Careful irreversible electroporation (IRE) protocol to avoid air bubble generation

Abstract

To provide irreversible electroporation (IRE) of cardiac tissue.SOLUTION: An irreversible electroporation (IRE) includes setting an initial IRE protocol for applying IRE pulses by electrodes of a catheter placed in contact with tissue in an organ. A notification is issued to a user upon determining that the initial IRE protocol is expected to cause bubbles in blood. In response to the notification, user input is received from the user, the user input selecting between the initial IRE protocol and an alternative protocol that is not expected to cause the bubbles. The IRE pulses are applied according to the initial IRE protocol or the alternative IRE protocol, depending on the user input.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates generally to invasive ablation, and more particularly to irreversible electroporation (IRE) of cardiac tissue. [Background technology]

[0002] Estimation of invasive ablation parameters and controlling ablation according to the estimation has been previously proposed in the patent literature. For example, US Patent Application Publication No. 2013 / 0006228 describes an apparatus for localized delivery of energy and a method of using such an apparatus, particularly for therapeutic treatment of living tissue. The disclosed method may include positioning and disposing an energy delivery member within a target site and delivering energy through the energy delivery member. In one embodiment, the radio frequency (RF) duty cycle and / or pulse duration may be configured to vary depending on one or more selected parameters, which may include the frequency of the treatment signal, the power of the treatment signal, or the tissue impedance to the treatment signal.

[0003] As another example, U.S. Patent Application Publication No. 2016 / 0066977 describes a medical system for ablating a tissue site with real-time monitoring during an electroporation treatment procedure. A pulse generator generates a pre-treatment test signal having a frequency of at least 1 MHz prior to the treatment procedure and an in-treatment test signal during the treatment procedure. A treatment control module determines impedance values ​​from the pre-treatment test signal and the in-treatment test signal, and determines an end point of electroporation and processing in real time based on the determined impedance values ​​while the treatment is in progress. Summary of the Invention [Means for solving the problem]

[0004] One embodiment of the present invention described below provides an irreversible electroporation (IRE) process that includes setting an initial IRE protocol for delivering an IRE pulse by an electrode of a catheter placed in contact with tissue within an organ. Upon determining that the initial IRE protocol is expected to cause air bubbles in the blood, a notification is issued to a user. In response to the notification, a user input is received from a user selecting between the initial IRE protocol and an alternative protocol that is not expected to cause air bubbles. In response to the user input, an IRE pulse is delivered according to the initial IRE protocol or the alternative IRE protocol.

[0005] In some embodiments, receiving the user input includes receiving a division of the series of IRE pulses of the initial IRE protocol into a given number of pulse trains with respective given pauses between the pulse trains.

[0006] In some embodiments, the initial IRE protocol and the alternate IRE protocol have the same total number of IRE pulses. In other embodiments, the alternate IRE protocol has fewer IRE pulses than the initial IRE protocol.

[0007] According to another embodiment of the present invention, there is additionally provided an irreversible electroporation (IRE) system including a user interface and a processor. The user interface is configured to set an IRE protocol for administering IRE pulses by an electrode of a catheter placed in contact with tissue within an organ. The processor is configured to (i) issue a notification to a user upon determining that an initial IRE protocol is expected to cause air bubbles in the blood, (ii) in response to the notification, receive user input via the user interface selecting either the initial IRE protocol or an alternative protocol that is not expected to cause air bubbles, and (iii) in response to the user input, administer the IRE pulses according to the initial IRE protocol or the alternative IRE protocol. [Brief description of the drawings]

[0008] The invention will be more fully understood from consideration of the following detailed description taken in conjunction with the drawings, in which: [Figure 1] FIG. 1 is a schematic, depiction of a catheter-based irreversible electroporation (IRE) system, in accordance with an exemplary embodiment of the present invention. [Diagram 2] FIG. 2 is a flow diagram that generally illustrates a method of applying an irreversible electroporation (IRE) pulse using the system of FIG. 1, in accordance with an exemplary embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] Overview Irreversible electroporation (IRE), also known as pulsed field ablation (PFA), can be used as an invasive therapeutic modality to kill tissue cells by exposing them to high voltage pulses. Specifically, IRE pulses have potential use to kill myocardial tissue cells to treat cardiac arrhythmias. Cell destruction occurs when the transmembrane potential exceeds a threshold, resulting in cell death and thus the development of tissue lesions. Thus, specifically, it relates to using high voltage bipolar electrical pulses (e.g., using a selected pair of electrodes in contact with tissue) to generate a high electric field to kill tissue cells between the electrodes.

[0010] However, IRE pulses used to ablate tissue can cause unintended and / or undesirable effects of potential clinical danger when the pulse is powerful enough. For example, a pulse voltage of 1 kV across a blood impedance of 100 Ω (both possible values) produces a local peak current of 10 A, i.e., 10 kW, instantaneously in the blood. This voltage can be applied between the electrodes to form a series of bipolar IRE pulses and can be high enough to generate sufficient Joule heating, which can generate bubbles in the blood if not dissipated quickly. Some physicians may choose to accept the risk of some bubble formation, while others may prefer not to, typically due to the patient's condition, e.g., recent stroke.

[0011] The embodiments of the invention described hereinafter provide methods and systems for IRE. In some embodiments, various IRE ablation protocols (also referred to as "initial protocols") are pre-evaluated to determine whether they may generate bubbles. The evaluation performed in the laboratory may also determine one or more alternative protocols that are proposed to the user. During the ablation procedure, if the physician (or other user) initially sets an IRE ablation protocol that may generate bubbles, the system notifies the physician, who is given the choice of using the "as is" or applied protocol (hereinafter "receive user input to select"), a more conservative IRE ablation protocol that does not generate bubbles.

[0012] In some embodiments, determining that a selected protocol may generate air bubbles means estimating or measuring the impedance between the electrodes of a given electrode pair and comparing the impedance to a threshold value. If the estimated or measured impedance is below the threshold value, the processor determines that the power dissipated in the blood between the electrode pair may generate air bubbles.

[0013] In some embodiments, a more conservative IRE ablation protocol divides the IRE pulse sequence of a selected protocol into pulse sequences that include multiple trains of pulses with pauses between them, allowing Joule heating from any pulse to dissipate sufficiently so that bubbles do not form.

[0014] In some embodiments, to maintain clinical efficacy, more conservative IRE ablation protocols do not change the overall energy dissipated. Rather, the protocols spread out the pulse application time to allow for more diffusion of the generated heat and reduce the maximum temperature caused by heating. Furthermore, pulse peak voltage is typically not reduced in conservative IRE ablation protocols, as this affects the generated electroporation field. Any reduction in peak voltage must be maintained above the predefined minimum level required for IRE ablation to be clinically effective.

[0015] In other embodiments, the physician (or other user) can modify any parameter of the discreet protocol from the user interface, particularly the number of pulse trains and the minimum pause length. For example, the physician can split the IRE pulse sequence of the selected protocol into a pulse sequence that includes multiple pulse trains with pauses between them. The pauses allow Joule heating from any pulse to dissipate sufficiently so that bubbles do not form. The user may further decide to lower the total number of pulses to further reduce the cumulative (i.e., overall) power delivered to the tissue.

[0016] In one embodiment, the system gates the pulse train applied synchronously with the heart beat, for example, so that it is applied during the refractory period of the tissue. Ventricular and atrial electrograms at the ventricular or atrial tissue location are acquired, for example, during electrophysiological mapping of the respective wall tissue portion of the respective heart chamber, typically by electrodes in contact with the tissue at the location catheter. The ventricular or atrial refractory period is the duration of quiescence of neural activity at the tissue location after activation has occurred there (in the tissue of either of the above mentioned chambers). The refractory period typically coincides approximately with the QRST interval portion of the cardiac cycle shown in the ventricular or atrial electrogram taken at that location. The refractory period can be intentionally induced in the tissue portion of the heart, for example, using a pacing catheter that slowly moves the tissue at the tissue location.

[0017] Cardiac IRE ablation may be performed in accordance with the disclosed techniques using an expandable frame (e.g., balloon or basket) attached to the distal end of an ablation catheter. In an exemplary procedure, the expandable frame, with ablation electrodes disposed thereon, is navigated through the cardiovascular system and inserted into the heart to, for example, ablate the openings of the pulmonary veins (PV).

[0018] By providing a more conservative protocol as an alternative to the initial IRE protocol, IRE ablation procedures may be safely performed using an expandable frame catheter, for example within the ostium of a PV, while maintaining clinical efficacy.

[0019] System Description 1 is a schematic, pictorial illustration of a catheter-based irreversible electroporation (IRE) system 20, in accordance with an embodiment of the present invention. System 20 includes a catheter 21, whose shaft 22 is inserted through a sheath 23 and into a heart 30 of a patient 28. A physician 30 then navigates a distal end 22a of shaft 22 to a target location inside the patient's heart 26, as shown in inset 25.

[0020] Once the distal end 22a of the shaft 22 reaches the target location, the physician 30 retracts the sheath 23 and expands the balloon 40, typically by pumping saline into the balloon 40. The physician 30 then manipulates the shaft 22 so that an electrode 50 disposed on the balloon 40 catheter engages the inner wall of the PV opening 51 and applies a high voltage IRE pulse via the electrode 50 to the opening 51 tissue.

[0021] As seen in insets 25 and 27, distal end 22a is fitted with an inflatable balloon 40 comprising multiple equidistant smooth edge IRE electrodes 50. Due to the flat shape of the distal portion of balloon 40, the distance between adjacent electrodes 50 remains approximately constant, even when electrodes 50 cover the distal portion. Thus, the configuration of balloon 40 allows for more effective electroporation (e.g., with approximately uniform field strength) between adjacent electrodes 50, while the smooth edges of electrodes 50 minimize undesirable thermal effects.

[0022] Certain aspects of inflatable balloons are addressed, for example, in U.S. Provisional Patent Application No. 62 / 899,259, entitled "Balloon Catheter with Force Sensor," filed on September 12, 2019, and U.S. Provisional Patent Application No. 16 / 726,605, entitled "Contact Force Spring with Mechanical Stops," filed on December 24, 2019, both of which are assigned to the assignee of the present patent application, the disclosures of which are incorporated herein by reference.

[0023] In the embodiments described herein, the catheter 21 may be used for any suitable diagnostic and / or therapeutic purposes, such as electrophysiological sensing of PV opening 51 tissue in the left atrium 45 of the heart 26 and / or the aforementioned IRE isolation.

[0024] The proximal end of catheter 21 is connected to a console 24 that includes an IRE pulse generator 38 configured to deliver IRE pulses between adjacent electrodes 50. The electrodes are connected to the IRE pulse generator 38 by electrical wires that run within the shaft 22 of catheter 21. A memory 48 of console 24 stores an IRE protocol, including IRE pulse parameters such as peak bipolar voltage and pulse width.

[0025] Console 24 includes a processor 41, typically a general purpose computer, with suitable front end and interface circuitry 37 for receiving signals from catheter 21 and from external electrodes 49, typically placed around the chest of patient 26. To this end, processor 41 is connected to external electrodes 49 by wiring that runs within cable 39.

[0026] During the procedure, the system 20 can track the position of each of the electrodes 50 within the heart 26 using the Active Current Location (ACL) method provided by Biosense-Webster (Irvine California), which is described in U.S. Pat. No. 8,456,182, the disclosure of which is incorporated herein by reference.

[0027] In some embodiments, if physician 30 is notified by processor 41 of the risk of air bubbles using the initially set IRE protocol, physician 30 may select a more conservative protocol that splits (divides) the IRE pulse delivery 55 of the selected protocol into multiple pulse trains 57 with pauses 59 between the pulse trains, as shown in inset 27. The pauses allow Joule heating from any pulses to dissipate sufficiently so that air bubbles do not form.

[0028] In other embodiments, the physician 30 can modify any of the parameters of the discreet protocol, particularly the number of pulse trains and the minimum pause length, from the user interface 47. For example, the user may decide to remove a pulse in a sequence to reduce the total number of pulses delivered. The user interface 47 may include any suitable type of input device, such as a keyboard, a mouse, a trackball, etc.

[0029] The processor 41 is typically programmed to carry out the functions described herein in software, which may be downloaded to the computer in electronic form, for example over a network, or alternatively or additionally may be provided and / or stored on a non-transitory tangible medium, such as a magnetic, optical or electronic memory.

[0030] 2, which enables processor 41 to perform the disclosed steps, as further described below. In particular, processor 41 is configured to instruct IRE pulse generator 38 to output IRE pulses according to a processing protocol that processor 41 uploads from memory 48.

[0031] Careful IRE protocol to avoid air bubble generation Figure 2 is a flow diagram that generally illustrates a method for delivering an irreversible electroporation (IRE) pulse using the system 20 of Figure 1, in accordance with an embodiment of the present invention. In the embodiment presented, the algorithm executes a process that begins when the physician 30 navigates the balloon catheter 40, for example, using electrode 50 as an ACL sensing electrode, in a balloon catheter navigation step 80, to a target tissue location within a patient's organ, such as a PV opening 51.

[0032] Next, in an IRE planning step 82, the processor 41 uploads the protocol originally set up by the physician 30 with parameters for the IRE pulses to be applied to the tissue. An example of IRE ablation settings in an initial protocol that may be used to ablate cardiac tissue using the disclosed balloon 40 is shown in Table I.

[0033] [Table 1]

[0034] Next, in a notification step 84, processor 41 provides notification to physician 30 that the initial IRE protocol may generate air bubbles in the blood. In response, the physician may decide to stick with the protocol (i.e., use the initial protocol) in a protocol decision step 86. Alternatively, in a protocol change decision step 88, the physician decides to change the protocol to, for example, an alternative protocol shown in Table II.

[0035] [Table 2]

[0036] As seen in Table II, a more conservative protocol would divide the series of pulses in Table I into eight pulse trains of five pulses each with a minimum rest of two seconds between pulse trains.

[0037] In one embodiment, physician 30 can modify any of the parameters of Table II, specifically the number of pulse trains and the minimum pause between pulse trains, from user interface 47. Alternatively, the parameters of the alternate protocols may be set automatically by processor 41. In one such embodiment, processor 41 maintains a respective alternate protocol for each supported initial protocol. In another embodiment, processor 41 derives the parameters of the alternate protocols from the parameters of the initial protocol according to some predefined rules or methodology.

[0038] Once an IRE protocol is selected (either an initial protocol per step 86 or an alternate protocol per step 88), processor 41 commands generator 38 to deliver an IRE pulse to tissue at an IRE therapy step 90. The IRE pulse is delivered between selected electrodes of balloon 40 to isolate arrhythmias originating or propagating through opening 51.

[0039] Although the embodiments described herein primarily address cardiac applications, the methods and systems described herein may also be used in other medical applications, such as neurological and ENT.

[0040] It will therefore be understood that the above-described embodiments are cited by way of example, and that the present invention is not limited to what has been particularly shown and described above. Rather, the scope of the present invention includes both combinations and subcombinations of the various features described in the above specification, as well as variations and modifications thereof that would occur to one skilled in the art upon reading the foregoing description, and that are not disclosed in the prior art. Documents incorporated by reference into this patent application are to be considered as part of this application, except that if any term is defined in these incorporated documents in a manner that is inconsistent with the definition expressly or impliedly given herein, then only the definition in this specification shall be considered.

[0041] [Embodiment] (1) A method of irreversible electroporation (IRE), comprising: establishing an initial IRE protocol for applying IRE pulses via an electrode of a catheter positioned in contact with tissue within the organ; issuing a notification to a user upon determining that the initial IRE protocol is expected to cause air bubbles in the blood; receiving user input from the user in response to the notification selecting between the initial IRE protocol and an alternative protocol that is not expected to cause the bubble; providing the IRE pulses according to the initial IRE protocol or the alternative IRE protocol in response to the user input; A method comprising: (2) The method of embodiment 1, wherein receiving the user input includes receiving a division of the series of the IRE pulses of the initial IRE protocol into a given number of the pulse trains with respective given pauses between the pulse trains. (3) The method of embodiment 1, wherein the initial IRE protocol and the alternative IRE protocol have the same total number of the IRE pulses. (4) The method of embodiment 1, wherein the alternative IRE protocol has a smaller number of IRE pulses than the initial IRE protocol. (5) An irreversible electroporation (IRE) system comprising: a user interface configured to set an IRE protocol for applying IRE pulses by electrodes of a catheter placed in contact with tissue within the organ; a processor, the processor comprising: issuing a notification to a user upon determining that the initial IRE protocol is expected to cause air bubbles in the blood; receiving, in response to the notification, a user input via the user interface selecting between the initial IRE protocol and an alternative protocol that is not expected to cause the bubbles; responsive to the user input, applying the IRE pulses according to the initial IRE protocol or the alternative IRE protocol; The system is configured as follows:

[0042] (6) The system of embodiment 5, wherein the processor is configured to receive in the user input a division of the series of IRE pulses into a given number of the pulse trains with respective given pauses between the pulse trains. (7) The system of embodiment 5, wherein the initial IRE protocol and the alternative IRE protocol have the same total number of the IRE pulses. (8) The system of embodiment 5, wherein the alternative IRE protocol has fewer pulses than the initial IRE protocol.

Claims

1. 1. An irreversible electroporation (IRE) system comprising: a user interface configured to set an IRE protocol for applying IRE pulses by electrodes of a catheter placed in contact with tissue within the organ; a processor, the processor comprising: issuing a notification to a user upon determining that the initial IRE protocol is expected to cause air bubbles in the blood; receiving, in response to the notification, a user input via the user interface selecting between the initial IRE protocol and an alternative protocol that is not expected to cause air bubbles; providing the IRE pulse according to the initial IRE protocol or the alternative protocol in response to the user input; The system is configured as follows:

2. 2. The system of claim 1, wherein the processor is configured to receive, at the user input, a division of the series of IRE pulses into a given number of said pulse trains with respective given pauses between the pulse trains.

3. The system of claim 1 , wherein the initial IRE protocol and the alternative protocol have the same total number of the IRE pulses.

4. The system of claim 1, wherein the alternative protocol has fewer pulses than the initial IRE protocol.

5. 1. A method of operating an irreversible electroporation (IRE) system, comprising: The irreversible electroporation (IRE) system comprises a user interface and a processor; the user interface setting an initial IRE protocol for delivering IRE pulses by electrodes of a catheter placed in contact with tissue within an organ; if the processor determines that the initial IRE protocol is expected to cause air bubbles in the blood, the processor issues a notification to a user; receiving, in response to the notification, a user input from the user selecting between the initial IRE protocol and an alternative protocol that is not expected to cause the air bubble; the processor providing the IRE pulses according to the initial IRE protocol or the alternative protocol in response to the user input; A method of operating an irreversible electroporation (IRE) system, comprising:

6. A method of operating the irreversible electroporation (IRE) system of claim 5, wherein the processor receiving the user input includes the processor receiving a division of a series of the IRE pulses of the initial IRE protocol into a given number of the pulse trains with respective given pauses between the pulse trains.

7. 6. The method of claim 5, wherein the initial IRE protocol and the alternative protocol have the same total number of the IRE pulses.

8. A method of operating an irreversible electroporation (IRE) system as described in claim 5, wherein the alternative protocol has a smaller number of IRE pulses than the initial IRE protocol.

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