Patent Description:
Tissue ablation is used in numerous medical procedures to treat a patient. In some examples, ablation procedures involve modification of target tissue, e.g., to stop electrical propagation through the tissue in patients with an arrhythmia. Such ablation procedures are often performed by passing energy, such as electrical energy, through one or more electrodes of an inserted catheter. The energy causes modifications to the target tissue. <CIT> discloses estimators for ablation effectiveness.

In the following all methods relating to treatment of the human body are disclosed but not claimed and are shown for illustrative purposes only.

Medical procedures, such as cardiac ablation using one or more energy modalities are frequently used to treat conditions such as atrial fibrillation and ventricular tachycardia. Some treatments may use radiofrequency ablation (RF) which heats target tissue in the heart to cause cell death and thus change conduction pathways in the heart to treat the disease state in a patient. Excessive application of RF energy can result in collateral damage. To help avoid collateral damage, the desired end to a treatment is assessed by using measurements such as temperature rise, contact force, total energy, and/or impedance measures for example to inform what thermal energy has been conveyed to and retained by the target tissue. Thermal transfer can take several seconds to minutes during which the heart and catheters continue to move. In contrast, pulsed electric field (PEF) ablation use an electric field to disrupt cellular membranes. The pulsed electric field can be generated with electrical pulses delivered in short bursts. The compromised cell membrane results in the desired cell death and is associated with other measurable phenomena, such as impedance changes resulting from the liberated exchange of ions through the permeabilized cell membranes. Different cell types may also be affected differently by PEF energy such that collateral structures typically affected by temperature rise induced by RF ablation may remain unaffected by PEF energy. The temperature rise should not be ignored for PEF ablation entirely however. The electric field in PEF ablation is established between conductive elements, such as electrodes, and currents flowing through the target tissue, which act as a resistive medium, result in energy dissipation and some temperature rise in the tissue and fluid. This temperature rise is generally smaller than the RF-induced temperature rises but still presents a risk to collateral structures, especially with several successive applications.

The techniques of this disclosure generally relate to assessment, mapping, and projection of pulsed electric field (PEF) energy delivery, and in some examples, to a correlation of a PEF field distribution based on the delivery of PEF energy to the target tissue and at least one metric of a therapeutic effect of the delivered PEF energy.

In one aspect, the present disclosure provides for a medical system. The medical system includes a generator configured to generate pulsed electric field (PEF) energy. A medical device is in electrical communication with the generator and has a plurality of electrodes configured to deliver the generated PEF energy to a target tissue to create electroporated regions in the target tissue. A delivery element tracking system is in communication with the generator and the medical device. The tracking system has processing circuitry configured to: measure a position of at least one of the plurality of electrodes proximate in time to a delivery of PEF energy to the target tissue with respect to the target tissue and correlate a PEF field distribution based on the delivery of PEF energy to the target tissue to determine or modify at least one metric of a therapeutic effect from the PEF delivery at positions other than the measured location of the plurality of electrodes.

In another aspect, the tracking system is further configured to correlate the determined at least one metric of a therapeutic effect into one or more zones.

In another aspect, the one or more zones are visually coded to represent a predetermined at least one metric of a therapeutic effect.

In another aspect, the tracking system is further configured to display the visually coded one or more zones on a display overlaying the target tissue.

In another aspect, the one or more zones are representative of thermal damage.

In another aspect, the one or more zones represent a region of tissue that has recovered from reversible effects.

In another aspect, the one or more zones are represented predictively based on set of anticipated PEF parameters and position data of electrodes delivering the PEF energy.

In another aspect, a first one of the visually coded one or more zones is indicated of a first region of the target tissue irreversibly electroporated and a second one of the visually coded one or more zones is indicated of second region of the target tissue reversibly electroporated.

In another aspect, the determined at least one metric of a therapeutic effect is determined based at least in part on at least one from the group consisting of a temperature of the plurality of electrodes during delivery of PEF energy, an impedance of the plurality of electrodes during delivery of PEF energy, and a proximity of the plurality of electrodes to the target tissue.

In another aspect, the at least one metric for therapeutic effect is a measure of the at least one metric of a therapeutic effect compared against a predetermined threshold.

In another aspect, the tracking system is further configured to display the at least one metric of a therapeutic effect on a display.

In another aspect, the displayed at least one metric for therapeutic effect is overlayed on a display of the target tissue.

In another aspect, the delivered PEF energy is sufficient to irreversibly electroporate at least a portion of the target tissue.

In one aspect, a method of determining a region of therapeutic effect in a pulsed electric field (PEF) energy delivery system includes measuring a position of at least one of a plurality of electrodes of a medical device prior to or after delivery of PEF energy to a target tissue with respect to the target tissue. PEF energy is then delivered to the target tissue sufficient to electroporate at least a portion of the target tissue. At least one metric of a therapeutic effect is determined or modified based at least in part on the measured position.

In another aspect, the method further includes correlating the determined at least one metric of a therapeutic effect into one or more zones.

In another aspect, the one or more zones are visually coded to represent the at least one metric of a therapeutic effect, and wherein the method further includes displaying the visually coded one or more zones on a display overlaying the target tissue.

In another aspect, the at least one metric of a therapeutic effect is based at least in part on a fidelity of the measured position of the plurality of electrodes.

In another aspect, a first one of the visually coded one or more zones is indicative of a first region of the target tissue irreversibly electroporated and a second one of the visually coded one or more zones is indicative of second region of the target tissue reversibly electroporated.

In another aspect, at least one metric of a therapeutic effect is determined based at least in part on at least one from the group consisting of a temperature of the plurality of electrodes during delivery of PEF energy, an impedance of the plurality of electrodes during delivery of PEF energy, and a proximity of the plurality of electrodes to the target tissue.

In another aspect, the at least one metric of a therapeutic effect is a measure of the at least one metric of a therapeutic effect compared against a predetermined threshold.

In another aspect, the method further includes displaying the at least one metric of a therapeutic effect on a display.

In another aspect, the displayed at least one metric of a therapeutic effect is overlayed on a display of the target tissue.

In another aspect, the measured position includes multiple independent measurements proximate in time to deliveries of PEF energy.

In another aspect, the measured position is predicted from cyclic, algorithmic, or patterned behavior in the measurements at the time of delivery of PEF energy.

In one aspect, a medical system includes a generator configured to generate pulsed electric field (PEF) energy. A first medical device is in electrical communication with the generator and has a plurality of electrodes configured to deliver the generated PEF energy to a target tissue to create a lesion in the target tissue. A second medical device has a plurality of electrodes and is configured to map the target tissue for at least one from the group consisting of geometric representation, spatial navigation, electrical signals, and temporal behavior of electrical signals. A tracking system is in communication with the generator, the first medical device, and the second medical device. The tracking system has processing circuitry configured to: measure a position of at least one of the plurality of electrodes proximate in time to a delivery of PEF energy to the target tissue with respect to the target tissue with the second medical device; and determine or modify at least one metric of a therapeutic effect based at least in part on the measured position.

In one aspect, a representation of the effect of a specified PEF delivery may be represented concurrent with the modeled space included to the already computed effects from previously completed PEF deliveries to be used as a predictive guide.

In another aspect, zones may be defined in spatial modeling application as points, volumes, or surfaces as practical representations and or addressable elements.

One example provides a medical treatment apparatus. The apparatus includes a catheter having a plurality of electrodes configured to deliver PEF energy to a target tissue and further configured for therapy assessment measurements in the target tissue, the therapy assessment measurements including a first measurement taken prior to a respective time instance of PEF-energy delivery and a second measurement taken after the respective time instance. The apparatus also includes a tracking system configured to track a position of a selected electrode of the plurality of electrodes or of a selected tracking element to determine a first displacement of the plurality of electrodes with respect to the target tissue between the first measurement and the respective time instance and a second displacement of the plurality of electrodes with respect to the target tissue between the respective time instance and the second measurement. The apparatus further includes a processing circuit configured to estimate a therapeutic effect of the PEF-energy delivery based on the first measurement, the second measurement, the first displacement, and the second displacement.

Another example provides a therapy assessment method. The method includes receiving, with a processing circuit, a stream of therapy assessment measurements obtained with a plurality of electrodes of a catheter configured to deliver PEF energy to a target tissue. The therapy assessment measurements include a first measurement taken prior to a respective time instance of PEF-energy delivery and a second measurement taken after the respective time instance. The method also includes determining, with the processing circuit, a first displacement of the plurality of electrodes with respect to the target tissue between the first measurement and the respective time instance and a second displacement of the plurality of electrodes with respect to the target tissue between the respective time instance and the second measurement. The determining operations are based on position measurements received from a tracking system configured to track a position of a selected electrode of the plurality of electrodes or of a selected tracking element. The method further includes estimating, with the processing circuit, a therapeutic effect of the PEF-energy delivery based on the first measurement, the second measurement, the first displacement, and the second displacement.

Yet another example provides a non-transitory computer-readable medium storing instructions that, when executed by an electronic processor, cause the electronic processor to perform operations comprising the above therapy assessment method.

Further disclosed herein is a medical system. The medical system includes a generator configured to generate pulsed electric field (PEF) energy. A medical device is in electrical communication with the generator and has a plurality of electrodes configured to deliver the PEF energy to a target tissue to create electroporated regions in the target tissue. A delivery element tracking system is in communication with the generator and the medical device. The tracking system has processing circuitry configured to: measure a position of at least one of the plurality of electrodes prior to delivery of PEF energy to the target tissue with respect to the target tissue and correlate a PEF field distribution based on the delivery of PEF energy to the target tissue to determine or modify at least one metric of a therapeutic effect from the PEF delivery at positions other than the measured location of the plurality of electrodes.

Referring now to the drawing figures in which like reference designations refer to like elements, an embodiment of a medical system constructed in accordance with principles of the present invention is shown in <FIG> and generally designated as "<NUM>. " The system <NUM> generally includes a medical device <NUM> that may be coupled directly to an energy supply, for example, a pulse field ablation (PFA) generator <NUM> including an energy control, delivering, and monitoring system or indirectly through a navigation system component or delivery element tracking system <NUM>. A remote controller <NUM> may further be included in communication with the generator <NUM> for operating and controlling the various functions of the generator <NUM> and in further communication with one or more surface electrodes <NUM> configured to measure and record electrograms. Surface electrodes <NUM> may also be optionally directly coupled to the generator <NUM> for assessment of energy application vectors. A display <NUM> may be in communication with the remote controller <NUM> and/or the navigation system component <NUM> to display the various maps and data generated by the various components described herein. In the example shown, the navigation system component <NUM> includes an impedance-based system configured to use the surface electrodes for orientation. In other examples, the navigation system component <NUM> may be based on other localization navigation methods, such as electromechanical or X-ray.

In one or more embodiments, the remote controller <NUM> may include processing circuitry <NUM> configured to carry out or otherwise control the various functions of the generator <NUM> and implement methods described herein. As shown, the processing circuitry includes a processor <NUM>, a memory <NUM>, and a waveform unit <NUM>.

The processing circuitry <NUM> may be configured to control any of the methods and/or processes described herein and/or to cause such methods, and/or processes to be performed, e.g., via the remote controller <NUM>. The processor <NUM> corresponds to one or more processors for performing functions described herein. The memory <NUM> is configured to store data, programmatic software code and/or other information described herein. In some embodiments, the software may include instructions that, when executed by the processor <NUM> and/or processing circuitry <NUM> causes the processor <NUM> and/or processing circuitry <NUM> to perform the processes described herein with respect to the remote controller <NUM>. For example, processing circuitry <NUM> of the remote controller <NUM> includes the waveform unit <NUM> configured to perform one or more functions described herein, such as with respect to pulse generation and control.

The medical device <NUM> may generally include one or more diagnostic or treatment regions for energetic, therapeutic and/or investigatory interaction between the medical device <NUM> and a treatment site. The treatment region(s) may deliver, for example, pulsed electric field (PEF) energy sufficient to reversibly or irreversibly electroporate a tissue area, or radiofrequency (RF) energy in proximity to the treatment region(s). The medical device <NUM> may include an elongate body or catheter <NUM> passable through a patient's vasculature and/or positionable proximate to a tissue region for diagnosis or treatment, such as a catheter, sheath, or intravascular introducer. The elongate body, shaft, or catheter <NUM> may define a proximal portion <NUM> and a distal portion <NUM> and may further include one or more lumens disposed within the elongate body <NUM> thereby providing mechanical, electrical, and/or fluid communication between the proximal portion <NUM> of the elongate body <NUM> and the distal portion <NUM> of the elongate body <NUM>. The distal portion <NUM> may generally define the one or more treatment region(s) of the medical device <NUM> that are operable to monitor, diagnose, and/or treat a portion of a patient. The treatment region(s) may have a variety of configurations to facilitate such operation. In the case of purely bipolar pulsed field delivery, distal portion <NUM> includes electrodes that form the bipolar configuration for energy delivery. A plurality of delivery elements <NUM>, for example, a plurality of electrodes <NUM>, may serve as one pole while a second device (e.g., second medical device <NUM>, electrodes <NUM>) containing one or more additional electrodes is placed to serve as the opposing pole of the bipolar configuration. The medical device <NUM>, as shown in <FIG>, may have a linear configuration with the plurality of delivery elements <NUM>. For example, the distal portion <NUM> may include six delivery elements <NUM> linearly disposed along a common longitudinal axis <NUM>. Alternatively, the distal portion <NUM> may include an electrode carrier arm or splines that is/are transitionable between a linear configuration and an expanded configuration in which the carrier arm or splines has an arcuate or substantially circular configuration. The carrier arm or splines may include the plurality of delivery elements <NUM> that are configured to deliver PEF energy. Further, the carrier arm when in the expanded configuration may lie in a plane that is substantially orthogonal to the longitudinal axis <NUM> of the elongate body <NUM>. The planar orientation of the expanded carrier arm may facilitate ease of placement of the plurality of delivery elements <NUM> in contact with the target tissue.

Continuing to refer to <FIG>, the remote controller <NUM> further includes the delivery element tracking system <NUM>, either integrated therein or a separate system, in communication with the generator <NUM> and configured to track and monitor the positions of the plurality of delivery elements <NUM> as the medical device <NUM> moves with respect to the target tissue. This communication or conveyance of information from delivery elements <NUM> to the navigation system occurs via the components <NUM> and <NUM>, which are illustratively shown as separate systems. In operation, the components <NUM> and <NUM> make use of the connection to the delivery catheter <NUM>, to gather additional information from the generator, e.g., for assessing cardiac cycle information for display/gating of the geometry. In some examples, the catheter <NUM> also communicates with the navigation system component <NUM>. In particular, the navigation system component <NUM> utilizes processing circuitry <NUM> to measure a position of at least one of the plurality of delivery elements <NUM> prior to, during, and/or after generation and delivery of PEF energy to the target tissue with respect to the target tissue. For example, as shown in <FIG>, a plurality of PEF delivery points <NUM> made by repeated application of a distal tip electrode 24A is shown about a mapped region <NUM> of the heart. These points can be identified before, during, and after the application of PEF energy to the target region, e.g., with a second medical device <NUM>, for example, a mapping catheter, such as the Achieve™ mapping catheter by Medtronic, Inc. The navigation system component 13can be used to navigate to the plurality of PEF delivery points <NUM> and correlate a PEF field distribution based on the delivery of PEF energy to the target tissue to determine at least one metric of a therapeutic effect from the PEF delivery at positions other than the measured location of the plurality of delivery elements <NUM>. In a representative example, an individual delivery point <NUM> corresponds to one PEF-energy pulse. Sequences of the individual delivery points <NUM> illustrated in <FIG> are produced when the distal tip electrode 24A is moved from one position to a next position with respect to the region <NUM> during the time interval between sequential PEF-energy pulses.

In one example, the determined at least one metric of a therapeutic effect is determined based at least in part on at least one from the group consisting of a temperature of the plurality of electrodes <NUM> during delivery of PEF energy, an impedance of the plurality of electrodes <NUM> during delivery of PEF energy, and a proximity of the plurality of electrodes <NUM> to the target tissue. Referring to <FIG>, in conventional ablation practice, such as with radiofrequency (RF) ablation, locations of therapeutic applications <NUM> are noted on maps of anatomic geometry. Placement and user selection of the icon size is meant to convey where treatment had likely happened in a typically diastolic static map and a therapeutic effect, such as ablation of a focal source or creating a line of block, when applied to treatment of atrial fibrillation, for example, as inferred from the proximity of such points and continuity of constructed lines to determine likelihood of success of the therapy. Because delivery of the RF energy generally relies on the imprecisely known or defined conduction of heat in what is an assumed homogeneous substrate (cardiomyocytes/vessel/scar/etc.), the area of effect is imprecisely characterized. In contrast, the PEF delivery points <NUM> in <FIG> can cause ablation or effect with defined field established by the electrodes <NUM> so the area of effects can be inferred, estimated, and/or calculated by predefined models or even empirical measurements. In one configuration, the processing circuity <NUM> of the controller <NUM> and/or delivery element tracking system <NUM> measures the aggregation of the intensity of the field(s) from applications of PEF energy to the delivery points <NUM> to determine if the geometric positions on the predetermined map of the target tissue region have been sufficiently affected to cause at least one metric of therapeutic effect, for example, irreversible electroporation.

For example, as shown in <FIG>, the tracking system <NUM> is configured to correlate the determined at least one metric of a therapeutic effect into one or more zones. For example, the zones may be visually coded (such as with at least one of a color, shading, transparency, or pattern) and displayed on the display <NUM> (shown in <FIG>) overlaying the mapped target tissue region. If a shift in the map occurs, then the stored information of the applications may be reapplied to new registered geometry models. In the example shown in <FIG>, the pattern-coded regions or zones circumferentially disposed about a single delivery point <NUM> show that the farther away from the delivery point <NUM> the more decreased therapeutic effect from the application of the electric field.

<FIG> show that successive applications of PEF energy, and the fidelity with which they inform the electric field that has been applied, are plotted on the map, and then the aggregated treatment of a PEF delivery point <NUM> may be displayed on the geometric map with some measure of completeness, such as with color/opacity. In <FIG>, the electroporation region <NUM> is shown in a bold dashed line indicating the area of tissue experiencing at least reversible electroporation. As shown in <FIG>, cumulative electroporation regions produced by successive applications of PEF energy to multiple delivery points <NUM> may have relatively complex geometries.

From the aggregated field effects of each application of PEF energy from delivery points <NUM>, a measure of completeness of a particular energy application may be imposed on the previously generated cardiac map. In this configuration, the pattern-coded regions may correspond to a measure of completeness. For example, one region may correspond to a measure of completeness of greater than <NUM>% if, for example, the region experiences multiple irreversible field exposures, where each point in the field may be assigned discrete count variables for such exposures in addition to any calculated values. Another region may correspond to a measure of completeness of <NUM>% if, for example, the region experiences at least one irreversible field exposure. Yet another region may correspond to a measure of completeness of <NUM>% if, for example, the region only experiences reversible field exposures. The above percentages are mere examples, and the field projected onto the geometric representation may change or may be modified with uncertainties coming from the location where the assessment data are collected versus where the catheter is when the field is applied. Measures of completeness can be computed incrementally and calculated in real-time. For example, a clinician can perform a set of ablations and the delivery element tracking system <NUM> may log and compute the field overlaps/aggregated treatments at each delivery point <NUM> when the map is requested by the clinician. Additionally, the measure of completeness does not have to be associated only with the geometric points, but may be done for any point within the volume being monitored by the navigation portion of the system <NUM>, that is the points which are generally displayed as containing the heart chamber of interest for example may move, but the information about completeness may still be computed for new geometries as it is a culmination of fields associated with single placement applications. The overlap of the aggregated electro-anatomical map, i.e., containing geometry and imposed delivery data, may be predictively computed and optionally displayed for a next application. For example, as the electric field is applied around the delivery elements <NUM> being tracked on the map, the system <NUM> can show where the treated region from a next therapeutic delivery is located and/or its effect as may be added to the already collected anatomical map. This may be useful for example in helping a user determine if a placement of the delivery elements <NUM> is likely to close a gap in cardiac conduction or ablate another identified or unintended structure, for example. Such a prediction representation may be further modified by the PEF system <NUM> providing information about therapy levels, profiles, or voltages to mapping/navigation system responsible for aggregating those data and using the appropriate models.

The examples of <FIG> additionally illustrate an idealized implementation where the field is assumed to be of a consistent form and applied to the map for example as associated very specifically with a specific position and orientation of the field or zones. Variables associated directly with the delivery may be used to determine completeness and uncertainty modifications as discussed later. If pre and post measures of variables are used to determine the completeness of a delivery, the positions at which those measures are taken can additionally affect the uncertainty associated with treatment of given regions as discussed with reference to <FIG>.

<FIG> show various examples of uncertainty in the field applied to a measure of completeness of particular application of field energy. When completeness is determined, at least in part, from measures such as temperature rise or impedance, for example, the real location of those measurements before and/or after a delivery can change the certainty of the relevance of those measures for assessing completeness based on their proximity to the delivery. Their proximity to one another can also be important when the difference in measurement from pre to post-delivery is important. For example, an ideal field as shown in <FIG> occurs when the delivery points <NUM> are the same points as assessment points. That is, where the field energy, i.e., current, or assessment values, are measured in the same place as where it is delivered. In such an embodiment, a measure of completeness more associated with the success of the delivery. The elements of the field shown in <FIG> are thus the same field regions as shown in <FIG>. However, as shown in <FIG>, when the delivery point <NUM> differs from the points at which the completeness/effectiveness is assessed before and after are slightly different, the field attributes are different than having been measured at the exact same location as the delivery and thus less certain to represent the success of a delivery. In the embodiment shown in <FIG>, the assessment points and delivery points <NUM> are significantly offset resulting in smaller regions of certainty for each zone.

In particular, as shown in <FIG>, it is possible that the point at which the field energy assessments are made after delivery, as indicated by <NUM> is different than the delivery point <NUM>, or the position in which the initial position of the electrodes <NUM> is measured for assessment, indicated by <NUM>. In an example application, assume that an impedance drop of at least <NUM>% results in a <NUM>% effective lesion. After a delivery, the impedance is measured to have dropped <NUM>% when measured at the same point as the delivery point <NUM>, as shown <FIG>. The maximum effect is applied to the model; the regions around the delivery elements <NUM> are computed at their maximum extent. In another similar delivery, a <NUM>% an impedance drop is measured from the same position as the delivery points <NUM>, and using a simple linear interpolation, this may be an <NUM>% effective delivery. The model that is applied has reduced regions accordingly, smaller areas of effect to represent a conservative application of certainty that regions further from the delivery point(s) have been adequately treated. Yet another delivery also measures a <NUM>% impedance drop, but the measurements are taken from positions that are different from the delivery point <NUM>, for example, as shown in <FIG>. The model applied has even smaller regions of effect applied. The <NUM>% effectiveness as given by the value of the impedance drop to be further reduced depending on how far away the values were measured from the delivery point <NUM> where the model may be imposed, and even from each other. Changes in the impedance may more likely represent regional differences in the heart the further away they are, reducing the effectiveness of such measures to represent the success of a delivery.

For a tracked point <NUM>, region, zone, volume, and/or surface on a mapping system, the motion of the plurality of delivery elements <NUM> affects how completely a region is likely to have been treated. If a delivery element <NUM> is moved during progressive application of pulses in a pulse train, or successive pulse trains of PEF energy, for example, the area being treated changes and is not as effective for treating the tissue initially targeted as the area of effect is reduced by motion. For example, a time between applications in a moving heart can see seconds to minutes pass between successive applications for the same intended treatment region. Moreover, as shown in <FIG>, when there is high uncertainty, application points <NUM> are offset from assessment points owing to, for example, inaccuracies with assessments based on impedance or temperature. In such an example, the displayed field may not include an irreversible region and all the fields, for example, reversible and stimulation regions, may be reduced. In some examples, the application of the positional effect may be implemented as a standard or selectable option, allowing for higher confidence, for example, in an operator's personal assessment of their position stability in relation to the target tissue in a heart exhibiting significant motion. Therapies or entire procedures may be recalculated to the anatomical geometries based on inclusion or exclusion of such various weighting values as noted herein (e.g., one or more of position, timing, heart cycle, impedance, and temperature may be retrospectively applied or removed in practice).

Assessment fidelity is also affected by motion considerations. If a delivery element <NUM> provides a baseline measurement (such as impedance) in one position and then moves or shifts between that measurement and the measurement which follows, the values may be in similar locations but are less relevant, the further apart the assessment measurements are made or the further away a delivery of therapy is applied. Hence, in general form, it may be advantageous to weight measurement and therapy effectiveness measures as a function of the spatial displacements. Additional weighting may be applied to uncertainty of the position measures themselves or using the weights as measures of the uncertainty for integration with a formal filter with multiple assessment variables. Thus, when PEF energy is applied, the delivery points and the assessed position of the electrodes <NUM> are usually registered as separate points to reference against the geometric model to inform an operator in what vicinity a treatment has been performed. Because standard thermal techniques rely on heat transfer (such as with RF or cryo methods), treatment metrics are only associated with the position, and not generally extensible to field considerations, as suggested in the present application can be done with PEF to inform/project completeness measures to the geometric points.

A bipolar delivery represents an example implementation, wherein the field between delivery elements <NUM> located proximate to one another produces a more predictable field distribution as compared with a unipolar delivery. Such implementations may still be used with appropriate modeling considerations of course. It should be noted similarly that the images in <FIG> and <FIG> represent such fields simplistically as point deliveries and circular fields of effects to convey the use of representative regions and implementation of uncertainty considerations. The field strength (in units of volts/cm, for example) which is an often-associated value important to the response of a particular cell type may follow the simplified geometry for regions of effect around a single conductor such as in a unipolar configuration, but the field may be far more complex between two or more delivery elements <NUM>. The model may be computed independently for each delivery set based on individual placements of such delivery elements <NUM>. Further, the orientation of the electric field as a vector field variable may also be incorporated into the completeness computations for a particular region as multiple orientations have been shown to be more effective at electroporating cells than with singly oriented applications (i.e., may use an angular difference in the field to assess the completeness level to which a point on the map has been treated).

Referring now to <FIG>, in an example method <NUM> of determining a region of therapeutic effect in a pulsed electric field (PEF) energy delivery system. The method <NUM> includes measuring a position of at least one of a plurality of electrodes <NUM> of a medical device <NUM> prior to or after delivery of PEF energy to a target tissue with respect to the target tissue, for example, a real or representative anatomical map (Step <NUM>). For example, the position of the plurality of electrodes <NUM> may be determined by the delivery element tracking system <NUM> either before, during, or after delivery of PEF energy. The measured position may also include multiple independent measurements prior to deliveries of PEF energy taken by the delivery element tracking system <NUM>. Moreover, the measured position may be predicted from cyclic, algorithmic, or patterned behavior in the measurements at the time of delivery of PEF energy. For example, based on the multiple independent measurements prior to the delivery, the delivery element tracking system <NUM> may predict the location of the plurality of electrodes <NUM> when PEF energy is actually delivered to the target tissue region. PEF energy is then delivered to the target tissue sufficient to electroporate at least a portion of the target tissue (Step <NUM>). At least one metric of a therapeutic effect is determined or modified based at least in part on the measured position (Step <NUM>). For example, based on the measured positioned of the plurality of electrodes <NUM> a measure of completeness may be determined and/or modified for a particular treatment region. In another words, as more information about the position of the plurality of electrodes <NUM> is determined, a prior measure of completeness may be updated with new measure of completeness.

Some embodiments may benefit from at least some features disclosed in <CIT>.

In some examples, a ratio of completeness C for each electrode <NUM> is determined based at least in part on calculating the following equation: <MAT> where k is a constant, Tf is a final temperature measured at an end of a time interval, Ti is the initial temperature measured at a beginning of the time interval, and ΔTn is the expected or predicted change in temperature over that time interval. In various implementations, the expected or predicted change ΔTn is derived from computer modeling or based on empirical observations. The expected or predicted values and model parameters for determining the expected or predicted values are stored in the memory <NUM>.

In some other examples, the ratio of completeness C is calculated using the following equation: <MAT> where k is a constant, Zf is the final impedance at the end of a time interval, Zi is the initial impedance at the beginning of the time interval, and ΔZn is the expected or predicted change in impedance over that time interval. In various implementations, the impedance values may be complex or real. In some cases of complex impedance values, the completeness may first be computed as a complex value, which may then be reduced to a real value for ease of understanding by the users. In various implementations, the expected or predicted change ΔZn is derived from computer modeling or based on empirical observations. In yet some other examples, voltage-, current-, and EGM-based calculations of the ratio of completeness C are implemented in the same or substantially similar manner.

In additional examples, a cumulative ratio of completeness Ctotal is calculated using the following equation: <MAT> where i is a summation index, ωi is the i-th weight, and Ci is the i-th individual ratio of completeness. In various examples, different values of the index i correspond to different time instances, different sensors, different electrode configurations, different displacement values, etc. In some of such examples, at least some of the i-th ratios Ci are determined in accordance with Eq. (<NUM>). In other ones of such examples, at least some of the i-th ratios Ci are determined in accordance with Eq. (<NUM>). In yet other ones of such examples, at least some of the i-th ratios Ci are determined based on the voltage-, current-, and/or EGM-based measurements and calculations.

In general, calculations in accordance with Eq. (<NUM>) can be performed based on measurements performed by any suitable set of sensors available for such measurements in the medical devices <NUM> and/or <NUM>. In some instances, the available set of sensors consists of sensors of a single type, such as temperature sensors or impedance sensors. In some other instances, the available set of sensors includes sensors of two or more different types, such as temperature sensors, impedance sensors, and so on. In various examples, some or all of the sensors are implemented using the electrodes <NUM>. For example, in some embodiments, a temperature sensor is implemented using copper and constantan wire leads connected to an electrode <NUM> to form an end of a thermocouple thereat. In various embodiments, sensing of the voltage and/or current between a selected pair of electrodes <NUM> is used for impedance measurements.

<FIG> is a schematic diagram illustrating how cyclic motion of the heart affects or may be used to calculate or infer the position of an electrode <NUM> with respect to the mapped region <NUM> of the heart during a medical procedure according to one example. Since motion of the heart is generally cyclical, such motion is represented in <FIG> by a looped trajectory <NUM>. A PEF energy pulse is delivered when the corresponding electrode <NUM> is at the application point <NUM>, e.g., as explained above in reference to <FIG> and <FIG>. Even when the electrode <NUM> is stationary in the tissue coordinate frame, the electrode <NUM> still moves with respect to the mapped region <NUM> along the looped trajectory <NUM> due to the motion of the heart. In some examples, the electrode(s) <NUM> may be in contact with the target tissue, and it is the motion of that tissue which presents itself as the motion relative to a static displayed anatomy. In some other examples, it may be the case that the cyclic motion not adjacent to the target tissue still induces motion of the electrode(s) <NUM> relative to the target tissue. As such, assessment measurements taken using the same electrode <NUM> may occur at locations that are different from the application point <NUM>, depending on the specific phase of the cardiac cycle. As an example, <FIG> illustrates three different points <NUM>, <NUM>, and <NUM> on the looped trajectory <NUM> for the same electrode <NUM> during different time instances of the medical procedure. More specifically, the point <NUM> marks the position of the electrode <NUM> at which the initial (baseline) measurement of the pertinent parameter (e.g., temperature or impedance) is taken. Similarly, the point <NUM> marks the position of the electrode <NUM> at which the post-delivery measurement of the pertinent parameter is taken. Both of the points <NUM> and <NUM> correspond to different respective phases of the cardiac cycle, which are also different from the phase corresponding to the application point <NUM>. This relative phase, such as a percentage estimation of the cardiac cycle based on electrocardiogram measures of the R-R interval may itself be incorporated into the timing and representation of the applied field and calculation of the completeness as it may be the case that different phases of contraction have a different response to therapy (e.g., the stimulation range of an electric field may have no value during a local refractory period).

In general, for a tracked point on a mapping system, the motion of the delivery elements, such as that of the electrodes <NUM>, affects how completely the mapped region <NUM> is treated. When an electrode <NUM> is moved during progressive application of pulses in a pulse train or successive pulse trains, the area of the mapped region <NUM> that is being treated changes accordingly. In some examples, the corresponding electrode movement includes a non-zero displacement component in the laboratory coordinate frame in addition to the movement component along the looped trajectory <NUM>. Due to these movements, the treatment effect may not be nearly the same as intended because such treatment effect is spatially dispersed by the above-indicated motion. However, corrective measures can beneficially be taken provided that the cumulative ratio of completeness Ctotal can be accurately estimated.

In various examples, assessment fidelity is also affected by similar motion considerations. For example, when an electrode <NUM> provides a baseline measurement (such as an impedance measurement or a temperature measurement) in the point <NUM> and then moves or shifts to the point <NUM> for the next measurement, the measured values are typically less relevant to the mapping than those putatively obtained at the application point <NUM>. In general, the relevance is diminished when the assessment measurements are made further apart or when the points <NUM>, <NUM> are further away from the application point <NUM>. The weights ωi (Eq. (<NUM>)) are therefore used to introduce an appropriate spatial-displacement dependence into the assessment of therapy effectiveness. In some implementations, additional weighting is applied to take into account the uncertainty in the measures of the positions <NUM>, <NUM>, and/or <NUM> themselves or to use the weights as measures of the uncertainty for integration with a filter configured for multiple assessment variables. Examples of such uncertainty are illustrated in <FIG>.

In general, the weights associated with the position are a function of the spatial positions for each of the relevant measures, e.g., as expressed by Eq. (<NUM>): <MAT> where F denotes a function; and X<NUM>, X<NUM>, and X<NUM> are the coordinates (in vector form) of the points <NUM>, <NUM>, and <NUM>, respectively. (<NUM>)-(<NUM>) are examples of the function F according to some implementations: <MAT> <MAT> where a and b are constants. Other suitable implementations of the function F are also possible.

In the above examples, the vector X is a position vector that represents geometric coordinates. In additional examples, the vector X is generalized to include a time component and/or a phase component. (<NUM>)-(<NUM>) provide mathematical expressions for different implementations of the vectors X to be used with the function F of Eq. (<NUM>): <MAT> <MAT> <MAT> <MAT> where x, y, z are the cartesian spatial coordinates; t is time; and ϕ is the phase of the cardiac cycle. In some examples, the phase ϕ is determined as follows: <MAT> where Tr<NUM> and Tr<NUM> are the times of two consecutive R-waves, and T is a time between the times Tr<NUM> and Tr<NUM>.

The spatial coordinates are important for the determination of the weights ωi for the above-indicated reasons. In some use cases, the time component is important to the physiological response. In some use cases, the phase component or an estimate thereof is important for correlation of the cyclic motion in the heart along the looped trajectory <NUM> with the cardiac cycle. For example, when an electrode <NUM> takes an assessment measure at one time and the spatial position is the same as at another time, but at a different phase of the cardiac cycle, it might not assertively be assumed that the same cardiac tissue is in proximity to the electrode <NUM> delivering the therapy. It should also be noted that increased permeabilization is observed to persist in cells only for a limited period of time after the PEF application when the cell is "reversibly" electroporated. In such cases, the cell will eventually recover, and the permeabilization will decrease over time as the cell progresses towards full recovery. However, this increased-permeabilization state makes it more likely for the cell to transition into being irreversibly electroporated with subsequent PEF-energy applications (e.g., pulse trains delivered on the order of seconds to minutes after the previous application) while the cell is still in the increased-permeabilization state. The time periods associated with the permeabilization are tissue dependent as well and may serve as model inputs. In a single variable application, the time variable may be used for mapping the rate of change of measured values, such as impedance, with multiple measures of the variable after a delivery to determine derivative values which may themselves be useful for assessing success/effect of a therapy.

<FIG> is a flowchart of a method <NUM> of delivering therapy to a target tissue according to some examples. The method <NUM> can be implemented using the medical system <NUM> (<FIG>) and includes operations directed at assessing completeness of the delivered therapy. The completeness-assessment operations of the method <NUM> take into account the above-described spatial dispersion of the delivered PEF energy and the relative displacements of the application point(s) <NUM> and assessment points <NUM>, <NUM>.

Initialization operations of the method <NUM> include operations of blocks <NUM>, <NUM>, and <NUM>. In a representative example, initialization operations of the block <NUM> include some or all of the following: (i) overall system setup; (ii) initialization of the catheter navigation subsystem of the system <NUM>; (iii) initialization of the PFA generator <NUM>; (iv) loading up a model of the selected therapy into the memory <NUM> and/or the processor <NUM>; (v) identifying and/or defining the target tissue; (vi) loading the geometry of the distal portion <NUM> of the catheter into the model and selecting delivery elements therein; (vii) creating or importing the initial map of the therapy-delivery area and loading the initial map into the memory <NUM> and/or the processor <NUM>, and the like. Operations of the block <NUM> include initializing a navigation subsystem (e.g., including element tracking system <NUM> or similar) of the medical system <NUM> and navigating the medical device(s) <NUM> and/or <NUM> through the vasculature to the therapy-delivery area using the navigation subsystem which may include creation of the initial mapping geometry (initial map). Operations of the block <NUM> include initializing a heart monitoring subsystem of the medical system <NUM> to start monitoring the patient's cardiac cycle. In various examples, such initializing involves appropriately positioning the one or more surface electrodes <NUM> on the skin of the patient and activating the signal recorder to record, e.g., the electrocardiogram (ECG) R-wave detection history. Depending on the specific embodiment of the medical system <NUM>, blocks <NUM>, <NUM>, and <NUM> may include additional appropriate initialization operations known to persons of ordinary skill in the pertinent art.

Upon completion of the above-described initialization operations, the method <NUM> proceeds to perform operations of blocks <NUM>, <NUM>, <NUM>, and <NUM>. The block <NUM> includes operations directed at pre-delivery assessment of the therapy-delivery area using baseline measurements performed in a sub-block <NUM> thereof. The block <NUM> includes delivering the PEF energy to the target tissue in a sub-block <NUM> with the actual PEF-energy delivery parameters being monitored in a sub-block <NUM>. The block <NUM> includes operations directed at post-delivery assessment of the therapy-delivery area using post-delivery measurements performed in a sub-block <NUM> thereof. The blocks <NUM>, <NUM>, <NUM> also include respective medical-device tracking operations <NUM>, <NUM>, <NUM>, wherein the navigation subsystem and/or other appropriate means are used to obtain pertinent values of the vectors X<NUM>, X<NUM>, and X<NUM>. For example, in some cases, the position tracking measurements in the block <NUM> are supplemented by calculations or indirect inferences to more-precisely pinpoint the location X<NUM> of the delivery element (e.g., the active electrode <NUM>) with respect to the region <NUM> during the actual (short) instance of the corresponding PEF pulse. Such calculations or inferences may not be needed for the sub-blocks <NUM> and/or <NUM> as the measurements <NUM>, <NUM> are performed on a different time scale than that of the PEF delivery of the sub-block <NUM>.

The block <NUM> includes operations <NUM> directed at determining or estimating a completeness measure of the therapy that is being applied. Numerical inputs for the operations <NUM> are provided by the position-tracking data obtained in the sub-blocks <NUM>, <NUM>, and <NUM>, the measurements (of temperature, impedance, etc.) taken in the sub-blocks <NUM> and <NUM>, the PEF-energy delivery parameters obtained in the sub-block <NUM>, and the cardiac-cycle data obtained via the block <NUM>. In various examples, the position-tracking data obtained in the sub-blocks <NUM>, <NUM>, and <NUM> provide the x, y, z components of the vectors X<NUM>, X<NUM>, and X<NUM>. The cardiac-cycle data obtained in the block <NUM> are used to determine the t and/or ϕ components of the vectors X<NUM>, X<NUM>, and X<NUM> (also see Eqs. (<NUM>)-(<NUM>)). The t component, as described above, may also depend on the time of delivery from previous deliveries (also see the block <NUM>. The operations <NUM> include a set of operations directed at computing the weights ωi based on the received numerical inputs and using the applicable form of the function F. In various examples, Eqs. (<NUM>)-(<NUM>) or functionally similar numerical or analytical models are used for such computations. The operations <NUM> further include a set of operations directed at computing measures of completeness based on the measurements obtained in the sub-blocks <NUM>, <NUM> and further based on the computed weights ωi. In various examples, Eqs. (<NUM>)-(<NUM>) or functionally similar numerical or analytical models are used for computing the measures of completeness. The block <NUM> also includes operations <NUM> directed at saving the parameters associated with the therapeutic deliveries for recomputing with any future model/display/preference changes. The block <NUM> further includes operations <NUM> directed at applying the estimated therapy effect to the applicable model of the treatment area, e.g., for assessment or prediction, and displaying the results to the operator. Examples of the estimated therapy effect for individual application points <NUM> are described above, e.g., in reference to <FIG> and <FIG>.

A block <NUM> of the method <NUM> includes operations directed at generating a treatment completeness map that reflects all previous PEF-energy applications to the treatment area based on the computations performed in the preceding instances of the block <NUM> for various application points <NUM>. An example of such treatment completeness map is shown in <FIG>. An example of how the computations corresponding to individual application points <NUM> are combined to generate the treatment completeness map in the block <NUM> are illustrated in <FIG>.

A decision block <NUM> of the method <NUM> is used to determine whether to end the treatment. The decision (Yes or No) made in the decision block <NUM> is based on the treatment completeness map generated in the block <NUM>. Upon sufficient completeness (which is determined based on the applicable medical criteria for the type of treatment that is being performed) indicated by the treatment completeness map ("Yes" at the decision block <NUM>), the method <NUM> is terminated. Otherwise ("No" at the decision block <NUM>), the processing of the method <NUM> is directed back to the operations of the block <NUM>, wherein position of the treatment elements is adjusted by navigating the same to the area of the target tissue that is indicated as being insufficiently treated in the treatment completeness map for additional PEF-energy applications. In various embodiments, the method <NUM> may be adapted to performing a local treatment, e.g., directed at isolating a vessel, or to performing a more comprehensive treatment as a complete therapeutic case, wherein multiple (e.g., disjoint) target areas are treated. In some examples associated with such embodiments, the "No" decision at the block <NUM> directs the processing of the method <NUM> to the block <NUM> or <NUM>, rather than to the block <NUM>.

<FIG> is a block diagram illustrating a program code (software) <NUM>, e.g., run by the processing circuitry <NUM>, to support the method <NUM> according to some examples. The program code <NUM> has several modules configured to handle different respective aspects of the method <NUM>. For example, a catheter module <NUM> is used to handle the catheter-related aspects, which include but are not limited to: (i) geometry (e.g., linear, circular, splined, or adjustable) of the distal portion (e.g., <NUM>, <FIG>) of the corresponding medical device; (ii) selection of the electrodes <NUM> for PEF-energy delivery and assessment measurements; (iii) geometric modality of the PEF-energy delivery (e.g., bipolar or unipolar); and (iv) sequences in which the selected electrodes <NUM> are engaged for various energy-delivery and assessment operations. A target-tissue module <NUM> is used to handle the target-tissue related aspects, as the same medical device can be used for treating different target tissues. Examples of the target tissues covered by target-tissue module <NUM> include but are not limited to atrial cardiomyocytes, ventricular cardiomyocytes, nerve, lung, cardiac smooth muscle, and cardiac scar tissue. In various examples, the target-tissue module <NUM> provides pertinent physiological models for each target tissue selection. An therapy-parameters module <NUM> is used to handle the energy-level aspects, as the same catheter can be used for delivering different PEF waveforms, and the catheter module <NUM> may inform the module <NUM> as to what the catheter is capable of delivering. Examples of waveform parameters covered by the module <NUM> include amplitudes of voltages and/or currents, pulse train parameters, individual pulse parameters, and various waveform-shape parameters, such as rise and fall times, interphase delays, cycle times, and voltage/current polarity (e.g., biphasic or monophasic). A measurement module <NUM> is used to handle the measurement aspects of the therapy delivery. Examples of the measurements handled via the measurement module <NUM> include but are not limited to: (i) tracking spatial, time, and phase components of the various pertinent vectors X; (ii) baseline values, e.g., obtained via the sub-block <NUM> of the method <NUM>; (iii) actual PEF-energy delivery parameters, e.g., obtained via the sub-block <NUM> of the method <NUM>; and (iv) post-delivery values, e.g., obtained via the sub-block <NUM> of the method <NUM>.

The modules <NUM>, <NUM>, <NUM>, and <NUM> feed the respective data sets into a computation pipeline <NUM> that is configurable for a variety of selected assessment values, such as temperature change, impedance change, time-dependent rates of the temperature and/or impedance changes, etc. A target computation module <NUM> of the pipeline <NUM> uses the data sets provided by the modules <NUM>, <NUM>, and <NUM> to compute various target values for the given catheter geometry, target tissue, and selected PEF-energy modality. The computed target values are then used as references against which the mapped completeness values Ctotal can be evaluated. In various examples, the mapped completeness values Ctotal are computed, via a matching computation module <NUM> and an optional filtering and combination module <NUM> of the pipeline <NUM>, based on the measurements Valuel-Valuen received via the measurement module <NUM>. The computations performed in the module <NUM> typically include computations of the weights ωi and individual completeness ratios Ci. When the optional filtering and combination operations of the module <NUM> are bypassed, the module <NUM> operates to compute the mapped completeness values Ctotal therein. In cases of multiple targets, the module <NUM> receives the weights ωi and completeness ratios Ci from the module <NUM> and operates to compute the mapped completeness values Ctotal after applying the pertinent filtering and combination operations therein.

An output module <NUM> receives the mapped completeness values Ctotal from the pipeline <NUM> for presentation to the operator and/or further evaluation. In one example, the output module <NUM> outputs a completeness map of the region <NUM> that is qualitatively similar to the completeness map shown in <FIG>. In some examples, the output module <NUM> enables the operator to input the user feedback into the completeness map, e.g., for taking responsive corrective actions via the return path <NUM>→<NUM> of the method <NUM>. In some other examples, the output module <NUM> presents a predicted image alone or in combination with the map of therapy already applied given the settings, position, and set, default, or estimated values for the therapy completeness.

According to one example disclosed above, e. g, in the summary section and/or in reference to any one or any combination of some or all of <FIG>, provided is a medical treatment apparatus, comprising: a catheter having a plurality of electrodes configured to deliver PEF energy to a target tissue and further configured for therapy assessment measurements in the target tissue, the therapy assessment measurements including a first measurement taken prior to a respective time instance of PEF-energy delivery and a second measurement taken after the respective time instance; a tracking system configured to track a position of a selected electrode of the plurality of electrodes to determine a first displacement of the plurality of electrodes with respect to the target tissue between the first measurement and the respective time instance and a second displacement of the plurality of electrodes with respect to the target tissue between the respective time instance and the second measurement; and a processing circuit configured to estimate a therapeutic effect of the PEF-energy delivery based on the first measurement, the second measurement, the first displacement, and the second displacement.

In some examples of the above medical treatment apparatus, the first measurement includes a first temperature measurement using a first electrode of the plurality of electrodes and a second temperature measurement using a second electrode of the plurality of electrodes; and wherein the second measurement includes a third temperature measurement using the first electrode and a fourth temperature measurement using the second electrode.

In some examples of any of the above medical treatment apparatus, the first measurement includes a first impedance measurement using a first electrode pair of the plurality of electrodes and a second impedance measurement using a second electrode pair of the plurality of electrodes; and wherein the second measurement includes a third impedance measurement using the first electrode pair and a fourth impedance measurement using the second electrode pair.

In some examples of any of the above medical treatment apparatus, the first measurement includes a first temperature measurement and a first impedance measurement; and wherein the second measurement includes a second temperature measurement and a second impedance measurement.

In some examples of any of the above medical treatment apparatus, the medical treatment apparatus further comprises a cardiac-cycle monitor, wherein the processing circuit is further configured to estimate the therapeutic effect based on one or more cardiac-cycle phases selected from the group consisting of: a first cardiac-cycle phase corresponding to the first measurement; a second cardiac-cycle phase corresponding to the time instant; and a third cardiac-cycle phase corresponding to the second measurement.

In some examples of any of the above medical treatment apparatus, the medical treatment apparatus further comprises a waveform generator in electrical communication with the plurality of electrodes to apply thereto a sequence of pulses of the PEF energy, wherein the processing circuit is further configured to estimate the therapeutic effect based on a time delay between a pair of consecutive pulses of the PEF energy in the sequence of pulses.

In some examples of any of the above medical treatment apparatus, the processing circuit is further configured to estimate the therapeutic effect based on a cumulative measure of completeness computed as a weighted sum of a plurality of different individual measures of completeness.

In some examples of any of the above medical treatment apparatus, the plurality of different individual measures of completeness includes two or more individual measures of completeness selected from the group consisting of: a pair of individual measures of completeness corresponding to different respective time instances of the PEF-energy delivery; a pair of individual measures of completeness corresponding to different respective types of measured values (e.g., temperature and impedance); a pair of individual measures of completeness corresponding to different respective subsets of the plurality of electrodes; and a pair of individual measures of completeness corresponding to different respective sets of displacement values.

In some examples of any of the above medical treatment apparatus, the processing circuit includes circuitry configured to generate a zoned PEF-energy effect map for an individual PEF-energy application point corresponding to the respective time instance based on the first measurement, the second measurement, the first displacement, and the second displacement.

In some examples of any of the above medical treatment apparatus, the circuitry is configured to generate a treatment completeness map by combining a plurality of zoned PEF-energy effect maps corresponding to different individual PEF-energy application points.

According to another example disclosed above, e.g., in the summary section and/or in reference to any one or any combination of some or all of <FIG>, provided is a therapy assessment method, comprising: receiving, with a processing circuit, a stream of therapy assessment measurements obtained with a plurality of electrodes of a catheter configured to deliver pulsed electric field (PEF) energy to a target tissue, the therapy assessment measurements including a first measurement taken prior to a respective time instance of PEF-energy delivery and a second measurement taken after the respective time instance; determining, with the processing circuit, a first displacement of the plurality of electrodes with respect to the target tissue between the first measurement and the respective time instance and a second displacement of the plurality of electrodes with respect to the target tissue between the respective time instance and the second measurement, the determining being based on position measurements received from a tracking system configured to track a position of a selected electrode of the plurality of electrodes; and estimating, with the processing circuit, a therapeutic effect of the PEF-energy delivery based on the first measurement, the second measurement, the first displacement, and the second displacement.

In some examples of the above therapy assessment method, the estimating is further based on one or more cardiac-cycle phases selected from the group consisting of: a first cardiac-cycle phase corresponding to the first measurement; a second cardiac-cycle phase corresponding to the time instant; and a third cardiac-cycle phase corresponding to the second measurement.

In some examples of any of the above therapy assessment methods, the estimating is further based on a time delay between a pair of consecutive pulses of the PEF energy in a sequence of pulses applied to the plurality of electrodes by a waveform generator.

In some examples of any of the above therapy assessment methods, the estimating is further based on a cumulative measure of completeness computed as a weighted sum of a plurality of different individual measures of completeness.

In some examples of any of the above therapy assessment methods, the estimating is further based on a cumulative measure of completeness computed as a weighted sum of a plurality of different individual measures of completeness.

In some examples of any of the above therapy assessment methods, the plurality of different individual measures of completeness includes two or more individual measures of completeness selected from the group consisting of: a pair of individual measures of completeness corresponding to different respective time instances of the PEF-energy delivery; a pair of individual measures of completeness corresponding to different respective types of measured values; a pair of individual measures of completeness corresponding to different respective subsets of the plurality of electrodes; and a pair of individual measures of completeness corresponding to different respective sets of displacement values.

In some examples of any of the above therapy assessment methods, the method further comprises generating, with the processing circuit, a zoned PEF-energy effect map for an individual PEF-energy application point corresponding to the respective time instance based on the first measurement, the second measurement, the first displacement, and the second displacement.

In some examples of any of the above therapy assessment methods, the method further comprises generating, with the processing circuit, a treatment completeness map by combining a plurality of zoned PEF-energy effect maps corresponding to different individual PEF-energy application points.

According to yet another example disclosed above, e.g., in the summary section and/or in reference to any one or any combination of some or all of <FIG>, provided is a non-transitory computer-readable medium storing instructions that, when executed by an electronic processor, cause the electronic processor to perform operations comprising any one of the above therapy assessment methods.

Computer-readable media may include non-transitory computer-readable media, which corresponds to a tangible medium such as data storage media (e. g, RAM, ROM, EEPROM, flash memory, or any other medium that can be used to store desired program code in the form of instructions or data structures and that can be accessed by a computer).

Claim 1:
A medical treatment apparatus, comprising:
a catheter having a plurality of electrodes configured to deliver pulsed electric field (PEF) energy to a target tissue and further configured for taking therapy assessment measurements in the target tissue including a first measurement and a second measurement;
a tracking system configured to track a position of a selected electrode of the plurality of electrodes or of a selected tracking element to determine a first displacement of the plurality of electrodes between the first measurement and a respective time instance of PEF-energy delivery and a second displacement of the plurality of electrodes with respect to the target tissue between the respective time instance and the second measurement; and
a processing circuit configured to estimate a therapeutic effect of the PEF-energy delivery based on the first measurement, the second measurement, the first displacement, and the second displacement,
wherein the first measurement is taken prior to the respective time instance; and
wherein the second measurement is taken after the respective time instance.