Systems and methods for pulsed field ablation with charge-balanced waveforms - Patents.com

Abstract

The invention relates to a generator G of substantially charge balanced pulses for application to at least one electrode pair 101 of a medical device, the generator comprising a pulse shaping output stage POS for coupling to the at least one electrode pair, an internal pulse generator for applying an internal pulse to the pulse shaping output stage, the pulse shaping output stage comprising a converter T and / or a capacitor system CS comprising at least one capacitor such that when coupled to the pulse shaping output stage POS the internal pulse is converted into a substantially charge balanced pulse at the at least one electrode pair I1. Further aspects relate to catheters, systems and methods.

Description

[Technical field]

[0001] The present invention relates to systems and methods for generating, delivering, and performing pulsed field ablation with charge-balanced waveforms. [Background technology]

[0002] In the medical field, various methods and medical devices are known for treating tissue based on electrical energy and / or power. For example, electrical energy / power can be used to ablate tissue. Tissue ablation can be performed to treat and / or prevent various diseases. For example, it is known to ablate cardiac tissue to treat cardiovascular diseases (e.g. cardiac arrhythmias, such as atrial fibrillation, ventricular tachycardia, etc.). The medical device in this case can be, for example, an ablation catheter. However, other types of tissue can also be treated based on electrical energy for medical purposes by other types of medical devices.

[0003] To allow reliable treatment, the application or source of electrical energy / power for tissue treatment usually needs to be controlled in a prescribed manner to ensure a desired medical outcome for the patient. In addition to reliable treatment, minimal or no damage to adjacent tissue structures is also required. For example, it is known that radiofrequency ablation can produce damage to the esophagus. In some cases, an atrioesophageal fistula develops. Such a condition can become life-threatening.

[0004] Therefore, energy modalities that do not harm collateral tissues are desirable. For example, pulsed-field ablation (PFA) procedures are known to harm the esophagus, phrenic nerve, and coronary structures. However, if not optimally designed, PFA waveforms can cause significant skeletal muscle irritation, which can be painful, or microbubbles that can become embolic.

[0005] Thus, the current state of affairs regarding generators that can be used in medical devices is not always optimal.Therefore, there is a need to find ways to improve generators for the treatment of cardiac conditions by PFA. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] WO2022 / 159665 Summary of the Invention

[0007] SUMMARY OF THE DISCLOSURE The aspects described herein address, at least in part, the above needs.

[0008] A first aspect relates to a generator of substantially charge-balanced pulses for application to at least one pair of treatment electrodes. The medical device may be a catheter comprising one or more electrodes. If the catheter carries only one electrode, a reference / return / ground electrode may be used to close the output circuit. Alternatively, the medical device may be a hand-held surgical wand, or a surgical energy instrument. The generator may comprise a pulse-shaping output stage for coupling to at least one pair of treatment electrodes. The generator may further comprise an internal pulse generator for applying an internal pulse to the pulse-shaping output stage. The pulse-shaping output stage may comprise a converter and / or a capacitor system, the capacitor system may comprise at least one capacitor such that the internal pulse is converted to a substantially charge-balanced pulse and applied to at least one pair of treatment electrodes when coupled to said output stage.

[0009] At least one treatment electrode pair may form an electrical load for the pulse shaping output stage. The electrical load may be associated with various medical treatment modalities (e.g., tissue treatment, e.g., tissue ablation, tissue stimulation, etc.), and the generator may be used to apply substantially charge-balanced pulses to the treatment target. The electrical load may also be (partially) defined by the tissue and / or a path through the tissue. By way of example, at least one pair of electrodes may facilitate tissue treatment by contacting respective tissues at a certain distance from each other. The two electrodes of the pair may thus form an electrical path through the tissue (or through the space defined by the two electrodes), which may also be considered to be part of the electrical load. However, in another example, the pulse shaping output stage may apply PFA energy to one or more single electrodes to facilitate treatment by the medical device. Such application may involve a reference / return / ground electrode closing an electrical circuit, and is therefore considered a monopolar energy delivery. Alternatively, the PFA energy may be applied in a bipolar mode to a pair of electrodes on one or more medical instruments.

[0010] A (substantially) charge-balanced output pulse may include a pulse having a substantially zero net charge. A charge-balanced pulse may, for example, include a (biphasic or multiphasic) voltage pulse having a substantially zero net charge over a defined time window. A charge-balanced pulse may include a positive phase and a negative phase, the absolute value of the charge of the positive phase being substantially equal to the absolute value of the charge of the negative phase. A system according to the invention may also deliver a pulse with multiple phases that are charge-balanced over the duration of the pulse. In another example, a charge-balanced pulse may also include a (biphasic or multiphasic) current pulse having a substantially zero net charge over a defined time window. The pulse may be a high voltage pulse.

[0011] For example, a (substantially) charge-balanced pulse may comprise a (biphasic or polyphasic) voltage comprising a positive phase and a negative phase, the absolute value of the charge of the positive phase being at least 90%, in particular at least 95%, at least 98%, at least 99% of the absolute value of the charge of the negative phase, or vice versa. A charge-balanced pulse may comprise a (biphasic or polyphasic) voltage pulse having a net charge of less than ±5 μC, in particular less than ±2 μC, in particular ±1 μC, over a defined time window. The defined time window may start when the positive (or negative) amplitude exceeds the measured noise level, in particular exceeds the noise level by a factor of 1.5, 2, and may end when the negative (or positive) amplitude falls below 2 times the noise level, in particular below 1.5 times the noise level, in particular below the noise level.

[0012] The generation of reliable charge-balanced pulses may, for example, prevent the injection of a net charge into the stimulated tissue via at least one electrode pair. Depending on the type of tissue and / or treatment to be treated, this may be highly beneficial. Charge balance may, for example, prevent the occurrence of electrolysis of blood and may minimize undesirable gas generation within the organism. Gas generation may be the cause of microbubbles. The microbubbles may then lead to embolism. For example, this may be highly beneficial when the treated tissue is within an organism that is surrounded by blood. The charge balance enabled by the generator may also prevent undesirable (skeletal) muscle contractions (which may, for example, be caused by direct or indirect stimulation of motor nerves). Furthermore, charge-balanced pulses may prevent electrical arcing caused by ionization of the medium between said at least one pair of electrodes.

[0013] In particular, (substantially) charge-balanced pulses may also enable medical procedures requiring the application of positive and negative charges, which may be desirable, for example, for tissue ablation (e.g., irreversible electroporation), and the system may be configured for tissue ablation.

[0014] The coupling of at least one electrode pair to the pulse shaping output stage of the generator during the application of a charge-balanced pulse as described herein may be considered as active coupling of the electrode pairs. For example, a medical device may comprise a number of electrode pairs that may be physically (e.g. mechanically) and in particular electrically connected to the pulse shaping output stage of the generator. However, the coupling of the (substantially) charge-balanced pulse may be performed, such as for selectively coupling only all or a subset of the electrode pairs. Such coupling may be enabled, for example, via a corresponding electrical circuit of the generator (e.g. comprising a switch) that activates all or a subset of the desired electrode pairs. Such coupling, such as operatively coupling the respective electrode pairs, may also be referred to herein as active coupling.

[0015] In one example, the internal pulse generator may be configured to apply an internal voltage and / or current pulse to the pulse shaping output stage for a defined pulse duration. The internal pulse may include a square pulse, although other types of internal pulses are contemplated (e.g., Gaussian pulses, cosine squared pulses, Dirac pulses, sinc pulses, etc.). The internal pulse may include only positive voltages and / or only positive currents (or only negative voltages and / or only negative currents).

[0016] The internal pulse may be applied as an input to a pulse shaping output stage. The internal electrical pulse may thus result in a (substantially) charge-balanced output pulse at at least one coupled electrode pair. In one example, the pulse shaping output stage of the generator may be part of the coupling circuit. In particular, a substantially charge-balanced pulse may be caused at at least one electrode pair by a dynamic response of the pulse shaping output stage to the internal pulse. In particular, with an internal pulse having a defined pulse duration, the internal pulse may be considered as a dynamic input to the pulse shaping output stage. The pulse shaping output stage may be configured to be adaptable to allow a desired dynamic response based on the characteristics of a given internal pulse and / or an electrical load involving at least one electrode pair. However, the characteristics of the internal pulse may also be adapted by the generator to allow a desired dynamic response of the pulse shaping output stage.

[0017] In one example, the pulse shaping output stage may comprise a capacitor system with at least one capacitor. The capacitor system may form a total capacitance of the pulse shaping output stage. Moreover, the pulse shaping output stage may be configured such that the total capacitance (dynamically) differentiates the voltage characteristics of the applied internal pulse. The resulting current and / or voltage characteristics at the at least one electrode pair may thus result in a (substantially) charge-balanced pulse as a (dynamic) response. For example, the differentiation of the voltage by the total capacitance may cause a corresponding current characteristic at the at least one electrode pair. The current characteristic may accordingly cause a corresponding voltage applied to the at least one electrode pair, which may be in the form of a (substantially) charge-balanced pulse.

[0018] In one example of the generator, at least one electrode pair may be coupled in series to a pulse shaping output stage. For example, one electrode pair may be coupled in series with a capacitor system. This example may also include that one or more electrode pairs may be in parallel with each other, said parallel circuit of electrode pairs being coupled in series to the pulse shaping output stage. In this example, the coupling circuit may thus be considered as having a total capacitance in series, and the total impedance of one or more electrode pairs is coupled to the capacitor system. The coupling circuit may thus form an RC circuit. In particular, in this case, the coupling circuit may function (at least in part) as an RC differentiation circuit that converts the internal pulse into a (substantially) charge-balanced pulse. In this regard, the voltage signal across the resistor of the RC differentiation circuit may be a voltage signal across the total impedance of one or more electrode pairs forming said electrical load. The dynamic output of the RC differentiation circuit may thus be configured such that a (substantially) charge-balanced pulse is provided to one or more electrode pairs. The RC differentiator circuit may be constructed (or adapted) based on, for example, the characteristics of the internal pulse, the total capacitance, and / or the total impedance of one or more electrode pairs to enable a desired dynamic response.

[0019] In one example, the pulse shaping output stage may comprise a capacitor system and the generator may be configured to set at least two total capacitances of the capacitor system. The total capacitance may thus be varied such that the overall electrical properties of the pulse shaping output stage may be similarly adapted (e.g., to enable its desired dynamic response). In one example, the capacitor system may comprise an electrical circuit comprising a plurality of capacitors arranged in one more circuit branch. In this case, the generator and / or the capacitor system may be configured to switch one or more circuit branches on or off to set at least two total capacitances. For example, for electrical load values ​​in the range of 15-25 Ω, the desired capacitance value may be in the range of 0.2-0.5 μF. For loads in the range of 25-50 Ω, the desired capacitance value may be in the range of 0.1-0.2 μF. Furthermore, for loads in the range of 50-150 Ω, the desired capacitance value may be less than 0.1 μF. Ideally, as the load value varies depending on the number of electrodes selected, the generator adjusts the capacitance value so that the equivalent time constant remains in the same range.

[0020] In another example, the generator may be configured to set at least three, preferably at least four, more preferably at least five, and most preferably at least six total capacitances of the capacitor system.

[0021] In one example, the capacitor system may comprise a variable capacitor, which may allow for setting at least two total capacitances of the capacitor system.

[0022] In one example, the generator may be configured to set the total capacitance of the capacitor system based at least in part on the impedance of the electrical load associated with at least one electrode pair. For example, the total capacitance may be automatically set based on the impedance of the electrical load associated with at least one electrode pair. When one or more electrode pairs are (actively) coupled to the pulse shaping output stage, the impedance of the electrode load associated with at least one electrode pair may include the total impedance of the one or more electrode pairs in the combined circuit. The total capacitance may therefore be set according to the total impedance present in the combined circuit. For example, as outlined herein, the combined circuit may comprise an RC circuit, and setting the total capacitance allows for adjusting the capacitance of the RC circuit. Also, when one electrode pair is coupled to the pulse shaping output stage, the total capacitance may only be set based on the impedance of the electrical load associated with one electrode pair.

[0023] For example, the impedance of an electrical load associated with at least one electrode pair and / or the total impedance may be measured by the generator (as described herein). The measurements may be performed based on current and / or voltage measurements (as described herein).

[0024] In another example, the generator may be configured to receive a total impedance. The total impedance may then be communicated to the generator so that the generator may adjust the total capacitance accordingly. For example, active coupling of the first and second electrode pairs of the medical device to the pulse shaping output stage may be predetermined to produce a first total impedance, and active coupling of the third and fourth electrode pairs may produce a second total impedance. In this example, the total impedance may be input, for example, by an operator, or may be received from an external device that performed the impedance measurement.

[0025] In one example, the generator may be configured to set the total capacitance of the capacitor system based at least in part on the number of electrode pairs (actively) coupled to the pulse shaping output stage. For example, the generator may be configured to receive the total number of electrode pairs (actively) coupled to the pulse shaping output stage. In another example, the generator may be configured to determine the number of electrode pairs (actively) coupled to the pulse shaping output stage. The number of electrode pairs (actively) coupled to the pulse shaping output stage may be indicative of (or serve as a benchmark for) the total impedance present in the coupling circuit device. Thus, the total capacitance may be set according to the total impedance present in the coupling circuit. The generator may be configured to automatically set the total capacitance of the capacitor system based on the (received or determined) number of electrode pairs. The automatic setting may be performed by a corresponding computer program capable of controlling the capacitor system, and the computer program may be included in the generator and / or an external device. The total capacitance may also be set manually (e.g., by an operator) based on the number of coupled electrode pairs.

[0026] In one example, setting the total capacitance may not only be based on the number of coupled electrode pairs, but also on the medical device (or type of medical device). The (total) impedance does not necessarily depend only on the number of coupled electrode pairs, but may also depend on the impedance of the electrical load associated with each electrode, which may vary depending on the medical device.

[0027] In one example, one or more electrode pairs may be in parallel with each other when coupled to the pulse shaping output stage. In this example, the impedance of each of the electrode pairs may also be substantially the same, for example, due to the design of the medical device or due to uniformity of the electrode-tissue contacts. Thus, the number of electrode pairs may indicate the number of parallel branches, each branch having substantially the same impedance. Thus, a larger number of coupled electrode pairs may indicate a smaller total impedance, and a relatively smaller number of coupled electrode pairs may indicate a relatively larger total impedance. Thus, the total capacitance may be adjusted accordingly. Notably, the above determination applies to both monopolar and bipolar energy application. Monopolar energy application requires a reference / return / ground electrode that closes an electrical circuit at the output of the generator.

[0028] For example, it may be envisioned that the total capacitance set by the generator is associated with a particular number of coupled electrode pairs. In this case, the generator may be configured such that when a first number of electrode pairs (of a particular medical device) are coupled to the generator, a first value of total capacitance may be set. When a second number of electrode pairs (of a particular medical device) are coupled to the generator, a second value of total capacitance may be set.

[0029] In particular, the parallel electrode pairs in the pulse shaping output stage may be enabled by the generator. In one example, the generator may include an interface relay board for connecting the electrode pairs of the medical device to the pulse shaping output stage. The interface relay board may include (controllable, e.g., switchable) relay circuitry for coupling the electrode pairs to the pulse shaping output stage in various manners. For example, the relay circuitry may allow the electrode pairs to be coupled to the pulse shaping output stage in parallel with each other. However, in some examples, the interface relay board may also allow the electrode pairs to be arbitrarily coupleable to the pulse shaping output stage (such as in series with each other, at least partially in series, and at least partially in parallel). In one example of the relay board, the relay board may include a first subgroup of relay channels that may be connected in parallel with each other, each relay channel may be coupled to a first node of the pulse shaping output stage. The relay board may include a second subgroup of relay channels that may be connected in parallel with each other, each relay channel may be coupled to a second node of the pulse shaping output stage.

[0030] In one example, the generator may be configured to set the total capacitance of the capacitor system such that the product of the total capacitance and the impedance of the electrical load associated with at least one electrode pair (i.e., the time constant) is within a predetermined range. For example, when one or more electrode pairs are coupled to a pulse shaping output stage, the impedance of the electrical load associated with at least one electrode pair may include the total impedance of the one or more electrode pairs in the combined circuit. In this case, the total capacitance and the total impedance may define an RC circuit in the combined circuit (as described herein). The product of the total capacitance and the total impedance may thus include an RC time constant τ (τ=R·C, where R may include the total impedance and C may include the total capacitance in this example). Thus, the generator may enable setting a desired RC time constant, which may define the dynamic response of the combined circuit. The RC time constant may be set such that when an internal pulse is applied to the pulse shaping output stage and the pulse shaping output stage is electrically connected to the electrode pair, a (substantially) charge balanced pulse may result at the electrode pair. This can be very beneficial since the dynamic response may not necessarily result in a (substantially) charge-balanced pulse in the absence of a corresponding RC time constant. Furthermore, the waveform of the (substantially) charge-balanced pulse may be shaped according to a set RC time constant. For example, it may be desirable to have a sufficient duration of the positive phase of the charge-balanced pulse and a sufficient duration of the negative phase, which may be varied via the RC time constant. Furthermore, it may be desirable for both durations to be substantially equal to create a (substantially) symmetric charge-balanced pulse for medical applications. Alternatively, the durations of the phases may be different to allow the net charge to be in balance. Also, alternatively, the total capacitance value may be different for the positive and negative phases. This may be achieved by implementing a pulse-shaping output stage that detects the transition from the positive to the negative phase and drives a capacitor block to adjust its total capacitance.Therefore, since the RC time constant may serve as one of the main performance parameters of the pulse shaping output stage, adjusting the RC time constant may allow the symmetry of the charge-balanced pulse to be adapted. In particular, some RC time constants may result in charge-balanced pulses with two abrupt positive and negative phases, respectively, of relatively short duration, which may not always be desirable in some medical procedures. Alternatively, one positive and one negative phase will produce a similar effect. Therefore, the generator may be set to allow only a certain range of RC time constants, such that extreme dynamic responses are avoided.

[0031] In another example, the generator may set the total capacitance such that the product of the total capacitance and impedance of an electrode pair is within a predetermined range. For example, the RC time constant for a single electrode pair may need to be adjusted, but not necessarily to the total impedance present in the combined circuit (the entire circuit comprising the generator and all electrode pairs) to account for the desired outcome of its dynamic response. For example, this may be the case when electrode pairs are coupled to a pulse shaping stage differently than in an assembly parallel to one another. For example, unipolar vs. bipolar electrode configurations may require different time constants.

[0032] In one example, the pulse shaping output stage may comprise a converter such that the internal pulse is converted into a substantially charge-balanced pulse and fed to at least one electrode pair when coupled to the pulse shaping output stage. In this case, the pulse shaping output stage may comprise a part of the converter (e.g., a coil or winding of the converter). This may ensure that the pulse shaping output stage has no direct electrical connection to the circuitry where the high-voltage internal pulse is generated (i.e., the stage is not DC-coupled). For example, a step-up converter may be used. This may allow galvanic isolation from the internal pulse generator. Additionally, the step-up converter may increase the output voltage without placing additional voltage stress on the components of the internal pulse generator. Also, in this case, the dynamic response of the coupling circuit may be adapted such that a (substantially charge-balanced pulse) is generated at at least one electrode pair. In this regard, it may be considered that the inductivity of the converter (e.g., of one of its coils) may be used in combination with the impedance of at least one electrode pair to shape the dynamic response accordingly. For example, when using a transducer (e.g. without a capacitor system), the combined circuit (the entire circuit comprising the generator and all electrode pairs) can comprise an RL circuit, and the dynamic response of the RL circuit to an internal pulse can be adjusted (e.g. by adapting the inductance L and / or impedance R).

[0033] In one example, the pulse shaping output stage comprises a converter and a capacitor system, and the generator is further configured such that an internal pulse is coupled from the internal pulse generator to the capacitor system via the converter. Thus, the output of the internal pulse generator may be coupled to the input of the converter, and the output of the converter may be coupled to the capacitor system. The converter may thus function as an intermediate element between the internal pulse generator and the capacitor system. This may allow galvanic isolation of the capacitor system from the internal pulse generator. Moreover, galvanic isolation from various other parts of the generator located on the input side of the converter may also be allowed.

[0034] In one example, the converter may be configured such that the voltage at the converter output (coupled to the capacitor system) is higher than the applied voltage at the converter input. The converter may thus function as a step-up converter, increasing the input voltage at its output by a predetermined amount (e.g., depending on the relationship of the converter's primary and secondary windings). The converter may increase the input voltage by at least 10% or 20%, or by at least 30%, preferably at least 50%, more preferably at least 80%, and most preferably at least 20-30%. This may be beneficial since technical limitations of the possible voltage swing of the internal pulse generator may be overcome. For example, the switching elements (e.g., FET transistors) of the internal pulse generator may be exposed for optimal current transient handling.

[0035] However, it is also contemplated that the converter may be configured such that the voltage at the converter output (coupled to the capacitor system) is lower than the applied voltage at the converter input.

[0036] In one example, the generator further comprises means for measuring the voltage and / or current of at least one electrode pair when the substantially charge-balanced pulse is applied, and means for determining the impedance of the at least one electrode pair based on the voltage and / or current measurements. For example, the means for measuring the voltage and / or current may be configured to measure the voltage across at least one electrode pair (or the voltage across multiple parallel electrode pairs). The means for measuring may function to measure the voltage across the total impedance of the combined circuit (e.g., the entire circuit comprises the generator and all electrode pairs). Furthermore, the means for measuring the voltage and / or current may be configured to measure the current in at least one electrode (or the current supplied to multiple parallel electrodes). The means for measuring may also function to measure the current through the total impedance of the combined circuit. The voltage and / or current measurements may allow tracking of the applied (substantially) charge-balanced pulse, for example during a medical procedure.

[0037] However, as such, voltage and / or current measurements may also be used for testing and / or calibration unrelated to the medical process. For example, the voltage and / or current measurement capability may be used to determine the impedance of at least one electrode pair and / or the total impedance present in the combined circuit (e.g., the entire circuit comprising the generator and all electrode pairs). Based on the determined impedance, the total capacitance may be set (e.g., by an operator and / or automatically by the generator) and then set for the actual medical procedure. The (substantially) charge-balanced pulse used to determine the impedance may not have the same characteristics as the charge-balanced pulse applied during the medical procedure to avoid medical reactions. To enable such functionality, the electrical energy and / or power of the applied charge-balanced pulse may be set lower during impedance measurement than during the medical procedure. For example, the amplitude of the internal pulse may be chosen lower for impedance measurement than for the medical procedure. For ablation procedures (e.g., irreversible electroporation of tissue), when charge-balanced pulses may generally be used, the amplitude for the impedance measurement may be chosen so as not to reach the ablation threshold (e.g., be within a safety margin).

[0038] The means for determining impedance may trigger voltage and / or current measurements necessary for impedance calculation. It may be envisaged that the impedance is determined based on the determined peak voltage and the corresponding current. However, more complex calculations may also be performed by the means for determining impedance (e.g. calculating a mean value, a median value, applying a fitting algorithm, e.g. a polynomial fitting algorithm, of the voltage / current to determine the impedance value).

[0039] A medical device as described herein may comprise one or more electrodes. For example, the medical device may include a catheter comprising one or more electrodes. In particular, the generator may also be configured to determine the impedance (or impedance value) of each electrode of the medical device. To enable such functionality, one electrode of the medical device may be set as a reference electrode. The impedance relative to the reference electrode is determined for each remaining electrode by applying a substantially charge-balanced pulse as a measurement pulse and determining the impedance as described herein. In particular, a sub-therapeutic charge-balanced pulse may be used to determine the impedance.

[0040] In one example, the generator may not necessarily comprise a means for determining the impedance of at least one electrode pair. It is also conceivable that the generator may comprise only a means for measuring the voltage and / or the current. For example, the means for measuring may still be triggered to perform the measurements necessary to determine the impedance. However, the actual calculation of the impedance may be performed by an external device that receives the impedance measurements from the generator.

[0041] In one example, the internal pulse generator comprises a high voltage source, the generator configured to form the internal pulse based at least in part on a high voltage output of the high voltage source, the high voltage source preferably being configurable by the generator to provide a high voltage amplitude of at least 1000V, preferably at least 1500V, more preferably at least 2000V, most preferably at least 3000V. The generator may thus enable an internal pulse with a high voltage amplitude to be generated. The pulse shaping output stage (or coupling circuitry) may thus enable a (substantially) charge-balanced pulse to be generated, also having a corresponding high voltage amplitude. In particular, if the generator comprises a converter configured as a step-up converter (as described herein), the voltage amplitude of the charge-balanced pulse may be even greater than the high voltage amplitude provided by the high voltage source. In one example, the high voltage amplitude provided by the generator can be in the range of 1000V to 4000V, 1500V to 3500V, 2000V to 3000V, and / or 2500V to 3500V.

[0042] In one example, the internal pulse generator may include a high-voltage capacitor, and the high-voltage source is configured to charge the high-voltage capacitor. In this case, the generator may be configured to form an internal pulse based at least in part on the high-voltage amplitude of the charged high-voltage capacitor. For example, during a medical application, the internal pulse generator may charge the high-voltage capacitor for a predetermined charging time such that the high-voltage capacitor can be considered essentially charged. One essential charge may allow for the generation of at least two internal pulses, preferably at least three internal pulses, more preferably at least four internal pulses, and most preferably at least five internal pulses. Preferably, the capacitor system is fully charged between pulses, or at least between pulse trains (e.g., every heartbeat if the generator is synchronized to the patient's cardiac cycle).

[0043] In one example, the internal pulse generator comprises a switching unit, the switching unit configured to switch an output of a high voltage source to generate an internal pulse, the switching unit preferably comprising an H-bridge circuit and / or a half H-bridge circuit. For example, the high voltage source (and / or a high voltage capacitor) may provide a stable output of a high voltage amplitude. The switching unit may relay the high voltage amplitude to the pulse shaping output stage of the first switch configuration for a certain period of time. Thereafter, the switching unit may stop relaying the high voltage amplitude to the pulse shaping output stage of the second switch configuration. In one example, the second switch configuration may actively drive the input voltage at the pulse shaping output stage to ground (e.g., to zero potential). Thus, an internal pulse with a defined internal pulse duration may be provided by the switching unit at the input of the pulse shaping output stage.

[0044] The switching unit may also further comprise power electronic circuitry or power electronic components such that a desired shape of the internal pulse can be produced through switching (e.g. rectangular shape, Gaussian shape, sinusoidal shape, tooth shape, sinc shape, etc.).

[0045] In one example, the internal pulse generator preferably comprises a timing unit for controlling the switching unit to set timing parameters of the internal pulses and / or to set several internal pulses such that a train of internal pulses is applied to the pulse shaping output stage. The timing parameters of the internal pulses may for example comprise a duration of the internal pulses and / or an interval between two internal pulses. The timing unit may further be configured to set several pulse trains, each train comprising a certain number of internal pulses.

[0046] The internal pulse duration may be at least 0.5 μs, preferably at least 10 μs, more preferably at least 20 μs, and most preferably at least 80 μs. In particular, the internal pulse duration set by the timing unit may be in the range of 0.5 μs to 200 μs, in the range of 1 μs to 100 μs, in the range of 1 μs to 80 μs, in the range of 1 μs to 50 μs, or in the range of 1 μs to 30 μs.

[0047] The interval between the two internal pulses may be at least 0.2 ms, preferably at least 0.4 ms, more preferably at least 5 ms, and most preferably at least 10 ms. In particular, the interval between the two internal pulses that can be set by the timing may be in the range of 0.1 ms to 20 ms, 0.2 ms to 15 ms, 0.3 ms to 12 ms, 0.4 ms to 10 ms, or 0.5 ms to 10 ms.

[0048] The number of internal pulses per train may be at least 5, preferably at least 10, more preferably at least 100, for example at least 500. In particular, the number of internal pulses per train that can be set by the timing may be in the range of 5 to 600, in the range of 10 to 500, in the range of 20 to 500, in the range of 100 to 500, or in the range of 200 to 500.

[0049] In one example, the timing unit is configured to control the switching unit such that the internal pulse is applied based at least in part on a trigger of the medical signal. For example, the generator may be configured to receive the medical signal. The medical signal may include an electrocardiogram signal. In one example, the medical signal may be provided with a trigger signal corresponding to the presence of a characteristic cardiac wave peak, a cardiac event, and / or a cardiac cycle (e.g., an R-wave peak, a QRS cycle, a P-wave peak, a T-wave peak, etc.). For example, the trigger signal may include a square pulse signal, and a rising edge of the trigger signal may correspond to the presence of the characteristic cardiac wave peak or cycle. For example, the internal pulse may be activated after a certain waiting time has elapsed after the R-wave peak. The certain waiting time may be predetermined such that the internal pulse may be applied within a refractory period of a cardiac cycle.

[0050] In another example, the generator may be configured to determine a trigger in the received medical signal. Determining the trigger may be performed by a timing unit or any other suitable unit of the generator. For example, determining the trigger may include determining a characteristic cardiac wave peak, a cardiac event, and / or a cardiac cycle through corresponding signal processing.

[0051] In one example, the generator is configured to apply a substantially charge-balanced pulse such that, when at least one electrode pair comprises two electrodes of a medical device (e.g., in the form of a catheter system), the substantially charge-balanced pulse induces irreversible electroporation (IRE) of human tissue in the vicinity of (at least one of) the two electrodes. The human tissue may include cardiac tissue, e.g., of the atrium and / or ventricle. However, the human tissue may also include tissue of veins and / or arteries (e.g., pulmonary veins and / or pulmonary arteries). In particular, the generator may be adapted such that an ablation threshold for irreversible electroporation is met in the vicinity of at least one of the two electrodes. In particular, the generator may be used to drive a bipolar configuration of electrodes and a monopolar configuration of electrodes of the medical device.

[0052] In one example, the generator may be configured to apply substantially charge-balanced pulses for PFA procedures that may be based on irreversible electroporation. The generator may thus enable controlled ablation of cardiac tissue, vascular tissue, or any other tissue (e.g., neural tissue, skin tissue, etc.) for medical PFA procedures.

[0053] In one example, the generator may comprise an interface unit for coupling to one or more external devices, such as a recording system, which may record, for example, an electrocardiogram signal acquired by the medical device. The interface unit may comprise corresponding output ports for connecting to the one or more external devices. In one example, the interface unit may be configured to relay a signal (e.g., an electrocardiogram signal) of at least one electrode pair to the output port.

[0054] In particular, features described herein of generators and / or systems according to other aspects of the invention may also be features and / or functions of the generator of the first aspect.

[0055] A second aspect relates to a catheter comprising a connector for connecting an electrode pair of the catheter to a generator as described herein. For example, the connector may be configured to mate with an electrode pair of the catheter to a pulse shaping output stage. In this regard, the connector may be adapted to mate with an interface relay board (as described herein) that may couple the electrode pair to the pulse shaping output stage of the generator in various ways.

[0056] A third aspect relates to a system comprising a generator as described herein (eg according to the first aspect) and a catheter as described herein (eg according to the second aspect).

[0057] A fourth aspect relates to a method for generating a substantially charge balanced pulse for application to at least one electrode pair of a medical device, the method comprising coupling the at least one electrode pair to a pulse shaping output stage of a generator, applying a predetermined internal pulse at an internal pulse generator of the generator to generate a substantially charge balanced pulse at the at least one electrode pair, the method may be implemented in a generator as described herein (e.g. according to the first aspect) and / or in a system as described herein (e.g. according to the third aspect).

[0058] In particular, further aspects relate to computer programs that may include instructions that, when executed by a computer, a generator of the first aspect, a catheter of the second aspect, and / or a system of the third aspect, cause the computer, the generator, the catheter, and / or the system to perform the method of the fourth aspect and / or the functional steps associated with the method as outlined herein. For example, the generator and / or the system may comprise means for executing the computer program instructions (e.g., a processing unit). The computer program may enable autonomous automated implementation of the aspects described herein. Thus, technical intervention from medical personnel may be minimized.

[0059] In one example, the computer, generator, catheter, and / or system may include one or more storage devices that may store one or more instructions that may be executed by the computer, generator, catheter, and / or system to perform the methods, functional steps, and / or operations of the generator, system, and / or catheter described herein.

[0060] A fifth aspect relates to a generator of substantially charge-balanced pulses for application to at least one electrode of a medical device, the generator comprising means for determining the impedance of at least one electrode by applying a substantially charge-balanced pulse. The impedance may include the impedance of a single electrode and / or an impedance value associated with a single electrode, e.g. a load value associated with said electrode. However, the impedance may also include the impedance between a pair of electrodes, or the total impedance of several electrode pairs. The impedance and / or the impedance value may be determined based on current and / or voltage measurements as described herein. The above aspects apply to both monopolar and bipolar ablation modalities.

[0061] In one example, the generator of the fifth aspect may be configured to send the determined impedance to a user interface and / or display the determined impedance via a user interface. For example, the user interface may include a display (e.g., a monitor, a touch screen, etc.) for displaying various information about the generator and / or electrodes of the medical device.

[0062] In one example, the generator of the fifth aspect may also be configured to automatically set a total capacitance of a capacitor system included in the generator based at least in part on the determined impedance.

[0063] The generator according to the fifth aspect may also comprise features described herein with reference to the other aspects.

[0064] In one example, the method may include (automatically) determining an impedance of at least one electrode and / or electrode pair of a medical device as described herein, and the method may further include (automatically) setting a (total) capacitance of an output capacitor system as described herein based at least in part on the determined impedance.

[0065] A sixth aspect relates to a system for coupling a substantially charge-balanced high-voltage (electrical) pulse to a medical device, the system comprising an output capacitor system configured to allow at least two total capacitances. The system of the sixth aspect may comprise a pulse shaping output stage as described herein. However, the system may also comprise a generator as described herein. In one example, the system of the sixth aspect may be implemented as a separate entity (e.g. as a separate substrate, as a separate device, etc.). In this case, the system of the sixth aspect may be for coupling to an input device, which may input the substantially charge-balanced high-voltage pulse or another high-voltage pulse to the system. The system may thus function as a (separate) intermediate device, for example between the pulse generator and the medical device. In particular, the system may also convert the high-voltage input pulse such that a substantially charge-balanced high-voltage pulse is coupled to the medical device. As described herein, the output capacitor system of the system of the sixth aspect may in this respect be coupled to an electrode pair of the medical device.

[0066] In one example, the system may be configured to set the total capacitance based at least in part on the number of electrodes of a medical device coupled to the system. The system may be configured to receive a selection of electrodes via a user interface and set the total capacitance based on the selection. The user interface may be configured to display a selection of electrodes, in particular only one or more selected subgroups of all available electrodes. In another example, the system may be configured for automatic detection of active electrodes to determine the number of electrodes coupled to the system.

[0067] In one example, the system may be configured to set the total capacitance based at least in part on a total impedance of one or more electrodes of a medical device coupled to the system. The system may be configured to receive and / or measure the impedance of the medical device as described herein. For example, the system may include means for measuring the current and / or voltage of one or more electrode pairs of the medical device.

[0068] The generator according to the sixth aspect may also comprise the features described herein with reference to the other aspects.

[0069] A seventh aspect relates to a generator of substantially charge-balanced pulses for application to at least one electrode of a medical device, the generator configured to apply the pulses as triggered by an electrocardiogram signal. The generator may be configured to receive the electrocardiogram signal from an external source. The generator may thus comprise means (e.g., an electronic receiving unit) for receiving the electrocardiogram signal. The electrocardiogram signal may include various signal channels, which may include a trigger signal channel. In one example, the substantially charge-balanced pulses may be applied as such based on the trigger signal channel or the electrocardiogram signal alone.

[0070] However, in another example, the generator may be configured to receive an electrocardiogram signal that may not necessarily include a trigger signal channel. Specifically, in this case, the generator may include and / or implement an event detector that may determine a cardiac event in the electrocardiogram signal. In one example, the generator may include means for determining a characteristic cardiac wave event in the electrocardiogram signal. In this example, a substantially charge-balanced pulse may be applied based on a detected event, for example as described herein. However, combinations may also be envisaged, where the pulse application is based on an event detected by the generator and the electrocardiogram signal (e.g., a trigger signal channel).

[0071] In one example, signal processing of the ECG signal (and corresponding control of the applied pulses) may be performed by a timing unit of the generator, although any other computing entity of the generator may also perform signal processing of the ECG signal (e.g., a synchronization unit, a central processing unit, a computer, a microprocessor, etc.).

[0072] In one example, the generator may comprise means for receiving a trigger command from a user interface, and the generator (or a computing entity of the generator) is configured to set a trigger signal based on the received trigger command and, for example, a characteristic cardiac wave event (e.g., the trigger signal may be set, for example, a particular time after an R-wave peak). A pulse may then be applied by the generator in response to the set trigger signal.

[0073] In particular, the generator of the seventh aspect may also comprise features or functionality of the generators and / or systems described with reference to the other aspects of the invention, for example functionality described herein with respect to medical signals (in the first aspect) may be further applicable to electrocardiogram signals of the seventh aspect (and vice versa).

[0074] An eighth aspect relates to a generator of substantially charge-balanced high voltage pulses for application to at least one electrode of a medical device, the generator comprising a recording system for recording the electrical activity of the at least one electrode. The generator may further comprise an overvoltage protection element for protecting the recording system from the high voltage pulses applied to the medical device, preferably for ablation of human tissue.

[0075] In one example, the recording of electrical activity may be performed when no high voltage pulses are applied to the at least one electrode. The electrical activity may thus include electrical activity sensed by the medical device. For example, the medical device may comprise a catheter, and the electrodes of the catheter may also be configured for sensing, monitoring, and / or mapping of electrophysiological activity (e.g., in the vicinity of tissue in contact with the electrodes). The recording system may further be used, for example, to record electrocardiogram signals (e.g., when the electrodes are placed on and / or in the vicinity of the heart). However, the recording system may be adapted to voltage and / or current ranges associated with sensing such that high voltage pulses may damage the recording system. Thus, the overvoltage protection element may ensure that the recording system can function reliably over long periods of time.

[0076] The overvoltage protection element may comprise one or more electrical elements to enable the protection function. For example, the overvoltage protection element may comprise a switch and / or a repeater such that the electrode signal may be blocked during application of the pulse. The overvoltage protection element may also comprise one or more voltage suppressors (e.g., transient voltage suppressors) to block any high voltage signals that may be coupled to the recording system.

[0077] In another example, the recording system may be implemented in an external device that may be coupled to the generator, in which case the generator may only include overvoltage protection elements so that the signal can be transmitted to the external recording device in a safe voltage range for recording.

[0078] In particular, features described herein of the generators and / or systems of the other aspects of the invention may also be features and / or functions of the generator of the eighth aspect.

[0079] It should be noted that method steps as described herein may include all aspects as described herein, even if they are not expressly described as method steps, but rather are described with reference to an apparatus (or device or system). Moreover, a generator (or system or device) as outlined herein may include means for performing all aspects as outlined herein, even if these may rather be described in the context of method steps.

[0080] The functions described herein, whether described as method steps, computer programs, and / or means, 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 includes 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 medium accessible by a general purpose or special purpose computer. By way of example, and not limitation, such computer-readable storage media may include RAM, ROM, EEPROM, FPGA, CD / DVD, or other optical disk storage, magnetic disk storage, or other magnetic storage devices, or any other medium usable to carry or store desired program code means in the form of instructions or data structures and accessible by a general purpose or special purpose computer, or a general purpose or special purpose processor. A control unit as described herein may also be implemented in hardware, software, firmware, and / or combinations thereof, for example by one or more general purpose or special purpose computers and / or general purpose or special purpose processors.

[0081] Listed below are figures of the present disclosure. [Brief description of the drawings]

[0082] [Figure 1] 1 is a schematic diagram of an exemplary embodiment of a generator according to the present invention; [Diagram 2] FIG. 13 is a schematic diagram of an output relay board of an exemplary embodiment of the generator. [Diagram 3] FIG. 2 is a schematic diagram of various components of an exemplary embodiment of a generator. [Figure 4a]FIG. 2 is a diagram of a first example of charge-balanced voltage and current pulses implemented by a generator according to the invention. [Figure 4b] FIG. 2 is a diagram of a first example of charge-balanced voltage and current pulses implemented by a generator according to the invention. [Figure 5a] FIG. 4 is a diagram of a second embodiment of charge-balanced voltage and current pulses implemented by a generator according to the invention. [Figure 5b] FIG. 4 is a diagram of a second embodiment of charge-balanced voltage and current pulses implemented by a generator according to the invention. [Figure 6a] FIG. 4 is a diagram of a third embodiment of charge-balanced voltage and current pulses implemented by a generator according to the invention. [Figure 6b] FIG. 4 is a diagram of a third embodiment of charge-balanced voltage and current pulses implemented by a generator according to the invention. [Figure 7] FIG. 4 is a diagram of a fourth embodiment of charge-balanced voltage and current pulses implemented by a generator according to the invention. [Figure 8] FIG. 13 is a diagram of an exemplary user interface of a generator according to the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0083] A currently preferred embodiment will now be outlined, primarily with reference to the figures above. It should be noted that further embodiments are of course possible, and the following description is provided merely by way of example and not by way of limitation.

[0084] Fig. 1 shows a schematic diagram of an exemplary embodiment of a generator G according to the present invention. In particular, the generator G of Fig. 1 may also comprise further elements not shown in Fig. 1 (but shown, for example, in Fig. 2 or Fig. 3). As outlined herein, the generator G may be used to generate substantially charge-balanced pulses for medical devices (e.g., for ablation catheters).

[0085] The generator G may comprise a high voltage source HV. The high voltage source HV may provide a voltage of at least 1000V. For example, the high voltage source may provide a voltage in the range of 1000V to 4000V. In other examples, the high voltage source may also provide an intermediate voltage (e.g., in the range of 100V to 1000V) and / or an even lower voltage (e.g., in the range of 5V to 100V). A supply voltage may be provided via a channel 110 to the high voltage source HV, which may be multiplied by the high voltage source HV to provide a desired (high) voltage swing.

[0086] The generator G may include a pulse timing board PTB. The pulse timing board PTB may control the high voltage source HV via the channel 120. For example, the pulse timing board PTB may be used to set the voltage amplitude of the high voltage source HV. The pulse timing board PTB may further be used to set the current provided by the high voltage source HV.

[0087] The generator may comprise a pulse generating substrate PGB, which may be coupled to a high voltage source HV. The pulse generating substrate PGB may comprise a high voltage capacitor 170. During operation, the high voltage source may charge the high voltage capacitor 170. The high voltage capacitor 170 may thus be used as an energy source and / or power source for generating internal pulses as described herein.

[0088] The pulse generation board PGB may comprise a switching unit. In the example of FIG. 1, the switching unit may comprise a half H-bridge circuit. The half H-bridge circuit of FIG. 1 comprises a first switch S1 and a second switch S2. The switches S1, S2 may be switched via drivers D1 and D2, respectively. However, another switching circuit may also be used in the generator G (e.g. an H-bridge circuit, or another suitable switching arrangement). The drivers D1, D2 of FIG. 1 may be controlled by the pulse timing board PTB via its driver control unit 140, which may be connected to the drivers D1, D2. The switching may make it possible to generate reliable internal pulses that may be coupled as inputs to the pulse shaping output stage POS of the generator.

[0089] The pulse-shaping output stage (POS) may comprise a converter T (as described herein) at its input. The converter T may function as a step-up converter such that the voltage at the input of the converter T is increased at the output of the converter in a defined ratio. Furthermore, the pulse-shaping output stage POS may comprise a capacitor system CS (as described herein). The output of the converter T may be coupled to the capacitor system CS. The capacitor system CS may comprise various branches with one or more capacitances. The capacitances of the branches may be activated by switches, as exemplarily shown in FIG. 1. The switches may be controlled via a capacitor switching unit 130, which may be controlled by a pulse timing board PTB. The generator G may be configured to set at least two total capacitances for the capacitor system CS, as described herein. In particular, the generator may be configured to set a wider plurality of capacitances (e.g., at least three, at least five, at least ten, at least fifty total capacitances) depending on the chosen circuit of the capacitor system CS. The transformer T and capacitor system CS may function as a pulse shaping output stage, as described herein.

[0090] The output of the pulse shaping output stage POS may be coupled to an output relay board ORB of the generator G. The output relay board ORB may couple the output of the pulse shaping output stage POS to at least one electrode pair 101 of the medical device C in a controlled manner. The medical device C may comprise one or more electrodes (e.g., two electrodes) as outlined herein. The electrode pair may therefore be considered as a load that the generator can drive. In the example of FIG. 1, each electrode of the medical device C may be individually coupled to the output relay board ORB. As can be seen in FIG. 1, the output relay board ORB is adapted to couple the paths of 16 electrodes to the generator, with four electrodes (for recording, as described herein) being coupled to different parts of the generator. An exemplary electrode pair 101 may include a connection between the path of a first electrode E1 (the first of the odd electrodes) and the path of the first of the even electrodes E2. A defined voltage and / or current may therefore be applied between the first electrode E1 and the second electrode E2, the two terminals of which may be controlled via a generator. In particular, the two terminals are relayed to a pulse shaping output stage POS such that the two terminals form at least a resistive part of the pulse shaping output stage.

[0091] The output relay substrate ORB may comprise one or more relay switches for actively coupling one or more desired electrode pairs to the pulse shaping output stage POS. The output relay substrate ORB may comprise a first relay switch group that may be coupled to a first number of electrodes of the medical device C (e.g., eight electrodes as shown in FIG. 1). The first relay switch group may connect the first number of electrodes to a first node of the pulse shaping output stage depending on a switch configuration. The output relay substrate ORB may also comprise a second relay switch group that may be coupled to a second number of electrodes of the medical device C (the second number may be equal to the first number, e.g., eight electrodes as shown in FIG. 1). The second relay switch group may connect the second number of electrodes to a second node of the pulse shaping output stage depending on a switch configuration. Thus, a defined voltage and / or current may be applied between the electrodes associated with the first relay switch group and the electrodes associated with the second relay switch group. Furthermore, substantially charge-balanced pulses may be applied across electrodes coupled to different relay switch groups.

[0092] By coupling the electrode pairs to the pulse-shaping output stage, as described herein, a combined circuit may be formed. The combined electrode pairs may therefore function (in total) as a resistive portion of the combined circuit. The combined circuit may therefore also be understood as an RC circuit, as described herein. The total impedance of the combined electrode pairs may therefore be considered to be the resistance R of the RC circuit. As shown in FIG. 1, the output relay board may couple various electrode pairs in parallel with each other (through relay switch circuit devices) to the pulse-shaping output stage. It can also be seen in FIG. 1 that the parallel arrangement of the electrode pairs may be coupled in series with the capacitance of the capacitor system CS. The total impedance of the combined circuit may therefore be defined by the parallel circuit of the electrode pairs. In particular, the capacitor system CS may comprise two capacitor subsystems (as shown in FIG. 1). The electrode pairs may, for example, be coupled in series between the first capacitor subsystem and the second capacitor subsystem.

[0093] The output relay board ORB may further comprise an interface unit 160 that may facilitate mechanical and / or communicative coupling of the output relay board ORB to a connector of the medical device C.

[0094] Next, the generation of a substantially charge-balanced pulse is discussed. To generate an internal pulse as input to the pulse shaping output stage POS, the voltage of the high voltage source needs to be applied for a specific duration. This can be achieved in a controlled manner by switching the switches S1, S2.

[0095] For example, when switch S1 is closed (and switch S2 is open), a high voltage provided by high voltage capacitor 170 may be coupled to the input of a pulse outcoupling board POB of generator G. For example, the high voltage may then be applied at converter T. When switch S1 is open and switch S2 is closed, the voltage at the input of the pulse shaping output stage POS (e.g., at the input of converter T) is actively set to ground. Thus, a defined pulse duration of the internal pulse may be achieved.

[0096] As described herein, a coupled circuit (e.g., an RC circuit) is formed by coupling one or more electrode pairs to a pulse shaping output stage. The dynamic response of the coupled circuit to an internal pulse causes a substantially charge balanced pulse to be applied at the coupled electrode pair or pairs. This also results in a substantially charge balanced pulse being applied via the electrodes. Thus, the coupled medical device C may be used to apply high voltage charge balanced pulses (e.g., to tissue for ablation procedures).

[0097] The generator G may further comprise means for measuring the voltage and / or current, for example to determine the impedance of the coupled electrode pair. For example, the pulse shaping output stage POS may comprise a voltage measurement unit VM. The voltage measurement unit VM may capture the voltage across the coupled electrode pair. For example, the voltage may be measured across the parallel circuit of the electrode pair caused by the output relay board ORB (as shown in FIG. 1). For example, the measured voltage may be related to the voltage applied across the (total) impedance R of the RC circuit formed by the coupling circuit.

[0098] The pulse shaping output stage POS may also comprise a current measurement unit IM. The current measurement unit IM may capture or measure the current in series with the coupled electrodes (e.g. in series with the parallel circuit of the electrode pair). For example, the measured current may be related to the current flowing through the RC circuit (e.g. the current passing through the (total) resistance R).

[0099] Instead of the described high voltage pulse, for example an internal pulse in the mid-voltage range or lower voltage range (as described herein) may be applied to enable impedance measurement. This may ensure that no actual high voltage application (which may have permanent medical effects) is performed during impedance measurement. However, during impedance measurement, a substantially charge-balanced pulse may also be triggered at one or more electrode pairs.

[0100] The voltage and / or current measurement data (e.g., of impedance measurement) may be converted to digital data for data analysis via an analog-to-digital converter ADC of the pulse shaping output stage POS. In particular, the ADC may also be used to convert analog data of the high voltage detection HV detection of the pulse generation substrate PG to digital values ​​for further analysis. The measurement results of the voltage measurement unit VM and the current measurement unit IM may be further processed by the generator G. The pulse shaping output stage POS may also comprise an open circuit closure unit 180. The open circuit closure unit 180 may determine whether an open circuit is present in the coupling circuit (for example, this may be the case when the electrode pair is not actively coupled to the pulse shaping output stage POS). The presence of an open circuit may be communicated to the pulse timing substrate PTB, which may be configured to not apply an internal pulse if an open circuit is present.

[0101] The current and / or voltage measurements may be used to determine the total impedance of the coupled electrode pairs. In this regard, the voltage drop across all actively coupled electrode pairs may be measured. Furthermore, the current passing through the total impedance may be measured by a current measurement unit. The measurement information may thus make it possible to determine the corresponding total impedance. The impedance calculation may be performed by the pulse shaping output stage POS, by the pulse timing board PTB and / or by any other suitable processing entity (e.g. processing unit) of the generator G.

[0102] To measure the impedance values ​​of the electrodes, one electrode may be set as a reference electrode. For example, the second electrode E2 (coupled to the second relay switch group) may function as a reference electrode. Then, each electrode of the first relay switch group may be (separately) activated for corresponding voltage and current measurements via applied measurement pulses. For example, a first circuit may be formed between the first and second electrodes for the impedance measurement of the first electrode, a second circuit may be formed between the third and fourth electrodes for the impedance measurement of the third electrode, etc.

[0103] The generator G may then analyze the measurements received from the measurement units VM and IM. Based on the peak voltage and peak current values ​​measured, impedance values ​​may be determined separately for each electrode, and if peak currents are determined from more than one voltage pulse per electrode, an intermediate value may be determined for each electrode.

[0104] To measure the impedance of an electrode connected to the second relay switch group, the same mechanism may be applied, and the reference electrode may be an electrode connected to the first relay switch group and / or an electrode pair, for example from the first and second relay switch groups.

[0105] In particular, the output relay board ORB may be provided with various other switching capabilities. Electrode impedance measurements may also be performed, for example, relative to a single reference electrode and separate impedance measurements may be performed relative to the remaining electrodes.

[0106] Information about the impedance of the actively coupled electrode pair may be used to adjust the total capacitance of the capacitor system CS. For example, a desired RC time constant may be set for the RC circuit to be within a desired range. Adapting the time constant may ensure sufficient control of the induced charge-balanced pulse (e.g., desired dynamic response, desired symmetry of the charge-balanced pulse). As previously mentioned, the impedance measurements may be used to determine the total impedance of the actively coupled electrode pair that may be coupled during the medical procedure. The RC time constant τ may be defined as τ=R·C (where R may include the total impedance and C may include the total capacitance of the coupled circuit). Thus, the desired RC time constant τ S If the (ideal) total capacitance C S is C S = τ S / R. Since it may not always be necessary to have a specific RC time constant value, the total capacitance may be chosen such that the RC time constant falls within a certain range. For example, the RC time constant may be 0.5·10 -6 s~30·10 -6 In particular, the RC time constant may also be chosen to be in the range of 3·10 -6 s~8·10 -6 may be chosen to be within the range of s.

[0107] The generator G may be configured to automatically set the capacitance of the capacitor system based on the determined total impedance such that the RC time constant falls within a predetermined range. Alternatively, the generator G may be configured to set the capacitance based on the value of the determined total impedance. For example, if the total impedance can fall within a first range (e.g., 15 Ohm to 25 Ohm), the generator may set a first total capacitance (e.g., 0.2 μF to 0.5 μF). If the total impedance can fall within a second range (e.g., 25 Ohm to 50 Ohm), the generator may set a second total capacitance (e.g., 0.1 μF to 0.3 μF). If the total impedance can fall within a third range (e.g., 50 Ohm to 200 Ohm), the generator may set a third total capacitance (e.g., 0.01 μF to 0.15 μF).

[0108] The set total capacitance may therefore be the total capacitance used in the pulse shaping output stage when a medical procedure (eg, an ablation procedure) is performed via the electrodes of the medical device C.

[0109] FIG. 2 shows a schematic diagram of an output relay board ORB of an exemplary embodiment of the generator. FIG. 2 shows the output relay board ORB of FIG. 1 more completely. The output relay board ORB may comprise a current sensor unit 201. The current sensor unit 201 may comprise one or more current sensors for sensing the current of the electrodes. The output relay board ORB may also comprise a channel current measurement unit 240. The channel measurement unit 240 may be communicatively connected to the current sensor unit 201 (e.g., to receive the sensed current of the electrode pair). The channel current measurement unit 240 may be configured to determine (or measure) a current for each coupled electrode pair based on the current sensed by the current sensor unit 201. The channel current measurement unit 240 may be coupled to a peak detection unit 250. The peak detection unit 250 may be communicatively connected to the current sensor unit 201 (e.g., to receive the sensed current of the electrode pair). The peak detection unit 250 may be used to determine current peaks (and / or voltage peaks) at the electrode pair based on the current sensed by the current sensor unit 201. The peak detection unit 250 may be communicatively coupled to the channel current measurement unit 240. For example, the current sensor unit 201, the channel current measurement unit 240, and the peak detection unit 250 may be used to determine peak currents when determining the impedance of the electrodes, as described herein.

[0110] The output relay substrate ORB may further include an FPGA unit 220. The output relay substrate ORB may also include an ADC unit 230, which may include one or more ADCs. The ADC unit 230 may be used to convert the analog signal of the channel current measurement unit 240 into a digital signal for processing. The FPGA unit 220 and the ADC unit 230 may also be part of a switch relay control unit 210. The switch relay control unit 210 may be configured to control the relays and their configuration in the output relay substrate ORB (e.g., to close and / or open relay switches). For example, the switch relay control unit 210 may control the coupling of electrode pairs to the pulse shaping output stage POS. For example, the switch relay control unit 210 may control the relays of the first and second relay switch groups.

[0111] The output relay board ORB may be controlled by one or more central processing units CPU of the generator G. The one or more central processing units CPU may control the components of the output relay board ORB (e.g., of the switch relay control unit 210). An exemplary central processing unit CPU is shown in FIG.

[0112] Returning to Fig. 2, the output relay board ORB may further comprise a connection to a recording system RS. The output relay board ORB may comprise paths connecting the electrodes (or electrode channels) of the medical device C to the recording system RS. Thus, the electrode signals may be transmitted to the recording system RS. In another example, the generator G may comprise the recording system RS.

[0113] As can be seen in FIG. 2, the output relay board ORB may comprise a first overvoltage protection element 260. The first overvoltage protection element 260 may be for coupling to an electrode of a medical device C that may perform high voltage application (e.g. tissue ablation). The first overvoltage protection element 260 may comprise a relay switch that may open or close a path from the electrode's signal to the recording system RS. An open relay may not allow any signal to be transmitted from the electrode (e.g. ablation electrode) to the recording system RS. Thus, high voltage signals may not be transmitted to the recording system if the relay switch is open during high voltage application.

[0114] The output relay board ORB may also include a second overvoltage protection element 270. The second overvoltage protection element 270 may also be coupled to the first overvoltage protection element 260 to enable additional support for its protection function. In particular, the second overvoltage protection element 270 may be for direct coupling to a sensing electrode of the medical device C, as shown by FIG. 2. The second overvoltage protection element 270 may include a transient voltage suppressor.

[0115] Figure 3 shows a schematic diagram of various components of an exemplary embodiment of a generator. In particular, the components may be components of the same exemplary generator partially shown in Figures 1 and 2. For example, Figure 3 also shows the pulse timing board PTB and the high voltage supply HV of Figure 1. In particular, the connections to the pulse generation board PGB, the connections to the pulse shaping output stage POS, and the connections to the output relay board ORB of the generator G are shown in Figure 3.

[0116] To generate the voltage for the pulses, the generator G may comprise various stages before the high voltage source HV. For example, the generator G may comprise a power entry module 301, which may be for coupling to an alternating current AC power source. The power entry module 301 may be coupled to a DC power source 302. The DC power source 302 may adapt the alternating current AC power source so that a DC voltage may be provided. For example, the DC power source 302 may provide a DC voltage of 48V. The DC power source 302 may be coupled to a DC-DC converter 303. The DC-DC converter 303 may further increase the DC voltage provided by the DC power source 302. For example, the DC-DC converter 303 may provide a voltage of 400V. However, other voltages may also be considered (for example in the range of 100V to 800V). The DC-DC converter 303 may be controlled by a pulse timing board PTB (for example to set the output voltage of the DC-DC converter 303). The DC voltage at the output of the DC-DC converter 303 may be provided at the input of the high voltage source HV. The high voltage supply HV may use the provided input voltage to produce a high voltage at its output. The output of the high voltage supply may then be coupled to a pulse generating substrate PGB as described herein.

[0117] The generator G may comprise a central processing unit CPU. The central processing unit may be provided with a voltage from a DC-DC converter 303. However, the voltage provided to the central processing unit CPU may be different from the voltage at the output of the DC-DC converter 303. For example, the central processing unit CPU may be provided with 24V (or 12V) by the DC-DC converter 303.

[0118] The central processing unit CPU may be communicatively connected to various components of the generator G and / or to external components. For example, the central processing unit CPU may be communicatively coupled to the pulse timing board PTB and / or to the output relay board OTB. Moreover, the central processing unit CPU may be communicatively coupled to the pulse generation board PGB and to the pulse shaping output stage POS via the pulse timing board PTB. Thus, the central processing unit CPU may receive various information from the components of the generator G and / or send various instructions to the components of the generator G. For example, the central processing unit CPU may receive the current and / or voltage values ​​of the impedance measurement and perform the necessary calculations to determine the corresponding impedance (as described herein).

[0119] The central processing unit CPU may be coupled to the user interface UI. The central processing unit CPU may thus receive information from the user interface UI and / or communicate information to the user interface UI for display on the user interface UI. For example, the central processing unit may receive a selection of electrodes of the medical device from the user interface UI (which may be entered, for example, by medical personnel). The central processing unit CPU may thus communicate, for example, instructions to activate components of the generator G such that the corresponding electrodes are actively coupled (e.g., via an output relay board). The central processing unit CPU may also communicate results of the impedance measurements (e.g., total impedance, as described herein, and / or impedance of the electrodes) to the user interface UI. The central processing unit may also perform the necessary calculations to determine which total capacitance should be set in the capacitor system CS by the pulse shaping output stage. For example, based on the determined total impedance (or alternatively, simply based on the number of actively coupled electrodes), the central processing unit CPU may calculate an appropriate total capacitance. A corresponding control signal may then be sent to the pulse shaping output stage POS to set the appropriate total capacitance. For example, the RC time constant (or a sufficient range of RC time constants) may also be input to the central processing unit via the user interface. This information may then be used by the central processing unit CPU to enable setting of the total capacitance relative to the total impedance and the appropriate RC time constant. Additionally or alternatively, these may be stored during manufacture. The user interface may also be used to display the total capacitance set by the generator. In particular, various other technical and / or medical information may be communicated to the user interface for display on the user interface.

[0120] In one example, the central processing unit CPU may receive a trigger command from the user interface UI. For example, the generator G may be for coupling to the synchronization unit SU. The synchronization unit SU may also be comprised by the generator G. The synchronization unit SU may receive an electrocardiogram signal from a patient, preferably from a patient undergoing a medical procedure performed via a medical device C to which the generator G delivers charge-balanced pulses. The synchronization unit SU may receive electrical activity from various electrocardiogram electrode leads, e.g., electrodes placed on the right arm RA, the left arm LA, the right leg RL, and the left leg LL. The synchronization unit SU may determine characteristic cardiac events (e.g., R-wave peak, QRS period, etc.). The synchronization unit SU may also provide a trigger signal that accompanies the electrocardiogram signal. For example, in case of an R-wave peak, a rising flank may be provided in the trigger signal. The trigger command that may be entered into the user interface UI may include a trigger time interval. After the occurrence of a particular cardiac event, the trigger time interval may be a period after which an internal pulse (or a train of internal pulses) should be generated. This may ensure that the application of the substantially charge-balanced pulse via the electrodes of the medical device C is synchronized to the cardiac event. For example, the time interval may be chosen such that the substantially charge-balanced pulse is applied in a refractory period of the cardiac cycle (and such that the capacitor 170 may be recharged, for example, in one or more periods between two refractory periods). It may also be conceivable that a characteristic cardiac event serving as a trigger may be entered into the user interface UI or displayed by the user interface UI. The synchronization unit SU may be directly coupled to the pulse timing board PTB. The electrocardiogram signal and / or its trigger signal may thus be directly communicated to a processing entity that controls the timing of the pulses. The trigger time interval (and / or the corresponding characteristic event) may be stored in the pulse timing board PTB, the trigger time interval being communicated to the pulse timing board PTB by the central processing unit. In particular, FIG. 3 also shows the optical isolation of the pulse timing board PTB for the input of the synchronization unit.

[0121] In one example, the central processing unit CPU may be configured to determine characteristic cardiac events in the electrocardiogram signal and may generate the trigger signal itself, in which case the synchronization unit SU may be communicatively connected directly to the central processing unit CPU.

[0122] The central processing unit CPU may also be provided with various connection capabilities. For example, the central processing unit CPU may be provided with a USB connection 330. The central processing unit CPU may also be provided with an ISO Ethernet connection 340.

[0123] 4a / 4b show diagrams of a first example of charge-balanced voltage and current pulses applied by electrodes of a medical device C, the pulses being provided to the electrodes by a generator G according to the invention. Channel 1 depicts the pulse voltage V scaled down by 100 times (e.g., 40V on channel 1 represents 4000V of pulse voltage). Channel 2 depicts the resulting current I displayed as a voltage scaled down by 10 times (e.g., 10V on channel 2 represents 100A of pulse current). In FIG. 4a / 4b, four electrode pairs were actively coupled to the generator. The total impedance of the coupling circuit was determined to be 40 Ohm. The total capacitance was set to 0.13 μF. It can be seen that a biphasic pulse with positive and negative sections was generated. Regarding the voltage characteristics, the amplitude of the voltage pulse in this example may peak at about +4000V and about -2000V. Regarding the current profile, the amplitude of the current pulse in this example may peak at about +100 A and about -60 A. The exemplary pulse shown on the oscilloscope display may be used as a suitable PFA waveform for tissue ablation. The circuitry of generator G may reliably ensure a substantially charge-balanced pulse for the PFA waveform.

[0124] FIG. 5a / 5b shows a diagram of a second example of charge-balanced voltage and current pulses implemented by a generator according to the present invention. The channel scaling corresponds to that of FIG. 4a / 4b. In FIG. 5a / 5b, eight electrode pairs were actively coupled to the generator. In this example, the total impedance was determined to be 15 Ohms. The total capacitance was set to 0.34 μF. For the voltage characteristics, the amplitude of the voltage pulses in this example may peak at about +2940V and about -1200V. For the current characteristics, the amplitude of the current pulses in this example may peak at about +198A and about -100A. The exemplary pulses shown on the oscilloscope display may also be used as suitable PFA waveforms for tissue ablation.

[0125] FIG. 6a / 6b shows a diagram of a third example of charge-balanced voltage and current pulses implemented by a generator according to the present invention. The channel scaling corresponds to that of FIG. 4a / 4b. In FIG. 6a / 6b, the total impedance was determined to be 90 Ohm. The total capacitance was set to 0.13 μF. For the voltage characteristics, the amplitude of the voltage pulses in this example may peak at about +4320V and about -800V. For the current characteristics, the amplitude of the current pulses in this example may peak at about +41.5A and about -15A. The exemplary pulses shown on the oscilloscope display may also be used as suitable PFA waveforms for tissue ablation.

[0126] Fig. 7 shows a diagram of a fourth example of charge-balanced voltage and current pulses implemented by a generator according to the invention. In Fig. 7, the total impedance was determined to be 90 Ohm. The total capacitance was set to 0.03 μF. This example makes it possible to qualitatively illustrate the effect of the chosen total capacitance, which is lower than that of the example of Fig. 6a / Fig. 6b, but with the same total impedance. Thus, by adapting the total capacitance, the symmetry of the waveform of the substantially charge-balanced pulse can be systematically adjusted.

[0127] FIG. 8 shows a diagram of a user interface UI, which may be communicatively coupled to or part of the generator according to the invention. FIG. 8 may also represent a display of the user interface UI. The user interface UI may be a touch screen. However, the user interface UI may also be implemented on a monitor and input to the user interface UI may be achieved via an input device (e.g., keyboard, mouse, etc.). The user interface UI may comprise a schematic display of a medical device C. The medical device C in this example may be an ablation catheter. The ablation catheter may comprise various ablation electrodes (e.g., E1, E2) as well as mapping electrodes 801 for sensing and / or mapping (e.g., the bottom four electrodes in FIG. 1 and FIG. 2 may correspond to such sensing and / or mapping electrodes). The electrodes of the medical device C may be shown on the schematic display of the catheter C. The user may select the electrodes for active coupling (and therefore for the medical procedure) via the user interface. In the example of FIG. 8, all ablation electrodes have been activated for active coupling to the generator. Thus, all electrodes (other than purely sensing or mapping electrodes) may be used to facilitate the ablation procedure. The selected electrodes and the number of electrodes may be communicated to a central processing unit CPU. The information may be used, for example, to determine the total impedance (as described herein) and / or the total capacitance to be set in the coupling circuit (as described herein).

[0128] At the bottom of the UI, for example, the impedance values ​​of the ablation electrodes of the medical device C may be shown. For example, the impedance value 803 of the first ablation electrode E1 can be seen in comparison with other impedance values ​​of the other ablation electrodes. For example, if the electrode impedance is relatively very high, the electrode impedance may be marked in the user interface UI. The high impedance may be due to an open circuit in the catheter. In such a case, not only may the user interface US mark such a condition, but also the generator may reject the treatment when a broken electrode is thus detected. In this case, the user may have to disable the broken electrode or replace the catheter.

[0129] Also, if the electrode impedance is relatively low, the electrode impedance may also be marked accordingly in the user interface UI. Low impedance may be due to an electrode being close to, or possibly touching, another electrode. This would be a possible arcing and / or bubble formation hazard. In such a case, not only may the user interface UI mark such a condition, but the generator may also reject the treatment when such a short condition is detected. In this case, the user may have to place the close electrode in a different ablation group or relocate the catheter. Furthermore, there may be a range of impedances defined where treatment is allowed but a warning is presented in the user interface UI that the electrodes are close.

[0130] The critical impedance threshold (or critical deviation) may be communicated from the generator (e.g., from its central processing unit CPU) to the user interface. Applicant's published WO2022 / 159665 discloses several schemes for determining critical impedance. The contents of this application are incorporated herein in their entirety. The user interface may include an activation button 802 that may initiate a procedure for applying a substantially charge-balanced pulse via the electrodes. The user interface UI may also show an electrocardiogram signal 804 of a patient that may be treated by the medical device C. The user interface UI may also include a trigger panel. Activating the trigger panel may set a trigger time interval for a characteristic cardiac event (e.g., an R-wave). The user interface UI may also include an impedance measurement panel. Activating the impedance measurement panel may trigger an impedance measurement (e.g., measuring total impedance and / or measuring electrode impedance). The user interface UI may also include a capacitor panel. Upon activation of the capacitor panel, the total capacitance of the capacitor system may be manually set by the user. Activation of the capacitor panel may trigger the central processing unit CPU to determine a corresponding total capacitance based on the selected electrodes. In this regard, activation of the capacitor panel may also trigger a measurement of the total impedance. The user interface UI may also include an RC time constant panel. Upon activation of the RC time constant panel, an RC time constant and / or a suitable RC time constant range for the coupling circuit may be entered by the user.

[0131] It should be noted that the above examples may be combined with further aspects as described herein, and details of the examples may also be omitted, as would be understood by a person skilled in the art.

Claims

1. A generator (G) of substantially charge-balanced pulses for application to at least one electrode pair (101) of a medical device, comprising: a pulse shaping output stage (POS) for coupling to said at least one electrode pair; an internal pulse generator for applying an internal pulse to the pulse shaping output stage; Equipped with the pulse shaping output stage comprises a converter (T) and / or a capacitor system (CS) comprising at least one capacitor so that the internal pulse is converted into a substantially charge-balanced pulse, The pulse shaping output stage is configured to supply the charge-balanced pulses to the at least one electrode pair (I1).

2. 2. The generator of claim 1, wherein the pulse shaping output stage comprises the capacitor system (CS), and the generator is configured to be able to set at least two total capacitances of the capacitor system.

3. 3. The generator of claim 2, wherein the generator is configured to set the total capacitance of the capacitor system based at least in part on the impedance of the at least one electrode pair.

4. 3. The generator of claim 2, wherein the generator is configured to set the total capacitance of the capacitor system based at least in part on a number of electrode pairs coupled to the pulse shaping output stage.

5. 3. The generator of claim 2, wherein the generator is configured to set the total capacitance of the capacitor system such that the product of the total capacitance and the impedance of the at least one electrode pair is within a predetermined range.

6. 2. The generator of claim 1, wherein the pulse shaping output stage comprises a transformer (T) and a capacitor system (CS), the generator further configured such that the internal pulse is coupled from the internal pulse generator to the capacitor system via the transformer.

7. The generator: means for measuring the voltage and / or current (I, V) associated with said at least one electrode pair; means for determining the impedance of said at least one electrode pair based on measurements of said voltage and / or said current; The generator of claim 1 further comprising:

8. 2. The generator of claim 1, wherein the internal pulse generator comprises a high voltage source (HV), the generator configured to form the internal pulses based at least in part on a high voltage output of the high voltage source (HV), the high voltage source (HV) preferably being configurable by the generator to provide a high voltage amplitude of at least 1000V, preferably at least 1500V, more preferably at least 2000V, and most preferably at least 3000V.

9. 2. The generator of claim 1, wherein the internal pulse generator comprises a switching unit (PGB), configured to switch the output of the high voltage source (HV) to generate the internal pulses, the switching unit preferably comprising an H-bridge circuit and / or a half H-bridge circuit.

10. 10. The generator according to claim 9, wherein the internal pulse generator preferably comprises a timing unit (PTB) for controlling the switching unit to set timing parameters of the internal pulses and / or to set the number of internal pulses so that a train of internal pulses is applied to the pulse shaping output stage (POS).

11. 11. The generator of claim 10, wherein the timing unit (PTB) is configured to control the switching unit (PGB) such that the internal pulse is applied based at least in part on a trigger of a medical signal.

12. 10. The generator of claim 1, wherein the generator is configured to apply substantially charge-balanced pulses such that when the at least one electrode pair is placed in proximity to human tissue, the substantially charge-balanced pulses cause irreversible electroporation of human tissue in the vicinity of the two electrodes.

13. 10. The generator of claim 1, comprising a user interface configured to receive and / or display the determined impedance of the at least one electrode pair.

14. 14. The generator of claim 13, wherein the generator is configured to receive a selection of electrodes via a user interface and set the total capacitance based on the selection.

15. The generator of claim 14 , wherein the user interface is configured to display only a selection of electrodes.

16. 14. The generator of claim 13, wherein the user interface is configured to receive a total capacitance of the capacitor system, an RC time constant, and / or a range of suitable RC time constants as set by the user.

17. A catheter, 10. A catheter comprising a connector for connecting an electrode pair of the catheter to the generator of claim 1.

18. 18. A system comprising the generator of claim 1 and the catheter of claim 17.

19. 1. A method for generating substantially charge-balanced pulses for application to at least one electrode pair of a medical device, comprising: coupling the at least one electrode pair to a pulse shaping output stage of a generator; applying a predetermined internal pulse with an internal pulse generator of said generator to generate a substantially charge-balanced pulse in said at least one electrode pair, said method being implemented in a generator as defined in claim 1 and / or a system as defined in claim 14.

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