SYSTEMS AND METHODS FOR AN ULTRASOUND CATHETER

Abstract

A catheter system includes an aspiration catheter (300) having a first end, a second end, and a body positioned between the first end and the second end. An ultrasound catheter (200) having a proximal end, a distal end, and a body positioned between the 2024/054648 proximal end and the distal end. 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 positioned between the proximal end and the distal end. The retriever catheter (400) configured to inserted through the body of the aspiration catheter.

Claims

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

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 according to any one of claim 1-3, wherein the distal end of the ultrasound catheter is configured to articulate.

5. The catheter system of claim 4, wherein the ultrasound catheter further includes a knob and at least one pull wire, the at least one pull wire connect to 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 a targeted ultrasound treatment.

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 within a range of 450 kHz-850 kHz.

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

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 a distal end of the ultrasound catheter is configured to articulate.

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

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

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

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

18. The catheter system of claim 17, wherein the retriever catheter includes a knob able to control movement of the retriever.

19. A method for treating a patient with a thromboembolism, the method comprising: advancing into a patient's vascular system a catheter having a first end, a second end, and a body positioned between the first end and the second end; advancing an ultrasound catheter having a proximal end, a distal end, and a lumen positioned between the proximal end and the distal end, through the catheter into a treatment site; with the ultrasound catheter, delivering ultrasound energy and a therapeutic compound to the treatment site; and after treating at least a portion of the treatment site with ultrasound energy and a therapeutic compound, using a retriever to retrieve thromboembolism from the treatment site.

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

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

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

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

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

25. The method of claim 19, further comprising aspirating the thromboembolism at the treatment site though the catheter.

26. A method for treating a patient with a thromboembolism, the method comprising: advancing an aspiration catheter having a first end, a second end, and a body positioned between the first end and the second end into a patient's vascular system; advancing an ultrasound catheter through the aspiration catheter and into a treatment site, the ultrasound catheter having a retriever catheter integrated within the ultrasound catheter configured to gather residual thrombus, the ultrasound catheter configured to insert through the aspiration catheter; emitting ultrasound energy to the treatment site; and retrieving the thromboembolism from the treatment site with the retriever catheter.

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

28. The method of claim 26 further comprising 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, microbubbles or nanodroplets.

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

30. The method of claim 29 further comprising articulating the distal end of the ultrasound catheter and delivering a targeted ultrasound treatment to the treatment site.

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

32. The method of claim 26 further comprising aspirating through the aspiration catheter and retracting the retriever catheter prior to aspirating the thromboembolism at the treatment site.

33. A catheter system comprising: an aspiration catheter having a first end, a second end, and a body positioned between the first end and the second end; an ultrasound catheter having a proximal end, a distal end, and a body positioned between the proximal end and the distal end, the ultrasound catheter configured to insert through the body of the aspiration catheter, wherein the distal end of the ultrasound catheter is configured to articulate; and a retriever catheter having a proximal end, a distal end, and a shaft positioned between the proximal end and the distal end, the retriever catheter configured to be inserted through the body of the aspiration catheter.

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

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

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

37. An ultrasound catheter system comprising: a body having a proximal end, a distal end, and a lumen from the proximal end to the distal end; and an ultrasound element, positioned at the distal end of an ultrasound catheter, wherein the distal end of the ultrasound catheter is configured to articulate.

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

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

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

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

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

43. A method for treating a patient with a thromboembolism, the method comprising: advancing an ultrasound catheter having a proximal end, a distal end, and a lumen positioned between the proximal end and the distal end into a treatment site having a clot; delivering ultrasound energy and a therapeutic compound to the treatment site; after an initial treatment period of the clot, advancing the ultrasound catheter further in to clot; and articulating a distal end of the ultrasound catheter to provide targeted treatment to a segment of the treatment site with the ultrasound catheter.

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

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

46. The method of claim 43 wherein delivering ultrasound energy and therapeutic compound to the treatment site with the ultrasound catheter comprising 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, microbubbles or a nanodroplets.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0068] Exemplary embodiments of systems and methods disclosed herein are illustrated in the accompanying drawings, which are for illustrative purposes only. The drawings comprise the following figures, in which like numerals indicate like parts.

[0069] FIG. 1 illustrates a side view of an embodiment of a catheter system that includes an aspiration catheter, an ultrasound catheter and a retriever catheter.

[0070] FIG. 1A illustrates a cross sectional view of the catheter system.

[0071] FIG. 2 illustrates a side view of the aspiration catheter of FIG. 1.

[0072] FIG. 2A illustrates another embodiment of an aspiration catheter that can be used with the ultrasound catheter system of FIG. 1.

[0073] FIG. 3 illustrates a side view of the ultrasound catheter of FIG. 1.

[0074] FIG. 3A illustrates an enlarged view of a distal tip of the ultrasound catheter of FIG. 3.

[0075] FIG. 3B is a block diagram of a feedback control system for use with the ultrasound catheter of FIG. 3.

[0076] FIG. 3C is a schematic illustration of control wires for articulating the ultrasound catheter of FIG. 3.

[0077] FIG. 3D is a schematic illustration of an electrical connection to an ultrasound element of the ultrasound catheter of FIG. 3.

[0078] FIG. 4 illustrates a side view of the retriever catheter of FIG. 1.

[0079] FIG. 5 illustrates another example embodiment of a catheter system that includes an aspiration catheter and a retriever catheter in combination with an ultrasound catheter.

[0080] FIG. 6 illustrates an enlarged side view of the aspiration catheter of FIG. 5.

[0081] FIG. 7 illustrates a side view of the retriever catheter in combination with an ultrasound catheter of FIG. 5.

[0082] FIG. 8 illustrates an enlarged side view of another embodiment of a retriever in combination with an ultrasound catheter that can be used with a catheter system.

[0083] FIG. 9A schematically illustrates an embodiment of a catheter system that includes an aspiration catheter and an ultrasound catheter being advanced to a treatment site.

[0084] FIG. 9B schematically illustrates an embodiment of an ultrasound catheter being advanced through a clot at a treatment site.

[0085] FIG. 9C schematically illustrates an embodiment of an aspiration catheter and a retriever catheter at a treatment site.

DETAILED DESCRIPTION

[0086] As used herein, the term ultrasonic energy is used broadly, includes its ordinary meaning, and further includes mechanical energy transferred through compression and rarefaction waves with a frequency greater than about 20 kHz. Ultrasonic energy waves can have a center frequency between about 440 kHz and about 25 MHz. In some embodiments, ultrasound transducers may use a multiplicity of ultrasound energy frequencies to enhance cavitation. For example, multiple ultrasound transducers can be used in parallel or series to enhance cavitation. Additionally, ultrasound transducers may operate at different frequencies to produce a broadband of frequencies. As used herein, the term catheter is used broadly, includes its ordinary meaning, and further includes an elongated flexible tube configured to be inserted into the body of a patient, such as into a body part, cavity, duct or vessel (both arterial vessels and venous vessels). As used herein, the term therapeutic compound is used broadly, includes its ordinary meaning, and encompasses drugs, medicaments, dissolution compounds, genetic materials, and other substances capable of effecting physiological functions. A mixture comprising such substances is encompassed within this definition of therapeutic compound. Specifically, for applications that treat human blood vessels that have become partially or completely occluded by plaque, thrombi (a thrombus), emboli or other substances that reduce the blood carrying capacity of a vessel, suitable therapeutic compounds include, but are not limited to, an aqueous solution containing heparin, urokinase, streptokinase, and/or rtPA and in certain aspects, therapeutic compound include but are not limited to micro or nano bubbles as described herein.

[0087] As expounded herein, ultrasonic energy is often used to enhance the delivery and/or effect of a therapeutic compound. For example, in the context of treating vascular occlusions, ultrasonic energy has been shown to increase enzyme mediated thrombolysis by enhancing the delivery of thrombolytic agents into a thrombus, where such agents lyse the thrombus by degrading the platelets of the thrombus. The thrombolytic activity of the agent is enhanced in the presence of ultrasonic energy in the thrombus because, for examples, the ultrasonic energy can create additional binding cites for the therapeutic compound. However, it should be appreciated that the present disclosure should not be limited to the mechanism by which the ultrasound enhances treatment unless otherwise stated. In other applications, ultrasonic energy has also been shown to enhance transfection of gene-based drugs into cells, and augment transfer of chemotherapeutic drugs into tumor cells. Ultrasonic energy delivered from within a patient's body has been found to be capable of producing non-thermal effects that increase biological tissue permeability to therapeutic compounds by up to or greater than an order of magnitude.

[0088] Use of an ultrasound catheter to deliver ultrasonic energy and a therapeutic compound directly to the treatment site mediates or overcomes many of the disadvantages associated with systemic drug delivery, such as low efficiency, high therapeutic compound use rates, and significant side effects caused by high dosage levels.

[0089] Microbubbles and/or metastable phase change nanodroplets may be added to the therapeutic compound. For example, the microbubbles and/or metastable phase change nanodroplets may be driven to cavitation by the ultrasound energy delivered by the ultrasound catheter. The microbubbles may be 500 nm-10 m in size. In some aspects, the microbubbles may have a size of 1 um-3 m. Similarly, the metastable phase change nanodroplets may be 100 nm to 1 m. In some aspects, the nanodroplets may have a size of 100 nm to 300 nm. The microbubbles and/or metastable phase change nanodroplets may be used in combination with or carry therapeutic agents, such as blood clot lysing agents. For example, when in combination with a therapeutic agent, the microbubbles and/or metastable phase change nanodroplets may be concentrated at 10{circumflex over ()}4 microbubbles/mL to 10{circumflex over ()}11 microbubbles/mL. In some aspects, the microbubbles and/or metastable phase change nanodroplets may be concentrated at approximately 10{circumflex over ()}8-10{circumflex over ()}9 microbubbles/mL. In aspects described herein, this mixture may contain 0 mg to 30 mg of rtPA. The microbubbles and/or nanodroplets can enhance the effectiveness of the ultrasound energy delivered to the treatment site. For example, ultrasound energy can be applied to the blood clot, including the microbubbles and/or metastable phase change nanodroplets within and/or surround the clot, causing the metastable phase change nanodroplets or microbubbles to oscillate, cavitate (both inertially and non-inertially), vaporize, and lyse the clot from within and/or surrounding the clot. Bioeffects may be achieved in result of the activation of the microbubbles from the ultrasound, which can include sonoporation, microstreaming and/or microjetting. The use of therapeutic agents (e.g., rtPA) in combination with microbubbles and/or metastable phase change nanodroplets to enhance sonothrombolysis can allow blood clots to be lysed more effectively and allows for the use of a reduced dosage of the therapeutic agent while the effectiveness of the treatment remains enhanced. The methods and systems for microbubbles and/or metastable phase change nanodroplets are further described in US 2020/0405258 and US 2021/0007759 the entirety of which is hereby incorporated herein by reference.

[0090] In some examples the catheter system can be used to treat the formation of a blood clot inside of a blood vessel (which can be referred to as a treatment site), obstructing the flow of blood through the circulatory system. Thrombosis can occur in veins (i.e., venous thrombosis) or in arteries (i.e., arterial thrombosis). In some examples, venous thrombosis leads to congestion of the affected part of the body, while arterial thrombosis may affect the blood supply to a part of the body which can lead to damage of the tissue supplied by the affected artery (e.g., ischemia and necrosis). Conditions that may arise from thrombosis and/or reduced blood flow can include deep vein thrombosis, peripheral artery disease, peripheral artery occlusion, and critical limb ischemia. In some examples, the catheter system can be used to treat treatment sites that include deep vein thrombosis, where a thrombus has formed in a deep vein, for example, in the legs or pelvis, or to treat pulmonary embolisms, where a thrombus has formed in the pulmonary vasculature. In some examples, the catheter system can be used to treat treatment sites that include arterial thrombosis, where a thrombus has formed in a coronary artery or in an artery that supplies the brain with blood. In some examples, the catheter system can be used to treat other treatment sites such as superficial vein thrombosis, where a thrombus has formed in a superficial vein, for example, in the legs. As will be explained below, in certain embodiments, a catheter system, that can include an ultrasound catheter can be used in combination with an aspiration catheter to provide suction (also referred to as aspiration) to the treatment site and assist in the removal of a clot (e.g., a thrombus resulting from thrombosis). For example, catheter system may be used to treat acute, subacute, and/or chronic clots. In certain aspects, the chronic clots may not include collagen. An acute clot may be softer or the softest of the three types of clots mentioned. Additionally, an acute clot may be the youngest (i.e., approximately 1-3 days) or newest clot and most porous clot. A chronic clot may be harder or the hardest of the three types of clots mentioned. Additionally, a chronic clot may be the oldest (i.e., approximately greater than 14 days) clot and least porous clot. A subacute clot may have a hardness, porosity, and age in between the characteristics described for an acute clot and a chronic clot. For example, a subacute clot may be approximately 3-14 days of age. While remnants of a thrombus may be left in the patient due to other forms of therapy, the use of an aspiration catheter can enhance the removal of the thrombus. In some embodiments, the catheter system can be used to minimize or eliminate the increased risk of bleeding complications by combining mechanisms and/or elements of action, which may be delivered through the catheter system. For example, in certain embodiments, the catheter (or catheter system) can form a multi-mechanism thrombectomy system that in certain embodiments utilizes microbubble-mediated cavitation as a mechanism of action to more effectively treat blood clots, without the increased risk of bleeding complications, and can combine four complementary mechanisms of action delivered through an integrated catheter system: (i) ultrasound, (ii) microbubbles (and/or nanodroplets), (iii) thrombolytic drug, and (iv) aspiration. Such a catheter system can also minimize blood loss and vessel wall damage arising from multiple passes of alternative thrombectomy devices. In certain embodiments, the catheter system can combine the benefits of mechanical thrombectomy and sonothrombolysis, while improving the reduction of thrombus burden and minimizing bleeding complications, blood loss, and vessel wall damage due to multiple passes resulting from alternative thrombectomy devices. Accordingly, the catheter or catheter system can form a multi-mechanism thrombectomy system that in certain embodiments utilizes microbubble-mediated cavitation as a mechanism of action to more effectively treat blood clots, without the increased risk of bleeding complications, and can combine four complementary mechanisms of action delivered through an integrated catheter system: (i) ultrasound, (ii) microbubbles (and/or nanodroplets), (iii) thrombolytic drug, (iv) aspiration and (v) a mechanical clot retriever. In certain embodiments, the catheter or catheter system can be used without microbubbles (and/or nanodroplets),

[0091] In some aspects, an ultrasound catheter may be introduced to a treatment site within a patient. The treatment site may have a clot (e.g., a thrombus) that may require treatment. The ultrasound catheter may be introduced through the blood vessels until it reaches the treatment site. The ultrasound catheter may include an ultrasound transducer element which can deliver ultrasound energy directly to the treatment site to treat the thrombus. The ultrasound transducer element may come in direct contact with the thrombus at the treatment site and/or be positioned near or adjacent to the thrombus such that ultrasound energy can be directed towards the thrombus. The ultrasound transducer element may deliver ultrasound energy and the catheter can also deliver microbubbles and/or lytic to the thrombus before, after and/or during delivery of ultrasound energy. For a long segment of 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 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 entirely or almost entirely fragmented and/or dissolved. In some examples, a distal end of the ultrasound catheter may be configured to articulate. This may allow a targeted ultrasound treatment to be delivered to the treatment site. Articulation of the distal end of the ultrasound catheter may allow for the thrombus to be treated from different angles and/or may allow for a greater area of the treatment site to be treated more effectively. This articulation and targeted ultrasound treatment can occur as the ultrasound catheter is advanced through the clot. For example, after imaging and identifying 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 the enhanced mechanical assistance/action in engaging thrombus for better/improved treatment which may allow new regions for treatment, more microchannels, and/or greater binding sites for lytic leading to improved performance and outcomes.

[0092] In some aspects, the ultrasound transducer element can operate at a frequency of approximately 440 kHz-25 MHz and in certain embodiments the frequency can be in the range of 450 kHz-850 kHz and in certain aspects 650 kHz. The frequency at which the ultrasound transducer element may operate at may be based on the location of the treatment site and/or the location of the thrombus within the treatment site. In some aspects, the frequency range of the ultrasound transducer may allow the generated ultrasonic waves to penetrate deeper into tissue where the treatment site may be located. In some aspects, the frequency range of the ultrasound transducer may allow the generated ultrasonic waves to penetrate a shallow depth of the tissue where the treatment site may be located.

[0093] In some aspects, once the ultrasound catheter delivers treatment to the treatment site (which can include an obstruction, such as a clot or thrombosis, to the flow of blood through the circulatory system.), the ultrasound catheter may be removed from the treatment site. In some aspects, the ultrasound catheter may remain at the treatment site. An aspiration catheter or aspiration sheath or sheath (used interchangeably throughout) may be advanced into the patient's vascular system and advanced towards the treatment site. In some aspects, the aspiration catheter may be advanced to an area near the treatment site. In some aspects, the aspiration catheter may be advanced to an area between an insertion site and the treatment site. In some aspects, an aspiration catheter can be used to gain access from outside the body to inside 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, an aspiration catheter can be used to track location of the treatment provided (e.g., a pulmonary embolism). In some aspects, this may be used when treating a pulmonary embolism. The aspiration catheter or aspiration sheath or sheath are used interchangeably herein in all embodiments and aspects. The aspiration catheter may be used in combination with a retriever catheter and the ultrasound catheter. The aspiration catheter can be referred to as an aspiration sheath and in certain embodiments aspiration can be applied to the vascular system through the aspiration catheter, however, in some aspects the aspiration need not be applied and the aspiration catheter/sheath can be used as an introducer catheter to deliver other instruments and catheter through the lumen of the aspiration sheath/catheter. In some aspects, the aspiration catheter may be introduced into the patient's vascular system prior to the ultrasound catheter being introduced into the patient such that the ultrasound catheter is advanced through the aspiration catheter and then advanced to the treatment site. In this manner, the ultrasound catheter may be inserted through the aspiration catheter. In some aspects, the aspiration catheter may include a funnel with an expanded opening that can guide elements of the fragmented and/or dissolved thrombus as the treatment site is aspirated. In some aspects the retriever catheter may be inserted through the ultrasound catheter. The retriever catheter may extend passed the distal end of the ultrasound catheter. In other aspects, the ultrasound catheter may be removed from the aspiration catheter to allow for the retriever catheter to be inserted through the aspiration catheter. This may be further described below with reference to FIGS. 9A and 9C. The retriever catheter may include a retriever that can engage the thrombus and/or elements of the fragments and/or dissolved thrombus. The retriever may break the thrombus further apart and/or dislodge it from the vessel wall to remove the thrombus from the treatment site as the retriever is withdrawn into the aspiration catheter. The retriever can capture the thrombus and the fragmented and/or dissolved thrombus elements. As the retriever removes the thrombus and the fragmented and/or dissolved thrombus elements from the treatment site, the aspiration catheter can be used to aspirate the area and/or treatment site. This can help to ensure the treatment site is effectively treated and the thrombus is effectively removed from the treatment site. Once the retriever removes the thrombus from the treatment site and the aspiration catheter can aspirate the area and/or the treatment site before, during, and/or after the removal of the thrombus. In other aspects, 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 vascular system and can be used to introduce other devices (such as, for example, the ultrasound catheter or retriever catheter). Aspiration of the area and/or treatment site may be based on the effectiveness of the removal of thrombus by the retriever. The combination of catheters can help to maximize the effectiveness of the removal of the thrombus from the treatment site and restore blood flow to the blood vessels. In certain embodiments described herein, features of the aspiration catheter and/or retriever can be combined with the ultrasound catheter. For example, in certain embodiments, the ultrasound catheter can be advanced through the aspiration catheter such that the aspiration catheter is positioned within the patient during treatment with the ultrasound, drug (e.g., lytic) and/or microbubbles (and/or nanodroplets). In such embodiments, the ultrasound catheter can be removed from the aspiration catheter and then the 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 withdraw and/or dislodge the clot after treatment.

[0094] In some aspects, an aspiration catheter (according to aspects described herein) may be introduced into the vascular system through an access site and in certain embodiments advanced towards the treatment site and in certain embodiments advanced to the treatment site (which may include an obstruction, as described above, to the flow of blood through the circulatory system.). After introduction of the aspiration catheter into the vascular system, an ultrasound catheter (according to aspects described herein) may be introduced to the treatment site as well. In certain aspects, the ultrasound catheter and aspiration catheter can be introduced together into the vascular system. The ultrasound catheter may be advanced through the aspiration catheter to then be 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, such as, closer to the access site. The ultrasound catheter may deliver microbubbles and/or metastable phase change nanodroplets and rtPA or other therapeutic compounds (e.g., a lytic) to the treatment site. The microbubbles and/or metastable phase change nanodroplets and rtPA or other therapeutic compounds (e.g., a lytic) can be delivered through a lumen in the ultrasound catheter and/or through another passage in the catheter system. This can allow for treatment of the thrombus located at the treatment site. For example, delivering microbubbles and/or metastable phase change nanodroplets can create microchannels within the thrombus. The ultrasound catheter can then deliver ultrasound energy or ultrasound treatment to the thrombus. The ultrasound catheter can continue to deliver treatment to the thrombus (ultrasound and/or microbubbles and/or metastable phase change nanodroplets and rtPA or other therapeutic compounds (e.g., a lytic) to the treatment site) as it is advanced through the length of the thrombus. For example, in certain aspects, the ultrasound catheter is first positioned near the thrombus or within the beginning of the thrombus and then after treatment with ultrasound and a therapeutic compound begins, the ultrasound catheter can be advanced into (or further into) the thrombus and further treatment can be provided with ultrasound and a therapeutic compound. Ultrasound can be provided within the frequency and power ranges described herein. For example, in some aspects, the ultrasound transducer element can operate at a frequency of approximately 440 kHz-25 MHz and in certain embodiments the frequency can be in the range of 450 kHz-850 kHz and in certain aspects 650 kHz. Advantageously, the microbubbles and/or metastable phase change nanodroplets and rtPA or other therapeutic compounds (e.g., a lytic) in combination with the ultrasound may aid in boring a hole or passage through the clot. For example, the ultrasound catheter can be advanced 25% through length of thrombus, 50% through length of thrombus, 100% through length of thrombus and deliver treatment all throughout. The ultrasound catheter can then be removed from the treatment site. A retriever catheter (according to aspects described herein) may then be introduced to the treatment site. The retriever catheter can be advanced through the aspiration catheter to be introduced to the treatment site. The retriever catheter may be advanced to the most outer end of the treatment (e.g., entirely or substantially through the clot) site and deploy a retriever. The retriever may capture the degraded and/or residual thrombus at the treatment site. The retriever catheter may then retract the retriever from the treatment site and into the aspiration catheter. The aspiration catheter may then aspirate the area and/or treatment site to direct the degraded and/or residual thrombus into the aspiration catheter. In other aspects, the aspiration catheter may not aspirate the area or treatment site. Aspiration of the area and/or treatment site may be based on the effectiveness of the removal of thrombus by the retriever. The advancement of the retriever catheter, deployment of the retriever, retraction of retriever, and aspiration of the treatment site may be repeated until the treatment site is free or mostly free of thrombus. In certain aspects, the retriever catheter can be inserted through the ultrasound catheter or alongside the ultrasound catheter such that the ultrasound catheter does not need to be removed before the retriever catheter is used to remove the clot.

[0095] The techniques disclosed herein can find utility with a wide variety of ultrasound catheters in addition to the ultrasound catheter embodiments described here. Certain of the techniques disclosed herein are compatible with ultrasound catheters and/or aspiration catheters that would be unable to generate cavitation at an intravascular treatment site but for the use of such techniques.

[0096] With reference to the illustrated embodiments, FIG. 1 illustrates an example of a catheter system 100 configured for use at a treatment site within a patient. For example, in certain 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 ultrasound energy to a treatment site within a patient to assist in dissolving or lysing a thrombus located at the treatment site. The catheter system 100 can also be used to aspirate the thrombus at the treatment site. Additionally or alternatively, the catheter system 100 can be used to mechanically retrieve the thrombus from the treatment site with the retriever catheter 400. The catheter system 100 can also include at least one valve 210 that may be used to connect the various elements of the catheter system 100. In some examples, the valve can include a Tuohy-Borst adapter, or a hemostasis valve, which can minimize fluid loss during use of the catheter system 100. In some examples, the hemostasis valve can include side port tubing. The aspiration catheter 300 can include a flared end 310. In some examples, the flared end 310 can aspirate a greater area of the thrombus at once and can aid in withdrawing a clot or thrombus retrieved by the retriever catheter 400 into the aspiration catheter 200. The flared end 310 may be a funnel that is connected or bonded to the aspiration catheter 300.

[0097] In some examples, the ultrasound catheter 200 can include an ultrasound element (described in more detail below) that may deliver 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 a distal tip of the ultrasound catheter 200 (as will be explained in more detail below). This may allow the catheter system 100 to more accurately direct or control where ultrasound energy is delivered. Additionally, this may allow the ultrasound catheter 200 to more effectively be advanced to the treatment site and the length of the thrombus. This may further allow the ultrasound catheter 200 to more effectively deliver ultrasound treatment to a thrombus that is relatively more lodged in the blood vessel.

[0098] In some examples, the retriever catheter 400 can include a retriever 410 located at a distal end of the retriever catheter 400. As further described below, in certain embodiments, the retriever catheter 400 may include an actuator that can be rotated (or otherwise actuated) to cause the retriever 410 to selectively expand or collapse. The expansion and collapsing of the retriever 410 may assist in the removal of the blood clot from the treatment site of the patient. In certain embodiments, the retriever 410 can be self-expandable once it is advanced past the distal end of the aspiration catheter 200 or ultrasound catheter 300.

[0099] With reference to the illustrated embodiments, FIG. 1A illustrates a schematic cross section of the catheter system 100 with reference to FIG. 1. As shown, the aspiration catheter 300, ultrasound catheter 200, and retriever catheter 400 may be concentric. In some examples, the aspiration catheter may include at least one aspiration lumen 301 (schematically illustrated in FIG. 1A). In some examples, the ultrasound catheter 200 may be inserted through the at least one aspiration lumen 301 of the aspiration catheter 300. In some examples, the ultrasound catheter 200 may include at least one lumen 201 (schematically illustrated in FIG. 1A) which can be used to deliver a therapeutic compound to the treatment site. The lumen 201 can also be used to advance the ultrasound catheter over a guidewire. In certain aspects, the ultrasound catheter can include multiple lumens. In some examples, the retriever catheter 400 may be inserted through the at least one lumen 201. For example, the retriever catheter 400 may be inserted into a proximal end of the ultrasound catheter 200 and extend through the at least one lumen 201 of the ultrasound catheter 200. In other examples, the retriever catheter 400 may be inserted through the at least one aspiration lumen 301 as described above. For example, the retriever catheter can be configured to be inserted into a proximal end of the aspiration catheter 300 and extend through the aspiration lumen 301 after the ultrasound catheter 200 is removed from the aspiration catheter 300. In other aspects, the retriever catheter can be inserted along the side of the ultrasound catheter 200 with the aspiration lumen 301. The retriever catheter 400 may extend through the at least one lumen 201 of the ultrasound catheter 200 and extend passed a distal end of the ultrasound catheter 200. Similarly, the ultrasound catheter 200 may be inserted into a proximal end of the aspiration catheter 300. The ultrasound catheter 200 may extend through the aspiration lumen 301 of the aspiration catheter 300 and extend passed a distal end of the aspiration catheter 300. In some examples, the retriever catheter 400 may be inserted through the at least one lumen 201 of the ultrasound catheter 200 as the ultrasound catheter 200 is inserted through the aspiration lumen 301 of the aspiration catheter 300. In some examples, the retriever catheter 400 may have a larger diameter and be configured to extend passed the aspiration catheter 300 when the ultrasound catheter 200 is removed from the aspiration catheter.

[0100] With reference to the illustrated embodiments, FIG. 2 illustrates the aspiration catheter 200 as referred to in FIG. 1, but now shown in isolation. As shown, the aspiration 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 extrusion 220 positioned between the distal and proximal end of the aspiration catheter 200, and an expandable funnel or flared end 230 at the second (distal) end of the aspiration catheter 200. The extrusion 220 can extend through the handle 210 and connect to a distal interface 240 of the aspiration catheter 200. The distal interface 240 can be molded and bonded to the extrusion 220 and the flared end 230. In some examples, 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 may have a first diameter and a second diameter; the first diameter may be smaller than the second diameter. The flared end 230 may include a body that connects the first diameter to the second diameter. In some examples, the flared end 230 can function as a lead-in feature of the aspiration catheter 200. The flared end 230 can help to maximize the amount of thrombus that is removed from the treatment site. In some examples, the flared end 230 can be collapsible and expand to the treatment site of the patient. For example, the flared end 230 can expand to a vessel wall of the treatment site of the patient. This can help to ensure the thrombus and/or debris is effectively removed from the treatment site. In some examples, the flared end 230 can direct aspiration of the aspiration catheter. For example, the flared end 230 can be open or closed to direct the aspiration. In some examples, the flared end 230 can be actively deployable. In some examples, the flared end (expandable funnel) 230 can be self-expandable. In some examples, the flared end 230 may include radiopaque features. In some examples, the flared end 230 may include nitinol. In some examples, the flared end 230 may have finger-like structures that may be connected by film which may or may not be perforated. In some examples, the flared end 230 may be actuated by use of an outer cover or tube that may slide over or cover and cause the finger-like structures to draw closer together until the structures are in an isodiametric arrangement. The aspiration catheter can also include tubing 250, a one-way stop cock 260, and a vacuum syringe port 270 to assist in aspiration. In some examples, the tubing 250 can include flexible, large bore tubing. The aspiration catheter 200 defines an aspiration lumen (not shown) that can extend through the aspiration catheter 200.

[0101] With reference to the illustrated embodiments, FIG. 2A illustrates an alternative embodiment of the aspiration catheter 200 as referred to in FIG. 2. As shown, the aspiration catheter 200 can include a knob 280 that may articulate a distal interface 240 of the aspiration catheter. The extrusion 220 can include pull wires that connect to the knob 280 and the distal interface 240 that may allow for 180-degree articulation of the aspiration catheter 200 and/or active expansion and/or contraction of the distal end of the aspiration catheter 200. In some examples, the distal interface 240 can be molded and bonded to the extrusion 220 and the flared end 230.

[0102] With reference to the illustrated embodiments, FIG. 3 illustrates an ultrasound catheter 300 as referred to in FIG. 1, but now shown in isolation. As shown, the ultrasound catheter 300 can include the handle 310, a knob 320, and an extrusion 330. The extrusion 330 can have a proximal end 340 and a distal end with a body positioned between the distal end and proximal end 340. The distal end 340 may be articulated by rotation of knob 320. In some examples, the handle 310 may have a length of approximately 3.0 in.-5.0 in. This can allow for a steerable ultrasound catheter. For example, a user can rotate the knob 320 (e.g., clockwise or counterclockwise direction) to control the deflection of the distal end 340. The articulation of the distal end 340 can better direct the delivery of the ultrasound energy to the treatment site within the patient. For example, articulation of the distal end 340 can help to better dislodge the thrombus from the treatment site by better targeting ultrasound towards a portion of the thrombus that may require additional treatment to dislodge or fragment. Additionally, articulation of the distal end 340 can better target the thrombus located in the treatment site as well. This can allow for treatment of the thrombus by visualization and/or target searching. This technique allows for localized treatment and minimizes or limits any potential for damage to healthy or surrounding tissue. The extrusion 330 can be a multi-lumen extrusion that includes one or more pull-wires 335 extending along the length of the catheter configured to articulate the distal end 340 by connecting the distal end 340 and the knob 320. The pull-wires 335 can allow articulation of the distal end 340 by approximately + or 180 degrees from the longitudinal axis of the catheter and in some embodiments + or 45 degrees longitudinal axis of the catheter. FIG. 3C schematically illustrates pull wires 335 which are connected to the distal end 340 for providing articulation. In some examples, the ultrasound catheter 300 can further include at least one lumen 201 and a pigtail cable 360 connected to a proximal end of the ultrasound catheter 300. The lumen 201, for example, a female luer, can extend through the ultrasound catheter 300 to allow for an introduction of fluids to the patient. For example, the fluids may consist of a therapeutic compound, flush, radiopaque contrast agents, etc. In some examples, the fluids may enter the ultrasound catheter through the at least one lumen 201 or another lumen of the ultrasound catheter. The lumen 201 may be welded or otherwise secured to the catheter 300. In certain embodiments, the ultrasound catheter 300 may have a length of approximately 1.0 m-1.5 m and a diameter of 0.6 in-0.8 in. 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 radiating element) 370 connected to the distal end 340.

[0103] With reference to the illustrated embodiments, FIG. 3A illustrates a zoomed in view of the distal end 340 as referred to in FIG. 3. As shown, the ultrasound element 370 can be bonded to a molded interface 380 which may be bonded to the extrusion 330. As explained above, the bonding can assist in allowing articulation of the distal end 340. This connection can further provide fluid ports for the distal end 340. In some examples, the ultrasound element 370 can be cylindrical and hollow and include a concave lens 390. In certain embodiments, the concave lens 390 may assist in focusing the ultrasonic field to assist in treatment or removal of the thrombus at the treatment site.

[0104] With continued reference to FIG. 3A, the distal end 340 of the ultrasound catheter 300 can include the ultrasound radiating element 380 (also referred to herein as an ultrasound element). In the illustrated embodiment, the ultrasound radiating element 370 comprises an ultrasound transducer, which may be radiopaque, which converts energy, for example, electrical energy into ultrasound energy. In a modified embodiment, the ultrasound energy can be generated by an ultrasound transducer that is remote from the ultrasound radiating element 380 and the ultrasound energy can be transmitted via, for example, a wire to the ultrasound radiating element 370. In some examples, ultrasound energy may be radiated by use of a vibrating wire, transducer or a laser. As mentioned above, in the illustrated embodiment, ultrasound energy is generated from electrical power supplied to the ultrasound radiating element 370. The electrical power can be supplied through a connector, which is connected to a pair of wires 365 (shown schematically in FIG. 3D) that extend through the body of the ultrasound catheter 300. In the illustrated arrangement, the first wire 362 can be connected to the hollow center of the ultrasound radiating element 370 while the second wire 364 is connected to the outer periphery of the ultrasound radiating element 380. Thus, in the illustrated embodiment, the ultrasound catheter includes at least one lumen 201 extending through the catheter and through the ultrasound radiating element 380. In certain aspects, a guidewire can be inserted through the at least one lumen 201 or another lumen of the ultrasound catheter. In certain aspects, the therapeutic compound and/or microbubbles and/or nanobubbles can be delivered to the treatment site through the at least one lumen 201 of the ultrasound catheter 300, or another lumen of the ultrasound catheter. The lumen 201 can also be used to advance the ultrasound catheter over a guidewire in certain embodiments. In the illustrated arrangement, a fenestrated ultrasound radiating element 370 can be used. In other aspects, a solid ultrasound radiating element 370 may be used, in which case the first wire can be connected to the outer periphery of the of the ultrasound radiating element 370. The ultrasound radiating element 370 is preferably, but not limited to, a transducer formed of a piezoelectric ceramic oscillator or a similar material. Piezoelectric ceramic oscillators typically comprise a crystalline material, such as quartz, that can change shape when an electrical current is applied to the material. This change in shape, when made oscillatory by an oscillating driving signal, can create ultrasonic sound waves. In other embodiments, ultrasonic energy can be generated by an ultrasonic transducer that is remote from the ultrasound radiating member, and the ultrasonic energy can be transmitted, via, for example, a wire that is coupled to the ultrasound radiating member such as that described in U.S. Pat. No. 8,668,709, the entirety which is hereby incorporated by reference herein. In other embodiments, the ultrasound radiating element can be a photoacoustic ultrasound element in which a material emits pressure waves in response to being illuminated by a light source (e.g., a laser). For example, the photoacoustic ultrasound element can be formed of a formed from a light-absorbing material and a thermal expansion material that can be in optical communication with a light guide such that light is absorbed by the photoacoustic transducer and converted into acoustic wave as the transducer changes shape such as described in U.S. Pat. No. 11,622,779, the entirety of which is hereby incorporated by reference herein.

[0105] While not illustrated, the ultrasound catheter 300 may include at least one temperature sensor and/or force sensor along the distal end. The temperature sensor and/or force sensor can be located on or near the ultrasound radiating 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 a Fabry-Perot sensor that uses thermochromic liquid crystals. Suitable force sensors include, among others, Fabry-Prot, fiber Bragg grating, resistors, load cells, and strain gauges. The temperature sensor and/or force sensor can operatively connect to a control box (not shown) through a control wire, which extends through the ultrasound catheter. The temperature sensor can be used to sense the temperature of the ultrasound radiating element 370 which can help to limit damage to the surrounding tissue.

[0106] With reference to the illustrated embodiments, FIG. 3B illustrates a feedback control system 68 that can be used with the ultrasound catheter as described with reference to FIG. 3 and FIG. 3A. The feedback control system 68 can allow the temperature at a temperature sensor 20 to be monitored and allows the output power of ultrasound radiating element to be adjusted accordingly. The feedback control system 68 can include an energy source 70 (i.e., ultrasound energy source) and power circuits 72 that may be coupled to the ultrasound radiating element 40. A thermometer device 76 may be coupled to the temperature sensor 20 in the body 12. A processing unit 78 may be coupled to the power calculation device 74, the power circuits 72 and a user interface 80. The thermometer device 76 may measure the temperature at the location of the temperature sensor. The measured temperature may be received by the processing unit 78 to then be displayed to the user. Additional sensors (e.g., a force sensor) can also be connected to the processing unit 78.

[0107] The power circuits 72 may adjust the power level, frequency, voltage, phase and/or current of the electrical energy supplied to the ultrasound radiating element 40 from the energy source 70. For example, the power may be reduced if the measured temperature at the location of the temperature sensor is higher than the desired or safe temperature. Similarly, for example, the power may be increased if the measured temperature at the location of the temperature sensor is lower than the desired temperature. As the power is adjusted, the processing unit 78 may monitor the temperature sensor 20.

[0108] In general, the feedback control system can be used to more efficiently provide treatment to the treatment site by helping to ensure the ultrasound radiating element remains at a desired temperature so that surrounding tissue is not damages and can remain at a desired temperature.

[0109] Additionally, the feedback control system may control the mode in which the ultrasound radiating element may operate in. For example, the ultrasound radiating element may operate in a pulsed mode or a continuous mode. The mode in which the ultrasound radiating element operates in may determine the power that is supplied to the ultrasound radiating element.

[0110] With reference to the illustrated embodiments, FIG. 4 illustrates the retriever catheter 400 referred to in FIG. 1 but shown here in isolation. 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 for example the extrusion 330 or central lumen (shown with reference to FIG. 3.) which can extend through the catheter and through the ultrasound element 370. In certain embodiments, the lumen through the which the retriever catheter 400 extends non-centrally through the ultrasound catheter, for example, along the side of the ultrasound element 370. In some examples, the retriever catheter can be positioned adjacent along a side of the ultrasound catheter 300. In some examples, the retriever catheter 400 can be inserted through the aspiration catheter 200 alongside the ultrasound catheter 370 or 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 located at the distal end of the retriever catheter 400. In some examples, the handle 410 can facilitate an action stop to prevent the stylet 420 from advancing too far into the retriever catheter. For example, the handle 410 can facilitate a push, pull, twist, etc. action. The retriever 430 can be bonded or welded to the stylet at a first end 440 of the retriever and may have a free end at a second end 450 of the retriever. The second end 450 can be a free end to allow the retriever to slide along the stylet 420. The retriever 430 can passively self-expand to retrieve a thrombus from the treatment site within the patient. In some examples, the retriever 430 may include a spiral basket 435 that may include at least one spline 438 (e.g., having six spiral splines, having two spiral splines, etc.). In some examples, the basket may contain nitinol. In some examples, the stylet 420 may be a guidewire. In some examples the guidewire may have a diameter of approximately 0.02 in. to approximately 0.04 in. The retriever 430 can be formed of a variety of materials such as, for example, nickel titanium (also known as nitinol).

[0111] In some examples, the catheter system may be used to remove a thrombus from the treatment site of the patient. The treatment site can be treated with ultrasound energy by use of the ultrasound catheter 300. In some examples, the treatment site may further be treated with an agent (e.g., a therapeutic compound). The agent may include microbubbles and/or phase changing nanodroplets that may assist in lysing the thrombus. The agent may be delivered to the treatment site by use of the ultrasound catheter and/or a separate catheter or device in certain combinations. A user can rotate the knob located on the ultrasound catheter, as described above, to direct the ultrasound energy (for example, at the frequencies described above) at various portion of the thrombus. This may soften or loosen the thrombus. In some aspects, the ultrasound catheter may delivery ultrasound energy at a power range of approximately 1 mW-25 W. In some aspects, the ultrasound transducer element can operate at a frequency of approximately 440 kHz-25 MHz and in certain embodiments the frequency can be in the range of 450 kHz-850 kHz and in certain aspects 650 kHz. The user can advance the ultrasound catheter through the length of the thrombus and continue to treat the thrombus with ultrasound energy as it is advanced. This can help to ensure the thrombus is effectively treated by delivering ultrasound energy to approximately the entire length of the thrombus. In some examples, the user can then insert the retriever catheter 400 and use the retriever to retrieve the thrombus and/or debris from the treatment site. In some examples, 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 element of the clot/thrombus, into the aspiration catheter. This may help to more effectively remove the thrombus and/or debris from the treatment site. This may also help to ensure any fragment of the clot/thrombus and/or debris captured by the retriever remains in the retriever as the retriever is removed from the treatment site. In some examples, the ultrasound catheter may remain at the treatment site within the patient. In some examples, the ultrasound catheter can automatically rotate.

[0112] With reference to the illustrated embodiments, FIG. 5 illustrates another embodiment of catheter system 500 that includes an aspiration catheter 600 and embodiment of an ultrasound catheter in combination with a retriever catheter 700. The catheter system 500 can be used to deliver ultrasound energy to a treatment site within a patient to assist in dissolving or lysing a thrombus located at the treatment site similar to the embodiment described above. The catheter system 500 can also be used to aspirate the thrombus at the treatment site. Additionally or alternatively, the catheter system 500 can be used to mechanically retrieve the thrombus from the treatment site. The catheter system 500 can also include at least one valve 610 that may be used to connect the 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 may further include an aspiration catheter with a flared end 620 which can be configured similar as the aspiration catheter and funnel described above. In some examples, the flared end can aspirate a greater area of the thrombus at once. In some examples, the ultrasound catheter in combination with the retriever catheter 700 can include an ultrasound element/ultrasound radiating element as described in the embodiments described above that may deliver ultrasound energy to a treatment site within a patient. In some examples, the ultrasound catheter in combination with the retriever catheter 700 can include a dial 720, which can control the deflection or movement of a distal tip of the ultrasound catheter in combination with the retriever catheter 700 through, for example, a pull wire as described in the embodiment described above. This may allow the catheter system 500 to more accurately direct or control where ultrasound energy is delivered. The ultrasound catheter in combination with the retriever catheter 700 can include a knob 730 that may be used to control the expansion or collapsing of a retriever 740 located at a distal end of the ultrasound catheter in combination with the retriever catheter 700.

[0113] With reference to the illustrated embodiments, FIG. 6 illustrates the aspiration catheter 600. In some examples, the aspiration catheter 600 can be similar to the aspiration catheter described above with reference to FIG. 2 and FIG. 2A. As shown, the aspiration catheter 600 includes a handle 610, an extrusion 620, and a flared end 630. The extrusion 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 extrusion 620 and the flared end 630. In some examples, the distal interface 640 can be radiopaque. The flared end 630 can be bonded to the distal interface 640. In some examples, the flared end 630 can function as a lead-in feature of the aspiration catheter 600. In some examples, the flared end 630 can be collapsible and expand to the treatment site of the patient. For example, the flared end 630 can expand to a vessel wall of the treatment site of the patient. In some examples, the flared end 630 can direct aspiration of the aspiration catheter. For example, the flared end 630 can be open or closed to direct the aspiration. In some examples, the flared end 630 can be actively deployable. In some examples, the flared end 630 may include radiopaque features. In some examples, the flared end 630 may include nitinol. In some examples, the flared end 630 may have finger-like structures that may be connected by film, and may or may not be perforated. In some examples, the flared end 630 may be actuated by use of an outer cover or tube that may slide over or cover and cause the finger-like structures to draw closer together until the structures are in an isodiametric arrangement. The aspiration catheter can also include tubing 650, a one-way stop cock 660, and a vacuum syringe port 670 to assist in aspiration. In some examples, the tubing 650 can include flexible, large bore tubing. In some examples, the aspiration catheter can be articulated as explained with reference to FIG. 2A.

[0114] With reference to the illustrated embodiments, FIG. 7 illustrates an ultrasound catheter in combination with a retriever catheter 700. In some examples, the ultrasound catheter element 710 of ultrasound catheter in combination with a retriever catheter 700 can be similar to the ultrasound catheter described above. The ultrasound catheter element 710 can include an ultrasound element that may deliver ultrasound energy to the treatment site within the patient. As shown, the ultrasound catheter element 710 can include a dial 720. In some examples, the dial 720 may be a level, knob, slider, etc. The dial 720 may articulate a distal tip 730 of the ultrasound catheter element 710. The articulation of the distal tip 730 may direct where at the treatment site the ultrasound energy is delivered. The articulation of the distal end 730 can better direct the delivery of the ultrasound energy to the treatment site within the patient. For example, articulation of the distal end 730 can help to better dislodge the thrombus from the treatment site by better targeting a portion of the thrombus that may require additional treatment to dislodge or fragment. Additionally, articulation of the distal end 730 can better target the thrombus located in the treatment site as well. In some examples, an extrusion 740 of the ultrasound catheter element 710 can include pull wires that can allow + or180-degree articulation of the distal tip 730. As shown, the retriever catheter element can include a knob 750 that may be located on the ultrasound catheter element 710. The knob 750 can be rotated to expand or collapse a retriever 760 located at the distal end of the ultrasound catheter in combination with a retriever catheter 700. As explained above, the retriever 760 can be used to retrieve a thrombus from the treatment site within the patient.

[0115] FIG. 8 illustrates a zoomed in view of the retriever 760 as referred to in FIG. 7. As shown, a distal end 810 of the retriever 760 may be connected to the distal tip 730 of the ultrasound catheter element. The distal end 810 can be molded and bonded to an inner extrusion 820 of the ultrasound catheter element. A proximal end 830 of the retriever 760 may be molded and bonded to an outer extrusion 840 of the ultrasound catheter element. In some examples the retriever and the outer extrusion can have radiopaque features and/or irrigation ports. As described above, the distal tip 730 can include an ultrasound element 850. In some examples, the ultrasound element 850 can be hollow, cylindrical, and include radiopaque features and/or irrigation ports. In some examples, the distal tip 730 can further include a concave lens 860. In certain aspects, the concave lens may be made of polycarbonate, ABS, PP, polysulfone, mylar, polystrene, Epotek 301, epoxy doped with alumina, syntactic foam, HDPE, glass, Perspex, paralene, or other materials of the like. In some aspects, the material of the concave lens may have a phase velocity greater than blood. This can allow the ultrasound energy to be focused towards a front of the ultrasound radiating element. In certain embodiments, the concave lens 860 may assist in focusing the field to assist in treatment or removal lor the thrombus at the treatment site. In some examples, the retriever 760 may include a nitinol basket 865 and a plurality of splines 868. In some examples, the retriever 760 can include multiple heat set splines 868. In some examples, the retriever 760 may be actively expanded by rotation of the knob 750. For example, the knob 750 may be in a rack and pinion gearset configuration. For example, although not illustrated, the retriever catheter may include an inner catheter shaft that includes a perpendicular protruding shaft, which can form a T-shape with the inner catheter. The knob 750 can be molded to have, on the inner portion, material removed in the pattern of threads (i.e., threads of a nut). The inner shaft can be placed within the knob 750 where the protruding perpendicular shaft inserts into the threads. As the knob 750 is rotated, it can cause linear movement of the inner shaft for expansion or collapsing of the retriever 760. In other embodiments, the retriever can be a self-expanding element that is retained within a sheath that when positioned over the retriever constrains the retriever and when removed from the retriever causes the retriever to expand.

[0116] In some examples, the catheter system may be used to remove a clot/thrombus from the treatment site of the patient. the treatment site can be treated with ultrasound energy by use of the ultrasound catheter element of the ultrasound catheter in combination with the retriever catheter. The user can articulate the ultrasound catheter element of the ultrasound catheter in combination with the retriever catheter to direct the delivery of ultrasound energy at the treatment site. In some examples, the treatment site may further be treated with an agent. The agent may include microbubbles or phase changing nanodroplets that can assist in lysing the thrombus. A user can rotate the knob located on the ultrasound catheter, as described above, to direct the ultrasound energy at various portion of the thrombus. This may soften or loosen the thrombus. In some examples, the user can then control the retriever catheter of the ultrasound catheter in combination with the retriever catheter to expand or collapse the retriever. The expansion or collapsing of the retriever can help to retrieve the thrombus from the treatment site. At the same or similar time, the user can use the aspiration catheter to aspirate the thrombus into the aspiration catheter. In some examples, the ultrasound catheter in combination with the retriever catheter may remain at the treatment site within the patient.

[0117] With reference to FIGS. 9A, 9B, and 9C, in some aspects, an aspiration catheter 300 (which can be according to aspects and embodiments described herein) may be introduced into a patient's vascular system through an access site and then advanced to the treatment site 1000. In some aspects, the aspiration catheter 300 may be advanced to an area near the treatment site. In some aspects, the aspiration catheter may be advanced to an area between an insertion site and the treatment site. After introduction of the aspiration catheter 300, an ultrasound catheter 200 (which can be according to aspects and embodiments described herein) may be introduced through the aspiration catheter 300 and advanced to the treatmensite. In certain embodiments, the ultrasound catheter can be advanced over a guidewire. The ultrasound catheter 200, in the illustrated embodiment, may be advanced through the aspiration catheter 300 to then be introduced to the treatment site 1000 which includes a clot 1001 (e.g., a thrombus). The ultrasound catheter 200 may be used to deliver ultrasound (through the ultrasound element), and/or deliver microbubbles and/or metastable phase change nanodroplets and rtPA or other therapeutic compounds as described herein (e.g., a lytic) to the treatment site as described above, for example, through the lumen 201 of the ultrasound catheter or through other passages in the catheter system or ultrasound catheter. This can allow for treatment of the thrombus located at the treatment site. For example, delivering microbubbles and/or metastable phase change nanodroplets can create microchannels within the thrombus. The ultrasound catheter can deliver ultrasound energy or ultrasound treatment to the thrombus. In certain aspects, the ultrasound catheter may deliver ultrasound energy at a power range of approximately 1 mW-25 W. In certain aspects, the ultrasound transducer element can operate at a frequency of approximately 440 kHz-25 MHz and in certain embodiments the frequency can be in the range of 450 kHz-850 kHz and in certain aspects 650 kHz. The ultrasound and therapeutic compound can be delivered simultaneously and/or not simultaneously. The ultrasound catheter 200 can continue to deliver treatment to the thrombus as it is advanced through the length of the thrombus (see FIG. 9B). For example, in certain aspects, the ultrasound catheter is first positioned near the thrombus or within the beginning of the thrombus and then after treatment with ultrasound and a therapeutic compound begins, the ultrasound catheter can be advanced into (or further into) the thrombus. Advantageously, the microbubbles and/or metastable phase change nanodroplets and rtPA or other therapeutic compounds (e.g., a lytic) in combination with the ultrasound may aid in boring a hole or passage through the clot. The ultrasound and microbubbles and/or metastable phase change nanodroplets and rtPA or other therapeutic compounds (e.g., a lytic) can be delivered together or sequentially with each other. In certain aspects, after an initial treatment period with the ultrasound and/or therapeutic compound wherein the distal end of the ultrasound catheter is positioned at, near, or with the beginning of a clot/obstruction, the ultrasound catheter can be advanced 25% through length of thrombus, 50% through length of thrombus, 100% through length of thrombus and then further treatment with ultrasound and/or therapeutic compound can be conducted such that the length of the thrombus can be treated. The ultrasound catheter can then be removed from the treatment site. As noted above, some examples, a distal end of the ultrasound catheter 200 may be configured to articulate. This may allow a targeted ultrasound treatment to be delivered to the treatment site particularly as the ultrasound catheter is advanced through a length of thrombus. Articulation of the distal end of the ultrasound catheter may allow for the thrombus to be treated from different angles and/or may allow for a greater area of the treatment site to be treated more effectively. This articulation and targeted ultrasound treatment can occur as the ultrasound catheter at the beginning of treatment (e.g., at the front of the clot or obstruction) and/or as the ultrasound catheter is advanced through the clot (and/or withdrawn or moved through the treatment site after an initial treatment period). For example, after imaging (e.g., by fluoroscopy or other imaging techniques) and identifying residual clot, the distal end of the ultrasound catheter can be articulated between + or 180 degrees from a longitudinal axis of the catheter and in certain aspects between + or 90 degrees longitudinal axis of the catheter and in certain aspects between + or 45 degrees longitudinal axis of the catheter to direct ultrasound energy to the identified residual clot. This targeted treatment can be conducted as the ultrasound catheter is advanced through the clot and/or before initially advancing the ultrasound catheter through the clot and/or after a segment of clot/obstruction has been treated and the ultrasound catheter is being removed. An advantage of targeted ultrasound and movement through the clot can be the enhanced mechanical assistance/action in engaging thrombus for better/improved treatment which may allow new regions for treatment, more microchannels, and/or greater binding sites for lytic leading to improved performance and outcomes. With reference to FIG. 9C, a retriever catheter 400 (according to aspects described herein) may then be introduced to the treatment site. The retriever catheter 400 can be advanced through the aspiration catheter to be introduced to the treatment site 100. The retriever catheter may be advanced to the most outer end of the treatment (e.g., entirely or substantially through the clot) site and deploy a retriever. The retriever may capture the degraded and/or residual thrombus at the treatment site. The retriever catheter may then retract the retriever from the treatment site and into the aspiration catheter. In certain aspects, aspiration is applied through the aspiration catheter as the retriever is withdrawn into the aspiration catheter. The aspiration catheter may then aspirate the treatment site to direct the degraded and/or residual thrombus into the aspiration catheter. The advancement of the retriever catheter, deployment of the retriever, retraction of retriever, and aspiration of the treatment site may be repeat until the treatment site is free or mostly free of thrombus. In certain embodiments, aspiration may not be applied as the retriever is withdrawn into the aspiration catheter and, in certain embodiments, aspiration may not be applied as the retriever captures the thrombus during treatment. As noted above, in certain aspects, the retriever catheter can be advanced through the ultrasound catheter or alongside the ultrasound catheter through the aspiration catheter. In certain aspects, the retriever can be formed on a portion of the ultrasound catheter as described above.

Combinations

[0118] The foregoing description and examples are set forth merely to illustrate the inventive concepts and are not intended as being limiting. Each of the disclosed aspects and examples of the present disclosure may be considered individually or in combination with other aspects, examples, and variations of the disclosure. In addition, unless otherwise specified, none of the steps of the methods of the present disclosure are confined to any particular order of performance. Reasonable modifications of the disclosed examples incorporating the spirit and substance of the disclosure are within the scope of the present disclosure. Furthermore, all references cited herein are incorporated by reference in their entirety. Headings used herein are for organizational purposes only and should not be used to unduly limit claim scope or embodiments.

[0119] While the methods and devices described herein may be susceptible to various modifications and alternative forms, specific examples thereof have been shown in the drawings and are herein described in detail. It should be understood, however, that the embodiments are not to be limited to the particular devices or methods disclosed, but, to the contrary, cover all reasonable modifications, equivalents, and alternatives falling within the spirit and scope of the various examples described and the appended claims. Further, the disclosure herein of any particular feature, aspect, method, property, characteristic, quality, attribute, element, or the like in connection with an example can be used in all other examples set forth herein. Any methods disclosed herein need not be performed in the order recited. Depending on the example, one or more acts, events, or functions of any of the algorithms, methods, or processes described herein can be performed in a different sequence, can be added, merged, or left out altogether (e.g., not all described acts or events are necessary for the practice of the algorithm). Algorithms, modules, blocks, steps, boxes, elements, features, etc. may be stored in machine-readable memory. In some examples, acts or events can be performed concurrently, e.g., through multi-threaded processing, interrupt processing, or multiple processors or processor cores or on other parallel architectures, rather than sequentially. Further, no element, feature, block, box, or step, or group of elements, features, blocks, boxes, or steps, arc necessary or indispensable to each example. Additionally, all possible combinations, subcombinations, and rearrangements of systems, methods, features, elements, modules, blocks, boxes, and so forth are within the scope of this disclosure. The use of sequential, or time-ordered language, such as then, next, after, subsequently, and the like, unless specifically stated otherwise, or otherwise understood within the context as used, is generally intended to facilitate the flow of the text and is not intended to limit the sequence of operations performed. Thus, some examples may be performed using the sequence of operations described herein, while other examples may be performed following a different sequence of operations.

[0120] 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 combinations of both. To clearly illustrate this interchangeability of hardware and software, 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 upon the particular application and design constraints imposed on the overall system. The described functionality can be implemented in varying ways for each particular application, but such implementation decisions should not be interpreted as causing a departure from the scope of the disclosure.

[0121] The various illustrative logical blocks and modules described in connection with the examples disclosed herein can be implemented or performed by a machine, 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 can be a microprocessor, but in the alternative, the processor can be a controller, microcontroller, or state machine, combinations of the same, or the like. A processor can also be implemented as a combination of computing devices, e.g., a combination of a DSP and a microprocessor, a plurality of microprocessors, one or more microprocessors in conjunction with a DSP core, or any other such configuration.

[0122] The blocks, operations, or steps of a method, process, or algorithm described in connection with the examples disclosed herein can be embodied directly in hardware, in a software module executed by a processor, or in a combination of the two. A software module can reside in RAM memory, flash memory, ROM memory, EPROM memory, EEPROM memory, registers, hard disk, a removable disk, an optical disc (e.g., CD-ROM or DVD), or any other form of volatile or non-volatile computer-readable storage medium known in the art. A storage medium can be coupled to the processor such that the processor can read information from, and write information to, the storage medium. In the alternative, the storage medium can be integral to the processor. The processor and the storage medium can reside in an ASIC. The ASIC can reside in a user terminal. In the alternative, the processor and the storage medium can reside as discrete components in a user terminal.

[0123] Conditional language used herein, such as, among others, can, might, may, e.g., and the like, unless specifically stated otherwise, or otherwise understood within the context as used, is generally intended to convey that some examples include, while other examples do not include, certain features, elements, and/or states. Thus, such conditional language is not generally intended to imply that features, elements, blocks, and/or states are in any way required for one or more examples or that one or more examples necessarily include logic for deciding, with or without author input or prompting, whether these features, elements and/or states are included or are to be performed in any particular example.

[0124] The methods disclosed herein may include certain actions taken by a practitioner; however, the methods can also include any third-party instruction of those actions, either expressly or by implication. For example, actions such as advancing a catheter include instructing advancing a catheter.

[0125] The ranges disclosed herein also encompass any and all overlap, sub-ranges, and combinations thereof. Language such as up to, at least, greater than, less than, between, and the like includes the number recited. Numbers preceded by a term such as about or approximately include the recited numbers and should be interpreted based on the circumstances (e.g., as accurate as reasonably possible under the circumstances, for example 5%, 10%, 15%, etc.). For example, about 1 mm includes 1 mm. Phrases preceded by a term such as substantially include the recited phrase and should be interpreted based on the circumstances (e.g., as much as reasonably possible under the circumstances). For example, substantially parallel includes parallel. Unless stated otherwise, 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 subsequent listing, not one type of each item in the subsequent listing. 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.

[0126] 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 the present disclosure pertains. As used herein, the singular forms a, an, and the can also include the plural forms, unless the context clearly indicates 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 preclude 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 and all combinations of one or more of the associated listed items. As used herein, the terms first, second, etc. should not limit the elements being described by these terms. These terms are only used to distinguish one element from another. Thus, a first element discussed below could also be termed a second element without departing from the teachings of the present disclosure. The sequence of operations (or acts/steps) is not limited to the order presented in the claims or figures unless specifically indicated otherwise.