Apparatus and method for reducing microbubble formation during cardiac ablation - Patents.com

Abstract

Various aspects of the present disclosure relate to devices, systems, and methods for electroporation ablation. An electroporation ablation catheter may include an electrode assembly. The electrode assembly includes one or more electrodes configured to generate an electric field in a target tissue in response to a plurality of electrical pulse sequences delivered in a plurality of treatment sections, and an ultrasound transducer configured to generate a first set of ultrasound signals during a first electrical pulse sequence of the plurality of electrical pulse sequences and generate a second set of ultrasound signals after the end of the first electrical pulse sequence and before the start of a second electrical pulse sequence that is an electrical pulse sequence following the first electrical pulse sequence.

Description

[Technical field]

[0001] The present disclosure relates to medical devices, systems, and methods for reducing or preventing microbubbles during cardiac ablation by irreversible electroporation. [Background technology]

[0002] Ablation procedures are used to treat many different conditions in patients. Ablation can be used to treat cardiac arrhythmias, benign tumors, cancerous tumors, and to control bleeding during surgery. Typically, ablation is accomplished by thermal ablation techniques, including radiofrequency (RF) ablation and cryoablation. In RF ablation, a probe is inserted into the patient and radiofrequency waves are transmitted through the probe to the surrounding tissue. The radiofrequency waves generate heat, which destroys the surrounding tissue and cauterizes blood vessels. In cryoablation, a hollow needle or cryoprobe is inserted into the patient and a cold, thermally conductive fluid is circulated through the probe to freeze and kill the surrounding tissue. RF ablation and cryoablation techniques indiscriminately kill tissue through cell necrosis, which can damage or kill otherwise healthy tissue, such as tissue in the esophagus, phrenic nerve cells, and tissue in the coronary arteries.

[0003] Another ablation technique uses electroporation. In electroporation or electropermeabilization, an electric field is applied to cells to increase the permeability of the cell membrane. Electroporation can be reversible or irreversible, depending on the strength of the electric field. If electroporation is reversible, the increased permeability of the cell membrane can be used to introduce chemicals, drugs, and / or deoxyribonucleic acid (DNA) into the cells before they heal and recover. If electroporation is irreversible, the affected cells die by apoptosis.

[0004] Irreversible electroporation (IRE) can be used as a non-thermal ablation technique. In IRE, a train of short high-voltage pulses is used to generate an electric field strong enough to kill cells by apoptosis. In ablation of cardiac tissue, IRE can be a safe and effective alternative to the indiscriminate killing of thermal ablation techniques such as RF ablation and cryoablation. IRE can be used to kill target tissues such as myocardial tissues by using an electric field strength and duration that kills the target tissue but does not permanently damage other cells or tissues such as non-target myocardial tissues, red blood cells, vascular smooth muscle tissues, endothelial tissues, and nerve cells.

[0005] In some IRE procedures, microbubbles may form during patient treatment. Microbubble formation can cause tissue damage and increase the risk of patient treatment. Methods to prevent microbubble formation during IRE procedures are needed. Summary of the Invention

[0006] In embodiment 1, the electroporation ablation catheter includes an electrode assembly, the electrode assembly including one or more electrodes configured to generate an electric field in a target tissue in response to a plurality of electrical pulse sequences delivered in a plurality of treatment sections, and an ultrasonic transducer configured to generate a first set of ultrasonic signals during a first electrical pulse sequence of the plurality of electrical pulse sequences and generate a second set of ultrasonic signals after the end of the first electrical pulse sequence and before the start of a second electrical pulse sequence that is a subsequent electrical pulse sequence to the first electrical pulse sequence, the first set of ultrasonic signals having a first average amplitude and the second set of ultrasonic signals having a second average amplitude, the first average amplitude being different from the second average amplitude.

[0007] In embodiment 2, in the electroporation ablation catheter of embodiment 1, the first average amplitude is smaller than the second average amplitude. In embodiment 3, in the electroporation ablation catheter of embodiment 1 or 2, the electrode assembly further comprises an internal component disposed in the internal cavity of the electrode assembly, and the ultrasonic transducer is disposed on the internal component.

[0008] In embodiment 4, the electroporation ablation catheter of any of embodiments 1 to 3 further comprises one or more wiring for supplying power to the ablation catheter and controlling at least one of the amplitudes and frequencies of the first set of ultrasound signals and the second set.

[0009] In embodiment 5, in the electroporation ablation catheter of any of embodiments 1 to 4, the electrode assembly further comprises a plurality of splines, and the ultrasonic transducer comprises one ultrasonic transducer disposed on one of the plurality of splines.

[0010] In embodiment 6, in the electroporation ablation catheter of any of embodiments 1 to 5, the first set of ultrasound signals has a first average frequency, the second set of ultrasound signals has a second average frequency, and the first average frequency is different from the second average frequency.

[0011] In embodiment 7, the electroporation ablation catheter includes an electrode assembly including one or more electrodes configured to generate an electric field in a target tissue in response to a plurality of electrical pulse sequences delivered in a plurality of treatment sections, an ultrasonic transducer configured to generate a plurality of ultrasonic signals, and an internal component disposed in an internal cavity of the electrode assembly, the ultrasonic transducer disposed on the internal component.

[0012] In embodiment 8, in the electroporation ablation catheter of embodiment 7, the ultrasonic transducer is further configured to generate a first set of ultrasonic signals during a first electrical pulse sequence of the multiple electrical pulse sequences, and to generate a second set of ultrasonic signals after the end of the first electrical pulse sequence and before the start of a second electrical pulse sequence, which is an electrical pulse sequence following the first electrical pulse sequence.

[0013] In embodiment 9, in the electroporation ablation catheter of any of embodiments 7 to 8, the first set of ultrasound signals has a first average amplitude, and the second set of ultrasound signals has a second average amplitude.

[0014] In embodiment 10, in the electroporation ablation catheter of embodiment 9, the first average amplitude is different from the second average amplitude. In embodiment 11, in the electroporation ablation catheter of any of embodiments 7 to 10, the first average amplitude is smaller than the second average amplitude.

[0015] In embodiment 12, in the electroporation ablation catheter of any of embodiments 7 to 11, the internal component includes an deployment shaft. In embodiment 13, the electroporation ablation catheter of any of embodiments 7 to 12 further comprises a catheter shaft having a proximal end and a distal end, the electrode assembly extending from the distal end of the catheter shaft, and the deployment shaft extending from the distal end of the catheter shaft.

[0016] In embodiment 14, in the electroporation ablation catheter of embodiment 7, the electrode assembly further comprises a plurality of splines, and the ultrasonic transducer comprises one ultrasonic transducer disposed on one of the plurality of splines.

[0017] In embodiment 15, in the electroporation ablation catheter of embodiment 14, the first set of ultrasound signals has a first average frequency, and the second set of ultrasound signals has a second average frequency, and the first average frequency is different from the second average frequency.

[0018] In a sixteenth embodiment, the electroporation ablation catheter includes an electrode assembly, the electrode assembly including one or more electrodes configured to generate an electric field in a target tissue in response to a plurality of electrical pulse sequences delivered in a plurality of treatment sections, and an ultrasonic transducer configured to generate a first set of ultrasonic signals during a first electrical pulse sequence of the plurality of electrical pulse sequences and generate a second set of ultrasonic signals after the end of the first electrical pulse sequence and before the start of a second electrical pulse sequence that follows the first electrical pulse sequence, the first set of ultrasonic signals having a first average amplitude and the second set of ultrasonic signals having a second average amplitude, the first average amplitude being different from the second average amplitude.

[0019] In embodiment 17, in the electroporation ablation catheter of embodiment 16, the first average amplitude is smaller than the second average amplitude. In embodiment 18, in the electroporation ablation catheter of embodiment 16, the electrode assembly further comprises an internal component disposed in the internal cavity of the electrode assembly, and the ultrasonic transducer is disposed on the internal component.

[0020] In embodiment 19, the electroporation ablation catheter of embodiment 16 further comprises one or more wiring for supplying power to the ablation catheter and controlling at least one of the amplitudes and frequencies of the first set of ultrasound signals and the second set.

[0021] In embodiment 20, in the electroporation ablation catheter of embodiment 16, the electrode assembly further comprises a plurality of splines, and the ultrasonic transducer comprises one ultrasonic transducer disposed on one of the plurality of splines.

[0022] In embodiment 21, in the electroporation ablation catheter of embodiment 16, the first set of ultrasound signals has a first average frequency, and the second set of ultrasound signals has a second average frequency, and the first average frequency is different from the second average frequency.

[0023] In a twenty-second embodiment, the electroporation ablation catheter includes an electrode assembly including one or more electrodes configured to generate an electric field in a target tissue in response to a plurality of electrical pulse sequences delivered in a plurality of treatment sections, an ultrasonic transducer configured to generate a plurality of ultrasonic signals, and an internal component disposed in an internal cavity of the electrode assembly, the ultrasonic transducer disposed on the internal component.

[0024] In embodiment 23, in the electroporation ablation catheter of embodiment 22, the ultrasonic transducer is further configured to generate a first set of ultrasonic signals during a first electrical pulse sequence of the multiple electrical pulse sequences, and to generate a second set of ultrasonic signals after the end of the first electrical pulse sequence and before the start of a second electrical pulse sequence, which is an electrical pulse sequence following the first electrical pulse sequence.

[0025] In embodiment 24, in the electroporation ablation catheter of embodiment 23, the first set of ultrasound signals has a first average amplitude, and the second set of ultrasound signals has a second average amplitude, and the first average amplitude is different from the second average amplitude.

[0026] In embodiment 25, in the electroporation ablation catheter of embodiment 24, the first average amplitude is smaller than the second average amplitude. In embodiment 26, in the electroporation ablation catheter of embodiment 22, the internal component includes a deployment shaft.

[0027] In embodiment 27, the electroporation ablation catheter of embodiment 26 further comprises a catheter shaft having a proximal end and a distal end, the electrode assembly extending from the distal end of the catheter shaft, and the deployment shaft extending from the distal end of the catheter shaft.

[0028] In embodiment 28, in the electroporation ablation catheter of embodiment 22, the electrode assembly further comprises a plurality of splines, and the ultrasonic transducer comprises one ultrasonic transducer disposed on one of the plurality of splines.

[0029] In embodiment 29, in the electroporation ablation catheter of embodiment 28, at least a portion of the multiple splines form an internal cavity. In embodiment 30, in the electroporation ablation catheter of embodiment 23, the first set of ultrasound signals has a first average frequency, and the second set of ultrasound signals has a second average frequency, and the first average frequency is different from the second average frequency.

[0030] In embodiment 31, a method for preventing microbubble formation during cardiac ablation includes positioning an electroporation catheter adjacent to a target tissue, the electroporation catheter comprising one or more electrodes and an ultrasound transducer, generating an electric field in the target tissue by the one or more electrodes in response to a plurality of electrical pulse sequences delivered in a plurality of treatment sections, the electric field having an electric field strength sufficient to ablate the target tissue by irreversible electroporation, and generating a set of ultrasound signals by the ultrasound transducer.

[0031] In embodiment 32, in the method of embodiment 31, the set of ultrasound signals includes a first set of ultrasound signals and a second set of ultrasound signals. In embodiment 33, in the method of embodiment 32, the first set of ultrasound signals is generated during a first electrical pulse sequence of the multiple electrical pulse sequences.

[0032] In embodiment 34, in the method of embodiment 32, a second set of ultrasound signals is generated after the end of the first electrical pulse sequence and before the initiation of the second electrical pulse sequence. In embodiment 35, in the method of embodiment 32, the first set of ultrasound signals has a first average amplitude, and the second set of ultrasound signals has a second average amplitude, and the first average amplitude is different from the second average amplitude.

[0033] While multiple embodiments are disclosed, still other embodiments of the present invention will become apparent to those skilled in the art from the following detailed description, which shows and describes illustrative embodiments of the invention. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature and not restrictive. [Brief description of the drawings]

[0034] [Figure 1] FIG. 1 illustrates an exemplary clinical setup for treating a patient and for treating the patient's heart using an electrophysiological system in accordance with an embodiment of the presently disclosed subject matter. [Figure 2A] 1A-1C show an exemplary electroporation ablation catheter with an ultrasound transducer, in accordance with an embodiment of the presently disclosed subject matter. [Figure 2B] 1A-1C show an exemplary electroporation ablation catheter with an ultrasound transducer, in accordance with an embodiment of the presently disclosed subject matter. [Figure 2C] 1A-1C show an exemplary electroporation ablation catheter with an ultrasound transducer, in accordance with an embodiment of the presently disclosed subject matter. [Diagram 3]FIG. 2 illustrates an example ultrasonic waveform of an ultrasonic transducer during a burst, in accordance with an embodiment of the disclosed subject matter. [Figure 4] 1A-1C show an exemplary electroporation ablation catheter with an ultrasound transducer, in accordance with an embodiment of the presently disclosed subject matter. [Diagram 5] 1 is a flow chart illustrating a method for reducing or preventing the formation of microbubbles during cardiac ablation by electroporation, according to an embodiment of the presently disclosed subject matter. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0035] While the invention is susceptible to various modifications and alternative forms, specific embodiments have been shown by way of example in the drawings and are described in detail below. The intention, however, is not to limit the invention to the specific embodiments described. Rather, the invention is intended to cover all modifications, equivalents, and alternatives falling within the scope of the invention as defined by the appended claims.

[0036] The following detailed description is exemplary in nature and is in no way intended to limit the scope, applicability, or configuration of the present invention. Rather, the following description provides some practical illustrations for implementing exemplary embodiments of the present invention. Examples of configurations, materials, and / or dimensions are provided for selected elements. Those skilled in the art will recognize that many of the described examples have a variety of suitable alternatives.

[0037] As used herein with respect to measurements (e.g., dimensions, characteristics, attributes, components, etc.) and ranges thereof of tangible (e.g., products, inventory, etc.) and / or intangible (e.g., data, electronic representations of currency, accounts, information, portions of things (e.g., percentages, portions), calculations, data models, dynamic system models, algorithms, parameters, etc.) the terms “about” and “approximately” may be used interchangeably to refer to measurements that include the stated measurement and any measurements that are reasonably close to the stated measurement, provided that the difference in the measurements that are reasonably close is subject to measurement error, measurement and / or This may be a reasonably small amount, as understood and readily identified by one of ordinary skill in the art, to be due to variations in calibration of manufacturing equipment, human error in reading and / or setting measurements, adjustments made to optimize performance and / or structural parameters in light of other measurements (e.g., measurements related to other objects), specific implementation scenarios, imprecise adjustment and / or manipulation of objects, settings, and / or measurements by humans, computing devices, and / or machines, system tolerances, control loops, machine learning, predictable variations (e.g., statistically insignificant variations, chaotic variations, system and / or model instability, etc.), preferences, etc.

[0038] Although the exemplary methodologies may be depicted in one or more diagrams (e.g., flow charts, communication flows, etc.), these diagrams should not be construed as implying that the various steps disclosed herein are required, or any particular order between those steps. However, in some particular embodiments, some particular steps and / or a particular order between certain steps may be required (e.g., performance of some steps may depend on the results of previous steps), as may be specified herein and / or understood by the nature of the steps themselves. Furthermore, a "set," "subset," or "group" of items (e.g., inputs, algorithms, data values, etc.) may include one or more items, and similarly, a subset or subgroup of items may include one or more items. "Plurality" means more than one.

[0039] As used herein, the term "based on" means, without limitation, to determine, identify, predict, calculate, etc., using at least the term following "based on" as an input. For example, predicting an outcome based on particular information may additionally or alternatively mean that the same determination is based on other information.

[0040] Irreversible electroporation (IRE) uses short (e.g., 100 microseconds or less) pulses of high voltage to kill cells by apoptosis. IRE can be targeted to kill myocardium, sparing other adjacent tissues, including esophageal vascular smooth muscle and endothelium. During the course of an IRE treatment section, microbubbles can be formed. A treatment section can include a treatment burst period and a quiet period. A treatment section (e.g., for a duration of about 10 milliseconds) can include multiple electrical pulses (e.g., 20 pulses, 30 pulses, etc.), also called treatment bursts, and are generated and delivered sequentially by an electroporation generator. A treatment burst period refers to the period of a treatment burst, and a quiet period refers to the period without a treatment burst. In some examples, microbubbles can be formed during the quiet period. The formation of microbubbles can cause tissue damage and increase the risk of treatment for a patient.

[0041] At least some embodiments of the present disclosure relate to systems and methods that use ultrasound technology to reduce, destroy, and / or prevent the formation of microbubbles during IRE ablation. In some embodiments, the electroporation ablation system includes an ultrasound transducer configured to generate an ultrasound signal capable of microbubble destruction. In certain embodiments, the ultrasound transducer is configured to generate an ultrasound signal having a higher amplitude during rest periods (i.e., periods between treatment bursts) than during treatment bursts.

[0042] 1 illustrates an exemplary clinical set-up 10 for treating a patient 20 and for treating a heart 30 of the patient 20 using an electrophysiological system 50, in accordance with an embodiment of the subject matter of the present disclosure. The electrophysiological system 50 includes an ultrasound generator 154, an electroporation device 60, and an optional localization field generator 80. The clinical set-up 10 also includes additional equipment, such as an imaging device 94 (represented by a C-arm), and various controller elements configured to allow an operator to control various aspects of the electrophysiological system 50. As will be appreciated by those skilled in the art, the clinical set-up 10 may have other components and arrangements of components not shown in FIG. 1.

[0043] The electroporation device 60 includes an electroporation catheter 105, an introducer sheath 110, an electrode assembly 150, a controller 90, and an electroporation generator 130. In an embodiment, the electroporation device 60 is configured to deliver electric field energy to a target tissue in the patient's heart 30 to cause tissue apoptosis and render the tissue unable to conduct an electrical signal. The controller 90 is configured to control functional aspects of the electroporation device 60. In an embodiment, the controller 90 is configured to send and receive timing signals for the electroporation generator 130 to generate electrical pulses. In an embodiment, the electroporation generator 130 is operable as a pulse generator for generating and delivering a pulse sequence to the electroporation catheter 105. In an embodiment, the electroporation generator 130 is operable to receive a sensed signal from the accelerometer 117 and functions as a pulse generator for generating and delivering a pulse sequence to the electroporation catheter 105 based on the received sensed signal.

[0044] In an embodiment, introducer sheath 110 is operable to provide a delivery conduit through which electroporation catheter 105 may be positioned to a particular target site within the patient's heart 30. It will be understood, however, that introducer sheath 110 is illustrated and described herein to provide context for the overall electrophysiology system 50.

[0045] In the illustrated embodiment, the electroporation catheter 105 includes a handle 105a, a shaft 105b, and an electrode assembly 150, which is described further below. The handle 105a is configured to be manipulated by a user to place the electrode assembly 150 at a desired anatomical location. The shaft 105b has a distal end 105c and generally forms a longitudinal axis of the electroporation catheter 105. As shown, the electrode assembly 150 is located at or proximal to the distal end 105c of the shaft 105b. In an embodiment, the electrode assembly 150 is electrically coupled to the electroporation generator 130 to receive an electrical pulse sequence or train, thereby selectively generating an electric field for ablating target tissue by irreversible electroporation.

[0046] In an embodiment, as shown in FIG. 1, the electrode assembly 150 includes an ultrasonic transducer 152 coupled to an ultrasonic generator 154. In some examples, the ultrasonic transducer 152 includes an ultrasonic piezoelectric transducer. In some embodiments, the ultrasonic generator 154 may be incorporated into the electroporation generator 130. In embodiments, the ultrasonic generator 154 may be separate from the electroporation generator 130. The controller 90 may be operatively connected to the ultrasonic generator 154 and may be configured to transmit and receive timing signals for the ultrasonic generator 154 to generate ultrasonic waveforms according to timing signals received from the electroporation generator 130 (described in more detail below with respect to FIG. 3). In an embodiment, the ultrasonic generator 154 is configured to generate ultrasonic signals (described in more detail below) for reducing, destroying, and / or preventing the formation of microbubbles during IRE ablation. In some embodiments, the ultrasonic generator 154 may be used to generate ultrasonic signals for reducing or preventing the formation of microbubbles. In some cases, the ultrasonic generator 154 may be controlled such that ultrasonic signals are generated at different amplitudes and / or frequencies between treatment burst periods and rest periods of the multiple treatment sections.

[0047] The electroporation device 60 is operable to generate IRE pulse sequences, including a preconditioning pulse sequence and an electroporation pulse sequence. The IRE pulse sequence is configured to ablate the target tissue. In an embodiment, the preconditioning pulse sequence is a series of electrical pulses of increasing amplitude to tetanize skeletal muscle tissue and to perform electrolysis near the target tissue. In an embodiment, the electroporation pulse sequence is a series of electroporation pulses configured to cause irreversible damage to the target tissue.

[0048] In an embodiment, the electroporation device 60 includes an accelerometer 117 that may be attached to the body of the patient 20, such as the patient's chest, and electrically coupled to the electroporation generator 130. The accelerometer 117 is configured to sense contractions of the patient's skeletal musculature to detect tetany. A signal from the accelerometer 117 is received by the electroporation generator 130, which processes the signal to determine whether the patient's skeletal musculature is contracting and whether tetany has been achieved. In an embodiment, the electroporation generator 130 is configured to provide an electroporation pulse sequence only after tetany has been achieved in the patient. In an embodiment, the controller 90 is operable to receive a sensed signal from the accelerometer 117 and control the electroporation generator 130 to generate and deliver a pulse sequence to the electroporation catheter 105 based on the received sensed signal.

[0049] In embodiments, electroporation device 60 operates as a closed system where surface accelerometer 117 monitors chest vibrations and electroporation generator 130 modulates pulses until tetany is onset, and then electroporation generator 130 delivers the electroporation pulses. Also, in embodiments, the local impedance of the target tissue and tissue surrounding the target tissue can be measured during this time to calculate pre- and post-ablation values ​​for assessment of the effectiveness of the injury.

[0050] According to embodiments, various components of the electrophysiological system 50 (e.g., the controller 90) may be implemented on one or more computing devices. The computing devices may include any type of computing device suitable for implementing embodiments of the present disclosure. Examples of computing devices include dedicated or general-purpose computing devices such as workstations, servers, laptops, portable devices, desktops, tablet computers, handheld devices, general purpose graphics processing units (GPGPUs), and the like, all of which are contemplated within the scope of FIG. 1 with respect to the various components of the electrophysiological system 50.

[0051] In some embodiments, a computing device includes a bus that directly and / or indirectly couples a processor, memory, input / output (I / O) ports, I / O components, and a power source. Any number of additional components, different components, and / or combinations of components may also be included in a computing device. A bus represents what may be one or more buses (e.g., an address bus, a data bus, or combinations thereof, etc.). Similarly, in some embodiments, a computing device may include multiple processors, multiple memory components, multiple I / O ports, multiple I / O components, and / or multiple power sources. Additionally, any number of these components or combinations thereof may be distributed and / or replicated across several computing devices.

[0052] In some embodiments, the electrophysiological system 50 includes a memory (not shown). The memory includes computer-readable media in the form of volatile and / or non-volatile memory, temporary and / or non-transient storage media, and may be removable, non-removable, or a combination thereof. Examples of media include random access memory (RAM), read-only memory (ROM), electronically erasable programmable read-only memory (EEPROM), flash memory, optical or holographic media, magnetic cassettes, magnetic tapes, magnetic disk storage devices or other magnetic storage devices, data transmission, and / or any other media that can be used to store information and that can be accessed by a computing device, such as, for example, a quantum state memory. In some embodiments, the memory stores computer-executable instructions for causing a processor (e.g., controller 90) to perform aspects of embodiments of the system components described herein and / or execute aspects of embodiments of the methods and procedures described herein.

[0053] Computer-executable instructions may include, for example, computer code, machine-usable instructions, etc., such as program components that may be executed by one or more processors associated with a computing device. The program components may be programmed using any number of different programming environments, including a variety of languages, development kits, frameworks, etc. Some or all of the functionality contemplated herein may additionally or alternatively be implemented in hardware and / or firmware.

[0054] In some embodiments, the memory may include a data repository that may be implemented using any one of the configurations described below. The data repository may include random access memory, flat files, XML files, and / or one or more database management systems (DBMS) running on one or more database servers or data centers. The database management system may be a relational database management system (RDBMS), a hierarchical database management system (HDBMS), a multidimensional database management system (MDBMS), an object-oriented database management system (ODBMS or OODBMS), or an object-relational database management system (ORDBMS), etc. The data repository may be, for example, a single relational database. In some cases, the data repository may include multiple databases that may exchange and aggregate data by a data integration process or software application. In an exemplary embodiment, at least a portion of the data repository may be hosted in a cloud data center. In some cases, the data repository may be hosted on a single computer, server, storage device, cloud server, etc. In some other cases, the data repository may be hosted on a series of networked computers, servers, or devices. In some cases, the data repository may be hosted on a hierarchy of data storage devices including local, regional, and central.

[0055] The various components of the electrophysiological system 50 can communicate or be coupled via a communication interface, e.g., a wired interface or a wireless interface. The communication interface includes, but is not limited to, any wired or wireless short-range and long-range communication interface. The wired interface can use a cable, an umbilical, or the like. The short-range communication interface can be, for example, an interface that conforms to a known communication standard, such as a local area network (LAN), a Bluetooth® standard, an IEEE 802 standard (e.g., IEEE 802.11), a ZigBee® or similar specification, such as one based on the IEEE 802.15.4 standard, or other public or proprietary wireless protocols. The long-range communication interface can be, for example, a wide area network (WAN), a cellular network interface, a satellite communication interface, or the like. The communication interface can be in a private computer network, such as an intranet, or on a public computer network, such as the Internet.

[0056] 2A-2C are partial perspective views of a distal end of a cardiac mapping catheter 200 according to an embodiment of the subject matter of the present disclosure. As shown in FIG. 2A, the electrode assembly 202 is deployed in a radially expanded state. The electrode assembly 202 may include one or more splines 204 and an end cap 206. Each of the splines 204 extends between a distal end 208 of the catheter 200 and the end cap 206 and forms an internal cavity 222. Each of the splines 204 may include a flexible polymer substrate 210 and a plurality of electrodes 212. In some embodiments, the flexible polymer substrate 210 may include a reinforcing element 214. The reinforcing element 214 may be, for example, a layer of Nitinol. The reinforcing element 214 may generate a force on each of the splines 204 that biases the electrode assembly 202 toward a non-deployed state or configuration (not shown). In some embodiments, there may be between 2 and 8 splines 204 connected to the distal end 208 of the catheter 200. In some embodiments, there may be more than 8 splines connected to the distal end 208 of the catheter 200.

[0057] In some embodiments, the electrodes 212 may be ablation electrodes and are configured to generate an electric field in the target tissue in response to multiple electrical pulse sequences delivered in multiple treatment sections. In some examples, at least a portion of the one or more electrodes 212 are disposed on one or more splines 204.

[0058] 2A, the deployment shaft 216 may extend from the end cap 206 into the catheter body 218 at the distal end 208. In some embodiments, the end cap 206 may be an electrode for cardiac stimulation or tissue ablation. In some embodiments, the end cap 206 may include a magnetic sensor for use in determining the position of the electrode assembly 202 within the body.

[0059] In some embodiments, the electrode assembly 202 includes an internal component 224 disposed in an internal cavity 222 of the electrode assembly 202. The deployment shaft 216 may be part of the internal component 224. In some embodiments, the electrode assembly further includes an ultrasonic transducer 220 disposed on the internal component 224. The ultrasonic transducer 220 may be used to destroy microbubbles that may be formed as a result of irreversible electroporation. During treatment, the ultrasonic transducer 220, as part of the electrode assembly 202, is placed directly in a liquid medium (i.e., blood or bodily fluids in the patient's heart) where absorption of the ultrasonic signal is greatest.

[0060] The reflection coefficient (r) is equal to (Z1-Z2) / (Z1+Z2), where Z1 is the acoustic impedance (resistance to the propagation of ultrasound through tissue) near the transducer 220 and Z2 is the acoustic impedance near any air bubbles (not shown) that may form during treatment. Because Z1 and Z2 are relatively close in value, the power required to destroy the air bubbles is also relatively small. Additionally, as described in more detail below, the power required by the transducer can be further reduced and minimized by synchronizing the ultrasound waves generated by the transducer with the burst trains generated by the ablation electrodes for treatment.

[0061] In some embodiments, as shown in FIG. 2B, one or more ultrasonic transducers 220 may be located on an inner surface of one or more splines 204. In some cases, one ultrasonic transducer may be disposed on each spline. In some cases, two or more ultrasonic transducers may be disposed on each spline. In some cases, selected spline(s) of the one or more splines 204 have one or more ultrasonic transducers 220 disposed on the selected spline. In one example, two of the four splines 204 include one ultrasonic transducer 220 disposed on the two splines 204.

[0062] In some embodiments, as shown in FIG. 2C, one or more ultrasound transducers 220 may be disposed on the end cap 206 of the electrode assembly 202. In some cases, there may be only one ultrasound transducer 220 disposed on the end cap 206 of the electrode assembly 202. In a particular example, three ultrasound transducers 220 are disposed on the end cap of the electrode assembly 202. In one example, the three ultrasound transducers 220 are equally spaced on the end cap 206. In some cases, there may be one or more ultrasound transducers 220 disposed on the distal end 208 of the catheter body 218. By having transducers at both the distal end of the electrode assembly 202 and the distal end of the catheter body 218, in some embodiments, the ultrasound may reduce, destroy, and / or prevent the formation of microbubbles in a larger area of ​​the patient's heart compared to having one or more transducers located within the internal cavity 222 of the electrode assembly 202.

[0063] FIG. 3 illustrates an ultrasonic waveform 304 generated by an ultrasonic transducer (shown in FIG. 2A) synchronized with a burst train 302 generated by a plurality of electrodes (shown in FIG. 2A). As shown in FIG. 3, one treatment burst 308, also referred to as an electrical pulse sequence, may include several positive pulses 322 and several negative pulses 324. In one example, the treatment burst 308 has a voltage greater than 500 volts. A rest period 318 may be provided between each treatment burst 308, 312. In an embodiment, a treatment section 326 may include a treatment burst 308 and a rest period 318. The frequency of the ultrasonic waveform 304 may be between 1-5 MHz. In some examples, the frequency of the ultrasonic waveform may be greater than 5 MHz. In some instances, the frequency of the ultrasonic waveform may be as high as 15 MHz. In some embodiments, the frequency of the ultrasonic waveform 304 between each treatment burst 308, 312 is about 2.9 MHz. In some embodiments, the frequency of the ultrasonic waveform 304 during each treatment burst 308, 312 is about 1 MHz. The amplitude of the ultrasonic waveform 304 may be between 0.5 and 3.5 MPa. In some embodiments, the amplitude of the ultrasonic waveform 304 may be about 0.5 MPa during treatment bursts 308, 312 and about 3.5 MPa during rest periods 318 between treatment bursts 308, 312. In one example, the ultrasonic signal has a voltage of about 100 volts.

[0064] In some embodiments, the ultrasonic transducer is configured to generate the first set of ultrasonic signals 306 during a first electrical pulse sequence 308 of the plurality of electrical pulse sequences and generate the second set of ultrasonic signals 310 after the end of the first electrical pulse sequence 308 and before the start of a second electrical pulse sequence 312, the second electrical pulse sequence 312 being an electrical pulse sequence subsequent to the first electrical pulse sequence 308. In some embodiments, the frequency of the first set of ultrasonic signals 306 is lower than the frequency of the second set of ultrasonic signals 310. In certain embodiments, the amplitude of the first set of ultrasonic signals 306 is less than the amplitude of the second set of ultrasonic signals 310. In some examples, the amplitude of the second set of ultrasonic signals 310 is at least three times the amplitude of the first set of ultrasonic signals 306. In some examples, the amplitude of the second set of ultrasonic signals 310 is at least four times the amplitude of the first set of ultrasonic signals 306.

[0065] In some examples, during the first electrical pulse sequence 308, the amplitude of the first set of ultrasonic signals 306 may be about 0.5 MPa. In some cases, during the pause period 318, the amplitude of the second set of ultrasonic signals 310 may be about 3.5 MPa. In some embodiments, a third set of ultrasonic signals 320 may be provided. As shown, the third set of ultrasonic signals 320 may be generated after the start of the second electrical pulse sequence 312. In some cases, the amplitude of the third set of ultrasonic signals 320 may be the same as the amplitude of the first set of ultrasonic signals 306. In some cases, the amplitude of the third set of ultrasonic signals 320 is less than the second set of ultrasonic signals 310.

[0066] As shown, the first set of ultrasonic signals 306 has a first average amplitude 314 and the second set of ultrasonic signals 310 has a second average amplitude 316. In some examples, the first average amplitude 314 is different from the second average amplitude 316. In some examples, the first average amplitude 314 is less than the second average amplitude 316. In some embodiments, the amplitude 314 may be about 0.5 MPa and the amplitude 316 may be about 3.5 MPa.

[0067] FIG. 4 illustrates an exemplary electroporation ablation catheter 400 with an ultrasound transducer, according to an embodiment of the subject matter of the present disclosure. As shown in FIG. 4, the catheter 400 includes a catheter shaft 402 having a longitudinal axis 405 and having a distal end 406. As used herein, a longitudinal axis refers to a line passing through the center of gravity of a cross-section of an object. The catheter 400 further includes an electrode assembly 407. In some embodiments, the electrode assembly 407 extends from the distal end 406 of the catheter shaft 402. In embodiments, the electrode assembly 407 is configured to assume a first contracted state and a second expanded state. In some cases, the electrode assembly 407 includes an expandable component 420 and a plurality of electrodes 425 disposed on the expandable component 420. The expandable component 420 can be contracted in the first state and expanded in the second state.

[0068] In some embodiments, the electrode assembly 407 includes a plurality of splines 404 that form an internal cavity 415 and an inflatable balloon (not shown) disposed within the cavity 415. In such embodiments, the plurality of splines 404 and the balloon collectively form an expandable component 420.

[0069] In some embodiments, the catheter 400 is configured to receive ablation energy (e.g., electroporation pulses) at the plurality of electrodes 425 and generate an electric field at the plurality of electrodes 425. In one embodiment, the electric field has an electric field strength sufficient to ablate the target tissue by irreversible electroporation. In some embodiments, the plurality of electrodes 425 includes a first group of electrodes 408 and a second group of electrodes 410. In some cases, the first group of electrodes 408 is disposed around the plurality of splines 404, and the second group of electrodes 410 is disposed adjacent to the distal end 412 of the catheter 400. In some cases, the first group of electrodes 408 is referred to as the proximal electrodes, the second group of electrodes 410 is referred to as the distal electrodes, and the distal electrodes 410 are disposed closer to the distal end 412 of the electroporation ablation catheter 400 than the proximal electrodes 408. In some implementations, the electrodes 425 can include a thin film of conductive ink or optical ink. The ink can be polymer-based. The ink may further include materials such as carbon and / or graphite in combination with the conductive material. The electrodes may include biocompatible low resistivity metals such as silver, silver flake, gold, and platinum, which are also radiopaque.

[0070] Each electrode in the first electrode group 408 and each electrode in the second electrode group 410 are configured to conduct electricity and to be operably connected to a controller and an ablation energy generator (see FIG. 1 ). In an embodiment, one or more of the electrodes in the first electrode group 408 and the second electrode group 410 include a flex circuit.

[0071] The electrodes in the first electrode group 408 are spaced apart from the electrodes in the second electrode group 410. The first electrode group 208 includes electrodes 408a-408f, and the second electrode group 410 includes electrodes 410a-410f. Additionally, the electrodes in the first electrode group 408, such as electrodes 408a-408f, are spaced apart from one another, and the electrodes in the second electrode group 410, such as electrodes 410a-410f, are spaced apart from one another.

[0072] The spatial relationship and orientation of the electrodes in the first electrode group 408 and the second electrode group 410 relative to other electrodes on the same catheter 400 are known or can be determined. In an embodiment, once the catheter is deployed, the spatial relationship and orientation of the electrodes in the first electrode group 408 and the second electrode group 410 relative to other electrodes on the same catheter 400 are constant.

[0073] Similar to the ultrasonic transducer 220 shown in FIG. 2A, in this balloon catheter, an ultrasonic transducer 422 may be disposed in the cavity 415 near the distal end 406 of the catheter 400. The ultrasonic transducer 422 is configured to destroy one or more microbubbles that may form during treatment of a patient. Alternatively or additionally, in some embodiments, one or more transducers (not shown) may be disposed on the distal end 412 of the electrode assembly 407, for example, on an end cap. In some embodiments, one or more transducers may be disposed on the distal end 406 of the catheter shaft 400 as well as on the distal end 412 of the electrode assembly 412 to cover a larger area to reduce, destroy, and / or prevent the formation of microbubbles in the patient's heart. In some embodiments, the catheter shaft may include wires for the transmission of power and signal control from the first electrode group 408, the second electrode group 410, and / or the one or more ultrasonic transducers 422 to a controller (not shown). The controller is configured to send and receive signals to the first group of electrodes 408, the second group of electrodes 410, and / or one or more ultrasonic transducers 422 to generate electroporation pulses and ultrasonic waveforms during the treatment section.

[0074] FIG. 5 is an exemplary flow diagram illustrating a method 500 for reducing or preventing the formation of microbubbles during cardiac ablation by electroporation, according to an embodiment of the subject matter of the present disclosure. Aspects of an embodiment of the method 500 may be performed, for example, by an electroporation ablation system / device (e.g., the electrophysiological system 50 depicted in FIG. 1). One or more steps of the method 500 are optional and / or may be modified by one or more steps of other embodiments described herein. In addition, one or more steps of other embodiments described herein may be added to the method 500. As shown in FIG. 5, an electroporation catheter may be positioned in proximity to a target tissue in a patient (505). In some embodiments, the electroporation catheter includes one or more electrodes and an ultrasound transducer. In some embodiments, the one or more electrodes generate an electric field in proximity to the target tissue in response to a plurality of electrical pulse sequences delivered in a plurality of treatment sections (510). The electric field has an electric field strength sufficient to ablate the target tissue by irreversible electroporation.

[0075] One or more sets of ultrasound signals may be generated (515, 520) to destroy one or more microbubbles that may be formed during treatment of a patient. The one or more sets of ultrasound signals may include a first set of ultrasound signals and a second set of ultrasound signals. In some examples, the first set of ultrasound signals is generated during a first electrical pulse sequence of the plurality of electrical pulse sequences. In some examples, the second set of ultrasound signals is generated by the ultrasound transducer after the end of the first electrical pulse sequence and before the start of the second electrical pulse sequence. In some examples, the first set of ultrasound signals has a first average amplitude and the second set of ultrasound signals has a second average amplitude. In some examples, the first average amplitude is different from the second average amplitude. In certain examples, the first average amplitude is less than the second average amplitude.

[0076] Various modifications and additions can be made to the exemplary embodiments described without departing from the scope of the present invention. For example, while the embodiments described above refer to certain features, the scope of the present invention also includes embodiments having different combinations of features and embodiments that do not include all of the described features. Accordingly, the scope of the present invention is intended to embrace all such alternatives, modifications, and variations that fall within the scope of the claims, together with all equivalents thereof. The technical ideas that can be understood from the above-described embodiment will be described below as supplementary notes. [Appendix 1] 1. An electroporation ablation catheter comprising: an electrode assembly, the electrode assembly comprising: one or more electrodes configured to generate an electric field at the target tissue in response to a plurality of electrical pulse sequences delivered at the plurality of treatment sections; an ultrasonic transducer configured to generate a first set of ultrasonic signals during a first electrical pulse sequence of the plurality of electrical pulse sequences and to generate a second set of ultrasonic signals after the first electrical pulse sequence ends and before a second electrical pulse sequence that follows the first electrical pulse sequence; the first set of ultrasonic signals having a first average amplitude; the second set of ultrasonic signals having a second average amplitude; An electroporation ablation catheter, wherein the first average amplitude is different from the second average amplitude. [Appendix 2] 2. The electroporation ablation catheter of claim 1, wherein the first average amplitude is smaller than the second average amplitude. [Appendix 3] The electrode assembly further includes an internal component disposed in an internal cavity of the electrode assembly; 2. The electroporation ablation catheter of claim 1, wherein the ultrasound transducer is disposed on the internal component. [Appendix 4] 4. The electroporation ablation catheter of any one of claims 1 to 3, further comprising one or more wiring for supplying power to the ablation catheter and controlling at least one of the amplitude and frequency of the first set of ultrasound signals and the second set of ultrasound signals. [Appendix 5] The electrode assembly further includes a plurality of splines; 2. The electroporation ablation catheter of claim 1, wherein the ultrasonic transducer includes an ultrasonic transducer disposed on one of the plurality of splines. [Appendix 6] 2. The electroporation ablation catheter of claim 1, wherein the first set of ultrasound signals has a first average frequency and the second set of ultrasound signals has a second average frequency, the first average frequency being different from the second average frequency. [Appendix 7] 1. An electroporation ablation catheter comprising: an electrode assembly, the electrode assembly comprising: one or more electrodes configured to generate an electric field at the target tissue in response to a plurality of electrical pulse sequences delivered at the plurality of treatment sections; an ultrasonic transducer configured to generate an ultrasonic signal; an internal component disposed in an internal cavity of the electrode assembly; The electroporation ablation catheter, wherein the ultrasound transducer is disposed on the internal component. [Appendix 8] 8. The electroporation ablation catheter of claim 7, wherein the ultrasonic transducer is further configured to generate a first set of ultrasonic signals during a first electrical pulse sequence of the plurality of electrical pulse sequences and to generate a second set of ultrasonic signals after completion of the first electrical pulse sequence and prior to initiation of a second electrical pulse sequence that follows the first electrical pulse sequence. [Appendix 9] 9. The electroporation ablation catheter of claim 8, wherein the first set of ultrasound signals has a first average amplitude and the second set of ultrasound signals has a second average amplitude. [Appendix 10] 10. The electroporation ablation catheter of claim 9, wherein the first average amplitude is different from the second average amplitude. [Appendix 11] 10. The electroporation ablation catheter of claim 9, wherein the first average amplitude is less than the second average amplitude. [Appendix 12] 8. The electroporation ablation catheter of claim 7, wherein the internal component includes a deployment shaft. [Appendix 13] a catheter shaft having a proximal end and a distal end, the electrode assembly extending from the distal end of the catheter shaft; 13. The electroporation ablation catheter of any one of claims 7 to 12, wherein the deployment shaft extends from the distal end of the catheter shaft. [Appendix 14] The electrode assembly further includes a plurality of splines; 8. The electroporation ablation catheter of claim 7, wherein the ultrasonic transducer includes an ultrasonic transducer disposed on one of the plurality of splines. [Appendix 15] 15. The electroporation ablation catheter of claim 14, wherein the first set of ultrasound signals has a first average frequency and the second set of ultrasound signals has a second average frequency, the first average frequency being different from the second average frequency.

Claims

1. 1. An electroporation ablation catheter comprising: an electrode assembly, the electrode assembly comprising: one or more electrodes configured to generate an electric field at the target tissue in response to a plurality of electrical pulse sequences delivered at the plurality of treatment sections; an ultrasonic transducer configured to generate a first set of ultrasonic signals during a first electrical pulse sequence of the plurality of electrical pulse sequences and to generate a second set of ultrasonic signals after the first electrical pulse sequence ends and before a second electrical pulse sequence begins that is a subsequent electrical pulse sequence to the first electrical pulse sequence; the first set of ultrasonic signals having a first average amplitude; the second set of ultrasonic signals having a second average amplitude; An electroporation ablation catheter, wherein the first average amplitude is different from the second average amplitude.

2. The electroporation ablation catheter of claim 1 , wherein the first average amplitude is less than the second average amplitude.

3. The electrode assembly further includes an internal component disposed in an internal cavity of the electrode assembly; The electroporation ablation catheter of claim 1 , wherein the ultrasound transducer is disposed on the internal component.

4. 4. The electroporation ablation catheter of claim 1, further comprising one or more wires for supplying power to the ablation catheter and controlling at least one of the amplitude and frequency of the first and second sets of ultrasound signals.

5. The electrode assembly further includes a plurality of splines; The electroporation ablation catheter of claim 1 , wherein the ultrasonic transducer comprises an ultrasonic transducer disposed on one of the plurality of splines.

6. 2. The electroporation ablation catheter of claim 1, wherein the first set of ultrasound signals has a first average frequency and the second set of ultrasound signals has a second average frequency, the first average frequency being different from the second average frequency.

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