Thrombectomy systems and related methods

Abstract

The present technology relates to systems and methods for removing a thrombus from a blood vessel of a patient. In some embodiments, the present technology is directed to a system including an elongate catheter having a distal portion configured to be positioned within a blood vessel of a patient, a proximal portion configured to be external to the patient, and a lumen extending therebetween. The system can also include a fluid delivery mechanism coupled to the fluid lumen and configured to apply a fluid to at least partially fragment the thrombus.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to U.S. Provisional Application No. 63 / 209,257, filed June 10, 2021, U.S. Provisional Application No. 63 / 250,089, filed September 29, 2021, U.S. Provisional Application No. 63 / 285,054, filed December 1, 2021, and U.S. Provisional Application No. 63 / 335,656, filed April 27, 2022, each of which is incorporated by reference in its entirety into this specification. Incorporation by Reference

[0002] All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. Field

[0003] TECHNICAL FIELD The present technology relates generally to medical devices, and more particularly to systems including aspiration and fluid delivery mechanisms for removing thrombi from mammalian blood vessels, and related methods. Summary of the Invention [Problem to be solved by the invention]

[0002]

[0004] Thrombotic material can lead to blockage of fluid flow within the mammalian vascular system. Such blockages can occur in various areas within the body, such as the pulmonary system, peripheral vasculature, deep vasculature, or within the brain. Pulmonary embolism typically occurs when a blood clot originating from another part of the body (e.g., the veins of the pelvis or legs) breaks off and travels to the lungs. Anticoagulation therapy is the current standard of care for treating pulmonary embolism, but may be ineffective in some patients. In addition, conventional devices for removing thrombotic material may be unable to navigate tortuous vascular anatomy, may be ineffective in removing thrombotic material, and / or may lack the ability to provide sensor data or other feedback to the clinician during the thrombectomy procedure. Existing thrombectomy devices operate based on simple suction, which works well against certain clots but is largely ineffective against difficult and organized clots. Many patients who present with deep vein thrombus (DVT) remain untreated as long as they are at low risk for limb ischemia. More urgent cases are treated with catheter thrombolysis or dissolution therapy to fragment the clot over hours or days. Recently, other tools such as thrombectomizers have been developed to treat DVT and pulmonary embolism (PE), but these tools have not been widely adopted due to limited effectiveness and additional cost relative to aspiration or standard of care. Other recent developments have focused on slicing or macerating the clot, but these mechanisms are designed to reduce the risk of catheter clogging and do not address the issues of hard, large, organized clots. There remains a need for devices that address these and other issues with existing venous thrombectomy techniques, including, but not limited to, rapid, easy-to-use, and effective devices for removing various clot morphologies. [Means for solving the problem]

[0003] Disclosure Summary

[0029] A thrombus removal device is provided that includes an elongate shaft including a working end, at least one fluid lumen within the elongate shaft, and two or more openings disposed at or near the working end, the two or more openings in fluid communication with the at least one fluid lumen and configured to generate two or more fluid streams that at least partially impinge at an interaction region, the two or more fluid streams having a flow rate sufficient to create cavitation in the interaction region configured to mechanically fragment a targeted thrombus.

[0004]

[0030] Also provided is a thrombus removal device comprising an elongate shaft including a working end, at least one fluid lumen within the elongate shaft, and two or more openings disposed at or near the working end, the two or more openings in fluid communication with the at least one fluid lumen and configured to generate two or more fluid streams that interact at an interaction region within or near the working end, the two or more fluid streams having sufficient flow rate and proximity to induce cavitation at the interaction region configured to mechanically fragment a target thrombus.

[0005]

[0031] In some embodiments, the two or more fluid streams each have a flow rate of between 50 m / s and 90 m / s.

[0006]

[0032] In other embodiments, the two or more fluid streams each have a flow rate of at least 50 m / s.

[0007]

[0033] In some examples, fluid flowing through at least one fluid lumen at a lumen flow rate of 3 m / s results in two or more fluid streams having flow rates of at least 50 m / s.

[0008]

[0034] In other embodiments, fluid flowing through at least one fluid lumen at a lumen flow rate of 4 m / s results in two or more fluid streams having flow rates of at least 70 m / s.

[0009]

[0035] In some examples, fluid flowing through at least one fluid lumen at a lumen flow rate of 5 m / s results in two or more fluid streams having flow rates of at least 90 m / s.

[0010]

[0036] In one embodiment, the interaction region comprises a focal point (or in other words, a converging point or location) of two or more fluid streams.

[0011]

[0037] In some embodiments, the two or more fluid streams are generally perpendicular to the longitudinal axis of the elongate shaft.

[0012]

[0038] In some examples, the two or more fluid streams are directed distally such that a focal point is distal to the two or more openings.

[0013]

[0039] In one embodiment, the two or more distally directed fluid streams are further configured to generate a cavitation column that extends distally from the focal point.

[0014]

[0040] In some embodiments, the two or more fluid streams are directed proximally such that a focal point is proximal to the two or more apertures.

[0015]

[0041] In one embodiment, the two or more proximally directed fluid streams are further configured to generate a cavitation column extending proximally from the focal point.

[0016]

[0042] In some examples, the cavitation detection sensor is disposed on or within the thrombectomy device.

[0017]

[0043] In some embodiments, the cavitation detection sensor is disposed on or in the infundibulum at the working end of the thrombectomy device.

[0018]

[0044] In another embodiment, the cavitation detection sensor is disposed on or within the aspiration lumen at the working end of the thrombectomy device.

[0019]

[0045] In some examples, the cavitation detection sensor includes an ultrasonic transducer element.

[0020]

[0046] In another embodiment, the cavitation detection sensor includes a hydrophone.

[0021]

[0047] In some examples, the cavitation detection sensor includes a laser.

[0022]

[0048] In another embodiment, the cavitation detection sensor includes a microphone.

[0023]

[0049] Another embodiment includes a real-time imaging device configured to image the cavitations in real-time. In some embodiments, the real-time imaging device includes an ultrasound imaging device. In some embodiments, the ultrasound imaging device includes an external ultrasound imaging probe. In other embodiments, the ultrasound imaging device includes a catheter-based ultrasound imaging device.

[0024]

[0050] A method of removing a thrombus from a blood vessel of a patient is provided, the method comprising the steps of introducing a distal portion of an elongate catheter to a location of the thrombus within the blood vessel, drawing at least a portion of the thrombus into the distal portion, and generating two or more fluid streams having a flow rate of at least 20 m / s that interact at an interaction region to cause cavitation within the thrombus.

[0025]

[0051] A method of removing a thrombus from a blood vessel of a patient is also provided, the method comprising the steps of introducing a distal portion of an elongate catheter to a location of the thrombus within the blood vessel, drawing at least a portion of the thrombus into the distal portion, and generating two or more fluid streams having a flow rate of at least 50 m / s that interact at an interaction region to cause cavitation within the thrombus.

[0026]

[0052] A method for removing a thrombus from a blood vessel of a patient is provided, the method comprising the steps of introducing a distal portion of an elongate catheter to a location of the thrombus within the blood vessel, drawing at least a portion of the thrombus into the distal portion, and generating two or more interacting fluid streams in or near the distal portion at an interaction region, the two or more fluid streams configured to apply at least four different rupture forces to the thrombus including: 1) slicing forces as the two or more fluid streams initially cut through the thrombus before meeting at the interaction region, 2) cavitation forces at the interaction region as the two or more fluid streams interact to generate cavitation, 3) shear forces caused by the two or more fluid streams moving relative to each other to generate shear cavitation, and 4) rotational fluid motion forces caused by the shear forces and the cavitation forces.

[0027]

[0053] In some embodiments, the drawing step is by suction applied via a suction lumen of the elongate catheter.

[0028]

[0054] In one embodiment, generating the two or more fluid streams further comprises directing the two or more fluid streams proximally relative to a fluid flow opening of the elongate catheter.

[0029]

[0055] In some embodiments, generating the two or more fluid streams further comprises directing the two or more fluid streams distally to a fluid flow opening of the elongate catheter.

[0030]

[0056] In one embodiment, generating the two or more fluid streams further comprises directing the two or more fluid streams generally perpendicular to a longitudinal axis of the elongate catheter.

[0031]

[0057] In some instances, only a portion of the two or more fluid streams interact at the interaction region.

[0032]

[0058] In other embodiments, a second portion of the two or more fluid streams that do not interact at the interaction region generates at least one shear cavitation flow in the thrombus.

[0033]

[0059] In some embodiments, a second portion of the two or more fluid flows that do not interact at the interaction region generates at least one halo cavitation flow in the thrombus.

[0034]

[0060] In one embodiment, the flow rate is between 20m / s and 90m / s.

[0035]

[0061] In some embodiments, the flow rate is between 50 m / s and 90 m / s.

[0036]

[0062] A method of removing a thrombus from a patient's blood vessel, the method comprising the steps of: introducing a distal portion of an elongate catheter to a location of the thrombus within the blood vessel; drawing at least a portion of the thrombus into the distal portion; directing two or more fluid streams into the thrombus to cut or partially cut the thrombus; removing at least a portion of the thrombus from the distal portion; continuing to direct the two or more fluid streams into the thrombus until the two or more streams meet and interact with another stream at an interaction region within the thrombus; maintaining a flow rate of the two or more fluid streams sufficient to generate cavitation in the interaction region; and removing at least a portion of the thrombus from the distal portion.

[0037]

[0063] In some embodiments, the flow rate is at least 20 m / s.

[0038]

[0064] In other embodiments, the flow rate is at least 50 m / s.

[0039]

[0065] In some embodiments, the flow rate is between 20 m / s and 90 m / s.

[0040]

[0066] In some embodiments, the method further comprises detecting the cavitation with a cavitation sensor.

[0041]

[0067] In one example, the method includes determining the absence of cavitation during the directing step.

[0042]

[0068] In some embodiments, the method further comprises indicating to a user the absence of cavitation.

[0043]

[0069] A method of removing a thrombus from a patient's blood vessel with a thrombus removal device is provided, the method comprising the steps of: introducing a distal portion of an elongated catheter to a location of the thrombus within the blood vessel; widening a funnel of the elongated catheter at the location of the thrombus; operating a suction source of the elongated catheter at a first vacuum level; capturing at least a portion of the thrombus within the funnel of the distal portion; determining that at least a portion of the thrombus has been captured within the funnel; directing fluid from at least two distinct injection ports of the elongated catheter toward the thrombus; and operating the suction source at a second vacuum level higher than the first vacuum level to remove the thrombus from the patient.

[0044]

[0070] In some embodiments, the drawing step is by suction applied via a suction lumen of the elongate catheter.

[0045]

[0071] In one embodiment, the fluid has an average velocity of at least 20 meters / second (m / s).

[0046]

[0072] In some embodiments, determining that at least a portion of the thrombus has been trapped within the infundibulum further includes identifying a pressure change associated with thrombus trapping at at least one injection port of the thrombus removal device.

[0047]

[0073] In one example, the pressure change includes a pressure drop below a pressure threshold.

[0048]

[0074] In another embodiment, the pressure change comprises a rate of change greater than a pressure threshold value.

[0049]

[0075] In some embodiments, the pressure change includes identifying a pressure fluctuation below a threshold value.

[0050]

[0076] In some examples, the pressure change includes an increase in pressure above the second vacuum level.

[0051]

[0077] In some embodiments, directing the fluid further comprises directing the fluid stream to interact with another fluid stream at an interaction region.

[0052]

[0078] In other embodiments, the step of directing the fluid further comprises crossing the fluid streams.

[0053]

[0079] In some instances, the fluid flow is perpendicular to the longitudinal axis of the elongate catheter.

[0054]

[0080] In another example, the fluid flow is directed proximally.

[0055]

[0081] In some examples, determining that at least a portion of the thrombus has been trapped within the infundibulum further includes detecting a change in impedance with a sensor positioned at a distal portion of the thrombus removal device.

[0056]

[0082] In another embodiment, the method includes determining when the thrombus has been removed.

[0057]

[0083] A method for removing a thrombus from a patient's blood vessel with a thrombus removal device is provided, the method comprising the steps of: introducing a distal portion of an elongated catheter to a location of the thrombus within the blood vessel; widening a funnel portion of the elongated catheter at the location of the thrombus; operating the aspiration lumen at a first suction level prior to engaging the thrombus; capturing at least a portion of the thrombus within the funnel portion of the distal portion; determining that at least a portion of the thrombus has been captured within the funnel portion; directing fluid toward the thrombus from at least two distinct injection ports of the elongated catheter; and operating the aspiration lumen at a second suction level higher than the first suction level to remove the thrombus from the patient.

[0058]

[0084] In some embodiments, the method includes determining whether the thrombus has been completely removed from the patient.

[0059]

[0085] In another embodiment, the method includes operating the aspiration lumen at a first suction level and ceasing to direct fluid.

[0060]

[0086] A method for removing a thrombus from a patient's blood vessel with a thrombus removal device is provided, the method including the steps of: introducing a distal portion of an elongate catheter to a location of the thrombus within the blood vessel; widening a funnel of the elongate catheter at the location of the thrombus; operating a suction source of the elongate catheter; measuring a flow rate of the suction source; capturing at least a portion of the thrombus within the funnel of the distal portion; determining based on the flow rate that at least a portion of the thrombus has been captured within the funnel; directing fluid toward the thrombus from at least two distinct points along respective fluid paths; and removing the thrombus from the patient with the suction source.

[0061]

[0087] In some embodiments, the drawing step is by suction applied via a suction lumen of the elongate catheter.

[0062]

[0088] In another embodiment, the method includes determining a rate of change of the flow rate.

[0063]

[0089] In some examples, the method includes determining that at least a portion of the thrombus is trapped within the infundibulum when the rate of change exceeds a predetermined threshold.

[0064]

[0090] In some embodiments, the method further includes determining that the thrombus is completely trapped within the infundibulum when the flow rate reaches zero.

[0065]

[0091] In one embodiment, the method includes indicating to a user that the thrombus has been completely captured.

[0066]

[0092] In some embodiments, the step of directing fluid occurs only after it is determined that at least a portion of the thrombus is trapped within the infundibulum.

[0067]

[0093] In another embodiment, the method includes directing fluid toward the thrombus at a lower flow rate for a first period of time.

[0068]

[0094] 1. A thrombus removal device comprising: an elongate catheter; a hemispherical funnel disposed at a distal end of the catheter; a suction source coupled to the hemispherical funnel by a suction lumen; a plurality of jets disposed within or near the hemispherical funnel; and a fluid source coupled to the plurality of jets and configured to direct fluid toward a common intersection.

[0069]

[0095] A thrombus removal device is provided that includes an elongate shaft including a working end, an aspiration lumen disposed on the elongate shaft and extending to the working end and coupled to a suction source, at least one fluid lumen within the elongate shaft, two or more openings disposed at or near the working end, the two or more openings in fluid communication with the at least one fluid lumen and configured to generate two or more fluid flows, at least one opening disposed in the aspiration lumen and in fluid communication with the at least one fluid lumen, the at least one opening configured to generate a suction fluid flow, and an electronic controller configured to control the suction source and direct the fluid flow into the at least one fluid lumen.

[0070]

[0096] In some embodiments, the aspiration fluid flow is configured to be directed proximally into the aspiration lumen.

[0071]

[0097] In another embodiment, the device includes a valve disposed within the aspiration lumen and operably coupled to the electronic controller.

[0072]

[0098] In some embodiments, in a normal operating mode, the electronic controller is configured to open the valves and direct fluid flow into two or more openings, but not into at least one opening in the aspiration lumen.

[0073]

[0099] In another embodiment, in the clog removal mode, the electronic controller is configured to close the valve and direct fluid flow into at least one opening in the aspiration lumen.

[0074]

[0005] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings. [Brief description of the drawings]

[0075] [Figure 1]

[0006] FIG. 1 illustrates a portion of a thrombus removal system including a distal portion of an elongated catheter configured in accordance with an embodiment of the present technology. [Figure 1A] FIG. 2 illustrates a cross section AA of the portion of the thrombus removal system. [Figure 1B] FIG. 13 illustrates a BB cross section of the portion of the thrombus removal system. [Figure 1C] FIG. 13 illustrates a BB cross section of the portion of the thrombus removal system. [Figure 1D] FIG. 13 illustrates a BB cross section of the portion of the thrombus removal system. [Figure 1E] FIG. 13 illustrates a BB cross section of the portion of the thrombus removal system. [Figure 1F] FIG. 13 illustrates a BB cross section of the portion of the thrombus removal system. [Figure 1G] FIG. 13 illustrates a BB cross section of the portion of the thrombus removal system. [Figure 1H] FIG. 13 illustrates a BB cross section of the portion of the thrombus removal system. [Figure 1I] FIG. 13 illustrates a BB cross section of the portion of the thrombus removal system. [Figure 1J] FIG. 13 illustrates a BB cross section of the portion of the thrombus removal system. [Figure 1K] FIG. 2 is a diagram illustrating the CC cross section of the portion of the thrombus removal system. [Figure 1L] FIG. 1 illustrates portions of a thrombus removal system. [Figure 2A] FIG. 2A is a plan view illustrating an irrigation port and fluid flow configuration of a thrombus removal system in accordance with an embodiment of the present technology. [Figure 2B] FIG. 2B is a plan view illustrating the above configuration. [Figure 2C] FIG. 2C is a plan view illustrating the above configuration. [Figure 2D] FIG. 2D is a plan view illustrating the above configuration. [Diagram 3]

[0008] Figure 3A is an elevation view illustrating a configuration of an irrigation port of a thrombus removal system in accordance with an embodiment of the present technology. Figure 3B is an elevation view illustrating the configuration. Figure 3C is an elevation view illustrating the configuration. Figure 3D is an elevation view illustrating the configuration. Figure 3E is an elevation view illustrating the configuration. Figure 3F is an elevation view illustrating the configuration. Figure 3G is an elevation view illustrating the configuration. Figure 3H is an elevation view illustrating the configuration. [Figure 4A]

[0009] FIG. 1 is an elevational view illustrating an irrigation port and fluid flow configuration of a thrombus removal system in accordance with an embodiment of the present technology. [Figure 4B] FIG. 2 is an elevational view illustrating the above configuration. [Figure 4C] FIG. 2 is an elevational view illustrating the above configuration. [Figure 4D] FIG. 2 is an elevational view illustrating the above configuration. [Figure 4E] FIG. 2 is an elevational view illustrating the above configuration. [Figure 4F] FIG. 2 is an elevational view illustrating the above configuration. [Figure 4G] FIG. 2 is a diagram illustrating a DD cross section of the above configuration. [Figure 4H] FIG. 2 is a diagram illustrating a DD cross section of the above configuration. [Figure 4I] FIG. 2 is an elevational view illustrating the above configuration. [Figure 4J] FIG. 2 is an elevational view illustrating the above configuration. [Figure 4K] FIG. 2 is an elevational view illustrating the above configuration. [Figure 4L] FIG. 1 is a diagram illustrating the above configuration. [Figure 4M] FIG. 1 is a diagram illustrating the above configuration. [Figure 4N] FIG. 1 is a diagram illustrating the above configuration. [Figure 4O] FIG. 1 is a diagram illustrating the above configuration. [Figure 4P] 1 is a photograph illustrating the above configuration. [Figure 5A]

[0010] FIG. 5A illustrates an example irrigation port configuration of a thrombus removal system in accordance with an embodiment of the present technology. [Figure 5B]FIG. 5B is a diagram illustrating an example of an E-E cross section of the above configuration. [Figure 5C] FIG. 5C is a diagram illustrating an E-E cross section of the above configuration. [Figure 5D] FIG. 5D is a diagram illustrating an E-E cross section of the above configuration. [Figure 5E] FIG. 5E is a diagram illustrating an E-E cross section of the above configuration. [Figure 5F] FIG. 5F is a diagram illustrating an E-E cross section of the above configuration. [Figure 5G] FIG. 5G is a diagram illustrating an E-E cross section of the above configuration. [Figure 6A]

[0011] FIG. 1 illustrates an embodiment of a thrombus removal system that includes a saline source, an aspiration system, and one or more controllers for controlling irrigation and / or aspiration of the system. [Figure 6B] FIG. 2 illustrates an embodiment of the system. [Figure 6C] FIG. 2 illustrates an embodiment of the system. [Figure 7]

[0012] Figures 7A, 7B, 7C, and 7D are diagrams illustrating configurations of the clog detection and / or clog removal features of the thrombus removal system. [Figure 8A] FIG. 8A illustrates one embodiment for controlling the various irrigation ports of the thrombus removal system. [Figure 8B] FIG. 8B illustrates the above embodiment. [Figure 8C] FIG. 8C illustrates the above embodiment. [Figure 9A]

[0014] FIG. 1 is a system schematic diagram of a thrombus removal system. [Figure 9B] FIG. 1 illustrates an embodiment of a thrombus removal system including one or more sensors configured to detect a clot. [Figure 10] 1 is a table illustrating various system states of the thrombus removal system. [Figure 11]1 is a procedural flow chart of various system states of the thrombus removal system. [Figure 12A] FIG. 12A is a diagram illustrating a pressure waveform graph during a clot engagement condition. [Figure 12B] FIG. 12B illustrates a pressure waveform graph during a clot-engaged condition. [Figure 13] 1 is a simplified system schematic diagram of a thrombus removal system. [Figure 14] FIG. 1 illustrates an embodiment of a flow waveform of a thrombus removal system. [Figure 15]

[0021] FIG. 1 is a diagram illustrating an aspiration method of a thrombus removal system. [Figure 16A]

[0022] FIG. 1 illustrates one embodiment of a thrombus removal system. [Figure 16B] FIG. 2 is a diagram illustrating the embodiment. [Figure 16C] FIG. 2 is a diagram illustrating the embodiment. [Figure 16D] FIG. 2 is a diagram illustrating the embodiment. [Figure 17] 13 illustrates various irrigation pump cycles of the thrombus removal system. [Figure 18]

[0024] FIG. 1 illustrates a thrombus removal system having a valve near the suction source. [Figure 19]

[0025] Figures 19A and 19B are diagrams illustrating a thrombus removal system having multiple struts in the infundibulum. [Figure 20A] FIG. 20A illustrates a thrombus removal system having a hemispherical funnel. [Figure 20B] FIG. 20B illustrates a thrombus removal system having a hemispherical funnel. [Figure 21] 1 is a flow chart illustrating a method for assessing the volume of clot removed during treatment. [Figure 22]4 is a flow chart illustrating various mechanisms of fluid flow action disclosed herein. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0076] Detailed Description

[0100] This application is related to the disclosures in International Application No. PCT / US2021 / 020915 (the '915 Application), filed March 4, 2021, the disclosures of which are incorporated herein by reference for all purposes. The '915 Application describes a general mechanism for capturing and removing a clot. For example, a catheter may include a capturing element, such as an auger, to break up and draw the clot material into an aspiration lumen. In another example, multiple fluid streams are directed toward the clot to fragment the material.

[0077]

[0101] The present technology is generally directed to clot removal systems and associated methods. A system configured according to an embodiment of the present technology can include, for example, an elongate catheter having a distal portion configured to be positioned within a patient's blood vessel, a proximal portion configured to be external to the patient, a fluid delivery mechanism configured to fragment the clot with pressurized fluid, an aspiration mechanism configured to aspirate the clot fragments, and one or more lumens extending at least partially from the proximal portion to the distal portion.

[0078]

[0102] The terms used in the description presented below are intended to be interpreted in the broadest possible manner, even when used in conjunction with a detailed description of certain specific embodiments of the present technology. Although certain terms may be emphasized below, any terms intended to be interpreted in some limited manner are clearly and specifically defined in the Detailed Description section of this invention. In addition, the present technology can include other embodiments that are within the scope of the examples but are not described in detail in connection with the figures.

[0079]

[0103] References throughout this specification to "one embodiment" or "an embodiment" mean that a particular feature, structure, or characteristic described in connection with an embodiment is included in at least one embodiment of the technology. Thus, the appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification do not necessarily all refer to the same embodiment. Furthermore, particular features or characteristics may be combined in any suitable manner in one or more embodiments.

[0080]

[0104] Throughout this specification, references to relative terms such as, for example, "generally," "approximately," and "about" are used herein to mean plus or minus 10% of the stated value.

[0081]

[0105] Although some embodiments herein are described in the context of thrombus removal, it is recognized that the technology can be used and / or modified to remove other types of emboli that may occlude blood vessels, such as fat, tissue, or foreign bodies. In addition, while some embodiments herein are described in the context of thrombus removal from the pulmonary artery (e.g., pulmonary embolectomy), the technology may be applied to the removal of thrombi and / or emboli from other parts of the vasculature (e.g., neurovascular, coronary, or peripheral applications). Also, while some embodiments are discussed in the context of macerating the thrombus with a fluid, the technology can be adapted to be used with other techniques (e.g., ultrasound, mechanical, enzymatic, etc.) for fragmenting the thrombus into smaller fragments or particles.

[0082]

[0106] The headings provided herein are for convenience only and do not interpret the scope or meaning of the claimed technology. System for thrombus removal

[0107] As presented above, the present technology is generally directed to a clot removal system. Such a system includes an elongated catheter having a distal portion positionable within a patient's blood vessel (e.g., an artery or vein), a proximal portion positionable outside the patient's body, a fluid delivery mechanism configured to fragment the clot with pressurized fluid, an aspiration mechanism configured to aspirate the clot fragments, and one or more lumens extending at least partially from the proximal portion to the distal portion. In some embodiments, the system herein is configured to engage a clot within a patient's blood vessel, fragment the clot into small fragments, and aspirate the fragments out of the patient's body. The pressurized fluid stream (e.g., jet) functions to cut or macerate the clot before, during, and / or after at least a portion of the clot enters the aspiration lumen or funnel of the system. Fragmentation helps prevent clogging of the aspiration lumen, and fragmentation allows the clot removal system to macerate large, hard clots that could not otherwise be aspirated. As used herein, "thrombus" and "embolism" are used somewhat interchangeably in various respects. It should be recognized that while descriptions may refer to the removal of a "thrombus," this should be understood to encompass the removal of thrombus fragments and other emboli as provided herein.

[0083]

[0108] According to embodiments of the present technology, a fluid delivery mechanism can provide multiple fluid streams (e.g., jets) to the fluid openings of the thrombus removal system to macerate, cut, fragment, pulverize and / or urge the thrombus to be removed from the proximal portion of the thrombus removal system. The thrombus removal system can include an aspiration lumen extending at least partially from the proximal portion to the distal portion of the thrombus removal system adapted for fluid communication with an aspiration pump (e.g., a vacuum source). In operation, the aspiration pump can generate a volume of lower pressure in the aspiration lumen near the proximal portion of the thrombus removal system to urge the aspiration of the thrombus from the distal portion.

[0084]

[0109] FIG. 1 illustrates a distal portion 10 of a clot removal system according to an embodiment of the present technology. Section AA of FIG. 1A illustrates an elevational cross-sectional view of the distal portion. The exemplary section AA of FIG. 1A depicts a funnel 20 positioned at the distal end of the distal portion 10, adapted to engage a clot and / or a tissue (e.g., blood vessel) wall to aid in fragmenting and / or removing the clot. The funnel can have a variety of shapes and constructions, as would be understood by one of ordinary skill in the art from the description herein. The exemplary section AA of FIG. 1A depicts a dual-walled clot removal device construction having an outer wall / tube 40 and an inner wall / tube 50. A suction lumen 55 is formed by the inner wall 50 and is centrally located. A generally annular volume forms at least one fluid lumen 45 between the outer wall 40 and the inner wall 50. The fluid lumen 45 is adapted for fluid communication with a fluid delivery mechanism. One or more openings (e.g., nozzles, orifices, or ports) 30 are positioned in the thrombus removal system such that they are in fluid communication with the fluid lumen 45 and the irrigation manifold 25. In operation, the ports 30 are adapted to direct (e.g., be pressurized) fluid toward a thrombus engaged with the distal portion 10 of the thrombus removal system.

[0085]

[0110] In various embodiments, the system can have an average flow velocity in the fluid lumen of up to 20 m / s to achieve consistent and successful aspiration of the clot. In some embodiments, the fluid source itself can deliver fluid to the jet in a pre-programmed sequence, including a pulsed sequence or some combination of pulsatile and constant flow. In these embodiments, the average pulsed fluid velocity can be up to 20 m / s, but the peak fluid velocity in the lumen can be up to 30 m / s or more during the pulsation of the fluid source. In some embodiments, the jet or opening is 0.0100 inches or more, or only 0.008 inches, to avoid undesirable spraying of the fluid. In some embodiments, the system can have a minimum vacuum or aspiration pressure of 15 inHg to remove the target clot after it has been macerated or comminuted at said jet.

[0086]

[0111] The thrombus removal system can be sized and configured to access and remove thrombus in various locations or vessels within a patient's body. The dimensions of the system may vary depending on the target location, but it should be understood that generally similar features and components described herein may be implemented in a thrombus removal system regardless of application. For example, a thrombus removal system configured to remove a pulmonary embolism (PE) from a patient may have an outer wall / tube sized approximately 3.7-4.3 mm (11-13 Fr), or preferably 4.0 mm (12 Fr), and an inner wall / tube sized approximately 2.3-3.0 mm (7-9 Fr), or preferably 2.7 mm (8 Fr). Meanwhile, deep vein thrombosis (DVT) devices may have an outer wall / tube size of approximately 3.0-3.7 mm (9-11 Fr), or preferably 3.3 mm (10 Fr), and an inner wall / tube size of 2.0-3.0 mm (6-9 Fr), or preferably 2.5 mm (7.5 Fr). Further applications are provided for ischemic stroke and peripheral embolism applications.

[0087]

[0112] Section BB in FIG. 1B illustrates in plan view a portion of the thrombus removal system proximal to the infundibulum and irrigation manifold. Section BB depicts outer wall 140, inner wall 150, aspiration lumen 155, and fluid lumen 145. In some embodiments, in cross section, aspiration lumen 155 is generally circular and fluid lumen 145 is generally toroidal shaped (e.g., cross section 70). It will be appreciated that alternative constructions and / or arrangements of inner wall 150 and outer wall 140 will produce variations in the cross-sectional shapes of aspiration lumen 155 and fluid lumen 145. For example, inner wall 150 can be shaped to form aspiration lumen 155 that is generally elliptical, circular, rectilinear, rectangular, pentagonal, or hexagonal in cross section. Inner wall 150 and outer wall 140 can be shaped and arranged to form fluid lumen 145 that is generally crescent-shaped, diamond-shaped, or irregular in cross section. For example, with reference to cross-section BB in Figure 1C, the region between inner wall 150 and outer wall 140 can include one or more wall structures 165 (e.g., as in cross-section 80) that form respective fluid lumens 145. Wall structures 165 can be formed by lamination between outer wall 140 and inner wall 150, or by extrusion of multiple lumens forming multiple wall structures.

[0088]

[0113] Sections BB in Figures 1D-1H show additional examples of portions of the thrombus removal system that are proximal to the infundibulum and irrigation manifold. Similar to the embodiments described above, the portions in these examples can include an outer wall 140, an inner wall 150, and an aspiration lumen 155. In addition, the illustrated portions of the thrombus removal system can include an intermediate wall 170 disposed between the outer wall 140 and the inner wall 150. The intermediate wall 170 allows for the annular space between the inner and outer walls to be further divided into multiple different fluid lumens and / or auxiliary lumens. For example, referring to Figure 1D, the intermediate wall can be generally hexagonal in shape, and the annular space can include multiple fluid lumens 145a-141 and multiple auxiliary lumens 175a-175f. As shown in Figure 1D, the fluid lumens can be formed by any combination of the outer wall 140 and the intermediate wall 170, or between the intermediate wall 170, the inner wall 150, and two auxiliary lumens. For example, fluid lumen 145a is formed in the space between outer wall 140 and intermediate wall 170. However, fluid lumen 145g is formed in the space between intermediate wall 170, inner wall 150, auxiliary lumen 175a, and auxiliary lumen 175b. In general, the fluid lumens are configured to carry a flow of fluid, such as saline, from a saline source of the system to one or more ports / openings / orifices of the system. The auxiliary lumens can be configured for multiple functions. In some embodiments, the auxiliary lumens can be coupled to a fluid / saline source and an opening used as an additional fluid lumen. In other embodiments, the auxiliary lumens can be configured as steering ports and can include guidewires or steering wires within the lumen for steering the thrombus removal system. Additionally, in other embodiments, the auxiliary lumens can be configured to carry electrical, mechanical, or fluid connections to one or more sensors. For example, the system may include one or more electrical, optical, or fluid-based sensors disposed along any length of the system. The sensors can be used to provide feedback to the system during therapy (e.g., sensors can be used to detect clogs and initiate a clog removal protocol, or determine the appropriate therapy mode based on sensor feedback, such as sequence of injection pulses, sequence of suction, etc.).Thus, the auxiliary port can be used to connect to sensors, for example, via electrical, optical, mechanical / wire, and / or fluid connections. It is also envisioned that the fluid and auxiliary lumens can be configured to carry and deliver other fluids, such as thrombolytic drugs or radiopaque contrast injections, to the target tissue site during treatment.

[0089]

[0114] It should be understood that in some embodiments, all fluid lumens are fluidly connected to all of the jets or openings of the thrombus removal device. Thus, when a flow of fluid is delivered from the fluid lumen(s) to the jets, all of the jets are actuated at once with a fluid jet. However, it should also be understood that in some embodiments, the fluid lumens are separate or different, and these different fluid lumens may be fluidly coupled to one or more jets, but not to all of the jets of the device. In these embodiments, a subset of the jets can be controlled by delivering fluid only to the fluid lumens that are coupled to the subset of jets. This allows for additional functionality of the device where designated jets can be actuated in a user-defined or pre-determined order.

[0090]

[0115] In various embodiments, the fluid pressure is generated by a pump (either in the console or handle). The fluid is accelerated as it exits a port at the distal end and is directed towards the target clot. In this manner, a wider variety of cost-effective components can be used to form the catheter while still maintaining a highly effective device for clot removal. As described in more detail below.

[0091]

[0116] Section BB of FIG. 1E illustrates another embodiment of the portion of the thrombus removal system that is proximal to the infundibulum and irrigation manifold. Similar to the embodiment of FIG. 1D, this embodiment also includes an intermediate wall 170. However, the intermediate wall in this example is generally rectangular, facilitating the formation of fluid lumens 145a-145k and auxiliary lumens 175a-175d. The example shown in section BB of FIG. 1F is similar to the example of the embodiment of FIG. 1E, but this embodiment includes only fluid lumens 145a-145d. Fluid lumens 145e-145k from the embodiment of FIG. 1E are not used as fluid lumens in this embodiment. They can be lumens that are, for example, empty, evacuated, filled with insulating material, and / or filled with radiopaque material or any other material that may be useful for visualizing the thrombus removal system during therapy. Embodiment 1F includes the same four auxiliary ports as illustrated and described in the embodiment of FIG. 1E.

[0092]

[0117] Section BB of FIG. 1G illustrates another example of a portion of the thrombus removal system that is proximal to the infundibulum and irrigation manifold. As with the embodiment described above, the illustrated portion of the thrombus removal system can include an intermediate wall 170 disposed between the outer wall 140 and the inner wall 150. However, this embodiment includes four distinct fluid lumens 145a-d formed by a wall structure 165. As with the embodiment of FIG. 1C, the wall structure 165 can be formed by lamination between the outer wall 140 and the inner wall 150 or by extrusion of multiple lumens forming multiple wall structures. As shown, this embodiment can include a pair of auxiliary lumens 175a and 175b, which can be used, for example, for steering or sensor connection as described above.

[0093]

[0118] Section BB in FIG. 1H is another similar embodiment in which a middle wall and an outer wall can be used to form fluid lumens 145a and 145b. Auxiliary lumens 175a and 175b can be formed in the space between the middle wall and the inner wall. It should be understood that the middle wall can contact the outer wall to create independent fluid lumens 145a and 145b. However, it should be understood that in other embodiments, the middle wall may not contact the outer wall, which would facilitate a single annular fluid lumen as shown by fluid lumen 145 in section BB in FIG. 1I. In another embodiment, as shown in section BB in FIG. 1J, inner wall 150 and outer wall 140 may not be concentric, which would facilitate the formation of a thicker or wider annular space and / or fluid lumen 145 on one side of the device relative to the other side. As shown in FIG. 1J, the distance between the exemplary outer wall 140 and the inner wall at the top (e.g., 12 o'clock) portion of the device is greater than the distance between the outer wall and the inner wall at the bottom (e.g., 6 o'clock) portion of the device.

[0094]

[0119] 1K illustrates in plan view a portion of the thrombus removal system including the irrigation manifold 225. View CC depicts an outer wall 240, an inner wall 250, a fluid lumen 245, an aspiration lumen 255, and ports 230 for directing the respective fluid flows 210.

[0095]

[0120] Detail view 101 of FIG. 1L illustrates an elevational cross-sectional view of a portion of irrigation manifold 25 including a plurality of ports 230 formed in inner wall 250. In some embodiments, the thickness of one or more walls of the thrombus removal system may vary along its axial length and / or its circumference. As shown in detail view 101, inner wall 250 has a first thickness 265 in a region 250 that is proximal to irrigation manifold 25 and a second thickness 270 in a region 235 that includes ports 230. In some embodiments, second thickness 270 is greater than first thickness 265. First thickness 265 can correspond to the overall wall thickness of inner wall 50 and / or outer wall 40, which can be about 0.10 mm to about 0.60 mm, or any value within the aforementioned range. The second thickness 270 can be about 0.20 mm to about 0.70 mm, about 0.70 mm to about 0.90 mm, or about 0.90 mm to about 1.20 mm. The second thickness 270 can be any value within the aforementioned ranges. The dimensions of the second thickness 270 can be selected to provide a fluid path through the port 230 that generates a generally laminar flow for the fluid flow directed therethrough when the fluid delivery mechanism delivers fluid through the fluid lumen 245 at a typical operating pressure. Such operating pressures can be about 10 psi to about 60 psi, about 60 psi to about 100 psi, or about 100 psi to about 150 psi. The operating pressure of the fluid delivery mechanism can be any value within the aforementioned ranges of values. In some embodiments, the fluid delivery mechanism operates in a high pressure mode having a pressure of about 150 psi to about 250 psi, about 250 psi to about 350 psi, about 350 psi to about 425 psi, or about 425 psi to about 500 psi. The operating pressure of the fluid delivery mechanism in the high pressure mode can be any value within the aforementioned range of values.

[0096]

[0121] The manifold is configured to increase the fluid pressure and / or flow rate of the fluid. When the fluid is delivered to the fluid lumen(s) by the fluid delivery mechanism at a first pressure and / or a first flow rate, the manifold is configured to increase the pressure of the fluid to a second pressure and / or increase the flow rate of the fluid to a second flow rate. The second pressure and / or the second flow rate can be higher than the first pressure and / or the first flow rate. As a result, the manifold can be configured to increase a relatively low operating pressure and / or flow rate generated by the fluid delivery mechanism to a relatively high pressure and / or high flow rate generated by the port / fluid stream.

[0097]

[0122] In some embodiments, the profile (cross-sectional dimension) of the port 230 varies along its length (e.g., is non-cylindrical). The variation in the cross-sectional dimension of the port can modify and / or adjust the characteristics of the fluid flow along the port 230. For example, a reduction in the cross-sectional dimension can accelerate the fluid flow through the port 230 (for a given volume of fluid). In some embodiments, the port 230 can be conical (e.g., tapered) along its length such that its smallest dimension is located at the distal end of the port 230, distal relative to the direction of fluid flow.

[0098]

[0123] In some embodiments, the ports 230 are configured to direct the fluid flow along a selected path. FIGS. 2A-2E illustrate various embodiments of arrangements of the ports 230 for directing the respective fluid streams 210. In some embodiments, such as those shown in FIGS. 2A and 2B, at least two ports 230 are arranged to generate (e.g., respective) fluid streams 210 that intersect at an intersection region 237 of the clot removal system. The intersection region 237 can be a region of increased fluid momentum and / or energy transfer relative to the individual fluid streams that are not directed to combine at the intersection. The increased fluid momentum and / or energy transfer at the intersection can advantageously fragment the clot more efficiently and / or quickly. As described above, the fluid streams can be configured to accelerate and cause cavitation and / or other effects to further promote fragmentation of the target clot. In some embodiments, the intersection region can be formed from at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, or at least 10 fluid streams 210. The intersection region can be generally near (e.g., 237) or away from (e.g., 238 and 239 in the embodiment of FIG. 2D) the central axis 290 of the thrombus removal system. In some embodiments, at least two intersection regions (e.g., 238 and 239) are formed. In some embodiments, one or more ports 230 are positioned to direct the fluid stream 210 along an oblique angle relative to the central axis of the thrombus removal system. The operating pressure of the fluid delivery mechanism can be selected to approach a minimum target fluid velocity for the fluid stream 210 delivered from the port 230. The target fluid velocity of the fluid stream 210 can be about 5 meters per second (m / s), about 8 m / s, about 10 m / s, about 12 m / s, or about 15 m / s. Additionally, the target fluid velocity in some embodiments can range from greater than 15 m / s up to 150 m / s. At these higher velocities (e.g., greater than about 15 m / s, or greater than 20 m / s), the fluid stream may be configured to generate cavitation in the targeted thrombus or tissue.It has been found that when fluid exits the ports at these flow rates, it can produce a cavitation effect at the focal area of ​​the intersecting or impinging fluid streams, or at the boundaries of one or more of the fluid streams in addition. The exact specifications may vary based on the size of the catheter, but in general, at least one of the fluid streams should be accelerated to such a high velocity to produce cavitation, as described in detail below. The target fluid velocity of the fluid stream 210 can be any value within the range of values ​​mentioned above. In some embodiments, the at least two ports 230 are adapted to deliver the respective fluid streams at different fluid velocities (i.e., speed and direction) for a given pressure of the fluid delivery mechanism. In some embodiments, the at least two ports 230 are adapted to deliver the respective fluid streams at substantially the same fluid velocity for a given pressure of the fluid delivery mechanism. In some embodiments, one port is adapted to deliver the fluid at a high velocity, and each one or more other ports are adapted to deliver the fluid at a relatively low velocity. Advantageously, the increased cross-sectional area of ​​the fluid lumen 145 reduces the required operating pressure of the fluid delivery mechanism to achieve a target fluid velocity of the fluid flow.

[0099]

[0124] In some embodiments, the fluid streams are configured to create angular momentum that is imparted to the clot. In some instances, angular momentum is imparted to the clot by application of a) at least one fluid stream 210 directed at an oblique angle from the port 230, and / or b) at least two fluid streams 210 having different fluid velocities. For example, fluid streams that pass close to, but do not necessarily intersect each other, may create a "swirl" or rotational energy in the clot material. Advantageously, the angular momentum created in the clot may impart a force (e.g., centrifugal force) that aids in the fragmentation and removal of the clot. Rotating the clot may facilitate delivery of the clot material to the jet. For example, in a large, amorphous clot, the soft material may be easily sucked or fragmented by the fluid stream, whereas the hard material may be located away from the fluid stream. Rotating or swirling the clot moves the material around and delivers the harder clot material to the jet. Swirling may also slam the clot against the inside of the infundibulum for further fragmentation.

[0100]

[0125] 3A-3H, the ports 330 can be positioned along various axial locations of the thrombus removal system. The thrombus removal system can include a flow axis 305 aligned with a general direction of flow (e.g., distal to proximal) for fluid aspirated therein. In some embodiments, the location of the ports 330 includes a) near the base, b) mid-portion, c) distal portion, or d) proximal of the funnel portion 320 of the thrombus removal system. In some embodiments, at least two ports 330 are aligned along the flow axis 305. In some embodiments, at least two ports 330 are positioned at different axial and / or angular locations along the flow axis 305. In some embodiments, at least two ports 330 are positioned along a given axial location of the flow axis 305 (e.g., along the circumference of the thrombus removal system).

[0101]

[0126] 4A-H depict various configurations of fluid streams 410 directed from respective ports 430. The fluid streams 410 can be directed along paths that are substantially orthogonal, proximal, and / or distal to a flow axis 405 (similar to flow axis 305). In some embodiments, at least two fluid streams are directed in different directions relative to the flow axis 405. In some embodiments, at least two fluid streams are directed in the same direction (e.g., proximal) relative to the flow axis 405. In some embodiments, at least a first fluid stream is directed orthogonally, at least a second fluid stream is directed proximally, and at least a third fluid stream is directed distally relative to the flow axis 405. Angle α may characterize the angle at which the fluid streams 410 are directed relative to an axis orthogonal to the flow axis 405 (e.g., as shown in cross sections DD of FIGS. 4G and 4H ). The fluid flow intersection region can be within an interior portion of the thrombus removal system and / or external (e.g., distal) to the thrombus removal system. In some embodiments, the fluid flow that is directed in a nominal direction (e.g., distal) by the port 430 is deflected along an altered path (e.g., proximally) by the (e.g., suction) pressure generated by the suction mechanism during operation.

[0102]

[0127] Cavitation Occurrence

[0128] The exemplary system includes fluid jets configured in a particular manner to enhance clot removal. The exemplary fluid streams or jets have been shown in benchmark studies to dramatically improve clot removal through various mechanisms of action, including but not limited to cavitation and water cutting. In contrast to conventional fluid mechanisms for thrombectomy, in some embodiments herein, the fluid streams 410 from each port 430 are delivered at a flow rate (and pattern) sufficient to create cavitation and / or other preferential effects to improve clot removal. In some examples, the cavitation effect is created by a large pressure drop and deceleration at the focal point and / or intersection of at least two fluid streams. Cavitation can provide a source of turbulent kinetic energy that can be used to mechanically fragment and / or liquefy the clot or other target tissue structure. If the fluid velocity is high enough, the material can accumulate impact energy, causing deformation and fragmentation. This may also modify the surface properties of the clot to allow the material to penetrate and cavitate within the clot. The impact or interaction of the high velocity jets creates hydrodynamic cavitation, whereby a pressure drop below the vapor pressure of the liquid creates bubbles that eventually collapse with great mechanical energy in the cavitation field, causing a kind of implosion in the clot material. Furthermore, with multiple jets directed toward a focal point or close enough to each stream, the closure velocity of the fluid particles is significantly higher (up to twice as high) than that of a single jet stream. This also pushes the fluid and / or particles out of the space between the fluid jets at high velocity. The velocity of the fluid jet is high enough to create a pressure drop below the vapor pressure such that the fluid vaporizes. When the pressure rises again, the bubbles collapse, causing cavitation. The force of the exemplary system and cavitation effect has been found to significantly exceed that of conventional fluid jet(s) and mechanical tools such as rotating screws. In some instances, the collapse of the bubbles can generate heat in or around the target tissue, further promoting the fragmentation of the clot. In baseline studies, systems according to various embodiments were able to remove certain clot material that could not be removed by simple suction or water jets.In other studies, the exemplary system was able to remove clot material in a fraction of the time of conventional systems.

[0103]

[0129] 4I-4K illustrate examples of cavitation 420 generation at the intersection, collision, or interaction of two or more fluid streams 410. With reference to FIG. 4I, fluid streams 410 from at least two ports 430 are directed generally parallel to another fluid stream and perpendicular to the flow axis 405 of the clot removal device. As shown in the embodiment of FIG. 4I, the cavitation 420 is generally confined to the region (e.g., focal point) of interaction between the fluid streams 410. As illustrated, the cavitation 420 can comprise a plurality of microbubbles. When a thrombus is engaged in the funnel of the thrombus removal device, the fluid streams 410 and / or the cavitation 420 can be used to break down, fragment, liquefy, and / or dissolve the thrombus to facilitate aspiration and removal of the thrombus with the device.

[0104]

[0130] In the embodiment of FIG. 4J, the fluid streams 410 from at least two ports 430 are not directed perpendicular to the flow axis 405, but instead are directed slightly distal to the ports to create cavitation 420 in an interaction region distal to the ports 430. In some embodiments, depending on the velocity / flow rate of the fluid streams, the resulting collision of the distally directed fluid streams can additionally create cavitation columns 422 that propagate and / or are distal to the cavitation 420 in the intersection region. When a thrombus is engaged in the funnel of the thrombus removal device in this embodiment, the fluid streams 410 and / or cavitation can be used to fragment, fragment, liquefy, and / or dissolve the thrombus to facilitate aspiration and removal of the thrombus with the device. Additionally, the cavitation columns 422 can provide additional kinetic energy to fragment, fragment, liquefy, and / or dissolve the portion of the thrombus distal to the cavitation 420. It should be understood that while the embodiment of Figure 4J is shown as including a funnel to aid in engaging and aspirating the thrombus, in other embodiments the device may not include a funnel. In these embodiments, cavitation 420 and cavitation column 422 may be used to break down, fragment, liquefy, and / or lyse thrombus located distal to the device and port 430.

[0105]

[0131] In the embodiment of FIG. 4K, the fluid flow 410 from at least two ports 430 is not directed perpendicular to the flow axis 405, but instead is directed slightly proximally from the ports to create cavitation 420 in an interaction region that is proximal to the ports 430. In some embodiments, depending on the fluid flow speed / flow rate, the resulting impingement of the proximally directed fluid flow can additionally create cavitation columns 422 that propagate and / or proximal to the cavitation 420 in the interaction region and are located in the same direction as the aspiration of the clot removal device. When a clot is engaged with the funnel of the clot removal device in this embodiment, the fluid flow 410 and / or cavitation can be used to break down, fragment, liquefy, and / or dissolve the clot to facilitate aspiration and removal of the clot with the device. Additionally, the cavitation column 422 can provide additional kinetic energy to fragment, fragment, liquefy, and / or lyse the portion of the thrombus that is proximal to the cavitation 420, further aiding in the aspirating of the thrombus into the device.

[0106]

[0132] 4L illustrates a top-down view of a thrombus removal device. In this embodiment, the device includes a total of four intersecting or interacting fluid streams 410. As discussed above, the interactions between the fluid streams and / or the flow rates of the fluid streams can create conditions sufficient to generate cavitation 420 in the region of fluid stream interaction. Although this embodiment shows four fluid streams, it should be understood that any number of fluid streams can be implemented to achieve cavitation, including two fluid streams, three fluid streams, or more than three fluid streams.

[0107]

[0133] As described above, the thrombus removal device can include one or more fluid lumens (e.g., fluid lumen 45 of FIG. 1A) configured to supply fluid to one or more openings (e.g., opening 30 of FIG. 1A or port 430 of FIG. 4A-4K). According to one aspect of the present disclosure, cavitation can form at an interaction region between at least two fluid streams when the flow rate of the fluid streams is high enough to create an appropriate pressure drop and deceleration at and around the focus and / or intersection of the streams. In one embodiment, a flow rate of approximately 3 m / s in the fluid lumen(s) of the thrombus removal device results in a fluid stream exiting the port with a flow rate of at least 50 m / s. In this embodiment, two or more fluid streams, each having a flow rate of at least 50 m / s, can be configured to generate cavitation at the interaction region of the fluid streams. In another embodiment, a flow rate of approximately 4 m / s in the fluid lumen(s) of the thrombus removal device results in a fluid stream exiting the port with a flow rate of at least 70 m / s. In this embodiment, two or more fluid streams, each having a flow rate of at least 70 m / s, can be configured to generate cavitation at the fluid stream interaction region. In yet another embodiment, a flow rate of approximately 5 m / s in the fluid lumen(s) of the clot removal device results in a fluid stream exiting the port at a flow rate of at least 90 m / s. In this embodiment, two or more fluid streams, each having a flow rate of at least 90 m / s, can be configured to generate cavitation at the fluid stream interaction region. In general, the clot removal device of the present disclosure is configured to supply fluid to one or more fluid lumens at a flow rate of 3-5 m / s, which correlates with a fluid stream exiting a jet, port, or opening at a flow rate of 50-90 m / s. Fluid streams at these flow rates are configured to generate the appropriate pressure drop and deceleration at the focal point or interaction region of the fluid stream to generate cavitation.

[0108]

[0134] In another embodiment, cavitation at a focus or interaction region of fluid streams can be characterized not by the flow rate of the fluid streams, but instead by the pressure drop at the intersection or passage / shear of the fluid streams. When the pressure drop exceeds a cavitation threshold, cavitation forms at that location. In one embodiment, this pressure drop can be at least 20 MPa. In other embodiments, the pressure drop can be any pressure drop greater than 25 MPa. Since the pressure drop is due to fluid shear, it is possible to produce cavitation at the boundary of a single jet (e.g., halo (i.e., annular) cavitation). Thus, in some embodiments, two fluid streams passing along some common boundary are variations in which the cavitation-producing shear can be produced by two fluid streams moving in both directions at lower velocities, as shown in Figures 4N and 4O and described in more detail below.

[0109]

[0135] In another embodiment, the ports can be arranged in a slightly offset configuration such that the crossing or intersecting fluid streams only partially impinge at the interaction region. In this embodiment, at least four different disruption forces can be applied to the target thrombus, including: 1) a "cutting" or slicing (in other words, slicing) force that initially cuts through the thrombus before the individual fluid streams meet at a focal point or interaction region, 2) cavitation at the focal point or interaction region as the fluid streams intersect, partially intersect, impinge, and / or partially impinge, 3) shear from the jets, focal point, and / or jets moving relative to each other on each side of the interaction region, and 4) swirling or halo rotational fluid motion caused by shear and cavitation forces.

[0110]

[0136] 4M shows a cross-sectional view of such a configuration, with ports 430a and 430b disposed generally opposite one another across the axis, funnel, or lumen of the thrombectomy device, but offset in a manner that prevents the entirety of one fluid stream from impinging with another. While this embodiment generally shows ports on either side of the lumen, funnel, or axis of the device, it should be understood that any of the configurations of ports illustrated herein can be used, so long as the ports are slightly offset to allow only partial impingement of transverse or intersecting fluid streams.

[0111]

[0137] Still referring to FIG. 4M, at least four different rupture forces enabled by this configuration will now be described. During initial actuation or "on" of the fluid flow from ports 430a and 430b, the fluid flow generally travels from the thrombus removal device through the thrombus toward the intersection. While the fluid flow is traveling in this direction, prior to collision, the fluid flow provides a "cutting" or slicing force to the thrombus engaged with the device. As shown, when the fluid flows eventually collide or intersect, ports 430a and 430b are partially offset so that only a first portion 431a of the fluid flow from port 430a directly intersects or collides with a first portion 431b of the fluid flow from port 431b. Such collision or intersection of the fluid flow portions will cause cavitation 420 at the intersection when the flow rate of the fluid flows is sufficient to cause cavitation, as described above. As also shown in FIG. 4L, the second portion(s) 432a of the fluid flow from port 430a does not collide or intersect with the second portion(s) 432b of the fluid flow from port 430b. As such, these second portion(s) of the fluid flow continue past the intersection and past the cavitation 420. However, with the fluid flows passing each other in both, opposing, or different directions, shear flows or shear cavitations 433a and 433b form in and / or around the thrombus, exerting another type of rupture force on the thrombus. In addition, the cavitations, shear flows, and / or interactions between the partially offset ports further result in swirl flows or halo cavitations 434a and 434b, exerting a fourth, different rupture force on the thrombus engaged with the device.

[0112]

[0138] 4N and 4O show additional views of a thrombus removal device that can include some or all of the rupture forces described above. FIG. 4N is a cross-sectional view of the thrombus removal device, and FIG. 4O is a longitudinal slice cut across the fluid stream, as represented by plane 440 in FIG. 4N. In FIG. 4N, the thrombus removal device can include multiple ports 430. In this embodiment, the ports are offset such that none of the fluid streams from each port cross or intersect any of the other fluid streams. However, the ports are positioned such that the fluid streams can pass immediately adjacent to adjacent fluid streams. In this example, a first fluid stream 441 passes immediately adjacent to an adjacent second fluid stream 442, which passes immediately adjacent to an adjacent third fluid stream 443, which passes immediately adjacent to an adjacent fourth fluid stream 444. The passage of close or adjacent fluid streams creates shear flow or shear cavitation 433 between the adjacent fluid streams, as shown. Additionally, as discussed above, the passage of nearby or adjacent fluid streams can further result in swirl or halo cavitation 434. It should be understood that the steady state scenarios described herein are likely to change over time as fluid flows resulting from interactions affect the speed / direction of the fluid flow.

[0113]

[0139] Figure 4O is a view of a thin slice cut across the fluid stream along plane 440 of Figure 4N, showing fluid streams 441 and 442, shear flow or cavitation 433, and swirling flow or halo cavitation 434. It can be seen that the halo cavitation 434 caused by the through flow can swirl or flow in a circle around the respective fluid stream and even pass through or merge into the shear flow or cavitation 433 at the center of the opposing flow. In combination, all of these rupture forces can provide additional rupture energy to act on, fragment, cut, and mechanically fragment a thrombus engaged by the device.

[0114]

[0140] Cavitation Detection

[0141] Because the thrombus removal device can generate cavitation at the intersection region of two or more fluid streams, the thrombus removal device can further include a cavitation detection capability to detect whether and when cavitation occurs within or near the target thrombus. In some embodiments, the cavitation detection capability can detect the location and / or intensity of cavitation. Cavitation detection further provides additional functionality in the operation of the device and provides an additional mechanism for detecting when the device is engaged with a thrombus.

[0115]

[0142] In some embodiments, cavitation detection can be used to determine the interaction between the jet or fluid stream and the target thrombus. For example, when the thrombus is initially engaged in the funnel of the device (e.g., by suction), the jet or fluid stream can be actuated to deliver two or more fluid streams inward toward the focal point or intersection of the two or more fluid streams. However, during this initial actuation of the jet or fluid stream, the thrombus may be positioned or located between the two or more fluid streams, thereby preventing the collision or intersection of the fluid streams. At this point in the therapy, the fluid streams may not yet have intersected, so the thrombus must first be "cut" or broken through. Depending on the flow rate of the fluid stream that initially "cuts" the thrombus, cavitation may not be present.

[0116]

[0143] Cavitation detection can be used to identify scenarios such as: 1) a clot is engaged in the infundibulum; 2) suction is activated; 3) jet or fluid flow is activated but cavitation is not present; and / or 4) jet or fluid flow is activated and cavitation is present. For example, pressure or flow measurements in the aspiration lumen while suction is activated can be used to determine whether a clot is engaged in the infundibulum. Then, if cavitation is simultaneously detected, the system can indicate to the user that a clot is engaged and the jet or fluid flow is creating cavitation in the clot. If cavitation is not detected, the system can indicate to the user that a clot is engaged and the jet or fluid flow is cutting the clot. In some embodiments, a display or indication can be made to the user as to whether cavitation is detected or not. Thus, an indication to the user as to whether cavitation is present or not can provide useful information to the user as to the status or state of the therapy (e.g., whether a clot is engaged, whether cutting is occurring, or whether cavitation is occurring).

[0117]

[0144] As the treatment progresses, the jets or fluid streams eventually cut the clot within the infundibulum, causing the two or more jets to intersect at a focal point. When this event occurs, if the fluid streams have sufficient flow rates (e.g., 20-90 m / s or more, as described above), the two or more intersecting fluid streams can be configured to generate cavitation at the focal point. It should be appreciated that in many circumstances, this cavitation can further provide mechanical fragmentation and / or liquefaction of the clot at the focal point, with the clot still engaged in the infundibulum of the clot removal device. In some embodiments, the therapy includes cycles of alternating "cutting" and cavitation. As the clot moves around within the infundibulum and is fragmented into smaller pieces or portions and aspirated into the clot removal device, the fluid streams may intersect, thus causing cavitation, or the fluid streams may not intersect (e.g., perhaps because the clot is preventing the intersect), but instead rely on the "cutting" nature of the jets to fragment the clot.

[0118]

[0145] In some embodiments, the ability to detect cavitation can be used to direct the jet and / or suction control scheme of the clot removal device. For example, it may be beneficial to alternate between a "cut" mode and a "cavitation" mode of the clot removal device. In one example, the jet is activated to "cut" the engaged clot until cavitation is detected. Once cavitation is detected, the jet can remain activated for a pre-set period of time. The jet can then be briefly pulsed or turned off while leaving the suction on, and the clot can migrate or move deeper into the infundibulum. The jet can then be reactivated to restart the cycle of "cut" mode followed by "cavitation" mode. In some embodiments, it may be desirable to avoid cavitation and instead rely solely on the cutting mechanism being activated. In this case, cavitation detection can be used to warn or indicate to the user that cavitation has formed. In some embodiments, the device automatically pauses or pulses jetting once cavitation is detected to allow the infundibulum to fill with clot and for the jet to resume the cutting process.

[0119]

[0146] Returning to FIG. 4I, in some embodiments, the thrombus removal device can include a cavitation detection sensor 424. The cavitation detection sensor can include, for example, an ultrasonic transducer element or a hydrophone. The sensor may detect cavitation by directly and / or indirectly monitoring the cavitation. In the case of indirect monitoring, the sensor monitors a characteristic of the fluid flow and identifies the desired cavitation based on a known correlation. The correlation may vary based on the size and shape of the catheter end (or funnel), the orientation of the jet and focus, etc. In the embodiment of FIG. 4I, the device is shown having a cavitation detection sensor 424 in the funnel and a second cavitation detection sensor 424 in the shaft / aspiration lumen of the device. While only the embodiment of FIG. 4I is illustrated as including a cavitation sensor(s), it should be understood that any embodiment or jet configuration described herein can further include one or more cavitation sensors. In general, these cavitation detection sensors can be directed or pointed toward the intersection of two or more fluid streams. It should be understood that in other embodiments, these devices can include one or more cavitation detection sensors. The sensor may be located only in the infundibulum, only in the shaft / aspiration lumen, or a combination of both, as shown. In general, the cavitation detection sensor can be located anywhere in or on the device that provides an acoustic path between the sensor and the target cavitation region. Although only the embodiment of FIG. 4I shows a device with a cavitation detection sensor, it should be understood that any of the thrombus removal devices described herein can include such functionality, including the embodiments of FIG. 4J and FIG. 4K. It should be understood that in these embodiments, the cavitation detection sensor can be configured to sense and / or detect both cavitation 420 and cavitation column 422, as those embodiments include distally and proximally directed fluid flows, respectively, thereby enabling the formation of cavitation columns.

[0120]

[0147] Other types of sensors are proposed, including microphones configured to detect cavitation, or lasers configured to detect temperature changes at the intersections when cavitation occurs.

[0121]

[0148] In addition to cavitation detection with sensors disposed on or within the device, in other embodiments, the thrombus removal device can be used in combination with a separate cavitation detection device, such as a real-time imaging device. For example, cavitation can be identified as a region of hyperechoicity in real-time B-mode ultrasound imaging. Thus, in one embodiment, the ultrasound imaging device can be directed toward the target thrombus and used to identify in real time when cavitation occurs, providing real-time feedback to the physician or surgeon during the thrombus removal procedure. The ultrasound imaging device can, for example, comprise an external ultrasound imaging probe (e.g., placed in contact with the patient's skin). Alternatively, the ultrasound imaging device can comprise an internal or catheter-based (in other words, attached to a catheter) ultrasound imaging probe configured to be advanced with or within the thrombus removal device to the target thrombus location.

[0122]

[0149] FIG. 4P is a photograph of a benchtop experiment showing the formation of cavitation at the interaction region of four interacting or intersecting jets or fluid streams. In this experiment, a fluid source (e.g., a water pump, etc.) was pulsed to have a peak operating pressure of 200 psi to 750 psi. The fluid source was then able to create a flow rate into the fluid lumen of the device that had an average velocity of 2 m / s to 10 m / s. The flow rate in the fluid lumen resulted in an average velocity from the jet orifice of 50 m / s to 200 m / s. With the same setup, the fluid source was operated with a pulsating pressure to create an average velocity from the jet orifice below 10 m / s and no cavitation was observed.

[0123]

[0150] 5A-5G show various exit aperture geometries in which the port 530 can be configured according to embodiments of the present technology. The aperture geometries can include oval, circular, cross ("x"), "t", rectangular, or square. The fluid flow delivered from the port 530 can include substantially laminar (e.g., at the aperture) or turbulent (e.g., fanning out) flow. The size of the port 530 can be adjusted to achieve appropriate exit velocity and acceleration of the fluid flow. In some embodiments, the size of these ports can be optimized to achieve flow rates of 50-90 m / s to create cavitation at the intersection of two or more fluid streams. In general, smaller ports create faster fluid flows, but at the expense of a smaller volume of fluid exiting the port, thus less kinetic energy being transferred.

[0124]

[0151] 6A-6C illustrate various configurations of a clot removal system 600 including a clot removal device 602, a vacuum source and canister 604, and a fluid source 606. In some embodiments, the vacuum source and canister and the fluid source are housed in a console unit that is removably connected to the clot removal device. A fluid pump can be housed in the console or in the handle of the device. The console can include one or more CPUs, electronic controllers, or microcontrollers configured to control all functions of the system. The clot removal device 602 can include a funnel 608, a flexible shaft 610, a handle 612, and one or more controllers 614 and 616. For example, in the embodiment shown in FIG. 6A, the device can include a finger switch or trigger 614 and a foot pedal or switch 616, which can be used to control aspiration and irrigation, respectively. Alternatively, as shown in the embodiment of FIG. 6B, the device can include only a foot switch 616 that can be used to control both functions, or in FIG. 6C, the device can include only a footstool 616 that is also used to control both functions. It is also envisioned that embodiments can include only a finger switch for controlling both the aspiration and irrigation functions. As shown in FIG. 6A, a vacuum source can be coupled to the aspiration lumen of the device with a vacuum line 618. Any blood clots or other debris removed from the patient during therapy can be stored in a vacuum canister 604. Similarly, a fluid source (e.g., a saline bag) can be coupled to the fluid lumen of the device with a fluid line 620.

[0125]

[0152] Still referring to FIG. 6A, electronics lines 622 can couple any electronics / sensors etc. from the device to the system console / controller. The system console including the CPUs / electronic controllers can be configured to monitor fluid and pressure levels and adjust automatically or in real time as needed. In some embodiments, the CPUs / electronic controllers are configured to control vacuum and irrigation as well as electromechanically stop and start both systems in response to sensor data such as pressure data, flow data etc.

[0126]

[0153] As mentioned above, suction occurs down a central lumen of the device and is provided by a vacuum pump in the console, which may include a container to collect any clots or debris that is removed from the patient. Blockage detection and clearing

[0154] In some circumstances, the device may become clogged with clots or other debris during therapy. Many clog detection and clog removal schemes can be implemented in the clot removal system. In general, clogs in the system or device can be detected with any number of sensors disposed in or around the device. For example, pressure sensors can be disposed in any number of locations, on or in the funnel, on or in the fluid lumen, or on or in the aspiration lumen of the device or system. The sensor data can then be used to monitor the operation of the device. For example, a pressure sensor in the aspiration lumen can indicate whether the device is clogged with clots or other debris. The system can monitor the pressure in the aspiration lumen, and a significant change in pressure from a normal operating pressure can indicate a problem with the device or therapy. For example, a pressure sensor reading that is significantly reduced from a normal operating pressure range can indicate that a clot or other debris is clogging the device or system proximal to the pressure sensor. Similarly, a pressure sensor reading that is significantly increased from the normal operating pressure range may indicate that a clot or other debris is clogging the device or system distal to the pressure sensor. Thus, pressure sensors disposed along the length of the device can be used in this manner to determine if the device is clogged and further identify where along the length of the device the clog is located based on which pressure sensors have higher than normal pressure readings and which pressure sensors have lower than normal pressure readings. Similarly, flow meters or flow sensors can be used to monitor the flow of fluid in the fluid lumens and / or the flow of debris, blood, and clots in the aspiration lumen. These flow sensor readings can be used to determine if the aspiration or flow lumens (and potentially the jets or openings) are clogged or blocked.

[0127]

[0155] In one embodiment, the system can be configured to generate the vacuum suction with a selectively controllable large volume piston pump, which can automatically shut off the vacuum if a pressure sensor and / or other sensor within the thrombectomy device detects a sudden change in vacuum pressure as a result of a clog. Once detected, the system can be configured to automatically shut off the irrigation jet and the vacuum piston that creates the vacuum, instantly removing the vacuum pressure to reduce blood loss and prevent overirrigation of the patient.

[0128]

[0156] In another embodiment, when the system detects a clogged device, the system can be configured to automatically stop irrigation and aspiration and then execute a clog removal routine that rapidly cycles vacuum pressure to induce a "fluid hammer" effect to dislodge the clot or clog.

[0129]

[0157] Additional embodiments are provided for removing clogs or clots from a device. With reference to FIG. 7A, a clot removal device can include multiple jets 730 disposed along the length of the device, including along the axis of the device. In some embodiments, the jets can be pointed at different angles to help move the clot or debris proximally along the device. For example, the jets can be aimed generally proximally along the axis of the device to push or urge the clot in that direction.

[0130]

[0158] In another embodiment, referring to Figures 7B and 7C, the clot removal device can include a valve 732 disposed on or within the aspiration lumen. The valve can include a flapper valve, a shunt valve, a duckbill valve, or the like. Figure 7B shows the valve in an open position, and Figure 7C shows the valve in a closed position. During normal operation of the system, the valve remains in the open position, allowing clots and other debris to be removed from the patient. If a clog is detected by the system, the valve can be closed to seal the aspiration lumen of the device, as shown in Figure 7C. With the valve closed, an irrigation jet 734 positioned proximal to the valve in the aspiration lumen can be activated to generate pressure behind (e.g., distal to) the clot, thereby pushing it out of the device and into a vacuum canister.

[0131]

[0159] 7D, another embodiment of the device includes a distal balloon 736 that can be inflated to seal the inner lumen of the device when a clot is detected. The system can then be configured to irrigate the blocked and sealed lumen with a jet 734, creating pressure behind the clot as described above.

[0132]

[0160] In some embodiments, a conventional vacuum pump via a peristaltic or diaphragm pump is used, another method to prevent blood loss by reducing the vacuum pressure can be to clear or shunt the vacuum chamber when a clot or blockage is removed. Injection control method

[0161] As mentioned above, in some embodiments, the fluid lumens can be different and separate, whereby individual jets can be controlled to deliver a fluid flow while other jets are not activated or delivering fluid. The system can be configured to respond to pressure sensing and the volume of fluid injected and removed. These control schemes can vary the amount of irrigation and aspiration, as well as sequence or pulse the individual lumens to provide different cutting or clog removal results. This facilitates many novel jet control schemes used by the clot removal device to fragment / macerate the clot and / or aid in removing the clot from the patient. For example, referring to Figures 8A-8C, a cross section of a clot removal device is shown along with an example of a jet control scheme. In this embodiment, jets 830a-830d can each be fluidly coupled to a fluid source with an independent or different fluid lumen. Thus, in Figure 8A, only jet 830d is activated and a fluid flow or jet can be delivered by jet 830d into the aspiration lumen of the device. Similarly, in FIG. 8B, only jet 830c is actuated, and in FIG. 8C, only jet 830b is actuated.

[0133]

[0162] It should be understood, then, that when the jets are delivered by separate fluid lumens, any number of jet control schemes can be incorporated into the treatment with the thrombectomy device. For example, with reference to FIG. 8A, in one embodiment, the device can rapidly cycle from delivering a jet of fluid from each of the jets in sequence (e.g., first jet 830a for a preset time, then jet 830b, then jet 830c, then jet 830d, etc.). Similarly, pairs or groupings of jets can be activated while other jets are not activated. For example, the order of jets can be cycled between activating only the opposing pair of jets 830a and 830c, and then activating only the opposing pair of jets 830b and 830d.

[0134]

[0163] While the above embodiment describes actuating one or more jets in a radial pattern around the circumference of the device, it should be understood that the jetting control scheme can also be used longitudinally along the device. Recall, for example, that the embodiment of FIG. 7A included multiple jets arranged along the length of the device. In one embodiment, a jetting control scheme can be implemented in the system to rapidly cycle between jetting in a distal to proximal direction (e.g., actuating the most distal set of jets first, then the most distal jets, etc., until the most proximal jets are actuated). It is envisioned that such a control scheme would move or urge along difficult, large, or stubborn clots to remove them from the device.

[0135]

[0164] The suction of the system can also be pulsed or timed with the irrigation jets to maximize effectiveness and reduce blood loss. For example, in some embodiments, the suction is pulsed to coincide with the jet irrigation. In other embodiments, the suction is pulsed or actuated between the jets of the jet.

[0136]

[0165] 9A and 9B are schematic diagrams of a clot removal system and a clot removal device, respectively. With reference to FIG. 9A, the system can include a pulmonary artery pressure (Ppa), a pressure vacuum source (Pvs), a pressure jet source (Pjs), a vacuum system fluid resistance (Rvs) and fluid capacitance (Cvs) of the aspiration / vacuum portion of the device, a fluid resistance (Rjs) and capacitance (Cjs) of the jet portion of the device, and multiple test points T1-T7 for testing the pressure or flow of the system. Any number or type of pressure and / or flow sensors can be implemented in the system. In addition, other types of sensors can be used. For example, electrodes or impedance sensors can be used to measure impedance at the distal end of the system (e.g., to characterize changes in electrical impedance associated with clots versus blood). In other embodiments, a temperature sensor (e.g., one or more thermistors) can be used to sense the temperature of the device or the target tissue. In additional embodiments, the vacuum source or jet source can be configured as a sensor, such as using a back-EMF or fluid column sensor connected to the aspiration or jet lumen.

[0137]

[0166] The pressure vacuum source (Pvs) can be a vacuum source (a trap where low pressure gas is maintained above the aspirate) or a positive displacement source, both of which induce a negative pressure distal to the CNTs (if present, as may not be required with positive displacement pumps). Engagement with a clot or the like can be characterized by either difference between the expected flow rate or rate of change of flow rate and the measured flow rate if the difference is large enough.

[0138]

[0167] Referring to FIG. 9B, CNTs represents a junction or connection between the pressure vacuum source and the thrombus removal device, and CNTj represents a junction or connection between the pressure jet source and the thrombus removal device. The valves of CNTs and CNTj can isolate the capacitance of the vacuum / jet source from the rest of the system, thereby minimizing the amount of blood drawn into the system when the vacuum system is stopped or terminated. Referring to FIG. 9A, test points T1 and T2 can represent pressure or flow sensor locations configured to provide pressure / flow readings at locations between the pressure vacuum source and the device, and between the pressure jet source and the device, respectively. Test points T4 and T3 can similarly represent pressure or flow sensor locations configured to provide pressure / flow readings at locations near the junction or connection between the device and the pressure vacuum source and pressure jet source, respectively. In addition, test points T5, T6, and T7 can represent pressure or flow sensor locations configured to provide pressure / flow readings at locations near the distal end of the device. For example, test point T5 can provide a flow / pressure reading at or near where the jet fluid exits the jet port or nozzle at the distal end of the device. Similarly, test points T6 and T7 can provide aspiration system pressure / flow readings at or near the distal end of the device, such as in the funnel (T6 in FIG. 9B) or in the thrombectomy device just proximal to the funnel (T7 in FIG. 9B). The test point locations in the system schematic illustrate potential test / sensor locations for pressure sensors, flow sensors, or other sensors that can be used in real time to control device operation, detect system operating parameters, detect clogs, etc.

[0139]

[0168] 9B, an embodiment of a thrombus removal device is shown that includes test points T6 and T7 for sensing flow and / or pressure in the infundibulum and the aspiration lumen of the device, and tactile sensors H1 and / or H2 for detecting contact with a clot or other debris in the patient. In some embodiments, the tactile sensors can comprise pressure sensors (positive or negative), optical sensors, electrical impedance sensors (DC, single frequency, or spectroscopic), or other sensors useful in the operation of the system.

[0140]

[0169] Procedures and System Controls

[0170] 10-12 illustrate schematic diagrams of procedural flow and system control for a thrombus removal system according to various embodiments, including clot detection, clot engagement, and clot removal.

[0141]

[0171] FIG. 10 is a table describing the various states of the clot removal system, including the associated sensor reading(s) found in each state. In general, the clot removal system can include searching for clot / no clot engaged state, engaged clot state, clot engaged state, clogged jet lumen state, clogged suction lumen state, and clot incipient engaged / leak state. As described above, sensors can be disposed throughout the system, including at or near the distal end of the device (e.g., at or in the infundibulum and / or in the suction lumen), at or near the proximal end of the device, and / or outside the device, at or in the pressure and / or jet / fluid source. These groupings of sensor readings can generally be used to determine which state the clot removal system is in, and can further be used to inform and control the device into the next state throughout therapy. With reference to the table of Figure 10, when the sensor is in a nominal or (+) state it reflects a signal indicative of engagement with a clot, and when the sensor is in a non-nominal or (-) state it reflects a signal indicative of the device not engaging a clot. In some embodiments, a nominal state may correspond to a sensed parameter within a given range (e.g., a specified pressure or flow range) and a non-nominal state may correspond to a sensed parameter (e.g., pressure or flow) exceeding a threshold pressure. In one embodiment, the nominal range of pressure may be approximately +13.546 to -84.660 kPa (+4 to -25 inHg).

[0142]

[0172] For example, referring to the table of Figure 10, when the clot removal system is searching for a clot-engaged / non-clot-engaged state, all of the sensors, including the distal sensor, the proximal sensor, and the source sensor, can be in a non-nominal state. However, when the system is engaged with a clot, both the source sensor and the distal sensor(s) can be in a nominal state, and the proximal sensor(s) remain in a non-nominal state. When the clot removal system is in a clot-engaged state, all of the sensors are in a nominal state, as shown in Figure 10.

[0143]

[0173] The sensors can also signal errors in the system, including clogged lumens (aspiration or jet lumens) and leaks in the system. For example, still referring to FIG. 10, the source and proximal sensors in a nominal state and the distal sensor in a non-nominal state can indicate that one or more of the jet lumens are clogged. Similarly, the source sensor in a nominal state and the proximal / distal sensors in a non-nominal state can indicate a clog in one or more of the aspiration lumens. Finally, the proximal and distal sensors in a nominal state and the source sensor(s) in a non-nominal state can indicate a leak in the system, or that a clot has initially engaged. Further details of the sensors, their measurements, and how the system determines the system state based on the measurements are discussed below.

[0144]

[0174] 11 is a flow chart illustrating the various system states that a thrombus removal system may cycle through during a thrombus removal procedure. Referring to step 1102 of the flow chart, a thrombus removal system or device may be inserted into a patient's vasculature and a distal end of the device may be advanced and delivered to a target tissue site containing one or more thrombi. At this point, a user of the device may initiate, push, or begin a clot retrieval routine in the thrombus removal system at step 1104 (e.g., by pushing a button on the handle of the system or a button on the generator, etc.). In some embodiments, the system may begin the clot retrieval routine automatically.

[0145]

[0175] When the clot removal system actively enters the clot retrieval routine in step 1104, the system monitors various sensors (such as flow or pressure sensors) to determine if / when the clot removal system has engaged one or more clots at the target tissue location. While in this clot retrieval state, the system can operate the suction source to pull a vacuum to help capture the clot into the infundibulum of the device. In some embodiments, suction can be at a normal level (e.g., the same level of suction that is applied when the clot is being removed), while in other embodiments, suction can be at a lower level or at some minimum level. In this state, jetting can also be turned off completely or at a lower or minimum level to help capture the clot. As discussed above, the system can include any number of pressure and / or flow sensors located at several locations on or within the system. The system can also use the jetting ports / jet lumens as sensors to notify the system of certain conditions and guide therapy steps.

[0146]

[0176] FIG. 12A illustrates a pressure waveform Pw of a distal sensor of a thrombus removal system, such as a distal sensor located on or in the infundibulum or distal lumen of the device, or using an injection port or lumen as a distal pressure sensor (negative pressure / no suction at injection opening to local pressure). This allows for measurements at lower flow rates than required for an aspiration lumen. With reference to the diagram of FIG. 12A, Ppa is the pulmonary artery pressure, Pab is the pressure at ambient or atmospheric pressure, and Pt is a predefined pressure threshold. Various regions of the pressure wave Pw are shown, including a. region indicating the device is not engaged with a clot and is measuring cardiac-induced pulmonary artery fluctuations, b. region indicating the sensed pressure is dropping as a function of engagement with a clot, c. region indicating the pressure is below a predefined threshold Pt where the fluctuations are masked, and d. region indicating either the time the pressure source is activated and / or the time the device begins to contact the clot.

[0147]

[0177] Many features of the pressure wave Pw in FIG. 12A can be used or identified to indicate that the device has engaged a clot. Typically, Ppa is measured prior to engaging a clot to provide a baseline of pressure at the target tissue location. In one embodiment, the pressure wave Pw can drop below a predefined pressure threshold Pt to indicate to the system that a clot has been engaged. This can move the system state to the engaged state 1108 in FIG. 11. Additionally, the system state can move to clot engagement if the pressure fluctuations disappear or drop below a threshold as in a percentage of area a of the pressure waveform. In another embodiment, the system state can move to the engaged state if the rate of change in area b of the pressure waveform is greater than a threshold level. The rate of change in area b can provide information on the quality of engagement, for example, a decrease or increase in the number of ports engaged at the port level, but essentially, if all ports are clot engaged, |DP / dt| as the capacitance of the system is smaller. Any combination of the above conditions can allow the system to identify or determine that a clot is engaged at the distal end of the device, in the infundibulum.

[0148]

[0178] FIG. 12B illustrates a pressure waveform Pw of a distal sensor of a thrombus removal system, such as a distal sensor located on or in the infundibulum or distal lumen of the device, or using an injection port or lumen as a distal pressure sensor (low positive pressure / suction on). Again, the figure includes various regions of the pressure wave Pw, including, for example, a. region indicating that the device is not engaged with a clot and is measuring cardiac-induced pulmonary artery fluctuations, b. region indicating that the sensed pressure is rising as a function of engagement with a clot, c. region indicating that the pressure is above a predefined threshold Pt where the fluctuations are hidden, and d. region indicating either the time when the pressure source is activated and / or the device begins to contact the clot. In FIG. 12B, engagement is determined when the pressure of the pressure waveform Pw increases above the aspiration pressure as the clot pushes against the distal pressure sensor (e.g., an injection port or a dedicated port or sensor not used for injection).

[0149]

[0179] In addition to the pressure changes measured by the sensor and described above in Figures 12A and 12B, clot engagement can be identified when the pressure changes are modulated by the intervention of one or any combination of the following scenarios:

[0150]

[0180] 1) Flow induced in a suction line either towards or away from a pressure vacuum source (Pvs). As mentioned above, the Pvs may be configured as a pressure source such as a vacuum trap, or as a positive displacement pump, or a combination of these.

[0151]

[0181] 2) Flow induced in one or more of the jet lines, either towards or away from a pressure jet source (Pjs), which may be configured as a pressure source, such as a volume of fluid maintained under pressure or periodically pressurized, or as a positive displacement pump, or a combination thereof.

[0152]

[0182] 3) A change in electrical impedance measured by a distal electrode or impedance sensor.

[0153]

[0183] 4) Any change in any combination of the above.

[0154]

[0184] The flow described in 1) and 2) above may be induced by a number of conditions, including a relatively constant delta P across the line or a pulsating pressure across the line. In some embodiments, the pulsation is configured to minimize the total amount of fluid displaced into or out of the system. For example, a small amount of fluid (e.g., 1-10 mL) can be drawn in and out of the aspiration line with the pulsation. In this example, dQ / dt is greater for inflow than outflow, increasing the flow resistance and inducing the clot into the infundibulum. Engagement is indicated by a sudden increase in pressure and / or flow rate. In another example, a smaller amount of fluid (e.g., 0.1-1 mL) can be drawn into the jet line or jet port. In this example, engagement is indicated by a decrease in pressure and / or flow rate. In yet another embodiment, clot engagement can be determined by discharging a volume of fluid at a constant flow rate by the jet while drawing fluid into the system by the aspiration, and noting the pressure increase on the pressure line, where engagement is indicated by an increase in pressure and / or flow rate.

[0155]

[0185] Once engagement with a clot is sensed as described above, the system can move to the Engagement Routine / Clot Removal State, as shown in FIG. 11. First, to confirm engagement, the system can turn off the jet flow (if activated), reduce the aspiration pressure to less than Pa_on (e.g., 33.864 kPa (10 inHg absolute), and test the rate of |dPa / dt|. If this tested rate is |dPa / dt|> / =Pa_on / sec, the system can begin aspiration and jetting to remove the clot. However, if that condition is not met, the test can continue. If engagement is not confirmed after repeated testing, the system can be removed.

[0156]

[0186] During blood clot removal / engagement, the system can continue to sense that engagement with the blood clot is maintained, as indicated by maintaining Pa < Pa_on. When engagement with the blood clot is maintained, the nozzle of the thrombus removal system can be actuated to provide an average fluid velocity Vjet greater than 10 m / s (and optionally greater than 20 m / s, or greater than 40 m / s). The flow of the jet from the nozzle can be any combination of pulsatility with a non-zero minimum value, pulsatility with a minimum value of zero, constant, or a negative minimum value.

[0157]

[0187] Pa can be continuously monitored during blood clot removal. If Pa > Pa_on, system changes can include either turning off the nozzle and returning to the blood clot engagement function (as described above) or gradually decreasing the jet average velocity Vjet. If Vjet < Vjet minimum value, the system can return to blood clot engagement. If Pa < Pa_on during continuous monitoring, the blood clot removal process can continue.

[0158]

[0188] In some embodiments, the system can monitor Qasp (flow in the suction line) and Qjet (flow in the jet line) and / or calculate Q’s from the resistance and capacitance of the system. In this embodiment, if Qjet >= Qasp, the system can return to engagement, otherwise blood clot removal can continue.

[0159]

[0189] After the engagement routine has progressed, and referring to FIG. 11, in step 1110, the system may move to determine whether the clot has been dislodged. If the system determines in step 1112 that the clot has been dislodged, the process flow chart may return to the pre-search routine state where the system is not actively searching for the clot or actively attempting to engage / remove the clot. Generally, however, the dislodged state or occlusion test procedure involves evaluating or monitoring the blood flow through the distal end of the thrombus removal system to evaluate an improvement in blood flow (as a result of the clot removal). In addition to identifying an increase in flow using a flow or pressure sensor, other techniques may be used by the system. For example, in some embodiments, flow monitoring may be accomplished using thermodilution and / or time of flight. For example, a volume of cold fluid (e.g., cooler than body temperature) may be delivered into the target tissue location and its temperature may be monitored at another sensor location. For example, the cold fluid may be delivered at test location T7 (FIG. 9B) and the temperature may be measured at test location T6. Alternatively, heated fluid can be delivered at T7 and the temperature monitored at T6. In another embodiment, the system can inject a contrast agent into the target location by an injection system or by a dedicated lumen, which can be visualized to determine if the clot has been removed.

[0160]

[0190] However, if the system determines that the device is clogged or the clot has not been dislodged, then in step 1114 the system may engage in a clog or clearance routine to attempt to unclog the device or remove the clot. Clearance / clearance protocols have been previously described in this disclosure, but in general the system may use any number of procedures including continuing to aspirate / inject, reversing the aspirate and / or jet pressure, aspirating without jetting or jetting without aspirating, or any number of other clearing or clogging routines. If the system determines in step 1116 that the clot has been dislodged, the process flow chart may return to a pre-search routine state where the system is not actively searching for a clot or actively attempting to engage / dislodge a clot.

[0161]

[0191] FIG. 13 is a simplified system schematic illustrating the system elements of the clot removal system required to perform the procedures and methods described above. In general, the system can include an electronic controller configured to control the operation of both the vacuum / suction source and the fluid (jet) source of the system. Sensors can be located throughout the system, including in the vacuum / fluid source and in the device (both proximal and distal). As described above, the sensors can include pressure, flow, impedance, etc. Sensor measurements, along with error signals, can be input into the controller to control the operation of the device. Blood flow in the vessel can also be monitored to help determine when a clot has been dislodged or engaged.

[0162]

[0192] In contrast to the above-described embodiments that use pressure sensing or pressure waveforms to aid in the device's control strategy, in other embodiments, the device can control system states based on flow measurements within the system, such as aspiration or irrigation flow rates. Additionally, any of the control strategies described herein can be combined with another. For example, a pressure control strategy can be combined with a flow control strategy. As shown in Figures 9A-9B and described above, multiple test points T1-T7 can be provided in the system to test the flow rate within the system. Any number or type of flow sensors can be implemented at the test points in the system or at other points in the system, particularly in the funnel and aspiration lumen(s) of the device.

[0163]

[0193] FIG. 14 illustrates an aspiration flow (Q) waveform that may be sensed by one or more flow sensors located within the system, such as at test points T1-T7, but particularly sensors associated with aspiration flow (e.g., test points T1, T4, T6, and T7). The waveform in FIG. 14 illustrates the aspiration flow over time as the system chases or seeks a new clot, engages the clot, and begins treating / removing the clot. Many features of the flow wave Q in FIG. 14 can be used or identified to indicate that the device has engaged a clot and provide insight into clot behavior within the device, including within the infundibulum. Any determinations the system makes as a result of the measured flow wave Q can be indicated to the user. For example, the system can indicate to the user (e.g., with a display, indicator, or audio signal) whether the system is partially engaged, fully engaged, or not engaged with the clot. Typically, Q is measured when suction is activated prior to engaging the clot, either at a clot-engaging level or at some aspiration flow level lower than the clot-engaging level (e.g., a clot-seeking level), to provide a baseline of flow rate at the target tissue location. Note that as shown in the embodiment of FIG. 14, suction is activated but the water jets have not yet been activated. However, in other embodiments, the water jets may be activated during any of the phases of the curve illustrated in FIG. 14. The flow rate Q while the system is searching for clots is shown in region a of the waveform in FIG. 14.

[0164]

[0194] In FIG. 14, as the flow wave Q begins to drop, as shown in region b, the measured flow rate can indicate to the system that the clot has been engaged. In some embodiments, the slope of the flow waveform, dQ / dt, can be used by the system to determine if there is clot engagement. In some embodiments, the rate or slope of the flow waveform can indicate the "quality" of the engagement with the clot. For example, the greater the rate of fall, the greater the resistance (reduced flow path around the clot) induced by the interface between the clot and the funnel. The actual rate depends on system parameters such as component volume, dimensions, source flow rate, component capacitance, and / or pressure. Eventually, the flow wave Q will be approximately zero (or some non-zero minimum), as shown in region c of FIG. 14, indicating that the clot is fully engaged or seated within the funnel of the device. This can result in the system state moving to the engaged state 1108 in FIG. 11. Additionally, the system state can move to the clot engaged state if the pressure fluctuation disappears or falls below a threshold, such as at a certain percentage of the flow waveform. For example, section d of the wave in Figure 14 is slightly above zero but below the threshold that indicates to the system that the clot is engaged or partially engaged. This above zero flow rate could be the result of the jet being turned on or it could be caused by the clot moving around and not fully engaging within the funnel of the device.

[0165]

[0195] The rate of change of area b can provide information regarding the quality of engagement. Any combination of the above conditions can result in the system identifying or determining that a clot is engaged in the infundibulum at the distal end of the device.

[0166]

[0196] Referring now to FIG. 15, in some embodiments, suction can be pulsed while searching for a clot (or prior to clot engagement) to reduce the amount of blood drawn into the system. Also, the suction waveform at the suction source can be monitored and used to determine when the system has engaged a clot. FIG. 15 illustrates two suction pulsation schemes that can be used with the clot removal system. Positive flow (+) in this diagram indicates positive flow in the direction of the suction source. In suction scheme 1, shown on the left side of FIG. 15, suction can pulse or cycle between zero flow rate Q and a positive flow rate Q, resulting in the illustrated square wave, as shown. In this example, the square wave begins to degrade or slope toward zero at the third pulse, indicating to the system that a clot has been engaged. Thus, in this embodiment, by pulsing the suction and monitoring the resulting suction flow waveform, the system can determine when a clot is engaged by the clot removal device. In Aspiration Mode 2, shown on the right side of FIG. 15, the suction is still pulsed, but instead of pulsating between zero flow and positive flow as in Aspiration Mode 1, in Aspiration Mode 2 the pulsating sequence transitions from positive flow to zero flow to negative flow and back to zero flow as shown. In this embodiment, a clot can be detected as engaged in the same manner as described above in Aspiration Mode 1. The function of the negative flow waveform is to push fluid back out of the device. As the device is chasing or searching for a clot, this negative pulsating waveform can result in less or limited blood being aspirated into the system and removed from the patient. It should be understood that the illustrated waveform is an example, but other waveforms such as triangular, sinusoidal, or "dedicated" waveforms can be used.

[0167]

[0197] Injection of fluid into the system from the jet when the clot is engaged in the funnel of the thrombectomy device creates additional challenges to maintain engagement of the clot in the funnel. For example, if the clot is fully engaged in the funnel and fluid or water injection is added to the system at the jet 30 (FIG. 16B), the clot can become permanently or temporarily dislodged from the funnel if the aspiration system cannot maintain negative pressure across the clot or if the momentum of the jet of fluid impinging on the clot is large enough to overcome the pressure gradient that holds the clot in place. FIG. 16B shows that when the jet 30 is actuated with the main clot in the funnel, pieces of the main clot can be fragmented, macerated, or severed from the main clot and aspirated into the aspiration lumen of the device. FIG. 16C shows a partially engaged clot.

[0168]

[0198] With further reference to FIGS. 16A-16C, when the device engages a clot, it creates a resistance R in the infundibulum distal to the jet. clot and the resistance R in the catheter proximal to the nozzle. cath The resistor R clot Since R varies as a function of engagement, this resistance will be high when the clot is fully engaged and low when the clot is partially engaged or not engaged in the infundibulum. This resistance, and therefore clot engagement, can be detected by the system using the suction / flow control described above.

[0169]

[0199] In some embodiments, referring to FIG. 16D, one or more conforming or easily deformed sections 1701 can be added to the funnel or catheter at or near where the jet injects fluid into the device. These conforming section(s) 1701 can be made of a material that is more conforming than the surrounding portions of the device, including the funnel. The conforming section(s) 1701 can be specifically designed and configured to expand when a bolus of fluid is injected into a clot fully contained or engaged by the jet. The conforming section allows the jet to turn on with the clot fully engaged without dislodging the clot from the funnel, thereby minimizing the chance of the clot becoming partially or fully detached.

[0170]

[0200] A control scheme is also provided for injecting fluid into the clot with the device, advantageously aiding in clot engagement. Referring to FIG. 17, an irrigation / injection pump cycle can include multiple different pump actuation sequences. For example, a given pump cycle Pc or irrigation cycle may include pump cycle a, pump cycle b, and pump cycle c, where Pc=a+b+c. When irrigation is turned on, pump cycle b can be performed in which water or fluid is injected from the jet toward the engaged clot at a velocity greater than 10 m / s up to 40-75 m / s or more. This initial blast of fluid from the jet at high velocity (e.g., 10 m / s-40 m / s) is intended to penetrate and detach a small portion of the main clot so that it can be more easily aspirated into the device with an aspiration system. Still referring to FIG. 17, once a small portion of the clot has been detached from the main clot with the initial bolus of fluid, pump cycle c can be performed, where the jet injects fluid at a lower flow rate than in pump cycle b to aid in the aspirating / transporting of the detached portion of the clot into the aspiration system. In one embodiment, the flow rate of irrigation from the jet in pump cycle c can be less than 10 m / s. The duration of the various pump cycles can be tweaked and adjusted based on the particular treatment, including the size of the clot, the type of clot, the hardness of the clot, etc. In some aspects, it may be desirable to irrigate for a longer period with the higher flow rate of pump cycle b to detach large or stubborn / hard clots. However, this results in a larger amount of fluid being added into the system, so the system must be sufficiently compatible to avoid dislodging the clot from the infundibulum. In other embodiments, pump cycle b can be performed for a short period of time to detach a portion of the clot, and then the system can cycle to pump cycle c to aid in the aspirating of the fragments or portions of the clot.

[0171]

[0201] In some embodiments, referring to Figure 18, a valve can be added to the aspiration system to allow for a large capacitance at the vacuum / suction source and full pressure with application of suction at the funnel. Figure 18 illustrates a schematic configuration in which such a valve is added near the suction source.

[0172]

[0202] Additional funnel designs are also provided. In one embodiment, referring to FIG. 19A and FIG. 19B, the funnel 20 can include expandable struts 2001 surrounding a conforming funnel 85 configured to add additional compliance into the funnel. The conforming funnel can be similar in function to 1701 described in FIG. 16D and can prevent clot dislodging when a bolus of fluid from a jet is added into the funnel. FIG. 19B is a top-down view of the funnel 20 with struts. In some embodiments, the struts and / or funnel can include strain sensors configured to sense engagement with the clot. Alternatively, the strain sensor can determine when the clot is partially engaged or dislodging from the funnel, for example, by detecting when the clot moves from a fully engaged to a partially engaged condition. Additionally, the strain gauge can be configured to sense deformation in the funnel or struts, which indicates a change in resistance of the clot interface.

[0173]

[0203] In Figures 20A and 20B, an alternative funnel design is provided. In contrast to the cone-shaped funnel described above, the funnel of Figures 20A and 20B forms a hemispherical shape. In some instances, this configuration is configured to enhance clot engagement during injection / aspiration and / or minimize collapse of distal engagement or capture portions that may be encountered with a cone-shaped funnel.

[0174]

[0204] Assessment of treatment effectiveness / completion

[0205] Provided herein are systems and methods for assessing the effectiveness and / or completion progress of a thrombectomy treatment. In some embodiments, the methods can be implemented entirely in software located on or in communication with the thrombectomy device itself. In other embodiments, the methods can be implemented in combination with hardware located on or within the device that provides additional information to the system / device regarding the progress of the treatment.

[0175]

[0206] In one embodiment, a method of assessing efficacy or monitoring progress of a treatment can include assessing or determining the amount of clot removal based on pre-treatment imaging (e.g., CT). With reference to the flow chart of FIG. 21, the method can include, at step 2102, obtaining a pre-treatment image of the clot to be removed or treated. In some embodiments, this can include a CT scan of the target clot. images , ultrasound images, MRI images, or other high resolution or quality images.

[0176]

[0207] At step 2104, the method may then include performing a thrombectomy procedure on the target clot or clots using any of the devices and methods described herein.

[0177]

[0208] Next, in step 2106, the method can include determining or calculating the amount of clot removed from the patient during the thrombectomy procedure. In some embodiments, this determination is made entirely in software, such as an algorithm that compares pre-treatment imaging to post-treatment imaging, determines the amount of pre-treatment clot relative to the post-treatment clot, and identifies the amount or percentage of clot removed.

[0178]

[0209] In other embodiments, the determination can be based on sensor feedback from the thrombectomy device. For example, flow and / or pressure sensors on the outside of the thrombectomy device or inside the aspiration lumen of the device can be used to measure or estimate the amount of clot removed in real time. Alternatively, contrast agent can be delivered into the target area during treatment, such as at the jet or another contrast agent lumen, to allow real time imaging of the clot removal. In some embodiments, contrast agent can be delivered from or near the infundibulum of the device. In some embodiments, an additive can be added to the contrast agent that can attach to the clot(s) and indicate when the clot is removed under real time imaging. This allows software or image processing solutions to estimate or determine the amount of clot removed during treatment.

[0179]

[0210] In some embodiments, completion of therapy can be determined or assessed based on a scoring system that is a composite of performance parameters (e.g., volume removed by step 2106 above) and / or physiological parameters (Sp02 increase / decrease, HR, respiratory rate, etc., return to normal range).

[0180]

[0211] Referring to FIG. 22, a chart is shown illustrating the relationship between the exit velocity or flow rate (average) of the jet(s) and the mechanism of action on one or more clots engaged by the clot removal device (i.e., engaged in the funnel or aspiration lumen). In general, when the jet flow rate is low (e.g., below 10 m / s depending on different parameters such as clot formulation and jet configuration), the jet serves to help sweep one or more clots into the aspiration lumen (especially when the funnel is blocked or partially blocked by a clot). Such sweeping can include pushing the clot into and / or through the aspiration lumen and also providing fluid into the funnel and into the aspiration lumen to aid in clot removal. Sweeping also helps break down soft and loose material on the surface of the clot, but cannot break through harder material. However, once the jet flow rate begins to exceed the cutting threshold 2202, in addition to clearing, the jets begin to cut the surface of one or more clots, fragmenting the clot into smaller pieces that can then be more easily aspirated into the aspiration lumen of the clot removal device. It has also been found that at a high enough velocity, the jet(s) will penetrate the clot surface and penetrate into the interior of the clot. In some embodiments, the threshold includes a jet flow rate in the range of 10-12 m / s. In other embodiments, the ideal cutting or penetrating flow rate of the jet is in the range of 10-15 m / s, or alternatively, 12-15 m / s. Once the jet flow rate begins to exceed the cavitation threshold 2204, in addition to clearing and cutting, the jets can be configured to create cavitation within the clot or within the infundibulum of the device, as described above, either individually or due to interaction with one or more other jets. As described herein, in some embodiments, cavitation is formed at jet flow rates of greater than 15 m / s, greater than 20 m / s, from 15-90 m / s, from 20-90 m / s, or from 50-90 m / s. Flow rates higher than 90 m / s can also be used to generate cavitation.

[0181]

[0212] Although the embodiments herein have been described as intended to remove blood clots from a patient's vasculature, other applications of this technology are provided. For example, the devices described herein can be used to break up and remove hardened stool from a patient's digestive tract, such as the patient's intestines or colon. In one embodiment, the device can be inserted into the patient's colon or intestines (such as through the anus) and advanced to the site of the hardened stool. The suction system can then be activated to engage the hardened stool with an engagement member (e.g., the infundibulum) of the device. Finally, the jet or irrigation can be activated to break off the hardened stool fragments and aspirate them into the system. Any of the techniques described above for controlling the system or removing blood clots can be applied to removing hardened stool.

[0182]

[0213] As one skilled in the art will appreciate from the disclosure herein, various components of the thrombus removal system described above may be omitted without departing from the scope of the present technology. As previously discussed, for example, the present technology may be used and / or modified to remove other types of emboli that may occlude blood vessels, such as fat, tissue, or foreign bodies. Additionally, although some embodiments herein are described in the context of thrombus removal from the pulmonary artery, the disclosed technology may be applied to the removal of thrombi and / or emboli from other parts of the vasculature (e.g., in neurovascular, coronary, or peripheral applications). Similarly, additional components not expressly described above may be added to the thrombus removal system without departing from the scope of the present technology. Thus, the systems described herein are not limited to those configurations expressly identified, but rather encompass variations and modifications of the described systems. conclusion

[0214] The above detailed description of the embodiments of the present technology is not intended to be exhaustive or to limit the present technology to the exact form disclosed above. Specific embodiments of the present technology, and examples thereof, are described above for illustrative purposes, but as those skilled in the art will recognize, various equivalent modifications are possible within the scope of the present technology. For example, although steps are presented in a given order, alternative embodiments may perform steps in a different order. Various embodiments described herein may be combined to provide further embodiments.

[0183]

[0215] From the above, it will be understood that, although specific embodiments of the present technology have been described herein for illustrative purposes, well-known structures and functions have not been shown or described in detail to avoid unnecessarily obscuring the description of the embodiments of the present technology. Where the context permits, singular or plural terms may also include plural or singular terms, respectively.

[0184]

[0216] Unless the context clearly dictates otherwise, throughout the description and examples, the words "comprises," "comprising," and the like, should be construed in an inclusive sense, i.e., "including, but not limited to," and not in an exclusive or exhaustive sense. As used herein, the terms "connected," "coupled," or any variation thereof, refer to any direct or indirect connection or coupling between two or more elements, and the coupling between the elements may be physical, logical, or a combination thereof. In addition, the words "herein," "above," "below," and words of similar import, when used in this application, refer to this application as a whole and not to any particular portions of this application. Where the context permits, words in the above detailed description using the singular or plural may each be in the plural or singular. As used herein, the term "and / or," such as "A and / or B," refers to A only, B only, and A and B. In addition, the term "comprising" is used throughout to mean including at least the recited feature(s), but not to the exclusion of any more of the same features and / or other features of additional types. Although specific embodiments have been described herein for purposes of illustration, it will also be understood that various modifications may be made without departing from the technology. Furthermore, while advantages associated with some embodiments of the technology have been described in the context of these embodiments, other embodiments may also exhibit such advantages, but not all embodiments necessarily exhibit such advantages to fall within the scope of the technology. Thus, the present disclosure and related technology may include other embodiments not expressly shown or described herein.

Claims

**Claim 1** An elongated shaft including an active end, At least one fluid lumen within the elongated shaft, Two or more openings disposed at or near the active end, wherein the two or more openings are in fluid communication with the at least one fluid lumen and are configured to generate two or more fluid streams that at least partially impinge in an interaction region, and the two or more fluid streams have a flow rate sufficient to create cavitation in the interaction region configured to mechanically fragment a target thrombus, a thrombus removal device. **Claim 2** An elongated shaft including an active end, At least one fluid lumen within the elongated shaft, Two or more openings disposed at or near the active end, wherein the two or more openings are in fluid communication with the at least one fluid lumen and are configured to generate two or more fluid streams that interact within or near the active end in an interaction region, and the two or more fluid streams have a flow rate and proximity sufficient to induce cavitation in the interaction region configured to mechanically comminute a target thrombus, a thrombus removal device. **Claim 3** The thrombus removal device according to claim 1 or 2, wherein each of the two or more fluid streams has a flow rate of 50 m / s to 90 m / s. **Claim 4** The thrombus removal device according to claim 1 or 2, wherein each of the two or more fluid streams has a flow rate of at least 50 m / s. **Claim 5** The thrombus removal device according to claim 1 or 2, wherein fluid flowing within the at least one fluid lumen at a lumen flow rate of 3 m / s provides the two or more fluid streams having a flow rate of at least 50 m / s. **Claim 6** The thrombus removal device according to claim 1 or 2, wherein fluid flowing within the at least one fluid lumen at a lumen flow rate of 4 m / s provides the two or more fluid streams having a flow rate of at least 70 m / s. **Claim 7** The thrombus removal device according to claim 1 or 2, wherein fluid flowing within the at least one fluid lumen at a lumen flow rate of 5 m / s provides the two or more fluid streams having a flow rate of at least 90 m / s. **Claim 8** The thrombus removal device according to claim 1 or 2, wherein the interaction region includes the focus of the two or more fluid streams. **Claim 9** The thrombus removal device according to claim 1 or 2, wherein the two or more fluid streams are generally orthogonal to the longitudinal axis of the elongated shaft. **Claim 10** The thrombus removal device according to claim 1 or 2, wherein the two or more fluid flows are directed distally such that the focus is distal to the two or more openings.

11. The thrombus removal device according to claim 10, wherein the two or more fluid flows directed distally are further configured to generate a cavitation column extending distally from the focus.

12. The thrombus removal device according to claim 1 or 2, wherein the two or more fluid flows are directed proximally such that the focus is proximal to the two or more openings.

13. The thrombus removal device according to claim 12, wherein the two or more fluid flows directed proximally are further configured to generate a cavitation column extending proximally from the focus.

14. The thrombus removal device according to claim 1 or 2, further comprising a cavitation detection sensor disposed on or within the thrombus removal device.

15. The thrombus removal device according to claim 14, wherein the cavitation detection sensor is disposed on or within a funnel portion at the working end of the thrombus removal device.

16. The thrombus removal device according to claim 14, wherein the cavitation detection sensor is disposed on or within a suction lumen at the working end of the thrombus removal device.

17. The thrombus removal device according to claim 14, wherein the cavitation detection sensor includes an ultrasonic transducer element.

18. The thrombus removal device according to claim 14, wherein the cavitation detection sensor includes a hydrophone.

19. The thrombus removal device according to claim 14, wherein the cavitation detection sensor includes a laser.

20. The thrombus removal device according to claim 14, wherein the cavitation detection sensor includes a microphone.

21. The thrombus removal device according to claim 1 or 2, further comprising a real-time imaging device configured to image the cavitation in real time.

22. The thrombus removal device according to claim 21, wherein the real-time imaging device includes an ultrasonic imaging device.

23. The thrombus removal device according to claim 21, wherein the ultrasonic imaging device includes an external ultrasonic imaging probe.

24. The thrombus removal device according to claim 21, wherein the ultrasonic imaging device includes a catheter-based ultrasonic imaging device.

25. An elongate catheter, a hemispherical funnel portion disposed at the distal end of the catheter, A suction source coupled to the hemispherical funnel portion via a suction lumen, a plurality of ejection ports disposed within or near the hemispherical funnel portion, and a fluid source coupled to the plurality of ejection ports and configured to direct fluid toward a common intersection point. A thrombus removal device comprising the above components.

26. An elongated shaft including an active end, a suction lumen disposed on the elongated shaft, extending to the active end, and coupled to a suction source, at least one fluid lumen within the elongated shaft, two or more openings disposed at or near the active end, in fluid communication with the at least one fluid lumen and configured to generate two or more fluid flows, at least one opening disposed in the suction lumen and in fluid communication with the at least one fluid lumen, the at least one opening being configured to generate a suction fluid flow, and an electronic controller configured to control the suction source and direct fluid flow into the at least one fluid lumen. A thrombus removal device comprising the above components.

27. The device according to claim 26, wherein the suction fluid flow is configured to be directed proximally into the suction lumen.

28. The device according to claim 26, further comprising a valve disposed within the suction lumen and operably coupled to the electronic controller.

29. In a normal operation mode, the electronic controller is configured to open the valve and direct fluid flow into the two or more openings, but not into the at least one opening within the suction lumen. The device according to claim 28.

30. In a clog removal mode, the electronic controller is configured to close the valve and direct fluid flow into the at least one opening within the suction lumen. The device according to claim 28.

Images