately 72D. 
     More proximal segments may comprise a durometer or durometers greater than approximately 72D and may extend to the proximal end of the catheter or extension catheter segment. For instance, an extension catheter segment may comprise a proximal portion greater than approximately 72D between about 1 cm and about 3 cm. In some embodiments, the proximal portion may be about 2 cm long. In some embodiments, the most distal segments (e.g.,  3038 - 3030 ) may comprise PEBAX™ and more proximal segments may comprise a generally stiffer material, such as Vestamid®. 
     The inner diameter of the catheter  3000  or catheter extension segment may be between approximately 0.06 and 0.08 inches, between approximately 0.065 and 0.075 inches, or between 0.068 and 0.073 inches. In some embodiments, the inner diameter is approximately 0.071 inches. 
     In some embodiments, the distal most portion may taper to a decreased inner diameter as described elsewhere herein. The taper may occur approximately between the distal highly flexible portion and the transition region (e.g., over the most proximal portion of the distal highly flexible portion). The taper may be relatively gradual (e.g., occurring over approximately 10 or more cm) or may be relatively steep (e.g., occurring over less than approximately 5 cm). The inner diameter may taper to an inner diameter between about 0.03 and 0.06 inches. For example, the inner diameter may be about 0.035 inches, about 0.045 inches, or about 0.055 inches at the distal end of the catheter  3000 . In some embodiments, the inner diameter may remain constant, at least over the catheter extension segment. 
     In some embodiments, the coil  3024  may extend proximally from a distal end of the catheter  3000  along the highly flexible distal portion ending at the distal end of the transition region. In other embodiments, the coil  3024  may extend from a distal end of the catheter to the proximal end of the transition region, to a point along the transition region, or proximally beyond the transition region. In other embodiments, the coil  3024  may extend the entire length of the catheter  3000  or catheter extension segment as described elsewhere herein. The braid  3010 , when present, may extend from the proximal end of the coil  3024  to the proximal end of the catheter  3000  or catheter extension segment. 
     The one or more axially extending filaments  3042  may be placed near or radially outside the tie layer  3012  or the inner liner  3014 . The one or more axially extending filaments  3042  may be placed near or radially inside the braid  3010  and/or the coil  3024 . The one or more axially extending filaments  3042  may be carried between the inner liner  3014  and the helical coil  3024 . 
     When more than one axially extending filaments  3042  are placed in the catheter wall, the axially extending filaments  3042  may be placed in a radially symmetrical manner. For example, the angle between the two axially extending filaments  3042  with respect to the radial center of the catheter may be about 180 degree. Alternatively, depending on desired clinical performances (e.g., flexibility, trackability), the axially extending filaments  3042  may be placed in a radially asymmetrical manner. The angle between any two axially extending filaments  3042  with respect to the radial center of the catheter may be less than about 180 degree, less than or equal to about 165 degree, less than or equal to about 150 degree, less than or equal to about 135 degree, less than or equal to about 120 degree, less than or equal to about 105 degree, less than or equal to about 90 degree, less than or equal to about 75 degree, less than or equal to about 60 degree, less than or equal to about 45 degree, less than or equal to about 30 degree, less than or equal to about 15 degree, less than or equal to about 10 degree, or less than or equal to about 5 degree. 
     The one or more axially extending filaments  3042  may be made of materials such as Kevlar, Polyester, Meta-Para-Aramide, or any combinations thereof. At least one of the one or more axially extending filaments  3042  may comprise a single fiber or a multi-fiber bundle, and the fiber or bundle may have a round or rectangular cross section. The terms fiber or filament do not convey composition, and they may comprise any of a variety of high tensile strength polymers, metals or alloys depending upon design considerations such as the desired tensile failure limit and wall thickness. The cross-sectional dimension of the one or more axially extending filaments  3042 , as measured in the radial direction, may be no more than about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 20%, 25%, or 30% of that of the catheter  3000 . The cross-sectional dimension of the one or more axially extending filaments  3042 , as measured in the radial direction, may be no more than about 0.001 inches, about 0.002 inches, about 0.003 inches, about 0.004 inches, about 0.005 inches, about 0.006 inches, about 0.007 inches, about 0.008 inches, about 0.009 inches, about 0.010 inches, about 0.015 inches, about 0.020 inches, about 0.025 inches, or about 0.030 inches. 
     The one or more axially extending filaments  3042  may increase the tensile strength of the distal zone of the catheter to at least about 1 pound, at least about 2 pounds, at least about 3 pounds, at least about 4 pounds, at least about 5 pounds, at least about 6 pounds, at least about 7 pounds, at least about 8 pounds, or at least about 10 pounds or more. 
     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, an angled blunted tip, or a sinusoidal tip, as described elsewhere herein. Referring to  FIG. 31D , 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. 
     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 . 
     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. 
     The angled face  3126  inclines at an angle A within the range of from about 45 degrees to about 80 degrees from the longitudinal axis of the catheter. For certain implementations, the angle is within the range of from about 55 degrees to about 65 degrees or within the range of from about 55 degrees to about 65 degrees from the longitudinal axis of the catheter. In one implementation the angle A is about 60 degrees. One consequence of an angle A of less than 90 degrees is an elongation of a major axis of the area of the distal port which increases the surface area of the port and may enhance clot aspiration or retention. Compared to the surface area of the circular port (angle A is 90 degrees), the area of the angled port is generally at least about 105%, and no more than about 130%, in some implementations within the range of from about 110% and about 125% and in one example is about 115%. 
     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. 
     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. 
     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 . 
     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 . 
     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. 
     Referring to  FIGS. 40A-40B , the angled face  3126  of the catheter of  FIG. 31D  is further modified into a blunted, angled face  4000 , such that leading edge tip (shown in  FIG. 31D ) is removed. As shown in  FIG. 40B , the catheter distal face  4000  comprises a first section  4012  that resides on a first plane which crosses a longitudinal axis of the tubular body at a first angle  4020  within the range of from about 35 degrees to about 55 degrees, and a second section  4014  that resides on second plane which crosses the longitudinal axis of the tubular body at a second angle  4010  within the range from about 55 degrees to about 90 degrees. Section  4016 , shown in  FIG. 40A , of distal face  4000 , shown in  FIG. 31D , is removed. One consequence of an angle  4020  of less than 90 degrees and a blunted length  4014  is an elongation of a major axis of the area of the distal port which increases the surface area of the port and may enhance clot aspiration or retention while also minimizing the potential for vessel wall damage. Compared to the surface area of the circular port (angle  4020  and angle  4010  are both 90 degrees), the area of the angled blunted port is generally at least about 105%, and no more than about 150%, in some implementations within the range of from about 110% and about 125% and in one example is about 115%. The degree of blunting can be defined by a ratio of unblunted axial length  4022  measured from trailing edge  4024  to leading edge  4026  to blunted axial length shown as section  4018 . As shown in  FIG. 40A , a blunting ratio of ¾ is shown. A length  4016  which tip  4000  is blunted may be 1-5 mm, 1-4 mm, 1-3 mm, 1-2 mm, 0.1-0.2 mm, 0.2-0.3 mm, 0.3-0.4 mm, 0.4-0.5 mm, 0.5-0.6 mm, 0.6-0.7 mm, 0.7-0.8 mm, 0.8-0.9 mm, 0.9-1.0 mm, 0.1-0.5 mm, 0.5-1.0 mm, less than 1 mm, more than 1 mm, at least 2 mm, at least 3 mm, at least 4 mm, at least 5 mm, or any range or subrange therebetween of a total catheter distal face  4022 . In some embodiments, length  4016  of distal face  4000  is defined by a percentage of the outer diameter of the catheter, for example length  4016  may be equal to a length of 10%-500%, 10%-20%, 20%-30%, 30%-40%, 40%-50%, 50%-60%, 60%-70%, 70%-80%, 80%-90%, 100%-200%, 200%-300%, 300%-400%, 400%-500%, or any range or subrange therebetween of the outer diameter of the catheter. 
     Referring to  FIG. 40B , angle  4020  of the first or angled section of distal face  4000  may be 5-10 degrees, 10-15 degrees, 15-20 degrees, 20-25 degrees, 25-30 degrees, 30-35 degrees, 35-40 degrees, 40-45 degrees, 45-50 degrees, 50-55 degrees, 55-60 degrees, 60-65 degrees, 65-70 degrees, 70-75 degrees, 75-80 degrees, 80-85 degrees, 85-90 degrees, 90-95 degrees, or any range or subrange therebetween. Angle  4020  of the first or angled section of distal face  4000  may be at least 10 degrees, at least 15 degrees, at least 20 degrees, at least 25 degrees, at least 30 degrees, at least 35 degrees, at least 40 degrees, at least 45 degrees, at least 50 degrees, at least 55 degrees, at least 60 degrees, at least 65 degrees, at least 70 degrees, at least 75 degrees, at least 80 degrees, at least 85 degrees, at least 90 degrees, or at least 95 degrees. In some embodiments, angle  4020  of the first or angled section of distal face equals 0-30 degrees, 30-60 degrees, 60-90 degrees, or any range or subrange therebetween. In some embodiments, angle  4020  equals 15-45 degrees, 45-75 degrees, 75-95 degrees, or any range or subrange therebetween. Angle  4010  of the second or blunted section of distal face  4000  may be 55-60 degrees, 60-65 degrees, 65-70 degrees, 70-75 degrees, 75-80 degrees, 80-85 degrees, 85-90 degrees, or any range or subrange therebetween. Angle  4010  of the second or blunted section of distal face  4000  may be at least 55 degrees, at least 60 degrees, at least 65 degrees, at least 70 degrees, at least 75 degrees, at least 80 degrees, at least 85 degrees, or at least 90 degrees. In some embodiments, angle  4010  of the second or blunted section of distal face  4000  equals 55-65 degrees, 65-75 degrees, 75-90 degrees, or any range or subrange therebetween. 
     Referring to  FIGS. 41A-41B , a sinusoidal distal face  4100  is shown comprising a first section or convex wave or shape or scoop or curve  4110  defined by a first radius of curvature transitioning into a second section or concave wave or shape or scoop or curve  4120  defined by a second radius of curvature. Each curve  4110 ,  4120  may have a diameter ranging from 0.02 inches to 0.05 inches, for example, depending on catheter size. Each curve  4110 ,  4120  is further defined by a radius of curvature  4112 ,  4114 , respectively, as shown in  FIG. 41B . In some embodiments, a first convex curve  4110  and a second concave curve  4120  have a same or similar or substantially similar (+/−5%) radius of curvature  4112 ,  4114 , respectively. In other embodiments, a first convex curve  4110  and a second concave curve  4120  have a different radius of curvature  4112 ,  4114 , respectively. A 2D profile (e.g., when projected onto the radial plane shown in  FIG. 41A ) of the distal face shape  4100  is given by the following equation: 
     
       
         
           
             
               
                 
                   z 
                   = 
                   
                     
                       Δ 
                       ⁢ 
                       z 
                     
                     
                       1 
                       + 
                       
                         e 
                         
                           
                             - 
                             m 
                           
                           ⁢ 
                           
                             r 
                             
                               r 
                               c 
                             
                           
                         
                       
                     
                   
                 
               
               
                 
                   ( 
                   1 
                   ) 
                 
               
             
           
         
       
     
     where Δz is the overall tip length  4130 ; 
     m is a slope factor; 
     r is a radial position; and 
     r c  is a catheter radius. 
     By changing the slope factor, a steepness of the wave-shape can be adjusted. 
     As shown in  FIG. 41A , a slope or angle of each curve  4110 ,  4120  can be defined by angle  4140  and  4150 , respectively. For example, for a calculation of each angle  4140 ,  4150 , an axis may be positioned at the transition point, falling along a longitudinal center of the catheter, between a first  4110  and second  4120  curve, such that angle  4140  and  4150  define the curve or shape of the distal face  4100 . In some embodiments, angle  4140  is 0-5 degrees, 5-10 degrees, 10-15 degrees, 15-20 degrees, 20-25 degrees, 25-30 degrees, 30-35 degrees, 35-40 degrees, 40-45 degrees, 45-50 degrees, 50-55 degrees, 55-60 degrees, 60-65 degrees, 65-70 degrees, 70-75 degrees, 75-80 degrees, 80-85 degrees, 85-90 degrees, or any range or subrange therebetween. In some embodiments, angle  4140  is 30-60 degrees, 15-85 degrees, or any range or subrange therebetween. In some embodiments, angle  4150  is 0-5 degrees, 5-10 degrees, 10-15 degrees, 15-20 degrees, 20-25 degrees, 25-30 degrees, 30-35 degrees, 35-40 degrees, 40-45 degrees, 45-50 degrees, 50-55 degrees, 55-60 degrees, 60-65 degrees, 65-70 degrees, 70-75 degrees, 75-80 degrees, 80-85 degrees, 85-90 degrees, or any range or subrange therebetween. In some embodiments, angle  4150  is 30-60 degrees, 15-85 degrees, or any range or subrange therebetween. 
     Referring to  FIG. 42 , a schematic of a numerical simulation model is shown. A Computational Fluid Dynamics (CFD) model was created to simulate the aspiration of a soft clot  4120  in a vessel  4210 , surrounded by blood  4130 , into a catheter  4140  with various distal face shapes or angles  4150 . 
     Exemplary CFD model data are shown in  FIGS. 43A-43B . Images of Numerical Simulation of clot aspiration show an initial state  4300  in  FIG. 43A  and an active aspiration state  4310  in  FIG. 43B . The amount of clot material aspirated over a given time was measured for various distal face shapes or angles  4150 . The value for the circular port (e.g., shown in  FIG. 18 ) was used as a baseline or control to benchmark the success of the proposed profiles. A particular distal face shape or angle was declared more successful if it could aspirate more material then the circular port shape. Greater aspiration rate indicates less resistance to aspiration and a lower chance of complications during an aspiration-thrombectomy. 
     Referring to  FIG. 44 , the percent increase in aspiration volume is shown as a function of distal face angle. For example, a distal face exhibiting a 60 degree angle had the greatest increase in aspiration efficiency as compared to faces with lesser angles (15 degrees to 45 degrees). The aspirated volume for a 60 degree angled face was increased by greater than 60% over a circular face, between 60-70% over a circular face, or 50-70% over a circular face. A 45 degree angled distal face had an increase in aspirated volume over a circular face of greater than 40%, between 40-50%, between 30-60%, or greater than 45%. A 30 degree angled distal face has an increase in aspirated volume over a circular face of greater than 20%, greater than 25%, between 20-30%, or between 15-40%. Even a distal face having a 15 degree angle showed a 10% improvement in aspirated volume over a circular face. Exemplary reasoning for this improvement in aspiration efficiency as a function of tip angle is: (1) increases a surface area of the catheter opening in contact with clot which increases the force on the clot (Pressure=Force/Area) and (2) increases a length of distance over which the clot is ingested (i.e., ingestion length) thereby smoothing its change in shape as it flows from the larger diameter vessel into the smaller diameter catheter. The later of these two design-theories is supported by an investigation of the flow profile during the aspiration experiments. For the more pronounced sinusoidal profile, the flow was more uniform and less disrupted upon entering the smaller diameter catheter. As shown in  FIG. 44 , as face angle increases, the percent increase in aspiration volume increases, collectively indicating that a larger face opening as a result of an angled face profile increases aspiration efficiency. 
     Turning to  FIGS. 45A-45C , which show CFD velocity field profile for various face angles (i.e., no angle or 0 degrees, 30 degree angle, and 60 degree angle). As shown in  FIG. 45A , the circular face profile showed a significant constriction of the flow thus increasing the resistance to clot ingestion. In contrast, a distal face having an angle of 30 degrees ( FIG. 45B ) or 60 degrees ( FIG. 45C ) dramatically increased clot ingestion, as shown in the respective plots. As shown in  FIG. 45C , the 60 degree angled face showed greater distance between adjacent contours and a leading edge  4500  of the velocity modulus extended further into the modeled catheter body as compared to the leading edge  4510  of the 30 degree angled face. 
     Turning to  FIGS. 46A-46B .  FIG. 46A  shows an ingestion length  4610  for an angled face  4600 , and  FIG. 46B  shows an ingestion length  4620  for a blunted, angled face  4650 . In some embodiments, length  4610  is equal to or substantially equal to length  4620 ; in other embodiments, length  4610  is greater than length  4620 , less than length  4620 , or different than length  4620 . Ingestion length  4610  is determine by calculating a difference between leading edge tip  4614  and trailing edge tip  4612 , the leading and trailing edges having been described in connection with  FIG. 31D . Similarly, ingestion length  4620  is determined by calculating a difference between leading edge tip  4624  and trailing edge tip  4622 . In exemplary, non-limiting embodiments, ingestion length ranges from 0.25 mm to 4.5 mm; 0.5 mm to 4 mm, 0.5 mm to 2.5 mm, 3.5 mm to 4 mm, 2 mm to 2.5 mm, 1.5 mm to 2 mm, 1 mm to 1.5 mm, 0.5 mm to 1 mm, etc. Ingestion length is directly related to percent increase in aspirated volume over circular face control. 
       FIG. 47  illustrates the percent increase in aspirated material for catheters with varying distal face profiles (i.e., angled, blunted angled, sinusoidal) as a function of ingestion length. All the proposed profiles showed improvement over the circular face profile. The improvement ranged from substantially 10% to substantially 70%. In addition, the blunted angled face and the sinusoidal face were just as successful as the angled face, which had the same ingestion length. This implies that blunted or smooth catheters can be as successful as sharp catheters as long as the ingestion length is the same, similar, or substantially similar. For example, as ingestion length for an angled face ranged from about 0.5 mm to about 4 mm and the percent increase in aspirated volume over circular face control increased from about 10% to about 70%. As ingestion length for an angled blunted face ranged from about 1 mm to about 1.6 or about 1 mm to about 1.75 mm and the percent increase in aspirated volume over circular face control increased from about 18% to about 38%. The sinusoidal face demonstrated about a 35% increase in aspirated volume over circular face control for an ingestion length of about 1.7 mm to about 1.7 mm. 
     Referring to  FIGS. 32A-32C , depending on whether the catheter  3000  is able to navigate sufficiently distally to reach the target site, an intraluminal catheter  3200  such as a telescopic extension segment having a proximally extending control wire as has been described elsewhere herein (e.g., distal segment  34  in  FIGS. 3A and 3B ) may be inserted through the catheter  3000  from the proximal end of the catheter  3000 . The intraluminal catheter  3200  is inserted such that the distal end of the intraluminal catheter  3200  reaches further distally beyond the distal end of the catheter  3000 . The outer diameter of the intraluminal catheter  3200  is smaller than the inner diameter of the catheter  3000 . This way, the intraluminal catheter  3200  can slide inside the lumen of the catheter  3000 . 
     The intraluminal catheter  3200  incorporates characteristics of the side wall construction of the catheter  3000  described herein. The axial length of the tubular extension segment may be less than about 50% and typically less than about 25% of the length of the catheter  3000 . The axial length of the tubular extension segment will generally be at least about 10 cm or 15 cm or 20 cm or 25 cm or more but generally no more than about 70 cm or 50 cm or 30 cm. 
     Referring to  FIGS. 33A-33C , the intraluminal catheter  3200  may have one or more axially extending filaments  3242 . The one or more axially extending filaments  3242  incorporate characteristics of the one or more axially extending filaments  3042  of the catheter  3000 , except the cross-sectional dimension as measured in the radial direction of the one or more axially extending filaments  3242  of the intraluminal catheter  3200  may be less than the corresponding dimension of the filament  3042  in the catheter  3000 . 
     Referring to  FIGS. 34A-34B , there is illustrated one example of an outer jacket segment stacking pattern for a progressive flexibility catheter of the type discussed in connection with  FIG. 30 . A distal segment  3038  may have a length within the range of about 1-3 cm, and a durometer of less than about 35D or 30D. An adjacent proximal segment  3036  may have a length within the range of about 4-6 cm, and a durometer of less than about 35D or 30D. An adjacent proximal segment  3034  may have a length within the range of about 4-6 cm, and a durometer of about 35D or less. An adjacent proximal segment  3032  may have a length within the range of about 1-3 cm, and a durometer within the range of from about 35D to about 45D (e.g., 40D). An adjacent proximal segment  3030  may have a length within the range of about 1-3 cm, and a durometer within the range of from about 50D to about 60D (e.g., about 55D). An adjacent proximal segment  3028  may have a length within the range of about 1-3 cm, and a durometer within the range of from about 35D to about 50D to about 60D (e.g., about 55D). An adjacent proximal segment  3026  may have a length within the range of about 1-3 cm, and a durometer of at least about 60D and typically less than about 75D. More proximal segments may have a durometer of at least about 65D or 70D. The distal most two or three segments may comprise a material such as Tecothane, and more proximal segments may comprise PEBAX or other catheter jacket materials known in the art. At least three or five or seven or nine or more discrete segments may be utilized, having a change in durometer between highest and lowest along the length of the catheter shaft of at least about 10D, preferably at least about 20D and in some implementations at least about 30D or 40D or more. 
     Performance metrics of a catheter include back-up support, trackability, pushability, and kink resistance. Back-up support means ability of the catheter to remain in position within anatomy and provide a stable platform through which endoluminal devices may advance. Referring to  FIG. 35 , when the devices are pushed through the catheter  3202 , if there is not enough back-up support in the catheter  3202 , the distal portion  3204  of the catheter  3202  may prolapse, pull out, or back out of a vessel  3206  that branches out of a main blood vessel (e.g., brachiocephalic artery  82 , common carotid artery  80 , or subclavian artery  84 ). Back-up support for the catheter  3202  may be improved by providing a proximal region with high durometer or modulus and a distal region with low durometer or modulus. Durometer or modulus of the proximal region of the catheter  3202  may be improved by braid reinforcement. The region of the catheter at which durometer or modulus is strengthened may be placed near branching points at which the aortic arch  1114 ,  1214  branches into brachiocephalic artery  82 , common carotid artery  80 , or subclavian artery  84  or near other anatomical structures (i.e., branching points) at which a main vessel branches into one or more smaller vessels, providing an opportunity for a catheter with poor back-up support to prolapse. For example, the region of the catheter at which durometer or modulus is strengthened may be placed within about 0.5 cm, about 1 cm, about 2 cm, about 3 cm, about 4 cm, about 5 cm, or about 6 cm from a branching point at which a main vessel branches into one or more smaller vessels. 
     Trackability means ability of the catheter to track further distally than other catheters (e.g., to M1). For example, a catheter that can reach a cerebral segment of the internal carotid artery (ICA) has better trackability than a catheter that can reach a cavernous or petrous segment of the ICA. Trackability of the catheter may be improved by using a catheter wall with low durometer or modulus or by adding a coating (e.g., a hydrophilic coating) on at least a portion of the catheter wall. In one embodiment, the hydrophilic coating may be placed along the distal most region of the catheter. The hydrophilic coating on the catheter may extend to about 1 cm, about 5 cm, about 10 cm, about 15 cm, or about 20 cm from the distal end of the catheter. The region with lower durometer or modulus may locate at the distal most region of the catheter. The region with lower durometer or modulus may extend to about 1 cm, about 5 cm, about 10 cm, about 15 cm, or about 20 cm from the distal end of the catheter. 
     Pushability means rigidity of the catheter sufficient to push through anatomy without “buckling”. Pushability of the catheter may be improved by increasing its durometer or modulus. Pushability of the catheter may also be improved by providing a proximal region with high durometer or modulus and a distal region with low durometer or modulus. A transition region of the catheter in which durometer or modulus changes along its longitudinal length (e.g., decreasing durometer or modulus from the proximal end to the distal end) may begin at about 50%, 60%, 70%, 75%, 80%, or more of the length of the catheter from its proximal end. 
     Kink resistance means resistance of the catheter to kinking. In addition, if the catheter does kink, kink resistance of the catheter helps it return to its original shape. Kink resistance is important in the distal segment of the catheter, which is more prone to kinking than the proximal segment. Kink resistance of the catheter may be improved by adding one or more NiTi coils (or a coil at least portion of which is Nitinol) to the catheter wall. 
       FIG. 36  describes a graph of durometer or modulus of a catheter in accordance with the present invention along the length of the catheter, from the proximal end (x=0) to the distal end (x=1). The catheter according to an embodiment may have a decreasing durometer or modulus (E) approaching its distal end. The proximal end of the catheter has higher durometer or modulus than that of the distal end of the catheter. High durometer or modulus near the proximal end provides superior back-up support of the catheter. Durometer or modulus of the catheter is substantially constant along its length near the proximal end  3302  of the catheter. Then, durometer or modulus of the catheter decreases near the distal end  3304  of the catheter. Durometer or modulus of the catheter may begin to decrease (i.e., transition region) at about 50%, 70%, 75%, 80%, or 90% of the length of the catheter from its proximal end. The catheter may have successively decreasing durometer or modulus near its distal end by using materials with less durometer or modulus or having a thinner catheter wall near the distal end. Decreased durometer or modulus near the distal end provides superior trackability of the catheter. 
       FIG. 37  describes flexibility test profiles of catheters in accordance with the present invention compared with conventional catheters. Flexibility of a catheter was measured by the three point flexural test with a span of one inch and a displacement of 2 mm. In other words,  FIG. 37  describes a force (i.e., flexural load) necessary to vertically displace an one-inch-long catheter segment by 2 mm with respect to distance from strain relief (i.e., proximal end of the catheter) to the point of force application. All catheters tested in  FIG. 37  show modulus or flexibility profiles similar to one shown in  FIG. 36 . Modulus of the catheters stays substantially constant along its length near the proximal end and then gradually decreases near the distal end. 
     Catheters according to the present invention have a flexural load that is substantially constant along the longitudinal length near the proximal end and a rapidly decreasing flexural load near the distal end. In a catheter having a length of about 125 cm, the catheters may have a flexural load greater than or equal to about 1.0 lbF, about 1.5 lbF, about 2.0 lbF, about 2.5 lbF, about 3.0 lbF, or about 3.5 lbF at about 85 cm from the proximal end. The catheters may have a flexural load less than or equal to about 2.5 lbF, about 2.0 lbF, about 1.5 lbF, about 1.0 lbF, or about 0.5 lbF at about 95 cm from the proximal end. The catheters may have a flexural load less than or equal to about 1.5 lbF, about 1.0 lbF, about 0.75 lbF, about 0.5 lbF, about 0.25 lbF, or about 0.1 lbF at about 105 cm from the proximal end. The catheters may have a flexural load less than or equal to about 1.0 lbF, about 0.75 lbF, about 0.5 lbF, about 0.4 lbF, about 0.3 lbF, about 0.2 lbF, or about 0.1 lbF at about 115 cm from the proximal end. For catheters having different lengths, the foregoing dimensions can be scaled from the distal end of the catheter as a percentage of catheter length. 
     In certain implementations constructed in accordance with  FIG. 30 , the flexural load is less than about 3.0 or 3.25 lbF at 65 cm from the proximal end and greater than about 2.25 or 2.5 lbF on average from 65 cm to 85 cm from the proximal end. Flexural load drops to no more than about 1.0 and preferably no more than about 0.5 lbF at about 95 cm from the proximal end. This provides enhanced backup support in the aorta while maintaining enhanced trackability into the distal vasculature. 
     In other embodiments, the catheters may have a flexural load greater than or equal to about 1.0 lbF, about 1.5 lbF, about 2.0 lbF, about 2.5 lbF, about 3.0 lbF, or about 3.5 lbF at about 60 cm from the proximal end. The catheters may have a flexural load less than or equal to about 2.0 lbF, about 1.5 lbF, about 1.0 lbF, or about 0.5 lbF at about 70 cm from the proximal end. The catheters may have a flexural load less than or equal to about 1.0 lbF, about 0.75 lbF, about 0.5 lbF, about 0.4 lbF, about 0.3 lbF, about 0.2 lbF, or about 0.1 lbF at about 80 cm from the proximal end. The catheters may have a flexural load less than or equal to about 1.0 lbF, about 0.75 lbF, about 0.5 lbF, about 0.4 lbF, about 0.3 lbF, about 0.2 lbF, or about 0.1 lbF at about 90 cm from the proximal end. 
     The catheters may have a transition region, in which its flexural load changes by greater than or equal to about 1.0 lbF, about 1.5 lbF, about 2.0 lbF, about 2.5 lbF, about 3.0 lbF, or about 3.5 lbF. The longitudinal length of the transition region may be less than or equal to about 20 cm, about 15 cm, about 10 cm, about 5 cm, about 3 cm, or about 1 cm. 
     Compared to Neuron Max (Penumbra, Inc.)  3402 , catheters according to the present invention (e.g.,  3404 ,  3406 ,  3408 ,  3410 ) have comparable modulus near its proximal end. This way, the catheters according to the present invention provide back-up support comparable to that of Neuron Max. In addition, the catheters have modulus that falls more rapidly near the transition region (between the proximal end and the distal end) than that of Neuron Max. 
     Compared to Ace 68 catheter (Penumbra)  3412 , Ace 64 catheter (Penumbra)  3414 , Benchmark 71 catheter (Penumbra)  3416 , and Sofia Plus (MicroVention)  3418 , the catheters according to the present inventions have greater modulus near its proximal end and comparable modulus near its distal end. This way, the catheters according to the present invention provide superior back-up support with comparable trackability compared to conventional catheters. The catheters according to the present invention may achieve this modulus profile even when their inner diameters (and thus lumen volumes) are greater than or equal to those of Ace 68, Ace 64, Benchmark 71, and Sofia Plus, which range from 0.064 inch to 0.071 inch. 
     Referring to  FIG. 38 , there is illustrated a transformable access sheath  200 . The access sheath  200  comprises an elongate flexible tubular body  202  extending between a proximal end  204  and a distal end  206 . A proximal access port  208  is in communication with a distal port  210  on the distal end  206  by way of a central lumen  212 . See  FIG. 39 . 
     At least one transition zone  214  is provided on the tubular body  202 . Transition zone  214  is controllably transformable between a relatively stiff configuration and a relatively flexible configuration. The access sheath  200  may be distally advanced through tortuous anatomy with at least one transition zone  214  in a relatively stiff configuration as desired such as to provide column strength or to facilitate the introduction of instruments therethrough. The transition zone  214  may be controllably transformed to a relatively flexible configuration as desired, such as to navigate tight bends in the vasculature. 
     In the illustrated embodiment, three transition zones  214  are shown. However, one or two or three or four or more transition zones may be utilized, depending upon the desired clinical performance. The transition zone  214  may be from about 1 cm to about 20 or 30 cm or more in length. In certain embodiments, the transition zones will be within the range of from about 2 cm to about 10 cm in length. The length and location of the transition zones may depend upon the target anatomy for the access catheter, and can be located accordingly. 
     Referring to  FIG. 39 , there is illustrated a cross-sectional view taken along the lines  18 - 18  of  FIG. 38 , through a transition zone  214 . The tubular body  202  comprises a sidewall  216  having at least one heating element  218  carried by or embedded within the sidewall  216 . In the illustrated embodiment, the heater  218  may be an electrically conductive filament, such as a filar on an electrically conductive helical coil or braid. The electrically conductive filament may be placed within or laminated within an inner layer and an outer layer of the sidewall  216 . In at least one embodiment, an inner layer of the sidewall  216  may comprise polytetrafluorothylene (PTFE) for lubricity. In at least one embodiment, an outer layer of the sidewall  216  may comprise biocompatible material preferably with a glass transition temperature from about 40° C. to about 80° C. 
     Alternatively, an electrically conductive polymer may be utilized to form the sidewall  216 . Electrically conductive coatings may alternatively be printed, laminated, embedded or otherwise applied to the outside, the inside, or laminated within an inner layer and an outer layer of the sidewall  216 . In at least one embodiment, the resistance of the heater  218  may be calibrated to a specific heating temperature, such as 40-80° C., for a predetermined voltage level of the power source. This may eliminate the need for a thermocouple and prevent potential overheating. 
     One or more electrical conductors may extend between the transition zone  214  and a proximal activation port  215 , adapted for coupling to a source of electricity from an external controller. In a mono polar construction, a single conductor for each transition zone  214  may extend proximally to the activation port  215 . A second conductor may lead to or comprise an electrically conductive surface on the tubular body  202 , for conducting electricity through the body of the patient to an external electrode as is understood in the art. Alternatively, in a bipolar embodiment, each transition zone  214  may be provided with at least two electrical conductors extending proximally to the activation port  215 . 
     At least the transition zone comprises a biocompatible material that is relatively firm at body temperature (e.g., 37° C.) but transitions to a relatively soft, flexible material upon application of heat. Typical suitable materials have a relatively low melting point so as to be softenable at temperatures not so high as to damage living vessels. In any event the material will have a softening point or a glass transition temperature above body temperature, with a melting point significantly above body temperature and above the temperature reached by activating the heating element  218 . In one embodiment, the biocompatible material preferably has a glass transition temperature from about 40° C. to about 80° C. Suitable materials may include polymers with a polymer chain orientation that causes the polymer to break when heated. 
     Examples of suitable biostable materials are polymers, typically thermoplastic polymers such as polyolefins and polyurethanes and most other biocompatible polymers. Typical suitable bioabsorbable materials include polyglycolide (PGA), poly(L-lactide) (PLLA), poly(.epsilon.-caprolactone) (PCL), and blends or combinations thereof. Polyglycolide for example has a glass transition temperature between 35-40° C., such having a considerably higher melting point. 
     Typical operating (softening) temperatures in this regard are on the order of between about 40 and 80° C., often between about 40° C. and 60° C. to cause a softening transition of the transition zone  214 , and allow a transition back to a firm state upon removal of power and reversion of the transition zone  214  back to body temperature. A temperature higher than about 80° C. may be acceptable for a short period of time, depending upon the total energy delivered. Any temperature to which the heater  218  is elevated is limited by what the body of the patient can handle without causing damage to the vessel wall or causing thrombus to form. For this reason, it may be desirable to remain within the lower end of the temperature ranges illustrated above if the eligible polymers exhibit suitable flexibility at the softening point temperature and suitable firmness at the lower body temperature. 
     Upon being heated, the biocompatible energy-activated transition zone  214  softens so that it may be navigated through a tight bend for example. The material is to be softened enough by the energy application so that it increases in flexibility, but retains the structural integrity necessary for navigation and retains its shape so that upon interruption of the heat source it will harden back to its original configuration. To maintain the integrity of the tubular body, side wall  216  may be provided with flexible reinforcing structures such as a helically wrapped wire, ribbon or polymeric strand such as polyimide, or other braid or weave as is understood in the neurovascular catheter arts. A resistance coil or other resistance filaments may also provide the mechanical reinforcing function while the transition zone is in the softened state. 
     Heating may alternatively be provided by positioning a heat source such as a resistance heat element carried by a heater catheter within the central lumen  212 . Once the catheter has reached its final position in the vasculature, the heater catheter may be proximally withdrawn from the central lumen  212 , which is now available for aspiration or to receive a distal section  34  therethrough. In either heater configuration, a power source may be provided within or electrically coupled to a proximal manifold on the aspiration catheter or heater catheter. 
     Access for the catheter of the present invention can be achieved using conventional techniques through an incision on a peripheral artery, such as right femoral artery, left femoral artery, right radial artery, left radial artery, right brachial artery, left brachial artery, right axillary artery, left axillary artery, right subclavian artery, or left subclavian artery. An incision can also be made on right carotid artery or left carotid artery in emergency situations. 
     Avoiding a tight fit between the guidewire  40  and inside diameter of guidewire lumen  28  enhances the slidability of the catheter over the guidewire. In ultra small diameter catheter designs, it may be desirable to coat the outside surface of the guidewire  40  and/or the inside surface of the wall defining lumen  38  with a lubricous coating to minimize friction as the catheter  10  is axially moved with respect to the guidewire  40 . A variety of coatings may be utilized, such as Paralene, Teflon, silicone, polyimide-polytetrafluoroethylene composite materials or others known in the art and suitable depending upon the material of the guidewire or inner tubular wall  38 . 
     Aspiration catheters of the present invention which are adapted for intracranial applications generally have a total length in the range of from 60 cm to 250 cm, usually from about 135 cm to about 175 cm. The length of the proximal segment  33  will typically be from 20 cm to 220 cm, more typically from 100 cm to about 120 cm. The length of the distal segment  34  will typically be in the range from 10 cm to about 60 cm, usually from about 25 cm to about 40 CM. 
     The catheters of the present invention may be composed of any of a variety of biologically compatible polymeric resins having suitable characteristics when formed into the tubular catheter body segments. Exemplary materials include polyvinyl chloride, polyethers, polyamides, polyethylenes, polyurethanes, copolymers thereof, and the like. In one embodiment, both the proximal body segment  33  and distal body segment  34  will comprise a polyvinyl chloride (PVC), with the proximal body segment being formed from a relatively rigid PVC and the distal body segment being formed from a relatively flexible, supple PVC. Optionally, the proximal body segment may be reinforced with a metal or polymeric braid or other conventional reinforcing layer. 
     The proximal body segment will exhibit sufficient column strength to permit axial positioning of the catheter through a guide catheter with at least a portion of the proximal body segment  33  extending beyond the guide catheter and into the patient&#39;s vasculature. The proximal body segment may have a shore hardness in the range from 50D to 100D, often being about 70D to 80D. Usually, the proximal shaft will have a flexural modulus from 20,000 psi to 1,000,000 psi, preferably from 100,000 psi to 600,000 psi. The distal body segment  34  will be sufficiently flexible and supple so that it may navigate the patient&#39;s more narrow distal vasculature. In highly flexible embodiments, the shore hardness of the distal body segment  34  may be in the range of from about 20 A to about 100 A, and the flexural modulus for the distal segment  34  may be from about 50 psi to about 15,000 psi. 
     The catheter body may further comprise other components, such as radiopaque fillers; colorants; reinforcing materials; reinforcement layers, such as braids or helical reinforcement elements; or the like. In particular, the proximal body segment may be reinforced in order to enhance its column strength and torqueability (torque transmission) while preferably limiting its wall thickness and outside diameter. 
     Usually, radiopaque markers will be provided at least at the distal end  14  and the transition region  32  at the distal end of proximal segment  33 . One radiopaque marker comprises a metal band which is fully recessed within or carried on the outside of the distal end of the proximal body segment  33 . Suitable marker bands can be produced from a variety of materials, including platinum, gold, and tungsten/rhenium alloy. Preferably, the radiopaque marker band will be recessed in an annular channel to produce a smooth exterior surface. 
     The proximal section  33  of tubular body  16  may be produced in accordance with any of a variety of known techniques for manufacturing interventional catheter bodies, such as by extrusion of appropriate biocompatible polymeric materials. Alternatively, at least a proximal portion or all of the length of tubular body  16  may comprise a polymeric or metal spring coil, solid walled hypodermic needle tubing, or braided reinforced wall, as is known in the microcatheter arts. 
     In a catheter intended for neurovascular applications, the proximal section  33  of body  16  will typically have an outside diameter within the range of from about 0.117 inches to about 0.078 inches. In one implementation, proximal section  33  has an OD of about 0.104 inches and an ID of about 0.088 inches. The distal section  34  has an OD of about 0.085 inches and an ID of about 0.070 inches. 
     Diameters outside of the preferred ranges may also be used, provided that the functional consequences of the diameter are acceptable for the intended purpose of the catheter. For example, the lower limit of the diameter for any portion of tubular body  16  in a given application will be a function of the number of fluid or other functional lumen contained in the catheter, together with the acceptable minimum aspiration flow rate and collapse resistance. 
     Tubular body  16  must have sufficient structural integrity (e.g., column strength or “pushability”) to permit the catheter to be advanced to distal locations without buckling or undesirable bending of the tubular body. The ability of the body  16  to transmit torque may also be desirable, such as to avoid kinking upon rotation, to assist in steering. The tubular body  16 , and particularly the distal section  34 , may be provided with any of a variety of torque and/or column strength enhancing structures. For example, axially extending stiffening wires, spiral wrapped support layers, braided or woven reinforcement filaments may be built into or layered on the tubular body  16 . See, for example, U.S. Pat. No. 5,891,114 to Chien, et al., the disclosure of which is incorporated in its entirety herein by reference. 
     In many applications, the proximal section  33  will not be required to traverse particularly low profile or tortuous arteries. For example, the proximal section  33  will be mostly or entirely within the relatively large diameter guide catheter. The transition  32  can be located on the catheter shaft  16  to correspond approximately with or beyond the distal end of the guide catheter. 
     For certain applications, such as intracranial catheterizations, the distal section  34  is preferably at least about 5 cm or 10 cm long and small enough in diameter to pass through vessels as low as 3 mm or 2 mm or lower. The distal section may have a length of at least about 20 cm or 30 cm or 40 cm or more, depending upon the intended target vessel or treatment site. 
     The distal section, whether carried within the proximal section as an integrated device, or is a separate device to be inserted into the proximal section during a procedure, is substantially shorter than the proximal section. When the distal end of the distal section and the distal end of the proximal section are axially aligned, the proximal end of the distal section is spaced distally apart from the proximal end of the proximal section. The control element such as a control wire or tube spans the distance between the proximal end of the distal section and the proximal manifold or proximal control. 
     In the foregoing configuration, the proximal end of the distal section will generally be spaced apart distally from the proximal end of the proximal section by at least about 25%, and in some embodiments at least about 50% or 70% or more of the length of the proximal section. 
     There is provided in according with one aspect, a telescoping catheter, comprising: an elongate, flexible tubular body, comprising a proximal section having at least one lumen and a distal section axially movably positioned within the lumen; and a control for advancing the distal section from a first, proximally retracted position within the proximal section to a second, extended position, extending distally beyond the proximal section; and an active tip on the distal end of the distal section, comprising a distal opening that is movable between a smaller and a larger configuration. 
     In one aspect of present disclosure, the control comprises a pull wire extending through the proximal section. In another aspect of present disclosure, the distal section is distally advanceable to extend beyond the proximal section for a distance of at least about 10 cm. In yet another aspect of present disclosure, the distal section is distally advanceable to extend beyond the proximal section for a distance of at least about 25 cm. 
     In one aspect of present disclosure, the distal opening is movable in response to movement of a control wire. In another aspect of present disclosure, the distal opening is movable between a smaller and a larger configuration in response to application of vacuum to the lumen. In yet another aspect of present disclosure, the size of the distal opening is changed by lateral movement of a side wall on the distal section. In yet another aspect of present disclosure, the distal opening comprises at least one movable jaw. In another aspect of present disclosure, the distal end of the distal section comprises a duck bill valve configuration. 
     In one aspect of present disclosure, the telescoping catheter may further comprise a controller for applying intermittent vacuum to the lumen. The controller may be configured to apply pulses of vacuum to the lumen spaced apart by spaces of neutral pressure. The controller may be configured to alternate between applying pulses of higher negative pressure and lower negative pressure. The distal tip of the catheter may axially reciprocate in response to application of pulses of vacuum to the lumen. 
     In accordance with one aspect, there is provided a system for aspirating a vascular occlusion from a remote site, comprising: an elongate, flexible tubular body, comprising at least one central lumen extending along its longitudinal length; an agitator extendable through the central lumen of the tubular body to position a distal end of the agitator near a distal end of the tubular body; a driver connectable to a proximal end of the agitator and configured to actuate the agitator; and a vacuum port near the proximal end of the tubular body and in fluid communication with the central lumen of the tubular body. 
     In one aspect of present disclosure, the agitator comprises an elongate tube. The agitator may comprise a wire extending through the elongate tube and having at least one bend near its distal end. In another aspect of present disclosure, the agitator comprises a proximal end, a distal end, and a loop at the distal end. In yet another aspect of present disclosure, the driver is configured to rotate the agitator cyclically in alternating directions. 
     In one aspect of present disclosure, the agitator comprises: at least one lumen along its longitudinal length, an influent port near its proximal end configured to allow fluid communication between the lumen of the agitator and a source of media, and at least one effluent port configured to allow fluid communication between the lumen of the agitator and the central lumen of the tubular body. The system for aspirating a vascular occlusion may further comprise a control, for expressing media from the effluent port of the agitator into the central lumen of the tubular body. The distal portion of the tubular body may be configured to vibrate in a transverse direction in response to the injection of media. 
     In one aspect of present disclosure, the system for aspirating a vascular occlusion further comprises a controller for applying a pulsatile vacuum cycle to the central lumen. In another aspect of present disclosure, the system for aspirating a vascular occlusion further comprises a rotating hemostasis valve coupled to the proximal end of the tubular body, the rotating hemostasis valve comprising: at least one main lumen along its longitudinal length, through which the proximal portion of the agitator is configured to pass, and an aspiration lumen bifurcating from the main lumen and provided with a vacuum port. In yet another aspect of present disclosure, the system further comprises a proximal drive assembly coupled to the proximal end of the tubular body, the proximal drive assembly comprising: at least one main lumen along its longitudinal length for receiving the agitator; a media injection port, into which media is injected, in fluid communication with the central lumen of the tubular body, and a proximal drive connection at the proximal end, which operably connects between the agitator and the driver. 
     In accordance with another aspect, there is provided a method of aspirating a vascular occlusion from a remote site, comprising: providing the system for aspirating a vascular occlusion; placing the tubular body adjacent to the occlusion; activating the driver to actuate the agitator and loosen the occlusion; and drawing occlusive material into the central lumen by applying vacuum to the central lumen. In one aspect of present disclosure, there is provided a method of aspirating a vascular occlusion from a remote site, comprising: providing the system for aspirating a vascular occlusion; placing the tubular body adjacent to the occlusion; activating the driver to cause the distal tip of the agitator to rotate; injecting media through the influent port; and aspirating occlusive material into the central lumen by applying vacuum to the central lumen. Actuation of the driver, aspiration, and media injection may be synchronized to facilitate the removal and/or aspiration of the occlusion. 
     In accordance with one aspect, there is provided a method of aspirating a vascular occlusion from a remote site, comprising: advancing a guidewire to a site at least as distal as the cavernous segment of the internal carotid artery; advancing a tubular body directly over the guidewire to a site at least as distal as the cavernous segment; removing the guidewire from the tubular body; and aspirating thrombus into the tubular body by applying vacuum to the tubular body. In one aspect of present disclosure, the method of aspirating a vascular occlusion comprises advancing the tubular body at least as distal as the cerebral segment of the internal carotid artery. In another aspect of present disclosure, the method of aspirating a vascular occlusion comprises advancing the guidewire at least as distal as the middle cerebral artery. 
     In yet another aspect of present disclosure, the method of aspirating a vascular occlusion further comprises providing sufficient back up support to the tubular body to resist prolapse of the tubular body into the aorta. In one aspect, the back up support may be provided by advancing the tubular body over a guidewire having a distal end positioned at least as distal as the cavernous segment of the internal carotid artery, and a diameter at the point the guidewire enters the brachiocephalic artery of at least about 0.030 inches. In another aspect, the back up support may be provided by advancing the tubular body over a guidewire having a distal end positioned at least as distal as the cavernous segment of the internal carotid artery, and a diameter at the point the guidewire enters the brachiocephalic artery of about 0.038 inches. The guidewire may be navigable to at least the cerebral segment of the internal carotid artery by having a distal segment having a diameter of no more than about 0.020 inches. The guidewire may be navigable to at least the cerebral segment of the internal carotid artery by having a distal segment having a diameter of about 0.016 inches. The distal segment may have a length of no more than about 25 cm. The distal segment may have a length of no more than about 20 cm. 
     In accordance with another aspect, there is provided a method of tracking an aspiration catheter from a femoral access site to at least as distal as the cavernous segment of the internal carotid artery, comprising the steps of: advancing a guidewire from the femoral access site to at least as distal as the cerebral segment of the internal carotid artery, the guidewire having a proximal section having a diameter of at least about 0.030 inches and a distal section having a length of no more than about 25 cm and a diameter of no more than about 0.020 inches; tracking an aspiration catheter directly over the guidewire and to a site at least as distal as the cavernous segment, the aspiration catheter having a distal end and a central lumen at the distal end with a diameter of at least about 0.080 inches and a beveled distal tip. In one aspect of present disclosure, the diameter of the proximal section of the guidewire is about 0.038 inches, and the diameter of the distal section is about 0.016 inches. 
     In another aspect of present disclosure, a distal segment of the catheter comprises a side wall defining the central lumen, the side wall comprising: a tubular inner liner; a soft tie layer separated from the lumen by the inner liner; a helical coil surrounding the tie layer, adjacent windings of the coil spaced progressively further apart in the distal direction; and an outer jacket surrounding the helical coil, the outer jacket formed from a plurality of tubular segments positioned coaxially about the coil; wherein a proximal one of the tubular segments has a durometer of at least about 60D and a distal one of the tubular segments has a durometer of no more than about 35D. The tubular liner may be formed by dip coating a removable mandrel and may comprise PTFE. The tie layer may comprise polyurethane. 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. The coil may comprise a shape memory material. 
     In accordance with one aspect, there is provided an enhanced flexibility neurovascular catheter, comprising: an elongate flexible body, having a proximal end, a distal end and a side wall defining a central lumen, a distal zone of the side wall comprising: a tubular inner liner; a soft tie layer separated from the lumen by the inner liner; a helical coil surrounding the tie layer, adjacent windings of the coil spaced progressively further apart in the distal direction; and an outer jacket surrounding the helical coil, the outer jacket formed from a plurality of tubular segments positioned coaxially about the coil; wherein a proximal one of the tubular segments has a durometer of at least about 60D and a distal one of the tubular segments has a durometer of no more than about 35D. In one aspect of present disclosure, the tubular liner is formed by dip coating a removable mandrel. In another aspect of present disclosure, the tubular liner comprises PTFE. 
     In yet another aspect of present disclosure, the tie layer comprises polyurethane. 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. In one aspect of present disclosure, the coil comprises a shape memory material. The coil may comprise Nitinol, and the Nitinol may comprise an Austenite state at body temperature. 
     In one aspect of present disclosure, the outer jacket is formed from at least five discrete tubular segments. The outer jacket may be formed from at least nine discrete tubular segments. The difference in durometer between a proximal one of the tubular segments and a distal one of the tubular segments may be at least about 20D. The difference in durometer between a proximal one of the tubular segments and a distal one of the tubular segments may be at least about 30D. 
     In another aspect of present disclosure, the enhanced flexibility neurovascular catheter, further comprises a tension support for increasing the tension resistance in the distal zone. The tension support may comprise a filament and 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 to at least about 1 pound, at least about 2 pounds, at least about 3 pounds, at least about 4 pounds, at least about 5 pounds at least about 6 pounds, at least about 7 pounds, at least about 8 pounds, or at least about 10 pounds or more. 
     In accordance with one aspect, there is provided an enhanced flexibility neurovascular catheter, comprising: an elongate flexible body, having a proximal end, a distal end and a side wall defining a central lumen, a distal zone of the side wall comprising: an outer jacket surrounding a helical coil, the outer jacket formed from a plurality of tubular segments positioned coaxially about the coil; wherein a proximal one of the tubular segments has a durometer of at least about 60D and a distal one of the tubular segments has a durometer of no more than about 35D; and an axially extending filament within the side wall, extending at least about the most distal 10 cm of the length of the catheter. The filament may extend at least about the most distal 15 cm of the length of the catheter. The filament may extend at least about the most distal 20 cm of the length of the catheter. The filament may comprise multiple fibers and may extend axially in between the coil and the inner liner. 
     In one aspect of present disclosure, the side wall further comprises: a tubular inner liner; a soft tie layer separated from the lumen by the inner liner; wherein the helical coil surrounds the tie layer, and adjacent windings of the coil are spaced progressively further apart in the distal direction. The tubular liner may be formed by dip coating a removable mandrel and may comprise PTFE. The tie layer may comprise polyurethane and may have a wall thickness of no more than about 0.005 inches. The tie layer may extend along at least the most distal 20 cm of the flexible body. The coil may comprise a shape memory material and may comprise Nitinol. The Nitinol may comprise an Austenite state at body temperature. 
     In one aspect of present disclosure, the outer jacket may be formed from at least five discrete tubular segments. In another aspect of present disclosure, the outer jacket may be formed from at least nine discrete tubular segments. The difference in durometer between a proximal one of the tubular segments and a distal one of the tubular segments may be at least about 20D. The difference in durometer between a proximal one of the tubular segments and a distal one of the tubular segments may be at least about 30D. In another aspect of present disclosure, the catheter can withstand at least about 3.5 pounds tension before failure. In yet another aspect, the catheter can withstand at least about 5 pounds tension before failure. 
     In accordance with one aspect, there is provided a method of making a high flexibility distal zone on a neurovascular catheter, comprising the steps of: dip coating a removable mandrel to form a tubular inner layer on the mandrel; coating the tubular inner layer with a soft tie layer; applying a helical coil to the outside of the tie layer; positioning a plurality of tubular segments on the helical coil; the plurality of segments having durometers that decrease in a distal direction; heating the tubular segments to form the high flexibility distal zone on the neurovascular catheter; and removing the mandrel. In one aspect of present disclosure, removing the mandrel step includes axially elongating the mandrel. In another aspect of present disclosure, the method of making a high flexibility distal zone on a neurovascular catheter comprises positioning at least seven segments on the helical coil. In yet another aspect of present disclosure, the method of making a high flexibility distal zone on a neurovascular catheter comprises positioning at least nine segments on the helical coil. 
     In one aspect of present disclosure, 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. The difference in durometer between a proximal one of the tubular segments and a distal one of the tubular segments may be at least about 30D. The tubular inner layer may comprise PTFE. In another aspect of present disclosure, the tie layer comprises polyurethane. The tie layer may have a wall thickness of no more than about 0.005 inches. The tie layer may extend along at least the most distal 20 cm of the flexible body. 
     In one aspect of present disclosure, the coil comprises a shape memory material. The coil may comprise Nitinol. The Nitinol may comprise an Austenite state at body temperature. In another aspect of present disclosure, the method of making a high flexibility distal zone on a neurovascular catheter further comprises the step of positioning at least one tensile strength enhancing filament in between the coil and the tie layer prior to heat shrinking the tubular segments. The filament may extend along at least about the most distal 15 cm of the length of the catheter. The filament may extend along at least about the most distal 20 cm of the length of the catheter. The filament may comprise multiple fibers. In yet another aspect of present disclosure, the method of making a high flexibility distal zone on a neurovascular catheter further comprises the step of positioning at least one tensile strength enhancing filament over the tie layer before the applying a helical coil step. 
     In accordance with one aspect, there is provided a method of aspirating a vascular occlusion from a remote site, comprising the steps of: advancing an elongate tubular body through a vascular access site and into a body vessel, the tubular body comprising a proximal end, a distal end and a central lumen; positioning the distal end at least as far distally as the cavernous segment of the middle cerebral artery; applying vacuum to the lumen to draw thrombus into the lumen; and mechanically disrupting the thrombus to facilitate entry into the lumen. 
     In one aspect of present disclosure, the mechanically disrupting step comprises introducing vibration at the distal end of the tubular body. The vibration may be introduced by rotating an agitator within the tubular body. The method of aspirating a vascular occlusion may comprise rotating a wire within the tubular body. The method of aspirating a vascular occlusion may comprise rotating a tube within the tubular body and may further comprise the step of introducing media through the tube. The method of aspirating a vascular occlusion may comprise the step of introducing a lubricant through the tube to facilitate advancing thrombus through the lumen and may comprise the step of introducing polyethylene glycol through the tube. 
     In another aspect of present disclosure, the applying vacuum step comprises applying pulsatile vacuum. In yet another aspect of present disclosure, the advancing an elongate tubular body step is accomplished directly over a guidewire without any intervening tubular bodies. The method of aspirating a vascular occlusion may comprise advancing the tubular body at least as distal as the cavernous segment of the internal carotid artery. The method of aspirating a vascular occlusion may comprise advancing the tubular body at least as distal as the cerebral segment of the internal carotid artery. The method of aspirating a vascular occlusion may comprise advancing the guidewire at least as distal as the middle cerebral artery. 
     In one aspect of present disclosure, the method of aspirating a vascular occlusion further comprises providing sufficient back up support to the tubular body to resist prolapse of the tubular body into the aorta. The back up support may be provided to the tubular body by advancing the tubular body over a guidewire having a distal end positioned at least as distal as the cavernous segment of the internal carotid artery, and a diameter at the point the guidewire enters the brachiocephalic artery of at least about 0.030 inches. The back up support may be provided to the tubular body by advancing the tubular body over a guidewire having a distal end positioned at least as distal as the cavernous segment of the internal carotid artery, and a diameter at the point the guidewire enters the brachiocephalic artery of about 0.038 inches. 
     In one aspect of present disclosure, the guidewire is navigable to at least the cerebral segment of the internal carotid artery by having a distal segment having a diameter of no more than about 0.020 inches. The guidewire may be navigable to at least the cerebral segment of the internal carotid artery by having a distal segment having a diameter of about 0.016 inches. In yet another aspect of present disclosure, the method of aspirating a vascular occlusion further comprises the step of introducing an agitator into the tubular body subsequent to the positioning step. A proximal section of the agitator may extend through a constraint tube, and a distal section of the agitator may extend beyond a distal end of the constraint tube. 
     In accordance with one aspect, there is provided a method of aspirating a vascular occlusion from a remote site, comprising: advancing a guidewire through a vascular access point and transvascularly to a site at least as distal as the cavernous segment of the internal carotid artery; accessing a site at least as distal as the cavernous segment by advancing a combined access and aspiration catheter directly over the guidewire; removing the guidewire; and aspirating thrombus through the combined access and aspiration catheter. In one aspect of present disclosure, the method of aspirating a vascular occlusion comprises advancing the combined access and aspiration catheter at least as distal as the cerebral segment of the internal carotid artery. In another aspect of present disclosure, the method of aspirating a vascular occlusion comprises advancing the guidewire at least as distal as the middle cerebral artery. 
     In yet another aspect of present disclosure, the method of aspirating a vascular occlusion further comprises providing sufficient back up support to the combined access and aspiration catheter to resist prolapse of the catheter into the aorta. The back up support may be provided to the combined access and aspiration catheter by advancing the combined access and aspiration catheter over a guidewire having a distal end positioned at least as distal as the cavernous segment of the internal carotid artery, and a diameter at the point the guidewire enters the brachiocephalic artery of at least about 0.030 inches. The back up support is provided to the combined access and aspiration catheter by advancing the combined access and aspiration catheter over a guidewire having a distal end positioned at least as distal as the cavernous segment of the internal carotid artery, and a diameter at the point the guidewire enters the brachiocephalic artery of about 0.038 inches. 
     In one aspect of present disclosure, the guidewire is navigable to at least the cerebral segment of the internal carotid artery by having a distal segment having a diameter of no more than about 0.020 inches. The guidewire may be navigable to at least the cerebral segment of the internal carotid artery by having a distal segment having a diameter of about 0.016 inches. The diameter of the proximal section of the guidewire may be about 0.038 inches, and the diameter of the distal section may be about 0.016 inches. 
     In another aspect of present disclosure, a distal segment of the combined access and aspiration catheter comprises a side wall defining a central lumen, the side wall comprising: a tubular inner liner; a tie layer separated from the lumen by the inner liner; a helical coil surrounding the tie layer, adjacent windings of the coil spaced progressively further apart in the distal direction; and an outer jacket surrounding the helical coil, the outer jacket formed from a plurality of tubular segments positioned coaxially about the coil; wherein a proximal one of the tubular segments has a durometer of at least about 60D and a distal one of the tubular segments has a durometer of no more than about 35D. The tubular liner may be formed by dip coating a removable mandrel. The tubular liner may comprise PTFE. The tie layer may comprise polyurethane, and may have a wall thickness of no more than about 0.005 inches. The tie layer may extend along at least the most distal 20 cm of the flexible body. 
     In one aspect of present disclosure, the coil comprises a shape memory material. In another aspect of present disclosure, the method of aspirating a vascular occlusion further comprises introducing an agitator into the combined access and aspiration catheter. The method of aspirating a vascular occlusion may further comprise vibrating a distal portion of the agitator during the aspirating step. The method of aspirating a vascular occlusion may further comprise introducing a fluid media through the agitator during the aspirating step. The method of aspirating a vascular occlusion may further comprise introducing polyethylene glycol through the agitator during the aspirating step. 
     In accordance with one aspect, there is provided a neurovascular catheter, comprising: 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 comprising: a tubular inner liner; a tie layer separated from the lumen by the inner liner; a helical coil surrounding the tie layer, adjacent windings of the coil spaced progressively further apart in the distal direction; an outer jacket surrounding the helical coil, and an opening at the distal end which is enlargeable from a first inside diameter for transluminal navigation to a second, larger inside diameter to facilitate aspiration of thrombus into the lumen. In one aspect of present disclosure, the distal opening is enlargeable in response to exposure to blood. In another aspect of present disclosure, the distal opening is enlargeable in response to exposure to body temperature. In yet another aspect of present disclosure, the distal opening is enlargeable in response to removal of a constraint. The constraint may comprise a polymer having a structural integrity that decreases in the intravascular environment. 
     In one aspect of present disclosure, the catheter body adjacent the distal opening comprises a radially outwardly biased embedded support. The catheter body adjacent the distal opening may comprise an embedded Nitinol frame. The support may comprise a wire mesh. The support may comprise a stent. In another aspect of present disclosure, the catheter body adjacent the distal opening comprises a hydrophilic blend. In yet another aspect of present disclosure, the tubular liner is formed by dip coating a removable mandrel. The tubular liner may comprise PTFE. 
     In one aspect of present disclosure, the tie layer comprises polyurethane. The tie layer may have a wall thickness of no more than about 0.005 inches. The tie layer may extend along at least the most distal 20 cm of the flexible body. In another aspect of present disclosure, the coil comprises a shape memory material. The coil may comprise Nitinol. The Nitinol may comprise an Austenite state at body temperature. In one aspect of present disclosure, the outer jacket is formed from at least five discrete tubular segments. The outer jacket may be formed from at least nine discrete tubular segments. The difference in durometer between a proximal one of the tubular segments and a distal one of the tubular segments may be at least about 20D. The difference in durometer between a proximal one of the tubular segments and a distal one of the tubular segments may be at least about 30D. 
     In accordance with one aspect, there is provided a neurovascular catheter extension segment, comprising: an elongate flexible control wire, having a proximal end and a distal end; a tubular extension segment having a side wall defining a central lumen carried by the distal end of the control wire, the side wall comprising: a tubular inner liner; a tie layer separated from the lumen by the inner liner; a helical coil surrounding the tie layer; and an outer jacket surrounding the helical coil. In one aspect of present disclosure, the outer jacket is formed from a plurality of tubular segments positioned coaxially about the coil. A proximal one of the tubular segments may have a durometer of at least about 60D, and a distal one of the tubular segments may have a durometer of no more than about 35D. 
     In another aspect of present disclosure, the tubular liner is formed by dip coating a removable mandrel. The tubular liner may comprise PTFE. In yet another aspect of present disclosure, the tie layer comprises polyurethane. The tie layer may have a wall thickness of no more than about 0.005 inches. The tie layer may extend along at least the most distal 20 cm of the tubular extension segment. In one aspect of present disclosure, the coil comprises a shape memory material. The coil may comprise Nitinol. The Nitinol may comprise an Austenite state at body temperature. 
     In one aspect of present disclosure, the outer jacket is formed from at least five discrete tubular segments. The outer jacket may be formed from at least nine discrete tubular segments. The difference in durometer between a proximal one of the tubular segments and a distal one of the tubular segments may be at least about 20D. The difference in durometer between a proximal one of the tubular segments and a distal one of the tubular segments may be at least about 30D. In another aspect of present disclosure, the control wire comprises a central lumen. The control wire central lumen may be in communication with the central lumen of the tubular extension segment. In yet another aspect of present disclosure, the inside diameter of the neurovascular catheter extension segment is at least 2× the inside diameter of the control wire central lumen. The inside diameter of the neurovascular catheter extension segment may be at least 3× the inside diameter of the control wire central lumen. 
     In accordance with another aspect, there is provided a neurovascular catheter extension segment system, comprising the neurovascular catheter extension segment described above and an agitator configured to extend through the control wire central lumen and into the central lumen of the tubular extension segment. 
     Although the present invention has been described in terms of certain preferred embodiments, it may be incorporated into other embodiments by persons of skill in the art in view of the disclosure herein. The scope of the invention is therefore not intended to be limited by the specific embodiments disclosed herein, but is intended to be defined by the full scope of the following claims.