RU2774573C1 - Protocol of careful irreversible electroporation (ire) for preventing the formation of bubbles - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: group of inventions relates to medicine, namely, to irreversible electroporation (IRE). The system includes the installation of the initial IRE protocol for applying IRE pulses by means of catheter electrodes placed in contact with the tissue of the organ. After determining that the initial IRE protocol will presumably lead to the formation of bubbles in the blood, a notification is issued to the user. User input data on the choice between the initial IRE protocol and an alternative protocol which presumably will not lead to the formation of bubbles, supplied in response to the notification, are received from the user. IRE pulses are applied in accordance with the initial IRE protocol or the alternative IRE protocol depending on the user input data.

EFFECT: group of inventions provides an increase in the reliability of irreversible electroporation systems for preventing the formation of bubbles.

8 cl, 2 tbl, 2 dwg

Description

Scope of the invention

The present invention relates essentially to invasive ablation and, in particular, to irreversible electroporation (IRE) of cardiac tissue.

Prerequisites for the creation of the invention

Estimation of invasive ablation parameters and control of ablation based on the results of the assessment have previously been proposed in the patent literature. For example, U.S. Published Application No. 2013/0006228 describes devices for localized energy delivery and methods for using such devices, in particular for the therapeutic treatment of biological tissues. The described methods may include the location and placement of elements for supplying energy to the desired area and the supply of energy using elements for supplying energy. In one embodiment of the invention, the radio frequency (RF) duty cycle and/or pulse width may be configured to vary depending on one or more selected parameters, which may include the frequency of the treatment signal, the power of the treatment signal, or the impedance of the tissue relative to the treatment. signal.

In another example, US Patent Application Publication No. 2016/0066977 describes a medical system for ablation of a tissue site using real-time monitoring during an electroporation treatment procedure. The pulse generator generates a pre-treatment test signal with a frequency of at least 1 MHz before the treatment procedure and intra-treatment test signals during the treatment procedure. The treatment control module determines the impedance values from the pre-treatment test signal and the intra-treatment test signals, determines the electroporation progress and the treatment endpoint in real time based on the determined impedance values during the treatment.

Statement of the Invention

In one embodiment of the present invention, which is described hereinafter, an irreversible electroporation (IEP) process is provided, including setting up an initial IEP protocol to deliver IEP pulses via catheter electrodes placed in contact with tissue in an organ. Upon determining that the initial IEP protocol is likely to cause bubbling in the blood, a notification is issued to the user. User input in response to the notification is received from the user to choose between the original NEP protocol and an alternative protocol that is not expected to generate bubbles. The NEP pulses are delivered in accordance with the original NEP protocol or an alternative NEP protocol depending on the user input data.

In some embodiments of the invention, receiving the user input data includes receiving data about dividing the NEP pulse train of the original NEP protocol into a predetermined number of pulse trains with corresponding predetermined pauses between the pulse trains.

In some embodiments, the original NEP protocol and the alternative NEP protocol contain the same total number of NEP pulses. In other embodiments of the invention, the alternative NEP protocol contains fewer NEP pulses than the original NEP protocol.

In accordance with another embodiment of the present invention, an irreversible electroporation (IRE) system is further provided, including a user interface and a processor. The user interface is configured to set NEP protocols for delivering NEP pulses via catheter electrodes placed in contact with the organ tissue. The processor is configured to (i) notify the user upon determining that the initial NEP protocol is expected to cause blisters in the blood, (ii) receive, through the user interface, user input data received in response to the notification to select between the initial NEP protocol and an alternative protocol. , which is not expected to produce bubbles, and (iii) delivering the IEP pulses according to the original IEP protocol or an alternative IEP protocol, depending on the user input.

Brief description of graphic materials

The present invention will be better understood from the following detailed description of the embodiments presented in conjunction with the following drawings, wherein

in FIG. 1 is a schematic graphical representation of an irreversible electroporation (IRE) system using a catheter in accordance with an embodiment of the present invention; and

in FIG. 2 is a flowchart that schematically illustrates a method for delivering irreversible electroporation (IRP) pulses using the system shown in FIG. 1 in accordance with an embodiment of the present invention.

Detailed description of embodiments

general description

Irreversible electroporation (IEP), also called pulsed field ablation (PFA), can be used as an invasive therapeutic method to kill tissue cells by exposing them to high voltage pulses. In particular, NEP pulses can potentially be used to kill cells in myocardial tissue for the treatment of cardiac arrhythmias. Cell destruction occurs when the transmembrane potential exceeds a threshold value, resulting in cell death and thus tissue damage. In this regard, of particular interest is the use of high voltage bipolar electrical pulses (eg, using a selected pair of electrodes in contact with tissue) to generate high electric fields (eg, above a certain threshold) to kill tissue cells between the electrodes.

However, ILE pulses used for tissue ablation may, at sufficient pulse intensity, also cause undesirable and/or adverse effects of potential clinical hazard. For example, a pulse voltage of 1 kV at a blood impedance of 100 Ώ (both possible values) instantly generates a local peak current of 10 A in the blood, i.e., 10 kW. This voltage, applied between the electrodes to produce a sequence of bipolar NEP pulses, can also be high enough to generate sufficient Joule heating, which can, if not dissipated quickly, lead to the formation of gas bubbles in the blood. Some physicians may choose to accept the risk of some blisters, while others may choose not to risk it, usually due to the patient's condition, such as a recent stroke.

In the embodiments of the present invention, which are described hereinafter, methods and systems for conducting IEP are provided. In some embodiments, various IEP ablation protocols (also referred to as "original protocols") are pre-evaluated to determine if they can lead to blistering. Assessments performed in the laboratory may also help determine one or more alternative protocols to be offered to the user. If, during an ablation procedure, a physician (or other user) initially sets an IEP ablation protocol that could result in bubbling, the system notifies the physician, who is then prompted to select the use (also referred to herein as "selection user input data reception") of the protocol. "as is" or an adapted more gentle ablation protocol that does not result in blistering.

In some embodiments of the invention, determining that the selected protocol can lead to the formation of bubbles means estimating or measuring the impedance between the electrodes in a given pair of electrodes and comparing this impedance with a threshold value. If the calculated or measured impedance is below a threshold value, then the processor determines that power dissipated in the blood between the pair of electrodes may be causing bubbles to form.

In some embodiments of the invention, in a more careful NEP ablation protocol, the IEP pulse sequence of the selected protocol is divided into a pulse sequence containing a plurality of pulse trains with pauses in between. The pauses allow the Joule heating from any pulse to dissipate enough to prevent bubbles from forming.

In some embodiments of the invention, in order to maintain the clinical effect, the protocol of more careful ablation of IEP does not lead to a change in the overall level of dissipated energy. Instead, the protocol stretches the pulse time to allow more diffusion of the generated heat and reduce the maximum temperature caused by the heat. Moreover, the peak voltage of the pulse is generally not reduced in the gentle IEP ablation protocol, as this affects the generated electroporation field. If the peak voltage is somewhat reduced, it must still be maintained above a predetermined minimum level necessary for ILE ablation to be clinically effective.

In other embodiments of the invention, the clinician (or other user) can change any of the parameters of the gentle ablation protocol, and in particular the number of pulse trains and the minimum pause duration, using the user interface. For example, a clinician may divide the IEP pulse train of a selected protocol into a pulse train containing multiple burst trains with pauses in between. The pauses allow the Joule heating from any pulse to dissipate enough to prevent bubbles from forming. The user may further choose to reduce the total number of pulses to further reduce the total (ie, end-to-end) electrical power delivered to the tissue.

In one of the embodiments of the invention, the system performs the delivery of pulses in synchronism with the heartbeat, for example, for use during the refractive period of the tissue. Ventricular and atrial electrograms at ventricular or atrial tissue sites are typically obtained using electrodes in contact with tissue at the site of a positional catheter, for example, during electrophysiological mapping of tissue sections of the wall of each of the respective heart chambers. The refractive period of the ventricles or atria is the duration of the pause in neuronal activity at the location of the tissue after activation has been performed (in the tissue of any of the above chambers of the heart). The refractive period usually largely coincides with the portion of the QRST interval of the cardiac cycle shown on a ventricular or atrial electrogram obtained at that location. The refractive period can be intentionally induced in a region of heart tissue, for example, by using an electrical stimulus catheter to stimulate the tissue at its location.

Ablation of IEP of cardiac tissue in accordance with the described techniques can be performed using an expandable frame (eg, balloon or basket) installed at the distal end of the ablation catheter. In an exemplary procedure, an expandable scaffold positioned with ablative electrodes is guided through the cardiovascular system and inserted into the heart, for example, to ablate the orifice of the pulmonary vein (PV).

By offering a more careful ablation protocol as an alternative to the original IEP protocol, it is possible to make IEP ablation procedures safer, for example, at the PV orifice with an expandable stent catheter, while maintaining clinical efficacy.

System description

On FIG. 1 is a schematic graphical representation of an irreversible electroporation (IRE) system 20 using a catheter in accordance with an embodiment of the present invention. The system 20 includes a catheter 21, with the clinician 30 inserting the shaft of the catheter 22 into the vascular system of the patient 28 through the sheath 23. The clinician 30 then guides the distal end 22a of the shaft 22 to the desired location within the heart 26 of the patient, as shown in insert 25.

Once the distal end 22a a of shaft 22 has reached the desired location, clinician 30 retracts sheath 23 and expands balloon 40, typically by injecting saline into balloon 40. Physician 30 then manipulates shaft 22 so that the electrodes 50 located on balloon catheter 40 were in contact with the inner wall of the mouth of the LV 51 for the supply of high-voltage NEP pulses through the electrodes 50 to the tissue of the mouth 51.

As shown in insets 25 and 27, the distal end 22a is equipped with an expandable balloon 40 containing a plurality of equidistant smooth-edged IEC electrodes 50. plot. Thus, the configuration of balloon 40 allows for more efficient (eg, approximately equal electric field strength) electroporation between adjacent electrodes 50, while the smooth edges of electrodes 50 minimize unwanted thermal effects.

Some aspects of inflatable balloons are addressed, for example, in U.S. Provisional Application No. 62/899,259, filed September 12, 2019, entitled "Balloon Catheter with Force Sensor" and in the U.S. Patent Application No. 16/726 605, filed December 24, 2019, entitled "Contact Force Spring with Mechanical Stops", both of which are assigned to the assignee of this patent application and the disclosures of which are incorporated herein by links.

In the embodiment described herein, the catheter 21 may be used for any suitable diagnostic and/or therapeutic purpose, such as electrophysiological recording and/or isolation of the IRE tissue of the orifice of the PV 51 in the left atrium 45 of the heart 26 as described above.

The proximal end of the catheter 21 is connected to the control panel 24, containing the NEP pulse generator 38, configured to apply NEP pulses between adjacent electrodes 50. The electrodes are connected to the NEP pulse generator 38 by an electrical wire passing in the shaft 22 of the catheter 21. In the memory device 48 of the control panel 24 stores NEP protocols containing NEP pulse parameters such as peak bipolar voltage and pulse duration.

The control console 24 includes a processor 41, typically a general purpose computer, with suitable front end and interface circuits 37 for receiving signals from the catheter 21 and from external electrodes 49, which are typically placed around the patient's chest 26. To do this, the processor 41 connected to the outer electrodes 49 by means of wires passing through the cable 39.

During the procedure, the system 20 can track the respective locations of the electrodes 50 within the heart 26 using the Active Current Location (ACL) method provided by Biosense-Webster (Irvine, Calif.), which is presented in US patent No. 8,456,182, the description of which incorporated herein by reference.

In some embodiments, if processor 41 provides physician 30 with information about the risk of bubble formation when using the initially established IEP protocol, physician 30 may select a more gentle ablation protocol that divides (splits) the IEP 55 pulse delivery of the selected protocol into multiple bursts 57 with pauses between pulse trains 59 as shown in inset 27. The pauses allow the Joule heating from any pulse to dissipate enough to prevent bubbles from forming.

In other embodiments, the clinician 30 can use the user interface 47 to change any of the parameters of the gentle ablation protocol, and in particular the number of pulse trains and the minimum pause length. For example, the user may decide to remove pulses in a sequence in order to reduce the total number of pulses that need to be applied. The user interface 47 may include any suitable type of input device such as a keyboard, mouse, trackball, and the like.

To perform the functions described herein, the processor 41 is typically installed with software. The software may be electronically downloaded to a computer, such as transmitted over a network, or in an alternative or additional embodiment, may be provided and/or stored on a tangible storage medium such as magnetic, optical or electronic memory.

In particular, the processor 41 executes the specific algorithm described herein and shown in FIG. 2, whereby the processor 41 performs the steps further described below. In particular, the processor 41 is configured to control the PET pulse generator 38 to deliver PET pulses in accordance with the treatment protocol that the processor 41 loads from the memory device 48.

CAUTION PROTOCOL TO PREVENT BUBBLING

On FIG. 2 is a flowchart that schematically illustrates a method for delivering irreversible electroporation (IRP) pulses using the system 20 shown in FIG. 1 in accordance with an embodiment of the present invention. The algorithm in accordance with the present embodiment provides a process that begins when the clinician 30 directs the balloon catheter 40 to the location of the desired tissue in the patient's organ, for example, at the PV orifice 51, using, for example, the electrode 50 as electrodes with ACL sensors in step direction of the balloon catheter 80.

Then, at the planning stage of the IEP 82, the processor 41 loads the protocol, originally set by the physician 30, with the parameters of the IEP pulses to be delivered to the tissue. An example of the IEP ablation settings in the original protocol that can be used to ablate cardiac tissue using the described balloon 40 is shown in Table I.

Parameter Range Preset peak voltage of the NEP 1000 V Pulse duration 0.5 ms Pulse frequency 1 Hz Number of pulses 40

Table I. Initial Protocol

Then, in notification step 84, processor 41 notifies clinician 30 that the initial IEP protocol may be causing blisters in the blood. In response, at decision step 86, the clinician may decide to apply the protocol "as is" (i.e., apply the original protocol). Alternatively, at the protocol change decision step 88, the clinician decides to change the protocol, for example to the alternative protocol shown in Table II.

Parameter Range Preset peak voltage of the NEP 1000 V Pulse duration 0.5 ms Pulse frequency 1 Hz Number of pulses 40 Number of pulse trains eight Number of impulses in one series 5 Minimum pause between series 2 sec

Table II. gentle ablation protocol

As can be seen from Table II, in the more gentle ablation protocol, the pulse sequence from Table I is divided into eight pulse trains of five pulses each; in this case, the minimum pause between the series of pulses is two seconds.

In one embodiment of the invention, the physician 30, using the user interface 47, can change any of the parameters from table II and, in particular, the number of pulse trains and the minimum pause between pulse trains. Alternatively, the alternative protocol parameters may be automatically set by the processor 41. In one such embodiment, the processor 41 contains an appropriate alternative protocol for each native protocol supported. In another embodiment, the processor 41 obtains the alternative protocol parameters based on the original protocol parameters in accordance with some predetermined rule or method.

Upon selection of an EEP protocol (either the original protocol according to step 86 or the alternative protocol according to step 88), the processor 41 instructs the generator 38 to deliver NEP pulses to the tissue during the treatment step with the NEP 90. The NEP pulses are applied between the selected balloon electrodes 40 to isolate the arrhythmia arising from mouth 51 or extending through it.

While the embodiments described herein primarily relate to cardiac applications, the methods and systems described herein may also be applied to other medical fields such as neurology and otorhinolaryngology.

Thus, it should be understood that the embodiments of the invention described above are given by way of example only and that the present invention is not limited to the embodiments shown and described in detail above herein. On the contrary, the scope of the present invention includes both combinations and subcombinations of the various features described above, as well as variations and modifications thereof, which will be apparent to those skilled in the art upon reading the above description and which have not been described in the prior art. Documents incorporated into this patent application by reference are to be considered an integral part of the application, except that if the definitions of terms in those incorporated documents conflict with definitions made explicitly or implicitly in the present description, only the definitions of the present description should be considered.

Claims (19)

1. The method of irreversible electroporation (IEP), including: setting up an initial NEP protocol for applying NEP pulses via catheter electrodes placed in contact with organ tissue; estimating or measuring the impedance between the electrodes in the pair of electrodes and comparing this impedance with a threshold value, wherein if the calculated or measured impedance is below the threshold value, then the processor determines that the power dissipated in the blood between the pair of electrodes may lead to the formation of bubbles; issuing a notification to the user upon determining that the initial IEP protocol is expected to result in bubbling; receiving user input in response to the notification to select between the original NEP protocol and an alternative protocol that is not expected to generate bubbles; and giving NEP pulses in accordance with the original NEP protocol or an alternative NEP protocol depending on the user input data. 2. The method of claim 1, wherein receiving the user input includes receiving data about dividing the NEP pulse train of the original NEP protocol into a predetermined number of pulse trains with corresponding predetermined pauses between the pulse trains. 3. The method of claim 1, wherein the original NEP protocol and the alternative NEP protocol contain the same total number of NEP pulses. 4. The method of claim 1, wherein the alternative NEP protocol contains fewer NEP pulses than the original NEP protocol. 5. The system of irreversible electroporation (IEP), containing: a user interface configured to set NEP protocols for delivering NEP pulses via catheter electrodes placed in contact with organ tissue; and a processor that is configured to: estimating or measuring the impedance between the electrodes in the pair of electrodes and comparing this impedance with a threshold value, wherein if the calculated or measured impedance is below the threshold value, then the processor determines that the power dissipated in the blood between the pair of electrodes may lead to the formation of bubbles; issuing a notification to the user upon determining that the initial IEP protocol is expected to result in blisters in the blood; receiving, through the user interface, the user input data received in response to the notification of a choice between the original NEP protocol and an alternative protocol that is not expected to generate bubbles; and delivering NEP pulses according to the original NEP protocol or an alternative NEP protocol depending on the user input data. 6. The system of claim. 5, in which the processor is configured to receive user input data about dividing the NEP pulse train into a predetermined number of pulse trains with corresponding predetermined pauses between pulse trains. 7. The system of claim 5, wherein the original NEP protocol and the alternative NEP protocol contain the same total number of NEP pulses. 8. The system of claim 5, wherein the alternative NEP protocol contains fewer pulses than the original NEP protocol.

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