Pulse-field ablation index (PI) metrics for lesion assessment

Abstract

This invention provides a method for assessing lesion formation associated with pulsed-field ablation (PFA) therapy performed at a location selected by a PFA catheter. [Solution] The method includes measuring pretreatment impedance using one or more electrodes placed on a PFA catheter and performing a first PFA application. Intratreatment / posttreatment impedance is measured using one or more electrodes placed on a PFA catheter, and a PFA index (PI) metric is calculated based on a model combining the measured pretreatment impedance, the measured intratreatment / posttreatment impedance, and the attributes of the performed first PFA application, the PI metric representing the likelihood that the lesion has reached a selected size.

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims the benefit and priority of U.S. Provisional Application No. 63 / 727,047, filed on December 2, 2024, entitled "PULSED FIELD ABLATION INDEX (PI) METRIC FOR LESION ASSESSMENT", the content of which is incorporated herein by reference.

[0002] The subject matter disclosed herein relates to electrophysiological procedures, and more particularly to the assessment of lesion formation associated with pulsed field ablation (PFA) therapy.

Background Art

[0003] Ablation therapy can be used to treat various conditions that afflict the anatomical structures of the human body. One such condition in which ablation therapy can be used is the treatment of cardiac arrhythmias. When tissue is ablated or at least exposed to ablation energy generated by an ablation generator and delivered by an ablation catheter, lesions or wounds are formed in the tissue. To improve conditions such as atrial arrhythmias (including, but not limited to, ectopic atrial tachycardia, atrial fibrillation, atrial flutter, etc.), tissue necrosis occurs in the cardiac tissue using electrodes attached to or inserted within an ablation catheter. Arrhythmias can cause various dangerous conditions such as the loss of synchronized atrioventricular contractions and blood flow stagnation. The main cause of atrial arrhythmias is thought to be abnormal electrical signals in the left or right atrium of the heart. The ablation catheter delivers ablation energy (such as high - frequency energy, cryo - ablation, lasers, chemicals, high - density focused ultrasound, etc.) to the cardiac tissue to form lesions in the cardiac tissue. These lesions disrupt unwanted electrical pathways, thereby limiting or preventing abnormal electrical signals that can lead to arrhythmias.

[0004] Electroporation is a non-thermal ablation technique that involves applying a strong electric field to induce pore formation in the cell membrane. The electric field can be induced by applying pulses with relatively short durations, for example, from nanoseconds to milliseconds. Such pulses may be repeated to form a pulse train (or "burst"). When such an electric field is applied to tissue in vivo, cells within the tissue receive a transmembrane potential, causing pores in the cell wall to open. Electroporation may be reversible (i.e., the temporarily opened pores close again) or irreversible (i.e., the pores remain open, leading to cell destruction). In certain therapeutic applications, cell destruction can be induced by a well-configured pulse train alone, for example, by inducing irreversible electroporation (IRE). In cardiac ablation to create transwall lesions, this is known as pulsed-field ablation (PFA).

[0005] To perform PFA treatment, the physician places the catheter (specifically, the electrode selected to deliver the PFA waveform) adjacent to the tissue to be treated and begins delivering the PFA waveform. It would be beneficial to provide the physician with a metric that explains the likelihood of a lesion of the desired size forming at a particular location. [Overview of the project]

[0006] In some embodiments, the techniques described herein relate to a computer-implemented method for assessing lesion formation associated with pulsed-field ablation (PFA) therapy performed at a location selected by a PFA catheter, the method comprising: measuring pre-treatment impedance using one or more electrodes placed on the PFA catheter; measuring intra-treatment / post-treatment impedance using one or more electrodes placed on the PFA catheter; and calculating a PFA index (PI) metric based on a model combining the measured pre-treatment impedance, the measured intra-treatment / post-treatment impedance, and the attributes of the PFA therapy performed, wherein the PI metric represents the likelihood that the lesion has reached a selected size.

[0007] In some embodiments, the techniques described herein relate to methods in which the measured pre-treatment impedance and measured intra-treatment / post-treatment impedance represent the tissue impedance associated with the tissue receiving the PFA therapy performed.

[0008] In some embodiments, the techniques described herein relate to methods, and the models utilize changes in tissue impedance calculated based on measured minimum and maximum tissue impedances.

[0009] In some embodiments, the techniques described herein relate to methods, further comprising measuring one or more other inputs related to the PFA therapy performed, and the model further combines one or more other inputs in generating a PI metric.

[0010] In some embodiments, the techniques described herein relate to methods, one or more inputs including a measured contact force between the catheter and adjacent tissue.

[0011] In some embodiments, the techniques described herein relate to methods in which the contact force is measured as the percentage of time during which the measured contact force is greater than or equal to a threshold.

[0012] In some embodiments, the techniques described herein relate to a method in which the PI metric calculated by the model is filtered to allow only increases in the value of the PI metric.

[0013] In some embodiments, the techniques described herein relate to methods wherein the PFA therapy performed comprises a first PFA application comprising a first plurality of PFA bursts, where pre-treatment and intra-treatment impedances are measured during the pre-burst interval preceding each of the first plurality of PFA bursts, and post-burst impedances are measured after the final PFA burst performed as part of the first PFA application.

[0014] In some embodiments, the techniques described herein relate to methods, and the attributes of the first PFA application implemented by the model include the number of PFA bursts implemented.

[0015] In some embodiments, the techniques described herein relate to methods, further comprising measuring one or more additional inputs during a pre-burst interval preceding each of a first plurality of PFA bursts, wherein the one or more additional inputs include contact force.

[0016] In some embodiments, the techniques described herein relate to methods, further comprising performing a second PFA application at a selected location when the PI metric is below a threshold, wherein the second PFA application includes a second plurality of PFA bursts.

[0017] In some embodiments, the techniques described herein relate to methods, further comprising measuring a first contact force associated with the catheter during the performance of a first PFA application, measuring a second contact force associated with the catheter during the performance of a second PFA application, and calculating the PI metric after the performance of the second PFA application, utilizing the cumulative contact force based on the first and second contact forces.

[0018] In some embodiments, the techniques described herein relate to a system for assessing lesion formation associated with pulsed-field ablation (PFA) therapy performed at a location selected by a PFA catheter, the system comprising a lesion assessment module operating on a computer system, the lesion assessment module being configured to receive pre-treatment impedance measured using one or more electrodes placed on the PFA catheter, receive intra-treatment / post-treatment impedance measured using one or more electrodes placed on the PFA catheter, and calculate a PFA index (PI) metric based on a model combining the measured pre-treatment impedance, measured intra-treatment / post-treatment impedance, and attributes of the PFA therapy performed, the PI metric representing the likelihood that the lesion has reached a predetermined size.

[0019] In some embodiments, the techniques described herein relate to a system in which the measured pre-treatment impedance and measured intra-treatment / post-treatment impedance represent the tissue impedance associated with the tissue receiving the PFA therapy performed.

[0020] In some embodiments, the techniques described herein relate to a system in which the model utilizes changes in tissue impedance calculated based on the measured minimum tissue impedance and the measured maximum tissue impedance.

[0021] In some embodiments, the technology described herein relates to a system in which the lesion assessment module is further configured to receive one or more other inputs measured with respect to the PFA therapy performed, and the model further combines one or more other inputs when generating a PI metric.

[0022] In some embodiments, the techniques described herein relate to a system in which one or more inputs measured include the contact force measured between the PFA catheter and the adjacent tissue.

[0023] In some embodiments, the technology described herein relates to a system, and the contact force is measured as a percentage of time that the measured contact force is above a threshold.

[0024] In some embodiments, the technology described herein relates to a system, and the PI metric calculated by a model is filtered to allow only an increase in the value of the PI metric.

[0025] In some embodiments, the technology described herein relates to a system, and the performed PFA therapy includes a first PFA application that includes a first plurality of PFA bursts, and the pre-treatment impedance and the during-treatment impedance are measured during a pre-burst interval preceding each of the first plurality of PFA bursts, and the post-burst impedance is measured after a final PFA burst performed as part of the first PFA application.

[0026] In some embodiments, the technology described herein relates to a system, and the attributes of the performed first PFA application utilized by a model include the number of PFA bursts performed.

[0027] In some embodiments, the technology described herein relates to a system, and the lesion assessment module is further configured to receive one or more additional inputs measured during a pre-burst interval preceding each of the first plurality of PFA bursts, and the one or more additional inputs include a contact force.

[0028] In some embodiments, the technology described herein relates to a method, and the lesion assessment module further receives a first contact force associated with a catheter during the performance of a first PFA application performed, receives a second contact force associated with the catheter during the performance of a second PFA application, and calculating a PI metric after the performance of the second PFA application utilizes a cumulative contact force based on the first contact force and the second contact force.

[0029] In some embodiments, the technology described herein relates to a computer-implemented method for assessing lesion formation associated with pulsed field ablation (PFA) therapy performed at a selected location by electrodes disposed on a catheter, the method comprising measuring tissue impedance both before and after implementation of a first PFA application to determine a change in tissue impedance, measuring a contact force between the catheter and adjacent tissue prior to implementation of the first PFA application, and calculating a PFA index (PI) metric based on a model that combines the change in tissue impedance, the contact force, and one or more attributes of the first PFA application, the PI metric representing the likelihood that a lesion has reached a selected size (i.e., a selected depth, a selected width, or a combination of the selected depth and the selected width).

[0030] In some embodiments, the technology described herein further relates to a computer-implemented method that includes performing a first PFA application at a selected location.

[0031] In some embodiments, the technology described herein relates to a computer-implemented method, wherein the attributes of the first PFA application utilized by the model include the number of PFA bursts performed, and the system is configured to perform a second PFA application at the selected location if the PI metric is below a threshold, the second PFA application including a second plurality of PFA bursts.

[0032] In some embodiments, the technology described herein relates to a method, wherein the model is a probabilistic model that maps the measured change in tissue impedance, the measured contact force, and one or more attributes of the first PFA application to the probability that a lesion has reached a selected size.

[0033] In some embodiments, the technology described herein further relates to a method that includes receiving user input regarding a selected size of a lesion and modifying the model to generate a PI metric representing the likelihood that the lesion has reached the selected size.

[0034] In some embodiments, the techniques described herein relate to a method in which the first PFA application includes one of a plurality of bursts.

[0035] In some aspects, the techniques described herein relate to a method in which tissue impedance is measured before each burst and after the final burst of the first PFA application, and contact force is measured before each burst.

[0036] In some embodiments, the techniques described herein relate to methods in which the change in tissue impedance is calculated by identifying the measured minimum and maximum tissue impedances and subtracting the minimum tissue impedance from the maximum tissue impedance.

[0037] In some embodiments, the techniques described herein relate to a method by which the contact force is calculated as the percentage of time for all measurements that the contact force exceeds a threshold.

[0038] In some embodiments, the techniques described herein relate to a method by which a second PFA application is performed when the PI metric is below a threshold.

[0039] In some embodiments, the techniques described herein relate to a method for assessing lesion formation associated with pulsed-field ablation (PFA) therapy performed at a location selected by a PFA catheter, the method comprising: measuring pre-treatment impedance using one or more electrodes placed on the catheter; performing a first PFA application; measuring intra-treatment / post-treatment impedance using one or more electrodes placed on the catheter; and calculating a PFA index (PI) metric based on a model combining the measured pre-treatment impedance, the measured intra-treatment / post-treatment impedance, and the attributes of the first PFA application performed, the PI metric representing the likelihood that the lesion has reached a selected size.

[0040] In some embodiments, the techniques described herein relate to a system for assessing lesion formation associated with pulsed-field ablation (PFA) therapy performed at a location selected by electrodes placed on a catheter, the system comprising a lesion assessment module operating on a computer system, the lesion assessment module configured to measure tissue impedance both before and after a first PFA application to determine a change in tissue impedance, measure the contact force between the catheter and adjacent tissue before the first PFA application, and calculate a PFA index (PI) metric based on a model combining the change in tissue impedance, the contact force, and one or more attributes of the first PFA application, the PI metric representing the likelihood that the lesion has reached a selected size.

[0041] In some embodiments, the techniques described herein relate to a method for assessing lesion formation associated with pulsed-field ablation (PFA) therapy performed at a location selected by electrodes placed on a catheter, the method comprising: delivering a first PFA application to the selected location, the first PFA application being defined by one or more attributes; measuring tissue impedance both before and after the first PFA application to determine a change in tissue impedance; measuring the contact force between the catheter and adjacent tissue before the first PFA application; and calculating a PFA index (PI) metric based on a model combining the change in tissue impedance, the contact force, and one or more attributes of the first PFA application, the PI metric representing the likelihood that the lesion has reached a selected size. [Brief explanation of the drawing]

[0042] [Figure 1A] Schematic and block diagrams of a system for performing pulsed-field ablation (PFA) therapy.

[0043] [Figure 1B]Schematic diagram of the ablation catheter used in relation to the system for performing PFA therapy shown in Figure 1A.

[0044] [Figure 2] A lateral view of lesion formation.

[0045] [Figure 3] A block diagram showing the inputs provided to the PFA metric (PI) model for calculating the PI metric.

[0046] [Figure 4] A graph showing the bounding of the PI metric.

[0047] [Figure 5] A flowchart showing the calculation of the PI metric based on the received impedance measurement.

[0048] [Figure 6] A flowchart illustrating the calculation of the PI metric based on impedance measurements, contact force measurements, and attributes of the PFA therapy performed.

[0049] [Figure 7] A schematic diagram showing the execution of multiple PFA bursts, the measurement window preceding each burst, and the measurement window following the last burst.

[0050] [Figure 8] This is a schematic diagram illustrating the implementation of the first and second applications of PFA therapy, with each application consisting of multiple bursts.

[0051] [Figure 9] A flowchart showing the aggregation of inputs measured across two or more PFA applications based on timing / position thresholds.

[0052] [Figure 10]A schematic diagram showing the timing thresholds between the first and second applications of PFA therapy. [Modes for carrying out the invention]

[0053] Figure 1A is a schematic block diagram of a system 10 for performing pulsed-field ablation (PFA) therapy. Generally, the system 10 includes an ablation catheter 12, such as a TactiFlex® ablation catheter or SensorEnabled® (Abbott Laboratories, Abbott Park, Illinois), which has a proximal end and a distal end that is navigated to a location within the patient 15. The distal end includes, among other things, one or more electrodes configured to perform pulsed-field ablation therapy (PFA) and one or more sensors. Furthermore, the system 10 includes a number of electronic devices 14, including an ablation generator 16, a computer system 18 including a processor (CPU) 20 and memory / storage unit 22, an input / output system 24, and a display 34. The ablation generator 16 is configured to receive commands from the computer system 18 and perform PFA application via the catheter 12 to one or more electrodes located at the distal end of the catheter 12. PFA application can involve the generation of various types of PFA waveforms (e.g., multiple bursts, single pulses, etc.), which are well understood and will not be discussed in detail here. The computer system 18 may provide instructions to the ablation generator 16 regarding the type of PFA waveform to be generated, and the ablation generator 16 may provide feedback to the computer system 18 regarding the PFA waveform that has been delivered. Applying PFA to one or more electrodes located at the distal end of the catheter 12 will cause lesions in the tissue adjacent to the electrodes.

[0054] As shown in Figure 1A, the computer system 18 may comprise, for example, a conventional general-purpose computer, a special-purpose computer, a distributed computer, or any other type of computer. The computer system 18 may include one or more processors 20, such as a single central processing unit ("CPU") or multiple processing units commonly referred to as a parallel processing environment, which may execute instructions to implement the various embodiments described herein. One or more processors 20 are configured to execute instructions stored in a storage medium 22 to implement the functionality described with respect to various elements, including a lesion assessment module 36 and a localization and navigation system 28. In addition, the computer system 18 receives inputs from various sources, such as an ECG monitor 26, an ablation generator 16, an input / output system 24, a display 34, a sensor input 32, etc.

[0055] As will be described in more detail below, the computer system 18 implements a lesion assessment module 36 that assesses lesions formed in tissue by a performed PFA application. In one example, the lesion assessment module 36 generates a PFA index (PI) metric representing the probability that a performed PFA application resulted in a lesion of a desired size, including (i) a desired depth, (ii) a desired width, or (iii) a combination of both depth and width. The PI metric may also be used as a feedback signal to determine whether a particular PFA application formed the desired lesion or whether an additional PFA application should be performed. The PI metric may also be displayed to the physician / user via a graphical user interface (GUI) via a display 34 that illustrates the location of the lesion and the PI metric associated with a given lesion. For example, the GUI may use color coding to explain to the physician whether a given lesion is likely to meet the lesion size requirements of a given application.

[0056] As will be described in more detail below, the lesion assessment module 36 generates a PI metric using a model that combines multiple inputs. In one example, the model is a multivariate probabilistic model that predicts lesion formation based on multiple inputs. At least some of the inputs are measured by one or more sensors placed on the catheter, as shown in the sensor input 32 in Figure 1A. Exemplary inputs include impedance measurements, impedance change measurements, tissue impedance measurements, tissue impedance change measurements, current measurements, contact force measurements, contact force stability measurements, irrigation flow rate, execution pathway (bipolar vs. monopolar), and temperature measurements. For example, the catheter 12 may typically include one or more electrodes placed at the distal end of the catheter 12 to perform impedance measurements by supplying an AC signal to one or more electrodes and measuring the voltage at one or more electrodes. The voltage may be measured between two or more electrodes placed on the catheter, or to another electrode placed on another catheter (i.e., a reference catheter), or to a reference electrode attached to the patient's skin. Furthermore, the model may utilize additional inputs related to the PFA application performed at a given location, including, for example, the deceleration zone (DZ), pulse width, pulse period, loop period, number of pulses per burst, inter-burst timing, number of bursts performed, voltage of the bursts performed, electric field, energy per pulse, energy per burst, polarity, etc. Based on these inputs, the model generates a PI metric representing the probability that the performed PFA application created a lesion of a desired size (e.g., the created lesion satisfies (i) a desired depth, (ii) a desired width, or (iii) a combination of both depth and width).

[0057] Furthermore, the multiple electronic devices 14 may also include components such as an electrocardiogram (ECG) monitor 26 and a localization and navigation system 28. The localization and navigation system 28 may utilize one or more well-known localization systems, including, for example, impedance-based localization and magnetic localization. Impedance-based localization utilizes multiple pairs of surface patch electrodes to generate a voltage field throughout the patient's body that may be sensed by an electrode placed at the distal end of the catheter and used to determine the three-dimensional position of the electrode within the patient's body 15. Magnetic localization utilizes a magnetic sensor (e.g., a coil) placed at the distal end of the catheter to sense an externally generated magnetic field and determine the three-dimensional position of the magnetic sensor within the patient's body 15.

[0058] Figure 1B schematically shows an ablation catheter 12. The ablation catheter 12 comprises one or more electrodes 112, 114, and 116, which may be used for a variety of diagnostic and / or therapeutic purposes, including but not limited to electrophysiological mapping, impedance-based localization, impedance measurement, and the performance of pulsed-field ablation (PFA) therapy. For example, and in some embodiments of this disclosure, two or more of the electrodes 112, 114, and 116 may be configured as a bipolar electrode assembly for use in bipolar-based PFA therapy. Specifically, the electrodes 112, 114, or 116 may be individually electrically coupled to an ablation generator 16 (e.g., via appropriate electrical wires 42 or other appropriate electrical conductors connected via an electrical connector 40, as will be discussed in more detail below, and may be configured to be selectively energized in opposite polarities (e.g., by the ablation generator 16 under the control of a closed-loop ablation processor 20) to generate potentials and corresponding electric fields therein for PFA therapy. In other words, one of electrodes 112, 114 or electrodes 114, 116 can be configured to function as a cathode, and the other can be configured to function as an anode for a predetermined PFA burst.

[0059] Electrodes 112, 114, and 116 may be any suitable electrodes. In exemplary embodiments, electrodes 112 and 114 are ring electrodes, but electrodes 112 and 114 may have other shapes or configurations without departing from the scope of the disclosure. Furthermore, although electrodes 112 and 114 are each illustrated as a single electrode, either or both of electrodes 112 and 114 may alternatively be embodied as two or more discrete electrodes. The distal electrode 116 may be a tip electrode.

[0060] Those skilled in the art will recognize that variations in the shape, size, and / or configuration of electrodes 112, 114, and 116 may result in variations in the parameters of the ablation therapy applied. For example, increasing the surface area of ​​electrodes 112, 114, and 116 will reduce the impedance, and consequently, the current that needs to be applied to achieve the voltage level required to cause tissue destruction in PFA therapy. Furthermore, PFA therapy performed via one or more electrodes 112, 114, and 116 may be bipolar or unipolar. In the case of bipolar implementation, a pair of electrodes (e.g., electrode pair 112 and 114, or electrode pair 114 and 116) is used to perform bipolar PFA therapy. In the case of unipolar implementation, a single electrode (e.g., electrode 112, 114, or 116) is used to perform unipolar PFA therapy.

[0061] In addition to performing PFA therapy, one or more of electrodes 112, 114, and 116 may be used as sensors to collect information used to assess the performance and effectiveness of the PFA therapy performed. For example, one or more of electrodes 112, 114, and 116 may be used to measure the impedance associated with one or more electrodes. For example, in one embodiment, a current signal is supplied between electrodes 114 and 116, and a corresponding voltage is measured with respect to each electrode (e.g., the voltage measured between each electrode and a reference electrode) to determine the impedance between each electrode 114 and 116 (i.e., three-terminal measurement). In another example, a current signal is supplied to one of the electrodes (e.g., electrode 116), and a voltage response is measured between the electrode and a reference electrode (e.g., a surface patch electrode) to determine the impedance associated with the region adjacent to the selected electrode (i.e., two-terminal measurement). The impedance measurements may be used to determine the proximity of the electrode to the adjacent tissue, the contact state between the electrode and the adjacent tissue, and / or tissue impedance. For example, if impedance is measured between electrodes 116 and 114, and electrode 116 is in contact with adjacent tissue, the measured impedance will reflect the tissue impedance value.

[0062] The catheter 12 may include several other sensors, including force contact sensors, shape sensors, and temperature sensors. For example, in the embodiment shown in Figure 1B, the catheter 12 includes a sensor 118 for detecting the contact force between the catheter 12 and the adjacent tissue. The sensor 118 may be implemented in various ways, including, for example, the use of a fiber optic cable containing multiple fiber Bragg gratings (FBGs) configured to detect force contact between the catheter 12 and the adjacent tissue and / or the shape of the catheter 12. In other embodiments, mechanical sensors, such as piezoelectric sensors and / or spring-based sensors, may be used to detect force contact between the catheter 12 and the adjacent tissue.

[0063] The electrical connector 40 is also shown in Figure 1B. As shown, the plug side of the electrical connector 40 is connected to the catheter 12, and the receptacle side of the electrical connector 40 is connected to the electronic device 14 via a cable 42. This arrangement can also be reversed without departing from the scope of the present disclosure. A person of the ordinary art will understand that when the plug and receptacle portions of the electrical connector 40 are mated, the catheter 12 is electrically coupled to the electronic device 14, allowing power, data, and other electrical signals to pass between them.

[0064] Figure 2 is a side view of lesions 204 and 206 formed in tissue 202. In the embodiment shown in Figure 2, an electrode 200 located at the distal end of the catheter performs PFA therapy. The lesion size is a function of the PFA therapy performed (e.g., type, duration, number of bursts, etc.), and therefore, attributes of the PFA therapy may be used as input to the PI model. Furthermore, the lesion size is a function of the position of the electrode 200 relative to the tissue 202 during the PFA therapy. Therefore, the PI model may utilize sensor inputs related to the position of the electrode 200 relative to the tissue 202 during the PFA therapy. For example, sensor inputs related to the contact force, tissue proximity, or tissue contact between the electrode 200 and the tissue 202 during the PFA therapy may be used as input to the PI model to generate PI metrics.

[0065] Furthermore, lesions result in tissue changes that may be sensed and utilized as inputs to the PI model. For example, tissue conductivity / impedance changes in response to lesion formation. Sensor inputs related to tissue impedance measurements, changes in tissue impedance, etc., may be used as inputs to the PI model to generate a PI metric. The PI model combines inputs related to the PFA therapy performed, the position of electrode 200 during the PFA therapy, and measured attributes of the tissue itself (e.g., tissue impedance) to generate a PI metric that represents the probability that the formed lesion meets the lesion size requirements.

[0066] In this example, tissue 202 has a depth of approximately 4 mm, and therefore it is desirable that the lesion formed from PFA therapy reaches a depth of at least 4 mm. Thus, the model used to generate the PI metric for such an application is configured to calculate the probability that the lesion PFA application reaches a depth of 4 mm or more. In addition to lesion depth, the model may also be used to calculate the probability that the lesion formed from PFA treatment reaches a desired width (e.g., 5 mm). In the example shown in Figure 2, a first PFA application forms a first lesion 204. The electrode is moved 4 mm, and a second PFA application is used to form a second lesion 206. By providing a PI metric that provides the probability that each lesion reaches a width (e.g., 5 mm) greater than the distance between adjacent lesions (e.g., 4 mm), it is ensured that the first lesion 204 and the second lesion 206 overlap each other, thus ensuring continuous lesions. In some cases, instead of a width threshold (e.g., 5 mm), a width range may be provided that allows physicians to adjust the depth / width trade-off in predicted lesion dimensions to suit their workflow (e.g., a PI metric that satisfies the lower limit of the width range may be acceptable for lesions located near adjacent lesions). In some cases, instead of calculating the probability that a lesion reaches a selected depth or a selected width, the model calculates the probability that a lesion reaches a combination of both a selected depth and a selected width. As described above, the model may be used to calculate the probability that a lesion formed from PFA therapy satisfies (i) a desired depth, (ii) a desired width, or (iii) a combination of both depth and width.

[0067] The PI metric provides physicians with a tool for assessing lesion formation. In particular, the PI metric is based not only on the PFA therapy administered, but also on additional inputs used to determine the probability that the formed lesion will meet the desired size requirements for a given application.

[0068] Figure 3 is a block diagram showing the inputs provided to the PFA index (PI) model 300 for calculating the PI metric. An unrestricted list of inputs to the PI model 300 includes location data 302, impedance measurements 304, contact / contact force measurements 306, other sensor measurements 308, attributes of the PFA application performed 310, and user inputs 312 (e.g., desired lesion depth, desired lesion width, anatomical structure, etc.). The PI model 300 generates the PI metric by combining two or more of the multiple inputs. As described above, in some embodiments, the PI model 300 is a probabilistic model that provides as an output the probability that a set of conditions (e.g., lesion depth, lesion width, or a combination of lesion depth and lesion width) are met. For example, Figure 4 is a graph showing the increase in the PI metric (y-axis) as a predictor variable or combination of predictor variables (x-axis) increases. The probability estimate initially corresponds to zero and increases to approximately 100% as the value of the predictor variable increases. As an alternative to expressing the PI index as a probability, the PI index may be expressed as the expected lesion size (e.g., expected lesion depth, expected lesion width, or a combination of lesion depth and lesion width).

[0069] Returning to Figure 3, each possible input to the PI model 300 is described in turn. Positional data 302 includes inputs related to the position of electrodes used to provide PFA therapy. Positional data 302 may also include the position of electrodes relative to some anatomical structure used to provide PFA therapy. Positional data may be used to generate an output that displays to the user the location where PFA therapy is performed and the PI metric associated with that location. The physician may use this display to select the location where additional PFA therapy should be performed. Furthermore, positional data may be used by the model to determine whether consecutive PFA applications should be cumulative or associated with separate locations. For example, if a first PFA application is performed at a first location and it is determined based on the PI metric that the first lesion is insufficient, a second PFA application is performed at the same location to increase the size of the first lesion. Performing the second PFA with the electrodes at the same location results in an increased probability value of the PI metric, which indicates a higher probability that the lesion size requirement has been met. However, if the catheter and corresponding electrode change position relative to the tissue between the first and second PFA application, the execution of the second PFA application will cause a second lesion to occur at a second location, and the PI metric from the first lesion should not be aggregated with the PI metric from the second lesion. Positional data may be generated via many well-known localization and navigation systems used in catheter systems, such as impedance-based localization systems and magnetic localization systems.

[0070] Impedance measurements include inputs related to impedance measured by catheter electrodes. Since tissue conductivity (inversely proportional to impedance) changes with lesion formation, this can be used to monitor lesion formation. Generally, lesion formation alters tissue impedance (e.g., decreases it). Therefore, measuring changes in tissue impedance can be a useful input when assessing lesion formation.

[0071] Impedance measurements can be performed in many ways using many circuit configurations. Generally, impedance is measured by passing a current of known amplitude (typically an alternating current) between two electrodes and measuring the voltage response. In some examples, the current is supplied between two electrodes located on a catheter electrode (e.g., between electrodes 116 and 114 as shown in Figure 1B), and the voltage measured at each electrode (measured relative to each other or relative to a reference electrode) is used to measure the impedance between the respective electrodes. In other examples, an alternating current of known amplitude is supplied to only one of the electrodes (e.g., electrode 116 as shown in Figure 1B), with a return path supplied through a reference electrode (e.g., a surface patch electrode or reference electrode on a reference catheter), and the voltage is measured between the electrode and the reference electrode to determine the impedance associated with or observed by the distal electrode 116. In other embodiments, various other configurations may be used to measure the impedance associated with one or more electrodes.

[0072] In some examples, it is important that the measured impedance represents the measured tissue impedance. For example, measuring the impedance between the distal electrode 116 and the second electrode 114 does not represent tissue impedance if neither electrode 114 nor 116 is adjacent to tissue. Many methods may be used to ensure that the measured impedance represents tissue impedance. For example, a threshold may be used to filter out impedance measurements that do not represent tissue impedance (i.e., impedance measured when the electrodes are in the blood pool). In general, when the electrode whose impedance is being measured (e.g., electrode 114) is located in the blood pool, the measured impedance will be significantly lower because the conductivity of blood is higher than that of tissue. In some embodiments, if the measured impedance is above a threshold related to blood impedance, the measured impedance is related to tissue impedance. In other embodiments, if the impedance is measured while the contact force (measured as the contact force between the distal electrode 116 and the adjacent tissue) is non-zero, the measured impedance is related to tissue impedance. Various other methods may be used to confirm that the measured impedance is related to tissue impedance.

[0073] In some embodiments, lesion formation using PFA therapy reduces tissue impedance, so tissue impedance, particularly changes in tissue impedance values, can be used as input to the PI model 300 for assessing lesion formation. In some embodiments, tissue impedance is measured before and after the administration of PFA therapy, and changes in tissue impedance are used as input for assessing lesion formation. Changes in tissue impedance typically require (tissue) impedance measurements before and after the administration of PFA. In applications where multiple PFA bursts (each PFA burst containing multiple PFA pulses) are administered, tissue impedance measurements may be performed between each of the bursts.

[0074] In some embodiments, impedance measurements may be used for reasons other than assessing changes in tissue impedance. For example, impedance measurements may be used to assess the proximity of an electrode (e.g., distal electrode 116) to tissue and / or contact between the electrode and tissue. Tissue proximity and / or contact based on impedance measurements may be useful in determining whether the electrode was in contact with tissue during the administration of PFA therapy.

[0075] The measurement of contact force involves inputs relating to the force generated between the catheter used to perform PFA therapy and the adjacent tissue. The contact force may be measured by mechanical sensors (e.g., spring mechanisms), optical fiber sensors, piezoelectric sensors, etc. If the distal electrode (e.g., distal electrode 116) is the catheter performing PFA therapy, the force-related contact force measurement provides an indicator of whether the electrode performing PFA therapy is in contact with the adjacent tissue. In some embodiments, raw contact force measurements may be utilized by the PI model 300. In other embodiments, several variations of the contact force measurement may be utilized, such as the average contact force or the percentage of time the measured contact force is above a threshold.

[0076] Additional sensor inputs may be provided as inputs to the PI Model 300. Examples of other sensor measurements include temperature measurements, sensed electrocardiogram signals, and ultrasound measurements.

[0077] The attributes of the PFA application performed may be provided as input to the PI model 300. In some examples, the physician may select from multiple PFA therapies, each having unique attributes (e.g., duration, pulse width, pulse amplitude, pulse period, total number of bursts, duration between bursts, electric field, energy per pulse, energy per burst, and polarity (e.g., unipolar, bipolar)). The attributes of the PFA therapy performed contribute to the formation of the expected lesion. In embodiments where only a single type of PFA therapy is possible, the attributes of the PFA therapy performed may not be required as input, but they would be hardcoded into the PFA model 300.

[0078] Furthermore, user input may be provided as input to the PFA model 300. For example, the user may indicate a desired lesion size (e.g., depth, width, or a combination of both) or an anatomical structure to receive PFA therapy. The PI model 300 may be modified based on the selected lesion size so that the PI metric generated by the PI model 300 reflects the probability that the performed PFA therapy will result in a lesion of the desired size.

[0079] In one embodiment, the PI model 300 is a probabilistic model that generates the probability that a lesion meets a specific requirement (e.g., a size threshold) based on one or more available inputs. A probabilistic model is defined herein as a model that calculates the probabilities of two possible outcomes. Several probabilistic models may be used. In one example, a logistic regression model is used as the PI model 300. For example, the PI model 300 calculates the probability that a lesion size requirement is met. The PI model 300 generates this probability based on one or more inputs received. In addition, the PI model 300 and the resulting PI metric are cumulative. That is, assuming that PFA applications are performed at the same location, the calculated PI metric is cumulative, taking into account each previously performed PFA application as well as the inputs received for previously performed PFA applications. In some examples, in addition to the need for PFA applications to be performed at the same location for it to be cumulative, the PFA applications must be performed within a given time interval (spacing) for it to be cumulative. In one example, the PI metric 314 generated for a given lesion is designed to be monotonically increasing (i.e., it remains the same or increases relative to its previous value).

[0080] The PI model 300 may utilize various input combinations to generate the PI metric 314. In one example, the inputs utilized by the PI model 300 include attributes of the PFA application performed and the impedance provided by the impedance measurement input 304, specifically the change in tissue impedance. In the example shown in Figure 1B, the impedance may be measured between the distal electrode 116 and the second shaft electrode 114. Assuming that the distal electrode 116 is in partial contact with the tissue where the ablation is formed, the measured impedance will represent the tissue impedance. Since the formation of a lesion within the tissue changes the tissue impedance, the change in tissue impedance represents the formation of a lesion. Similarly, attributes of the PFA application performed may include the number of bursts performed as part of the PFA application. In this example, the PI model 300 combines the number of bursts performed and the measured change in tissue impedance to calculate the PI metric 314. Since the PI metric is cumulative, the PI metric may increase in response to additional PFA applications being performed on the target tissue, indicating an increased probability of reaching the desired lesion size. For example, the PI metric may be calculated in response to a first PFA application consisting of five bursts being performed on the target tissue, along with the measured changes in tissue impedance. Assuming the calculated PI metric is not greater than or equal to a desired value, a second PFA application may be performed, and an updated PI metric is calculated that takes into account the performance of both the first and second PFA applications, along with the measured changes in tissue impedance across both the first and second PFA applications. In some examples, the calculated PI metric may be compared to a range of selected or desired values, rather than to a selected or desired value, which allows for adjustment of the predicted lesion depth / width trade-off to suit the physician's workflow across tissues of varying thicknesses.

[0081] In another example, in addition to the attributes and impedance changes of the PFA application performed, the PI model 300 utilizes contact force measurements. In some embodiments, contact force measurements are performed during the PFA application to assess whether PFA pulses were delivered to the electrode while the electrode was in contact with the target tissue. However, in embodiments where the contact sensor is not activated during the delivery of PFA pulses, contact force measurements may be performed at an interval prior to the delivery of PFA pulses. In one example, the contact force measurement may be expressed as the average contact force measured over a predetermined interval, or as the percentage of time during which the measured contact force is above a threshold (indicating good contact between the electrode performing the PFA therapy and the target tissue). As described above, the PI model 300 cumulatively combines multiple inputs to calculate a PI metric that indicates the probability of a lesion of a desired size occurring.

[0082] Figure 5 is a flowchart illustrating the calculation of the PI metric based on received impedance measurements, which may be used by the lesion assessment module 36. In step 500, pretreatment impedance measurements are received from one or more electrodes. As described above, impedance measurements may be measured using a variety of methods and configurations, including two-terminal measurements, three-terminal measurements, or other configurations of impedance measurement circuits. In some examples, the impedance measurements used are taken when the electrodes are in contact with the target tissue, such that the measured impedance represents the tissue impedance.

[0083] In step 502, additional input is measured. The measurement of additional input may be performed simultaneously with the administration of PFA therapy in step 504. For example, the measurement of additional input in step 502 may include measuring the contact force between the electrode performing PFA therapy and the adjacent tissue. In some cases, the measurement of additional input cannot be performed simultaneously with the administration of PFA therapy. In such situations, the additional input may be measured before or after the administration of PFA therapy. For example, the contact force may be measured immediately before the administration of PFA therapy and used to estimate the contact force between the electrode and the adjacent tissue during PFA therapy. The PFA therapy performed in step 504 may be selected by the physician / user and may be a standard waveform expected to form a lesion of the desired size. In one example, the PFA therapy performed in step 504 is performed using at least one of the electrodes used to measure pretreatment impedance. For example, if distal electrode 116 (shown in Figure 1B) is used to perform PFA therapy, distal electrode 116 is one of the electrodes used to measure pretreatment impedance. This is because the impedance measured by the distal electrode 116 is used to measure the tissue impedance associated with the lesion formed by the PFA therapy performed by the distal electrode 116.

[0084] In step 506, after the first PFA therapy is performed, intra- and post-treatment impedance measurements are received from one or more electrodes. As described with respect to step 500, impedance measurements may be performed using a variety of methods and configurations. Generally, the same methods / configurations used to measure impedance in step 500 are also used in step 506.

[0085] In step 508, the PFA index (PI) metric is calculated based on the PFA therapy performed, pre-treatment impedance measurements, intra-treatment / post-treatment impedance measurements, and any other additional input values ​​measured. As mentioned above, the model used to generate the PI metric may be a logistic regression model that calculates the probabilities of two possible outcomes: the lesion meets the desired size requirement, or the lesion does not meet the desired size requirement.

[0086] In step 510, the PI metric is provided as output. In some examples, the PI metric is displayed to the user using display 34 (shown in Figure 1A). For example, a graphical user interface (GUI) may display the location of the lesion relative to a 3D model of the tissue being treated. The display may utilize color coding or shapes to indicate the value of the PI metric to the physician / user.

[0087] In step 512, the PI metric is used to determine whether to initiate additional PFA therapy. In one example, the decision to initiate another PFA therapy in step 512 is automatically initiated in response to the PI metric being below a threshold. Similarly, the decision not to initiate another PFA therapy and to terminate therapy in step 514 is made in response to the PI metric being greater than a threshold. In other embodiments, the physician / user manually decides whether to initiate another PFA therapy based on the displayed PI metric. In some examples, the threshold may be an adaptive threshold. For example, the adaptive threshold may be modified based on the thickness of the tissue at a given location, or based on the expected or actual distance between adjacent lesions. In some examples, a range of thresholds may be used instead of a single threshold. A range of thresholds allows for adjustment of the depth / width trade-off of the predicted lesion dimensions to suit the physician's workflow across varying tissue thicknesses.

[0088] Figure 6 is a flowchart illustrating the calculation of the PI metric based on impedance measurements, contact force measurements, and attributes of the performed PFA therapy that can be used by the lesion assessment module 36. The steps described in Figure 6 are described in relation to the therapy description shown in Figure 7. In the example shown in Figure 7, PFA therapy 700 (single application) includes multiple PFA bursts 702a, 702b, 702c, 702d, and 702e. In this example, no measurements are taken during the execution of each of the PFA bursts 702a through 702e. Measurements are taken during the pre-burst intervals associated with each PFA burst 702a through 702e, and during the post-burst interval 710 following the execution of the last PFA burst 702e. In the example shown in Figure 7, the length of the pre-burst intervals 704a and 704b (related to PFA bursts 702a and 702b) is approximately 500 ms and ends before the execution of the corresponding PFA bursts. For example, the first pre-burst interval 704a ends a set time 706a (e.g., 200 ms) prior to the execution of the first PFA burst 702a. Similarly, the second pre-burst interval 704b begins at a set length of time 708a (e.g., 400 ms) following the execution of the previous PFA burst 702a. By providing intervals on both sides of each PFA burst, measurements are not affected or distorted by the execution of adjacent PFA bursts.

[0089] In step 600, the pre-burst impedance is measured with respect to one or more electrodes. For example, the impedance may be measured between the distal electrode 116 and the second electrode 114. In the embodiment shown in Figure 7, the pre-burst impedance is measured during the pre-burst interval 704a associated with the PFA burst 702a. In some examples, the pre-burst impedance represents tissue impedance. In some examples, the measured impedance is confirmed to represent tissue impedance based on a threshold (e.g., a minimum value representing blood pool impedance). In some examples, the pre-burst impedance is confirmed to represent tissue impedance when the measured contact force is also greater than a threshold (indicating that the distal electrode is in contact with the target tissue).

[0090] In step 602, the contact force before the burst is measured. As mentioned above, this example assumes that the contact force cannot be measured during the PFA burst because the PFA burst may interfere with the measurement. In some embodiments, the pre-burst contact force is measured continuously during the pre-burst interval 704a. In one example, the contact force measurements are averaged to generate an average contact force parameter or intermediate contact force parameter. In another example, the continuously measured contact force is compared to a threshold, and the percentage of time during which the measured contact force is above the threshold is used as the contact force measurement. For example, if the continuously measured contact force is above the threshold during the pre-burst interval 704a, the measured contact force is equal to 100%. If the continuously measured contact force is above the threshold for half of the pre-burst interval 704a, the measured contact force is equal to 50%.

[0091] In step 604, the next PFA burst (e.g., PFA burst 702a) is performed. In step 606, a determination is made as to whether the last PFA burst in a given application has been performed. If the last PFA burst has not been performed, the process proceeds to step 600, where pre-burst impedance measurement, pre-burst contact force measurement, and the performance of the next PFA burst are continued. In the embodiment shown in Figure 7, five pre-burst impedance and pre-burst contact force measurements are taken for five PFA bursts 702a through 702e. If the last PFA burst in a given application has been performed (e.g., PFA burst 702e), in step 608, the post-burst impedance is measured corresponding to a post-burst interval 710 that occurs at a set length of time 708e after the completion of the last PFA burst 702e. The post-burst impedance measurement utilizes the same technique described with respect to step 600. In this example, the impedance measurement again represents tissue impedance. For measurements such as tissue impedance, which measures the attributes of formed lesions, post-burst measurements are useful for assessing lesion formation. For measurements such as contact force, which relates to the relative position of the electrode to the tissue during PFA therapy, post-burst measurements are not necessary.

[0092] In step 610, the PI metric is calculated based on a combination of pre-burst impedance measurements, contact force measurements, post-burst impedance measurements, and attributes of the PFA therapy performed (e.g., number of bursts). In some examples, the PI metric is calculated after the first PFA application has been performed (e.g., after all five bursts 702a through 702e have been performed). In other examples, the PI metric is calculated whenever new data becomes available (e.g., whenever pre-burst impedance and contact force measurements are taken). In this example, the PFA application consists of a predetermined number of PFA bursts 702a through 702e. That is, the PI metric may be continuously updated based on data made available during the pre-burst interval 704a through 704e, but in this example, the PI metric is not used to determine whether additional PFA applications are needed until after the last PFA burst (e.g., PFA burst 702e) has been performed and the updated PI metric has been calculated based on data collected during the post-burst interval 710.

[0093] In one example, pre-burst and post-burst impedance measurements are used to calculate the change in impedance (e.g., the difference between the maximum and minimum impedance values). In one example, the measured impedance represents the measured tissue impedance. If the PI metric is calculated whenever new data becomes available (e.g., whenever measurements are taken during pre-burst intervals 704a, 704b, etc.), the change in impedance is calculated based on the minimum and maximum impedances measured for each available pre-burst interval. If the PI metric is calculated only at the end of each burst, the change in impedance is calculated based on the minimum and maximum impedances measured during each pre-burst interval 704a through 704e and post-burst interval 710. As mentioned above, in some examples, it is important that the impedance measurements represent the tissue impedance.

[0094] In one embodiment, the contact force measurement is expressed as the percentage of time during which the measured contact force is above a threshold. In other embodiments, the contact force measurement is expressed as the arithmetic mean or other mean or average of the contact forces. In some embodiments, the contact force measurement is the accumulation of measurements obtained during each of several pre-burst intervals 704a to 704e, each secured before the execution of each PFA burst 702a to 702e. In other embodiments, the contact force measurements taken during each pre-burst interval (e.g., pre-burst interval 704a) are used to calculate a PI metric related to the execution of the subsequent PFA burst (e.g., PFA burst 702a).

[0095] Furthermore, the PI metric is calculated based on the attributes of the PFA therapy performed. In one example, the attribute of the PFA therapy used is the number of bursts performed. Each time a PFA burst is performed, the number of bursts performed is incremented.

[0096] In step 612, the PI metric is displayed / output. In some examples, the PI metric is displayed to the user using display 34 (shown in Figure 1A). For example, a graphical user interface (GUI) may display the location of the lesion relative to a 3D model of the tissue being treated. The display may utilize color coding or shapes to indicate the value of the PI metric to the physician / user.

[0097] In step 614, the PI metric is used to determine whether to initiate additional PFA therapy. In some cases, the PI metric is compared to a threshold. If the PI metric is greater than the threshold, no additional treatment is needed, and the physician / user moves the catheter to the next treatment location, ending the process in step 618. If the PI metric is less than the threshold, additional PFA therapy is applied, and the process is repeated. In some cases, if the PI metric is less than the threshold, the decision of whether to perform another PFA therapy is made automatically. In some cases, the physician / user decides whether to perform additional PFA therapy based on the feedback received.

[0098] In the example shown in Figure 7, the PFA therapy performed consisted of five PFA bursts 702a to 702e. In the example shown in Figure 8, the PFA therapy consisted of a first PFA application 800a and a second PFA application 800b. The first PFA application 800a consisted of five bursts 802a to 802e, and the second PFA application 800b consisted of five bursts 802f to 802j. In this example, the first PFA application 800a was delivered to the target tissue, and the PI metric after the first PFA application 800a was below the threshold. As a result, the second PFA application 800b was delivered to the target tissue. In one example, measurements are taken during each of the pre-burst intervals 804a to 804j, and during the first post-burst interval 806a (after the first PFA application 800a) and the second post-burst interval 806b (after the second PFA application 800b).

[0099] In one example, measurements across the first and second PFA applications 800a and 800b are cumulative. For example, the contact force measurement used to calculate the final PI metric (following the post-burst interval 806b) would include the percentage of time during which the measured contact force (measured during each of the multiple pre-burst intervals 804a to 804e and 804f to 804j) was greater than a threshold. In other embodiments, the contact force may be the arithmetic mean or other mean or average of the contact forces measured over each of the multiple pre-burst intervals 804a to 804j. Similarly, the measured impedance change may be cumulative over the multiple pre-burst intervals 804a to 804j and the multiple post-burst intervals 806a and 806b. As will be discussed in more detail with respect to Figure 9, the rules for determining whether the measurements taken for the first PFA application 800a and the second PFA application 800b (or subsequent PFA applications not shown) are cumulative include whether the first and second PFA applications were performed at approximately the same location (e.g., the difference in location is less than a certain threshold) and whether they were performed within a predetermined time interval (e.g., less than a certain time threshold).

[0100] For measurements such as impedance change, based on the minimum and maximum measured impedance values, the measurement can only increase, not decrease. However, for other measurements such as contact force, the cumulative measurement may decrease. In some situations, the PI metric calculated based on these inputs may decrease even after PFA therapy is added. To prevent such counterintuitive outputs from being provided to the user, in some examples, monotonicity rules are applied to the PI metrics displayed or output to the user. For example, the monotonicity rule may filter the raw PI metric to prevent a decrease in the output or displayed PI metric.

[0101] Figure 9 is a flowchart showing the aggregation of inputs measured across two or more PFA applications based on timing / location thresholds. The steps described in Figure 9 are related to the treatment description illustrated in Figure 10. In the example shown in Figure 10, the PFA therapy consists of a first PFA application 1000a and a second PFA application 1000b. The first PFA application 1000a consists of five bursts 1002a to 1002e, and the second PFA application 1000b consists of five bursts 1002f to 1002j. In this example, the first PFA application 1000a was administered to the target tissue, and the PI metric after the administration of the first PFA application 1000a was below the threshold. As a result, the second PFA application 1000b was administered to the target tissue. Figure 10 shows the conditions that must be met to determine whether the PI metric should be accumulated across both PFA applications 1000a and 1000b. In particular, if the electrode positions for the first and second PFA applications 1000a and 1000b change by more than a threshold distance, the PI metric should be reset for the application of the second PFA application 1000b. Similarly, if the time interval 1004 between the application of the first PFA therapy 1000a and the application of the second PFA therapy 1000b is greater than a threshold amount, the PI metric is reset for the application of the second PFA application 1000b. In the example shown in Figure 10, the threshold time interval 1004 is measured between the end of the last PFA burst 1002e performed for the first PFA application 1000a and the start of the first PFA burst 1002f performed for the second PFA application 1000b.

[0102] Figure 9 is a flowchart showing the aggregation of lesion assessment inputs across multiple pulsed-field ablation (PFA) applications based on spatial and temporal criteria. In step 900, the PFA index (PI) metric and all corresponding inputs (e.g., impedance, contact force, and other lesion assessment parameters) are initialized or reset before the implementation of the PFA application (e.g., the first PFA application 1000a shown in Figure 10). Furthermore, the device position (more specifically, the position of the electrode providing treatment) is measured along with the time associated with the implementation of the next PFA application (e.g., PFA application 1000a). In one example, the position associated with the first PFA application 1000a is calculated as the median position measured during the duration implementation of all bursts 1002a to 1002e that comprise the first PFA application 1000a. In other examples, the position may be measured before the implementation of the first PFA application 1000a, during the implementation of the first PFA application 1000a, or after the implementation of the first PFA application.

[0103] In step 902, a PFA burst (e.g., 1002a) is performed as part of a PFA application (e.g., PFA application 1000a), and relevant inputs are collected (e.g., impedance measurements, contact force, etc.). The collected inputs may include data collected before or after the burst.

[0104] In step 904, inputs related to PFA applications performed since the last reset are accumulated. This may include inputs collected before a burst for several PFA bursts (e.g., PFA bursts 1002 to 1002e related to the first PFA application 1000a), inputs collected after a burst for a given PFA application (e.g., PFA application 1000a), or inputs collected for previous PFA applications. For example (assuming the PI metric and other inputs were not initialized / reset in step 900), inputs collected for separate PFA applications (e.g., inputs collected during the period of the first PFA application 1000a and the second PFA application 1000b) may be accumulated, provided that the position / time conditions are met as described below.

[0105] In step 906, the PI metric is calculated based on the inputs collected and accumulated in step 904 and any additional inputs relevant to the calculation of the PI metric described above. In this example, the PI metric is updated whenever new inputs become available, which includes updating the PI metric during the execution of each of several individual bursts (e.g., bursts 1002a to 1002e) using inputs collected before the burst, and updating the PI metric after the execution of the PFA application (e.g., PFA application 1000a) using inputs collected both before and after the burst.

[0106] In step 908, a decision is made as to whether the PFA application is complete. For example, with respect to the first PFA application shown in Figure 10, the PFA application 1000a is completed after the execution of the last burst 1002e. If the PFA application is not complete, the process returns to step 902, and the next PFA burst, which is included as part of the PFA application, is performed. If the PFA application is complete, in step 910, the PI metric calculated in step 906 is compared to a threshold or range of values ​​to determine whether additional treatment is needed. In some examples, especially when the PI metric is compared to a range of values, the physician or operator may make a final decision as to whether the performed PFA application is sufficient or whether additional PFA applications are needed. In step 910, if the PI metric is greater than (or otherwise satisfactory) the threshold, the therapy at that particular location is terminated in step 916. If the therapy is terminated at that location, the PI metric and associated inputs are initialized or reset in step 900, and the process continues. In step 910, if the PI metric is below a threshold (or otherwise considered unsatisfactory), in step 912, a decision is made to provide a subsequent or second PFA application (e.g., PFA application 1000b), and in step 912, the location and / or time of the subsequent or second PFA application are measured. As described above, the location may include the location of the apparatus performing the second or subsequent PFA application, or more specifically, the electrode or electrode that will perform the second or subsequent PFA application. In one example, the median location measured over all bursts of the first PFA application 1000a is compared to the electrode location measured before the implementation of the second PFA application 1000b to determine the electrode displacement between the respective first and second PFA applications 1000a, 1000b.

[0107] In step 914, the positional and / or temporal information collected in step 912 is compared to a threshold to determine whether the PI metric and other inputs can be accumulated. In particular, if the position of the device or electrode performing the therapy moves significantly between the execution of the previous PFA application (e.g., PFA application 1000a) and the execution of the subsequent PFA application (e.g., PFA application 1000b), the change in position will be greater than the threshold, and the PI metric and other inputs cannot be accumulated. Similarly, if the time difference between the previous PFA application (e.g., PFA application 1000a) and the subsequent PFA application (e.g., PFA application 1000b) is greater than the threshold, the PI metric and other inputs cannot be accumulated. In some examples, only positional information is used to determine whether the PI metric and other inputs can be accumulated with respect to consecutive PFA applications. In other examples, both positional and temporal information are used to determine whether the PI metric and other inputs can be accumulated.

[0108] If it is determined in step 914 that the PI metric and other inputs are cumulative because the change in position is below a threshold and / or the time between PFA applications is below a threshold, the method proceeds to step 902 to continue with the execution of the next PFA burst associated with the next PFA application, and the subsequent cumulative accumulation of the collected inputs and PI metrics. With respect to the example shown in Figure 10, if the change in position of the electrodes configured to perform PFA applications 1000a and 1000b is below a threshold, and the elapsed time between the execution of the first PFA application 1000a and the execution of the second PFA application 1000b (e.g., measured between the end of the last burst 1002e of the first PFA application 1000a and the start of the first burst 1002f associated with the second PFA application 1000b, as indicated by the time duration 1004) is below a threshold, the PI metric calculated for the first PFA application 1000a is not reset, but is instead allowed to monotonically increase as the second PFA application 1000b is performed. Similarly, the inputs used to calculate the PI metric are also accumulated with respect to the first PFA application 1000a and the second PFA application 1000b.

[0109] Although the present invention has been described with reference to exemplary embodiments, it will be understood by those skilled in the art that various modifications can be made without departing from the scope of the invention, and that equivalents may be substituted for the elements. Furthermore, many modifications can be made to adapt the teachings of the invention to specific situations or materials without departing from the essential scope of the invention. Accordingly, the present invention is not limited to the specific embodiments disclosed, but is intended to include all embodiments that fall within the scope of the appended claims.

[0110] Clause 1. A computer-implemented method for assessing lesion formation associated with pulsed-field ablation (PFA) therapy performed at a location selected by a PFA catheter, the method comprising: measuring pre-treatment impedance using one or more electrodes placed on the catheter; measuring intra-treatment / post-treatment impedance using one or more electrodes placed on the catheter; and calculating a PFA index (PI) metric based on a model combining the measured pre-treatment impedance, the measured intra-treatment / post-treatment impedance, and the attributes of the PFA therapy performed, wherein the PI metric represents the likelihood that the lesion has reached a selected size.

[0111] Clause 2. The measured pre-treatment impedance and measured intra-treatment / post-treatment impedance represent the tissue impedance associated with the tissue receiving the PFA therapy performed, as described in Clause 1.

[0112] Clause 3. The method according to Clause 1 or 2, wherein the model utilizes the change in tissue impedance calculated based on the measured minimum tissue impedance and the measured maximum tissue impedance.

[0113] Clause 4. The method according to Clauses 1 to 3, further comprising measuring one or more other inputs related to the PFA therapy performed, wherein the model further combines one or more other inputs in generating a PI metric.

[0114] The method described in Clause 5.1, where one or more other inputs include the contact force measured between the catheter and the adjacent tissue.

[0115] Clause 6. The contact force is measured as the percentage of time during which the measured contact force is greater than or equal to a threshold, as described in Clause 5.

[0116] Clause 7. The method according to Clauses 1 to 6, wherein the PI metric calculated by the model is filtered to allow only increases in the value of the PI metric.

[0117] Clause 8. The method according to Clauses 1 to 7, wherein the PFA therapy performed comprises a first PFA application consisting of a first group of PFA bursts, the pre-treatment impedance and intra-treatment impedance are measured during the pre-burst interval preceding each of the first group of PFA bursts, and the post-burst impedance is measured after the final PFA burst performed as part of the first PFA application.

[0118] Clause 9. The attributes of the first PFA application implemented by the model are as described in Clause 8, including the number of PFA bursts sent.

[0119] Clause 10. The method of Clause 8 or 9, further comprising measuring one or more additional inputs during the pre-burst interval preceding each of the first plurality of PFA bursts, wherein the one or more additional inputs include contact force.

[0120] The method according to Clauses 8 to 10, further comprising performing a second PFA application at a selected location when the PI metric is below a threshold, wherein the second PFA application includes a second multiple PFA burst.

[0121] Clause 12. The method of Clauses 8 to 11, further comprising measuring a first contact force associated with the catheter during the performance of the first PFA application performed, and measuring a second contact force associated with the catheter during the performance of the second PFA application performed, and calculating the PI metric after the performance of the second PFA application, utilizing the cumulative contact force based on the first and second contact forces.

[0122] Clause 13. A system for assessing lesion formation associated with pulsed-field ablation (PFA) therapy performed at a location selected by a PFA catheter, the system comprising a lesion assessment module operating on a computer system, the lesion assessment module being configured to receive pre-treatment impedance measured using one or more electrodes placed on the catheter, receive intra-treatment / post-treatment impedance measured using one or more electrodes placed on the catheter, and calculate a PFA index (PI) metric based on a model combining the measured pre-treatment impedance, measured intra-treatment / post-treatment impedance, and attributes of the PFA therapy performed, the PI metric representing the likelihood that the lesion has reached a predetermined size.

[0123] Clause 14. The measured pre-treatment impedance and measured intra-treatment / post-treatment impedance represent the tissue impedance associated with the tissue receiving the PFA therapy performed, as described in Clause 13.

[0124] Clause 15. The model is a system as described in Clause 13 or 14, which utilizes the change in tissue impedance calculated based on the measured minimum tissue impedance and the measured maximum tissue impedance.

[0125] Clause 16. The lesion assessment module is further configured to receive one or more other inputs measured with respect to the PFA therapy performed, and the model further combines one or more other inputs when generating the PI metric, as described in Clauses 13 to 15.

[0126] Clause 17. One or more other inputs measured include the contact force measured between the catheter and the adjacent tissue, as described in Clause 16.

[0127] Clause 18. Contact force is measured as the percentage of time the measured contact force is greater than or equal to a threshold, in the system described in Clause 17.

[0128] Clause 19. The system described in Clauses 13 to 18, wherein the PI metrics calculated by the model are filtered to allow only increases in the value of the PI metrics.

[0129] Clause 20. The system described in Clauses 13 to 19, wherein the PFA therapy performed includes a first PFA application consisting of a first group of PFA bursts, the pre-treatment impedance and intra-treatment impedance are measured during the pre-burst interval preceding each of the first group of PFA bursts, and the post-burst impedance is measured after the final PFA burst performed as part of the first PFA application.

[0130] Clause 21. The attributes of the first PFA application implemented by the model are the system described in Clause 20, including the number of PFA bursts implemented.

[0131] Clause 22. The lesion assessment module is further configured to receive one or more additional inputs measured during the pre-burst interval preceding each of the first plurality of PFA bursts, the system as described in Clause 20 or 21, wherein the one or more additional inputs include contact force.

[0132] Clause 23. The lesion assessment module is further configured to receive a first contact force associated with the catheter during the performance of a first PFA application and a second contact force associated with the catheter during the performance of a second PFA application, and to calculate the PI metric after the performance of the second PFA application using the cumulative contact force based on the first and second contact forces, as described in Clauses 20 to 22.

[0133] Clause 24. A computer-implemented method for assessing lesion formation associated with pulsed-field ablation (PFA) therapy performed at a location selected by electrodes placed on a catheter, the method comprising: measuring tissue impedance both before and after a first PFA application to determine a change in tissue impedance; measuring the contact force between the catheter and adjacent tissue before the first PFA application; and calculating a PFA index (PI) metric based on a model combining the change in tissue impedance, the contact force, and one or more attributes of the first PFA application, wherein the PI metric represents the likelihood that the lesion has reached a selected size.

[0134] Clause 25. The computer implementation method described in Clause 24, further comprising performing the first PFA application at the selected location.

[0135] The computer implementation method described in Clause 25, wherein the attributes of the first PFA application performed by the model include the number of PFA bursts performed, and if the PI metric is below a threshold, a second PFA application is performed at the selected location, and the second PFA application includes a second set of PFA bursts.

[0136] Clause 27. The method according to Clause 26, wherein the model is a logistic regression model that maps the measured change in tissue impedance, the measured contact force, and one or more attributes of the first PFA application to the probability that the lesion has reached a selected size.

[0137] Clause 28. The method of Clause 26 or 27, further comprising receiving user input regarding the size of a selected lesion and modifying the model to generate a PI metric representing the likelihood that the lesion has reached the selected size.

[0138] Clause 29. The first PFA application consists of multiple bursts, as described in Clauses 26, 27, or 28.

[0139] Clause 30. Tissue impedance is measured before each burst and after the final burst of the first PFA application, and contact force is measured before each burst, as in the method of Clause 29.

[0140] Clause 31. The change in tissue impedance is calculated according to the method of Clauses 26 to 30, by identifying the measured minimum and maximum tissue impedances and subtracting the minimum tissue impedance from the maximum tissue impedance.

[0141] Clause 32. Contact force is calculated as the percentage of time the contact force exceeds a threshold for all measurements, as described in Clauses 26 to 30.

[0142] The method described in Clauses 33.32, wherein a second PFA application is implemented if the PI metric is below a threshold.

[0143] Clause 34. A method for assessing lesion formation associated with pulsed-field ablation (PFA) therapy performed at a location selected by a PFA catheter, the method comprising: measuring pre-treatment impedance using one or more electrodes placed on the catheter; performing a first PFA application; measuring intra-treatment / post-treatment impedance using one or more electrodes placed on the catheter; and calculating a PFA index (PI) metric based on a model combining the measured pre-treatment impedance, the measured intra-treatment / post-treatment impedance, and the attributes of the first PFA application performed, the PI metric representing the likelihood that the lesion has reached a selected size.

[0144] Clause 35. A system for assessing lesion formation associated with pulsed-field ablation (PFA) therapy performed at a location selected by electrodes placed on a catheter, the system comprising a lesion assessment module operating on a computer system, the lesion assessment module being configured to measure tissue impedance both before and after a first PFA application to determine a change in tissue impedance, measure the contact force between the catheter and adjacent tissue before the first PFA application, and calculate a PFA index (PI) metric based on a model combining the change in tissue impedance, the contact force, and one or more attributes of the first PFA application, the PI metric representing the likelihood that the lesion has reached a selected size.

[0145] Clause 36. A method for assessing lesion formation associated with pulsed-field ablation (PFA) therapy performed at a location selected by electrodes placed on a catheter, the method comprising: delivering a first PFA application to the selected location, the first PFA application being defined by one or more attributes; measuring tissue impedance both before and after the first PFA application to determine a change in tissue impedance; measuring the contact force between the catheter and adjacent tissue before the first PFA application; and calculating a PFA index (PI) metric based on a model combining the change in tissue impedance, the contact force, and one or more attributes of the first PFA application, the PI metric representing the likelihood that the lesion has reached a selected size.

Claims

1. A computer-implemented method for assessing lesion formation associated with pulsed-field ablation (PFA) therapy performed at a location selected by a PFA catheter, wherein the method is: The pretreatment impedance is measured using one or more electrodes placed on the PFA catheter, The impedance during / after treatment is measured using one or more electrodes placed in the PFA catheter, A method comprising calculating a PFA index (PI) metric based on a model combining the measured pre-treatment impedance, the measured intra-treatment / post-treatment impedance, and the attributes of the PFA therapy performed, wherein the PI metric represents the likelihood that the lesion has reached a selected size.

2. The further comprising measuring one or more other inputs related to the PFA therapy performed, The computer implementation method according to claim 1, wherein the model further combines one or more other inputs when generating the PI metric.

3. The computer implementation method according to claim 2, wherein the one or more other inputs include a contact force measured between the PFA catheter and the adjacent tissue.

4. The computer implementation method according to claim 3, wherein the contact force is measured as the percentage of time during which the measured contact force is equal to or greater than a threshold.

5. The computer implementation method according to claim 1, wherein the PI metric calculated by the model is filtered to allow only increases in the value of the PI metric.

6. The computer implementation method according to claim 1, wherein the PFA therapy performed comprises a first PFA application comprising a first plurality of PFA bursts, the pre-treatment impedance and the intra-treatment impedance are measured during a pre-burst interval preceding each of the first plurality of PFA bursts, the post-burst impedance is measured after the final PFA burst performed as part of the first PFA application, and the attributes of the performed first PFA application utilized by the model include the number of PFA bursts performed.

7. The computer implementation method according to claim 6, further comprising measuring one or more additional inputs during the pre-burst interval preceding each of the first plurality of PFA bursts, wherein the one or more additional inputs include contact force.

8. The computer implementation method according to claim 6, further comprising performing a second PFA application at the selected location if the PI metric is less than a threshold, wherein the second PFA application includes a second plurality of PFA bursts.

9. The first contact force associated with the PFA catheter is measured during the execution of the first PFA application that has been performed, The further includes measuring a second contact force associated with the PFA catheter during the execution of the second PFA application that has been performed, The computer implementation method according to claim 8, wherein the calculation of the PI metric after the application of the second PFA utilizes the cumulative contact force based on the first and second contact forces.

10. A system for assessing lesion formation associated with pulsed-field ablation (PFA) therapy performed at a location selected by a PFA catheter, The system includes a lesion assessment module that operates on a computer system, The aforementioned lesion assessment module is The pretreatment impedance measured using one or more electrodes placed in the PFA catheter is received. The intra-treatment / post-treatment impedance measured using one or more electrodes placed in the PFA catheter is received. It is configured to calculate the PFA index (PI) metric based on a model that combines the measured pre-treatment impedance, the measured intra-treatment / post-treatment impedance, and the attributes of the PFA therapy performed. The PI metric represents the possibility that the lesion has reached a predetermined size.

11. The lesion assessment module is further configured to receive one or more other inputs measured in relation to the PFA therapy performed, The system according to claim 10, wherein the model further combines one or more other inputs when generating the PI metric.

12. The system according to claim 11, wherein the one or more other inputs measured include a contact force measured between the PFA catheter and the adjacent tissue.

13. The system according to claim 12, wherein the contact force is measured as the percentage of time during which the measured contact force is greater than or equal to a threshold.

14. The system according to claim 10, wherein the PFA therapy performed comprises a first PFA application comprising a first plurality of PFA bursts, the pre-treatment impedance and the intra-treatment impedance are measured during a pre-burst interval preceding each of the first plurality of PFA bursts, the post-burst impedance is measured after the final PFA burst performed as part of the first PFA application, and the attributes of the performed first PFA application utilized by the model include the number of PFA bursts performed.

15. The lesion assessment module is further configured to receive one or more additional inputs measured during the pre-burst interval preceding each of the first plurality of PFA bursts, wherein the one or more additional inputs include contact force, according to claim 14.

16. A computer-implemented method for assessing lesion formation associated with pulsed-field ablation (PFA) therapy performed at a location selected by electrodes placed on a catheter, wherein the method is: In order to determine the change in tissue impedance, the tissue impedance is measured both before and after the application of the first PFA, Before performing the first PFA application, the contact force between the catheter and the adjacent tissue is measured, The method comprises calculating a PFA index (PI) metric based on a model combining the change in tissue impedance, the contact force, and one or more attributes of the first PFA application, The PI metric represents the likelihood that the lesion has reached a selected size.

17. The computer implementation method according to claim 16, wherein the attributes of the first PFA application performed and utilized by the model include the number of PFA bursts performed, and if the PI metric is less than a threshold, a second PFA application is performed at the selected location, the second PFA application includes a second plurality of PFA bursts.

18. The computer implementation method according to claim 17, wherein the model is a logistic regression model that maps the measured change in tissue impedance, the measured contact force, and one or more attributes of the first PFA application to the probability that the lesion has reached the selected size.

19. Receiving user input regarding the selected size of the lesion, The computer implementation method according to claim 17, further comprising modifying the model to generate a PI metric representing the possibility that the lesion has reached the selected size.

20. The computer mounting method according to claim 17, wherein the first PFA application consists of a plurality of bursts, the tissue impedance is measured before each burst of the first PFA application and after the final burst, and the contact force is measured before each burst.

Images