Pulse wave optimization to minimize neuromuscular stimulation during pulse field ablation therapy

Abstract

A method and apparatus for performing a medical ablation procedure. In one example, a medical device includes an ablation waveform generator and an electronic controller. The ablation waveform generator is configured to apply an electrical waveform to a treatment element positionable proximate a treatment site of a patient. The electronic controller is configured to control the ablation waveform generator. The electronic controller is further configured to cause the ablation waveform generator to generate a biphase waveform having an inter-phase delay and an inter-pulse delay greater than the inter-phase delay. The electronic controller is configured to cause the ablation waveform generator to apply the biphasic waveform to the treatment element.

Description

Technical Field

[0001] This application relates in general to methods and systems associated with ablation catheters, ablation generators, and other medical devices and components used in various ablation procedures. Background Technology

[0002] Delivery of some types of ablation therapy involves the use of reliable, powerful, and precisely controlled electrical energy, such as in the form of a high-voltage pulse generator or a radio frequency (RF) generator. In the case of pulsed field ablation (PFA), electrical pulses or continuous wave (CW) sine waves are delivered to the intended treatment site to perform reversible or irreversible electroporation, and thermally induced necrosis is achieved via RF using an ablation therapy delivery device. Summary of the Invention

[0003] Pulsed field ablation (PFA) therapy delivers electrical pulses to the treatment site by generating biphasic waveforms. These waveforms are characterized by phase delays (the delay between the positive and negative phases of the pulse, e.g., ...). Figure 2 (204, 206, and d1 in the text) and inter-pulse delay (the delay between pulses, for example, Figure 2 d2 in the pulse width (e.g., Figure 2 T p Other parameters, such as cycle length and rise and fall times, are also considered. PFA targets treatment sites, such as the pulmonary veins in the left atrium or arrhythmogenic matrix in the ventricles. While the area causing irreversible electroporation (IRE) is closest to the ablation electrode, the electric field generated by PFA treatment can extend significantly beyond the IRE area, resulting in undesirable stimulation of neuromuscular structures. For example, pulsed fields can excite certain tissues, including nerves, as well as smooth and striated muscles (e.g., skeletal muscles), which can cause discomfort and involuntary movements in the patient. This may adversely require deeper sedation during treatment. Some pulsed fields can also directly stimulate pain fibers (e.g., A-δ and / or C-fibers), resulting in corresponding pain / discomfort. Stimulation of vagal structures can cause bradycardia and a cough reflex. The vagus nerve, also known as the 10th cranial nerve, cranial nerve X, or CN X, is a cranial nerve that intersects with the parasympathetic control of the heart, lungs, and digestive tract. The vagus nerve is the longest nerve in the human autonomic nervous system and includes both sensory and motor fibers. Furthermore, stimulation of smooth muscle cells and / or the autonomic nerves innervating blood vessels can lead to vasoconstriction and possible vasospasm, including coronary artery vasospasm. The electric field will also be applied at a distance from the catheter (e.g., at...). Figure 3 In region 304, it captures / stimulates cardiomyocytes (i.e., heart tissue), thereby potentially causing acute arrhythmias.

[0004] By utilizing relatively short interphase and interpulse delays in the waveform, undesirable effects are reduced. However, the resulting higher-frequency waveform can generate excessive heat and / or microbubbles. Increasing interphase and interpulse delays mitigates temperature rise, which may lead to condensation and bubble formation. However, increasing interpulse delay can increase undesirable effects, particularly neuromuscular stimulation.

[0005] To address these issues, the embodiments and aspects presented herein provide selectable, modified, and / or adjustable ablation waveforms that reduce (e.g., minimize) adverse effects while still achieving the intended therapeutic purpose. Using the examples presented herein, waveforms with increased inter-pulse delay and shorter (relative to inter-pulse delay) phase delays are generated. Using such waveforms, the embodiments presented herein apply PFA treatment while reducing undesirable neuromuscular stimulation and patient discomfort.

[0006] This document discloses various aspects, features, and implementation schemes of methods and devices for performing various ablation procedures. One example provides a medical device. This medical device includes an ablation waveform generator and an electronic controller. The ablation waveform generator is configured to apply an electrical waveform to a therapeutic element that can be placed near a treatment site on a patient. The electronic controller is configured to control the ablation waveform generator. The electronic controller is also configured to cause the ablation waveform generator to generate a biphasic waveform having an interphase delay and an interpulse delay greater than the interphase delay. The electronic controller is configured to cause the ablation waveform generator to apply the biphasic waveform to the therapeutic element.

[0007] In some respects, the technology described herein relates to a medical method comprising: generating a biphasic waveform using an ablation waveform generator, the biphasic waveform having an interphase delay and an interpulse delay greater than the interphase delay; and applying the biphasic waveform to a therapeutic element that can be placed near a treatment site on a patient.

[0008] In some respects, the techniques described herein relate to a non-transitory computer-readable medium containing executable instructions that, when executed by one or more electronic processors, cause the one or more electronic processors to: generate a biphasic waveform using an ablation waveform generator, the biphasic waveform having an interphase delay and an interpulse delay greater than the interphase delay; and apply the biphasic waveform to a therapeutic element that can be placed near a treatment site on a patient. Attached Figure Description

[0009] The same reference numerals in the accompanying drawings denote the same or similarly functional elements in the various views, and are incorporated in and form part of the specification together with the following detailed description, and are also used to illustrate various embodiments, examples, aspects and features including the claimed subject matter, and to explain the various principles and advantages of the aspects of those embodiments, examples, aspects and features.

[0010] Figure 1A and Figure 1B This is a block diagram illustrating various examples of medical systems.

[0011] Figure 2 The diagram illustrates the usability of various examples. Figure 1A and Figure 1B The electrical waveforms delivered by the medical system to the treatment site.

[0012] Figure 3 The illustrations illustrate the use of various examples. Figure 1A and Figure 1B During the medical system, the patient's treatment site and surrounding area are treated.

[0013] Figure 4 These are examples of configurations available based on various examples. Figure 1A and Figure 1B A table of plans for the medical system.

[0014] Figure 5 and Figure 6 The diagram illustrates the usability of various examples. Figure 4 The plan and Figure 1A and Figure 1B The electrical waveforms delivered by the medical system to the treatment site.

[0015] Figure 7A and Figure 7B This is an example based on various examples. Figure 1A and Figure 1B A bar chart showing various aspects of the operation of the medical system.

[0016] Figure 8 This is an example based on various examples. Figure 1A and Figure 1B Line diagrams illustrating various aspects of the operation of the medical system.

[0017] Figure 9A and Figure 9B This is an example based on various examples. Figure 1A and Figure 1B A bar chart showing various aspects of the operation of the medical system.

[0018] Figure 10 This is an example based on various examples. Figure 1A and Figure 1B Line diagrams illustrating various aspects of the operation of the medical system.

[0019] Figure 11 Examples are given based on various examples. Figure 1A and Figure 1B The flowchart shows the methods implemented by the medical system.

[0020] Figure 12A and Figure 12B This is an example based on various examples. Figure 1A and Figure 1B A bar chart showing various aspects of the operation of the medical system.

[0021] Figure 13 This is an example based on various examples. Figure 1A and Figure 1B Line diagrams illustrating various aspects of the operation of the medical system.

[0022] Figure 14 This is an example based on various examples. Figure 1A and Figure 1B Line diagrams illustrating various aspects of the operation of the medical system.

[0023] Those skilled in the art will understand that the elements in the accompanying drawings are illustrated for simplicity and clarity and are not necessarily drawn to scale. For example, the dimensions of some elements in the drawings may be enlarged relative to other elements to aid in understanding the illustrated examples, aspects, and features.

[0024] In some instances, device and method components have been indicated by conventional symbols in the accompanying drawings where appropriate, so as to show only those specific details relevant to understanding the various embodiments, examples, aspects and features, so as not to confuse the contents of this disclosure with details that are readily apparent to those skilled in the art and have the benefit of the description herein. Detailed Implementation

[0025] For ease of description, some or all of the exemplary systems presented herein are illustrated by a single example of each of their components. Some examples may not describe or illustrate all components of the system. Other exemplary embodiments may include more or fewer of each of the illustrated components, may combine some components, or may include additional or alternative components.

[0026] It should be understood that although some of the figures presented herein illustrate hardware and software located within a particular device, these depictions are for illustrative purposes only. In some embodiments, the illustrated components may be combined or divided into separate software, firmware, and / or hardware. For example, instead of being located within and executed by a single electronic processor, logic and processing may be distributed across multiple electronic processors. Regardless of how they are combined or divided, hardware and software components may reside on the same computing device or may be distributed among different computing devices connected by one or more networks or other suitable communication links.

[0027] Figure 1A and Figure 1B This is a block diagram illustrating a medical system 100 based on various examples. More specifically, Figure 1A It is a block diagram illustrating the overall view of system 100, and Figure 1B This is a block diagram illustrating the electronic controller used in system 100.

[0028] In a representative example, system 100 includes a medical device 112 and an electronic controller 114 communicating with the medical device 112. In operation, the medical device 112 is used to deliver energy (e.g., PFA or electroporation energy) to treat or ablate areas of target tissue. In various examples, the medical device 112 is also used to deliver one or more test pulses or waveforms to assess the correctness of its location or the likelihood of adverse reactions caused by the delivery of such energy.

[0029] In the example shown, the medical device 112 includes a catheter 102, a magnified view of a portion 101 of which is shown. Figure 1A As shown in the diagram, catheter 102 has electrodes 118 for therapeutic interaction with selected treatment sites within or on a patient's body. In operation, electrodes 118 deliver energy (e.g., PFA energy, electroporation energy, test pulses and waveforms, and / or other transferred energy) to the treatment site. Catheter 102 includes an elongated body 120 capable of passing through a patient's vascular system to allow the electrodes 118 to be positioned near the patient's treatment site for diagnostic and / or therapeutic purposes. The elongated body 120 has a proximal portion 122 and a distal portion 124, and typically includes one or more lumens providing mechanical, electrical, and / or fluid communication between the proximal and distal portions 122 and 124. In some examples, the elongated body 120 has a central or guidewire lumen 130 that accommodates a shaft 132 and a carrier arm 128. The shaft 132 is movable within and relative to the guidewire lumen 130 longitudinally. In operation, the longitudinal movement of shaft 132 is used to transform carrier arm 128 between a first (e.g., substantially linear) configuration and a second (e.g., annular) configuration. As an example, Figure 1AThe carrier arm 128 in a ring configuration is shown. The carrier arm 128 and the electrode 118 may be referred to herein as therapeutic elements.

[0030] The medical device 112 also includes a handle 140 connected to the proximal portion 122 of the elongated body 120. In various examples, the handle 140 includes circuitry and structures for proper operation and manipulation of the catheter 102. Additionally, the handle 140 typically includes one or more connectors 104 for electrically connecting the circuitry to, for example, an electronic controller 114, to establish electrical paths between various relevant portions of the medical device 112 and relevant components or portions of the electronic controller 114. The handle 140 also typically has one or more actuating or control features that enable a physician to control, deflect, steer, or otherwise manipulate the distal portion 124 via the proximal portion 122.

[0031] In some examples, system 100 also includes a navigation system 142 for guiding medical treatment procedures. In the example shown, medical device 112 is coupled to electronic controller 114 via navigation system 142. In some other examples, both medical device 112 and navigation system 142 are directly coupled to electronic controller 114. Navigation system 142 is designed to help visualize the real-time position and orientation of catheter 102 within the patient's body to increase the accuracy of targeted ablation and reacquiring pacemaker sites for re-ablation. In a typical example, navigation system 142 uses three magnetic sources 152, 154, and 156 as references to calculate the position and orientation of catheter tip 108. Navigation system 142 typically relies on a calibrated and computer-controlled static magnetic field. Due to the nature of the magnetic field, the orientation of carrier arm 128 can be calculated even when tip 108 is stationary. By calculating the strength and orientation of the magnetic field at a given location, the Cartesian coordinates (x, y, z) of tip 108 are typically calculated together with the roll, pitch, and yaw angles of carrier arm 128.

[0032] In various examples, the electronic controller 114 includes components and circuitry for delivering one or more energy modes to the electrode 118. Figure 1B In the example shown, the electronic controller 114 includes an ablation waveform generator 144, control circuitry 146, and input / output (I / O) devices 160. The control circuitry 146 includes processing circuitry (e.g., a general-purpose processor) 148 and memory 150. The I / O devices 160 of the electronic controller 114 typically provide multiple I / O channels, for example, including one or more channels 162 for communicating with external monitoring devices, and at least one I / O channel 164 for operatively connecting the waveform generator 144 to the medical device 112 (see also...). Figure 1AThe electronic controller 114 is capable of operating in multiple operating modes, which can be selected as needed or as appropriate for specific medical procedures.

[0033] In various examples, memory 150 includes buffers for temporarily storing received data and non-volatile data storage devices for more permanent storage of data and program code. In operation, memory 150 provides relevant data and program code to processing circuitry 148. When executed by processing circuitry 148, the program code enables electronic controller 114 to perform signal processing and generate various control and communication signals. In some examples, processing circuitry 148 performs rendering processing on input signals received from external monitoring devices and outputs corresponding visual images, charts, and / or graphs via I / O devices 160 for viewing on an external display.

[0034] In various examples, the medical monitoring device includes one or more devices from the following group of devices: diaphragmatic or chest displacement assessment device; accelerometer; electromyography (EMG) machine; ECG recorder; vital signs monitor; airway pressure monitor; and expiratory carbon dioxide monitor. In other examples, other suitable patient monitoring devices are similarly used and linked to the electronic controller 114 via I / O device 160. In some examples, I / O device 160 includes at least one I / O interface device for supporting a wireless data link.

[0035] In some examples, the electronic controller 114 is also connected to the operator interface device 170 via I / O device 160. In various examples, the operator interface device 170 includes: a touchscreen; buttons, knobs, and / or keypads; light indicators (e.g., colored light-emitting diodes, LEDs); a speaker; a switch; a joystick; and other control accessories connected and configured to enable the operator to correctly operate the electronic controller 114 and the medical device 112. The operator interface device 170 also typically allows the operator to see on it at least some indicators generated by the electronic controller 114 in response to signals received from the medical monitoring device via I / O device 160.

[0036] Figure 2 The electrical waveform 200 delivered to a treatment site by a usable system 100 according to various examples is illustrated graphically. The electrical waveform 200 includes a sequence of N biphasic pulses 202, which are labeled 2021, 2022, ..., 202... N Each biphase pulse in biphase pulse 202 comprises a positive pulse 204 and a negative pulse 206. Both the positive pulse 204 and the negative pulse 206 have an amplitude αV0 and a pulse width T. p, where α is a scaling factor, for example, in the range between 0.1 and 10. The time delay between positive pulse 204 and negative pulse 206 is d1. Parameter d1 is referred to as the phase delay in this paper. The time delay between two consecutive biphase pulses 202 in waveform 200 is d2. Parameter d2 is referred to as the pulse delay in this paper. Amplitude V0, pulse width T p The parameters α, N, d1 and d2 of waveform 200 can be selected and controlled via waveform generator 144.

[0037] Figure 3 The diagram schematically illustrates the patient's area during treatment using the medical system 100. Specifically, Figure 3 An example is illustrated of the effective region of placement relative to the carrier arm 128 of catheter 102. In region 302, both irreversible and reversible electroporation of the tissue occurs. In region 304, as described herein, neuromuscular stimulation and application of PFA waveforms (e.g., Figure 2 Other undesirable effects of waveform 200. Irreversible and reversible electroporation occur in region 302, independent of the values ​​of d1 and d2 of the applied waveform. However, the occurrence of undesirable effects is influenced by the values ​​of d1 and d2 of the applied waveform. Due to the low threshold of transmembrane voltage (TMV), the area and / or volume of neural excitation extends beyond the volume of cell membrane permeability.

[0038] The following text is relative to Figures 4 to 10 The undesirable effects that may accompany PFA treatment can be reduced by selecting the values ​​of d1 and d2 without affecting the effectiveness of the desired treatment (i.e., the levels of irreversible and reversible electroporation).

[0039] Figure 4 This is a table illustrating multiple scenarios, each representing a different variation of waveform 200. For example... Figure 4 As shown, each scheme uses T p The values ​​of d1, d2, and N define its waveform; these values ​​are the pulse parameters of the biphase pulse scheme. All schemes have the same total on-time, i.e., N×2T. p =1ms. T p Specifies the pulse width (equal for positive and negative phases), N is the number of pulses, d1 specifies the inter-phase delay, and d2 specifies the inter-pulse delay. As shown in the figure, T... p The values ​​of N vary for each group (1-3, 4-6, 7-9) of the three schemes, but are the same within the group. Schemes 1, 3, 4, 6, 7 and 9 specify a waveform in which the interphase delay (d1) is less than the interpulse delay (d2). Figure 5An exemplary waveform 502 of this type is illustrated. Schemes 2, 5, and 8 specify waveforms where the interphase delay (d1) is greater than the interpulse delay (d2). Figure 6 An exemplary waveform 602 of this type is shown.

[0040] Figure 7A , Figure 7B and Figure 8 The results of PFA treatment administered using, for example, medical system 100 using protocols 1, 2, and 3 were compared. Figure 4 As shown, T in schemes 1-3 p The value is 0.5 μs, and N is 1000. In Scheme 1, the inter-phase delay (d1) is 2 μs, and the inter-pulse delay (d2) is 100 μs. In Scheme 2, the inter-phase delay (d1) is 100 μs, and the inter-pulse delay (d2) is 2 μs. In Scheme 3, the inter-phase delay (d1) is 2 μs, and the inter-pulse delay (d2) is 800 μs. Figure 7A This is a bar graph illustrating unwanted neuromuscular contractions caused by the application of the waveforms described in schemes 1-3. (As shown from...) Figure 7A It is evident that, across a certain range of amplitude, the incidence of unwanted neuromuscular contractions is low in schemes 1 and 3. Figure 7B This is a bar graph illustrating the pain index (as reported by the patient) resulting from the application of the waveforms described in schemes 1-3. (As from...) Figure 7B It is evident that, across a certain range of amplitude, schemes 1 and 3 have lower pain indices. Figure 8 This illustrates region 302 as caused by the waveforms applied according to schemes 1 and 2 (see...). Figure 3 A line graph showing the percentages of permeability (i.e., reversible electroporation) and survival rate (i.e., irreversible electroporation) in [the context of electroporation]. For example... Figure 8 As shown, the differences in penetration rate and survival rate between schemes 1 and 2 are basically the same.

[0041] Figure 9A , Figure 9B and Figure 10 The results of PFA treatment administered using, for example, medical system 100 according to protocols 4, 5, and 6 were compared. Figure 4 As shown, T in scheme 4-6 p The value is 5 μs, and N is 100. In Scheme 4, the inter-phase delay (d1) is 2 μs, and the inter-pulse delay (d2) is 100 μs. In Scheme 5, the inter-phase delay (d1) is 100 μs, and the inter-pulse delay (d2) is 2 μs. In Scheme 6, the inter-phase delay (d1) is 2 μs, and the inter-pulse delay (d2) is 800 μs. Figure 9AThis is a bar graph illustrating unwanted neuromuscular contractions caused by the application of the waveforms described in schemes 4-6. (As shown from...) Figure 9A It is evident that, across a certain range of amplitude, the incidence of unwanted neuromuscular contractions in schemes 4 and 6 is lower than that in scheme 5. Figure 9B This is a bar graph illustrating the pain index (as reported by the patient) caused by the application of the waveforms described in schemes 4-6. (See the image below.) Figure 9B It is evident that, across a certain range of amplitude, the pain indexes of schemes 4 and 6 are lower than those of scheme 5. Figure 10 This shows region 302 caused by the waveforms applied according to schemes 4 and 5 (see...). Figure 3 A line graph showing the percentages of permeability (i.e., irreversible electroporation) and survival rate (i.e., reversible electroporation) in [the context of electroporation]. For example... Figure 10 As shown, the differences in penetration rate and survival rate between schemes 4 and 5 are basically the same.

[0042] Figure 11 This is a flowchart illustrating a method 1100 for performing pulsed field ablation therapy according to various examples. In some examples, method 1100 is implemented in a fully automatic mode via electronic controller 114, wherein no additional input from a human operator from the system is required after the method is initiated. In some other examples, method 1100 has one or more checkpoints where human decision-making or prompting is requested. In such examples, the remainder of method 1100 is still executed automatically by the corresponding controller circuitry of electronic controller 114, for example, by running corresponding program code.

[0043] Method 1100 includes generating a biphase waveform using an ablation waveform generator, the biphase waveform having an interphase delay and an interpulse delay greater than the interphase delay (in block 1102). In some examples, electronic controller 114 causes ablation waveform generator 144 to generate a waveform similar to... Figure 2 The waveform is illustrated. In some examples, the ablation waveform generator 144 uses... Figure 4 The parameters specified for schemes 1, 4, or 7 generate waveform 200. In some examples, the ratio between inter-pulse delay and inter-phase delay is 50:1. In some examples, the pulse width of the waveform remains constant regardless of the values ​​of inter-pulse delay and inter-phase delay.

[0044] Method 1100 includes applying an electrical waveform to a treatment element (in block 1104) that can be placed near a patient's treatment site. In some examples, an electronic controller 114 causes an ablation waveform generator 144 to apply a biphasic waveform 200 to the electrodes 118 of a carrier arm 128 to apply the electrical waveform to the patient's treatment site.

[0045] In some alternative examples, the electronic controller 114 causes the ablation waveform generator 144 to generate a waveform in which the interphase delay and interpulse delay are modulated during PFA treatment. In some alternative examples, the electronic controller 114 causes the ablation waveform generator 144 to generate a waveform in which the interphase delay and interpulse delay are modulated relative to the pulse width. In some alternative examples, the electronic controller 114 causes the ablation waveform generator 144 to generate a waveform in which the interphase delay and interpulse delay are modulated relative to the amplitude. In some alternative examples, the electronic controller 114 causes the ablation waveform generator 144 to generate a waveform in which the interphase delay and interpulse delay are modulated in response to patient discomfort. In some alternative examples, the electronic controller 114 causes the ablation waveform generator 144 to generate a waveform in which the interphase delay and interpulse delay are set before treatment using short sub-treatment pulses to establish patient sensitivity.

[0046] Figure 12A , Figure 12B and Figure 13 The results of PFA treatment administered using, for example, medical system 100 according to protocols 7, 8, and 9 were compared. Figure 4 As shown, T in scheme 7-9 p The value is 5 μs, and N is 10. In Scheme 7, the inter-phase delay (d1) is 2 μs, and the inter-pulse delay (d2) is 100 μs. In Scheme 8, the inter-phase delay (d1) is 100 μs, and the inter-pulse delay (d2) is 2 μs. In Scheme 9, the inter-phase delay (d1) is 100 μs, and the inter-pulse delay (d2) is 800 μs. Figure 12A This is a bar graph illustrating unwanted neuromuscular contractions caused by the application of the waveforms described in schemes 7-9. (As shown from...) Figure 12A It is evident that, across a certain range of amplitude, the incidence of unwanted neuromuscular contractions in scheme 7 is lower than that in schemes 8 and 9. Figure 12B This is a bar graph illustrating the pain index (as reported by the patient) caused by the application of the waveforms described in schemes 7-9. (As from...) Figure 12B It is evident that, across a certain range of amplitude, the pain index of scheme 8 is lower than that of schemes 7 and 9. Figure 13 This shows region 302 caused by the waveforms applied according to schemes 7 and 8 (see...). Figure 3 A line graph showing the percentages of permeability (i.e., irreversible electroporation) and survival rate (i.e., reversible electroporation) in [the context of electroporation]. For example... Figure 10 As shown, the differences in penetration rate and survival rate between schemes 7 and 9 are basically the same.

[0047] Figure 14This is a graph illustrating the increased number of bursts for protocols 1, 2, 4, 5, 7, and 8 for the CHO cell line. Results are shown as mean (per point) ± standard deviation (vertical bars) of three replicates.

[0048] Regarding the processes, systems, methods, and inspirations described herein, it should be understood that although the steps of such processes are described as occurring according to an ordered sequence, such processes can be practiced using the described steps performed in an order other than that described herein. It should also be understood that some steps may be performed simultaneously, other steps may be added, or some steps described herein may be omitted. In other words, the description of processes herein is provided for the purpose of illustrating certain embodiments and should in no way be construed as limiting the claims.

[0049] Therefore, it should be understood that the above description is intended to be illustrative rather than restrictive. Many embodiments and applications beyond the examples provided will become apparent upon reading the above description. The scope should not be determined by reference to the above description, but rather by reference to the appended claims and the full scope of their equivalents. Future developments are anticipated and intended in the art discussed herein, and the disclosed systems and methods will be incorporated into such future embodiments. In conclusion, it should be understood that modifications and variations are possible in this application.

[0050] Unless expressly indicated otherwise herein, all terms used in the claims are intended to be given their broadest reasonable structure and their common meaning as understood by one skilled in the art described herein. In particular, the use of singular articles such as “a,” “the,” “the,” etc., should be understood to enumerate one or more of the elements shown, unless expressly limited to the contrary is set forth in the claims.

[0051] Unless otherwise explicitly stated, every value and range should be interpreted as an approximation, as if the words “approximately” or “about” preceded the value or range.

[0052] In this document, the reference to “an embodiment” or “implementation” means that a particular feature, structure, or characteristic described in connection with an embodiment may be included in at least one embodiment of this disclosure. The appearance of the phrase “in an embodiment” in various places in the specification does not necessarily refer to the same embodiment, nor is it necessarily a single or alternative embodiment that is mutually exclusive with other embodiments. The same applies to the term “implementation.”

[0053] Unless otherwise specified herein, the use of ordinal adjectives such as “first,” “second,” “third,” etc., to refer to one of a plurality of similar objects merely indicates that different instances of such similar objects are being referred to, and does not imply that the similar objects referred to in this way must have a corresponding order or sequence in time, space, ranking, or any other way.

[0054] Unless otherwise specified herein, the conjunction “if” may also be interpreted, in addition to its explicit meaning, as “when”, “in response to determination”, or “in response to detection”, depending on the specific context. For example, the phrase “if determination” or “if detection [the condition]” may be interpreted as “when determination” or “in response to determination”, “in response to detection [the condition or event]”, or “in response to detection [the condition or event]”.

[0055] Furthermore, for the purposes of this specification, the terms “coupled” and “connected” refer to any manner known in the art or subsequently developed, in which energy is allowed to be transferred between two or more elements, and the insertion of one or more additional elements is considered, but not required. Conversely, the terms “direct coupling,” “direct connection,” etc., imply the absence of such additional elements. The same type of distinction applies to the use of the terms “attachment” and “direct attachment” when applied to the description of physical structures. For example, such a “direct attachment” of two corresponding parts in such a physical structure may be implemented using a relatively thin layer of adhesive or other suitable bonding agent.

[0056] The described embodiments should be considered illustrative rather than restrictive in all respects. In particular, the scope of this disclosure is indicated by the appended claims, and not by the description and drawings herein. All modifications falling within the meaning and scope of the equivalents of the claims are to be covered by the claims.

[0057] The functionality of the various elements shown in the accompanying figures, including any functional blocks labeled “processor” and / or “controller,” can be provided using dedicated hardware and hardware capable of executing software in association with appropriate software. When provided by a processor, the functionality can be provided by a single dedicated processor, a single shared processor, or multiple separate processors, some of which may be shared. Furthermore, the explicit use of the terms “processor” or “controller” should not be construed as referring only to hardware capable of executing software, and may implicitly include, but is not limited to, digital signal processor (DSP) hardware, network processors, application-specific integrated circuits (ASICs), field-programmable gate arrays (FPGAs), read-only memory (ROM), random access memory (RAM), and non-volatile memory for storing software. Other conventional and / or custom hardware may also be included. Similarly, any switches shown in the accompanying figures are conceptual only. Their functionality can be implemented through the operation of program logic, through dedicated logic, through the interaction of program control and dedicated logic, or even manually, with the specific technology selectable by the implementer, as understood more specifically from the context.

[0058] As used herein, the term "circuit" may refer to one or more or all of the following: (a) a hardware-only circuit implementation (such as an implementation in analog and / or digital circuits only); (b) a combination of hardware circuitry and software, such as (if applicable): (i) a combination of analog and / or digital hardware circuitry with software / firmware, and (ii) a hardware processor with software (including digital signal processors), software, and any part of memory that works together to enable a device (such as a mobile phone or server) to perform various functions; and (c) hardware circuitry and / or processors, such as microprocessors or parts thereof, that require software (e.g., firmware) to operate, but may be absent when the software is not required to operate. "The definition of 'circuit' applies to all uses of the term in this application, including in any claim. As a further example, as used in this application, the term 'circuit' also covers implementations of hardware circuitry or processors (or processors) or portions thereof and their accompanying software and / or firmware. The term 'circuit' also covers (e.g., and if applicable to a particular claim element) baseband integrated circuits or processor integrated circuits for mobile devices or similar integrated circuits in servers, cellular network devices, or other computing or networking devices."

[0059] Those skilled in the art will understand that any block diagram herein represents a conceptual view of an exemplary circuit embodying the principles of this disclosure. Similarly, it should be understood that any flowchart, flow diagram, state transition diagram, pseudocode, etc., represents various processes that can be represented substantially in a computer-readable medium and executed by a computer or processor, whether or not such a computer or processor is explicitly shown.

[0060] The following paragraphs provide various embodiments of the implementation schemes disclosed herein.

[0061] Example 1. A medical device comprising: an ablation waveform generator configured to apply an electrical waveform to a therapeutic element that can be placed near a treatment site of a patient; and an electronic controller configured to control the ablation waveform generator, the electronic controller further configured to: cause the ablation waveform generator to generate a biphasic waveform having an interphase delay and an interpulse delay greater than the interphase delay; and cause the ablation waveform generator to apply the biphasic waveform to the therapeutic element.

[0062] Example 2. The medical device according to Example 1, wherein the electronic controller is further configured to: cause the ablation waveform generator to generate the biphasic waveform, wherein the ratio of the inter-pulse delay to the inter-phase delay is in the range of 50:1 to 1000:1.

[0063] Example 3. The medical device according to Example 1, wherein the electronic controller is further configured to: cause the ablation waveform generator to generate the biphasic waveform, wherein the ratio of the inter-pulse delay to the inter-phase delay is 50:1.

[0064] Example 4. The medical device according to any one of Examples 1 to 3, wherein the value of the interphase delay is 2 microseconds and the value of the interpulse delay is 100 microseconds.

[0065] Example 5. The medical device according to any one of Examples 1 to 4, wherein the electronic controller is further configured to: cause the ablation waveform generator to generate the biphasic waveform having a pulse width, wherein the pulse width remains constant regardless of the values ​​of the inter-pulse delay and the inter-phase delay.

[0066] Example 6. The device according to any one of Examples 1 to 5, wherein the device is configured to perform a medical procedure selected from the group consisting of: pulsed field ablation, radiofrequency ablation, reversible electroporation, and irreversible electroporation.

[0067] Example 7. A medical method comprising: generating a biphasic waveform using an ablation waveform generator, the biphasic waveform having an interphase delay and an interpulse delay greater than the interphase delay; and applying the biphasic waveform to a therapeutic element that can be placed near a treatment site on a patient.

[0068] Example 8. The medical method according to Example 7, the method further comprising: generating the biphasic waveform, wherein the ratio of the inter-pulse delay to the inter-phase delay is in the range of 50:1 to 1000:1.

[0069] Example 9. The medical method according to Example 7, the method further includes: generating the biphasic waveform, wherein the ratio of the inter-pulse delay to the inter-phase delay is 50:1.

[0070] Example 10. The medical method according to any one of Examples 7 to 9, wherein the value of the interphase delay is 2 microseconds and the value of the interpulse delay is 100 microseconds.

[0071] Example 11. The medical method according to any one of Examples 7 to 10, the method further comprising: generating the biphasic waveform having a pulse width, wherein the pulse width remains constant regardless of the values ​​of the inter-pulse delay and the inter-phase delay.

[0072] Example 12. The medical method according to any one of Examples 7 to 11, the method further comprising: performing a medical procedure selected from the group consisting of: pulsed field ablation, radiofrequency ablation, reversible electroporation, and irreversible electroporation.

[0073] Example 13. A non-transitory computer-readable medium containing executable instructions that, when executed by one or more electronic processors, cause the one or more electronic processors to: generate a biphasic waveform using an ablation waveform generator, the biphasic waveform having an interphase delay and an interpulse delay greater than the interphase delay; and apply the biphasic waveform to a therapeutic element that can be placed near a treatment site on a patient.

[0074] Example 14. The non-transitory computer-readable medium according to Example 13, wherein the executable instructions further cause the one or more electronic processors to: generate the biphase waveform, wherein the ratio of the inter-pulse delay to the inter-phase delay is in the range of 50:1 to 1000:1.

[0075] Example 15. The non-transitory computer-readable medium according to Example 13, wherein the executable instructions further cause the one or more electronic processors to: generate the biphase waveform, wherein the ratio of the inter-pulse delay to the inter-phase delay is 50:1.

[0076] Example 16. A non-transitory computer-readable medium according to any one of Examples 13 to 15, wherein the value of the interphase delay is 2 microseconds and the value of the interpulse delay is 100 microseconds.

[0077] Example 17. A non-transitory computer-readable medium according to any one of Examples 13 to 16, wherein the executable instructions further cause the one or more electronic processors to: generate the biphase waveform having a pulse width, wherein the pulse width remains constant regardless of the values ​​of the inter-pulse delay and the inter-phase delay.

[0078] Example 18. A non-transitory computer-readable medium according to any one of Examples 13 to 17, wherein the executable instructions further cause the one or more electronic processors to: control one or more medical devices to perform a medical procedure selected from the group consisting of pulsed field ablation, radiofrequency ablation, reversible electroporation, and irreversible electroporation.

Claims

1. A medical device, the medical device comprising: An ablation waveform generator configured to apply an electrical waveform to a treatment element that can be placed near the treatment site of a patient; and An electronic controller, configured to control the ablation waveform generator, is further configured to: The ablation waveform generator generates a biphase waveform, the biphase waveform having an interphase delay and an interpulse delay greater than the interphase delay; and The ablation waveform generator applies the biphasic waveform to the treatment element.

2. The medical device according to claim 1, wherein the electronic controller is further configured to: The ablation waveform generator generates the biphase waveform, wherein the ratio of the inter-pulse delay to the inter-phase delay is in the range of 50:1 to 1000:

1.

3. The medical device according to claim 1, wherein the electronic controller is further configured to: The ablation waveform generator generates the biphase waveform, wherein the ratio of the inter-pulse delay to the inter-phase delay is 50:

1.

4. The medical device according to any one of claims 1 to 3, wherein the value of the interphase delay is 2 microseconds and the value of the interpulse delay is 100 microseconds.

5. The medical device according to any one of claims 1 to 4, wherein the electronic controller is further configured to: The ablation waveform generator generates the biphase waveform with a pulse width, wherein the pulse width remains constant regardless of the values ​​of the inter-pulse delay and the inter-phase delay.

6. The device according to any one of claims 1 to 5, wherein the device is configured to perform a medical procedure selected from the group consisting of: pulsed field ablation, radiofrequency ablation, reversible electroporation, and irreversible electroporation.

7. A medical method, the method comprising: A biphase waveform is generated using an ablation waveform generator, the biphase waveform having an interphase delay and an interpulse delay greater than the interphase delay; as well as The biphasic waveform is applied to a treatment element that can be placed near the patient's treatment site.

8. The medical method according to claim 7, further comprising: The biphase waveform is generated, wherein the ratio of the inter-pulse delay to the inter-phase delay is in the range of 50:1 to 1000:

1.

9. The medical method according to claim 7, further comprising: The biphase waveform is generated, wherein the ratio of the inter-pulse delay to the inter-phase delay is 50:

1.

10. The medical method according to any one of claims 7 to 9, wherein the value of the interphase delay is 2 microseconds and the value of the interpulse delay is 100 microseconds.

11. The medical method according to any one of claims 7 to 10, further comprising: The biphase waveform with a pulse width is generated, wherein the pulse width remains constant regardless of the values ​​of the inter-pulse delay and the inter-phase delay.

12. The medical method according to any one of claims 7 to 11, further comprising: Perform medical procedures selected from the following groups of procedures: pulsed field ablation, radiofrequency ablation, reversible electroporation, and irreversible electroporation.

13. A non-transitory computer-readable medium comprising executable instructions, said executable instructions causing said one or more electronic processors, when executed, to: A biphase waveform is generated using an ablation waveform generator, the biphase waveform having an interphase delay and an interpulse delay greater than the interphase delay; and The biphasic waveform is applied to a treatment element that can be placed near the patient's treatment site.

14. The non-transitory computer-readable medium of claim 13, wherein the executable instructions further cause the one or more electronic processors to: The biphase waveform is generated, wherein the ratio of the inter-pulse delay to the inter-phase delay is in the range of 50:1 to 1000:

1.

15. The non-transitory computer-readable medium of claim 13, wherein the executable instructions further cause the one or more electronic processors to: The biphase waveform is generated, wherein the ratio of the inter-pulse delay to the inter-phase delay is 50:

1.

16. The non-transitory computer-readable medium according to any one of claims 13 to 15, wherein the value of the interphase delay is 2 microseconds and the value of the interpulse delay is 100 microseconds.

17. The non-transitory computer-readable medium according to any one of claims 13 to 16, wherein the executable instructions further cause the one or more electronic processors to: The biphase waveform with a pulse width is generated, wherein the pulse width remains constant regardless of the values ​​of the inter-pulse delay and the inter-phase delay.

18. The non-transitory computer-readable medium according to any one of claims 13 to 17, wherein the executable instructions further cause the one or more electronic processors to: Control one or more medical devices to perform medical procedures selected from the following groups of procedures: pulsed field ablation, radiofrequency ablation, reversible electroporation, and irreversible electroporation.

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