SYSTEMS AND METHODS FOR REMOVAL OF BLOOD AND THROMBOTIC MATERIAL

A system for aspirating thrombus includes an aspiration catheter including a supply lumen and an aspiration lumen each extending within an elongate shaft, and an opening at or near the distal end of the supply lumen, the opening configured to allow the injection of pressurized fluid into the aspiration lumen at or near the distal end of the aspiration lumen when the pressurized fluid is pumped through the supply lumen, a tubing set including tubing and having a distal end configured to couple to the aspiration lumen of the aspiration catheter and a proximal end configured to couple to a vacuum source, a tubing compression element configured to externally engage the tubing of the tubing set, and an activation interface configured to activate the tubing compression element to compress the tubing at a location between the proximal end of the tubing set and the distal end of the tubing set.

BACKGROUND OF THE INVENTION

Field of the Invention

The present disclosure pertains generally to medical devices and methods of their use. More particularly, the present invention pertains to aspiration and thrombectomy devices and methods of use thereof.

Description of the Related Art

Several devices and systems already exist to aid in the removal of thrombotic material. These include simple aspiration tube type devices using vacuum syringes to extract thrombus into the syringe, simple flush-and-aspirate devices, more complex devices with rotating components the pull in, macerate and transport thrombotic material away from the distal tip using a mechanical auger, systems that use very high pressure to macerate the thrombus and create a venturi effect to flush the macerated material away.

All of the devices described above have limitations as a result of individual design characteristics. For example, simple aspiration catheters offer ease of use and rapid deployment but may become blocked or otherwise inoperable when faced with older, more organized thrombotic material. Such devices must be removed and cleared outside the body and then re-inserted into the vasculature, which lengthens the time needed for the procedure and increases the opportunity to kink the catheter shaft. Such kinks may reduce performance by decreasing the cross-sectional area of the catheter or may render the device inoperable.

Mechanical rotary devices use an auger to grab and carry the thrombus away from the target area. Some create transport force via vacuum bottles while others create differential pressure at the distal tip of the device with the auger acting as a low pressure pump. These devices typically work slowly and offer the physician no feedback as to when the device should be advanced further into the lesion.

Flushing type devices include manual flush type devices in which the physician manipulates a hand-driven pump to provide flowing saline at the tip of the device to break up and aspirate the thrombus material, which may introduce performance variations based on the ability of the physician to consistently pump the device over the duration of the procedure. Flushing devices also include high pressure flushing devices that macerate the thrombus and then, using a vortex created by the high pressure fluid, transport the emulsified thrombotic material to a collection bag. These devices are effective at removing all levels of thrombotic material, but the pressure created by the device is so great that its action against certain vessel walls may interrupt the heart muscle stimulation mechanism and create a bradycardia event in certain patients, sometimes requiring that a pacing lead be placed in the patient prior to use. Further, interacting with the thrombotic material outside of the catheter may allow loose material to escape the capture mechanism.

SUMMARY OF THE INVENTION

In one embodiment of the present disclosure, a system for aspirating thrombus includes an aspiration catheter including an elongate shaft configured for placement within a blood vessel of a subject, a supply lumen and an aspiration lumen each extending within the shaft, the supply lumen having a proximal end and a distal end, and the aspiration lumen having a proximal end and an open distal end, and an opening at or near the distal end of the supply lumen, the opening configured to allow the injection of pressurized fluid into the aspiration lumen at or near the distal end of the aspiration lumen when the pressurized fluid is pumped through the supply lumen, a tubing set including tubing and having a distal end configured to couple to the aspiration lumen of the aspiration catheter and a proximal end configured to couple to a vacuum source, a tubing compression element configured to externally engage the tubing of the tubing set at a location between the proximal end of the tubing set and the distal end of the tubing set, and an activation interface configured to activate the tubing compression element to compress the tubing at the location between the proximal end of the tubing set and the distal end of the tubing set.

In another embodiment of the present disclosure, a system for aspirating thrombus includes an aspiration catheter including an elongate shaft configured for placement within a blood vessel of a subject, a supply lumen and an aspiration lumen each extending within the shaft, the supply lumen having a proximal end and a distal end, and the aspiration lumen having a proximal end and an open distal end, and an opening in a wall separating the supply lumen and the aspiration lumen, the opening at or adjacent the distal end of the supply lumen and in fluid communication with the interior of the aspiration lumen, the opening located proximally of the open distal end of the aspiration lumen, wherein the opening is configured to create a jet when pressurized fluid is pumped through the supply lumen of the aspiration catheter, a pressure sensor configured to be in fluid communication with the aspiration lumen of the aspiration catheter and to output a signal indicative of measured pressure, a tubing set including tubing and configured to extend proximally from the pressure sensor and to be in fluid communication with the aspiration lumen of the aspiration catheter, the tubing set having a proximal end configured to couple to a vacuum source, a tubing compression element configured to externally engage the tubing of the tubing set at a location between the proximal end of the tubing set and the pressure sensor, and an activation interface configured to activate the tubing compression element to compress the tubing at the location between the proximal end and the pressure sensor.

In yet another embodiment of the present disclosure, a system for aspirating thrombus includes an aspiration catheter including an elongate shaft configured for placement within a blood vessel of a subject, a supply lumen and an aspiration lumen each extending within the shaft, the supply lumen having a proximal end and a distal end, and the aspiration lumen having a proximal end and an open distal end, and an opening at or near the distal end of the supply lumen, the opening configured to allow the injection of pressurized fluid into the aspiration lumen at or near the distal end of the aspiration lumen when the pressurized fluid is pumped through the supply lumen, a pressure sensor configured to be in fluid communication with the aspiration lumen of the aspiration catheter and to output a signal indicative of measured pressure, a tubing set including tubing and configured to extend proximally from the pressure sensor and to be in fluid communication with the aspiration lumen of the aspiration catheter, the tubing set having a proximal end configured to couple to a vacuum source, a tubing compression element configured to externally engage the tubing of the tubing set at a location between the proximal end of the tubing set and the pressure sensor, and an activation interface configured to activate the tubing compression element to compress the tubing at the location between the proximal end and the pressure sensor.

In still another embodiment of the present disclosure, a system for aspirating thrombus includes an aspiration catheter including a supply lumen and an aspiration lumen, the supply lumen having a proximal end and a distal end, the aspiration lumen having a proximal end and an open distal end, an opening at or adjacent the distal end of the supply lumen, in fluid communication with the interior of the aspiration lumen, the opening located proximally of the open distal end of the aspiration lumen, wherein the opening is configured to create a jet when pressurized fluid is pumped through the supply lumen, a connector hydraulically coupled to the proximal end of the aspiration lumen, the connector having an interior cavity, a proximal end and a distal end, and a pressure sensor located within the interior cavity of the connector, and a measurement device configured to receive signals from the pressure sensor.

In yet another embodiment of the present disclosure, a system for aspirating thrombus includes an aspiration catheter including a supply lumen and an aspiration lumen, the supply lumen having a proximal end and a distal end, the aspiration lumen having a proximal end and an open distal end, an opening at or adjacent the distal end of the supply lumen, in fluid communication with the interior of the aspiration lumen, the opening located proximally of the open distal end of the aspiration lumen, wherein the opening is configured to create a jet when pressurized fluid is pumped through the supply lumen, a connector hydraulically coupled to the proximal end of the aspiration lumen, the connector having an interior cavity, a proximal end and a distal end, and wherein the opening includes a slit in a wall of a tubular structure which encloses the supply lumen.

In still another embodiment of the present disclosure, a method for removing thrombus from a patient includes providing an aspiration catheter including a supply lumen and an aspiration lumen, the supply lumen having a proximal end and a distal end, the aspiration lumen having a proximal end and an open distal end, an opening at or adjacent the distal end of the supply lumen, in fluid communication with the interior of the aspiration lumen, the opening located proximally of the open distal end of the aspiration lumen, wherein the opening is configured to create a jet when pressurized fluid is pumped through the supply lumen, a connector hydraulically coupled to the proximal end of the aspiration lumen, the connector having an interior cavity, a proximal end and a distal end, and a pressure sensor coupled to the proximal end of the supply lumen, coupling or causing to couple the supply lumen of the aspiration catheter to a fluid source, coupling or causing to couple the aspiration lumen of the aspiration catheter to a vacuum source, coupling or causing to couple a pump for injecting fluid from the fluid source through the supply lumen and through the opening into the aspiration lumen, providing a control unit configured to adjust the settings on the pump, and setting the pump with the control unit such that an input pressure of the supply lumen is between about 650 pounds per square inch and about 1200 pounds per square inch.

In yet another embodiment of the present disclosure, a system for aspirating thrombus includes an aspiration catheter including a supply lumen and an aspiration lumen, the supply lumen having a proximal end and a distal end, the aspiration lumen having a proximal end and an open distal end, an opening at or adjacent the distal end of the supply lumen, in fluid communication with the interior of the aspiration lumen, the opening located proximally of the open distal end of the aspiration lumen, wherein the opening is configured to create a jet when pressurized fluid is pumped through the supply lumen, and a connector hydraulically coupled to the proximal end of the aspiration lumen, the connector having an interior cavity having an inner surface, a proximal end and a distal end, wherein the connector includes a first sideport communicating with the interior cavity of the connector and in fluid communication with the aspiration lumen of the aspiration catheter, and wherein the first sideport is the nearest significant interruption of the inner surface to the distal end of the connector.

In still another embodiment of the present disclosure, a method for removing thrombus from a patient includes providing an aspiration catheter including a supply lumen and an aspiration lumen, the supply lumen having a proximal end and a distal end, the aspiration lumen having a proximal end and an open distal end, an opening at or adjacent the distal end of the supply lumen, in fluid communication with the interior of the aspiration lumen, the opening located proximally of the open distal end of the aspiration lumen, wherein the opening is configured to create a jet when pressurized fluid is pumped through the supply lumen, and a connector hydraulically coupled to the proximal end of the aspiration lumen, the connector having an interior cavity, a proximal end and a distal end, placing the distal end of a guiding catheter into a blood vessel, the guiding catheter having an inner lumen configured for placement of the aspiration catheter, placing the aspiration catheter through the inner lumen of the guiding catheter and into the blood vessel such that a distal end of the aspiration catheter is adjacent a thrombus, coupling or causing to couple the supply lumen of the aspiration catheter to a fluid source, coupling or causing to couple the aspiration lumen of the aspiration catheter to a vacuum source, coupling or causing to couple a first pump for injecting fluid from the fluid source through the supply lumen and through the opening into the aspiration lumen, causing an injection of fluid from the fluid source through the supply lumen of the aspiration catheter via the first pump with the vacuum source actively coupled to the aspiration lumen, determining that aspiration of the thrombus through the aspiration lumen of the aspiration catheter is not occurring at a desired thrombus aspiration rate, and injecting an inj ectate through the inner lumen of the guiding catheter and into the blood vessel to increase the thrombus aspiration rate.

In yet another embodiment of the present disclosure, a method for removing thrombus from a patient includes providing an aspiration catheter including a supply lumen and an aspiration lumen, the supply lumen having a proximal end and a distal end, the aspiration lumen having a proximal end and an open distal end, an opening at or adjacent the distal end of the supply lumen, in fluid communication with the interior of the aspiration lumen, the opening located proximally of the open distal end of the aspiration lumen, wherein the opening is configured to create a jet when pressurized fluid is pumped through the supply lumen, and a connector hydraulically coupled to the proximal end of the aspiration lumen, the connector having an interior cavity, a proximal end and a distal end, placing the distal end of a guiding catheter into a blood vessel, the guiding catheter having an inner lumen configured for placement of the aspiration catheter, placing the aspiration catheter through the inner lumen of the guiding catheter and into the blood vessel such that a distal end of the aspiration catheter is adjacent a thrombus, coupling or causing to couple the supply lumen of the aspiration catheter to a fluid source, coupling or causing to couple the supply lumen of the aspiration catheter to a fluid source, coupling or causing to couple a first pump for injecting fluid from the fluid source through the supply lumen and through the opening into the aspiration lumen, causing an injection of fluid from the fluid source through the supply lumen of the aspiration catheter via the first pump with the vacuum source actively coupled to the aspiration lumen, determining that aspiration of the thrombus through the aspiration lumen of the aspiration catheter is not occurring at a desired thrombus aspiration rate, and rotating the guiding catheter within the blood vessel to increase the thrombus aspiration rate.

In still another embodiment of the present disclosure, a method for removing thrombus from a patient includes providing an aspiration catheter including a supply lumen and an aspiration lumen, the supply lumen having a proximal end and a distal end, the aspiration lumen having a proximal end and an open distal end, an opening at or adjacent the distal end of the supply lumen, in fluid communication with the interior of the aspiration lumen, the opening located proximally of the open distal end of the aspiration lumen, wherein the opening is configured to create a jet when pressurized fluid is pumped through the supply lumen, and a connector hydraulically coupled to the proximal end of the aspiration lumen, the connector having an interior cavity, a proximal end and a distal end, placing the aspiration catheter into a blood vessel such that a distal end of the aspiration catheter is adjacent a thrombus, coupling or causing to couple the supply lumen of the aspiration catheter to a fluid source, coupling a first port of a four-way stopcock to the aspiration lumen of the aspiration catheter, coupling a second port of the four-way stopcock to a pressure sensor, the pressure sensor configured to send a signal to a controller, coupling a third port of the four-way stopcock to a vacuum source, coupling or causing to couple a pump between the fluid source and the aspiration lumen, causing an injection of fluid from the fluid source through the supply lumen of the aspiration catheter via the pump with the vacuum source actively coupled to the aspiration lumen, wherein the four-way stopcock is in a first state such that the pressure sensor, the aspiration lumen, and the vacuum source are all in fluid communication, wherein the controller is configured to stop the pump when the pressure sensor sends signals indicative of the pressure sensor not being in fluid communication with the vacuum source, and adjusting the four-way stopcock to a second state such that the pressure sensor remains in fluid communication with the vacuum source, but each of the pressure sensor and the vacuum source is no longer in fluid communication with the aspiration lumen, such that the controller maintains operation of the pump while the aspiration lumen is not in fluid communication with the vacuum source.

In yet another embodiment of the present disclosure, a first connector configured for removable connection proximal to an aspiration catheter, the aspiration catheter including a supply lumen and an aspiration lumen, the supply lumen having a proximal end and a distal end, the aspiration lumen having a proximal end and an open distal end, an opening at or adjacent the distal end of the supply lumen in fluid communication with the interior of the aspiration lumen, the opening located proximally of the open distal end of the aspiration lumen, wherein the opening is configured to create a jet when pressurized fluid is pumped through the supply lumen, and a second connector hydraulically coupled to the proximal end of the aspiration lumen, the second connector having an interior cavity, the first connector including a body having an interior, a distal end including a connection configured to sealably couple to the proximal end of the aspiration lumen of the aspiration catheter, a proximal end including an openable and closable seal configured for sealing over a guidewire, an aspiration port in fluid communication with an interior of the body and configured to couple to a vacuum source, and a pressure sensor in fluid communication with the interior of the body.

In still another embodiment of the present disclosure, a system for aspirating thrombus includes an aspiration catheter including a supply lumen and an aspiration lumen, the supply lumen having a proximal end, a distal end and a wall, the aspiration lumen having a proximal end and an open distal end, an orifice at or adjacent the distal end of the supply lumen, in fluid communication with the interior of the aspiration lumen, the orifice located proximally of the open distal end of the aspiration lumen, wherein the orifice is configured to create a jet when pressurized fluid is pumped through the supply lumen when a distal end of the aspiration catheter is immersed within an aqueous environment, and a first connector hydraulically coupled to the proximal end of the aspiration lumen, and a pressure sensor having an internal passageway and including a distal connector configured to hydraulically couple to the first connector, a proximal connector configured to couple to a vacuum source, and a valve disposed between the distal connector and the proximal connector, the valve having an open state and a closed state.

In yet another embodiment of the present disclosure, a method for removing thrombus from a patient includes providing an aspiration catheter including a supply lumen and an aspiration lumen, the supply lumen having a proximal end, a distal end and a wall, the aspiration lumen having a proximal end and an open distal end, an orifice at or adjacent the distal end of the supply lumen, in fluid communication with the interior of the aspiration lumen, the orifice located proximally of the open distal end of the aspiration lumen, wherein the orifice is configured to create a jet when pressurized fluid is pumped through the supply lumen when a distal end of the aspiration catheter is immersed within an aqueous environment, and a first connector hydraulically coupled to the proximal end of the aspiration lumen, providing a pressure sensor having an internal passageway and including a distal connector configured to hydraulically couple to the first connector, a proximal connector configured to couple to a vacuum source, and a valve disposed between the distal connector and the proximal connector, the valve having an open state and a closed state, coupling the distal connector of the pressure sensor to the first connector of the aspiration catheter, coupling the proximal connector of the pressure sensor to a vacuum source, coupling the supply lumen of the aspiration catheter to a pump having control circuitry, the control circuitry capable of receiving a signal from the pressure sensor, inserting at least a distal portion of the aspiration catheter into the vasculature of a subject near or adjacent a thrombus, and changing the valve from one of the open state and closed state to the other of the open state and closed state such that a change in pressure may be detected by the control circuitry.

DETAILED DESCRIPTION OF THE ILLUSTRATED EMBODIMENTS

FIG. 1is a diagrammatic figure depicting an assisted aspiration system10. The aspiration system10includes a remote hand piece12that contains a fluid pump26and an operator control interface6. In one contemplated embodiment, the system10is a single use disposable unit. The aspiration system10may also include extension tubing14, which contains a fluid irrigation lumen2(or high pressure injection lumen) and an aspiration lumen4, and which allows independent manipulation of a catheter16without requiring repositioning of the hand piece12during a procedure performed with the aspiration system10. Extension tubing14may also act as a pressure accumulator. High pressure fluid flow from the pump26, which may comprise a displacement pump, pulses with each stroke of the pump26, creating a sinusoidal pressure map with distinct variations between the peaks and valleys of each sine wave. Extension tubing14may be matched to the pump26to expand and contract in unison with each pump pulse to reduce the variation in pressure caused by the pump pulses to produce a smooth or smoother fluid flow at tip of catheter16. Any tubing having suitable compliance characteristics may be used. The extension tubing14may be permanently attached to the pump26or it may be attached to the pump26by a connector44. The connector44is preferably configured to ensure that the extension tubing14cannot be attached to the pump26incorrectly.

An interface connector18joins the extension tubing14and the catheter16together. In one contemplated embodiment, the interface connector18may contain a filter assembly8between high pressure fluid injection lumen2of the extension tubing14and a high-pressure injection lumen36of the catheter16(FIG. 3). The catheter16and the extension tubing14may be permanently joined by the interface connector18. Alternatively, the interface connector18may contain a standardized connection so that a selected catheter16may be attached to the extension tubing14.

Attached to the hand piece12are a fluid source20and a vacuum source22. A standard hospital saline bag may be used as fluid source20; such bags are readily available to the physician and provide the necessary volume to perform the procedure. Vacuum bottles may provide the vacuum source22, or the vacuum source22may be provided by a vacuum canister, syringe, a vacuum pump or other suitable vacuum sources.

In one contemplated embodiment, the catheter16has a variable stiffness ranging from stiffer at the proximal end to more flexible at the distal end. The variation in the stiffness of the catheter16may be achieved with a single tube with no radial bonds between two adjacent tubing pieces. For example, the shaft of the catheter16may be made from a single length of metal tube that has a spiral cut down the length of the tube to provide shaft flexibility. Variable stiffness may be created by varying the pitch of the spiral cut through different lengths of the metal tube. For example, the pitch of the spiral cut may be greater (where the turns of the spiral cut are closer together) at the distal end of the device to provide greater flexibility. Conversely, the pitch of the spiral cut at the proximal end may be lower (where the turns of the spiral cut are further apart) to provide increased stiffness. In some embodiments, a single jacket may cover the length of the metal tube to provide for a vacuum tight catheter shaft. An inner layer or lining of a lubricious material, such as a fluoropolymer including PTFE and an outer layer or jacket of PEBAX may together encapsulate or sandwich the spiral-cut metal tube. The spiral-cut tube can be encapsulated in a manner such that it stops short of the distal end of the catheter16, so that a more flexible tip is provided. Other features of catheter16are described with reference toFIG. 3.

FIG. 2is a diagrammatic view showing more detail of the hand piece12and the proximal portion of assisted catheter aspiration system10. The hand piece12includes a control box24where the power and control systems are disposed. The pump26may in some embodiments be a motor driven displacement pump that has a constant output. The pump displacement relationship to the catheter volume, along with the location of the orifice42(exit) of the catheter high pressure lumen36within the aspiration lumen38(FIG. 3), ensures that no energy is transferred to the patient from the saline pump as substantially all pressurized fluid is evacuated by the aspiration lumen. A prime button28is mechanically connected to a prime valve30. When preparing the device for use, it is advantageous to evacuate all air from the pressurized fluid system to reduce the possibility of air embolization. By depressing the prime button28, the user connects the fluid source20to the vacuum source22via the pump26. This forcefully pulls fluid (for example 0.9% NaCl solution, or “saline”, or “normal saline”, or heparinized saline) through the entire pump system, removing all air and positively priming the system for safe operation. A pressure/vacuum valve32is used to turn the vacuum on and off synchronously with the fluid pressure system. One contemplated valve32is a ported one-way valve. Such a valve is advantageous with respect to manual or electronic valve systems because it acts as a tamper proof safety feature by mechanically and automatically combining the operations of the two primary systems. By having pressure/vacuum valve32, the possibility of turning the vacuum on without also activating the fluid system is eliminated.

The operator control interface6is powered by a power system48(such as a battery or an electrical line), and may comprise an electronic control board50, which may be operated by a user by use of one or more switches52and one or more indicator lamps54. The control board50also monitors and controls several device safety functions, which include over pressure detection, air bubble detection, and vacuum charge. A pressure sensor64monitors pressure (i.e. injection pressure), and senses the presence of air bubbles. Alternatively, or in conjunction, an optical device66may be used to sense air bubbles. In one contemplated embodiment, the pump pressure is proportional to the electric current needed to produce that pressure. Consequently, if the electric current required by pump26exceeds a preset limit, the control board50will disable the pump26by cutting power to it. Air bubble detection may also be monitored by monitoring the electrical current required to drive the pump26at any particular moment. In order for a displacement pump26to reach high fluid pressures, there should be little or no air (which is highly compressible) present in the pump26or connecting system (including the catheter16and the extension tubing14). The fluid volume is small enough that any air in the system will result in no pressure being generated at the pump head. The control board monitors the pump current for any abrupt downward change that may indicate that air has entered the system. If the rate of drop is faster than a preset limit, the control board50will disable the pump26by cutting power to it until the problem is corrected. Likewise, a block in the high-pressure lumen36(FIG. 3), which may be due to the entry of organized or fibrous thrombus, or a solid embolus, may be detected by monitoring the electrical current running the pump26. In normal use, the current fluxuations of the pump26are relatively high. For example, the pump26may be configured so that there is a variation of 200 milliAmps or greater in the current during normal operation, so that when current fluxuations drop below 200 milliAmps, air is identified, and the system shuts down. Alternatively, current fluxuations in the range of, for example, 50 milliAmps to 75 milliAmps may be used to identify that air is in the system. Additionally, an increase in the current or current fluxuations may indicate the presence of clot or thrombus within the high-pressure lumen36. For example, a current of greater than 600 milliAmps may indicate that thrombus it partially or completely blocking the high-pressure lumen36, or even the aspiration lumen38(FIG. 3).

A vacuum line56, connected to the vacuum source22, may be connected to a pressure sensor58. If the vacuum of the vacuum source22is low (i.e. the absolute value pressure has decreased) or if a leak is detected in the vacuum line56, the control board50disables the pump26until the problem is corrected. The pressure sensor58may also be part of a safety circuit60that will not allow the pump26to run if a vacuum is not present. Thereby, a comprehensive safety system62, including the safety circuit60, the pressure sensor64and/or the optical device66, and the pressure sensor58, requires both pump pressure and vacuum pressure for the system to run. If a problem exists (for example, if there is either a unacceptably low pump pressure or an absence of significant vacuum), the control board50will not allow the user to operate the aspiration system10until all problems are corrected. This will keep air from being injected into a patient, and will assure that the aspiration system10is not operated at incorrect parameters. Alternatively, in lieu of a direct connection (e.g., electrical, optical), the pressure sensor58can be configured to send a wireless signal to the control board50, or any other component (e.g., antenna) coupled to or in communication with the control board50, to remotely control operation of the pump26. The remote control may be possible, whether the pump is within the sterile filed or outside the sterile field.

FIG. 3is a diagrammatic view of the distal end portion68of the assisted catheter aspiration system10, showing more details of the catheter16. The catheter16in some embodiments is a single-operator exchange catheter and includes a short guidewire lumen34attached to the distal end of the device. The guidewire lumen34can be between about 1 and about 30 cm in length, or between about 5 and about 25 cm in length, or between about 5 and about 20 cm in length, or approximately 13.5 cm in length. In other embodiments, a full-length guidewire lumen (extending the length of the catheter16) may be used. For example, a catheter16sized to be used on peripheral blood vessels, including peripheral arteries, may incorporate a full-length guidewire lumen. In some embodiments, the aspiration itself may also serve as a guidewire lumen. An aspiration lumen38includes a distal opening40which allows a vacuum (for example, from vacuum source22) to draw thrombotic material into the aspiration lumen38. A high-pressure lumen36includes a distal orifice42that is set proximally of distal opening40by a set amount. For example, distal orifice42can be set proximally of distal opening40by about 0.508 mm (0.020 inches), or by 0.508 mm±0.076 mm (0.020 inches±0.003 inches) or by another desired amount. The orifice42is configured to spray across the aspiration lumen to macerate and/or dilute the thrombotic material for transport to vacuum source22, for example, by lowering the effective viscosity of the thrombotic material. The axial placement of the fluid orifice42is such that the spray pattern interaction with the opposing lumen wall preferably produces a spray mist and not a swirl pattern that could force embolic material out from the distal opening40. The spray pattern may be present at least when a distal end of the catheter16is within an aqueous environment, such as a body lumen, including a blood vessel. The aqueous environment may be at body temperature, for example between about 35.0° C. and about 40.0° C., or between about 36.0° C. and about 38.0° C. The system may be configured so that the irrigation fluid leaves the pump at a pressure of between about 3.447 megapascal (500 pounds per square inch) and about 10.342 megapascal (1500 pounds per square inch). In some embodiments, after a pressure head loss along the high-pressure lumen36, the irrigation fluid leaves orifice42at between about 4.137 megapascal (600 pounds per square inch) and about 8.274 megapascal (1200 pounds per square inch), or between about 4.816 megapascal (650 pounds per square inch) and about 5.861 megapascal (850 pounds per square inch).

FIG. 4illustrates a system for aspirating thrombus100according to an embodiment of the present disclosure. The system for aspirating thrombus100depicted inFIG. 4represents disposable components101, comprising a tubing set103and an aspiration catheter118, which are configured to attach to a vacuum source22, a fluid source20(FIGS. 1 and 2), a pressure monitor (not shown), and a pump base200(FIG. 12). The system for aspirating thrombus100is also configured to be used with a guidewire. Beginning with the components of the tubing set103, a spike102(shown in more detail inFIG. 5) is configured to couple to a fluid source20such as a saline bag. The saline bag may have a volume of saline equal to about 1000 ml or about 500 ml. The saline may comprise normal saline, and may be heparinized, or may contain one or more therapeutic agents. Other fluids may be used in place of normal saline or a saline mixture, including lactated Ringer's solution, hypertonic saline, or even solutions containing blood products. The saline, or other fluid, may be at room temperature, or may be warmed or cooled (e.g., to permanently or temporarily increase or decrease activity). A connector104(shown in more detail inFIG. 7), for example a luer connector, is configured to couple to a vacuum source22. The vacuum source22may be a vacuum bottle or canister having a volume of between 20 ml and 500 ml. The vacuum source22may instead be a 60 ml syringe whose plunger is pulled back after coupling to the connector104. This may be a lockable plunger, which is locked in order to maintain the evacuated plunger position. In some cases, the vacuum source22may be a 20 ml syringe or a 30 ml syringe. An exemplary syringe with a lockable plunger is the VacLok® syringe sold by Merit Medical Systems, Inc. of South Jordan, Utah, USA. The vacuum source22may also be a vacuum pump, with or without a collection container. A pressure transducer106capable of measuring vacuum (including positive pressure sensors that are configured to measure positive pressure, but are capable of measuring negative pressure) is coupled to a vacuum line108via a y-connector110. Signals from the pressure transducer106travel along a cable112(FIG. 7), which also supplies voltage to the pressure transducer106. A connector114(also shown inFIG. 6) couples the cable112to a pressure monitor or to the pump base200. A cassette116is a disposable component attachable to the pump base200(FIG. 12) for allowing pressurized injection of a liquid injectate (such as saline). The cassette116is described in more detail in relation toFIG. 6. The aspiration catheter118having a distal end120is shown in more detail inFIG. 8.

Turning toFIG. 5, the spike102communicates with extension tubing122. Liquid injectate is pumped downstream at the piston pump, which pulls more liquid injectate (for example from a saline bag) through a check valve126and through a supply tube130. An injection port128may be used for injecting other materials into the system, or for removing air or priming the system. The spike102may be packaged with a removable protective spike cover124.

The cassette116, as seen inFIG. 6, pulls liquid injectate from the supply tube130, and pressurizes (in conjunction with the pump base200) an injection tube152. More detail of the cassette116will be described along with the description of the entire piston pump.FIG. 7shows more detail of the pressure transducer106for measuring the vacuum. The pressure transducer106connects to the y-connector110with a luer fitting154. The injection tube152and the vacuum line108communicate to lumens of a catheter shaft142. For example, the injection tube152may be fluidly connected to a distal supply tube168(FIGS. 9-11), for example a polyimide or stainless steel or nitinol tube having high strength thin walls. This distal supply tube168may reside within the catheter shaft142, with the annulus between forming an aspiration lumen160(FIGS. 9-11). A strain relief156protects the catheter shaft142from kinking and other damage. In any cases in which luer fittings154are used (at any of the connections), a custom luer with an added o-ring may be used in order to allow the connection to withstand elevated pressures. In some embodiments, a bespoke connector may be utilized, to increase high pressure endurance. In some embodiments, pressures as high as 6.89 megapascal (1,200 pounds per square inch) or greater may be achieved without leakage or without causing decoupling of the catheter.

Turning toFIG. 8, the aspiration catheter118is illustrated as a single-operator exchange catheter and includes a guidewire tube132attached to the distal end120on one side of the aspiration catheter118. The guidewire tube132can be between about 1 and about 30 cm in length, or between about 5 and about 25 cm in length, or between about 5 and about 20 cm in length, or approximately 13.5 cm in length. The guidewire tube132has a distal end136and a proximal end138, and a single guidewire lumen134passing between the two ends136,138. The guidewire lumen134may be configured to be compatible with a 0.014″ guidewire, a 0.018″ guidewire, or a number of other guidewire diameters. A lumen inner diameter may be about 0.406 mm (0.016 inches) for compatibility with a 0.014″ guidewire. The guidewire tube132may be constructed of a number of materials, including nylon, polyethylene, PEBAX®, polyester, PET, or may be constructed from composite or coextruded materials. For example an inner layer may comprise high density polyethylene or FEP, PTFE, ETFE, or other materials for high lubricity, and an outer layer may include PEBAX, nylon or other materials, for combination mechanical strength and flexibility. A tie layer may be used between the inner and outer layers, for example linear low density polyethylene. The catheter118may include a composite catheter shaft142having an inner support structure144covered with a polymer jacket146. The inner support structure144may be a tubular braid or one or more helical coils, for example, made with stainless steel flat or round wires. The inner support structure144may also be spiral cut hypodermic tubing, for example made from 304 stainless steel or nickel-titanium. The spiral cut hypodermic tubing may have a pitch measuring about 4 to 6 millimeters, or about 5 millimeters at the proximal end for increased stiffness, transitioning to a pitch of about 0.75 to 1 mm or about 0.87 mm, at the distal end150of the inner support structure144. In between these two different pitch sections, may be intermediate pitch sections, for example, a section having a pitch of between about 2 mm and about 5 mm, and another section having a pitch of about 1 mm to about 2.5 mm. The inner support structure144may end at a transition zone148, so that the polymer jacket146alone extends to the distal end136of the aspiration catheter118. A catheter tip portion140is described in more detail in relation toFIGS. 9-11.

FIGS. 9-11show an open distal end158of an aspiration lumen160for aspirating thrombus. A skive162may be formed in the polymer jacket146, to aid entry of thrombus164that is aspirated into the aspiration lumen160(in the direction of arrow180) by the combination of the vacuum created by the vacuum source22. The skive162also minimizes the chances of the open distal end158being sucked against a blood vessel wall166. A distal supply tube168has a closed distal end170, for example, it may be occluded during manufacture using adhesive, epoxy, hot melt adhesive or an interference member. Alternatively, the distal supply tube168may be closed off by melting a portion of it. The distal supply tube168has a lumen176extending its length and an orifice172formed through its wall174at a location adjacent and proximal to the closed distal end170. The orifice172may have a diameter between about 0.0508 mm (0.002 inches) and about 0.1016 mm (0.004 inches), or about 0.0787 mm (0.0031 inches). The inner diameter of the distal supply tube168may be between about 0.3048 mm (0.012 inches) and about 0.4826 mm (0.019 inches), or between about 0.3556 mm (0.014 inches and about 0.4318 mm (0.017 inches) or about 0.3937 mm (0.0155 inches). The lumen176of the distal supply tube168is a continuation of an overall flow path emanating from the fluid source20including the extension tubing122, the supply tube130, the interior of the cassette116, and the injection tube152. In some embodiments, the lumen176of the distal supply tube168may taper, for example, from an inner diameter of about 0.3937 mm (0.0155 inches) at a proximal portion to an inner diameter of about 0.2974 mm (0.011 inches) at a distal portion. In some embodiments, the equivalent of a taper may be achieved by bonding different diameter tubing to each other, resulting in a stepped-down tubing inner diameter. In some embodiments, different diameter tapered tubing may be bonded to each other, for a combination of tapering and step-down of diameter. As described in conjunction with the piston pump, a pump output pressure wave of about 4.137 megapascal (600 pounds per square inch) to about 5.516 megapascal (800 pounds per square inch) causes a liquid injectate to flow through the flow path, including a distal supply tube168(arrows182), and causes a fluid jet178to exit the orifice172at a high velocity. The fluid jet178, in absence of flow through the aspiration lumen160(for example if there is no vacuum), would impinge upon an inner wall181of the aspiration lumen160directly adjacent the orifice172. Depending on the amount of vacuum present, the fluid jet, may curve as shown. The fluid jet178serves to macerate thrombus164that enters the aspiration lumen160, and dilutes it. The flow rate of the liquid injectate (e.g. saline) and the amount of vacuum are controlled so that about 50% to about 95% of the volume of the mixture of the saline and blood flowing through the proximal aspiration lumen160is blood. Or about 90% of the volume is blood. In other embodiments, the flow rate of the liquid injectate (e.g. saline) and the amount of vacuum are controlled so that about 50% to about 70% of the volume of the mixture of the saline and blood flowing through the proximal aspiration lumen160is blood. Or, about 60% of the volume is blood. This maceration and dilution assures that there is continuous flow through the aspiration lumen160so that it will not clog. The fluid jet178is configured to be contained within the aspiration lumen160, and to not exit into a blood vessel or other body lumen.

The axial center of the orifice172is about 0.3302 mm (0.013 inches) to about 0.8382 mm (0.033 inches), or about 0.4064 mm (0.016 inches) to about 0.6604 mm (0.026 inches) proximal to the most proximal portion of the open distal end158, as illustrated by distance D inFIG. 11.FIG. 14is a cross-section of the catheter tip portion140at the axial center of the orifice172. The orifice172it is oriented approximately along a vertical midline184of the aspiration lumen160, or within a range of ±a, there where angle a is about 20°. The angle a, may be varied in different embodiments between about 1° and about 45°, or between about 20° and about 35°. The guidewire tube132may be secured to the polymer jacket146with attachment materials186, such as adhesive, epoxy, hot melt or other materials. The guidewire tube132may be secured along its entire length, or at discrete locations along its length, in order to maximize flexibility. The distal supply tube168may be secured within the aspiration lumen160with attachment materials188, such as adhesive, epoxy, hot melt or other materials. The polymer jacket146may comprise a number of different materials, including PEBAX, nylon, or polyurethane. In some embodiments, the polymer jacket may be partially melt bonded to the distal supply tube162and/or the guidewire tube132, in order to minimize the wall thickness of the assembly.

FIG. 12illustrates a pump base200for coupling the cassette116of the system for aspiration of thrombus100. A housing202is attached to an IV pole clamp204, and contains the control circuitry and the motor for operating a piston pump system300(FIG. 13) which comprises the combined pump base200and the cassette116. By action of a motor and cam within the pump base200, a saddle206is cyclically actuated (up and down) within a window208to move a piston210within the cassette116(FIG. 13). Pegs212of the cassette116insert into cavities216in the pump base200. Biased snaps214lock into one or more grooves218in the pump base200. Either the cavities216or the grooves218, may have one or more switches which sense the presence of the cassette116. For example, the cassette for one particular model may have a first number (or combination) of pegs212or biased snaps214, which another particular model may have a different number (or combination) of pegs212or biased snaps214, which is recognized by the system. A smooth surface224of an elastomeric frame222engages edges220of the cassette116, for enhanced protection. An upper space226is configured to engage, or closely match the supply tube130and a lower space228is configured to engage, or closely match the injection tube152. The saddle206has a semi-cylindrical cavity236which snaps over a cylindrical engagement surface238on the piston210. The saddle also has an upper edge240and a lower edge242for axially engaging a first abutment244and a second abutment246, respectively, of the piston210. A user interface230on the pump base200has one or more buttons232and one or more indicators234, which allow the user to operate and assess the operation of the system100. For example, the buttons may include a start button to begin pumping, a stop button to stop pumping, a prime button to prime the system with a fluid injectate and purge out air, or a temporary pause button. Other data entry keys are also possible. The cassette116may include one or more interface components248. For example, a resistor, whose value the pump base200is able to measure via contacts247,249when the cassette116is attached to the pump base200. This allows the pump base200to determine the appropriate parameter for operating a specific model of the system100. For example, a first resistor having a first resistance may be used with a first model and a second resistor having a second resistance may be used with another model. Alternatively, the interface component248may incorporate an RFID chip, such as a read RFID chip or a read/write RFID chip. This may allow specific data (pump operating pressures, RPM of motor output, etc.) to be recorded within the pump base200or to connected hardware and identified for each patient.

FIGS. 15 and 16illustrate the cassette116with most of its internal components visible.FIG. 16is a sectional view of the cassette116. The cassette116comprises an internal supply cylinder252and an internal injection cylinder254, which are cylindrical cavities extending within the cassette116. The piston210includes a supply side shaft256and an injection side shaft258, the supply side shaft256including an o-ring266for sealably interfacing with the supply cylinder252and the injection side shaft258including an o-ring268for sealably interfacing with the injection cylinder254. Each of the o-rings266,268are within a cylindrical groove290,292around each respective shaft portion256,258. An internal ball valve272(FIG. 16) stops injectate (saline) from flowing through an internal channel274in the supply side shaft256of the piston210when the piston210moves in a first direction276, but the internal ball valve272allows injectate to flow through the internal channel274and through an internal channel282in the injection side shaft258when the piston210moves in a second direction278. The ball valve272is axially held between a spherical annular recess284in the interior of the supply side shaft256and a recess having thru channels286in the injection side shaft258. The supply side shaft256and the injection side shaft258may be held together with a threaded connection288. When the piston210moves in the first direction276, the injection side shaft258of the piston210and o-ring268force injectate through the injection tube152. A protective tube280is shown over the injection tube152. InFIG. 15, the injection side shaft258is shown at the bottom of an injection pulse. Injectate is filtered through an in-line filter262, which may be a 40 to 50 micron filter, having an approximate thickness of 0.762 mm (0.030 inches). The in-line filter262is configured to keep particulate out of the injectate. Even though injectate is circulated through the aspiration catheter118, and not into the blood vessel, the filtering provided by the in-line filter262is an extra safety step. However, this step helps assure that particulate does not block the small orifice172(FIG. 11). When the piston210moves in the second direction278, the supply side shaft256of the piston210and the o-ring266sealably move together within the supply cylinder252, but the ball valve272allows the injectate to pass through the internal channels274,282of the piston210and fill the injection cylinder254. The injectate is able to enter from the supply tube130through a check valve assembly270comprising an o-ring264and a check valve250. The check valve250allows injectate to enter the interior of the cassette116from the supply tube130, but not to move from the cassette116to the supply tube130. The check valve250may be configured so that air, due at least in part to its low viscosity, will not be able to cause the check valve250to move (open), thus not allowing air to progress through the system. In some embodiments, the piston210may be a single piece (monolithic) design with a bore into which a check-valve is press-fit or bonded. A check valve compatible with this assembly may be supplied by the Lee Company of Westbrook, Conn., USA.

The volume of injectate injected per cycle may range from about 0.02 ml to about 41 ml, or from about 0.04 ml to about 2.0 ml, or about 0.06 ml to about 0.08 ml, or about 0.07 ml. The usable volume (volume that can be injected) of the injection cylinder254may be configured to be less than the usable volume (volume that can be filled from) of the supply cylinder252, in order to assure sufficient filling of the injection cylinder254. For example, the usable volume of the injection cylinder254may be about 0.05 ml to about 0.12 ml, and the usable volume of the supply cylinder252may be about 0.07 ml to about 0.16 ml. A usable volume ratio RUof between about 1.15 and about 2.00, or between about 1.25 and about 1.85, or about 1.40 is contemplated, where:

VSCU=Usable volume of the supply cylinder252, and

VICU=Usable volume of the injection cylinder254.

A mean flow rate of between about 5 ml/minute and about 100 ml/minute. In some embodiments for use in coronary applications, 20 ml/minute may be desired. In some embodiments for use in peripheral applications, 50 ml/minute may be desired.

FIG. 18illustrates a graph600of a pressure (P) vs. time (T) curve602of a piston pump. Peaks604and valley606of the curve602can be dependent upon the design of the piston and cylinders of the piston pump, particularly of the usable volume ratio RU. Turning toFIG. 19, a piston608is illustrated having a first diameter D1and a second diameter D2measured at the compressed o-rings601,603(when placed within cylinders605and607of a cassette609). The diameters of the cylinders605,607are thus also defined as diameters D1and D2. When the diameters D1, D2, and the lengths of the cylinders605,607are adjusted such that the usable volume ratio RUis optimized as previously described, a curve610as illustrated inFIG. 20may be produced. The curve610has less-defined peaks614and valleys616, and thus produces less variation of flow amplitude, and a more balanced injection.

The partially exploded pump base200inFIG. 17illustrates the internal mechanisms for linear (up and down) actuation of the saddle206, which is attached to a saddle stage310. A motor302is controlled by a circuit board304and operated by the user interface230(FIG. 12), whose indicators234are lit by LEDs306. The motor302turns a cam316, in which includes a path330. The saddle stage310has a pin318extending from its back side. The pin318may be press fit, bonded or screwed in place within the saddle stage310. The saddle stage310is secured with screws to two slides312,314through holes326,328, such that rotary motion of the cam316causes the pin318to track along the path330of the cam316, thus causing the saddle stage310attached to the slides312,314to slide upward and downward in cyclic motion. The shape of the cam determines the amount of acceleration and deceleration in the motion. Upper posts322and lower posts324serve as guides and/or stops of the saddle stage310. The connector114of the pressure transducer106for measuring vacuum may be plugged into socket308(also shown inFIG. 12), and pressure related signals may be processed by the circuit board304. The entire pump base200is reusable.

The inner contour diameter of the cam316may be sized and/or shaped to control the stroke length of the piston210and the amount of pulsatility (i.e., the difference between the high and low pressure). In some cases, decreasing the stroke length decreases the amount of pulsatility. In applications within the heart, such as coronary artery applications, lowering the amount of pulsatility can reduce the incidence of bradycardia. To compensate for a lower stroke length, and to maintain a sufficient total flow rate, the speed of the rotation of the cam (i.e. rotations per minute), can be increased, for example by increasing motor output speed, either by gearing or by increased applied voltage.

Another embodiment of a system for aspirating thrombus800is illustrated inFIG. 21. The system for aspirating thrombus800includes, three major components: the pump base200ofFIG. 12, an aspiration catheter818, and a tubing set803. The aspiration catheter818and the tubing set803represent disposable components801, and the pump base200is a reusable component. It is not necessary to sterilize the pump base200as it is kept in a non-sterile field or area during use. The aspiration catheter818and the tubing set803may each be supplied sterile, after sterilization by ethylene oxide gas, electron beam, gamma, or other sterilization methods. The aspiration catheter818may be packaged and supplied separately from the tubing set803, or the aspiration catheter818and the tubing set803may be package together and supplied together. Alternatively, the aspiration catheter818and tubing set may be packaged separately, but supplied together (i.e., bundled). As shown inFIGS. 21 and 22. The aspiration catheter818and tubing set803share many of the same features as the aspiration catheter118and tubing set103ofFIG. 4, but are configured to allow easier separation from each other, and additional procedural adaptability. The aspiration catheter818has a distal end820comprising a guidewire tube832having a distal tip836, and a proximal end819comprising a y-connector810. The catheter shaft842of the aspiration catheter818is connected to the y-connector810via a protective strain relief856. In other embodiments, the catheter shaft842may be attached to the y-connector810with a luer fitting. The y-connector810may comprise a first female luer851which communicates with a catheter supply lumen (as in the catheter118ofFIGS. 4, 8-11), and a second female luer855which communicates with a catheter aspiration lumen (as in catheter118ofFIGS. 4, 8-11).

Turning toFIG. 23, the tubing set803is shown in more detail. A spike802for coupling to a fluid source20(FIG. 1) allows fluid to enter through extension tubing822and a check valve826, and into supply tube830. An optional injection port828allows injection of materials or removal of air, as described in relation to previous embodiments. A cassette816is used in conjunction with the pump base200, and is similar in structure and function to the cassette116inFIGS. 15-16. Fluid is pumped into injection tube852from cassette816. A male luer854is configured to attach to the female luer851of the y-connector810.

Returning toFIG. 21, accessories857are illustrated that are intended for applying a vacuum source22, including a syringe849having a plunger867, to the catheter818. The syringe849is attached to syringe extension tubing859via the luer865of the syringe849. A stopcock847may be used to hold maintain the vacuum, or the plunger867may be a locking variety of plunger. A luer861of the syringe extension tubing859is connected to an pressure transducer806, the pressure transducer806having a male luer863for connection to a connector (e.g., female luer)804of vacuum line808. A male luer853at the end of the vacuum line808may be detachably secured to the female luer855of the y-connector810of the aspiration catheter818. Signals from the pressure transducer806are carried through cable812to a connector814. The connector814is plugged into the socket308(FIG. 12) of the pump base200. Pressure related signals may be processed by the circuit board304of the pump base200. The pressure transducer806may be power from the pump base200, via cable812. The accessories857may also be supplied sterile to the user.

In use, the pump base200resides outside the sterile field. Because operation of the pump base200may be controlled by the presence or absence of a pressure, a user who is working in the sterile field may turn the pump on or off without touching the non-sterile pump base200. For example, the pump may be started by placing a vacuum on the system (e.g., pulling the plunger867of the syringe849). The pump may in turn be stopped by removing the vacuum on the system (unlocking the plunger867of the syringe849and allowing to release, or opening the stopcock847). The syringe849or the combination syringe849and stopcock847may act as a sterile on/off button of the pump vase200. Alternatively, the aspiration catheter818may be initially used without the pump base200, with only aspiration being applied to the aspiration lumen. If in certain cases, if the aspiration lumen becomes clogged, the distal end820of the aspiration catheter818may be backed off of the thrombus, and the pump base200and tubing set803may be coupled to the aspiration catheter818, to then operate with forced saline injection, for increased aspiration, and clear the aspiration lumen. This will also help stop any thrombus that is blocking the aspiration lumen from being inadvertently delivered into the blood vessel of the patient.

FIGS. 24 and 25illustrate a saline pump drive unit400having a completely disposable pump head500. The saline pump drive unit400is configured to be usable with the catheters16,118described herein, or other embodiments of aspiration systems comprising fluid injection. InFIG. 24, a bottom case402and a top case404having a label406are secured together with screws408. Contained within the bottom case402and top case404are a battery pack410and an electronic control module412. A battery cover416holds the battery pack410in place. In some embodiments, the battery pack410may supply a voltage of 18 Volts DC, but systems utilizing other voltages are possible. A user interface414enables operation of the saline pump drive unit. A vacuum bottle sleeve418may be used when a vacuum bottle is incorporated as the vacuum source22. A spike420is connectable to a fluid source20, and fluid injectate passes from the fluid source20through extension tubing422to a disposable piston pump head500. Saline may be primed through the system by an automatic priming (“self-priming”) system described herein in relation to prior embodiments, or may be primed by gravity from a saline bag that is located (for example on an IV pole) above the rest of the system. A valve on the lowest portion of the system may be opened in order to prime the entire system.

As illustrated inFIG. 25, the disposable piston pump head500is configured to couple to a motor shaft504of a motor502, that is powered by the battery pack410of the saline pump drive unit400. A motor plate506and a main body508of the disposable piston pump head500are secured to each other with screws510, and hold the internal components of the disposable piston pump head500. First and second follower plates512,514are held together with screws516and bosses518extending from the first follower plate512. The first and second follower plates512,514rotatably hold a cam520. The cam may be asymmetric (as illustrated) or alternatively may be symmetric. The asymmetry may be incorporated in order to control the amount of noise in the pump, the contours serving to customize the shape of the pressure wave, and of the function of the pump. First and second bushings522,524are rotatably held on first and second pins526,528. The pins526,528insert into cylindrical cavities530,532in each of the follower plates512,514.

In use, a user attaches the disposable piston pump head500to the motor502of the saline pump drive unit400by bringing the motor plate506close to the motor shaft504so that a d-shaped hole534in the cam520can be pressed over the d-shaped motor shaft504. Alternatively, the d-shapes may be other non-circular shapes, including, but not limited to elliptical, oval, or rectangular. In operation the motor502turns the motor shaft504, which in turn turns the cam520. The cam520turns, forcing the bushings522,524to push the first and second follower plates512,514back and forth in a first direction536and a second direction538. A saddle544is carried on the second follower plate514, and a piston210may be coupled to the saddle544in the same manner as described herein with other embodiments. A supply cylinder552and an injection cylinder554in the main body508are analogous to the supply cylinder252and injection cylinder254of the cassette116of the system100. The piston210of the cassette116may be used in the disposable piston pump head500. The labelled components related to the piston210inFIG. 25are similar to those described in relation to the piston210inFIGS. 15 and 16. The outer diameter of the cam520may be sized and/or shaped to control the stroke length of the piston210and the amount of pulsatility (i.e., the difference between the high and low pressure). In some cases, decreasing the stroke length decreases the amount of pulsatility. In applications within the heart, such as coronary artery applications, lowering the amount of pulsatility can reduce the incidence of bradycardia. To compensate for a lower stroke length, and to maintain a sufficient total flow rate, the speed of the rotation of the cam (i.e. rotations per minute), can be increased, for example by increasing motor output speed, either by gearing or by increased applied voltage. In some embodiments, it may be desired to control the pulsatility in order to tailor the size of the pieces of thrombus that are being cut by the fluid jet178(FIG. 11). A pulse frequency of 250 pulses per minute (4.167 Hz) or more can be effective in insuring that the pieces of thrombus cut by the fluid jet are relatively small, and that the feed of these pieces through the aspiration lumen160during aspiration is adequate such that clogging does not tend to occur. A vacuum spike546is used for coupling to the vacuum source22, for example a vacuum bottle held within the vacuum bottle sleeve418. A vacuum switch valve540, which is activated against the bias of a spring542, may be used to allow pump activation. For example, the electronic control module412may be configured to initiate the operation of the motor502automatically when the vacuum switch valve540sends a signal corresponding to movement of the vacuum switch valve540, which occurs when a significant vacuum is achieved. This control may be instead of or in addition to control from a vacuum pressure transducer, such as pressure transducer106. The turning on of the vacuum may thus be used to simultaneously turn on the motor502, so that a single input begins the operation of the saline pump drive unit400. Additionally, a vacuum source22may be controlled by the electronic control module412(for example, by opening or closing a solenoid), when a minimum injectate pressure is measured by an additional pressure transducer. For example, when a pressure of about 0.62 megapascal (90 pounds per square inch) or greater is measured, the vacuum may be activated or communicated to the system. An advantage of the saline pump drive unit400is that the user is required only to assemble a single component onto the shaft504of the motor502.

As previously described, the systems according to any of the embodiments of the present disclosure may be configured such that active flow of saline (or other) injectate is not possible without concurrent vacuum being applied for aspiration. Also, the systems may be configured such aspiration is not possible without saline (or other) injectate flow. The systems according to any of the embodiments of the present disclosure may be configured such that current driving the pump (for example the current driving the motor302,502) is monitored, or by any alternative monitoring method, such that when a change in condition occurs, for example, air in the injection system, or clogs in any of the catheter lumens or extension tubes, or leaks within the system, the system shuts down, in order to avoid events such as injection of air into the blood vessels, or catheter or system failure.

FIG. 26illustrates an aspiration catheter700inserted within a blood vessel165. The aspiration catheter700includes a guidewire lumen702secured to the distal end704of the aspiration catheter700which allows the aspiration catheter700to be tracked over a guidewire706. A supply lumen708is secured within an aspiration lumen710. The supply lumen708extends through a tapering tube712. In some embodiments, the tapering tube712may be constructed of polyimide. In some embodiments, the tapering tube712may have a luminal inner diameter that tapers from its proximal end to its distal end. For example, in some embodiments, the luminal inner diameter may taper from about 0.3937 mm (0.0155 inches) to about 0.2794 mm (0.011 inches). The supply lumen708extends generally parallel to the aspiration lumen710, however a distal end714of the tapering tube712curves towards an interior wall surface716of the aspiration lumen710, thus allowing an open end718of the supply lumen708to act as an orifice for applying a spray pattern720. The open end718of the supply lumen708may further promote a jet or spray effect by having an internal diameter that is less than about 0.203 mm (0.008 inches). In some embodiments, the open end718of the supply lumen708may have an internal diameter that is between about 0.076 mm (0.003 inches) and about 0.102 mm (0.004 inches). The center of the open end718orifice may in some embodiments be about 0.3302 mm (0.013 inches) to about 0.4826 mm (0.019 inches) proximal to the most proximal portion724of the open distal end722of the aspiration lumen710, as illustrated by distance D inFIG. 26. The most distal portion726of the open distal end722of the aspiration lumen710is slightly distal of the most proximal portion724in the embodiment illustrated, and thus has an angled skive, but the skive angle Asis not severe. A skive angle Asof between about 75° and about 89°, or between about 80° and about 85° may be used, in order to allow a large portion of thrombus being pulled into the open distal end722of the aspiration lumen710to be struck by high velocity exiting jet (e.g. saline) flow, as illustrated with the spray pattern720.

FIG. 27illustrates the catheter700ofFIG. 26being utilized to deliver a drug730to a target site732within a blood vessel165. The target site732may include an atherosclerotic lesion728and/or a thrombus734. Whereas the aspiration of thrombus, as inFIG. 26, involves actively applying a vacuum (e.g., from a vacuum source) on the aspiration lumen710, the drug delivery illustrated inFIG. 27, though utilizing the same catheter700, allows the metering of a fine, precision volume flow rate of drug730to be delivered into the vessel. This is achieved by having significantly less vacuum applied to the aspiration lumen710, or no vacuum applied to the aspiration lumen. The precision metering in small, controlled volumes, provides efficient use of typically expensive drugs, with minimal wasted drug. In addition, the relatively small volume, or dead space, of the supply lumen708, because of its relatively small diameter, assures that upon stopping the infusion of a drug730, very little volume of inadvertent injection is even possible.

In some embodiments, the drug730may be delivered at body temperature. In other embodiments, the drug730may be warmed, and delivered at an elevated temperature, for example, to increase the activity and effectiveness of a drug. This may be done, for example, to get a more effective dose, with a smaller volume of drug. In other embodiments, the drug730may be cooled and delivered at a reduced temperature (i.e., in relation to the body temperature). The drug730may be cooled to control the activity level, or to delay the activity of the drug (e.g., so that it is active downstream, at a location that is not reachable by the catheter700). In some cases, the drug730may be cooled in order to apply a conjunctive therapeutic cooling effect on the tissue being treated. In some cases, the therapeutic cooling effect may be achieved from cooled saline or other aqueous non-drug media alone.

Some of the drugs730which may be delivered include thrombolytic agents (clot busting drugs), such as streptokinase, tissue plasminogen activator (t-PA), recombinant or genetically-engineered tissue plasminogen activator, tenecteplase (TNK), urokinase, staphylokinase, and reteplase. Alternatively, stem cells or “cocktails” containing stem cells may be delivered. In some cases, glycoprotein inhibitos (GPI's) may be injected through the supply lumen708of the aspiration catheter700. Saline or other aqueous solutions may be delivered alone for selective dilution of blood at the target site732. In some applications, a solution may be used which is capable of exhibiting a phase change, for example, when its pressure or temperature is changed. In these applications, a liquid may be injected that becomes a gas when exiting from a small orifice, for example at the open end718of the supply lumen708. Alternatively, a gas may be injected that becomes a liquid when being force through a small orifice, such as the open end718of the supply lumen708. In any of the applications in which drugs730or other materials are injected intravascularly through the catheter700, the injection of the drugs730or other materials may occur before, during, after, or instead of an aspiration procedure. Returning to the aspiration catheter818ofFIGS. 21-22, if, during an aspiration procedure, it is desired to deliver drugs down the supply lumen and into the vessel, the tubing set803may be removed from the aspiration catheter818by disconnecting the male luer854of the tubing set803from the female luer851of the aspiration catheter818, and the drug may be injected directly into the supply lumen at the female luer851, for example, by a syringe or metering system, including a syringe/syringe pump combination. By also removing the vacuum source from the female luer855of the aspiration catheter818, when aspiration lumen now serves as an overflow, so that the fluid being delivered into the patient (e.g., intravascularly) is maintained at a controlled rate. The volume of the supply lumen is relatively very small, so only a small volume of drug is needed to fill the supply lumen, and thus reach the distal top of the aspiration catheter818. This, at the end of the procedure, very little drug is wasted, or needs to be disposed, allowing for a very cost-effective procedure.

In the embodiments described herein, a sterile fluid path is provided extending all the way from the fluid source20to the distal opening40/open distal end158of the catheter16,118. In both the embodiments of the system100ofFIGS. 4-17, the system800ofFIGS. 21-23, and the embodiments ofFIGS. 24-25, a disposable catheter and disposable pump set are configured to be supplied sterile, and coupled to a non-sterile (reusable) pump base200or pump motor502. These combinations allow for reusability of the more expensive components, and for reusability (and maximized sterility) of the less expensive components, thus maximizing cost containment and patient safety at the same time.

FIG. 28illustrates an aspiration catheter900including a shaft901having an aspiration lumen902and a supply tube903having a supply lumen904(high pressure lumen). The supply tube903is secured to an inner wall906of the shaft901, for example, by adhesive, epoxy, mechanical securement, or thermal bonding or tacking. The supply lumen904is configured to carry pressurized fluid912, which may include saline, lytic (thrombolytic) agents, contrast agents, or other agents. In use, the pressurized fluid912exits in a spray pattern914from an orifice908adjacent the distal end910of the supply lumen904, impinging against an interior wall surface916of the aspiration lumen902. The agent or agents may be undiluted or may be diluted (e.g., with saline). A jet spray impact911against the interior wall surface916may form a distal component and/or a proximal component, as described in further detail inFIGS. 32, 36, and 40. The distal component or proximal component may be substantially distally-oriented or substantially proximally-oriented, in part or in whole, because of factors such as: the particular level of positive pressure of the pressurized fluid912within the supply lumen904, or because of the particular geometry of the orifice908, or because of the particular level of negative pressure on the aspiration lumen902, or because of the particular geometry of the interior wall surface916, separately, or in any type of combination. A pump, syringe, or other source of pressurization may be coupled to the proximal end of the supply lumen904, to allow pressurization or pulsation of the supply lumen904. In some embodiments, the pump base200(FIG. 12) may be used to supply and pressurize the supply lumen904with the fluid912. The supply tube903includes a plug918which blocks the end of the supply lumen904, forcing pressurized fluid912through the orifice908and into the aspiration lumen902, and, when operated to supply sufficient pressure, against the interior wall surface916.

The spray pattern914may be directed by the orifice908toward the interior wall surface916perpendicularly (i.e., at a 90° angle)914ain relation to the longitudinal axis917of the aspiration catheter900and/or may impact the interior wall surface916at an oblique angle that is distally-oriented914bor an oblique angle that is proximally-oriented914c. The spray pattern914may comprise two or three of these elements914a,914b,914ctogether.

An alternative embodiment of an aspiration catheter915is illustrated inFIG. 29, and includes a shaft921having an aspiration lumen922and a supply tube923having a supply lumen924(high pressure lumen). The supply tube923is secured to an inner wall926of the shaft921. The supply lumen924is configured to carry pressurized fluid912, which may include saline, lytic (thrombolytic) agents, contrast agents, or other agents. The agent or agents may be undiluted or may be diluted (e.g., with saline). The pressurized fluid912exits in a spray pattern919from an orifice928adjacent the distal end920of the supply lumen924and impinges against an interior wall surface909of the aspiration lumen922. The interior wall surface909includes an additional element929(e.g., deflection element) which is configured for deflecting at least a portion of the spray pattern919either proximally or distally. The deflection element929includes a forward ramp927and a reverse ramp925which converge at a dividing line931. The forward ramp927is configured to deflect at least a portion of the spray pattern919distally and the reverse ramp925is configured to deflect at least a portion of the spray pattern919proximally. A jet spray impact against the interior wall surface909may include a distal component and/or a proximal component, as described in further detail inFIGS. 33 and 37. In other embodiments, the interior wall surface909may simply be a deformation of a portion of the inner wall926itself. The deformation may take the place of the deflection element929and thus act as the deflection element929. The deformation may an angulation or formation of the distal end907of the aspiration catheter900that causes the inner wall926to have, for example, one or more ramps or angled, or curvilinear surfaces.

A distal component or proximal component may be substantially distally-oriented or substantially proximally-oriented in part or in whole because of factors such as: the particular level of positive pressure of the pressurized fluid912within the supply lumen924, or because of the particular geometry of the orifice928, or because of the particular level of negative pressure on the aspiration lumen922, or because of the particular geometry of the interior wall surface909, separately, or in any type of combination. A pump, syringe, or other source of pressurization may be coupled to the proximal end of the supply lumen924, to allow pressurization or pulsation of the supply lumen924. The supply tube923includes a plug932which blocks the distal end920of the supply lumen924, forcing pressurized fluid912through the orifice928and into the aspiration lumen922and, when operated to supply sufficient pressure, against the interior wall surface909comprising ramps925,927. In some embodiments, a portion of the spray pattern919that strikes the forward ramp927is deflected distally. In some embodiments, a portion of the spray pattern919that strikes the reverse ramp925is deflected proximally. In some embodiments, the specific amount of negative pressure being applied on the aspiration lumen922(e.g., by a vacuum source) controls how much of the spray pattern919impinges upon each of the ramps925,927.

In the aspiration catheter915ofFIG. 29, the ramps925,927of the element929extend from the dividing line931in a linear fashion, wherein the effective inner radius of the aspiration lumen changes linearly in relation to the longitudinal location along the ramp925,927. In contrast,FIG. 30illustrates an aspiration catheter934having non-linear ramps942,944(e.g., curvilinear) extending between a dividing line933. The aspiration catheter934includes a shaft935having an aspiration lumen936and a supply tube937having a supply lumen938(high pressure lumen). The aspiration catheter934further includes a deflection element940with ramps942,944that each include a concave contour946,948, such that the effective inner radius of the aspiration lumen changes non-linearly in relation to the longitudinal location along the ramp942,944. In some embodiments, the deflection element940may be configured for directing and/or deflecting a spray pattern947(emanating from orifice949) that is narrow and/or that comprises a jet. In other embodiments, the deflection element929of the aspiration catheter915ofFIG. 29may be configured for directing and/or deflecting a spray pattern919that is wider or which significantly diverges or spreads.

FIG. 31illustrates an aspiration catheter950which includes a shaft951having an aspiration lumen952and a supply tube953having a supply lumen954(high pressure lumen). The aspiration catheter950further includes a deflection element956with a single distally-oriented ramp958which is configured to deflect at least a portion of a spray pattern960emanating from an orifice962in a substantially distal direction.

FIG. 32illustrates the aspiration catheter900ofFIG. 28in use within a blood vessel964as part of an aspiration system10or system for aspirating thrombus100,800.FIG. 32illustrates the aspiration catheter900in a first mode of operation configured to cause substantial aspiration of thrombi966. A venturi effect is created by the spray pattern914, which may comprise a jet. Suction is thus created at the distal opening968of the aspiration lumen902causing the thrombi966to be aspirated into the aspiration lumen902. In addition, an aspiration pressure (negative pressure) may be applied at a proximal end of the aspiration lumen902(e.g., with a vacuum source, such as a syringe, vacuum chamber or vacuum pump), thus maintaining the flow of the thrombi966through the aspiration lumen902. The impingement of the spray pattern914of the pressurized fluid912against the interior wall surface916of the aspiration lumen902, opposite the orifice908, may also macerate the thrombi966into smaller pieces970which can help to lower the effective viscosity of the composite fluid flowing through the aspiration lumen902. By applying a significant vacuum/aspiration pressure on the proximal end of the aspiration lumen902, the removal of thrombi966and any smaller pieces970of thrombi966can be optimized. The spray pattern914is at least partially diverted into a substantially proximally-oriented flow955after impingement upon the interior wall surface916.

FIG. 33illustrates the aspiration catheter915ofFIG. 29in use within a blood vessel964as part of an aspiration system10or system for aspirating thrombus100,800.FIG. 33illustrates the aspiration catheter915in a first mode of operation configured to cause substantial aspiration of thrombi966. A venturi effect is created by the spray pattern919, which may comprise a jet. Suction is thus created at the distal opening972of the aspiration lumen922causing the thrombi966to be aspirated into the aspiration lumen922. In addition, an aspiration pressure (negative pressure) may be applied at a proximal end of the aspiration lumen922(e.g., with a vacuum source, such as a syringe, vacuum chamber or vacuum pump), thus maintaining the flow of the thrombi966through the aspiration lumen922. The impingement of the spray pattern919of the pressurized fluid912against the reverse ramp925of the deflection element929, opposite the orifice928, may also macerate the thrombi966into smaller pieces970which can help to lower the effective viscosity of the composite fluid flowing through the aspiration lumen902. By applying a significant vacuum/aspiration pressure on the proximal end of the aspiration lumen922, the removal of thrombi966and any smaller pieces970of thrombi966can be optimized. The spray pattern919is at least partially diverted into a substantially proximally-oriented flow957after impingement upon the reverse ramp925of the deflection element929.

FIG. 34illustrates the aspiration catheter934ofFIG. 30in use within a blood vessel964as part of an aspiration system10or system for aspirating thrombus100,800.FIG. 34illustrates the aspiration catheter934in a first mode of operation configured to cause substantial aspiration of thrombi966. A venturi effect is created by the spray pattern947, which may comprise a jet. Suction is thus created at the distal opening974of the aspiration lumen936causing the thrombi966to be aspirated into the aspiration lumen936. In addition, an aspiration pressure (negative pressure) may be applied at a proximal end of the aspiration lumen936(e.g., with a vacuum source, such as a syringe, vacuum chamber or vacuum pump), thus maintaining the flow of the thrombi966through the aspiration lumen936. The impingement of the spray pattern947of the pressurized fluid912against the reverse ramp944of the deflection element940, opposite the orifice949, may also macerate the thrombi966into smaller pieces970which can help to lower the effective viscosity of the composite fluid flowing through the aspiration lumen936. By applying a significant vacuum/aspiration pressure on the proximal end of the aspiration lumen936, the removal of thrombi966and any smaller pieces970of thrombi966can be optimized. The spray pattern947is at least partially diverted into a substantially proximally-oriented flow959after impingement upon the reverse ramp944of the deflection element940.

FIG. 35illustrates the aspiration catheter950ofFIG. 31in use within a blood vessel964as part of an aspiration system10or system for aspirating thrombus100,800.FIG. 35illustrates the aspiration catheter950in a first mode of operation configured to cause substantial aspiration of thrombi966. A venturi effect is created by the spray pattern960, which may comprise a jet. Suction is thus created at the distal opening976of the aspiration lumen952causing the thrombi966to be aspirated into the aspiration lumen952. In addition, an aspiration pressure (negative pressure) may be applied at a proximal end of the aspiration lumen952(e.g., with a vacuum source, such as a syringe, vacuum chamber or vacuum pump), thus maintaining the flow of the thrombi966through the aspiration lumen952. The impingement of the spray pattern960of the pressurized fluid912against the interior wall surface978which is proximal to the deflection element956, opposite the orifice962, may also macerate the thrombi966into smaller pieces970which can help to lower the effective viscosity of the composite fluid flowing through the aspiration lumen952. By applying a significant vacuum/aspiration pressure on the proximal end of the aspiration lumen952, the removal of thrombi966and any smaller pieces970of thrombi966can be optimized. The spray pattern960is at least partially diverted into a substantially proximally-oriented flow961after impingement upon the interior wall surface978which is proximal to the deflection element956.

FIG. 36illustrates the aspiration catheter900ofFIG. 28in use within a blood vessel964as part of an aspiration system10or system for aspirating thrombus100,800.FIG. 36illustrates the aspiration catheter900in a second mode of operation configured to deliver a fluid (such as a fluid comprising an agent) distally out the distal opening968of the aspiration lumen902. The impingement of the spray pattern914of the pressurized fluid912against the interior wall surface916of the aspiration lumen902, opposite the orifice908, at least partially diverts the spray pattern914into a substantially distally-oriented flow963. In addition, an aspiration pressure (negative pressure) may be reduced, completely stopped, or simply not applied at a proximal end of the aspiration lumen902, thus allowing at least some of the spray pattern914to transform into the substantially distally-oriented flow963after impingement upon the interior wall surface916. In some embodiments, the orifice908and/or the interior wall surface916may be configured such that in some conditions, the substantially distally-oriented flow963may itself be a jet. The agent may comprise a lytic agent, such as a thrombolytic agent, or may comprise a contrast agent. The substantially distally-oriented flow963may comprise 50% or more of the spray pattern914(upon deflection), or 60% or more, or 70% or more, or 80% or more, or 90% or more, or even 100%.

FIG. 37illustrates the aspiration catheter915ofFIG. 29in use within a blood vessel964as part of an aspiration system10or system for aspirating thrombus100,800.FIG. 37illustrates the aspiration catheter915in a second mode of operation configured to deliver a fluid (such as a fluid comprising an agent) distally out the distal opening972of the aspiration lumen922. The impingement of the spray pattern919of the pressurized fluid912against the forward ramp927of the deflection element929, opposite the orifice928, at least partially diverts the spray pattern919into a substantially distally-oriented flow965. In addition, an aspiration pressure (negative pressure) may be reduced, completely stopped, or simply not applied at a proximal end of the aspiration lumen922, thus allowing at least some of the spray pattern919to transform into the substantially distally-oriented flow965after impingement upon the forward ramp927of the deflection element929. In some embodiments, the orifice928and/or the forward ramp927of the deflection element929may be configured such that in some conditions, the substantially distally-oriented flow965may itself be a jet. The agent may comprise a lytic agent, such as a thrombolytic agent, or may comprise a contrast agent.

FIG. 38illustrates the aspiration catheter934ofFIG. 30in use within a blood vessel964as part of an aspiration system10or system for aspirating thrombus100,800.FIG. 38illustrates the aspiration catheter934in a second mode of operation configured to deliver a fluid (such as a fluid comprising an agent) distally out the distal opening974of the aspiration lumen936. The impingement of the spray pattern947of the pressurized fluid912against the forward ramp942of the deflection element940, opposite the orifice949, at least partially diverts the spray pattern947into a substantially distally-oriented flow967. In addition, an aspiration pressure (negative pressure) may be reduced, completely stopped, or simply not applied at a proximal end of the aspiration lumen936, thus allowing at least some of the spray pattern947to transform into the substantially distally-oriented flow967after impingement upon the forward ramp942of the deflection element940. In some embodiments, the orifice949and/or the forward ramp942of the deflection element940may be configured such that in some conditions, the substantially distally-oriented flow967may itself be a jet. The agent may comprise a lytic agent, such as a thrombolytic agent, or may comprise a contrast agent.

FIG. 39illustrates the aspiration catheter950ofFIG. 31in use within a blood vessel964as part of an aspiration system10or system for aspirating thrombus100,800.FIG. 39illustrates the aspiration catheter950in a second mode of operation configured to deliver a fluid (such as a fluid comprising an agent) distally out the distal opening976of the aspiration lumen952. The impingement of the spray pattern960of the pressurized fluid912against the distally-oriented ramp958of the deflection element956, opposite the orifice962, at least partially diverts the spray pattern960into a substantially distally-oriented flow969. In addition, an aspiration pressure (negative pressure) may be reduced, completely stopped, or simply not applied at a proximal end of the aspiration lumen952, thus allowing at least some of the spray pattern960to transform into the substantially distally-oriented flow969after impingement upon the distally-oriented ramp958of the deflection element956. In some embodiments, the orifice962and/or the distally-oriented ramp958of the deflection element956may be configured such that in some conditions, the substantially distally-oriented flow969may itself be a jet. The agent may comprise a lytic agent, such as a thrombolytic agent, or may comprise a contrast agent.

The delivery of an agent comprising a drug using the second mode of operation described inFIGS. 36-39in relation to aspiration catheters900,915,934,950may be achieved in a precise manner which allows for correct dosage, without wasting often-expensive drugs. The small inner diameter of transverse internal dimension of the supply lumen904,924,938,954not only allows for precision and small volume introduction of the agent, but also avoids unwanted loss of agent when it is desired to suddenly stop injection. This is a significant improvement over standard, gravity-fed injection systems. In addition, the use of the pump base200(FIG. 12) to pressurize the supply lumen904,924,938,954to deliver the agent adds additional precision, control, and lack of waste. This decreases the cost of a procedure, increases the accuracy of the drug treatment (or, for example, contrast delivery), and may also speed up the procedure, because of fewer errors to correct or steps to repeat. This in itself may be another element for saving cost. Though the word “aspiration” is used in defining the aspiration lumen902,922,936,952and the aspiration catheters900,915,934,950, it should be apparent that a user may choose to use the aspiration catheters900,915,934,950in the second mode only, as described in relation toFIGS. 36-39, and may in some cases choose to do so without any aspiration whatsoever.

FIG. 40illustrates the aspiration catheter900ofFIG. 28in use within a blood vessel964as part of an aspiration system10or system for aspirating thrombus100,800.FIG. 40illustrates the aspiration catheter900in a third mode of operation configured to deliver a fluid (such as a fluid comprising an agent) distally out the distal opening968of the aspiration lumen902while also causing at least some aspiration of thrombi966. The impingement of the spray pattern914of the pressurized fluid912against the interior wall surface916of the aspiration lumen902, opposite the orifice908, at least partially splits the spray pattern914into a substantially distally-oriented flow963and a substantially proximally-oriented flow955. An aspiration pressure (negative pressure) may be applied, adjusted, increased, or reduced at a proximal end of the aspiration lumen902, thus allowing at least some of the spray pattern914to transform into the substantially distally-oriented flow963after impingement upon the interior wall surface916and at least some of the spray pattern914to transform into the substantially proximally-oriented flow955after impingement upon the interior wall surface916. In some embodiments, the orifice908and/or the interior wall surface916may be configured such that in some conditions, the substantially distally-oriented flow963may itself be a jet. The agent may comprise a lytic agent, such as a thrombolytic agent, or may comprise a contrast agent.

FIG. 41illustrates the aspiration catheter934ofFIG. 30in use within a blood vessel964as part of an aspiration system10or system for aspirating thrombus100,800.FIG. 41illustrates the aspiration catheter934in a third mode of operation configured to deliver a fluid (such as a fluid comprising an agent) distally out the distal opening974of the aspiration lumen936while also causing at least some aspiration of thrombi966. The impingement of the spray pattern947of the pressurized fluid912against the ramps942,944of the deflection element940, opposite the orifice949, at least partially splits the spray pattern947into a substantially distally-oriented flow967and a substantially proximally-oriented flow959. An aspiration pressure (negative pressure) may be applied, adjusted, increased, or reduced at a proximal end of the aspiration lumen936, thus allowing at least some of the spray pattern947to transform into the substantially distally-oriented flow967after impingement upon the forward ramp942of the deflection element940and at least some of the spray pattern947to transform into the substantially proximally-oriented flow959after impingement upon the reverse ramp944of the deflection element940. In some embodiments, the orifice949and/or the forward ramp942of the deflection element940may be configured such that in some conditions, the substantially distally-oriented flow967may itself be a jet. The agent may comprise a lytic agent, such as a thrombolytic agent, or may comprise a contrast agent.

FIG. 42illustrates an aspiration catheter1000including a shaft1001having an aspiration lumen1002, a first supply tube1003having a first supply lumen1004and a second supply tube1005having a second supply lumen1006. The first supply tube1003and second supply tube1005are secured to an inner wall1008of the shaft1001. The first supply lumen1004is configured to carry pressurized fluid912, which may include saline, lytic (thrombolytic) agents, contrast agents, or other agents. The pressurized fluid912exits a first orifice1010of the first supply lumen1004in a spray pattern1014that is directed at an oblique, distally-oriented angle1016with respect to a longitudinal axis1018of the aspiration catheter1000. The second supply lumen1005is configured to carry pressurized fluid912, which may include saline, lytic (thrombolytic) agents, contrast agents, or other agents. The pressurized fluid912exits a second orifice1020of the second supply lumen1006in a spray pattern1022that is directed at an oblique, proximally-oriented angle1024with respect to the longitudinal axis1018of the aspiration catheter1000. The agent or agents may be undiluted or may be diluted (e.g., with saline).

A first curved hollow tip extension1026includes an outer diameter at its proximal end1012that is inserted within the first supply lumen1004of the first supply tube1003. The curve of the first curved hollow tip extension1026aims the spray pattern1014that exits the first orifice1010in the oblique, distally-oriented angle1016such that a substantially distally-oriented flow1028is directed, or oriented, outside the open distal end1030of the aspiration lumen1002. A second curved hollow tip extension1032includes an outer diameter at its proximal end1034that is inserted within the second supply lumen1006of the second supply tube1005. The curve of the second curved hollow tip extension1032aims the spray pattern1022that exits the second orifice1020in the oblique, proximally-oriented angle1024such that a substantially proximally-oriented flow1038is oriented towards an inner wall surface1040the aspiration lumen1002. The application and adjustment of a negative pressure on a proximal end of the aspiration lumen1002may be used to adjust the extent of aspiration (e.g., of thrombus or blood) and the extent of delivery of an agent distally through the first orifice1010.

FIG. 43illustrates an aspiration catheter1050including a shaft1051having an aspiration lumen1052, and a first supply tube1053having a first supply lumen1054. The first supply tube1053bifurcates into a first tubular branch1046having a first branch lumen1047and a second tubular branch1048having a second branch lumen1049. The first tubular branch1046and second tubular branch1048are secured to an inner wall1056of the shaft1051. The first supply lumen1054, first tubular branch1046, and second tubular branch1048are configured to carry pressurized fluid912, which may include saline, lytic (thrombolytic) agents, contrast agents, or other agents. The pressurized fluid912exits a first orifice1058of the first branch lumen1047in a spray pattern1060that is directed at an oblique, distally-oriented angle1062with respect to a longitudinal axis1064of the aspiration catheter1050. The pressurized fluid912exits a second orifice1066of the second branch lumen1049in a spray pattern1068that is directed at an oblique, proximally-oriented angle1070with respect to the longitudinal axis1064of the aspiration catheter1050. The agent or agents may be undiluted or may be diluted (e.g., with saline). One or more deflection members1072having one or more ramps1074,1076(e.g., forward ramp1074and reverse ramp1076) may be carried on an inner wall1078of the aspiration lumen1052for deflecting one or both spray patterns1060,1068to produce a distally-oriented flow1080and/or proximally-oriented flow1082. In other embodiments, the forward ramp1074and/or reverse ramp1076may simply be projections of the inner wall1078, or may be formed by a deflection of the shaft1001.

FIG. 44Aillustrates a catheter1200having a shaft1202having a lumen1203and a supply tube1204having a supply lumen1206. The supply tube1204is secured to an inner wall1208of the shaft1202and includes an orifice1210configured for directing pressurized fluid to exit in a spray pattern1212, which may form a jet. The spray pattern1212is directed against an opposing deflection member1214which may either be a separate component secured to the inner wall1208of the shaft1202, or may be a formed portion of the shaft1202. The lumen1204is a guidewire lumen configured for allowing the catheter1200to track over the guidewire (not shown). In use, the catheter1200is operated as an infusion catheter, and the guidewire may be retracted proximally to the orifice1210and deflection member1214so that they are able to function with less potential interference. In some cases, the guidewire may be removed entirely. In other embodiments, the lumen1204may be an aspiration lumen, configured for aspiration of material such as thrombus or other emboli. The lumen may alternatively have other purposes, for example as a conduit for larger volume injections or infusions. The deflection member1214has a flat surface extending transversely, or radially and is configured to deflect the spray pattern1212. For example, the deflection member1214may be configured to deflect the spray pattern1212so that at least some of an agent carried by the spray pattern1212is urged out of the distal opening1215of the lumen1204.

FIG. 44Billustrates a catheter1216including a shaft1218having a lumen1220and a supply tube1222having a supply lumen1224. The supply tube1222is secured to an inner wall1226of the shaft1218and includes an orifice1228configured for directing pressurized fluid to exit in a spray pattern1230, which may form a jet. The spray pattern1230is directed against an opposing deflection member1232which may either be a separate component secured to the inner wall1226of the shaft1218, or may be a formed portion of the shaft1218. The lumen1220, like the lumen1203of the catheter1200ofFIG. 44A, may be a guidewire lumen and/or an aspiration lumen, or may have other purposes. The deflection member1232has a flat surface extending longitudinally, or axially, and is configured to deflect the spray pattern1230. For example, the deflection member1232may be configured to deflect the spray pattern1230so that at least some of an agent carried by the spray pattern1230is urged out of the distal opening1234of the lumen1220.

FIG. 45Aillustrates a catheter1236having a shaft1238having a lumen1240and a supply tube1242having a supply lumen1244. The supply tube1242is secured to an inner wall1246of the shaft1238and includes an orifice1248configured for directing pressurized fluid to exit in a spray pattern1250, which may form a jet. The spray pattern1250is directed against an opposing deflection member1252which may either be a separate component secured to the inner wall1246of the shaft1238, or may be a formed portion of the shaft1238. The lumen1240is a guidewire lumen configured for allowing the catheter1236to track over the guidewire (not shown). In use, the catheter1236is operated as an infusion catheter, and the guidewire may be retracted proximally to the orifice1248and deflection member1252so that they are able to function with less potential interference. In some cases, the guidewire may be removed entirely. In other embodiments, the lumen1240may be an aspiration lumen, configured for aspiration of material such as thrombus or other emboli. The lumen may alternatively have other purposes, for example as a conduit for larger volume injections or infusions. The deflection member1252has a convex surface when viewed from an end view, and is configured to deflect the spray pattern1250. For example, the deflection member1252may be configured to deflect the spray pattern1250so that at least some of an agent carried by the spray pattern1250is urged out of the distal opening1254of the lumen1240.

FIG. 45Billustrates a catheter1256including a shaft1258having a lumen1260and a supply tube1262having a supply lumen1264. The supply tube1262is secured to an inner wall1266of the shaft1258and includes an orifice1268configured for directing pressurized fluid to exit in a spray pattern1270, which may form a jet. The spray pattern1270is directed against an opposing deflection member1272which may either be a separate component secured to the inner wall1266of the shaft1258, or may be a formed portion of the shaft1258. The lumen1260may be a guidewire lumen and/or an aspiration lumen, or may have other purposes. The deflection member1272has a convex surface when viewed from the side, and is configured to deflect the spray pattern1270. For example, the deflection member1272may be configured to deflect the spray pattern1270so that at least some of an agent carried by the spray pattern1270is urged out of the distal opening1274of the lumen1260.

FIGS. 46A and 46Billustrate a catheter1276having a shaft1278having a lumen1280and a supply tube1282having a supply lumen1284. The supply tube1282is secured to an inner wall1286of the shaft1278and includes an orifice1288configured for directing pressurized fluid to exit in a spray pattern1290, which may form a jet. The spray pattern1290is directed against an opposing adjustable deflection member1292having at least two states, a first state (FIG. 46A) and a second state (FIG. 46B). In the embodiment shown, the adjustable deflection member1292comprises a balloon secured to the inner wall1286of the shaft1278such that it may be inflated or deflated via a fluid passage1294within or carried by the shaft1278. An inflation device with or without a volume measurement device, pressure sensor, and/or pressure gauge may be coupled to a proximal end of the fluid passage1294, to thus aid in the inflation or deflation of the balloon. The lumen1280is a guidewire lumen, configured for allowing the catheter1276to track over the guidewire (not shown). In use, the catheter1276is operated as an infusion catheter, and the guidewire may be retracted proximally to the orifice1288and adjustable deflection member1292so that they are able to function with less potential interference. In some cases, the guidewire may be removed entirely. In other embodiments, the lumen1280may be an aspiration lumen, configured for aspiration of material such as thrombus or other emboli. The lumen may alternatively have other purposes, for example as a conduit for larger volume injections or infusions.

The adjustable deflection member1292, in at least one of its two or more states, is configured to deflect the spray pattern1290. For example, the adjustable deflection member1292may be configured to deflect the spray pattern1290so that at least some of an agent carried by the spray pattern1290is urged out of the distal opening1296of the lumen1280. In a first state displayed inFIG. 46A, the adjustable deflection member1292is deflated, or in other words, its interior volume1298is substantially empty. This first state may be desired if, for example, passing the catheter1276over a guidewire that extends through the lumen1280, or if aspirating through the lumen1280(with or without the guidewire in place). In another version of the first state, a vacuum (negative pressure) may additionally be placed and held on the fluid passage1294(e.g., from an evacuated syringe or evacuated locking syringe on the proximal end of the fluid passage1294) to minimize the profile of the deflated adjustable deflection member1292and thus maximize the cross-sectional area of the lumen1280in this area. In a second state displayed inFIG. 46B, fluid has been injected through the fluid passage1294(e.g., by a syringe or other type of inflation device) and into the interior volume1298of the adjustable deflection member1292through an aperture1299between the fluid passage1294and the interior volume1298. The adjustable deflection member1292in its second state is configured to deflect the spray pattern1290in a desired direction, such as at least partially out through the distal opening1296of the lumen1280. The shape of the inflated adjustable deflection member1292is depicted inFIG. 46Bas having a convex nature, but in other embodiments, the balloon or other structure constituting the adjustable deflection member1292may be fabricated to form one or more linear ramps, or other shapes. In addition, there may be several different shapes or sizes that may be achieved by adjusting the adjustable deflection member1292into several different states, by injecting different volumes of fluid into the interior volume1298. During fabrication, the shape of the adjustable deflection member1292may be heat formed by use of one or more molds or fixtures. An additional state may even be possible, wherein the adjustable deflection member1292in inflated enough to substantially or completely block off the lumen1280, or to partially or completely block the orifice1288. This additional state may be desired, for example, in cases during which an embolus is aspirated into the catheter, and it is desired to maintain the embolus within the catheter1276securely, while removing the catheter1276from the patient.

FIG. 47illustrates a supply tube1300having a lumen1302, a wall1304, and an orifice1306through the wall1304. A spray pattern1308exiting the orifice1306, emanating from pressurized fluid within the lumen1302, has a substantially solid or straight stream, wherein the width (or diameter) W of the stream does not significantly increase.FIG. 48illustrates a supply tube1310having a lumen1312, a wall1314, and an orifice1316through the wall1314. A spray pattern1318exiting the orifice1316, emanating from pressurized fluid within the lumen1312, has a divergent stream having an included angle x.FIG. 49illustrates a three-dimensional depiction of a spray pattern1320having a divergent stream, which thus gives the spray pattern1320a conical shape1322.

FIG. 50illustrates a supply tube1324having a lumen1326, a wall1328, and an orifice1330through the wall1328. A spray pattern1332exiting the orifice1330, emanating from pressurized fluid within the lumen1326, has a stream having a hollow conical shape1334.FIG. 51illustrates a supply tube1336having a lumen1338, a wall1340, and a rectangular orifice1342through the wall1340. A spray pattern1344exiting the rectangular orifice1342, emanating from pressurized fluid within the lumen1338, has a stream having a divergent wedge shape1346.

FIG. 52illustrates a supply tube1348having a lumen1350, a wall1352, and an orifice1354through the wall1352. A spray pattern1356exiting the orifice1354, emanating from pressurized fluid within the lumen1350, has a directional vector V that is angled at an angle y with respect to an axis AO of the orifice1354. The directional vector represents a central portion of the spray pattern1356. The spray pattern1356diverges and has an included angle x. The spray pattern has a distal-most extremity1355and a proximal-most extremity1357. The distal-most extremity1355forms an angle zDwith the axis AO of the orifice1354and the proximal-most extremity1357forms an angle zPwith the axis AO of the orifice1354. In other embodiments, the spray pattern1356may have a shape similar to any of the spray patterns1308,1318,1320,1332,1344ofFIGS. 47-51, or any other shape.

Any of the shapes of the spray patterns1308,1318,1320,1332,1344,1356may be tailored by modifying the structure of the orifice in the wall of the supply tube (transverse dimension, diameter, length or wall thickness, angle, taper angle, cross-sectional shape), which facilitates the spray pattern(s) interfacing with the interior wall surface916,1040,1078or deflection elements/members929,940,956,1072,1214,1232,1252,1272,1292to create a number of different flow shapes, including substantially distally-oriented flow and/or substantially proximally-oriented flow. The spray patterns1308,1318,1320,1332,1344,1356may be tailored to comprise a jet, a stream, a mist, or other spray physical characteristics. The spray patterns1308,1318,1320,1332,1344,1356may convertible between any of these different modes or shapes with the aid of varying the pressure of the pressurized fluid.

FIG. 53illustrates an aspiration catheter1360which has been inserted into a blood vessel1362(artery, vein, etc.) and advanced such that the open distal end1364of the aspiration lumen1366is adjacent a thrombus/clot1368. The aspiration catheter1360also includes a supply tube1370having a supply lumen1372, and a guiding tube1374having a guidewire lumen1376configured for tracking over a guidewire1378. A dilute or nondilute contrast media is pressurized by syringe, pump or other means through the supply lumen1372such that it exits the orifice1380at the distal end1382of the supply lumen1372. A jet spray1384may include a distal component and/or a proximal component. The distal component1386(FIG. 54) may be a substantially distally-oriented component, and may at least partially exit the open distal end1364of the aspiration lumen1366. The distal component1386, as it fills a volume around the thrombus/clot1368(FIG. 54), may be viewed under radiography or fluoroscopy to identify a boundary1388of the thrombus/clot1368. If the boundary1388is located within a desired proximity to the open distal end1364the aspiration lumen1366of the aspiration catheter1360, the user may desire to inject or pump (e.g., with syringe or pump), using a high pressure, through the supply lumen1372, to start or to continue a thrombolysis procedure. In some cases, the user may use the dilute or non-dilute contrast media to perform the thrombolysis procedure. In some cases, the dilute or non-dilute contrast media may be combined or mixed with a lytic agent. In other cases, the user may replace the dilute or non-dilute contrast media with saline or a lytic agent, for example, by priming the supply lumen. If instead the boundary1388is located distal to the open distal end1364of the aspiration lumen1366of the aspiration catheter1360by more than a desired amount, the user may choose to advance the aspiration catheter1360until the open distal end1364is within the desired proximity to the boundary1388of the thrombus/clot1368. In some cases, the desired proximity may be when the open distal end1364is flush with the boundary1388of the thrombus/clot1368. In some cases, the desired proximity may be when the open distal end1364is about one mm from the boundary1388of the thrombus/clot1368. In some cases, the desired proximity may be when the open distal end1364is about five mm from the boundary1388of the thrombus/clot1368. Once the user advances the aspiration catheter1360such that the open distal end1364is within the desired proximity of the boundary1688of the thrombus/clot1368, the user may start or continue the thrombolysis procedure.

FIG. 55illustrates a method in which a user continually or temporarily injects or “puffs” small amounts1396of contrast agent (or contrast agent mixtures as described), in order to continually delineate the boundary1388of the thrombus/clot1368, and the proximity of the open distal end1364of the aspiration lumen1366of the aspiration catheter1360. In any of the embodiments presented herein, the distal end1390of the aspiration catheter1360may comprise a radiopaque marker or marker band1392. In some embodiments, the catheter tubing1394may be radiopaque tubing, comprising radiopaque materials, including, but not limited to barium-sulfate, tantalum oxide, or titanium oxide.

FIG. 56illustrates a catheter system1400comprising a catheter1402having a supply lumen1404, and lumen1406. A wall1410surrounding the supply lumen1404includes an orifice1408. A mandrel1412having a proximal end1414and a distal end1416extends through the lumen1406. The distal end1416may have a curved portion1418(or hook portion) that includes a concavity1420for engaging a wall1422of the catheter1402. The mandrel1412may be configured for insertion through the lumen1406such that the concavity1420engages the distal end1424of the wall1422(e.g., at the open distal end1426) in a manner that traction (arrow,FIG. 57) may be placed by a user on the mandrel1412, thereby pulling the distal end1428of the catheter1402in a proximal direction. This traction, coupled with the column strength of the catheter1402, causes the distal end1428of the catheter1402to flex, as shown inFIG. 57. In some cases, the amount of flexure may be controlled by a particular force applied on the proximal end1414of the mandrel1412(e.g., by hand, or by a grasping tool which is connected to the proximal end1414by a collet or other lock), such that the jet of fluid1430exiting the orifice1408is steered such that it impinges on an adjacent structure (such as a thrombus/clot1432). In some embodiments, the lumen1406may serve as an aspiration lumen, according to other embodiments described herein, and may also be used to aspirate at least some of the thrombus1432. In this embodiment, the mandrel1412may also be used to disengage the lumen1406from a thrombus1432, in cases where the thrombus1432becomes engaged, via vacuum, with the open distal end1426of the lumen1406. Contrast media may be added to the fluid being delivered through the supply lumen1404, in order to better visualize the location and status of the thrombus1432. Contrast media may even be delivered through the lumen1406, if the lumen1406is not actively being used to aspirate. A user may flex the distal end1428of the catheter1402back and forth such that the jet of fluid1430disrupts various areas/regions of the thrombus1432. Additionally, the user applies a vacuum to the lumen1406to remove disrupted/macerated thrombus from the blood vessel1362. A more thorough and efficient removal of the thrombus1432is thus possible.

FIG. 58illustrates a catheter system1434having most of the characteristics of the catheter system1400ofFIGS. 56 and 57, but with an additional preformed shape. A mandrel1436is configured to flex the distal end1438of the catheter1440, but the distal end1438of the catheter1440additionally has a preformed curve1442. Thus, a large flexure angle F range is possible, allowing the jet1444itself to strike a thrombus with many different possible trajectories.

FIGS. 59A and 59Billustrate an aspiration system1450comprising an aspiration catheter1452having a supply lumen1454, an aspiration lumen1456and an orifice1458communicating between the supply lumen1454and the aspiration lumen1456, and a mandrel1460having a proximal end1462and a distal end1464, the distal end1464including an enlarged portion1466. The enlarged portion1466of the mandrel1460may include a hook (e.g., shepherd's crook), a curve, or other structure which is effective in disrupting a thrombus1468when the mandrel1460(and thus the enlarged portion1466) is made to rotate1470and/or to longitudinally translate1472. The mandrel1460may be inserted through the aspiration lumen1456of the aspiration catheter1452and may be rotated by attaching the proximal end1462of the mandrel1460to a rotation device1474. The rotation device1474may also translate the mandrel1460back-and-forth longitudinally. The rotation device1474may include comprise such devices as a SPINR™ device marketed by Merit Medical Systems, Inc., (South Jordan, Utah, USA) or a FireBow™ device marketed by Vesatek, LLC (Irvine, Calif., USA). The enlarged portion1466may be used to disrupt a fibrous and/or calcified cap1476at one end of a thrombus1468by applying a disruptive force through rotation and/or cyclic longitudinal displacement. A convex or blunt portion1478of the enlarged portion1466may form an atraumatic end to the mandrel1460. The rotation device1474comprises a handle1480, a motor1482, a rotatable chuck or lock1484, and a transmission1486that is configured to couple movement from the motor into movement (e.g., rotation and/or longitudinal translation) of the rotatable chuck or lock1484. The transmission1486may in some embodiments include gearing. A switch1488may be pressed by a user while the user holds the handle1480, to turn the rotation/movement on or off. In some embodiments, the mandrel1460may also be usable in the manner of the mandrel1412ofFIGS. 56 and 57or the mandrel1436ofFIG. 58.

FIG. 60illustrates as system for removing intracranial thrombus or intracranial hematoma (illustrated simply as BC-blood clots) through a window, aperture, or hole in the cranium of a patient. The window, aperture, or hole may be made by any suitable device, including, but not limited to a hand drill having a burr or other cutting element. Referring toFIG. 60, a trocar1156, for example a four-channel trocar, can be introduced through an introducer1100close to the treatment area where blood clots BC are located. A visualization device1158such as a scope device, including but not limited to the NeuroPen (Medtronic Inc.) or the Epic Microvision (Codman, J&J Company, Piscataway, N.J.), may be introduced in the visualization channel of the trocar1156, and an ultrasound device1112may be introduced into the working channel of the trocar1156. The ultrasound device1112may transmit, for example, at frequencies between about 1 kHz and about 20 MHz, and may be configured to disrupt or break up the blood clot BC.

FIG. 60shows a cross sectional view of a human skull and brain, showing an introducer1100placed through the aperture in the skull. The trocar device1156is placed through the introducer1100and positioned within the treatment area where blood clots BC are located. The middle cerebral artery MCA is also shown. Often, the trocar1156can be introduced directly into the aperture in the skull without use of the introducer1100. A visualization device1158may be introduced through the visualization channel of the trocar1156. The visualization device1158is connected to a monitor (not shown) through a cable1159. Some visualization devices (such as scopes) have an ocular element that can be used for visualization instead of a monitor. An ultrasound device1112having a handle1157is introduced through the working channel of the trocar1156. Before the procedure, the physician directs the trocar1156under the visualization device1158to the location of the blood clots BC, and then positions the distal end of the ultrasound device1112inside the blood clots and activates ultrasound energy delivery. The physician has the ability to simultaneously observe the field of therapy with a visualization device1158while the therapeutic device1112dissolves and aspirates blood clots from the patient's head. Blood clots maybe aspirated through an irrigation or overflow channel, which is analogous to the aspiration lumens of the aspiration catheters described herein. Also, blood clots may be aspirated through the ultrasound device1112. Suitable systems for removing intracranial thrombus or intracranial hematoma are described by Nita in U.S. Patent Application Publication No. 2012/0330196, published Dec. 27, 2012, and titled Method and Apparatus for Removing Blood Clots and Tissue from the Patient's Head, which is hereby incorporated by reference in its entirety for all purposes.

To further improve the ability to dissolve blood clots BC, delivery of one or more pharmacologic agents or microbubbles or nanobubbles to the clot location may be helpful. Such pharmacologic agents, microbubbles or nanobubbles can be delivered directly or in mixture with a conventional saline to the treatment location.

Cerebral temperature has been recognized as a strong factor in ischemic brain damage. Clinical evidence has shown that hypothermia ameliorates brain damage. Also, a therapeutic cooling to between 30° C. or 35° C. that includes the patient head or a whole body (systemic cooling) may reduce ischemic brain damage; reduce intracranial pressure and edema after ICH. Focused cranial cooling can be achieved with a simple method of placing ice or cold gel packs around the head or neck. Systemic cooling maybe be done by infusing ice-cold saline using intravenous (IV) approach.

Any of the embodiments described herein may be used conjunction with the Apollo™ System (Penumbra, Inc., Alameda, Calif., USA).

A system for aspirating thrombus1900is illustrated inFIG. 61, and comprises an aspiration catheter1930, a tubing set1904configured for injection of a fluid at high pressure through at least a portion of the aspiration catheter1930, and a vacuum set1928, configured to couple a vacuum source1929to the aspiration catheter1930. The aspiration catheter1930includes a y-connector1910having a female luer1912hydraulically coupled to its high-pressure injection lumen1934and a female luer1914hydraulically coupled to its aspiration lumen1932. The high-pressure injection lumen1934may have similar characteristics to the high-pressure injection lumen36of the catheter16ofFIG. 3. The aspiration lumen1932may have similar characteristics to the aspiration lumen38of the catheter16ofFIG. 3. The tubing set1904may be coupled to a fluid source and a pump, for example, the fluid source20and pump26ofFIG. 1. The tubing set1904includes an injection tube1906connected to a male luer1908, which may be removably coupled to the female luer1912of the y-connector1910of the aspiration catheter1930. The aspiration lumen1932of the aspiration catheter1930also serves as a guidewire lumen, for the placement of a guidewire1902. The aspiration lumen/guidewire lumen1932extends the entire length of the aspiration catheter1930, providing an “over-the-wire” system which can be delivered or tracked over the guidewire1902. A y-connector1916having a Touhy-Borst1922is attached to the y-connector1910of the aspiration catheter1930via its distal male luer1918which is hydraulically coupled to the female luer1914of the y-connector1910. The Touhy-Borst1922may be adjusted an appropriate amount to create a seal over the guidewire1902. The Touhy-Borst1922may in some cases even be adjusted so that a slow, steady drip of blood (e.g., Heparinized blood or non-Heparinized blood) occurs out through the Touhy-Borst1922. This may be done in order to minimize any stagnation of blood within the aspiration lumen1932. The Touhy-Borst1922may alternatively be replaced by any other type of seal that is configured to permanently, adjustably, or removably seal around a guidewire1902. The vacuum set1928includes a luer fitting154(for example, a male luer) that is configured to attach to a female luer1920of the y-connector1916. The vacuum set1928includes a pressure transducer106having an internal passage which is carried in line with a stopcock1924. Proximal to the stopcock1924, a vacuum line1926is configured to connect to the vacuum source1929(via a connector or by direct attachment). Signals from the pressure transducer106are carried by a cable112(e.g., to the circuit board304of the pump base200(FIG. 17). In alternate embodiments, the male luer1918and female luer1914may be replaced by two connectors/connections that are permanently attached to each other, or the y-connector1910and y-connector1916may be integrally constructed. Other disposable components101are similar to those described in the system for aspirating thrombus100ofFIG. 4.

FIG. 62illustrates the distal end of the aspiration catheter1930and the guidewire1902. The guidewire1902is free to be moved distally or proximally in the longitudinal direction, or to be rotated within the aspiration lumen/guidewire lumen1932. The distal end of the guidewire1902may be shapeable, for example, to create a “J”-tip for selectability of vessels or through stenoses or obstructions. The high-pressure injection lumen1934is contained within a tube1936having a large diameter portion1938and a small diameter portion1940. The small diameter portion1940may transition from the large diameter portion1938via a neckdown or tapered portion1942. The small diameter portion1940is blocked using a blocking material1944, which may include a polymer, adhesive, or epoxy adhered to the internal walls of the small diameter portion1940. Alternatively, the small diameter portion1940may be crimped, tied off, sealed, or otherwise occluded, without the use of a blocking material1044. An orifice1946in a wall1948of the tube1936is configured to create a jet from high pressure fluid injected through the high-pressure injection lumen1934. The jet exiting the high-pressure injection lumen1934and entering the aspiration lumen1932may be configured to impinge on an inner wall1950of the aspiration lumen/guidewire lumen1932. Aspiration may be performed with the guidewire1902in place within the aspiration lumen/guidewire lumen1932, or may be performed with the guidewire1902retracted proximally of the longitudinal location of the orifice1946. In cases where the guidewire is left in place (as shown inFIG. 62), during aspiration the guidewire1902may be rotated so that it does not significantly impede the jetting through the orifice1946, or in some cases, the jet itself may be sufficient to force the guidewire1902into a position that does not impede the jetting against the inner wall1950.

Returning toFIG. 61, the stopcock1924may be manipulated by the user (physician, technician, etc.) to turn the system1900on and off. The pressure transducer106sends its signals via the cable112to pump, such as the pump base200(FIG. 12). Circuitry, e.g., contained in the circuit board304of the pump base200(FIG. 17), such as a microprocessor or microcontroller, may be configured or configurable (e.g., programmable), such that a change in pressure to a particular pressure value, or a change in pressure having a particular slope of pressure change over time initiates the pump to start or stop. The user, who may be wearing sterile gloves, is thus able to turn the system on and off, without requiring the help of any external (e.g., non-sterile, non-scrubbed) personnel, simplifying and speeding up the procedure. In alternate embodiments, an extension tube may be placed between the stopcock1924and the pressure transducer106. Though a one-way stopcock is generally illustrated inFIG. 61, other types of stopcocks may be used. In alternate embodiments, the stopcock1924may be replaced with other types of valves having on and off positions. In some embodiments, the circuitry (e.g. circuit board304) is configured to provide a delay between the receipt of the signal from the pressure transducer106/cable112and a signal commanding initiation of the pumping action of the pump base200. The purpose of the delay may be so that the vacuum applied initially engages a thrombus without any injection of fluid, and then, after the delay, allows the injection on fluid (e.g., to macerate the thrombus) once the thrombus is engaged, and in position to be macerated. In some embodiments, the circuitry is configured to allow a delay of between about 0.01 second and about 1.00 second. In some embodiments, the circuitry is configured to allow a delay of between about 0.10 second and about 0.25 second.

A representative method for using the system for aspirating thrombus is presented inFIG. 63. In step1952, a user inserts a distal portion of the aspiration catheter1930into a subject's vasculature, for example, in a target area near or adjacent a thrombus. The user may choose to perform step1952after connecting the aspiration catheter1930to other components. In step1954, the user couples a vacuum source1929to the aspiration lumen1932of the aspiration catheter1930by coupling the luer fitting154to the female luer1920of the y-connector1916and the vacuum line1926to the vacuum source1929. The connection may be a luer connection in the case of a syringe, or a friction fitting, or a spike, or other type of connection. In some cases, the user may start with the stopcock1924in a closed position between the vacuum source1929and the pressure sensor106. In step1956, the user couples the supply lumen1934of the aspiration catheter1930to the fluid source20and pump base200by coupling the male luer1908of the tubing set1904to the female luer1912of the y-connector1910of the aspiration catheter1930. In step1958, the user may turn on the pump base200, for example, by pressing an “ON” button. Step1958may be optional, for example, in an embodiment of a pump base200that is configured to automatically sense the attachment of the aspiration catheter1930, or components such as the cassette116and/or the connector114. Some examples include proximity sensors, RFID chips, a resisitor having a particular value, or a switch carried on one or more connectors.

In step1960, the user changes the position or configuration of the valve of the stopcock1924. For example, the user may turn the stopcock1924from the off position to the on position. With the stopcock1924in the off position, the pressure sensor106is blocked from being able to sense the internal pressure (e.g., negative pressure) of the vacuum source1929, and thus does not sense pressures that are below a particular pressure threshold programmed into the circuitry (e.g., circuit board304). The circuitry is configured (or configurable) to not allow the motor302of the pump base200to operate when this condition is sensed, so that no pressurized fluid is forced through the supply lumen1934and into the aspiration lumen1932. By assuring that the motor302does not cause the pumping of pressurized fluid if the vacuum source1929is not actively causing aspiration through the aspiration lumen1932, the disruption of thrombus within the patient's vasculature is avoided. Disruption of the thrombus without aspiration could potentially create thromboemboli that could migrate or be circulated to portions of the vasculature and body where they could cause damage (occlusion, stroke, myocardial infarction, etc.). When the user opens the stopcock1924, as in step1960, and a pressure below a particular pressure threshold is sensed by the pressure sensor106, the control circuitry initiates the motor302to force pressurized fluid through the supply lumen1934and into the aspiration lumen1932, causing thrombus to be safely aspirated through the aspiration catheter1930. The user may choose to move the aspiration catheter1930in the blood vessel (distally or proximally or rotating it), while aspirating.

In step1962, the user returns the position of the stopcock1924to its original position. For example, if the stopcock1924was turned to its on position in step1960, then the stopcock1924is turned to its off position in step1962. As an example, after the user turns the stopcock1924to its on position in step1960, and uses the system1900to aspirate thrombus, the user may desire to terminate the aspiration, and does so by turning the stopcock1924to its off position in step1962. When the user closes the stopcock1924, as in step1962, and a pressure at or above a particular pressure threshold is sensed by the pressure sensor106, the control circuitry stops the motor302to stop pressurized fluid from being pumped through the supply lumen1934and into the aspiration lumen1932, causing the aspiration of thrombus to be safely terminated. The user is able, thus, to control when aspiration occurs by simply turning the stopcock1924on and off. The stopcock1924functions as an electric switch via the pressure measurement by the pressure sensor106and the control by the circuit board304. This allows a user, who has likely “scrubbed” and is operating in a sterile field, to avoid any switches (on the pump base200or other) that may either be non-sterile and/or remote or out of reach. The user does not have to shout voice commands to other medical personnel, which would not have the same one-to-one effect. Thus, the user is able to rapidly and immediately stop and start aspiration, to best respond to critical events. For example, when the user is aspirating thrombus with the aspiration catheter1930, and suddenly sees (e.g., via fluoroscopy) that something in the blood vessel has changed, the user can immediately turn the stopcock1924to the off position and stop aspiration. The user may move back and forth between steps1960and1962, while moving the aspiration catheter1930or stopping the aspiration catheter1930, to optimize the aspiration procedure.

In an alternative embodiment, the pressure sensor106may be coupled to the vacuum source1929, but not the aspiration catheter1930, in order to be used in an analogous manner of an on/off switch. For example, the pump base200of the system for aspirating thrombus100or the saline pump drive unit400of the piston pump system300may be operated for pumping a drug730through the supply lumen708of the aspiration catheter700, while no aspiration is being performed through the aspiration lumen710. Distal to the pressure sensor106, a plug or closed stopcock (or other closed valve) may be placed, while the cable112extending from the pressure sensor106is electrically coupled to the pump base200or piston pump system300. Thus, signals from the pressure sensor106may be used to turn the pump base200or piston pump system300on or off by the turning the vacuum source1929on or off (or by connecting or disconnecting the vacuum source1929or otherwise adjusting the vacuum source1929). This is done even though the vacuum source1929is not connected to the aspiration lumen710of the aspiration catheter700. Thus, automatic injection of the drug730may be initiated or ended by manipulation of the vacuum source1929alone (e.g., switch, power, etc.). In yet another embodiment, the aspiration catheter may be replaced by another catheter that does not even have an aspiration lumen710, but does have a supply lumen708. In this embodiment, if connected as described above, would still allow automatic injection of the drug730by manipulation of the vacuum source1929.

In any one of the embodiments in which the pump base200or the saline pump drive unit400may be used to deliver a drug730, a precision delivery of the drug730is achieved, which is an improvement over standard gravity-fed infusion systems, having somewhat limited precision.

Alternative embodiments are contemplated, wherein either the system for aspirating thrombus100or the piston pump system300includes a standard on/off power switch that can be used to initiate or suspend pumping. The switch may be carried on the system for aspirating thrombus100or the piston pump system300itself, for example, on the pump base200or on the saline pump drive unit400. Alternatively, the switch may be remote from the pump base200or the saline pump drive unit400, and may even be supplied sterile or sterilizable, so that it can be maintained on a sterile field on or in the vicinity of the patient. The separate switch may in some embodiments include a vacuum switch valve540or the vacuum sensing method described above in order to control its operation (on/off). In some embodiments, the switch may be used to control other parameters than on and off, for example it may control the speed of the pump motor, or may control certain safety features. In the embodiment in which the switch controls the speed of the pump motor, there may be particular embodiments, in which the switch includes a potentiometer for allowing the adjustment of a changeable electrical resistance. Though the aspiration catheter1930ofFIGS. 61-62is shown as an over-the-wire catheter (with guidewire1902internal to the aspiration catheter1930substantially the entire length of the aspiration catheter1930), alternatively, the aspiration catheter1930may be a single operator exchange catheter with a short guidewire lumen (similar to the guidewire tube132of the aspiration catheter118ofFIG. 8).

Another embodiment of a system for aspirating thrombus2000is illustrated inFIG. 64. The system for aspirating thrombus2000includes, three major components: the pump base200ofFIG. 12, an aspiration catheter2018, and a tubing set2003. The aspiration catheter2018and the tubing set2003represent disposable components2001, and the pump base200is a reusable component. It is not necessary to sterilize the pump base200as it is kept in a non-sterile field or area during use. The aspiration catheter2018and the tubing set2003may each be supplied sterile, after sterilization by ethylene oxide gas, electron beam, gamma, or other sterilization methods. The aspiration catheter2018may be packaged and supplied separately from the tubing set2003, or the aspiration catheter2018and the tubing set2003may be packaged together and supplied together. Alternatively, the aspiration catheter2018and tubing set2003may be packaged separately, but supplied together (i.e., bundled). The aspiration catheter2018and tubing set2003share many of the same features as the aspiration catheter118and tubing set103ofFIG. 4and the aspiration catheter818and tubing set803ofFIG. 21. The aspiration catheter2018has a distal end2020and includes an over-the-wire guidewire lumen/aspiration lumen2032extending between a distal tip2036, and a proximal end2019comprising a y-connector2010. The catheter shaft2042of the aspiration catheter2018is connected to the y-connector2010via a protective strain relief2056. In other embodiments, the catheter shaft2042may be attached to the y-connector2010with a luer fitting. The y-connector2010comprises a first female luer2055which communicates with a catheter supply lumen2093(FIG. 65), and a second female luer2051which communicates with the guidewire lumen/aspiration lumen2032.

A spike2002for coupling to a fluid source20(FIG. 1) allows fluid to enter through extension tubing2022and flow into a supply tube2030. An optional injection port2028allows injection of materials or removal of air, as described in relation to previous embodiments. A cassette2016is used in conjunction with the pump base200, and is similar in structure and function to the cassette116inFIGS. 15 and 16and cassette816inFIGS. 21 and 23. Fluid is pumped into the injection tube2052from action of the cassette2016as applied by the pump base200. A male luer2054, coupled to the distal end of the injection tube2052, is configured to attach to the female luer2055of the y-connector2010.

Accessories2057are illustrated that are intended for applying a vacuum source22, such as a syringe2049having a plunger2067and a barrel2099, to the aspiration lumen2032of the catheter2018. The syringe2049is attached to a vacuum line2008via the luer2065of the syringe2049. A stopcock2047may be used to maintain the vacuum, or, the plunger2067may be a locking variety of plunger that is configured to be locked in the retracted (vacuum) position. A male luer2053at the end of the vacuum line2008may be detachably secured to the female luer2051of the y-connector2010of the aspiration catheter2018. As shown in more detail inFIG. 66, a pressure sensor2006is secured inside an internal cavity2097of the y-connector2010proximal to the female luer2055and the female luer2051. A valve2095, for example a Touhy-Borst, at the proximal end of the y-connector2010allows hemostasis of the guidewire lumen/aspiration lumen2032around a guidewire2091. In other embodiments, the valve2095may comprise a longitudinally spring-loaded seal. The guidewire2091may be inserted entirely through the guidewire lumen/aspiration lumen2032. Signals from the pressure sensor2006are carried through a cable2012to a connector2014. The connector2014is plugged into the socket308(FIG. 12) of the pump base200. Pressure related signals may be processed by the circuit board304of the pump base200. The pressure transducer2006may be powered from the pump base200, via the cable2012. The accessories2057may also be supplied sterile to the user. In some embodiments, the pressure sensor2006may comprise a sensor that is utilized in the single use LD20 Liquid Flow Sensor manufactured by Sensirion AG of Stafa, Switzerland.

As an alternative to the on/off switching function of the stopcock1924of the system for aspirating thrombus1900ofFIG. 61, a foot pedal2021is configured to operate a pinch valve2023for occluding or opening the vacuum line2008. The foot pedal2021comprises a base1025and a pedal2027and is configured to be placed in a non-sterile area, such as on the floor, under the procedure table/bed. The user steps on the pedal2027causing a signal to be sent along a cable2029which is connected via a plug2041to an input jack2037in the pump200. The vacuum line2008extends through a portion of the pump200. The circuit board304of the pump (FIG. 17) may include a controller configured to receive one or more signals indicating on or off from the foot pedal2021. The controller of the circuit board304may be configured to cause an actuator2031carried by the pump200to move longitudinally to compress and occlude the vacuum line2008between an actuator head2033attached to the actuator2031and an anvil2035, also carried by the pump200. By stepping on the pedal2027, the user is able to thus occlude the vacuum line2008, stopping the application of a negative pressure. Also, by stepping on the pedal2027, the user may cause the opposite action, wherein the actuator head2033opens the vacuum line2008, by moving away from the anvil2035. The anvil2035may have a flat (planar) shape, or a U-shape (e.g., semi-cylindrical), or a V-shape (e.g., a V-block) where it contacts the tubing of the vacuum line2008. Furthermore, the actuator head2033may have a flat (planar) shape, or a U-shape (e.g., semi-cylindrical), or a V-shape (e.g., a V-block) where it contacts the vacuum line2008. The foot pedal2021may operate by alternately causing the actuator2031to move in a first direction and a second, opposite direction, respectively, with alternate hits on the pedal2027. In some embodiments, as the pedal2027of the foot pedal2021is depressed, the controller may be configured to open the pinch valve2023. The pressure transducer2006thus senses a negative pressure and sends a signal, causing the controller to start the motor302of the pump200. As the effect via the electronics is substantially immediate, the motor302starts pumping almost immediately after the pedal2027is depressed. As the pedal2027of the foot pedal2021is released, the controller then causes the pinch valve2023to close. The pressure transducer2006thus senses that no negative pressure is present and causes the motor302of the pump200to shut off. Again, the effect via the electronics is substantially immediate, and thus the motor302stops pumping almost immediately after the pedal2027is depressed. During sterile procedures, the main interventionalist is usually “scrubbed” such that the hands only touch items in the sterile field. However, the feet/shoes/shoe covers are not in the sterile field. Thus again, a single user may operate a switch (via the pedal2027) while also manipulating the catheter2018and guidewire2091. However, this time, it is the sterile field hands and non-sterile field feet that are used. Alternatively, the foot pedal2021may comprise two pedals, one for occlude and one for open. In an alternative foot pedal embodiment, the pedal2027may operate a pneumatic line to cause a pressure activated valve or a cuff to occlude and open the vacuum line2008, for example, by forcing the actuator head2033to move. In another alternative embodiment, the pedal2027may turn, slide, or otherwise move a mechanical element, such as a flexible pull cable or push rod that is coupled to the actuator2031, to move the actuator head2033. The cable2029may be supplied sterile and connected to the base2025prior to a procedure. The occlusion and opening of the vacuum line2008thus acts as a on and off switch for the pump200(via the pressure sensor2006), as described in relation toFIG. 61. The on/off function may thus be performed by a user whose hands can focus on manipulating sterile catheters, guidewires, and accessories, and whose foot can turn the pump on and off in a non-sterile environment. This allows a single user to control the entire operation or the majority of operation of the system for aspirating thrombus2000. This can be an advantage both in terms of a rapid, synchronized procedure, but is also helpful in laboratories where additional assistants are not available. The actuator2031and anvil2035may be controlled to compress the vacuum line2008with a particular force, and the actuator2031may be controlled to move at a particular speed, either when compressing or when removing compression. Speed and force control allows appropriate response time, but may also be able to add durability to the vacuum line2008, for example, by not overcompressing.

A particular configuration for a system for aspirating thrombus1600is illustrated inFIG. 77, and comprises a pump1602, a vacuum line1606, and a pressure sensor1608having a cable1604for connecting to the pump1602and carrying signals from the pressure sensor1608. A pinch valve1610is operable by a foot pedal (not shown, but similar to the foot pedal2021of the system for aspirating thrombus2000inFIG. 64). The foot pedal2021may communicate with the pinch valve1610via a wired connection through the pump1602or may communicate with the pinch valve1610wirelessly. The pinch valve1610extends from the pump1602and includes a pinch valve housing1609having an opening1611which is configured to hold a portion of the vacuum line1606. Internal to the housing1609are components similar to the actuator head2033, actuator2031, and anvil2035of the pinch valve2023ofFIG. 64, which are configured to compress an external portion of the tubing of the vacuum line1606when the foot pedal2021is depressed. The foot pedal2021may then be depressed a second time to release the compression on (decompress) the vacuum line1606. The compression of the vacuum line1606may be configured to be a complete occlusion of the tubing, thus isolating the vacuum source22from the pressure sensor1608. An input port1612to the pressure sensor1608may include a septum1614for adding or removing fluid within the vacuum line1606(e.g., via a hypodermic needle), or alternatively may include a luer connector and valve. The pressure sensor1608is thus configured to reside in a non-sterile field, and is capable of detecting the presence of vacuum (negative pressure) or the lack of vacuum when the foot pedal is depressed by the foot of a user. For example, with the pinch valve1610closed via a signal (or resultant mechanical action) from foot pressure on the foot pedal, and thus no vacuum applied within the vacuum line1606, fluid (such as saline) may be injected (proximal to distal) through the aspiration lumen of an aspiration catheter connected to the vacuum line1606, and into the blood vessel of a patient. The pump1602may be configured (via an internal controller) to not pump saline when the lack of vacuum in the vacuum line1606is determined. Additionally, if vacuum is present, but is suddenly lost, the pump1602will shut down. As seen inFIG. 77, the pinch valve1610is located between the vacuum source22and the pressure sensor1608, thus when the pinch valve1610shuts off the aspiration catheter2018from the vacuum source22, the pressure sensor1608is still able to sense the condition within the aspiration lumen2032of the aspiration catheter2018. In most cases, after the pinch valve1610is caused to close, the negative pressure within the aspiration lumen2032will rise toward the ambient pressure rather quickly. This change will be sensed by the pressure sensor1608. However, in cases in which a piece of thrombus causes a temporary or permanent clog in the aspiration lumen2032, the pressure sensor1608is able to sense these occurrences. For example, a large moving thrombus will delay the time that the internal pressure of the aspiration lumen2032rises to ambient after the pinch valve1610is closed. A complete occlusion of the aspiration lumen2032by a thrombus may cause at least some level of negative pressure to remain in the aspiration lumen. Each of these potential occurrences can be identified by the pressure measured by the pressure sensor1608. The controller may be configured to error or indicate that there is a temporary or permanent clog in the aspiration lumen2032, for example, with a display, or a visual, audible, or tactile warning or alarm. The user may respond to this indication by removing and unclogging the aspiration catheter2018, e.g., by moving a guidewire back and forth, or may determine that the aspiration catheter2018needs to be replaced. Thus, the ability of the pressure sensor1608to monitor aspiration lumen pressure, regardless of whether the pinch valve1610is open or closed, offers an important safety control, as well as a general diagnostic of the state of the system (catheter flow status, etc.). Another general advantage of using a pinch valve2023,1610is that blood only contacts the internal diameter of the vacuum line2008,1606, and thus is not forced within interstices of rotatable valves or other moving parts that otherwise could begin to stick or foul with biological material. The vacuum line2008,1606is simply compressed an uncompressed, allowing a robust and durable design. The internal volume of the vacuum line2008,1606easily maintains sterility. And, as the pinch valve2023,1610is isolated from blood/thrombus, it is reusable. The co-location of two or more of the vacuum source22, the pinch valve, the pump1602and the push button1607may also be an advantage because it allows a quick assessment by an attending physician or medical personnel in a quick glance, for example, if otherwise focused on catheter manipulation in the sterile field.

An additional advantage supplied by the pinch valve1610is that the controller may be configured to cause the pump to operate whenever the pinch valve is in the open condition. Thus, there will always be at least some jet-induced maceration of thrombus while a vacuum is being applied to the aspiration lumen2032. This minimizes or prevents aspiration lumen clogging which could occur if vacuum is being applied to a large portion of thrombus without any maceration (breaking into smaller pieces).

As an alternative or in addition to the foot pedal2021, a push button1607may be provided on the pump1062, or in a remote component. In a first embodiment, the push button1607may simply allow manual opening and closing of the pinch valve1610on the vacuum line1606. A first push to compress the vacuum line1606and isolate the pressure sensor1608from the vacuum source22, and a second push to decompress the vacuum line1606. Alternatively, the push button1607may act as a reset button, and be configured to always open the pinch valve1610(when it is closed), or to make no change if the pinch valve1610is already open. In an embodiment having both the foot pedal2021and the push button1067, with the push button1607configured as a reset button, activation of the foot pedal2021toggles the pinch valve1610open and closed, while activation of the push button1607always places or maintains the pinch valve1610in the open position. The push button1607may be a mechanical (doorbell) type button, or may be a touch switch (e.g., capacitive, resistive, or piezo), or in some embodiment my even be a toggle or rocker switch.

Returning toFIG. 64, the plug2041contains an identification component2043, which may be read by the circuitry (e.g., circuit board304) coupled to the input jack2037of the pump200. In some embodiments, the identification component2043comprises a resistor having a particular value. When the plug2041is connected to the input jack2037, the circuitry of the input jack2037sends a current through the resistor, resulting in the pump200being electronically placed into a “foot pedal” mode, wherein the foot pedal2021can be used to control the operation of the pinch valve1610. Alternatively, when the plug2041is detached from the input jack2037, and the circuitry is not able to identify the resistor, the pump200is placed in a “manual” mode, wherein the pump is controllable only by buttons232(FIG. 12). In other embodiments, instead of a resistor, the identification component2043may comprise an RFID (radio-frequency identification) chip, which is read by the circuitry when the plug2041is connected to the input jack2037. In other embodiments, a proximity sensor, such as a Hall-effect device, may be utilized to determine whether the plug2041is or is not connected to the input jack2037.

In should be noted that in certain embodiments, the pinch valve2023,1610and the foot pedal2021may be incorporated for on/off operation of the pinch valve2023,1610on the vacuum line2008,1606, without utilizing the pressure sensor2006,1608. In fact, in some embodiments, the pressure sensor2006,1608may even be absent from the system for aspirating thrombus2000,1600, the foot pedal2021being used as a predominant control means.

Turning toFIG. 65, a supply tube2087, which contains the catheter supply lumen2093, freely and coaxially extends within the over-the-wire guidewire lumen/aspiration lumen2032. A distal end2089of the supply tube2087is secured to an interior wall2085of the guidewire lumen/aspiration lumen2032of the catheter shaft2042by adhesive, epoxy, hot melt, thermal bonding, or other securement modalities. A plug2083is secured within the catheter supply lumen2093at the distal end2089of the supply tube2087. The plug2083blocks the exit of pressurized fluid, and thus the pressurized fluid is forced to exit through an orifice2081in the wall2079of the supply tube2087. The free, coaxial relationship between the supply tube2087and the catheter shaft2042along their respective lengths, allows for improved flexibility. In some embodiments, in which a stiffer proximal end of the aspiration catheter2018is desired (e.g., for pushability or even torquability), the supply tube2087may be secured to the interior wall2085of the guidewire lumen/aspiration lumen2032of the catheter shaft2042along a proximal portion of the aspiration catheter2018, but not along a distal portion. This may be appropriate if, for example, the proximal portion of the aspiration catheter2018is not required to track through tortuous vasculature, but the distal portion is required to track through tortuous vasculature. The free, substantially unconnected, coaxial relationship between the supply tube2087and the catheter shaft2042along their respective lengths, may also be utilized to optimize flow through the guidewire lumen/aspiration lumen2032, as the supply tube2087is capable of moving out of the way due to the forces of flow (e.g., of thrombus/saline) over its external surface, such that the remaining inner luminal space of the guidewire lumen/aspiration lumen2032self-optimizes, moving toward the lowest energy condition (least fluid resistance) or toward the largest cross-sectional space condition (e.g., for accommodating and passing pieces of thrombus).

InFIG. 67, the distal end2089of the supply tube2087is shown in relation to the distal tip2036. The orifice2081is a circumferential slit in the wall2079of the supply tube2087having a width W and an arc length L (FIG. 68). In catheters having a diameter of between about 3 French and about 14 French, or between about 5 French and about 10 French, or about 8 French, the width W of the slit may range between about 0.0005 inch and about 0.0025 inch, or between about 0.0010 inch and about 0.0020 inch, and the arc length L may range between about 0.002 inch and about 0.015 inch, or between about 0.004 inch and about 0.012 inch, or between about 0.005 inch and about 0.010 inch.

Pressurization of fluid (e.g., saline) by the pump base200/cassette2016combination and through the catheter supply lumen2093and out the orifice2081may form a spray pattern2077, whose shape is at least partially controlled by the dimensions of the orifice2081, as well as by the wall thickness of the wall2079, the viscosity of the fluid or slurry being aspirated and the flow characteristics (e.g., flow rate) of the fluid or slurry being aspirated. The spray pattern2077caused by the circumferential slit orifice2081is particularly effective at cutting or disrupting portions of thrombus within a significant sector of the interior wall2085of the guidewire lumen/aspiration lumen2032.

Turning toFIG. 69, the y-connector2010having a distal end2075and a proximal end2073is shown in use during a thrombus aspiration procedure. The structure of the y-connector2010is particular in order to optimize the flow2071of the fluid or slurry being aspirated, for example, to minimize turbulence, maximize flow rate, and/or minimize pressure head loss. The second female luer2051(sideport) is closer to the distal end2075of the y-connector2010than is the first female luer2055(sideport). The y-connector2010has an internal cavity2097having an inner surface2063The second female luer2051has an interior space2069and an opening2101which communicates with the internal cavity2097of the y-connector2010, the opening2101having a distal extreme2061and a proximal extreme2059. The opening2101of the second female luer2051is the first significant discontinuity or interruption in the inner surface2063of the internal cavity2097of the y-connector2010when moving from the distal end2075to the proximal end2073. Thus, flow of the aspirant (aspirated fluid/slurry) is efficiently diverted from the internal cavity2097to the interior space2069of the second female luer2051before it is able to significantly touch or interface with other portions of the interior of the y-connector2010. For example, the first female luer2055(sideport) has an interior space2103, much of which is filled with the proximal portion2105of the supply tube2087, and bonding material2111(e.g., adhesive, epoxy, hot melt) which secures the proximal portion2105of the supply tube2087to the interior wall2107of the first female luer2055. A projection2109of the bonding material2111and/or proximal portion2105of the supply tube2087into the internal cavity2097of the y-connector2010is the second significant discontinuity or interruption in the inner surface2063of the internal cavity2097of the y-connector2010when moving from the distal end2075to the proximal end2073. Because the second female luer2051(sideport) is closer to the distal end2075of the y-connector1010than is the first female luer2055(sideport), the flow2071of the fluid or slurry being aspirated avoids contact with the second discontinuity/interruption. The internal cavity2097, the interior space2069, and the interior space2103may each have a circular cross-section having a cylindrical-shaped inner surface. Alternatively, each or all may have a non-circular cross-section (e.g., elliptical). In addition to the second female luer2051(sideport) being closer to the distal end2075of the y-connector2010, the inner diameter of the interior space2069can be made large enough that it is not flow limiting. The length of the interior space2069can also be made short enough that it is not flow limiting.

In use, the first female luer2055of the system for aspirating thrombus2000is coupled to a fluid source20and the second female luer2051is coupled to a vacuum source (e.g., syringe2049) by a user or by an assistant. The cassette2016is then coupled to the pump base200as described herein. The pump base200is then operated such that fluid from the fluid source20is injected through the supply lumen2093and through the orifice2081into the aspiration lumen2032. The pump base200is manipulated or commanded in order to adjust the settings on the pump base200. For example, the pump base200may be operated such that an input pressure of the supply lumen2093is between about 650 pounds per square inch and about 1200 pounds per square inch. The pump base200may be operated such that an input pressure of the supply lumen2093is between about 650 pounds per square inch and about 1000 pounds per square inch. The pump base200may be operated such that an input pressure of the supply lumen1093is between about 800 pounds per square inch and about 1000 pounds per square inch. In addition, the pulsatility of the pump may be adjusted, such that the frequency of injection pulses is increased or decreased. A total flow rate of between about 25 milliliters per minute and about 35 milliliters per minute may be utilized, or between about 28 milliliters per minute and about 33 milliliters per minute, or between about 30 milliliters per minute and about 32 milliliters per minute.

FIG. 70illustrates an aspiration catheter2018A with a y-connector2200having a distal end2202and a proximal end2204shown in use during a thrombus aspiration procedure. The aspiration catheter2018A is similar to the aspiration catheter2018described in relation toFIG. 64. The structure of the y-connector2200, as in the y-connector2010ofFIG. 69, is particular in order to optimize the flow2071of the fluid or slurry being aspirated, for example, to minimize turbulence, maximize flow rate, and/or minimize pressure head loss. The second female luer2206(sideport) is closer to the distal end2202of the y-connector2200than is the first female luer2208(sideport). The y-connector2200has an internal cavity2210having an inner surface2212. The second female luer2206has an interior space2214and an opening2216which communicates with the internal cavity2210of the y-connector2200, the opening2216having a distal extreme2218and a proximal extreme2220. The opening2216of the second female luer2206is the first significant discontinuity or interruption in the inner surface2212of the internal cavity2210of the y-connector2200when moving from the distal end2202to the proximal end2204. Thus, flow of the aspirant (aspirated fluid/slurry) is efficiently diverted from the internal cavity2210to the interior space2214of the second female luer2206before it is able to significantly touch or interface with other portions of the interior of the y-connector2200. For example, the first female luer2208(sideport) has an interior space2222, much of which is filled with the proximal portion2224of the supply tube2226, and bonding material2228(e.g., adhesive, epoxy, hot melt) which secures the proximal portion2224of the supply tube2226to the interior wall2230of the first female luer2208. A projection2232of the bonding material2228and/or proximal portion2224of the supply tube2226into the internal cavity2210of the y-connector2200is the second significant discontinuity or interruption in the inner surface2212of the internal cavity2210of the y-connector2200when moving from the distal end2202to the proximal end2204. Because the second female luer2206(sideport) is closer to the distal end2202of the y-connector2200than is the first female luer2208(sideport), the flow2071of the fluid or slurry being aspirated avoids contact with the second discontinuity/interruption. The internal cavity2210, the interior space2214, and the interior space2222may each have a circular cross-section having a cylindrical-shaped inner surface. Alternatively, each or all may have a non-circular cross-section (e.g., elliptical).

A sensor connector2234and a valved connector2236are connected in series to the y-connector2200. A male luer2238at the distal end2240of the sensor connector2234is connected to a female luer2242at the proximal end2204of the y-connector2200. A male luer2244at the distal end2246of the valved connector2236is connected to a female luer2248at the proximal end2250of the sensor connector2234. The sensor connector2234has an inner bore2252, and includes a pressure sensor2006within the inner bore2252. Signals from the pressure sensor2006are carried through a cable2012, as described in earlier embodiments herein. A valve2254, for example a Touhy-Borst, at the proximal end2235of the valved connector2236allows hemostasis of the guidewire lumen/aspiration lumen2032around a guidewire2091. In other embodiments, the valve2254may comprise a spring-loaded seal. The guidewire2091may be inserted entirely through the guidewire lumen/aspiration lumen2032, passing also through a bore2256in the valved connector2236, the inner bore2252in the sensor connector2234, and the internal cavity2210in the y-connector2200. With this configuration, the sensor connector2234and/or the valved connector2236may be easily replaced, if necessary, while maintaining the aspiration catheter2018A in position, for example, within a blood vessel.

FIG. 71illustrates an aspiration catheter2018B with a y-connector2300having a distal end2302and a proximal end2304shown in use during a thrombus aspiration procedure. The aspiration catheter2018B is similar to the aspiration catheter2018described in relation toFIG. 64. The structure of the y-connector2300, as in the y-connector2010ofFIG. 69, is particular in order to optimize the flow2071of the fluid or slurry being aspirated, for example, to minimize turbulence, maximize flow rate, and/or minimize pressure head loss. The second female luer2306(sideport) is closer to the distal end2302of the y-connector2300than is the first female luer2308(sideport). The y-connector2300has an internal cavity2310having an inner surface2312. The second female luer2306has an interior space2314and an opening2316which communicates with the internal cavity2310of the y-connector2300, the opening2316having a distal extreme2318and a proximal extreme2320. The opening2316of the second female luer2306is the first significant discontinuity or interruption in the inner surface2312of the internal cavity2310of the y-connector2300when moving from the distal end2302to the proximal end2304. Thus, flow of the aspirant (aspirated fluid/slurry) is efficiently diverted from the internal cavity2310to the interior space2314of the second female luer2306before it is able to significantly touch or interface with other portions of the interior of the y-connector2300. For example, the first female luer2308(sideport) has an interior space2322, much of which is filled with the proximal portion2324of the supply tube2326, and bonding material2328(e.g., adhesive, epoxy, hot melt) which secures the proximal portion2324of the supply tube2326to the interior wall2330of the first female luer2308. A projection2332of the bonding material2328and/or proximal portion2324of the supply tube2326into the internal cavity2310of the y-connector2300is the second significant discontinuity or interruption in the inner surface2312of the internal cavity2310of the y-connector2300when moving from the distal end2302to the proximal end2304. Because the second female luer2306(sideport) is closer to the distal end2302of the y-connector2300than is the first female luer2308(sideport), the flow2071of the fluid or slurry being aspirated avoids contact with the second discontinuity/interruption. The internal cavity2310, the interior space2314, and the interior space2322may each have a circular cross-section having a cylindrical-shaped inner surface. Alternatively, each or all may have a non-circular cross-section (e.g., elliptical).

A sensor connector2334and a valved connector2336are connected to the y-connector2300. A male luer2338at the distal end2340of the valved connector2336is connected to a female luer2342at the proximal end2304of the y-connector2300. A male luer2344at the distal end2346of the sensor connector2334is connected to a female luer2348at an intermediate portion2350of the valved connector2336. The sensor connector2334has an inner bore2352, and includes a pressure sensor2006within the inner bore2352. Signals from the pressure sensor2006are carried through a cable2012, as described in earlier embodiments herein. A valve2354, for example a Touhy-Borst, at the proximal end2335of the valved connector2336allows hemostasis of the guidewire lumen/aspiration lumen2032around a guidewire2091. In other embodiments, the valve2354may comprise a spring-loaded seal. The guidewire2091may be inserted entirely through the guidewire lumen/aspiration lumen2032, passing also through a bore2356in the valved connector2336, and the internal cavity2310in the y-connector2300. With this configuration, the sensor connector2334and/or the valved connector2336may be easily replaced, if necessary, while maintaining the aspiration catheter2018B in position, for example, within a blood vessel. The sensor connector2334additionally includes an inlet2358, which may be used to inject fluid, such as saline or contrast media or a mixture of the two. The inlet2358may comprise a female luer configured for coupling a male luer of a syringe. In some embodiments, the inlet2358may comprise a rubber septum2360, configured for repeatable penetration of the needle of a syringe therethrough. In alternative embodiments, the pressure sensor2006may be placed at a number of different alternate locations.

FIGS. 72-74illustrate a system for aspirating thrombus2400. The system for aspirating thrombus2400includes many similarities to and uses several components of the system for aspirating thrombus1900ofFIG. 61, including the aspiration catheter1930, y-connector1910, having a female luer1912hydraulically coupled to the high pressure injection lumen1934(FIG. 62) and a female luer1914hydraulically coupled to the aspiration lumen1932(FIG. 62), an additional y-connector1916having a male luer1918and female luer1920and a touhy-borst1922, an injection tube1906having a male luer1908, a pressure transducer106electrically-connected to a cable112, and a vacuum line1926having a luer fitting2455. The luer fitting2455in the system for aspirating thrombus2400ofFIGS. 72-74is a male luer connector, through in alternate embodiments, may be another type of connector. The aspiration catheter1930has been inserted through a guiding catheter2450having a hemostasis valve2452configured for sealing around the shaft2454of the aspiration catheter1930. Fluid (e.g., saline) may be injected through the interior lumen2456of the guiding catheter2450, and around the shaft2454of the aspiration catheter1930by attaching a syringe or pump to the luer connection2458of an extension tube2460while the stopcock2462coupled to the luer connection2458is in an open condition. The stopcock2462is shown, however, in a closed condition inFIGS. 72-74. A guidewire1902can be used in conjunction with the system for aspirating thrombus2400.

A new feature in the system for aspirating thrombus2400ofFIGS. 72-74is a four-way stopcock2402connected between the vacuum line1926, the pressure transducer106, and the aspiration catheter1930. The four-way stopcock2402includes a male luer2404, that is fluidly coupled to the female luer1920of the y-connector1916, a female luer2406, that is fluidly coupled to the (male) luer fitting2455of the vacuum line1926, and a female luer2408, that is fluidly coupled to a male luer2457of the pressure transducer106. The four-way stopcock2402includes a main housing2410having three inlets/outlets2412,2414,2416, and a rotatable valve body2418which is rotated via a projection2420. InFIG. 72, the valve body2418is in an “aspiration” position, which allows fluid communication between all of the pressure transducer106, the vacuum line1926(and thus, the syringe2049), and the aspiration lumen1932of the aspiration catheter1930. The distal end1997of the aspiration catheter1930is shown within a blood vessel1999having a thrombus1995. The projection2420points in the direction of the “closed” side of the valve body2418, and thus, inFIG. 72is not closing off any of the three inlets/outlets2412,2414,2416. A controller, for example, carried on the circuit board304ofFIG. 17, is configured to receive signals from the pressure transducer106to obtain information as to the pressure sensed by the pressure transducer106. The controller is further configured to stop operation of the pump200if the signals received from the pressure transducer106indicate that the pressure transducer is not communicating with a negative pressure (“vacuum”), with an intention to assure that injection of fluid occurs through the high-pressure injection lumen1934only when the vacuum source is actively causing the aspiration lumen1932to aspirate thrombus1995. For example, inFIG. 73, the user has turned the valve body2418to an “off” position in relation to the vacuum line1926and syringe2049. The inlets/outlets2412,2414are open and the inlet/outlet2416is closed. Thus, the pressure transducer106does not measure the negative pressure of the vacuum line1926, and instead measures the pressure near the proximal end of the aspiration lumen1932(actually the pressure adjacent the interior of the female luer1920of the y-connector1916). After the valve body2418is turned to this particular “off” position, the pressure measured by the pressure transducer106will increase, causing the controller to stop the operation of the pump200. The intention is to insure not to inject into the blood vessel or disrupt thrombus in the blood vessel when not aspiration is actively being performed.

However, there are instances in which it may be desired to perform a power pulse or power injection with the pump200, without an active vacuum applied on the aspiration lumen1932of the aspiration catheter1930. The four-way stopcock2402allows the pressure transducer106(and thus, the controller) to be “tricked” without having to reprogram or reconfigure the controller. Turning toFIG. 74, the valve body2418has been turned by the user to a “power inject” position, wherein the pressure transducer106is in fluid communication with the vacuum line1926(and vacuum source/syringe2049), but the aspiration lumen1932of the aspiration catheter1930is not in fluid communication with the vacuum line1926(or vacuum source/syringe2049), or the pressure transducer106. The inlet/outlet2412is closed, isolating the aspiration lumen1932from the pressure transducer106and the vacuum line1926. The inlets/outlets2414/2416are open, and only allow fluid communication between the pressure transducer106and the vacuum line1926. Thus, still allowing (via the controller) injection of fluid through the high-pressure injection lumen1934, and out the orifice1946(FIG. 62) of the high-pressure injection lumen1934and out the distal orifice of the aspiration lumen1932into the blood vessel1999. The power pulse or power injection may be used to deliver a forceful disturbance to thrombus1995in the blood vessel1999, or may be used to increase the amount of lower viscosity fluid (e.g., saline)1993around the thrombus1995(to aid in subsequent aspiration attempts). Contrast media may also be added to the injection fluid or may be used as the injection fluid, so that the power pulse increases the radiopacity within the blood vessel1999, in the vicinity of the thrombus1995.

In certain situations, aspiration of thrombus1995may become difficult through the aspiration lumen1932of the aspiration catheter1930during an aspiration procedure. One reason that may cause this is if the thrombus1995surrounding the distal end1997of the aspiration catheter1930is of a substantially high viscosity, thus making it difficult for the thrombus1995to begin flowing into the distal opening and through the aspiration lumen1932of the aspiration catheter1930. In these situations, a syringe, or a second pump may be attached to the luer connection2458of the extension tube2460(with the stopcock2062in the open position) and saline (and/or contrast media) may be injected through the interior lumen2456of the guiding catheter2450. The outer diameter of the aspiration catheter1930is sized sufficiently smaller than the inner diameter of the interior lumen2456of the guiding catheter2450such that a hand injection is possible without straining. The use of at least some contrast media allows for a visual diagnostic of the catheter flow status (e.g., aspiration) as well as the thrombus location and even thrombus shape or contour. The distal end2451of the guiding catheter may be moved (if needed) to place it in sufficient proximity with the distal end1997of the aspiration catheter1930and/or the target portion of thrombus1995to be aspirated. By injecting a bolus of fluid having substantially the viscosity of water or saline, or at least a fluid whose viscosity is on the same order as that of water or saline, or even blood, the initiation of aspiration at the target thrombus site and entry into the aspiration lumen1932of the aspiration catheter1930is facilitated. This may happen because the overall (bulk) viscosity is lowered. Once the somewhat diluted thrombus1991begins to flow through the aspiration catheter with the application of the pump to the high-pressure injection lumen1934, the aspiration procedure tends to continue, as it is now in a dynamic state, instead of an initially static state. The procedure may be continually or continuously assessed using the pressure sensor106, or by visualization with angiography/fluoroscopy. In some embodiments, a second pump (not shown) may be attached to the luer connection2458of the extension tube2460, and may be triggered by a controller which is carried on either the first pump200,400or on the pressure sensor106. The second pump may be turned on or turned off based on a threshold pressure measured by the pressure sensor106that is met or crossed.

Alternatively, saline, contrast, or other fluids may even be injected in a retrograde fashion, by turning the valve body2418of the four-way stopcock2402to the particular “off” position ofFIG. 73. This will stop the action of the pump200, if the pump has not already been stopped by other means. A luer cap2422on the pressure transducer106may now be removed and the fluid may be injected (e.g., with a syringe) retrograde through the access luer2424of the pressure transducer106and through the aspiration lumen1932from proximal end to distal end and out the distal opening of the aspiration lumen1932into the blood vessel. The valve body2418may be used as a sterile on/off switch to perform a number of different sub-procedures within the aspiration/thrombectomy procedure.

FIG. 75illustrates the system for aspirating thrombus2400further comprising a guiding catheter2426(or long sheath) configured for placing the aspiration catheter1930therethrough. A blood vessel2428includes thrombus2430therein. The guiding catheter2426includes a tubular shaft2434, a distal opening2436, and a proximal end2438having a valve2440with a sideport extension tube2442having a luer2444for injection and a stopcock2446. The luer2444of the extension tube2442may be fluidly coupled to sources of fluids, such as a saline bottle or bag, or a contrast media bottle or bag. In use, as shown inFIG. 75, the distal end1997of the aspiration catheter1930has been extended out of the distal opening2436of the guiding catheter2426in order to perform a thrombectomy procedure according to embodiments described herein. If during the procedure, a user determines that aspiration of the thrombus2430through the aspiration lumen1932of the aspiration catheter1930is not occurring at a desired thrombus aspiration rate (flow rate, mass removal rate, etc.), the user grasps the guiding catheter2426by the tubular shaft2434and spins the guiding catheter2426(arrow) within the blood vessel2428to increase the thrombus aspiration rate. The circumferential shear caused by the rotating cylindrical surface area of the tubular shaft2434of the guiding catheter2426serves to disrupt or macerate the thrombus, particularly in the area near the distal opening2436. The status of the aspiration of thrombus may be determined by data received from the pressure transducer106, or by visual evidence (amount of thrombus seen passing through clear tubing or connectors). The guiding catheter2426may be spun around axis2427while the aspiration catheter1930has fluid injected through the high-pressure injection lumen1934and/or while the vacuum source (syringe2049) is applied to the aspiration lumen1932. Alternatively, the pump200and or vacuum source may be temporarily stopped while the rotation of the guiding catheter2426is performed. As shown inFIG. 75, the extension tube2442and luer2444have been decoupled from any fluid sources in order to facilitate the untethered rotatability of the guiding catheter2426. The inner material of the valve2440is typically low friction and allows a smooth and sealed rotation over the shaft of the aspiration catheter1930. Alternatively, instead of the valve2440, the guiding catheter may have a proximal luer connector and may be attached to a rotatable y-connector or other rotatable (swivel) connector, which also allows rotation of the guiding catheter2426.

FIG. 76illustrates an aspiration catheter1518with a y-connector1500having a distal end1502and a proximal end1504configured for use in a thrombus aspiration procedure. The y-connector1500includes a first female luer1508(sideport) which allows injection through the interior of a supply tube1526of the aspiration catheter1518. The first female luer1508(sideport) has an interior space1522, much of which is filled with the proximal portion1524of the supply tube1526and bonding material1528(e.g., adhesive, epoxy, hot melt) which secures the proximal portion1524of the supply tube1526to the interior wall1530of the first female luer1508. A projection1532of the bonding material1528and/or proximal portion1524of the supply tube1526into the internal cavity1510of the y-connector1500may cause a discontinuity or interruption in the inner surface1512of the internal cavity1510of the y-connector1500. The internal cavity1510and the interior space1522may each have a circular cross-section having a cylindrical-shaped inner surface. Alternatively, each or all may have a non-circular cross-section (e.g., elliptical). The female luer1508is configured for attaching a male luer2054of an injection tube2052so that pressurized saline may be injected through the supply tube1526. The proximal end1504of the y-connector1500includes a female luer1542.

A combined connector1536includes a male luer1538at its distal end1540which is configured to be connected to the female luer1542of the y-connector1500. The combined connector1536includes a first inner bore1556and a second inner bore1552which are co-communicating, the second inner bore1552including a pressure sensor2006communicating therein. Signals from the pressure sensor2006are carried through a cable2012, as described in earlier embodiments herein. A valve1554, for example a Touhy-Borst, at the proximal end1535of the combined connector1536allows hemostasis of the guidewire lumen/aspiration lumen2032around a guidewire2091. In other embodiments, the valve1554may comprise a spring-loaded seal. The guidewire2091may be inserted entirely through the guidewire lumen/aspiration lumen2032, passing also through the bore1556in the combined connector1536, and the internal cavity1510in the y-connector1500. The combined connector1536further comprises a female luer1506configured for attaching the male luer2053of the vacuum line2008. With this configuration, the combined connector1536may be easily replaced, if necessary, while maintaining the aspiration catheter1518in position, for example, within a blood vessel. The combined connector1536additionally includes an inlet1558, which may be used to inject fluid, such as saline or contrast media or a mixture of the two, for example, when aspiration is not actively occurring. The inlet1558may comprise a female luer configured for coupling a male luer of a syringe. In some embodiments, the inlet1558may comprise a rubber septum1560, configured for repeatable penetration of the needle of a syringe therethrough. During aspiration, a vacuum is applied to the female luer1506and the pressure is measured by the pressure sensor2006.

FIG. 78illustrates a connector1620for use in subsequently presented embodiments of aspiration catheters, including the aspiration catheter1616ofFIG. 79. The connector1620comprises a molded, cast or otherwise formed body which may comprise a rigid polymer, such as polycarbonate, acrylic, polyester-polycarbonate blend, or acrylnitrile-butadiene-styrene (ABS). The connector1620includes a main body1619including a proximal female luer1634having male threads1635. The connector1620further includes a first sideport1622having a female luer1621and male threads1637. The connector1620further includes a second, dual-use sideport1628having a female luer1629and male threads1639. The sideport1628also includes a barbed fitting1633, thus allowing either attachment of a male luer to the female luer1629(or if threaded, to the female luer1629and threads1639) or a frictional fitting (tubular inner diameter) to the barbed fitting1633. The barbed fitting1633may be particularly useful for frictionally attaching tubing from a vacuum line. The multi-purpose utility of the sideport1628allows it to be easily used with a variety of commercially available vacuum sources, including, but not limited to, syringes, VacLok® syringes, vacuum pumps, house vacuum lines, vacuum canisters, or vacuum bottles. When the sideport1628is used for infusion, the female luer1629would be commonly used, but the barbed fitting1633also allows for alternative infusion connections.

FIG. 79illustrates an aspiration catheter1616comprising a shaft1618and a connector1620. The connector1620includes a female luer sideport1622which allows injection through the interior of a supply tube1623of the aspiration catheter1616via a fluid supply line1624having a male luer1626. The male luer1626is connected to the female luer1621of the sideport1622. The connector1620includes a barbed fitting sideport1628which is configured for attachment of a vacuum line1630having a plastic or elastomeric tubular end1632configured for sealingly forcing over the barbed fitting1628. The tubular end may comprise Tygon®, PVC, or silicone or other appropriate materials. The connector1620further includes a proximal female luer1634, which is shown capped off by a luer cap1636. If the aspiration catheter1616is used without a guidewire, the luer cap1636may be left in place over the luer1643. If a guidewire is used, the luer cap1636may be removed from the luer1634, and the guidewire inserted through the interior of the connector1620and through the aspiration lumen of the aspiration catheter1616. Alternatively, with the luer cap1636removed, an additional pump and injection tube having a male luer may be attached to the female luer1634of the connector1620, to access the aspiration lumen of the aspiration catheter1616. The pump may be used to apply a positive pressure and force saline distally, for example, when vacuum is not being significantly applied or applied at all to the aspiration lumen via the vacuum line1630. The purpose of the injection of fluid through the additional pump may be for potential declogging of the aspiration lumen. Declogging may be particularly helpful in venous cases, where any distal emboli of clog material (e.g., clot) ejected from the aspiration lumen into the vein is of lesser concern than in a procedure located in a coronary or cerebral artery. In some cases, the fluid injected to unblock the aspiration lumen may be alternated with the injection of contrast media (undiluted or dilute) to aid in the visualization of the target area, e.g., via fluoroscopy. The injection of fluid through the aspiration lumen may also aid in lowering the bulk viscosity of the thrombus and blood surrounding the thrombus (e.g., at the target site) to aid in its subsequent aspiration into the aspiration lumen of the aspiration catheter1616.

FIG. 80illustrates an aspiration catheter1638comprising a shaft1640and a connector1642. The connector1642includes a female luer sideport1644which allows injection through the interior of a supply tube1647of the aspiration catheter1638via a fluid supply line1646having a male luer1648. The connector1642includes a barbed fitting1650(sideport) which is configured for attachment of a vacuum line1652having a plastic or elastomeric tubular end1654configured for sealingly forcing over the barbed fitting1650. In some embodiments, the barbed fitting1650may also include a female luer. The connector1642further includes a Touhy-Borst valve1656which may be sealed (closed) is a guidewire is not used, and may be opened to allow the passage of a guidewire through the connector1642and the aspiration lumen of the aspiration catheter1638, and may be sealed over the guidewire. The Touhy-Borst valve1656may include a distal male luer1657configured to secure to a female luer1659at the proximal end of the connector1642. In alternate embodiments, the Touhy-Borst valve1656may be permanently connected or formed on the connector1642. As an alternative to the foot switch2021operated actuation (FIG. 64) of the pinch valve1610(FIG. 77), the vacuum line1652(FIG. 80) can be manually clamped and unclamped in order to close and open the vacuum line1652. The manual clamping would be performed at a location on the vacuum line that is between the vacuum source22and the pressure sensor1608(FIG. 77), and, if there is a pinch valve1610along the vacuum line1652, the pinch valve1610would have to be open to allow this manual clamping functionality. Alternatively, instead of a manual clamp, the vacuum line1652may be removed by pulling the elastomeric tubular end1654from the barbed fitting1650, and capping off or otherwise occluding the lumen of the vacuum line1652.

FIG. 81illustrates an aspiration catheter1658comprising a shaft1660and a connector1662. The connector1662includes a female luer sideport1664which allows injection through the interior of a supply tube1667of the aspiration catheter1658via a fluid supply line1666having a male luer1668. The connector1662includes a barbed fitting1670(sideport) which is configured for attachment of a vacuum line1672having a plastic or elastomeric tubular end1674configured for sealingly forcing over the barbed fitting1670. In some embodiments, the barbed fitting1670may also include a female luer. The connector1662further includes a proximal female luer1676. A y-connector1678includes a male luer1680which is attached to the female luer1676of the connector1662. The y-connector1678further includes a Touhy-Borst valve1682which may be sealed (closed) is a guidewire is not used, and may be opened to allow the passage of a guidewire through the y-connector1678, the connector1662, and the aspiration lumen of the aspiration catheter1658, and may be sealed over the guidewire. The y-connector1678further includes a female luer sideport1684to which a syringe or other implement may be connected, for example to inject fluids or drugs. An additional pump and injection tube having a male luer may be attached to the luer sideport1684of the y-connector1678, to access the aspiration lumen of the aspiration catheter1658. The pump may be used to apply a positive pressure and force saline distally, for example, when vacuum is not being significantly applied or applied at all to the aspiration lumen via the vacuum line1672. The purpose of the injection of fluid through the additional pump may be for potential declogging of the aspiration lumen. Declogging may be particularly helpful in venous cases, where any distal emboli of clog material (e.g., clot) ejected from the aspiration lumen into the vein is of lesser concern than in a procedure located in a coronary or cerebral artery. In some cases, the fluid injected to unblock the aspiration lumen may be alternated with the injection of contrast media (undiluted or dilute) to aid in the visualization of the target area, e.g., via fluoroscopy. The injection of fluid through the aspiration lumen may also aid in lowering the bulk viscosity of the thrombus and blood surrounding the thrombus (e.g., at the target site) to aid in its subsequent aspiration into the aspiration lumen of the aspiration catheter1658. Injection of contrast or saline, or other fluid, may be performed by a pump, or by hand/syringe injection, via attachment to the female luer sideport1684. Alternatively, the y-connector1678may be removed by detaching the male luer1680from the female luer1676of the connector1662, and then attaching the pump or syringe to the female luer1676and injecting.

In some cases, parts or all of the devices described herein may be doped with, made of, coated with, or otherwise include a radiopaque material. Radiopaque materials are understood to be materials capable of producing a relatively bright image on a fluoroscopy screen or another imaging technique during a medical procedure. Some examples of radiopaque materials can include, but are not limited to, gold, platinum, palladium, tantalum, tungsten alloy, polymer material loaded with a radiopaque filler, and the like. One or more hydrophilic or hydrophobic lubricious coatings may be used in order to improve trackability of the aspiration catheter118through the blood vessels.

In some instances, a degree of MRI compatibility may be imparted into parts of the devices described herein. For example, to enhance compatibility with Magnetic Resonance Imaging (MRI) machines, it may be desirable to make various portions of the devices described herein from materials that do not substantially distort MRI images or cause substantial artifacts (gaps in the images). Some ferromagnetic materials, for example, may not be suitable as they may create artifacts in an MRI image. In some cases, the devices described herein may include materials that the MRI machine can image. Some materials that exhibit these characteristics include, for example, tungsten, cobalt-chromium-molybdenum alloys (e.g., UNS: R30003 such as ELGILOY®, PHYNOX®, and the like), nickel-cobalt-chromium-molybdenum alloys (e.g., UNS: R30035 such as MP35-N® and the like), nitinol, and the like, and others.

In some instances, some of the devices described herein may include a coating such as a lubricious coating or a hydrophilic coating. Hydrophobic coatings such as fluoropolymers provide a dry lubricity. Lubricious coatings improve steerability and improve lesion crossing capability. 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, polyvinylpyrrolidones, polyvinylalcohols, hydroxy alkyl cellulosics, algins, saccharides, caprolactones, 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.

It should be understood that this disclosure is, in many respects, only illustrative. Changes may be made in details, particularly in matters of shape, size, and arrangement of steps without exceeding the scope of the disclosure. The scope of the disclosure is, of course, defined in the language in which the appended claims are expressed.

While embodiments of the present disclosure have been shown and described, various modifications may be made without departing from the scope of the present disclosure. Embodiments of the present disclosure are contemplated to have utility in a variety of blood vessels, including but not limited to coronary arteries, carotid arteries, intracranial/cerebral arteries, inferior and superior vena cavae and other veins (for example, in cases of deep venous thrombosis or pulmonary embolism), peripheral arteries, shunts, grafts, vascular defects, and chambers of the heart. This includes, but is not limited to, any vessel having a diameter of bout two mm or greater. An aspiration catheter118outer diameter of about seven French or less is contemplated for many of the applications, though in certain applications, it may be larger. In some embodiments, an aspiration catheter118diameter of about six French or less is contemplated. Embodiments of the present disclosure may even be used in non-vascular applications, for example body lumens or cavities having material accumulations that need to be macerated and/or removed.

It is contemplated that various combinations or subcombinations of the specific features and aspects of the embodiments disclosed above may be made and still fall within one or more of the embodiments. Further, the disclosure herein of any particular feature, aspect, method, property, characteristic, quality, attribute, element, or the like in connection with an embodiment can be used in all other embodiments set forth herein. Accordingly, it should be understood that various features and aspects of the disclosed embodiments can be combined with or substituted for one another in order to form varying modes of the disclosed embodiments. Thus, it is intended that the scope of the present disclosure herein disclosed should not be limited by the particular disclosed embodiments described above. Moreover, while the present disclosure is susceptible to various modifications, and alternative forms, specific examples thereof have been shown in the drawings and are herein described in detail. It should be understood, however, that the present disclosure is not to be limited to the particular forms or methods disclosed, but to the contrary, the present disclosure is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the various embodiments described and the appended claims. Any methods disclosed herein need not be performed in the order recited. The methods disclosed herein include certain actions taken by a practitioner; however, they can also include any third-party instruction of those actions, either expressly or by implication.

The ranges disclosed herein also encompass any and all overlap, sub-ranges, and combinations thereof. Language such as “up to,” “at least,” “greater than,” “less than,” “between,” and the like includes the number recited. Numbers preceded by a term such as “approximately”, “about”, and “substantially” as used herein include the recited numbers (e.g., about 10%=10%), and also represent an amount close to the stated amount that still performs a desired function or achieves a desired result. For example, the terms “approximately”, “about”, and “substantially” may refer to an amount that is within less than 10% of, within less than 5% of, within less than 1% of, within less than 0.1% of, and within less than 0.01% of the stated amount.