Method and apparatus for delivering alternating electric field to target tissue

Abstract

A computer-implemented method for determining the position of a transducer to apply a tumor therapy electric field to a target tissue of a subject, the method comprising: obtaining a three-dimensional model of at least a portion of the subject having the target tissue within a unilateral lung of the subject; determining a first location (anterior of the thorax) on the model to place a first transducer; determining a second location (posterior of the thorax) on the model to place a second transducer, wherein the lung of the subject is located between the first transducer and the second transducer; determining a third location (torso) on the model to place a third transducer; determining a fourth location (the torso) on the model to place a fourth transducer; and outputting representations of the first, second, third and fourth locations of the subject.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Application No. 63 / 416,152 filed on October 14, 2022 and U.S. Patent Application No. 18 / 379,504 filed on October 12, 2023, the contents of which are incorporated herein by reference in their entirety. Background Art

[0003] Tumor Treatment Fields (TTFields) are low-intensity alternating electric fields in the mid-frequency range (e.g., 50 kHz to 1 MHz) that can be used to treat tumors, as described in U.S. Patent No. 7,565,205. TTFields are non-invasively induced into a region of interest by transducers placed on the patient's body and applying an alternating current (AC) voltage between the transducers. Traditionally, a first pair of transducers and a second pair of transducers are placed on the subject's body. An AC voltage is applied between the first pair of transducers for a first time interval to produce an electric field having field lines extending generally in a front-to-back direction. Then, an AC voltage is applied between the second pair of transducers at the same frequency for a second time interval to produce an electric field having field lines extending generally in a left-to-right direction. The system then repeats this two-step sequence throughout the treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0004] Figure 1 A flow chart depicting an example computer-implemented method for determining a position of a transducer to apply TTFields to a target tissue of a subject's body is illustrated.

[0005] Figure 2 A flow chart depicting an example method for applying TTFields to a subject's body is illustrated.

[0006] FIG. 3A to FIG. 3C Depicted are two example transducer layouts for applying TTFields to a subject's body.

[0007] FIG. 4A to FIG. 4C Depicted are three example transducer layouts for applying TTFields to a subject's body to target a unilateral lung.

[0008] FIG. 5A to FIG. 5E Examples of average field strength in the lung resulting from different transducer layouts are depicted.

[0009] Figure 6 An example apparatus for applying an alternating electric field to a subject's body is depicted.

[0010] FIG. 7A to FIG. 7B A schematic diagram illustrating an exemplary design of a transducer for applying an alternating electric field is shown.

[0011] Figure 8 An example computer device is depicted. DETAILED DESCRIPTION

[0012] The present application describes exemplary methods and apparatus for determining a position of a transducer to apply an alternating electric field (eg, tumor treating fields (TTFields)) to target tissue of a subject's body and applying the alternating electric field to the subject's body.

[0013] As realized by the inventors, a goal of administering TTFields therapy to a subject may be to maximize the energy focused on a tumor, and a subject with lung cancer may have tumors in both lungs or in one lung. In addition, a subject with lung cancer or other cancers may have chemotherapy infusion ports, shunts, sensitive scar areas (e.g., from surgery or radiation therapy), or anatomical sites to be avoided (e.g., ears or nipples), and a goal of administering TTFields therapy to a subject may be to avoid such areas when positioning transducers on the subject. In considering how to address these issues, the inventors discovered that a particular layout of transducers used to apply TTFields may be more beneficial to subjects who have tumors in one lung rather than both lungs, and / or that certain areas may need to be avoided when placing transducers on the subject. The inventors have discovered that placing at least two pairs of transducers at specific locations on the subject's body can provide increased TTFields energy to a target tissue (e.g., a tumor). As an example, if a subject has a tumor in one lung rather than both lungs, the present invention can be used to focus TTFields on one lung, thereby providing increased TTFields energy to the tumor. Furthermore, the inventors have discovered that by using computer simulations to determine the impact of different transducers and their locations, avoiding certain areas of a subject may be part of a subject's TTFields treatment planning.

[0014] Figure 1 A flow chart depicting an example computer-implemented method 100 for determining a position of a transducer to apply TTFields to a target tissue of a subject's body is illustrated. Certain steps of the method 100 are described as computer-implemented steps. A computer may be, for example, any device including one or more processors and a memory that is accessible by the one or more processors and stores instructions that, when executed by the one or more processors, cause the computer to perform the relevant steps of the method 100. The method 100 may be implemented by any suitable system or apparatus, such as a computer program product. Figure 8 Although for illustrative purposes Figure 1 An order of operations is indicated in the drawings, but the timing and order of such operations may be varied where appropriate without negating the purposes and advantages of the examples set forth in detail herein.

[0015] refer to Figure 1 , at step 102, method 100 may include obtaining a three-dimensional model of at least a portion of the subject's body. The three-dimensional model may be obtained locally or from a computer memory over a network. The three-dimensional model may be generated based on one or more images of the subject's region of interest. In some embodiments, the one or more images are medical images. The medical image may, for example, include at least one of a magnetic resonance imaging (MRI) image, a computed tomography (CT) image, an X-ray image, an ultrasound image, a nuclear medicine image, a positron emission tomography (PET) image, an arthrography image, a myelography image, or any image of the subject's body that provides an internal view of the subject's body. Each medical image may include an external shape of a portion of the subject's body and an area corresponding to the region of interest (e.g., a tumor) within the subject's body. As an example, the medical image may be a three-dimensional (3D) MRI image. In another example, the three-dimensional model may be a computer phantom designed to simulate a real subject.

[0016] In some embodiments, the portion of the subject's body comprises the target tissue. The target tissue may comprise cancer, a tumor, a lung, a brain, or a combination thereof. In some embodiments, a single lung of the subject's body comprises the target tissue.

[0017] At step 104, method 100 may include determining a first location on the three-dimensional model to place a first transducer. In some embodiments, the first location may be the front of the thorax of the subject's body. As an example, the thorax of the subject's body may be the area of ​​the subject's body between the subject's neck and abdomen. As an example, the thorax of the subject's body may be the cavity of the subject's body that contains the subject's heart and lungs.

[0018] At step 106, method 100 may include determining a second location on the three-dimensional model to place a second transducer. In some embodiments, the second location may be the posterior portion of the thorax of the subject's body.

[0019] In some embodiments, a unilateral lung of the subject may be located between the first transducer and the second transducer. In some embodiments, the first transducer and the second transducer may form a first pair of transducers for applying TTFields to the subject. In some embodiments, the first transducer and the second transducer may be capacitively coupled. In some embodiments, the transducers may not be capacitively coupled.

[0020] At step 108, method 100 may include determining a third location on the three-dimensional model to place a third transducer. In some embodiments, the third location may be located on the trunk of the subject's body. As an example, the trunk of the subject's body may be the area of ​​the subject's body from the subject's neck to the groin. As an example, the trunk of the subject's body may be the subject's body excluding the subject's head and limbs.

[0021] At step 110, method 100 may include determining a fourth location on the three-dimensional model to place a fourth transducer. In some embodiments, the fourth location may be located on the torso of the subject's body. In some embodiments, the first location and the second location may not overlap with the third location or the fourth location.

[0022] As an example, the third position may be located at the left armpit of the subject, and the fourth position may be located at the right armpit of the subject. As an example, the third position may be located at the front of the thorax of the subject's body, and the fourth position may be located at the armpit of the subject, wherein the third position does not overlap with the first position. As an example, the third position may be located at the rear of the thorax of the subject's body, and the fourth position may be located at the armpit of the subject, wherein the third position does not overlap with the second position.

[0023] The third transducer and the fourth transducer may form a second pair of transducers for applying TTFields to the subject. The third transducer and the fourth transducer may be capacitively coupled. As another example, the transducers may not be capacitively coupled.

[0024] In some embodiments, the first transducer and the second transducer in the first pair of transducers may have the same number of electrode elements and may have the same shape, and the third transducer and the fourth transducer in the second pair of transducers may have the same number of electrode elements and may have the same shape. The first transducer and the second transducer may have at least one of: a different number of electrode elements than the third transducer and the fourth transducer, or a different shape than the third transducer and the fourth transducer. As an example, the first transducer and the second transducer may each have 20 electrode elements, and the third transducer and the fourth transducer may each have 13 electrode elements. As an example, the first transducer and the second transducer may each have a substantially elliptical shape, and the third transducer and the fourth transducer may each have a substantially circular shape. Other combinations of electrode elements and shapes may be used.

[0025] The transducers and their positions determined in steps 104, 106, 108, and 110 may be determined automatically and / or based on user input. In some embodiments, the one or more transducer placement positions (e.g., the transducer and its position) may be generated based on, for example, the region of interest of the subject's body corresponding to the target tissue (e.g., a tumor in a unilateral lung). As an example, the one or more transducer placement positions may be intended to optimize the TTFields dose delivered to the region of interest of the subject's body.

[0026] At step 112, method 100 may include simulating the application of TTFields to the subject using the three-dimensional model of the subject, the first transducer at the first position, the second transducer at the second position, the third transducer at the third position, and the fourth transducer at the fourth position, and determining a TTFields dose applied to the target tissue based on the simulation results. These calculations in step 112 may involve solving complex algorithms using large data sets using the three-dimensional model of the subject, thereby requiring the use of a computer device because the human mind cannot perform the required calculations. If the determined TTFields dose is sufficient, the transducer layout may be recommended for the subject and may be provided as an output in step 114.

[0027] In some embodiments, because at least one of the third and fourth transducers has a smaller size and / or a different shape than the first and second transducers, certain areas of the subject may be avoided when the third and fourth transducers are placed on the subject, such as avoiding chemotherapy ports, shunts, sensitive scar areas (e.g., from surgery or radiation therapy), or anatomical sites to be avoided (e.g., ears or nipples). Thus, by using method 100 to determine the impact of different transducers and their locations, avoiding certain areas of the subject may be part of the TTFies treatment plan for the subject.

[0028] At step 114, method 100 may include outputting a representation of the first, second, third, and fourth positions on the subject's body and / or the transducer. As an example, a display may be used to show the representation of the first, second, third, and fourth positions on the subject's body and / or the transducer. As an example, a document may be used to show the representation of the first, second, third, and fourth positions on the subject's body and / or the transducer.

[0029] When the transducer is positioned based on the position determined according to method 100, the transducer can induce an alternating electric field (e.g., TTFields). As an example, the first transducer and the second transducer can generate a first alternating electric field, and the third transducer and the fourth transducer can generate a second alternating electric field. In some embodiments, when the first alternating electric field and the second alternating electric field are induced, the average electric field strength of the unilateral lung of the subject with the tumor can be higher than the other lung of the subject.

[0030] Figure 2 A flow chart depicting an example method 200 for applying TTFields to a subject's body is illustrated. Certain steps of method 200 are described as computer-implemented steps. A computer may be, for example, any device including one or more processors and a memory that is accessible by the one or more processors and stores instructions that, when executed by the one or more processors, cause the computer to perform the relevant steps of method 100. Method 200 may be implemented by any suitable system or apparatus, such as a computer program product. Figure 6 systems and / or Figure 8 Although for illustrative purposes Figure 2 An order of operations is indicated in the drawings, but the timing and order of such operations may be varied where appropriate without negating the purposes and advantages of the examples set forth in detail herein.

[0031] refer to Figure 2 At step 202, method 200 may include positioning a first transducer at a first location on the subject's body. In some embodiments, the first location may be the front of the thorax of the subject's body.

[0032] At step 204, method 200 may include positioning a second transducer at a second location on the subject's body. In some embodiments, the second location may be the posterior portion of the thorax of the subject's body. In some embodiments, a single lung of the subject may be located between the first transducer and the second transducer.

[0033] At step 206, method 200 can include positioning a third transducer at a third location on the subject's body. In some embodiments, the third location can be located on the torso of the subject's body.

[0034] At step 208, method 200 can include positioning a fourth transducer at a fourth location on the subject's body. In some embodiments, the fourth location can be located on the torso of the subject's body.

[0035] As an example, the third position may be located at the left armpit of the subject, and the fourth position may be located at the right armpit of the subject. As an example, the third position may be located at the front of the thorax of the subject's body, and the fourth position may be located at the armpit of the subject, wherein the third position does not overlap with the first position. As an example, the third position may be located at the rear of the thorax of the subject's body, and the fourth position may be located at the armpit of the subject, wherein the third position does not overlap with the second position.

[0036] At step 210 , method 200 may include inducing a first electric field between at least a portion of the first transducer and at least a portion of the second transducer by applying an AC voltage between the first pair of transducers.

[0037] At step 212, method 200 may include inducing a second electric field between at least a portion of the third transducer and at least a portion of the fourth transducer by applying an AC voltage between the first pair of transducers. The process loops between steps 210 and 212 to generate an alternating electric field at specific intervals within a specific time period according to the determined TTFields dose.

[0038] As an example, an alternating electric field (e.g., a TTField) can be applied to a target tissue (e.g., a tumor or cancer in the lungs), a cell, or an area of ​​a subject. In some embodiments, the alternating electric field can be applied using predetermined parameters. As an example, the alternating electric field can include a frequency within a frequency range of about 50 kHz to about 1 MHz. As an example, the alternating electric field can include a frequency within a frequency range of about 50 kHz to about 10,000 kHz. As an example, the frequency of the alternating electric field can be between about 50 kHz and about 1000 kHz, or between about 100 kHz and about 300 kHz. As an example, the frequency of the alternating electric field can be about 100 kHz, about 150 kHz, about 200 kHz, about 250 kHz, or about 300 kHz.

[0039] As an example, an alternating electric field (e.g., TTField) can include an intensity ranging from about 1 V / cm to about 10 V / cm. As an example, the intensity of the alternating electric field can be between about 1 V / cm and about 4 V / cm. Other possible exemplary parameters of the alternating electric field can include an effective time, a turndown time, and a duty cycle (all of which can be measured, for example, in milliseconds), as well as other parameters. These parameters can be modified based on the condition of the subject (e.g., the size of the target tissue, the type of tumor, the age or gender of the subject) or the purpose of the treatment. As an example, for treating tumor cells / cancer cells, the intensity of the alternating electric field can be between about 1 V / cm and about 4 V / cm, and the frequency of the alternating electric field can be between about 150 kHz and about 250 kHz. In some embodiments, the alternating electric field can be applied using two pairs of transducer arrays placed on the subject and directed toward the subject's target tissue (e.g., a tumor).

[0040] In some embodiments, when the first electric field and the second electric field are induced, the average electric field strength of one lung of the subject can be higher than that of the other lung of the subject. In some embodiments, when the alternating electric field is applied, the average electric field strength of the one lung can be at least 1.0 V / cm.

[0041] As discussed herein, various combinations of transducer pairs or similar transducer pairs can be used together. Various positions of the transducer can be used, such as those positions or other positions discussed herein. The transducer can be used in a single pair of transducers or in two or more pairs of transducers. The transducers, transducer positions, transducer pairs, and two or more pairs of transducers discussed herein are not exhaustive.

[0042] Experimental Results

[0043] TTFields can be considered a new anti-mitotic therapy that uses low-intensity alternating electric fields to prevent cell proliferation. TTFields can be delivered using two pairs of transducers placed on the skin of a subject. The distribution of the electric field is determined by the electrical properties of the tissue and the geometry of the subject and the system. Therefore, the location of the transducers on the subject's body may have a significant impact on the TTFields dose that the subject can receive. The transducer layout can be prescribed according to clinical guidelines for thoracic diseases, taking into account the patient's body size. However, the actual placement of the transducers can pose challenges. In many cases, shunts in lung cancer patients may also overlap with the location of the transducer array. In addition, areas of skin damage due to surgery or radiation therapy may prevent the array from being placed in these locations, ultimately resulting in an electric field distribution that is different from that expected. Therefore, as discovered by the inventors, exemplary methods and devices can be used to determine the location of the transducers to apply alternating electric fields to target tissues of the subject's body, and to apply alternating electric fields to the subject's body to treat one or more cancers / tumors in the subject's body.

[0044] The electric field distribution was simulated in a healthy human model (Duke, developed by ITI'S Foundation, Zurich) using Sim4Life V6.2 (ZMT Zurich). Dirichlet boundary conditions were applied on surfaces of different sizes (25% to 121% of the area of ​​the actual transducer for the thorax) attached to the skin of the model. These surfaces were placed in different locations: at the top of the clavicle, at the top of the heart, at the bottom of the lungs so that the bottom edge coincided with the diaphragm. The electric field distribution in the lungs resulting from each surface placement was then analyzed and compared to the distribution of a surface roughly the same size as the actual transducer. In addition, the resistance of the model was analyzed in each case, as this has a direct impact on the actual current delivery during treatment.

[0045] The delivery of TTFields to the lungs was evaluated by placing arrays of either 13 or 20 ceramic disks on the skin of a realistic human computer phantom. The TTFields distribution was then simulated using Sim4Life v6.0 software. Five layouts of TTFields distribution were evaluated. First, FIG. 3A to FIG. 3C Depicted are two example transducer layouts for applying TTFields to a subject's body. For both layouts recommended by the guidelines ( FIG. 3A to FIG. 3C ), four arrays are placed at the front and back of the thorax and coupled in a cross-formation (i.e., the left back is coupled to the right front and vice versa), forming an approximately diagonal electric field in the body. FIG. 3A to FIG. 3C Shown is the transducer layout used to treat lung cancer in a male patient. Figure 3A The first cross-transducer layout is shown (both pairs have 20-disk transducer arrays), and Figure 3BA second interleaved transducer layout is shown (each pair of back sides has a 20-disk transducer array and each front side has a 13-disk transducer array). Figure 3C Front and back views of two transducer locations (eg, a first transducer pair and a second transducer pair) are shown.

[0046] Secondly, FIG. 4A to FIG. 4C Depicted are three example transducer layouts for applying TTFields to a subject's body to target a unilateral lung. According to some embodiments, for the three unilateral lung transducer layouts ( FIG. 4A to FIG. 4C ), one channel focused on the right lung (anteroposterior channel) and paired with a channel where two transducers were placed in each axilla, or one transducer was placed in the anterior or posterior of the left lung and the other in the right axilla. The current was set to 4.0 A for channels with a 20-disc transducer array and 2.6 A for channels with at least one 13-disc transducer array. The average electric field strength delivered to each lung was calculated for each layout. FIG. 4A to FIG. 4C The transducer layout targeting the right lung is shown. For this example, each transducer includes two 20-disc transducer arrays placed on top of a single (right) lung. Figure 4A The second channel consists of two 13-disc transducer arrays placed in each axilla. Figure 4B and Figure 4C The second channel includes the first 1 3 disc transducer array placed in the right axilla and the second channel placed in the back of the left lung ( Figure 4B ) or front ( Figure 4C )'s second 13-disk transducer array.

[0047] The region of the lung with peak field strength shifts depending on the position of the transducer and generally remains around the centerline connecting the transducers. While therapeutic levels may still be achieved outside of this region, the field strength tends to decrease with increasing distance from the transducer. Resistance analysis showed that resistance is highly sensitive to transducer size, with resistance increasing by a factor of 2.5 over baseline size. However, the effect of transducer position on resistance is minimal, with a maximum change of 5Ω at a resistance of 45Ω (for the smallest transducer). The vertical position of the region with higher field strength shifts with the vertical position of the transducer relative to the lung. This positioning effect decreases as the transducer becomes larger. However, even with relatively small transducers, therapeutic levels of TTFields can still be achieved in most of the lung regardless of the vertical position of the transducer.

[0048] FIG. 5A to FIG. 5E Examples of the average field strength in the lungs resulting from different layouts are depicted. Figure 5A and Figure 5B (corresponding to Figure 3A and Figure 3B As can be seen in the transducer layouts in Figure 5C , Figure 5D and Figure 5E (corresponding to the transducer layouts of Figure 4A , Figure 4B and Figure 4C respectively), these transducer layouts focus on the target (right) lung and cover the lower part of the right lung, while the values for the upper part of the right lung and the entire left lung are lower. In terms of the local minimum power density (LMiPD), the transducer layout recommended by the guidelines ( Figure 3A ) provides 0.83 mW / cm 3 for both lungs, while the transducer layouts of the present invention ( Figure 4A , Figure 4B and Figure 4C ) provide 0.62 to 0.81 mW / cm 3 and 0.22 to 0.27 mW / cm 3 for the right lung and the left lung respectively.

[0049] Table 1 below provides the simulation results of five transducer layouts of Figure 3A , Figure 3B , Figure 4A , Figure 4B and Figure 4C , as well as their corresponding average field strengths in Figure 5A , Figure 5B , Figure 5C , Figure 5D and Figure 5E respectively. For the transducer layout recommended by the guidelines ( Figure 3A ), the average field strength generated by the recommended layout is 1.69 V / cm for each lung. The transducer layouts of the present invention ( Figure 4A , Figure 4B and Figure 4C ) provide 1.60 V / cm to 1.69 V / cm for the right lung and 0.88 V / cm to 0.99 V / cm for the left lung. The values in Table 1 are obtained by locally averaging the field strengths on the two channels of each transducer layout.

[0050] Table 1 Field strengths generated by each transducer layout within each lung.

[0051]

[0052]

[0053] The results disclosed indicate that the field strength in the lung is sensitive to the location of the array. The magnitude of this sensitivity depends on the size of the array. The need for a smaller array in the axilla may limit the expected output current of the device. In addition, the location of the smaller array may prevent the electric field strength from adequately covering the area surrounding the mediastinum. However, if the tumor is located in a single lung of the subject, some embodiments of the transducer layout for applying TTFields may be more beneficial because they can focus the energy of the TTFields on a single lung rather than both lungs. In addition, using a smaller transducer can still provide TTFields treatment volumes similar to unilateral lung energy, and it is also possible to avoid certain areas (chemotherapy infusion ports, shunts, sensitive scar areas (e.g., from surgery or radiation therapy), or anatomical sites to be avoided (e.g., ears or nipples)) when the smaller transducer is placed on the subject.

[0054] Exemplary Devices

[0055] Figure 6 An example device for applying an alternating electric field (e.g., TTFields) to a subject's body is depicted. A first transducer array 601 includes 13 electrode elements 603, which are located on a substrate 604, and the electrode elements 603 are electrically and mechanically connected to each other through conductive wires 609. A second transducer array 602 includes 13 electrode elements 605, which are located on a substrate 606, and the electrode elements 605 are electrically and mechanically connected to each other through conductive wires 610. The first transducer array 601 and the second transducer array 602 are connected to an AC voltage generator 607 and a controller 608. The controller 608 may include one or more processors and a memory accessible by the one or more processors. The memory may store instructions that, when executed by the one or more processors, control the AC voltage generator 607 to implement one or more embodiments of the present invention. In some embodiments, the AC voltage generator 607 and the controller 608 may be integrated in the first transducer array 601 and the second transducer array 602, and form a first electric field generator and a second electric field generator.

[0056] The structure of the transducer can take many forms. The transducer can be fixed to the subject's body or attached to or incorporated into clothing covering the subject's body. The transducer can include suitable materials for attaching the transducer to the subject's body. For example, these suitable materials can include cloth, foam, flexible plastic and / or conductive medical gel. The transducer can be conductive or non-conductive.

[0057] The transducer may include any desired number of electrode elements. These electrode elements may use a variety of shapes, sizes, and materials. Any structure that is capable of: (a) delivering TTFields to the subject's body, and (b) being positioned at the locations specified herein, may be used to implement a transducer (or electric field generating device) for use with embodiments of the present invention. In some embodiments, at least one electrode element of the first transducer, the second transducer, the third transducer, or the fourth transducer may include at least one ceramic disk that is suitable for generating an alternating electric field. In some embodiments, at least one electrode element of the first transducer, the second transducer, the third transducer, or the fourth transducer may include a polymer film that is suitable for generating an alternating electric field. In some embodiments, the disclosed system may have more than four transducers.

[0058] Fig. 7A A schematic diagram illustrating an exemplary design of a transducer for applying an alternating electric field is shown. The transducer array 701 includes 20 electrode elements 702, which are located on a substrate 703 and are electrically and mechanically connected to each other by conductive wires 704. In some embodiments, the electrode elements 702 may include ceramic disks.

[0059] Figure 7B A schematic diagram of an exemplary design of a transducer for applying an alternating electric field is illustrated. The transducer 705 may include a substantially flat electrode element 706. In some embodiments, the electrode element 706 is a non-ceramic dielectric material located on a flat conductor. Examples of non-ceramic dielectric materials located on a flat conductor may include a polymer film disposed on a pad on a printed circuit board or on a flat piece of metal. In some embodiments, such polymer films have a high dielectric constant, such as, for example, a dielectric constant greater than 10. In some embodiments, the electrode element 706 may have a variety of shapes. For example, these electrode elements may be triangular, rectangular, circular, elliptical, quasi-elliptical, oval, or standard elliptical in shape, or may be substantially triangular, substantially rectangular, substantially circular, substantially elliptical, substantially quasi-elliptical, substantially oval, or substantially standard elliptical in shape. In some embodiments, each electrode element in the electrode element 706 may have the same shape, similar shapes, and / or different shapes.

[0060] Figure 8 An example computer device for use with embodiments herein is depicted. As an example, device 800 may be a computer that implements certain inventive techniques disclosed herein. As an example, Figure 1 and Figure 2The method may be performed by a computer (such as device 800). As an example, device 800 may be a controller device for applying an alternating electric field (e.g., TTField) according to embodiments herein. Controller device 800 may be used as Figure 6 The controller 608 of the embodiment of the present invention. The apparatus 800 may include one or more processors 802, a memory 803, one or more input devices (not shown) and one or more output devices 805.

[0061] In some embodiments, based on input 801, one or more processors 802 can generate control signals to control the voltage generator to implement one or more embodiments of the present invention. As an example, input 801 is user input. As an example, input 801 can come from another computer in communication with device 800. Input 801 can be received in conjunction with one or more input devices (not shown) of device 800.

[0062] The memory 803 may be accessible by the one or more processors 802 (e.g., via the link 804) such that the one or more processors 802 may read information from and write information to the memory 803. The memory 803 may store instructions that, when executed by the one or more processors 802, implement one or more embodiments described herein. The memory 803 may be a non-transitory computer-readable medium (or non-transitory processor-readable medium) having a set of instructions contained thereon, which, when executed by a processor (such as the one or more processors 802), causes the processor to perform one or more methods disclosed herein.

[0063] The one or more output devices 805 may provide the state of the computer-implemented techniques herein. According to some embodiments of the invention, the one or more output devices 805 may provide visualization data.

[0064] The device 800 may include: one or more processors (such as one or more processors 802); and a memory (such as memory 803) accessible by the one or more processors, the memory storing instructions that, when executed by the one or more processors, cause the device to perform one or more methods disclosed herein.

[0065] Illustrative Embodiments

[0066] The invention includes other illustrative embodiments such as those shown below.

[0067] Exemplary embodiment 1 A computer-implemented method for determining the position of a transducer to apply a tumor treatment electric field to a target tissue of a subject's body, the computer-implemented method comprising: obtaining a three-dimensional model of at least a portion of the subject's body, wherein the portion of the subject's body includes the target tissue, wherein a unilateral lung of the subject's body includes the target tissue; determining a first position on the three-dimensional model to place a first transducer, wherein the first position is the front of the thorax of the subject's body; determining a second position on the three-dimensional model to place a second transducer, wherein the second position is the back of the thorax of the subject's body, wherein the unilateral lung of the subject is located between the first transducer and the second transducer; determining a third position on the three-dimensional model to place a third transducer, wherein the third position is located on the torso of the subject's body; determining a fourth position on the three-dimensional model to place a fourth transducer, wherein the fourth position is located on the torso of the subject's body; and outputting representations of the first position, the second position, the third position, and the fourth position on the subject's body.

[0068] Exemplary embodiment 2 The computer-implemented method according to exemplary embodiment 1, wherein the third position is located at the left armpit of the subject and the fourth position is located at the right armpit of the subject.

[0069] Exemplary embodiment 3 According to the computer-implemented method described in Exemplary embodiment 1, the third position is located at the front of the thorax of the subject's body, and the fourth position is located at the armpit of the subject, wherein the third position does not overlap with the first position.

[0070] Exemplary embodiment 4: A computer-implemented method according to exemplary embodiment 1, wherein the third position is located at the rear of the thorax of the subject's body, and the fourth position is located at the armpit of the subject, wherein the third position does not overlap with the second position.

[0071] Exemplary embodiment 5 is a computer-implemented method according to exemplary embodiment 1, wherein a first alternating electric field is simulated to be generated by the first transducer at the first position and the second transducer at the second position, wherein a second alternating electric field is simulated to be generated by the third transducer at the third position and the fourth transducer at the fourth position, wherein for the simulated first alternating electric field and the simulated second alternating electric field, the average electric field strength of the unilateral lung is higher than that of the other lung.

[0072] Exemplary Embodiment 6 The computer-implemented method according to Exemplary Embodiment 5, wherein the simulated average electric field strength of the unilateral lung is at least 1.0 V / cm.

[0073] Exemplary embodiment 7 is a computer-implemented method according to exemplary embodiment 1, wherein the first transducer and the second transducer have the same number of electrode elements and the same shape, wherein the third transducer and the fourth transducer have the same number of electrode elements and the same shape, and wherein the first transducer and the second transducer have at least one of the following: a different number of electrode elements than the third transducer and the fourth transducer, or a different shape than the third transducer and the fourth transducer.

[0074] Exemplary embodiment 8 A system for applying a tumor treatment electric field to a subject's body, the system comprising: a first transducer, the first transducer being adapted to be positioned at a first position of the subject's body, wherein the first position is the front of the thorax of the subject's body; a second transducer, the second transducer being adapted to be positioned at a second position of the subject's body, wherein the second position is the back of the thorax of the subject's body, wherein a unilateral lung of the subject is located between the first position and the second position; a third transducer, the third transducer being adapted to be positioned at a third position of the subject's body, wherein the third position is located on the torso of the subject's body; and a fourth transducer, the fourth transducer being adapted to be positioned at a third position of the subject's body, wherein the third position is located on the torso of the subject's body. a transducer adapted to be positioned at a fourth location on the subject's body, wherein the fourth location is on the torso of the subject's body; a voltage generator adapted to provide a first voltage to the first transducer, a second voltage to the second transducer, a third voltage to the third transducer, and a fourth voltage to the fourth transducer; and a controller coupled to the voltage generator, wherein the controller is adapted to instruct the voltage generator to induce a first alternating electric field between at least a portion of the first transducer and at least a portion of the second transducer, and to induce a second alternating electric field between at least a portion of the third transducer and at least a portion of the fourth transducer.

[0075] Exemplary Embodiment 9 The system according to Exemplary Embodiment 8, wherein the third position is located at the left armpit of the subject, and the fourth position is located at the right armpit of the subject.

[0076] Exemplary embodiment 10 In the system according to exemplary embodiment 8, the third position is located at the front of the thorax of the subject's body, and the fourth position is located at the armpit of the subject, wherein the third position does not overlap with the first position.

[0077] Exemplary embodiment 11 The system according to exemplary embodiment 8, wherein the third position is located at the rear portion of the thorax of the subject's body, and the fourth position is located at the armpit of the subject, wherein the third position does not overlap with the second position.

[0078] Exemplary Embodiment 12 In the system according to Exemplary Embodiment 8, when the first alternating electric field and the second alternating electric field are induced, the average electric field strength of the unilateral lung is higher than that of the other lung.

[0079] Exemplary embodiment 13 The system according to exemplary embodiment 8, wherein at least one electrode element of the first transducer, the second transducer, the third transducer or the fourth transducer includes at least one ceramic disk, and the at least one ceramic disk is suitable for generating an alternating electric field.

[0080] Exemplary Embodiment 14 The system according to Exemplary Embodiment 8, wherein the at least one electrode element of the first transducer, the second transducer, the third transducer, or the fourth transducer comprises a polymer film suitable for generating an alternating electric field.

[0081] Exemplary embodiment 15 A method for applying a tumor treatment electric field to a subject's body, the method comprising: positioning a first transducer at a first position on the subject's body, wherein the first position is the front of the thorax of the subject's body; positioning a second transducer at a second position on the subject's body, wherein the second position is the back of the thorax of the subject's body, wherein a unilateral lung of the subject is located between the first transducer and the second transducer; positioning a third transducer at a third position on the subject's body, wherein the third position is located on the torso of the subject's body; positioning a fourth transducer at a fourth position on the subject's body, wherein the fourth position is located on the torso of the subject's body; inducing a first alternating electric field between at least a portion of the first transducer and at least a portion of the second transducer; and inducing a second alternating electric field between at least a portion of the third transducer and at least a portion of the fourth transducer.

[0082] Exemplary Embodiment 16 The method according to Exemplary Embodiment 15, wherein the third position is located at the left armpit of the subject, and the fourth position is located at the right armpit of the subject.

[0083] Exemplary embodiment 17 According to the method described in Exemplary embodiment 15, the third position is located at the front of the thorax of the subject's body, and the fourth position is located at the armpit of the subject, wherein the third position does not overlap with the first position.

[0084] Exemplary Embodiment 18 The method according to Exemplary Embodiment 15, wherein the third position is located at the rear portion of the thorax of the subject's body, and the fourth position is located at the armpit of the subject, wherein the third position does not overlap with the second position.

[0085] Exemplary Embodiment 19 According to the method described in Exemplary Embodiment 15, when the first alternating electric field and the second alternating electric field are induced, the average electric field strength of the unilateral lung is higher than that of the other lung.

[0086] Exemplary Embodiment 20 The method according to Exemplary Embodiment 19, wherein the average electric field strength of the unilateral lung is at least 1.0 V / cm.

[0087] EXAMPLE EMBODIMENT 21 An apparatus, method and / or system substantially as shown and described.

[0088] Embodiments shown under any heading or any section of this disclosure may be combined with embodiments shown under the same or any other heading or other section of this disclosure unless otherwise indicated herein or clearly contradicted by context.

[0089] Numerous modifications, changes and variations may be made to the described embodiments without departing from the scope of the invention as defined by the claims. It is intended that the present invention not be limited to the described embodiments, but rather have the full scope defined by the language of the following claims and their equivalents.

Claims

1. A computer-implemented method for determining a position of a transducer to apply a tumor treatment electric field to a target tissue of a subject's body, the computer-implemented method include: obtaining a three-dimensional model of at least a portion of the subject's body, wherein the portion of the subject's body includes the target tissue, wherein a single lung of the subject's body includes the target tissue; determining a first location on the three-dimensional model to place a first transducer, wherein the first location is an anterior portion of a thorax of the subject's body; determining a second location on the three-dimensional model to place a second transducer, wherein the second location is a posterior portion of the thorax of the subject's body, wherein the unilateral lung of the subject is located between the first transducer and the second transducer; determining a third location on the three-dimensional model to place a third transducer, wherein the third location is located on the torso of the subject's body; determining a fourth location on the three-dimensional model to place a fourth transducer, wherein the fourth location is located on the torso of the subject's body; as well as Representations of the first, second, third, and fourth locations on the subject's body are output. 2 . The computer-implemented method of claim 1 , wherein the third location is located at the subject's left armpit and the fourth location is located at the subject's right armpit.

3. The computer-implemented method of claim 1, the third location being located at the front of the thorax of the subject's body, and the fourth location being located at an armpit of the subject, wherein the third location does not overlap with the first location.

4. The computer-implemented method of claim 1, wherein the third location is located at the posterior portion of the thorax of the subject's body and the fourth location is located at an armpit of the subject, wherein the third location does not overlap with the second location.

5. The computer-implemented method of claim 1 , wherein a first alternating electric field is simulated as being generated by the first transducer at the first position and the second transducer at the second position, wherein a second alternating electric field is simulated to be generated by the third transducer at the third position and the fourth transducer at the fourth position, For the simulated first alternating electric field and the simulated second alternating electric field, the average electric field strength of the unilateral lung is higher than that of the other lung.

6. A system for applying a tumor treating electric field to a subject's body, the system include: a first transducer adapted to be positioned at a first location on the subject's body, wherein the first location is an anterior portion of the thorax of the subject's body; a second transducer adapted to be positioned at a second location on the subject's body, wherein the second location is a posterior portion of the thorax of the subject's body, wherein a single lung of the subject will be positioned between the first location and the second location; a third transducer adapted to be positioned at a third location on the subject's body, wherein the third location is located on the torso of the subject's body; a fourth transducer adapted to be positioned at a fourth location on the subject's body, wherein the fourth location is located on the torso of the subject's body; a voltage generator adapted to provide a first voltage to the first transducer, a second voltage to the second transducer, a third voltage to the third transducer, and a fourth voltage to the fourth transducer; and a controller coupled to the voltage generator, wherein the controller is adapted to instruct the voltage generator to induce a first alternating electric field between at least a portion of the first transducer and at least a portion of the second transducer, and to induce a second alternating electric field between at least a portion of the third transducer and at least a portion of the fourth transducer.

7. The system of claim 6, wherein the third location is located at the subject's left armpit and the fourth location is located at the subject's right armpit.

8. The system of claim 6, the third location being located at the front of the thorax of the subject's body, and the fourth location being located at an armpit of the subject, wherein the third location does not overlap with the first location.

9. The system of claim 6, wherein the third location is located at the posterior portion of the thorax of the subject's body and the fourth location is located at an armpit of the subject, wherein the third location does not overlap with the second location.

10. The system of claim 6, wherein at least one electrode element of the first transducer, the second transducer, the third transducer, or the fourth transducer comprises at least one ceramic disk adapted to generate an alternating electric field.

11. The system of claim 6, wherein the at least one electrode element of the first transducer, the second transducer, the third transducer, or the fourth transducer comprises a polymer film adapted to generate an alternating electric field.

12. A method for applying a tumor treating electric field to a subject's body, the method include: positioning a first transducer at a first location on the subject's body, wherein the first location is an anterior portion of the thorax of the subject's body; positioning a second transducer at a second location on the subject's body, wherein the second location is a posterior portion of the thorax of the subject's body, wherein a single lung of the subject is located between the first transducer and the second transducer; positioning a third transducer at a third location on the subject's body, wherein the third location is on the torso of the subject's body; positioning a fourth transducer at a fourth location on the subject's body, wherein the fourth location is on the torso of the subject's body; inducing a first alternating electric field between at least a portion of the first transducer and at least a portion of the second transducer; as well as A second alternating electric field is induced between at least a portion of the third transducer and at least a portion of the fourth transducer.

13. The method of claim 12, wherein the third location is located at the subject's left armpit and the fourth location is located at the subject's right armpit.

14. The method of claim 12, the third location being located at the anterior portion of the thorax of the subject's body, and the fourth location being located at an armpit of the subject, wherein the third location does not overlap with the first location.

15. The method of claim 12, wherein the third location is located at the posterior portion of the thorax of the subject's body and the fourth location is located at an armpit of the subject, wherein the third location does not overlap with the second location.

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