Systems and methods for ultrasound catheters

Abstract

The catheter system includes an aspiration catheter (300) having a first end, a second end, and a body disposed between the first and second ends. An ultrasound catheter (200) has a proximal end, a distal end, and a body disposed between the proximal and distal ends. The ultrasound catheter (200) is configured to be inserted through the body of the aspiration catheter (300). The distal end of the ultrasound catheter is configured to articulate. A retriever catheter (400) has a proximal end, a distal end, and a shaft disposed between the proximal and distal ends. The retriever catheter (400) is configured to be inserted through the body of the aspiration catheter.

Description

[Technical Field]

[0001] Incorporation by reference to priority applications This application claims priority to U.S. Provisional Application No. 63 / 375,038, filed September 8, 2022, which is hereby incorporated by reference in its entirety for all purposes. Any and all applications for which a foreign or domestic priority claim is identified in an Application Data Sheet filed with this application are hereby incorporated by reference pursuant to 37 CFR § 1.57.

[0002] The present disclosure relates generally to catheter systems, and more particularly to catheter systems including ultrasound catheters that in some embodiments utilize aspiration catheters or aspiration sheaths and / or retriever catheters. [Background technology]

[0003] Ultrasonic energy has been used to enhance the intravascular delivery and / or efficacy of various therapeutic compounds. In one system, an ultrasound catheter is used to deliver ultrasound energy and the therapeutic compound to a treatment site within a patient's vasculature. Such an ultrasound catheter can include an elongated member configured to advance through the patient's vasculature and an ultrasound assembly disposed near a distal portion of the elongated member. The ultrasound assembly is configured to emit ultrasound energy. Such an ultrasound catheter can include a fluid delivery lumen used to deliver the therapeutic compound to the treatment site. In this manner, ultrasound energy is delivered to the treatment site to enhance the penetration and / or delivery of the therapeutic compound. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] US Patent Application Publication No. 2020 / 0405258 [Patent Document 2] U.S. Patent Application Publication No. 2021 / 0007759 [Patent Document 3] U.S. Patent No. 8,668,709 [Patent Document 4] U.S. Patent No. 1,162,2779 Summary of the Invention [Means for solving the problem]

[0005] In some embodiments, the catheter system includes an aspiration catheter having a first end, a second end, and a body disposed between the first and second ends; an ultrasound catheter having a proximal end, a distal end, and a body disposed between the proximal and distal ends, the ultrasound catheter configured for insertion through the body of the aspiration catheter; and a retriever catheter having a proximal end, a distal end, and a shaft disposed between the proximal and distal ends, the retriever catheter configured for insertion through the body of the aspiration catheter.

[0006] In some embodiments, the suction catheter comprises an expandable funnel at the second end.

[0007] In some embodiments, the expandable funnel is self-expandable.

[0008] In some embodiments, the distal end of the ultrasound catheter is configured to articulate.

[0009] In some embodiments, the ultrasound catheter further comprises a knob and at least one pull wire, the at least one pull wire connecting to the distal end of the ultrasound catheter and to the knob.

[0010] In some embodiments, the knob is configured to rotate to articulate the distal end of the ultrasound catheter.

[0011] In some embodiments, the ultrasound catheter delivers targeted ultrasound therapy.

[0012] In some embodiments, the ultrasound catheter further comprises at least one lumen extending between the proximal end and the distal end.

[0013] In some embodiments, the distal end of the ultrasound catheter is configured to articulate between + or - 180 degrees from the longitudinal axis of the ultrasound catheter.

[0014] In some embodiments, the ultrasound catheter is configured to deliver ultrasound at a frequency in the range of 450 kHz to 850 kHz.

[0015] In some embodiments, a catheter system for treating a patient with thromboembolism includes an aspiration catheter having a first end, a second end, and a body disposed between the first end and the second end, and an ultrasound catheter having a retriever, the retriever extending from the ultrasound catheter, and the ultrasound catheter configured to be inserted through the body of the aspiration catheter.

[0016] In some embodiments, the suction catheter comprises an expandable funnel at the second end.

[0017] In some embodiments, the distal end of the ultrasound catheter is configured to articulate.

[0018] In some embodiments, the ultrasound catheter further comprises at least one wire connecting the distal end to a dial disposed on the ultrasound catheter, the dial configured to control articulation of the distal end.

[0019] In some embodiments, the ultrasound catheter delivers targeted ultrasound therapy.

[0020] In some embodiments, the expandable funnel is configured to self-expand.

[0021] In some embodiments, the retriever catheter includes a retriever disposed at the distal end of the retriever catheter that is configured to actively expand or contract.

[0022] In some embodiments, the retriever catheter includes a knob that can control movement of the retriever.

[0023] In some embodiments, a method for treating a patient with thromboembolism includes: advancing an aspiration catheter having a first end, a second end, and a body disposed between the first and second ends into the patient's vasculature; advancing an ultrasound catheter having a proximal end, a distal end, and a lumen disposed between the proximal and distal ends through the aspiration catheter and into a treatment site; delivering ultrasound energy and a therapeutic compound with the ultrasound catheter to the treatment site; and retrieving thromboemboli from the treatment site using a retriever after treating at least a portion of the treatment site with the ultrasound energy and the therapeutic compound.

[0024] In some embodiments, delivering the therapeutic compound comprises delivering microbubbles to the treatment site through a lumen of an ultrasound catheter. In some embodiments, delivering the therapeutic compound comprises delivering microbubbles mixed with the therapeutic compound to the treatment site through a lumen of an ultrasound catheter.

[0025] In some embodiments, the catheter comprises an expandable funnel at the second end.

[0026] In some embodiments, the method further comprises articulating the distal end of the ultrasound catheter.

[0027] In some aspects, the method further comprises articulating the ultrasound catheter to deliver targeted ultrasound therapy to the treatment site.

[0028] In some embodiments, the method further comprises removing the ultrasound catheter from the aspiration catheter and then advancing a retriever through the aspiration catheter and using the retriever to retrieve thromboemboli from the treatment site with the retriever.

[0029] In some embodiments, the method further comprises aspirating thromboemboli at the treatment site through the aspiration catheter.

[0030] In some embodiments, a method for treating a patient with thromboembolism includes: advancing an aspiration catheter into the patient's vasculature, the aspiration catheter having a first end, a second end, and a body disposed between the first end and the second end; advancing an ultrasound catheter through the aspiration catheter into a treatment site, the ultrasound catheter having a retriever catheter integrated within the ultrasound catheter configured to collect residual thrombus, the ultrasound catheter configured for insertion through the aspiration catheter; delivering ultrasonic energy to the treatment site; and retrieving thromboemboli from the treatment site with the retriever catheter.

[0031] In some embodiments, the suction catheter comprises an expandable funnel at the second end.

[0032] In some embodiments, the method further comprises delivering microbubbles to the treatment site through a lumen of the ultrasound catheter.

[0033] In some embodiments, the distal end of the ultrasound catheter is configured to articulate.

[0034] In some aspects, the method further comprises articulating the distal end of the ultrasound catheter to deliver targeted ultrasound therapy to the treatment site.

[0035] In some embodiments, the method further comprises rotating the retriever catheter to control movement of the retriever to retrieve thromboemboli from the treatment site.

[0036] In some embodiments, the method further comprises applying aspiration through the aspiration catheter and retracting the retriever catheter before aspirating thromboemboli at the treatment site.

[0037] In some embodiments, the catheter system includes an aspiration catheter having a first end, a second end, and a body disposed between the first and second ends; an ultrasound catheter having a proximal end, a distal end, and a body disposed between the proximal and distal ends, the ultrasound catheter configured for insertion through the body of the aspiration catheter, and the distal end of the ultrasound catheter configured for articulation; and a retriever catheter having a proximal end, a distal end, and a shaft disposed between the proximal and distal ends, the retriever catheter configured for insertion through the body of the aspiration catheter.

[0038] In some embodiments, the suction catheter comprises an expandable funnel at the second end.

[0039] In some embodiments, the expandable funnel is self-expandable.

[0040] In some embodiments, the ultrasound catheter further comprises at least one lumen disposed between the proximal end and the distal end.

[0041] In some embodiments, an ultrasound catheter system includes a body having a proximal end, a distal end, and a lumen extending from the proximal end to the distal end, and an ultrasound element disposed at the distal end of the ultrasound catheter, the distal end of the ultrasound catheter being configured to articulate.

[0042] In some embodiments, the catheter system includes an aspiration catheter having a first end, a second end, and a body disposed between the first and second ends; an ultrasound catheter having a proximal end, a distal end, and a body disposed between the proximal and distal ends, the ultrasound catheter configured for insertion through the body of the aspiration catheter; and a retriever catheter having a proximal end, a distal end, and a shaft disposed between the proximal and distal ends, the retriever catheter configured for insertion through the body of the aspiration catheter.

[0043] In some embodiments, the suction catheter comprises an expandable funnel at the second end.

[0044] In some embodiments, the expandable funnel is self-expandable.

[0045] In some embodiments, the distal end of the ultrasound catheter is configured to articulate.

[0046] In some embodiments, the ultrasound catheter further comprises a knob and at least one pull wire, the at least one pull wire connecting to the distal end of the ultrasound catheter and to the knob.

[0047] In some aspects, a method for treating a patient with thromboembolism includes advancing an ultrasound catheter having a proximal end, a distal end, and a lumen disposed between the proximal and distal ends into a treatment site having a clot; delivering ultrasound energy and a therapeutic compound to the treatment site; after an initial period of treating the clot, advancing the ultrasound catheter further into the clot; and articulating the distal end of the ultrasound catheter to provide targeted therapy to a portion of the treatment site with the ultrasound catheter.

[0048] In some embodiments, the method further comprises advancing an aspiration catheter into the patient's vasculature before advancing the ultrasound catheter, and advancing the ultrasound catheter through the aspiration catheter and then into the treatment site.

[0049] In some embodiments, the suction catheter comprises an expandable funnel at the second end.

[0050] In some embodiments, delivering ultrasound energy and a therapeutic compound to a treatment site with an ultrasound catheter comprises delivering microbubbles and a therapeutic compound through a lumen of the ultrasound catheter and delivering ultrasound energy through an ultrasound element at a distal end of the ultrasound catheter.

[0051] In some embodiments, a catheter system includes an aspiration catheter having a first end (which may also be referred to as a proximal end), a second end (which may also be referred to as a distal end), and a body disposed between the first and second ends; an ultrasound catheter having a proximal end, a distal end, and a lumen disposed between the proximal and distal ends, the ultrasound catheter configured for insertion through the body of the aspiration catheter; and a retriever configured for insertion through the lumen of the ultrasound catheter.

[0052] In some embodiments, the suction catheter includes an expandable funnel at the second end.

[0053] In some embodiments, the distal end of the ultrasound catheter is configured to articulate.

[0054] In some embodiments, a catheter system includes an aspiration catheter having a first end, a second end, and a body disposed between the first end and the second end, and an ultrasound catheter having a retriever, the retriever extending from the ultrasound catheter and configured to collect, and the ultrasound catheter configured for insertion through the body of the aspiration catheter.

[0055] In some embodiments, the suction catheter includes an expandable funnel at the second end.

[0056] In some embodiments, the distal end of the ultrasound catheter is configured to articulate.

[0057] In some embodiments, the retriever is configured to self-expand.

[0058] In some embodiments, the retriever is configured to actively expand or contract.

[0059] In some embodiments, the ultrasound catheter further includes at least one wire connecting the distal end to a dial disposed on the ultrasound catheter, the dial configured to control articulation of the distal end.

[0060] In some embodiments, the collector is configured to rotate to control movement of the collector.

[0061] In some embodiments, a method for treating a patient with thromboembolism includes the steps of: advancing an ultrasound catheter having a proximal end, a distal end, and a lumen disposed between the proximal and distal ends, the ultrasound catheter configured for insertion into a treatment site through an aspiration catheter; emitting ultrasonic energy at the treatment site; advancing the aspiration catheter having a first end, a second end, and a body disposed between the first and second ends into the treatment site; aspirating thromboemboli at the treatment site; and retrieving thromboemboli from the treatment site with a retriever configured for insertion through the lumen of the aspiration catheter.

[0062] In some embodiments, the suction catheter includes an expandable funnel at the second end.

[0063] In some embodiments, the distal end of the ultrasound catheter is configured to articulate.

[0064] In some embodiments, a method for treating a patient with thromboembolism includes the steps of: advancing an ultrasound catheter into a treatment site, the ultrasound catheter having a retriever catheter integrated therein configured to collect thromboemboli, the ultrasound catheter configured for insertion through an aspiration catheter; emitting ultrasonic energy at the treatment site; advancing the aspiration catheter into the treatment site, the aspiration catheter having a first end, a second end, and a body disposed between the first and second ends; aspirating thromboemboli at the treatment site; and retrieving the thromboemboli from the treatment site with the mechanical catheter.

[0065] In some embodiments, the suction catheter includes an expandable funnel at the second end.

[0066] In some embodiments, the distal end of the ultrasound catheter is configured to articulate.

[0067] In some embodiments, the retriever catheter rotates to control the movement of the retriever to retrieve thromboemboli from the treatment site.

[0068] In some embodiments, the ultrasound catheter controls the movement of the distal end of the ultrasound catheter to direct the emission of ultrasound energy.

[0069] Exemplary embodiments of the systems and methods disclosed herein are illustrated in the accompanying drawings, which are for purposes of illustration only, and include the following figures, in which like numerals indicate like parts: [Brief explanation of the drawings]

[0070] [Figure 1]FIG. 1 is a side view of one embodiment of a catheter system including a suction catheter, an ultrasound catheter, and a retriever catheter. [Figure 1A] FIG. 1 is a cross-sectional view of a catheter system. [Figure 2] FIG. 2 is a side view of the suction catheter of FIG. 1. [Figure 2A] 1. FIG. 3 illustrates another embodiment of an aspiration catheter that can be used with the ultrasound catheter system of FIG. [Figure 3] FIG. 2 is a side view of the ultrasound catheter of FIG. 1. [Figure 3A] FIG. 4 is an enlarged view of the distal tip of the ultrasound catheter of FIG. 3. [Figure 3B] FIG. 4 is a block diagram of a feedback control system for use with the ultrasound catheter of FIG. 3. [Figure 3C] FIG. 4 is a schematic diagram of a control wire for articulating the ultrasound catheter of FIG. 3. [Figure 3D] FIG. 4 is a schematic diagram of the electrical connections to the ultrasound elements of the ultrasound catheter of FIG. 3. [Figure 4] FIG. 2 is a side view of the retriever catheter of FIG. 1. [Figure 5] FIG. 10 illustrates another example embodiment of a catheter system including a suction catheter and a retriever catheter in combination with an ultrasound catheter. [Figure 6] FIG. 6 is an enlarged side view of the suction catheter of FIG. 5. [Figure 7] FIG. 6 is a side view of a retriever catheter combined with the ultrasound catheter of FIG. 5. [Figure 8] FIG. 10 is an enlarged side view of another embodiment of a retriever combined with an ultrasound catheter that can be used with the catheter system. [Figure 9A] FIG. 1 is a schematic diagram illustrating one embodiment of a catheter system including an aspiration catheter and an ultrasound catheter being advanced to a treatment site. [Figure 9B] 1A-1C are schematic diagrams illustrating an embodiment in which an ultrasound catheter is advanced through a clot at a treatment site. [Figure 9C] FIG. 10 is a schematic diagram illustrating one embodiment of an aspiration catheter and a retriever catheter at a treatment site. DETAILED DESCRIPTION OF THE INVENTION

[0071] As used herein, the term "ultrasonic energy" is used broadly and includes its ordinary meaning, further including mechanical energy transmitted through compressional and rarefaction waves at frequencies greater than about 20 kHz. Ultrasonic energy waves can have a center frequency between about 440 kHz and about 25 MHz. In some embodiments, an ultrasonic transducer can use multiple ultrasonic energy frequencies to enhance cavitation. For example, multiple ultrasonic transducers can be used in parallel or in series to enhance cavitation. Additionally, ultrasonic transducers can operate at different frequencies to generate a broadband of frequencies. As used herein, the term "catheter" is used broadly and includes its ordinary meaning, further including an elongated, flexible tube configured to be inserted into a patient's body, for example, into a body part, cavity, duct, or blood vessel (both arterial and venous). As used herein, the term "therapeutic compound" is used broadly and includes its ordinary meaning, further including drugs, pharmaceuticals, dissolving compounds, genetic material, and other substances capable of affecting physiological function. Mixtures containing such substances are included in this definition of "therapeutic compound." Specifically, for use in treating human blood vessels that are partially or completely occluded by plaque, thrombus, emboli, or other substances that reduce the blood-carrying capacity of the vessel, suitable therapeutic compounds include, but are not limited to, aqueous solutions containing heparin, urokinase, streptokinase, and / or rtPA, and in some embodiments, "therapeutic compounds" include, but are not limited to, micro- or nanobubbles as described herein.

[0072] As described herein, ultrasonic energy is often used to enhance the delivery and / or efficacy of therapeutic compounds. For example, in the context of treating vascular occlusions, ultrasonic energy has been shown to augment enzyme-mediated thrombolysis by enhancing the delivery of thrombolytic agents into thrombi; such agents dissolve thrombi by breaking down platelets in the thrombus. For example, the thrombolytic activity of therapeutic compounds is enhanced in the presence of ultrasonic energy in the thrombus because ultrasonic energy can create additional binding sites for the therapeutic compounds. However, it should be understood that unless otherwise specified, the present disclosure is not limited to the mechanism by which ultrasound enhances treatment. In other applications, ultrasonic energy has also been shown to enhance the transfection of gene-based drugs into cells and to enhance the transport of chemotherapeutic agents into tumor cells. It has been found that ultrasonic energy delivered from within a patient's body can produce non-thermal effects that increase the permeability of biological tissues to therapeutic compounds by up to an order of magnitude or more.

[0073] By using an ultrasound catheter to deliver ultrasound energy and therapeutic compounds directly to the treatment site, many of the drawbacks associated with systemic drug delivery, such as low efficiency, high therapeutic compound utilization, and significant side effects caused by high dose levels, are mitigated or overcome.

[0074] Therapeutic compounds can be added to microbubbles and / or metastable phase change nanodroplets. For example, microbubbles and / or metastable phase change nanodroplets can be driven into cavitation by ultrasound energy delivered by an ultrasound catheter. The microbubbles can be sized between 500 nm and 10 μm. In some embodiments, the microbubbles can be sized between 1 μm and 3 μm. Similarly, metastable phase change nanodroplets can be sized between 100 nm and 1 μm. In some embodiments, the nanodroplets can be sized between 100 nm and 300 nm. The microbubbles and / or metastable phase change nanodroplets can be used in combination with or deliver therapeutic agents, such as clot dissolving agents. For example, when combined with a therapeutic agent, the microbubbles and / or metastable phase change nanodroplets can be concentrated to between 10^4 microbubbles / mL and 10^11 microbubbles / mL. In some embodiments, the microbubbles and / or metastable phase change nanodroplets can be concentrated to approximately 10^8 microbubbles / mL and 10^9 microbubbles / mL. In embodiments described herein, the mixture can contain 0 mg to 30 mg of rtPA. Microbubbles and / or nanodroplets can enhance the effectiveness of ultrasound energy delivered to a treatment site. For example, application of ultrasound energy to a clot can cause microbubbles and / or metastable phase-change nanodroplets to be present within and / or around the clot, and the metastable phase-change nanodroplets or microbubbles can undergo vibration, cavitation (both inertial and non-inertial), and evaporation, dissolving the clot from within and / or around it. Bioeffects can be achieved as a result of microbubble activation from ultrasound, which can include sonoporation, microstreaming, and / or microjetting. Enhanced sonothrombolysis using a therapeutic agent (e.g., rtPA) in combination with microbubbles and / or metastable phase-change nanodroplets can enable more effective clot lysis, potentially reducing the dosage of the therapeutic agent while enhancing the therapeutic effect.Methods and systems for microbubbles and / or metastable phase change nanodroplets are further described in US Pat. Nos. 5,629,999 and 5,729,999, both of which are hereby incorporated by reference in their entireties.

[0075] In some instances, a catheter system can be used to treat the formation of a blood clot inside a blood vessel (which can be referred to as a treatment site) that obstructs blood flow through the circulatory system. Thrombosis can occur in veins (i.e., venous thrombosis) or arteries (i.e., arterial thrombosis). In some instances, venous thrombosis leads to congestion in an affected area of ​​the body, while arterial thrombosis can affect blood supply to a part of the body, which can lead to damage (e.g., ischemia and necrosis) to tissue supplied by the affected artery. Symptoms that can result from thrombosis and / or reduced blood flow can include deep vein thrombosis, peripheral arterial disease, peripheral arterial occlusive disease, and critical limb ischemia. In some instances, a catheter system can be used to treat a treatment site including a deep vein thrombosis, for example, where a blood clot has formed in a deep vein in the leg or pelvis, or to treat a pulmonary embolism, where a blood clot has formed in the pulmonary vasculature. In some instances, a catheter system can be used to treat a treatment site including an arterial thrombosis, where a blood clot has formed in a coronary artery or in an artery supplying blood to the brain. In some instances, the catheter system can be used to treat other treatment sites, such as superficial vein thrombosis, where a blood clot has formed in a superficial vein in the leg. As described below, in some embodiments, a catheter system, which may include an ultrasound catheter, can be used in combination with an aspiration catheter to provide suction (also called aspiration) to the treatment site to assist in the removal of clots (e.g., thrombi resulting from thrombosis). For example, the catheter system can be used to treat acute, subacute, and / or chronic thrombi. In some embodiments, chronic thrombi may not contain collagen. Acute thrombi may be softer or the softest of the three types of thrombi. Additionally, acute thrombi may be the youngest (i.e., approximately 1-3 days old), or the newest and most porous thrombi. Chronic thrombi may be harder or the hardest of the three types of thrombi. Additionally, chronic thrombi may be the oldest (i.e., greater than approximately 14 days old) and the least porous thrombi.Subacute thrombi may have a consistency, porosity, and age that is between the characteristics described for acute and chronic thrombi. For example, subacute thrombi may be approximately 3 to 14 days old. While thrombus debris may remain in the patient due to other treatments, the use of an aspiration catheter can enhance thrombus removal. In some embodiments, a catheter system can be used to minimize or eliminate the increased risk of bleeding complications by combining mechanisms of action and / or elements that can be delivered through the catheter system. For example, in some embodiments, a catheter (or catheter system) can form a multi-mechanism thrombus removal system that utilizes microbubble-mediated cavitation as a mechanism of action to more effectively treat clots without increasing the risk of bleeding complications. This system can combine four complementary mechanisms of action: (i) ultrasound, (ii) microbubbles (and / or nanodroplets), (iii) thrombolytic drugs, and (iv) aspiration, delivered through an integrated catheter system. Such a catheter system can also minimize blood loss and vessel wall damage resulting from multiple passes of alternative thrombus removal devices. In some embodiments, a catheter system can combine the benefits of mechanical thrombectomy and ultrasonic thrombus dissolution while improving thrombus burden reduction and minimizing bleeding complications, blood loss, and vessel wall damage resulting from multiple passes of alternative thrombectomy devices. Thus, in some embodiments, a catheter or catheter system can form a multi-mechanism thrombectomy system that utilizes microbubble-mediated cavitation as a mechanism of action to more effectively treat clots without increasing the risk of bleeding complications. This system can combine four complementary mechanisms of action delivered through an integrated catheter system: (i) ultrasound, (ii) microbubbles (and / or nanodroplets), (iii) thrombolytic drugs, (iv) aspiration, and (v) mechanical clot retrievers. In some embodiments, a catheter or catheter system can be used without microbubbles (and / or nanodroplets).

[0076] In some embodiments, an ultrasound catheter can be introduced to a treatment site within a patient. The treatment site can have a clot (e.g., a thrombus) that may require treatment. The ultrasound catheter can be introduced through a blood vessel until the treatment site is reached. The ultrasound catheter can include ultrasound transducer elements that can deliver ultrasound energy directly to the treatment site to treat the thrombus. The ultrasound transducer elements can be positioned near or adjacent to the thrombus so that they can directly contact the thrombus at the treatment site and / or direct ultrasound energy to the thrombus. The ultrasound transducer elements can deliver ultrasound energy, and the catheter can also deliver microbubbles and / or lytic agents to the thrombus before, after, and / or during delivery of the ultrasound energy. For long sections of the thrombus, as the thrombus begins to fragment or dissolve, the ultrasound catheter can be advanced through the thrombus site and continue to deliver ultrasound energy, microbubbles, and / or lytic agents to the thrombus. The ultrasound catheter can be advanced through the length of the thrombus until the length of the thrombus is minimized and the thrombus is completely or nearly completely fragmented and / or dissolved. In some examples, the distal end of the ultrasound catheter can be configured to articulate, which can allow for the delivery of targeted ultrasound therapy to the treatment site. Articulation of the distal end of the ultrasound catheter can allow the thrombus to be treated from a different angle and / or allow for more effective treatment of a larger area of ​​the treatment site. This articulation and targeted ultrasound therapy can occur as the ultrasound catheter advances through the clot. For example, after imaging and identifying a residual clot, the distal end of the ultrasound catheter can be articulated to direct ultrasound energy to the identified residual clot. An advantage of targeted ultrasound can be enhanced mechanical assistance / action in engaging the thrombus for better / improved treatment, which can allow for new areas for treatment, more microchannels, and / or larger binding sites for lysis, leading to improved performance and outcomes.

[0077] In some embodiments, the ultrasonic transducer elements can operate at frequencies between approximately 440 kHz and 25 MHz, in some embodiments the frequency can range from 450 kHz to 850 kHz, and in some embodiments, 650 kHz. The frequencies at which the ultrasonic transducer elements can operate can be based on the location of the treatment site and / or the location of a thrombus within the treatment site. In some embodiments, the frequency range of the ultrasonic transducer can allow the generated ultrasonic waves to penetrate deeper into tissue where the treatment site may be located. In some embodiments, the frequency range of the ultrasonic transducer can allow the generated ultrasonic waves to penetrate shallower depths into tissue where the treatment site may be located.

[0078] In some aspects, once the ultrasound catheter delivers therapy to the treatment site (which may contain an obstruction, such as a clot or thrombus, to the flow of blood through the circulatory system), the ultrasound catheter can be removed from the treatment site. In some aspects, the ultrasound catheter can remain at the treatment site. An aspiration catheter or aspiration sheath or sheath (used interchangeably throughout) can be advanced into the patient's vascular system and advanced toward the treatment site. In some aspects, the aspiration catheter can be advanced to a region near the treatment site. In some aspects, the aspiration catheter can be advanced to a region between the insertion site and the treatment site. In some aspects, the aspiration catheter can be used to access the inside of the body from outside the body, and in such embodiments, the aspiration catheter can be used as an access sheath through which other devices can be inserted. In some aspects, the aspiration catheter can be used in treating deep vein thrombosis. In some aspects, the aspiration catheter can be used to track the location of the provided therapy (e.g., pulmonary embolism). In some aspects, this can be used when treating pulmonary embolism. Aspiration catheter or aspiration sheath or sheath are used interchangeably herein in all embodiments and aspects. Aspiration catheters can be used in combination with retriever catheters and ultrasound catheters. The aspiration catheter can be referred to as an aspiration sheath, and in some embodiments, suction can be applied to the vasculature through the aspiration catheter, although in some embodiments, suction need not be applied and the aspiration catheter / sheath can be used as an introduction catheter to deliver other instruments and catheters through the lumen of the aspiration sheath / catheter. In some embodiments, the aspiration catheter can be introduced into the patient's vasculature before the ultrasound catheter is introduced into the patient, such that the ultrasound catheter is advanced through the aspiration catheter and then to the treatment site. In this manner, the ultrasound catheter can be inserted through the aspiration catheter.In some embodiments, the aspiration catheter can include a funnel with an enlarged opening that can guide fragmented and / or lysed thrombus elements as the treatment site is aspirated. In some embodiments, a retriever catheter can be inserted through the ultrasound catheter. The retriever catheter can extend beyond the distal end of the ultrasound catheter. In other embodiments, the ultrasound catheter can be removed from the aspiration catheter to allow the retriever catheter to be inserted through the aspiration catheter. This can be further described below with reference to FIGS. 9A and 9C . The retriever catheter can include a retriever that can engage the thrombus and / or fragmented and / or lysed thrombus elements. The retriever can further fragment the thrombus and / or detach the thrombus from the vessel wall as the retriever is retracted into the aspiration catheter, removing the thrombus from the treatment site. The retriever can capture the thrombus and fragmented and / or lysed thrombus elements. Once the retriever has removed the thrombus and fragmented and / or lysed thrombus elements from the treatment site, the aspiration catheter can be used to aspirate the area and / or treatment site. This can help ensure that the treatment site is effectively treated and that the thrombus is effectively removed from the treatment site. Once the retriever removes the thrombus from the treatment site, an aspiration catheter can aspirate the area and / or treatment site before, during, and / or after removal of the thrombus. In other embodiments, the aspiration catheter may not aspirate the area or treatment site. In such embodiments, the aspiration catheter or sheath can be used to provide access to the vasculature and can be used to introduce other devices (such as an ultrasound catheter or a retriever catheter). Aspiration of the area and / or treatment site can be based on the effectiveness of the retriever's removal of the thrombus. The combination of catheters can help maximize the effectiveness of thrombus removal from the treatment site and restore blood flow to the vessel. In some embodiments described herein, features of the aspiration catheter and / or retriever can be combined with an ultrasound catheter.For example, in some embodiments, an ultrasound catheter can be advanced through the aspiration catheter such that the aspiration catheter is positioned within the patient during treatment with ultrasound, a drug (e.g., a lytic agent), and / or microbubbles (and / or nanodroplets). In such embodiments, the ultrasound catheter can be removed from the aspiration catheter, and then a retriever catheter can be advanced through the aspiration catheter after removal of the ultrasound catheter. In other embodiments, a retriever can be positioned on the ultrasound catheter, and the retriever on the ultrasound catheter can be used to retract and / or remove the clot after treatment.

[0079] In some embodiments, an aspiration catheter (according to embodiments described herein) can be introduced into the vasculature through an access site and, in some embodiments, advanced toward the treatment site, which, as described above, may include an obstacle to blood flow through the circulatory system. After the aspiration catheter is introduced into the vasculature, an ultrasound catheter (according to embodiments described herein) can be similarly introduced to the treatment site. In some embodiments, the ultrasound catheter and the aspiration catheter can be introduced together into the vasculature. The ultrasound catheter can be advanced through the aspiration catheter and then introduced to the treatment site. The distal end of the aspiration catheter can be positioned near the treatment site or further away from the treatment site, for example, near the access site. The ultrasound catheter can deliver microbubbles and / or metastable phase-change nanodroplets and rtPA or other therapeutic compounds (e.g., lytic agents) to the treatment site. The microbubbles and / or metastable phase-change nanodroplets and rtPA or other therapeutic compounds (e.g., lytic agents) can be delivered through a lumen in the ultrasound catheter and / or through another passageway in the catheter system. This can enable treatment of thrombus located at the treatment site. For example, microchannels can be created within the thrombus by delivering microbubbles and / or metastable phase-change nanodroplets. The ultrasound catheter can then deliver ultrasound energy or ultrasound therapy to the thrombus. The ultrasound catheter can continue to deliver therapy to the thrombus (ultrasound and / or microbubbles and / or metastable phase-change nanodroplets and rtPA or other therapeutic compounds (e.g., lytic agents) to the treatment site) as it advances through the length of the thrombus. For example, in some embodiments, the ultrasound catheter is initially positioned near or within the beginning of the thrombus, and then, after treatment with ultrasound and a therapeutic compound has begun, the ultrasound catheter can be advanced into (or further into) the thrombus to provide further treatment with ultrasound and a therapeutic compound. Ultrasound can be provided within the frequency and power ranges described herein.For example, in some embodiments, the ultrasound transducer elements can operate at frequencies between approximately 440 kHz and 25 MHz, and in some embodiments, the frequency can range from 450 kHz to 850 kHz, and in some embodiments, 650 kHz. Advantageously, combining ultrasound with microbubbles and / or metastable phase-change nanodroplets and rtPA or other therapeutic compounds (e.g., lytic agents) can assist in opening holes or passageways through the clot. For example, an ultrasound catheter can be advanced 25% of the length of the clot, 50% of the length of the clot, or 100% of the length of the clot to deliver treatment throughout. The ultrasound catheter can then be removed from the treatment site. A retriever catheter (according to embodiments described herein) can then be introduced into the treatment site. The retriever catheter can be advanced through the aspiration catheter and introduced into the treatment site. The retriever catheter can be advanced to the outermost end of the treatment site (e.g., completely or substantially through the clot), and a retriever can be deployed. The retriever can capture dissolved and / or remaining clot at the treatment site. The retriever catheter can then retract the retriever from the treatment site into the aspiration catheter. The aspiration catheter can then aspirate the area and / or treatment site to direct the dissolved and / or remaining thrombus into the aspiration catheter. In other embodiments, the aspiration catheter may not aspirate the area or treatment site. Aspirating the area and / or treatment site can be based on the effectiveness of the retriever's removal of thrombus. Advancement of the retriever catheter, deployment of the retriever, retraction of the retriever, and aspirating the treatment site can be repeated until the treatment site is free or nearly free of thrombus. In some embodiments, the retriever catheter can be inserted through or alongside the ultrasound catheter so that the ultrasound catheter does not need to be removed before using the retriever catheter to remove the clot.

[0080] The techniques disclosed herein may find utility in a wide variety of ultrasound catheters in addition to the ultrasound catheter embodiments described herein. Some of the techniques disclosed herein are compatible with ultrasound catheters and / or aspiration catheters that would not otherwise be able to generate cavitation at an endovascular treatment site.

[0081] Referring to the illustrated embodiment, FIG. 1 shows an example of a catheter system 100 configured for use at a treatment site within a patient. For example, in some embodiments, the catheter system 100 includes an ultrasound catheter 200, an aspiration catheter 300, and a retriever catheter 400. The catheter system 100 can be used to deliver ultrasonic energy to a treatment site within a patient to assist in the breakdown or dissolution of a thrombus located at the treatment site. The catheter system 100 can also be used to aspirate a thrombus at the treatment site. Additionally or alternatively, the catheter system 100 can be used to mechanically retrieve a thrombus from the treatment site with the retriever catheter 400. The catheter system 100 can also include at least one valve 210 that can be used to connect various elements of the catheter system 100. In some examples, the valve can include a Tuohy-Borst adapter, or a hemostatic valve, which can minimize fluid loss during use of the catheter system 100. In some examples, the hemostatic valve can include side port tubing. The aspiration catheter 300 can include a flared end 310. In some instances, the flared end 310 can aspirate a larger area of ​​thrombus at a time and can assist in drawing the clot or thrombus retrieved by the retriever catheter 400 into the aspiration catheter 200. The flared end 310 can be a funnel that is connected or coupled to the aspiration catheter 300.

[0082] In some examples, the ultrasound catheter 200 can include an ultrasound element (described in more detail below) capable of delivering ultrasound energy to a treatment site within a patient. In some examples, the ultrasound catheter 200 can include a handle 220, which can control the deflection of the distal tip of the ultrasound catheter 200 (described in more detail below). This can allow the catheter system 100 to more precisely aim or control where the ultrasound energy is delivered. Additionally, this can allow the ultrasound catheter 200 to be more effectively advanced to the treatment site and the length of the thrombus. This can further allow the ultrasound catheter 200 to more effectively deliver ultrasound therapy to thrombus that is relatively heavily lodged in the blood vessel.

[0083] In some examples, the retriever catheter 400 can include a retriever 410 disposed at the distal end of the retriever catheter 400. As described further below, in some embodiments, the retriever catheter 400 can include an actuator that can be rotated (or otherwise actuated) to selectively expand or contract the retriever 410. The expansion and contraction of the retriever 410 can assist in the removal of a blood clot from a treatment site in a patient. In some embodiments, the retriever 410 can be self-expandable upon advancement beyond the distal end of the aspiration catheter 200 or ultrasound catheter 300.

[0084] Referring to the illustrated embodiment, FIG. 1A shows a schematic cross-section of the catheter system 100 shown in FIG. 1. As shown, the suction catheter 300, the ultrasound catheter 200, and the retriever catheter 400 can be concentric. In some examples, the suction catheter can include at least one suction lumen 301 (shown schematically in FIG. 1A). In some examples, the ultrasound catheter 200 can be inserted through the at least one suction lumen 301 of the suction catheter 300. In some examples, the ultrasound catheter 200 can include at least one lumen 201 (shown schematically in FIG. 1A) that can be used to deliver a therapeutic compound to a treatment site. The lumen 201 can also be used to advance the ultrasound catheter over a guidewire. In some embodiments, the ultrasound catheter can include multiple lumens. In some examples, the retriever catheter 400 can be inserted through at least one lumen 201. For example, the retriever catheter 400 can be inserted into the proximal end of the ultrasound catheter 200 and extend through the at least one lumen 201 of the ultrasound catheter 200. In other examples, a retriever catheter 400 can be inserted through at least one suction lumen 301 as described above. For example, the retriever catheter can be configured to be inserted into the proximal end of the suction catheter 300 and extend through the suction lumen 301 after the ultrasound catheter 200 is removed from the suction catheter 300. In other embodiments, the retriever catheter can be inserted along the side of the ultrasound catheter 200 with the suction lumen 301. The retriever catheter 400 can extend through at least one lumen 201 of the ultrasound catheter 200 and extend past the distal end of the ultrasound catheter 200. Similarly, the ultrasound catheter 200 can be inserted into the proximal end of the suction catheter 300. The ultrasound catheter 200 can extend through the suction lumen 301 of the suction catheter 300 and extend past the distal end of the suction catheter 300.In some examples, when the ultrasound catheter 200 is inserted through the aspiration lumen 301 of the aspiration catheter 300, a retriever catheter 400 can be inserted through at least one lumen 201 of the ultrasound catheter 200. In some examples, the retriever catheter 400 can have a larger diameter and be configured to extend through the aspiration catheter 300 when the ultrasound catheter 200 is removed from the aspiration catheter.

[0085] Referring to the illustrated embodiment, FIG. 2 shows a suction catheter 200, as referenced in FIG. 1, here alone. As shown, the suction catheter 200 has a first (distal) end, a second (proximal) end, a handle 210 at the proximal end, a body formed by a shaft or extruded portion 220 disposed between the distal and proximal ends of the suction catheter 200, and an expandable funnel or flared end 230 at the second (distal) end of the suction catheter 200. The extruded portion 220 extends through the handle 210 and can be connected to a distal interface 240 of the suction catheter 200. The distal interface 240 can be molded and bonded to the extruded portion 220 and the flared end 230. In some instances, the distal interface 240 can be radiopaque. The flared end 230 can be bonded to the distal interface 240. In some examples, the flared end 230 has a first diameter and a second diameter, where the first diameter can be smaller than the second diameter. The flared end 230 can include a body connecting the first diameter to the second diameter. In some examples, the flared end 230 can function as a lead-in for the aspiration catheter 200. The flared end 230 can help maximize the amount of thrombus removed from the treatment site. In some examples, the flared end 230 is contractible and can expand to the patient's treatment site. For example, the flared end 230 can expand to the blood vessel wall of the patient's treatment site. This can help ensure that thrombus and / or debris are effectively removed from the treatment site. In some examples, the flared end 230 can guide suction of the aspiration catheter. For example, the flared end 230 can open or close to guide suction. In some examples, the flared end 230 can be actively expandable. In some examples, the flared end (expandable funnel) 230 can be self-expandable. In some examples, the flared tip 230 can include radiopaque features. In some examples, the flared tip 230 can include Nitinol.In some examples, the flared end 230 can have finger-like structures that can be connected by a film that may or may not be perforated. In some examples, the flared end 230 can be actuated by using an outer cover or tube that can slide over or cover the finger-like structures and move them toward each other until they are in an isodiametric arrangement. The suction catheter can also include tubing 250 to assist in suction, a one-way stopcock 260, and a vacuum syringe port 270. In some examples, the tubing 250 can include flexible, large-bore tubing. The suction catheter 200 defines an aspiration lumen (not shown) that can extend therethrough.

[0086] Referring to the illustrated embodiment, Figure 2A shows an alternative embodiment of the suction catheter 200 as referenced in Figure 2. As shown, the suction catheter 200 can include a knob 280 that can articulate the distal interface 240 of the suction catheter. The pusher 220 can include a pull wire connecting to the knob 280 and the distal interface 240, which can allow 180-degree articulation of the suction catheter 200 and / or active expansion and / or contraction of the distal end of the suction catheter 200. In some examples, the distal interface 240 can be molded and bonded to the pusher 220 and flared end 230.

[0087] Referring to the illustrated embodiment, FIG. 3 shows an ultrasound catheter 300, such as that referenced in FIG. 1, shown here alone. As shown, the ultrasound catheter 300 can include a handle 310, a knob 320, and a pusher 330. The pusher 330 can have a proximal end 340 and a distal end, with a body disposed between the distal end and the proximal end 340. Rotation of the knob 320 can articulate the distal end 340. In some examples, the handle 310 can have a length of approximately 3.0 inches to 5.0 inches, which can enable a steerable ultrasound catheter. For example, a user can rotate the knob 320 (e.g., clockwise or counterclockwise) to control the deflection of the distal end 340. Articulation of the distal end 340 can better guide the delivery of ultrasound energy to a treatment site within a patient. For example, articulation of the distal tip 340 can aid in better removal of a thrombus from the treatment site by better targeting ultrasound toward portions of the thrombus that may require additional treatment to remove or fragment. Additionally, articulation of the distal tip 340 can also better target thrombus located at the treatment site, allowing for visualization and / or targeted retrieval for treatment of the thrombus. This technique allows for localized treatment and minimizes or limits any potential damage to healthy or surrounding tissue. The pusher 330 can be a multi-lumen pusher that includes one or more pull wires 335 extending along the length of the catheter, configured to articulate the distal tip 340 by connecting the distal tip 340 to the knob 320. The pull wires 335 can allow articulation of the distal tip 340 approximately + or − 180 degrees from the longitudinal axis of the catheter, and in some embodiments, + or − 45 degrees from the longitudinal axis of the catheter. 3C schematically illustrates a pull wire 335 connected to the distal end 340 to provide articulation. In some examples, the ultrasound catheter 300 can further include at least one lumen 201 and a pigtail cable 360 ​​connected to the proximal end of the ultrasound catheter 300.A lumen 201, e.g., a female luer, can extend through the ultrasound catheter 300 to allow for the introduction of fluid into the patient. For example, the fluid can consist of a therapeutic compound, a flush, a radiopaque contrast agent, etc. In some examples, the fluid can enter the ultrasound catheter through at least one lumen 201 or another lumen of the ultrasound catheter. The lumen 201 can be welded or otherwise secured to the catheter 300. In some embodiments, the ultrasound catheter 300 can have a length of approximately 1.0 m to 1.5 m and a diameter of 0.6 inches to 0.8 inches. As shown in FIG. 3 and further described in FIG. 3A below, the ultrasound catheter 300 can include an ultrasound element (also referred to herein as an ultrasound-emitting element) 370 connected to a distal end 340.

[0088] Referring to the illustrated embodiment, Figure 3A shows a close-up view of the distal tip 340 as referenced in Figure 3. As shown, the ultrasonic element 370 can be bonded to a molded interface 380, which can be bonded to the extrusion 330. As explained above, the bond can help allow for articulation of the distal tip 340. This connection can also provide a fluid port for the distal tip 340. In some examples, the ultrasonic element 370 is cylindrical and hollow and can include a concave lens 390. In some embodiments, the concave lens 390 can help focus the ultrasonic field to aid in the treatment or removal of a blood clot at the treatment site.

[0089] Continuing with reference to FIG. 3A, the distal end 340 of the ultrasound catheter 300 can include an ultrasound-emitting element 370 (also referred to herein as an ultrasound element). In the illustrated embodiment, the ultrasound-emitting element 370 includes an ultrasound transducer, which may be radiopaque, that converts energy, e.g., electrical energy, into ultrasound energy. In a modified embodiment, the ultrasound energy can be generated by an ultrasound transducer separate from the ultrasound-emitting element 370, e.g., transmitted to the ultrasound-emitting element 370 via a wire. In some examples, the ultrasound energy can be emitted using a vibrating wire, a transducer, or a laser. As noted above, in the illustrated embodiment, the ultrasound energy is generated from electrical power supplied to the ultrasound-emitting element 370. The electrical power can be supplied through a connector, which is connected to a pair of wires 365 (schematically shown in FIG. 3D) that extend through the body of the ultrasound catheter 300. In the illustrated arrangement, a first wire 362 can be connected to the hollow center of the ultrasound-emitting element 370, and a second wire 364 can be connected to the outer periphery of the ultrasound-emitting element 370. Thus, in the illustrated embodiment, the ultrasound catheter includes at least one lumen 201 extending through the catheter and through the ultrasound-emitting element 370. In some embodiments, a guidewire can be inserted through the at least one lumen 201 or another lumen of the ultrasound catheter. In some embodiments, therapeutic compounds and / or microbubbles and / or nanobubbles can be delivered to a treatment site through the at least one lumen 201 of the ultrasound catheter 300 or another lumen of the ultrasound catheter. In some embodiments, the lumen 201 can also be used to advance the ultrasound catheter over a guidewire. In the illustrated arrangement, a fenestrated ultrasound-emitting element 370 can be used. In other embodiments, a solid ultrasound-emitting element 370 can be used, in which case a first wire can be connected to the outer periphery of the ultrasound-emitting element 370.The ultrasound-emitting element 370 is preferably, but not limited to, a transducer formed from a piezoelectric ceramic oscillator or similar material. Piezoceramic oscillators typically include crystalline materials, such as quartz, that can change shape when an electric current is applied to the material. This change in shape can create ultrasound waves when vibrated by a vibrational drive signal. In other embodiments, ultrasound energy can be generated by an ultrasound transducer separate from the ultrasound-radiating member, for example, transmitted via a wire coupled to the ultrasound-radiating member, such as that described in U.S. Patent No. 6,229,693, which is incorporated herein by reference in its entirety. In other embodiments, the ultrasound-radiating element can be a photoacoustic ultrasound element in which the material emits pressure waves in response to irradiation by a light source (e.g., a laser). For example, the photoacoustic ultrasound element can be formed from a light-absorbing material and a thermally expanding material that can be in optical communication with a light guide, such that light is absorbed by the photoacoustic transducer and converted into sound waves when the transducer changes shape, as described in U.S. Patent No. 6,229,693, which is incorporated herein by reference in its entirety.

[0090] Although not shown, the ultrasound catheter 300 may include at least one temperature and / or force sensor along its distal end. The temperature and / or force sensor may be located on or near the ultrasound-emitting element 370. Suitable temperature sensors include, but are not limited to, diodes, thermistors, thermocouples, resistance temperature detectors (RTDs), and fiber optic temperature sensors such as Fabry-Perot sensors using thermochromic liquid crystals. Suitable force sensors include Fabry-Perot, fiber Bragg gratings, resistors, load cells, and strain gauges, among others. The temperature and / or force sensor may be operably connected to a control box (not shown) through control wires extending through the ultrasound catheter. The temperature sensor may be used to sense the temperature of the ultrasound-emitting element 370, which may help limit damage to surrounding tissue.

[0091] Referring to the illustrated embodiment, FIG. 3B shows a feedback control system 68 that can be used in an ultrasound catheter such as that described with reference to FIGS. 3 and 3A. The feedback control system 68 can enable monitoring of the temperature at the temperature sensor 20 and adjusting the output of the ultrasound-emitting element accordingly. The feedback control system 68 can include an energy source 70 (i.e., an ultrasound energy source) and a power circuit 72 that can be coupled to the ultrasound-emitting element 40. A thermometer device 76 can be coupled to the temperature sensor 20 on the body 12. A processing unit 78 can be coupled to the power calculation device 74, the power circuit 72, and a user interface 80. The thermometer device 76 can measure the temperature at the temperature sensor. The measured temperature can be received by the processing unit 78 and then displayed to the user. Additional sensors (e.g., force sensors) can also be connected to the processing unit 78.

[0092] The power circuitry 72 can adjust the power level, frequency, voltage, phase, and / or current of the electrical energy supplied from the energy source 70 to the ultrasound radiating elements 40. For example, if the temperature measured at the temperature sensor location is higher than a desired or safe temperature, the power can be reduced. Similarly, for example, if the temperature measured at the temperature sensor location is lower than a desired temperature, the power can be increased. As the power is adjusted, the processing unit 78 can monitor the temperature sensor 20.

[0093] Generally, a feedback control system can be used to more efficiently deliver treatment to the treatment site by helping to ensure that the ultrasound-emitting elements remain at a desired temperature so that the surrounding tissue is not damaged and remains at the desired temperature.

[0094] Additionally, the feedback control system can control the mode in which the ultrasound-emitting elements can operate. For example, the ultrasound-emitting elements can operate in a pulsed mode or a continuous mode. The mode in which the ultrasound-emitting elements operate can determine the power supplied to the ultrasound-emitting elements.

[0095] Referring to the illustrated embodiment, FIG. 4 shows the retriever catheter 400 referenced in FIG. 1 , here alone. The retriever catheter 400 can be inserted through the ultrasound catheter 300 in the catheter system 100. For example, in the illustrated embodiment, the retriever catheter 400 can be inserted through a lumen extending through the ultrasound catheter, such as the pusher section 330 or central lumen (shown with reference to FIG. 3 ), which can extend through the catheter and through the ultrasound element 370. In some embodiments, the lumen through which the retriever catheter 400 passes extends off-center of the ultrasound catheter, for example, along the side of the ultrasound element 370. In some instances, the retriever catheter can be positioned adjacent to the side of the ultrasound catheter 300. In some instances, the retriever catheter 400 can be inserted alongside the ultrasound catheter 300 or through the aspiration catheter 200 after the ultrasound catheter 300 has been removed. The retriever catheter 400 can include a handle 410 and a stylet 420 that connects to a retriever 430 disposed at the distal end of the retriever catheter 400. In some examples, the handle 410 can facilitate a stop to prevent the stylet 420 from advancing too far within the retriever catheter. For example, the handle 410 can facilitate pushing, pulling, twisting, etc. The retriever 430 can be bonded or welded to the stylet at a retriever first end 440 and have a free end at a retriever second end 450. The second end 450 can be free to allow the retriever to slide along the stylet 420. The retriever 430 can passively self-expand to retrieve thrombus from a treatment site within a patient. In some examples, the retriever 430 can include a spiral basket 435 that can include at least one spline 438 (e.g., having six spiral splines, having two spiral splines, etc.). In some examples, the basket can include nitinol. In some examples, the stylet 420 can be a guidewire.In some instances, the guidewire can have a diameter of approximately 0.02 inches to approximately 0.04 inches. The retriever 430 can be formed from a variety of materials, such as, for example, nickel titanium (also known as nitinol).

[0096] In some examples, a catheter system can be used to remove a blood clot from a treatment site on a patient. The treatment site can be treated with ultrasonic energy using the ultrasound catheter 300. In some examples, the treatment site can be further treated with a drug (e.g., a therapeutic compound). The drug can include microbubbles and / or phase-change nanodroplets that can assist in dissolving the blood clot. The drug can be delivered to the treatment site using the ultrasound catheter and / or a separate catheter or device in some combination. As described above, a user can rotate a knob located on the ultrasound catheter to direct ultrasonic energy (e.g., at the frequencies described above) to different portions of the blood clot, which can soften or loosen the blood clot. In some embodiments, the ultrasound catheter can deliver ultrasonic energy at a power range of approximately 1 mW to 25 W. In some embodiments, the ultrasound transducer elements can operate at a frequency of approximately 440 kHz to 25 MHz, and in some embodiments, the frequency can range from 450 kHz to 850 kHz, and in some embodiments, 650 kHz. The user can advance the ultrasound catheter through the length of the blood clot and continue to treat the blood clot with ultrasonic energy as the ultrasound catheter advances. This can help ensure that the thrombus is effectively treated by delivering ultrasonic energy to nearly the entire length of the thrombus. In some instances, the user can then insert a retriever catheter 400 and use the retriever to retrieve the thrombus and / or debris from the treatment site. In some instances, the retriever catheter 400 can be inserted through the aspiration catheter 200. At the same or similar time, the user can use the aspiration catheter 200 to aspirate the clot / thrombus, or any elements of the clot / thrombus, into the aspiration catheter. This can help more effectively remove the thrombus and / or debris from the treatment site. This can also help ensure that any pieces of clot / thrombus and / or debris captured by the retriever remain within the retriever when the retriever is removed from the treatment site.In some instances, the ultrasound catheter can remain at the treatment site within the patient. In some instances, the ultrasound catheter can rotate automatically.

[0097] Referring to the illustrated embodiment, FIG. 5 shows another embodiment of a catheter system 500 including an ultrasound catheter embodiment combined with an aspiration catheter 600 and a retriever catheter 700. Similar to the above-described embodiments, the catheter system 500 can be used to deliver ultrasonic energy to a treatment site within a patient to assist in the breakdown or dissolution of thrombus located at the treatment site. The catheter system 500 can also be used to aspirate thrombus at the treatment site. Additionally or alternatively, the catheter system 500 can be used to mechanically retrieve thrombus from the treatment site. The catheter system 500 can also include at least one valve 610 that can be used to connect various elements of the catheter system 500. In some examples, the valve 610 can include a hemostasis valve, which can minimize fluid loss during use of the catheter system 500. In some examples, the hemostasis valve 610 includes side port tubing. The catheter system 500 can further include an aspiration catheter with a flared end 620, which can be configured similarly to the aspiration catheter and funnel described above. In some examples, the flared end can aspirate a larger area of ​​thrombus at a time. In some examples, the ultrasound catheter combined with the retriever catheter 700 can include an ultrasound element / ultrasound-emitting element as described in the above embodiments that can deliver ultrasound energy to a treatment site within a patient. In some examples, the ultrasound catheter combined with the retriever catheter 700 can include a dial 720 that can control the deflection or movement of the distal tip of the ultrasound catheter combined with the retriever catheter 700, for example, through a pull wire as described in the above embodiments. This can allow the catheter system 500 to more precisely aim or control where the ultrasound energy is delivered. The ultrasound catheter combined with the retriever catheter 700 can include a knob 730 that can be used to control the expansion or contraction of a retriever 740 located at the distal end of the ultrasound catheter combined with the retriever catheter 700.

[0098] Referring to the illustrated embodiment, FIG. 6 shows an aspiration catheter 600. In some instances, the aspiration catheter 600 can be similar to the aspiration catheter described above with reference to FIGS. 2 and 2A. As shown, the aspiration catheter 600 includes a handle 610, a pushed-out portion 620, and a flared end 630. The pushed-out portion 620 can extend through the handle 610 and connect to a distal interface 640 of the aspiration catheter. The distal interface 640 can be molded and bonded to the pushed-out portion 620 and the flared end 630. In some instances, the distal interface 640 can be radiopaque. The flared end 630 can be bonded to the distal interface 640. In some instances, the flared end 630 can serve as a lead-in for the aspiration catheter 600. In some instances, the flared end 630 is contractible and can expand to a treatment site in a patient. For example, the flared end 630 can expand to a blood vessel wall in the treatment site in a patient. In some instances, the flared end 630 can guide suction of the aspiration catheter. For example, the flared end 630 can be opened or closed to induce suction. In some examples, the flared end 630 can be actively deployable. In some examples, the flared end 630 can include radiopaque features. In some examples, the flared end 630 can include Nitinol. In some examples, the flared end 630 can have finger structures that can be connected by a film and may or may not be perforated. In some examples, the flared end 630 can be actuated by using an outer cover or tube that slides over or covers the finger structures and can move them toward each other until they are in an isodiametric arrangement. The suction catheter can also include tubing 650 to assist suction, a one-way stopcock 660, and a vacuum syringe port 670. In some examples, the tubing 650 can include flexible, large-bore tubing. In some examples, the suction catheter can be articulated as described with reference to FIG. 2A.

[0099] Referring to the illustrated embodiment, FIG. 7 shows an ultrasound catheter in combination with a retriever catheter 700. In some examples, the ultrasound catheter element 710 of the ultrasound catheter in combination with the retriever catheter 700 can be similar to the ultrasound catheters described above. The ultrasound catheter element 710 can include an ultrasound element capable of delivering ultrasound energy to a treatment site within a patient. As shown, the ultrasound catheter element 710 can include a dial 720. In some examples, the dial 720 can be a level, knob, slider, or the like. The dial 720 can articulate a distal tip 730 of the ultrasound catheter element 710. Articulation of the distal tip 730 can direct the location of the treatment site to which the ultrasound energy is delivered. Articulation of the distal tip 730 can better guide the delivery of the ultrasound energy to the treatment site within the patient. For example, articulation of the distal tip 730 can help better remove a clot from the treatment site by better targeting portions of the clot that may require additional treatment to remove or fragment. Additionally, articulation of the distal tip 730 can also better target thrombus located at the treatment site. In some examples, the pusher section 740 of the ultrasound catheter element 710 can include a pull wire that can enable articulation of the distal tip 730 + or - 180 degrees. As shown, the retriever catheter element can include a knob 750 that can be disposed on the ultrasound catheter element 710. Rotating the knob 750 can expand or contract a retriever 760 that is disposed at the distal end of the ultrasound catheter combined with the retriever catheter 700. As described above, the retriever 760 can be used to retrieve thrombus from a treatment site within a patient.

[0100] FIG. 8 shows an enlarged view of the retriever 760 as referenced in FIG. 7 . As shown, the distal end 810 of the retriever 760 can be connected to the distal tip 730 of the ultrasound catheter element. The distal end 810 can be molded and bonded to the inner extrusion 820 of the ultrasound catheter element. The proximal end 830 of the retriever 760 can be molded and bonded to the outer extrusion 840 of the ultrasound catheter element. In some examples, the retriever and outer extrusion can have radiopaque features and / or irrigation ports. As described above, the distal tip 730 can include an ultrasonic element 850. In some examples, the ultrasonic element 850 is hollow, cylindrical, and can include radiopaque features and / or irrigation ports. In some examples, the distal tip 730 can further include a concave lens 860. In some embodiments, the concave lens can be made of polycarbonate, ABS, PP, polysulfone, Mylar, polystyrene, Epotec 301, alumina-doped epoxy, syntactic foam, HDPE, glass, Perspex, Paralene, or other similar materials. In some embodiments, the material of the concave lens can have a phase velocity greater than that of blood, which can allow ultrasound energy to be focused toward the front face of the ultrasound-emitting element. In some embodiments, the concave lens 860 can assist in focusing the field to aid in the treatment or removal of a thrombus at the treatment site. In some examples, the retriever 760 can include a nitinol basket 865 and multiple splines 868. In some examples, the retriever 760 can include multiple heat-set splines 868. In some examples, the retriever 760 can be actively expanded by rotating the knob 750. For example, the knob 750 can be configured as a rack-and-pinion gear set. For example, although not shown, the retriever catheter can include an inner catheter shaft including a vertically protruding shaft that can form a T-shape with the inner catheter. The knob 750 can be molded such that the inner portion has material removed in the pattern of the threads (ie, the threads of the nut).The inner shaft can be positioned within knob 750, with a protruding vertical shaft inserted into the threads. Rotating knob 750 can translate the inner shaft linearly to expand or contract retriever 760. In other embodiments, the retriever can be a self-expanding element held within a sheath that constrains the retriever when placed over it and expands it when removed from it.

[0101] In some examples, a catheter system can be used to remove a clot / thrombus from a treatment site in a patient. The treatment site can be treated with ultrasonic energy by using an ultrasound catheter element of an ultrasound catheter in combination with a retriever catheter. A user can articulate the ultrasound catheter element of an ultrasound catheter combined with a retriever catheter to direct the delivery of ultrasonic energy at the treatment site. In some examples, the treatment site can be further treated with a drug. The drug can include microbubbles or phase-change nanodroplets that can assist in lysing the clot. As described above, a user can rotate a knob located on the ultrasound catheter to direct ultrasonic energy to various portions of the clot, thereby softening or loosening the clot. In some examples, a user can then control the retriever catheter of an ultrasound catheter combined with a retriever catheter to expand or contract the retriever. The expansion or contraction of the retriever can help retrieve the clot from the treatment site. At the same or similar time, a user can use an aspiration catheter to aspirate the clot into the aspiration catheter. In some examples, the ultrasound catheter combined with the retriever catheter can remain at the treatment site within the patient.

[0102] 9A, 9B, and 9C, in some embodiments, a suction catheter 300 (which may be according to aspects and embodiments described herein) can be introduced into the patient's vasculature through an access site and then advanced to the treatment site 1000. In some embodiments, the suction catheter 300 can be advanced to a region near the treatment site. In some embodiments, the suction catheter can be advanced to a region between the insertion site and the treatment site. After introduction of the suction catheter 300, an ultrasound catheter 200 (which may be according to aspects and embodiments described herein) can be introduced through the suction catheter 300 and advanced to the treatment site. In some embodiments, the ultrasound catheter can be advanced over a guidewire. In the illustrated embodiment, the ultrasound catheter 200 can be advanced through the suction catheter 300 and then introduced to the treatment site 1000 containing a clot 1001 (e.g., a thrombus). The ultrasound catheter 200 can be used to deliver ultrasound (through the ultrasound elements) and / or deliver microbubbles and / or metastable phase-change nanodroplets and rtPA or other therapeutic compounds (e.g., lytic agents) as described herein to a treatment site, for example, through the lumen 201 of the ultrasound catheter or through other passages in the catheter system or ultrasound catheter. This can enable treatment of a thrombus located at the treatment site. For example, microchannels can be created within the thrombus by delivering microbubbles and / or metastable phase-change nanodroplets. The ultrasound catheter can deliver ultrasound energy or ultrasound therapy to the thrombus. In some embodiments, the ultrasound catheter can deliver ultrasound energy at a power range of approximately 1 mW to 25 W. In some embodiments, the ultrasound transducer elements can operate at a frequency of approximately 440 kHz to 25 MHz, and in some embodiments, the frequency can range from 450 kHz to 850 kHz, and in some embodiments, 650 kHz. The ultrasound and therapeutic compounds may or may not be delivered simultaneously.The ultrasound catheter 200 can continue to deliver therapy to the thrombus as it advances through the length of the thrombus (see FIG. 9B ). For example, in some embodiments, the ultrasound catheter is initially positioned near or within the beginning of the thrombus, and then, after treatment with ultrasound and a therapeutic compound has begun, the ultrasound catheter can be advanced into (or further inward from) the thrombus. Advantageously, microbubbles and / or metastable phase-change nanodroplets and rtPA or other therapeutic compounds (e.g., lytic agents) can be combined with ultrasound to help open holes or passageways through the clot. Ultrasound and microbubbles and / or metastable phase-change nanodroplets and rtPA or other therapeutic compounds (e.g., lytic agents) can be delivered together or sequentially with each other. In some embodiments, after an initial treatment period with ultrasound and / or a therapeutic compound in which the distal end of the ultrasound catheter is positioned at, near, or with the beginning of the clot / obstruction, the ultrasound catheter can be advanced 25% through the length of the thrombus, 50% through the length of the thrombus, or 100% through the length of the thrombus, and then further treatment with ultrasound and / or a therapeutic compound can be administered to treat the length of the thrombus. The ultrasound catheter can then be removed from the treatment site. As described above, in some examples, the distal end of the ultrasound catheter 200 can be configured to articulate. This can allow for the delivery of targeted ultrasound therapy to the treatment site, particularly as the ultrasound catheter advances through the length of the thrombus. Articulation of the distal end of the ultrasound catheter can allow the thrombus to be treated from different angles and can allow for more effective treatment of a larger area of ​​the treatment site. This articulation and targeted ultrasound therapy can occur when the ultrasound catheter is at the beginning of the treatment (e.g., in front of the clot or obstruction) and / or as the ultrasound catheter advances through the clot (and / or is retracted or moved through the treatment site after the initial treatment period).For example, after imaging and identifying the residual clot (e.g., via fluoroscopy or other imaging techniques), the distal end of the ultrasound catheter can be articulated between + or − 180 degrees from the longitudinal axis of the catheter, and in some embodiments, between + or − 90 degrees from the longitudinal axis of the catheter, and in some embodiments, between + or − 45 degrees from the longitudinal axis of the catheter to direct ultrasound energy to the identified residual clot. This targeted treatment can be performed as the ultrasound catheter is being advanced through the clot, and / or before initially advancing the ultrasound catheter through the clot, and / or after a portion of the clot / obstruction has been treated and the ultrasound catheter has been removed. The benefit of targeted ultrasound and movement through the clot can be enhanced mechanical assistance / action in engaging the thrombus for better / improved treatment, which can allow for new areas for treatment, more microchannels, and / or larger binding sites for lysis, leading to improved performance and outcomes. Referring to FIG. 9C , a retriever catheter 400 (according to embodiments described herein) can then be introduced to the treatment site. The retriever catheter 400 can be advanced through the aspiration catheter and introduced into the treatment site 1000. The retriever catheter can be advanced to the outermost end of the treatment site (e.g., completely or substantially through the clot) and the retriever deployed. The retriever can capture dissolved and / or remaining thrombus at the treatment site. The retriever catheter can then retract the retriever from the treatment site into the aspiration catheter. In some embodiments, suction is applied through the aspiration catheter as the retriever is retracted into the aspiration catheter. The aspiration catheter can then aspirate the treatment site to direct dissolved and / or remaining thrombus into the aspiration catheter. Advancement of the retriever catheter, deployment of the retriever, retraction of the retriever, and aspiration of the treatment site can be repeated until the treatment site is free or nearly free of thrombus. In some embodiments, suction may not be applied when the retriever is retracted into the aspiration catheter, and in some embodiments, suction may not be applied when the retriever captures thrombus during treatment.As noted above, in some embodiments, a retriever catheter can be advanced through the ultrasound catheter or through the aspiration catheter along the ultrasound catheter. In some embodiments, the retriever can be formed on a portion of the ultrasound catheter, as described above.

[0103] combination The foregoing description and examples are presented merely to illustrate the concepts of the invention and are not intended to be limiting. Each of the disclosed aspects and examples of the present disclosure can be considered individually or in combination with other aspects, examples, and variations of the present disclosure. In addition, unless otherwise specified, none of the steps of the methods of the present disclosure are limited to a particular order of execution. Reasonable modifications of the disclosed examples that incorporate the spirit and content of the present disclosure are within the scope of the present disclosure. Furthermore, all references cited herein are incorporated by reference in their entirety. The headings used herein are for organizational purposes only and should not be used to unduly limit the scope of the claims or embodiments.

[0104] While the methods and apparatuses described herein are susceptible to various modifications and alternative forms, specific examples thereof have been shown in the drawings and are described in detail herein. It should be understood, however, that the embodiments are not limited to the particular apparatus or methods disclosed, but rather cover all reasonable modifications, equivalents, and alternatives falling within the spirit and scope of the various described examples and the appended claims. Furthermore, any particular feature, aspect, method, characteristic, feature, quality, attribute, element, etc. disclosed herein relating to one example can be used in all other examples described herein. Any method disclosed herein need not be performed in the order described. Depending on the example, one or more acts, events, or functions of any of the algorithms, methods, or processes described herein may be performed in a different order, added, merged, or omitted entirely (e.g., not all described acts or events are necessary to execute an algorithm). Algorithms, modules, blocks, steps, boxes, elements, functions, etc. may be stored in machine-readable memory. In some examples, acts or events may be performed simultaneously rather than sequentially, for example, through multithreading, interrupt processing, or multiple processors or processor cores, or in other parallel architectures. Furthermore, no element, feature, block, box, or step, or group of elements, features, blocks, boxes, or steps, is necessary or essential to each example. Additionally, all possible combinations, subcombinations, and rearrangements of systems, methods, features, elements, modules, blocks, boxes, and the like are within the scope of the present disclosure. The use of sequential or chronological language such as "then," "next," "after," "subsequently," and the like, unless specifically stated otherwise or understood otherwise within the context as used, is generally intended to facilitate the flow of statements and is not intended to limit the order of operations performed. Thus, while some examples may be performed using the order of operations described herein, other examples may be performed according to a different order of operations.

[0105] The various illustrative logical blocks, boxes, modules, processes, methods, and algorithms described in connection with the examples disclosed herein can be implemented as electronic hardware, computer software, or a combination of both. To clearly illustrate this interchangeability of hardware and software, the various illustrative components, blocks, modules, operations, and steps have been described above generally in terms of their functionality. Whether such functionality is implemented as hardware or software depends on the particular application and design constraints imposed on the overall system. The described functionality can be implemented in varying ways for each particular application, and such implementation decisions should not be interpreted as causing a departure from the scope of the disclosure.

[0106] The various illustrative logic blocks and modules described in connection with the examples disclosed herein may be implemented or performed by machines such as a general-purpose processor, a digital signal processor (DSP), an application-specific integrated circuit (ASIC), a field-programmable gate array (FPGA) or other programmable logic device, discrete gate or transistor logic, discrete hardware components, or any combination thereof designed to perform the functions described herein. A general-purpose processor may be a microprocessor, but alternatively, the processor may be a controller, microcontroller, or state machine, combinations thereof, or the like. A processor may also be implemented as a combination of computing devices, e.g., a combination of a DSP and a microprocessor, multiple microprocessors, one or more microprocessors in conjunction with a DSP core, or any other such configuration.

[0107] The blocks, operations, or steps of a method, process, or algorithm described in connection with the examples disclosed herein may be embodied directly in hardware, in a software module executed by a processor, or in a combination of the two. The software module may reside in RAM memory, flash memory, ROM memory, EPROM memory, EEPROM memory, registers, a hard disk, a removable disk, an optical disk (e.g., a CD-ROM or DVD), or any other form of volatile or non-volatile computer-readable storage medium known in the art. The storage medium may be coupled to the processor such that the processor can read information from, and write information to, the storage medium. Alternatively, the storage medium may be integral to the processor. The processor and the storage medium may reside in an ASIC. The ASIC may reside in a user terminal. Alternatively, the processor and the storage medium may reside as discrete components in a user terminal.

[0108] In particular, conditional language used herein, such as "can," "may," "could," "for example," and the like, unless specifically stated otherwise or understood otherwise within the context as used, is intended to generally convey that some examples include particular features, elements, and / or states, while other examples do not. Thus, such conditional language is generally not intended to imply that features, elements, blocks, and / or states are somehow required in one or more examples, or that one or more examples necessarily include logic for determining whether those features, elements, and / or states are included in or performed in a particular example, with or without author input or prompting.

[0109] The methods disclosed herein may include some actions taken by a physician, but may also include, explicitly or implicitly, third-party direction of these actions. For example, an action such as "advancing a catheter" includes "directing the advancement of the catheter."

[0110] Ranges disclosed herein encompass any and all overlaps, subranges, and combinations thereof. Phrases such as "up to," "at least," "greater than," "less than," and "between" are inclusive of the recited number. Numbers preceded by terms such as "about" or "approximately" are inclusive of the recited number and should be interpreted in the context (e.g., as precisely as reasonably possible under the circumstances, e.g., ±5%, ±10%, ±15%, etc.). For example, "about 1 mm" includes "1 mm." Phrases preceded by terms such as "substantially" are inclusive of the recited number and should be interpreted in the context (e.g., as precisely as reasonably possible under the circumstances). For example, "substantially parallel" includes "parallel." Unless otherwise specified, all measurements are at standard conditions, including temperature and pressure. The phrase "at least one of" is intended to require at least one item from the following list, rather than one of each item in the following list. For example, "at least one of A, B, and C" can include A, B, C, A and B, A and C, B and C, or A, B, and C.

[0111] Unless otherwise defined, all technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. As used herein, the singular forms "a," "an," and "the" can also include the plural unless the context clearly dictates otherwise. As used herein, the terms "comprises" and / or "comprising" can specify the presence of stated features, steps, operations, elements, components, and / or groups, but do not exclude the presence or addition of one or more other features, steps, operations, elements, components, and / or groups. As used herein, the term "and / or" can include any combination of one or more of the associated listed items. As used herein, terms such as "first," "second," etc., should not limit the elements described by these terms. These terms are used only to distinguish one element from another. Thus, a "first" element discussed below could also be referred to as a "second" element without departing from the teachings of the present disclosure. The order of operations (or acts / steps) is not limited to the order presented in the claims or figures unless specifically indicated otherwise. [Explanation of symbols]

[0112] 100 Catheter System 200 Ultrasound Catheter 300 Suction Catheter 400 Retriever Catheter 210 Valve 310 Flare End 220 Handle 410 Recoverer 301 Suction lumen 201 Lumen 200 Suction Catheter 210 Handle 220 Extrusion section 230 Flare End 240 Distal Interface 250 Tubing 260 One-way stopcock 270 Vacuum Syringe Port 280 Knob 300 Ultrasound Catheter 310 Handle 320 Knob 330 Extrusion section 340 distal end 335 pull wire 360 Pigtail Cable 370 Ultrasonic element 380 Molding Interface 390 concave lens 362 First Wire 364 Second Wire 68 Feedback Control System 20 Temperature Sensor 70 Energy Sources 40 Ultrasonic emitting element 72 Power circuit 76 Thermometer device 78 Processing Unit 80 User Interface 410 Handle 420 Stylet 430 Recoverer 440 first end 450 Second End 435 Spiral Basket 438 Spline 500 Catheter System 600 Suction Catheter 700 Retriever Catheter 720 Dial 730 Knob 740 Recoverer 600 Suction Catheter 610 Handle 620 Extrusion section 630 Flare End 640 Distal Interface 650 Tubing 660 One-way stopcock 670 Vacuum Syringe Port 700 Retriever Catheter 710 Ultrasound Catheter Element 720 Dial 730 Distal Tip 740 Extrusion section 750 knob 760 Recoverer 810 distal end 820 Inner extrusion part 830 proximal end 840 Outer extrusion 850 ultrasonic element 860 concave lens 865 Nitinol Basket 868 Spline 1000 treatment areas 1001 Clot

Claims

1. an aspiration catheter having a first end, a second end, and a body disposed between the first end and the second end; an ultrasound catheter having a proximal end, a distal end, and a body disposed between the proximal end and the distal end, the ultrasound catheter configured for insertion through the body of the aspiration catheter; a retriever catheter having a proximal end, a distal end, and a shaft disposed between the proximal end and the distal end, the retriever catheter configured for insertion through the body of the aspiration catheter; A catheter system comprising:

2. The catheter system of claim 1 , wherein the aspiration catheter includes an expandable funnel at the second end.

3. The catheter system of claim 2 , wherein the expandable funnel is self-expandable.

4. The catheter system of claim 1 , wherein the distal end of the ultrasound catheter is configured to articulate.

5. The catheter system of claim 4 , wherein the ultrasound catheter further comprises a knob and at least one pull wire, the at least one pull wire connecting the distal end of the ultrasound catheter and the knob.

6. The catheter system of claim 5 , wherein the knob is configured to rotate to articulate the distal end of the ultrasound catheter.

7. The catheter system of claim 6 , wherein the ultrasound catheter delivers targeted ultrasound therapy.

8. The catheter system of claim 1 , wherein the ultrasound catheter further includes at least one lumen extending between the proximal end and the distal end.

9. The catheter system of claim 1 , wherein the distal end of the ultrasound catheter is configured to articulate between + or −180 degrees from a longitudinal axis of the ultrasound catheter.

10. The catheter system of claim 1 , wherein the ultrasound catheter is configured to deliver ultrasound at a frequency in the range of 450 kHz to 850 kHz.

11. 1. A catheter system for treating a patient with thromboembolic disease, comprising: an aspiration catheter having a first end, a second end, and a body disposed between the first end and the second end; an ultrasound catheter having a retriever extending therefrom and configured to be inserted through the body of the aspiration catheter; A catheter system comprising:

12. The catheter system of claim 11 , wherein the aspiration catheter includes an expandable funnel at the second end.

13. The catheter system of claim 11 , wherein the distal end of the ultrasound catheter is configured to articulate.

14. 14. The catheter system of claim 13, wherein the ultrasound catheter further includes at least one wire connecting the distal end to a dial disposed on the ultrasound catheter, the dial configured to control articulation of the distal end.

15. The catheter system of claim 14 , wherein the ultrasound catheter delivers targeted ultrasound therapy.

16. The catheter system of claim 12 , wherein the expandable funnel is configured to self-expand.

17. The catheter system of claim 11 , wherein the retriever catheter includes a retriever disposed at a distal end of the retriever catheter that is configured to actively expand or contract.

18. The catheter system of claim 17 , wherein the retriever catheter includes a knob capable of controlling movement of the retriever.

19. 1. A method for treating a patient with thromboembolic disease, comprising: advancing a catheter into a patient's vasculature, the catheter having a first end, a second end, and a body disposed between the first end and the second end; advancing an ultrasound catheter having a proximal end, a distal end, and a lumen disposed between the proximal end and the distal end through the catheter and into a treatment site; delivering ultrasound energy and a therapeutic compound to the treatment site with the ultrasound catheter; treating at least a portion of the treatment site with ultrasound energy and a therapeutic compound, and then retrieving thromboemboli from the treatment site using a retriever; A method comprising:

20. 20. The method of claim 19, wherein delivering a therapeutic compound comprises delivering one or more of microbubbles, nanodroplets, or a lytic agent through the lumen of the ultrasound catheter to the treatment site.

21. 20. The method of claim 19, wherein the catheter includes an expandable funnel at the second end.

22. 20. The method of claim 19, further comprising the step of articulating the distal end of the ultrasound catheter.

23. 23. The method of claim 22, further comprising articulating the ultrasound catheter to deliver targeted ultrasound therapy to the treatment site to enhance mechanical assistance and action in engaging the thrombus.

24. 20. The method of claim 19, further comprising removing the ultrasound catheter from the catheter and then advancing the retriever through the catheter and using the retriever to retrieve thromboemboli from the treatment site with the retriever.

25. 20. The method of claim 19, further comprising aspirating the thromboemboli at the treatment site through the catheter.

26. 1. A method for treating a patient with thromboembolic disease, comprising: advancing an aspiration catheter into the patient's vasculature, the aspiration catheter having a first end, a second end, and a body disposed between the first end and the second end; advancing an ultrasound catheter through the aspiration catheter into the treatment site, the ultrasound catheter having a retriever catheter integrated therein configured to collect residual thrombus, the ultrasound catheter configured to be inserted through the aspiration catheter; delivering ultrasonic energy to the treatment site; retrieving the thromboemboli from the treatment site with the retriever catheter; A method comprising:

27. 27. The method of claim 26, wherein the suction catheter includes an expandable funnel at the second end.

28. 27. The method of claim 26, further comprising the step of delivering a therapeutic compound to the treatment site through a lumen of the ultrasound catheter, wherein the therapeutic compound comprises at least one of a lytic agent, microbubbles, or nanodroplets.

29. 27. The method of claim 26, wherein the distal end of the ultrasound catheter is configured to articulate.

30. 30. The method of claim 29, further comprising articulating the distal end of the ultrasound catheter to deliver targeted ultrasound therapy to the treatment site.

31. 27. The method of claim 26, further comprising rotating the retriever catheter to control movement of a retriever to retrieve the thromboemboli from the treatment site.

32. 27. The method of claim 26, further comprising the steps of applying suction through the aspiration catheter and retracting the retriever catheter before aspirating the thromboemboli at the treatment site.

33. an aspiration catheter having a first end, a second end, and a body disposed between the first end and the second end; an ultrasound catheter having a proximal end, a distal end, and a body disposed between the proximal end and the distal end, the ultrasound catheter configured for insertion through the body of the aspiration catheter, and the distal end of the ultrasound catheter configured for articulation; a retriever catheter having a proximal end, a distal end, and a shaft disposed between the proximal end and the distal end, the retriever catheter configured to be inserted through the body of the aspiration catheter; A catheter system comprising:

34. 34. The catheter system of claim 33, wherein the aspiration catheter includes an expandable funnel at the second end.

35. 35. The catheter system of claim 34, wherein the expandable funnel is self-expandable.

36. 36. The catheter system of any one of claims 33 to 35, wherein the ultrasound catheter further comprises at least one lumen disposed between the proximal end and the distal end.

37. a body having a proximal end, a distal end, and a lumen extending from the proximal end to the distal end; an ultrasound element disposed at the distal end of the ultrasound catheter; Including, the distal end of the ultrasound catheter is configured to articulate; Ultrasound catheter system.

38. an aspiration catheter having a first end, a second end, and a body disposed between the first end and the second end; an ultrasound catheter having a proximal end, a distal end, and a body disposed between the proximal end and the distal end, the ultrasound catheter configured for insertion through the body of the aspiration catheter; a retriever catheter having a proximal end, a distal end, and a shaft disposed between the proximal end and the distal end, the retriever catheter configured for insertion through the body of the ultrasound catheter; A catheter system comprising:

39. 39. The catheter system of claim 38, wherein the aspiration catheter includes an expandable funnel at the second end.

40. 40. The catheter system of claim 39, wherein the expandable funnel is self-expandable.

41. 41. The catheter system of any one of claims 38 to 40, wherein the distal end of the ultrasound catheter is configured to articulate.

42. 42. The catheter system of claim 41, wherein the ultrasound catheter further comprises a knob and at least one pull wire, the at least one pull wire connecting to the distal end of the ultrasound catheter and the knob.

43. 1. A method for treating a patient with thromboembolic disease, comprising: advancing an ultrasound catheter having a proximal end, a distal end, and a lumen disposed between the proximal end and the distal end into a treatment site having a coagulation; delivering ultrasound energy and a therapeutic compound to the treatment site; after an initial treatment period for the clot, further advancing the ultrasound catheter into the clot; articulating a distal end of the ultrasound catheter to provide targeted therapy to a portion of the treatment site with the ultrasound catheter; A method comprising:

44. 44. The method of claim 43, further comprising advancing an aspiration catheter into the patient's vasculature before advancing the ultrasound catheter, and advancing the ultrasound catheter through the aspiration catheter and then into the treatment site.

45. 45. The method of claim 44, wherein the suction catheter includes an expandable funnel at a distal end of the suction catheter.

46. 44. The method of claim 43, wherein the step of delivering ultrasound energy and a therapeutic compound to the treatment site with the ultrasound catheter comprises delivering the therapeutic compound through a lumen of the ultrasound catheter and delivering ultrasound energy through an ultrasound element at the distal end of the ultrasound catheter, wherein the therapeutic compound comprises at least one of a lytic agent, microbubbles, or nanodroplets.

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