Patent Publication Number: US-2020289136-A1

Title: Aspiration catheter systems and methods of use

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     The present application is a continuation-in-part of co-pending U.S. patent application Ser. No. 16/414,532, filed May 16, 2019, which claims the benefit of priority under 35 U.S.C. § 119(e) to U.S. Provisional Patent Application Ser. No. 62/673,009, filed May 17, 2018. The disclosure of the applications are hereby incorporated by reference in their entireties. 
    
    
     FIELD 
     The present technology relates generally to medical devices and methods, and more particularly, to aspiration catheter systems and their methods of use. 
     BACKGROUND 
     Acute ischemic stroke (AIS) usually occurs when an artery to the brain is occluded, preventing delivery of fresh oxygenated blood from the heart and lungs to the brain. These occlusions are typically caused by a thrombus or an embolus lodging in the artery and blocking the artery that feeds a territory of brain tissue. If an artery is blocked, ischemia injury follows, and brain cells may stop working. Furthermore, if the artery remains blocked for more than a few minutes, the brain cells may die, leading to permanent neurological deficit or death. Therefore, immediate treatment is critical. 
     Two principal therapies are employed for treating ischemic stroke: thrombolytic therapy and endovascular treatment. The most common treatment used to reestablish flow or re-perfuse the stroke territory is the use of intravenous (IV) thrombolytic therapy. The timeframe to enact thrombolytic therapy is within 3 hours of symptom onset for IV infusion (4.5 hours in selected patients) or within 6 hours for site-directed intra-arterial infusion. Instituting therapy after this window has no proven benefit and may expose the patient to greater risk of bleeding due to the thrombolytic effect. Endovascular treatment most commonly uses a set of tools to mechanically remove the embolus, with our without the use of thrombolytic therapy. 
     The gamut of endovascular treatments include mechanical embolectomy, which utilizes a retrievable structure, e.g., a coil-tipped retrievable stent (also known as a stent retriever or a STENTRIEVER), a woven wire stent, or a laser cut stent with struts that can be opened within a clot in the cerebral anatomy to engage the clot with the stent struts, create a channel in the emboli to restore a certain amount of blood flow, and to subsequently retrieve the retrievable structure by pulling it out of the anatomy, along with aspiration techniques. Other endovascular techniques to mechanically remove AIS-associated embolus include Manual Aspiration Thrombectomy (MAT) (also known as the “ADAPT” technique). ADAPT/MAT is an endovascular procedure where large bore catheters are inserted through the transfemoral artery and maneuvered through complex anatomy to the level of the embolus, which may be in the extracranial carotids, vertebral arteries, or intracranial arteries. Aspiration techniques may be used to remove the embolus through the large bore catheters. Another endovascular procedure is STENTRIEVER-Mediated Manual Aspiration Thrombectomy (SMAT) (similar to the STENTRIEVER-assisted “Solumbra” technique). SMAT, like MAT, involves accessing the embolus through the transfemoral artery. After access is achieved, however, a retrievable structure is utilized to pull the embolus back into a large bore catheter. 
     To access the cerebral anatomy, guide catheters or guide sheaths are used to guide interventional devices to the target anatomy from an arterial access site, typically the femoral artery. The length of the guide is determined by the distance between the access site and the desired location of the guide distal tip. Interventional devices such as guidewires, microcatheters, and intermediate catheters used for sub-selective guides and aspiration, are inserted through the guide and advanced to the target site. Often, devices are used in a co-axial fashion, namely, a guidewire inside a microcatheter inside an intermediate catheter is advanced as an assembly to the target site in a stepwise fashion with the inner, most atraumatic elements, advancing distally first and providing support for advancement of the outer elements. The length of each element of the coaxial assemblage takes into account the length of the guide, the length of proximal connectors on the catheters, and the length needed to extend from the distal end. 
     Typical tri-axial systems such as for aspiration or delivery of stent retrievers and other interventional devices require overlapped series of catheters, each with their own rotating hemostatic valves (RHV) on the proximal end. For example, a guidewire can be inserted through a Penumbra Velocity microcatheter having a first proximal RHV, which can be inserted through a Penumbra ACE68 having a second proximal RHV, which can be inserted through a Penumbra NeuronMAX 088 access catheter having a third proximal RHV positioned in the high carotid via a femoral introducer. Maintaining the coaxial relationships between these catheters can be technically challenging. The three RHVs must be constantly adjusted with two hands or, more commonly, four hands (i.e. two operators). Further, the working area of typical tri-axial systems for aspiration and/or intracranial device delivery can require working area of 3-5 feet at the base of the operating table. 
     The time required to access the site of the occlusion and restore, even partially, flow to the vessel is crucial in determining a successful outcome of such procedures. Similarly, the occurrence of distal emboli during the procedure and the potentially negative neurologic effect and procedural complications such as perforation and intracerebral hemorrhage are limits to success of the procedure. There is a need for a system of devices and methods that allow for rapid access, optimized catheter aspiration and treatment to fully restore flow to the blocked cerebral vessel. 
     SUMMARY 
     In an aspect described is a coaxial catheter system including a catheter and a catheter advancement element. The catheter includes a distal, catheter portion having a lumen and a distal end having an opening from the lumen, the lumen having an inner diameter at the distal end of at least about 0.052″; and a proximal extension coupled to and extending proximally from the distal, catheter portion, the proximal extension being less flexible than the distal, catheter portion. The catheter advancement element includes a tubular portion having an inner diameter that is at least about 0.014″ up to about 0.024″ and an outer diameter having at least one snug point. A difference between the inner diameter of the distal, catheter portion and the outer diameter of the tubular portion at such snug point is no more than about 0.010″. The catheter advancement element includes a proximal extension coupled to and extending proximally from the tubular portion, the proximal extension being less flexible than the tubular portion; and a tip portion located distal to the at least one snug point of the tubular portion. The tip portion has a length and tapers along at least a portion of the length of the tip portion. The coaxial catheter system has an advancement configuration characterized by the catheter advancement element positioned coaxially within the lumen of the distal catheter portion, the at least one snug point of the tubular portion is substantially aligned with the distal end of the distal catheter portion. The advancement configuration is also characterized by the tip portion in the advancement configuration has at least three points spaced along the length of the tip portion. The at least three points include a distal point of the at least three points located a distance proximal from the distal-most end of the catheter advancement element, the distal point having a first bending force that is no greater than about 0.05 Newtons; an intermediate point of the at least three points located a distance proximal from the distal point, the intermediate point having a second bending force; and a proximal point of the at least three points located a distance proximal from the intermediate point, the proximal point having a third bending force. The advancement configuration is also characterized by the coaxial system having at least two system points along a length of the coaxial system. The at least two system points include a first system point of the at least two system points located proximal to the distal end of the catheter portion, the first system point having a first system bending force; and a second system point of the at least two system points located distal to the first system point by a distance that is at least about 1 mm distal to the distal end of the catheter portion, wherein the second system point can be the same or different from the proximal point, the second system point having a second system bending force. 
     A difference between the second bending force and the first bending force divided by the distance between the distal point and the intermediate point can equal a first flexibility slope. A difference between the third bending force and the second bending force divided by a distance between the intermediate point and the proximal point can equal a second flexibility slope. An average of the first flexibility slope and the second flexibility slope can define an average tip portion flexibility slope. A difference between the first system bending force and the second system bending force divided by the distance between the first system point and the second system point can equal a third flexibility slope. A ratio of the third flexibility slope to the average tip portion flexibility slope can be less than about 25. 
     The proximal extension of the catheter advancement element can have at least one stiffness point located within about 125 cm from the distal-most end of the catheter advancement element, the at least one stiffness point has a bending force. A ratio of the bending force of the at least one stiffness point to the first bending force of the distal point can be at least about 100. The proximal extension of the catheter advancement element can have at least one stiffness point located within about 125 cm from the distal-most end of the catheter advancement element, the at least one stiffness point has a bending force, wherein a ratio of the bending force of the at least one stiffness point to the first bending force of the distal point is at least about 200. The proximal extension of the catheter advancement element can have at least one stiffness point located within about 125 cm from the distal-most end of the catheter advancement element, the at least one stiffness point has a bending force. A ratio of the bending force of the at least one stiffness point to the first bending force of the distal point can be greater than at least about 300. The length of the tip portion can be at least about 1 cm up to about 4 cm. A ratio of the third bending force of the proximal point to the first bending force of the distal point can be at least 2. A ratio of the first system bending force to the first bending force of the distal point can be at least 2. The distal, catheter portion can have a catheter point located a distance of at least 5 mm proximal from the distal end, the catheter point having a catheter bending force. The first bending force of the distal point can be about 5%-15% the catheter bending force. The third bending force of the proximal point can be about 50%-90% the catheter bending force. A difference between the first bending force at the distal point to the third bending force at the proximal point can be a function of wall thickness. The inner diameter at the distal end of the distal, catheter portion can be about 0.054″ and the difference at the snug point can be about 0.006″ to about 0.008″. The inner diameter at the distal end of the distal, catheter portion can be about 0.070″ up to about 0.088″ and the difference at the snug point can be no more than about 0.006″ to about 0.008″. 
     The tubular portion of the catheter advancement element can have a radiopaque marker band embedded within or positioned over a wall of the tubular portion, the radiopaque marker band positioned at the snug point. The radiopaque marker band can have a proximal edge, a distal edge, and a width between the proximal edge and the distal edge. When in the advancement configuration, the proximal edge of the radiopaque marker band can align substantially with the distal end of the distal, catheter portion such that the radiopaque marker band remains external to the lumen of the distal, catheter portion. The outer diameter of the tubular portion can have a length that is at least about 5 cm up to about 10 cm. The snug point can be located along at least a portion of the length. The outer diameter can be substantially uniform along the length. The outer diameter can be substantially non-uniform along the length. The distal point can be located a distance of at least 5 mm proximal from the distal-most end of the catheter advancement element. The first system point can be located at least about 5 mm proximal to the distal end of the catheter portion. 
     In an interrelated aspect, described is a coaxial catheter system including a catheter and a catheter advancement element. The catheter includes a distal, catheter portion having a lumen and a distal end having an opening from the lumen, the lumen having an inner diameter at the distal end of at least about 0.052″. The catheter includes a proximal extension coupled to and extending proximally from the distal, catheter portion, the proximal extension being less flexible than the distal, catheter portion. The catheter advancement element includes a tubular portion having an inner diameter that is at least about 0.014″ up to about 0.024″, an outer diameter. The outer diameter has at least one snug point. A difference between the inner diameter of the distal, catheter portion and the outer diameter of the tubular portion at the snug point is no more than about 0.010″. The catheter advancement element includes a tip portion located distal to the at least one snug point of the tubular portion. The tip portion has a length and tapers along at least a portion of the length of the tip portion. The tip portion has a distal point located a distance of at least 5 mm proximal from the distal-most end of the catheter advancement element, the distal point having a bending force that is no greater than about 0.05 Newtons. 
     In an interrelated aspect, described is a method of performing a medical procedure in a cerebral vessel of a patient. The method includes advancing a first assembled coaxial system of devices toward an occlusion within a cerebral blood vessel. The first assembled coaxial system of device includes a first catheter having a first catheter portion having a lumen, a proximal opening into the lumen, a distal opening from the lumen, and a distal end. A first proximal extension is coupled to and extending proximally from the first catheter portion, the first proximal extension being less flexible than the first catheter portion. The first assembled coaxial system of device includes a first delivery element having a flexible, elongate body and a soft, tapered distal tip portion. At least a portion of the elongate body positioned within the lumen of the first catheter portion and the tapered distal tip portion extending distal to the distal end of the first catheter portion. The method includes withdrawing the first delivery element proximally from the lumen of the first catheter portion and advancing a second assembled coaxial system of devices through the lumen of the first catheter portion, out the distal opening from the lumen, and to a location near a proximal face of the occlusion within the cerebral blood vessel. The second assembled coaxial system of devices includes a second catheter and a second delivery element. The second catheter includes a second catheter portion having a lumen, a proximal opening into the lumen, a distal opening from the lumen, and a distal end; and a second proximal extension coupled to and extending proximally from the second catheter portion, the second proximal extension being less flexible than the second catheter portion. The second delivery element includes a flexible, elongate body and a soft, tapered distal tip portion, at least a portion of the elongate body positioned within the lumen of the second catheter portion and the tapered distal tip portion extending distal to the distal end of the second catheter portion. The second assembled coaxial system of devices is advanced together after the distal end of the second catheter portion is distal to the petrous portion of the internal carotid artery. The method includes withdrawing the second delivery element proximally from the lumen of the second catheter portion; applying aspiration pressure through the lumen of the second catheter portion; anchoring the distal end of the second catheter portion onto the occlusion via the aspiration pressure; and applying a proximally-directed force on the second catheter to reduce slack in the second catheter relative to surrounding anatomy while the distal end of the second catheter portion remains anchored onto the occlusion. 
     The method can further include withdrawing the second catheter from the cerebral blood vessel, the distal end of the second catheter portion has attached occlusive material. The method can further include advancing the first catheter over the second catheter while anchoring the distal end of the second catheter portion onto the occlusion via the aspiration pressure. The method can further include positioning the distal end of the first catheter portion near the proximal face of the occlusion. The method can further include withdrawing the second catheter into the lumen of the first catheter; and automatically applying aspiration pressure through the lumen of the first catheter portion upon withdrawal of the second catheter into the lumen. The aspiration pressure applied through the lumen of the first catheter portion and the lumen of the second catheter portion can be applied from a single source of aspiration. The distal end of the second catheter portion can be attached occlusive material. 
     The method can further include withdrawing the second catheter from the lumen of the first catheter while the first catheter maintains the aspiration pressure through the lumen of the first catheter portion. The method can further include advancing a guide sheath from an access location, wherein the guide sheath comprises a tubular sheath body having a central lumen, a proximal end, a distal opening, and a connector operably connected with the proximal end of the sheath body. Advancing the first assembled coaxial catheter system can include advancing the first assembled coaxial catheter system through the guide sheath. The first catheter portion can have an outer diameter configured to seal with the central lumen of the guide sheath upon application of the aspiration pressure. The second catheter portion can have an outer diameter configured to seal with the lumen of the first catheter upon application of the aspiration pressure. An outer surface of the second catheter portion can seal with an inner surface of the first catheter portion forming a contiguous lumen between the distal opening of the second catheter portion to the proximal end of the guide sheath. The connector can include a single or two-headed rotating hemostatic valve. Both the first and second assembled coaxial catheter systems can be advanced through the connector. The method can further include advancing the guide sheath comprises advancing the distal opening of the guide sheath to a location in a distal internal carotid artery (ICA). The second catheter can have an inner diameter that is between 0.054″ and 0.070″, the first catheter has an inner diameter between 0.072″ and 0.088″, and the guide sheath is between 6 Fr to 8 Fr. The method can further include advancing a guidewire across the occlusion. The occlusion need not be penetrated during the method. The first assembled coaxial catheter system can further include a guidewire. When assembled, the guidewire can be positioned within a lumen of the flexible, elongate body of the first delivery element and the first delivery element can be positioned within the lumen of the first catheter portion such that the tapered distal tip portion extends distal to the distal end of the first catheter portion and the guidewire extends distal to the tapered distal tip portion. An outer surface of the second catheter portion can seal with an inner surface of the first catheter portion forming a contiguous lumen between the distal opening of the second catheter portion and the proximal opening of the first catheter portion. 
     In an interrelated aspect, described is a method of performing a medical procedure in a cerebral vessel of a patient. The method includes advancing a first assembled coaxial catheter system to a location near a proximal face of an occlusion within a cerebral blood vessel. The first assembled coaxial catheter system includes a first catheter and a first delivery element. The first catheter includes a first catheter portion having a lumen, a proximal opening into the lumen, a distal opening from the lumen, and a distal end; and a first proximal extension coupled to and extending proximally from the first catheter portion, the first proximal extension being less flexible than the first catheter portion. The first delivery element includes a flexible, elongate body and a soft, tapered distal tip portion, at least a portion of the elongate body positioned within the lumen of the first catheter portion and the tapered distal tip portion extending distal to the distal end of the first catheter portion. The first assembled coaxial system of devices is advanced together after the distal end of the first catheter portion is distal to the petrous portion of the internal carotid artery. The method includes withdrawing the first delivery element proximally from the lumen of the first catheter portion; applying aspiration pressure through the lumen of the first catheter portion; anchoring the distal end of the first catheter portion onto the occlusion via the aspiration pressure; applying a proximally-directed force on the first catheter to reduce slack in the first catheter relative to surrounding anatomy while the distal end of the first catheter remains anchored onto the occlusion; and advancing a second catheter over the first catheter while anchoring the distal end of the first catheter portion onto the occlusion via the aspiration pressure. The second catheter includes a second catheter portion having a lumen, a proximal opening into the lumen, a distal opening from the lumen, and a distal end; and a second proximal extension coupled to and extending proximally from the second catheter portion. The second proximal extension is less flexible than the second catheter portion. 
     The method can further include withdrawing the first catheter from the cerebral blood vessel. The distal end of the first catheter portion may have attached occlusive material. The method can further include positioning the distal end of the second catheter portion near the proximal face of the occlusion. The method can further include withdrawing the first catheter into the lumen of the second catheter; and automatically applying aspiration pressure through the lumen of the second catheter portion upon withdrawal of the first catheter into the lumen. The aspiration pressure can be applied through the lumen of the first catheter portion and the lumen of the second catheter portion is applied from a single source of aspiration. The distal end of the first catheter can have attached occlusive material. The method can further include withdrawing the first catheter from the lumen of the second catheter while the second catheter maintains the aspiration pressure through the lumen of the second catheter portion. The method can further include advancing a guide sheath from an access location. The guide sheath can include a tubular sheath body having a central lumen, a proximal end, a distal opening, and a connector operably connected with the proximal end of the sheath body. The second catheter portion can include an outer diameter configured to seal with the central lumen of the guide sheath upon application of the aspiration pressure. The first catheter portion can have an outer diameter configured to seal with the lumen of the second catheter upon application of the aspiration pressure. An outer surface of the first catheter portion can seal with an inner surface of the second catheter portion forming a contiguous lumen between the distal opening of the first catheter portion to the proximal end of the guide sheath. The connector can include a single or two-headed rotating hemostatic valve. Both the first assembled coaxial catheter system and the second catheter can be advanced through the connector. 
     The method can include advancing the guide sheath comprises advancing the distal opening of the guide sheath to a location in a distal internal carotid artery (ICA). The first catheter can have an inner diameter between 0.054″ and 0.070″. The second catheter can have an inner diameter between 0.072″ and 0.088″. The guide sheath can be between 6 Fr to 8 Fr. The method can further include advancing a guidewire across the occlusion. The occlusion need not be penetrated during the method. An inner surface of the second catheter portion can seal with an outer surface of the first catheter portion forming a contiguous aspiration lumen between the distal opening of the first catheter portion and the proximal opening of the second catheter portion. 
     In an interrelated aspect, disclosed is a system of devices for performing a medical procedure in a cerebral vessel of a patient including a first catheter and a second catheter. The first catheter includes a first catheter portion having a lumen, a proximal opening into the lumen, a distal opening from the lumen, and a distal end; and a first proximal extension coupled to and extending proximally from the first catheter portion, the first proximal extension being less flexible than the first catheter portion. The second catheter is configured to be coaxially disposed within the lumen of the first catheter portion. The second catheter includes a second catheter portion having a lumen, a proximal opening into the lumen, a distal opening from the lumen, and a distal end; and a second proximal extension coupled to and extending proximally from the second catheter portion, the second proximal extension being less flexible than the second catheter portion. The system includes a guide sheath having a tubular sheath body with a central lumen, a proximal end, a distal opening, and a connector operably connected with the proximal end of the sheath body. A single, shared vacuum source is coupled to the connector of the guide sheath and configured to apply aspiration pressure through the central lumen of the guide sheath, the lumen of the first catheter portion, and the lumen of the second catheter portion. An outer surface of the second catheter portion can seal with an inner surface of the first catheter portion forming a contiguous lumen between the distal opening of the first catheter portion and the proximal opening of the second catheter portion. 
     In an interrelated aspect, disclosed is a method of performing a medical procedure in a cerebral vessel of a patient. The method includes advancing a first catheter towards an occlusion within a cerebral blood vessel. The first catheter includes a first catheter portion having a lumen, a proximal opening into the lumen, a distal opening from the lumen, and a distal end; and a first proximal extension coupled to the first catheter portion near the proximal opening, the first proximal extension being less flexible than the first catheter portion. The method includes advancing a second catheter through the lumen of the first catheter portion, out the distal opening from the lumen, and to a location near a proximal face of the occlusion within the cerebral blood vessel. The second catheter includes a second catheter portion having a lumen, a proximal opening into the lumen, a distal opening from the lumen, and a distal end; and a second proximal extension coupled to the second catheter portion near the proximal opening, the second proximal extension being less flexible than the second catheter portion. The method includes forming a seal between an outer diameter of the second catheter portion and an inner diameter of the first catheter portion; and applying aspiration pressure through at least one of the lumen of the second catheter portion, the lumen of the first catheter portion, or a contiguous aspiration lumen formed by the lumens of the first and second catheter portions. The contiguous aspiration lumen extends from the distal end of the second catheter portion towards the proximal opening of the first catheter portion. The method can further include anchoring the distal end of the second catheter portion onto the occlusion via the aspiration pressure. The method can further include applying a proximally-directed force on the second catheter to reduce slack in the second catheter relative to surrounding anatomy while the distal end of the second catheter portion remains anchored onto the occlusion. 
     In an interrelated aspect, provided is a method of performing a medical procedure in a cerebral vessel of a patient including advancing a catheter system towards an embolus within a cerebral blood vessel. The catheter system includes a first catheter having a first catheter portion having a lumen, a proximal opening into the lumen, a distal opening from the lumen, and a distal end and a first proximal extension coupled to the first catheter portion near the proximal opening, the first proximal extension being less flexible than the first catheter portion. The catheter system includes a second catheter having a second catheter portion having a lumen, a proximal opening into the lumen, a distal opening from the lumen, and a distal end and a second proximal extension coupled to the second catheter portion near the proximal opening, the second proximal extension being less flexible than the second catheter portion. The catheter system includes a guide sheath having a working lumen. An outer diameter of the second catheter portion and an inner diameter of the first catheter portion are configured to provide a first seal. The method further includes applying aspiration pressure through the lumen of the second catheter portion for a time sufficient to anchor the embolus to the distal end of the second catheter portion and withdrawing the second catheter with respect to the first catheter. Withdrawal of the second catheter into the first catheter automatically increases the aspiration pressure at the distal end of the first catheter portion such that the embolus is captured at least partially within the lumen of the first catheter portion. 
     The method can further include anchoring the distal end of the second catheter portion onto the embolus via the aspiration pressure. Withdrawing the second catheter with respect to the first catheter further can include applying a proximally-directed force on the second catheter to reduce slack in the second catheter relative to surrounding anatomy while the distal end of the second catheter portion remains anchored onto the embolus. The catheter system can further include a single aspiration source connected to the guide sheath. The single aspiration source can provide the aspiration pressure within the second catheter that automatically increases at the distal end of the first catheter portion upon withdrawal of the second catheter into the first catheter. The aspiration pressure can be applied through the lumen of the first catheter portion and the lumen of the second catheter portion from a single source of aspiration. An outer surface of the second catheter portion can seal with an inner surface of the first catheter portion forming a contiguous lumen between the distal opening of the second catheter portion to a proximal end of the guide sheath. The system can include a connector having a single or two-headed rotating hemostatic valve, wherein both the first and second catheters are advanced through the connector. The method can further include advancing the catheter system comprises advancing a distal opening of the guide sheath to a location in an internal carotid artery (ICA). 
     The second catheter can have an inner diameter that is between 0.054″ and 0.070″, the first catheter has an inner diameter between 0.072″ and 0.088″, and the guide sheath is between 6 Fr to 8 Fr. The embolus may not penetrated by a guidewire or a microcatheter during the method. The method can further include a third catheter having a third catheter portion having a lumen, a proximal opening into the lumen, a distal opening from the lumen, and a distal end. The third catheter also can have a third proximal extension coupled to the third catheter portion new the proximal opening of the third catheter. The third catheter portion can have an outer diameter sized to extend through the lumen of the second catheter portion. The second catheter portion can have an outer diameter sized to extend through the lumen of the third catheter portion. The third catheter portion can have an inner diameter that is about 0.052″ to about 0.055″, the second catheter portion can have an inner diameter that is about 0.070″ to about 0.073″, and the first catheter portion can have an inner diameter that is about 0.087″ to about 0.089″. 
     The first catheter portion can have an outer diameter that is larger than an outer diameter of the first proximal extension. The second catheter portion can have an outer diameter that is larger than an outer diameter of the second proximal extension. The first proximal extension can be a ribbon, spine or hypotube. The first proximal extension can be solid. The step of withdrawing the second catheter with respect to the first catheter can increase a minimum gap between the second catheter outer diameter and the first catheter inner diameter from less than 0.005 inches to greater than 0.005 inches. The outer diameter of the second catheter portion can form a proximal sealing zone and can be greater than an outer diameter of a remainder of the second catheter portion. The proximal sealing zone can have a length of less than 15 mm. The first catheter portion and the second catheter portion each can have a length and the proximal sealing zone can have a location, the lengths and the location can be arranged such that the first seal automatically at least partially releases as the distal end of the second catheter portion passes into the distal end of the first catheter portion. Withdrawal of the second catheter into the first catheter can automatically at least partially releases the first seal. The automatic at least partial release of the first seal can occur when the distal ends of the first and second catheters are substantially aligned. The automatic at least partial release of the first seal can occur when the distal ends of the first and second catheters are within 5 mm of each other. The automatic at least partial release of the first seal can occur when the distal end of the second catheter has been withdrawn into the first catheter at least 5 mm and no more than 20 mm proximal to the distal end of the first catheter. The automatic at least partial release of the first seal can occur due to the first seal moving from the lumen of the first catheter portion out of the proximal opening of the lumen during withdrawal of the second catheter. 
     In an interrelated aspect, provided is a method of performing a medical procedure in a cerebral vessel of a patient that includes advancing a catheter system towards an embolus within a cerebral blood vessel. The catheter system includes a first catheter having a first catheter portion having a lumen, a proximal opening into the lumen, a distal opening from the lumen, and a distal end and a first proximal extension coupled to the first catheter portion near the proximal opening, the first proximal extension being less flexible than the first catheter portion. The catheter system includes a second catheter having a second catheter portion having a lumen, a proximal opening into the lumen, a distal opening from the lumen, and a distal end and a second proximal extension coupled to the second catheter portion near the proximal opening, the second proximal extension being less flexible than the second catheter portion. The catheter system includes a guide sheath having a working lumen. An outer diameter of the second catheter portion and an inner diameter of the first catheter portion are configured to provide a first seal. The method includes capturing the embolus with the distal end of the second catheter portion by applying aspiration pressure through the lumen of the second catheter portion. The method includes withdrawing the second catheter with respect to the first catheter. Withdrawal of the second catheter into the first catheter automatically transfers the embolus captured by the distal end of the second catheter portion to being captured by the distal end of the first catheter portion due to an increase in the aspiration pressure through the distal end of the first catheter portion. The lumen of the second catheter portion can fluidly communicate with the lumen of the first catheter portion that fluidly communicates with the working lumen of the guide sheath forming a contiguous lumen formed of three sections of increasingly larger dimensions towards a proximal end of the catheter system forming a second seal between an outer diameter of the first catheter portion and the guide sheath. 
     In an interrelated aspect, provided is a method of performing a medical procedure in a cerebral vessel of a patient including advancing a catheter system towards an embolus within a cerebral blood vessel. The catheter system includes a first catheter having a first catheter portion having a lumen, a proximal opening into the lumen, a distal opening from the lumen, a distal end, and a length between the proximal opening and the distal end, the first catheter having a first proximal extension coupled to the first catheter portion near the proximal opening, the first proximal extension being less flexible than the first catheter portion. The catheter system includes a second catheter having a second catheter portion having a lumen, a proximal opening into the lumen, a distal opening from the lumen, a distal end, and a length between the proximal opening and the distal end, the second catheter having a second proximal extension coupled to the second catheter portion near the proximal opening, the second proximal extension being less flexible than the second catheter portion. The catheter system includes a guide sheath having a working lumen. An outer diameter of the second catheter portion and an inner diameter of the first catheter portion are configured to provide a seal having a seal length and a seal location. The method includes applying aspiration pressure through the lumen of the second catheter portion to anchor the embolus to the distal end of the second catheter portion; and withdrawing the second catheter with respect to the first catheter. The lengths of the first and second catheter portions, the seal length, and the seal location are arranged to automatically at least partially release the seal as the distal end of the second catheter portion passes into the distal end of the first catheter portion. 
     The seal can be provided by an enlarged outer diameter section of the second catheter portion and the seal length is 2-30 mm. The seal location can be located within 20 mm of the second catheter portion proximal opening. The lengths of the first catheter portion and the second catheter portion can be the same or can be different by no more than 5 cm. The seal can automatically at least partially release upon exit of a proximal end length of the second catheter portion through the proximal opening of the first catheter portion. The proximal end length of the second catheter portion can be the same as the seal length or less than the seal length. 
     In an interrelated aspect, provided is a system for performing a medical procedure in a patient. The system includes an outer catheter having an outer catheter portion having a lumen, a proximal opening into the lumen, a distal opening from the lumen, a distal end, and a length between the proximal opening and the distal end; and an outer catheter proximal extension coupled to the outer catheter portion near the proximal opening, the outer catheter proximal extension being less flexible than the outer catheter portion. The system includes an inner catheter having an inner catheter portion having a lumen, a proximal opening into the lumen, a distal opening from the lumen, a distal end, and a length between the proximal opening and the distal end; and an inner catheter proximal extension coupled to the inner catheter portion near the proximal opening, the inner catheter proximal extension being less flexible than the inner catheter portion. When the inner catheter portion is assembled within the outer catheter portion, an outer diameter of the inner catheter portion and an inner diameter of the outer catheter portion are configured to provide a seal having a seal length and a seal location. The lengths of the outer and inner catheter portions, the seal length, and the seal location are arranged to automatically at least partially release the seal as the distal end of the inner catheter portion is withdrawn into the distal end of the outer catheter portion. 
     The seal can be provided by an enlarged outer diameter section of the inner catheter portion and the seal length is 2-30 mm. The seal location can be located within 20 mm of the inner catheter portion proximal opening. The lengths of the outer catheter portion and the inner catheter portion can be the same or are different by no more than 5 cm. The seal can automatically at least partially release upon exit of a proximal end length of the inner catheter portion through the proximal opening of the outer catheter portion. The proximal end length of the inner catheter portion can be the same as or less than the seal length. 
     The system can further include a third catheter having a third catheter portion having a lumen, a proximal opening into the lumen, a distal opening from the lumen, and a distal end. The third catheter also can have a third proximal extension coupled to the third catheter portion new the proximal opening of the third catheter. The third catheter portion can have an outer diameter sized to extend through the lumen of the inner catheter portion. The inner catheter portion can have an outer diameter sized to extend through the lumen of the outer catheter portion. The third catheter portion can have an inner diameter that is about 0.052″ to about 0.055″, the inner catheter portion can have an inner diameter that is about 0.070″ to about 0.073″, and the outer catheter portion can have an inner diameter that is about 0.087″ to about 0.089″. 
     In some variations, one or more of the following can optionally be included in any feasible combination in the above methods, apparatus, devices, and system. More details of the methods, apparatus, devices, and systems are set forth in the accompanying drawings and the description below. Other features and advantages will be apparent from the description and drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       These and other aspects will now be described in detail with reference to the following drawings. Generally speaking the figures are not to scale in absolute terms or comparatively, but are intended to be illustrative. Also, relative placement of features and elements may be modified for the purpose of illustrative clarity. 
         FIGS. 1A-1B  illustrate the course of the terminal internal carotid artery through to the cerebral vasculature; 
         FIG. 1C  illustrates the aortic arch including the take-offs of the brachiocephalic BT, left common carotid LCC, and left subclavian arteries LSA from the aortic arch AA; 
         FIG. 2A  is an exploded view of an implementation of an aspiration catheter system; 
         FIG. 2B  is an assembled view of the aspiration catheter system of  FIG. 2A ; 
         FIG. 2C  is a detail view of  FIG. 2A  taken at circle C-C; 
         FIG. 2D  illustrates an implementation of an arterial access device having a distal occlusion balloon; 
         FIG. 3  is a side view of an implementation of a spined distal access catheter; 
         FIG. 4A  is a cross-sectional view of first implementation of a proximal control element of a spined distal access catheter; 
         FIG. 4B  is a cross-sectional view of another implementation of a proximal control element of a spined distal access catheter; 
         FIG. 4C  is a cross-sectional view of the proximal control element of  FIG. 4A  within a working lumen of an access sheath; 
         FIG. 4D  is a cross-sectional view of the proximal control element of  FIG. 4B  within a working lumen of an access sheath having a catheter advancement element extending therethrough; 
         FIG. 4E  is a cross-sectional, schematic view comparing the surface area of the proximal control element of  FIG. 4A  and the proximal control element of  FIG. 4B  within the working lumen of an access sheath of  FIG. 4D ; 
         FIGS. 4F-4G  are cross-sectional, schematic views comparing trapezoid- and D-shaped proximal extensions, respectively, relative to a working lumen of an access sheath; 
         FIG. 5A  is a side elevational view of an implementation of a spined distal access catheter; 
         FIG. 5B  is a top plan view of the spined distal access catheter of  FIG. 5A ; 
         FIG. 5C  is a cross-sectional view of the spined distal access catheter taken along line C-C of  FIG. 5B ; 
         FIG. 5D  is a cross-sectional view of the spined distal access catheter taken along line D-D of  FIG. 5B ; 
         FIGS. 5E-5F  are partial perspective views of the spined distal access catheter of  FIG. 5A ; 
         FIG. 6A  is a side elevational view of an implementation of a spined distal access catheter; 
         FIG. 6B  is a top plan view of the spined distal access catheter of  FIG. 6A ; 
         FIG. 6C  is a cross-sectional view of the spined distal access catheter taken along line C-C of  FIG. 6B ; 
         FIG. 6D  is a cross-sectional view of the spined distal access catheter taken along line D-D of  FIG. 6B ; 
         FIGS. 6E-6F  are partial perspective views of the spined distal access catheter of  FIG. 6A ; 
         FIG. 7A  is a side view of an implementation of a catheter advancement element; 
         FIG. 7B  is a cross-sectional view of the catheter advancement element of  FIG. 7A ; 
         FIG. 7C  is a detail view of  FIG. 7B  taken along circle C-C; 
         FIG. 7D  is a side view of another implementation of a catheter advancement element; 
         FIG. 7E  is cross-sectional view of an implementation of a proximal portion the catheter advancement element of  FIG. 7D ; 
         FIGS. 7F-7J  are various views of an implementation of a proximal hub for coupling to the proximal portion shown in  FIG. 7E ; 
         FIG. 8A  is a side view of an implementation of a catheter; 
         FIG. 8B  is a schematic cut-away view of the distal end region of the catheter of  FIG. 8A ; 
         FIG. 8C  is a schematic cross-sectional view of the distal end region of the catheter of  FIG. 8A ; 
         FIGS. 9A-9C  are various views of a proximal extension connector; 
         FIG. 10A  is a schematic cross-sectional view of an implementation of a catheter advancement element; 
         FIG. 10B  is a schematic cross-sectional view of a distal end region of the catheter advancement element of  FIG. 10A ; 
         FIG. 10C  is a schematic cross-sectional view of a middle region of the catheter advancement element of  FIG. 10A ; 
         FIG. 11  is a schematic of an implementation of a catheter aligned with an implementation of a catheter advancement element illustrating staggered material transitions; 
         FIG. 12  is a schematic of an implementation of a bending force testing system; 
         FIG. 13A  is a schematic of a distal end region of a catheter advancement element extending through a catheter and points tested for bending force; 
         FIG. 13B  illustrates bending force in Newtons (N) along a length of a catheter system including a catheter and a catheter advancement element in the advancement configuration (hashed line), the catheter advancement element alone (hash-dot-hash line), and the catheter alone (solid line); 
         FIG. 14A  is a graph of the bending forces along a length of a catheter system formed of a catheter advancement element configured to extend through a catheter having an inner diameter of 0.054″; 
         FIG. 14B  is a graph of the bending forces along a length of a catheter system formed of a catheter advancement element configured to extend through a catheter having an inner diameter of 0.070″; 
         FIG. 14C  is a graph of the bending forces along a length of a catheter system formed of a catheter advancement element configured to extend through a catheter having an inner diameter of 0.070″; 
         FIG. 14D  is a graph of the bending forces along a length of a catheter system formed of a catheter advancement element configured to extend through a catheter having an inner diameter of 0.088″; 
         FIG. 14E  is a graph of the bending forces along a length of another catheter system; 
         FIG. 15  illustrates an implementation of a nested catheter system; 
         FIG. 16  illustrates an implementation of a method of aspiration thrombectomy. 
     
    
    
     It should be appreciated that the drawings are for example only and are not meant to be to scale. It is to be understood that devices described herein may include features not necessarily depicted in each figure. 
     DETAILED DESCRIPTION 
     Navigating the carotid anatomy in order to treat various neurovascular pathologies at the level of the cerebral arteries, such as acute ischemic stroke (AIS), requires catheter systems having superior flexibility and deliverability. The internal carotid artery (ICA) arises from the bifurcation of the common carotid artery (CCA) at the level of the intervertebral disc between C3 and C4 vertebrae. As shown in  FIG. 1A , the course of the ICA is divided into four parts—cervical Cr, petrous Pt, cavernous Cv and cerebral Cb parts. In the anterior circulation, the consistent tortuous terminal carotid is locked into its position by bony elements. The cervical carotid Cr enters the petrous bone and is locked into a set of turns as it is encased in bone. The cavernous carotid is an artery that passes through a venous bed, the cavernous sinus, and while flexible, is locked as it exits the cavernous sinus by another bony element, which surrounds and fixes the entry into the cranial cavity. Because of these bony points of fixation, the petrous and cavernous carotid (Pt and Cv) and above are relatively consistent in their tortuosity. The carotid siphon CS is an S-shaped part of the terminal ICA. The carotid siphon CS begins at the posterior bend of the cavernous ICA and ends at the ICA bifurcation into the anterior cerebral artery ACA and middle cerebral artery MCA. The ophthalmic artery arises from the cerebral ICA, which represents a common point of catheter hang-up in accessing the anterior circulation. The MCA is initially defined by a single M1 segment and then further bifurcates in two or three M2 segments and then further arborizes to create M3 segments. These points of catheter hang-up can significantly increase the amount of time needed to restore blood perfusion to the brain, which in the treatment of AIS is a disadvantage with severe consequences. 
     With advancing age, the large vessels often enlarge and lengthen. Fixed proximally and distally, the cervical internal carotid artery often becomes tortuous with age. The common carotid artery CCA is relatively fixed in the thoracic cavity as it exits into the cervical area by the clavicle. The external and internal carotid arteries ECA, ICA are not fixed relative to the common carotid artery CCA, and thus they develop tortuosity with advancing age with lengthening of the entire carotid system. This can cause them to elongate and develop kinks and tortuosity or, in worst case, a complete loop or so-called “cervical loop”. If catheters used to cross these kinked or curved areas are too stiff or inflexible, these areas can undergo a straightening that can cause the vessel to wrap around or “barbershop pole” causing focused kinking and folding of the vessel. These sorts of extreme tortuosity also can significantly increase the amount of time needed to restore blood perfusion to the brain, particularly in the aging population. In certain circumstances, the twisting of vessels upon themselves or if the untwisted artery is kinked, normal antegrade flow may be reduced to a standstill creating ischemia. Managing the unkinking or unlooping the vessels such as the cervical ICA can also increase the time it takes to perform a procedure. 
     A major drawback of current catheter systems for stroke intervention procedures is the amount of time required to restore blood perfusion to the brain, including the time it takes to access the occlusive site or sites in the cerebral artery and the time it takes to completely remove the occlusion in the artery. Because it is often the case that more than one attempt must be made to completely remove the occlusion, reducing the number of attempts as well as reducing the time required to exchange devices for additional attempts is an important factor in minimizing the overall time. Additionally, each attempt is associated with potential procedural risk due to device advancement in the delicate cerebral vasculature. Another limitation is the need for multiple operators to deliver and effectively manipulate long tri-axial systems with multiple RHVs typically used with conventional guide and distal access catheters. 
     Described herein are catheter systems and methods for treating various neurovascular pathologies, such as acute ischemic stroke (AIS). The systems described herein provide quick and simple single-operator access to distal target anatomy, in particular tortuous anatomy of the cerebral vasculature at a single point of manipulation. The medical methods, devices and systems described herein allow for navigating complex, tortuous anatomy to perform rapid and safe aspiration and removal of cerebral occlusions for the treatment of acute ischemic stroke. The medical methods, devices and systems described herein can also be used to deliver intracranial medical devices, with or without aspiration for the removal of cerebral occlusions in the treatment of acute ischemic stroke. The systems described herein can be particularly useful for the treatment of AIS whether a user intends to perform aspiration alone as a frontline treatment for AIS. Further, the extreme flexibility and deliverability of the distal access catheter systems described herein allow the catheters to take the shape of the tortuous anatomy rather than exert straightening forces that alter the natural vascular architecture. The distal access catheter systems described herein can pass through tortuous loops while maintaining the natural curves of the anatomy therein decreasing the risk of vessel straightening. The distal access catheter systems described herein can thereby create a safe conduit through the neurovasculature maintaining the natural tortuosity of the anatomy for other catheters to traverse (e.g. larger bore aspiration catheters). 
     The devices, systems, and methods of use described herein are related to and can be used in combination and in the alternative with the devices, systems, and methods of use described in U.S. Publication No. 2013/0035628, filed Aug. 3, 2012; U.S. Publication No. 2015/0173782, filed Dec. 19, 2014; and U.S. Publication No. 2016/0220741, filed Feb. 4, 2016. The disclosures of each of these publications are incorporated by reference herein in their entireties. 
     While some implementations are described herein with specific regard to accessing a neurovascular anatomy for application of aspiration, the systems and methods described herein should not be limited to this and may also be applicable to other uses. For example, the catheter systems described herein may be used to deliver working devices to a target vessel of a coronary anatomy or other vasculature anatomy. Where the phrase “distal access catheter” or “aspiration catheter” is used herein that the catheter can be used for aspiration, the delivery of fluids to a treatment site or as a support catheter, or distal access providing a conduit that facilitates and guides the delivery or exchange of other devices such as a guidewire or interventional devices such as stent retrievers. Alternatively, the access systems described herein may also be useful for access to other parts of the body outside the vasculature. Similarly, where the working device is described as being an expandable cerebral treatment device, such as, but not limited to, a stent retriever or a self-expanding stent, it is contemplated that other interventional devices can be delivered using the access systems described herein. 
     Referring now to the drawings,  FIGS. 2A-2B  illustrate a system  100  including devices for accessing and removing a cerebral occlusion to treat acute ischemic stroke. The system  100  can be a single operator system such that each of the components and systems can be delivered and used together by one operator through a single point of manipulation requiring minimal hand movements. As will be described in more detail below, all wire and catheter manipulations can occur at or in close proximity to a single rotating hemostatic valve (RHV)  434  or multi-head RHV or through one or more RHV&#39;s co-located on the same device. The system  100  can include one or more catheter delivery systems  150 , each having a catheter  200  and a catheter advancement element  300 . In some implementations, two catheters nested within one another may be advanced with a single catheter advancement element. A larger-bore catheter can include a smaller-bore catheter positioned within its lumen and a catheter advancement element positioned within the lumen of the smaller-bore catheter forming a catheter delivery system for advancement toward the occlusion. The catheter delivery system  150  is configured to be advanced through an access guide sheath  400 . The catheter  200  is configured to be received through the guide sheath  400  and is designed to have exceptional deliverability. The catheter  200  can be a spined, distal access catheter co-axial with a lumen of the guide sheath  400  thereby providing a step-up in inner diameter within the conduit. The catheter  200  can be delivered using a catheter advancement element  300  inserted through a lumen  223  of the catheter  200 . The system  100  can be a distal access system that can create a variable length from point of entry at the percutaneous arteriotomy (e.g. the femoral artery or other point of entry) to the target control point of the distal catheter. Conventional distal access systems for stroke intervention typically include a long guide sheath or guide catheter placed through a shorter “introducer” sheath (e.g. 11-30 cm in length) at the groin. The long guide sheath is typically positioned in the ICA to support neurovascular interventions including stroke embolectomy (sometimes referred to as “thrombectomy”). For added support, these can be advanced up to the bony terminal petrous and rarely into the cavernous or clinoid or supraclinoid terminal ICA when possible. To reach targets in the M1 or M2 distribution for ADAPT/MAT or Solumbra/SMAT approaches, an additional catheter may be inserted through the long guide catheter. These catheters are typically large-bore aspiration catheters that can be, for example 130 cm in length or longer. As will be described in more detail below, the distal access systems  100  described herein can be shorter, for example, only 115 cm in length when taken as a system as measured from the access point, typically the common femoral artery. Additionally, the single operator can use the systems described herein by inserting them through a single rotating hemostatic valve (RHV)  434  on the guide sheath  400  or more than one RHV co-located in the same device such as a dual-headed RHV. Thus, what was once a two-person procedure can be a one-person procedure. 
     Using current commercially available catheters and guide sheaths requires the physician to properly select the appropriate length of both the guide sheath and the catheter such that the guide sheath can be advanced into the ICA a sufficient distance to provide support for the catheter disposed within the lumen of the guide sheath to reach the M1 or M2. However, as described above, anatomy of each person can vary and vessels may lengthen and/or straighten when a guide sheath and/or catheter are disposed within them. In practice, a physician may find that the length of guide sheath that they selected may be too short and cannot be advanced into the ICA sufficiently to provide support. Conversely, the selected guide sheath may be too long, therefore extending outside the patient too much, such that when the catheter is disposed within the lumen of the guide sheath, the hub of the catheter touches the RHV of the guide sheath before the distal end of the catheter can be placed at the M1 or M2. If this occurs, the physician would need to either replace the guide sheath with a shorter guide sheath or use a longer catheter, if a longer catheter is available. Either option adds significant time to the procedure as well as added costs of opened but un-used products. The catheter  200  eliminates the sizing problem described above. The physician does not need to guess what length of catheter to use. Instead, the physician can advance and retract catheter  200  within the guide sheath to reach the M1 or M2. A portion of the luminal portion  222  can remain within the lumen of the guide sheath. Aspiration can be performed or other cerebral treatment devices can be delivered to the desired location. The catheter advancement element  300  may be first advanced past the ophthalmic take-off, and then the catheter may be advanced over the catheter advancement element  300 . The tapered tip of the catheter advancement element  300  provides a smooth transition to easily pass beyond the ophthalmic take-off without hanging up at the bifurcation of the ophthalmic and carotid arteries. 
     Each of the various components of the various systems will now be described in more detail. 
     Access Guide Sheath 
     Again with respect to  FIGS. 2A-2D , the distal access system  100  can include an access guide sheath  400  having a body  402  through which a working lumen extends from a proximal hemostasis valve  434  coupled to a proximal end region  403  of the body  402  to a distal opening  408  of a distal end region. The working lumen is configured to receive the catheter  200  therethrough such that a distal end of the catheter  200  can extend beyond a distal end of the sheath  400  through the distal opening  408 . The guide sheath  400  can be used to deliver the catheters described herein as well as any of a variety of working devices known in the art. For example, the working devices can be configured to provide thrombotic treatments and can include large-bore catheters, aspiration embolectomy (or thrombectomy), advanced catheters, wires, balloons, retrievable structures such as coil-tipped retrievable stents “stent retriever”. The guide sheath  400  in combination with the catheter  200  can be used to apply distal aspiration as will be described in more detail below. 
     The guide sheath  400  can be any of a variety of commercially available guide sheaths. For example, the guide sheath  400  can have an ID between 0.087″-0.089″ such as the Cook SHUTTLE 6F (Cook Medical, Inc., Bloomington, Ind.), Terumo DESTINATION 6F (Terumo Europe NV), Cordis VISTA BRITE TIP (Cordis Corp., Hialeah, Fla.), and Penumbra NEURON MAX 088 (Penumbra, Inc., Alameda, Calif.), Stryker Infinity (Stryker Neurovascular, Fremont, Calif.) or comparable commercially available guiding sheath. Generally, sheath sizes are described herein using the French (F) scale. For example, where a sheath is described as being 6 French, the inner diameter of that sheath is able to receive a catheter having a 6F outer diameter, which is about 1.98 mm or 0.078″. A catheter may be described herein as having a particular size in French to refer to the compatibility of its inner diameter to receive an outer diameter of another catheter. A catheter may also be described herein as having a particular size in French to refer to its outer diameter being compatible with another catheter having a particular inner diameter. 
     The guide sheath  400  can be a variety of sizes to accept various working devices, such as catheter  200 , and can be accommodated to the operator&#39;s preference. The working lumen of the guide sheath  400  can be sized to receive its respective catheter  200  in a sliding fit. Generally, it is desirable to minimize the overall size of the vessel insertion site by limiting the outer diameter of the guide sheath  400  to under 0.122″. It is also desirable to select corresponding outer and inner diameters to provide a good sliding fit between the catheter  200  and the guide sheath  400 . The working lumen of the guide sheath may have an inner diameter that is at least 0.001″ larger than a maximum outer diameter of any catheter  200  it is intended to receive, particularly if the catheter  200  is to be used for aspiration. The working lumen can have an inner diameter sized to accommodate at least 6 French catheters (1.98 mm or 0.078″), or at least 6.3 French catheters (2.079 mm or 0.082″ OD), or at least 7 French (2.31 mm or 0.091″ OD) catheters or 8 French (2.64 mm or 0.104″ OD) or larger catheters. The inner diameter of the guide sheath  400 , however, may be smaller or larger to be compatible with other catheter sizes. Regardless of the length and inner diameter, the guide sheath  400  is resistant to kinking during distal advancement through the vessels. 
     The aspiration catheters described herein can have an ID of between 0.054″ to 0.088″. If the catheter  200  has a 0.088″ inner diameter and have a maximum outer diameter of between 0.105″ and 0.107″. The guide sheath  400  can, in turn, have a working lumen with an inner diameter that is between 0.106″ and 0.108″. Generally, the difference or clearance between the maximum outer diameter of the catheter  200  and the inner diameter of the guide sheath  400  is less than about 0.002″, for example between 0.001″ up to 0.002″. The region of low clearance between the maximum outer diameter of the catheter  200  and the inner diameter of the guide sheath  400  can be limited to a localized region. Meaning, the low clearance fit between the two can extend only a fraction of a cylindrical length of the catheter  200  and the sheath  400 . Thus, the OD-ID difference between the catheter  200  and the guide sheath  400  can be greater than or equal to 0.002″ along a first cylindrical length of where the two devices overlap during use and below 0.002″ along a different cylindrical length of the overlap, thereby providing a localized region of low clearance within the overlap. This allows for a convenient relative slidability and sufficient sealing when placed under aspiration pressure as will be described in more detail below. For example, a distal region of the guide sheath  400  can have a first inner diameter at a distal end region and a second, different inner diameter at a proximal end region such that the low clearance of the sliding fit with the catheter  200  varies along its length. In some implementations, the catheter  200  has a first outer diameter at a distal end region and a second, larger outer diameter at a proximal end region. The second, larger outer diameter can be less than 0.002″ the inner diameter of the sheath  400  and the first outer diameter greater than 0.002″ the inner diameter of the sheath  400 . The provides a tighter overall fit between the guide sheath  400  and the proximal end region of the catheter  200  at the location of this second, larger outer diameter. 
     Again, with respect to  FIGS. 2A-2D , the sheath body  402  can extend from a proximal furcation or rotating hemostatic valve (RHV)  434  at a proximal end region  403  to a tip  406  at a distal end of the body  402 . The proximal RHV  434  may include one or more lumens molded into a connector body to connect to the working lumen of the body  402  of the guide sheath  400 . The working lumen can receive the catheter  200  and/or any of a variety of working devices for delivery to a target anatomy. The RHV  434  can be constructed of thick-walled polymer tubing or reinforced polymer tubing. The RHV  434  allows for the introduction of devices through the guide sheath  400  into the vasculature, while preventing or minimizing blood loss and preventing air introduction into the guide sheath  400 . The RHV  434  can be integral to the guide sheath  400  or the guide sheath  400  can terminate on a proximal end in a female Luer adaptor to which a separate hemostasis valve component, such as a passive seal valve, a Tuohy-Borst valve or RHV may be attached. The RHV  434  can have an adjustable opening that is open large enough to allow removal of devices that have adherent clot on the tip without causing the clot to dislodge at the RHV  434  during removal. Alternately, the RHV  434  can be removable such as when a device is being removed from the sheath  400  to prevent clot dislodgement at the RHV  434 . The RHV  434  can be a dual RHV or a multi-head RHV. 
     The RHV  434  can form a Y-connector on the proximal end  403  of the sheath  400  such that the first port of the RHV  434  can be used for insertion of a working catheter into the working lumen of the sheath  400  and a second port into arm  412  can be used for another purpose. For example, a syringe or other device can be connected at arm  412  via a connector  432  to deliver a forward drip, a flush line for contrast or saline injections through the body  402  toward the tip  406  and into the target anatomy. Arm  412  can also connect to a vacuum source  505  (see  FIG. 2B ). The vacuum source  505  can be an active source of aspiration such as an aspiration pump, a regular or locking syringe, a hand-held aspirator, hospital suction, or the like, configured to draw suction through the working lumen. In an embodiment, the vacuum source  505  is a locking syringe (for example a VacLok Syringe) attached to a flow controller. The user can pull the plunger on the syringe back into a locked position while the connection to the flow line is closed prior to an embolectomy step of the procedure. During the procedure when the distal tip of the catheter is near or at the face of the occlusion, the user may open the connection to the aspiration syringe. This allows for a maximum communication of aspiration force being applied through the working lumen of the sheath  400  and any catheter extending through the sheath  400  that in turn is in communication with the vessel at its distal end. A single user at the single, shared source can apply the aspiration in a rapid fashion. In another implementation, the arm  412  can be connected to a vacuum source  505  that is a pump configured to apply an aspiration pressure through the working lumen of the guide sheath  400 . The single, shared source of aspiration is sufficient to draw aspiration through the entire system  100 , even when multiple aspiration catheters  200  are nested within one another through the working lumen of the guide sheath  400 . The arm  412  can also allow the guide sheath  400  to be flushed with saline or radiopaque contrast during a procedure. The working lumen can extend from a distal end to a working proximal port of the proximal end region  403  of the sheath body  402 . 
     The vacuum source  505  can increase in aspiration level when the flow rate is slow and decrease when the flow rate is increased. In this manner, the force is greatest when the catheter is clogged or partially clogged, but decreases to a minimal level when there is free flow to ensure protection from distal emboli but limit the volume of aspirated blood. In this manner, the system optimizes the embolus aspiration while limiting the amount of blood aspirated. Alternately, the vacuum source  505  can include a vacuum gauge. When the flow in the catheter  200  is blocked or restricted the pump creates a higher level of vacuum. In this example, the aspiration force may be configured to rise when higher vacuum is detected. Alternatively, the vacuum gauge may be incorporated into the RHV or the Luer or proximal end of the guide sheath  400 . Use of the term “embolus” is not intended to be limiting and may be referred to herein as a “clot,” a “thrombus,” “occlusion” and the like. 
     The embolus may be captured by the catheter such that at least a portion of the embolus is contained within the lumen of the catheter while another portion of the embolus remains outside the lumen of the catheter. Capture of the embolus where a portion of the embolus remains outside the catheter lumen can be referred to herein as “corked” or “corking” the catheter and can also be referred to herein as the embolus being “anchored” or “captured” by the catheter. Generally, a corked catheter is one where full evacuation of the embolus into the proximal canister is not possible and instead the catheter is withdrawn carrying the corked or anchored or captured embolus with it. The corked embolus significantly limits the flow through the corked catheter and the catheter has sufficient grasp or force on the catheter to move the embolus within the vessel during withdrawal of the catheter. The embolus may be captured by the catheter such that a majority of the embolus is contained within the catheter lumen while a small portion or no portion of the embolus remains outside the catheter lumen. Capture of the embolus where a majority of the embolus is contained within the lumen can be referred to herein as being “engulfed” by the catheter. An embolus that is engulfed in the catheter lumen may still progress towards the proximal canister under aspiration pressure or the engulfed embolus may move only minimally within the catheter lumen and ultimately a surgeon withdraw the catheter in order to remove the embolus from the patient. 
     The length of the catheter body  402  is configured to allow the distal tip  406  of the body  402  to be positioned as far distal in the internal carotid artery (ICA), for example, from a transfemoral approach, with additional length providing for adjustments if needed. In some implementations (e.g. femoral or radial percutaneous access), the length of the body  402  can be in the range of 80 to 90 cm or can be longer, for example, up to about 100 cm or up to about 105 cm. In implementations, the body  402  length is suitable for a transcarotid approach to the bifurcation of the carotid artery, in the range of 20-25 cm. In further implementations, the body  402  length is suitable for a percutaneous transcarotid approach to the CCA or proximal ICA, and is in the range of 10-15 cm. The body  402  is configured to assume and navigate the bends of the vasculature without kinking, collapsing, or causing vascular trauma, even, for example, when subjected to high aspiration forces. 
     In some implementations, the system  100  can further include a select tool for advancing the guide sheath  400 . The select tool can have an outer diameter configured to be received within the working lumen of the guide sheath  400  such that a distal end region of the select tool extends a distance distal to the distal end of the guide sheath  400 . The outer diameter of the select tool sufficiently fills the inner diameter of the working lumen of the guide sheath  400  to minimize the lip at the distal opening  408  of the guide sheath  400 . For example, if the working lumen of the guide sheath  400  has an inner diameter that is between about 0.087″ to about 0.113″, the outer diameter of the select tool can be about 0.006″ less than this, or between about 0.081″ to about 0.107″. The brachiocephalic take-off (BT) is typically a very severe turn off the aortic arch AA for a transfemorally-delivered catheter seeking the right-sided cerebral circulation (shown in  FIG. 1C ). A catheter traverses from the femoral artery through the iliac circulation into the descending aorta DA. The catheter turns as it approaches the aortic arch AA and reaches across the take-off of other great vessels to reach the brachiocephalic take-off (BT), which is the furthest “reach” of the great vessels of the aortic arch AA.  FIG. 1C  shows the substantial and obligatory S-turn created by that anatomy. A catheter must traverse this S-turn along a path of insertion from a femoral artery insertion location in order to reach the internal carotid artery (ICA). The left ICA often takes off from the brachiocephalic and thus, has a similar challenge and can create an even tighter S-turn. Should the left ICA have a typical take-off between the brachiocephalic BT and the left subclavian artery LSA take-off, then the reach may be less severe, but an S-turn still develops of lesser severity. The distal end region of the select tool can be tapered and/or shaped to provide support and guidance to advance the sheath  400  around this turn into the ICA. In some implementations, the select tool can have a Bernstein Select-style or a Simmons-style reverse curve catheter tip as is known in the art. 
     The tip  406  of the guide sheath  400  can have a same or similar outer diameter as a section of the body  402  leading up to the distal end. Accordingly, the tip  406  may have a distal face orthogonal to a longitudinal axis passing through the body  402  and the distal face may have an outer diameter substantially equal to a cross-sectional outer dimension of the body  402 . In an implementation, the tip  406  includes a chamfer, fillet, or taper, making the distal face diameter slightly less than the cross-sectional dimension of the body  402 . In a further implementation, the tip  406  may be an elongated tubular portion extending distal to a region of the body  402  having a uniform outer diameter such that the elongated tubular portion has a reduced diameter compared to the uniform outer diameter of the body  402 . Thus, the tip  406  can be elongated or can be more bluntly shaped. Accordingly, the tip  406  may be configured to smoothly track through a vasculature and/or to dilate vascular restrictions as it tracks through the vasculature. The working lumen may have a distal end forming a distal opening  408 . 
     The guide sheath  400  may include a tip  406  that tapers from a section of the body  402  leading up to the distal end. That is, an outer surface of the body  402  may have a diameter that reduces from a larger dimension to a smaller dimension at a distal end. For example, the tip  406  can taper from an outer diameter of approximately 0.114″ to about 0.035″ or from about 0.110″ to about 0.035″ or from about 0.106″ to about 0.035″. The angle of the taper of the tip  406  can vary depending on the length of the tapered tip  406 . For example, in some implementations, the tip  406  tapers from 0.110″ to 0.035″ over a length of approximately 50 mm. 
     In an implementation, the guide sheath  400  includes one or more radiopaque markers  411 . The radiopaque markers  411  can be disposed near the distal tip  406 . For example, a pair of radiopaque bands may be swaged, painted, embedded, or otherwise disposed in or on the body  402 . In some implementations, the radiopaque markers  411  include a barium polymer, tungsten polymer blend, tungsten-filled or platinum-filled marker that maintains flexibility of the distal end of the device and improves transition along the length of the guide sheath  400  and its resistance to kinking. In some implementations, the radiopaque marker  411  is a tungsten-loaded PEBAX or polyurethane that is heat welded to the body  402 . The markers  411  are shown in the figures as rings around a circumference of one or more regions of the body  402 . However, the markers  411  can have other shapes or create a variety of patterns that provide orientation to an operator regarding the position of the distal opening  408  within the vessel. Accordingly, an operator may visualize a location of the distal opening  408  under fluoroscopy to confirm that the distal opening  408  is directed toward a target anatomy where a catheter  200  is to be delivered. For example, radiopaque marker(s)  411  allow an operator to rotate the body  402  of the guide sheath  400  at an anatomical access point, e.g., a groin of a patient, such that the distal opening provides access to an ICA by subsequent working device(s), e.g., catheters and wires advanced to the ICA. In some implementations, the radiopaque marker(s)  411  include platinum, gold, tantalum, tungsten or any other substance visible under an x-ray fluoroscope. Any of the various components of the systems described herein can incorporate radiopaque markers. 
     In some implementations, the guide sheath  400  can have performance characteristics similar to other sheaths used in carotid access and AIS procedures in terms of kinkability, radiopacity, column strength, and flexibility. The inner liners can be constructed from a low friction polymer such as PTFE (polytetrafluoroethylene) or FEP (fluorinated ethylene propylene) to provide a smooth surface for the advancement of devices through the inner lumen. An outer jacket material can provide mechanical integrity to the inner liners and can be constructed from materials such as PEBAX, thermoplastic polyurethane, polyethylene, nylon, or the like. The body  402  can include a hydrophilic coating. A third layer can be incorporated that can provide reinforcement between the inner liner and the outer jacket. The reinforcement layer can prevent flattening or kinking of the inner lumen of the body  402  to allow unimpeded device navigation through bends in the vasculature as well as aspiration or reverse flow. The body  402  can be circumferentially reinforced. The reinforcement layer can be made from metal such as stainless steel, Nitinol, Nitinol braid, helical ribbon, helical wire, cut stainless steel, or the like, or stiff polymer such as PEEK. The reinforcement layer can be a structure such as a coil or braid, or tubing that has been laser-cut or machine-cut to be flexible. In another implementation, the reinforcement layer can be a cut hypotube such as a Nitinol hypotube or cut rigid polymer, or the like. The outer jacket of the body  402  can be formed of increasingly softer materials towards the distal end. The flexibility of the body  402  can vary over its length, with increasing flexibility towards the distal portion of the body  402 . The variability in flexibility may be achieved in various ways. For example, the outer jacket may change in durometer and/or material at various sections. A lower durometer outer jacket material can be used in a distal section of the guide sheath compared to other sections of the guide sheath. Alternately, the wall thickness of the jacket material may be reduced, and/or the density of the reinforcement layer may be varied to increase the flexibility. For example, the pitch of the coil or braid may be stretched out, or the cut pattern in the tubing may be varied to be more flexible. Alternately, the reinforcement structure or the materials may change over the length of the sheath body  402 . In another implementation, there is a transition section between the distal-most flexible section and the proximal section, with one or more sections of varying flexibilities between the distal-most section and the remainder of the sheath body  402 . In this implementation, the distal-most section is about 2 cm to about 5 cm, the transition section is about 2 cm to about 10 cm and the proximal section takes up the remainder of the sheath length. In some implementations, the proximal region of the body  402  can be formed of a material such as Nylon, a region of the body  402  distal to the proximal region of the body  402  can have a material hardness of 72D whereas areas more distal can be increasingly more flexible and formed of materials having a material hardness of 55D, 45D, 35D extending towards the distal tip  406 , which can be formed of a material having a material hardness of 35D, for example. 
     The working lumen of the guide sheath  400  can have different inner diameters configured to receive different outer diameter catheters  200 . In some implementations, the working lumen of a first guide sheath  400  can have an inner diameter sized to receive a 6F catheter and the working lumen of a second guide sheath  400  can have an inner diameter sized to receive an 8F catheter. The guide sheaths  400  can receive catheters having an outer diameter along at least a length that is snug to the inner diameter dimension of the guide sheath  400 . The guide sheath  400  (as well as any of the variety of components used in combination with the sheath  400 ) can be an over-the-wire (OTW) or rapid exchange type device, which will be described in more detail below. 
     The sheath  400  can include a body  402  formed of generally three layers, including a lubricious inner liner, a reinforcement layer, and an outer jacket layer. The reinforcement layer can include a braid to provide good torqueability optionally overlaid by a coil to provide good kink resistance. In sheaths where the reinforcement layer is a braid alone, the polymers of the outer jacket layer can be generally higher durometer and thicker to avoid issues with kinking. The wall thickness of such sheaths that are braid alone with thicker polymer can be about 0.011″. The wall thickness of the sheaths  400  described herein having a braid with a coil overlay provide both torqueability and kink resistance and can have a generally thinner wall, for example, a wall thickness of about 0.0085″. The proximal end outer diameter can thereby be reduced to less than 0.112″, for example, about 0.107″ outer diameter. It is generally beneficial to limit the overall OD of the guide sheath  400  such that the entry wound into the patient (e.g. at the femoral artery) can be kept to a minimum size. Thus, the sheath  400  is a high-performance sheath  400  that has good torque and kink resistance with a thinner wall providing an overall lower profile to the system. The thinner wall and lower profile allows for a smaller insertion hole through the vessel without affecting overall lumen size. In some implementations, the wall thickness of the guide sheath  400  can slowly step down to be thinner towards a distal end of the sheath compared to a proximal end. 
     The system can include localized points of low clearance between the guide sheath  400  and the catheter  200  extending through it. The localized points of low clearance can provide localized sealing between the structures. In some implementations, the localized sealing can be near the distal end region of the guide sheath  400  and in others, the localized sealing can be a distance away from the distal end of the guide sheath  400 . The catheter  200  can have an increase in OD near a proximal end region creating a cylindrical region of the catheter that forms a snug fit (e.g. less than about 0.002″ clearance) with the ID of the guide sheath  400 . The length of this low clearance sealing region can vary and depend on the overall clearance between the ID and OD. Greater differences in ID/OD (i.e. higher clearance) can provide sufficient sealing at aspirational pressures by increasing the length of the cylindrical sealing region. Smaller differences in ID/OD (i.e. lower clearance) can provide sufficient sealing at aspirational pressures while having a shorter cylindrical length. In other words, a shorter sealing zone may have a closer fit or lower clearance whereas a longer sealing zone need not have such a close fit and can have a higher clearance. 
     The guide sheath  400  can also include additional localized sealing points with the catheter extending through its working lumen. In some implementations, the localized sealing can occur a distance away from the distal end  406  of the sheath  400 . In some implementations, a localized sealing can occur at the distal end  406  of the sheath  400 . For example, the guide sheath  400  may include a distal tip  406  that is designed to seal well with an outer diameter of a catheter extending through its working lumen. The distal tip  406  can be formed of soft material that is devoid of both liner and reinforcement layers. The lubricious liner layer and also the reinforcement layer can extend through a majority of the body  402  except for a length of the distal tip  406  (see  FIG. 2C ). The length of this unlined, unreinforced portion of the distal tip  406  of the sheath  400  can vary. In some implementations, the length is between about 3 mm to about 6 mm of the distal end region of the sheath  400 . Thus, the liner  409  of the sheath  400  can terminate at least about 3 mm away from the distal-most terminus of the sheath  400  leaving the last 3 mm unlined soft material forming the distal tip  406 . In some implementations, the coil and braid of the reinforcement layer can have their ends held in place by a radiopaque markers  411 , such as a marker band positioned near a distal-most terminus of the sheath  400 . The liner layer  409  can extend at least a length distal to the marker band  411  before terminating, for example, a length of about 1 mm. The staggered termination of the wall layers can aid in the transition from the marker band  411  to the soft polymer material  407  of the distal tip  406 . The soft polymer material  407  can extend a length beyond the liner layer  409 . The unlined, soft material  407  forming the distal tip  406  can be a PEBAX material having a durometer of no more than about 40D, no more than about 35D, no more than about 62A, or no more than about 25D. The softness of the material and the length of this unlined distal tip  406  of the sheath  400  can vary. Generally, the material is soft enough to be compressed down onto the outer diameter of the catheter  200  extending through the lumen of the sheath  400 , such as upon application of a negative pressure through the lumen. The length of this unlined, unreinforced region  407  of the distal tip  406  is long enough to provide a good seal, but not so long as to cause problems with accordioning or folding over during relative sliding between the sheath  400  and the catheter  200  that might blocking the sheath lumen or negatively impacting slidability of the catheter  200  within the sheath lumen. 
     The distal tip  406  can have an inner diameter that approaches the outer diameter of the catheter  200  that extends through the sheath  400 . In some implementations, the inner diameter of the distal tip  406  can vary depending on what size catheter is to be used. For example, the inner diameter of the sheath at the distal tip  406  can be about 0.106″ when the outer diameter of the catheter near the proximal end is about 0.101″ such that the difference in diameters is about 0.005″. Upon application of a vacuum, the soft unlined and unreinforced distal tip  406  can move to eliminate this 0.005″ gap and compress down onto the outer diameter of the catheter  200  near its proximal end region upon extension of the catheter  200  out its distal opening  408 . The difference between the inner diameter of the distal tip  406  and the outer diameter of the catheter can be between about 0.002″-0.006″. The inner diameter of the distal tip  406  can also be tapered such the inner diameter at the distal-most terminus of the opening  408  is only 0.001″ to 0.002″ larger than the outer diameter of the proximal end of the catheter  200  extending through the working lumen. In some implementations, the distal tip  406  is shaped such that the walls are beveled at an angle relative to a central axis of the sheath  400 , such as about 60 degrees. 
     In some instances it is desirable for the sheath body  402  to also be able to occlude the artery in which it is positioned, for example, during procedures that may create distal emboli. Occluding the artery stops antegrade blood flow and thereby reduces the risk of distal emboli that may lead to neurologic symptoms such as TIA or stroke.  FIG. 2D  shows an arterial access device or sheath  400  that has a distal occlusion balloon  440  that upon inflation occludes the artery at the position of the sheath distal tip  406 . At any point in a procedure, for example, during removal of an occlusion by aspiration and/or delivery of a stent retriever or other interventional device, the occlusion balloon  440  can be inflated to occlude the vessel to reduce the risk of distal emboli to cerebral vessels. The sheath  400  can include an inflation lumen configured to deliver a fluid for inflation of the occlusion balloon  440  in addition to the working lumen of the sheath  400 . The inflation lumen can fluidly connect the balloon  440 , for example, to arm  412  on the proximal adaptor. This arm  412  can be attached to an inflation device such as a syringe to inflate the balloon  440  with a fluid when vascular occlusion is desired. The arm  412  may be connected to a passive or active vacuum source to further reduce the risk of distal emboli. 
     According to some implementations, the length of the guide sheath  400  is long enough to access the target anatomy and exit the arterial access site with extra length outside of a patient&#39;s body for adjustments. For example, the guide sheath  400  (whether having a distal occlusion balloon  440  or not) can be long enough to access the petrous ICA from the femoral artery such that an extra length is still available for adjustment. 
     The sealing clearance between the guide sheath  400  and the catheter  200  can be a function of localized low clearance regions in ID/OD. The size of the clearance can change depending on whether aspiration pressure is applied through the system. For example, the catheter  200  can also include a slit  236  in the luminal portion  222  (shown in  FIG. 5B ) configured to widen slightly upon application of suction from a vacuum source and improve sealing between the catheter  200  and the guide sheath  400 . Additionally or alternatively, the distal tip  406  of the sheath  400  can be designed to move downward onto the outer diameter of the catheter  200  to improve sealing. The strength of the localized seal(s) achieved allows for a continuous aspiration lumen from the distal tip of the catheter  200  to a proximal end  403  of the guide sheath  400  where it is connected to the vacuum source, even in the presence of lower suction forces, with minimal to no leakage. Generally, when there is enough overlap between the catheter  200  and the guide sheath  400  there is no substantial leakage. However, when trying to reach distal anatomy, the catheter  200  may be advanced to its limit and the overlap between the catheter  200  and the guide sheath  400  is minimal. Thus, additional sealing can be desirable to prevent leakage around the catheter  200  into the sheath  400 . The sealing between the catheter  200  and the guide sheath  400  can prevent this leakage upon maximal extension of catheter  200  relative to sheath  400 . 
     Distal Access Catheters 
     Again, with respect to  FIGS. 2A-2B , the distal access system  100  can include one or more catheters  200  configured to extend through and out the distal end of the guide sheath  400 . The catheter  200  can be a distal access, support, or aspiration catheter depending on the method being performed.  FIG. 3  illustrates a side elevational view of an implementation of the catheter  200 . The catheter  200  can include a relatively flexible, distal luminal portion  222  coupled to a stiffer, kink-resistant proximal extension or proximal control element  230 . The term “control element” as used herein can refer to a proximal region configured for a user to cause pushing movement in a distal direction as well as pulling movement in a proximal direction. The control elements described herein may also be referred to as spines, tethers, push wires, push tubes, or other elements having any of a variety of configurations. The proximal control element can be a hollow or tubular element. The proximal control element can also be solid and have no inner lumen, such as a solid rod, ribbon or other solid wire type element. Generally, the proximal control elements described herein are configured to move its respective component (to which it may be attached or integral) in a bidirectional manner through a lumen. 
     The catheter  200  provides a quick way to access stroke locations with simplicity even through the extreme tortuosity of the cerebral vasculature. The catheters described herein have a degree of flexibility and deliverability that makes them optimally suitable to be advanced through the cerebral vascular anatomy without kinking or ovalizing even when navigating hairpin turns. For example, the distal luminal portion  222  can perform a 180 degree turn (see turn T shown in  FIG. 1B  near the carotid siphon) and maintain a folded width across of 4.0 mm without kinking or ovalizing. Further, the distal luminal portion  222  has a degree of flexibility that maintains the natural tortuosity of the vessels through which it is advanced without applying straightening forces such that the natural shape and curvature of the anatomy is maintained during use. The catheter  200 , particularly in combination with a catheter advancement element  300 , which will be described in more detail below, provides an extended conduit beyond the guide sheath  400  having exceptional deliverability through convoluted anatomy that allows for delivering aspirational forces to a target stroke site as well as for the delivery of stroke interventional devices such as another aspiration catheter, or a device such as a stent retriever, stent, flow diverter or other working devices. 
     A single, inner lumen  223  extends through the luminal portion  222  between a proximal end and a distal end of the luminal portion  222 . The inner lumen  223  of the catheter  200  can have a first inner diameter and the working lumen of the guide sheath  400  can have a second, larger inner diameter. Upon insertion of the catheter  200  through the working lumen of the sheath  400 , the lumen  223  of the catheter  200  can be configured to be fluidly connected and contiguous with the working lumen of the sheath  400  such that fluid flow into and/or out of the system  100  is possible, such as by applying suction from a vacuum source coupled to the system  100  at a proximal end. The combination of sheath  400  and catheter  200  can be continuously in communication with the bloodstream during aspiration at the proximal end with advancement and withdrawal of catheter  200 . 
     The spined catheter system can create advantages for distal access over conventional, full-length catheters particularly in terms of aspiration. The step change in the internal diameter of the catheter (i.e. from the inner lumen  223  of the catheter to the working lumen of the sheath  400 ) creates a great advantage in aspiration flow and force that can be generated by the spined catheter  200  in combination with the conventional guide catheter. For example, where a spined catheter  200  with a 0.070″ internal diameter is paired with a standard 6F outer diameter/0.088″ internal diameter guide catheter (e.g. Penumbra Neuron MAX 088) can create aspiration physics where the 0.088″ catheter diameter will predominate and create a 0.080 equivalent flow in the entire system. This improvement can be mathematically approximated using the Hagen-Poiseulle equation where the pressure drop between the catheter tip and its connection to the vacuum system (dP) is equal to 8 uLQ/piR 4  where L is the catheter length, u is the dynamic viscosity of the liquid, Q is the volumetric flow rate, and R is the catheter radius. Rearranging the equation to solve for volumetric flow rate (an analog for catheter effectiveness) is Q=dPpiR 4 /8 uL. Different catheter designs having different effective radii can be compared within the same system by holding all other variables constant (e.g. vacuum pressure, fluid, length). Volumetric flow is directly proportional to the radius of the catheter to the fourth power. Thus, increasing the effective catheter radius has significant benefits in terms of volumetric flow rate and catheter performance. 
     In addition to aspiration procedures, the catheter  200  and distal access system  100  can be used for delivery of tools and interventional working devices. For example, a typical stent retriever to be delivered through the catheter  200  can have a long push wire control element (e.g. 180 cm long). The distal access system  100  having a spined support catheter  200  allows for reaching distal stroke sites using much shorter lengths (e.g. 120 cm-150 cm). The overall length can be as important as diameter and radius on aspiration through the catheter. The shorter lengths in combination with the elimination of the multiple RHVs typical in tri-axial systems allows for a single-operator use. 
     Where the catheter is described herein as an aspiration catheter, it should not be limited to only aspiration. Similarly, where the catheter is described herein as a way to deliver a stent retriever or other working device it should not be limited as such. The systems described herein can be used to perform procedures that incorporate a combination of treatments. For example, the catheter  200  can be used for the delivery of a stent retriever delivery system, optionally in the presence of aspiration through the catheter  200 . As another example, a user may start out performing a first interventional procedure using the systems described herein, such as aspiration embolectomy (sometimes referred to as “thrombectomy”), and switch to another interventional procedure, such as delivery of a stent retriever or implant. 
     The terms “support catheter,” “spined catheter,” “tethered catheter,” “distal access catheter,” “aspiration catheter,” and “intermediate catheter” may be used interchangeably herein. 
     It is desirable to have a catheter  200  having an inner diameter that is as large as possible that can be navigated safely to the site of the occlusion, in order to optimize the aspiration force in the case of aspiration and/or provide ample clearance for delivery of a working device. A suitable size for the inner diameter of the distal luminal portion  222  may range between 0.040″ and 0.100″, or more preferably between 0.054″ and 0.088″, depending on the patient anatomy and the clot size and composition. The outer diameter of the distal luminal portion  222  can be sized for navigation into cerebral arteries, for example, at the level of the M1 segment or M2 segment of the cerebral vessels. The outer diameter (OD) should be as small as possible while still maintaining the mechanical integrity of the catheter  200 . In an implementation, the difference between the OD of distal luminal portion  222  of the catheter  200  and the inner diameter of the working lumen of the guide sheath  400  is between 0.001″ and 0.002″. In another implementation, the difference is between 0.001″ and 0.004″. The clearance between inner diameter of the guide sheath  400  and the outer diameter of the catheter  200  can vary throughout the length of the catheter  200 . For example, the distal luminal portion  222  of the catheter  200  can have localized regions of enlarged outer diameter creating localized low clearance regions (e.g. about 0.001″ difference) configured for localized sealing upon application of aspiration pressure through the system. 
     In some implementations, the distal luminal portion  222  of the catheter  200  has a maximum outer diameter (OD) configured to fit through a 6F introducer sheath (0.070″-0.071″) and the lumen  223  has an inner diameter (ID) that is sized to receive a 0.054″ catheter. In some implementations, the distal luminal portion  222  has a lumen and a distal end having an opening from the lumen, the lumen can have an inner diameter (ID) at the distal end that is at least about 0.052″. In some implementations, the distal luminal portion  222  of the catheter  200  has a maximum OD configured to fit through an 8F introducer sheath (0.088″) and the lumen  223  has an ID that is sized to receive a 0.070″ or 0.071″ catheter. In some implementations, the maximum OD of the distal luminal portion  222  is 2.1 mm and the lumen  223  has an ID that is 0.071″. In some implementations, the lumen  223  has an ID that is 0.070″ to 0.073″. The outer diameter of the guide sheath  400  can be suitable for insertion into at least the carotid artery, with a working lumen suitably sized for providing a passageway for the catheter  200  to treat an occlusion distal to the carotid artery towards the brain. In some implementations, the ID of the working lumen can be about 0.074″ and the OD of the body of the guide sheath  400  can be about 0.090″, corresponding to a 5 French sheath size. In some implementations, the ID of the working lumen can be about 0.087″ and the OD of the body of the guide sheath  400  can be about 0.104″, corresponding to a 6 French sheath size. In some implementations, the ID of the working lumen can be about 0.100″ and the OD of the body of the guide sheath  400  can be about 0.117″, corresponding to a 7 French sheath size. In some implementations, the guide sheath  400  ID is between 0.087″ and 0.088″ and the OD of the distal luminal portion  222  of the catheter  200  is approximately 0.082″ and 0.086″ such that the difference in diameters is between 0.001″ and 0.005″. Smaller or larger sheath sizes are considered. For example, in some implementations the ID of the lumen  223  is about 0.088″ and the OD of the distal luminal portion is between 0.101″-0.102″. However, a conventional 7 French sheath has an ID that is only about 0.100″ and a conventional 8 French sheath has an ID that is about 0.113″ such that it would not provide a suitable sealing fit with the OD of the distal luminal portion of the catheter for aspiration embolectomy (i.e. 0.011″ clearance). Thus, the guide sheath  400  can be designed to have an inner diameter that is better suited for the 0.088″ catheter, namely between 0.106″-0.107″. Additionally, the 0.088″ catheter can have a step-up in OD from 0.101″-0.102″ to about 0.105″-0.107″ OD near a proximal end region to provide a localized area optimized for sealing with the guide sheath during application of high pressure. 
     In an implementation, the luminal portion  222  of the catheter  200  has a uniform diameter from a proximal end to a distal end. In other implementations, the luminal portion  222  of the catheter  200  is tapered and/or has a step-down towards the distal end of the distal luminal portion  222  such that the distal-most end of the catheter  200  has a smaller outer diameter compared to a more proximal region of the catheter  200 , for example, near where the distal luminal portion  222  seals with the guide sheath  400 . In another implementation, the luminal portion  222  of the catheter OD steps up at or near an overlap portion to more closely match the sheath inner diameter as will be described in more detail below. This step-up in outer diameter can be due to varying the wall thickness of the catheter  200 . For example, the catheter  200  can have a wall thickness that is slightly thicker near the proximal end to provide better sealing with the sheath compared to a wall thickness of the catheter  200  near the distal end. The catheter  200  can have a thicker wall at this location while maintaining a uniform inner diameter. This implementation is especially useful in a system with more than one catheter suitable for use with a single access sheath size. In some implementations, a thicker wall can be created by embedding a radiopaque material (e.g. tungsten) such that the localized step-up in OD can be visualized during a procedure. The catheter  200  may have a step-up in outer diameter near the proximal end region that does not result from a thicker wall. For example, the inner diameter of the lumen may also step-up such that the wall thickness remains uniform, but the lumen size increases thereby increasing the overall OD at this location. 
     The length of the luminal portion  222  can be shorter than a length of the working lumen of the guide sheath  400  such that upon advancement of the luminal portion  222  towards the target location results in an overlap region  348  between the luminal portion  222  and the working lumen (see  FIG. 2B ). The length of the overlap region  348  can vary depending on the length of the distal luminal portion  222  and the distance to the target location relative to the distal end of the guide sheath  400 . Taking into account the variation in occlusion sites and sites where the guide sheath  400  distal tip  406  may be positioned, the length of the luminal portion  222  may range from about 10 cm to about 80 cm, or between 35 cm to about 75 cm, or between about 45 cm to about 70 cm, or between about 50 cm to about 65 cm. In some implementations, the distal luminal portion  222  of the catheter  200  can be between 45 cm-70 cm and the control element  230  of the catheter  200  can be between about 90 cm to about 100 cm. In some implementations, the catheter  200  can have a total working length that is approximately 115 cm. In other implementations, the working length of the catheter  200  between a proximal end of the catheter to a distal end of the catheter can be greater than 115 cm up to about 130 cm. In some implementations, the catheter  200  can have a working length greater than 130 cm between a proximal tab  234  (or proximal hub) and the distal tip, for example, between about 130 cm and about 150 cm. The distal luminal portion  222  can have a shaft length of about 40 cm±3 cm. The distal luminal portion  222  can have a shaft length that is at least about 45 cm up to a length that is shorter than the working length of the sheath  400 . The body  402  of the guide sheath  400  can be between about 80 cm to about 90 cm. 
     The length of the luminal portion  222  of a first catheter can be the same or different from the length of the luminal portion  222  of a second catheter that is nested within it. The relative lengths of the first and second catheters can depend on the location and length of the proximal sealing zone or region. In some implementations, the first catheter has a luminal portion  222  that is shorter than a length of the luminal portion  222  of the second catheter. For example, the first catheter can have a luminal portion  222  that is at least 35 cm up to about 75 cm and the second catheter can have a luminal portion  222  that is shorter by about 1 cm, 2 cm, 3 cm, 4 cm, 5 cm, up to about 10 cm. In other implementations, the first catheter has a luminal portion  222  that is longer than a length of the luminal portion  222  of the second catheter. In some implementations, when the length of the luminal portion  222  is longer than a length of the second catheter luminal portion  222 , the difference can be no more than about 5 cm. For example, the first catheter can have a luminal portion  222  that is at least 35 cm up to about 75 cm and the second catheter can have a luminal portion  222  that is longer by about 1 cm, 2 cm, 3 cm, 4 cm, 5 cm, up to about 10 cm. 
     The length of the luminal portion  222  can be less than the length of the body  402  of the guide sheath  400  such that as the catheter  200  is extended from the working lumen there remains an overlap region  348  of the catheter  200  and the inner diameter of the working lumen. A seal can be formed within a region of the overlap region  348 . In some implementations, the length of the luminal portion  222  is sufficient to reach a region of the M1 segment of the middle cerebral artery (MCA) and other major vessels from a region of the internal carotid artery while the proximal end region of the luminal portion  222  of the catheter  200  is still maintained proximal to certain tortuous anatomies (e.g. brachiocephalic take-off BT, the aortic arch AA, or within the descending aorta DA). In an implementation, the luminal portion  222  of the catheter has a length sufficient to position its distal end within the M1 segment of the MCA and a proximal end within the aortic arch proximal to take-offs from the arch. In an implementation, the luminal portion  222  of the catheter has a length sufficient to position its distal end within the M1 segment of the MCA and a proximal end within the descending aorta DA proximal to the aortic arch AA. Used in conjunction with a guide sheath  400  having a sheath body  402  and a working lumen, in an implementation where the catheter  200  reaches the ICA and the distance to embolus can be less than 20 cm. 
     The distal luminal portion  222  having a length that is less than 80 cm, for example approximately 45 cm up to about 70 cm. The distal luminal portion  222 , can allow for an overlap region  348  with the body  402  within which a seal forms with the sheath while still providing sufficient reach to intracranial vessels. The carotid siphon CS is an S-shaped part of the terminal ICA beginning at the posterior bend of the cavernous ICA and ending at the ICA bifurcation into the anterior cerebral artery ACA and middle cerebral artery MCA. In some implementations, the distal luminal portion  222  can be between about 35 cm-80 cm, or between 40 cm-75 cm, or between 45 cm-60 cm long to allow for the distal end of the catheter  200  to extend into at least the middle cerebral arteries while the proximal control element  230  and/or the sealing element on the proximal end region of the distal luminal portion  222  remains proximal to the carotid siphon, and preferably within the aorta as will be described in more detail below. 
     The distal luminal portion  222  can have a length measured from its point of attachment to the proximal control element  230  to its distal end that is long enough to extend from a region of the internal carotid artery (ICA) that is proximal to the carotid siphon to a region of the ICA that is distal to the carotid siphon, including at least the M1 region of the brain. There exists an overlap region  348  between the luminal portion  222  of the catheter  200  and the working lumen of the guide sheath  400  upon extension of the luminal portion  222  into the target anatomy. A seal to fluid being injected or aspirated can be achieved within the overlap region  348  where the OD of the catheter  200  along at least a portion of the distal luminal portion  222  substantially matches the inner diameter of the guide sheath  400  or the difference can be between 0.001″-0.002″. The difference between the catheter OD and the inner diameter of the guide sheath  400  can vary, for example, between 1-2 thousandths of an inch, or between 1-4 thousandths of an inch, or between 1-12 thousandths of an inch. This difference in OD/ID between the sheath and the catheter can be along the entire length of the distal luminal portion  222  or can be a difference in a discrete region of the distal luminal portion  222 , for example, a cylindrical, proximal end region of the distal luminal portion  222 . In some implementations, a seal to fluid being injected or aspirated between the catheter and the sheath can be achieved within the overlap  348  between their substantially similar dimensions without incorporating any separate sealing structure or seal feature. In some implementations, an additional sealing structure located near the proximal end region of the distal luminal portion  222  provides sealing between the inner diameter of the sheath and the outer diameter of the catheter. 
     The length of the overlap region  348  between the sheath and the distal luminal portion varies depending on the distance between the distal end of the sheath and the embolus as well as the length of the luminal portion  222  between its proximal and distal ends. The overlap region  348  can be sized and configured to create a seal that allows for a continuous aspiration lumen from the distal tip region of the catheter  200  to a proximal end region  403  of the guide sheath  400  where it can be connected to a vacuum source. In some implementations, the strength of the seal achieved can be a function of the difference between the outer diameter of the catheter  200  and the inner diameter of the working lumen as well as the length of the overlap region  348 , the force of the suction applied, and the materials of the components. For example, the sealing can be improved by increasing the length of the overlap region  348 . However, increasing the length of the overlap region  348  can result in a greater length through which aspiration is pulled through the smaller diameter of the luminal portion  222  rather than the larger diameter of the working lumen. As another example, higher suction forces applied by the vacuum source can create a stronger seal between the luminal portion  222  and the working lumen even in the presence of a shorter overlap region  348 . Further, a relatively softer material forming the luminal portion and/or the body  402  can still provide a sufficient seal even if the suction forces are less and the overlap region  348  is shorter. In an implementation, the clearance of the overlap region  348  can enable sealing against a vacuum of up to approximately 28 inHg with minimal to no leakage. The clearance of the overlap region can enable sealing against a vacuum of up to about 730 mmHg with minimal to no leakage. 
     In other implementations, the overlap region  348  itself does not provide the sealing between the body  402  and the luminal portion  222 . Rather, an additional sealing element positioned within the overlap region  348 , for example, a discreet location along a region of the luminal portion  222  narrows the gap between their respective ID and ODs such that sealing is provided by the sealing element within the overlap region  348 . In this implementation, the location of the seal between the luminal portion  222  and the body  402  can be positioned more proximally relative to certain tortuous regions of the anatomy. For example, the proximal end region of the luminal portion  222  can have a discreet step-up in outer diameter that narrows the gap between the OD of the luminal portion  222  and the ID of the body  402 . This step-up in outer diameter of the luminal portion  222  can be positioned relative to the overall length of the luminal portion  222  such that the sealing region between the two components avoids making sharp turns. For example, the sealing region can include the proximal end region of the luminal portion  222  a certain distance away from the distal tip of the catheter and this sealing region can be designed to remain within the descending aorta DA when the distal end region of the luminal portion  222  is advanced through the aortic arch, into the brachiocephalic trunk BT, the right common carotid RCC, up to the level of the petrous portion of the internal carotid artery and beyond. Maintaining the sealing region below the level of the aortic arch while the distal end of the catheter is positioned within, for example, the M1 region of the MCA is a function of the length of the luminal portion  222  as well as the length and position of the sealing portion on the catheter. The sealing region on the luminal portion  222  can be located a distance from the distal tip of the catheter that is at least about 40 cm, 45 cm, 50 cm, 55 cm, 60 cm, 65 cm, 70 cm, up to about 75 cm from the distal tip of the catheter. 
     Use of the term “seal” in the context of the catheter and the guide sheath refers to a condition where upon application of an aspiration force fluid is prevented from substantially passing from one side of the seal to the other. For example, the low clearance between the OD of the catheter and the ID of the sheath at the seal can prevent, upon application of aspiration pressure through the system, substantial passage of blood between outer surface of the catheter and the inner surface of the sheath and thereby create a seal. The seal does not necessarily mean the entire catheter system is sealed. For example, even when the catheter is “sealed” with the sheath, blood can still be aspirated into the lumen of the catheter and through the guide sheath (at least until “corking” of the distal end of the catheter  200  where a full seal of the entire system may occur). 
     The catheter  200  can telescope relative to the sheath (and/or relative to another catheter  200 ) such that the distal end of the distal luminal portion  222  can reach cerebrovascular targets within, for example, the M1, M2 regions while the proximal end of the distal luminal portion  222  remains proximal to or below the level of severe turns along the path of insertion. For example, the entry location of the catheter system can be in the femoral artery and the target embolus can be distal to the right common carotid artery (RCC), such as within the M1 segment of the middle cerebral artery on the right side. The proximal end region of the distal luminal portion  222  (e.g. where the sealing element is located and/or where the material transition to the proximal control element  230  occurs) can remain within a vessel that is proximal to severely tortuous anatomy: the carotid siphon, the right common carotid RCC, the brachiocephalic trunk BT, the take-off of the brachiocephalic artery from the aortic arch, the aortic arch AA as it transitions from the descending aorta DA. The descending aorta DA is a consistently straight segment in most anatomies.  FIG. 1C  illustrates the aortic arch AA, which separates the ascending aorta AscA and descending aorta DA. The distal-most carotid from a femoral access point is the right common carotid RCC artery, which takes off from the brachiocephalic trunk BT (or the left common carotid LCC, which takes off from the same brachiocephalic trunk BT in some patients—the so-called “bovine anatomy”). The distal luminal portion  222  may have a length that, when inserted into the RCC, is configured to extend from a target location in the M1 or M2 regions down to the brachiocephalic trunk BT, or down to the level of the aortic arch AA, or down to the descending aorta DA, which is sometimes referred to herein as being “below the takeoff” of the brachiocephalic trunk BT. This avoids inserting the stiffer proximal control element  230 , or the material transition between the stiffer proximal control element  230  and the distal luminal portion  222 , from taking the turn of the aortic arch or the turn of the brachiocephalic take-off, which can often be very severe. The turn of the aortic arch and the takeoff of the brachiocephalic are often the first severe turns catheters are likely to traverse as they ascend to the brain via the RCC artery. The less flexible portions of the catheter segment are able to avoid the regions of increased tortuosity near the level of the internal carotid artery. The distal luminal portion  222  can transition in flexibility towards the proximal region to approach the flexibility of the stiffer proximal control element  230 . The distal end of the catheter can be used to target the left cerebral circulation while the proximal control element  230  of the catheter  200  as well as the material transitions of the distal luminal portion  222  near the proximal control element  230  remain below the level of tortuosity of the brachiocephalic turn (e.g., within the aorta, proximal to the take-off of the left common carotid (LCC) artery, and preferably within the descending aorta DA). Similarly, the sealing region or a majority of the sealing region between the distal luminal portion  222  and the sheath preferably remains proximal to these severe turns. 
     In some implementations, the distal luminal portion  222  can have a length that allows the distal end of the distal luminal portion  222  to reach distal to the carotid siphon into the cerebral portion of the internal carotid artery while at the same time the proximal end of the distal luminal portion  222  (e.g. where it transitions to the proximal control element  230  as will be described in more detail below) remains within the aorta proximal to the take-off of the brachiocephalic trunk BT, for example within the descending aorta DA (see  FIG. 2C ). In this implementation, the distal luminal portion can be between about 35 cm and 75 cm in length, for example, between 45 cm-70 cm, or 65 cm long. 
     The attachment region between the more rigid, proximal control element  230  and the more flexible, distal luminal portion  222  creates a transition in material and flexibility that can be prone to kinking. Thus, it is preferable to avoid advancing the attachment region into extreme curvatures. For example, the distal luminal portion  222  can have a length that allows the point of attachment to be advanced no further than the first turn of the carotid siphon, or no further than the brachiocephalic artery take-off  610 , or nor further than the aortic arch AA, or no further than the descending aorta DA when the catheter is advanced from a femoral access site. In some implementations, the distal luminal portion  222  has a length sufficient to allow the point of attachment to remain within the descending aorta DA while still accessing M1 or M2 regions of the neurovasculature. Locating the material transition within the extreme turn of the brachiocephalic take-off BT from the aortic arch AA is generally avoided when the distal luminal portion  222  has a length that is between about 35 cm to about 75 cm, or 45 cm-70 cm, or 65 cm. 
     A seal can be created at and/or within the overlap region  348  between the distal luminal portion  222  and the sheath body  402 . It can be generally desirable to position the sealing between the distal luminal portion  222  and the sheath body  402  outside of extreme curvatures of the neurovasculature. In some implementations, the distal luminal portion  222  can have a length that allows for the distal end of the distal luminal portion  222  to extend distal to the carotid siphon into the cerebral portion of the internal carotid artery while at the same time the sealing region with the sheath body  402  remains proximal to the brachiocephalic takeoff BT, the aortic arch AA, or within the descending aorta DA. In this implementation, the length can be between about 35 cm to about 75 cm, about 40 cm to about 65 cm, or greater than 40 cm up to a length that is less than the working length of the sheath body  402 . 
     With respect to  FIG. 2C , the unreinforced region  407  of the distal tip  406  of the sheath  400  can have a length that allows it to provide sufficient sealing force onto the outer surface of the catheter  200  upon application of a negative pressure. The distal luminal portion  222  of the catheter  200  used with this implementation of sheath  400  can have a length that is shorter than 60 cm, shorter than 50 cm, shorter than 40 cm, shorter than 35 cm, shorter than 30 cm to about 10 cm. For example, the distal luminal portion  222  of the catheter  200  when used with a sheath  400  having an unreinforced region  407  configured for sealing against the outer diameter of the catheter  200  can be less than about 30 cm, for example, between about 10 cm and about 30 cm. 
     Sealing within the overlap region  348  can be due to the small difference in inner and outer diameters. The proximal end region of the distal luminal portion  222  can have a step-up in outer diameter (e.g. increased wall thickness) providing a region of localized sealing with the inner diameter of the guide sheath. Additionally or alternatively, the localized sealing can be due to an additional sealing element positioned on an external surface of the distal luminal portion or an inner surface of the sheath body. A sealing element can include a stepped up diameter or protruding feature in the overlap region. The sealing element can include one or more external ridge features. The one or more ridge features can be compressible when the luminal portion is inserted into the lumen of the sheath body. The ridge geometry can be such that the sealing element behaves as an O-ring, quad ring, or other piston seal design. The sealing element can include one or more inclined surfaces biased against an inner surface of the sheath body lumen. The sealing element can include one or more expandable members actuated to seal. The inflatable or expandable member can be a balloon or covered braid structure that can be inflated or expanded and provide sealing between the two devices at any time, including after the catheter is positioned at the desired site. Thus, no sealing force need be exerted on the catheter during positioning, but rather applied or actuated to seal after the catheter is positioned. The sealing element can be positioned on the external surface of the distal luminal portion, for example, near the proximal end region of the distal luminal portion and may be located within the overlap region. More than a single sealing element can be positioned on a length of the catheter. 
     The additional sealing element of the distal luminal portion  222  can be a cup seal, a balloon seal, or a disc seal formed of a soft polymer positioned around the exterior of the distal luminal portion near the overlap region to provide additional sealing. The sealing element can be a thin-wall tubing with an outer diameter that substantially matches the inner diameter of the sheath body lumen. The tubing can be sealed on one end to create a cup seal or on both ends to create a disc or balloon seal. The balloon seal can include trapped air that creates a collapsible space. One or more slits can be formed through the wall tubing such that the balloon seal can be collapsible and more easily passed through an RHV. The balloon seal need not include slits for a less collapsible sealing element that maintains the trapped air. The sealing element can be tunable for sheath fit and collapse achieved. 
     In some implementations, the system can include one or more features that restrict extension of the catheter  200  relative to the sheath  400  to a particular distance such that the overlap region  348  achieved is optimum and/or the catheter  200  is prevented from being over-inserted. For example, a tab can be positioned on a region of the catheter  200  such that upon insertion of the catheter  200  through the sheath  400  a selected distance, the tab has a size configured to abut against the port through which the catheter  200  is inserted to prevent further distal extension of the catheter  200  through the sheath  400 . A tab can also be positioned on a region of the catheter advancement element  300  to ensure optimum extension of the catheter advancement element  300  relative to the distal end of the catheter  200  to aid in advancement of the catheter  200  into the intracranial vessels. 
     Again with respect to  FIG. 3 , the proximal control element  230  is configured to move the distal luminal portion  222  in a bidirectional manner through the working lumen of the guide sheath  400  such that the distal luminal portion  222  can be advanced out of the guide sheath  400  into a target location for treatment within the target vessel. In some implementations and as shown in  FIG. 3 , the proximal control element  230  of the catheter  200  can have a smaller outer diameter than the outer diameter of the distal luminal portion  222  forming a proximal spine or tether to the catheter  200 . A smaller outer diameter for the proximal control element  230  than the outer diameter of the distal luminal portion  222  allows for the larger diameter working lumen of the sheath  400  to maintain greater aspiration forces than would otherwise be provided by the smaller diameter luminal portion  222  of the catheter  200  or allow for the delivery of working devices through the lumen with less frictional forces. The markedly shorter length of the luminal portion  222  results in a step-up in luminal diameter between the luminal portion  222  contiguous with the working lumen providing a markedly increased radius and luminal area for delivery of a working device and/or aspiration of the clot, particularly in comparison to other systems where the aspiration lumen runs along the entire inner diameter of the aspiration catheter. More particularly, the combined volume of the luminal area of the catheter  200  and the luminal area of the working lumen proximal to the distal luminal portion  222  is greater than the luminal area of the large bore catheter along the entire length of the system. Thus, the likelihood of removing the embolus during a single aspiration attempt may be increased. More particularly, the stepped up luminal diameter along the proximal control element  230  may enable a greater aspiration force to be achieved resulting in improved aspiration of the embolus. Further, this configuration of the catheter  200  and proximal control element  230  greatly speeds up the time required to retract and re-advance the catheter  200  and/or working devices through the working lumen out the distal opening  408 . The proximal control element  230  of the catheter  200  has a length and structure that extends through the working lumen of the sheath-guide  400  to a proximal end of the system  100  such that the proximal control element  230  can be used to advance and retract the catheter  200  through the working lumen. The proximal control element  230  of the catheter  200 , however, takes up only a fraction of the luminal space of the system  100  resulting in increased luminal area for aspiration and/or delivery of working devices. The stepped up luminal diameter also increases the annular area available for forward flushing of contrast, saline, or other solutions while devices such as microcatheters or other devices may be coaxially positioned in the luminal portion  222  of the catheter  200  and/or the working lumen. This can increase the ease and ability to perform angiograms during device navigation. 
     In an implementation, the distal luminal portion  222  of the catheter  200  is constructed to be flexible and lubricious, to be able to safely navigate to the target location. The distal luminal portion  222  can be kink resistant and collapse resistant when subjected to high aspiration forces to be able to effectively aspirate a clot. The luminal portion  222  can have increasing flexibility towards the distal end with smooth material transitions along its length to prevent any kinks, angulations or sharp bends in its structure, for example, during navigation of severe angulations such as those having 90° or greater to 180° turns, for example at the aorto-iliac junction, the left subclavian artery LSA take-off from the aorta AA, the takeoff of the brachiocephalic (innominate) artery BT from the ascending aorta AscA and many other peripheral locations just as in the carotid siphon. The distal luminal portion  222  can transition from being less flexible near its junction with the proximal control element  230  to being more flexible at the distal-most end. For example, a first portion of the distal luminal portion  222  can be formed of a material having a material hardness of 72D along a first length, a second portion can be formed of a material having a material hardness of 55D along a second length, a third portion can be formed of a material such as Pebax or MX1205 having a material hardness of 40D along a third length, a fourth portion can be formed of a material having a material hardness of 35D along a fourth length, a fifth portion can be formed of a material having a material hardness of 25D along a fifth length, a sixth portion can be formed of a material such as Tecoflex having a material hardness of 85A along a sixth length, and a final distal portion of the catheter can be formed of a material such as Tecoflex having a material hardness of 80A. In some implementations, the final distal portion of the distal luminal portion  222  of the catheter  200  can be formed of a material such as Tecothane having a material hardness of 62A. Thus, the distal luminal portion  222  transitions from being less flexible near its junction with the proximal control element  230  to being more flexible at the distal-most end where, for example, a distal tip of the catheter advancement element  300  can extend from the distal end of the catheter  200 . Other procedural catheters described herein can have a similar construction providing a variable relative stiffness that transitions from the proximal end towards the distal end of the catheter as will be described elsewhere herein. The change in flexibility from proximal to distal end of the distal luminal portion  222  can be achieved by any of a variety of methods. 
     The distal luminal portion  222  can include two or more layers. In some implementations, the distal luminal portion  222  includes an inner lubricious liner, a reinforcement layer, and an outer jacket layer, each of which will be described in more detail. 
     The lubricious inner liner can be a PTFE liner, with one or more thicknesses along variable sections of flexibility. The PTFE liner can be a tubular liner formed by dip coating or film-casting a removable mandrel, such as a silver-plated copper wire as is known in the art. Various layers can be applied having different thicknesses. For example, a base layer of etched PTFE can be formed having a thickness of about 0.005″. A second, middle layer can be formed over the base layer that is Tecoflex SG-80A having a thickness of about 0.0004″. A third, top layer can be formed over the middle layer that is Tecoflex SG-93A having a thickness of about 0.0001″ or less. A reinforcement layer and/or reinforcement fiber can be applied to the inner liner, followed by the outer jacket layer and/or additional outer coating prior to removing the mandrel by axial elongation. 
     The reinforcement layer is a generally tubular structure formed of, for example, a wound ribbon or wire coil or braid. The material for the reinforcement structure may be stainless steel, for example 304 stainless steel, Nitinol, cobalt chromium alloy, or other metal alloy that provides the desired combination of strengths, flexibility, and resistance to crush. In some implementations, the distal luminal portion  222  has a reinforcement structure that is a Nitinol ribbon wrapped into a coil. For example, the coil reinforcement can be a tapered ribbon of Nitinol set to a particular inner diameter (e.g. 0.078″ to 0.085″ inner diameter) and having a pitch (e.g. between 0.012″ and 0.016″). The ribbon can be 304 stainless steel (e.g. about 0.012″×0.020″). The coil can be heat-set prior to transferring the coil onto the catheter. The pitch of the coil can increase from proximal end towards distal end of the distal luminal portion  222 . For example, the ribbon coils can have gaps in between them and the size of the gaps can increase moving towards the distal end of the distal luminal portion  222 . For example, the size of the gap between the ribbon coils can be approximately 0.016″ gap near the proximal end of the distal luminal portion  222  and the size of the gap between the ribbon coils near the distal end can be larger such as 0.036″ gap. This change in pitch provides for increasing flexibility near the distal-most end of the distal luminal portion  222 . The distal luminal portion  222  can additionally incorporate one or more reinforcement fibers (see  FIGS. 8B-8C ) configured to prevent elongation of the coils, as will be described in more detail below. The reinforcement structure can include multiple materials and/or designs, again to vary the flexibility along the length of the distal luminal portion  222 . 
     The outer jacket layer may be composed of discreet sections of polymer with different durometers, composition, and/or thickness to vary the flexibility along the length of the distal luminal portion  222 . 
     At least a portion of the outer surface of the catheter  200  can be coated with a lubricious coating such as a hydrophilic coating. In some implementations, the coating may be on an inner surface and/or an outer surface to reduce friction during tracking. The coating may include a variety of materials as is known in the art. The proximal control element  230  may also be coated to improve tracking through the working lumen. Suitable lubricious polymers are well known in the art and may include silicone and the like, hydrophilic polymers such as high-density polyethylene (HDPE), polytetrafluoroethylene (PTFE), polyarylene oxides, polyvinylpyrolidones, polyvinylalcohols, hydroxy alkyl cellulosics, algins, saccharides, caprolactones, HYDAK coatings (e.g. B-23K, HydroSleek), and the like, and mixtures and combinations thereof. Hydrophilic polymers may be blended among themselves or with formulated amounts of water insoluble compounds (including some polymers) to yield coatings with suitable lubricity, bonding, and solubility. 
     In some implementations, the distal luminal portion  222  includes two or more layers. In some implementations, the distal luminal portion  222  includes an inner lubricious liner, a reinforcement layer, and an outer jacket layer. The outer jacket layer may be composed of discreet sections of polymer with different durometers, composition, and/or thickness to vary the flexibility along the length of the distal luminal portion  222 . In an implementation, the lubricious inner liner is a PTFE liner, with one or more thicknesses along variable sections of flexibility. In an implementation, the reinforcement layer is a generally tubular structure formed of, for example, a wound ribbon or wire coil or braid. The material for the reinforcement structure may be stainless steel, for example 304 stainless steel, nitinol, cobalt chromium alloy, or other metal alloy that provides the desired combination of strengths, flexibility, and resistance to crush. In an implementation, the reinforcement structure includes multiple materials and/or designs, again to vary the flexibility along the length of the distal luminal portion  222 . In an implementation, the outer surface of the catheter  200  is coated with a lubricious coating such as a hydrophilic coating. The proximal control element  230  may also be coated to improve tracking through the working lumen. Suitable lubricious polymers are well known in the art and may include silicone and the like, hydrophilic polymers such as high-density polyethylene (HDPE), polytetrafluoroethylene (PTFE), polyarylene oxides, polyvinylpyrolidones, polyvinylalcohols, hydroxy alkyl cellulosics, algins, saccharides, caprolactones, and the like, and mixtures and combinations thereof. 
     Again with respect to  FIGS. 2A-2B , the distal luminal portion  222  of the catheter  200  can have a plurality of radiopaque markings. A first radiopaque marker  224   a  can be located near the distal tip region to aid in navigation and proper positioning of the tip under fluoroscopy. Additionally, a proximal region of the catheter  200  may have one or more proximal radiopaque markers  224   b  so that the overlap region  348  can be visualized as the relationship between a radiopaque marker  411  on the guide sheath  400  and the radiopaque marker  224   b  on the catheter  200 . The proximal region of the catheter  200  may also have one or more radiopaque markings providing visualization, for example, of the proximal opening into the single lumen of the catheter as will be described in more detail below. In an implementation, the two radiopaque markers (marker  224   a  at distal tip and a more proximal marker  224   b ) are distinct to minimize confusion of the fluoroscopic image, for example the catheter proximal marker  224   b  may be a single band and the marker  411  on the guide sheath  400  may be a double band and any markers on a working device delivered through the distal access system can have another type of band or mark. The radiopaque markers  224  of the distal luminal portion  222 , particularly those near the distal tip region navigating extremely tortuous anatomy, can be relatively flexible such that they do not affect the overall flexibility of the distal luminal portion  222  near the distal tip region. The radiopaque markers  224  can be tungsten-loaded or platinum-loaded markers that are relatively flexible compared to other types of radiopaque markers used in devices where flexibility is not paramount. In some implementations, the radiopaque marker can be a band of tungsten-loaded PEBAX having a durometer of 35D. 
     As best shown in  FIGS. 8B-8C , at least one reinforcement fiber  801  can be incorporated within a wall of the distal luminal portion  222  to prevent elongation of a coiled reinforcement layer  803 . The fiber  801  can be positioned between the liner layer  805  and the reinforcement layer  803 . The fiber  801  can extend along the longitudinal axis A of the catheter  200  from a proximal end region of the distal luminal portion  222  to a distal end region of the portion  222 . The proximal end of the fiber  801  can be coupled to a region of the distal luminal portion  222  near where it couples to the proximal control element  230 . A distal end of the fiber  801  can terminate near the distal end of the distal luminal portion  222 . The distal end of the fiber  801  can be captured between the distal marker band  224   a  and an end of the reinforcement layer  803 . The distal marker band  224   a  can be fully encapsulated between the inner liner  805  and the outer jacket  807 . In some implementations, the distal end of the fiber  801  extends distal to the last coil of the reinforcement layer  803  running under the marker band  224   a  and then looping around the band  224   a  back in a proximal direction. The free end of the fiber  801  is thereby captured under the reinforcement layer  803  and the marker band  224   a . The reinforcement fiber  801  thus terminates at the location the reinforcement layer  803  terminates thereby leaving a length of between about 10 cm-12 cm of the unreinforced distal-most tip region. The catheter  200  can include a plurality of reinforcement fibers  801  extending longitudinally along the distal luminal portion  222 , such as two, three, four, or more fibers  801  distributed around the circumference of the portion  222  and aligned parallel with one another and with the longitudinal axis A of the catheter  200 . The reinforcement fiber  801  may also terminate at a more distal location or at a more proximal location than the location of the distal terminal marker  224   a . The material of the reinforcement fiber  801  can vary, including but not limited to various high tenacity polymers like polyester, PEEK, and other similar materials. 
     The distal luminal portion  222  of the catheter  200  can have a proximal control element  230  coupled near a proximal opening into the single lumen of the distal luminal portion  222 . The distal luminal portion  222  and the proximal control element  230  can be attached to one another by a coupling band  901  (see  FIGS. 9A-9C ). A proximal end  905  of the coupling band  901  can attach to a distal end of the proximal control element  230  and a distal end of the coupling band  901  can attach to the distal luminal portion  222 . The proximal end  905  of the coupling band  901  may include a slot  907  configured to be welded with the proximal control element  230  of the catheter  200 . The catheter  200  may include a strain relief along a skive length such as a tungsten loaded PEBAX. The distal end of the coupling band  901  can be cut to form a plurality of spirals  903 . These spirals  903  are configured to intersperse with the coils of the reinforcement layer  803  at the proximal end region of the distal luminal portion  222 . The size of the gap between the spirals  903  of the coupling band  901  can be substantially similar to the size of the gap between the coils of the reinforcement layer  803  such that they can neatly intersperse with one another without creating any localized areas of increased wall thickness due to overlap. The thickness of the spirals  903  can, but need not, be similar to the thickness of the ribbon forming the reinforcement layer  803 . For example, the coiled reinforcement layer  803  can be formed of a Nitinol ribbon having a thickness of about 0.003″. The coupling band  901  can have a wall thickness that is about 0.003″ such that the spirals  903  and the coils of the reinforcement layer  803  can be similar in material thickness. This similarity in material thickness between the coils and the spirals  903  contribute to a generally uniform outer profile that can be kept to a minimum and avoid creating a substantially increased wall thickness in this coupling region. A low profile proximal end of the distal luminal portion  222  aids in maximizing the inner diameter while keeping the outer diameter as small as possible, for example, such that the inner diameter of the guide sheath to a minimum (e.g. less than about 0.113″ or about 0.107″). The coupling band  901  can include an aperture  911  through middle region  909  that is configured to receive a proximal end of the reinforcement fiber  801  extending longitudinally through the distal luminal portion  222 . The region of overlap between the distal end of the proximal control element and the distal luminal portion  222  can vary, but can be at least about 5 mm, at least about 7 mm, at least about 10 mm to provide a smooth and even transition. The overlap between the proximal control element and the distal luminal portion  222  may be about 5 mm up to about 15 mm. 
     As mentioned the distal end of the proximal control element  230  can be welded to the proximal end  905  of the coupling band  901 . In some implementations, the distal end region of the proximal control element  230  is skived in places and is flat in other places. The proximal control element  230  can be a stainless steel ribbon (e.g. 0.012″×0.020″ or 0.014″×0.020″ along a majority of its length). A distal end region of the proximal control element  230  can have a discontinuous taper that allows for the thickness of the ribbon to transition from the thickness of 0.012″ or 0.014″ down to a thickness that matches or is not significantly different from a thickness of the spirals  903  on the coupling band  901  that is attached to a proximal end region of the distal luminal portion  222 . The discontinuous taper can include a flat length bound on proximal and distal ends by a tapered length. The flat length allows for a more uniform, minimum material thickness between the distal luminal portion  222  and the proximal control element  230  that avoids introducing weak points that are more prone to kinking. For example, the distal end region of the proximal control element  230  can have a first tapered length that transitions in thickness from 0.012″ to a thickness of 0.008″ and a second tapered length that transitions from the flat length thickness down to about 0.003″. In other implementations, the distal end region of the proximal control element  230  can have a first tapered length that transitions in thickness from 0.014″ to a thickness of 0.010″ and a second tapered length that transitions from the flat length thickness down to about 0.003″. The spirals  903  of the coupling band  901  can have a thickness matches this terminal thickness of the proximal control element  230 . The lengths of the tapered and flat portions can vary. In some implementations, the first tapered length can be approximately 0.12 cm, the flat length can be approximately 0.2 cm, and the second tapered length can be approximately 0.15 cm. The uniform thickness along this flat length provides for a useful target in terms of manufacturing the catheter. The catheter need not incorporate a ribbon proximal control element  230  and can have any of a variety of configuration as described elsewhere herein. 
     As mentioned previously, the proximal control element  230  is configured to allow distal advancement and proximal retraction of the catheter  200  through the working lumen of the guide sheath  400  including passage out the distal opening  408 . In an implementation, the length of the proximal control element  230  is longer than the entire length of the guide sheath  400  (from distal tip to proximal valve), such as by about 5 cm to 15 cm. The length of the body  402  can be in the range of 80 to 90 cm or up to about 100 cm or up to about 105 cm and the length of the proximal control element  230  can be between 90-100 cm. 
     Again with respect to  FIG. 3 , the proximal control element  230  can include one or more markers  232  to indicate the overlap between the distal luminal portion  222  of the catheter  200  and the sheath body  402  as well as the overlap between the distal luminal portion  222  of the catheter  200  and other interventional devices that may extend through the distal luminal portion  222 . At least a first mark  232   a  can be an RHV proximity marker positioned so that when the mark  232   a  is aligned with the sheath proximal hemostasis valve  434  during insertion of the catheter  200  through the guide sheath  400 , the catheter  200  is positioned at the distal-most position with the minimal overlap length needed to create the seal between the catheter  200  and the working lumen. At least a second mark  232   b  can be a Fluoro-saver marker that can be positioned on the control element  230  and located a distance away from the distal tip of the distal luminal portion  222 . In some implementations, a mark  232  can be positioned about 100 cm away from the distal tip of the distal luminal portion  222 . 
     The proximal control element  230  can include a gripping feature such as a tab  234  on the proximal end to make the proximal control element  230  easy to grasp and advance or retract. The tab  234  can couple with one or more other components of the system as will be described in more detail below. The proximal tab  234  can be designed to be easily identifiable amongst any other devices that may be inserted in the sheath proximal valve  434 , such as guidewires or retrievable stent device wires. A portion of the proximal control element  230  and/or tab  234  can be colored a bright color, or marked with a bright color, to make it easily distinguishable from guidewire, retrievable stent tethers, or the like. Where multiple catheters  200  are used together in a nesting fashion to reach more distal locations within the brain, each proximal control element  230  and/or tab  234  can be color-coded or otherwise labeled to clearly show to an operator which proximal control element  230  of which catheter  200  it is coupled to. The proximal portion  366  of the catheter advancement element  300  can also include a color to distinguish it from the proximal control element  230  of the catheter  200 . 
     The tab  234  can be integrated with or in addition to a proximal hub coupled to a proximal end of the control element  230 . For example, as will be described in more detail below, the proximal control element  230  can be a hypotube having a lumen. The lumen of the hypotube can be in fluid communication with the proximal hub at a proximal end of the control element  230  such that aspiration forces and/or fluids can be delivered through the hypotube via the proximal hub. The proximal control element  230  can also be a solid element and need not include a lumen to direct aspiration forces to the distal end of the catheter  200 . 
     The proximal control element  230  can be configured with sufficient stiffness to allow advancement and retraction of the distal luminal portion  222  of the catheter  200 , yet also be flexible enough to navigate through the cerebral anatomy as needed without kinking. The configuration of the proximal control element  230  can vary. In some implementations, the proximal control element  230  can be a tubular element having an outer diameter that is substantially identical to the outer diameter of the distal luminal portion  222  similar to a typical catheter device. In other implementations, the outer diameter of the proximal control element  230  is sized to avoid taking up too much luminal area in the lumen of the guide sheath  400  to provide a step-up in inner diameter for aspiration. 
     The proximal control element  230  can be a solid metal wire that is round, rectangular, trapezoid, D-shape, or oval cross-sectional shape (see  FIGS. 4A-4G ). The proximal control element  230  can be a flattened ribbon of wire having a rectangular cross-sectional shape as shown in  FIG. 4A . The flattened ribbon of wire can also have square, rectangular, or other cross-sectional shape. The ribbon of wire can be curved into a circular, oval, c-shape, or quarter circle or other cross-sectional area along an arc. As such, an inner-facing surface of the ribbon can be substantially flat and an outer-facing surface of the ribbon (i.e. the surface configured to abut against an inner diameter of the access sheath through which it extends) can be substantially curved (see  FIGS. 4F-4G ). The curvature of the surface can substantially match the curvature of the inner surface of the access sheath. The resulting cross-sectional shape of such a ribbon can be generally trapezoidal. The overall dimensions of the ribbon can vary depending on its cross-sectional shape and the size of the distal luminal portion. The 0.054″ sized catheter  200  can have a proximal control element  230  that is trapezoidal or D-shaped in cross-section. The inner-facing, flat surface can have a width that is approximately 0.020″ wide and in the case of the trapezoidal-shaped implementation, the outer-facing, curved surface can extend along an arc that is approximately 0.030″ long. The 0.070″ sized catheter  200  can have a proximal extension that is trapezoidal or D-shaped in cross-section, and the width of the inner-facing, flat surface is slightly greater, for example, approximately 0.025″ and in the case of the trapezoidal-shaped implementation, the outer-facing, curved surface can extend along an arc that is approximately 0.040″ long. The 0.088″ sized catheter  200  can have a proximal extension that is trapezoidal or D-shaped in cross-section, and the width of the inner-facing, flat surface is approximately 0.035″ and the outer-facing, curved surface of the trapezoidal-shaped implementation can extend along an arc that is approximately 0.050″ long. 
     The proximal control element  230  can be a hollow wire having a lumen  235  extending through it, such as a hypotube as shown in  FIG. 4B . The hypotube can have an oval or circular shape. In an implementation, the proximal control element  230  is a ribbon of stainless steel having dimensions of about 0.012″×0.020″. In an implementation, the proximal control element  230  is a ribbon of stainless steel having dimensions of about 0.014″×0.020″. In an implementation, the proximal control element  230  is a round wire, with dimensions from 0.014″ to 0.018″. In another implementation, the proximal control element  230  is a ribbon with dimensions ranging from 0.010″ to 0.015″ thick, and 0.015″ thick to 0.025″ thick. In an implementation, the proximal control element  230  is a hypotube formed from a flattened ribbon of stiff material rolled into a tubular shape to have a lumen  235 . In some implementations, the proximal control element  230  can be formed of a flattened ribbon of stainless steel and rolled into a hypotube such that the proximal control element  230  has a wall thickness of about 0.007″, an inner diameter of about 0.004″ and an outer diameter of about 0.018″ before the hypotube is modified into an oval cross-sectional shape. The ovalized hypotube can maintain an inner diameter that is at least 0.001″ along at least a first dimension and an outer diameter that is at least 0.015″ along at least a first dimension. In an implementation, the proximal control element  230  material is a metal such as a stainless steel or nitinol as well as a plastic such as any of a variety of polymers. 
     In an implementation, the proximal control element  230  is a stainless steel hypotube having an oval cross-sectional shape (see  FIG. 4B ). The oval tubular shape can increase the column strength, pushability and kink resistance of the proximal control element  230  for improved advancement through tortuous anatomy. The cross-sectional area of an oval hypotube minimizes the impact of the catheter  200  on movement of other tools through the working lumen of the sheath  400 .  FIG. 4C  illustrates a cross-sectional view of the working lumen of the sheath  400  having a proximal control element  230  extending therethrough. The proximal control element  230  has a rectangular cross-sectional shape.  FIG. 4D  illustrates a cross-sectional view of the working lumen having an ovalized hypotube proximal control element  230  and a catheter advancement element  300  extending therethrough.  FIG. 4E  illustrates the comparison of surface area between the rectangular-shaped ribbon and the oval hypotube. The oval hypotube has less surface area compared to the rectangular-shaped ribbon allowing for a greater flow rate through the working lumen, for example, during application of aspirating forces. The materials, dimensions, and shape of the proximal control element  230  can be selected based on the materials, dimensions, and shape of the distal luminal portion  222 . For example, the proximal control element  230  can be a rectangular ribbon of 340 stainless steel that is 0.012″×0.020″ and the distal luminal portion  222  can have an inner diameter of about 0.054″ to about 0.072″. In a further implementation, the proximal control element  230  can be a rectangular ribbon of 340 stainless steel that is 0.014″×0.020″ and the distal luminal portion  222  can have an inner diameter of about 0.088″. The additional heft of the stainless steel ribbon  230  can be useful in advancing a larger inner diameter catheter without kinking. 
     Now with respect to  FIGS. 5A-5F , the junction between the distal luminal portion  222  of the catheter  200  and the proximal control element  230  can be configured to allow a smooth transition of flexibility between the two portions so as not to create a kink or weak point. The smooth transition at the joint between the distal luminal portion  222  and the proximal control element  230  also allows for smooth passage of devices through the contiguous inner lumen created by the working lumen of the guide sheath  400  and the lumen  223  of the luminal portion  222  of the catheter  200 . In an implementation, the distal luminal portion  222  has a transition section  226  near the proximal opening into the single lumen and where the luminal portion  222  couples to the proximal control element  230  (see  FIG. 5A ). The transition section  226  can have an angled cut such that there is no abrupt step transition from the working lumen of the guide sheath  400  to the inner lumen  223  of the catheter  200 . The angled cut can be generally planer. In an alternate implementation, the angled cut is curved or stepped to provide a more gradual transition zone. The proximal end region of the distal luminal portion  222  can be angled in an oblique manner relative to a longitudinal axis of the catheter  200  such that the proximal end and proximal opening into the lumen are at an angle other than 90° to the longitudinal axis of the catheter  200 , for example between approximately 0°, 5°, 10°, 15°, 20°, 25°, 30°, 35°, 40°, or 45° up to less than 90°. The proximal end region of the distal luminal portion  222  can also be aligned substantially perpendicular to the longitudinal axis of the catheter  200  such that the proximal end and proximal opening into the lumen are substantially 90° to the longitudinal axis of the catheter  200 . Similarly, the distal end region of the distal luminal portion  222  can be angled in an oblique manner relative to a longitudinal axis of the catheter  200  such that the distal end and distal opening from the lumen  223  are at an angle other than 90° to the longitudinal axis of the catheter  200 , for example between approximately 0°, 5°, 10°, 15°, 20°, 25°, 30°, 35°, 40°, or 45° up to less than 90°. The distal end region of the distal luminal portion  222  can also be aligned substantially perpendicular to the longitudinal axis of the catheter  200  such that the distal end and distal opening into the lumen are substantially 90° to the longitudinal axis of the catheter  200 . 
     The proximal control element  230  can be coupled to a proximal end region of the catheter  200  and/or may extend along at least a portion of the distal luminal portion  222  such that the proximal control element  230  couples to the distal luminal portion  222  a distance away from the proximal end defining the proximal opening into the lumen, for example via the coupling band  901 . The proximal control element  230  can be coupled to the distal luminal portion  222  by a variety of mechanisms including bonding, welding, gluing, sandwiching, stringing, tethering, or tying one or more components making up the proximal control element  230  and/or portion  222 . The distal luminal portion  222  and the proximal control element  230  may be joined by a weld bond, a mechanical bond, an adhesive bond, or some combination thereof. In some implementations, the proximal control element  230  and luminal portion  222  are coupled together by sandwiching the proximal control element  230  between layers of the distal luminal portion  222 . For example, the proximal control element  230  can be a hypotube or rod having a distal end that is skived, ground or cut such that the distal end can be laminated or otherwise attached to the layers of the catheter portion  222  near a proximal end region. The skive length of the proximal control element  230  can be about 7 mm and can incorporate a tungsten loaded Pebax strain relief along the length. The region of overlap between the distal end of the proximal control element  230  and the portion  222  can be at least about 1 cm. This type of coupling allows for a smooth and even transition from the proximal control element  230  to the luminal portion  222 . 
     Still with respect to  FIGS. 5A-5F , the transition section  226  of the distal luminal portion  222  can open up into a proximal tail  238  extending a length proximal to the transition section  226 . In some implementations, the proximal tail  238  has a cross-sectional geometry that is substantially curved. For example, the proximal tail  238  can extend along an arc of the longitudinal axis of the catheter  200  between about 20 to about 90 degrees. In some implementations, the proximal tail  238  is curved to create a funnel-shape and aids in loading and reloading a catheter advancement element  300  into the lumen of the catheter  200 . In other implementations, the edges of the proximal tail  238  curve such that the proximal tail  238  is not substantially flat. The curved shape can vary including a tear-drop shape that allows for a smooth transition and better loading/reloading of the catheter advancement element  300  into the lumen and avoids flat edges that can abut and catch the component as it is inserted. In other implementations, the proximal tail  238  is substantially flat. The proximal tail  238  can provide a smooth transition between distal luminal portion  222  and proximal control element  230  when the device is forced to bend. This can reduce the likelihood of kinking and facilitate pushing against resistance. 
     The dimensions of the proximal tail  238  can vary. The proximal tail  238  shown in  FIGS. 5A-5F  is relatively wide compared to the width of the proximal control element  230  and, in turn, can have a greater length without negatively impacting the ability of other devices to insert through the proximal opening into the lumen at the transition region  226 . In other implementations, the proximal tail  238 , defined by a region that is unsupported by the coils of the reinforcement layer  803  and located proximal to the coupling band  901 , can have a shorter length. The width of this proximal tail  238  can taper along this shorter length to a width of the proximal control element  230 . The tapered shorter proximal tail  238  can mitigate issues with insertion of tools into the proximal opening. Generally speaking, wide proximal tails  238  can be longer than proximal tails  238  that taper down to the width of the proximal control element  230 . 
     A proximal region of the distal luminal portion  222  can incorporate one or more markers to provide visualization under fluoro during loading/reloading of the catheter advancement element  300 . For example, the proximal end region can include a region of Pebax (e.g. 35D) loaded with tungsten (80%) for radiopacity. In some implementations, the proximal tail  228  and/or the transition section  226  defining the proximal opening into the lumen of the luminal portion  222  can be coated or embedded with a radiopaque material such that the opening into the lumen can be fully visualized during use. The radiopaque material embedded in this proximal end region can create a step-up in outer diameter. 
     The distal end of the proximal control element  230  and/or the distal luminal portion  222  may have features that facilitate a mechanical joint during a weld, such as a textured surface, protruding features, or cut-out features. During a heat weld process, the features would facilitate a mechanical bond between the polymer distal luminal portion  222  and the proximal control element  230 . For example, as shown in  FIGS. 6A-6F  the proximal end of the distal luminal portion  222  can include a short mating sleeve  240  coupled to a proximal edge  221  of the distal luminal portion  222 . The sleeve  240  can include an inner lumen extending between a proximal opening  242  and a distal opening  241 . The distal end of the proximal control element  230  can insert through the proximal opening  242  and within the inner lumen of the sleeve  240  to couple the proximal control element  230  to the distal luminal portion  222 . In some implementations, the proximal control element  230  can couple with the distal luminal portion  222  such that a distal opening  231  of the hypotube forming the proximal control element  230  can communicate with the lumen  223  of the distal luminal portion  222 , for example, through the distal opening  241  of the sleeve  240 . The sleeve  240  can also provide transition between distal luminal portion  222  and proximal control element  230  similar to the proximal tail  238 . The distal luminal portion  222  need not include a mating sleeve  240  to couple with the proximal control element  230 . For example, the distal end of the proximal control element  230  can insert through a wall of the proximal tail  238  at the proximal end of the distal luminal portion  222  (see  FIG. 5A, 5E-5F ). The distal end of the proximal control element  230  can extend along the length of the proximal tail  238  and along at least a length of the wall of the distal luminal portion  222 . 
     The luminal portion  222  of the catheter  200  can have a uniform diameter or wall thickness from a proximal end to a distal end or the luminal portion  222  can have different outer diameters or wall thicknesses along its length. For example, the distal-most end of the distal luminal portion  222  can have a smaller outer diameter compared to a more proximal region of the distal luminal portion  222 .  FIGS. 5A-5B, 5E-5F  as well as  FIGS. 6A-6B, 6E-6F , and  FIG. 8A  show a distal luminal portion  222  having a distal tubular region or distal tube  245  having a smaller outer diameter and a proximal tubular region or proximal tube  246  have a larger outer diameter. The distal tube  245  transitions via a step-up  247  to the proximal tube  246 . As best shown in  FIGS. 5A and 6A , the inner diameters of distal tube  245  and the proximal tube  246  are substantially the same providing a smooth inner wall surface for the lumen  223 . The outer diameter of the distal tube  245  may be smaller than the outer diameter of the proximal tube  246 . The step-up  247  is formed by a transition in wall thickness between the distal tube  245  and the proximal tube  246 . In some implementations, the outer diameter of the distal tube  245  can be about 0.080″ to about 0.084″ and the outer diameter of the proximal tube  246  can be about 0.087″ to about 0.088″. In other implementations, the outer diameter of the proximal tube  246  can be 0.106″ to about 0.107″. The relative lengths of the proximal and distal tubes  245 ,  246  may vary as described elsewhere herein. For example, the proximal tube  246  can create a proximal sealing zone that is a cylindrical segment having a length that is about 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, up to about 10 mm, or 15 mm. The proximal sealing zone can be located adjacent the proximal opening of the distal tube or can be located a distance distal of the proximal opening, such as about 5-30 mm distal from the proximal opening or within 5 mm, 10 mm, 15 mm, or 20 mm of the proximal opening. The proximal sealing zone can have a length of less than about 15 mm. The proximal sealing zone can have a length of between 2 mm and 30 mm, or between 2 mm and 15 mm. The proximal sealing zone of the proximal tube  246  may have a larger OD compared to the OD of the distal tube. In some implementations, the distal tube may have an OD that is about 0.082″, the proximal tube  246  at the proximal sealing zone may have an OD that is about 0.087″. In other implementations, where the distal tube may have an OD that is about 0.102″, and the proximal tube  246  at the proximal sealing zone may have an OD that is about 0.105″. The proximal sealing zone of the aspiration catheters described herein may provide sealing with the base sheath or may provide sealing with another aspiration catheter when the aspiration catheters are nested together in telescoping fashion. 
     A difference in OD of one catheter to an ID of another catheter through which it extends can be defined by an annular gap separating the two catheters. The size of this gap can change depending on the relative extension of the catheters to one another. Additionally, the size of the gap can change depending on whether it is measured within the sealing zone between the two catheters (i.e., a sealing zone gap) or outside of the sealing zone between the two catheters (i.e., a non-sealing zone gap). The sealing zone gap can be less than the non-sealing zone gap. For example, the sealing zone gap can be less than about 0.01″, less than about 0.007″, or less than about 0.005″. The non-sealing zone gap can be greater than about 0.005″ or greater than about 0.007″. The sealing zone gap can be a function of the step-up in outer diameter near a proximal end region of the catheter that forms the proximal sealing zone. Thus, the non-sealing zone gap is a function of the outer diameter distal to this step-up. 
     As an example, a first aspiration catheter can have a second aspiration catheter nested within its lumen in telescoping fashion. The second aspiration catheter can be advanced relative to the first aspiration catheter so that a distal tip of the second aspiration catheter extends distal to the distal tip of the first aspiration catheter and the proximal step-up seals with an inner lumen of the first catheter. This advancement narrows the non-sealing zone gap to the sealing zone gap forming a seal between the first and second aspiration catheters. As the second aspiration catheter is withdrawn proximally relative to the first aspiration catheter so that the distal tip of the second aspiration catheter slides proximally past the distal tip and within the lumen of the first aspiration catheter, the proximal step-up slides out the proximal opening of the first catheter and no longer seals with the proximal end region of the first catheter. This withdrawal widens the sealing zone gap to the non-sealing zone gap breaking or releasing a seal between the first and second aspiration catheters. The gap size between the nested catheters can at least double or at least triple when the seal releases. The term “release” with respect to the seal between the first and second aspiration catheters includes the at least partial release of the restriction to flow provided by the sealing zone. The release or partial release of the seal can at least partially transfers the aspiration force from the second (or inner) aspiration catheter to the first (or outer) aspiration catheter, or increase the aspiration force of the first catheter while simultaneously automatically reducing the aspiration force on the second catheter. 
     At least a portion of the wall of the larger outer diameter proximal tube  246  can be discontinuous such that it includes a slit  236  (see  FIGS. 5A-5C, 5E-5F, 6A-6C, and 6E-6F ). The slit  236  can extend a distance along the length of the proximal tube  246 . The slit  236  can extend from an edge  221  of the proximal tube  246  at least about 2 cm of a length of the proximal tube  246 . The slit  236  can, but need not, extend along the entire length of the proximal tube  246  to the location of the step-up  247 . Additionally, the proximal tube  246  can include more than one slit  236 . The slit  236  can be positioned in the larger diameter proximal tube  246  at a location opposite from where the distal end of the proximal control element  230  couples with the wall of the distal luminal portion  222 . As such that distal end of the proximal control element  230  embedded within the wall of the proximal tube  246  lies opposite the slit  236  (see  FIGS. 5C and 6C ). The slit  236  can be positioned around the proximal tube  246  at another location. 
     The slit  236  can allow for the proximal tube  246  to expand slightly such that the ends of the wall forming the slit  236  separate forming a gap therebetween. For example, upon insertion of the catheter  200  through the working lumen of the sheath  400 , the outer diameter can be received in a sliding fit such that at least an overlap region  348  remains. Upon application of an aspirational force through the working lumen, for example, by applying suction from a vacuum source coupled to the proximal end  403  of the guide sheath  400 , the sealing provided at the overlap region  348  can be enhanced by a slight widening of the gap formed by the slit  236 . This slight expansion provides for better sealing between the outer diameter of the proximal tube  246  and the inner diameter of the working lumen of the sheath  400  because the outer surface of the walls of the catheter  200  can press against the inner surface of the working lumen creating a tight fit between the catheter  200  and the sheath  400 . This improved sealing between the outer surface of the catheter  200  and the inner surface of the working lumen minimizes the seepage of blood from the vessel into the working lumen directly through the distal opening  408 . Thus, the larger outer diameter of the proximal tube  246  in combination with the slit  236  can enhance sealing between the catheter  200  and the sheath  400  by accommodating for variations of sheath inner diameters. The slit  236  can effectively increase the outer diameter of the proximal tube  246  depending on whether the walls forming the slit  236  are separated a distance. The walls forming the slit  236  can separate away from one another and increase a width of slit. The outer diameter of the proximal tube  246  including the increased width upon separation of the walls forming the slit  236  can be the same size or larger than the inner diameter of the sheath through which the proximal tube  246  is inserted. This allows for a single catheter to be compatible with a larger range of inner diameters. In some implementations, the outer diameter of the proximal tube  246  can be 0.081″ or about 0.100″ when the walls forming the slit  236  abut one another and no gap is present. The outer diameter of the proximal tube  246  can increase up to about 0.087″ or up to about 0.106″ when the walls forming the slit  236  are separated a maximum distance away from one another. Additionally, the increased wall thickness of the proximal tube  246  allows for creating a more robust joint between the distal luminal portion  222  and the proximal control element  230  of the catheter. 
     Additionally or alternatively, the distal tip  406  of the sheath  400  can include one or more features that improve sealing between the inner diameter of the working lumen of the sheath  400  and the outer diameter of the proximal end region of the catheter  200 . 
     Catheter Advancement Element 
     The distal access system  100  can, but need not, include a catheter advancement element  300  for delivery of the catheter  200  to the distal anatomy. Similarly, the catheter advancement element  300  can be used together to advance other catheters besides the catheter  200  described herein. For example, the catheter advancement element  300  can be used to deliver commercially available catheters such as, but not limited to: Sofia, Sofia Flow Plus and Sofia Plus (MicroVention Terumo, Aliso Viejo, Calif.), AXS Vectra (Stryker Neurovascular, Fremont, Calif.), React Catheters (Medtronic, Minneapolis, Minn.), Mivi Q Distal Access Catheter (Mivi Neuroscience, Eden Prairie, Minn.), Zoom Aspiration Catheters (Imperative Care, Campbell, Calif.), and the Jet, Ace and MAX Reperfusion Catheters (Penumbra, Inc. Alameda, Calif.) for clot removal in patients with acute ischemic stroke or other reperfusion catheters known in the art. Although the catheter advancement element  300  is described herein in reference to catheter  200  it can be used to advance other catheters and it is not intended to be limiting to its use only with the catheters described herein. 
     The distal access system  100  is capable of providing quick and simple access to distal target anatomy, particularly the tortuous anatomy of the cerebral vasculature. The flexibility and deliverability of the distal access catheter  200  allow the catheter  200  to take the shape of the tortuous anatomy and avoids exerting straightening forces creating new anatomy. The distal access catheter  200  is capable of this even in the presence of the catheter advancement element  300  extending through its lumen. Thus, the flexibility and deliverability of the catheter advancement element  300  is on par or better than the flexibility and deliverability of the distal luminal portion  222  of the distal access catheter  200  in that both are configured to reach the middle cerebral artery (MCA) circulation without straightening out the curves of the anatomy along the way. 
     The catheter advancement element  300  may be used instead of a guidewire to provide catheter access to cerebrovascular targets. In this implementation, the catheter advancement element  300  may be advanced independently without being disposed within the lumen of a catheter to provide guidewire access. In another implementation, the catheter advancement element  300  may be inserted into a lumen of a catheter and “locked” in a position relative to the catheter with an RHV. In the locked embodiment, the catheter advancement element  300  and the catheter are advanced together as a unit to the desired location. Should the operator encounter tortuous anatomy while in the locked configuration, the RHV can be opened allowing the catheter advancement element  300  to be advanced independently of the catheter. After advancing the catheter advancement element  300  to a desired position, the catheter can then be advanced over the catheter advancement element  300 , using the catheter advancement element  300  as a guide. 
     The catheter advancement element  300  can include a non-expandable, flexible elongate body  360  coupled to a proximal portion  366 . The catheter advancement element  300  and the catheter  200  described herein may be configured for rapid exchange or over-the-wire methods. For example, the flexible elongate body  360  can be a tubular portion extending the entire length of the catheter advancement element  300  and can have a proximal opening from the lumen of the flexible elongate body  360  that is configured to extend outside the patient&#39;s body during use. Alternatively, the tubular portion can have a proximal opening positioned such that the proximal opening remains inside the patient&#39;s body during use. The proximal portion  366  can be a proximal element coupled to a distal tubular portion and extending proximally therefrom. A proximal opening from the tubular portion can be positioned near where the proximal element couples to the tubular portion. Alternatively, the proximal portion  366  can be a proximal extension of the tubular portion having a length that extends to a proximal opening near a proximal terminus of the catheter advancement element  300  (i.e. outside a patient&#39;s body). 
     The configuration of the proximal portion  366  can vary. In some implementations, the proximal portion  366  is simply a proximal extension of the flexible elongate body  360  that does not change significantly in structure but in flexibility. For example, the proximal portion  366  transitions from the very flexible distal regions of the catheter advancement element  300  towards less flexible proximal regions of the catheter advancement element  300 . The proximal portion  366  provides a relatively stiff proximal end suitable for manipulating and torqueing the more distal regions of the catheter advancement element  300 . In other implementations, the proximal portion  366  is a hypotube. The hypotube may be exposed or may be coated by a polymer. In still further implementations, the proximal portion  366  may be a polymer portion reinforced by a coiled ribbon. The proximal portion  366  can have the same outer diameter as the flexible elongate body or can have a smaller outer diameter as the flexible elongate body. 
     The proximal portion  366  need not include a lumen. For example, the proximal portion  366  can be a solid rod, ribbon, or wire have no lumen extending through it that couples to the tubular elongate body  360 . Where the proximal portion  366  is described herein as having a lumen, it should be appreciated that the proximal portion  366  can also be solid and have no lumen. The proximal portion  366  is generally less flexible than the elongate body  360  and can transition to be even more stiff towards the proximal-most end of the proximal portion  366 . Thus, the catheter advancement element  300  can have an extremely soft and flexible distal-most tip that transitions proximally to a stiff proximal portion  366  well suited for torqueing and pushing the distal elongate body  360 . The transition in flexibility of the catheter advancement element  300  and the system as a whole is described in more detail below and in the Examples. 
     The elongate body  360  can be received within and extended through the internal lumen  223  of the distal luminal portion  222  of the catheter  200  (see  FIG. 2B ). The elongate body  360  or tubular portion can have an outer diameter. The outer diameter of the tubular portion can have at least one snug point, a difference between the inner diameter of the catheter  200  and the outer diameter of the tubular portion at the snug point can be no more than about 0.010″, for example, from 0.003″ up to about 0.010″, preferably about 0.006″ to about 0.008″. As will be described in more detail below, the catheter advancement element  300  can also include a tip portion or distal tip  346  located distal to the at least one snug point of the tubular portion. The tip portion can have a length and taper along at least a portion of the length. The distal tip  346  of the catheter advancement element  300  can be extended beyond the distal end of the catheter  200  as shown in  FIG. 2B . The proximal portion  366  of the catheter advancement element  300  or proximal extension is coupled to a proximal end region of the elongate body  360  and extends proximally therefrom. The proximal portion  366  can be less flexible than the elongate body  360  and configured for bi-directional movement of the elongate body  360  of the catheter advancement element  300  within the luminal portion  222  of the catheter  200 , as well as for movement of the catheter system  100  as a whole. The elongate body  360  can be inserted in a coaxial fashion through the internal lumen  223  of the luminal portion  222 . The outer diameter of at least a region of the elongate body  360  can be sized to substantially fill at least a portion of the internal lumen  223  of the luminal portion  222 . 
     The overall length of the catheter advancement element  300  (e.g. between the proximal end through to the distal-most tip) can vary, but generally is long enough to extend through the support catheter  200  plus at least a distance beyond the distal end of the support catheter  200  while at least a length of the proximal portion  366  remains outside the proximal end of the guide sheath  400  and outside the body of the patient. In some implementations, the overall length of the catheter advancement element  300  is about 145 to about 150 cm and has a working length of about 140 cm to about 145 cm from a proximal tab or hub to the distal-most tip. The elongate body  360  can have a length that is at least as long as the luminal portion  222  of the catheter  200  although the elongate body  360  can be shorter than the luminal portion  222  so long as at least a minimum length remains inside the luminal portion  222  when a distal portion of the elongate body  360  is extended distal to the distal end of the luminal portion  222  to form a snug point or snug region with the catheter. In some implementations, this minimum length of the elongate body  360  that remains inside the luminal portion  222  when the distal tip  346  is positioned at its optimal advancement configuration is at least about 5 cm, at least about 6 cm, at least about 7 cm, at least about 8 cm, at least about 9 cm, at least about 10 cm, at least about 11 cm, or at least about 12 cm up to about 50 cm. In some implementations, the shaft length of the distal luminal portion  222  can be about 35 cm up to about 75 cm and shorter than a working length of the guide sheath and the insert length of the elongate body  360  can be at least about 45 cm, 46 cm, 47 cm, 48 cm, 48.5 cm, 49 cm, 49.5 cm up to about 85 cm. 
     The length of the elongate body  360  can allow for the distal end of the elongate body  360  to reach cerebrovascular targets within, for example, the M1 or M2 regions while the proximal end region of the elongate body  360  remains proximal to or below the level of severe turns along the path of insertion. For example, the entry location of the catheter system can be in the femoral artery and the target embolus can be distal to the right common carotid RCC artery, such as within the M1 segment of the middle cerebral artery on the right side. The proximal end region of the elongate body  360  where it transitions to the proximal portion  366  can remain within a vessel that is proximal to severely tortuous anatomy such as the carotid siphon, the right common carotid RCC artery, the brachiocephalic trunk BT, the take-off into the brachiocephalic artery from the aortic arch, the aortic arch AA as it transitions from the descending aorta DA. This avoids inserting the stiffer proximal portion  366 , or the material transition between the stiffer proximal portion  366  and the elongate body  360 , from taking the turn of the aortic arch or the turn of the brachiocephalic take-off from the aortic arch, which both can be very severe. The lengths described herein for the distal luminal portion  222  also can apply to the elongate body  360  of the catheter advancement element. 
     The proximal portion  366  can have a length that varies as well. In some implementations, the proximal portion  366  is about 90 cm up to about 95 cm. The distal portion extending distal to the distal end of the luminal portion  222  can include distal tip  346  that protrudes a length beyond the distal end of the luminal portion  222  during use of the catheter advancement element  300 . The distal tip  346  of the elongate body  360  that is configured to protrude distally from the distal end of the luminal portion  222  during advancement of the catheter  200  through the tortuous anatomy of the cerebral vessels, as will be described in more detail below. The proximal portion  366  coupled to and extending proximally from the elongate body  360  can align generally side-by-side with the proximal control element  230  of the catheter  200 . The arrangement between the elongate body  360  and the luminal portion  222  can be maintained during advancement of the catheter  200  through the tortuous anatomy to reach the target location for treatment in the distal vessels and aids in preventing the distal end of the catheter  200  from catching on tortuous branching vessels, as will be described in more detail below. 
     In some implementations, the elongate body  360  can have a region of relatively uniform outer diameter extending along at least a portion of its length and the distal tip  346  tapers down from the uniform outer diameter. The outer diameter of the elongate body  360  can include a step-down at a location along its length, for example, a step-down in outer diameter at a proximal end region where the elongate body  360  couples to the proximal portion  366 . Depending upon the inner diameter of the catheter  200 , the clearance between the catheter  200  and the outer diameter of the elongate body  360  along at least a portion of its length can be no more than about 0.010″, such as within a range of about 0.003″-0.010″ or between 0.006″-0.008″. 
     The elongate body  360  can have an overall shape profile from proximal end to distal end that transitions from a first outer diameter having a first length to a tapering outer diameter having a second length. The first length of this first outer diameter region (i.e. the snug-fitting region between the distal luminal portion  222  and the elongate body  360 ) can be at least about 5 cm, or 10 cm, up to about 50 cm. The length of the tapering outer diameter can be between 1 cm and 4 cm. When the catheter advancement element  300  is inserted through the catheter  200 , this tapered distal tip  346  is configured to extend beyond and protrude out through the distal end of the luminal portion  222  whereas the more proximal region of the body  360  (i.e. the first length described above) remains within the luminal portion  222 . 
     As mentioned, the distal end of the luminal portion  222  can be blunt and have no change in the dimension of the outer diameter whereas the distal tip  346  can be tapered providing an overall elongated tapered geometry of the catheter system. The outer diameter of the elongate body  360  also approaches the inner diameter of the luminal portion  222  such that the step-up from the elongate body  360  to the outer diameter of the luminal portion  222  is minimized. Minimizing this step-up prevents issues with the lip formed by the distal end of the luminal portion  222  catching on the tortuous neurovasculature, such as around the carotid siphon near the ophthalmic artery branch, when the distal tip  346  in combination with the distal end region of the catheter  200  bends and curves along within the vascular anatomy. In some implementations, the inner diameter of the luminal portion  222  can be at least about 0.052″, about 0.054″ and the maximum outer diameter of the elongate body  360  can be about 0.048″ such that the difference between them is about 0.006″. In some implementations, the inner diameter of the luminal portion  222  can be about 0.070″ and the maximum outer diameter of the elongate body  360  can be about 0.062″ such that the difference between them is about 0.008″. In some implementations, the inner diameter of the luminal portion  222  can be about 0.088″ and the maximum outer diameter of the elongate body  360  can be about 0.080″ such that the difference between them is about 0.008″. In some implementations, the inner diameter of the luminal portion  222  can be about 0.072″ and the maximum outer diameter of the elongate body  360  is about 0.070″ such that the difference between them is only 2 thousandths of an inch (0.002″). In other implementations, the maximum outer diameter of the elongate body  360  is about 0.062″ such that the difference between them is about 0.010″. Despite the outer diameter of the elongate body  360  extending through the lumen of the luminal portion  222 , the luminal portion  222  and the elongate body  360  extending through it in co-axial fashion are flexible enough to navigate the tortuous anatomy leading to the level of M1 or M2 arteries without kinking and without damaging the vessel. 
     The dimensions provided herein are approximate and each dimensions may have an engineering tolerance or a permissible limit of variation. Use of the term “about” or “approximately” are intended to provide such permissible tolerance to the dimension being referred to. Where “about” or “approximately” is not used with a particular dimension herein that that dimension need not be exact. 
     The length of the distal tip  346  (e.g. the region of the catheter advancement element  300  configured to extend distal to the distal end of the catheter  200  during use to obtain the optimum advancement configuration) can vary. In some implementations, the length of the distal tip  346  can be in a range of between about 0.50 cm to about 4.0 cm from the distal-most terminus of the elongate body  360  or between about 1.0 cm to about 3.0 cm. In other implementations, the length of the distal tip  346  is between 2.0 cm to about 2.5 cm. In some implementations, the length of the distal tip  346  varies depending on the inner diameter of the catheter  200  with which the catheter advancement element  300  is to be used. For example, the length of the distal tip  346  can be as shorter (e.g. 1.2 cm) for a catheter advancement element  300  sized to be used with a catheter  200  having an inner diameter of about 0.054″ and can be longer (e.g. 2.5 cm) for a catheter advancement element  300  sized to be used with a catheter  200  having an inner diameter of about 0.088″. The distal tip  346  can be a constant taper from the outer diameter of the elongate body  360  (e.g. the distal end of the marker  344   b ) down to a second smaller outer diameter at the distal-most terminus (e.g. the proximal end of the marker  344   a ) as shown in  FIG. 7C . In some implementations, the constant taper of the distal tip  346  can be from about 0.048″ outer diameter down to about 0.031″ outer diameter over a length of about 1 cm. In some implementations, the constant taper of the distal tip  346  can be from 0.062″ outer diameter to about 0.031″ outer diameter over a length of about 2 cm. In still further implementations, the constant taper of the distal tip  346  can be from 0.080″ outer diameter to about 0.031″ outer diameter over a length of about 2.5 cm. The length of the constant taper of the distal tip  346  can vary, for example, between 0.8 cm to about 2.5 cm, or between 1 cm and 3 cm, or between 2.0 cm and 2.5 cm. The angle of the taper can vary depending on the outer diameter of the elongate body  360 . For example, the angle of the taper can be between 0.9 to 1.6 degrees relative to horizontal. The angle of the taper can be between 2-3 degrees from a center line of the elongate body  360 . 
     The catheter advancement element  300  can include a distal tip  346  that tapers over a length. The elongate body  360  of the catheter advancement element  300  can have an inner diameter that does not change over its length even in the presence of the tapering of the distal tip  346 . Thus, the inner diameter of the lumen extending through the tubular portion of the catheter advancement element  300  can remain uniform and the wall thickness of the distal tip  346  can decrease to provide the taper. The wall thickness can thin distally along the length of the taper. Thus, the material properties in combination with wall thickness, angle, length of the taper can all contribute to the overall maximum flexibility of the distal-most end of the distal tip  346 . The catheter advancement element  300  undergoes a transition in flexibility from the distal-most end towards the snug point where it achieves an outer diameter that is no more than about 0.010″ different from the inner diameter of the catheter  200 . 
     The distal tip  346  need not taper and can achieve its soft, atraumatic and flexible characteristic due to a material property other than due to a change in outer dimension to facilitate endovascular navigation to an embolus in tortuous anatomy. Additionally or alternatively, the distal tip  346  of the elongate body  360  can have a transition in flexibility along its length. The most flexible region of the distal tip  346  can be its distal terminus. Moving along the length of the distal tip  346  from the distal terminus towards a region proximal to the distal terminus. For example, the distal tip  346  can be formed of a material having a material hardness of no more than 35D or about 62A and transitions proximally to be less flexible near where it is formed of a material having a material hardness of no more than 55D and 72D up to the proximal portion  366 , which can be a stainless steel hypotube, or a combination of a material property and tapered shape. The materials used to form the regions of the elongate body  360  can include PEBAX (such as PEBAX 25D, 35D, 55D, 72D) or a blend of PEBAX (such as a mix of 25D and 35D, 25D and 55D, 25D and 72D, 35D and 55D, 35D and 72D, 55D and 72D, where the blend ratios may range from 0.1% up to 50% for each PEBAX durometer), with a lubricious additive compound, such as Mobilize (Compounding Solutions, Lewiston, Me.). In some implementations, the material used to form a region of the elongate body  360  can be Tecothane 62A. Incorporation of a lubricious additive directly into the polymer elongate body means incorporation of a separate lubricious liner, such as a Teflon liner, is unnecessary. This allows for a more flexible element that can navigate the distal cerebral anatomy and is less likely to kink. Similar materials can be used for forming the distal luminal portion  222  of the catheter  200  providing similar advantages. The flexibility of the distal tip  346  can be achieved by a combination of flexible lubricious materials and tapered shapes. For example, the length of the tip  346  can be kept shorter than 2 cm-3 cm, but maintain optimum deliverability due to a change in flexible material from distal-most tip towards a more proximal region a distance away from the distal-most tip. In an implementation, the elongate body  360  is formed of PEBAX (polyether block amide) embedded silicone designed to maintain the highest degree of flexibility. The wall thickness of the distal end of the luminal portion  222  can also be made thin enough such that the lip formed by the distal end of the luminal portion  222  relative to the elongate body  360  is minimized. 
     The elongate body  360  has a benefit over a microcatheter in that it can have a relatively large outer diameter that is just 0.003″-0.010″ smaller than the inner diameter of the distal luminal portion  222  of the catheter  200  and still maintaining a high degree of flexibility for navigating tortuous anatomy. When the gap between the two components is too tight (e.g. less than about 0.003″), the force needed to slide the catheter advancement element  300  relative to the catheter  200  can result in damage to one or both of the components and increases risk to the patient during the procedure. The gap results in too tight of a fit to provide optimum relative sliding. When the gap between the two components is too loose (e.g. greater than about 0.010″), the distal end of the catheter  200  forms a lip that is prone to catch on branching vessels during advancement through tortuous neurovasculature, such as around the carotid siphon where the ophthalmic artery branches off. 
     The gap in ID/OD between the elongate body  360  and the distal luminal portion  222  can be in this size range (e.g. 0.003″-0.010″) along a majority of their lengths. For example, the elongate body  360  can have a relatively uniform outer diameter that is between about 0.048″ to about 0.080″ from a proximal end region to a distal end region up to a point where the taper of the distal tip  346  begins. Similarly, the distal luminal portion  222  of the catheter  200  can have a relatively uniform inner diameter that is between about 0.054″ to about 0.088″ from a proximal end region to a distal end region. As such, the difference between their respective inner and outer diameters along a majority of their lengths can be within this gap size range of 0.003″ to 0.010″. The distal tip  346  of the elongate body  360  that is tapered will have a larger gap size relative to the inner diameter of the distal luminal portion  222 . During use, however, this tapered distal tip  346  is configured to extend distal to the distal end of the catheter  200  such that the region of the elongate body  360  having an outer diameter sized to match the inner diameter of the distal luminal portion  222  is positioned within the lumen of the catheter  200  such that it can minimize the lip at the distal end of the catheter  200 . 
     The elongate body  360  can be formed of various materials that provide a suitable flexibility and lubricity. Example materials include high density polyethylene, 72D PEBAX, 90D PEBAX, or equivalent stiffness and lubricity material. At least a portion of the elongate body  360  can be reinforced to improve navigation and torqueing (e.g. braided reinforcement layer). The flexibility of the elongate body  360  can increase towards the distal tip  346  such that the distal region of the elongate body  360  is softer, more flexible, and articulates and bends more easily than a more proximal region. For example, a more proximal region of the elongate body can have a bending stiffness that is flexible enough to navigate tortuous anatomy such as the carotid siphon without kinking. If the elongate body  360  has a braid reinforcement layer along at least a portion of its length, the braid reinforcement layer can terminate a distance proximal to the distal tip  346 . For example, the distance from the end of the braid to the distal tip can be about 10 cm to about 15 cm or from about 4 cm to about 10 cm or from about 4 cm up to about 15 cm. 
     In some implementations, the elongate body  360  can be generally tubular along at least a portion of its length such that it has a single lumen  368  extending parallel to a longitudinal axis of the catheter advancement element  300  (see  FIG. 7A-7C  and also  FIG. 10A-10C ). In an implementation, the single lumen  368  of the elongate body  360  is sized to accommodate a guidewire, however use of the catheter advancement element  300  generally eliminates the need for a guidewire lead. Methods of using the catheter advancement element  300  without a guidewire to deliver a catheter to distal regions of the brain are described in more detail below. 
     A guidewire can extend through the single lumen  368  generally concentrically from a proximal opening to a distal opening through which the guidewire can extend. In some implementations, the proximal opening is at the proximal end of the catheter advancement element  300  such that the catheter advancement element  300  is configured for over-the-wire (OTW) methodologies. In other implementations, the proximal opening is a rapid exchange opening  362  through a wall of the catheter advancement element  300  such that the catheter advancement element  300  is configured for rapid exchange rather than or in addition to OTW. In this implementation, the proximal opening  362  extends through the sidewall of the elongate body and is located a distance away from a proximal tab  364  and distal to the proximal portion  366  (see  FIGS. 7A-7B and 7D ). The proximal opening  362  can be located a distance of about 10 cm from the distal tip  346  up to about 20 cm from the distal tip  346 . In some implementations, the proximal opening  362  can be located near a region where the elongate body  360  is joined to the proximal portion  366 , for example, just distal to an end of the hypotube (see  FIG. 7B ). In other implementations, the proximal opening  362  is located more distally such as about 10 cm to about 18 cm from the distal-most end of the elongate body  360  (see  FIG. 7D ). A proximal opening  362  that is located closer to the distal tip  346  allows for easier removal of the catheter advancement element  300  from the catheter  200  leaving the guidewire in place for a “rapid exchange” type of procedure. Rapid exchanges can rely on only a single person to perform the exchange. The catheter advancement element  300  can be readily substituted for another device using the same guidewire that remains in position. The single lumen  368  of the elongate body  360  can be configured to receive a guidewire in the range of 0.014″ and 0.018″ diameter, or in the range of between 0.014″ and 0.022″. In this implementation, the inner luminal diameter of the elongate body  360  can be between 0.020″ and 0.024″. The guidewire, the catheter advancement element  300 , and the catheter  200  can all be assembled co-axially for insertion through the working lumen of the guide sheath  400 . The inner diameter of the lumen  368  of the elongate body  360  can be 0.019″ to about 0.021″. 
       FIG. 7D  shows another implementation of the catheter advancement element  300  configured for rapid exchange. Rapid exchange configurations can dramatically shorten device length, decreases staffing requirements, and reduces fluoroscopy. As with other implementations described herein, the catheter advancement element  300  can include a non-expandable, flexible elongate body  360  coupled to a proximal portion  366  coupled to a proximal tab  364  or hub  375 . The region near the distal tip  346  can be tapered such that the outer diameter tapers over a length of about 1 cm to about 4 cm. In some implementations, the distal taper length is 2.5 cm. In some implementations, the distal tip  346  tapers from about 0.080″ to about 0.031″. Also, the distal tip  346  can be formed of a material having a material hardness (e.g. 62A and 35D) that transitions proximally towards increasingly harder materials having (e.g. 55D and 72D) up to the proximal portion  366 . For example,  FIG. 7D  illustrates segment  371  of the elongate body  360  including the distal tip  346  formed of a material having a material hardness of 35D and a length of about 10 cm to about 12.5 cm. Segment  371  of the elongate body  360  including the distal tip  346  formed of a material having a material hardness of 62A and a length of about 10 cm to about 12.5 cm. Segment  372  of the elongate body  360  formed of a material having a material hardness of 55D and have a length of about 5 cm to about 8 cm. Segment  373  of the elongate body  360  formed of a material having a material hardness of 72D can be about 25 cm to about 35 cm in length. The three segments  371 ,  372 ,  373  combined can form an insert length of the elongate body  360  from where the proximal portion  366  couples to the elongate body  360  to the terminus of the distal tip  346  that can be about 49 cm in length. 
       FIGS. 10A-10C  illustrate an implementation of a catheter advancement element  300  incorporating a reinforcement layer  380 . The reinforcement layer  380  can be a braid or other type of reinforcement to improve the torqueability of the catheter advancement element  300  and help to bridge the components of the catheter advancement element  300  having such differences in flexibility. The reinforcement layer  380  can bridge the transition from the rigid, proximal portion  366  to the flexible elongate body  360 . In some implementations, the reinforcement layer  380  can be a braid positioned between inner and outer layers of Pebax  382 ,  384  (see  FIG. 10C ). The reinforcement layer  380  can terminate a distance proximal to the distal tip portion  346 . For example,  FIG. 10A  illustrates the elongate body  360  having segment  371  and segment  373  located proximal to segment  371 . Segment  371  can include the distal tip  346  formed of a material having a material hardness of at most about 35D. Segment  371  is unreinforced polymer having a length of about 4 cm up to about 12.5 cm. Segment  373  of the elongate body  360  located proximal to segment  371  can include the reinforcement layer  380  and can extend a total of about 37 cm up to the unreinforced distal segment  371 . A proximal end region of the reinforcement layer  380  can overlap with a distal end region of the proximal portion  366  such that a small overlap of hypotube and reinforcement exists near the transition between the proximal portion  366  and the elongate body  360 . 
     Again with respect to  FIG. 7D , an entry port  362  for a procedural guidewire can be positioned a distance away from the distal-most end of the elongate body  360 . In some implementations, the entry/exit port  362  can be about 18 cm from the distal-most end creating a rapid exchange wire entry/exit segment  370 . The outer diameter of the elongate body  360  within segment  370  (segments  371  and  372 ) can be about 0.080″-0.082″ whereas segment  373  proximal to this rapid exchange wire entry/exit segment  370  can have a step-down in outer diameter such as about 0.062″-0.064″. 
     The tubular portion of the catheter advancement element can have an outer diameter that has at least one snug point. A difference between the outer diameter at the snug point and the inner diameter of the lumen at the distal end of the distal, catheter portion can be no more than about 0.010″. The at least one snug point of this tubular portion can be a point along the length of the tubular portion. The at least one snug point of this tubular portion can have a length that is at least about 5 cm up to about 50 cm, including for example, at least about 6 cm, at least about 7 cm, at least about 8 cm, at least about 9 cm, at least about 10 cm, at least about 11 cm, or at least about 12 cm up to about 50 cm. This length need not be uniform such that the length need not be snug alone its entire length. For example, the snug point region can include ridges, grooves, slits, or other surface features. 
     In other implementations, the entire catheter advancement element  300  can be a tubular element configured to receive a guidewire through both the proximal portion  366  as well as the elongate body  360 . For example, the proximal portion  366  can be a hypotube or tubular element having a lumen that communicates with the lumen  368  extending through the elongate body  360  (shown in  FIG. 3 ). In some implementations, the proximal portion  366  can be a skived hypotube of stainless steel coated with PTFE having an outer diameter of 0.026″. In other implementations, the outer diameter can be between 0.024″ and 0.030″. In some implementations, such as an over-the-wire version, the proximal portion  366  can be a skived hypotube coupled to a proximal hub  375 . The proximal portion  366  can extend eccentric or concentric to the distal luminal portion  222 . As best shown in  FIG. 7E , the proximal portion  366  can be a stainless steel hypotube. The proximal portion  366  can be a solid metal wire that is round or oval cross-sectional shape. The proximal portion  366  can be a flattened ribbon of wire having a rectangular cross-sectional shape. The ribbon of wire can be curved into a circular, oval, c-shape, or quarter circle, or other cross-sectional shape along an arc. The proximal portion  366  can have any of variety of cross-sectional shapes whether or not a lumen extends therethrough, including a circular, oval, C-shaped, D-shape, or other shape. In some implementations, the proximal portion  366  is a hypotube having a D-shape such that an inner-facing side is flat and an outer-facing side is rounded. The rounded side of the proximal portion  366  can be shaped to engage with a correspondingly rounded inner surface of the sheath  400 . The hypotube can have a lubricious coating such as PTFE. The hypotube can have an inner diameter of about 0.021″, an outer diameter of about 0.0275″, and an overall length of about 94 cm providing a working length for the catheter advancement element  300  that is about 143 cm. Including the proximal hub  375 , the catheter advancement element  300  can have an overall length of about 149 cm. In some implementations, the hypotube can be a tapered part with a length of about 100 mm, starting proximal with a thickness of 0.3 mm and ending with a thickness of 0.10 mm to 0.15 mm. In still further implementations, the elongate body  360  can be a solid element coupled to the proximal portion  366  having no guidewire lumen. 
     The proximal portion  366  is shown in  FIGS. 2A, 7A-7D, and 10A  as having a smaller outer diameter compared to the outer diameter of the elongate body  360 . The proximal portion  366  need not step down in outer diameter and can also have the same outer diameter as the outer diameter as the elongate body  360 . For example, the proximal portion  366  can incorporate a hypotube or other stiffening element that is coated by one or more layers of polymer resulting in a proximal portion  366  having substantially the same outer diameter as the elongate body  360 . 
     As best shown in  FIGS. 7F-7J , the proximal end of the proximal portion  366  can be coupled to a proximal hub  375 . The proximal hub  375  can be an over-molded component having a luer thread  377  and a luer taper  378  formed on an inside of the proximal hub  375 . The proximal hub  375  can incorporate a tab  364  providing for easier gripping by a user. The proximal hub  375  prevents advancement of the catheter advancement element  300  and the catheter  200  beyond the distal tip of the base sheath  400  or guide catheter by limiting insertion into the proximal RHV  434  providing critical functional and safety features for proper operation of the system  10 . 
     At least a portion of the solid elongate body  360 , such as the elongate distal tip  346 , can be formed of or embedded with or attached to a malleable material that skives down to a smaller dimension at a distal end. The distal tip  346  can be shaped to a desired angle or shape similar to how a guidewire may be used. The malleable length of the elongate body  360  can be at least about 1 cm, 3 cm, 5 cm, and up to about 10 cm, 15 cm, or longer. In some implementations, the malleable length can be about 1%, 2%, 5%, 10%, 20%, 25%, 50% or more of the total length of the elongate body  360 . In some implementations, the catheter advancement element  300  can have a working length of about 140 cm to about 143 cm and the elongate body  360  can have an insert length of about 49 cm. The insert length can be the PEBAX portion of the elongate body  360  that is about 49.5 cm. As such, the malleable length of the elongate body  360  can be between about 0.5 cm to about 25 cm or more. The shape change can be a function of a user manually shaping the malleable length prior to insertion or the tip can be pre-shaped at the time of manufacturing into a particular angle or curve. Alternatively, the shape change can be a reversible and actuatable shape change such that the tip forms the shape upon activation by a user such that the tip can be used in a straight format until a shape change is desired by the user. The catheter advancement element  300  can also include a forming mandrel extending through the lumen of the elongate body  360  such that a physician at the time of use can mold the distal tip  346  into a desired shape. As such, the moldable distal tip  346  can be incorporated onto an elongate body  360  that has a guidewire lumen. 
     The elongate body  360  can extend along the entire length of the catheter  200 , including the distal luminal portion  222  and the proximal control element  230  or the elongate body  360  can incorporate the proximal portion  366  that aligns generally side-by-side with the proximal control element  230  of the catheter  200 . The proximal portion  366  of the elongate body  360  can be positioned co-axial with or eccentric to the elongate body  360 . The proximal portion  366  of the elongate body  360  can have a lumen extending through it. Alternatively, the portion  366  can be a solid rod or ribbon having no lumen. 
     Again with respect to  FIGS. 7A-7D , like the distal luminal portion  222  of the catheter  200 , the elongate body  360  can have one or more radiopaque markers  344  along its length. The one or more markers  344  can vary in size, shape, and location. One or more markers  344  can be incorporated along one or more parts of the catheter advancement element  300 , such as a tip-to-tip marker, a tip-to-taper marker, an RHV proximity marker, a Fluoro-saver marker, or other markers providing various information regarding the relative position of the catheter advancement element  300  and its components. In some implementations and as best shown in  FIG. 7C , a distal end region can have a first radiopaque marker  344   a  and a second radiopaque marker  344   b  can be located to indicate the border between the tapering of the distal tip  346  and the more proximal region of the elongate body  360  having a uniform or maximum outer diameter. This provides a user with information regarding an optimal extension of the distal tip  346  relative to the distal end of the luminal portion  222  to minimize the lip at this distal end of the luminal portion  222  for advancement through tortuous anatomy. In other implementations, for example where the distal tip  346  is not necessarily tapered, but instead has a change in overall flexibility along its length, the second radiopaque marker  344   b  can be located to indicate the region where the relative flexibilities of the elongate body  360  (or the distal tip  346  of the elongate body  360 ) and the distal end of the luminal portion  222  are substantially the same. The marker material may be a platinum/iridium band, a tungsten, platinum, or tantalum-impregnated polymer, or other radiopaque marker that does not impact the flexibility of the distal tip  346  and elongate body  360 . In some implementations, the radiopaque markers are extruded PEBAX loaded with tungsten for radiopacity. In some implementations, the proximal marker band can be about 2.0 mm wide and the distal marker band can be about 2.5 mm wide to provide discernable information about the distal tip  346 . 
     The proximal control element  230  of the catheter  200  can include a proximal tab  234  on the proximal end of the proximal control element  230 . Similarly, the proximal portion  366  coupled to the elongate body  360  can include a tab  364 . The tabs  234 ,  364  can be configured to removably and adjustable connect to one another and/or connect to their corresponding proximal portions. The coupling allows the catheter advancement element  300  to reversibly couple with the catheter  200  to lock (and unlock) the relative extension of the distal luminal portion  222  and the elongate body  360 . This allows the catheter  200  and the catheter advancement element  300  to be advanced as a single unit. In the locked configuration, the tab  364  or proximal portion  366  can be engaged with the catheter tab  234 . In the unlocked configuration, the tab  364  may be disengaged from the catheter tab  234 . The tab  364  or proximal portion  366  may attach, e.g., click or lock into, the catheter tab  234  in a fashion as to maintain the relationships of corresponding section of the elongate body  360  and the catheter  200  in the locked configuration. The tab  364  can be a feature on the proximal hub  375  such as the hub  375  shown in  FIGS. 7F-7J . 
     Such locking may be achieved by, e.g., using a detent on the tab  364  that snaps into place within a recess formed in the catheter tab  234 , or vice versa. For example, the tab  234  of the catheter  200  can form a ring having a central opening extending therethrough. The tab  364  of the body  360  can have an annular detent with a central post sized to insert through the central opening of the tab  234  such that such that the ring of the tab  234  is received within the annular detent of tab  364  forming a singular grasping element for a user to advance and/or withdraw the catheter system through the access sheath. The tabs  234 ,  364  may be affixed or may be slideable to accommodate different relative positions between the elongate body  360  and the luminal portion  222  of the catheter  200 . In some implementations, a proximal end of the proximal control element  230  of the catheter  200  can include a coupling feature  334 , such as clip, clamp, c-shaped element or other connector configured to receive the proximal portion  366  of the catheter advancement element  300  (see  FIG. 2A ). The coupling feature  334  can be configured to snap together with the proximal portion  366  through an interference fit such that a first level of force is needed in order to insert the proximal portion  366  into the clip of the tab  234  and a second, greater level of force is needed to remove the proximal portion  366  from the clip of the tab  234 . However, upon inserting the proximal portion  366  into the coupling feature  334  the catheter advancement element  300  and the catheter  200  can still be slideably adjusted relative to one another along a longitudinal axis of the system. The amount of force needed to slideably adjust the relative position of the two components can be such that inadvertent adjustment is avoided and the relative position can be maintained during use, but can be adjusted upon conscious modification. The configuration of the coupling between the proximal portion  366  of the catheter advancement element  300  and the proximal control element  230  of the catheter  200  can vary. Generally, however, the coupling is configured to be reversible and adjustable while still providing adequate holding power between the two elements in a manner that is relatively user-friendly (e.g. allows for one-handed use) and organizes the proximal ends of the components (e.g. prevents the proximal control element  230  and proximal portion  366  from becoming twisted and entangled with one another). The coupling feature  334  configured to prevent entanglement and aid in the organization of the proximal portions can be integrated with the tabs or can be a separate feature located along their proximal end region. 
     The catheter advancement element  300  can be placed in a locked configuration with the catheter  200  configured for improved tracking through a tortuous and often diseased vasculature in acute ischemic stroke. Other configurations are considered herein. For example, the elongate body  360  can include one or more detents on an outer surface. The detents can be located near a proximal end region and/or a distal end region of the elongate body  360 . The detents are configured to lock with correspondingly-shaped surface features on the inner surface of the luminal portion  222  through which the elongate body  360  extends. The catheter advancement element  300  and the catheter  200  can have incorporate more than a single point of locking connection between them. For example, a coupling feature  334 , such as clip, clamp, c-shaped element or other connector configured to hold together the catheter advancement element  300  and proximal control element  230  or tab  234  of the catheter  200 . 
     In some implementations, the proximal control element  230  of the catheter  200  can run alongside or within a specialized channel of the proximal portion  366 . The channel can be located along a length of the proximal portion  366  and have a cross-sectional shape that matches a cross-sectional shape of the catheter proximal control element  230  such that the proximal control element  230  of the catheter  200  can be received within the channel and slide smoothly along the channel bi-directionally. Once the catheter  200  and elongate body  360  are fixed, the combined system, i.e., the catheter  200 -catheter advancement element  300  may be delivered to a target site, for example through the working lumen of the guide sheath  400  described elsewhere herein. 
     The catheter advancement element  300  (whether incorporating the reinforcement layer or not) loaded within the lumen of the catheter  200  may be used to advance the catheter  200  to distal regions of the brain (e.g. level of the MCA). The traditional approach to the Circle of Willis is to use a triaxial system including a guidewire placed within a conventional microcatheter placed within an intermediate catheter. The entire coaxial system can extend through a base catheter or sheath. The sheath is typically positioned such that the distal tip of the sheath is placed in a high cervical carotid artery. The coaxial systems are often advanced in unison up to about the terminal carotid artery where the conventional coaxial systems must then be advanced in a step-wise fashion in separate throws. This is due to the two sequential 180 degree or greater turns (see  FIGS. 1A-1C ). The first 180 degree turn is at the level of the petrous to the cavernous internal carotid artery. The second 180 degree turn is at the terminal cavernous carotid artery as it passes through the bony elements and reaches the bifurcation into the anterior cerebral artery ACA and middle cerebral artery MCA. This S-shape region is referred to herein as the “siphon” or “carotid siphon”. The ophthalmic artery arises from the cerebral ICA, which represents a common point of catheter hang-up in accessing the anterior circulation. 
     Conventional microcatheter systems can be advanced through to the anterior circulation over a guidewire. The inner diameter of the conventional microcatheter is significantly larger than the outer diameter of the guidewire over which it is advanced thereby forming a lip on a distal end region of the system that can catch on these side branches during passage through the siphon. Conventional microcatheter systems (i.e. guidewire, microcatheter, and intermediate catheter) are advanced through the bends of the carotid siphon sequentially to distal target sites rather than in a single, smooth pass. The bends of the carotid siphon are taken one at a time in a step-wise advancement technique. For example, to pass through the carotid siphon, the conventional microcatheter is held fixed while the guidewire is advanced alone a first distance (i.e. through the first turn of the siphon). Then, the guidewire is held fixed while the conventional microcatheter is advanced alone through the first turn over the guidewire. Then, the conventional microcatheter and guidewire are held fixed while the intermediate catheter is advanced alone through the first turn over the microcatheter and guidewire. The process repeats in order to pass through the second turn of the siphon, which generally is considered the more challenging turn into the cerebral vessel. The microcatheter and intermediate catheter are held fixed while the guidewire is advanced alone a second distance (i.e. through the second turn of the siphon). Then, the guidewire and interventional catheter are held fixed while the microcatheter is advanced alone through that second turn over the guidewire. Then, the guidewire and the microcatheter are held fixed while the interventional catheter is advanced alone through the second turn. This multi-stage, step-wise procedure is a time-consuming process that requires multiple people performing multiple hand changes on the components. For example, two hands to fix and push the components over each other forcing the user to stage the steps. The step-wise procedure is required because the stepped transitions between these components (e.g. the guidewire, microcatheter, and intermediate catheter) makes advancement too challenging. 
     In contrast, the catheter  200  and catheter advancement element  300  eliminate this multi-stage, step-wise component advancement procedure to access distal sites across the siphon. The catheter  200  and catheter advancement element  300  can be advanced as a single unit through the both turns of the carotid siphon CS. Both turns can be traversed in a single smooth pass or throw to a target in a cerebral vessel without the step-wise adjustment of their relative extensions and without relying on the conventional step-wise advancement technique with conventional microcatheters. The catheter  200  having the catheter advancement element  300  extending through it allows a user to advance them in unison in the same relative position from the first bend of the siphon through the second bend beyond the terminal cavernous carotid artery into the ACA and MCA. Importantly, the advancement of the two components can be performed in a single smooth movement through both bends without any change of hand position. 
     The catheter advancement element  300  can be in a juxtapositioned relative to the catheter  200  that provides an optimum relative extension between the two components for single smooth advancement. The catheter advancement element  300  can be positioned through the lumen of the catheter  200  such that its distal tip  346  extends beyond a distal end of the catheter  200 . The distal tip  346  of the catheter advancement element  300  eliminates the stepped transition between the inner member and the outer catheter  200  thereby avoiding issues with catching on branching vessels within the region of the vasculature such that the catheter  200  may easily traverse the multiple angulated turns of the carotid siphon CS. The optimum relative extension, for example, can be the distal tip  346  of the elongate body  360  extending distal to a distal end of the catheter  200 . A length of the distal tip  346  extending distal to the distal end of the catheter  200  during advancement can be between 0.5 cm and about 4 cm. This juxtaposition can be a locked engagement with a mechanical element or simply by a user holding the two components together. 
     The components can be advanced together with a guidewire, over a guidewire pre-positioned, or without any guidewire at all. In some implementations, the guidewire can be pre-assembled with the catheter advancement element  300  and catheter  200  such that the guidewire extends through a lumen of the catheter advancement element  300 , which is loaded through a lumen of the catheter  200 , all prior to insertion into the patient. The pre-assembled components can be simultaneously inserted into the sheath  400  and advanced together up through and past the turns of the carotid siphon. 
     The optimum relative extension of the catheter  200  and catheter advancement element  300  can be based additionally on the staggering of material transitions.  FIG. 11  is a schematic illustrating approximate locations of the material transitions in the catheter advancement element  300  and the approximate locations of the material transitions in the catheter  200 . For example, the catheter advancement element  300  can include a proximal portion  366 , which can be a hypotube, having a material hardness of approximately 72D. The proximal portion  366  transitions at a location  1101   a  to a region having a material hardness of about 55D that transitions at a location  1101   b  to a region having a material hardness of about 35D that transitions at a location  1101   c  to a region have a material hardness of 35D. Similarly, the catheter  200  can include a proximal control element  230  that is a stainless steel ribbon. The proximal control element  230  transitions at a location  1103   a  to a region having a material hardness of 72D that transitions at a location  1103   b  to a region having a hardness of 55D that transitions at a location  1103   c  to a region having a material hardness of about 40D that transitions at a location  1103   d  to a region having a material hardness of about 35D that transitions at a location  1103   e  to a region have a material hardness of 25D that transitions at a location  1103   f  to a region having a material hardness of about 85A that transitions at a location  1103   g  to a region having a material hardness of about 80A. A distal-most region of the catheter advancement element  300  can be formed of Tecothane having a material hardness of about 62A. The locations  1101  of the catheter advancement element  300  and the locations  1103  of the catheter  200  can be staggered such that the locations are off-set from one another. More or fewer material transitions may exist within the catheter advancement element and catheter. 
     The catheter  200  and catheter advancement element  300  can be pre-assembled at the time of manufacturing such that an optimum length of the catheter advancement element  300  extends distal to the distal end of catheter  200  and/or the material transitions are staggered. An optimum length of extension can be such that the entire length of the tapered distal tip of the catheter advancement element  300  extends outside the distal end of the catheter  200  such that the outer diameter of the catheter advancement element  300  where the at least one snug point is located aligns substantially with the distal end of the catheter  200 . This can result in the snug outer diameter region of the elongate body  360  aligned substantially with the distal end of the catheter  200  such that it remains inside the lumen of the catheter  200  and only the tapered region of the distal tip  346  extends distal to the lumen of the catheter  200 . This relative arrangement provide the best arrangement for advancement through tortuous vessels where a lip at the distal end of the system would pose the greatest difficulty. This optimal pre-assembled arrangement can be maintained by a coupler configured to engage with both the proximal control element  230  of the catheter  200  and the proximal portion  366  of the catheter advancement element  300 . The coupler can be used during a procedure. Alternatively, the coupler can be removed prior to a procedure. 
     Different regions of the distal luminal portion  222  and the elongate body  360  of the catheter advancement element  300  can have different bending stiffness. Bending stiffness in N-mm 2  can be measured by assessing the force in Newtons (N) generated upon deflecting the device a certain distance using a particular gauge length.  FIG. 12  is a schematic of a testing system  1205  for assessing bending stiffness or bending force of the various components described herein. The testing system  1205  can vary as is known in the art. The testing system shown in  FIG. 12  includes a pin  1210  forming a fixed point, an anvil  1215  connected by a lever  1222  to a strain gauge  1220  forming a gauge point. The pin  1210  can hold the specimen  1201  to be tested such that a gauge length  1225  of the specimen  1201  is exposed. The anvil  1215  is attached to the strain gauge  1220  via the lever  1222  and can be urged against a portion of the specimen  1201  that is positioned away from the pin  1210  by the gauge length  1225 . The anvil  1215  can displace this portion such that the portion triggers a force measurable by the strain gauge  1220 . The gauge length  1225  can be about 5 mm. The anvil  1215  can have a width, for example, about 2 mm, resulting in a minimum gauge length of about 3 mm. The length can vary depending on the testing system. 
     The bending stiffness (Elastic modulus×area moment of inertia) can be calculated according to the equation EI=FL 3 /3δ, where F is deflection force, L is gauge length, and δ is deflection. For example, using a 3 mm gauge length (L=3 mm) and deflecting a tip of the catheter 2 mm (δ=2 mm), 0.05-0.5 N of force can be generated. In some implementations, the distal-most end of the distal luminal portion can range in bending stiffness between 0.225-2.25 N-mm 2 . As a comparison, the flexibility of the catheter advancement element  300  based on similar deflection measurements and calculations can be as follows. Upon 2 mm deflection and force gauge length of 3 mm, the distal tip of the catheter advancement element  300  can range in bending force between 0.005-0.05 N or can range in bending stiffness between 0.0225-0.225 N-mm 2 . Other procedural catheters described herein can have a similar flexibility ranges providing a variable relative stiffness that transitions from the proximal end towards the distal end of the catheter as will be described elsewhere herein. 
       FIGS. 13A-13B  illustrate, in schematic, points along the catheter system that can be tested using the testing system shown in  FIG. 12 . The points may vary depending on the overall size of the catheter system. The various points of catheter system  150  can be tested when the catheter system  150  is placed in an advancement configuration. The catheter  200  can have a lumen and a distal end having an opening from the lumen  223 . The lumen can have an inner diameter at the distal end that is at least about 0.052″. The tubular portion  360  of the catheter advancement element  300  can have an outer diameter having at least one snug point, where a difference between the inner diameter and the outer diameter at the snug point can be no more than about 0.010″. The at least one snug point can be the point on the catheter advancement element  300  located just proximal to the tapered distal tip  346 . When the catheter advancement element  300  is in the advancement configuration and is positioned coaxially within the lumen of the distal luminal portion  222  of the catheter  200 , the at least one snug point of the tubular portion  360  can substantially align with the distal end of the catheter  200 . When in this configuration, the distal tip portion  346  of the catheter advancement element  300  extends distal to the distal end of the catheter  200 . In some implementations, the difference at the snug point is nor more than about 0.010″ or between about 0.006″ and 0.008″. 
     The tubular portion  360  of the catheter advancement element  300  can have a radiopaque marker band embedded within or positioned over a wall of the tubular portion  360  near the distal end region. A first radiopaque marker band  344   a  can be found at the distal end of the tapered tip portion  346  and a second radiopaque marker band  344   b  can be found at the proximal end of the tapered tip portion  346 . The proximal radiopaque marker band  344   b  can have a proximal edge, a distal edge, and a width between the proximal and distal edges. When in the advancement configuration, the proximal edge of the radiopaque marker band  344   b  can align substantially with the distal end of the distal, catheter portion  222  such that the radiopaque marker band  344   b  remains external to the lumen  223  of the distal, catheter portion  222 . At least a portion of the radiopaque marker band  344   b  can be positioned at the snug point, or the point of the catheter advancement element  300  where the outer diameter is no more than about 0.010″, preferably between about 0.006″ and 0.008″ smaller than the inner diameter of the catheter  200  it is positioned within. The at least one snug point of the tubular portion  360  can be located proximal to the tip portion  346  and can be where the taper of the tip portion  346  substantially ends. This allows for full extension of the tapered tip portion  346  outside the distal end of the catheter  200  and the snug point aligned substantially within the distal opening from the lumen  223  of the distal, catheter portion  222  thereby minimizing any distal-facing lip that might be created by the catheter  200 . The snug point can be located along at least a portion of a length of the outer diameter of the tubular portion  360  that has a length of at least about 5 cm up to about 10 cm, the outer diameter being substantially uniform or non-uniform. 
     The tip portion  346  can include at least three points (see, e.g., P1, P2, P3 of  FIGS. 13A-13B ) spaced along the length of the tip portion. The distal point P1 of the at least three points can be located a distance proximal from the distal-most end of the catheter advancement element  300 . The distance can be a minimum distance needed to create a gauge length for the testing system, for example at least about 3 mm to about 5 mm. An intermediate point P2 of the at least three points can be located a distance proximal to the distal point P1. A proximal point P3 of the at least points can be located a distance proximal to the intermediate point P2. Additional points can be measured on the tapered tip portion  346  and that these are provided as illustrative. 
       FIG. 13A  also illustrates points that can be tested on the system  150  as a whole. The coaxial catheter system  150  in the advancement configuration can include at least two system points along a length of the coaxial system  150 . A first system point S1 of the at least two system points can be located proximal to the distal end of the catheter  200 . The first system point S1 generally takes into account the combined bending force of the catheter  200  and the bending force of the catheter advancement element  300  extending through the catheter  200  (see hashed line in  FIG. 13B ). The first system point S1 can be located proximal to the distal end of the catheter  200  by a gauge length of about 5 mm. A second system point S2 of the at least two system points can be located distal to the first system point S1, for example, by a distance that is at least about 1 mm distal to the distal end of the catheter portion. The second system point S2 can take into account the bending force of the catheter advancement element  300  extending outside the catheter  200 . The second system point S2 is illustrated in  FIG. 13A  as being a different point from P3, but the second system point S2 can be the same as the proximal portion P3 or the same as another point such as P4. The points are provided for illustrative purposes and are not intended to be limiting. Other points are considered herein. 
       FIG. 13B  illustrates theoretical bending forces (N) of a catheter system  150  at various points along a length of the system  150 . The at least three points on the tip portion  346  include P1, P2, P3, and also P4 spaced along the length of the tip portion  346  of the catheter advancement element  300  (represented by a hash-dot-hash line). Each of these points can be located distal to the distal end of the catheter  200  (solid line) when in the advancement configuration and, as such, take into account the bending force of only the catheter advancement element  300 . A fifth point P5 along the length of the catheter advancement element  300  is also shown in  FIG. 13B  and can be at a location positioned inside the catheter  200  when the system  150  is in the advancement configuration. P5, however, takes into account the bending force measurement of only the catheter advancement element  300 . 
     The catheter  200  and catheter advancement element  300  can each have any of a variety of material transitions from distal end towards the proximal end such that when the catheter advancement element  300  is positioned coaxially within the catheter  200  in the advancement configuration, the flexibility of the system  150  transitions linearly from the flexibility of the distal tip of the catheter advancement element  300  towards more proximal regions of the system  150 . In other words, the transition in flexibility from distal tip  346  of the catheter advancement element  300  (positioned external to the distal end of the catheter  200  when in the advancement configuration) to the flexibility of the system  150  as a whole (i.e. catheter advancement element  300  plus the catheter  200 ) can be defined by a slope that includes no significant step increase and is substantially constant. 
       FIG. 13B  illustrates this additive stiffness of the system  150  moving proximally along a length of the system  150 .  FIG. 13B  shows the distal end of the catheter advancement element  300  at P1 has a bending force that is significantly lower than the bending force of the distal end of the catheter  200  through which it extends (e.g. greater than at least about 2×). In some implementations, the bending force of the distal end of the catheter advancement element  300  at P1 is no more than about 0.05 N. The bending force of the catheter advancement element  300  can increase over the length of the distal tip portion  346  to approach the higher bending force of the distal end of the catheter  200 . For example, the distal tip portion  346  can increase in stiffness over its length by at least 2× to approach the higher bending force of the distal end of the catheter  200 . The bending force of the catheter system  150  over its length can have a generally constant slope. This generally constant slope of increasing bending force for the distal tip portion of the catheter advancement element  300  (shown as a hash-dot-hash line in  FIG. 13B ) can transition to a generally constant slope of increasing bending force for the combined system  150  (shown as a hashed line in  FIG. 13B ) such that there is no significant step-up or change in slope between the two. The bending force of the distal tip portion  346  can have a constant slope up to where it transitions to the constant slope of the system  150  as a whole (i.e. additive bending force between catheter  200  and catheter advancement element  300  shown by hashed line). The bending force of the catheter advancement element  300  can continue to increase along a length of the tip portion  346  (e.g. from P1 to P2 to P3 to P4) and then decrease again, for example, proximal to the at least one snug point (e.g. see P5 of  FIG. 13B ). The bending force of the catheter advancement element  300  can decrease proximal to this snug point and remain significantly lower than the bending force of the catheter  200  over a length. In some implementations, a proximal marker band  344   b  identifying the proximal end of the tapered distal tip  346  of the catheter advancement element  300  can locally increase stiffness of the catheter advancement element  300  at this point (e.g. near P3, P4, S2 of  FIG. 13B ) thereby minimizing the step-up in stiffness from the distal tip portion  346  of the catheter advancement element  300  to the distal end of the catheter  200  of the assembled system  150 . Tables 1, 3, 4, and 5 of Example 1 in the Experimental section below describes the bending forces of the various points along a length of different catheter systems. 
     The bending forces along the length of the catheter system  150  can be used to calculate slopes of various segments of the system  150 . A difference between the bending force of P2 and the bending force of P1 divided by the distance between P2 and P1 and/or a difference between the bending force of P3 and the bending force of P2 divided by the distance between P3 and P2 can provide a first flexibility slope. A difference between the bending force of P3 and the bending force of P2 divided by the distance between P3 and P2 can provide a second flexibility slope. An average of the first flexibility slope and the second flexibility slope can define an average tip portion flexibility slope. In some implementations, a fourth distal tip point can be measured such that the average tip portion flexibility slope can take into account this additional segment in calculating the average slope (e.g. segment between P3 and P4). A difference between the bending force of S1 and the bending force of S2 (whether P3 or P4) divided by the distance between S1 and S2 (whether P3 or P4) can provide a first system flexibility slope. 
     In some implementations, the bending force of the distal end of the catheter advancement element  300  can be no more than about 0.05 N. The average tip portion flexibility slope can be at least about 0.005 N/mm. The system flexibility slope can be between about 0.01 N/mm to about 0.03 N/mm. A ratio between the system flexibility slope to the average tip portion flexibility slope can be less than about 25, less than about 15, and preferably less than about 5, such as about 3 down to about 1. The slopes can be substantially constant or close to constant and substantially devoid of step-increases in bending force slope from one segment to the next along the length of the catheter system  150 . In particular, the catheter systems described herein avoid large step-increases in slope from the flexibility of the portion extending distal to the distal end of the catheter and the flexibility of the system as a whole (see also  FIGS. 14A-14D  described below in Example 1). 
     The bending force of the distal tip of the catheter advancement element  300  at P1 can be a fraction of the bending forces of the distal end of the catheter  200 , such as between about 5%-15%. In contrast, the bending force of the snug point on the catheter advancement element  300  near the proximal end of the distal tip  346  (e.g., P3 or P4 or S2) can be about 50%-90% the bending force (or flexibility) of the distal end of the catheter  200 . Thus, the bending force at the snug point of the catheter advancement element  300  can be closer to the bending force of the distal end of the catheter  200 . In some implementations, a portion of the catheter advancement element  300  that is proximal to the tapered distal tip  346  can have a length of about 5 cm to about 10 cm and this portion can have a bending force (or flexibility) that can be about 40%-90% the bending force of the distal end of the catheter  200 . 
     The smooth transition in flexibility over the length of the catheter systems described herein provide optimum navigability without risk of kinking. The catheter systems described herein can have a distal end that is exceptionally flexible and transition towards a proximal end that is exceptionally stiff for optimum torqueing and manipulation. Thus, the bending force of P1 of the catheter advancement element  300  can be a fraction of a bending force of a portion of the proximal portion  366  of the catheter advancement element  300 . The proximal portion  366  can include at least one stiffness point that is within about 20 cm proximal to the tubular portion  360 . The stiffness point can have a bending force that is relatively high, for example, between about 5 N up to about 15 N. A ratio of the bending force of the at least one stiffness point to the first bending force of P1 can be at least about 100, at least about 200, or at least about 300. The proximal portion  366  of the catheter advancement element  300  can be more than 300 times stiffer than the distal tip P1 of the catheter advancement element at P1. The bending force of the catheter advancement element  300  at the distal tip P1 can be no more than about 0.30% of the bending force of the proximal portion  366 , for example between 0.10% to about 0.50%. 
     Methods of Use 
     In an implementation shown in  FIG. 15 , a guide sheath  400  can be deployed such that the distal end of the sheath  400  is advanced to a location in, for example, the internal carotid artery (ICA). The sheath  400  can be advanced to the carotid artery over a guidewire and using an advancement tool. The guidewire and advancement tool, if used, can be removed or exchanged for a smaller guidewire that can be advanced further distal into the cerebral vessels or no guidewire at all as described in more detail below. A first catheter  200   a  can be advanced through the working lumen of the guide sheath  400  and out the distal end. The first catheter  200   a  can have a distal luminal portion  222   a  coupled to a proximal control element  230   a . The proximal control element  230   a  can have a smaller outer diameter compared to the outer diameter of the distal luminal portion  222   a  and can be coupled near a proximal opening from the lumen of the distal luminal portion  222   a . The first catheter  200   a  can be advanced using a catheter advancement element and without the help of a guidewire. The catheter advancement element can aid the advancement of the first catheter  200   a  through the vessel without hanging up on a severe angulation and/or a branching vessel. The first catheter  200   a  can be advanced through the working lumen of the guide sheath  400  and then through the vessel to a first target location. The catheter advancement element  300  can be removed from the lumen of the first catheter  200   a . A second catheter  200   b  having a second catheter advancement element  300  can be advanced through the lumen of the first catheter  200   a . The second catheter  200   b  can also include a distal luminal portion  222   b  coupled to a proximal control element  230   b  near a proximal opening from the lumen of the distal luminal portion  222   b . Similar to the first catheter  200   a , the proximal control element  230   b  of the second catheter  200   b  can have a smaller outer diameter compared to the outer diameter of the distal luminal portion  222   b . The distal end of the second catheter  200   b  can be extended using its proximal control element  230   b  to extend past the distal end of the first catheter  200   a  such that the smaller diameter second catheter  200   b  can reach a target site located to a distal vessel having a narrower dimension than the location of the first catheter  200   a . In this implementation, the first spined catheter  200   a  can act as a support catheter for the second spined catheter  200   b . The second catheter  200   b  can be advanced with or without a guidewire in place. Upon removal of the second catheter advancement element  300 , the inner lumen of the second spined catheter  200   b  can fluidly communicate with the inner lumen of the first spined catheter  200   a  that fluidly communicates with the working lumen of the guide sheath  400  forming a contiguous lumen formed of three sections of increasingly larger dimensions towards the proximal end of the catheter system. For example, the first catheter  200   a  can have a distal luminal portion  222   a  having an inner diameter of about 0.088″ and the second catheter  200   b  can have a distal luminal portion  222   b  having an inner diameter of about 0.070″. More than two nested spined catheters is considered and that their respective inner and outer diameters are sized to receive one another for use together. The corresponding ID and OD of the catheters can be sized such that they slide relative to one another, but still provide sufficient sealing. For example, the contiguous lumens created by the nested arrangement can seal against one another such that aspiration can be drawn through them and an appropriate pressure can be applied through the nested catheters to accomplish, for example, aspiration force sufficient for aspiration embolectomy of distant clots. 
     The proximal end of the nested catheter system can incorporate various gripping, organizing, and attachment features. For example, the guide sheath  400  can include a proximal end coupled to a rotating hemostatic valve  434  that provides access to the working lumen through which the catheters can be inserted. Each of the components of the catheter system can extend proximally out from the valve  434 . For example, the proximal control elements  230   a ,  230   b  of the catheters  200   a ,  200   b  can extend through the valve  434 . Proximal extensions of their respective catheter advancement elements (not shown in  FIG. 15 ) can also extend proximally through the valve  434 . Each of these components in the nesting or telescoping catheter set can incorporate identifying features at their proximal end regions that distinguish them from one another. For example, each proximal control element  230   a ,  230   b  can include a tab  234   a ,  234   b  having a distinguishing shape, color, or other visual characteristic that is unique to that particular catheter. Each proximal control element  230   a ,  230   b  can include a coupling feature, such as a clip or other connector, that organizes the various control elements and prevents entanglement. Nesting catheters and their respective catheter advancement elements can be incorporated within a kit. 
     The systems described herein contemplate using a base sheath and a catheter that can pass through the sheath and having sufficient length to reach the intracerebral target, such as the M1 segment of the middle cerebral artery. The use of a delivery catheter or catheter advancement element with a tapered tip allow for large bore catheter delivery of full-length “over-the-wire” catheters or catheters such as those described herein having a proximal extension. The catheter advancement element can include a pair of radiopaque markers configured to aid the operator in delivery of the system. The distal marker near the distal-most end of the catheter advancement element can be differentiated from the distal marker on the catheter by its characteristic appearance under fluoroscopy as well as by simply jogging back and forth the atraumatic catheter advancement element to understand the relationship and positioning of the catheter advancement element relative to the catheter. The second marker on the catheter advancement element that is proximal to the distal-most tip marker can delineate the taper of the distal tip, i.e. where the outer diameter of the catheter advancement element has a sufficient size to reduce the “lip” of the transition between the catheter advancement element and the catheter through which it is inserted and configured to deliver. The markers aid in positioning the catheter advancement element relative to the distal end of the large-bore catheter such that the tip of the catheter is aligned with the taper of the catheter advancement element and the best alignment is facilitated. 
     The relationship between the distal tip marker of the large-bore catheter is at or ideally just proximal to the taper marker of the catheter advancement element (i.e. the proximal marker identifying the start of the taper) is identifiable with the tandem marker system. The paired elements are in a “tip-to-taper” position. The relative extension between the catheter advancement element and the catheter can be adjusted at the insertion of the system into the RHV. However, the relative extension can become altered with advancement through the sheath or guide catheter. As the system exits the guide catheter, the large bore catheter and the catheter advancement element can be adjusted to that the tip-to-taper position is assumed as the system traverses the often tortuous proximal vessel (e.g. the cervical internal carotid artery) towards more distal targets. The system of the large bore catheter and the catheter advancement element can be locked into their relative extension so that the juxtaposition of the catheter advancement element and the large-bore catheter is maintained. As the large-bore catheter is visualized within the sheath distal end or even slightly beyond the distal end of the sheath, the catheter advancement element can be adjusted to assume the proper position relative to the catheter before advancement resumes. The optimum relative extension between the distal marker of the catheter to the taper marker on the catheter advancement element can be maintained through as much of the anatomy as possible to maximize the delivery capability of the catheter advancement element to navigate both tortuosity and to avoid side branches such as the ophthalmic artery. Once the target is reached, the catheter advancement element is then held fixed and the large-bore catheter then advanced over the catheter advancement element towards the target without crossing the target. 
     The catheter advancement element is designed specifically such that the catheter can be delivered without a need for a guidewire. This ability to deliver without crossing the embolus and without a guidewire is based upon the smooth transitions between the outer diameter of the catheter advancement element and the large-bore catheter as well as the smooth transition in flexibility between the two. When the catheter advancement element is bent into an arc of greater than 180 degrees, the softness and flexibility creates a smooth arc without severe bends or kinks in the geometry of the catheter. Thus, the catheter advancement element seeks the larger lumens and goes where the majority of blood flow goes as opposed to into the smaller branch arteries. The distal tip of the catheter advancement element can facilitates a strong preference to seek out the larger vessels during advancement into the distal vessels. This propensity to stay within the main channel allows for the advancement of large bore catheters without the aid of a guidewire. The propensity to follow the main channels of blood flow aligns with acute ischemic stroke pathophysiology where major emboli tend to follow these same routes to a point where the embolus lodges and interrupts antegrade blood flow. As well, these major channels are often ideal for placement of access catheters as these conduit arteries allow for smaller catheters to pass into specific target arteries for therapeutic intervention. 
     Standard neurovascular intervention, and nearly all endovascular intervention, is predicated on the concept that a guidewire leads a catheter to a target location. The guidewires are typically pre-shaped and often find side-branches of off-target locations where the guidewire will bunch or prolapse causing time-consuming nuisances during interventions that often require repeated redirection of the guidewire by the operator to overcome. In addition, this propensity of a guidewire to enter side-branches can be dangerous. Guidewires are typically 0.014″ to 0.018″ in the neuroanatomy and will find and often traumatize small branches that accommodate this size, which can lead to small bleeds or dissections and occlusion. In a sensitive area like the brain these events can be catastrophic. The tendency of a guidewire to bunch and prolapse can also cause a leading edge to the guidewire that can be advanced on its own or as part of a triaxial system to create dissection planes and traumatize small vessels. 
     In contrast, the catheter advancement element described herein preferentially stays in the larger lumen of a conduit vessel. In the setting of stroke treatment an embolus is driven to certain anatomies because of the blood flow that the arterial system draws in the cerebral anatomy. The catheter advancement element tends to traverse a path identical to the path an embolus will take, particularly an embolus driven from a location such as cardiac or carotid etiology. The catheter advancement element delivers to the largest lumen within the anatomy even in light of the highly tortuous anatomy and curves being navigated. The catheter advancement element can preferentially take the larger lumen at a bifurcation while also following the current of the greatest blood flow thereby maintaining the general direction and angulations of the parent vessel. 
     In viewing the standard anatomy found in the cerebral vasculature, the Circle of Willis is fed by two vertebral and two carotid conduit arteries. As these four arteries are the access points to the cerebral anatomy—the course of the catheter advancement element can be identified and has been validated in standard cerebral anatomy models. In the anterior circulation where the conduit artery point of entry for cerebral endovascular procedures is the internal carotid artery (ICA), the catheter advancement element can guide the large-bore catheter to the M1 segment of the middle cerebral artery (MCA). The very flexible nature of the catheter advancement element combined with the distal flexible nature of most cerebral catheters combine to allow delivery through severe tortuosity. Independent of the tortuous nature of the course of the arteries, the catheter advancement element tends to navigate the turns and deliver to the largest offspring from a parent artery, for example, ICA to M1 segment of the MCA. The M2 level branching of the M1 can be variable, but is often seen to have two major M2 branches (superior and inferior) and, depending on the anatomy, which can vary significantly between patients, may be seen to bifurcate “equally” or “unequally.” If the caliber of the M2 branching is of similar size and angulation, the catheter advancement element may take one of the two branches. If the target for catheter placement is not in a favorable angulation or size of artery, the catheter advancement element may need to be curved (e.g. via shaping of a malleable distal tip) and directed or a guidewire may be used. 
     In some anatomies where the M2 bifurcation is “even” in size, a back-and-forth motion may aid in selecting one branch then the other while still avoid the need or use of a guidewire or a curved distal tip of the catheter advancement element. The back-and-forth motion can allow for the catheter advancement element to be directed into either branch of the M2. The catheter advancement element, even when initially straight, achieves some curvature that aids in directing it into a branch vessel. Thus, when an operator encounters an M2 bifurcation and there is a desire to cannulate either branch of an evenly divided bifurcation, selection of either branch is possible using the catheter advancement element without a guidewire. 
     Thus, main channels such as the ICA, the middle cerebral artery and its tributaries in the anterior circulation will naturally be the pathway of preference for the described catheter advancement element and subsequence large-bore catheter delivery (via access from the ICA). A similar phenomenon can occur in the posterior circulation, which is accessed via the vertebral arteries arising from the subclavian arteries on the right and the left. The catheter advancement element will take the main channels in this circulation as well by traversing the vertebral arteries to the basilar artery and to the major tributaries of the basilar: the posterior cerebral artery and superior cerebellar arteries in the posterior circulation. 
     Navigation using the catheter advancement element can provide maximal deliverability with minimal vascular trauma. Catheters can cause “razoring” effects in a curved vessel because the blunt end of a large bore catheter can tend to take the greater curve in rounding a vessel when pushed by the operator. This blunt end can gouge or “razor” the greater curve with its sharp edge increasing the risk for dissection along an anatomic plane within the multilayered mid- or large-sized artery or vein (see, e.g.  Catheter Cardiovasc. Interv.  2014 February; 83(2):211-20). Placement of a partially-inflated balloon and guidewire through the catheter in this setting can mitigate this “razor” effect by taking the edge off the large-bore catheter. Similarly, the catheter advancement element can serve to minimize the edge of these catheters. Positioning the catheter advancement element within the lumen of the large-bore catheter such that the taper marker of the catheter advancement element is aligned optimally with the distal tip marker of the catheter minimizes the edge and thereby eliminates “razoring” as the large-bore catheter is advanced through turns of the vessel. This is particularly useful for the cerebral anatomy. Stroke treatments are typically needed in regions distal to the carotid siphon, particularly distal to the ophthalmic artery takeoff from the greater curve of the severe tortuosity of the final turn of the carotid siphon “5-turn”, the “anterior genu” of the carotid siphon typically seen as part of the terminal internal carotid artery (ICA). The specifics of the catheter advancement element in proper alignment within the large bore catheter (the “tip-to-taper” position noted by the distal tip marker) relative to the taper marker of the catheter advancement element maximize the likelihood that razoring and hang-up on the ophthalmic artery are avoided. The taper marker of the catheter advancement element can be positioned at or past the take-off of the ophthalmic artery to minimize these deleterious effects and allows the large-bore catheter to pass the ophthalmic artery without incident. In a relatively straight segment, which is common after passing the siphon, the large-bore catheter can be advanced over the catheter advancement element, which serves still as a guiding element to the target. The transition between the catheter advancement element and the distal edge of the large-bore catheter is insignificant, especially compared to the step changes present with a typical microcatheter or guidewire, which do not prevent hand-ups on branches such as the ophthalmic artery. The catheter advancement element allows for maneuvering of the large-bore catheter clear to the face of the embolus without use of a microcatheter or guidewire and without crossing and/or fragmenting the embolus in any way. 
     Conventional techniques to treat AIS whether with a stent retriever, aspiration techniques, or a combination of the two, require crossing the target occlusion with a guidewire and a microcatheter. Crossing of the embolus with a guidewire and then microcatheter can create fragmentation of the occlusion, which can be friable and thrombotic in nature. Thus, an aspiration technique where the embolus is removed en toto without any crossing of the occlusion with any device is advantageous. 
     A stent retriever cannot cross or engage the target occlusion without the “unsleeving” of the stent retriever across the embolus. ADAPT is a frontline aspiration-only technique that avoids crossing the target occlusion with a stent retriever thereby lessening the risk of fragmentation. However, the ADAPT approach still requires crossing the target occlusion with both a guidewire and microcatheter (see Turk et al.  J. Neurointerv. Surg.  2014 Apr. 1; 6(3):231-7). A guide catheter such as Neuron Max (Penumbra) is positioned as distally as possible. A microcatheter and a micro guidewire are advanced through the guide catheter and distal to the occlusion. Using the microcatheter and micro guidewire as support, a reperfusion catheter such as Penumbra 5 Max is advanced to the occlusion. Aspiration is applied until the occlusion corks or wedges within the tip of the reperfusion catheter. The reperfusion catheter is withdrawn and removed while maintaining aspiration and the occlusion within the catheter tip. 
     The systems described herein need not incorporate a guidewire or microcatheter. And, if a guidewire and microcatheter are used, they need not be advanced to cross the target occlusion. Thus, the systems described herein can incorporate relatively large bore catheters that are delivered without disturbing the target occlusion, reducing the risk for stroke and downstream effects from fragmentation of the occlusion, and having improved efficiency. Additionally, the systems described herein are single-operator systems allowing the operator to work at a single RHV and, in the case of spined components, can manipulate all the elements being used to navigate the anatomy with single-handed “pinches.” This is sometimes referred to herein as “monopoint.” 
     As described above, the catheter advancement element can be arranged coaxially within the single lumen of the distal catheter portion forming a coaxial catheter system. The catheter can have a distal, catheter portion and a proximal extension. The distal, catheter portion can have an inner diameter defining the single lumen and a distal end defining a distal opening from the lumen. The proximal extension can be coupled to and extend proximally from the distal, catheter portion. The catheter advancement element can have a tubular, polymeric portion having an inner diameter defining a lumen, a first outer diameter that is substantially uniform along a length, and a radiopaque marker band embedded within or positioned over a wall of the tubular, polymeric portion. The radiopaque marker band can create a second outer diameter that is located distal to and that is larger than the first outer diameter. A tapered, polymeric tip can be located distal to the second outer diameter that terminate at a distal opening from the lumen of the tubular portion. The tapered, polymeric tip can have a length that is between about 0.5 cm up to about 4 cm, for example, between about 1 cm and about 3 cm, or about 2.5 cm. The catheter advancement element can also include a proximal extension coupled to and extending proximally from the tubular, polymeric portion. 
     The coaxial catheter system can have an advancement configuration where the tapered, polymeric tip of the catheter advancement element extends distal to the distal end of the distal, catheter portion and the radiopaque marker band is substantially aligned with the distal end of the distal, catheter portion, and the first outer diameter is positioned within the lumen of the distal, catheter portion. 
     The operator can work from a single RHV of the guide sheath to manipulate both the catheter and the catheter advancement element. The coaxial catheter system can be advanced together, maintaining the advancement configuration. The relative relationship between the radiopaque marker band on the catheter advancement element and a second marker band near the distal end of the catheter can aid in maintaining the advancement configuration during delivery. The operator can hold the two in relative position to one another using a single pinch and advance this coaxial catheter system. 
     The coaxial catheter system can be advanced as far distal as possible until the catheter advancement element is positioned at the face of the embolus. The proximal extension of the catheter advancement element can be held “fixed” at the RHV and the catheter advanced over the catheter advancement element so that the distal end of the distal, catheter portion is advanced over the catheter advancement element to the face of the embolus. No guidewire or microcatheter is needed to advance the coaxial catheter system to the face of the embolus. Importantly, no devices need cross the embolus. 
     The catheter advancement element can then be withdrawn from the coaxial catheter system and removed from the single RHV while the catheter is held in position at the face of the embolus. The system is ready for initiation of aspiration as will be described in more detail below. 
     In some implementations, the first coaxial catheter system may not be able to reach the face of the embolus. Thus, the catheter advancement element of the coaxial catheter system can be removed leaving the lumen of the distal, catheter portion open for advancing a second coaxial catheter system through the first catheter. The second coaxial catheter system can include a second catheter and a second catheter advancement element and be advanced similarly as the first coaxial catheter system (i.e. via monopoint manipulations), but through the first catheter acting as a support catheter. 
     Once the catheter is in position at the face of the embolus, the RHV can be sealed and aspiration initiated through the same RHV such as via a side-arm. The embolus can be aspirated from the body through the catheter via the aspiration pressure alone. Alternatively, the catheter having the embolus corked at the distal opening of the catheter can be slowly withdrawn, for example towards a lumen of a larger bore catheter, as aspiration is applied to effect embolus removal. 
     Withdrawing an embolus corked at the distal opening of the catheter back to the distal opening of the guide sheath can increase the risk of fragmentation and embolization depending on the distance it must be withdrawn before being fully encapsulated within a lumen. Thus, it is desirable to use a nested system of successively larger catheter sizes to create a family of aspiration catheters all working from a single point of operation via the single RHV. This allows for the smallest bore catheter advanced most distal to withdraw only a short distance into a larger bore catheter, which in turn can suction the embolus en toto, or, if needed, be withdrawn another short distance into a larger bore catheter that can suction the embolus from the body. The likelihood of the captured clot from fragmenting is thereby reduced and the likelihood of the clot being aspirated en toto is increased. 
     The guide sheath can be a large 7F sheath configured to receive a larger bore catheter having an inner diameter of approximately 0.088″, which in turn can receive an intermediate bore catheter having an inner diameter of approximately 0.070″, which in turn can receive a smaller bore catheter having an inner diameter of approximately 0.054″. In some implementations, the system can include a larger bore catheter having an inner diameter of approximately 0.087″ to about 0.089″, a smaller bore catheter can be inserted within the larger bore catheter and having an inner diameter of about 0.070″ to about 0.073″ and a second smaller bore catheter can be inserted through the first smaller bore catheter that has an inner diameter of about 0.052″ to about 0.055″. Any of a variety of sizes is considered herein and that these examples are not intended to be limiting. 
     Although the larger bore catheter can more efficiently capture the embolus by aspiration, there is a possibility that the substantially larger dimension of the larger bore catheter can prevent it being advanced to reach the embolus without additional manipulations. In some implementations, a smaller bore catheter extending through the lumen of the larger bore catheter can be advanced to the face of the embolus. The smaller bore catheter (and its catheter advancement element) can be held fixed such that the larger bore catheter is advanced over the smaller bore catheter as distal as possible. If the larger bore catheter crawling over the smaller bore catheter is able to reach the embolus in this way, the catheter advancement element can be removed from the smaller bore catheter, the RHV closed to a seal, and aspiration initiated. Both the distal end of the smaller bore catheter and the distal end of the larger bore catheter are positioned at the face of the embolus. The smaller bore catheter can be removed from the system under continuous aspiration. If free flow is established with aspiration (e.g. as seen by the flow into the vacuum source), the operator can leave the larger bore catheter in place and consider whether to perform angiography to confirm establishment reconstitution of antegrade flow and resolution of the obstruction after insuring that the large-bore catheter is completely free of debris with aggressive aspiration and flushing. If free flow is not established, the aspiration can be continued and removal of the smaller bore catheter can be followed by removal of the larger bore catheter thereby removing the embolus from the body using the higher flow and forces generated by the larger bore catheter under full aspiration without the smaller bore catheter positioned within its lumen obstructing flow. A single, shared aspiration source may be used during removal of both the smaller bore and the larger bore catheters. 
     If the larger bore catheter is not able to reach the target embolus by crawling over the smaller bore catheter, the larger bore catheter and the catheter advancement element for the smaller bore catheter can be held fixed at the RHV such that the smaller bore catheter can be advanced between them to the face of the embolus. The smaller bore catheter can then provide a rail for another attempt at advancing the larger bore catheter towards the face of the embolus. These steps can be repeated in sequence to “inch” the larger bore catheter toward the embolus until both the distal end of the smaller bore catheter and the distal end of the larger bore catheter are positioned near the face of the embolus such that aspiration embolectomy can be performed through them. 
     The smaller bore catheter can be attached to the embolus and withdraw the embolus towards the larger bore catheter. Thus, where the embolus may be too large to fully enter the lumen of the smaller bore catheter it may be engulfed or retrieved by the lumen of the larger bore catheter. The smaller bore catheter having embolus attached to the distal end by aspiration can be withdrawn followed immediately by capture and withdrawal of the embolus via the larger bore catheter under aspiration. 
     Tension can get stored in a catheter system advanced through tortuous cerebral anatomy. Downward and lateral forces may be created on the supporting catheter system as the distal tip of the catheter meets resistance. The entire system can propel forward as the distal tip of the catheter is released past these points of resistance. The resistance can occur at the tortuosity in the vessel or at obstructions or bifurcations or due to preexisting implants or other causes. Typically, the tension is stored without loss of position. The resultant effect is a back-and-forth type movement of the system to reach the target and the steady storage of tension in the guide sheath as it is relentlessly pushed downward (i.e. proximally back against the direction of insertion). 
     In the case of aspiration systems for stroke, the same stored tension can occur with advancement of a larger bore catheter (e.g. an 0.088″ ID catheter). As the larger bore catheter develops stored tension and the operator tries to advance it to the target embolus (e.g. in the M1 branch of the MCA), the larger bore catheter traverses the anatomy in a “greater curve to greater curve” manner introducing an amount of slack in the system. The stored tension creates the resistance that causes a catheter to jam at a point and not reach a target. Should the larger bore catheter not reach the target, a smaller bore catheter can be advanced to reach the embolus due to smaller diameter and better deliverability. The smaller bore catheter can navigate the stored tension and also navigate the anatomy in a “greater curve to greater curve” manner as the larger bore catheter did. The smaller bore catheter can anchor onto the embolus via the aspiration pressure applied through the system. The smaller bore catheter can be fixed at the point of occlusion and aspiration turned on to maximum (e.g. via a pump). This affixes or anchors the smaller bore catheter to the embolus such that the operator can “straighten” the entire system and thereby apply a proximally-directed force on the smaller bore catheter to remove slack relative to the surrounding anatomy while the distal end of the smaller bore catheter remains anchored onto the occlusion. The catheters once the slack is reduced now traverse the anatomy in a “lesser curve to lesser curve” manner rather than a “greater curve to greater curve” manner thereby straightening their course relative to the surrounding anatomy. A straightened course allows the larger bore catheter to be advanced over the anchored smaller bore catheter such that its distal end can also reach the embolus target. Aspiration and anchoring through the smaller bore catheter is maintained and the operator creates a straighter, tension-free course to “rail” the larger bore catheter through it over the smaller bore catheter. Once the larger bore catheter is in place—even if the larger catheter does not reach the embolus—substantial embolic protection is afforded and off-target-embolization avoided, particularly if the larger bore catheter is placed distal to the nearest bifurcation proximal to the embolus site. 
     Once the larger bore catheter is in position, the smaller bore catheter extending through it can be withdrawn. Aspiration may still be applied by the single aspiration source and the seal between the corked embolus maintained as the smaller bore catheter is withdrawn towards the distal end of the larger bore catheter. Once the smaller bore catheter is pulled into the distal end of the larger bore catheter, the aspiration pressure may be automatically turned on, transferred, or increased within the larger bore catheter such that the embolus is captured within the lumen of the larger bore catheter. Due to the larger inner diameter, the embolus under continuous aspiration pressure via the single, shared aspiration source will likely evacuate the embolus. The smaller bore catheter and the larger bore catheter can both be withdrawn from the system. 
     Many operators prefer to assemble coaxially the devices to be used in sequence. An interrelated variant of an aspiration-only thrombectomy method involves preassembling a larger bore catheter and a smaller bore catheter so that they may be advanced together through the base sheath with a catheter advancement element sized for the smaller bore catheter. Each of the methods can be performed without a guidewire or microcatheter and without any component being advanced distal to the embolus. The smaller bore catheter and matching catheter advancement element can be preassembled outside the patient coaxially within the larger bore catheter. 
       FIG. 16  illustrates a method of aspiration-only thrombectomy using a system of nested aspiration catheters. A base sheath is inserted into a vessel (Box  1302 ). The vessel can be the common femoral artery and the base sheath may be an 8 Fr long sheath inserted over a guidewire. The base sheath is advanced until a distal end region of the base sheath is positioned distal to the common carotid artery such as within the ICA (Box  1304 ). The base sheath may be back bled and placed on continuous flush with an RHV. A navigation catheter may be advanced to the ICA over a 0.035″ guidewire. The base sheath can be advanced over the guidewire until its distal tip is in the mid- to lower cervical ICA. The preassembled system of devices (e.g., catheter advancement element CAE, smaller bore aspiration catheter SBC, and larger bore aspiration catheter LBC) is inserted as a unit into the base sheath (Box  1306 ) and advanced out through the distal end of the base sheath. The smaller bore catheter SBC may be an 0.070″ aspiration catheter having a suitably sized catheter advancement element CAE positioned within its lumen. The larger bore catheter LBC may be an 0.088″ aspiration catheter configured to receive the 0.070″ aspiration catheter. The catheter advancement element CAE and the smaller bore catheter SBC may be advanced to the site of the occlusion while the larger bore catheter LBC is maintained at a proximal location. In some implementations, the catheter advancement element CAE of the smaller bore catheter SBC may reach the target location. The catheter advancement element CAE can be held fixed (Box  1308 ) and its smaller bore catheter SBC advanced over it to the embolus face (Box  1310 ). In some implementations, the larger bore catheter LBC may be advanced over the smaller bore catheter SBC either to the occlusion or to a more proximal position where it approximates the caliber of the vessel lumen. 
     The catheter advancement element CAE is removed while the smaller bore catheter SBC is held fixed (Box  1312 ). The RHV is sealed and aspiration initiated via the single vacuum source for the system (Box  1314 ). The vacuum source can be an electric pump coupled to a port on the RHV of the base sheath. The inner lumen of the smaller bore catheter SBC fluidly communicates with the inner lumen of the larger bore catheter LBC that fluidly communicates with the working lumen of the base sheath. A contiguous lumen is formed of the three sections of increasingly larger dimension toward the proximal end of the catheter system. A first seal can be formed between an outer diameter of the smaller bore catheter SBC and an inner diameter of the larger bore catheter LBC. A second seal can be formed between an outer diameter of the larger bore catheter LBC and the base sheath. The smaller bore catheter SBC is left in place for a period (e.g. greater than about 90 seconds) and aspiration tubing assessed for free flow (Box  1316 ). If after this period the aspiration tubing has not shown free flow, the smaller bore catheter SBC is slowly withdrawn under aspiration into the lumen of the larger bore catheter LBC, which is held in place (Box  1318 ). Aspiration pressure can be applied through the lumen of the smaller bore catheter SBC for a time sufficient to anchor the embolus to the distal tip of the SBC. Withdrawal of the smaller bore catheter SBC into the larger bore catheter LBC can automatically reduce or at least partially release the first seal and automatically increase or transfer the aspiration pressure to a distal tip of the larger bore catheter LBC. The embolus is captured by the distal end or within the lumen of the larger bore catheter LBC. The aspiration forces being applied by the distal tip of the smaller bore catheter SBC onto the embolus during the withdrawal can be transferred or handed off to the distal tip of the larger bore catheter LBC as the distal tip of the smaller bore catheter SBC withdraws proximally into the lumen of the larger bore catheter LBC (Box  1320 ). Aspiration is continued for another period (e.g., greater than about 90 seconds) (Box  1322 ). If there is minimal flow through the aspiration tubing then the larger bore catheter LBC is slowly withdrawn (Box  1324 ). 
     This withdrawal of the inner catheter into the outer catheter can automatically transfer of the aspiration forces on the embolus to the larger bore catheter LBC. The larger bore catheter LBC can exact a greater capture force on the embolus compared to the capture force capable of the smaller bore catheter SBC. The transfer to the greater capture force can occur while applying the same vacuum from the single vacuum source coupled at a single attachment on the base sheath. In other words, greater capture forces are applied to the embolus as the distal tip of the smaller bore catheter SBC is withdrawn into the lumen of the larger bore catheter LBC without ever changing the vacuum flow rate at the vacuum source coupled to the base sheath. There is an effective switching from a lower capture force applied on the embolus by the smaller bore catheter SBC to the higher capture force applied on the embolus by the larger bore catheter LBC due to the act of withdrawing the smaller bore catheter SBC inside of the larger bore catheter LBC. This provides a greater ease of use and convenience to the user in addition to a greater effective thrombectomy provided by the larger bore catheter LBC. The telescopic design of the system and automatic switching provides uninterrupted aspiration force on the embolus to ingest any fragments and reduce the chance of incomplete clot ingestion and embolism. 
     The catheter system can include a single source of vacuum connected to the contiguous lumen formed by the nested components. The single source of vacuum provides the aspiration pressure within the distal-most tip of the smaller bore catheter SBC, which is automatically turned on, transferred, or increased within the larger bore catheter LBC upon withdrawal of the smaller bore catheter SBC into the larger bore catheter LBC. Withdrawing the smaller bore catheter SBC with respect to the larger bore catheter LBC can automatically reduce or at least partially release the seal formed between the OD of the smaller bore catheter SBC and the ID of the larger bore catheter LBC as the distal tip of the smaller bore catheter SBC passes into the distal tip of the larger bore catheter LBC. The aspiration pressure applied through the lumen of the smaller bore catheter SBC to anchor or capture the embolus at the distal tip of the smaller bore catheter SBC can be maintained upon withdrawal into the larger bore catheter LBC and need not be released or reduced to no pressure. Rather, the greater aspiration forces of the larger bore catheter LBC dominate once the smaller bore catheter SBC is withdrawn within the lumen of the larger bore catheter LBC so that the aspiration pressure to anchor or capture the embolus is now coming primarily from the distal tip of the larger bore catheter LBC. Thus, withdrawal of the smaller bore catheter SBC automatically “hands off” the embolus to the larger bore catheter LBC and increases aspiration pressure or capture force applied to the embolus without any manipulations or adjustments of the vacuum source attached to the base sheath. 
     The automatic reduction or at least partial release of the seal and/or increase in aspiration forces on the embolus by the larger bore catheter LBC can occur when the distal tips of the telescoping catheters are substantially aligned or at least about within 5 mm of each other. The automatic reduction or at least partial release of the seal and/or increase in aspiration forces on the embolus by the larger bore catheter LBC can occur when the distal tip of the smaller bore catheter SBC has been withdrawn into the larger bore catheter LBC at least about 5 mm and no more than about 20 mm. The seal between the inner diameter of the larger bore catheter LBC and the outer diameter of the smaller bore catheter SBC can be automatically reduced or at least partially released during withdrawal of the smaller bore catheter SBC as the proximal sealing zone of the smaller bore catheter SBC slides proximally out of the proximal opening of the larger bore catheter LBC and thus, out of sealing engagement with the inner diameter of the larger bore catheter LBC. In some implementations, the seal can automatically at least partially release upon exit of a proximal end length of the distal luminal portion of the smaller bore catheter SBC through the proximal opening of the distal luminal portion of the larger bore catheter LBC. 
     Withdrawal and at least partial release of the seal can increase a minimum gap between the OD of the smaller bore catheter SBC and the ID larger bore catheter LBC. The minimum gap before withdrawal can be less than 0.005″ and after withdrawal can be greater than 0.005″. As described elsewhere herein, the aspiration catheters may include a proximal sealing zone that has an increased outer diameter (OD) compared to the OD of a remainder of the tubular portion of the aspiration catheter. The length of this proximal sealing zone can vary and can vary depending on the overall length of the tubular portions of the catheters. In some implementations, the smaller bore catheter SBC can include a distal tubular portion that is about 60-75 cm and a proximal sealing zone that is adjacent the proximal opening and less than about 15 mm and the larger bore catheter LBC can include a distal tubular portion that is about 60-75 cm and a proximal sealing zone that is adjacent the proximal opening and less than about 15 mm. The proximal end region of the distal luminal portion of the aspiration catheters described herein can be skived or angled in an oblique manner near where the luminal portion and the proximal control element meet. In an implementation, the proximal sealing zone can extend from a location on the luminal portion that is immediately adjacent the proximal opening skive near where the luminal portion is fully tubular in shape up to about 15 mm away from that location. In another implementation, the proximal sealing zone can be located some distance distal of the proximal opening, such as about 5-30 mm distal of the proximal opening. 
     The automatic release of the seal can occur when the distal end of the smaller bore catheter SBC has been withdrawn into the larger bore catheter LBC so that the distal ends are substantially aligned. The release of the seal can occur due to the seal moving from the lumen of the larger bore catheter portion out of the proximal opening of the lumen during withdrawal of the smaller bore catheter LBC. Further, the release of the seal can occur when the distal ends of the catheters are within about 5 mm of each other or when the distal end of the smaller bore catheter SBC has been withdrawn into the larger bore catheter LBC at least about 5 mm and no more than about 20 mm proximal to the distal end of the larger bore catheter LBC. The lengths of the two catheters&#39; distal luminal portions and the location of the seal as well as the length of the seal are arranged such that the seal automatically at least partially releases from the larger bore catheter LBC proximal opening as the distal end of the smaller bore catheter SBC passes into the distal end of the larger bore catheter LBC. 
     An outer diameter of the distal luminal portion of the smaller bore catheter SBC and an inner diameter of the larger bore catheter LBC can be configured to provide a seal having a seal length and a seal location. The lengths of the distal luminal portions of the smaller bore catheter SBC and the larger bore catheter LBC as well as the seal length and the seal location can be arranged to automatically at least partially release the seal as the distal end of the smaller bore catheter SBC passes or is withdrawn into the distal end of the larger bore catheter LBC. The seal can be provided by an enlarged outer diameter section of the smaller bore catheter SBC as discussed elsewhere herein. The seal length can be between about 2 mm and 30 mm and the seal location can be located within about 20 mm of the proximal opening of the larger bore catheter LBC. The lengths of the two catheters&#39; distal luminal portions can be the same or can be different by no more than about 5 cm. 
     The seal can automatically at least partially release upon exit of a proximal end length of the distal luminal portion of the smaller bore catheter SBC through the proximal opening of the distal luminal portion of the larger bore catheter LBC. This proximal end length can vary. The proximal end length can be the same as the seal length or can be less than the seal length. 
     Where the nested catheter system is described herein as having a larger bore catheter and a smaller bore catheter or an inner catheter and an outer catheter used together to capture an embolus, it should be appreciated that the nested catheter system can have more than just the two catheters. For example, a third catheter can be positioned within the lumen of the smaller bore catheter positioned inside the lumen of the larger bore catheter. The automatic transfer of capture forces between two catheters can occur between the third catheter and the smaller bore catheter as well as between the smaller bore catheter and the larger bore catheter. 
     As discussed above, the method can be performed without a guidewire or microcatheter and without any component being advanced distal to the embolus. However, the method can include the use of a guidewire (whether in the one-at-at-time approach or the preloaded approach). The guidewire can be positioned within the catheter advancement element and exit the RHV either directly or out the hub of a delivery catheter designed to have a guidewire its full-length. The guidewire can be advanced to the target and then held in position with the lead coaxial system is advanced over it. The guidewire can also be advanced to a fixed distance ahead of the lead coaxial system so that it “leads” the advancement of the entire system of components. The guidewire can also be positioned within the lead coaxial system, but not leading it. Rather, the guidewire can be withdrawn yet available should a guidewire be needed to advance the lead coaxial system to the target. The guidewire usage may be adjusted based upon operator preference, anatomic challenges, clinical features of the patient, etc. 
     The catheter advancement element allows for the delivery of much larger size catheters to the levels of the cerebral anatomy typically seen in large vessel occlusion in acute ischemic stroke. As an example, the target embolus can be in the M1 segment of the middle cerebral artery, which can accommodate a larger bore catheter having an ID much greater than 0.050″, such as an 0.088″ inner diameter catheter that can have an outer diameter of 2.6 mm or greater. A typical M1 segment as measured from a population of computed tomographic images of stroke patients is 3.1±0.4 mm suggesting a distribution where 95% of the population will accommodate a 2.6 mm catheter (see Rai A. T. et al. “Cerebrovascular geometry in the anterior circulation: an analysis of diameter, length and the vessel taper”  JNIS  2013; 5:371-375). As the size of the catheter gets closer and closer to the size of the offending embolus, the likelihood that the aspiration catheter will engulf and completely evacuate the embolus into the syringe or pump canister increases. This will also increase the likelihood the aspiration catheter will be successful in the primary removal of the embolus and recanalization of the artery rather than the embolus “corking” in the catheter tip. Withdrawing a catheter corked with an embolus has the drawbacks of potential fragmentation and distal embolization within the vessel as the exposed embolus is traumatized during withdrawal through narrow vessels and tortuous bends. 
     Catheters having an 0.088″ inner diameter can be navigated through tortuous anatomy, for example, with the help of the catheter advancement element described herein, to reach an embolus having a diameter that approximates the inner diameter of the catheter. Aspiration applied through these large-bore catheters can capture and fully engulf the embolus more quickly and with fewer drawbacks of fragmentation and distal embolization. 
     Emboli found in stroke can be heterogeneous from patient to patient. The ability of a catheter to fully engulf an embolus in the stroke setting may vary depending on the consistency of the embolus and patient conditions. The likelihood the catheter will successfully engulf the embolus increases for the larger bore sized catheters assuming the distal end of the catheter can be brought into close approximation with the embolic target. If the distal end of the catheter is too far away from the embolus target, aspiration through the catheter will simply draw in blood from the intrinsic antegrade flow proximal to the embolic occlusion. The catheter advancement element aids in advancing larger bore catheters that come close in size the target vessel directly to the face of the embolus thereby improving recanalization rates with a variety of embolic types due to the increased likelihood of complete engulfment of the clot and any embolic fragments that would otherwise travel downstream. The catheters described herein can include a proximal control element (see, for example, proximal control element  230  in  FIG. 3 ) and thus, undergo a significant step-up in inner diameter moving proximally along the system. The aspiration performance is greatly improved compared to standard catheters in which no significant step-up in inner diameter occurs, which can further contribute to increased likelihood of full engulfment (see, e.g., Arslanian R. A. et al. “Pump or Syringe? Evaluation of Aspiration Efficacy with Neurovascular Catheters.” SNIS, 2018). Additionally, standard catheters in which no step-up in inner diameter occurs do not provide the automatic switching of aspiration forces at the distal tip when nested together. 
     In some implementations, the aspiration catheter systems described herein can be coupled by a vacuum line to a single vacuum source  505 , for example, a single vacuum source coupled at a single attachment to the base sheath for the system. It should also be appreciated the multiple vacuum sources can be applied to the system, if desired. The vacuum source  505  can vary in its configuration. The vacuum source  505  can be an active source of aspiration such as an aspiration pump, a regular or locking syringe, a hand-held aspirator, hospital suction, or the like, configured to draw suction through the working lumen of the base sheath. As described above, the RHV of the base sheath may be sealed and aspiration initiated via a side arm of the RHV. The side arm of the RHV can be coupled to one of any of a variety of vacuum sources. In a preferred implementation, the vacuum source  505  is an aspiration pump such as the Gomco  405  Tabletop Aspirator (Allied Healthcare Products, Inc., St. Louis, Mo.). The aspiration pump may incorporate a programmable pump motor, such as motor controlled by a pulse width modulation, a brushless motor and controller or similar controllable motors. In another preferred implementation the vacuum source  505  is a locking syringe, such as a VacLok type syringe. Material aspirated from the aspiration catheter system can be collected within a proximal vacuum canister connected to the vacuum line. In some implementations, the proximal vacuum canister can itself be the vacuum source  505 , such as a barrel of a locking syringe. In other implementations, the proximal vacuum canister is coupled to the vacuum source  505  via tubing. 
     Aspiration forces may be applied to the side arm of the RHV creating a single point of aspiration for both the smaller bore catheter SBC withdrawal and later for removal of the larger bore catheter LBC as well as for clearing the sheath with aspiration as a final cleansing step. 
     The spined catheters described herein can transmit aspiration forces through a stepped aspiration column that includes the distal catheter inner diameter that steps up to the larger inner diameter of the more proximal access sheath. For example, a distal catheter having an 0.070″ inner diameter (ID) can extend beyond the distal end of a sheath having an 0.088″ inner diameter. The ID of the aspiration column can step up from 0.070″ to 0.088″. The much larger ID of the proximal aspiration column can change the transmission of forces to the embolus. In contrast, standard catheters undergo no step-up in inner diameter along the aspiration column. The fixed ID for the entire length in a standard catheter system results in a muted transmission of aspiration forces where the walls of the catheter create resistance. 
     In the case of nested catheters described above, a smaller bore catheter (e.g., 0.070″ ID) having a reduced OD proximal control element can telescope from a larger bore catheter (e.g., 0.088″ ID) also having a reduced OD proximal control element can telescope from an even larger base sheath (e.g., 0.106″ sheath). The much larger conduit proximal to the narrower conduit more effectively transmits the capture force of the aspiration further down the column before the narrower conduit is reached. This results in a more direct communication of the capture force to a point that represents the majority of the length of the aspiration column before narrowing to the smaller ID telescoping segment. 
     The emboli can be engulfed initially into the catheter tip during aspiration for stroke thrombectomy/embolectomy. The nature of the emboli varies widely. A softer, more “thrombotic” or “fresh” clot is generally friable and may dissociate into multiple fragments and evacuate in a matter of seconds through the thrombectomy catheter. If the clot is more “organized” or more like “chewing gum” in nature, the clot more commonly will lodge in the lumen of the thrombectomy catheter. The clot may not progress down the catheter or may progress very slowly at a certain velocity. A slow moving, organized embolus may take a matter of minutes to traverse a long catheter length. A stepped aspiration column can help to minimize the duration of embolus travel through the catheter. The majority of the length of the aspiration column will likely be the larger bore size in a system of spined catheters. The slowly traversing embolus will almost instantly evacuate at the transition to the step-up in inner diameter within the system (i.e. where the distal luminal portion ends and the proximal control element begins) once relieved of the side wall friction in the smaller inner diameter of the telescoping extension catheter. The time of evacuation will therefore be shortened compared to conventional, full length catheters as the embolus will traverse a much shorter distance at the slow pace before reaching the point of rapid evacuation into the pump canister or syringe barrel. The time of full evacuation is a key parameter to be optimized during a procedure. If the clot is fully engulfed within the catheter, but not traversing through the catheter quickly, the surgeon may have little to no feedback. For example, the surgeon may be unable to see that the clot is removed without the use of time-consuming imaging techniques. 
     Delivery of larger bore catheters with maximum inner diameter aided with the catheter advancement element described herein to reach the face of the clot facilitates complete engulfment. The catheter best suited to remove an embolus is one that approximates the size of the vessel within which the embolus is found. An additional benefit of choosing a catheter that approximates the size of the vessel is that the distal tip of the catheter will be more centered within the lumen of the vessel. When aspiration is performed, the embolus is positioned more in-line with the bore of the catheter for improved retrieval during aspiration. The catheter advancement elements described herein ensure these larger bore catheters having a size that approximates the size of the vessel can be advanced as far distal as possible to the face of the clot. 
     Materials 
     One or more components of the catheters described herein may include or be made from a variety of materials including one or more of a metal, metal alloy, polymer, a metal-polymer composite, ceramics, hydrophilic polymers, polyacrylamide, polyethers, polyamides, polyethylenes, polyurethanes, copolymers thereof, polyvinyl chloride (PVC), PEO, PEO-impregnated polyurethanes such as Hydrothane, Tecophilic polyurethane, Tecothane, PEO soft segmented polyurethane blended with Tecoflex, thermoplastic starch, PVP, and combinations thereof, and the like, or other suitable materials. 
     Some examples of suitable metals and metal alloys include stainless steel, such as 304V, 304L, and 316LV stainless steel; mild steel; nickel-titanium alloy such as linear-elastic and/or super-elastic nitinol; other nickel alloys such as nickel-chromium-molybdenum alloys (e.g., UNS: N06625 such as INCONEL® 625, UNS: N06022 such as HASTELLOY® C-22®, UNS: N10276 such as HASTELLOY® C276®, other HASTELLOY® alloys, and the like), nickel-copper alloys (e.g., UNS: N04400 such as MONEL® 400, NICKELVAC® 400, NICORROS® 400, and the like), nickel-cobalt-chromium-molybdenum alloys (e.g., UNS: R30035 such as MP35-N® and the like), nickel-molybdenum alloys (e.g., UNS: N10665 such as HASTELLOY® ALLOY B2®), other nickel-chromium alloys, other nickel-molybdenum alloys, other nickel-cobalt alloys, other nickel-iron alloys, other nickel-copper alloys, other nickel-tungsten or tungsten alloys, and the like; cobalt-chromium alloys; cobalt-chromium-molybdenum alloys (e.g., UNS: R30003 such as ELGILOY®, PHYNOX®, and the like); platinum enriched stainless steel; titanium; combinations thereof; and the like; or any other suitable material and as described elsewhere herein. 
     Inner liner materials of the catheters described herein can include low friction polymers such as PTFE (polytetrafluoroethylene) or FEP (fluorinated ethylene propylene), PTFE with polyurethane layer (Tecoflex). Reinforcement layer materials of the catheters described herein can be incorporated to provide mechanical integrity for applying torque and/or to prevent flattening or kinking such as metals including stainless steel, Nitinol, Nitinol braid, helical ribbon, helical wire, cut stainless steel, or the like, or stiff polymers such as PEEK. Reinforcement fiber materials of the catheters described herein can include various high tenacity polymers like Kevlar, polyester, meta-para-aramide, PEEK, single fiber, multi-fiber bundles, high tensile strength polymers, metals, or alloys, and the like. Outer jacket materials of the catheters described herein can provide mechanical integrity and can be contracted of a variety of materials such as polyethylene, polyurethane, PEBAX, nylon, Tecothane, and the like. Other coating materials of the catheters described herein include paralene, Teflon, silicone, polyimide-polytetrafluoroetheylene, and the like. 
     EXAMPLES 
     The catheter systems described herein were tested using a system such as that shown in  FIG. 12  for measuring bending forces and the data is provided below. A first catheter system incorporated a catheter advancement element having an outer diameter sized to extend through a catheter having an inner diameter of about 0.054″ (Version A). A second catheter system incorporated a catheter advancement element having an outer diameter sized to extend through a catheter having an inner diameter of about 0.070″ (Versions B1 and B2). A third catheter system incorporated a catheter advancement element having an outer diameter sized to extend through a catheter having an inner diameter of about 0.088″ (Version C). 
     At least three points along the tapered tip portion of the catheter advancement elements were tested (see P1, P2, P3, P4 of  FIGS. 13A-13B ). The distal point P1 of the at least three points was located a distance of about 5 mm proximal from the distal-most end of the catheter advancement element. The second point P2 of the distal tip portion was an intermediate point of the at least three points located a distance proximal from the distal point P1. For Version A, the second point P2 was about 12 mm proximal from the distal-most end of the catheter advancement element. For Versions B1, B2, and C, the second point P2 was about 20 mm proximal from the distal-most end of the catheter advancement element. A proximal point P3 of the at least points can be located a distance proximal from the intermediate point P2 and was about 13 mm proximal from the distal-most end of the catheter advancement element for Version A and about 25 mm proximal for Versions B1, B2, and C. Some catheter system versions included a fourth point P4. P4 was measured for both Versions B1, B2, and Cat about 27 mm, 27 mm, and 28 mm, respectively. 
     The catheter systems were placed in the advancement configuration and soaked in a bath at 37° C. for a period of time prior to testing. The advancement configuration for the experiment is when the catheter advancement element is positioned coaxially within the lumen of the distal catheter portion of the catheter such that the at least one snug point of the tubular portion is substantially aligned with the distal end of the catheter and the distal tip portion of the catheter advancement element extends distal to the distal end of the catheter. The region near P3 on the catheter advancement element formed a snug point with the catheter where the difference between the inner diameter and the outer diameter at the snug point was no more than about 0.010″. The difference was about 0.006″ for Version A and about 0.008″ for Versions B1 and C. Each of points P1, P2, P3, and P4 (where appropriate) were located on the tip portion of the catheter advancement element and extended distal to the distal end of the catheter. 
     A fifth point P5 was measured for all versions providing a bending force for the catheter advancement element only proximal to the snug point (see  FIG. 13B ). The fifth point P5 was at a location positioned inside the catheter when the system is in the advancement configuration, however, P5 took into account the bending force measurement of only the catheter advancement element. For Version A, this fifth point P5 was measured about 16 mm proximal to the distal terminus of the catheter advancement element. For Versions B1 and C, the fifth point P5 was about 30 mm proximal to the distal terminus of the catheter advancement element. When the components of the catheter system are in the advancement configuration, this fifth point P5 on the catheter advancement element can be located inside the catheter. Thus, P5 was measured on the catheter advancement element without the catheter being present. 
     At least two points along the catheter system were also tested to measure bending force of the system while in the advancement configuration (see S1 and S2 of  FIGS. 13A-13B ). The first system point S1 took into account the combined bending force of the catheter and the bending force of the catheter advancement element extending through the catheter and is represented by a hashed line in  FIG. 13B . The first system point S1 of the at least two system points was located proximal to the distal end of the catheter by a gauge length of about 5 mm or about 19 mm from the distal-most terminus of the catheter system for Version A and about 33 mm and 34 mm, respectively, from the distal-most terminus of the catheter system for Versions B1/B2 and C. 
     A second system point S2 of the at least two system points was located distal to the first system point S1 by a distance. The second system point S2 took into account the bending force of the catheter advancement element extending outside the catheter. In some tests, the second system point S2 was distal to the distal end of the catheter and was the same as the proximal point P3 or the proximal point P4 (where available). 
     Table 1 below provides bending forces measured in Newtons (N) of the various points along the length of the catheter systems in the advancement configuration. The points referred to in the table correlate generally to the point shown in  FIGS. 13A-13B , although are not represented to scale. The points are illustrative only and different points can be measured. 
     
       
         
           
               
               
               
               
               
               
               
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 Catheter 
                 P1 
                 P2 
                 P3 
                 P4 
                   
                 S2 
                 S1 
               
            
           
           
               
               
               
               
            
               
                 System Tested 
                 Distal Tip Points (catheter advancement element only) 
                 P5 
                 System Points 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Version A 
                 0.023 
                 N 
                 0.079 
                 N 
                 0.087 
                 N 
                 n/a 
                 0.061 
                 N 
                 0.087 
                 N 
                 0.208 
                 N 
               
               
                 0.054″ 
               
               
                 Distance along 
                 5 
                 mm 
                 12 
                 mm 
                 13 
                 mm 
                 n/a 
                 16 
                 mm 
                 13 
                 mm 
                 19 
                 mm 
               
               
                 length of system 
               
               
                 from distal-most 
               
               
                 terminus 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Version B1 
                 0.025 
                 N 
                 0.180 
                 N 
                 0.211 
                 N 
                 0.233 
                 N 
                 0.155 
                 N 
                 0.211 
                 N 
                 0.442 
                 N 
               
               
                 0.070″ 
               
               
                 Distance along 
                 5 
                 mm 
                 20 
                 mm 
                 25 
                 mm 
                 27 
                 mm 
                 30 
                 mm 
                 25 
                 mm 
                 33 
                 mm 
               
               
                 length of system 
               
               
                 from distal-most 
               
               
                 terminus 
               
               
                 Version B2 
                 0.025 
                 N 
                 0.180 
                 N 
                 0.211 
                 N 
                 0.233 
                 N 
                 0.155 
                 N 
                 0.211 
                 N 
                 0.345 
                 N 
               
               
                 0.070″ 
               
               
                 Distance along 
                 5 
                 mm 
                 20 
                 mm 
                 25 
                 mm 
                 27 
                 mm 
                 30 
                 mm 
                 25 
                 mm 
                 33 
                 mm 
               
               
                 length of system 
               
               
                 from distal-most 
               
               
                 terminus 
               
               
                 Version C 
                 0.029 
                 N 
                 0.210 
                 N 
                 0.245 
                 N 
                 0.299 
                 N 
                 0.219 
                 N 
                 0.245 
                 N 
                 0.415 
                 N 
               
               
                 0.088″ 
               
               
                 Distance along 
                 5 
                 mm 
                 20 
                 mm 
                 25 
                 mm 
                 28 
                 mm 
                 30 
                 mm 
                 25 
                 mm 
                 34 
                 mm 
               
               
                 length of system 
               
               
                 from distal-most 
               
               
                 terminus 
               
               
                   
               
            
           
         
       
     
     Table 1 shows the bending force of the distal end of the catheter advancement element at P1 was no more than about 0.05 N. A difference between the bending force of P2 and the bending force of P1 divided by the distance between P2 and P1 and/or a difference between the bending force of P3 and the bending force of P2 divided by the distance between P3 and P2 provided a first flexibility slope. The first flexibility slope was about 0.008 N/mm for Version A, 0.010 N/mm for Version B1, and 0.012 N/mm for Version C. A difference between the bending force of P3 and the bending force of P2 divided by the distance between P3 and P2 provided a second flexibility slope. The second flexibility slope was about 0.008 N/mm for Version A, 0.006 N/mm for Version B1, and 0.007 N/mm for Version C. An average of the first flexibility slope and the second flexibility slope defined an average tip portion flexibility slope. In some tests, a fourth distal tip point was measured such that the average tip portion flexibility slope took into account this additional segment in calculating the average slope (e.g. segment between P3 and P4). The average tip portion flexibility slope for each version of the catheter systems tested was at least 0.005 N/mm. For example, the average tip portion flexibility slope for Version A and Version B1 was about 0.008 N/mm, and for Version C was about 0.010 N/mm. A difference between the bending force of S1 and the bending force of S2 (whether P3 or P4) divided by the distance between S1 and S2 (whether P3 or P4) provided a first system flexibility slope. The first system flexibility slope using P3 as S2 was about 0.024 N/mm for Version A, 0.013 N/mm for Version B1, and about 0.009 N/mm for Version C. In this calculation, a ratio between the first system flexibility slope to the average tip portion flexibility slope for Version A was about 3.0, the ratio for Version B was about 1.6, and the ratio for Version C was about 0.9. The first system flexibility slope using P4 as S2 was about 0.035 N/mm for Version B1 and about 0.02 N/mm for Version C. In this calculation, a ratio between the first system flexibility slope to the average tip portion flexibility slope for Version B1 was about 4.4, and the ratio for Version C was about 2.0. Regardless which point is used for S2 (whether P3 or P4), the ratio between the first system flexibility slope to the average tip portion flexibility slope was less than about 5 for each version. 
       FIGS. 14A-14D  illustrate the bending forces of the various points described above versus distance in mm along a length of the system.  FIG. 14A  illustrates data for Version A system incorporating a catheter advancement element  300  having an outer diameter sized to extend through a catheter having an inner diameter of about 0.054″.  FIG. 14B  illustrates data for Version B1 system incorporating a catheter advancement element  300  having an outer diameter sized to extend through a catheter having an inner diameter of about 0.070″.  FIG. 14C  illustrates data for another version (Version B2) of a catheter system incorporating a catheter advancement element  300  having an outer diameter sized to extend through a catheter having an inner diameter of about 0.070″.  FIG. 14D  illustrates data for Version C system incorporating a catheter advancement element  300  having an outer diameter sized to extend through a catheter having an inner diameter of about 0.088″. 
       FIGS. 14A-14D  illustrate how the slopes of the lines are substantially constant or close to constant and substantially devoid of step-increases in bending force slope from one segment to the next along the length of the catheter system. In particular, each of the versions tested had no step-increases in bending force between the distal tip points (i.e. the points of the catheter advancement element extending distal to the distal end of the catheter) and the system point (i.e. the combination of the catheter and the catheter advancement element). As such, the overall slope of the system when in the advancement configuration is substantially constant over a length of the system, for example, a length being from a distal-most terminus (0 mm) to about 35 mm proximal to the distal-most terminus of the system. 
     In each version tested, the bending force of the distal end of the catheter advancement element at P1 was significantly lower than the bending force of the distal end of the catheter through which it extends (e.g. greater than at least about 2×) (see also Table 4 below). The bending force of the distal end of the catheter advancement element at P1 was no more than about 0.05 N. The bending force of the catheter advancement element increased over the length of the distal tip portion to approach the higher bending force of the distal end of the catheter. For example, the distal tip portion increased in stiffness over its length by at least 2× to approach the bending force of the distal end of the catheter. The bending force of the catheter system over its length had a generally constant slope. This generally constant slope of increasing bending force for the distal tip portion of the catheter advancement element (shown as a hash-dot-hash line in  FIG. 13B ) transitioned to a generally constant slope of increasing bending force for the combined system (shown as a hashed line in  FIG. 13B ) such that there is no significant step-increase in slope between the two. The bending force of the distal tip portion had a slope that transitioned to the slope of the system as a whole (i.e. additive bending force between catheter and catheter advancement element shown by hashed line) without a significant step-increase in slope from one segment to the next. 
     Corresponding points on a different catheter system (GUIDELINER Navigational catheter system; Vascular Solutions, Minneapolis, Minn.) were tested as a comparison. The data is provided in Table 2 below and also in  FIG. 14E , which illustrates the bending force of the various points versus distance in mm along a length of the GUIDELINER system. 
     
       
         
           
               
               
               
               
               
             
               
                   
                 TABLE 2 
               
             
            
               
                   
                   
               
               
                   
                 P1 
                 P2 
                 P3 
                   
               
            
           
           
               
               
               
               
            
               
                   
                 Distal Tip Points 
                 S2 
                 S1 
               
            
           
           
               
               
               
            
               
                 Catheter System 
                 (Navigational catheter only) 
                 System Points 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 8F GUIDELINER 
                 0.114 
                 N 
                 0.137 
                 N 
                 0.141 
                 N 
                 0.141 
                 N 
                 0.636 
                 N 
               
               
                 Navigational catheter 
               
               
                 Distance along length 
                 5 
                 mm 
                 10 
                 mm 
                 15 
                 mm 
                 15 
                 mm 
                 20 
                 mm 
               
               
                 of system from distal- 
               
               
                 most terminus 
               
               
                   
               
            
           
         
       
     
     The first bending force of P1 was greater than 0.05 N, specifically about 0.114 N. Various calculations using the bending force data shown in Table 2 were performed. The first flexibility slope for the GUIDELINER system was about 0.005 N/mm. The second flexibility slope for the GUIDELINER system was about 0.001 N/mm. The average tip portion flexibility slope for the GUIDELINER system was about 0.003 N/mm. The first system flexibility slope for the GUIDELINER system was about 0.10 N/mm. The ratio between the first system flexibility slope to the average tip portion flexibility slope for the GUIDELINER system was greater than 30. This ratio illustrates numerically what can be seen graphically in  FIG. 14E .  FIG. 14E  shows the GUIDELINER catheter system undergoes a large step-increase in slope from the flexibility of the portion of the navigation catheter extending distal to the distal end of the catheter through which it extends and the flexibility of the system as a whole. These large step-increases in slope means that there are sharp transitions in stiffness along the length of the catheter system that prevent the GUIDELINER catheter system from being advanced around curves of the tortuous vessels traversing the bony anatomy of the skull. The catheter tip is prevented from passing through such curves. In contrast, the catheter systems described herein have smaller slope ratios, which illustrate they possess the smoothest possible transition in stiffness from distal to proximal end and thus, are suitable for delivery through tortuous anatomy. 
     Table 3 below shows slopes of the catheter systems described herein compared to the slopes of the GUIDELINER Navigation Catheter system. “Average tip portion flexibility slope” was calculated. More specifically, the average tip portion flexibility slope is the average of the slopes of segments P1 to P2, P2 to P3, and P3 to P4, where available. Additional segments of the tip portion can be included. “Slope of segment S2-S1” is the slope of the segment between system points S2 and S1. The system point S2 can be the same point or a different point as one of the other points (e.g. P4 or P3). “Slope of segment P1-S1” is the slope of a line drawn from distal-most point P1 directly to the system point S1. 
     
       
         
           
               
               
               
               
               
               
               
               
               
               
             
               
                 TABLE 3 
               
               
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                 Average tip 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                 portion 
                 Slope of 
                 Slope of 
               
               
                 Catheter 
                   
                   
                   
                   
                   
                   
                 flexibility 
                 segment 
                 segment 
               
               
                 System 
                 P1 (N) 
                 P2 (N) 
                 P3 (N) 
                 P4 (N) 
                 S2 (N) 
                 S1 (N) 
                 slope (N/mm) 
                 S2-S1 (N/mm) 
                 P1-S1 (N/mm) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Version A 
                 0.023 
                 0.079 
                 0.087 
                 n/a 
                 0.087 
                 0.208 
                 0.0080 
                 0.0202 
                 0.0132 
               
               
                 0.054″ 
               
               
                 Ratio to 
                   
                   
                   
                   
                   
                   
                 1 
                 2.52 
                 1.65 
               
               
                 average tip 
               
               
                 portion 
               
               
                 flexibility 
               
               
                 slope 
               
               
                 Version B1 
                 0.025 
                 0.180 
                 0.211 
                 0.233 
                 0.233 
                 0.442 
                 0.0093 
                 0.0349 
                 0.0149 
               
               
                 0.070″ 
               
               
                 Ratio to 
                   
                   
                   
                   
                   
                   
                 1 
                 3.76 
                 1.61 
               
               
                 average tip 
               
               
                 portion 
               
               
                 flexibility 
               
               
                 slope 
               
               
                 Version B2 
                 0.025 
                 0.180 
                 0.211 
                 0.233 
                 0.233 
                 0.345 
                 0.0093 
                 0.0187 
                 0.0114 
               
               
                 0.070″ 
               
               
                 Ratio to 
                   
                   
                   
                   
                   
                   
                 1 
                 2.01 
                 1.23 
               
               
                 average tip 
               
               
                 portion 
               
               
                 flexibility 
               
               
                 slope 
               
               
                 Version C 
                 0.029 
                 0.210 
                 0.245 
                 0.299 
                 0.299 
                 0.415 
                 0.0124 
                 0.0193 
                 0.0133 
               
               
                 0.088″ 
               
               
                 Ratio to 
                   
                   
                   
                   
                   
                   
                 1 
                 1.56 
                 1.07 
               
               
                 average tip 
               
               
                 portion 
               
               
                 flexibility 
               
               
                 slope 
               
               
                 GUIDELINER 
                 0.114 
                 0.137 
                 0.141 
                 n/a 
                 0.141 
                 0.636 
                 0.0026 
                 0.0990 
                 0.0348 
               
               
                 Navigation 
               
               
                 Catheter 
               
               
                 Ratio to 
                   
                   
                   
                   
                   
                   
                 1 
                 37.40 
                 13.13 
               
               
                 average tip 
               
               
                 portion 
               
               
                 flexibility 
               
               
                 slope 
               
               
                   
               
            
           
         
       
     
     The tapered distal tip portion underwent a change in bending force over its length that was at least a 2-fold increase. The tapered distal tip portion of the catheter advancement element of Versions A, B1, B2, and C had a minimum slope of at least 0.005 N/mm. In contrast, the GUIDELINER increase in bending force over its length was only about 1.2 times. Further, the GUIDELINER had an average tip portion flexibility slope that was less than about 0.003 N/mm. The slope of each of the catheter systems (Versions A, B1, B2, and C) increased from distal point P1 to system point S1 no more than about 5 times whereas the GUIDELINER increased by more than 30 times from 0.114. 
     Table 4 below shows the bending forces of the distal tip of the catheter advancement element relative to the bending forces of the distal end of the catheter. The point measured and referred to in the table 4 below as “Catheter Point C1” was a point along a length of the catheter nearest the distal end that is measurable using the systems described herein, for example, a gauge length of the catheter from the distal-most end of the catheter of at least about 5 mm. The bending force (or flexibility) of the distal tip at P1 was about 16% the bending force (or flexibility) of C1 for Version A, about 10% for Version B1 and about 8% for Version C. Thus, the bending force at P1 was between about 5% and 15% the bending force at C1. The bending force (or flexibility) of the snug point near the proximal end of the distal tip (e.g., P3 or P4) was about 59% for Version A, about 91% for Version B1, and about 82% for Version C. Thus, the bending force at the snug point was between about 50% and 90% the bending force (or flexibility) of C1. In contrast, the distal tip point P1 on the GUIDELINER was stiffer compared to the same point on versions A, B1, or C. The proximal point P3 on the GUIDELINER had a greater bending force compared to its distal tip point P1, but this bending force was much lower compared to the bending force of the catheter point C1 (i.e. only 23% the stiffness of the catheter point C1). Thus, there was a larger difference between the bending force of the navigation catheter at P3 compared to the bending force of the catheter at C1 compared to the versions of the catheter systems described herein. This difference contributes to the larger step-increase in slopes of the GUIDELINER catheter system as best visualized in  FIG. 14E , 
     
       
         
           
               
               
               
               
             
               
                   
                 TABLE 4 
               
             
            
               
                   
                   
               
               
                   
                 Distal 
                 Proximal 
                 Catheter 
               
               
                   
                 Tip P1 (N) 
                 Point P3/P4 (N) 
                 Point C1 (N) 
               
            
           
           
               
               
               
            
               
                   
                 (Catheter Advancement 
                 Catheter 
               
               
                 Catheter System 
                 Element only) 
                 only 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Version A 
                 0.023 
                 0.087 
                 0.147 
               
               
                 0.054″ 
               
               
                   
                 16% 
                 59% 
                 100% 
               
               
                 Version B1 
                 0.025 
                 0.233 
                 0.256 
               
               
                 0.070″ 
               
               
                   
                 10% 
                 91% 
                 100% 
               
               
                 Version C 
                 0.029 
                 0.299 
                 0.366 
               
               
                 0.088″ 
               
               
                   
                  8% 
                 82% 
                 100% 
               
               
                 8F GUIDELINER 
                 0.114 
                 0.141 
                 0.624 
               
               
                 Navigational catheter 
               
               
                   
                 18% 
                 23% 
                 100% 
               
               
                   
               
            
           
         
       
     
     Table 5 below shows the bending force of P1 of the catheter advancement element relative to a bending force of a portion of the proximal extension of the catheter advancement element. Point E1 on the proximal extension that was selected for testing was within about 20 cm proximal to the tubular portion of the catheter advancement element. The point E1 had a bending force that was about 9.21 N. The bending force of the catheter advancement element at the distal tip P1 was no more than about 0.30% of the bending force of the proximal extension at E1. The ratio of the bending force of point E1 to the first bending force at distal tip point P1 was at least about 300. The proximal extension of the catheter advancement element of Version C was about 318 times stiffer than the distal tip of the catheter advancement element at P1, Version B1 was about 368 times stiffer, and Version A was about 400 times stiffer. 
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 5 
               
               
                   
               
               
                 Catheter System 
                 P1 (N) 
                 E1 (N) 
                 % stiffness 
                 Ratio 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Version A 
                 0.023 
                 9.21 
                 0.25% 
                 400 
               
               
                 0.054″ 
               
               
                 Version B1 
                 0.025 
                 9.21 
                 0.27% 
                 368 
               
               
                 0.070″ 
               
               
                 Version C 
                 0.029 
                 9.21 
                 0.30% 
                 318 
               
               
                 0.088″ 
               
               
                 GUIDELINER 
                 0.114 
                 17.52 
                 0.65% 
                 154 
               
               
                 Navigation 
               
               
                 Catheter 
               
               
                 Orion-21 
                 0.137 
                 8.36 
                 1.64% 
                 61 
               
               
                   
               
            
           
         
       
     
     Two other catheter systems were analyzed as a comparison. The bending force of the GUIDELINER navigation catheter at E1 was greater than any of the versions tested at about 17.52N. The bending force of the distal tip at P1 was also higher compared to the catheter system versions described herein. The bending force of the navigation catheter at the distal tip P1 was about 0.65% the bending force of the proximal extension at E1. Further, the bending force at point E1 of the GUIDELINER navigation catheter was only 154 times more than the distal tip P1. The ORION-21 catheter (Medtronic, Minneapolis, Minn.) had a bending force at the distal tip P1 that was about 1.64% the bending force at E1. The bending force at point E1 of the ORION-21 was only about 60 times stiffer than its distal tip at P1. 
     The data described herein provides a numerical picture of the smooth transition in flexibility over the length of the various catheter systems described herein that provides optimum navigability without risk of kinking. The catheter systems described herein have distal ends that are exceptionally flexible that transition towards proximal ends that are exceptionally stiff for optimum torqueing and manipulation. The transitions in flexibility along the length of the system are managed such that the two components work seamlessly together as if they were a single component and without any large step-increases in stiffness from one segment to another. 
     Implementations describe catheters and delivery systems and methods to deliver catheters to target anatomies. However, while some implementations are described with specific regard to delivering catheters to a target vessel of a neurovascular anatomy such as a cerebral vessel, the implementations are not so limited and certain implementations may also be applicable to other uses. For example, the catheters can be adapted for delivery to different neuroanatomies, such as subclavian, vertebral, carotid vessels as well as to the coronary anatomy or peripheral vascular anatomy, to name only a few possible applications. Although the systems described herein are described as being useful for treating a particular condition or pathology, that the condition or pathology being treated may vary and are not intended to be limiting. Use of the terms “embolus,” “embolic,” “emboli,” “thrombus,” “occlusion,” “clot”, etc. that relate to a target for treatment using the devices described herein are not intended to be limiting. The terms may be used interchangeably and can include, but are not limited to a blood clot, air bubble, small fatty deposit, or other object carried within the bloodstream to a distant site or formed at a location in a vessel. The terms may be used interchangeably herein to refer to something that can cause a partial or full occlusion of blood flow through or within the vessel. 
     In various implementations, description is made with reference to the figures. However, certain implementations may be practiced without one or more of these specific details, or in combination with other known methods and configurations. In the description, numerous specific details are set forth, such as specific configurations, dimensions, and processes, in order to provide a thorough understanding of the implementations. In other instances, well-known processes and manufacturing techniques have not been described in particular detail in order to not unnecessarily obscure the description. Reference throughout this specification to “one embodiment,” “an embodiment,” “one implementation, “an implementation,” or the like, means that a particular feature, structure, configuration, or characteristic described is included in at least one embodiment or implementation. Thus, the appearance of the phrase “one embodiment,” “an embodiment,” “one implementation, “an implementation,” or the like, in various places throughout this specification are not necessarily referring to the same embodiment or implementation. Furthermore, the particular features, structures, configurations, or characteristics may be combined in any suitable manner in one or more implementations. 
     The use of relative terms throughout the description may denote a relative position or direction. For example, “distal” may indicate a first direction away from a reference point. Similarly, “proximal” may indicate a location in a second direction opposite to the first direction. The reference point used herein may be the operator such that the terms “proximal” and “distal” are in reference to an operator using the device. A region of the device that is closer to an operator may be described herein as “proximal” and a region of the device that is further away from an operator may be described herein as “distal”. Similarly, the terms “proximal” and “distal” may also be used herein to refer to anatomical locations of a patient from the perspective of an operator or from the perspective of an entry point or along a path of insertion from the entry point of the system. As such, a location that is proximal may mean a location in the patient that is closer to an entry point of the device along a path of insertion towards a target and a location that is distal may mean a location in a patient that is further away from an entry point of the device along a path of insertion towards the target location. However, such terms are provided to establish relative frames of reference, and are not intended to limit the use or orientation of the catheters and/or delivery systems to a specific configuration described in the various implementations. 
     While this specification contains many specifics, these should not be construed as limitations on the scope of what is claimed or of what may be claimed, but rather as descriptions of features specific to particular embodiments. Certain features that are described in this specification in the context of separate embodiments can also be implemented in combination in a single embodiment. Conversely, various features that are described in the context of a single embodiment can also be implemented in multiple embodiments separately or in any suitable sub-combination. Moreover, although features may be described above as acting in certain combinations and even initially claimed as such, one or more features from a claimed combination can in some cases be excised from the combination, and the claimed combination may be directed to a sub-combination or a variation of a sub-combination. Similarly, while operations are depicted in the drawings in a particular order, this should not be understood as requiring that such operations be performed in the particular order shown or in sequential order, or that all illustrated operations be performed, to achieve desirable results. Only a few examples and implementations are disclosed. Variations, modifications and enhancements to the described examples and implementations and other implementations may be made based on what is disclosed. 
     In the descriptions above and in the claims, phrases such as “at least one of” or “one or more of” may occur followed by a conjunctive list of elements or features. The term “and/or” may also occur in a list of two or more elements or features. Unless otherwise implicitly or explicitly contradicted by the context in which it is used, such a phrase is intended to mean any of the listed elements or features individually or any of the recited elements or features in combination with any of the other recited elements or features. For example, the phrases “at least one of A and B;” “one or more of A and B;” and “A and/or B” are each intended to mean “A alone, B alone, or A and B together.” A similar interpretation is also intended for lists including three or more items. For example, the phrases “at least one of A, B, and C;” “one or more of A, B, and C;” and “A, B, and/or C” are each intended to mean “A alone, B alone, C alone, A and B together, A and C together, B and C together, or A and B and C together.” 
     Use of the term “based on,” above and in the claims is intended to mean, “based at least in part on,” such that an unrecited feature or element is also permissible. 
     The catheter system disclosed herein may be packaged together in a single package, where the catheters and catheter advancement element are packaged in a coil tube. The finished package would be sterilized using sterilization methods such as Ethylene oxide or radiation and labeled and boxed. Instructions for use may also be provided in-box or through an internet link printed on the label.