Devices and methods for irreversible electroporation of tissue

Abstract

An apparatus and method for electroporation is described. An exemplary embodiment of the device has a catheter and a signal generator-evaluation unit connected to a proximal end of the catheter.

Description

Technical Field

[0001] Provided herein are an apparatus and method for irreversible electroporation of tissue. Background Art

[0002] In recent years, the treatment of tissues by pulsed electric fields has become an increasingly important clinical technique. However, the use of short high-voltage pulses and the high electric field strengths associated therewith acting on tissues has been the subject of intensive research for more than 40 years. This application method is classified as a non-thermal process because it is based on the delivery of short pulses with high voltage amplitudes that generate a local strong electric field of up to several hundred volts per centimeter between active electrode pairs. This electric field strength leads to the formation of pores in the cell membrane. If the electric field exceeds the specific threshold value required to form a hole in the lipid bilayer of the cell membrane, and if the tissue is exposed to the electric field within a critical time period, electroporation becomes irreversible. These holes remain permanently open, which ultimately leads to programmed cell death (apoptosis) of the cells in question.

[0003] Irreversible electroporation (IRE) is a primarily non-thermal process that only slightly raises tissue temperature by a few degrees within milliseconds. This differs significantly from conventional RF ablation (RF: radiofrequency), in which tissue temperature rises by 20°C to 70°C and cells are thermally destroyed. In IRE, bipolar pulses—a combination of positive and negative pulses—are typically used to minimize muscle contraction, which typically occurs with the application of DC voltage. These pulses can be applied between the two bipolar electrodes of a catheter or between the catheter electrodes and a surface electrode, which is typically applied to the patient's back.

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

[0005] Bipolar pulsed field ablation pulses (bipolar PFA pulses) for IRE include positive and negative pulses applied between two electrodes with a pulse width of 1 to 5 μs and an interval between the positive and negative pulses of 1 to 5 μs. The bipolar pulses are combined to form a pulse train, wherein each train may include more than one hundred bipolar pulses with a pulse-to-pulse interval of 1 to 10 ms. The pulse train forms a burst in each case, wherein the entire pulse package for IRE ablation consists of 1 to 20 bursts / burst units, each burst / burst unit having a burst-to-burst interval of 1 to 1000 ms. The total duration of the ablation can be up to 10 seconds.

[0006] Document US 2022 / 0192741 A1 discloses a spherical structure having a plurality of elongated elements, on each of which a plurality of converters are arranged.

[0007] Document US2021 / 0169567 A1 discloses a shaft of a catheter suitable for insertion into a patient's organ. An inflatable balloon is connected to the distal end of the catheter. A plurality of electrodes are arranged on the outside of the balloon membrane.

[0008] Document WO 2022 / 256218 A1 discloses a catheter having a catheter shaft and a balloon. The balloon is arranged at the distal end of the catheter shaft. One or more electrodes are arranged on the outer surface or the inner surface of the balloon.

[0009] Document CN 216495608 U discloses a balloon-shaped catheter with a plurality of electrodes arranged on the outer side thereof.

[0010] Document US 2022 / 0222954 A1 discloses a balloon catheter having a plurality of electrodes arranged thereon.

[0011] Document WO 2019 / 181634 A1 discloses a balloon catheter having a plurality of electrodes arranged around the balloon.

[0012] Document WO 2021 / 116774 A1 discloses a balloon catheter having a plurality of electrodes arranged at the distal end of the balloon catheter.

[0013] Document US2021 / 0153935 A1 discloses a balloon catheter with electrodes wrapped around its outer shell. An annular catheter spirally protrudes from the distal end of the balloon catheter, and the annular catheter electrode is arranged thereon.

[0014] There are also known documents US2022 / 0233236A1, EP 3 456 278 A2 and US

[0015] 2022 / 0241008A1. Summary of the Invention

[0016] The present invention solves the problem of shortening the electroporation time.

[0017] For this purpose, a device 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 patient tissue is proposed. The device comprises a catheter. The catheter comprises a proximal end and a (e.g. single), in particular separate / single, distal electrode (end electrode) arranged at the distal end, in particular at the outermost end, of the catheter. The catheter comprises a membrane arranged between the distal end and the proximal end. The membrane is adapted to assume a first, in particular tubular or collapsed shape state and a second, in particular balloon-like or expanded shape state. The catheter comprises a plurality of electrodes, in particular (spatially) separated from the distal electrode. The plurality of electrodes are arranged on the membrane. The device comprises a signal generator-evaluation unit, which is connected to the proximal end of the catheter and is adapted to perform tissue impedance determination, in particular local tissue impedance determination and / or ablation.

[0019] The signal generator-evaluation unit may have a signal generator unit and / or an evaluation unit and / or a control unit.The signal generator-evaluation unit may be adapted to perform a tissue impedance determination or ablation, or a tissue impedance determination and eg a subsequent ablation.

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

[0021] The signal generator-evaluation unit can be adapted to deliver a first electrical signal to the tissue via an electrode constellation. The signal generator-evaluation unit can be adapted to deliver the first electrical signal to the tissue via the electrode constellation and to receive a second electrical signal from the tissue. An electrode constellation can be understood as a paired association of electrodes. The signal generator-evaluation unit can be adapted to drive electrode pairs and / or electrode constellations and / or switch between electrodes (electrode pairs) and / or electrode constellations.

[0022] The electrode constellation may be defined by / formed by / composed of 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 (particularly in the first shape state).

[0023] The electrode constellation may be defined by / formed by / composed of 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 (particularly in the second shape state).

[0024] The electrode constellation can be composed of a plurality of electrodes as a first electrode pair (arranged adjacent to each other with one electrode ) two electrodes and is defined / formed / composed of a distal electrode as a second electrode pair (particularly in a second configuration) and a further electrode of the plurality of electrodes, particularly located between two electrodes arranged one adjacent to the other. Electrodes arranged one adjacent to the other may be understood as electrodes or electrode pairs with conventional, directly (immediately) adjacent electrodes between them.

[0025] In the first operating phase, the first electrical signal can be configured as a current signal and the second electrical signal can be configured as a voltage signal. In the first operating phase, the signal generator-evaluation unit can be adapted to determine at least one tissue impedance, in particular a local tissue impedance, from the current signal transmitted into the tissue (=first electrical signal) and the voltage signal received from the tissue (=second electrical signal).

[0026] The signal generator-evaluation unit can be adapted to determine at least two, in particular local, tissue impedances by means of at least two electrode constellations / electrode pairs / electrodes (to be driven) selected / switched in in particular (time) sequence.

[0027] The signal generator-evaluation unit may be adapted to drive at least one further first and / or second electrode pair within the electrode constellation, in particular in a time-sequential manner, and to determine at least two, in particular local, tissue impedances of the electrode constellation. In other words, the signal generator-evaluation unit may be adapted to drive further electrodes within the first and / or second electrode pair within the selected electrode constellation, thereby forming a new first and / or new second electrode pair, with which a tissue impedance, in particular a local tissue impedance, may be determined, in particular due to different signal paths through the tissue.

[0028] For the proximal electrode and the distal electrode as a first electrode pair and one of the plurality of electrodes and an additional electrode (in particular in the second shape state) as a second electrode pair, the signal generator-evaluation unit can be adapted to drive the second electrode pair at least once from at least one further electrode and the additional electrode (in particular in the second shape state) of the plurality of electrodes and to determine at least one further, in particular local, tissue impedance.

[0029] In other words, for one electrode constellation, a first electrode pair may be formed by the proximal electrode and the distal electrode, and a second electrode pair may be formed by one electrode of the plurality of electrodes and the additional electrode. The signal generator-evaluation unit may be adapted to drive another electrode of the plurality of electrodes and the additional electrode after each measurement of the second electrical signal / voltage signal until the second electrical signal / voltage signal has been measured at all possible electrode combinations of the plurality of electrodes and the additional electrode.

[0030] The signal generator-evaluation unit may be adapted to form (an electrode constellation) two electrodes of the plurality of electrodes (arranged one adjacent to each other) as a first electrode pair, and the distal electrode and another electrode of the plurality of electrodes (in particular located between the two electrodes arranged one adjacent to each other, in particular in the second configuration) as a second electrode pair. The signal generator-evaluation unit may be adapted to at least once drive / form the first electrode pair from two further electrodes of the plurality of electrodes arranged one adjacent to each other, in particular in the second configuration, and to drive / form the second electrode pair from the distal electrode and another electrode of the plurality of electrodes (in particular located between the two further electrodes arranged one adjacent to each other, in particular in the second configuration), and to determine at least one further, in particular local, tissue impedance.

[0031] In the second operating phase, the electrical signal can be configured as a voltage signal. The signal generator-evaluation unit can be adapted to generate the voltage signal according to a pulse train signal protocol to be selected and transmit the signal to the tissue via the first electrode pair. The signal generator-evaluation unit can particularly drive an electrode pair in the second operating phase.

[0032] The first electrode pair can be formed, in particular in the second shape state, by the distal electrode and one of the plurality of electrodes.The first electrode pair can be formed, in particular in the second shape state, by two, in particular (immediately) adjacent electrodes of the plurality of electrodes.

[0033] The device may include a counter electrode, in particular a body surface counter electrode, connected to the signal generator / evaluation unit. A first electrode pair may be formed by one of the plurality of electrodes and the counter electrode, in particular in the second configuration. The first electrode pair may be formed by the distal electrode and the counter electrode, in particular in the first configuration.

[0034] In a first operating phase, the first electrical signal can be configured as a current signal, and the second electrical signal can be configured as a voltage signal. In the first operating phase, the signal generator-evaluation unit can be adapted to determine at least one, in particular global and / or local, tissue impedance based on the current signal delivered to the tissue and the voltage signal received from the tissue. The first electrical signal can be delivered to the tissue via a first electrode pair. The second electrical signal can be received via the first electrode pair. In other words, current can be delivered to the tissue and voltage can be received via the same electrode pair.

[0035] The signal generator-evaluation unit can be adapted to switch within or starting from an electrode pair, in particular in a chronological sequence, to at least one other electrode from the plurality of electrodes. In other words, one electrode in an electrode pair can be replaced by another electrode from the plurality of electrodes. In this way, new electrode pairs can be formed. This can be repeated, in particular in a chronological sequence.

[0036] The electrodes (in particular, a plurality of electrodes, a proximal electrode, a distal electrode and / or additional electrodes) can be connected to the signal generator-evaluation unit via the proximal end of the catheter by means of electrical wires, which are insulated from one another and from the immediate surroundings and are in particular arranged externally or internally on / in the catheter.

[0037] The signal generator-evaluation unit may be adapted, in particular in the first and / or second operating phase, to generate a first electrical signal based on a pulse train signal protocol and to transmit / send said signal to the first electrode pair.

[0038] The format of the pulse train signal sequence protocol may specify the properties and energy amount of each pulse train. The format may include: a first number of pulse trains within the pulse train signal sequence, at least one first time interval between at least two consecutive pulse trains within the pulse train signal sequence, a second number of bipolar pulses within the pulse train, at least one second time interval between at least two consecutive bipolar pulses within the pulse train, a third time interval between a positive pulse and a negative pulse of at least one bipolar pulse, a pulse width of a positive pulse and / or a negative pulse of at least one bipolar pulse, and / or a pulse deflection value of a positive pulse and / or a negative pulse of at least one bipolar pulse.

[0039] The first number of bursts within the burst signal sequence may lie within a value range from 1 to 100 burst units.

[0040] At least one first time interval between two consecutive pulse trains of the pulse train signal sequence may lie in a value range from 1 ms to 1000 ms.The second number of bipolar pulses within a pulse train may lie in a value range from 1 to 300 bipolar pulse units.

[0041] At least one second time interval between at least two consecutive bipolar pulses within a pulse train may lie in a value range from 1 to 10 ms.A third time interval between a positive pulse and a negative pulse may lie in a value range between 1 μ8 and 5 μ8.

[0042] The pulse width of the positive pulse and / or the negative pulse may be in a value range between 1 μs and 10 μs.The pulse width of the positive pulse may be different from the pulse width of the negative pulse.

[0043] The value of the pulse deflection of the positive pulse may lie in a value range of 200 to 2000 V. The value of the pulse deflection of the negative pulse may lie in a value range of -200 to -2000 V.

[0044] According to a second aspect, a method for irreversible electroporation of patient tissue is provided. The method includes providing a catheter. The catheter has a proximal end and a distal electrode arranged at the distal end of the catheter. The catheter has a membrane arranged between the distal end and the proximal end. The membrane is adapted to assume a first or second shape state. The catheter has a plurality of electrodes arranged on the membrane. The method includes providing a signal generator-evaluation unit connected to the proximal end of the catheter. The method includes performing a tissue impedance determination and / or performing an ablation. In other words, the method includes (i) performing a tissue impedance determination or (ii) performing an ablation or (iii) performing a tissue impedance determination and performing an ablation, for example, performing an ablation after or following the tissue impedance determination.

[0045] Further features, properties, advantages and possible modifications will become apparent to those skilled in the art from the following description with reference to the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] Figure 1 is a schematic diagram of a bipolar IRE pulse according to an exemplary embodiment of the present invention.

[0047] Figure 2 is a schematic diagram of a pulse protocol having multiple trains or bursts of bipolar pulses according to an exemplary embodiment of the present invention.

[0048] Figure 3 A schematic diagram of the device with an expanded balloon membrane is shown.

[0049] Figure 4 Shown from Figure 3 Schematic diagram of a device in which the membrane is folded in a focal configuration.

[0050] Figure 5 Schematic connections of electrodes for local impedance measurement of a focusing catheter configuration are shown.

[0051] Figure 6 Schematic connection of electrodes for local impedance measurement for a "one-shot" catheter configuration is shown.

[0052] Figure 7 Schematic further connections of electrodes for local impedance measurement for a "disposable" catheter configuration are shown.

[0053] Figure 8 Possible ablation modes of the device in the expanded shape of the membrane are schematically shown.

[0054] Figure 9 Possible ablation modes of the device for the collapsed shape state of the membrane are schematically shown.

[0055] Figure 10The measurement of the overall tissue impedance of the device in the expanded state of the membrane is schematically shown.

[0056] Figure 11 The measurement of the overall tissue impedance of the device in the collapsed state of the membrane is schematically shown. DETAILED DESCRIPTION

[0057] Figure 1 A schematic diagram illustrates a bipolar pulse 100 generated by a signal generator / evaluation unit when the signal generator / evaluation unit generates a first electrical signal according to a pulse train signal sequence protocol during a first operating phase of the device. In this example, the format for determining the characteristics of bipolar pulse 100 has been predefined by the user. In the illustrated example, the pulse deflections kV+ and kV- of positive pulse 101 and negative pulse 104 have values ​​of ±500 kV. A third time interval 103 between positive pulse 101 and negative pulse 104 is 2.5 μs. The pulse width 102 of positive pulse 101 differs from the pulse width 105 of negative pulse 104. Figure 1 For an explanation of the tissue impedance measurement using an electrode constellation driven by a signal generator-evaluation unit, refer to Figures 4 to 9 .

[0058] Figure 2 The first electrical signal in the second operating phase of the device is schematically shown. The first electrical signal is configured as a pulse train signal sequence. Two pulse trains can be seen, one of which is marked with reference numeral 110. Each pulse train has two bipolar pulses 100. Each bipolar pulse 100 appearing in the pulse train signal sequence has the characteristics of the format described in the aforementioned figures. Prior to the first operating phase, the user has defined a first number of pulse trains (here, two as an example), a second time interval 111, and a first time interval 112 between consecutive pulse trains 110. The pulse train signal sequence that can be seen extends over a duration 113, which corresponds to the duration of irreversible electroporation.

[0059] Figure 3A schematic diagram of the device is shown, with the membrane 304 expanded. The device is in a "disposable" configuration 300. The device comprises a shaft 302 and a filling membrane 304 permanently secured thereto. The shaft 302 can be in a controllable or uncontrollable configuration. For example, controllability refers to the ability to impart bending to the device and manipulate it within a patient's organ by rotating a handle disposed on the shaft. A distal electrode 301 and an additional electrode 303 are disposed on the shaft 302. The additional electrode 303 is disposed on the distal side of the membrane 304. A proximal electrode 306 is disposed on the proximal side of the membrane 304. Electrodes 301, 303, and 306 are electrically connected via one or more lines extending from the proximal end through the shaft to the electrodes and are electrically insulated from one another. A plurality of electrodes 305_n are disposed on the outer surface of the membrane 304, where n corresponds to the number of electrodes, and as an example and not limitation, up to 15 electrodes may be present. These are electrically connected via one or more ribbon conductors that extend from the proximal end of the device through the shaft to the electrodes 305_n. The one or more ribbon conductors are covered so that they are electrically insulated from each other and from the external environment.

[0060] Figure 4 A schematic diagram of the device is shown, wherein the membrane 304 is collapsed / folded. The device is in a focusing configuration 310. The device has a shaft 302, which can be in a controllable or uncontrollable configuration, and a membrane 307, which is permanently fastened to the shaft 302 in a collapsed shape. A distal electrode 301 and an additional electrode 303 are arranged on the shaft 302. The additional electrode 303 is arranged distally with respect to the membrane 304. A proximal electrode 306 is arranged on the proximal side of the membrane 304. Electrodes 301, 303, and 306 are in electrical contact, wherein these conductors are guided to the proximal end of the device via electrical wires and are electrically insulated from one another. A plurality of electrodes 305_n are arranged on the outer surface of the membrane 307, wherein n corresponds to the number of electrodes, and as an example and not limited thereto, there may be up to 15 electrodes. These are electrically connected via one or more ribbon conductors that extend from the proximal end of the device across the shaft to the electrodes. The one or more ribbon conductors are covered so that they are electrically insulated from one another and from the external environment.

[0061] Figure 5 A device for driving electrodes and determining the local impedance of tissue is shown in a focusing configuration 310. The device comprises 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; the membrane is collapsed. A plurality of electrodes 305_n are arranged on the membrane 307. The first electrical signal is configured as a current signal 313. The second electrical signal is configured as a voltage signal. A signal generator and evaluation unit (not shown here) drives the corresponding electrode constellation using the corresponding electrode pairs.

[0062] 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 delivered 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 constellation. Local tissue impedance can be determined based on the relationship between the current delivered via the first electrode pair and the voltage received via the second electrode pair using Ohm's law.

[0063] Figure 6 A device for driving electrodes and for determining the local tissue impedance of tissue is shown in a "disposable" configuration 300. The device comprises a distal electrode 301, an additional electrode 303, and a proximal electrode 306. A membrane 304, arranged between the additional electrode 303 and the proximal electrode 306, is in a second shape; the membrane 304 is expanded. A plurality of electrodes 305_n are arranged on the membrane 304. The first electrical signal is configured as a current signal 311. The second electrical signal is configured as a voltage signal 311. A signal generator-evaluation unit (not shown here) drives a corresponding electrode constellation with a corresponding electrode pair in order to transmit a current into the tissue and measure a voltage at the tissue via the electrode constellation.

[0064] A current 311 is applied between the distal electrode 301 and the proximal electrode 306 (first electrode pair). In this case, the proximal electrode 306 is configured as a ring electrode. For determining the tissue impedance using 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 this end, once a measurement has been made between one of the plurality of electrodes 305_n and the additional electrode 303, the signal generator-evaluation unit controls / switches to another electrode from the plurality of electrodes 305_n until all of the plurality of electrodes 305_n have been driven for the measurement of 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, so that the same number of determined local impedances is also obtained accordingly, and the properties of the target tissue can be determined very selectively.

[0065] Figure 7A device for driving electrodes and determining the local tissue impedance of tissue in a "disposable" configuration 300 is schematically shown. The device comprises a distal electrode 301, an additional electrode 303, and a proximal electrode 306. A membrane 304, arranged between the additional electrode 303 and the proximal electrode 306, is in a second shape; the membrane 304 is expanded. A plurality of electrodes 305_n are arranged on the membrane 304. 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 generator and evaluation unit (not shown here) drives the corresponding electrode constellation using the corresponding electrode pairs.

[0066] A current 314_m is applied between two electrodes of the plurality of electrodes 305_n that are arranged adjacent to each other (a first electrode pair). To determine tissue impedance using Ohm's law, a voltage 315_n is measured between one of the plurality of electrodes and the distal electrode 301 (a second electrode pair). One of the electrodes of the second electrode pair is an electrode shared as an immediately adjacent electrode by the electrodes of the plurality of electrodes 305_n of the first electrode pair that are arranged adjacent to each other. A voltage is then measured between one of the electrodes of the second electrode pair and the distal electrode 301, and tissue impedance is determined using Ohm's law.

[0067] The signal generator-evaluation unit is adapted to apply the current 314_m continuously between all possible electrodes arranged next to one another, for example by means of a multiplexer circuit, so that one electrode of the plurality of electrodes is always omitted for which a voltage is measured.

[0068] In this case, the plurality of electrodes 305_n is configured as 15 electrodes, for example. With the above-described driving, when current has been continuously applied to all possible electrodes arranged adjacent to each other and current has been measured across omitted electrodes, 15 local tissue impedances can be determined from the measured values.

[0069] Figure 8 A device in a "one-shot" configuration 300 for driving electrodes and delivering IRE pulses is shown. The device has 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 shape; the membrane is expanded. A plurality of electrodes 305_n are disposed on the membrane 304. The first electrical signal is configured as a voltage signal (321_n, 322_p, 323_n).

[0070] A signal generator-evaluation unit (not shown here) drives a first electrode pair via which ablation is performed. In the schematic diagram, three (1)(2)(3) first electrode pairs are shown via which ablation is performed: (1) two electrodes from 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.

[0071] If the signal generator-evaluation unit drives the third (3) first electrode pair, a delivery of an IRE pulse 323_n occurs via this electrode pair and a resulting electric field is formed in each case between one of the plurality of electrodes 305_n and the counter electrode 320. By means of a signal generator-evaluation unit having, for example, a multiplexer circuit for this purpose, all further electrodes of the plurality of electrodes 305_n are driven successively, so that each of the plurality of electrodes 305_n is activated at least once after the ablation procedure has been performed and an IRE pulse 323_n can in each case be delivered to the counter electrode.

[0072] If the signal generator-evaluation unit drives the second (2) first electrode pair, the ablation process proceeds as in the preceding paragraph, but the IRE pulses 321_n are delivered in each case to the distal electrode 301 .

[0073] If the signal generator-evaluation unit drives the first (1) first electrode pair, an IRE pulse 322_p is delivered via this electrode pair and a resulting electric field is formed between two immediately adjacent electrodes of the plurality of electrodes 305_n.

[0074] By means of a signal generator-evaluation unit, which for this purpose has, for example, a multiplexer circuit, all electrodes are connected consecutively in pairs until all electrodes have been activated at least once.

[0075] For the iterative through-connection of electrodes of the third first electrode pair, this is an electrode from the current iteration of the driving / switching process having electrodes from a plurality of electrodes in common with the first electrode pair of the previous iteration. Due to the multiplexing, all three electrode pairs allow for the generation of a circular lesion pattern surrounding the pulmonary vein. Driving of electrode pairs (1) and (2) each represents a unipolar ablation configuration. Ablation via the third (3) first electrode pair represents a bipolar ablation configuration.

[0076] Figure 9 The apparatus is shown in a focused configuration 310 for driving an electrode pair for IRE pulse delivery. Here too, a body surface electrode 320 is used, which serves as a counterpole to the distal electrode 301. Thus, an IRE pulse 324 can be delivered. This ablation represents a monopolar ablation configuration.

[0077] Figure 10A schematic diagram illustrates measurement of the overall impedance of a device in an expanded membrane state for determining the overall tissue impedance of a tissue. The device comprises 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 shape; the membrane 304 is expanded. A plurality of electrodes 305_n are disposed on the membrane 304. A first electrical signal is configured as a current signal 317_n. A second electrical signal is configured as a voltage signal 316_n. A signal generator-evaluation unit (not shown here) drives a first electrode pair. The first electrode pair is formed by an electrode from the plurality of electrodes 305_n and the counter electrode 320. A current is transmitted into the tissue, and a voltage is measured via the first electrode pair. The signal generator-evaluation unit (not shown) determines the overall tissue impedance from the current and voltage using Ohm's law.

[0078] Figure 11 The measurement of the overall impedance of the device in the collapsed state of the membrane is schematically shown. The device has a distal electrode 301, an additional electrode 303, a proximal electrode 306, and a counter electrode 320. The membrane 304 arranged between the additional electrode 303 and the proximal electrode 306 is in a first shape state; the membrane 304 is collapsed. A plurality of electrodes 305_n are arranged on the membrane 304. The first electrical signal is configured as a current signal 319 here. The second electrical signal is configured as a voltage signal 318. A signal generator-evaluation unit (not shown here) drives the first electrode pair. The first electrode pair is formed by the distal electrode 301 and the counter electrode 320. Current is sent into the tissue, and the voltage is measured via the first electrode pair. The signal generator-evaluation unit (not shown) determines the global tissue impedance from the current and voltage using Ohm's law.

Claims

1. A device for irreversible electroporation of patient tissue, comprising: - a catheter comprising: - a proximal end, and a distal electrode arranged at a distal end of the catheter; - a membrane arranged between said distal end and said proximal end and adapted to assume a first shape state and a second shape state; - a plurality of electrodes arranged on the membrane; - A signal generator-evaluation unit connected to the proximal end of the catheter and adapted to perform tissue impedance determination and / or ablation.

2. The device according to claim 1, wherein The device comprises: - a proximal electrode arranged at the proximal end of the catheter; and / or - at least one additional electrode arranged between said membrane and said distal electrode.

3. The device according to claim 1 or 2, wherein: The signal generator-evaluation unit is adapted to deliver a first electrical signal into the tissue via an electrode constellation or to deliver a first electrical signal into the tissue via the electrode constellation and to receive a second electrical signal from the tissue.

4. The device according to claim 3, wherein The electrode constellation comprises: - the proximal electrode and the distal electrode function as a first electrode pair, and the additional electrode and the distal electrode function as a second electrode pair, in particular in the first shape state; or - the proximal electrode and the distal electrode act as a first electrode pair, and one of the plurality of electrodes and the additional electrode, in particular in the second shape state, act as a second electrode pair; or - two electrodes of the plurality of electrodes arranged adjacent to each other with one another serve as a first electrode pair, and the distal electrode and another electrode of the plurality of electrodes, in particular located between the two electrodes arranged adjacent to each other with one another, in particular in the second shape state, serve as a second electrode pair.

5. The device according to any one of claims 1 to 4, wherein In the first operational phase: - the first electrical signal is configured as a current signal and the second electrical signal is configured as a voltage signal; and The signal generator-evaluation unit is adapted to determine at least one tissue impedance, in particular a local tissue impedance, from the current signal transmitted into the tissue and the voltage signal received from the tissue.

6. The device according to claim 5, wherein The signal generator-evaluation unit is suitable for determining at least two tissue impedances, in particular local tissue impedances, by means of at least two electrode constellations, in particular by selection / switching in a (time) sequence.

7. The device according to any one of claims 2 to 6, wherein: The signal generator-evaluation unit is adapted to drive at least one further first and / or second electrode pair within the electrode constellation, in particular in a chronological sequence, and to determine at least two tissue impedances, in particular local tissue impedances, for the electrode constellation.

8. The device according to any one of claims 2 to 7, wherein: The signal generator-evaluation unit is suitable for - the proximal electrode and the distal electrode function as a first electrode pair, and one of the plurality of electrodes and the additional electrode, in particular in the second shape state, function as a second electrode pair, In particular, in the second morphological state, the second electrode pair is driven at least once from at least one further electrode of the plurality of electrodes and the additional electrode and at least one further, in particular local, tissue impedance is determined, and / or the signal generator-evaluation unit is adapted to, for - two electrodes of the plurality of electrodes that are arranged adjacent to each other as a first electrode pair, and the distal electrode and a further electrode of the plurality of electrodes, particularly located between the two electrodes that are arranged adjacent to each other, particularly in the second shape state, as a second electrode pair, The first electrode pair is driven at least once from two further electrodes of the plurality of electrodes that are arranged adjacent to each other, in particular in the second shape state, and the distal electrode and the further electrode of the plurality of electrodes that are particularly located between the two further electrodes that are arranged adjacent to each other, in particular in the second shape state, serve as the second electrode pair and are suitable for determining at least one further tissue impedance, in particular a local tissue impedance.

9. The device according to any one of claims 1 to 8, wherein In the second operational phase: - the electrical signal is configured as a voltage signal; and - the signal generator-evaluation unit is adapted to generate the voltage signal according to a pulse train signal protocol to be selected and to transmit the signal to the tissue via the first electrode pair; - the distal electrode and one of the plurality of electrodes, in particular in the second shape state, are configured as the first electrode pair, or Two of the plurality of electrodes, in particular adjacent electrodes, in particular in the second shape state, are configured as a first electrode pair.

10. The device according to any one of claims 1 to 9, wherein The device further comprises a counter electrode, in particular a body surface counter electrode, connected to the signal generator-evaluation unit, wherein: - one of the plurality of electrodes and the counter electrode, in particular in the second shape state, are configured as the first electrode pair; and / or - the distal electrode and the counter electrode, in particular in the first shape state, are configured as the first electrode pair, and / or In the first operational phase: - the first electrical signal is configured as a current signal and the second electrical signal is configured as a voltage signal; and The signal generator-evaluation unit is adapted to determine at least one tissue impedance, in particular a global tissue impedance, from the current signal, in particular transmitted into the tissue via the first electrode pair, and the voltage signal, in particular received from the tissue via the first electrode pair.

11. The device according to claim 9 or 10, wherein The signal generator-evaluation unit is adapted to switch within an electrode pair, in particular to switch in chronological order, to at least one further electrode of the plurality of electrodes.

12. The device according to any one of claims 1 to 11, wherein The electrodes, in particular the plurality of electrodes, the proximal electrode, the distal electrode, and the additional electrode, are connected to the signal generator-evaluation unit via the proximal end of the catheter by electrical wires, which are insulated from one another and from the immediate surroundings and are in particular arranged outside the catheter.

13. A method for irreversible electroporation of patient tissue, comprising the steps of: -Providing a catheter comprising: - a proximal end, and a distal electrode arranged at a distal end of the catheter; - a membrane arranged between said distal end and said proximal end and adapted to assume a first shape state and a second shape state; - a plurality of electrodes arranged on the membrane; - providing a signal generator-evaluation unit connected to the proximal end of the catheter; and - performing a tissue impedance determination or performing an ablation, in particular performing a tissue impedance determination and subsequently performing an ablation.

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