Irreversible electroporation (IRE) based on field, contact force, and time

Abstract

The present invention provides a method comprising applying an irreversible electroporation (IRE) pulse to tissue using a probe for a period of time to form an ablation lesion in the tissue. A contact force applied by the probe to the tissue during the period of time is measured. An IRE index is calculated based on the measured contact force and the power level of the IRE pulse. In response to the calculated IRE index reaching a pre-specified target IRE index value, application of the IRE pulse to the tissue is stopped.

Description

Technical Field

[0001] The present invention relates generally to irreversible electroporation (IRE) of cardiac tissue, and particularly to the estimation of the size of lesions formed during IRE. Background Art

[0002] Estimation of cardiac radiofrequency (RF) ablation parameters and control of RF ablation based on the estimation have been previously proposed in the patent literature. For example, U.S. Patent Application Publication 2017 / 0014181 describes a method comprising ablating tissue for a period of time, measuring the contact force applied during the period of time, and measuring the power used during the period of time. The method also includes stopping ablation of the tissue when a desired size of a lesion created in the tissue is reached, the desired size being estimated using an integral over the period of time of the product of the contact force raised to a first non-unity exponent and the power raised to a second non-unity exponent.

[0003] As another example, U.S. Patent Application Publication No. 2016 / 0213282 describes a method and apparatus that utilizes force-time integration to estimate lesion size in a catheter-based ablation system in real time. The apparatus measures the force applied to the target tissue by a contact ablation probe and integrates the force over the time that the ablation probe is energized. The force-time integral can be calculated and utilized to provide an estimated lesion size (depth, volume, and / or area) in real time. The force-time integral can also take into account changes in power delivered to the target tissue in real time to provide an improved estimate of lesion size. In one embodiment, the force measurement can be used as feedback to establish a desired power level delivered to the probe to prevent steam popping. In other embodiments, in addition to or in lieu of reducing or disabling energization, the control system can be adapted to increase flushing. Summary of the Invention

[0004] An exemplary embodiment of the present invention provides a method comprising applying an irreversible electroporation (IRE) pulse to tissue using a probe for a period of time to form an ablation lesion in the tissue. A contact force applied by the probe to the tissue during the period of time is measured. An IRE index is calculated based on the measured contact force and a power level of the IRE pulse. In response to the calculated IRE index reaching a pre-specified target IRE index value, application of the IRE pulse to the tissue is stopped.

[0005] In some exemplary embodiments, calculating the IRE index includes calculating an integral over a time period of a product of the contact force raised to a first calibrated power and the power level raised to a second calibrated power.

[0006] In some exemplary embodiments, the method further comprises presenting the IRE index and a pre-specified target IRE index value to the user.

[0007] In an exemplary embodiment, the IRE index corresponds to the estimated volume of the lesion. In another exemplary embodiment, the IRE index corresponds to the estimated depth of the lesion. In another exemplary embodiment, the IRE index corresponds to the estimated diameter of the lesion.

[0008] In some exemplary embodiments, the method further comprises measuring the power level by measuring the peak voltage of the IRE pulse.

[0009] In some exemplary embodiments, the method further comprises simulating the electric field generated by the IRE pulse to estimate the planned depth of the ablation lesion.

[0010] According to another exemplary embodiment of the present invention, a system including a probe and a processor is further provided. The probe is configured to apply an irreversible electroporation (IRE) pulse to tissue for a period of time to form an ablation lesion in the tissue. The processor is configured to (a) measure a contact force applied by the probe to the tissue during the period of time, (b) calculate an IRE index based on the measured contact force and a power level of the IRE pulse, and (c) stop applying the IRE pulse to the tissue in response to the calculated IRE index reaching a pre-specified target IRE index value. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] The present disclosure will be more fully understood through the following detailed description of embodiments of the present disclosure in conjunction with the accompanying drawings, in which:

[0012] Figure 1 is a schematic illustration of a catheter-based system for irreversible electroporation (IRE) treatment according to an exemplary embodiment of the present invention;

[0013] Figure 2A is a graph of force and power versus time according to an exemplary embodiment of the present invention, Figure 2B is a graph of depth versus time according to an exemplary embodiment of the present invention, Figure 2C is a graph of IRE index versus time according to an exemplary embodiment of the present invention;

[0014] Figure 3 To schematically illustrate the use of an exemplary embodiment according to the present invention Figure 1 A flowchart of a method for IRE processing performed by a system; and

[0015] Figure 4 To schematically illustrate the embodiment of the present invention when driven by an IRE pulse. Figure 1Diagram of a simulation of the electric field generated by the catheter's electrodes. DETAILED DESCRIPTION

[0016] Overview

[0017] Ablation lesions in tissue, typically tissue in a portion of a patient's heart undergoing cardiac surgery, can be created using irreversible electroporation (IRE) with a catheter. The catheter is inserted so that it contacts the tissue, and high-voltage bipolar pulses are applied to the tissue between the catheter electrodes, resulting in cell destruction and creation of ablation lesions.

[0018] To predict and control IRE treatment, it is desirable to have a universal linear IRE scale corresponding to lesion size. A possible scale may correspond to the size S of the lesion, which is assumed to be proportional to the product of the force F applied by the catheter to the tissue, the power P consumed during the IRE procedure, and the time T of the procedure. Although the possible scale relates to the power P, the relationship to lesion size is related to the IRE pulse generator RMS output current (I), based on the following formula: P = H·I 2 , where H is a constant. This formula applies to all the following discussions.

[0019] Therefore, the scale for estimating the size S of the lesion under this assumption can be given by using S in Equation 1:

[0020] S=K·F·P·T (Formula 1)

[0021] where K is the proportionality constant, and Where V p is the peak output voltage of the IRE pulse generator, and the peak electric field in the tissue E p With V p The proportionality constant depends on the type of catheter, including the spacing between the electrodes.

[0022] It is obvious from Equation 1 that the estimate of the size of the ablation lesion given by the formula is linearly proportional to F, P and T because each of these variables is raised to the power of 1 in the formula; that is, according to Equation 1, the size S is a linear function of F, P and T.

[0023] In practice, the relationship between lesion size and F, P, and T has been shown to be nonlinear, and therefore the sought-after IRE scaling will also be nonlinear. Following this observation, exemplary embodiments of the disclosed invention provide a more accurate estimate of lesion size based on the values ​​of F, P, and T, wherein the more accurate estimate of lesion size is obtained by integrating an expression over time that contains a nonlinear function of F, P, and T. This estimate can be applied during IRE of tissue separately from estimating the volume of the lesion, the depth of the lesion, and / or the diameter of the lesion created in the tissue, so that IRE can be stopped when the desired size is reached.

[0024] In an exemplary embodiment of the present invention, a general IRE linear scale (hereinafter referred to as the "IRE index") is derived by calculating the integral of the product of the contact force raised to a first calibrated non-first power and the power raised to a second calibrated non-first power over a time period.

[0025] In some exemplary embodiments, an IRE index is provided, which is the time integral of the force applied and power dissipated by the IRE pulse. The value of the IRE index (for lesions of different sizes / volumes) is determined experimentally and calibrated. For a given type of cardiac structure and given tissue characteristics, the value of the IRE index is expected to be a reproducible predictor of lesion size. Furthermore, due to differences in structure and tissue characteristics, the lesion size for a given IRE index value may vary.

[0026] In some exemplary embodiments, a physician irreversibly electroporates tissue using a catheter over a period of time to form an ablation lesion in the tissue. During the period of time, the contact force applied by the catheter and the irreversible electroporation power applied to the tissue are measured. Based on the measured contact force and irreversible electroporation power, an IRE index is derived (e.g., calculated), and when the calculated IRE index reaches a pre-specified target IRE index value, irreversible electroporation of the tissue is stopped. Using a universal linear IRE index ensures that the IRE treatment can be stopped when the estimated size reaches the desired size.

[0027] Some exemplary embodiments of the present invention further simulate the electric field generated by the electrodes in the IRE system and graphically display the field values. Before actually generating the IRE pulse, the physician uses the displayed graph to position the electrodes so that the appropriate field is applied to destroy tissue. In exemplary embodiments, the processor can adjust the displayed theoretical field by taking into account the IRE index, the contact force between the electrode and the battery, and / or the proximity of the battery to the electrode.

[0028] By providing an IRE index, catheter-based IRE treatment can be made safer and more effective. DETAILED DESCRIPTION

[0030] Figure 1 is a schematic illustration of a catheter-based system 12 for irreversible electroporation (IRE) treatment according to an exemplary embodiment of the present invention. Figure 3 Flowchart of the procedure using an estimate of lesion size that can be derived using the aforementioned IRE index.

[0031] The IRE procedure is performed by a physician 14 , and by way of example, it is assumed that the procedure in the following description involves IRE of a portion of the myocardium 16 of the heart of a human patient 18 .

[0032] To perform an ablation, a physician 14 inserts a probe 20, such as a lasso catheter (manufactured by BiosenseWebster, Inc. of Irvine, California), into a patient's lumen, such that the distal end 22 of the probe enters the patient's heart. As shown in inset 25, the distal end 22 includes a plurality of electrodes 24 mounted on the outside of the articulation segment 40 of the distal end 22, which contact the myocardium. The distal end 22 also includes a force sensor 45. The probe 20 also includes a proximal end 28.

[0033] The system 12 is controlled by a system processor 46 located in an operating console 48 of the system. The console 48 includes controls 49 used by the physician 14 to communicate with the processor. During a procedure, the processor 46 typically tracks the position and orientation of the distal end 22 of the probe using any method known in the art. For example, the processor 46 may use a magnetic tracking method in which a magnetic transmitter outside the patient 18 generates a signal in a coil located at the distal end. The system uses such tracking methods. As another example, the position and orientation of distal tip 22 can be tracked using the Advanced Catheter Positioning (ACL) system manufactured by Biosense-Webster, Inc., which is described in U.S. Patent No. 8,456,182, the disclosure of which is incorporated herein by reference. In the ACL system, a processor estimates the respective positions of multiple electrodes 24 based on impedance measured between each of the electrodes 24 and multiple surface electrodes coupled to the skin of patient 18.

[0034] Software for processor 46 can be downloaded electronically to the processor, for example, over a network. Alternatively or in addition, the software can be provided via non-transitory tangible media, such as optical, magnetic, or electronic storage media. Tracking of distal tip 22 is typically displayed on a three-dimensional representation 60 of the heart of patient 18 on screen 62. The progress of the IRE treatment performed by system 12 is also typically displayed on screen 62 as a graphic 64 and / or alphanumeric data 66.

[0035] To operate the system 12, the processor 46 communicates with a memory 50 having a plurality of modules used by the processor to operate the system. Thus, the memory 50 includes a power control module 54 and a force module 56. The power control module 54 delivers IRE power to the electrodes 24 and also typically controls the IRE power by measuring the instantaneous peak voltage V delivered by the electrodes. p(t) To measure the instantaneous power P(t) delivered at time t. If the waveform is stationary, the instantaneous RMS voltage V RMS(t) To determine V p(t) The force module 56 measures the instantaneous contact force at time t by acquiring and evaluating the signal from the force sensor 45 in the distal end 22. The memory 50 may also include other modules, such as a temperature measurement module and an irrigation module. For simplicity, such other modules are not further described in this patent application. The modules of the memory 50 also include hardware and software components.

[0036] Derivatives of the IRE index

[0037] A general estimate of the lesion volume resulting from IRE of tissue can be written as:

[0038]

[0039] in

[0040] V(T) is the volume of the ablation lesion produced by IRE in the time period T;

[0041] C is the proportionality constant;

[0042] CF(t) is the value of the instantaneous contact force applied to the tissue at time t during ablation;

[0043] P(t) is the value of the instantaneous power dissipated at time t during ablation; and

[0044] α, β are powers whose values ​​are not equal to 1 (one).

[0045] Because, as mentioned above, the power P can be used to flow with the peak voltage V p Expressed as So formula 2 can also be written as:

[0046]

[0047] where H is a constant, and where V p (t) is the value of the instantaneous peak voltage applied at time t.

[0048] In the description of the following results, the units of each variable used to estimate Equation 2 and Equation 2a are assumed and shown in Table 1 by way of example:

[0049]

[0050] Table I

[0051] Alternative formulas for Formula 2 and Formula 2a are Formula 3 and Formula 4, as shown below:

[0052]

[0053] wherein each of the terms is as defined above with respect to Equation 2 and Equation 2a, and wherein Depth is the lesion depth in mm, and γ is a value raised to a power not equal to 1 (one).

[0054]

[0055] wherein each of the terms is as defined above with respect to Equation 2 and Equation 2a, and wherein Diam is the lesion diameter in mm, and δ is a value raised to a power not equal to one.

[0056] The degree of approximation of the formula

[0057] Formula 2, Formula 2a, Formula 3, and Formula 4 can be approximated by assuming that CF, P, or I do not change during time period T. The following description describes the approximation of Formula 3, but one of ordinary skill in the art will be able to apply similar approximations to Formula 2 and Formula 4.

[0058] For simplicity, in the following description, Equation 3 is used with power instead of current:

[0059]

[0060] If it is assumed that P has a fixed value during the ablation period T, then Equation 3′ can be rewritten as:

[0061]

[0062] If CF is almost constant or if but

[0063]

[0064] where ACF is the average of CF over time T.

[0065] Substituting Equation 6 into Equation 5 yields:

[0066] Depth γ =C·ACF α ·P β T (Formula 7)

[0067] The values ​​of C, α, β, and γ

[0068] Taking the logarithm on both sides of Equation 7 yields:

[0069]

[0070]

[0071] The values ​​of C, α, β, and γ in Equation 8 can be derived and calibrated experimentally, including using linear regression analysis to evaluate C, α, β, and γ.

[0072] integral In this paper, it is called IRE index and is denoted as therefore,

[0073]

[0074] Figure 2A is a graph of force and power versus time according to an embodiment of the present invention, Figure 2B is a graph of depth versus time according to an embodiment of the present invention, Figure 2C FTP according to an embodiment of the present invention IRE These graphs show the appearance of the estimated depth and IRE index as both power and force are varied. The graphs of IRE index versus time show that the estimated IRE index is designed to increase linearly with the duration of the IRE treatment.

[0075] For a given type of cardiac structure and given tissue characteristics, the value of the IRE index is expected to be a reproducible predictor of lesion size. In addition, due to differences in structural and tissue properties, the lesion size for a given ablation index value may vary.

[0076] Figure 3 To schematically illustrate the use of an exemplary embodiment according to the present invention Figure 1 FIG1 is a flow chart of a method for IRE treatment performed by the system 12 of FIG1 . In an initial step 100, the physician selects a target IRE index value to form a planned ablation lesion. For example, the physician may select a target IRE index value to produce a desired depth within the range of 1 mm to 5 mm. In addition, the physician selects the values ​​of C, α, β, and γ to be used in the depth estimation formula to be used (herein, assumed to be Formula 3).

[0077] In a start IRE treatment step 102, the physician uses control 49 to select a voltage waveform having a given peak voltage that produces a nominal power to be delivered by power control module 54. Typically, the resulting power is in the range of a few milliwatts, but powers outside this range may also result. After selecting the peak nominal voltage, the physician uses control 49 to start the IRE treatment.

[0078] In a measurement step 104 , as ablation is performed, power control module 54 measures the instantaneous power P(t) consumed by electrode 24 , which may differ from the derived nominal power. Additionally, force module 56 measures the instantaneous contact force CF(t) on distal tip 22 .

[0079] In calculation step 106, as the IRE process proceeds, the processor 46 repeatedly calculates the integral value used in Formula 5, i.e., the ablation index I in Formula 9. FTP_IRE In the IRE index estimation step 108, the processor calculates the value of the estimated IRE index using Formula 9.

[0080] In decision step 110, the processor checks whether the estimated IRE index is equal to the target IRE index value. If a positive decision is returned in the final step 112, the processor stops the IRE processing. If a negative decision is returned, the processor continues the IRE processing in the continue ablation step 114, and the flowchart returns to the measurement step 104.

[0081] To further estimate the planned depth of the lesion formed by the IRE pulse, the disclosed technique also includes simulating the electric field generated by the IRE pulse. Figure 4 To schematically illustrate the embodiment of the present invention when driven by an IRE pulse. Figure 1 Diagram of a simulation of the electric field generated by the catheter's 24 electrodes. Figure 4 Theoretical field lines 60 are shown for the RMS value generated by the bipolar electrodes on the lasso 40 catheter.

[0082] Before actually generating the IRE pulse, physician 14 uses the displayed graphics to position electrode 24 so that the appropriate field is applied to the tissue cells desired to be destroyed.

[0083] As shown, the simulated field penetrates to a depth 70 in space, and the depth 70 can be used to plan the intensity of the IRE pulse (e.g., peak voltage V p ).

[0084] Although Figure 4 Not shown, but some exemplary embodiments may adjust the theoretical fields shown by taking into account the contact force of the electrode to the battery and / or the proximity of the battery to the electrode.

[0085] Although the exemplary embodiments described herein are primarily directed to cardiac applications, the methods and systems described herein may also be used in other medical applications, such as neurology, renal denervation, and otolaryngology.

[0086] It should therefore be understood that the embodiments described above are cited by way of example, and that the present invention is not limited to what is specifically shown and described above. On the contrary, the scope of the present invention includes combinations and subcombinations of the various features described above, as well as variations and modifications thereof, which will occur to those skilled in the art upon reading the above description and which are not disclosed in the prior art. The documents incorporated by reference into this patent application are considered an integral part of this application, except that if any term defined in these incorporated documents conflicts with a definition explicitly or implicitly given in this specification, only the definition in this specification shall be considered.

Claims

1. A system for applying an irreversible electroporation (IRE) pulse to tissue, the system comprising: a probe configured to apply an IRE pulse to the tissue within a certain period of time to form an ablation lesion having a planned depth in the tissue; as well as a processor configured to: simulating an electric field that will be generated in the tissue by the IRE pulse and setting a power level of the IRE pulse that will achieve the planned depth of the lesion; measuring a contact force applied by the probe to the tissue during the time period; calculating an IRE index based on the measured contact force and the power level of the IRE pulse; and In response to the calculated IRE index reaching a pre-specified target IRE index value, applying the IRE pulse to the tissue is stopped.

2. The system according to claim 1, wherein: The processor is configured to calculate the IRE index by integrating over the time period the product of the contact force raised to a first calibrated power and the power raised to a second calibrated power.

3. The system according to claim 1, wherein: The processor is further configured to present the IRE index and the pre-specified target IRE index value to a user.

4. The system according to claim 1, wherein: The IRE index corresponds to an estimated volume of the ablation lesion.

5. The system according to claim 1, wherein The IRE index corresponds to an estimated depth of the ablation lesion.

6. The system according to claim 1, wherein: The IRE index corresponds to an estimated diameter of the ablation lesion.

7. The system according to claim 1, wherein: The processor is further configured to measure the power level by measuring a peak voltage of the IRE pulse.

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