Systems for pre-ablation pulses in pulsed field ablation applications

Abstract

To provide a system, a device, and a method for electroporation ablation therapy.SOLUTION: A system includes a signal generator for generating pre-ablation signals and pulse waveforms for medical ablation therapy that may be coupled to an ablation device including at least one electrode for ablation pulse delivery to tissue. The signal generator may generate and deliver pre-ablation signals to subsets of electrodes of the ablation device and measure currents associated with the delivery to determine whether the currents meet one or more predetermined criteria. The signal generator may further generate voltage pulses meeting the criteria and deliver the voltage pulses in a form of a pulse waveform to the ablation device.SELECTED DRAWING: Figure 1A

Description

[Background technology]

[0001] Pulsed electric field energy delivery, also known as pulsed field ablation (PFA), utilizes short pulses of high voltage to generate localized, high electric fields that can cause cell membrane disruption and lead to cell death. This process is also known as irreversible electroporation. In fluid media (e.g., blood), high-voltage pulses can cause electrolysis and associated gas bubble formation. In some cases, depending on the pulse amplitude and waveform, the electric field very close to the electrode end may become too high, causing localized thermal effects or localized arc flash events, which may be undesirable for clinical applications such as cardiac ablation. Therefore, it may be desirable to ensure that the device is properly positioned and deployed relative to the target tissue before delivering ablation energy. Summary of the Invention

[0002] Described herein are systems, devices, and methods for ablating tissue by irreversible electroporation. In some embodiments, the system includes an ablation device including a set of electrodes configured to be positioned within a patient's anatomy; a signal generator including: an energy source connected to the set of electrodes and a sensing circuit connected to the set of electrodes; and a processor operably connected to the energy source and the sensing circuit, the processor configured to: generate a set of pre-ablation signals using the energy source; deliver the set of pre-ablation signals to a first subset of electrodes from the set of electrodes; measure a set of one or more currents passing through a current sensing resistor of the sensing circuit using the sensing circuit in response to delivery of the set of pre-ablation signals; determine whether the set of currents meets a predetermined criterion; and, in response to a determination that the set of currents meets the predetermined criterion, generate and deliver a pulse waveform to a second subset of electrodes from the set of electrodes, such that the second subset of electrodes generates a pulsed electric field for ablating tissue.

[0003] In some embodiments, the signal generator or separate measurement device can include an analog optocoupler connected to the sensing circuit and an analog-to-digital converter (ADC), wherein the analog optocoupler is configured to separate high voltage noise from the signal measured by the sensing circuit, and the analog-to-digital converter (ADC) is configured to digitize the signal after the analog optocoupler has separated the high voltage noise from the signal and pass the signal to the processor, and the processor can be configured to determine whether the set of currents meets a predetermined criterion after receiving the signal from the ADC.

[0004] In some embodiments, the signal generator or separate measurement device may include: a current sensing resistor connected to a set of electrodes of an ablation device positionable within a patient's anatomy; a current measurement circuit configured to measure a current through the current sensing resistor generated in response to a pre-ablation pulse applied to a first subset of electrodes of the set of electrodes; a comparator configured to determine whether the current meets a predetermined criterion and to generate a digital output indicative of whether the current meets the predetermined criterion; and a processor configured to: receive the digital output indicative of the current meeting the predetermined criterion, deliver a pulse waveform to a second subset of electrodes of the set of electrodes such that the second subset of electrodes generates a pulsed electric field for ablation; and receive the digital output indicative of the current not meeting the predetermined criterion, inhibit delivery of a pulse waveform to the second subset of electrodes.

[0005] In some embodiments, generating a set of pre-ablation signals using an energy source; delivering the set of pre-ablation signals to a first set of a subset of electrodes of the set of electrodes of an ablation device positioned within a patient's anatomical structure; measuring a set of one or more currents passing through a current sensing resistor of the sensing circuit using a sensing circuit connected to the set of electrodes in response to delivery of the set of pre-ablation signals; determining whether the set of currents meets a predetermined criterion; and, in response to a determination that the set of currents meets a predetermined criterion, generating and delivering a pulse waveform to a second set of the subset of electrodes of the set of electrodes, thereby causing the second set of the subset of electrodes to generate a pulsed electric field for ablating tissue. [Brief explanation of the drawings]

[0006] [Figure 1A]1A and 1B illustrate schematic diagrams of a set of pre-ablation voltage pulses followed by a set of ablation pulses or ablation waveforms, according to some embodiments. [Figure 1B] 10A-10C schematically illustrate a set of pre-ablation voltage pulses, each applied to a separate paired set of electrodes, according to some embodiments. [Figure 2] 1 illustrates multiple sets of pre-ablation voltage pulses, each set including pulses applied to a separate paired set of electrodes, according to some embodiments. [Figure 3] 1 illustrates multiple sets of pre-ablation voltage pulses, each set applied to a separate paired set of electrodes, according to some embodiments. [Figure 4A] 1A-1C are schematic illustrations of a deployable multi-spline catheter in a basket configuration, according to some embodiments, where the distal portion of the catheter includes multiple splines that are deployable across various configurations. [Figure 4B] FIG. 1 is a schematic diagram of a front view of a deployed basket configuration of a deployable multi-spline catheter, according to some embodiments, where the distal portion of the catheter includes multiple splines that are deployable across various configurations, and the splines are unevenly spaced due to anatomical constraints. [Figure 5] FIG. 1 is a schematic diagram of a front view of an expanded petal configuration of an expandable multi-spline catheter, according to some embodiments, where the distal portion of the catheter includes multiple splines that are expandable across various configurations, and the splines or petals are unevenly spaced due to anatomical constraints. [Figure 6A] 1A-1C schematically illustrate a linear focal catheter having multiple electrodes disposed along a distal portion extending from a sheath, with all electrodes exposed beyond the distal end of the sheath, according to some embodiments. [Figure 6B] 1A-1C schematically illustrate linear focal catheters having multiple electrodes disposed along a distal portion extending from a sheath, with some, but not all, of the electrodes exposed beyond the distal end of the sheath, according to some embodiments. [Figure 7] 1 illustrates a circuit topology for generating high voltage pulses for application to a set of electrodes and measuring the associated current, according to some embodiments. [Figure 8] 1 illustrates a schematic circuit topology for generating a pre-ablation pulse, according to some embodiments. [Figure 9] 10 illustrates another schematic circuit topology for generating a pre-ablation pulse using a second capacitor charged to a lower voltage than the first capacitor, according to some embodiments. [Figure 10] 1 illustrates another schematic circuit topology for generating a pre-ablation pulse utilizing high speed switching and a resistor-capacitor network, according to some embodiments. [Figure 11] FIG. 1 is a block diagram of an apparatus for fast measurement of a current associated with a voltage pulse, according to some embodiments. [Figure 12] FIG. 1 is a block diagram of an alternative apparatus for ultrafast measurement of current associated with a voltage pulse, according to some embodiments. [Figure 13A] FIG. 1 is a block diagram of a system for ablation, according to some embodiments. [Figure 13B] Same as above. [Figure 14] 1 illustrates a method of tissue ablation, according to some embodiments. DETAILED DESCRIPTION OF THE INVENTION

[0007] Detailed Description The systems, devices, and methods described herein can be configured to determine the sufficiency of electrode placement of an ablation device relative to tissue and control operation of the ablation device based on such determination. For example, the systems described herein can include a signal generator configured to generate a pre-ablation pulse and a measurement circuit configured to measure the current of the pre-ablation pulse. The measured current can be analyzed to determine the distribution of the electrodes relative to the tissue. In some embodiments, it can be useful to ensure that the current delivered to a given electrode pair is within a desired range with a high voltage applied to the electrode pair, or that the current is not excessively large, or that the current meets other constraints for optimal therapeutic effect. This can be useful for assessing device deployment for optimal ablation delivery. The systems, devices, and methods described herein deliver and measure a pre-ablation current before an ablation waveform is delivered to ensure proper device deployment before ablation delivery.

[0008] Status signals can be output and used to control the delivery of ablation energy to tissue. For example, if electrode distribution does not meet predetermined criteria, delivery of ablation energy can be inhibited. A user warning can be output prior to delivery of ablation energy to prompt redeployment / repositioning of the device. Pre-ablation pulses as described herein can be generated and associated current measurements taken using a variety of interventional or minimally invasive devices, such as catheters for cardiac ablation.

[0009] In general, the systems and devices described herein include one or more devices (e.g., catheters) configured to ablate tissue within the heart (e.g., the left atrium of the heart). FIG. 13A shows a system 1300 configured to deliver pre-ablation and ablation signals, according to some embodiments. The system 1300 may include an ablation device 1310, a signal generator 1320, and optionally a sensing system 1328, a protection device or module 1329, and a diagnostic device 1330. The ablation device 1310 may include one or more electrodes 1312, and the diagnostic device 1330 may include one or more electrodes 1332. The ablation device 1310 and the diagnostic device 1330 may be disposable within the patient's body BD. The ablation device 1310 may be connected to a signal generator 1320 that includes a processor 1324, a memory 1326, and an input / output device 1327. In some embodiments, the signal generator 1320 may include a capacitor bank that stores energy to generate a pulse waveform that can be delivered to the ablation device 1310. In some embodiments, the generation and delivery of the pulse waveform may be controlled by one or more processors 1324. Suitable examples of signal generators are described in U.S. Patent Application No. 9,987,081, entitled "SYSTEMS, DEVICES, AND METHODS FOR SIGNAL GENERATION," filed April 27, 2017 (now issued as U.S. Patent No. 9,987,081), the disclosure of which is incorporated herein by reference.

[0010] Each of the one or more processors 1324 may be any suitable processing device configured to run and / or execute a set of instructions or code. The processor 1324 may be, for example, a general-purpose processor, a field-programmable gate array (FPGA), an application-specific integrated circuit (ASIC), a digital signal processor (DSP), a microcontroller, a microprocessor, and / or the like (e.g., multiple processors and / or a combination including multiple types of processors). The underlying device technology may be provided in a variety of component types, for example, metal-oxide-semiconductor field-effect transistor (MOSFET) technology such as complementary metal-oxide-semiconductor (CMOS), bipolar technology such as emitter-coupled logic (ECL), polymer technology (e.g., silicon-conjugated polymer and metal-conjugated polymer-metal structures), mixed analog and digital, etc. In some embodiments, the processor 1324 may be configured to control the generation and / or delivery of pre-ablation pulses and / or ablation waveforms to the ablation device 1310.

[0011] The memory 1326 may include a database (not shown) and may be, for example, random access memory (RAM), a memory buffer, a hard drive, erasable programmable read-only memory (EPROM), electrically erasable read-only memory (EEPROM), read-only memory (ROM), flash memory, etc. The memory 1326 may store instructions for causing the processor 1324 to execute modules, processes, and / or functions, for example, for pre-ablation pulse and / or pulse waveform generation.

[0012] The input / output devices 1327 can include one or more components configured to receive input and / or generate output to a user. For example, the input / output devices 1327 can include a user interface such as a display, an audio device, a touchscreen device, etc. The input / output devices 1327 can include one or more interfaces for communicating with external devices, such as the ablation device 1310, the diagnostic device 1330, the protection module 1329, and / or the sensing system 1328.

[0013] Ablation device 1310 can be any suitable device configured to deliver ablation energy to tissue. In some embodiments, ablation device 1310 can include a catheter with a set of electrodes 1312 configured to generate a pulsed electric field to ablate tissue by irreversible electroporation. In some embodiments, ablation device 1310 can be movable or transitionable between multiple configurations. In some embodiments, ablation device 1310 can have a basket-shaped structure, a wire-shaped structure, a flower-shaped structure, a lasso-shaped structure, a balloon-shaped structure, and / or any other suitable structure for delivering ablation energy to tissue. Suitable examples of ablation devices are disclosed in International Application No. PCT / US2018 / 029938, filed April 27, 2018, entitled "SYSTEMS, DEVICES, AND METHODS FOR DELIVERY OF PULSED ELECTRIC FIELD ABLATIVE ENERGY TO ENDOCARDIAL TISSUE," International Application No. PCT / US2020 / 026682, filed April 3, 2020, entitled "SYSTEMS, DEVICES, AND METHODS FOR FOCAL ABLATION," International Application No. PCT / US2020 / 037948, filed June 16, 2020, entitled "SYSTEMS, DEVICES, AND METHODS FOR FOCAL ABLATION," and International Application No. PCT / US2020 / 037948, filed September 12, 2018, entitled "SYSTEMS, DEVICES, AND METHODS FOR VENTRICULAR FOCAL ABLATION." and International Application No. PCT / US2018 / 050660, entitled "ABLATION," the contents of each of which are incorporated herein by reference in their entirety.

[0014] The protection module 1329 can be connected to the sensing system 1328, the diagnostic device 1330, and the signal generator 1320. The signal generator 1320 can be connected to the ablation device 1310 and can be configured to generate and deliver a high-voltage signal to the electrode 1312. The electrode 1312 can be positioned near cardiac tissue in the subject's heart. The diagnostic device 1330, including the sensor 1332, can be positioned near the electrode 1312, for example, within a cardiac chamber, or on or near the external surface of the subject. In some embodiments, delivery of a high-voltage signal (e.g., a pulsed ablation waveform) to the electrode 1312 of the ablation device 1310 can induce high currents and / or high voltages in the sensor 1332. These large unbalanced currents and / or voltages can disrupt the operation of the sensing system 1328. Thus, by configuring protection module 1329 to isolate sensing system 1328 from diagnostic device 1330 during a time interval associated with delivery of a high voltage signal to ablation device 1310, sensing system 1328 can be protected from high currents and / or high voltages induced in diagnostic device 1330. Suitable examples of protection modules and protection devices are described in International Application No. PCT / US20 / 061564, filed November 20, 2020, and entitled "SYSTEMS, APPARATUSES, AND METHODS FOR PROTECTING ELECTRONIC COMPONENTS FROM HIGH POWER NOISE INDUCED BY HIGH VOLTAGE PULSES," the disclosure of which is incorporated herein by reference.

[0015] In some embodiments, sensing system 1328, when connected to diagnostic device 1330, may be configured to receive measured signals from sensor 1332 of diagnostic device 1330. In some embodiments, diagnostic device 1330 may be an electrophysiology (EP) catheter configured to measure electrical signals from the subject's body. In some embodiments, the measured signals may include electrocardiogram (ECG) signals. In some embodiments, sensing system 1328 may be configured to detect whether there is ectopic activity and / or pacing capture and send one or more signals to signal generator 1320 to control the delivery of one or more pulse waveforms. For example, sensing system 1328 may be configured, upon detection of ectopic activity, to send a signal to signal generator 1320 notifying the signal generator 1320 of the ectopic activity and / or a signal instructing the signal generator 1320 to pause or terminate generation of the signal waveform. Alternatively or additionally, upon confirmation of pacing capture, sensing system 1328 can be configured to send a signal to signal generator 1320 indicating that pacing capture has been confirmed and / or instructing signal generator 1320 to begin generating a signal waveform. In some embodiments, one or more of the sensing functions, such as detecting ectopic activity and confirming pacing capture, can be performed by signal generator 1320 based on signals received from protection module 1329. Suitable examples of controllers or devices for sensing information about a subject are described in "SYSTEMS, APPARATUSES, AND METHODS FOR DETECTING ECTOPIC ACTIVITY" filed on September 17, 2019. ELECTROCARDIOGRAM SIGNALS DURING PULSED No. 16 / 573,704 (now issued as U.S. Pat. No. 10,625,080) entitled "ELECTRIC FIELD ABLATION," the disclosure of which is incorporated herein by reference.

[0016] In some embodiments, the signal generator 1320 can be configured to generate a pre-ablation pulse waveform and / or an ablation pulse waveform. For example, the signal generator 1320 can be a voltage pulse waveform generator that generates and delivers a pre-ablation signal waveform and / or an ablation pulse waveform to the ablation device 1310. In some embodiments, the processor 1324 can execute instructions stored in the memory 1326 and / or incorporate data stored in the memory 1326 and / or received from the input / output device 1327 to control the signal generator 1320 to generate a pre-ablation signal or pulse waveform having predetermined parameters (e.g., timing, amplitude, pulse width, delay, etc.). The memory 1326 can store instructions that cause the signal generator 1320 to perform modules, processes, and / or functions, such as pre-ablation deployment verification and pulse waveform generation. For example, the memory 1326 can be configured to store one or more of pre-ablation data and pulse waveform data. In some embodiments, the pre-ablation pulse and / or the ablation pulse can have an amplitude of 100V, 200V, 300V, 400V, 500V, 1 kV, 5 kV, 10 kV, or 20 kV, including all values ​​and ranges therebetween. In some embodiments, the pre-ablation pulse can have a smaller amplitude than the ablation pulse waveform. In some embodiments, the pre-ablation pulse can have the same amplitude as the ablation pulse waveform. In some embodiments, the pre-ablation pulse can have a smaller pulse width than the pulse of the ablation pulse waveform. In some embodiments, the pre-ablation pulse can have the same pulse width as the pulse of the ablation pulse waveform.

[0017] In some embodiments, processor 1324 can be configured to analyze signals measured at a current sensing resistor (not shown) and control pulse ablation delivery based on the measured signals. For example, a sensing circuit including a current sensing resistor can be connected to the path of a current passing through electrodes 1312 of ablation device 1310, and the current passing through the sensing circuit can be processed and / or analyzed by processor 1324. In some embodiments, processor 1324 can control signal generator 1320 to generate and deliver pre-ablation pulses to electrodes 1312 of ablation device 1310, and the signals passing through the sensing circuit can be processed and / or analyzed to determine whether they meet one or more predetermined measures or criteria. For example, the sensed signals can be analyzed to check that they each fall within predetermined minimum and maximum values. In some embodiments, the check can include determining that no signals exceed a predetermined threshold (e.g., a maximum value). In some embodiments, the check can include determining that no signals fall below a predetermined threshold (e.g., a minimum value). In some embodiments, the check can include calculating a metric, such as an average value, of the sensed signals. In some embodiments, the check may include calculating a metric such as the variance of the sensed signals, calculating a metric such as the ratio of the maximum sensed signal to the minimum sensed signal, or calculating a metric based on some other generally non-linear function of the sensed signals. In some embodiments, the check may include any combination of these calculations (e.g., a metric based on one or more of the calculations described herein), and then determining whether the calculated metrics are within a predetermined range or whether they are below or above (e.g., greater than or less than) an appropriate predetermined threshold. For example, in one embodiment, the check may be to determine whether the variance of the measured currents is within a particular range. As another example, in one embodiment, the check may be to determine whether the ratio of the maximum current to the minimum current is below a threshold.In some embodiments, the threshold may be greater than about 1 and less than about 5, greater than about 1 and less than about 10, greater than about 1 and less than about 20, including all subvalues ​​and ranges therebetween. In one embodiment, the predetermined range or threshold may be user adjustable, for example, via input received from input / output device 1327. In some embodiments, the check and / or predetermined range and value may vary depending on the type of ablation device used, for example, a linear ablation device, a basket-type device, or a lasso-type device.

[0018] 13B illustrates a system 1300′ configured to deliver pre-ablation signals and ablation waveforms, according to some embodiments. System 1300′ may include structurally and / or functionally similar components to other ablation systems described herein, including ablation system 1300. For example, system 1300′ may include an ablation device 1310′, a signal generator 1320, a protection module 1329, a sensing system 1328, and a diagnostic device 1330. Additionally, system 1300′ may include a mapping system 1353, a protection module 1351 connected to signal generator 1320 and ablation device 1310′. Ablation device 1310′ may be structurally and / or functionally similar to ablation device 1310, except that ablation device 1310′ may further include a sensor 1342 (e.g., electrode, sensor) that may be configured to receive and sense signals from a magnetic field, e.g., to determine the position, location, and / or orientation of ablation device 1310′. The ablation device 1310' and the diagnostic device 1330 may be placed in the patient's body BD. The ablation device 1310' may be connected to a signal generator 1320, which may include a processor 1324, a memory 1326, and an input / output device 1327.

[0019] In use, a signal waveform generated by signal generator 1320 may be delivered to ablation device 1310′, for example, via second protection module 1351 in some embodiments. Signals received from one or more of sensors 1342 of ablation device 1310′ may be received by mapping system 1353, for example, via protection module 1351. In some embodiments, protection module 1351 may be a modular extension of protection module 1329 (shown in FIG. 13B by the dotted line from protection module 1329 to protection module 1351). For example, a single protection module may include multiple channels configured to isolate different electronic devices, e.g., sensing system 1329 and / or mapping system 1353, from high voltages and high currents induced in the device during ablation delivery. Thus, protection modules 1329, 1351 may be part of a signal protection device. In some embodiments, multiple protection devices including separate protection modules 1329 and 1351 may be used. In some embodiments, one or more protection modules may form an accessory device attached to the signal generator.

[0020] Mapping system 1353 can be used in conjunction with sensor 1342 to determine the position, location, and / or orientation of ablation device 1310'. For example, mapping system 1353 can include a field generator for generating an electric and / or magnetic field. The electric and / or magnetic fields can cause sensor 1342 to receive a signal that can be sent back to a processor (e.g., processor 1324 or a processor (not shown) of mapping system 1353). The processor then processes the signal to determine the position, location, and / or orientation of ablation device 1310'. Suitable examples of mapping systems and how they can be used with the ablation devices described herein are described in U.S. Patent Application No. 16 / 785,392, filed February 7, 2020, and International Patent Application No. PCT / US20 / 61809, filed November 23, 2020, both entitled "METHODS, SYSTEMS, AND APPARATUSES FOR TRACKING ABLATION DEVICES AND GENERATING LESION LINES," the disclosures of each of which are incorporated herein by reference.

[0021] Systems 1300, 1300′ may communicate with other devices (not shown), for example, through one or more networks, each of which may be any type of network. A wireless network refers to any type of digital network that is not connected by any type of cable. However, wireless networks may connect to wired networks to interface with the Internet, other carrier voice and data networks, business networks, and personal networks. Wired networks are typically transmitted over stranded copper wire, coaxial cable, or fiber optic cable. There are various types of wired networks, including wide area networks (WANs), metropolitan area networks (MANs), local area networks (LANs), campus area networks (CANs), global area networks (GANs) such as the Internet, and virtual private networks (VPNs). Hereinafter, a network refers to any combination of wireless, wired, public, and private data networks interconnected, typically through the Internet, to provide integrated networking and information access solutions.

[0022] Overall, the spatial placement of electrodes on a device (e.g., a catheter such as ablation device 1310, 1310′) can play a critical role in the delivery of PFA energy therapy. Optimal distribution or placement of electrodes (e.g., electrode 1312) can ensure that treatment is delivered safely and effectively. For example, one or more of the local anatomy, shape, and device placement may result in suboptimal distribution of electrodes on a device. The systems, devices, and methods described herein can identify suboptimal distribution of electrodes and alert the user to reposition or reposition the ablation device to optimize the deployment or placement of the ablation device.

[0023] In some embodiments, pre-ablation pulses may be generated and delivered to tissue via medical device electrodes (e.g., electrodes 1312), and the associated current may be measured to enable a determination of whether to proceed with ablation energy delivery. In some embodiments, ablation energy delivery may proceed if the measured current is within a predetermined range (e.g., the current is not excessively large) or meets predetermined constraints or criteria. In some embodiments, ablation delivery may proceed immediately (e.g., with a small time delay) after meeting predetermined constraints based on the measured current. If one or more of the constraints are not met, delivery of ablation energy is not performed, and a message may be output to the user (e.g., a visual display, an audible sound). In some embodiments, a user interface display (e.g., input / output device 1327) of the ablation system may prompt the user to reposition and / or redeploy the ablation device (e.g., ablation device 1310, 1310′). After repositioning the ablation device, another set of pre-ablation pulses may be generated, for example, to evaluate whether further repositioning is necessary before delivery of PFA.

[0024] 1A schematically illustrates an example of a pre-ablation signal followed by an ablation signal, according to some embodiments. The pre-ablation signal may include a set 21 of pre-ablation voltage pulses 12 followed by a set 25 of ablation pulses 16 (also referred to as an ablation waveform), which engage tissue within a target anatomy and are delivered to a medical device (e.g., an ablation device 1310, 1310′) connected to a pulsed field ablation generator (e.g., a signal generator 1320). A pre-ablation current measurement of the set 21 of pre-ablation pulses may determine whether the set 25 of ablation pulses 16 is delivered after a time delay 23. In some embodiments, the time delay 23 between the end of the set of pre-ablation pulses 21 and the start of the set 25 of ablation pulses 16 may range from about several microseconds to several milliseconds, or from about several milliseconds to several seconds, including all ranges and subvalues ​​therebetween. Although FIG. 1A shows a biphasic pre-ablation pulse 12 and a biphasic ablation pulse 16, it will be appreciated that in other embodiments, one or more of the pre-ablation pulses may include a monophasic pulse.

[0025] FIG. 1B is a schematic diagram of a set of pre-ablation voltage pulses, each applied to a separate pair or group of electrode subsets of an ablation device (e.g., ablation devices 1310, 1310′). For example, pulses 112, 115, 116, and 118 are each biphasic voltage pulses applied to a separate pair of electrode subsets, with each subset in each pair being of opposite electrical polarity. Successive pulses, such as 112 and 115, applied to electrode subsets of different pairs can be separated by a time delay 121. The time delay 121 can range from about 1 microsecond to about 1 millisecond, or from about tens of nanoseconds to about several seconds, including all values ​​and subranges therebetween. In some embodiments, each pair of electrode subsets that receives an individual pre-ablation pulse is an electrode subset pair that can also receive a pulse waveform during ablation delivery. Alternatively, different electrode subsets can receive pre-ablation and ablation pulse waveforms. For example, a first set of the subset of electrodes can receive a pre-ablation pulse and a second set of the subset of electrodes can receive an ablation pulse waveform for delivery of the ablation therapy. The current delivered during each pre-ablation pulse can be measured as described in more detail with respect to later figures presented herein.

[0026] While FIG. 1B depicts four distinct pulses 112, 115, 116, and 118, it will be apparent to one skilled in the art that any number of pulses may be utilized, corresponding to the number of distinct pairs of electrode subsets required for the measurement. For example, in some embodiments, the number of pulses may correspond to the number of electrode subsets receiving ablation energy. Alternatively, the number of pulses may be greater or less than the number of electrode subsets receiving ablation energy. Similarly, while FIG. 1B depicts biphasic pre-ablation pulses 112, 115, 116, and 118, the pre-ablation pulses may include monophasic pulses.

[0027] FIG. 2 is a schematic diagram of multiple sets of pre-ablation voltage pulses, each set including multiple pulses applied to a separate pair or group of electrode subsets of an ablation device (e.g., ablation devices 1310, 1310′). A first pulse set 225 includes four biphasic pulses 212, 214, 216, and 218, each applied to a different pair of electrode subsets. For example, first pulse set 225 may be followed by a second pulse set 227 including pulses applied to a different pair of electrode subsets, followed by additional pulse sets. In some embodiments, each pair of electrode subsets receiving an individual pre-ablation pulse is an electrode subset pair that can also receive a pulse waveform during ablation delivery. Alternatively, different electrode subsets may receive pre-ablation and ablation pulse waveforms. For example, a first set of electrode subsets can receive a pre-ablation pulse, and a second set of electrode subsets can receive an ablation pulse waveform for delivery of ablation therapy. The current delivered during each pre-ablation pulse can be measured as described in more detail with respect to later figures presented herein. By repeating the pulse set, multiple measurements can be obtained for each paired electrode subset, which can be used for averaging, noise reduction, etc.

[0028] While FIG. 2 shows four separate pulses in each pulse set, it will be apparent to one skilled in the art that any number of pulses can be utilized, corresponding to the number of separate pairs of electrode subsets required for measurement. For example, the number of pulses can correspond to the number of paired electrode subsets receiving ablation energy. In some embodiments, any number of pulse sets or repetitions can be implemented as convenient for measurement purposes. In some embodiments, the number of pulse sets can range from about 1 set to about 15 sets, with each set including at least one pulse applied to one pair of electrode subsets. Similarly, while FIG. 2 shows biphasic pre-ablation pulses 212, 214, 216, and 218, the pre-ablation pulses can also include monophasic pulses.

[0029] FIG. 3 is a schematic diagram of multiple sets of pre-ablation voltage pulses, each set applied to a separate paired set of electrodes (e.g., a subset of electrodes) of an ablation device (e.g., ablation device 1310, 1310′). FIG. 3 shows four pulse sets 321, 323, 325, and 327. First pulse set 321 can include multiple biphasic pulses 312 applied to a first pair of electrodes in the electrode subset. Second pulse set 323 can include multiple biphasic pulses 314 applied to a second pair of electrodes in the electrode subset. Third pulse set 325 can include multiple biphasic pulses 316 applied to a third pair of electrodes in the electrode subset. Fourth pulse set 327 can include multiple biphasic pulses 318 applied to a fourth pair of electrodes in the electrode subset. The current delivered during each pre-ablation pulse can be measured as described in more detail herein. By repeating the pulses applied to particular pairs of electrode subsets in each pulse set, multiple measurements can be obtained for each paired electrode subset, which can be used for averaging, noise reduction, etc.

[0030] While FIG. 3 illustrates four pulse sets, it will be understood that any number of pulse sets can be utilized depending on the number of distinct pairs of electrode subsets required for measurement. For example, in some embodiments, the number of pulse sets can correspond to the number of paired electrode subsets receiving ablation energy. In some embodiments, any number of pulse sets or repetitions can be implemented as is convenient for measurement purposes. In some embodiments, the number of pulse sets can range from about 1 set to about 15 sets, with each pulse in a given set being applied to the same pair of electrode subsets. Similarly, while FIG. 3 illustrates biphasic pre-ablation pulses 312, 314, 316, and 318, the pre-ablation pulses can also include monophasic pulses. In some embodiments, the pulse width of the pre-ablation pulses can be the same as the pulse width of the pulses used for ablation energy delivery. In some embodiments, the pulse width of the pre-ablation pulses can be smaller than the pulse width of the pulses used for ablation energy delivery. In some embodiments, the pulse width of the pre-ablation pulses can be larger than the pulse width of the pulses used for ablation energy delivery. In some embodiments, the pulse width of the pre-ablation pulses shown in FIGS. 1A-3 can range from about a few nanoseconds to about a few hundred microseconds.

[0031] FIG. 4A schematically illustrates an ablation device (e.g., ablation devices 1310, 1310′) implemented as a deployable multi-spline catheter 400. The multi-spline catheter 400 can be deployed in a basket configuration, with the distal portion of the catheter 400 including multiple splines that can be deployed across various configurations. In some embodiments, each spline can have one or more electrodes configured for energy delivery, with each electrode disposed along the length of the spline. In some embodiments, the devices, systems, and methods disclosed herein can include one or more of the devices, systems, and methods described in International Application No. PCT / US2018 / 29938 (incorporated by reference above). The basket catheter 400 can include a first shaft 402 (e.g., an outer shaft) including a distal end 423. A second shaft 404 (e.g., an inner shaft) can extend through the first shaft 402, and the second shaft 404 can include a distal cap 418. The second shaft 404 can be configured to be deployed from a proximal catheter handle (not shown). In some embodiments, a guidewire lumen 421 can be configured to extend through the length of the second shaft 404 so that the catheter device 400 can be delivered over a guidewire to a desired anatomical region.

[0032] In some embodiments, each of the distal splines 406, 408, 410, 412, and 414 has one or more electrodes (not shown) disposed along its length. For example, the number of electrodes can range from 1 to 20, depending on the implementation. Each spline is attached at its distal end to a distal cap 418 and at its proximal end to the distal end 423 of the outer shaft. When the inner shaft 404 is fully extended, the splines extend approximately parallel to the inner shaft and are in an undeployed configuration with only a slight convexity in the middle. When the inner shaft 404 is retracted by manipulating the controls on the catheter handle, the ends of the splines move toward each other, causing the splines to flex or curve outward, thereby deploying the basket. In some embodiments, the distal cap at the end of the inner shaft can be retracted to a position approximately at the distal end 423 of the outer shaft, causing the basket splines to fold or curve like petals. The fully deployed basket assumes a flower shape, as described in International Application No. PCT / US2018 / 29938 (incorporated by reference above). The partially or fully deployed splines can be used to engage portions of the patient's anatomy, such as the pulmonary vein ostia of the left atrium. Upon proper engagement, pulsed field ablation can be delivered. For optimal therapy delivery, the splines in a partially deployed basket configuration, or in a fully deployed flower-shaped configuration, will be fairly uniformly distributed around the long axis of the inner shaft 404. Significant non-uniformity in the spatial distribution of the splines can potentially result in suboptimal therapy delivery or excessive current.

[0033] FIG. 4B is a schematic diagram of a front view of a deployed basket configuration of a deployable multi-spline catheter 400. The distal portion of the catheter 400 includes multiple splines that can be deployed across various configurations, with the splines being non-uniformly spaced due to anatomical constraints. FIG. 4B shows the spline basket from the distal end, where the distal cap 418 is visible along with the splines 406, 408, 410, 412, and 414. Each of the distal splines 406, 408, 410, 412, and 414 may include one or more electrodes (not shown) disposed along its length for energy delivery. For example, the number of electrodes may range from about 1 electrode to about 20 electrodes. As shown in FIG. 4B, splines 406 and 408 form a first angle 432, and splines 408 and 414 form a second angle 430. The second angle 430 is greater than the first angle 432, indicating a significantly non-uniform spline distribution. This type of non-uniform spline placement may be the result of local anatomical constraints, such as non-circular pulmonary vein anatomy 450 or a steep pulmonary vein projection angle relative to the left atrium. In this example, if ablation is attempted with a non-uniform spline distribution and the non-uniformity of the spline distribution is sufficient to cause one or more pre-ablation current analysis checks to fail, the pulsed field ablation system may output a message to the user on the user interface (e.g., display on input / output device 1327) prompting the user to reposition the device without delivering the ablation waveform. The user may then detach and redeploy the device from the target anatomy, re-engage with the target anatomy, verify the uniformity of the spline distribution in one or more fluoroscopic views, and then attempt to deliver ablation energy again. If the pre-ablation current analysis passes upon delivery of the set of pre-ablation pulses, the ablation waveform may then be delivered.

[0034] FIG. 5 is a schematic illustration of a front view (e.g., view from the distal end) of a fully deployed, flower-shaped configuration of a deployable multi-spline catheter 500 (e.g., ablation device 1310, 1310′). The distal portion of catheter 500 includes multiple splines that can be deployed in various configurations, and the splines (which may be shaped like petals) may be unevenly spaced due to anatomical constraints, such as a pulmonary vein 550 with an eccentric cross-section. In FIG. 5 , splines 503, 505, 507, 509, and 511 are deployed such that each spline assumes the shape of a petal. In some embodiments, each of distal splines 503, 505, 507, 509, and 511 may include one or more electrodes (not shown) positioned along its length for energy delivery. In some embodiments, the number of electrodes on each spline may range from about 1 electrode to about 20 electrodes. Apex lines 521, 522, 523, 524, and 525 may be drawn from distal cap 518 to the vertices of each of splines 503, 505, 507, 509, and 511 (e.g., the point on each spline farthest from distal cap 518). A first angle 515 formed by splines 503 and 505 may be measured as the angle between the respective apex lines 521 and 522. A second angle 519 formed by splines 509 and 511 may be measured as the angle between the respective apex lines 524 and 525. Second angle 519 is significantly larger than first angle 515, thereby representing the non-uniform petal distribution of pulmonary veins 550.

[0035] The non-uniform spline (e.g., petal) distribution shown in Figures 4B and 5, respectively, can result in suboptimal therapy delivery and / or excessive current. In such situations, the distribution of pre-ablation current measured using pre-ablation pulses can provide information that can prompt a decision to proceed with ablation or reposition the device before delivering the ablation, as described in more detail herein. While Figures 4A, 4B, and 5 show a basket with five splines, these embodiments are non-limiting and are provided for illustrative purposes only. It will be apparent that basket embodiments having other numbers of splines, e.g., from about 3 splines to about 16 splines, can also be advantageously implemented depending on the application. In some embodiments, one or more spline electrodes can also be used to record electrocardiogram data corresponding to the electrical activity of the heart.

[0036] FIG. 6A schematically illustrates a linear focal catheter 600 (e.g., ablation device 1310, 1310′) with multiple electrodes disposed along a distal portion extending from a sheath, all of which are exposed beyond the distal end of the sheath. For example, catheter 621 may be configured to advance through a sheath or delivery device 603, which may have a fixed or steered curvature, to navigate focal catheter 600 to a region of interest, such as a target anatomical location. Catheter 621 may include a distal portion extending beyond distal end 605 of sheath 603 and may include multiple electrodes 607, 609, 611 and a distal tip electrode 613 disposed at the distal end of catheter 621. In FIG. 6A , all of distal electrodes 607, 609, 611, 613 of catheter 621 are exposed outside sheath 603. While four distal electrodes are shown in the example illustrated in FIG. 6A , a different number of electrodes may be implemented. For example, other embodiments can have from about 2 to about 20 electrodes engaged for pulsed field ablation energy delivery.

[0037] In some pulsed field ablation applications, when using paired electrode subsets to deliver ablation energy, it may be desirable to engage at least a minimum number of electrodes for bipolar ablation energy delivery. For example, a bipolar ablation delivery scheme may be used for pulsed field ablation using a linear focal catheter. For example, the devices, systems, and methods disclosed herein may include one or more of the devices, systems, and methods described in International Application No. PCT / US2020 / 37948 (incorporated by reference above). Delivering energy to a minimum number of electrodes for pulsed field ablation energy delivery facilitates treatment delivery and avoids excessively large local current densities and associated thermal effects. For example, in some cardiac applications, at least a minimum number of electrodes may extend beyond the sheath 603 into the blood pool, and the distal catheter tip electrode 613 may be positioned at the ablation site to deliver localized ablation energy to the site for lesion generation. In some embodiments, the catheter 600 may include a position sensor (e.g., electromagnetic) configured to track the position of the catheter tip within the cardiac chamber. In some embodiments, the position of the catheter tip may be displayed on an anatomical or electroanatomical map of the heart chamber.

[0038] FIG. 6B schematically illustrates a linear focal catheter 600 with multiple electrodes positioned along its distal portion, with some but not all of the electrodes extending from a sheath 603. For example, the catheter 621 passes through a sheath or delivery device 603, which may have a fixed or steered curve, to navigate the focal catheter 600 to a region of interest, such as a target anatomical location. The portion of the catheter 621 extending beyond the distal end 605 of the sheath 603 may include three electrodes 609, 611, and a distal tip electrode 613 positioned along its length, while electrode 607 is internal to the sheath 603 and not exposed. In this example, four electrodes are engaged for optimal pulsed field ablation energy delivery. In some embodiments, the configuration shown in FIG. 6A may be suboptimal, resulting in insufficient lesion generation from pulsed field ablation energy delivery due to the electrode 607 not being exposed. In such situations, the pre-ablation current measured using the pre-ablation pulses can provide information that can prompt a decision to proceed with ablation or reposition the device before delivering ablation energy. For example, the number of exposed electrodes can be determined by measuring the current of the pre-ablation pulses, and the user can be prompted to reposition and / or redeploy the device to ensure a predetermined number of electrodes are exposed. If an insufficient number of exposed electrodes are present, the measured current of the set of pre-ablation pulses can prompt redeployment of the device. In some embodiments, the pulsed field ablation system can display a message on the user interface requesting the user to reposition the device while inhibiting delivery of the ablation waveform. The user can use visualization (e.g., under an imaging modality such as fluoroscopy) to disengage the device from the target anatomy and re-engage it to redeploy the device and ensure exposure of the ablation electrodes. The ablation waveform can be delivered based on a set of subsequent pre-ablation signal current measurements that pass predetermined checks.

[0039] 6A and 6B show a linear catheter having four electrodes, the number of electrodes shown is non-limiting and is provided for illustrative purposes only, and it will be apparent that embodiments having other numbers of electrodes, for example, from about 2 electrodes to about 20 electrodes, are possible as desired.

[0040] FIG. 7 shows a circuit diagram for generating high-voltage pulses to a set of electrodes for pulsed field ablation and associated current measurement, according to some embodiments. The circuit diagram shown in FIG. 7 can be connected to or part of a signal generator, such as signal generator 1320. In some embodiments, the devices, systems, and methods disclosed herein can include one or more of the devices, systems, and methods described in International Application No. PCT / US2018 / 19552 (incorporated by reference above). FIG. 7 shows an energy source implemented as a capacitor bank 704 configured to charge to a predetermined power supply voltage using a charging power circuit (not shown) and to store energy for release to the electrodes for pre-ablation pulse delivery and / or pulsed field ablation energy delivery. In some variations, the capacitors 704 can be charged to a voltage between about 500 V and about 10,000 V or more to generate lesions with pulsed field ablation. In some variations, the ablation waveform may be generated by a series of upper half-bridge switches 711 and 731 (e.g., transistors) and lower half-bridge switches 713 and 733 (e.g., transistors), where corresponding upper and lower transistors may be paired to form a full-bridge circuit depending on the desired electrode pairing for bipolar energy delivery. The outputs 707, 709 are connected to corresponding electrodes (not shown). Each upper transistor 711 and lower transistor 713 may have corresponding upper drive circuit 715 and lower drive circuit 717 for opening and closing the switches to provide a predetermined pulse waveform output. A processor implemented as a driving FPGA 722 (e.g., any of the processors 1324 described with reference to FIGS. 13A and 13B ) is configured to execute instructions to open and close the switches (e.g., switches 711, 713, 731, 733) at the appropriate times to output a predetermined pulse waveform to the electrodes, e.g., for delivery of a pre-ablation pulse waveform or for delivery of an ablation waveform (typically different from the pre-ablation pulse waveform).The return path to the capacitor ground or lower terminal may pass through components of the sensing circuit, including, for example, current sense resistor 720 and corresponding pulse current measurement circuit 725. Typically, capacitor bank 704 may be charged based on a voltage input provided by a user on a user interface (e.g., part of input / output device 1327) of the pulsed field ablation system for ablation energy delivery. In some embodiments, the capacitor voltage may be greater than the ablation voltage input provided by the user on the user interface, e.g., to account for resistive losses. In some embodiments, the voltage amplitude used for ablation energy delivery may be the voltage amplitude used for the pre-ablation pulse.

[0041] In some embodiments, the voltage amplitude of the pre-ablation pulse may be less than the voltage amplitude of the ablation pulse. FIG. 8 shows a schematic circuit diagram for generating a pre-ablation pulse, according to some embodiments. The circuit may include an energy source implemented as a capacitor 807, such as a capacitor bank (e.g., capacitor bank (704)), connected to a network of switch 808 and resistor 810. Switch 808 may be switched between an open state and a closed state. Switch 808 is open when a low-voltage pre-ablation voltage pulse is to be output. For example, resistor 810 is connected to capacitor 807 to create a voltage drop such that power supply voltage 812 (e.g., the voltage supplied to pulse switches 711 and 713) is less than the capacitor voltage of capacitor 807. When an ablation pulse is to be output (e.g., when a check of the measured pre-ablation pulse current passes a predetermined criterion), switch 808 may be closed so that the current path is directly through the switch and not through resistor 810, such that power supply voltage 812 is the same as the capacitor voltage of capacitor 807. In some embodiments, switch 808 may be one or more of a solid-state switch (e.g., IGBT, MOSFET) or a relay. In some embodiments, resistor 810 may have a resistance that can be varied, for example, a resistance that can be set based on input provided by a user.

[0042] FIG. 9 shows another schematic circuit diagram for generating a pre-ablation pulse using a second capacitor charged to a lower voltage than the first capacitor, according to some embodiments. The circuit may include a first energy source implemented as a first capacitor 901, such as a capacitor bank (e.g., capacitor bank (704)), connected to a second capacitor 903 and a second energy source implemented as a switch network 905. The second capacitor 903 can be charged to a lower voltage than the voltage of the first capacitor 901 and can be used for a lower-voltage pre-ablation pulse. The switch 905 can be configured to switch between a first position and a second position. In some embodiments, the switch 905 can be set to a closed position 911 (e.g., the first position) to close a circuit including the second capacitor 903 when a pre-ablation pulse is desired. The lower voltage of the second capacitor 903 corresponds to a power supply voltage 917 (e.g., supplied to pulse switches 711, 713) to deliver a pre-ablation signal or pulse. When an ablation pulse is to be output (e.g., when a check of the measured pre-ablation pulse current passes a predetermined criterion), switch 905 may be set to an open position 909 (e.g., a second position), thereby closing a circuit including first capacitor 901 such that the voltage across first capacitor 901 corresponds to power supply voltage 917 (e.g., supplied to pulse switches 711, 713) to deliver the ablation pulse. In some embodiments, switch 905 may be one or more of a solid-state switch (e.g., IGBT, MOSFET) and a relay.

[0043] 10 shows another schematic circuit diagram for generating a pre-ablation pulse using fast switching and a second capacitor, according to some embodiments. The circuit may include an energy source implemented as a first capacitor 1002, such as a capacitor bank (e.g., capacitor bank 704), connected to a resistor-capacitor network, such as a switch 1004 having a resistor 1006 and a second capacitor 1008. The switch 1004 may include a solid-state device, such as a MOSFET device, that can rapidly switch between an open configuration and a closed configuration when the pre-ablation pulse is output. The resistor 1006 may have a resistance on the order of about 10 ohms or less to limit the voltage drop across the resistor 1006. Furthermore, the values ​​of the resistor 1006 and the second capacitor 1008 may be selected so that the time constant (RC) is shorter than the pulse width used for either the pre-ablation pulse or the ablation pulse.

[0044] For example, when a pre-ablation pulse is output, the switch 1004 may rapidly switch between on and off states (e.g., switch between closed and open states) at a frequency f such that:

[0045]

number

[0046] where R is the resistance of resistor 1006 and C is the capacitance of capacitor 1008. The RC circuit can then act like a voltage divider, with the net voltage across second capacitor 1008 being less than the voltage across first capacitor 1002. In some embodiments, the voltage across second capacitor 1008 corresponds to the pre-ablation pulse power supply voltage 1012 (e.g., supplied to pulse switches 711, 713). When an ablation pulse is output (e.g., when a check of the measured pre-ablation pulse current passes a predetermined criterion), switch 1004 remains closed, and the voltage across first capacitor 1002 can roughly correspond to the power supply voltage provided to pulse switches 711, 713 for delivery of the ablation pulse (given the constraints that resistance R is small and the time constant RC is much shorter than the pulse width used for the ablation pulse).

[0047] 11 provides a block diagram for measuring a current corresponding to a voltage pulse (e.g., delivery of a pre-ablation signal), according to some embodiments. The current flowing through a current sensing resistor (e.g., current sensing resistor 720) can be sensed (e.g., in the form of a voltage drop) by measurement circuitry at 1100. The signal can be filtered and amplified at 1104, for example, by appropriate filters, amplifiers, or other electronic components. At 1106, an analog optocoupler isolates high-voltage noise in the signal from low-voltage circuitry. At 1108, a high-speed analog-to-digital converter (ADC) digitizes the signal to generate a digital output.

[0048] The digitized values ​​or digital output may be received 1110 by a microcontroller (e.g., a processor such as processor 1324 described with reference to FIGS. 13A and 13B ) and buffered for analysis. One or more samples of the measured current (in the form of digitized values ​​or digital output) may be analyzed by the microcontroller to condition the current measurements. For example, if multiple pre-ablation pulses are delivered to a given electrode subset pair, the corresponding multiple current measurements may be filtered or conditioned according to several methods known in the art, such as averaging, discarding outliers and then averaging, weighted averaging, etc. The measured currents from pre-ablation pulses delivered to several electrode subset pairs may be analyzed by the microcontroller to determine whether such currents meet one or more predetermined criteria. For example, the measured currents may be analyzed to determine whether they fall within predetermined minimum and maximum values. In some embodiments, the criteria may include determining that no measured currents exceed a predetermined threshold (e.g., a maximum value) or that no measured currents are less than a predetermined threshold (e.g., a minimum value). In some embodiments, the criteria may include calculating a metric such as the average value of the measured currents. In some embodiments, the metric may include one or more of calculating the variance of the measured currents, calculating the ratio of the maximum measured current to the minimum measured current, or roughly calculating the output of a non-linear function of the measured currents. In some embodiments, the criteria may include any combination of the calculations described herein and further determine whether the calculated quantity falls within a predetermined range. For example, the predetermined criteria may include determining whether the variance of the measured currents falls within a predetermined range. As another example, the predetermined criteria may include determining whether the ratio of the maximum current to the minimum current is below a threshold. In some embodiments, the predetermined range or threshold may be user adjustable.

[0049] In some embodiments, the microcontroller is coupled at 1112 to a driving FPGA (e.g., FPGA 722) that drives the generation of pulses and waveforms. If any of the predetermined criteria for the measured pre-ablation current are not met, the microcontroller may send a signal to the FPGA to inhibit delivery of ablation energy and / or to alert the user (e.g., by generating an alert). For example, the microcontroller may output a message or alert on a graphical user interface (e.g., part of input / output device 1327) requesting the user to reposition or redeploy the device before ablation energy delivery. If the predetermined criteria for the pre-ablation pulse are met, the FPGA may be instructed to deliver ablation energy. Upon completion of ablation energy delivery, the FPGA may send a message to the microcontroller indicating successful completion of ablation energy delivery. In this manner, pre-ablation pulse delivery and subsequent ablation delivery can occur seamlessly. By appropriately selecting the measured current criteria and corresponding thresholds, ablation energy can be delivered seamlessly when device deployment is appropriate.

[0050] FIG. 12 shows a block diagram of a current measurement device configured for ultrafast measurement of current associated with a voltage pulse, according to some embodiments. Such measurement may be useful, for example, when the pre-ablation pulse is a very short pulse (less than a few microseconds) and an analog-to-digital converter is not available with a sufficient readout speed or when a sufficient number of channels is not available. Certain components described with respect to FIG. 12 may be structurally and / or functionally similar to those described with respect to FIG. 11. Therefore, some description with respect to FIG. 12 may be omitted in light of such description provided with respect to FIG. 11. In FIG. 12, the pre-ablation pulse current passing through a current sensing resistor (e.g., current sensing resistor 720) is sensed (in the form of a voltage drop) by measurement circuitry at 1204. The signal is filtered and amplified at 1206, e.g., via appropriate filters, amplifiers, and / or other electronic circuitry. At 1208, the signal is received by a comparator (e.g., a differential amplifier), where the analog signal is checked to ensure, for example, that the current measurement meets predetermined criteria, such as within a predetermined range or window, or above or below a predetermined threshold. At 1210, the result of this comparison is passed through a digital optocoupler configured to isolate low-voltage circuitry from high-voltage noise. The signal is then received at 1212 by a driving FPGA (e.g., driving FPGA 722 of FIG. 7). If the current meets the predetermined criteria, for example, if it is within a predetermined range or above or below a predetermined threshold, the FPGA may notify a microcontroller (e.g., a processor such as processor 1324 as described with reference to FIGS. 13A and 13B) at 1208, which may proceed to deliver an ablation waveform at 1214. If the current is not within a predetermined range or fails the predetermined threshold check at 1208, the FPGA may notify the microcontroller and inhibit delivery of the ablation energy.For example, the microcontroller may output a message or warning on a graphical user interface (e.g., part of the input / output device 1327) requesting the user to reposition or redeploy the device before delivering ablation energy.

[0051] In some embodiments, the predetermined range (or window) of current values ​​may be user adjustable. In response to a user ablation request, the microcontroller may send an input range of current values ​​or current thresholds to the driving FPGA, which may then send them to a digital-to-analog converter (DAC) for conversion to an analog signal at 1216. The analog range of current values ​​or current thresholds may be passed through an analog optocoupler at 1218 and then through a comparator to ensure isolation of low-voltage circuits (such as the digital-to-analog converter) from any high-voltage noise. The analog signal may be used to set the window range or threshold in the comparator at 1208. In embodiments where the predetermined range or window of current values ​​or thresholds are not user adjustable, predetermined or default values ​​may be stored in the microcontroller, and the window range in the window comparator may be set in the same manner as described herein.

[0052] The apparatus and methods disclosed herein can verify device deployment or placement prior to delivery of ablation energy. While specific device embodiments are described herein for illustrative purposes, it will be apparent that other device embodiments can be implemented as convenient, without limitation, as determined by one of ordinary skill in the art.

[0053] 14 is an exemplary method 1400 of tissue ablation. In some embodiments, the current of the pre-ablation signals described herein can be measured and used to determine whether the device delivers ablation energy or is repositioned prior to ablation delivery. Method 1400 includes, at 1402, positioning a device (e.g., device 400, 500, 600, 1310, 1310′) in a target anatomical structure (e.g., in an endocardial cavity, such as the left or right atrium or left or right ventricle) for ablation energy delivery. At 1404, a pre-ablation signal can be generated and applied to the device to confirm proper device placement / deployment. For example, a set of pre-ablation signals can be generated by a signal generator (e.g., signal generator 1320). Each pre-ablation signal can be delivered to a subset of electrode channels or a subset of electrodes, e.g., according to a predetermined order. At 1406, a pre-ablation current (e.g., a current passing through a sensing resistor or measurement circuitry described herein) may be measured for each pre-ablation signal delivered to a subset of electrode channels or a subset of electrodes. At 1408, a determination may be made whether the device placement / deployment passes a predetermined set of checks or criteria based on the measured pre-ablation currents. For example, as described herein, the measured pre-ablation currents may be analyzed to check that each falls within predetermined minimum and maximum values. In some embodiments, the check may include determining that no pre-ablation current exceeds a predetermined maximum value. In some embodiments, the check may include determining that no pre-ablation current falls below a predetermined minimum value. In some embodiments, the check may include calculating a metric such as the mean value of the pre-ablation current. In some embodiments, the check may include calculating a metric such as the variance of the pre-ablation current, the ratio of the maximum pre-ablation current to the minimum pre-ablation current, or some other generally non-linear function of the pre-ablation current.In some embodiments, the check can include any combination of these calculations (e.g., calculating one or more metrics based on one or more of these calculations), and then determining whether the calculated metrics are within a predetermined range or whether they are below or above an appropriate predetermined threshold. For example, in one embodiment, the check can be to determine whether the variance of the measured current is within a particular range. As another example, in one embodiment, the check can be to determine whether the ratio of the maximum current to the minimum current is below a threshold. In some embodiments, this threshold can be greater than about 1 and less than about 5, greater than about 1 and less than about 10, greater than about 1 and less than about 20, including all subvalues ​​and ranges therebetween. If the measured current does not meet one or more predetermined criteria, the user can be prompted (e.g., warned) to reposition the device at 1402. If the device is properly positioned, ablation energy can be delivered to the device at 1410, for example, in the form of an ablation pulse waveform. The device can be moved to the next target anatomical location, and the procedure continues in this manner until the ablation treatment is completed at 1412.

[0054] Ablation pulse waveforms can include multiple levels of hierarchy to optimize delivery of pulsed field ablation energy, as described, for example, in International Patent Application No. PCT / US2019 / 031135, filed May 7, 2019, entitled "SYSTEMS, APPARATUSES AND METHODS FOR DELIVERY OF ABLATIVE ENERGY TO TISSUE," the contents of which are incorporated herein by reference in their entirety. In some embodiments, tissue ablation performed in this manner can be delivered synchronously with paced heartbeats or natural cardiac ECG activity in the absence of ectopic cardiac activity to reduce the risk of atrial fibrillation and / or ventricular fibrillation and damage to healthy tissue. It will be understood that any of the ablation devices described herein (e.g., devices 400, 500, 600, 1310, 1310′), or various other ablation devices, can be used to ablate tissue, as appropriate, using the methods described herein, along with at least one electrode for delivering pulsed field ablation energy.

[0055] In some embodiments, the ablation devices described herein (e.g., devices 400, 500, 600, 1310, 1310') can be used for epicardial and / or endocardial ablation. Examples of suitable ablation catheters are described in International Application No. PCT / US2019 / 014226 (incorporated by reference above).

[0056] As used herein, the term "electroporation" refers to the application of an electric field to a cell membrane to change the permeability of the cell membrane to the extracellular environment. As used herein, the term "reversible electroporation" refers to the application of an electric field to a cell membrane to temporarily change the permeability of the cell membrane to the extracellular environment. For example, the cell membrane of a cell undergoing reversible electroporation exhibits the temporary and / or intermittent formation of one or more pores that close when the electric field is removed. As used herein, the term "irreversible electroporation" refers to the application of an electric field to a cell membrane to permanently change the permeability of the cell membrane to the extracellular environment. For example, the cell membrane of a cell undergoing irreversible electroporation exhibits the formation of one or more pores that persist even when the electric field is removed.

[0057] The pulse waveforms for electroporation energy delivery disclosed herein can improve the safety, efficiency, and effectiveness of energy delivery to tissue by lowering the electric field threshold associated with irreversible electroporation, thus producing more effective ablative lesions with reduced total delivered energy. In some embodiments, the voltage pulse waveforms disclosed herein can be hierarchical and nested. For example, a pulse waveform can include hierarchical groups of pulses with related time scales. In some embodiments, the methods, systems, and devices disclosed herein can include one or more of the methods, systems, and devices described in International Application No. PCT / US2019 / 014226 (incorporated by reference above).

[0058] While the examples herein identify separate monophasic and biphasic waveforms, it is understood that combined waveforms can also be generated, where some portions of the waveform hierarchy are monophasic and other portions are biphasic. Hierarchical voltage pulse waveforms can be applied (optionally with time delays) across different anode-cathode subsets. It is understood that the steps described in a particular figure can be combined or modified as needed.

[0059] It should be understood that the examples and illustrations in this disclosure are for illustrative purposes, and that deviations and variations, such as the number of splines, the number of electrodes, etc., can be constructed and deployed in accordance with the teachings herein without departing from the scope of the present invention. While certain parameters, such as sampling frequency, time intervals, etc., are provided in the description herein for illustrative purposes only, those skilled in the art will understand that, based on the teachings presented in this disclosure, other values ​​for the various parameters can be used as convenient for the application.

[0060] As used herein, the terms "about" and / or "approximately," when used in conjunction with numerical values ​​and / or ranges, generally refer to numerical values ​​and / or ranges that are close to the stated numerical value and / or range. In some cases, the terms "about" and "approximately" can mean within ±10% of the stated value. For example, in some cases, "about 100 units" can mean within ±10% of 100 (e.g., 90 to 110). The terms "about" and "approximately" are sometimes used interchangeably.

[0061] Some embodiments described herein relate to computer storage products with a non-transitory computer-readable medium (which may also be referred to as a non-transitory processor-readable medium) having instructions or computer code for performing various computer-implemented operations. The computer-readable medium (or processor-readable medium) is non-transitory in the sense that it does not itself comprise a transitory propagating signal (e.g., a propagating electromagnetic wave carrying information over a transmission medium such as space or a cable). The medium and computer code (which may also be referred to as code or an algorithm) may be designed and constructed for a specific purpose. Examples of non-transitory computer-readable media include, but are not limited to, magnetic recording media such as hard disks, floppy disks, and magnetic tapes; optical recording media such as compact disks / digital video disks (CDs / DVDs), compact disk read-only memories (CD-ROMs), and holographic devices; magneto-optical recording media such as optical disks; carrier wave signal processing modules; and hardware devices specially configured to store and execute program code, such as application-specific integrated circuits (ASICs), programmable logic devices (PLDs), read-only memories (ROMs), and random access memory (RAM) devices. Other embodiments described herein relate to computer program products that may include, for example, instructions and / or computer code disclosed herein.

[0062] The systems, devices, and / or methods described herein may be implemented by software (executed on hardware), hardware, or a combination thereof. Hardware modules may include, for example, general-purpose processors (or microprocessors or microcontrollers), field-programmable gate arrays (FPGAs), and / or application-specific integrated circuits (ASICs). Software modules (executed on hardware) may be expressed in various software languages ​​(e.g., computer code), including C, C++, Java, Ruby, Visual Basic, and / or other object-oriented, procedural, or other programming languages ​​and development tools. Examples of computer code include, but are not limited to, microcode or microinstructions, machine instructions such as those produced by a compiler, code used to create web services, and files containing high-level instructions executed by a computer using an interpreter. Additional examples of computer code include, but are not limited to, control signals, encryption code, and compression code.

[0063] The specific examples and descriptions herein are exemplary in nature and embodiments may be developed by those skilled in the art based on the teachings herein without departing from the scope of the invention.

Claims

1. a current sensing resistor connected to a set of electrodes of an ablation device positionable within the patient's anatomy; a current measurement circuit configured to measure a current through the current sensing resistor generated in response to a pre-ablation pulse applied to a first subset of electrodes of the set of electrodes; a comparator configured to determine whether the current meets a predetermined criterion and configured to generate a digital output indicative of whether the current meets the predetermined criterion; 1. A processor, comprising: receiving the digital output indicating that the current meets the predetermined criterion, delivering a pulse waveform to a second subset of electrodes of the set of electrodes, such that the second subset of electrodes generates a pulsed electric field for ablation; the processor configured to inhibit delivery of a pulse waveform to the second subset of electrodes in response to the digital output indicating that the current does not meet the predetermined criterion; An apparatus comprising:

2. 10. The apparatus of claim 1, wherein the processor includes a field programmable gate array (FPGA) configured to execute instructions to open and close a set of switches to effect delivery of the pulse waveform to the second subset of electrodes.

3. 10. The apparatus of claim 1, wherein the processor is further configured to receive the digital output indicating that the current does not meet the predetermined criteria and generate a warning instructing a user to reposition the ablation device.

4. 10. The apparatus of claim 1, further comprising a digital optocoupler coupled to the comparator, the digital optocoupler configured to isolate high voltage noise from the digital output.

5. 10. The apparatus of claim 1, wherein the comparator is configured to determine whether the current meets the predetermined criteria by at least one of determining whether the current is greater than a predetermined threshold, determining whether the current is less than a predetermined threshold, or determining whether the current is within a predetermined range of values.

6. The apparatus of claim 1 , wherein the processor is configured to set the predetermined criteria based on input received from a user.

7. The input includes a threshold or range of values, and the processor: passing the threshold or range of values ​​to a digital-to-analog converter (DAC), the DAC generating an analog signal representing the threshold or range of values; the predetermined reference is set by a comparator based on the analog signal; The apparatus of claim 6 , configured to set the predetermined criterion by:

8. 8. The apparatus of claim 7, further comprising an analog optocoupler configured to isolate high voltage noise from the analog signal before the analog signal is passed to the comparator.

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