Application of Tumor Treating Fields (TTFields) to the Neck

Abstract

To provide a first method of treating a tumor developed in or near a person's neck or preventing the tumor from metastasis.SOLUTION: A method of driving first and second sets of electrode elements causes a computer to execute the steps of: acquiring a 3D model of electrical conductivity or electrical resistivity of an anatomical volume with a given frequency; identifying the place of a target tissue within the anatomical volume; and in order to select one of a plurality of layouts, analyzing an electric field associated to the layouts for the first and second sets of the electrode elements, on the basis of the respective layouts, the 3D model of the electrical conductivity or the electrical resistivity, and the place of the target tissue. Therefore, the first set of the electrode elements is located on the head, and the second set of the electrode elements is located on the chest.SELECTED DRAWING: Figure 5A

Description

Technical Field

[0001] Cross - reference to Related Applications This application claims the benefit of U.S. Provisional Application No. 62 / 893,876, filed Aug. 30, 2019, which is hereby incorporated by reference in its entirety.

Background Art

[0002] TTFields are alternating electric fields in the intermediate frequency range (e.g., 100 - 300 kHz) at low intensities (e.g., 1 - 4 V / cm) and can be used to treat tumors as described in U.S. Patent No. 7,565,205, which is hereby incorporated by reference in its entirety. TTFields therapy is an approved mono - treatment for recurrent glioblastoma (GBM) and an approved combination therapy with chemotherapy for newly diagnosed GBM patients. TTFields can also be used to treat tumors in other parts of the human body (e.g., lungs, ovaries, pancreas). TTFields are non - invasively induced in the region of interest by transducer arrays (i.e., arrays of capacitive coupling electrode elements) placed directly on the patient's body (e.g., using the Novocure Optune™ system) and by applying an AC voltage between the transducer arrays.

[0003] In the context of GBM, the conventional approach for positioning the transducer arrays is to position the first pair of transducer arrays before and after the head and the second pair of transducer arrays to the left and right of the head. Also, in the context of treating mesothelioma, the conventional approach for positioning the transducer arrays is to position the first pair of transducer arrays before and after the torso and the second pair of transducer arrays to the left and right of the torso. The AC voltage generator applies an AC voltage (e.g., 200 kHz in the context of GBM or 150 kHz in the context of mesothelioma) between the first pair of transducer arrays at a first time interval (e.g., 1 second), which generally generates an electric field with electric field lines running in the front - back direction. Then, the AC voltage generator applies an AC voltage of the same frequency between the second pair of transducer arrays at a second time interval (e.g., 1 second), which generally generates an electric field with electric field lines running in the left - right direction. Then, the system repeats this two - step sequence over the duration of the treatment.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Summary of the Invention

Means for Solving the Problems

[0005] One aspect of the present invention is directed to a first method for treating or preventing metastasis of a tumor located in or near a person's neck. The first method includes attaching a first set of electrode elements having a first center of gravity to the person's head with the first center of gravity positioned on the person's head, attaching a second set of electrode elements to the person's chest, and applying an alternating voltage between the first set of electrode elements and the second set of electrode elements. Applying is performed after attaching the first set and the second set of electrode elements.

[0006] In some instances of the first method, the first and second sets of electrode elements are capacitively coupled. In some instances of the first method, the alternating voltage applied between the first set of electrode elements and the second set of electrode elements has a frequency between 100 kHz and 300 kHz. In some instances of the first method, the first set of electrode elements comprises a plurality of electrode elements wired in parallel, and the second set of electrode elements comprises a plurality of electrode elements wired in parallel. In some instances of the first method, the first center of gravity is positioned at the crown of the head. In some instances of the first method, the first center of gravity is positioned on the upper surface of the person's head. In some instances of the first method, the second set of electrode elements is positioned just below the base of the neck.

[0007] Another aspect of the present invention is directed to a second method of planning the positioning of first and second sets of electrode elements on a subject's body. The second method includes obtaining a 3D model of the electrical conductivity or resistivity of an anatomical volume located in or near a person's neck within the subject's body at a given frequency, and identifying the location of a target tissue within the anatomical volume. The second method also includes analyzing the electric fields associated with a plurality of layouts for the first and second sets of electrode elements based on each layout, the 3D model of electrical conductivity or resistivity, and the identified location of the target tissue, and selecting one of the plurality of layouts based on the results of the analysis. The first set of electrode elements has a first center of gravity. In each of the plurality of layouts, (a) the first set of electrode elements is positioned on the person's head with the first center of gravity positioned on the person's head, and (b) the second set of electrode elements is positioned on the person's chest.

[0008] In some instances of the second method, the first center of gravity is positioned at the vertex of the head. In some instances of the second method, the first center of gravity is positioned on the upper surface of the person's head. In some instances of the second method, the second set of electrode elements is positioned just below the base of the neck. In some instances of the second method, the given frequency is between 100 and 300 kHz. In some instances of the second method, the 3D model of electrical conductivity or resistivity is a 3D model of electrical conductivity.

[0009] Some instances of the second method further include attaching the first and second sets of electrode elements to the subject's body at positions corresponding to the selected layout, and applying an electrical signal between the first and second sets of electrode elements following the attaching step so as to apply an electric field to the target tissue.

[0010] Another aspect of the present invention is directed to a third method for treating or preventing metastasis of a tumor located in or near a person's neck. The third method includes attaching a first set of electrode elements to the back of a person's neck, attaching a second set of electrode elements to the person's chest, and applying an alternating voltage between the first set of electrode elements and the second set of electrode elements. Applying is performed after attaching the first set and the second set of electrode elements.

[0011] In some instances of the third method, the first and second sets of electrode elements are capacitively coupled. In some instances of the third method, the alternating voltage applied between the first set of electrode elements and the second set of electrode elements has a frequency between 100 kHz and 300 kHz. In some instances of the third method, the first set of electrode elements comprises a plurality of electrode elements wired in parallel, and the second set of electrode elements comprises a plurality of electrode elements wired in parallel. In some instances of the third method, the second set of electrode elements is positioned just below the base of the neck. BRIEF DESCRIPTION OF THE DRAWINGS

[0012]

Figure 1

Figure 2A

Figure 2B

Figure 2C

Figure 2D

Figure 3A

Figure 3B

Figure 3C

Figure 3D

Figure 4A

Figure 4B

Figure 4C

Figure 4D

Figure 5A

Figure 5B

Figure 5C

Figure 6A

Figure 6B

Figure 6C

Figure 7A

Figure 7B

Figure 7C

Figure 8

Figure 9

DETAILED DESCRIPTION OF THE INVENTION

[0013] In the following, various embodiments will be described in detail with reference to the accompanying drawings, and similar reference numerals represent similar elements.

[0014] The present application describes a number of transducer array layouts that can be used to treat cancer in the region of interest (ROI) depicted in FIGS. 1A and 1B. This ROI was taken around the larynx and included all tissues except the vertebrae, intervertebral discs, and internal air.

[0015] In the context of treating brain tumors, positioning a pair of transducer arrays in front of and behind the head and another pair of transducer arrays on the left and right of the head is a practical approach. However, in the context of treating neck tumors, positioning transducer arrays all around the neck can be uncomfortable and may also limit the patient's movement. The transducer array layouts described in the present application provide improvements in comfort and range of motion with respect to the conventional four-sided approach.

[0016] Preclinical experiments suggest that for TTFields to exert a therapeutic effect, the electric field strength should exceed a threshold of approximately 1 V / cm. However, in the context of treating cancers within the ROI depicted in FIGS. 1A and 1B (such as upper cervical cancers like head and neck squamous cell carcinoma (SCC), as well as some cases of esophageal SCC and adenocarcinoma), many layouts for positioning the transducer arrays do not provide the desired level of electric field strength.

[0017] FIGS. 2A and 2B show an example of a layout for a pair of transducer arrays that provides an appropriately high electric field strength within the region of interest. In this layout, one transducer array containing 13 round electrode elements (hereinafter referred to as disks) is positioned with its centroid on the vertex of the subject's head and on the upper surface of the subject's head, and another transducer array containing 13 disks is positioned vertically oriented on the upper thorax. The resulting gray-scale maps of the electric field strength for this layout are shown in FIGS. 2C and 2D. (FIG. 8 shows the scale for all gray-scale maps of this application.) In this layout, the average intensity is 3.4 V / cm, the median electric field strength is 3.41 V / cm, and 99.27% of the region of interest had an intensity higher than 1 V / cm.

[0018] FIGS. 3A and 3B show another example of a layout for a pair of transducer array layouts that provides an appropriately high electric field strength within the region of interest. In this layout, one transducer array containing 13 round disks is positioned at the upper rear part of the subject's head, and another transducer array containing 13 disks is positioned vertically oriented on the upper thorax. The resulting gray-scale maps of the electric field strength for this layout are shown in FIGS. 3C and 3D. In this layout, the average intensity is 3.22 V / cm, the median electric field strength is 3.25 V / cm, and 99.07% of the region of interest had an intensity higher than 1 V / cm.

[0019] Figures 4A and 4B show an example of another layout for a pair of transducer arrays that provide appropriately high electric field strength within the region of interest. In this layout, one transducer array containing 13 round disks is positioned at the posterior neck of the subject, and another transducer array containing 13 disks is positioned vertically oriented at the upper chest. The resulting gray scale maps of the electric field strength for this layout are shown in Figures 4C and 4D. In this layout, the average intensity is 1.47 V / cm, the median of the electric field strength is 1.39 V / cm, and 73.22% of the region of interest had an intensity higher than 1 V / cm. In particular, the results for this layout are not as good as those shown in Figures 2 and 3.

[0020] Figure 5A shows an example of another layout for a pair of transducer arrays that provide appropriately high electric field strength within the region of interest. In this layout, one transducer array containing 9 round disks is positioned at the vertex of the subject's head, and another transducer array containing 9 disks is positioned horizontally oriented at the upper chest. The resulting gray scale maps of the electric field strength for this layout are shown in Figures 5B and 5C. In this layout, the average intensity is 2.55 V / cm, the median of the electric field strength is 2.55 V / cm, and 98.79% of the region of interest had an intensity higher than 1 V / cm.

[0021] In contrast to the above layout, other layouts did not result in a sufficiently high electric field strength in the region of interest. For example, in the layout of FIG. 6A, one transducer array including nine round disks was positioned on the left side of the subject's neck, and another transducer array including nine disks was positioned at the height of the shoulder immediately to the right of the subject's backbone. The gray-scale maps of the electric field strength obtained as a result of this layout are shown in FIGS. 6B and 6C. In this layout, the average strength was 1.83 V / cm, the median of the electric field strength was 1.32 V / cm, and 64.83% of the region of interest had a strength higher than 1 V / cm. Even though these numerical results may not seem so bad, it should be noted that these numerical results are misleading because, as can be clearly seen from FIGS. 6B and 6C, most of the energy is dissipated on the skin.

[0022] In the layout of FIG. 7A, one transducer array including nine round disks was positioned on the right side of the subject's neck, and another transducer array including nine disks was positioned at the height of the shoulder immediately to the left of the subject's backbone. The gray-scale maps of the electric field strength obtained as a result of this layout are shown in FIGS. 7B and 7C. In this layout, the average strength was 1.67 V / cm, the median of the electric field strength was 1.21 V / cm, and 60.10% of the region of interest had a strength higher than 1 V / cm. Again, even though these numerical results may not seem so bad, it should be noted that these numerical results are misleading because, as can be clearly seen from FIGS. 7B and 7C, most of the energy is dissipated on the skin.

[0023] It should be noted that all the electric field strengths depicted and described in this specification were generated by performing simulations at 150 kHz using the DUKE model from ZMT (Zurich). In the simulated layouts, a transducer array of either 9 disks or 13 disks was used. The simulation with 9 disks was normalized to a current of 1 A, and the simulation with 13 disks was normalized to a current of 1.3 A. The results show that by placing one transducer array above the scalp and another transducer array above the thorax, voltages of 1.47 V / cm or more up to a maximum of 3.4 V / cm are applied to the region of interest. This holds true regardless of whether a 9-disk array or a 13-disk array is used. Also, when the upper array is moved downward, the electric field strength decreases. This is particularly pronounced in the embodiment of FIG. 4, where the electric field strength decreased to less than half of that in the embodiment of FIG. 2.

[0024] When the transducer array is positioned as described above, the same structure as that of the transducer arrays used at other anatomical locations may be used. An example of a conventional transducer array is the transducer array used in the Novocure Optune® system. These transducer arrays have a flexible backing configured to be affixed to the human body. Materials suitable for the flexible backing include cloth, foam, and flexible plastics (e.g., similar to the corresponding materials used in bandages). Inside the flexible backing, a plurality of capacitively coupled electrode elements are positioned, with each of the capacitively coupled electrode elements having a conductive plate with an inward dielectric layer disposed thereon. Optionally, a temperature sensor (e.g., a thermistor) may be positioned under each of the electrode elements in a manner similar to the conventional arrangement used in the Novocure Optune® system.

[0025] A set of conductive lines is connected to the conductive plates of each of the plurality of capacitive coupling electrode elements. The conductive lines can be implemented, for example, using discrete wiring or using traces on a flexible circuit. A layer of adhesive is configured to apply to the human body a flexible backing portion that is not covered by any of the electrode elements.

[0026] In the embodiments depicted in FIGS. 2-5, each transducer array is configured as an array of 9 or 13 individual electrode element disks, and the center of gravity of the array coincides with the center of the central disk. However, in alternative embodiments, each transducer array may comprise a different number (e.g., between 4 and 24) of electrode elements. For example, a given transducer array may be configured as a 2×2 array of individual electrode element disks. In this situation, the center of gravity may be within the region located between all 4 disks. In other alternative embodiments, a given set of electrode elements may include only a single electrode element (which may be of any suitable shape, including but not limited to circular and rectangular). In this situation, the center of gravity will coincide with the center of that single electrode element. It should also be noted that in the embodiments described herein, the upper and lower transducer arrays each use the same number of disks. However, in alternative embodiments, the number of disks in the upper and lower transducer arrays may be different (e.g., 9 disks in the upper array and 13 disks in the lower array).

[0027] Alternative structures of the transducer array may also be used, which include, for example, transducer arrays using ceramic elements that are not disk-shaped, and transducer arrays using non-ceramic dielectric materials positioned on a plurality of flat conductor lines. Examples of the latter include polymer films disposed on pads of a printed circuit board or on flat metal pieces. Transducer arrays using non-capacitively coupled electrode elements may also be used. In this situation, each element of the transducer array is implemented using a region of conductive material configured to be applied to the human body, and the insulating dielectric layer is not disposed between the conductive element and the body. Other alternative structures for implementing the transducer array may be used as long as (a) they can apply TTFields to the human body and (b) they are positioned at the locations specified herein. Optionally, in any of the embodiments described herein, a layer of hydrogel may be disposed between the transducer array and the human body.

[0028] Regarding the layouts described above in connection with FIGS. 2-7, the average intensity, the median electric field strength, and the percentage of the ROI having an intensity exceeding 1 V / cm were all obtained by simulating the electric field when the electrode elements within each transducer array were positioned as depicted in FIGS. 2-7. However, the position of the transducer array (and / or the elements within each of those arrays) may be varied from the exact locations depicted in those figures as long as the movement is small enough that each of the above anatomical descriptions remains unchanged. For example, the electrode elements positioned on the head in FIG. 3B can be moved up and down or left and right as long as they remain positioned on the upper part of the subject's occiput. Similarly, the electrode elements positioned on the chest in FIG. 3A can be moved up and down or left and right as long as they remain positioned on the upper part of the rib cage.

[0029] Within this limited movement range, the optimal position for each of the transducer arrays can be determined by using simulations (e.g., finite element simulations) for each individual to calculate the resulting electric fields for each combination of positions for the transducer arrays and selecting the combination that provides the best results (e.g., the highest percentage of ROI having an intensity exceeding 1 V / cm). The indication of the selected combination is then output to the medical personnel, for example, using a suitable display or printout. The medical personnel then attach the transducer array to the person at the positions indicated by the output, attach the set of electrode elements to the AC signal generator 50, and initiate TTFields treatment.

[0030] Figure 9 shows an example of using simulations to determine the optimal position for each of the transducer arrays. First, at step S20, a 3D model of the AC electrical conductivity of the relevant anatomical volume (at the frequency used for TTFields treatment) is obtained using any of a variety of approaches that will be apparent to those skilled in the art. This model specifies the conductivity of each voxel.

[0031] Optimization of the array layout means finding an array layout that optimizes the electric field within the ROI. This optimization can be implemented by performing the following four steps: (S21) identifying the volume to be treated (target volume) within the model; (S22) automatically placing the transducer array and setting boundary conditions in the model; (S23) calculating the electric field that occurs within the model after the array is placed on the model and the boundary conditions are applied; and (S24) running an optimization algorithm to find the layout that causes an optimal electric field distribution within the target volume. One detailed example for implementing these four steps is presented below, but alternative approaches that will be apparent to those skilled in the art can be used instead of the steps described below.

[0032] Step S21 involves identifying the location of the target volume within the model (i.e., defining the region of interest). The first step in finding a layout that will result in an optimal electric field distribution within the patient's body is to correctly identify the location where the electric field is to be optimized and the target volume.

[0033] In some embodiments, the target volume is either the gross tumor volume (GTV) or the clinical target volume (CTV). The GTV is the overall demonstrable extent and location of the tumor, while the CTV, when present, includes the demonstrated tumor and any other tissue having an assumed tumor. Often, the CTV is found by defining a volume that encompasses the GTV and adding a margin of a predefined width around the GTV.

[0034] To identify the GTV or CTV, it may be necessary to identify the volume of the tumor within the MRI image. This can be performed manually by the user, automatically, or using a semi - automatic approach where a user - assisted algorithm is used. When performing this task manually, the MRI data is presented to the user, and the user may be asked to outline the volume of the CTV on the data. The user may be asked to draw the contour of the CTV on the 3D volumetric representation of the MRI or may be given the option of looking at individual 2D slices of the data and marking the boundaries of the CTV on each slice. After the boundaries are marked on each slice, the CTV within the anatomical volume (and thus within the model) can be found. In this case, the volume marked by the user corresponds to the GTV. In some embodiments, the CTV can be found by adding a margin of a predefined width to the GTV. Similarly, in other embodiments, the user may be asked to mark the CTV using a similar procedure.

[0035] An alternative means to the manual approach is to use an automatic segmentation algorithm to find the CTV. These algorithms execute an automatic segmentation algorithm to identify the CTV using the structural MRI data.

[0036] Optionally, a semi - automatic segmentation approach for MRI data can be implemented. In an example of these approaches, the user iteratively provides inputs to the algorithm (e.g., the location of the tumor on the image, roughly indicating the boundaries of the tumor, defining the boundaries of the region of interest where the tumor is located), and then it is used by the segmentation algorithm. The user can then be given the option to refine the segmentation in order to obtain a better estimate of the location and volume of the CTV in the body.

[0037] Regardless of whether an automatic approach or a semi - automatic approach is used, the identified tumor volume corresponds to the GTV, and then the CTV can be automatically found by expanding the GTV volume by a pre - defined amount (e.g., defining the CTV as a volume that includes a 20 - mm wide margin around the tumor).

[0038] Note that in some cases, it is sufficient for the user to simply define the region of interest for which the electric field is to be optimized. This region of interest can be, for example, a box - shaped volume, a spherical volume, or a volume of any shape within the anatomical volume that includes the tumor. When this approach is used, a complex algorithm for accurately identifying the tumor may not be necessary.

[0039] Step S22 involves automatically calculating the position and orientation of the array on the model for a given iteration. Each transducer array used for TTField application includes a set of ceramic disk electrodes, which are coupled to the patient's body through a layer of medical gel. When the array is worn on an actual patient, the disks are naturally aligned parallel to the skin and the medical gel deforms to fit the body's contours, resulting in good electrical contact between the array and the skin. However, the virtual model is made from a precisely defined geometric shape. Therefore, placing the array on the model requires an accurate way to find the orientation and contour of the model surface at the location where the array is to be placed, and further to find the gel thickness / geometry necessary to ensure good contact between the model array and the patient model. These calculations must be performed automatically in order to enable fully automated optimization of the electric field distribution.

[0040] Various algorithms for performing this operation may be used, and one such algorithm is described in U.S. Patent No. 10,188,851, which is hereby incorporated by reference in its entirety.

[0041] Step S23 involves calculating the electric field distribution within the model for a given iteration. After the model has been constructed and the transducer array (i.e., the electrode array) used to apply the electric field is placed on the model, a volume mesh suitable for finite element (FE) method analysis can be created. Next, boundary conditions can be applied to the model. Examples of boundary conditions that may be used include the Dirichlet boundary condition (constant voltage) of the transducer array, the Neumann boundary condition (constant current) of the transducer array, or a floating potential boundary condition where the potential is set at the boundary such that the integral value of the normal component of the current density equals a specified amplitude. The model can then be solved using a suitable finite element solver (e.g., a low-frequency quasi-static electromagnetic solver), or alternatively a finite difference (FD) algorithm. Meshing the model, imposing boundary conditions, and solving can be performed with existing software packages such as Sim4Life, Comsol Multiphysics, Ansys, or Matlab. Alternatively, custom computer code implementing an FE (or FD) algorithm can be created. This code can utilize existing open-source software resources such as C-Gal (for creating meshes) or FREEFEM++ (software for rapid testing and finite element simulations written in C++). The final solution of the model results in a dataset that describes the electric field distribution or related quantities such as the potential within the computational phantom for a given iteration.

[0042] Step S24 is an optimization step. An optimization algorithm is used to find an array layout that optimizes the application of the electric field to the diseased region (e.g., a tumor) of the patient's body. The optimization algorithm utilizes a method for automatic array placement and a method for solving the electric field within the model in a properly defined order to find the optimal array layout. The optimal layout is one that maximizes or minimizes some objective function of the electric field in the diseased region of the body. This objective function may be, for example, the maximum intensity within the diseased region or the average intensity within the diseased region. The optimal layout is then selected for subsequent use.

[0043] There are a number of approaches that can be used to find the optimal array layout for a patient, two of which are described below. One optimization approach is exhaustive search. In this approach, the optimizer comprises a bank having a finite number of array layouts to be tested. The optimizer performs simulations of all the array layouts in the bank (e.g., by repeating steps S22 and S23 for each layout), and selects the array layout that causes the optimal electric field strength in the tumor (the optimal layout is the layout in the bank that causes the highest (or lowest) value for an optimization objective function, e.g., the electric field strength applied to the tumor).

[0044] Another optimization approach is iterative search. This approach involves the use of algorithms such as the steepest descent optimization method and the simplex search optimization. By using this approach, the algorithm iteratively tests different array layouts on the body and calculates the objective function of the electric field in the tumor for each layout. Thus, this approach also involves repeating steps S22 and S23 for each layout. In each iteration, the algorithm automatically selects a configuration to test based on the results of the previous iteration. The algorithm is designed to converge to maximize (or minimize) a defined objective function for the electric field in the tumor.

[0045] Note that alternative optimization schemes can be used to find the array layout that optimizes the electric field within the diseased region of the body. For example, there are algorithms that combine the various approaches described above.

[0046] After the layout that optimizes the electric field within the diseased region of the patient's body has been determined (e.g., using any of the approaches described herein), the electrodes can be affixed at the determined positions.

[0047] After attaching the transducer array as described above, proceed to step S25 where an alternating voltage is applied across the transducer array (e.g., as described in U.S. Patent No. 7,565,205, which is incorporated herein by reference) to treat a disease. In some embodiments, the frequency of the alternating voltage is between 100 kHz and 300 kHz. In some embodiments, the frequency of the alternating voltage is 150 kHz.

[0048] Advantageously, the layout described herein can be used to apply TTFields at a therapeutically effective level (i.e., greater than 1 V / cm) to the neck.

[0049] While the embodiments described herein show a transducer array positioned on the surface of a subject's skin, it should also be noted that the transducer array or a subset thereof can be implanted beneath the surface of the subject's skin.

[0050] The present invention has been disclosed with reference to several embodiments, but numerous modifications, alterations, and changes to the described embodiments are possible without departing from the scope and range of the present invention as defined in the appended claims. Accordingly, the present invention is not intended to be limited to the described embodiments, but rather is intended to have the full scope defined by the language of the following claims and their equivalents.

Description of the Reference Numerals

[0051] 50 AC signal generator

Claims

1. A method of driving first and second sets of electrode elements, comprising the steps of: obtaining, by a computer, a 3D model of the electrical conductivity or resistivity of an anatomical volume at a given frequency; a computer identifying a location of a target tissue within the anatomical volume; and a computer analyzing electric fields associated with a plurality of layouts for the first and second sets of electrode elements based on the respective layouts, the 3D model of electrical conductivity or resistivity, and a location of a target tissue to select one of the plurality of layouts; This method results in a first set of electrode elements being positioned on the head and a second set of electrode elements being positioned on the chest.

2. The method of claim 1 , wherein the given frequency is between 100 kHz and 300 kHz.

3. The method of claim 1 , wherein the 3D model of electrical conductivity or electrical resistivity is a 3D model of electrical conductivity.

Images