Index for lesion prediction and safety using pulsed field ablation

Abstract

The present disclosure relates to an apparatus for estimating a tissue ablation comprising: means for determining an impedance value associated with an electrode of an ablation catheter in contact with the tissue and connectable to the apparatus for applying one or more ablation pulses to the tissue; means for estimating a dimension of the tissue ablation based at least in part on the impedance value.

Description

[0001] INDEX FOR LESION PREDICTION AND SAFETY USING PULSED FIELD ABLATION

[0002] This international application claims priority to U.S. Provisional Application No. 63 / 565,661, filed March 15, 2024, entitled “Index for Lesion Prediction and Safety using Pulsed Field Ablation” and European Application No. 24172171.1, filed April 24, 2024, entitled “Index for Lesion Prediction and Safety using Pulsed Field Ablation” both of which are incorporated herein by reference in their entirety.

[0003] The present invention generally relates to an apparatus, a system and corresponding methods and a computer program.

[0004] In the medical field, various methods and devices for ablating a tissue are known. Usually, the tissue ablation may be performed for treating and / or preventing various diseases. For example, it is known to ablate cardiac tissue for treating cardiovascular diseases (e.g., cardiac arrythmias, such as atrial fibrillation, ventricular tachycardia, etc.). However, also other types of tissue may be ablated for medical purposes.

[0005] The tissue ablation process usually needs to be controlled in a defined way to ensure a desired medical outcome for the patient. Usually, a defined spatial characteristic and / or geometry of the ablated tissue may be needed to achieve a desired medical effect (e.g., to achieve an electrical isolation within a cardiac tissue and / or with respect to another tissue). To that regard, it may be necessary to estimate and / or determine a dimension of the ablated tissue that is evoked by the ablation process. For example, this may ensure that the ablated tissue is within a desired range. In another example, it may also be useful to know the geometric information of the ablated tissue for medical and / or technical purposes and to avoid overtreatment and / or damage to adjacent tissue as well.

[0006] A known approach for estimating a size of a lesion caused by a tissue ablation process requires to measure a contact force applied to the tissue by the probe that is inducing the ablation reaction. However, integrating a contact force sensor within an ablation apparatus (e.g., an ablation catheter) may comprise significant technical effort and / or may increase the technical complexity of the ablation apparatus and its system components. Moreover, the effects of the ablation procedure (e.g., a high voltage / current pulse applied during a pulsed field ablation PFA treatment and / or an alternating current applied during a radio frequency ablation RFA treatment) may interfere with the contact force measurement such that unreliable lesion sizes may be estimated in turn.

[0007] Hence, the currently known techniques do not always lead to an optimal estimation of the dimension of the ablated tissue. Therefore, there is a need to find ways to improve the estimation of the dimension of an ablated tissue.

[0008] The aspects described herein address the above need at least in part.

[0009] A first aspect relates to an apparatus for estimating a tissue ablation, in particular the size or dimension of the lesion created by the ablation. The apparatus may comprise means for determining an impedance value associated with an electrode of an ablation catheter in contact with the tissue and connectable to the apparatus. The apparatus may further comprise means for estimating a dimension of the tissue ablation based at least in part on the impedance value. The tissue ablation may be caused by one or more ablation pulses applied to the tissue by the electrode.

[0010] The invention may thus comprise to use the determined impedance value of an electrode of the ablation catheter to estimate the dimension of the tissue ablation.

[0011] For example, the ablation catheter may comprise one or more electrodes which may interact with the tissue to evoke an ablation of the tissue. For example, by establishing a contact of an electrode with the tissue, one or more ablation pulses may be coupled to the tissue via the electrode. An ablation pulse may, for example, comprise any type of pulse of an electrical energy that may cause an ablation in the tissue, at least in the vicinity of the electrode and / or in an effective area surrounding the electrode. However, the ablation reaction may not only depend on a characteristic of the ablation pulse but also on a property of the electrode that is applying the ablation pulse. To that regard, the ablation reaction may depend on an impedance value of the electrode that is applying the ablation pulse. The inventors have found out that in turn the impedance value of the electrode may be used to estimate the dimension of the ablated tissue.

[0012] The impedance value may comprise a contact impedance of the electrode. For example, the contact impedance may comprise a measured and / or determined impedance of the electrode when it is actually or supposed to be contacting a tissue to be ablated, e.g., when the catheter is in an ablation position. Hence, the resistive and / or conductive properties of the electrode may be referred to the tissue which may in turn function as a figure of merit to estimate the dimension of the tissue ablation. The contact impedance of the electrode may for example be measured and / or determined according to known principles in the art.

[0013] In an example, the apparatus for estimating may comprise a generator for generating one or more ablation pulses that may be coupled to the one or more electrodes of the connectable ablation catheter. The apparatus for estimating may thus also be configured to generate ablation pulses that can be coupled to the one or more electrodes of the ablation catheter. To enable such a function, the apparatus for estimating may comprise one or more terminals which may be connectable to the one or more electrodes of the ablation catheter. This may enable, for example, to apply an ablation pulse between at least two selected electrodes of the ablation catheter. In this case, the the apparatus for estimating may determine the impedance in a bipolar way. In addition or alternatively, an ablation pulse may be applied between at least one selected electrode and an unipolar ground electrode. In this case, the apparatus for estimating may determine the impedance in a unipolar way between the at least one electrode and the indifferent. In addition or alternatively an ablation pulse may be applied to all electrodes at one (e.g. multiple bipolar ablation pulses at the same time applied to all electrodes) and the apparatus for estimating may determine the impedance for each electrode by determining the current through each individual electrode.

[0014] Notably, the ablation catheter may be controlled such that the ablation pulse is provided between two electrodes in a near vicinity of the tissue (e.g., in a bipolar manner). However, the ablation catheter may also be controlled such that the ablation pulse is provided between two electrodes configured in a unipolar manner wherein one electrode is in the vicinity of the tissue and the other electrode functions as a counter electrode at a position removed from the near vicinity of the tissue.

[0015] Notably, in all arrangements described above the impedance value associated with at least one of the electrodes may be used to estimate the dimension of the tissue ablation.

[0016] The dimension of the tissue ablation may comprise a characteristic geometry of the ablated tissue. For example, the dimension may comprise an ablation depth of the ablated tissue with respect to a reference point (e.g., a tissue interface, an ablation catheter position, an electrode position etc.). The ablation depth (e.g., the penetration of the ablated tissue) may thus be estimated with respect to the reference point. For example, the ablation catheter may be positioned on the tissue, such that the electrode is substantially contacting the tissue on a tissue surface. In this case, the reference point of the ablation depth may be defined as a point of contact of the electrode on the tissue surface. It may also be conceivable that the reference point may be defined as another point of contact of the ablation catheter on the tissue surface (e.g., a point in between two electrodes of the ablation catheter).

[0017] In an example, the dimension of the tissue ablation may also comprise a diameter and / or length of the tissue ablation. In another example, the dimension of the tissue ablation may comprise a volume of the tissue ablation.

[0018] The ablation of the tissue, as described herein, may be understood as any type of ablation known in the field. For example, the ablation may comprise adapting a property of the tissue such that it can be considered ablated. Adapting a property of the tissue may for example comprise changing the permeability of the tissue, creating local pores in the tissue and / or causing cell death within the tissue (e.g., irreversible electroporation). For example, the ablation of the tissue may comprise a pulsed field ablation (PF A).

[0019] In an example, the means for determining may be configured to apply a test pulse to the at least one electrode to determine the impedance value when the ablation catheter is in an ablation position. The ablation position may comprise a position of the ablation catheter that is substantially equal to the position of the ablation catheter during the application of the one or more ablation pulses to the tissue. In the ablation position, it may be desired that at least the electrode (or electrodes) applying the ablation pulses should have a reliable contact with the tissue. However, the state of the contact of the electrode with the tissue may vary which may alter the evoked ablation reaction for the tissue. Hence, when the state of the electrode during an ablation procedure is not considered, the estimation of the dimension of the tissue ablation may be impaired. For example, the electrode may only be partly in contact with the tissue or not be in contact with the tissue at all. The state of the contact may also vary depending on the force the electrode is pressed against the tissue (e.g., via the positioning of the ablation catheter).

[0020] However, by determining the impedance value of the electrode when the ablation catheter is in the ablation position such effects can be reliably considered when estimating the dimension of the tissue ablation. Moreover, the state (e.g., impedance) of the electrode can be easily determined (in-situ) via the application of the test pulse without (necessarily) requiring further sensory components in the vicinity of the electrode. For example, the test pulse may comprise a pulse of an electrical energy (e.g., a voltage and / or current pulse) which, however, may not trigger an ablation of the tissue. In this case, the electrode may thus only apply a low energy pulse to the tissue causing no (significant) medical effect. The test pulse may thus be safely used for measurement purposes to determine the impedance value of the electrode.

[0021] In this example, the impedance value of the electrode may be understood as a contact impedance of the electrode with respect to the tissue. For example, the impedance value of the electrode may be determined based on applying the test pulse between the electrode and at least one reference electrode of the ablation catheter. Notably, the impedance value of one or more electrodes of the ablation catheter may be determined with respect to the same reference electrode to have comparable impedance values.

[0022] In this example, the means for determining may be configured for measuring a voltage and / or a current of the test pulse to determine the impedance value of the electrode according to known approaches in the art. For example, the means for measuring the voltage may measure the voltage applied between the electrode and the reference electrode during the test pulse. The means for measuring the current may measure the current flowing through the electrode and / or the reference electrode during the test pulse. Based on the measured voltage and the current an impedance value may be determined for the electrode.

[0023] The determined impedance value of the electrode may indicate the state of the contact of the electrode. For example, the ablation catheter may be positioned in a blood environment wherein it may be desired to (directly) contact a cardiac tissue with the one or more electrodes of the ablation catheter. In this case, the electrical conductivity of the cardiac tissue may be comparatively lower than the electrical conductivity of blood. Hence, a comparatively higher impedance value of the electrode (e.g., determined via the test pulse) may indicate that the contact of the electrode to the tissue is more pronounced than a comparatively lower impedance value of the electrode. However, the impedance value may not only qualitatively indicate the state of the electrode but may also be used as a quantitative value to estimate the dimension of the tissue ablation, as described herein.

[0024] In an example, the test pulse to determine the impedance value of the electrode may be applied before an ablation procedure. However, the test pulse may also be applied during an ablation procedure (e.g., in between ablation pulses) and / or after an ablation procedure. In addition or alternatively, the voltage and current of an applied therapeutic pulse during the ablation procedure may be used to determine the impedance value. This may ensure to track the impedance value over the course of the ablation procedure which in turn may be used to reliable estimate the dimension of the tissue ablation as described herein.

[0025] In an example, the means for estimating may be configured to estimate the impedance value based at least in part on a predetermined characteristic impedance value associated with the electrode. The predetermined characteristic impedance value may comprise a set value of the impedance value under ideal conditions. For example, it may be predetermined which impedance value of the electrode can be expected under an ideal condition. To illustrate an example, if the impedance value of the electrode is ideal, the impedance value may correspond to the predetermined characteristic impedance value. An ideal condition may, for example, comprise a reproducible condition of the electrode with respect to its environment. For example, an ideal condition may comprise that no interface perturbation of the electrode to the surrounding environment is present or likely. To that regard, the ideal condition may comprise a desired contact of the electrode to the tissue (e.g., when a defined area of the electrode is directly contacting the tissue and / or a defined pressure is applied to the electrode). The predetermined impedance value may be predetermined, for example, based at least in part on a simulation, gathered clinical data and / or calibration data. The predetermined characteristic impedance value may be stored in the apparatus for estimating. To that regard, the means for estimating may be configured to retrieve the predetermined characteristic impedance value when estimating the dimension of the tissue ablation. In an example, the means for estimating may be configured to estimate the dimension of the tissue ablation based at least in part on a comparison of the predetermined characteristic impedance value with the determined impedance value. In an example, the means for estimating may be configured to estimate the dimension of the tissue ablation based at least in part on a ratio of the predetermined characteristic impedance value with the determined impedance value.

[0026] In an example, the predetermined characteristic impedance value may comprise an impedance value of the electrode measured when the electrode has an ideal contact with the tissue and / or a corresponding tissue. For example, the predetermined impedance value may be based on a calibration measurement in a stable environment that enables a precise control of the ablation catheter and the measurement conditions (e.g., enabling a precise control of the electrode positioning and / or pressure applied to the electrode, stable tissue / environment conditions, etc.). The effort of a calibration measurement may not always be possible during a medical ablation procedure, for example, during a surgical procedure comprising the application of the ablation pulses onto a patient’s tissue. Hence, for estimating the dimension of the tissue ablation during a medical ablation procedure, it may suffice to determine the current impedance value and compare it with the (ideal) predetermined characteristic impedance value. Notably, the predetermined characteristic impedance value may be based on a calibration measurement with a corresponding tissue, for example, a tissue that may have similar characteristics as the tissue the ablation pulses are applied to for medical purposes. The corresponding tissue may thus comprise any suitable tissue (e.g., a corresponding animal tissue, a corresponding organic tissue, etc.).

[0027] In an example, multiple predetermined characteristic impedance values may be used. The multiple predetermined characteristic impedance values may be based on calibration measurements as set out above using ablation pulses at multiple frequencies (e.g. ablation pulses with different pulse lengths and / or delays between the pulses). In this example frequency dependent predetermined characteristic impedance values may be determined.

[0028] In an example, the means for estimating may be configured to estimate the dimension based at least in part on a first estimation term comprising: wherein Z may comprise the determined impedance value of the electrode, and Zo may comprise the predetermined characteristic impedance value. In an example, a may comprise a predetermined exponential impedance factor. For example, the predetermined exponential impedance factor a may be in the range of 0.3 to 3, in the range of 0.5 to 2, in the range of 0.7 to 1.3, or in the range of 0.8 to 1.2.

[0029] In an example where frequency dependent predetermined characteristic impedance values are available, the means for estimating may be configured to estimate the dimension based wherein Z(f) may comprise the determined impedance value of the electrode at a certain frequency, and Zo(f) may comprise the predetermined characteristic impedance value at a similar frequency, in particular at the same frequency. In an example, a may comprise a predetermined exponential impedance factor. For example, the predetermined exponential impedance factor a may be in the range of 0.3 to 3, in the range of 0.5 to 2, in the range of 0.7 to 1.3, or in the range of 0.8 to 1.2.

[0030] In an example, the first estimation term may comprise a mean value of all first estimation terms of a plurality of electrodes that may be involved in ablation. In another example, the estimation may comprise a separate estimation of the dimension for each electrode of the ablation catheter. In an example, the means for determining may be configured to determine the impedance value for each electrode of a plurality of electrodes of the ablation catheter. For example, the ablation catheter may comprise a first group of electrodes that may be connectable to a first terminal of the apparatus and a second group of electrodes that may be connectable to a second terminal of the apparatus. An electrical pulse (e.g., an ablation pulse and / or a test pulse) may be applied between the two terminals of the apparatus and thus between electrodes of two separate groups. The electrodes may be separately connectable to the corresponding terminals. Subsequently, an example is illustrated of determining an impedance value for each electrode. For example, an electrode of the first group may function as a reference electrode to the second group wherein the remaining electrodes of the first group are not connected to the terminal. Each electrode of the second group may thus form a (separate) circuit to the reference electrode of the first group. For each circuit, the impedance may be determined (e.g., based on a test pulse as described herein). Each determined impedance may be considered as an impedance value for the corresponding electrode of the second group. Subsequently, an electrode of the second group may function as a reference electrode to the first group wherein the remaining electrodes of the second group are not connected to the terminal. Each electrode of the first group may thus form a (separate) circuit to the reference electrode of the second group. For each circuit, the impedance may be determined (e.g., based on a test pulse as described herein). Accordingly, an impedance value for the electrodes of the first group may be derived. However, also other impedance values may be derived, for example, by using two or more electrodes of the respective other group as a (combined) reference electrode.

[0031] The means for determining may be further configured to determine a contact uniformity index based at least in part on the determined impedance value of each electrode, wherein the means for estimating is configured to estimate the dimension based at least in part on the contact uniformity index CU.

[0032] The contact uniformity index may be based on impedance measurement values of adjoining electrodes on the ablation catheter. The ablation catheter may be configured such that the adjoining electrodes comprise an electrode from the first group and an electrode from the second group. Thus, a (bipolar) impedance measurement between two adjoining electrodes (in a similar fashion as described above) may be implemented by the apparatus. The (bipolar) impedance measurement may be performed for all electrode pairs and may be used to determine the contact uniformity index.

[0033] In an example, the contact uniformity index may comprise comparing the standard deviation of the bipolar impedance measurement values with the mean value of the impedance measurement values. For example, the contact uniformity index may comprise: wherein o comprises the mean value of the impedance values between two adjoining electrodes and p comprise the standard deviation of the impedances between two adjoining electrodes.

[0034] In addition or alternatively, the contact uniformity index may comprise comparing the standard deviation of the impedance measurement value of each electrode with the mean value of the impedance measurement values, whereby the impedance measurement values for each electrode may be determined by the voltage and current at each electrode. In this example a quasi-unipolar impedance measurement may be used, where a pulse is applied to all electrodes simultaneously and the current through each electrode is determined. In this embodiment a test pulse or a therapeutic pulse may be used. For example, the contact uniformity index may comprise: o({Zn})

[0035] CU = 1 -

[0036] H({Zn})’ wherein o comprises the mean value of the impedance values of the electrodes and p comprise the standard deviation of the impedances of the electrodes. This embodiment would allow to calculate the contact uniformity during the ablation procedure using therapeutic pulses. To that regard, the means for estimating may be configured to estimate the dimension based at least in part on the contact uniformity index CU. For example, the herein described first estimation term may comprise: CUa, wherein a may comprise the predetermined exponential impedance factor as described herein.

[0037] Notably, also other contact uniformity derivation may be conceivable for estimation of the dimension.

[0038] In an example, the means for estimating may be further configured to estimate the dimension based at least in part on an electrical parameter of the ablation pulse. As described herein, the ablation pulse may comprise a pulse of an electrical energy and may thus comprise various electrical parameters. For example, the means for determining may be configured to determine one or more electrical parameters of the ablation pulse. For example, the means for determining may be configured for measuring a voltage and / or a current of the ablation pulse to determine one or more electrical parameters of the ablation pulse (e.g., in a similar fashion as when measuring the voltage / current of the test pulse as described herein). Hence, the means for estimating may, in turn, use the one or more electrical parameters of the ablation pulse to estimate the dimension of the tissue ablation based thereon. In an example, the means for estimating may thus estimate the dimension based at least in part on the impedance value of at least one electrode and one or more electrical parameters of the ablation pulse. In some examples the electrical parameter may not be determined based on measurements but instead a preset value of the apparatus may be used (e.g., if the apparatus is set to apply a pulse with a certain parameter, this parameter may be used).

[0039] In an example, the means for estimating may be configured to estimate the dimension based at least in part on a characteristic voltage and / or a duration of the ablation pulse. For example, the characteristic voltage may comprise a voltage amplitude of the ablation pulse. In an example, the characteristic voltage may also comprise a peak-to-peak voltage of the ablation pulse and / or an RMS voltage of the ablation pulse (e.g., a square root of the mean square of instantaneous values of the voltage of the ablation pulse). In another example, the means for estimating may be configured to estimate the dimension based at least in part on a characteristic current. For example, the characteristic current may comprise a current amplitude of the ablation pulse. In an example, the characteristic current may also comprise a peak-to-peak current of the ablation pulse and / or an RMS current of the ablation pulse.

[0040] Notably, the characteristic voltage and / or current, as well as the duration of the ablation pulse may be considered electrical parameters of the ablation pulse and may thus be determined by the means for determining (as described herein).

[0041] In an example, the means for estimating may be configured to estimate the dimension based at least in part on a predetermined linear factor associated with the ablation catheter that is multiplied by the characteristic voltage. For example, if a certain characteristic voltage was determined, the means for estimating may be configured to multiply the determined characteristic voltage by the predetermined linear factor. In an example, the multiplication of the characteristic voltage by the predetermined linear factor may be considered a second estimation term. Notably, the means for estimating may be configured to estimate the dimension by multiplying the first estimation term by the second estimation term. In an example, the result may be a first estimation result. It may also be conceivable that only the second estimation term may (or the first estimation term) may function as an estimation result.

[0042] In an example, the predetermined linear factor may comprise a first predetermined linear factor component and a second predetermined linear factor component. The first predetermined linear factor component may comprise a linear factor that was determined based on a reference ablation catheter. For example, it may be conceivable that the first predetermined linear factor component may be based on a simulation with a simulated reference ablation catheter and a simulated tissue. In that case, the first predetermined linear factor component may be determined based on a linear regression of simulation results showing the dimension of the tissue ablation (e.g., the ablation depth) as a function of the simulated characteristic voltage (e.g., the voltage amplitude). Notably, the inventors have found out that the dimension of the tissue ablation (e.g., the ablation depth) may scale linearly with voltage (e.g., a constant voltage amplitude) applied to a (simulated) tissue.

[0043] However, the linear scaling factor may also depend on the ablation catheter type and / or its electrode configuration. For example, the linear scaling factor may vary depending on the spacing of the electrodes, the dimensions of the electrodes, etc. It may also be conceivable that the linear factor varies depending on the alignment of the ablation axis of the ablation catheter comprising the electrodes (e.g., a circular ablation axis alignment, a spiral shape ablation axis alignment, a linear shape ablation axis alignment, etc.). The second predetermined linear factor component may take into account these effects of catheter type and / or electrode configuration. Notably, the second predetermined linear factor component may also be determined based on a simulation in a similar fashion as determining the first predetermined linear factor.

[0044] Accordingly, the means for estimating may, for example, be configured to estimate the dimension based at least in part on the predetermined linear factor comprising: s • c , wherein s comprises the first predetermined linear factor component (for example in units of ablation depth / voltage, e.g. mm / V) and c comprises the second predetermined linear factor component. Notably, the second predetermined linear factor component may be normalized to unity for an ablation catheter of the reference ablation catheter type. As stated herein, the second estimation term may thus comprise: s • c • V, wherein V comprises the characteristic voltage (e.g., the voltage amplitude of the ablation pulse).

[0045] For example, the predetermined linear factor (and / or the first and second predetermined linear factor components) may be stored in the apparatus for estimating.

[0046] Since the linear scaling factor(s) depend on the electrode configuration and the catheter type, the electrode configuration (and / or ablation catheter type) may be coded in the catheter, e.g., in a chip carried by the catheter. In an example, ID resistors may be used to differentiate catheter configuration. A measurement block of the apparatus for estimating may be configured to read the information regarding electrode configuration and / or ablation catheter type, for example, the catheter ID information. Depending on the electrode configuration (and / or ablation catheter type) the according second predetermined linear factor component may then be used by the means for estimating in the second estimation term to estimate a dimension of the tissue ablation. In other examples, no first and second linear factors may be used, but simply a single factor may be used specific for each catheter.

[0047] In an example, the means for estimating may be configured to estimate the dimension based at least in part on a number of ablation pulses of one or more ablation pulse trains and / or an effective pulse duration associated with the number of ablation pulses of the one or more ablation pulse trains. For example, an ablation pulse train may comprise one or more ablation pulses. The ablation pulses of an ablation pulse train may be spaced apart (substantially) equal in time. It may be conceivable that during an ablation procedure various pulse trains may be applied to the tissue. Hence, the invention may consider that this dynamic input to the tissue has a direct effect on the dimension of the tissue ablation.

[0048] For example, the dimension may depend on the total number of ablation pulses applied to the tissue, wherein the total number of ablation pulses may be applied via more than one ablation pulse train. For example, the ablation procedure may comprise ten ablation pulse trains wherein each ablation pulse train comprises ten ablation pulses. In this example, the total number of ablation pulses of the one or more ablation pulse trains thus comprises one hundred ablation pulses.

[0049] The effective pulse duration may comprise the sum of all pulse durations of the ablation pulses of the one or more pulse trains. The effective pulse duration may thus be considered a total time period for which the tissue has experienced the effect of all ablation pulses. For example, the ablation pulses of the ablation pulse trains may comprise a pulse duration of 1 ps. Considering such a pulse duration for the above-described example, that comprises in total hundred ablation pulse trains the effective pulse duration for said example comprises 100 ps. In an example, the means for estimating may be configured to estimate the dimension based at least in part on a predetermined model comprising that the dimension approaches a maximum value as the number of ablation pulses applied to the tissue increases. Notably, the inventors have found out that the number of ablation pulses and / or the effective pulse duration of the one or more ablation pulse trains may not constitute a linear effect as the number of ablation pulses increases. It was found out that the dimension of the tissue ablation eventually may saturate and that the dimension of the tissue ablation may approach a maximum value. Hence, considering this effect in the predetermined model may enable a reliable estimation of the dimension.

[0050] In an example, the predetermined model may be based at least in part on a term comprising a predetermined time constant such that when the effective pulse duration reaches the predetermined time constant at least sixty percent of the maximum value of the dimension is ablated. The predetermined time constant may comprise a range between 50 ns and 50 ms, preferably between 100 ps and 10 ms, more preferably between 500 ps and 2 ms, most preferably between 800 ps and 1.5 ms. These time constants may be applicable to PF A pulses applied to myocardium.

[0051] The predetermined model may be based on a simulation with a simulated reference ablation catheter and a simulated tissue. The simulation may be based on applying a dynamic input to the tissue comprising a number of ablation pulses. For example, the predetermined time constant may be determined based on a plot depicting the simulation results showing the simulated characteristic voltage (e.g., the voltage amplitude) and the corresponding dimension of the tissue ablation (e.g., the ablation depth). Based thereon a curve fit may be implemented assuming an approach to a maximum value of the dimension.

[0052] In an example, a third estimation term may be derived from the predetermined model and / or the corresponding simulation. The third estimation term may comprise the term wherein T comprises the effective pulse duration and To comprises a predetermined time constant. The predetermined time constant (as described herein) may also be derived based on the predetermined model and / or the curve fit of the simulation results. In another example, the third estimation term may comprise the term wherein N comprises the number of ablation pulses and No comprises a predetermined ablation number constant. No may depend on the pulse duration.

[0053] In an example, the means for estimating may be configured to estimate the dimension based at least in part on a multiplication of the first estimation term, the second estimation term and the third estimation term. For example, the means for estimating may be configured to estimate the dimension based at least in part on the according multiplication term:

[0054] Therefore the estimated dimension of the tissue ablation may be calculated as a dimension (e.g. as an index for the ablation procedure) in mm as:

[0055] In an example, the apparatus may be configured to display the estimated dimension before, during and / or after the application of one or more ablation pulses to the tissue. For example, the apparatus may be configured to receive a set of ablation parameters associated with an ablation procedure. For example, the set of ablation parameters may comprise parameters used for an ablation procedure to be implemented. Notably, the set of ablation parameters may comprise information regarding the one or more ablation pulses to be applied to the tissue to estimate the dimension of the tissue ablation as described herein. For example, the set of ablation parameters may comprise an electrical parameter of the ablation pulse (e.g., a voltage amplitude), a number of ablation pulses in a pulse train, a number of pulse trains, etc. To that respect, the means for estimating may be configured to estimate the dimension based on the herein described concepts and the received set of ablation parameters. For example, after or prior to receiving the set of ablation parameters the impedance of the one or more electrodes of the ablation catheter may be determined as described herein. Subsequently, the apparatus may then display the accordingly estimated dimension. However, the apparatus may also be configured to display the estimated dimension during the application of the one or more ablation pulses. For example, during the ablation procedure the means for estimating may be configured to estimate the dimension as the ablation procedure progresses. For example, the estimated dimension may be updated after an ablation pulse train has been applied (and / or after each ablation pulse). This may enable that the medical personnel accompanying the ablation procedure may view the progress of the ablation procedure in real time on the apparatus. If necessary, the medical personnel may intervene and, for example, abort the ablation procedure. It may be conceivable that for an estimation during the ablation procedure, the impedance value of the electrode is not determined for each pulse but only the initially determined impedance value (e.g., prior to the ablation procedure) may be used for the estimation. However, in another example, an impedance of the one or more electrodes may be determined during the ablation procedure. For example, such an impedance may be derived from measured voltage and current characteristics of the ablation pulses and / or applying test pulses to determine the impedance during the ablation procedure.

[0056] Notably, after the ablation procedure is finished, the apparatus may display the estimated dimension associated with the total ablation procedure. The medical personnel may thus be informed about the estimated dimension of the tissue ablation accomplished with the ablation procedure. If necessary, a further ablation sequence may be triggered, for example, to further increase the dimension of the ablated tissue.

[0057] The estimated dimension may be displayed on a general user interface comprised by the apparatus for estimating. The general user interface may, for example, comprise a monitor and / or a touchscreen sensitive monitor display.

[0058] In addition or alternatively, the estimated dimension may also be communicated to another system, in particular to mapping system. The mapping system, in particular an electo- anatomical mapping system, is to be understood as system configured to map and display the anatomical structure of the treatment region. The mapping system may be further configured to localize and display the position, in particular in real time, of the catheter within the treatment region. The estimated dimension may be displayed in the anatomical structure of the treatment region.

[0059] The apparatus may be configured to receive information regarding the position of the ablation catheter with respect to the anatomy of the treatment region from the mapping system. The position information may in particular comprise information regarding the contact or distance of the ablation catheter, in particular the ablation section of the ablation catheter, with the or to the tissue to be treated. The position information may be used in addition to the impedance information for estimating a dimension of the tissue ablation.

[0060] In an example, the apparatus may be configured to compare the estimated dimension with a preset dimension during a tissue ablation procedure and / or to control the tissue ablation procedure based on the comparison. For example, the preset dimension may be received by the apparatus prior to the ablation procedure. As described herein, the dimension may be estimated during the ablation procedure in various ways.

[0061] In some examples, in combination with the preset dimension, a control loop can be formed. For example, the control may be based on an open loop control and / or a closed loop control.

[0062] In another example, the apparatus may be configured to compare the estimated dimension with a preset dimension during a tissue ablation procedure without (necessarily) implementing a control. For example, if the preset dimension is reached in this case an alarm may be triggered (e.g., a sound, a visual display on the general user interface). In another example, if there is a discrepancy between the estimated and the preset dimension, application of a pulse may be aborted (in particular if the estimated dimension would exceed the preset dimension).

[0063] A second aspect relates to a system comprising an apparatus of the first aspect and an ablation catheter connectable to the apparatus.

[0064] A third aspect relates to a method for estimating tissue ablation dimension comprising: determining an impedance value associated with an electrode of an ablation catheter in contact with the tissue; estimating a dimension of the tissue ablation based at least in part on the impedance value.

[0065] A fourth aspect relates to a method for calibrating an apparatus for estimating a tissue ablation dimension comprising: measuring an impedance value associated with an electrode of an ablation catheter connectable to the apparatus when the electrode has an ideal contact with the tissue and / or a corresponding tissue; storing the impedance value on the apparatus.

[0066] In an example, the apparatus of the method of the fourth aspect may comprise the apparatus of the first aspect as herein described.

[0067] In an example of the fourth aspect, the method may comprise storing the measured impedance value as a characteristic impedance value associated with the ablation catheter and / or a type of the ablation catheter on the apparatus.

[0068] In an example of the fourth aspect, the method may comprise measuring the impedance value for each of the electrodes of the ablation catheter and wherein each impedance value is stored as the characteristic impedance value of the corresponding electrode of the ablation catheter and / or the type of the ablation catheter on the apparatus.

[0069] In an example of the fourth aspect, the method may comprise measuring the impedance value for each of the electrodes of the ablation catheter for at least two ablation catheters and / or at least two types of ablation catheters. In an example, the method may further comprise storing the measured impedance values as characteristic impedance values for the corresponding ablation catheter and / or type of ablation catheter.

[0070] A fifth aspect relates to a computer program comprising instructions that when executed by a computer, an apparatus according to the first aspect, and / or a system according to the second aspect cause the computer, the apparatus and / or the system to perform a method according to the third aspect and / or a method according to the fourth aspect. In an example, the apparatus of the first aspect may comprise a computer. The computer program may comprise instructions that may cause the performing of various other tasks, control functions and / or data analysis of the apparatus and / or the system as described herein. The computer may comprise one or more storage devices that may store one or more instructions that may be executed by the computer to perform the herein described functions of the apparatus and / or system via corresponding method steps.

[0071] It is noted that the method steps as described herein may include all aspects described herein, even if not expressly described as method steps but rather with reference to an apparatus (or system or computer). Moreover, the apparatuses, systems and computer programs as outlined herein may include means for implementing all aspects as outlined herein, even if these may rather be described in the context of method steps.

[0072] Whether described as method steps, computer program and / or means, the functions described herein may be implemented in hardware, software, firmware, and / or combinations thereof. If implemented in software / firmware, the functions may be stored on or transmitted as one or more instructions or code on a computer-readable medium. Computer-readable media include both computer storage media and communication media including any medium that facilitates transfer of a computer program from one place to another. A storage medium may be any available media that can be accessed by a general purpose or special purpose computer. By way of example, and not limitation, such computer-readable storage media can comprise RAM, ROM, EEPROM, FPGA, CD / DVD or other optical disk storage, magnetic disk storage or other magnetic storage devices, or any other medium that can be used to carry or store desired program code means in the form of instructions or data structures and that can be accessed by a general-purpose or special-purpose computer, or a general-purpose or special-purpose processor.

[0073] Fig. 1 : Simulations results of a simulated ablation catheter applying a static voltage to a simulated tissue showing an electrical field distribution in the simulated tissue evoked by the voltage application. Fig. 2: Simulation results of a simulated ablation catheter applying a static voltage to a simulated tissue showing three simulated static voltages and the corresponding ablation depth, as well as a linear regression based thereon.

[0074] Figs. 3a / b: An exemplary embodiment of an ablation catheter that was used for the simulation model of the simulation of Fig. 2.

[0075] Fig. 4: Experimental results of an ablation catheter applying voltage pulses via pulse trains to potato tissue showing four values of pulse trains and the corresponding ablation depths, as well as a fitted curve based thereon.

[0076] Fig. 5: Schematic representation of an exemplary ablation procedure implemented by the apparatus for estimating comprising an estimation of the ablation depth according to the invention.

[0077] Fig. 6: Representation of exemplary estimated ablation dimension as derived by an exemplary ablation procedure

[0078] Fig. 1 shows simulations results of a simulated ablation catheter applying a static voltage to a simulated tissue. Specifically, Fig. 1 shows an electrical field distribution E (V / cm) in the simulated tissue evoked by the voltage application via two electrodes of the ablation catheter as a function of tissue depth d (mm), for various distances between the two electrodes. Fig. 1 can thus illustrate how a dimension (here: depth) of a tissue ablation may vary depending on the electrode configuration of the ablation catheter. The simulation was based on a finite element method (FEM) simulation.

[0079] For the simulation, a 4000 V potential difference was applied between the two electrodes that are in contact with the outer surface of the tissue. The x-axis of the diagram of Fig. 1 shows a distance d starting from a reference point in the middle of the two electrodes in the catheter section and extending perpendicular into the tissue. The distance d may thus be referred to as tissue depth d. The y-axis of the diagram shows the electrical field. Fig. 1 can illustrate the electrical field depending on the tissue depth d (in the plane perpendicular to the catheter section in the middle of the two electrodes) for variable electrode distances. The electrical field is shown for the electrode distances 101, 102, 103, 104. The electrode distance 101 in the simulation was 0.1 mm, the electrode distance 102 in the simulation was 1.1 mm, the electrode distance 103 in the simulation was 3.1 mm, the electrode distance 104 in the simulation was chosen as 5.1 mm.

[0080] Fig. 1 may indicate a trend how the dimension of the ablated tissue may vary depending on the electrode distance between two electrodes. Since the simulated electrical field of the simulation shows the electrical field depending on the tissue depth it may thus indicate the penetration depth of the tissue ablation caused by an electrical pulse applied to the tissue. For example, for an ablation of tissue to occur it may be necessary that a certain ablation threshold of an electrical field is reached within the tissue. For example, an irreversible electroporation may require that the electrical field of targeted tissue is increased beyond a value of approximately 500 V / cm to irreversibly damage the tissue and thus cause an ablation. The ablation threshold may depend on the type of tissue which may comprise a cardiac tissue, for example, the myocardium. For example, the ablation threshold may also comprise 350 V / cm, 400 V / cm, 600 V / cm, 700 V / cm, etc.

[0081] For example, in Fig. 1 electrical fields above 500 V / cm may indicate that an ablation of the tissue occurs in the corresponding tissue depth d. The tissue depth d where the electrical field equals the ablation threshold (e.g., 500 V / cm) may thus be considered the ablation depth. As can be seen in the results with increasing electrode distance the ablation depth increases. In medical practice the ablated tissue (as described herein) may be referred as a lesion. Thus, the simulation can be used to check for the transmurality of a lesion to gain an understanding of the lesion geometry within the tissue. For example, assuming an ablation threshold of 500 V / cm of the tissue and an ablation catheter with an electrode distance between two electrodes of 1.1 mm (electrode distance 102) the ablation depth (i.e., lesion depth) may be approximately 5 mm based on the simulation results of Fig. 1 (with 4000 V applied between two electrodes).

[0082] The simulations as described herein may be used to derive parameters, factors and / or fit curves that may be used to estimate the dimension of the ablated tissue (as described herein). Fig. 2 shows simulation results of a simulated ablation catheter applying a static voltage to a simulated tissue showing three simulated static voltages and the corresponding ablation depth, as well as a linear regression based thereon. The simulation model was based on the ablation catheter C shown in Fig. 3a / b. As can be seen in Fig. 3a, the ablation catheter modeled in the simulation was a ring ablation catheter (also referred as circular ablation catheter) with its main axis comprising the electrodes E that are aligned in a circular (i.e., ring) shape. Fig. 3b shows that the ablation catheter comprises eight ablation electrodes 302. The distance 303 between two ablation electrodes 302 is 4 mm. The diameter 301 of the ring is 23 mm. For a medical ablation procedure, the ablation catheter C may be positioned in a cylindrical cavity (e.g., a vein and / or an artery) to ablate the circumference of the tissue surrounding the cylindrical cavity. For example, the ablation catheter may be positioned in the pulmonary vein for an ablation procedure.

[0083] The ring (circular) type structure of the ablation catheter C with its electrodes 302 was modeled in the simulation of Fig. 2 wherein the ablation catheter C was placed in a cylindrical environment to simulate the electrical field applied radially to the surrounding tissue.

[0084] Coming back to Fig. 2, the simulation results show the ablation depth depending on three static voltages applied between two adjoining electrodes of the ablation catheter (wherein the electrode distance between adjoining electrodes was chosen as 4 mm to model the ablation catheter of Fig. 3). The corresponding ablation depth (i.e., lesion depth) was based on an ablation threshold of 400 V / cm.

[0085] As can be seen in Fig. 2 the lesion depth scales approximately linearly with the applied voltage. A linear regression was performed based on the three simulation results. The corresponding linear curve was also plotted in Fig. 2. Hence, the slope s of the linear curve can be used as a scaling factor to estimate the ablation depth for a particular voltage applied via the ablation catheter. It was found out that the slope s (in units of [mm / V]) may range from 0.001 to 0.003, preferably from 0.0015 to 0.0025. It is noted that the results shown in Fig. 2 for the catheter shown in Fig. 3a / b are merely exemplary, and similar results can be obtained for other catheters.

[0086] Notably, the linear curve and the slope s may be specific to the electrode configuration of the ablation catheter (e.g., the slope s may depend on the distance between two (adjoining) electrodes). The slope s may be considered the first predetermined linear factor component as described herein. The slope s may thus be associated with a reference catheter type and / or a reference electrode configuration. For a different electrode configuration and / or a different ablation catheter type a different linear scale may be present. This effect may be considered via a second predetermined linear factor component (as described herein) that may be multiplied by the first predetermined linear factor.

[0087] The second predetermined linear factor component may depend on the electrode configuration (e.g., a distance between electrodes, an electrode area, a type of electrode) and / or the ablation catheter type (e.g., a circular catheter, a linear catheter, an elliptical catheter). For example, the second predetermined linear factor component c may be in the range of 0.5 to 2, preferably in the range of 0.8 to 1.2. The second predetermined linear factor may be determined based on a further simulation model that comprises the corresponding electrode configuration and / or ablation catheter type. It may also be conceivable that the second predetermined component may be derived based on a mathematical relationship that, for example, considers the effect of the adapted electrode spacing to the linear characteristics of the first predetermined linear factor component. As described herein, this may result in the second estimation term: s • c • V, wherein V may comprise the voltage amplitude of the ablation pulse.

[0088] The electrode configuration (and / or ablation catheter type) may be coded in the catheter, e.g., in a chip carried by the catheter. In an example, ID resistors may be used to differentiate catheter configuration. A measurement block of the apparatus for estimating (e.g., a PFA generator) may be configured to read, for example, the catheter ID information. Such information may then be passed to a central processing unit CPU of the apparatus for estimating. Depending on the electrode configuration (and / or ablation catheter type) the according second predetermined linear factor component may then be used by the means for estimating in the second estimation term to estimate a dimension of the tissue ablation. In other examples, no first and second linear factors may be used, but simply a single factor may be used specific for each catheter.

[0089] Fig. 4 shows experimental results of an ablation catheter applying voltage pulses via pulse trains to potato tissue showing four values of pulse trains and the corresponding ablation depths, as well as a fitted curve based thereon. Notably, the ablation threshold (e.g., for a pulsed field ablation PFA procedure) may be dependent on the pulse duration and the number of pulses applied to the tissue. The FEM simulations of Fig. 1 and 2 were carried out statically, i.e., the electric field was evaluated from a constantly applied potential difference. Usually, when ablating a tissue via an ablation pulse (e.g., for a PFA procedure) more than one ablation pulse may be applied to the tissue. For example, the ablation pulses may be applied in pulse trains wherein each pulse train may comprise various ablation pulses with a certain pulse duration. The duration of an ablation pulse may range from 1 ns to 900 ms. To consider the effects of the dynamic application of pulses, a factor may need to be applied to the estimation based on static assumptions that takes into account the effective duration of the ablation procedure. The inventors have found out that this factor may approach unity for large pulse durations and / or a larger number of pulses. Hence, the dimension of the tissue ablation (e.g., the ablation depth) may approach a maximum value as the number of pulses and / or the pulse duration increases.

[0090] This effect can be seen in Fig. 4. The x-axis of the diagram shows the number of pulse trains. The y-axis shows the corresponding lesion depth. In the experiment, each pulse train was comprised of twenty pulses. The voltage amplitude of a pulse was chosen as 2000 V. Each pulse duration was chosen as 2 ps. The experimental results were fitted by a fitting curve. The fitting curve considers that the lesion depth approaches a maximum value as the number of pulses (and / or pulse trains) increases. The fitting curve may thus be used as a model to estimate the lesion depth for a given dynamic input to the tissue, wherein the model comprises that the dimension approaches a maximum value as the number of ablation pulses applied to the tissue increases. For example, the pulse durations of the total number of pulses applied to the tissue can be added up to an effective pulse duration T. The inventors have found out that the fitting curve may thus be described as a third estimation term 1 - e-^, wherein T comprises the effective pulse duration and To comprises a predetermined time constant. For cardiac tissue the fitting time constant To may be between 100 ps and 10 ms, preferably between 500 ps and 2 ms.

[0091] Notably, the duration of a pulse may only be equal to its width when applying rectangular pulses. When using e.g. exponentially decaying pulses or sinusoidal pulses the effective pulse duration has to be reduced accordingly to take into account the reduced effect on the transmembrane potential, which in turn results in reduced efficacy of ablation.

[0092] The second estimation term and / or the third estimation term may be based on simulation results. However, the invention considers that in an actual ablation procedure the state of the electrodes may not (always) be perfectly positioned and / or may vary. The effect of the impedance value of the one or more electrodes of the ablation catheter may be considered via the first estimation term as described herein.

[0093] For example, the first estimation may take into account scenarios where one or more electrodes are not in contact with the tissue but e.g. have a distance of up to 2 mm. To that regard, one can measure the impedance Z of each electrode (e.g., as described herein). The ( z \aresulting lesion depth may then be given by the first estimation term: I — I . Zo may \Z0Z comprise the predetermined characteristic impedance value for each individual electrode assuming ideal contact with the tissue (which e.g., may depend on electrode length, radius and / or thickness). In an example, a may comprise an empirical dimensionless factor which may also be referred to herein as a predetermined exponential impedance factor. For example, the predetermined exponential impedance factor a may be in the range of 0.3 to 3, preferably in the range of 0.7 to 1.3, more preferably in the range of 0.8 to 1.2. In another example a may be in the range of 0.5 to 2, preferably in the range of 0.7 to 1.3. Zo may be measured either by applying a non-therapeutic PFA pulse with identical pulse shape as the therapeutical pulse (e.g., using voltages of 100 to 500 V) or a sinusoidal testpulse with a frequency in the range of 1 kHz to 1 MHz, preferably 10 kHz to 500 kHz.

[0094] To enable an estimation via the first estimation term, the impedance value Z has to be within a certain range. It may also be conceivable that the contact uniformity index CU (as described herein) has to be greater than 0.6, preferably 0.7, more preferably, 0.8, most preferably 0.9, for example in order to accept the estimation.

[0095] In another example, the contact uniformity (index) may be comprised in the first estimation term as CUa. To give valid values in that example, the apparatus may be configured to implement additional checks to avoid e.g. the case where CU ~ 1 and none of the electrodes are in contact with the tissue. The additional checks may be assisted by medical and / or technical personnel accompanying the ablation procedure. For both definitions of the first estimation, the same ranges of the predetermined exponential impedance factor a may apply.

[0096] As described herein, the first, second and / or third estimation term may be used by the means for estimating to estimate, for example, the lesion depth for an ablation procedure. In an example, the lesion depth may correspond to the multiplication of the first, second and third estimation term.

[0097] Fig. 5 shows a schematic representation of an exemplary ablation procedure implemented by the apparatus for estimating comprising an estimation of the ablation depth according to the invention. The schematic representation may thus represent a method which may be executed using at least the apparatus for estimating and a connectable ablation catheter. As described herein, the apparatus for estimating may also be configured as a generator for generating ablation pulses for the ablation catheter.

[0098] Initially, the method may comprise placing 501 the catheter at a target tissue. The target tissue may comprise a tissue where the ablation should take place. Subsequently, the method may comprise selecting 502 a target PFA lesion depth. The lesion depth may, for example, be selected from a general user interface of the apparatus displaying various possible lesion depths. In another example, a (freely chosen) lesion depth may be inputted to the apparatus (via the general user interface). Notably, the selecting 502 may comprise receiving a lesion depth by the apparatus. Steps 501 and 502 may be interchanged. This also applies to further steps shown in Fig. 5 whenever this is technically meaningful, even though this may not be expressly stated in all instances.

[0099] Subsequently, the method may comprise beginning 503 PFA treatment. The beginning 503 of the PFA treatment may be initiated by the medical / technical personnel via an input to the apparatus for estimating.

[0100] A first step of the PFA treatment phase may be executing 504 one or more subtherapeutic test pulses for measuring one or more electrode impedances of the ablation catheter. The impedances of the one or more electrodes may be measured as described herein.

[0101] Subsequently, an assessing 505 of the (one or more) impedances of the electrodes and / or the contact uniformity index (as described herein) may be performed. The assessing may comprise whether the (one or more) impedances and / or contact uniformity index is within a specified range. If this is the case the ablation procedure may be initiated and ablation pulses may be applied to the tissue, e.g., in the form of ablation pulse trains. However, when the impedances and / or the contact uniformity index are not within the specified range the method may comprise aborting 509 the ablation. Subsequently, an assessing 510 may be performed, wherein the assessing 510 may comprise checking whether the one or more electrodes are broken. If it is determined that the electrodes are not broken, the method may comprise repositioning 511 the catheter. Subsequently, the method step of beginning 503 the PFA treatment may be initiated again. If it is determined that the electrodes are broken, the method may comprise replacing 512 the catheter. Afterwards the method may comprise placing 501 the replaced catheter at the target tissue and continuing accordingly with the method.

[0102] Coming back to the step of assessing 505 of the (one or more) impedances of the electrodes and / or the contact uniformity index. If the assessment is positive (i.e., the impedances and / or contact uniformity index being within a specified range) ablation pulses may be applied to the tissue. In that case, the method may comprise the step of measuring 506 a voltage and / or current and / or (total) pulse duration while ablating. For example, the method may comprise measuring the voltage and / or current of the ablation pulses. Based thereon a characteristic voltage and / or current of the ablation pulses may be determined (e.g., a voltage amplitude of an ablation pulse, a current amplitude of an ablation pulse). The measuring of the pulse duration may comprise measuring the duration of a single ablation pulse. It may also comprise determining the effective pulse duration (as described herein) based on the measured duration of each single ablation pulse applied.

[0103] Notably, the measured voltage and / or current of the ablation pulses may be used to determine one or more impedances of the electrodes while ablating. For example, for each ablation pulse one or more impedances may be determined. Also in between ablation pulses, one or more test pulses may be applied (e.g., in a similar fashion as the subtherapeutic test pulses of step 504 and / or as otherwise described herein) that may not (necessarily) cause a tissue ablation. The voltage and / or current of the one or more test pulses may be measured to determine the impedance of the one or more electrodes during the time the ablation pulses are applied to the tissue.

[0104] Hence, during the ablation process various parameters may be measured and / or determined in real time. These parameters may be received by the means for estimating to estimate the ablation depth (as described herein) in real time during the ablation process. In Fig. 5 said step of the method, namely, estimating the dimension of the tissue ablation (e.g., the lesion depth) is not shown. For example, the means for estimating may estimate the lesion depth based on the characteristic voltage (e.g., voltage amplitude), characteristic current and / or the pulse duration determined in the step 506. For example, the means for estimating may estimate and / or refresh the estimation of the ablation depth after each ablation pulse that is applied to the tissue. The means for estimating may also estimate and / or refresh the estimation of the ablation depth after an ablation pulse train was applied to the tissue. The estimation may use the electrode impedance(s) determined in step 504. Additionally or alternatively, also impedance(s) determined in step 506 may be used.

[0105] The method may also comprise the step of assessing 507 whether the lesion depth was reached. The lesion depth of step 507 may comprise the lesion depth selected in step 502. For example, in step 507 the selected lesion depth may be compared with the estimated lesion depth. If the estimated lesion depth is smaller than the selected lesion depth the lesion depth according to step 507 was not reached. In that case, the method may comprise the subsequent step of applying 508 one or more pulse trains. The applying 508 may be accompanied by the step of measuring 506 as described herein.

[0106] Step 507 may comprise the assessment that the lesion depth is reached. For example, the estimated lesion depth may be equal to the selected lesion depth (to within a certain threshold) and / or be higher than the selected lesion depth.

[0107] Subsequently, the method may comprise the step of ending 550 the PF A treatment. The ending 550 may be implemented automatically. For example, by the apparatus for estimating. However, the ending 550 may also be performed manually by an operator. For example, the estimated lesion depth may be displayed during the ablation procedure on the general user interface of the apparatus. The operator may judge whether the desired lesion depth is reached and may then manually end the ablation procedure.

[0108] Fig 6 shows an exemplary representation of a graphic user interface as part of an apparatus for estimating an ablation dimension (e.g. an estimated ablation depth). A schematic representation of the distal ablation section 601 of an ablation catheter is displayed at the treatment location at the ostium of the pulmonary vein 602. The apparatus is configured to receive information regarding the anatomical structure of the treatment region as well as the position of the ablation catheter with respect to the anatomy of the treatment region from the mapping system. The estimated ablation depth is displayed as color code directly at the physiological anatomy. A color code bar 603 indicates the estimated ablation depth in different ranges. A first range 604 may be in one color corresponding to an estimated ablation depth below a certain selected low threshold where no transmural ablation at the treatment site is expected, e.g. below an estimated ablation depth of 2 mm. The second range 605 may be a color range set between the low threshold and a selected target lesion depth as set in step 502, e.g. an estimated ablation depth of 5mm. The third range 606 may be in one color corresponding to estimated ablation depth where the selected target lesion depth is already achieved, e.g. an estimated ablation depth of at least 5 mm. In an example of the invention, a safety index may be derived from the estimated dimension (e.g., the estimated lesion depth). The safety index may allow the assessment of safety with respect to an unwanted ablation of surrounding tissue. Notably, the ablation threshold (e.g., the irreversible electroporation (IRE) threshold) may vary for different types of tissues. For example, during an ablation procedure (e.g., a PF A treatment) it may be desired to ablate myocardial tissue. However, other tissue types may be present within and / or around the myocardial tissue (as well as the electrodes of the ablation catheter). By considering a safety index it may be ensured to what extent the tissue which is not desired to be ablated will experience the ablation reaction. For different tissues, different safety indices may be derived.

[0109] In the following example, two safety indices are described, one for (blood) vessels and one for nerves with respect to a myocardial tissue (as a desired ablation tissue). Notably, the myocardial tissue may comprise a lower ablation threshold than the ablation threshold of vessel tissue and / or nerve tissue. However, when applying the ablation pulse to the myocardial tissue to a certain extent the (blood) vessel tissue and / or the nerve tissue may experience high electrical fields. The safety index may consider this effect such that the ablation procedure may be assessed (prior to applying the ablation pulses) in view of the safety index for surrounding tissue.

[0110] For example, for vessels, a first safety index may be defined in the following way: dsafety,v=fv ’ dPFA, wherein fv comprises a factor considering the higher IRE threshold of vessels compared to myocardial tissues. For example, fv may be between 0.2 and 0.5.

[0111] For example, for (myelinated) nerves a second safety index may be defined in the following way: dsafety n= fn• dPFA, wherein fncomprises a factor considering the higher IRE threshold of nerves compared to myocardial tissues. For example, fn may be between 0.1 and 0.3. The second safety index may, for example, be derived with respect to the phrenic nerve, which may be in the vicinity of the ablated tissue (e.g., the myocardial tissue). Depending on the ablated region, e.g., vicinity to the phrenic nerve or the aorta, the different safety indexes may be chosen. Certain ablation pulses may then only be applied if the safety index or the safety indices are below certain thresholds.

[0112] Notably, the herein described estimation of the dimension of the tissue ablation (e.g., the lesion / ablation depth) may, for example, be applied for any type of cardiac tissue (e.g., atrial and / or ventricular myocardium).

[0113] When applying the ablation pulses to other desired ablation tissues (e.g., in other organs, regions of the human body) different indexes may be created that may be calculated the same way but may consider other tissue ablation thresholds.

[0114] Notably, effects such as but not limited to bubble formation caused by electrolysis or arcing caused by ionization processes may impair the ablation result. However, the apparatus for estimating (e.g., the PFA generator) may be configured to not be able to deliver waveforms that cause said effects in a way that may be critical for the safety of a patient.

[0115] In summary, the invention may enable to estimate a dimension of a tissue ablation (e.g., a lesion depth) without requiring complex sensory components (e.g., a contact force sensor in the catheter). The aspect described herein benefit the physician (who, for example, may be accustomed to having an ablation index during radio frequency ablation treatment to assess an ablation procedure). Notably, implementing the features of the invention, may, for example, only require an additional software update and / or a reconfiguration of a generator that may be configured to drive an ablation catheter in the field. Thus, an exchange of hardware may be avoided. The invention may thus, for example, enable a reliable and easy to implement approach for estimating a lesion depth for a pulsed field ablation treatment.

Claims

Claims1. Apparatus for estimating a tissue ablation dimension comprising: means for determining an impedance value associated with an electrode of an ablation catheter in contact with the tissue and connectable to the apparatus; means for estimating a dimension of the tissue ablation based at least in part on the impedance value.

2. Apparatus according to claim 1, wherein the means for determining is configured to apply a test pulse to the electrode to determine the impedance value when the ablation catheter is in an ablation position.

3. Apparatus according to claim 1 or 2, wherein the means for estimating is configured to estimate the impedance value based at least in part on a predetermined characteristic impedance value associated with the electrode.

4. Apparatus according to claim 3, wherein the predetermined characteristic impedance value comprises an impedance value of the electrode measured when the electrode has an ideal contact with the tissue and / or a corresponding tissue.

5. Apparatus according to any of claims 1-4, wherein the means for estimating is further configured to estimate the dimension based at least in part on an electrical parameter of the ablation pulse.

6. Apparatus according to claim 5, wherein the means for estimating is configured to estimate the dimension based at least in part on a characteristic voltage and / or a duration of the ablation pulse.

7. Apparatus according to claim 5 or 6, wherein the means for estimating is configured to estimate the dimension based at least in part on a predetermined linear factor associated with the ablation catheter that is multiplied by the characteristic voltage.

8. Apparatus according to any of claims 5-7, wherein the means for estimating is configured to estimate the dimension based at least in part on a number of ablation pulses of one or more ablation pulse trains and / or an effective pulse duration associated with the number of ablation pulses of the one or more ablation pulse trains.

9. Apparatus according to claim 8, wherein the means for estimating is configured to estimate the dimension based at least in part on a predetermined model comprising that the dimension approaches a maximum value as the number of ablation pulses applied to the tissue increases.

10. Apparatus according to claim 9, wherein the predetermined model is based at least in part on a term comprising a predetermined time constant such that when the effective pulse duration reaches the predetermined time constant at least sixty percent of the maximum value of the dimension is ablated, wherein the predetermined time constant comprises a range between 50 ns and 50 ms, preferably between 100 ps and 10 ms, more preferably between 500 ps and 2 ms, most preferably between 800 ps and 1.5 ms.

11. Apparatus according to any of claims 1-10, wherein the apparatus is configured to display the estimated dimension before, during and / or after the application of one or more ablation pulses to the tissue; and / or wherein the apparatus is configured to compare the estimated dimension with a preset dimension during a tissue ablation procedure and to control the tissue ablation procedure based on the comparison.

12. System comprising an apparatus according to any of the claims 1-11 and an ablation catheter connectable to the apparatus.

13. Method for estimating tissue ablation dimension comprising: determining an impedance value associated with an electrode of an ablation catheter for applying one or more ablation pulses to the tissue;estimating a dimension of the tissue ablation based at least in part on the impedance value.

14. Method for calibrating an apparatus for estimating a tissue ablation dimension comprising: measuring an impedance value associated with an electrode of an ablation catheter connectable to the apparatus when the electrode has an ideal contact with the tissue and / or a corresponding tissue; storing the impedance value on the apparatus.

15. Computer program comprising instructions that when executed by a computer, an apparatus according to any of the claims 1-11, and / or a system according to claim 12 cause the computer, the apparatus and / or the system to perform a method according to claim 13 and / or a method according to claim 14.

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