IRE Temperature Control

Abstract

To provide a medical apparatus.SOLUTION: A medical apparatus includes a probe, which includes: an insertion tube configured for insertion into a body cavity of a patient; a distal structure connected distally to the insertion tube and including a plurality of electrodes, which are configured to contact tissue within the body; and temperature sensors fixed to the distal structure and configured to output signals indicative of a temperature of the tissue contacted by the electrodes. The apparatus further includes: an electrical signal generator configured to apply, to between one or more pairs of the electrodes, bipolar pulses having an amplitude sufficient to cause irreversible electroporation (IRE) in the tissue contacted by the spines; and a controller configured to control timing of the bipolar pulses applied by the electrical signal generator responsively to the signals output by the temperature sensors.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates generally to medical devices, and more particularly to devices and methods for ablating tissue within the body. [Background technology]

[0002] Irreversible electroporation (IRE) is a soft tissue ablation technique that applies short pulses of intense electric fields to create permanent, and therefore lethal, nanopores in cell membranes, thereby disrupting cellular homeostasis (internal physical and chemical conditions). Cell death after IRE is due to apoptosis (programmed cell death) and not necrosis (cell injury that leads to the destruction of the cell through the action of the cell's own enzymes) as in other and other radiation-based ablation techniques. IRE is commonly used in tumor ablation in areas where precision and the preservation of the extracellular matrix, blood flow, and nerves are critical. Summary of the Invention [Means for solving the problem]

[0003] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The embodiments of the present invention described below provide improved systems and methods for ablating tissue within the body.

[0004] Thus, in accordance with an embodiment of the present invention, there is provided a medical device including a probe. The probe includes an insertion tube configured for insertion into a body cavity of a patient and a distal structure connected distally to the insertion tube. The distal structure includes a plurality of electrodes configured to contact tissue within the body and a temperature sensor secured to the distal structure and configured to output a signal indicative of a temperature of tissue contacted by the electrodes. The medical device further includes an electrical signal generator configured to apply bipolar pulses between one or more pairs of electrodes having an amplitude sufficient to cause irreversible electroporation (IRE) in tissue contacted with the spine, and a controller configured to control timing of the bipolar pulses applied by the electrical signal generator in response to the signal output by the temperature sensor.

[0005] In a disclosed embodiment, the controller is configured to modify the bipolar pulse applied by the signal generator while the signal output by the temperature sensor indicates that the temperature of the tissue contacted by a given pair of electrodes exceeds a preset threshold.

[0006] In a further disclosed embodiment, modifying the bipolar pulse includes preventing the electrical signal generator from applying the bipolar pulse between a given pair of electrodes. Additionally or alternatively, the controller is configured to apply the bipolar pulse to another pair of electrodes while waiting for the temperature sensor to indicate that the temperature of the tissue contacted by the given pair of electrodes has dropped below a preset threshold.

[0007] In some embodiments, modifying the bipolar pulses includes modifying a number of consecutive bipolar pulses applied by the signal generator to a given pair of electrodes. Additionally or alternatively, modifying the bipolar pulses includes delaying application of the bipolar pulses to a given pair of electrodes.

[0008] In a disclosed embodiment, the distal structure comprises a basket assembly comprising a plurality of elastic spines configured to contact tissue, with temperature sensors secured to the spines.

[0009] In a further embodiment, the spines have respective proximal and distal tips, the proximal tips of the spines are mechanically joined to the proximal end of the basket assembly and the distal tips of the spines are mechanically joined to the distal end of the basket assembly, and when the basket assembly is deployed within the body cavity, the spines deflect radially outward, thereby contacting tissue within the body cavity.

[0010] In yet a further embodiment, the spine comprises a conductive material, such as a nickel-titanium alloy, and is configured to function as an electrode.

[0011] In the disclosed embodiments, each spine is divided into two or more mechanically connected but electrically isolated portions, and the electrically isolated portions of a given spine can be electrically connected together to function as electrodes for applying bipolar pulses.

[0012] In a further embodiment, the electrical signal generator is configured to apply a bipolar pulse between a first set and a second set of spines, at least one of the sets including two or more of the spines.

[0013] In yet another embodiment, the insertion tube includes a flexible catheter configured for insertion into a chamber of the patient's heart, and the electrodes are configured to contact and apply the electrical signal to myocardial tissue within the chamber.

[0014] In a disclosed embodiment, the bipolar pulses applied by the electrical signal generator include a sequence of bipolar pulses having an amplitude of at least 200 V, each of the bipolar pulses having a duration of less than 20 μs. Alternatively or additionally, the sequence of bipolar pulses includes pairs of pulses, each pair including a positive pulse and a negative pulse.

[0015] There is further provided, in accordance with an embodiment of the present invention, a method of medical treatment comprising: inserting a probe comprising an insertion tube and a distal structure including a plurality of electrodes into a body cavity of a patient such that the electrodes contact tissue within the body cavity; applying bipolar pulses between two or more sets of electrodes, each set including one or more of the electrodes, having an amplitude sufficient to cause irreversible electroporation (IRE) in tissue contacted with the electrodes; measuring a temperature of the tissue contacted with the electrodes; and controlling timing of the applied bipolar pulses in response to the measured temperature. [Brief description of the drawings]

[0016] The invention will be more fully understood from consideration of the following detailed description taken in conjunction with the drawings, in which: [Figure 1] 1 is a schematic, pictorial illustration of a system for use in an IRE ablation procedure, in accordance with an exemplary embodiment of the present invention. [Diagram 2] 1 is a schematic side view of a basket assembly, according to an exemplary embodiment of the present invention; [Diagram 3] FIG. 2 is a schematic diagram of a bipolar IRE pulse, in accordance with an exemplary embodiment of the present invention. [Figure 4] 2 is a schematic diagram of a burst of bipolar pulses, in accordance with an exemplary embodiment of the present invention; [Diagram 5] FIG. 2 is a block diagram that generally illustrates an IRE module, in accordance with an exemplary embodiment of the present invention. [Figure 6] 1 is a flow chart that generally illustrates a method of control in an IRE treatment utilizing tissue temperature, in accordance with an exemplary embodiment of the present invention. [Figure 7] 11 is a flow chart that generally illustrates a method of control in an IRE treatment utilizing tissue temperature, in accordance with another exemplary embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0017] Overview IRE is a primarily non-thermal process that raises tissue temperature by at most a few degrees for a few milliseconds. Therefore, IRE differs from RF (radio frequency) ablation, which raises tissue temperature by 20-70°C and destroys cells by heating. IRE utilizes bipolar pulses, i.e., a combination of positive and negative pulses, to avoid muscle contraction due to DC voltage.

[0018] For application of electroporation to large tissue areas, a basket catheter with conductive spines can be used. This type of basket catheter is described, for example, in U.S. Patent Application No. 16 / 842,648, filed April 7, 2020, the entire disclosure of which is incorporated herein by reference. All or a portion of the spines contact tissue within a body cavity, such as myocardial tissue within the heart. Each spine acts as an electrode, and an electrical signal generator applies a bipolar pulse between one or more pairs of spines with an amplitude sufficient to induce IRE in the tissue in contact with the spines.

[0019] Basket catheters with conductive spines of this kind generally do not include irrigation due to the added complexity, however, the lack of irrigation can result in overheating of the tissue because irrigation fluid is not available to carry away the thermal energy injected by the IRE signal into the tissue.

[0020] The exemplary embodiments of the invention described herein address this problem by providing a temperature sensor affixed to the spine of the catheter. The temperature sensor outputs a signal indicative of the temperature of tissue in contact with the spine. A controller controls the timing of the bipolar IRE pulses in response to the signal output by the temperature sensor.

[0021] In some exemplary embodiments, the controller applies a novel control algorithm with the goal of maintaining the temperature of the tissue below a certain limit. In one exemplary embodiment, the control algorithm prevents the electrical signal generator from applying a bipolar pulse while the signal output by the temperature sensor indicates that the temperature of the tissue exceeds a preset threshold. The bipolar pulse is not applied to a given pair of spines due to the high temperature of the tissue adjacent to these spines, but the control algorithm can direct the application of the bipolar pulse to another pair of spines.

[0022] In another exemplary embodiment, the control algorithm reduces the number of bipolar pulses applied in a given pulse train until application of this reduced pulse train is found to maintain the tissue temperature below a preset threshold.

[0023] System Description 1 is a schematic pictorial diagram of a multi-channel IRE system 20 used in an IRE ablation procedure, according to an exemplary embodiment of the present invention. In the following description, the IRE ablation procedure is also referred to as "IRE ablation" or "IRE procedure." In the exemplary embodiment shown, a physician 22 uses the system 20 to perform an IRE ablation procedure in a heart 23 of a subject 24. The physician 22 performs the procedure using an ablation catheter 26 comprising an insertion tube 28 having a longitudinal axis 27, the distal end 29 of which is connected to a basket assembly 31 comprising a plurality of electrically conductive spines 30 (shown in more detail in FIG. 2). A plurality of thermal sensors 21, such as thermocouples, are attached to the spines 30 to monitor the temperature of tissue 62 of the heart 23.

[0024] The IRE system 20 includes a processor 32, an IRE module 34, and a temperature controller 25. The IRE module 34 includes an IRE generator 36 and an IRE controller 38, with the IRE generator 36 including a dedicated pulse generator, as described further below. The IRE generator 36 generates an IRE signal under the control of the IRE controller 38, which generates an IRE signal including a train of bipolar electrical pulses. The pulses are directed to selected spines 30, which function as electrodes for performing an IRE procedure, causing an electroporation current 72 to flow through the tissue 62. The processor 32 handles the input and output interface between the IRE system 20 and the physician 22, as well as communications to the IRE controller 38. The bipolar electrical pulses and the IRE module 34 are further described below with reference to FIGS. 3-5.

[0025] During IRE ablation, the current 72 also heats the tissue 62 by Joule heating. Due to the complexity of adding irrigation to the basket assembly 31, the tissue 62 may not be adequately cooled by the natural circulation of bodily fluids and may overheat, causing, for example, charring or bubbles in the surrounding blood. To prevent overheating, the thermocouple 21 and temperature controller 25 are deployed to provide feedback to the IRE controller 38. On this basis, the IRE controller 38 gates the timing and delivery of IRE pulses by the IRE module 34 such that the temperature of the tissue 62 remains below a preset limit. Further details of the temperature control strategy used by the temperature controller 25 are provided below.

[0026] The processor 32 typically includes a programmable processor that is programmed with software and / or firmware to perform the functions described herein. The IRE controller 38 and the temperature controller 25 are similarly implemented with software and / or firmware on either the same or another programmable processor. Alternatively or additionally, those components of the system 20 may include hardwired and / or programmable hardware logic circuits that perform at least some of their functions. The temperature controller 25 further includes circuitry such as an analog-to-digital converter for receiving and converting analog signals from the thermocouples 21 to digital form. The IRE generator 36 includes analog and digital components and assemblies for generating the IRE signal directed to the spine 30. The processor 32, the IRE generator 36, the IRE controller 38, and the temperature controller 25 are shown in the figures as separate monolithic functional blocks for simplicity, although in practice some of their functions may be combined within a single processing and control unit.

[0027] The processor 32, IRE module 34 and temperature controller 25 typically reside within a console 40. The console 40 includes input devices 42, such as a keyboard and mouse. A display screen 44 is located adjacent to (or integral with) the console 40. The display screen 44 may optionally include a touch screen, thereby providing another input device.

[0028] The IRE system 20 may further include one or both of the following modules (typically resident within the console 40 ), connected to suitable interfaces and devices within the system 20 . An electrocardiogram (ECG) module 46 is coupled via a cable 48 to ECG electrodes 50 attached to the subject 24. The ECG module 46 is configured to measure the electrical activity of the heart 23. The tracking module 52 is coupled to one or more electromagnetic position sensors 54 at the distal end of the insertion tube 28 and, optionally, within the basket assembly 31. In the presence of an external magnetic field generated by one or more magnetic field generators 56, the electromagnetic position sensors 54 output signals that vary with the position of the sensor. Based on these signals, the tracking module 52 tracks the position of the spine 30 within the heart 23.

[0029] The above-mentioned modules 46 and 52 typically include both analog and digital components and are configured to receive analog signals and transmit digital signals. Each module may further include hardwired and / or programmable hardware logic circuitry that performs at least a portion of the module's functionality.

[0030] The catheter 26 is connected to the console 40 via an electrical interface 58, such as a port or socket. Thus, the IRE signal is transmitted from the IRE generator 36 through the interface 58 and wiring inside the insertion tube 28 to the spine 30 in the basket assembly 31. The temperature signal from the thermocouple 21 is conveyed from the distal tip 28 to the temperature controller 25 via the interface 58. Similarly, signals for tracking the position and orientation of the distal tip 28 may be received by the tracking module 52 via the interface 58.

[0031] An external electrode 60, or “return patch,” may additionally be coupled externally between the subject 24, typically on the skin of the subject's torso, and the IRE module 34. The external electrode 60 may be used to couple the IRE signal between one of the spines 30 and the external electrode, and thus may be used to achieve deeper localized electroporation within the tissue 62.

[0032] The processor 32 receives setup parameters 66 for the procedure from the physician 22 (or from another user) prior to and / or during the IRE procedure. Using one or more suitable input devices 42, the physician 22 sets the setup parameters 66 to select one or more pairs of spines 30 and electrodes for activation (to receive the IRE signal) and the order in which the electrodes are activated, and to define the characteristics (timing and amplitude) of the IRE signal. The physician 22 also sets a preset limit T for tissue temperature that is utilized by the temperature controller 25 in the temperature control process. th Alternatively, the limits may be automatically set to default values. Additionally, processor 32 may display setup parameters 66 on display screen 44.

[0033] As used herein, the terms "one or more pairs of spines" and "electrode pair" are not limited to one spine and adjacent spines (or one electrode and adjacent electrodes), but rather refer to all possible configurations that allow for the delivery of biphasic energy between (a) two single spines acting as two separate electrodes or (b) two groups of multiple spines. In case (a), an example of two single spines acting as an electrode "pair" may be spine 30a in FIG. 2 as one electrode in concert with adjacent spine 30b, thus defining an "electrode pair" when a biphasic voltage is delivered to this pair of spines 30a and 30b. Alternatively, spine 30a can be paired with non-adjacent spine 30c as an "alternate pair," non-adjacent spine 30d can be paired with spine 30a as yet another "electrode pair," distal spine 30f can be paired with spine 30a as a further "electrode pair," or distal spine 30d can be paired with spine 30b as yet another "pair." In a further example of case (a), alternating spines 30a and 30c can be energized as one "electrode pair," and alternating spines 30b and 30d can be energized with various permutations as different "electrode pairs," etc. In case (b), which concerns a group of spines acting as one electrode in cooperation with another group of different spines acting as another electrode of the "electrode pair", two or more spines (e.g., 30a and 30b) can act as one electrode and operate with two or more spines (30c and 30d) grouped together as another electrode, thus defining an "electrode pair" for delivering biphasic energy to the electrodes (i.e., defining spines 30a and 30b as one electrode and spines 30c and 30d as the other electrode to define an "electrode pair"). Various permutations of single spines acting as a pair of electrodes may be combined with a group of spines acting as an electrode pair and are considered to be within the scope of the present invention. For example, the spines shown in FIG. 2 can be utilized to define two electrode pairs. Spines 30a and 30b define one electrode pair, while spines 30c+30d (as one electrode) and spines 30e+30f (as another electrode) define a second electrode pair.

[0034] In some exemplary embodiments, based on signals received from the tracking module 60, the processor 32 displays on the display 44 a relevant image 68 of the target anatomy, e.g., a map of the ventricles of the heart 23, annotated to indicate, for example, the current position and orientation of the basket assembly 31. Alternatively or additionally, based on signals received from the ECG module 46, the processor 32 may display, on the display screen 44, the electrical activity of the heart 23.

[0035] To begin the procedure, the physician 22 inserts the catheter 26 into the subject 24, for example, via the subject's vasculature, and then navigates the insertion tube 28, using the control handle 70, to an appropriate site inside or outside the heart 23. During the insertion and navigation phase, the basket assembly 31 is generally in a folded configuration inside a sheath (not shown) to provide for easy insertion into the subject 24.

[0036] Once the insertion tube 28 is positioned in the required region within the heart 23, the basket assembly 31 is advanced from the sheath, assuming an expanded configuration. A more detailed description of the basket assembly 31 is shown in FIG. 2 below. Now, as shown diagrammatically in inset 71, the physician 22 brings the basket assembly 31 into contact with tissue 62 of the heart 23, such as myocardial or epicardial tissue. The IRE generator 36 under the control of the IRE controller 38 then generates an IRE signal comprising a train of pulses (shown in detail in FIG. 4). The IRE signal is delivered via the catheter 26 to pairs of spines 30 via different corresponding electrical conductors (not shown), causing a current 72 generated by the IRE signal to flow between each pair of spines (bipolar ablation) and to effect the desired irreversible electroporation of the tissue 62 across the expanded region between the spines. During the IRE procedure, the temperature controller 25 continuously measures the temperature of the tissue 62 via the thermocouple 21 and, in conjunction with the IRE controller 38, controls the timing of the IRE signal generated by the IRE module 34 to regulate the tissue temperature within a preset limit T thKeep it below.

[0037] Commonly used T th The default value of T is chosen as 5°C higher than the temperature baseline of 38°C, i.e., T th is selected to be 43° C. Alternatively, physician 22 may choose to reduce T by selecting a lower baseline value (typically), especially if catheter 26 is equipped with irrigation. th In this case, the value of the preset limit T th The temperature may be adjusted to a range of 38°C to 43°C.

[0038] Further details of the temperature control strategy used by the temperature controller 25 are provided below.

[0039] FIG. 2 is a schematic side view of a basket assembly 31, according to an exemplary embodiment of the invention. The basket assembly 31 includes spines 30, individually labeled in FIG. 2 as 30a, 30b, 30c, 30d, 30e, and 30f. (In some of the following description, general indexes such as 30i and 30j are used.) The spines 30a-30f include long segments of elastic material that are electrically conductive or have an electrically conductive coating or member attached thereto. For example, the spines 30a-30f may include a nickel-titanium alloy known as Nitinol. Each spine 30 has one or more thermocouples 21 attached thereto for measuring the local temperature of tissue 62 adjacent the thermocouples.

[0040] The proximal tips 74 of the spines 30a-30f are mechanically joined at the proximal end 76 of the basket assembly 31, and the distal tips 78 of the spines are mechanically joined at the distal end 80 of the basket assembly. However, the proximal tips 74 and distal tips 78 of the spines 30a-30f are electrically insulated from one another so that the spines can function as separate electrodes. The spines 30a-30f are fabricated such that the basket assembly 31 has an expanded state as its stable state. Thus, the spines 30a-30f bow radially outward when the basket assembly is placed in the body cavity, thereby contacting tissue 62 within the body cavity. The spines 30a-30f are electrically coupled to the IRE generator 36 (FIG. 1) via conductors in the catheter 26 to receive the IRE ablation signal, and the thermocouple 21 is similarly electrically coupled to the temperature controller 25.

[0041] The IRE signal received from IRE generator 36 is coupled, for example, between spines 30a and 30b, causing electroporation to occur between these two spines. Due to the applied IRE signal, a current 72 (FIG. 1) flows along the entire length between spines 30a and 30b, thus causing electroporation over a large area within tissue 62. For example, application of basket assembly 31 to pulmonary vein ablation will cause electroporation over a 6-12 mm wide ring around the pulmonary vein.

[0042] The IRE signal may be coupled between any pair of spines 30a-30f, but typically the signal is applied between adjacent pairs of spines. Additionally or alternatively, the signal may be applied simultaneously or alternately between several pairs of spines. Although the basket assembly 31 is shown in FIG. 2 as including six spines, other numbers of spines, both more and less than six spines, may be used. Additionally or alternatively, a set of multiple spines 30 may be electrically connected together to form a larger "virtual electrode" including multiple spines. The IRE signal may be applied between one or more pairs of these "virtual electrodes" or sets.

[0043] In further exemplary embodiments, each spine 30 may be divided into two or more sub-electrodes for measuring and mapping electrophysiological signals. In other words, each spine 30 is divided into two or more mechanically connected but electrically isolated portions. For electroporation, the sub-electrodes on each spine 30 are connected together (shorted) so that each spine functions as a single electroporation electrode.

[0044] FIG. 3 is a schematic diagram of a bipolar IRE pulse 100, in accordance with one embodiment of the present invention.

[0045] Curve 102 shows the voltage V of a bipolar IRE pulse 100 as a function of time t in an IRE ablation procedure. The bipolar IRE pulse 100 includes a positive pulse 104 and a negative pulse 106, where the terms "positive" and "negative" refer to the arbitrarily selected polarities of the two spines 30 to which the bipolar pulse is applied. The amplitude of the positive pulse 104 is labeled V+, and the time width of the pulse is labeled t+. Similarly, the amplitude of the negative pulse 106 is labeled V-, and the time width of the pulse is labeled t-. The temporal separation between the positive pulse 104 and the negative pulse 106 is labeled t 間隔 Exemplary values ​​for the parameters of the bipolar pulse 100 are shown in Table 1 below.

[0046] FIG. 4 is a schematic diagram of a burst 200 of bipolar pulses, according to one embodiment of the present invention.

[0047] In an IRE procedure, the IRE signal is delivered to the spine 30 as one or more bursts 200, as shown by curve 202. The bursts 200 are arranged in a series of N P N bipolar pulses, 100 T The length of the pulse train 204 is t T The period of the bipolar pulse 100 in the pulse train 204 is t PP and the spacing between successive columns is Δ T and during which no signal is applied. Exemplary values ​​for the parameters of burst 200 are shown in Table 1 below.

[0048] [Table 1]

[0049] 5 is a block diagram that generally illustrates details of the IRE module 34, in accordance with an exemplary embodiment of the present invention. As described above with reference to FIG. 1, the IRE module 34 includes an IRE generator 36 and an IRE controller 38. The IRE generator 36 comprises a pulse generation assembly 406 and a pulse routing assembly 408. The pulse generation assembly 406 is configured to receive a control signal from the IRE controller 38 (as described below) and transmit a sequence of bipolar pulses having an amplitude and duration responsive to the control signal. The pulse routing assembly 408 comprises a configurable network of switches that are adapted to receive a control signal from the IRE controller 38, receive a sequence of bipolar pulses from the pulse generation assembly 406, select a pair of spines 30 in response to the received control signal, and transmit the sequence of bipolar pulses via the selected pair.

[0050] The IRE controller 38 communicates with the processor 32 via bidirectional signals 410, which communicates commands to the IRE controller that reflect the setup parameters 66. The IRE controller 38 further communicates digital command signals 418 derived from the setup parameters 66 to the pulse generation assembly 406 that instruct the IRE generator 36 to generate IRE pulses, such as those shown in Figure 4 above. These IRE pulses are sent to the pulse routing assembly 408 as analog pulse signals 420 that are directed by the IRE controller 38.

[0051] The IRE controller 38 receives a command signal 426 from the temperature controller 25 issued in response to the signal 428 output by the thermocouple 21. The temperature controller 25 therefore controls the timing of the IRE pulses applied to the spine 30 by the IRE module 34 such that the temperature of the tissue 62 adjacent to the spine does not exceed a preset limit.

[0052] The pulse routing assembly 408 is coupled to the spines 30 via output channels 422 and (optionally) to the return patch 60 via connections 424. For example, if the pulse routing assembly 408 is coupled to the six spines 30a-30f of the basket assembly 31 (FIG. 2), then six of the output channels 422 are coupled to the spines. The pulse routing assembly 408 is driven by the IRE controller 38 to couple IRE pulses to the spines 30 as defined by the setup parameters 66. Specifically, the IRE controller 38 drives the pulse routing assembly 408 to couple IRE pulses to one or more selected pairs of spines 30. The routing assembly 408 may also electrically couple multiple spines 30 together to form a set that can function as a "virtual electrode." Thus, the IRE controller 38 controls both the generation and routing of IRE pulses to the spines 30.

[0053] Although FIG. 5 shows ten channels 422, the IRE generator 36 may alternatively include a different number of channels, such as, for example, eight, sixteen, or twenty channels, or any other suitable number of channels.

[0054] FIG. 6 is a flow chart 500 that generally illustrates controlling tissue temperature during an IRE procedure, in accordance with an embodiment of the present invention.

[0055] In flow chart 500, the relevant functions of IRE module 34 and temperature controller 25 are indicated by dotted line frames 501 and 502, respectively. The IRE procedure begins at start step 503. At set up step 504, physician 22 (FIG. 1) sets a preset limit T for the temperature of tissue 62. th The IRE module 34 defines setup parameters 66 including: a) IRE signal generation for electroporation in a start electroporation step 506. The IRE module 34 selects a spine pair 30i, 30j in a next spine pair step 508, and generates and applies a new IRE pulse train to the spine pair in a next pulse train step 510.

[0056] After and / or during application of the pulse train, the temperature controller 25 measures the maximum temperature T of the thermocouples 21 in the tissue 62 adjacent to the spines 30i and 30j in a temperature measurement step 512. i and T j In a temperature comparison step 514, the temperature controller 25 compares the maximum temperature T i and T j The preset temperature limit T th Compare with the maximum measured temperature T i and T j is the preset limit T th As long as the pulse width is less than 100 s (either immediately after the IRE pulse or burst or after a suitable delay), the temperature controller 25 indicates to the IRE controller 38 that the IRE module 34 may generate the next train of IRE pulses.

[0057] temperature T i Or T j Either of the following is T th If T exceeds the preset limit T, the temperature controller 25 continues to measure the temperature of the tissue 62. Meanwhile, as shown in alternative pair step 516, electroporation continues on the alternative pair of spines 30i′, 30j′ with the associated temperature measurements and th Thus, the temperature controller 25 gates the delivery of new IRE pulse trains to the spines 30i, 30j in response to the maximum temperature of the tissue 62 adjacent to those spines, specifically, when the tissue temperature exceeds a preset limit T th Prevents a new pulse from being emitted if the temperature T i and T j T th When the temperature T drops below 100° C., the temperature controller 25 signals this to the IRE controller, which reverts to generating pulse trains to the spines 30i, 30j until a preset number of electroporation pulses have been fired through those spines. i and T j Again, T th If so, the process loops back to the alternative pair step 516 again to possibly select another alternative pair of spines.

[0058] In pulse train control step 518, the IRE controller 38 checks against the setup parameters 66 whether additional IRE pulse trains in the spines 30i, 30j are needed. If the answer is yes, the IRE module 34 generates another pulse train in step 510. If more pulses are not needed in the spines 30i, 30j, the IRE controller 38 checks against the setup parameters 66 whether electroporation signals need to be issued through additional pairs of spines in spine control step 520. If the answer is yes, the IRE module 34 selects the next pair in next spine pair step 508. If no more spine pairs are left for electroporation, the IRE controller 38 ends the IRE procedure in end step 522.

[0059] 7 is a flowchart 600 that generally illustrates a method for controlling tissue temperature during an IRE procedure, in accordance with an embodiment of the present invention. Most of the steps in flowchart 600 are similar or identical to steps in flowchart 500 (FIG. 6) and are labeled with the same numbers.

[0060] In this exemplary embodiment, the tissue temperature is controlled by reducing the number of pulses in the pulse train. Thus, in step 514, the temperature T i and T j Either or both of these are limited by a preset limit T を超 If so, the IRE controller 38 reduces the preset number of pulses in the pulse train applied to the pulse pair 30i, 30j in a pulse train reduction step 602. i and T j T th When the temperature T drops below 100° C. (or after a suitable delay), this reduced pulse train is applied to the spine pair. i and T j T tThe length of the pulse train is further shortened until it remains below h. The number of pulse trains is increased to maintain the total number of IRE pulses falling on a given spine pair at a preset value. Alternatively, the pulse widths t+ and t- and / or pulse spacing t 間隔 (Figure 3) shows the temperature T i and T j may be adjusted to be lower.

[0061] In the described control process, to avoid endless control loops, a maximum time for the IRE process can be set and a maximum number of electroporation attempts with a given spine pair is set. When the maximum time or number is reached, the process is terminated.

[0062] The described control process may also be applied, mutatis mutandis, to other types of catheters attached to electrodes attached to other types of distal structures, such as circular (lasso) catheters, balloon catheters, and linear catheters, as well as focal ablation catheters having a single tip electrode.

[0063] It will be understood that the above-described embodiments are given by way of example, and that the present invention is not limited to what is specifically shown and described herein above. Rather, the scope of the present invention includes both combinations and subcombinations of the various features described herein above, as well as variations and modifications thereof not disclosed in the prior art that would occur to one skilled in the art upon reading the foregoing description.

[0064] [Embodiment] (1) A medical device for use in IRE, A probe comprising: an insertion tube configured for insertion into a body cavity of a patient; a distal structure connected distally to the insertion tube and including a plurality of electrodes configured to contact tissue within the body; a temperature sensor secured to the distal structure and configured to output a signal indicative of a temperature of the tissue contacted by the electrode; an electrical signal generator configured to apply bipolar pulses between one or more pairs of electrodes having an amplitude sufficient to induce irreversible electroporation (IRE) in the tissue in contact with the spine; a controller configured to control timing of the bipolar pulses applied by the electrical signal generator in response to the signal output by the temperature sensor. (2) The device of embodiment 1, wherein the controller is configured to modify the bipolar pulse applied by the signal generator while the signal output by the temperature sensor indicates that the temperature of the tissue contacted by a given pair of electrodes exceeds a preset threshold. (3) The apparatus of embodiment 2, wherein modifying the bipolar pulse includes preventing the electrical signal generator from applying the bipolar pulse between the given pair of electrodes. (4) The device of embodiment 3, wherein the controller is configured to apply the bipolar pulses to another pair of electrodes while waiting for the temperature sensor to indicate that the temperature of the tissue contacted by the given pair of electrodes has dropped below the preset threshold. (5) The apparatus of embodiment 2, wherein modifying the bipolar pulses includes modifying the number of consecutive bipolar pulses applied by the signal generator to the given pair of electrodes.

[0065] (6) The apparatus of embodiment 2, wherein modifying the bipolar pulse includes delaying application of the bipolar pulse to the given pair of electrodes. (7) The device of embodiment 1, wherein the distal structure comprises a basket assembly having a plurality of elastic spines configured to contact the tissue, and the temperature sensor is secured to the spines. (8) The device of embodiment 7, wherein the spines have respective proximal and distal tips, the proximal tips of the spines are mechanically joined at the proximal end of the basket assembly, and the distal tips of the spines are mechanically joined at the distal end of the basket assembly, and when the basket assembly is deployed within the body cavity, the spines deflect radially outward, thereby contacting the tissue within the body cavity. (9) The device of embodiment 7, wherein the spine comprises a conductive material and is configured to function as the electrode. (10) The device of claim 9, wherein the conductive material comprises a nickel-titanium alloy.

[0066] (11) The device of embodiment 9, wherein each spine is divided into two or more mechanically connected but electrically isolated portions, and the electrically isolated portions of a given spine can be electrically connected together to function as one of the electrodes for applying the bipolar pulses. (12) The device of embodiment 9, wherein the electrical signal generator is configured to apply the bipolar pulse between a first set and a second set of the spines, at least one of the sets including two or more of the spines. (13) The device of embodiment 1, wherein the insertion tube comprises a flexible catheter configured for insertion into a chamber of the patient's heart, and the electrodes are configured to contact myocardial tissue within the chamber and apply the electrical signal. (14) The apparatus of embodiment 1, wherein the bipolar pulses applied by the electrical signal generator include a sequence of bipolar pulses having an amplitude of at least 200 V, each of the bipolar pulses having a duration of less than 20 μs. (15) The apparatus of embodiment 14, wherein the sequence of bipolar pulses includes pairs of pulses, each pair including a positive pulse and a negative pulse.

[0067] (16) A method of medical treatment comprising: inserting a probe, the probe comprising an insertion tube and a distal structure including a plurality of electrodes, into a body cavity of a patient such that the electrodes contact tissue within the body cavity; applying a bipolar pulse between two or more sets of electrodes, each set including one or more of the electrodes, having an amplitude sufficient to induce irreversible electroporation (IRE) in the tissue contacted with the electrodes; measuring the temperature of the tissue in contact with the electrodes; and controlling timing of the applied bipolar pulses in response to the measured temperature. (17) The method of embodiment 16, wherein controlling the timing of the bipolar pulses in response to the measured temperature comprises modifying the applied bipolar pulses while the temperature of the tissue contacted by a given pair of electrodes exceeds a preset threshold. (18) The method of embodiment 17, wherein modifying the bipolar pulse comprises preventing application of the bipolar pulse between the given pair of electrodes. (19) The method of embodiment 18, comprising applying a bipolar pulse to another pair of electrodes while waiting for the temperature of the tissue contacted by the given pair of electrodes to drop below the preset threshold. (20) The method of embodiment 17, wherein modifying the bipolar pulses includes modifying the number of consecutive bipolar pulses applied to the given pair of electrodes.

[0068] (21) The method of embodiment 17, wherein modifying the bipolar pulse comprises delaying application of the bipolar pulse to the given pair of electrodes. (22) The method of embodiment 16, wherein the distal structure comprises a basket assembly comprising a plurality of elastic spines in contact with the tissue and comprising a temperature sensor secured to the spines. (23) The method of embodiment 22, wherein the spines have respective proximal and distal tips, the proximal tips of the spines are mechanically joined at the proximal end of the basket assembly, and the distal tips of the spines are mechanically joined at the distal end of the basket assembly, and when the basket assembly is deployed within the body cavity, the spines deflect radially outward, thereby contacting the tissue within the body cavity. 24. The method of claim 22, wherein the spine comprises a conductive material and is configured to function as the electrode. 25. The method of claim 24, wherein the conductive material comprises a nickel-titanium alloy.

[0069] (26) The method of embodiment 24, wherein each spine is divided into two or more mechanically connected but electrically isolated portions, and applying the bipolar pulse comprises connecting the electrically isolated portions of a given spine together to function as one of the electrodes for applying the bipolar pulse. (27) The method of embodiment 24, wherein applying the bipolar pulse comprises applying the bipolar pulse between a first set and a second set of spines, at least one of the sets comprising two or more of the spines. (28) The method of embodiment 16, wherein the insertion tube comprises a flexible catheter, and inserting the probe into the patient's body cavity comprises inserting the catheter into a ventricle of the patient's heart, whereby the electrode contacts myocardial tissue within the ventricle and applies the electrical signal to the myocardial tissue. (29) The method of embodiment 16, wherein applying the bipolar pulses comprises applying a sequence of bipolar pulses having an amplitude of at least 200 V, each of the bipolar pulses having a duration of less than 20 μs. (30) The method of embodiment 29, wherein the sequence of bipolar pulses includes pairs of pulses, each pair including a positive pulse and a negative pulse.

Claims

1. A medical device for irreversible electroporation, comprising: A probe comprising: an insertion tube configured for insertion into a body cavity of a patient; a distal structure including a plurality of elastic spines connected distally to the insertion tube and including a conductive material that acts as a plurality of electrodes configured to contact tissue within the body; a temperature sensor secured to the plurality of elastic spines of the distal structure and configured to output a signal indicative of a temperature of the tissue contacted by the plurality of elastic spines; an electrical signal generator configured to apply a bipolar pulse between one or more pairs of electrodes having an amplitude sufficient to cause the irreversible electroporation in the tissue in contact with the plurality of elastic spines; a controller configured to control timing of the bipolar pulses applied by the electrical signal generator in response to the signal output by the temperature sensor; the bipolar pulses applied by the electrical signal generator include a sequence of bipolar pulses having an amplitude of at least 200V; wherein the sequence of bipolar pulses comprises pairs of pulses, each pair comprising a positive pulse and a negative pulse, the width of the positive and negative pulses being 5 μS, the interval between the positive and negative pulses being 0.1 μS, and the period of each pair being 20 μS.

2. 2. The apparatus of claim 1, wherein the controller is configured to modify the number of bipolar pulses applied by the electrical signal generator while the signal output by the temperature sensor indicates that the temperature of the tissue contacted by a given pair of the electrodes exceeds a preset threshold.

3. The apparatus of claim 2 , wherein modifying the number of bipolar pulses comprises preventing the electrical signal generator from applying the bipolar pulse between the given pair of electrodes.

4. 4. The apparatus of claim 3, wherein the controller is configured to apply the bipolar pulses to another pair of electrodes while waiting for the temperature sensor to indicate that the temperature of the tissue contacted by the given pair of electrodes has dropped below the preset threshold.

5. The apparatus of claim 2 , wherein modifying the number of bipolar pulses comprises modifying a number of consecutive bipolar pulses applied by the electrical signal generator to the given pair of electrodes.

6. The device of claim 1 , wherein the distal structure comprises a basket assembly comprising the plurality of elastic spines.

7. 7. The device of claim 6, wherein the plurality of elastic spines have respective proximal and distal tips, the proximal tips of the plurality of elastic spines are mechanically joined at a proximal end of the basket assembly, and the distal tips of the plurality of elastic spines are mechanically joined at a distal end of the basket assembly, and when the basket assembly is deployed within the body cavity, the plurality of elastic spines deflect radially outward, thereby contacting the tissue within the body cavity.

8. The device of claim 1 , wherein the conductive material comprises a nickel-titanium alloy.

9. The device described in claim 7, wherein the proximal and distal tips of each of the multiple elastic spines are electrically insulated from one another.

10. 2. The apparatus of claim 1, wherein the electrical signal generator is configured to apply the bipolar pulse between a first set and a second set of the plurality of elastic spines, the first set and the second set including two or more of the plurality of elastic spines.

11. 2. The apparatus of claim 1, wherein the insertion tube comprises a flexible catheter configured for insertion into a chamber of the patient's heart, and the electrodes are configured to contact myocardial tissue within the chamber and apply the bipolar pulses.

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