Low frequency radiofrequency ablation system

Abstract

Systems, methods of use, and kits are described herein, including a method comprising: applying one or more pairs of transducer arrays to a skin surface of a patient; placing a probe within the patient such that the tip of the probe is disposed at a specified location within the patient; and activating the electric field generator to supply an alternating current (AC) electrical signal to the one or more pairs of transducer arrays. The designated position is located between the one or more pairs of transducer arrays. The probe tip is configured to heat when disposed within the electric field. The frequency of the AC electrical signal is in the range of 50 kHz to 1 MHz. The one or more pairs of transducer arrays receiving the AC electrical signal generate an electric field between the one or more pairs of transducer arrays such that the designated location is within the electric field.

Description

[0001] Citation of relevant applications This patent application claims priority to U.S. Provisional Application No. 63 / 586,816, filed September 29, 2023. The entire contents of that Provisional Patent Application are hereby incorporated herein by reference. Background Technology

[0002] Tumor therapeutic electric fields (TTFields or TTFs) are low-intensity (e.g., 1 V / cm to 3 V / cm) alternating current electric fields in the mid-frequency range (e.g., 50 kHz to 1 MHz, such as 50 kHz to 500 kHz) that target solid tumors by interfering with mitosis. This non-invasive therapeutic targeting of solid tumors is described, for example, in U.S. Patent Nos. 7,016,725; 7,089,054; 7,333,852; 7,565,205; 8,244,345; 8,715,203; 8,764,675; 10,188,851; and 10,441,776. TTFields are typically delivered via two pairs of transducer arrays that generate a vertical electric field within the tumor being treated; each pair of these arrays is positioned on opposite sides of the body site being treated. More specifically, for the OPTUNE® system, one pair of electrodes from the transducer array is located on the left and right sides of the tumor (LR), and the other pair is located on the anterior and posterior sides of the tumor (AP). TTFields are approved for the treatment of glioblastoma multiforme (GBM) and can be delivered, for example, via the OPTUNE® system (Novocure Limited, St. Helier, Jersey), which includes transducer arrays placed on the patient's laser head. Recently, TTFields therapy has been approved in combination with chemotherapy as a treatment for malignant pleural mesothelioma (MPM) and can be used to treat tumors in other parts of the body. Summary of the Invention

[0003] A method and system are disclosed. In one aspect, this disclosure relates to a method comprising: applying a pair or more pairs of transducer arrays to the skin surface of a patient; placing a probe within the patient such that the probe tip is positioned at a designated location within the patient, the designated location being between the pair or more pairs of transducer arrays, the probe tip being configured to heat when positioned within an electric field; and activating an electric field generator to supply an alternating current (AC) signal with a frequency in the range of 50 kHz to 1 MHz to the pair or more pairs of transducer arrays, thereby generating the electric field between the pair or more pairs of transducer arrays such that the designated location is within the electric field for a certain period of time.

[0004] In another aspect, this disclosure relates to a system comprising: an electric field generator capable of operating to generate an AC electrical signal with a frequency in the range of 50 kHz to 1 MHz; one or more pairs of transducer arrays configured to be electrically connected to the electric field generator and capable of operating to generate an electric field based on the AC electrical signal; and a probe having a probe tip of a size and dimensions suitable for insertion into a patient's body.

[0005] In another aspect, this disclosure relates to a kit comprising: an electric field generator operable to generate an AC electrical signal with a frequency in the range of 50 kHz to 1 MHz; a pair of transducer arrays configured to be electrically connected to the electric field generator and operable to generate an electric field based on the AC electrical signal; and a probe having a probe tip operable to generate heat when placed within the electric field.

[0006] In another aspect, this disclosure relates to a non-transitory processor-readable medium storing processor-executable instructions that, when executed by a processor, cause the processor to: obtain a model of AC conductivity in a portion of a patient's body including a region of interest; determine a plurality of heating potentials, wherein each heating potential corresponds to a probe tip location and a pair of transducer array locations, the determination being made by: using the model of AC conductivity to simulate an indication of the heating potential in the region of interest for the plurality of probe tip locations adjacent to the region of interest and the particular pair of transducer array locations within the patient's body when an electric field is induced between a particular pair of transducer array locations of a plurality of pairs of transducer array locations surrounding the region of interest; selecting one or more pairs of suggested transducer array locations and one or more corresponding suggested probe tip locations based at least in part on the model of AC conductivity and one or more corresponding heating potentials; and outputting the one or more pairs of suggested transducer array locations and the one or more corresponding suggested probe tip locations. Attached Figure Description

[0007] One or more specific embodiments described herein are illustrated in conjunction with the accompanying drawings, which are incorporated in and form part of this specification, and these embodiments are explained together with the description. The drawings are not intended to be drawn to scale, and for clarity and simplicity, certain features and views may be shown to scale or as enlarged schematically. Not every component may be labeled in every drawing. The same reference numerals in the drawings may indicate and refer to the same or similar elements or functions. In the drawings: Figure 1 This is a schematic diagram of an exemplary embodiment of an electrode applied to living tissue according to the present disclosure; Figure 2A This is a schematic diagram of an exemplary embodiment of an electronic device configured to generate a TTField according to the present disclosure; Figure 2B yes Figure 2A A schematic diagram of another exemplary embodiment of the electronic device shown; Figure 3 This is a schematic diagram of an exemplary embodiment of the transducer array position and probe tip position on a patient's body according to the present disclosure; and Figure 4 This is a schematic diagram of an exemplary embodiment of the method for ablation of target tissue according to the present disclosure; Figure 5 This is a schematic diagram of an exemplary embodiment of a method for providing recommendations on transducer array placement and ablation probe placement according to the present disclosure; Figure 6A This is a top view of an exemplary embodiment of an experimental apparatus for performing verification experiments according to the present disclosure; Figure 6B yes Figure 6A The experimental setup shown is a front perspective view; and Figure 7 Is using Figure 6A and Figure 6B The diagram shows the experimental test results determined by the experimental setup shown. Detailed Implementation

[0008] Before explaining in detail at least one embodiment of the inventive concept through exemplary language and results, it should be understood that the application of the inventive concept is not limited to the details of the construction and arrangement of the components set forth in the following description. The inventive concept can be implemented in other ways or practiced or performed in various manner. Therefore, the language used herein is intended to give the broadest possible scope and meaning; and these embodiments are intended to be exemplary rather than exhaustive. Furthermore, it should be understood that the wording and terminology used herein are for descriptive purposes and should not be considered limiting.

[0009] The headings are provided for convenience only and should not be construed as limiting this disclosure in any way. Embodiments illustrated under any heading or in any part of this disclosure may be combined with embodiments illustrated under the same or any other heading or other part of this disclosure. Unless otherwise stated herein or clearly contradicted by the context, this disclosure covers any combination of the elements described herein in all possible variations.

[0010] Unless the context requires otherwise, singular terms should include plural terms, and plural terms should include singular terms.

[0011] All compositions, components, systems, kits, and / or methods disclosed herein can be prepared and performed without excessive experimentation. Where a method claim does not specifically state in the claims or specification that the steps are limited to a particular order, no inference is ever made in any respect of the order. This applies to any possible non-expressive basis used for interpretation, including logical questions about the arrangement of steps or procedures, direct meanings derived from grammatical organization or punctuation, or the number or type of examples described in the specification.

[0012] When used in conjunction with the term "comprising" in the claims and / or description, the term "a" or "an" may mean "one," but is also consistent with the meanings of "one or more," "at least one," and "one or more." The term "a plurality of" means "two or more."

[0013] Furthermore, the use of the term "at least one of X, Y, and Z" will be understood to include X alone, Y alone, and Z alone, as well as any combination of X, Y, and Z. The use of ordinal terms (e.g., "first," "second," "third," "fourth," etc.) is for the purpose of distinguishing two or more items only and does not imply any order or sequence or importance of one item relative to another, or any order of addition.

[0014] The term “or” used in the claims is used to mean inclusive “and / or”, unless it is explicitly stated that it refers only to alternatives, or unless the alternatives are mutually exclusive.

[0015] As used herein, a circuit may be an analog and / or digital component, or one or more appropriately programmed processors (e.g., microprocessors) and associated hardware and software, or hardwired logic. Furthermore, a “component” may perform one or more functions. The term “component” may include hardware such as a processor (e.g., a microprocessor), an application-specific integrated circuit (ASIC), a field-programmable gate array (FPGA), and / or a combination of hardware and software. As used herein, the term “processor” refers to a single processor or multiple processors that work individually or together to perform a task. A processor may communicate with a non-transitory computer-readable medium that stores computer-executable instructions that, when used by the processor, further cause the processor to perform a specified function. Exemplary non-transitory computer-readable media may include non-volatile memory, random access memory (RAM), read-only memory (ROM), CD-ROM, hard disk drive, solid-state drive, flash memory drive, memory card, DVD-ROM, Blu-ray disc, laser disc, magnetic disk, optical disc drive, and / or combinations thereof.

[0016] As used herein, the term TTField (TTFields or TTF) refers to a low-intensity (e.g., 1 V / cm to 4 V / cm) alternating electric field of medium frequency (about 50 kHz to 1 MHz, and more preferably from about 50 kHz to 500 kHz) that, when applied via electrodes to a conductive medium (such as the human body), can be used, for example, to treat tumors, as described in Palti’s U.S. Patents 7,016,725, 7,089,054, 7,333,852, 7,565,205, 7,805,201, and 8,244,345 (each of which is incorporated herein by reference), and Kirson’s publication (see Eilon D. Kirson et al., “Disruption of Cancer Cell Replication by Alternating Electric Fields”, Cancer Res. 2004 64:3288-3295). TTFields have been shown to specifically affect cancer cells and are used, among other uses, to treat cancer. TTFields therapy is an approved monotherapy for recurrent glioblastoma (GBM) and an approved combination therapy with chemotherapy for newly diagnosed GBM patients.

[0017] As used herein, the term "transducer array" refers to a conductive transducer array or a non-conductive transducer array. Exemplary transducer arrays may include, for example, the patches disclosed in either U.S. Patent Publication No. 2021 / 0346693 entitled "CONDUCTIVE PAD GENERATING TUMOR TREATING FIELD AND METHODS OF PRODUCTION AND USE THEREOF" or U.S. Patent Application No. 63 / 128,265 entitled "OPTIMIZATION OF COMPOSITE ELECTRODE," all of which are hereby expressly incorporated herein by reference in their entirety.

[0018] As used herein, unless the context explicitly indicates otherwise, all numerical values ​​or ranges include values ​​and fractions of integers within such ranges. The numerical ranges specified herein include endpoints, all values ​​within that range, subranges of values, and values ​​and fractions of integers within said range. Therefore, according to embodiments of this disclosure, any two values ​​within, for example, the range of 1 mm to 10 m can be used to set the lower and upper boundaries of a range.

[0019] Now refer to the attached diagram, especially Figure 1 An exemplary embodiment of a dividing cell 10 under the influence of an external TTField (generally indicated by line 14) generated by a negatively charged first electrode 18a and a positively charged second electrode 18b is shown. Microtubules 22, known to have very strong dipole moments, are also shown. This strong polarization makes microtubules 22, as well as other polar macromolecules (and especially those polar macromolecules with specific orientations within or around the cell 10), susceptible to the influence of an electric field. The positive charge of the microtubules 22 is located at two centrosomes 26, while two sets of negative poles are located at the center 30 of the dividing cell 10 and at the attachment point 34 of the microtubules 22 to the cell membrane. The positions of the charges form multiple sets of bipolar poles and are therefore susceptible to electric fields in different directions. In one embodiment, the cell undergoes electroporation, that is, DNA or chromosomes are introduced into the cell using electrical pulses to briefly open pores in the cell membrane.

[0020] Now for reference Figure 2A The document illustrates a device constructed according to this disclosure for administering medication to patient 94 ( Figure 3 An exemplary embodiment of system 38 for applying TTFields is shown. System 38 typically includes an electric field generator 42 and multiple conductive leads, which apply TTFields in... Figure 1The diagram shows a first conductive lead 46a and a second conductive lead 46b (collectively referred to as "conductive leads 46"). Although system 38 is... Figure 1 The diagram shows two conductive leads 46, but in other embodiments, system 38 may include more or fewer than two conductive leads 46.

[0021] The electric field generator 42 is operable to supply power and generate an electrical signal (i.e., a TTField signal), which can be an alternating current (AC) signal or a pulsed electrical signal with a frequency in the range of 50 kHz to 1 MHz (or preferably, 100 kHz to 500 kHz). The voltage of the TTField signal can cause the intensity of the electric field (i.e., TTField) in the tissue within the treatment area to be in the range of 0.1 V / cm to 10 V / cm.

[0022] The first conductive lead 46a has a first end 50a and a second end 50b, and the second conductive lead 46b has a first end 52a and a second end 52b. The conductive lead 46 is an insulated conductor with a flexible metal shielding layer and is preferably grounded, thereby preventing the diffusion of any electric field generated by the conductive lead 46.

[0023] Each conductive lead 46 is electrically connected to an electric field generator 42. Therefore, the first end 50a of the first conductive lead 46a and the first end 52a of the second conductive lead 46b are electrically connected to the electric field generator 42. The conductive leads 46 are also electrically connected to a plurality of transducer arrays, which in... Figure 1 The diagram shows a first transducer array 58a and a second transducer array 58b (collectively referred to as "transducer array 58"). Therefore, the second end 50b of the first conductive lead 46a and the second end 52b of the second conductive lead 46b are electrically connected to the first transducer array 58a and the second transducer array 58b, respectively.

[0024] Each transducer array in transducer array 58 is supplied with a TTField signal. The supply of TTField signals to transducer array 58 causes current to flow between transducer arrays 58, thereby generating TTFields between transducer arrays 58. When transducer arrays 58 are applied to a treatment area on patient 94 (shown in Figure 2), this results in the generation of TTFields in a region of interest 106 within patient 94 (shown as dashed lines in Figure 2). The target region may include one or more tumors, and the generation of TTFields may selectively disrupt and / or inhibit the growth of at least one tumor. While system 38 is in Figure 1 The diagram shows two transducer arrays 58, but in other embodiments, system 38 may include more or fewer than two transducer arrays 58.

[0025] To optimize the distribution of TTFields, transducer array 58 can be configured differently based on the specific application using transducer array 58. Furthermore, transducer array 58 can have a specific shape and positioning to generate TTFields with the desired configuration, orientation, and / or intensity at and only in the treatment area, thereby focusing treatment on the target region. The user can apply transducer array 58 to the treatment area on patient 94 (i.e., to the skin surface of patient 94) to result in the generation of TTFields within the target region. TTFields can be of a widely distributed type or a localized type (e.g., for treating skin tumors or lesions near the skin surface).

[0026] Users may be medical professionals, such as doctors, nurses, caregivers, therapists, or other persons acting under the guidance of doctors, nurses, caregivers, or therapists. In some embodiments, the user may be a patient 94 (i.e., patient 94 and / or an assistant may apply transducer array 58 to the treatment area).

[0027] In some embodiments, system 38 further includes a controller 62. The controller 62 typically includes circuitry operable to control the output of the electric field generator 42, for example, setting the output between a minimum value that causes ablation of the treatment area and a maximum value that does not cause overheating of the treatment area. The controller 62 may issue a warning or similar warning when the temperature of the treatment area (as sensed by one or more temperature sensors 82, hereinafter referred to as “temperature sensors 82”, discussed in more detail below) exceeds a preset limit. Temperature sensors 82 may be mechanically connected to or otherwise associated with one or more ablation probes 86 (hereinafter referred to as “ablation probes 86”) to sense the temperature of the treatment area adjacent to the probe tip 90 of the ablation probes 86, as described in more detail below. Ablation probes 86 may be in the form of a rod or needle made of a conductive and biocompatible material, such as stainless steel or titanium.

[0028] Temperature sensor 82 is typically configured to measure temperature. In some embodiments, temperature sensor 82 is a thermistor (i.e., a variable resistor with resistance based on temperature changes). In such embodiments, controller 62 may receive a resistance reading from temperature sensor 82 indicating the resistance of temperature sensor 82.

[0029] The probe tip 90 of the ablation probe 86 is sized and dimensional to be inserted into the body of the patient 94. In use, the user inserts the probe tip 90 of the ablation probe 86 into the body of the patient 94, positioning the probe tip 90 at the designated location. Without being bound by theory, it is believed that positioning the probe tip 90 in an electric field can cause an increase in the electric field strength immediately adjacent to the probe tip 90. This increase in the electric field strength immediately adjacent to the probe tip 90 may result in the delivery of thermal energy to the target tissue adjacent to the probe tip 90, thereby treating, removing, or destroying the target tissue.

[0030] In some embodiments, the circuitry of controller 62 includes one or more processors 66 (hereinafter referred to as "processor 66") and one or more non-transitory processor-readable media 70 (hereinafter referred to as "memory 70"). Memory 70 may store processor-executable instructions 74 and / or data storage areas 78. The processor-executable instructions 74, when executed by processor 66, may cause processor 66 to perform one or more actions described herein. For example, processor 66 may communicate with temperature sensor 82, ablation probe 86, and / or other circuitry (e.g., analog-to-digital converter, digital-to-analog converter, multimeter, ohmmeter, voltmeter, and / or ammeter). In some embodiments, the processor-executable instructions 74, when executed by processor 66, may cause processor 66 to perform one or more steps of the methods described herein.

[0031] In some embodiments, if the temperature sensed by temperature sensor 82 reaches or exceeds a comfort threshold, controller 62 may turn off or reduce the power of the TTField signal generated by electric field generator 42. In one embodiment, the comfort threshold is the temperature at which patient 94 would feel uncomfortable when using the first transducer array 58a, the second transducer array 58b, and the ablation probe 86. For example, the comfort threshold may be 40 degrees Celsius or a temperature of about 40 degrees Celsius. In one embodiment, the comfort threshold is a temperature between about 39 degrees Celsius and 42 degrees Celsius, or a specific selected temperature between about 39 degrees Celsius and 42 degrees Celsius.

[0032] In some embodiments, after a sufficient period of time has elapsed to allow the probe tip 90 to heat to the treatment temperature (i.e., a temperature sufficient for ablation), the controller 62 may turn off or reduce the power of the TTField signal generated by the electric field generator 42.

[0033] Now for reference Figure 2B , which shows Figure 2AAnother exemplary embodiment of the system 38a shown. In some embodiments, the conductive lead 46 includes a first conductive lead 46a, a second conductive lead 46b, a third conductive lead 46c, and a fourth conductive lead 46d. In such embodiments, the third conductive lead 46c has a first end 54a electrically connected to the electric field generator 42 and a second end 54b electrically connected to the third transducer array 58c, and the fourth conductive lead 46d has a first end 56a electrically connected to the electric field generator 42 and a second end 56b electrically connected to the fourth transducer array 58d.

[0034] In some embodiments having a third transducer array 58c and a fourth transducer array 58d, the processor 66 may communicate with a first temperature sensor 82a and a second temperature sensor 82b. The first temperature sensor 82a may be mechanically connected to and / or otherwise associated with a first ablation probe 86a having a first probe tip 90a, and the second temperature sensor 82b may be mechanically connected to and / or otherwise associated with a second ablation probe 86b having a second probe tip 90b.

[0035] Now for reference Figure 3 The diagram shows multiple potential transducer array locations, such as a first potential transducer array location 98a, a second potential transducer array location 98b, a third potential transducer array location 98c, and a fourth potential transducer array location 98d (collectively referred to as "potential transducer array locations 98"), and multiple potential probe tip locations, such as a first potential probe tip location 102a, a second potential probe tip location 102b, a third potential probe tip location 102c, and a fourth potential probe tip location 102d (collectively referred to as "potential probe tip locations 102").

[0036] Potential transducer array positions 98 and potential probe tip positions 102 can be determined based on the region of interest 106. That is, one or more potential probe tip positions 102 can be determined to be adjacent to the region of interest 106, and one or more potential transducer array positions 98 can be determined to surround the region of interest 106. The region of interest 106 may include target tissue selected for ablation using system 38. Although the potential transducer array positions 98 and potential probe tip positions 102 are... Figure 3 The potential transducer array position 98 and the potential probe tip position 102 are shown as being located on or in the torso of the patient 94, but it should be understood that the potential transducer array position 98 and the potential probe tip position 102 may be located on or in any part of the body of the patient 94.

[0037] As described herein, a pair of potential transducer array positions 98 may include any combination of two potential transducer array positions 98. The region of interest 106 may be located between combinations of two potential transducer array positions 98. For example, a pair of potential transducer array positions 98 may include any two of a first potential transducer array position 98a, a second potential transducer array position 98b, a third potential transducer array position 98c, and a potential fourth transducer array position 98d.

[0038] Now for reference Figure 4 An exemplary embodiment of a method 200 for ablation of target tissue according to the present disclosure is shown. Figure 4 As shown, method 200 typically includes the following steps: applying one or more pairs of transducer arrays 58 to a first location on the skin surface of patient 94 (i.e., any two potential transducer array locations 98) (step 204); placing an ablation device within patient 94 such that the probe tip 90 of ablation probe 86 is positioned at a designated location within patient 94 (i.e., one of the potential probe tip locations 102) (step 208); and activating an electric field generator to supply an AC electrical signal with a frequency in the range of 50 kHz to 1 MHz to one or more pairs of transducer arrays, thereby generating an electric field between one or more pairs of transducer arrays 58 such that the designated location is within the electric field for a certain period of time (step 212).

[0039] This time period can be at least a sufficient period of time for the probe tip 90 of the ablation probe 86 to be heated to the treatment temperature (i.e., a temperature sufficient to perform ablation). In some embodiments, method 200 further includes: after the time period has elapsed, deactivating the electric field generator 42 to stop supplying AC electrical signals to one or more pairs of transducer arrays 58.

[0040] In some embodiments, method 200 may further include: after deactivating electric field generator 42, moving one or more pairs of transducer arrays 58 to a second location (i.e., two additional potential transducer array locations 98) on the skin surface of patient 94.

[0041] In some embodiments of system 38a including a first ablation probe 86a and a second ablation probe 86b, method 200 may further include: placing the second ablation probe 86b within a patient 94 such that the second probe tip 90b of the second ablation probe 86b is positioned at a second designated location within the patient 94 (i.e., another potential probe tip location in potential probe tip locations 102).

[0042] In some embodiments, method 200 may further include: activating an electric field generator 42 to supply an AC electrical signal with a frequency in the range of 50 kHz to 1 MHz to one or more pairs of transducer arrays 58 at the second location, thereby generating an electric field between one or more pairs of transducer arrays 58 at the second location, such that the second designated location is within the electric field for a second time period.

[0043] In some embodiments of system 38a including a first pair of transducer arrays 58 (e.g., first transducer array 58a and second transducer array 58b) and a second pair of transducer arrays 58 (e.g., third transducer array 58c and fourth transducer array 58d), method 200 may further include: activating electric field generator 42 to supply an AC electrical signal with a frequency in the range of 50 kHz to 1 MHz to the second pair of transducer arrays 58, thereby generating an electric field between the second pair of transducer arrays 58 such that a second designated location (i.e., another potential probe tip location in potential probe tip location 102) is within the electric field for a second time period.

[0044] The second time period may be at least a sufficient period of time for the second probe tip 90b of the second ablation probe 86b to be heated to the treatment temperature (i.e., a temperature sufficient to perform ablation). In some embodiments, method 200 further includes: after the time period has elapsed, deactivating the electric field generator 42 to stop supplying AC electrical signals to the second pair of transducer arrays 58.

[0045] In some embodiments of system 38a including a first ablation probe 86a and a second probe 86b, method 200 may further include: placing the second ablation probe 86b within a patient 94 such that the second probe tip 90b of the second ablation probe 86b is positioned at a second designated location within the patient 94 (i.e., another potential probe tip location in potential probe tip locations 102).

[0046] In some embodiments of system 38a including a first pair of transducer arrays 58 (e.g., first transducer array 58a and second transducer array 58b) and a second pair of transducer arrays 58 (e.g., third transducer array 58c and fourth transducer array 58d), method 200 may further include: activating electric field generator 42 to supply an AC electrical signal with a frequency in the range of 50 kHz to 1 MHz to the second pair of transducer arrays 58, thereby generating an electric field between the second pair of transducer arrays 58 such that a second designated location (i.e., another potential probe tip location in potential probe tip location 102) is within the electric field for a second time period.

[0047] In some embodiments, method 200 further includes determining the temperature at probe tip 90 based on a resistance reading indicating the resistance of temperature sensor 82. In such embodiments, method 200 may further include determining whether the temperature at probe tip 90 is higher than a predetermined threshold (step 216); and, in response to determining that the temperature at probe tip 90 is higher than the predetermined threshold, deactivating electric field generator 42 to stop supplying AC signals to one or more pairs of transducer arrays 58 (step 220). Processor 66 may monitor the temperature of probe tip 90 and, when the temperature of probe tip 90 is lower than the predetermined threshold, actuate electric field generator 42 to begin supplying AC signals to one or more pairs of transducer arrays 58.

[0048] Now for reference Figure 5 An exemplary embodiment of a method 300 for providing a suggested placement of transducer array 58 and ablation probe 86 according to this disclosure is shown. Figure 5 As shown, method 300 typically includes the following steps: obtaining a model of AC conductivity in a portion of the region of interest 106 of the patient's body 94 (step 304); determining a plurality of heating potentials, wherein each heating potential corresponds to a potential probe tip location 102 and a pair of potential transducer array locations 98, the determination being made by: using the model of AC conductivity to simulate an indication of the heating potential for the region of interest 106 for the potential probe tip locations 102 and the specific pair of potential transducer array locations 98 adjacent to the region of interest 106 within the patient's body 94 when an electric field is induced between the specific pair of potential transducer array locations 98 surrounding the region of interest 106 (step 308); selecting one or more pairs of proposed potential transducer array locations 98 and one or more corresponding proposed potential probe tip locations 102 based at least in part on the model of AC conductivity and one or more corresponding heating potentials (step 312); and outputting one or more pairs of proposed potential transducer array locations 98 and one or more corresponding proposed potential probe tip locations 102 (step 316).

[0049] In some embodiments, obtaining the AC conductivity model (step 304) is further defined as: obtaining a three-dimensional model of the AC conductivity of a portion of the patient 94’s body, including the region of interest 106, using any of a plurality of methods obvious to a person skilled in the art (e.g., at a frequency to be used for TTFields treatment). The three-dimensional model of AC conductivity may include a plurality of voxels representing that portion of the patient 94’s body (including the region of interest 106), and the conductivity of each of the plurality of voxels may be specified.

[0050] In some embodiments, determining a plurality of heating potentials (step 308) is further defined as: selecting a plurality of pairs of potential transducer array positions 98; selecting a plurality of potential probe tip positions 102; and for each specific pair of potential transducer array positions 98 and the corresponding specific potential probe tip position 102, using a model of AC conductivity to simulate an electric field induced between the specific pair of potential transducer array positions 98 at the corresponding specific potential probe tip position 102, thereby simulating a specific indication of the heating potential of the region of interest 106 for the specific pair of potential transducer array positions 98 and the corresponding specific potential probe tip position 102.

[0051] In some embodiments, selecting one or more pairs of proposed potential transducer array positions 98 and one or more corresponding proposed potential probe tip positions 102 (step 312) is further defined as: sorting the simulation results for each specific pair of potential transducer array positions 98 and corresponding specific potential probe tip positions 102; and selecting one or more sorted simulation results as one or more pairs of proposed potential transducer array positions 98 and one or more corresponding proposed potential probe tip positions 102. In some such embodiments, sorting the simulation results is further defined as: sorting the simulation results for each specific pair of potential transducer array positions 98 and corresponding specific potential probe tip positions 102 based on a specific heating potential of each specific pair of potential transducer array positions 98 and corresponding specific potential probe tip positions 102.

[0052] In some embodiments, method 300 includes the following steps: instead of determining a plurality of heating potentials (step 308), determining a plurality of indications of heating potentials for region of interest 106, each particular indication of heating potential corresponding to a particular potential probe tip position 102 and a particular pair of potential transducer array positions 98, the determination being made by: using a model of AC conductivity to simulate an induced electric field between multiple pairs of potential transducer array positions 98 surrounding region of interest 106 on the body of patient 94 for a plurality of potential probe tip positions 102 adjacent to region of interest 106 (step 308a).

[0053] Now for reference Figure 6A and Figure 6BThe present invention illustrates an exemplary embodiment of an experimental apparatus 400 for performing verification experiments according to the present disclosure. In the experimental apparatus 400, an ablation probe 86 having a probe tip 90 is disposed within a gel 404 configured to approximate human tissue. The ablation probe 86 is aligned with a longitudinal axis L, and a pair of transducer arrays (including a first transducer array 58a and a second transducer array 58b) are applied to the gel 404 on both sides of the ablation probe 86 along the longitudinal axis L. In the experimental apparatus 400, the ablation probe 86 is a titanium rod with a diameter of 4.76 mm and a length of 152.4 mm. A first temperature sensor 82a, a second temperature sensor 82b, a third temperature sensor 82c, a fourth temperature sensor 82d, a fifth temperature sensor 82e, and a sixth temperature sensor 82f are respectively positioned relative to the ablation probe 86 at an edge, a distal position, an end position, a quarter position, a half position, and a distal superior position within the gel 404. An AC signal of 50V is supplied to the first transducer array 58a and the second transducer array 58b to generate an electric field within the gel 404.

[0054] Now for reference Figure 7 Figure 500 shows experimental test results determined using the experimental apparatus 400 according to this disclosure. In Figure 500, the horizontal axis represents time, and the vertical axis represents temperature measured by the temperature sensor 82. At a first time 504, the electric field generator 42 is activated and begins to supply an AC signal with a frequency of 200 kHz and a current of 1.5 A to the transducer array 58, thereby generating an electric field between the transducer arrays 58, causing the gel 404 (and thus the ablation probe 86 with probe tip 90) to be positioned within the electric field. At a second time 508, the electric field generator 42 is deactivated, and the supply of the AC signal to the transducer arrays 58 is stopped, resulting in the collapse of the electric field between the transducer arrays 58. Thus, the probe tip 90 is positioned within the electric field for a first time period 512 of approximately 23 minutes, and then outside the electric field for a second time period 516.

[0055] like Figure 7As shown, at the location closest to the probe tip 90 (i.e., the first temperature sensor 82a and the third temperature sensor 82c located at the edge location), the temperature rises sharply during the first time period 512, reaching a maximum temperature of 47.80 degrees Celsius. It is believed that if the probe tip 90 is positioned within the electric field for a longer period, the temperature near the probe tip 90 will continue to rise, reaching the therapeutic temperature (i.e., the temperature suitable for ablation). Furthermore, at locations along the length of the ablation probe 86 (i.e., the fourth temperature sensor 82d located at the quarter location and the fifth temperature sensor 82e located at the half location), the temperature rises slightly, indicating a lower thermal conductivity of the material. Finally, at locations farther from the ablation probe 86 (i.e., the second temperature sensor 82b located at the far location and the sixth temperature sensor 82f located at the far upper location), the temperature rise is minimal, which is believed to be related to heat propagation within the gel 404 and / or the instability of the temperature sensor 82 readings.

[0056] Non-limiting exemplary embodiments of the present invention The following is a list of non-limiting exemplary embodiments of the inventive concept disclosed herein: Exemplary Example 1. A method comprising: applying a pair or more pairs of transducer arrays to the skin surface of a patient; placing a probe within the patient such that the probe tip is positioned at a designated location within the patient, the designated location being located between the pair or more pairs of transducer arrays, the probe tip being configured to heat when positioned within an electric field; and activating an electric field generator to supply an alternating current (AC) signal with a frequency in the range of 50 kHz to 1 MHz to the pair or more pairs of transducer arrays, thereby generating the electric field between the pair or more pairs of transducer arrays such that the designated location is within the electric field for a certain period of time.

[0057] Example 2. The method according to Example 1, wherein the probe is a first probe, the probe tip is a first probe tip, the designated location is a first designated location, and the method further includes: placing a second probe inside the patient such that the second probe tip of the second probe is positioned at a second designated location inside the patient.

[0058] Exemplary Example 3. The method according to Exemplary Example 2, wherein the time period is at least a sufficient time period for the probe tip to be heated to the treatment temperature, and the method further comprises: after the time period has elapsed, deactivating the electric field generator to stop supplying the AC electrical signal to the one or more pairs of transducer arrays.

[0059] Exemplary Example 4. According to the method of Exemplary Example 3, wherein the pair or more pairs of transducer arrays include a first pair of transducer arrays and a second pair of transducer arrays, the first designated position is located between the first pair of transducer arrays, the second designated position is located between the second pair of transducer arrays, and activating the electric field generator is further defined as: activating the electric field generator to supply the AC electrical signal with a frequency in the range of 50 kHz to 1 MHz to the first pair of transducer arrays, thereby generating the electric field between the first pair of transducer arrays, such that the first designated position is within the electric field for the time period.

[0060] Example 5. The method according to Example 4, wherein the time period is a first time period, and the method further comprises: activating the electric field generator to supply the AC electrical signal with a frequency in the range of 50 kHz to 1 MHz to the second pair of transducer arrays, thereby generating the electric field between the second pair of transducer arrays, such that the second designated position is within the electric field for a second time period.

[0061] Exemplary Example 6. The method according to Exemplary Example 5, wherein the second time period is at least a sufficient time period for heating the probe tip to the treatment temperature, and the method further comprises: after the second time period has elapsed, deactivating the electric field generator to stop supplying the AC electrical signal to the second pair of transducer arrays.

[0062] Exemplary Example 7. The method according to Exemplary Example 3, wherein applying the pair or more pairs of transducer arrays to the patient's skin surface is further defined as: applying the pair or more pairs of transducer arrays to the patient's skin surface at a first location, the first designated location being between the pair or more pairs of transducer arrays at the first location; activating the electric field generator is further defined as: activating the electric field generator to supply the AC electrical signal with a frequency in the range of 50 kHz to 1 MHz to the pair or more pairs of transducer arrays at the first location, thereby generating the electric field between the pair or more pairs of transducer arrays at the first location, such that the first designated location is within the electric field for the time period; and the method further includes: after deactivating the electric field generator, moving the pair or more pairs of transducer arrays to a second location on the patient's skin surface, the second designated location being between the pair or more pairs of transducer arrays at the second location.

[0063] Example 8. The method according to Example 7, wherein the time period is a first time period, and the method further comprises: activating the electric field generator to supply the AC electrical signal with a frequency in the range of 50 kHz to 1 MHz to the pair or more pairs of transducer arrays located in the second position, thereby generating the electric field between the pair or more pairs of transducer arrays located in the second position, such that the second designated position is within the electric field for a second time period.

[0064] Exemplary Example 9. The method according to Exemplary Example 8, wherein the second time period is at least a sufficient time period for heating the probe tip to the treatment temperature, and the method further comprises: after the second time period has elapsed, deactivating the electric field generator to stop supplying the AC electrical signal to the one or more pairs of transducer arrays in the second position.

[0065] Exemplary Example 10. The method according to any one of Exemplary Examples 1 to 8, wherein the probe further includes a thermistor adjacent to the tip of the probe, wherein the thermistor is a variable resistor having a resistance based on temperature changes, and the method further includes: determining the temperature at the tip of the probe based on a resistance reading indicating the resistance of the thermistor.

[0066] Exemplary Example 11. The method according to Exemplary Example 10, the method further comprising: determining whether the temperature at the probe tip is higher than a predetermined threshold; and in response to determining that the temperature at the probe tip is higher than the predetermined threshold, deactivating the electric field generator to stop supplying the AC electrical signal to the one or more pairs of transducer arrays.

[0067] Exemplary Example 12. A system comprising: an electric field generator operable to generate an alternating current (AC) signal with a frequency in the range of 50 kHz to 1 MHz; one or more pairs of transducer arrays configured to be electrically connected to the electric field generator and operable to generate an electric field based on the AC signal; and a probe having a probe tip of a size and dimensions suitable for insertion into a patient's body.

[0068] Exemplary Example 13. The system according to Exemplary Example 12, wherein the pair or more pairs of transducer arrays includes a first pair of transducer arrays and a second pair of transducer arrays.

[0069] Exemplary Example 14. The system according to any one of Exemplary Examples 12 or 13, wherein the probe further includes a thermistor adjacent to the tip of the probe, wherein the thermistor is a variable resistor having resistance based on temperature changes.

[0070] Exemplary Example 15. The system according to Exemplary Example 14 further includes a controller configured to communicate with the electric field generator and the thermistor. The controller has a processor and a non-transitory processor-readable medium storing processor-executable instructions that, when executed by the processor, cause the processor to: activate the electric field generator to supply the AC electrical signal to the one or more pairs of transducer arrays, thereby generating an electric field between the one or more pairs of transducer arrays, such that the probe tip is positioned within the electric field for a certain period of time; and receive a resistance reading indicating the resistance of the thermistor.

[0071] Exemplary Example 16. The system according to Exemplary Example 15, wherein the processor-executable instructions, when executed by the processor, further cause the processor to: determine whether the temperature at the probe tip is higher than a predetermined threshold based on the resistance reading; and in response to determining that the temperature at the probe tip is higher than the predetermined threshold, deactivate the electric field generator to stop supplying the AC electrical signal to the one or more pairs of transducer arrays.

[0072] Exemplary Example 17. A kit comprising: an electric field generator operable to generate an alternating current (AC) signal with a frequency in the range of 50 kHz to 1 MHz; a pair of transducer arrays configured to be electrically connected to the electric field generator and operable to generate an electric field based on the AC signal; and a probe having a probe tip operable to generate heat when placed within the electric field.

[0073] Exemplary Example 18. The kit according to Exemplary Example 17, wherein the probe further includes a thermistor adjacent to the tip of the probe, wherein the thermistor is a variable resistor having resistance based on temperature changes.

[0074] Exemplary Example 19. The kit according to Exemplary Example 18 further includes a controller configured to communicate with the electric field generator and the thermistor, the controller having a processor and a non-transitory processor-readable medium storing processor-executable instructions that, when executed by the processor, cause the processor to: activate the electric field generator to supply the AC electrical signal to the one or more pairs of transducer arrays, thereby generating an electric field between the pairs of transducer arrays, such that the probe tip is positioned within the electric field for a certain period of time; and receive a resistance reading indicating the resistance of the thermistor.

[0075] Exemplary Example 20. The kit according to Exemplary Example 19, wherein the processor-executable instructions, when executed by the processor, also cause the processor to: determine whether the temperature at the probe tip is higher than a predetermined threshold based on the resistance reading; and in response to determining that the temperature at the probe tip is higher than the predetermined threshold, disable the electric field generator to stop supplying the AC electrical signal to the transducer array.

[0076] Exemplary Example 21. A non-transitory processor-readable medium storing processor-executable instructions that, when executed by a processor, cause the processor to: obtain a model of alternating current (AC) conductivity in a portion of a patient's body, including a region of interest; determine a plurality of heating potentials, wherein each heating potential corresponds to a probe tip location and a pair of transducer array locations, the determination being made by: using the model of AC conductivity to simulate an indication of the heating potential for the region of interest for a plurality of probe tip locations adjacent to the region of interest and the specific pair of transducer array locations within the patient's body when an electric field is induced between a particular pair of transducer array locations of a plurality of pairs of transducer array locations surrounding the region of interest; selecting a pair or more suggested transducer array locations and one or more corresponding suggested probe tip locations based at least in part on the model of AC conductivity and one or more corresponding heating potentials; and outputting the pair or more suggested transducer array locations and the one or more corresponding suggested probe tip locations.

[0077] Exemplary Example 22. A non-transitory processor-readable medium according to Exemplary Example 21, wherein determining the plurality of heating potentials is further defined as: selecting the plurality of pairs of transducer array positions; selecting the plurality of probe tip positions; and for each specific pair of transducer array positions and the corresponding specific probe tip position, using the model of AC conductivity to simulate an electric field induced between the specific pairs of transducer array positions at the corresponding specific probe tip position, thereby simulating a specific indication of the heating potential of the region of interest for the specific pair of transducer array positions and the corresponding specific probe tip position.

[0078] Exemplary Example 23. The non-transitory processor-readable medium according to Exemplary Example 22, wherein selecting the pair or more pairs of proposed transducer array positions and the one or more corresponding proposed probe tip positions is further defined as: sorting the simulation results for each specific pair of transducer array positions and the corresponding specific probe tip positions; and selecting one or more sorted simulation results as the pair or more pairs of proposed transducer array positions and the one or more corresponding proposed probe tip positions.

[0079] Exemplary Example 24. The non-transitory processor-readable medium according to Exemplary Example 22, wherein sorting the simulation results is further defined as: sorting the simulation results for the specific pair of transducer array positions and the corresponding specific probe tip positions based on a specific heating potential for each specific pair of transducer array positions and the corresponding specific probe tip positions.

[0080] Exemplary Example 25. A non-transitory processor-readable medium according to Exemplary Example 21, wherein determining the plurality of heating potentials is defined as: determining a plurality of indications of heating potentials for the region of interest, each particular indication of the heating potential corresponding to a particular probe tip position and a particular pair of transducer array positions, the determination being made by: using the model of AC conductivity to simulate an induced electric field between multiple pairs of transducer array positions surrounding the region of interest on the patient's body for a plurality of probe tip positions adjacent to the region of interest.

[0081] in conclusion The foregoing description provides examples and descriptions, but is not intended to be exhaustive or to limit the inventive concept to the precise forms disclosed. Modifications and variations are possible in accordance with the foregoing teachings, or may be obtained from the practice of the methods set forth in this disclosure.

[0082] Even if specific combinations of features are listed in the claims and / or disclosed in the specification, these combinations are not intended to limit this disclosure. In fact, many of these features can be combined in ways not specifically stated in the claims and / or disclosed in the specification. While each dependent claim listed below may be directly dependent on only one other claim, this disclosure includes every dependent claim in combination with all other claims in the claim set.

[0083] Elements, actions, or instructions used in this application should not be construed as critical or necessary to the invention unless explicitly described otherwise in the preferred embodiments. Furthermore, the phrase "based on" is intended to mean "at least partially based on," unless otherwise explicitly stated.

Claims

1. A method, the method comprising: Apply one or more pairs of transducer arrays to the patient's skin surface; The probe is placed inside the patient such that the probe tip is positioned at a designated location inside the patient, the designated location being located between one or more pairs of transducer arrays, and the probe tip is configured to heat when positioned within an electric field; as well as An electric field generator is activated to supply an alternating current (AC) signal with a frequency in the range of 50 kHz to 1 MHz to the one or more pairs of transducer arrays, thereby generating the electric field between the one or more pairs of transducer arrays, such that the designated location is within the electric field for a certain period of time.

2. The method of claim 1, wherein the time period is at least a sufficient time period for heating the probe tip to the treatment temperature, and the method further comprises: After the said time period has elapsed, the electric field generator is deactivated to stop supplying the AC electrical signal to the one or more pairs of transducer arrays.

3. The method of claim 2, wherein the pair or more pairs of transducer arrays comprises a first pair of transducer arrays and a second pair of transducer arrays, a first designated position is located between the first pair of transducer arrays, a second designated position is located between the second pair of transducer arrays, and activating the electric field generator is further defined as: activating the electric field generator to supply the AC electrical signal with a frequency in the range of 50 kHz to 1 MHz to the first pair of transducer arrays, thereby generating the electric field between the first pair of transducer arrays such that the first designated position is within the electric field for the time period.

4. The method according to claim 3, wherein the time period is a first time period, and the method further comprises: The electric field generator is activated to supply the AC electrical signal with a frequency in the range of 50 kHz to 1 MHz to the second pair of transducer arrays, thereby generating the electric field between the second pair of transducer arrays, such that the second designated position is within the electric field for a second time period.

5. The method of claim 4, wherein the second time period is at least a sufficient time period for heating the probe tip to the treatment temperature, and the method further comprises: After the second time period has elapsed, the electric field generator is deactivated to stop supplying the AC electrical signal to the second pair of transducer arrays.

6. The method of claim 2, wherein applying the pair or more pairs of transducer arrays to the skin surface of the patient is further defined as: applying the pair or more pairs of transducer arrays to the skin surface of the patient at a first location, the first designated location being between the pair or more pairs of transducer arrays at the first location; activating the electric field generator is further defined as: activating the electric field generator to supply the AC electrical signal with a frequency in the range of 50 kHz to 1 MHz to the pair or more pairs of transducer arrays at the first location, thereby generating the electric field between the pair or more pairs of transducer arrays at the first location, such that the first designated location is within the electric field for the time period, and the method further comprises: After the electric field generator is deactivated, the one or more pairs of transducer arrays are moved to a second location on the patient's skin surface, the second designated location being between the one or more pairs of transducer arrays at the second location.

7. The method of claim 6, wherein the time period is a first time period, and the method further comprises: The electric field generator is activated to supply the AC electrical signal with a frequency in the range of 50 kHz to 1 MHz to the one or more pairs of transducer arrays located in the second position, thereby generating the electric field between the one or more pairs of transducer arrays located in the second position, such that the second designated position is within the electric field for a second time period.

8. The method of claim 7, wherein the second time period is at least a sufficient time period for heating the probe tip to the treatment temperature, and the method further comprises: After the second time period has elapsed, the electric field generator is deactivated to stop supplying the AC electrical signal to the one or more pairs of transducer arrays located in the second position.

9. The method according to any one of claims 1 to 8, wherein the probe further comprises a thermistor adjacent to the tip of the probe, wherein the thermistor is a variable resistor having resistance based on temperature changes, and the method further comprises: The temperature at the probe tip is determined based on the resistance reading of the thermistor.

10. The method according to claim 9, further comprising: Determine whether the temperature at the probe tip is higher than a predetermined threshold. as well as In response to determining that the temperature at the probe tip is higher than the predetermined threshold, the electric field generator is deactivated to stop supplying the AC electrical signal to the one or more pairs of transducer arrays.

11. A system comprising: An electric field generator capable of operating to generate alternating current (AC) signals with frequencies ranging from 50 kHz to 1 MHz; One or more pairs of transducer arrays, the one or more pairs of transducer arrays being configured to be electrically connected to the electric field generator and capable of operating to generate an electric field based on the AC electrical signal; and A probe having a probe tip of a size and dimensions suitable for insertion into a patient's body.

12. The system of claim 11, wherein the one or more pairs of transducer arrays comprises a first pair of transducer arrays and a second pair of transducer arrays.

13. The system of claim 11 or 12, wherein the probe further comprises a thermistor adjacent to the tip of the probe, wherein the thermistor is a variable resistor having resistance based on temperature changes.

14. The system of claim 13, further comprising a controller configured to communicate with the electric field generator and the thermistor, the controller having a processor and a non-transitory processor-readable medium storing processor-executable instructions that, when executed by the processor, cause the processor to perform the following operations: Activate the electric field generator to supply the AC electrical signal to the one or more pairs of transducer arrays, thereby generating an electric field between the one or more pairs of transducer arrays, such that the probe tip is positioned within the electric field for a certain period of time; and Receive the resistance reading of the thermistor that indicates its resistance.

15. The system of claim 14, wherein the processor-executable instructions, when executed by the processor, further cause the processor to perform the following operations: Based on the resistance reading, determine whether the temperature at the probe tip is higher than a predetermined threshold; and In response to determining that the temperature at the probe tip is higher than the predetermined threshold, the electric field generator is deactivated to stop supplying the AC electrical signal to the one or more pairs of transducer arrays.

Images