Patent Description:
Many medical procedures use medical devices to remove an obstruction (such as clot material) from a body lumen, vessel, or other organ. An inherent risk in such procedures is that mobilizing or otherwise disturbing the obstruction can potentially create further harm if the obstruction or a fragment thereof dislodges from the retrieval device. If all or a portion of the obstruction breaks free from the device and flows downstream, it is highly likely that the free material will become trapped in smaller and more tortuous anatomy. In many cases, the physician will no longer be able to use the same retrieval device to again remove the obstruction because the device may be too large and/or immobile to move the device to the site of the new obstruction.

Procedures for treating ischemic stroke by restoring flow within the cerebral vasculature are subject to the above concerns. The brain relies on its arteries and veins to supply oxygenated blood from the heart and lungs and to remove carbon dioxide and cellular waste from brain tissue. Blockages that interfere with this blood supply eventually cause the brain tissue to stop functioning. If the disruption in blood occurs for a sufficient amount of time, the continued lack of nutrients and oxygen causes irreversible cell death. Accordingly, it is desirable to provide immediate medical treatment of an ischemic stroke.

To access the cerebral vasculature, a physician typically advances a catheter from a remote part of the body (typically a leg) through the abdominal vasculature and into the cerebral region of the vasculature. Once within the cerebral vasculature, the physician deploys a device for retrieval of the obstruction causing the blockage. Concerns about dislodged obstructions or the migration of dislodged fragments may increase the duration of the procedure at a time when restoration of blood flow is paramount. Furthermore, a physician might be unaware of one or more fragments that dislodge from the initial obstruction and cause blockage of smaller more distal vessels.

Many physicians currently perform thrombectomies (i.e., clot removal) with stents to resolve ischemic stroke. Typically, the physician deploys a stent into the clot in an attempt to push the clot to the side of the vessel and re-establish blood flow. Tissue plasminogen activator ("tPA") is often injected into the bloodstream through an intravenous line to break down a clot. However, it takes time for the tPA to reach the clot because the tPA must travel through the vasculature and only begins to break up the clot once it reaches the clot material. tPA is also often administered to supplement the effectiveness of the stent. Yet, if attempts at clot dissolution are ineffective or incomplete, the physician can attempt to remove the stent while it is expanded against or enmeshed within the clot. In doing so, the physician must effectively drag the clot through the vasculature, in a proximal direction, into a guide catheter located within vessels in the patient's neck (typically the carotid artery). While this procedure has been shown to be effective in the clinic and easy for the physician to perform, there remain some distinct disadvantages to using this approach.

For example, one disadvantage is that the stent may not sufficiently retain the clot as it pulls the clot to the catheter. In such a case, some or all of the clot might remain in the vasculature. Another risk is that, as the stent mobilizes the clot from the original blockage site, the clot might not adhere to the stent as the stent is withdrawn toward the catheter. This is a particular risk when passing through bifurcations and tortuous anatomy. Furthermore, blood flow can carry the clot (or fragments of the clot) into a branching vessel at a bifurcation. If the clot is successfully brought to the end of the guide catheter in the carotid artery, yet another risk is that the clot may be "stripped" or "sheared" from the stent as the stent enters the guide catheter.

In view of the above, there remains a need for improved devices and methods that can remove occlusions from body lumens and/or vessels.

<CIT> discloses an apparatus for removal of a thrombus from a body of a subject. <CIT> discloses a thrombectomy system.

The system for removing a thrombus according to the invention is defined in claim <NUM>. The methods of operation disclosed are not explicitly recited in the claims but are considered useful for understanding the invention.

Mechanical thrombectomy (e.g., clot-grabbing and removal) has been effectively used for treatment of ischemic stroke. Although most clots can be retrieved in a single pass attempt, there are instances in which multiple attempts are needed to fully retrieve the clot and restore blood flow through the vessel. Additionally, there may be complications due to detachment of the clot from the interventional element during the retrieval process as the interventional element and clot traverse through tortuous intracranial vascular anatomy. For example, the detached clot or clot fragments can obstruct other arteries leading to secondary strokes. The failure modes that may contribute to clot release during retrieval include: (a) boundary conditions at bifurcations; (b) changes in vessel diameter; and/or (c) vessel tortuosity, amongst others.

Certain blood components, such as platelets and coagulation proteins, display negative electrical charges. In some embodiments, the treatment systems of the present technology include an interventional element and a signal generator configured to positively charge at least a portion of the interventional element during one or more stages of a thrombectomy procedure. For example, the signal generator can apply an electrical signal to the interventional element in a manner that positively charges the interventional element. The positively charged interventional element can attract negatively charged blood components, thereby improving attachment of the thrombus to the interventional element and reducing the number of device passes or attempts necessary to fully retrieve the clot.

In some embodiments, the treatment system includes an elongate core assembly extending between the signal generator and the interventional element. The interventional element and/or a component of the core assembly can serve as a first electrode, and the treatment system can further include a second electrode that may be disposed at a number of different locations. For example, the second electrode can be a component of the core assembly, such as a conductive element coupled to or integrated within the core assembly. Additionally or alternatively, the second electrode can take the form of a needle, a grounding pad, a conductive element carried by one or more catheters of the treatment system, a separate guide wire, and/or any other suitable conductive element configured to complete an electrical circuit with the first electrode and the extracorporeally positioned signal generator. When the interventional element is placed in the presence of blood (or any other electrolytic medium), current can travel from a first terminal of the signal generator to the core assembly and the interventional element, through the blood, to the second electrode, and back to a second terminal of the signal generator, thereby positively charging at least a portion of the interventional element and adhering clot material thereto.

While applying an electrical signal to positively charge the thrombectomy device can improve attachment of the thrombus to the retrieval device, certain waveforms and power delivery parameters may be particularly effective for promoting thrombus attachment. In some embodiments, it is important to provide sufficient current and power to enhance clot-adhesion without ablating tissue or generating new clots (i.e., the delivered power should not be significantly thrombogenic) or causing the creation of bubbles or gas on the surface of the interventional element. The clot-adhesion effect appears to be driven by the peak current of the delivered electrical signal. In some embodiments, periodic waveforms may advantageously provide the desired peak current without delivering excessive total energy. In particular, providing a periodic waveform with intermittent polarity reversal (e.g., a predominantly positive waveform that includes periods of intermittent negative polarity) can provide effective clot adhesion while reducing the risk of new clot formation or bubble formation on the interventional element. For example, in some embodiments, a waveform can alternate between positive peaks (e.g., of around <NUM> mA) that deliver positive electrical charge to the interventional element and slightly negative troughs (e.g., of around -<NUM> mA) interspersed between the positive peaks. In some instances, the negative troughs have been found to reduce adverse events such as new clot formation and gas formation on the interventional element while still allowing for enhanced clot adhesion.

Additional features and advantages of the present technology are described below, and in part will be apparent from the description, or may be learned by practice of the present technology. The advantages of the present technology will be realized and attained by the structure particularly pointed out in the written description and claims hereof as well as the appended drawings. The present technology is illustrated, for example, according to various aspects described below. These are provided as examples and do not limit the present technology.

In one aspect of the present technology, a system for removing a thrombus is provided. The system can include an interventional element configured to be disposed proximate to or adjacent to a thrombus within a blood vessel, and a signal generator in electrical communication with the interventional element. The signal generator can be configured to deliver an electrical signal to the interventional element. The electrical signal can include a waveform having a positive phase having a peak positive current and a first duration, and a negative phase having a peak negative current and a second duration. A magnitude of the peak positive current can be greater than a magnitude of the peak negative current, and the first duration can be greater than the second duration.

In some embodiments, the first duration is at least <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%,<NUM>%, or <NUM>% of a period of the waveform. The second duration can be no more than <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, or <NUM>% of a period of the waveform. The magnitude of the peak positive current can be at least <NUM> times, <NUM> times, <NUM> times, <NUM> times, <NUM> times, <NUM> times, <NUM> times, <NUM> times, or <NUM> times greater than the magnitude of the peak negative current. The peak positive current can be within a range from <NUM> mA to <NUM> mA. The peak negative current can be within a range from -<NUM> mA to -<NUM> mA.

In some embodiments, the waveform has a frequency within a range from <NUM> to <NUM>. The waveform can include a square waveform, a triangular waveform, a sawtooth waveform, a trapezoidal waveform, a sinusoidal waveform, or a combination thereof. Optionally, the positive phase can include a plurality of repeated pulses. The plurality of repeated pulses can include a plurality of square pulses, triangular pulses, sawtooth pulses, trapezoidal pulses, sinusoidal pulses, or a combination thereof. In some embodiments, the positive phase includes two to ten repeated pulses.

In some embodiments, the interventional element includes a self-expanding mesh structure. Optionally, the system can further include a core assembly. The core assembly can include a first conductor coupled to the interventional element, and a second conductor extending distally from the first conductor. The signal generator can be configured to deliver the electrical signal to the first and second conductors. The second conductor can include a distal tip having a linear, curved, hooked, helical, spiral, spherical, or spheroidal shape.

In another aspect of the present technology, a method for removing a thrombus is provided. The method can include applying a periodic electrical signal to an interventional element positioned near a thrombus in a blood vessel. The periodic electrical signal can include a positive signal portion having a peak positive current, and a negative signal portion having a peak negative current. The peak positive current can have a greater magnitude than the peak negative current, and the positive signal portion can have a greater duty cycle than the negative signal portion.

In some embodiments, the positive signal portion has a duty cycle greater than or equal to <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%,<NUM>%, or <NUM>%. The negative signal portion can have a duty cycle less than or equal to <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, or <NUM>%. The peak positive current can have a magnitude at least <NUM> times, <NUM> times, <NUM> times, <NUM> times, <NUM> times, <NUM> times, <NUM> times, <NUM> times, or <NUM> times greater than a magnitude of the peak negative current.

In some embodiments, the periodic electrical signal is applied for no more than <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minute, or <NUM> seconds. The periodic electrical signal can be applied during a single session having a duration of no more than <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minute, or <NUM> seconds. Alternatively, the periodic electrical signal can be applied during a plurality of sessions, each session having a duration of no more than <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minute, or <NUM> seconds. The plurality of sessions can include <NUM> sessions, <NUM> sessions, <NUM> sessions, <NUM> sessions, <NUM> sessions, <NUM> sessions, <NUM> sessions, <NUM> sessions, or <NUM> sessions. The sessions can be spaced apart by at least <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minute, or <NUM> seconds.

In some embodiments, the interventional element forms a first electrode, and the method further includes applying the periodic electrical signal to at least one second electrode spaced apart from the first electrode. The at least one second electrode can be located on a conductive element positioned in the blood vessel and spaced apart from the interventional element. Optionally, the conductive element can include a main body and a distal tip connected to the main body, the distal tip forming the second electrode. In some embodiments, the at least one second electrode includes at least one external electrode. Optionally, the method can further include generating a positive charge on the interventional element with the periodic electrical signal.

In a further aspect of the present technology, a method for removing a thrombus from a patient is provided. The method can include positioning an interventional element near or adjacent to a thrombus within a blood vessel. The method can also include promoting adhesion of the thrombus to the interventional element by delivering an electrical signal to the interventional element. The electrical signal can have a waveform including a positive phase and a negative phase. The positive and negative phases can be asymmetric so as to positively charge at least a portion of the interventional element.

In some embodiments, the positive phase has a first pulse width, and the negative phase has a second pulse width shorter than the first pulse width. Optionally, the positive phase can have a first amplitude, and the negative phase can have a second amplitude smaller than the first amplitude. The waveform can have a frequency within a range from <NUM> to <NUM>.

In some embodiments, the method further includes delivering the electrical signal to one or more electrodes spaced apart from the interventional element. The one or more electrodes can include a conductive element positioned distal to the interventional element. The one or more electrodes can include an electrode external to the patient's body.

Additional features and advantages of the present technology will be set forth in the description below, and in part will be apparent from the description, or may be learned by practice of the present technology. The advantages of the present technology will be realized and attained by the structure particularly pointed out in the written description and claims hereof as well as the appended drawings.

According to the invention, there is provided a system for removing a thrombus, the system comprising: an interventional element configured to be disposed proximate to or adjacent to a thrombus within a blood vessel; and a signal generator in electrical communication with the interventional element, the signal generator configured to deliver an electrical signal to the interventional element, wherein the electrical signal includes a waveform having: a positive phase having a peak positive current and a first duration; and a negative phase having a peak negative current and a second duration, wherein a magnitude of the peak positive current is greater than a magnitude of the peak negative current, and the first duration is greater than the second duration.

Optionally, the first duration is at least <NUM>% of a period of the waveform.

Optionally, the second duration is no more than <NUM>% of a period of the waveform.

Optionally, the magnitude of the peak positive current is at least <NUM> times greater than the magnitude of the peak negative current.

Optionally, the peak positive current is within a range from <NUM> mA to <NUM> mA.

Optionally, the peak negative current is within a range from -<NUM> mA to -<NUM> mA.

Optionally, the waveform has a frequency within a range from <NUM> to <NUM>.

Optionally, the waveform is a square waveform, a triangular waveform, a sawtooth waveform, a trapezoidal waveform, a sinusoidal waveform, or a combination thereof.

Optionally, the positive phase includes a plurality of repeated pulses.

Optionally, wherein the plurality of repeated pulses includes a plurality of square pulses, triangular pulses, trapezoidal pulses, sinusoidal pulses, or a combination thereof.

Optionally, the positive phase includes two to ten repeated pulses.

Optionally, the interventional element includes a self-expanding mesh structure.

Optionally, the system further comprises a core assembly including:.

Optionally, the second conductor includes a distal tip having a linear, curved, hooked, helical, spiral, spherical, or spheroidal shape.

Many aspects of the present disclosure can be better understood with reference to the following drawings. The components in the drawings are not necessarily to scale. Instead, emphasis is placed on clearly illustrating the principles of the present disclosure.

The present technology provides devices, systems, and methods for removing clot material from a blood vessel lumen. Although many of the embodiments are described below with respect to devices, systems, and methods for treating a cerebral or intracranial embolism, other applications and other embodiments, in addition to those described herein, are within the scope of the technology. For example, the treatment systems and methods of the present technology may be used to remove emboli from body lumens other than blood vessels (e.g., the digestive tract, etc.) and/or may be used to remove emboli from blood vessels outside of the brain (e.g., pulmonary, abdominal, cervical, or thoracic blood vessels, or peripheral blood vessels including those within the legs or arms, etc.). In addition, the treatment systems and methods of the present technology may be used to remove luminal obstructions other than clot material (e.g., plaque, resected tissue, foreign material, etc.). In some embodiments, aspects of the present technology can be applied to medical devices and systems that are not configured for removal of material from vessel lumens, for example, systems and devices for neuromodulation, or any other suitable medical procedure.

<FIG> illustrate an electrically enhanced treatment system <NUM> according to one or more embodiments of the present technology. Specifically, <FIG> is a perspective view of the treatment system <NUM> and <FIG> illustrate various components of the treatment system <NUM>. Referring first to <FIG>, the treatment system <NUM> includes a signal generator <NUM> and a treatment device <NUM>. The treatment device <NUM> includes a proximal portion 104a configured to be coupled to the signal generator <NUM> and a distal portion 104b configured to be intravascularly positioned within a blood vessel (such as an intracranial blood vessel) at a treatment site at or proximate a thrombus. The treatment device <NUM> includes an interventional element <NUM> at the distal portion 104b, a handle <NUM> at the proximal portion 104a, and a plurality of elongated shafts or members extending therebetween. For example, in the illustrated embodiment, the treatment device <NUM> includes a first catheter <NUM> (such as a guide catheter or balloon guide catheter), a second catheter <NUM> (such as a distal access catheter or aspiration catheter) configured to be slidably disposed within a lumen of the first catheter <NUM>, a third catheter <NUM> (such as a microcatheter) configured to be slidably disposed within a lumen of the second catheter <NUM>, and a core assembly <NUM> configured to be slidably disposed within a lumen of the third catheter <NUM>. In other embodiments, however, the treatment device <NUM> may not include some of the components shown in <FIG>, such as the first catheter <NUM> and/or the second catheter <NUM>.

The interventional element <NUM> can be or include any suitable device for restoring blood flow in a patient's vasculature (e.g., cerebral vasculature), such as a clot removal device, a thrombectomy device, or other suitable medical device. For example, the interventional element <NUM> can be a stent and/or stent retriever, such as Medtronic's Solitaire™ Revascularization Device, Stryker Neurovascular's Trevo® ProVue™ Stentriever, or other suitable devices. In some embodiments, the interventional element <NUM> is or includes a coiled wire, a weave, and/or a braid formed of a plurality of braided filaments. Examples of suitable interventional elements <NUM> include any of those disclosed in <CIT>, <CIT>, <CIT>, and <CIT>.

The interventional element <NUM> can be configured in many ways. For example, the interventional element <NUM> can have a low-profile, constrained, and/or compressed configuration for intravascular delivery to the treatment site within the treatment device <NUM>, such as within the third catheter <NUM>, and an expanded configuration for securing and/or engaging clot material and/or for restoring blood flow at the treatment site. In some embodiments, the interventional element <NUM> is or includes a mesh structure (e.g., a braid, a stent, etc.) formed of a superelastic material (e.g., nitinol) or other resilient or self-expanding material configured to self-expand when released from the third catheter <NUM>. The mesh structure can include a plurality of struts and open spaces between the struts. In some embodiments, the struts and spaces may be situated along the longitudinal direction of the interventional element <NUM>, the radial direction, or both.

The interventional element <NUM> can be coupled to a distal portion of the core assembly <NUM>. The core assembly <NUM> can be an elongated structure extending between the proximal portion 104a and distal portion 104b of the treatment device <NUM>. In the illustrated embodiment, for example, the core assembly <NUM> includes a first conductor <NUM> and a second conductor <NUM>. The first conductor <NUM> can be a first elongate member (e.g., a wire, tube (such as a hypotube), coil, rod, shaft, or any combination thereof) configured to advance the interventional element <NUM> to a treatment site within a blood vessel. The second conductor <NUM> can be a second elongate member (e.g., a wire, tube (such as a hypotube), coil, rod, shaft, or any combination thereof) configured to secure or retain a position of the interventional element <NUM> relative to the first conductor <NUM>, and electrically isolated from the first conductor <NUM>. In some embodiments, the first conductor <NUM> is an elongate tubular member defining a lumen therethrough, and the second conductor <NUM> is disposed within and extends through the lumen of the first conductor <NUM>. The first conductor <NUM> and second conductor <NUM> can be coaxial. The first conductor <NUM> and second conductor <NUM> can be slidably or non-slidably coupled together.

The first conductor <NUM> and second conductor <NUM> can be sized and configured to be advanced through a corporeal lumen to a treatment site within the patient's body. For example, the first and second conductors <NUM>, <NUM> can each have a length sufficient to extend from a location outside the patient's body, through the vasculature, and proximate a thrombus within a lumen of a blood vessel, such as within a patient's neurovasculature. In some embodiments, the first and second conductors <NUM>, <NUM> are conductive elements for transmitting electrical signals during the treatment procedure. Additional features of the first conductor <NUM> and second conductor <NUM> are described in greater detail below with respect to <FIG>.

The core assembly <NUM> can be slidably disposed within the lumen of the third catheter <NUM>. The third catheter <NUM> can be generally constructed to track over a conventional guidewire in the cervical anatomy and into the cerebral vessels associated with the brain, and can also be chosen according to several standard designs that are generally available. For example, the third catheter <NUM> can have a length of at least <NUM>, and more particularly may have a length within a range from about <NUM> to about <NUM> long. Other designs and dimensions are also contemplated. The second catheter <NUM> can be configured to slidably receive the third catheter <NUM> therethrough. The first catheter <NUM> can be configured to slidably receive both the second catheter <NUM> and the third catheter <NUM> therethrough. In some embodiments, the first catheter <NUM> is a balloon guide catheter having an inflatable balloon or other expandable member surrounding the catheter shaft at or near its distal end. Alternatively, the first catheter <NUM> can be a guide catheter without a balloon. The first catheter <NUM> can optionally be coupled to or incorporate the handle <NUM>.

In some embodiments, the catheters <NUM>, <NUM>, and <NUM> are each formed as a generally tubular member extending along and about a central axis. The bodies of the catheters <NUM>, <NUM>, and/or <NUM> can be made from various materials, such as thermoplastics, e.g., polytetrafluoroethylene (PTFE or TEFLON®), fluorinated ethylene propylene (FEP), high-density polyethylene (HDPE), polyether ether ketone (PEEK), etc. Optionally, the inner and/or outer surfaces of any of the catheters <NUM>, <NUM>, and <NUM> can be coated with one or more materials, depending on the desired results. For example, the inner and/or outer surfaces can be lined with a hydrophilic material such as polyvinylpyrrolidone (PVP) or some other plastic coating.

In some embodiments, the treatment system <NUM> includes a suction source <NUM> (e.g., a syringe, a pump, etc.) configured to be fluidically coupled (e.g., via a connector <NUM>) to a proximal portion of one or more of the first catheter <NUM>, the second catheter <NUM>, and/or the third catheter <NUM> to apply negative pressure therethrough. For example, a proximal portion of the second catheter <NUM> can be coupled to the suction source <NUM> in order to supply negative pressure to a treatment site. The treatment system <NUM> can optionally include a fluid source <NUM> (e.g., a fluid reservoir, a syringe, pump, etc.) configured to be fluidically coupled (e.g., via the connector <NUM> or a different connector) to a proximal portion of one or more of the first catheter <NUM>, the second catheter <NUM>, and/or the third catheter <NUM> to supply fluid (e.g., saline, contrast agents, a drug such as a thrombolytic agent, etc.) to the treatment site.

In some embodiments, the signal generator <NUM> is configured to deliver an electrical signal (e.g., an electrical current) to one or more portions of the treatment device <NUM> to enhance thrombus engagement and/or removal. For example, the signal generator <NUM> can be electrically coupled to the interventional element <NUM> to deliver electrical current thereto, e.g., to positively charge at least a portion of the interventional element <NUM> to attract negatively-charged blood components and/or otherwise improve attachment of clot material to the interventional element106. The interventional element <NUM> can be an electrically conductive thrombectomy device that includes and/or is made of a metallic and/or electrically conductive material, such as stainless steel, nitinol, cobalt-chromium, platinum, tantalum, alloys thereof, or any other suitable material.

The signal generator <NUM> can be coupled to a proximal portion of the core assembly <NUM>, the third catheter <NUM>, the second catheter <NUM>, and/or first catheter <NUM> to provide electric signals to the interventional element <NUM>. For example, in the illustrated embodiment, the signal generator <NUM> is coupled to the core assembly <NUM> (e.g., to the first conductor <NUM>, the second conductor <NUM>, or both) to deliver electrical signals to the interventional element <NUM> and thereby provide an electrically charged environment at the distal portion 104b of the treatment device <NUM>. The coupling between the signal generator <NUM> and the core assembly <NUM> can also provide a conductive pathway for electrical current to return from the electrically charged environment to the signal generator <NUM>. For example, in some embodiments, when the interventional element <NUM> is placed in the presence of blood (or thrombus, and/or any other electrolytic medium which may be present, such as saline) and voltage is applied via the electrical connectors of the signal generator <NUM>, current flows from the signal generator <NUM>, along the first conductor <NUM> to the interventional element <NUM> and through the surrounding media (e.g., blood, tissue, thrombus, etc.), returning proximally along the second conductor <NUM> to the signal generator <NUM>, thereby positively charging at least a portion of the interventional element <NUM> and promoting clot adhesion.

<FIG> are schematic views of different embodiments of the signal generator <NUM>. With reference to <FIG>, the signal generator <NUM> can include a power source <NUM>, a first terminal <NUM>, a second terminal <NUM>, and a controller <NUM>. The first and second terminals <NUM>, <NUM> can be connectors, electrodes, etc., for electrically coupling the signal generator <NUM> to another component of the treatment system <NUM>, such as to the core assembly <NUM>. For example, the first terminal <NUM> can be electrically coupled to the first conductor <NUM>, and the second terminal <NUM> can be electrically coupled to the second conductor <NUM>, or vice-versa. The controller <NUM> includes a processor <NUM> coupled to a memory <NUM> that stores instructions (e.g., in the form of software, code or program instructions executable by the processor or controller) for causing the power source <NUM> to deliver electrical signals according to certain parameters provided by the software, code, etc. The controller <NUM> can be used to control various parameters of the energy output by the power source or generator, such as waveform, intensity, amplitude, duration, frequency, duty cycle, and/or polarity. For example, the signal generator <NUM> can provide a voltage within a range from about <NUM> volts to about <NUM> volts (positive or negative) and a current within a range from about <NUM> mA to about <NUM> mA (positive or negative). The power source <NUM> of the signal generator <NUM> may include a DC power supply, an AC power supply, and/or a power supply switchable between DC and AC.

<FIG> illustrates another embodiment of the signal generator <NUM>, in which the controller <NUM> of <FIG> is replaced with drive circuitry <NUM>. In this embodiment, the signal generator <NUM> can include hardwired circuit elements to provide the desired waveform delivery, rather than the software-based generator of <FIG>. The drive circuitry <NUM> can include, for example, analog circuit elements (e.g., resistors, diodes, switches, etc.) that are configured to cause the power source <NUM> to deliver electrical current via the first and second terminals <NUM>, <NUM> according to the desired parameters. For example, the drive circuitry <NUM> can be configured to cause the power source <NUM> to deliver periodic waveforms via the first and second terminals <NUM>, <NUM>.

<FIG> and <FIG> are side views of the treatment device <NUM> including the interventional element <NUM> and core assembly <NUM> (<FIG> shows the interventional element <NUM> in an unrolled and/or flattened state, and <FIG> shows the interventional element <NUM> in a rolled and/or coiled state). As illustrated in <FIG> and <FIG>, the interventional element <NUM> has a proximal portion including an attachment portion 106a that can be coupled to the first conductor <NUM>, and a distal portion including an open cell framework or body 106b. When in the rolled and/or coiled state, the body 106b of the interventional element <NUM> can be generally tubular (e.g., cylindrical-best seen in <FIG>), and the proximal portion of the interventional element <NUM> can taper proximally to form the attachment portion 106a.

In some embodiments, the interventional element <NUM> is coupled to a distal portion 116b of the first conductor <NUM> and extends distally beyond the first conductor <NUM>. The first conductor <NUM> and the interventional element <NUM> can be coupled at a connection <NUM> to secure the interventional element <NUM> relative to the first conductor <NUM> and/or to complete an electrical pathway between the first conductor <NUM> and the interventional element <NUM>, as described in greater detail below. The second conductor <NUM> can extend through the lumen of the first conductor <NUM> and distally beyond the first conductor116, such that a distal portion of the second conductor <NUM> extends through and/or beyond an interior region of the interventional element <NUM> (best seen in <FIG>).

The first conductor <NUM> can be a monolithic structure or can be formed of multiple joined segments. In some embodiments, the first conductor <NUM> is or includes a laser-cut hypotube having a spiral cut pattern (or other pattern of cut voids) formed in its sidewall along at least a portion of its length. The first conductor <NUM> can be metallic and/or otherwise electrically conductive to deliver electrical signals from the signal generator <NUM> to the interventional element <NUM>. For example, the first conductor <NUM> can include or consist of nickel titanium alloy, stainless steel, or other metals or alloys. In embodiments where the first conductor <NUM> includes multiple joined segments, the segments may be formed of the same or different materials. For example, some or all of the first conductor <NUM> can be formed of stainless steel, or other suitable materials known to those skilled in the art. Nickel titanium alloy may be preferable for kink resistance and reduction of imaging artifacts.

The second conductor <NUM> can be a monolithic structure or can be formed of multiple joined segments. The second conductor <NUM> can be metallic and/or otherwise electrically conductive to deliver electrical signals from the signal generator <NUM> to the surrounding media (e.g., blood, tissue, thrombus, etc.). For example, the second conductor <NUM> can include or consist of nickel titanium alloy, stainless steel, or other metals or alloys. In embodiments where the second conductor <NUM> includes multiple joined segments, the segments may be formed of the same or different materials. For example, some or all of the second conductor <NUM> can be formed of stainless steel, or other suitable materials known to those skilled in the art. Nickel titanium alloy may be preferable for kink resistance and reduction of imaging artifacts.

<FIG> illustrates an enlarged perspective view of the connection <NUM> between the first conductor <NUM> and the interventional element <NUM>. In some embodiments, the interventional element <NUM> and the first conductor <NUM> are substantially permanently attached together at the connection <NUM> such that, under the expected use conditions of the treatment device <NUM>, the interventional element <NUM> and the first conductor <NUM> will not become unintentionally separated from one another. In some embodiments, the treatment device <NUM> includes a portion (e.g., located proximally or distally of the connection <NUM>) that is configured for selective detachment of the interventional element <NUM> from the first conductor <NUM>. For example, such a portion can comprise an electrolytically severable segment of the first conductor <NUM>. In other embodiments, however, the treatment device <NUM> can be devoid of any feature that would permit selective detachment of the interventional element <NUM> from the first conductor <NUM>.

In some embodiments, the first conductor <NUM> includes a distally located joining element <NUM> including an aperture <NUM> configured to receive the attachment portion 106a of the interventional element <NUM> and/or at least a portion of the second conductor <NUM>. The attachment portion 106a of the interventional element <NUM> can be configured to mechanically interlock with the joining element <NUM> to secure the interventional element <NUM> to the core assembly <NUM>. In some embodiments, the second conductor <NUM> is disposed within the aperture <NUM>, e.g., at a radially adjacent position relative to the attachment portion 106a, to facilitate such securement. Further, the second conductor <NUM> may be affixed to the joining element <NUM> via a weld, an adhesive, a threaded connection, an interference fit, or any other suitable connection.

Optionally, the connection <NUM> can include a bonding agent, in addition or alternatively to the joining element <NUM> and/or second conductor <NUM>. The bonding agent can be or include an adhesive, solder, welding flux, brazing filler, etc., disposed within the joining element <NUM> (e.g., within the aperture <NUM>), adjacent to the joining element <NUM>, proximal to the joining element <NUM>, and/or distal of the joining element <NUM>. In some embodiments, the bonding agent bonds to the other components of the connection <NUM> (e.g., to the first conductor <NUM>, attachment portion 106a, joining element <NUM>, and/or second conductor <NUM>) without applying heat. For example, the bonding agent can be or include a UV-curable adhesive. In embodiments where the other components of the connection <NUM> include polymeric materials (e.g., a polymer coating on the first and/or second conductors <NUM>, <NUM>; polymer tubing) use of a bonding agent that avoids application of heat that would damage the polymer may be preferred.

Referring again to <FIG> and <FIG> together, the treatment device <NUM> can comprise one or more electrically insulating materials, such as a polymer (e.g., polyimide, Parylene, or PTFE). For example, the first conductor <NUM> and/or the second conductor <NUM> can be electrically insulated along at least a portion of their respective lengths, e.g., to prevent electrical shorting. An insulating material can be disposed along an entire length of the first conductor <NUM> and/or the second conductor <NUM>, or the insulating material can be disposed along select portions of the first conductor <NUM> and/or the second conductor <NUM>. Moreover, an insulating material can be disposed over an outer surface of the interventional element <NUM> and/or along at least a portion of the length of the interventional element <NUM>.

For example, as shown in <FIG>, an insulating material <NUM> can be disposed over an outer surface of the first conductor <NUM> and/or along at least a portion of a length of the first conductor <NUM>, e.g., to direct current through the first conductor <NUM> and prevent current loss from the first conductor <NUM> to the surrounding environment. In the illustrated embodiment, the insulating material <NUM> is disposed near or adjacent to a proximal portion 116a of the first conductor <NUM>. Alternatively or in combination, the insulating material <NUM> can be disposed near or adjacent to a distal portion 116b of the first conductor <NUM>, and/or at select locations along the length of the first conductor <NUM> between the proximal and distal portions 116a, 116b. Optionally, the insulating material <NUM> can be disposed within a lumen of the first conductor <NUM> to electrically isolate the first conductor <NUM> from the second conductor <NUM> and/or the attachment portion 106a of the interventional element <NUM>.

As another example, as shown in <FIG>, an insulating material <NUM> can be disposed on one or more portions of the second conductor <NUM>, e.g., to electrically isolate the second conductor <NUM> from the first conductor <NUM>, the connection <NUM>, and/or the interventional element <NUM>. Alternatively or in combination, the insulating material <NUM> can be used to define one or more individual electrodes along the length of the second conductor <NUM>. In such embodiments, the insulating material <NUM> can be disposed at selected locations of the second conductor <NUM>, such that the second conductor <NUM> includes at least one insulated portion and at least one uninsulated portion that can serve as an electrode. The uninsulated portion(s) can be exposed sections of electrically conductive material configured to conduct current to and/or from surrounding media (e.g., blood, tissue, thrombus, etc.) at a treatment site.

The number, positioning, and geometry (e.g., size, shape) of the insulated portions and uninsulated portions of the second conductor <NUM> can be varied as desired. In the embodiment of <FIG>, for example, the insulating material <NUM> extends only partially along the length of the second conductor <NUM>, such that a main body <NUM> of the second conductor <NUM> is insulated while a distal tip <NUM> of the second conductor <NUM> distal to the main body <NUM> remains uninsulated. The distal tip <NUM> can also extend distally beyond the interventional element <NUM>. In some embodiments, the distal tip <NUM> is configured to enable the interventional element <NUM> to maintain a desirable electrical charge distribution. For example, positioning the distal tip <NUM> distal to the interventional element <NUM> may encourage more current to flow through the distal portions of the interventional element <NUM> toward the distal tip <NUM>, which in turn may enable the interventional element <NUM> to maintain a favorable electrical charge distribution (e.g., with sufficiently high charge density at the distal region of the interventional element <NUM>, along the working length of the interventional element <NUM>, or other suitable charge distribution). Although the distal tip <NUM> is illustrated as having a generally straight, linear shape, in other embodiments, the distal tip <NUM> can have a different shape, as described in greater detail below with respect to <FIG>.

Alternatively or in combination, the uninsulated portions can be at other locations along the second conductor <NUM>, such as at one or more locations proximal to the distal tip <NUM>. For example, in the embodiment of <FIG>, an insulating material is used to cover select regions of the main body <NUM> of the second conductor <NUM>, thus forming a plurality of insulated portions <NUM> interspersed with a plurality of uninsulated portions <NUM>. The insulated portions <NUM> can be larger than, smaller than, or have the same size as the uninsulated portions <NUM>. Although the illustrated embodiment shows the uninsulated portions <NUM> as being evenly spaced along the main body <NUM> of the second conductor <NUM>, in other embodiments, the uninsulated portions <NUM> can be spaced differently, e.g., some or all of the uninsulated portions <NUM> can be localized to the proximal portion of the second conductor <NUM>, localized to the distal portion of the second conductor <NUM>, localized to the portion of the second conductor <NUM> adjacent or near the interventional element <NUM>, etc..

Referring again to <FIG>, some or all of the uninsulated portions of the second conductor <NUM> can optionally be covered with or otherwise coupled to an electrically conductive material <NUM>. For example, the conductive material <NUM> can be coupled to the distal tip <NUM>. In such embodiments, the conductive material <NUM> can surround the distal tip <NUM> along at least a portion of the length of the distal tip <NUM>. In some embodiments, the surface area defined by the conductive material <NUM> coupled to the distal tip <NUM> is within a range from about <NUM>% to about <NUM>% of the surface area defined by the conductive material coupled to the interventional element <NUM>. Coupling the conductive material <NUM> to the distal tip <NUM> can increase the electrical conductivity of the distal tip <NUM>. The conductive material <NUM> can be or include a material that has a higher electrical conductivity than the material used to form the distal tip <NUM>. For example, the conductive material <NUM> can be formed from a gold coating while the distal tip <NUM> can be formed from stainless steel. By coupling a more electrically conductive material to the distal tip, an electrical current can more easily pass through the distal tip <NUM> via the conductive material <NUM>, thus increasing the electrical conductivity of the distal tip <NUM>. In other embodiments, however, the distal tip <NUM> (or any of the other uninsulated portions of the second conductor <NUM>) can be provided without the conductive material <NUM>.

Referring again to <FIG>, the treatment system <NUM> can include multiple (e.g., two or more) distinct conductive paths or channels for delivering electrical signals. Each conductive path can be electrically coupled to a respective electrode. For example, the first conductor <NUM> can serve as a first conductive path and the interventional element <NUM> can serve as a first electrode. The second conductor <NUM> can serve as a second conductive path and the uninsulated portion(s) of the second conductor <NUM> (e.g., the distal tip <NUM> and/or portions <NUM>) can serve as the second electrode(s). In other embodiments, however, the second electrode can be separate from the second conductor <NUM>. For example, the second electrode can be carried by one or more of the third catheter <NUM>, the second catheter <NUM>, or first catheter <NUM>. Alternatively or in combination, the treatment system <NUM> can also include one or more external electrodes that serve as the first or second electrodes, such as a needle puncturing the patient or a grounding pad applied to the patient's skin. In such embodiments, either the first conductor <NUM> or the second conductor <NUM> may be omitted from the core assembly <NUM>. For example, the second conductor <NUM> can be omitted altogether, the first conductor <NUM> can be a solid shaft or wire without a lumen, and the second electrode can be an external component separate from the treatment device <NUM>, such as a needle or grounding pad in contact with the patient's skin.

The signal generator <NUM> can be coupled to each of the conductive paths to provide electrical signals to the respective electrodes. For example, the first terminal <NUM> of the signal generator <NUM> can be coupled to the proximal portion 116a of the first conductor <NUM> such that the first conductor <NUM> functions as a first conductive path and the interventional element <NUM> serves as a first electrode. The second terminal <NUM> of the signal generator <NUM> can be coupled to a proximal portion of the second conductor <NUM> such that the second conductor <NUM> functions as a second conductive path and the uninsulated portion(s) of the second conductor <NUM> serve as a second electrode or electrodes. Optionally, the connectivity can be reversed, e.g., the first terminal <NUM> can be coupled to the second conductor <NUM> and the second terminal <NUM> can be coupled to the first conductor <NUM>.

In some embodiments, the signal generator <NUM> is configured to deliver a DC signal, such as a constant DC signal or a pulsed DC signal. In such embodiments, the first terminal <NUM> can be a positive terminal, the first conductor <NUM> can serve as a positive conductive path, and the interventional element <NUM> can serve as a positive electrode. The first conductor <NUM> and interventional element <NUM> can transmit current from the signal generator <NUM> to the treatment site. The second terminal <NUM> can be a negative terminal, the second conductor <NUM> can serve as a negative conductive path, and the uninsulated portion(s) of the second conductor <NUM> can serve as a negative electrode or electrodes. The second conductor <NUM> and uninsulated portion(s) can therefore transmit current from the treatment site to the signal generator <NUM>. Optionally, the polarities of the signal generator <NUM> can be switched, so that the negative terminal is electrically coupled to the first conductor <NUM> and the positive terminal is electrically coupled to the second conductor <NUM>. This can be advantageous when, for example, attempting to attract predominantly positively charged material to the interventional element <NUM>, or when attempting to break up a clot rather than grasp it with an interventional element <NUM>.

Alternatively or in combination, the signal generator <NUM> can be configured to deliver AC signals. In certain instances, AC signals may advantageously help break apart a thrombus or other material. When the signal generator <NUM> is outputting an AC signal, the polarities of the first terminal <NUM>, first conductor <NUM>, interventional element <NUM>, second terminal <NUM>, second conductor <NUM>, and uninsulated portion(s) of the second conductor <NUM> can vary over time. Similarly, the directionality of the current traveling through the treatment system <NUM> and the environment at the treatment site can also vary over time. The signal generator <NUM> can output any suitable type of AC signal. For example, in some embodiments, the signal generator <NUM> is configured to output an AC signal having a waveform that delivers a greater amount of positive current than negative current, also referred to herein as "intermittent negative polarity. " A waveform with intermittent negative polarity can include positive phases having a greater peak magnitude and/or duration than the negative phases. The use of intermittent negative polarity waveforms can reduce the risk of certain adverse events such as new clot formation or bubble formation on the interventional element <NUM>. Additional examples and features of waveforms having intermittent negative polarity are described in greater detail below.

A representative example of a method of operating the treatment system <NUM> will now be described. First, the treatment device <NUM> is positioned within a patient at a treatment site (e.g., a site of a blood clot within a vessel). The first catheter <NUM> can first be advanced through the vessel and then its balloon (if present) can be expanded to anchor the first catheter <NUM> in place and/or arrest blood flow from areas proximal of the balloon, e.g., to enhance the effectiveness of aspiration performed via the first catheter <NUM> and/or other catheter(s). Next, the second catheter <NUM> can be advanced through the first catheter <NUM> until the distal end of the second catheter <NUM> extends distally beyond the distal end of the first catheter <NUM>. The distal end of the second catheter <NUM> can be positioned adjacent or proximal to the treatment site. The third catheter <NUM> can then be advanced through the second catheter <NUM> until the distal end of the third catheter <NUM> extends distally beyond the distal end of the second catheter <NUM>. The interventional element <NUM> and core assembly <NUM> can then be advanced through the third catheter <NUM> for delivery to the treatment site.

Once the treatment device <NUM> is properly positioned, the user can expand the interventional element <NUM> so that the interventional element <NUM> engages with the thrombus. After the interventional element <NUM> engages with the thrombus, the user can couple the core assembly <NUM> to the signal generator <NUM>. In some embodiments, the core assembly <NUM> is previously coupled to the signal generator <NUM>. The user can interact with the signal generator <NUM> to deliver an electrical signal via the interventional element <NUM> and/or core assembly <NUM> (e.g., via the first conductor <NUM> and/or second conductor <NUM>). As described elsewhere herein, the electrical signal can be configured to enhance engagement with the thrombus, and can be or include an AC signal, a DC signal, or combination thereof. After the electrical signal is delivered to the treatment device <NUM> for the desired duration, the user can interact with the signal generator <NUM> to stop the delivery of the electrical signal. The user can then proximally retract the treatment device <NUM>, including the thrombus, into a surrounding catheter, and then remove the entire assembly from the patient.

The components of the treatment system <NUM> of <FIG> to IF can be configured in many different ways. For example, the geometry (e.g., size, shape) of the distal tip <NUM> of the treatment device <NUM> can be modified to alter and/or improve the surface charge density along the surface of the second conductor <NUM>. In some embodiments, the distal tip has structural features (e.g., curves, spiral shape, an expandable spheroid shape, etc.) that provide an enlarged surface area, e.g., compared to a straight wire or rod. This enlarged surface area may enable a more even distribution of charge density throughout the surface of the distal tip, which may reduce the risk of hydrogen and chlorine gas bubbles forming along the surface of the second conductor <NUM>.

<FIG> are side views of a portion of the treatment device <NUM> illustrating distal tips 136a-c with various geometries according to one or more embodiments of the present technology. <FIG> illustrates a distal tip 136a have a curved or hooked shape. As shown in <FIG>, the distal tip 136a can form a "J" shape, with a first portion that extends distally from the main body <NUM> of the second conductor <NUM>, a second portion that curves and/or extends laterally relative to the main body <NUM>, and a third portion that extends proximally towards the main body <NUM>. The length and curvature of the distal tip 136a can be varied as desired.

<FIG> illustrates a distal tip 136b having a helical or spiral shape. The distal tip 136b can extend distally from the main body <NUM> of the second conductor <NUM> and can have any suitable number of turns or coils (e.g., at least one, two, three, four, five, or more). Additionally, the coil size can of the distal tip 136b can varied as desired. For example, the distal tip 136b can have coils that increase in size (e.g., diameter) along a distal direction, decrease in size along a distal direction, are uniform in size, etc..

<FIG> illustrates a distal tip 136c having a spherical or spheroid shape. As illustrated in <FIG>, the distal tip 136c includes a plurality of curved members <NUM> (e.g., wires, struts, strips) forming a partially hollowed sphere. The distal tip 136c can have a larger radial dimension and/or surface area compared to the main body <NUM> of the second conductor <NUM>. In some embodiments, the distal tip 136c can be configured as an embolization protection element, for example, a basket, mesh, or filter, etc., configured to capture any fragments that separate from the thrombus during engagement with the interventional element <NUM>.

Although <FIG> illustrate certain examples of shapes for the distal tip of the second conductor <NUM>, other shapes can also be used, such as a serpentine shape, a zig-zag shape, a circular or oval shape, a polygonal shape, or any suitable combination thereof. Additionally, the features of the distal tips 136a-c illustrated in <FIG> can be combined with each other and/or any of the other embodiments described herein. Additionally, any of the geometries described herein in connection with the distal tip of the second conductor <NUM> can alternatively or additionally be incorporated into portions of the second conductor <NUM> that are proximal to the distal tip of the second conductor <NUM>. For example, one or more portions of the main body <NUM> of the second conductor <NUM> can be formed with any of the "distal tip" geometries described herein (e.g., curved, helical, spherical, spheroidal, etc.).

In some embodiments, the present technology provides waveforms and related parameters that can be used with any of the embodiments described herein, such as the treatment system <NUM> and associated devices and methods described above with respect to <FIG>, as well as other device configurations and techniques. In each of these embodiments, the waveforms and parameters can be beneficially employed to promote clot adhesion with little or no damage to surrounding tissue. Additionally, although the waveforms and parameters disclosed herein may be used for treating a cerebral or intracranial embolism, other applications and other embodiments in addition to those described herein are within the scope of the technology. For example, the waveforms and parameters disclosed herein may be used to electrically enhance removal of emboli from body lumens other than blood vessels (e.g., the digestive tract, etc.) and/or may be used to electrically enhance removal of emboli from blood vessels outside of the brain (e.g., pulmonary blood vessels, blood vessels within the legs, etc.).

While applying a continuous uniform DC signal to negatively charge the interventional element can improve its attachment to the thrombus, this approach may risk damage to surrounding tissue (e.g., ablation), and sustained current at a relatively high level may also be thrombogenic (i.e., may generate new clots). For achieving effective clot-grabbing without ablating tissue or generating substantial new clots at the target site, periodic waveforms (e.g., pulsed DC or AC waveforms) have been found to be particularly useful. Without wishing to be bound by theory, the clot-adhesion effect appears to be most closely related to the peak current of the delivered electrical signal. Periodic waveforms can advantageously provide the desired peak current without delivering excessive total energy or total electrical charge. In some embodiments, for example, periodic, non-square waveforms are well suited to deliver a desired peak current while reducing the amount of overall delivered energy or charge, e.g., as compared to either uniform applied DC waveforms or square waveforms.

In some embodiments, the periodic waveforms described herein are biphasic waveforms having a first phase with a first polarity (e.g., a positive polarity) and a second phase with a second, opposite polarity (e.g., a negative polarity). The first and second phases can be asymmetric so that the waveform results in application of a net charge to the interventional element. For example, the first phase can have a longer duration and/or a greater amplitude (e.g., peak current and/or voltage magnitude) than the second phase. In some embodiments, as discussed above, the waveform can have an intermittent negative polarity in that the waveform predominantly outputs a positive current interspersed with relatively short periods of negative current. This approach can advantageously reduce the risk of adverse events such as new clot formation or bubble formation at the treatment site.

<FIG> illustrates a square waveform 500a having intermittent negative polarity according to one or more embodiments of the present technology. The waveform 500a can be used with the devices and methods described above with respect to <FIG>, as well as with other devices and techniques. The waveform 500a includes a repeating cycle 502a having a positive phase or signal portion 504a, and a negative phase or signal portion 506a. In the illustrated embodiment, the positive phase 504a is a positive square wave pulse and the negative phase 506a is a negative square wave pulse. In other embodiments, the positive phase 504a and/or the negative phase 506a can have a different shape, as described in greater detail below with respect to <FIG>.

As shown in <FIG>, the positive phase 504a has a duration or pulse width tp, and the negative phase 506a has a duration or pulse width tn. The duration tp of the positive phase 504a can be greater than the duration tn of the negative phase 506a, such that the waveform 500a predominantly delivers positive current. For example, the ratio of the duration tp to the period p of the waveform 500a (also referred to herein as the duty cycle of the positive phase 504a or the "positive duty cycle") can be at least <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, or <NUM>%. The ratio of the duration tn to the period p of the waveform 500a (also referred to herein as the duty cycle of the negative phase 506a or the "negative duty cycle") can be no more than <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, or <NUM>%.

In the illustrated embodiment, the positive phase 504a has a peak positive current cp and the negative phase 506a has a peak negative current cn. The amplitude of the positive phase 504a (e.g., the magnitude of the peak positive current cp) is greater than the amplitude of the negative phase 506a (e.g., the magnitude of the peak negative current cn). The magnitude of the peak positive current cp can be at least <NUM> times, <NUM> times, <NUM> times, <NUM> times, <NUM> times, <NUM> times, <NUM> times, <NUM> times, <NUM> times, <NUM> times, or <NUM> times greater than the magnitude of the peak negative current cn. In some embodiments, the peak positive current cp is within a range from <NUM> mA to <NUM> mA, or from <NUM> mA to <NUM> mA. The peak positive current cp can be less than or equal to <NUM> mA, <NUM> mA, <NUM> mA, <NUM> mA, <NUM> mA, <NUM> mA, <NUM> mA, or <NUM> mA. The peak negative current cn can be within a range from of -<NUM> mA to -<NUM> mA, or from -<NUM> mA to -<NUM> mA. In some embodiments, the peak negative current cn is greater than or equal to -<NUM> mA, -<NUM> mA, -<NUM> mA, -<NUM> mA, -<NUM> mA, -<NUM> mA, -<NUM>. 125mA, -<NUM> mA, -<NUM> mA, -<NUM> mA, -<NUM> mA, or -<NUM> mA.

The waveform 500a can have any suitable frequency (e.g., corresponding to the inverse of the period p shown in <FIG>), such as a frequency within a range from <NUM> to <NUM>, or from <NUM> to <NUM>. In some embodiments, the waveform 500a has a frequency greater than or equal to <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, or <NUM>.

<FIG> illustrate additional examples of periodic waveforms 500b-500e having intermittent negative polarity according to one or more embodiments of the present technology. The waveforms 500b-e can be used with the devices and methods described above with respect to <FIG>, as well as with other devices and techniques. The characteristics of the waveforms 500b-500e can be generally similar to the waveform 500a of <FIG> (e.g., with respect to peak positive current cp, peak negative current cn, positive duty cycle, negative duty cycle, period, and/or frequency). Accordingly, like reference numbers and labels in <FIG> are used to identify similar or identical features, and the discussion of the waveforms 500b-500e of <FIG> will be limited to those features that differ from the waveform 500a of <FIG>.

<FIG> illustrates a triangular waveform 500b. As shown in <FIG>, the triangular waveform 500b includes a repeating cycle 502b with a positive phase 504b and a negative phase 506b. The positive phase 504b has a triangular shape including an upward ramp followed by a sharp drop (e.g., a sawtooth shape), such that the peak positive current cp corresponds to the apex of the upward ramp. In other embodiments, however, the positive phase 504b can have a different shape, such as a sharp rise followed by a downward ramp (e.g., a reverse sawtooth shape), an upward ramp followed by a downward ramp (e.g., a symmetric triangular shape), etc. The negative phase 506b of the triangular waveform 500b can have a square shape, trapezoidal shape, triangular shape, or any other suitable shape. In some embodiments, the triangular waveform 500b has the same positive and negative amplitudes as the square waveform 500a of <FIG>, but the triangular waveform 500b is able to deliver the same peak current as the square waveform 500a, with only half of the total charge delivered and less total energy delivered.

<FIG> illustrates a composite waveform 500c including a square waveform superimposed on a triangular waveform. The waveform 500c includes a repeating cycle 502c with a positive phase 504c and a negative phase 50bc. As shown in <FIG>, the positive phase 504c has a triangular (e.g., sawtooth) portion and a square portion. The triangular portion can have a greater peak positive current than the square portion, such that the peak positive current cp of the positive phase 504c corresponds to the peak current of the triangular portion. Alternatively, the square portion can have the same or a greater peak positive current than the triangular portion. Although <FIG> illustrates the triangular portion as preceding the square portion, in other embodiments, the square portion can precede the triangular portion. The negative phase 506c of the composite waveform 500c can have a square shape, trapezoidal shape, triangular shape, or any other suitable shape.

The composite waveform 500c shown in <FIG> can deliver additional efficacy compared to the triangular waveform 500b of <FIG> while delivering less overall energy than the square waveform 500a of <FIG>. This is because the delivered energy is proportional to the square of current and the brief high peak in the composite waveform 500c of FIG. 4C can ensure that current is supplied without dispensing excessive energy. In other embodiments, however, the composite waveform 500c can alternatively or additionally include other types of waveforms, such as trapezoidal waves, sinusoidal waves, etc. The composite waveform 500c can include any suitable number of superimposed waveforms, such as two, three, four, or more superimposed waveforms.

<FIG> illustrates a trapezoidal waveform 500d. The trapezoidal waveform 500d includes a repeating cycle 502d with a positive phase 504d and a negative phase 506d. In the illustrated embodiment, the positive phase 504d has a trapezoidal shape with an upward ramp <NUM> having a duration tu, a flat portion <NUM> having a duration t<NUM>, and a downward ramp <NUM> having a duration td. The peak positive current cp of the positive phase 504d can correspond to the current of the flat portion <NUM> of the positive phase 504d. In some embodiments, the upward and downward ramps <NUM>, <NUM> at the beginning and end of each trapezoidal pulse can provide periods of reduced current compared to square waveforms. The respective durations tu, td of the upward and downward ramps <NUM>, <NUM> can each independently be less than or equal to <NUM>%, <NUM>%, <NUM>%, or <NUM>% of the duration tp of the positive phase 504d, such as within a range from <NUM>% to <NUM>% of the duration tp. The duration tu of the upward ramp <NUM> can be the same as the duration td of the downward ramp <NUM>, such that the trapezoidal pulses are symmetrical. Alternatively, the duration tu of the upward ramp <NUM> can be different (e.g., shorter or longer) than the duration td of the downward ramp <NUM>, such that the trapezoidal pulses are asymmetrical. The duration t<NUM> of the flat portion <NUM> can be greater than or equal to <NUM>%, <NUM>%, <NUM>%, or <NUM>% of the duration tp, such as within a range from <NUM>% to <NUM>% of the duration tp. The negative phase 506d of the trapezoidal waveform 500d can have a square shape, trapezoidal shape, triangular shape, or any other suitable shape.

<FIG> illustrates a sinusoidal waveform 500e. The trapezoidal waveform 500e includes a repeating cycle 502e with a positive phase 504e and a negative phase 506e. As shown in <FIG>, the positive phase 504e has a positive sinusoidal pulse, with the apex of the pulse corresponding to the peak positive current cp. The negative phase 506e has a negative sinusoidal pulse, with the apex of the pulse corresponding to the negative positive current cn.

<FIG> illustrates a waveform 500f having a nested periodic pattern. The waveform 500f includes a repeating cycle 502f with a positive phase 504f and a negative phase 506f. The positive phase 504f includes a repeating pattern of pulses <NUM>. Each pair of neighboring pulses <NUM> can be separated by an interpulse portion <NUM>. The frequency of the repeating pattern of the positive phase 504f can be represented as n × f, where n is the number of repeated pulses <NUM> and f is the frequency of the overall waveform 500f. In the illustrated embodiment, the positive phase 504f includes a periodic trapezoidal waveform and the pulses <NUM> are trapezoidal pulses. In other embodiments, the positive phase 504f can include a different type of waveform (e.g., square, triangular, sinusoidal, etc., or a combination thereof) and/or a different number of pulses <NUM> (e.g., three, four, five, six, seven, eight, nine, ten, or more pulses <NUM>). The negative phase 506f of the waveform 500f can have a square shape, trapezoidal shape, triangular shape, or any other suitable shape.

As shown in <FIG>, the peak current of each pulse <NUM> can correspond to the peak positive current cp of the positive phase 504f. The interpulse portion <NUM> can be a flat portion of the waveform having a constant or substantially constant current cp1 that is less than the peak positive current cp. For example, the current cp1 of the interpulse portion <NUM> can be no more than <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, or <NUM>% of the peak positive current cp, and/or within a range from <NUM>% to <NUM>% of the peak positive current cp. The current cp1 of the interpulse portion <NUM> can be greater than or equal to zero.

In the illustrated embodiment, the waveform of the positive phase 504f includes an upward ramp <NUM> having a duration tu, an intermediate portion <NUM> having a duration t<NUM>, and a downward ramp <NUM> having a duration td. The respective durations tu, td of the upward and downward ramps <NUM>, <NUM> can each independently be less than or equal to <NUM>%, <NUM>%, <NUM>%, or <NUM>% of the duration tp of the positive phase 504f, such as within a range from <NUM>% to <NUM>% of the duration tp. The duration tu of the upward ramp <NUM> can be the same as the duration td of the downward ramp <NUM>, or can be different (e.g., shorter or longer) than the duration td of the downward ramp <NUM>. The duration t<NUM> of the intermediate portion <NUM> can be greater than or equal to <NUM>%, <NUM>%, <NUM>%, or <NUM>% of the duration tp, such as within a range from <NUM>% to <NUM>% of the duration tp. Optionally, the upward ramp <NUM> can be omitted such that at the beginning of the positive phase 504f, the waveform 500f transitions instantaneously or near-instantaneously from zero current to the peak positive current cp. Similarly, the downward ramp <NUM> can be omitted such that at the end of the positive phase 504f, the waveform 500f transitions instantaneously or near-instantaneously from the peak positive current cp to zero current.

Although <FIG> illustrate various examples of waveforms 500a-500e, in other embodiments, other types of waveforms can be used, depending on the desired power delivery characteristics and/or other considerations. For example, any non-square waveform, a superposition of a square waveform with any non-square waveform, etc., can be used with the devices and methods described above with respect to <FIG>, as well as with other devices and techniques.

The characteristics of the waveforms described herein (e.g., the waveforms 500a-500e of <FIG>) can be configured to achieve desired power delivery parameters, such as overall electrical charge, total energy, and peak current delivered to the interventional element. For example, the overall electrical charge delivered to the interventional element can be within a range from <NUM> mC to <NUM> mC, or from <NUM> mC to <NUM> mC, or from <NUM> mC to <NUM> mC. In some embodiments, the total electrical charge delivered to the interventional element is less than or equal to <NUM> mC, <NUM> mC, <NUM> mC, <NUM> mC, <NUM> mC, <NUM> mC, <NUM> mC, <NUM> mC, <NUM> mC, <NUM> mC, <NUM> mC, <NUM> mC, <NUM> mC, <NUM> mC, or <NUM> mC. The total energy delivered to the interventional element can be within a range from <NUM> mJ to <NUM> mJ, or from <NUM> mJ to <NUM> mJ, or from <NUM> mJ to <NUM> mJ. In some embodiments, the total energy delivered to the interventional element is less than or equal to <NUM> mJ, <NUM> mJ, <NUM> mJ, <NUM> mJ, <NUM> mJ, <NUM> mJ, <NUM> mJ, <NUM> mJ, <NUM> mJ, <NUM> mJ, <NUM> mJ, <NUM> mJ, <NUM> mJ, <NUM> mJ, <NUM> mJ, or <NUM> mJ.

The duration of signal delivery is another parameter that can be controlled to achieve the desired clot-adhesion effects without damaging tissue at the target site or generating new clots. In some embodiments, the total signal delivery time is no more than <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, or <NUM> seconds. As used herein, the "total signal delivery time" refers to the time period during which the waveform is supplied to the interventional element (including those periods of time between pulses of current).

In some embodiments, the waveforms described herein are delivered during a single session having a total duration or signal delivery time of no more than <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, or <NUM> seconds. Alternatively, the waveforms described herein can be delivered during multiple sessions, such as at least <NUM> sessions, <NUM> sessions, <NUM> sessions, <NUM> sessions, <NUM> sessions, <NUM> sessions, <NUM> sessions, <NUM> sessions, or <NUM> sessions. The individual sessions can each have the same duration, or some or all of the sessions can have different durations. In some embodiments, each session can independently have a duration of no more than <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, or <NUM> seconds. For example, the waveforms described herein can be delivered over <NUM> sessions of <NUM> minutes each. The sessions can be spaced apart by at least <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, or <NUM> seconds. The sessions can each use the same waveforms and/or power delivery parameters, or some or all of the sessions can use different waveforms and/or power delivery parameters.

<FIG> and <FIG> are tables illustrating example waveform characteristics and power delivery parameters according to one or more embodiments of the present technology. The parameters in <FIG> and <FIG> are calculated for a square waveform applied to a circuit having an assumed resistance of <NUM> kohm in the table of <FIG>, and an assumed resistance of <NUM> ohm in the table of <FIG>. The waveform characteristics and parameters in <FIG> and <FIG> can be used with the devices and methods described above with respect to <FIG>, as well as with other devices and techniques.

The descriptions of embodiments of the technology are not intended to be exhaustive or to limit the technology to the precise form disclosed above. Where the context permits, singular or plural terms may also include the plural or singular term, respectively. Although specific embodiments of, and examples for, the technology are described above for illustrative purposes, various equivalent modifications are possible within the scope of the technology, as those skilled in the relevant art will recognize. For example, while steps are presented in a given order, alternative embodiments may perform steps in a different order. The various embodiments described herein may also be combined to provide further embodiments.

Moreover, unless the word "or" is expressly limited to mean only a single item exclusive from the other items in reference to a list of two or more items, then the use of "or" in such a list is to be interpreted as including (a) any single item in the list, (b) all of the items in the list, or (c) any combination of the items in the list. Additionally, the term "comprising" is used throughout to mean including at least the recited feature(s) such that any greater number of the same feature and/or additional types of other features are not precluded. As used herein, the phrase "and/or" as in "A and/or B" refers to A alone, B alone, and A and B.

Claim 1:
A system (<NUM>) for removing a thrombus, the system (<NUM>) comprising:
an interventional element (<NUM>) configured to be disposed proximate to or adjacent to a thrombus within a blood vessel; and
a signal generator (<NUM>) in electrical communication with the interventional element (<NUM>), the signal generator (<NUM>) configured to deliver an electrical signal to the interventional element (<NUM>), wherein the electrical signal includes a waveform having:
a positive phase having a peak positive current (cp) and a first duration; and
a negative phase having a peak negative current (cn) and a second duration,
wherein a magnitude of the peak positive current (cp) is greater than a magnitude of the peak negative current (cn), and the first duration is greater than the second duration.