Device and method for irreversible electroporation of tissue

Abstract

To provide a device and method for irreversible electroporation of tissue.SOLUTION: A device and a method for the electroporation are described. An exemplary embodiment of the device has a catheter and a signal generator-evaluation unit connected to the proximal end of the catheter.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] A device and method for irreversible electroporation of tissue is presented herein. [Background technology]

[0002] In recent years, the treatment of tissue with pulsed electric fields has become increasingly established as a relevant clinical technique. However, the use of short high-voltage pulses and the associated high field strengths acting on tissue has been the subject of intensive research for over 40 years. This application method is classified as a non-thermal procedure because it is based on the delivery of short high-voltage pulses that generate locally intense electric fields of up to several hundred volts per centimeter between active electrode pairs. This electric field strength results in the formation of pores in cell membranes. Electroporation becomes irreversible if the electric field exceeds a certain threshold required for pore formation in the lipid bilayer of the cell membrane, and if the tissue is exposed to such an electric field for a critical period of time. The pores remain permanently open, ultimately leading to the programmed cell death (apoptosis) of the affected cells.

[0003] Irreversible electroporation (IRE) is a primarily non-thermal procedure, resulting in only a small increase in tissue temperature of a few degrees over a few milliseconds. This distinguishes IRE from conventional RF ablation (RF: radio frequency), in which tissue temperatures rise from 20°C to 70°C and cells are thermally destroyed. In IRE, bipolar pulses, i.e., a combination of positive and negative pulses, are typically used to minimize muscle contraction, which typically occurs when direct current voltage is applied. These pulses can be applied between two bipolar electrodes on a catheter or between an electrode on the catheter and a body surface electrode, typically attached to the patient's back.

[0004] For an IRE pulse to generate the desired pores in tissue, the electric field strength E defined by the pulse in the tissue between at least two electrode pairs must exceed a tissue-dependent threshold Eth. For example, the threshold for cardiac cells is approximately 500 V / cm, while that for bone cells is 3000 V / cm. These differences in field strength thresholds allow for selective application of IRE to different tissues. To achieve the required field strength, the voltage applied to the electrode pair depends on the distance between the target tissue and the electrodes and the size of the electrodes themselves. These parameters also affect the input of thermal energy during ablation and, therefore, the peak temperature that can occur in the treated tissue. The applied voltage can reach 2000 V, significantly higher than the 10-200 V voltages typically used for thermal RF ablation.

[0005] IRE bipolar pulsed electric field ablation pulses (bipolar PFA pulses) comprise positive and negative pulses applied between two electrodes with a pulse width of 1 to 5 microseconds and an interval between the positive and negative pulses of 1 to 5 microseconds. The bipolar pulses are combined to form pulse trains, each of which may comprise 100 or more bipolar pulses with an interval between pulses of 1 to 10 milliseconds. The pulse trains in each case form bursts, and the entire IRE ablation pulse packet consists of 1 to 20 burst units, each with an interval between bursts of 1 to 1000 milliseconds. The total ablation time can be up to 10 seconds.

[0006] US Patent Application Publication No. 2022 / 019274 discloses a spherical structure having multiple elongated elements with multiple transducers disposed on each element.

[0007] U.S. Patent Application Publication No. 2021 / 0169567 discloses a catheter shaft configured to be inserted into a patient's organ. An inflatable balloon is connected to the distal end of the catheter. A plurality of electrodes are disposed on the exterior of a membrane of the balloon.

[0008] WO 2022 / 256218 discloses a catheter having a catheter shaft and a balloon. The balloon is disposed at the distal end region of the catheter shaft. One or more electrodes are disposed on the outer or inner surface of the balloon.

[0009] Chinese Utility Model Registration No. 216495608 discloses a balloon-shaped catheter with multiple electrodes arranged on the outside.

[0010] US Patent Application Publication No. 2022 / 0222954 discloses a balloon catheter having multiple electrodes disposed thereon.

[0011] WO 2019 / 181634 discloses a balloon catheter having multiple electrodes arranged around the balloon.

[0012] WO 2021 / 116774 discloses a balloon catheter having multiple electrodes disposed at the distal end of the balloon catheter.

[0013] US Patent Application Publication No. 2021 / 0153935 discloses a balloon catheter having electrodes wound around an outer shell, the loop catheter spirally projecting from the distal end of the balloon catheter where the electrodes of the loop catheter are located.

[0014] Further known documents include US Patent Application Publication No. 2022 / 0233236, EP Patent No. 3456278, and US Patent Application Publication No. 2022 / 0241008. [Prior art documents] [Patent documents]

[0015] [Patent Document 1] US Patent Application Publication No. 2022 / 019274 [Patent Document 2] U.S. Patent Application Publication No. 2021 / 0169567 [Patent Document 3] International Publication No. 2022 / 256218 [Patent Document 4] China Utility Model Registration No. 216495608 [Patent Document 5] US Patent Application Publication No. 2022 / 0222954 [Patent Document 6] International Publication No. 2019 / 181634 [Patent Document 7] International Publication No. 2021 / 116774 [Patent Document 8] U.S. Patent Application Publication No. 2021 / 0153935 [Patent Document 9] US Patent Application Publication No. 2022 / 0233236 [Patent Document 10] European Patent No. 3456278 [Patent Document 11] US Patent Application Publication No. 2022 / 0241008 Summary of the Invention [Problem to be solved by the invention]

[0016] The present invention addresses the problem of accelerated electroporation. [Means for solving the problem]

[0017] To achieve this goal, an apparatus according to claim 1 and a method according to claim 13 are proposed.

[0018] According to a first aspect, a device for irreversible electroporation of tissue of a patient is proposed. The device comprises a catheter. The catheter has a proximal end and a distal electrode (tip electrode), particularly a separate / monopolar electrode, (e.g., one), located at the distal end, particularly the outermost part, of the catheter. The catheter has a membrane located between the distal end and the proximal end. The membrane is configured to have a first configuration, particularly a cylindrical or collapsed shape, and a second configuration, particularly a balloon or inflated shape. The catheter comprises a plurality of electrodes, particularly spatially separated from the distal electrode. The plurality of electrodes are located on the membrane. The device comprises a signal generating and evaluating unit connected to the proximal end of the catheter and configured to perform tissue impedance determination, particularly local tissue impedance determination and / or ablation.

[0019] The signal generating and evaluating unit may comprise a signal generating unit and / or an evaluating unit and / or a controller. The signal generating and evaluating unit may be configured to perform tissue impedance determination or ablation, or tissue impedance determination and, e.g., subsequent ablation.

[0020] The device may further include a proximal electrode disposed at the proximal end of the catheter. Additionally or alternatively, the device may include at least one additional electrode disposed between the membrane and the distal electrode.

[0021] The signal generating and evaluating unit may be configured to transmit a first electrical signal to the tissue via an electrode constellation. The signal generating and evaluating unit may be configured to transmit the first electrical signal to the tissue and receive a second electrical signal from the tissue via the electrode constellation. An electrode constellation may be understood as a pairwise combination of electrodes. The signal generating and evaluating unit may be configured to activate electrode pairs and / or electrode constellations and / or switch electrodes (electrode pairs) and / or electrode constellations.

[0022] The electrode group may be defined, particularly in the first configuration state, by forming / configuring a proximal electrode and a distal electrode as a first electrode pair and an additional electrode and a distal electrode as a second electrode pair.

[0023] The electrode group may be defined, particularly in the second configuration state, by forming / configuring a proximal electrode and a distal electrode as a first electrode pair and one of the plurality of electrodes and an additional electrode as a second electrode pair.

[0024] The electrode group may be defined, particularly in the second configuration state, by being formed / configured as a first electrode pair consisting of two electrodes of the plurality of electrodes arranged one spaced apart from each other, and a second electrode pair consisting of a distal electrode and a further electrode arranged between the two electrodes of the plurality of electrodes, particularly the two electrodes arranged one spaced apart from each other, which may be understood as an electrode or electrode pair having a common directly adjacent electrode between them.

[0025] In the first operating phase, the first electrical signal may be configured as a current signal and the second electrical signal may be configured as a voltage signal. In the first operating phase, the signal generating and evaluating unit may be configured to determine at least one particularly local tissue impedance from the current signal (=first electrical signal) transmitted to the tissue and the voltage signal (=second electrical signal) received from the tissue.

[0026] The signal generating and evaluating unit may be configured to determine impedances of at least two particularly local tissues, in particular by means of at least two (activated) electrode groups / electrode pairs / electrodes selected / switched in succession (in time).

[0027] The signal generating and evaluating unit may be configured to activate at least one different first and / or second electrode pair among the group of electrodes, in particular sequentially in time, to identify at least two particularly local tissue impedances in the group of electrodes, in other words, the signal generating and evaluating unit may be configured to activate different electrodes among the first and / or second electrode pairs among the selected group of electrodes, thereby forming new first and / or new second electrode pairs from which tissue impedance, in particular local tissue impedance, can be identified by a different signal path through the tissue.

[0028] The signal generating and evaluating unit may be configured, in particular when in the second configuration state the proximal electrode and the distal electrode (of the electrode group) form a first electrode pair and one of the plurality of electrodes and the additional electrode form a second electrode pair, to activate the second electrode pair at least once from at least one further electrode of the plurality of electrodes and the additional electrode in the second configuration state, and to identify the impedance of at least one further tissue, in particular locally.

[0029] In other words, in one electrode group, a first electrode pair may be formed by a proximal electrode and a distal electrode, and a second electrode pair may be formed by one of the plurality of electrodes and an additional electrode. The signal generating and evaluating unit may be configured to activate a further electrode of the plurality of electrodes and the additional electrode after each measurement of the second electrical signal / voltage signal until second electrical signals / voltage signals have been measured for all possible electrode combinations of the plurality of electrodes and the additional electrode.

[0030] In particular, in the second configuration state, the signal generating and evaluating unit may be configured to form a first electrode pair from two electrodes (of the electrode group) located one spaced apart from one another of the plurality of electrodes, and a second electrode pair from the distal electrode and a further electrode, particularly located between the two electrodes located one spaced apart from one another of the plurality of electrodes. The signal generating and evaluating unit may be configured to activate / form at least once a first electrode pair from two further electrodes located one spaced apart from one another of the plurality of electrodes, in particular in the second configuration state, and a second electrode pair from the distal electrode and a further electrode, particularly located between the two electrodes located one spaced apart from one another of the plurality of electrodes, in particular in the second configuration state, to determine the impedance of at least one further local tissue, in particular.

[0031] In the second operating phase, the electrical signal may be configured as a voltage signal. The signal generating and evaluating unit may be configured to generate the voltage signal according to a selected burst signal protocol and transmit the signal to the tissue via the first electrode pair. In particular, in the second operating phase, the signal generating and evaluating unit may activate one electrode pair.

[0032] In particular, in the second configuration state, the first electrode pair may be formed by the distal electrode and one of the plurality of electrodes, and in particular, in the second configuration state, the first electrode pair may be formed by two, particularly (closely) adjacent, electrodes of the plurality of electrodes.

[0033] The device may have a counter electrode, particularly a body surface counter electrode, connected to the signal generating and evaluating unit. In particular, in the second configuration, a first electrode pair may be formed by one of the electrodes and the counter electrode. In particular, in the first configuration, the first electrode pair may be formed by the distal electrode and the counter electrode.

[0034] In the first operating phase, the first electrical signal may be configured as a current signal, and the second electrical signal may be configured as a voltage signal. In the first operating phase, the signal generating and evaluating unit may be configured to determine at least one, particularly global and / or local tissue impedance, from the current signal transmitted to the tissue and the voltage signal received from the tissue. The first electrical signal may be transmitted to the tissue via a first electrode pair. The second electrical signal may be received via the first electrode pair. In other words, a current may be transmitted to the tissue and a voltage may be received via the same electrode pair.

[0035] The signal generating and evaluating unit may be configured to switch between or from an electrode pair, in particular sequentially in time, at least one further electrode of the plurality of electrodes. In other words, one electrode of an electrode pair may be replaced by a further electrode of the plurality of electrodes. In this way, new electrode pairs may be formed. This may be performed repeatedly, in particular sequentially in time.

[0036] The electrodes (especially multiple electrodes, proximal electrodes, distal electrodes and / or additional electrodes) may be connected to the signal generating and evaluating unit via the proximal end of the catheter by electrical wires insulated from each other and from the immediate surroundings and particularly located externally on the catheter or internally within the catheter.

[0037] In particular during the first and / or second operating phases, the signal generating and evaluating unit may be configured to generate a first electrical signal based on a burst signal protocol and transmit / send said signal to the first electrode pair.

[0038] The format of the burst signal sequence protocol can specify characteristics and amounts of energy per burst, and may include a first number of bursts in the burst signal sequence, at least one first time interval between at least two consecutive bursts in the burst signal sequence, a second number of bipolar pulses in a burst, at least one second time interval between at least two consecutive bipolar pulses in a burst, a third time interval between a positive and negative pulse of the at least one bipolar pulse, pulse widths of the positive and / or negative pulses of the at least one bipolar pulse, and / or pulse deflection values ​​of the positive and / or negative pulses of the at least one bipolar pulse.

[0039] The first number of bursts in the burst signal sequence can range in value from 1 to 100 burst units.

[0040] At least one first time interval between two consecutive bursts of the burst signal sequence can range in value from 1 millisecond to 1000 milliseconds, and the second number of bipolar pulses in the burst can range in value from 1 to 300 bipolar pulse units.

[0041] At least one second time interval between at least two consecutive bipolar pulses in a burst can have a value ranging from 1 to 10 milliseconds, and a third time interval between positive and negative pulses can have a value ranging from 1 to 5 microseconds.

[0042] The pulse width of the positive and / or negative pulses can range from 1 to 10 microseconds. The pulse width of the positive pulses can be different from the pulse width of the negative pulses.

[0043] The pulse deflection value for a positive pulse can range from 200 to 2000 V. The pulse deflection value for a negative pulse can range from −200 to −2000 V.

[0044] According to a second aspect, a method for irreversible electroporation of tissue of a patient is proposed. The method comprises providing a catheter. The catheter has a proximal end and a distal electrode disposed at the distal end of the catheter. The catheter has a membrane disposed between the distal end and the proximal end. The membrane is configured to assume a first or second configuration. The catheter has a plurality of electrodes disposed on the membrane. The method comprises providing a signal generating and evaluating unit connected to the proximal end of the catheter. The method comprises performing tissue impedance characterization and / or performing ablation. In other words, the method comprises (i) performing tissue impedance characterization or (ii) performing ablation or (iii) performing tissue impedance characterization and ablation, e.g., performing ablation after or subsequent to tissue impedance characterization.

[0045] Further features, characteristics, advantages and possible modifications will become apparent to those skilled in the art from the following description taken in conjunction with the accompanying figure figures. [Brief explanation of the drawings]

[0046] [Figure 1] FIG. 1 is a schematic diagram of a bipolar IRE pulse according to an exemplary embodiment of the invention. [Figure 2] FIG. 2 is a schematic diagram of a pulse protocol having multiple trains or bursts of bipolar pulses according to an exemplary embodiment of the invention. [Figure 3] FIG. 3 shows a schematic diagram of the device with an inflated balloon membrane. [Figure 4] FIG. 4 shows a schematic diagram of the device of FIG. 3 with the membrane folded in a focal configuration. [Figure 5] FIG. 5 shows a wiring schematic of electrodes in a focal catheter configuration for local impedance measurements. [Figure 6] FIG. 6 shows the electrode wiring schematic for a "one-shot" catheter configuration for local impedance measurements. [Figure 7]FIG. 7 shows a further wiring schematic of the electrodes in a "one-shot" catheter configuration for local impedance measurements. [Figure 8] FIG. 8 shows a schematic representation of the possible ablation modes of the device in the expanded membrane configuration. [Figure 9] FIG. 9 shows a schematic representation of the possible ablation modes of the device in the collapsed membrane configuration. [Figure 10] FIG. 10 shows a schematic of the overall tissue impedance measurement of the device in the inflated membrane state. [Figure 11] FIG. 11 shows a schematic of the device's overall tissue impedance measurement in the collapsed membrane state. DETAILED DESCRIPTION OF THE INVENTION

[0047] FIG. 1 shows a schematic diagram of a bipolar pulse 100 generated by the signal generating and evaluating unit when the signal generating and evaluating unit generates a first electrical signal according to a burst signal sequence protocol during a first operational phase of the device. In this example, the manner in which the characteristics of the bipolar pulse 100 are determined is predefined by the user. The pulse deflection kV+, kV- values ​​of the positive pulse 101 and the negative pulse 104 are ±500 kV in the illustrated example. The third time interval 103 between the positive pulse 101 and the negative pulse 104 is 2.5 microseconds. The pulse width 102 of the positive pulse 101 is different from the pulse width 105 of the negative pulse 104. The difference in pulse width is not shown in FIG. 1. For the purpose of illustrating tissue impedance measurement using electrodes activated by the signal generating and evaluating unit, reference numerals are assigned to FIGS. 4 through 9.

[0048] FIG. 2 shows a schematic representation of a first electrical signal during the second operating phase of the device. The first electrical signal is configured as a burst signal sequence. Two bursts are visible, one of which is designated by reference numeral 110. Each burst has two bipolar pulses 100. Each bipolar pulse 100 occurring in the burst signal sequence has the characteristics of the type described in the previous figure. The first number of bursts, here two bursts by way of example, the second time interval 111, and the first time interval 112 between two consecutive bursts 110 are defined by the user prior to the first operating phase. The visible burst signal sequence continues beyond a period 113, which corresponds to the duration of irreversible electroporation.

[0049] FIG. 3 shows a schematic diagram of the device with the membrane 304 inflated. The device is in a "one-shot" configuration 300. The device has a shaft 302, which may be in a controllable or uncontrollable configuration, and an inflated membrane 304 permanently fixed to the shaft. For example, controllability refers to the possibility of adding a flexure to the device via a handle disposed on the shaft through rotational movement of the handle, allowing the device to be guided into a patient's organ. A distal electrode 301 and an additional electrode 303 are disposed on the shaft 302. The additional electrode 303 is disposed distal to the membrane 304. A proximal electrode 306 is disposed proximally from the membrane 304. Electrodes 301, 303, and 306 are electrically contacted by one or more electrically insulated wires that run through the shaft from the proximal end to the electrodes. A plurality of electrodes 305_n are disposed on the outer surface of the membrane 304, where n corresponds to the number of electrodes; by way of example and not limitation, there may be up to 15 electrodes. These are electrically connected by one or more strip conductors that run through the shaft from the proximal end of the device to the electrodes 305_n, and are covered so as to be electrically insulated from each other and from the external environment.

[0050] FIG. 4 shows a schematic diagram of the device with the membrane 304 collapsed / folded. The device is in a focal configuration 310. The device has a shaft 302, which may or may not be a controllable structure, and a membrane 307 in a collapsed form permanently fixed to the shaft. A distal electrode 301 and an additional electrode 303 are disposed on the shaft 302. The additional electrode 303 is disposed distal to the membrane 304. A proximal electrode 306 is disposed proximally from the membrane 304. The electrodes 301, 303, and 306 are electrically connected, and these lines are guided to the proximal end of the device via electrical wires and are electrically insulated from each other. A plurality of electrodes 305_n are disposed on the outer surface of the membrane 307, where n corresponds to the number of electrodes; by way of example and not limitation, there can be up to 15 electrodes. These are electrically connected by one or more strip conductors that run through the shaft from the proximal end of the device to the electrodes. The one or more strip conductors are covered so as to be electrically insulated from each other and from the external environment.

[0051] 5 shows a device in a focal configuration 310 for activating electrodes and determining local tissue impedance. The device includes a distal electrode 301, an additional electrode 303, and a proximal electrode 306. A membrane 307, disposed between the additional electrode 303 and the proximal electrode 306, is in a first configuration in which the membrane is collapsed. A plurality of electrodes 305_n are disposed on the membrane 307. Here, the first electrical signal is configured as a current signal 313. The second electrical signal is configured as a voltage signal. A signal generating and evaluating unit (not shown here) activates the corresponding electrode groups together with the corresponding electrode pairs.

[0052] An electrical signal 311 is applied between distal electrode 301, also referred to as the tip electrode, and proximal electrode 306, forming a first electrode pair through which current is transmitted to tissue in contact with the electrode pair. A voltage signal 315 is measured via a second electrode pair, here distal electrode 301 and additional electrode 303. The first electrode pair formed by electrodes 301 and 306 and the second electrode pair formed by electrodes 301 and 303 together form an electrode group. Local tissue impedance can be determined using Ohm's Law based on the current transmitted via the first electrode pair and the voltage received via the second electrode pair.

[0053] 6 shows a device in a "one-shot" configuration 300 for activating electrodes and determining local tissue impedance. The device includes a distal electrode 301, an additional electrode 303, and a proximal electrode 306. A membrane 304, disposed between the additional electrode 303 and the proximal electrode 306, is in a second configuration in which the membrane 304 is expanded. A plurality of electrodes 305_n are disposed on the membrane 304. Here, the first electrical signal is configured as a current signal 311. The second electrical signal is configured as a voltage signal 311. A signal generating and evaluating unit (not shown here) activates the corresponding electrode group together with the corresponding electrode pair to transmit a current to the tissue via the electrodes and measure the voltage in the tissue.

[0054] A current 311 is applied between the distal electrode 301 and the proximal electrode 306 (first electrode pair). In this example, the proximal electrode 306 is configured as a ring electrode. To determine the tissue impedance by Ohm's law, a voltage 313_n is measured from each of the plurality of electrodes 305_n to the additional electrode 303 (second electrode pair). To achieve this goal, the signal generating and evaluating unit controls / switches further electrodes of the plurality of electrodes 305_n once a measurement is made between one of the plurality of electrodes 305_n and the additional electrode 303, until all of the plurality of electrodes 305_n are activated to measure the voltage 313_n between the plurality of electrodes 305_n and the additional electrode 303. Here, n again corresponds to the number of electrodes on the membrane 304, and accordingly, the same number of determined local impedances are obtained and the characteristics of the target tissue can be determined very selectively.

[0055] 7 schematically illustrates an apparatus in a "one-shot" configuration 300 for activating electrodes and determining local tissue impedance. The apparatus includes a distal electrode 301, an additional electrode 303, and a proximal electrode 306. A membrane 304, disposed between the additional electrode 303 and the proximal electrode 306, is in a second configuration in which the membrane 304 is expanded. A plurality of electrodes 305_n are disposed on the membrane 304. Here, the first electrical signal is configured as a current signal 314_m. The second electrical signal is configured as a voltage signal 315_n. A signal generating and evaluating unit (not shown here) activates the corresponding electrode groups together with the corresponding electrode pairs.

[0056] A current 314_m is applied between two electrodes (a first electrode pair) that are spaced apart from one another of the plurality of electrodes 305_n. A voltage 315_n between one electrode of the plurality of electrodes and the distal electrode 301 (a second electrode pair) is measured to determine tissue impedance by Ohm's law. One electrode of the plurality of electrodes of the second electrode pair is an electrode that is shared as a closely adjacent electrode by the next-spaced electrode of the plurality of electrodes 305_n of the first electrode pair. Then, a voltage between one electrode of the plurality of electrodes 305_n of the second electrode pair and the distal electrode 301 is measured, and tissue impedance is determined by Ohm's law.

[0057] The signal generating and evaluating unit is configured, for example by a multiplexer circuit, to apply a current 314_m successively between all possible electrodes arranged one after the other, so that one electrode from the plurality of electrodes at which a voltage is measured is always excluded.

[0058] In this example, the plurality of electrodes 305_n is illustratively composed of 15 electrodes. If, by the above operation, current is applied sequentially to all possible electrodes placed next to each other and the current between the excluded electrodes is measured, 15 local tissue impedances can be identified from the measured values.

[0059] 8 shows a device in a "one-shot" configuration 300 for activating electrodes and delivering IRE pulses. The device includes a distal electrode 301, an additional electrode 303, a proximal electrode 306, and a counter electrode 320. A membrane 304, disposed between the additional electrode 303 and the proximal electrode 306, is in a second configuration in which the membrane is expanded. A plurality of electrodes 305_n are disposed on the membrane 304. Here, a first electrical signal is configured as voltage signals (321_n, 322_p, 323_n).

[0060] A signal generating and evaluating unit (not shown here) activates the first electrode pairs on which ablation is performed. In the schematic diagram, three first electrode pairs (1), (2), and (3) on which ablation is performed are shown: (1) two electrodes of the plurality of electrodes 305_n, (2) one of the plurality of electrodes and the distal electrode 301, and (3) one of the plurality of electrodes and the counter electrode 320.

[0061] When the signal generation and evaluation unit activates a third (3) first electrode pair, transmission of an IRE pulse 323_n occurs via said electrode pair, and a resulting electric field forms in each case between one of the plurality of electrodes 305_n and the counter electrode 320. All further electrodes of the plurality of electrodes 305_n are successively activated, for example by the signal generation and evaluation unit having a multiplexer circuit at its end, so that after an ablation procedure has been performed, each of the plurality of electrodes 305_n has been activated at least once and an IRE pulse 323_n is transmitted in each case to the counter electrode.

[0062] If the signal generation and evaluation unit activates the second (2) first electrode pair, the ablation procedure proceeds as in the previous paragraph, but an IRE pulse 321_n is delivered to the distal electrode 301 in each case.

[0063] When the signal generation and evaluation unit activates the first (1) first electrode pair, an IRE pulse 322_p is transmitted through the electrode pair and the resulting electric field forms between two closely adjacent electrodes of the plurality of electrodes 305_n.

[0064] For example, a signal generating and evaluating unit having a multiplexer circuit at its end connects all the electrodes successively through the pairs until all the electrodes have been activated at least once.

[0065] Due to the repeated feedthrough of electrodes in the third first electrode pair, the first electrode pair in the current activation / switching process iteration has one electrode of the plurality of electrodes in common with the first electrode pair in the previous iteration. By multiplexing, all three electrode pairs allow a circular lesion pattern surrounding the pulmonary vein to be created. Activation of electrode pairs (1) and (2) in each case represents a monopolar ablation configuration. Ablation with the third (3) first electrode pair represents a bipolar ablation configuration.

[0066] 9 shows the device in a focal configuration 310 for activating an electrode pair and delivering an IRE pulse. Again, a body surface electrode 320 is used, which serves as a counter electrode to the distal electrode 301. An IRE pulse 324 can be delivered in this manner. This ablation illustrates a monopolar ablation configuration.

[0067] FIG. 10 schematically illustrates the overall impedance measurement of the device in an inflated membrane state for determining the overall impedance of tissue. The device includes a distal electrode 301, an additional electrode 303, a proximal electrode 306, and a counter electrode 320. The membrane 304, located between the additional electrode 303 and the proximal electrode 306, is in a second configuration in which the membrane 304 is inflated. Multiple electrodes 305_n are disposed on the membrane 304. Here, the first electrical signal is configured as a current signal 317_n. The second electrical signal is configured as a voltage signal 316_n. A signal generating and evaluating unit (not shown) activates a first electrode pair. The first electrode pair is formed by one of the multiple electrodes 305_n and the counter electrode 320. Via the first electrode pair, a current is sent to the tissue, and a voltage is measured. The signal generating and evaluating unit (not shown) determines the overall tissue impedance from the current and voltage using Ohm's law.

[0068] FIG. 11 schematically illustrates the overall impedance measurement of the device in a collapsed membrane state. The device includes a distal electrode 301, an additional electrode 303, a proximal electrode 306, and a counter electrode 320. The membrane 304, located between the additional electrode 303 and the proximal electrode 306, is in a first collapsed configuration. Multiple electrodes 305_n are disposed on the membrane 304. Here, the first electrical signal is configured as a current signal 319. The second electrical signal is configured as a voltage signal 318. A signal generating and evaluating unit (not shown) activates a first electrode pair. The first electrode pair is formed by the distal electrode 301 and the counter electrode 320. Via the first electrode pair, a current is sent to the tissue, and a voltage is measured. The signal generating and evaluating unit (not shown) determines the overall tissue impedance from the current and voltage using Ohm's law.

Claims

1. 1. A device for irreversible electroporation of tissue in a patient, comprising: A catheter, the catheter comprising: a proximal end and a distal electrode disposed at a distal end of the catheter; a membrane disposed between the distal end and the proximal end, the membrane configured to assume first and second configurations; a plurality of electrodes disposed on the membrane; a catheter comprising: a signal generating and evaluating unit connected to the proximal end of the catheter and configured to determine tissue impedance and / or perform ablation; An apparatus comprising:

2. The device comprises: a proximal electrode disposed at the proximal end of the catheter; and / or at least one additional electrode disposed between the membrane and the distal electrode; The apparatus of claim 1 , comprising:

3. 3. The device of claim 1, wherein the signal generating and evaluating unit is configured to transmit a first electrical signal to the tissue via a group of electrodes, or to transmit a first electrical signal to the tissue via the group of electrodes and receive a second electrical signal from the tissue.

4. The electrode group includes: In particular in the first configuration state, the proximal electrode and the distal electrode as a first electrode pair and the additional electrode and the distal electrode as a second electrode pair; or In particular in the second configuration, the proximal electrode and the distal electrode as a first electrode pair, and one of the plurality of electrodes and the additional electrode as a second electrode pair; or In particular in the second configuration, two electrodes of the plurality of electrodes arranged next to each other as a first electrode pair, and the distal electrode and in particular a further electrode arranged between the two electrodes of the plurality of electrodes arranged next to each other as a second electrode pair, The apparatus of claim 3 comprising:

5. In a first operating phase, the first electrical signal is configured as a current signal, and the second electrical signal is configured as a voltage signal; 5. The device according to claim 1, wherein the signal generating and evaluating unit is configured to determine at least one tissue impedance, in particular a local one, from the current signal transmitted to the tissue and the voltage signal received from the tissue.

6. 6. The device according to claim 5, wherein the signal generating and evaluating unit is configured to determine impedances of at least two tissues, in particular localized, in particular by means of at least two groups of electrodes selected / switched in time successively.

7. 7. The device according to claim 2, wherein the signal generating and evaluating unit is configured to activate at least one different first and / or second electrode pair in the electrode group, in particular successively in time, and to determine impedances of at least two tissues, in particular localized, in the electrode group.

8. In particular, in the second configuration state, when the proximal electrode and the distal electrode are the first electrode pair, and one of the plurality of electrodes and the additional electrode are the second electrode pair, the signal generating and evaluating unit: and / or configured to activate the second electrode pair at least once, in particular from at least one further electrode of the plurality of electrodes and the additional electrode in the second configuration state, and to determine the impedance of at least one further tissue, in particular locally; and / or In particular, in the second configuration state, the signal generating and evaluating unit is configured such that when two electrodes arranged next to each other among the plurality of electrodes are defined as the first electrode pair, and when the distal electrode and a further electrode arranged between the two electrodes arranged next to each other among the plurality of electrodes are defined as the second electrode pair, 8. The device according to claim 2, configured to activate the first electrode pair at least once and determine the impedance of at least one further tissue, in particular localized, from two further electrodes arranged one next to each other of the plurality of electrodes in the second configuration state, in particular from a further electrode arranged between the distal electrode and the two further electrodes arranged one next to each other of the plurality of electrodes as the second electrode pair in the second configuration state.

9. In a second operating phase, the electrical signal is configured as a voltage signal; the signal generation and evaluation unit is configured to generate the voltage signal according to a selected burst signal protocol and transmit the signal to the tissue via a first electrode pair; In particular, in the second configuration, the distal electrode and one of the plurality of electrodes are configured as the first electrode pair, or The device according to claim 1 , wherein, particularly in the second configuration, two adjacent electrodes of the plurality of electrodes are configured as the first electrode pair.

10. the device further comprises a counter electrode, in particular a body surface counter electrode, connected to the signal generating and evaluating unit; In particular, in the second configuration, one of the plurality of electrodes and the counter electrode are configured as the first electrode pair; and / or In particular, in the first configuration, the distal electrode and the counter electrode are configured as the first electrode pair; and / or In a first operating phase, the first electrical signal is configured as a current signal, and the second electrical signal is configured as a voltage signal; 10. The device according to claim 1, wherein the signal generating and evaluating unit is configured to determine an impedance, in particular an overall impedance, of at least one tissue from the current signal, in particular transmitted to the tissue via the first electrode pair, and the voltage signal, in particular received from the tissue via the first electrode pair.

11. 11. The device according to claim 9 or 10, wherein the signal generating and evaluating unit is configured to switch at least one further electrode of the plurality of electrodes among electrode pairs, in particular successively in time.

12. 12. The device according to claim 1, wherein the electrodes, in particular the plurality of electrodes, the proximal electrode, the distal electrode and the additional electrode are connected to the signal generating and evaluating unit via the proximal end of the catheter by electrical wires insulated from each other and from the immediate surroundings and arranged in particular outside the catheter.

13. 1. A method for irreversible electroporation of tissue in a patient, comprising: Providing a catheter, The catheter comprises: a proximal end and a distal electrode disposed at a distal end of the catheter; a membrane disposed between the distal end and the proximal end, the membrane configured to assume first and second configurations; a plurality of electrodes disposed on the membrane; and providing a signal generating and evaluating unit connected to the proximal end of the catheter; - determining tissue impedance or performing ablation, in particular performing ablation after determining tissue impedance; A method for providing the above.

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