Impedance Tomography Using Electrodes of the Tumor Treating Fields (TTFields) System

Abstract

Treatment of a target region with alternating electric fields (e.g., TTFields) may be planned by determining a first impedance in each of a plurality of voxels corresponding to the target region based on a plurality of impedance measurements obtained during a first time window. A plan for treating the target region with the alternating electric field is then generated based on the first impedance. The electric field may then be induced in the target region based on the plan. In some embodiments, a baseline MRI of the target region is obtained and a concurrent baseline impedance is registered to the MRI. In these embodiments, the plan for treating the target region is further based on a comparison between the first impedance and the baseline impedance.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 63 / 169,098, filed March 31, 2021, which is incorporated herein by reference in its entirety. [Background technology]

[0002] Tumor Treating Fields (TTFields) are an effective anti-tumor therapeutic modality delivered by non-invasive application of low intensity, mid-frequency (e.g., 100-500 kHz) alternating electric fields. The prior art Optune® system delivers TTFields to the tumor via two pairs of transducer arrays (each containing nine or more electrode elements all wired in parallel) placed on the subject's skin in close proximity to the tumor. Typically, one pair of transducer arrays is positioned on the left and right sides of the tumor, and the other pair of transducer arrays is positioned in front and behind the tumor. The transducer arrays are connected via cables to an AC signal generator. The AC signal generator (a) sends an AC current through the left and right pair of arrays during a first period that induces an electric field in a first direction through the tumor, then (b) sends an AC current through the front and back pair of arrays during a second period that induces an electric field in a second direction through the tumor, then repeats steps (a) and (b) for the duration of the treatment.

[0003] The effectiveness of TTFields treatment depends on the electric field strength (or power density) of the electric field delivered to the tumor. Several experiments have shown, for example, that TTFields is more effective when the electric field strength is at least 1 V / cm.

[0004] Traditional approaches to estimating the electric field strength (or power strength) delivered to a tumor rely on numerical simulation techniques that (a) generate a model of the electrical characteristics of the relevant body part from MRI, (b) position model electrodes on the model body part, and (c) calculate what the electric field strength will be within the tumor when a given AC voltage is applied to the model electrodes. While this technique can be extremely useful in determining where on a subject's body the array should be positioned, and what voltage must be applied, to achieve a desired electric field strength, the technique relies on assumptions about the electrical characteristics (e.g., conductivity) of the tissue between the electrodes.

[0005] For example, in the case of a brain tumor, an MRI of the brain is obtained, the MRI is segmented into different types of tissue (e.g., white matter, gray matter, cerebrospinal fluid, etc.), conductivity values ​​obtained from the chemical literature are assigned to each type of tissue, and the assigned conductivities are used to create a 3D model of the brain, skull, and scalp. Model electrodes are then positioned on the 3D model, and a numerical simulation technique is used to determine the electric field strength within the tumor when a voltage is applied to the model electrodes. However, because this technique uses literature-derived conductivity values ​​for each type of tissue (instead of using the actual conductivity of each voxel for the particular subject about to be treated with TTFields), this technique can only provide an estimate of the electric field strength or power density within the tumor. Summary of the Invention [Problem to be solved by the invention]

[0006] Some aspects of the present application are directed to providing methods for determining optimized field strength and / or optimized positioning of an electrode array on the body when applying TTFields to a subject. [Means for solving the problem]

[0007] One aspect of the present invention is directed to a first method of planning treatment of a target region in a subject's body using an alternating electric field. The first method includes the steps of positioning a first set of N electrode elements on or within the subject's body on a first side of the target region, where N is at least 4, and positioning a second set of M electrode elements on or within the subject's body on a second side of the target region, where M is at least 4, the second side being opposite the first side. The first method also includes the steps of continuously measuring a respective impedance or conductance between each of the N electrode elements in the first set and each of the M electrode elements in the second set during a first time window, and calculating a first impedance or conductance in each of at least 27 voxels corresponding to the target region based on the impedance or conductance measurements. The first method also includes the step of generating a plan for treating the target region with an alternating electric field based on the first impedance or conductance of the voxels.

[0008] Some examples of the first method further include positioning a third set of X electrode elements on or within the subject's body on a third side of the target area, where X is at least 4, positioning a fourth set of Y electrode elements on or within the subject's body on a fourth side of the target area, where Y is at least 4, the fourth side being opposite the third side, and continuously measuring a respective impedance or conductance between each of the X electrode elements in the third set and each of the Y electrode elements in the fourth set during the first time window. The calculation of the first impedance or conductance at each of the at least 27 voxels is also based on the measured impedance or conductance between the electrode elements in the third set and the electrode elements in the fourth set.

[0009] Some examples of the first method further include, after the step of generating the plan, (a) applying an alternating voltage between a majority of the electrode elements in the first set and a majority of the electrode elements in the second set to induce an electric field in the target area, and (b) applying an alternating voltage between a majority of the electrode elements in the third set and a majority of the electrode elements in the fourth set to induce an electric field in the target area.

[0010] In some examples of the first method, the plan includes generating a recommendation for moving at least one set of electrode elements to different locations on or within the subject's body. Optionally, these examples may further include, prior to generating the plan, (a) obtaining an MRI and (b) registering voxels to the MRI, where the recommendation to move at least one set of electrode elements to different locations is also based on the MRI.

[0011] In some examples of the first method, N is at least 9, X is at least 9, M is at least 9, and Y is at least 9.

[0012] Some examples of the first method further include obtaining a baseline MRI of the target region at a baseline time prior to the first time window, calculating a baseline impedance or conductance in each of at least 27 voxels corresponding to the target region based on baseline impedance or conductance measurements obtained within 30 days of the baseline time, and registering the baseline impedance or conductance of the voxels to the baseline MRI. A plan for treating the target region with the alternating electric field is further based on a comparison between the first impedance or conductance and the baseline impedance or conductance.

[0013] Another aspect of the present application is directed to a second method for planning treatment of a target region in a subject's body using an alternating electric field, the second method including determining a first impedance or conductance in each of at least 27 voxels corresponding to the target region based on a plurality of impedance or conductance measurements obtained during a first time window, and generating a plan for treating the target region with the alternating electric field based on the first impedance or conductance of the voxels.

[0014] In some examples of the second method, the multiple impedance or conductance measurements are obtained by positioning at least ten electrode elements on or in the subject's body and applying multiple electrical signals to the electrode elements.

[0015] Some examples of the second method further include treating a tumor in the target region by applying an alternating voltage between the multiple electrode elements to induce an electric field in the target region.

[0016] Some examples of the second method further include obtaining a baseline MRI of the target region at a baseline time prior to the first time window, calculating a baseline impedance or conductance in each of at least 27 voxels corresponding to the target region based on baseline impedance or conductance measurements obtained within 30 days of the baseline time, and registering the baseline impedance or conductance of the voxels to the baseline MRI. A plan for treating the target region with the alternating electric field is further based on a comparison between the first impedance or conductance and the baseline impedance or conductance.

[0017] Another aspect of the present application is directed to a third method of adaptively treating a cancer patient by administering an alternating electric field to a target region within the patient's body combined with an in situ measurement of cancer progression or regression or redistribution within the target region. The third method includes the steps of positioning a first set of N electrode elements on or within the patient's body on a first side of the target region, where N is at least 4, and positioning a second set of M electrode elements on or within the patient's body on a second side of the target region, where M is at least 4, the second side being opposite the first side. The third method also includes the steps of sequentially applying a plurality of electrical signals to the electrode elements in the first set and the electrode elements in the second set during a first period of time, and determining a first impedance or conductance in each of at least 27 voxels corresponding to the target region based on the applied electrical signals. The third method also includes determining a first target location of at least one first target selected from the following cancer targets: tumor or residual tumor, cancer cell cluster, cancer cell, or border area of ​​cancer cells and healthy tissue. The third method also includes delivering an AC electric field treatment to the first target at the first target location within the patient's body, and monitoring changes in electrical impedance or conductance of voxels over a second time period using electrical impedance or conductance measurements, at least a portion of the second time period including time during which the patient is receiving the AC electric field treatment. The third method also includes administering an AC electric field to at least one second target within the target area using altered electric field strength or altered positioning, or both, for at least one set of electrode elements in response to the observed changes in electrical impedance or conductance of the voxels, and optionally repeating one or more of the steps one or more times.

[0018] Some examples of the third method further include positioning a third set of X electrode elements on or within the patient's body on a third side of the target region, where X is at least 4, positioning a fourth set of Y electrode elements on or within the patient's body on a fourth side of the target region, where Y is at least 4, the fourth side being opposite the third side, and sequentially applying a plurality of electrical signals to the electrode elements in the third set and the electrode elements in the fourth set during a first period of time. Determining a first impedance or conductance in each of the at least 27 voxels is also based on the plurality of electrical signals applied to the electrode elements in the third set and the electrode elements in the fourth set.

[0019] In some examples of the third method, the step of delivering alternating current electric field therapy to a first target at a first target location within the patient's body includes the steps of: (a) applying an alternating current voltage between a majority of the electrode elements in the first set and a majority of the electrode elements in the second set to induce an electric field in the target area; and (b) applying an alternating current voltage between a majority of the electrode elements in the third set and a majority of the electrode elements in the fourth set to induce an electric field in the target area.

[0020] In some examples of the third method, N is at least 9, M is at least 9, X is at least 9, and Y is at least 9.

[0021] Some examples of the third method further include generating a baseline tomographic image of the target region based on the first impedance or conductance at each voxel corresponding to the target region before determining a first target position of the at least one first target and before delivering an alternating electric field treatment to the first target. Optionally, these examples may further include (a) obtaining a baseline MRI of the target region and (b) registering the first impedance or conductance at each voxel to the baseline MRI or registering the baseline tomographic image of the target region based on the first impedance or conductance at each voxel to the baseline MRI before determining a first target position of the at least one first target and before delivering an alternating electric field treatment to the first target, where determining the first target position of the at least one first target is also based on the baseline MRI.

[0022] In some examples of the third method, monitoring the change in electrical impedance or conductance of the voxel over a second period of time is used to assess progression or regression of cancer occurring at the first target location or growth of new cancer away from the first target location. In some examples of the third method, monitoring the change in electrical impedance or conductance of the voxel over a second period of time includes measuring the electrical impedance or conductance of the voxel simultaneously with administering an alternating electric field to the target region.

[0023] Some examples of the third method include an iterative process of performing one or more steps of the method over a third time period to identify one or more additional cancer targets at one or more new locations of cancer growth away from the first target location, and administering an alternating electric field to at least one of the additional cancer targets.

[0024] Some examples of the third method further include an iterative process of performing one or more steps of the method over a fourth time period to predict a new location of cancer growth away from the first target location and administering the alternating electric field to the new location.

[0025] Another aspect of the present application is directed to a fourth method of planning treatment of a target region in a subject's body using an alternating electric field. The fourth method includes positioning a first set of at least four electrode elements on or within the subject's body on a first side of the target region, and positioning a second set of four electrode elements on or within the subject's body on a second side of the target region, the second side being opposite the first side. The fourth method also includes applying a plurality of first electrical signals to the electrode elements in the first set and the electrode elements in the second set during a first time window, and determining a plurality of first electrical characteristics of the target region while the plurality of first electrical signals are being applied. The fourth method also includes generating a first tomographic image of the target region based on the determined plurality of first electrical characteristics, and generating a plan based on the first tomographic image to treat the target region with an alternating electric field.

[0026] Some examples of the fourth method further include, after the step of generating the plan, applying an alternating voltage between a majority of the electrode elements in the first set and a majority of the electrode elements in the second set to induce an electric field in the target area.

[0027] In some examples of the fourth method, the planning includes generating a recommendation for moving at least one set of electrode elements to different locations on the subject's body prior to initiation of treatment.

[0028] In some examples of the fourth method, the plan includes selecting a plurality of first electrode elements from a first set and selecting a plurality of second electrode elements from a second set. Optionally, these examples may further include, after generating the plan, applying an alternating voltage between the plurality of first electrode elements and the plurality of second electrode elements to induce an electric field in the target region.

[0029] Some examples of the fourth method further include, prior to the step of generating a plan, (a) obtaining an MRI and (b) registering the first tomographic image to the MRI, where the plan is also based on the MRI.

[0030] In some examples of the fourth method, each set of electrode elements includes at least nine electrode elements and the first tomographic image includes at least 64 voxels.

[0031] Some examples of the fourth method further include obtaining a baseline MRI of the target region at a baseline time prior to the first time window, generating a baseline tomographic image of the target region based on baseline impedance or conductance measurements obtained within 30 days of the baseline time, and registering the baseline tomographic image to the baseline MRI. The plan to treat the target region with the alternating electric field is further based on a comparison between the first tomographic image and the baseline tomographic image.

[0032] Some examples of the fourth method further include positioning a third set of at least four electrode elements on or within the subject's body on a third side of the target area, positioning a fourth set of at least four electrode elements on or within the subject's body on a fourth side of the target area, the fourth side being opposite the third side, applying a plurality of second electrical signals to the electrode elements in the third set and the electrode elements in the fourth set, and determining a plurality of second electrical characteristics of the target area while the plurality of second electrical signals are being applied. The first tomographic image of the target area is also based on the determined plurality of second electrical characteristics.

[0033] Some examples of the fourth method further include the steps of positioning a third set of at least four electrode elements on or within the subject's body on a third side of the target area, positioning a fourth set of at least four electrode elements on or within the subject's body on a fourth side of the target area, the fourth side being opposite the third side, applying a plurality of second electrical signals to the electrode elements in the third set and the electrode elements in the fourth set, and determining a plurality of second electrical characteristics of the target area while the plurality of second electrical signals are being applied. The first tomographic image of the target area is also based on the determined plurality of second electrical characteristics. These examples further include, after the step of generating the plan, (a) applying an alternating voltage between a majority of the electrode elements in the first set and a majority of the electrode elements in the second set to induce an electric field in the target area, and (b) applying an alternating voltage between a majority of the electrode elements in the third set and a majority of the electrode elements in the fourth set to induce an electric field in the target area. Optionally, in these examples, each of the sets of electrode elements includes at least 9 electrode elements and the first tomographic image includes at least 64 voxels.

[0034] Another aspect of the present application is directed to a first apparatus for generating an output identifying a location for one or more electrode arrays to apply an alternating electric field to a target region using a first set of at least four electrode elements positioned on or within the subject's body on a first side of a target region within the subject's body and a second set of at least four electrode elements positioned on or within the subject's body on a second side of the target region opposite the first side, the first apparatus comprising a processor programmed to sequentially measure a respective first impedance or conductance between each of the electrode elements in the first set and each of the electrode elements in the second set during a first time window, calculate a first impedance or conductance in each of at least 27 voxels corresponding to the target region based on the first impedance or conductance measurements, and generate a first output identifying a location for the electrode array based on the first impedance or conductance of the voxel for applying the alternating electric field to a first target within the target region.

[0035] In some embodiments of the first device, the processor is further programmed to input a baseline MRI of the target region at a baseline time prior to the first time window, calculate a baseline impedance or conductance in each of at least 27 voxels corresponding to the target region based on baseline impedance or conductance measurements obtained within 30 days of the baseline time, and register the baseline impedance or conductance of the voxels to the baseline MRI. The first output, identifying a location for the electrode array to apply the alternating electric field to the first target in the target region, is further based on a comparison between the first impedance or conductance and the baseline impedance or conductance.

[0036] In some embodiments of the first device, the processor is further programmed to: continuously measure, during the first time window, a respective first impedance or conductance between each of the electrode elements in the third set and each of the electrode elements in the fourth set using a third set of at least four electrode elements positioned on or within the subject's body on a third side of the target area and a fourth set of at least four electrode elements positioned on or within the subject's body on a fourth side of the target area opposite the third side; and calculate a first impedance or conductance in each of the at least 27 voxels also based on the measured impedance or conductance between the electrode elements in the third set and the electrode elements in the fourth set.

[0037] Optionally, in the embodiment of the previous paragraph, the processor may be further programmed to: continuously re-measure, during the second time window, at least a portion of the second time window that includes a time during which the alternating electric field is applied to the target region, and each second impedance or conductance between each of the electrode elements in the first set and each of the electrode elements in the second set, and between each of the electrode elements in the third set and each of the electrode elements in the fourth set based on the impedance or conductance measurements; re-calculate a second impedance or conductance in each of at least 27 voxels corresponding to the target region, calculate a difference between the second impedance or conductance and the first impedance or conductance in each of the at least 27 voxels corresponding to the target region; and generate a second output that identifies a modified position for one or more of the electrode arrays based on the difference between the second impedance or conductance and the first impedance or conductance in each of the at least 27 voxels corresponding to the target region for applying the alternating electric field to a new target within the target region.

[0038] Another aspect of the present application is directed to a second device for generating an output identifying a location for one or more electrode arrays to apply an alternating electric field to a target region using a first set of at least four electrode elements positioned on or within the subject's body on a first side of a target region within the subject's body and a second set of at least four electrode elements positioned on or within the subject's body on a second side of the target region, the second side being opposite the first side. The second device includes a processor programmed to: apply a plurality of first electrical signals to the electrode elements in the first set and the electrode elements in the second set during a first time window, determine a plurality of first electrical characteristics of the target region while the plurality of first electrical signals are being applied, generate a first tomographic image of the target region based on the determined plurality of first electrical characteristics, and generate an output identifying a location for the electrode array based on the first tomographic image for applying the alternating electric field to the target region.

[0039] In some embodiments of the second device, the processor is further programmed to input a baseline MRI of the target region at a baseline time prior to the first time window, generate a baseline tomographic image of the target region based on baseline impedance or conductance measurements obtained within 30 days of the baseline time, and register the baseline tomographic image to the baseline MRI. The output identifying a location for the electrode array to apply the alternating electric field to the target region is further based on a comparison between the first tomographic image and the baseline tomographic image. [Brief description of the drawings]

[0040] [Figure 1A] FIG. 1 illustrates a transducer array used to apply TTFields to a target region within a subject's body. [Figure 1B] FIG. 1 illustrates a transducer array used to apply TTFields to a target region within a subject's body. [Figure 1C]FIG. 1 illustrates a transducer array used to apply TTFields to a target region within a subject's body. [Figure 1D] FIG. 1 illustrates a transducer array used to apply TTFields to a target region within a subject's body. [Diagram 2] 2A-2C illustrate one approach for implementing each of the transducer arrays shown in FIG. 1. [Diagram 3] FIG. 1 is a block diagram of a system that uses four transducer arrays to apply TTFields to a subject's body. [Figure 4A] FIG. 4 illustrates the situation where TTFields are applied between the left and right transducer arrays shown in FIG. 3. [Figure 4B] FIG. 4 illustrates a situation where TTFields are applied between the front and rear transducer arrays shown in FIG. [Figure 5A] 1 is a schematic diagram of impedance measurements being made between individual elements of a right transducer array and an individual element of a left transducer array. [Figure 5B] 1 is a schematic diagram of impedance measurements being made between individual elements of the front and rear transducer arrays; [Figure 5C] 1 is a schematic diagram of impedance measurements being made between individual elements of the left transducer array and individual elements of the front transducer array. [Figure 5D] 1 is a schematic diagram of impedance measurements being made between individual elements of the right transducer array and individual elements of the rear transducer array. [Figure 6] FIG. 1 illustrates a method of using a set of electrodes positioned on a subject's body to generate a plan for treating a target region within the subject's body using TTFields. [Figure 7]FIG. 1 illustrates a method of using both an MRI and a set of electrodes positioned on a subject's body to generate a plan for treating a target region within the subject's body using TTFields. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0041] Various embodiments are described in detail below with reference to the accompanying drawings, in which like reference numerals refer to like elements.

[0042] The embodiments described herein rely on actual measurements of electrical characteristics (e.g., impedance) obtained from actual subjects being treated (or to be treated) with TTFields. This approach can provide a significant improvement over the prior art approaches described above that use conductivity values ​​obtained from the scientific literature.

[0043] 1A-1D show four transducer arrays 50A / 50P / 50L / 50R (where A, P, L and R mean anterior, posterior, left and right, respectively) placed on a subject's skin in close proximity to a tumor (e.g., on the head of a person with glioblastoma). The transducer arrays 50 are arranged in two pairs, with each transducer array connected to an AC signal generator via a multi-wire cable.

[0044] Figure 2 illustrates one approach for implementing each of the arrays 50A, 50P, 50L, and 50R shown in Figures 1A-1D. Unlike prior art configurations (where all of the electrode elements in any given transducer array are wired in parallel), this embodiment of Figure 2 provides individual conductors for each of the electrode elements 52 in each of the transducer arrays 50, which individual conductors terminate at connectors 57. This allows current to be independently turned on and off for any given individual electrode element 52 in any one of the arrays 50. Although Figure 2 illustrates nine electrode elements 52 in any given transducer array 50, the number of electrode elements may vary (e.g., between four and fifty).

[0045] Each transducer array 50 includes at least four electrode elements 52, labeled E1-E9 in the example of FIG. 2. In some embodiments, each of these electrode elements 52 is implemented using a conductive substrate (e.g., a round metal substrate) with a dielectric layer disposed thereon. In some preferred embodiments, each of these electrode elements 52 is a disk-shaped capacitively coupled electrode element (e.g., having a diameter of 2 cm) similar to the prior art electrode elements used in the Optune® system, with the dielectric layer comprising a thin layer of a ceramic material having a very high dielectric constant (e.g., >200). In other preferred embodiments, each of the electrode elements is implemented using conductive pads on a flex circuit, with the dielectric layer comprising a thin layer of a polymer having a high dielectric constant (e.g., >10). In some preferred embodiments, the electrical connection to each of the electrode elements 52 comprises one or more traces on the flex circuit and / or one or more conductive wires.

[0046] In some preferred embodiments, each electrode element 52 is sandwiched between a layer of conductive medical gel (on the side facing the subject) and a support structure 59. The support structure 59 holds the entire array 50 in place on the subject (e.g., using an adhesive) against the subject's body, so that the dielectric layer of the electrode elements 52 can be positioned facing and in contact with the subject's body. Optionally, this support structure 59 may include a flexible backing (e.g., a layer of foam material). A layer of hydrogel is preferably disposed between the dielectric layer of the electrode elements 52 and the subject's body when the transducer array 50 is placed against the subject's body. Construction of the support structure 59 may be performed using any of a variety of conventional approaches that will be apparent to those skilled in the art, including, but not limited to, self-adhesive fabrics, foams, or plastic sheathes.

[0047] The connector 57 has at least four pins. In the illustrated embodiment, the number of pins is the same as the number of electrode elements 52, with each first pin corresponding to each of these electrode elements 52. It should be noted that as used herein, the term "pin" can refer to either male or female pins of the connector 57. Each transducer array 50 also has a number of conductors, with the number of these first conductors depending on the number of electrode elements 52. Each of these conductors provides a conductive path between the conductive substrate of one of the electrode elements 52 and a respective one of the pins in the connector 57. Each of these conductors may be implemented using, for example, multiple segments of wire and / or multiple traces on a flex circuit.

[0048] Because the connector 57 has individual pins corresponding to each individual electrode element 52, a system that mates with the connector 57 can selectively excite or not excite each of the electrode elements 52 individually by either applying or not applying a signal to the respective pin on the connector 57.

[0049] 3 is a block diagram of a system that uses four copies of transducer array 50 (described above in connection with FIG. 2) to apply TTFields to a subject. These four copies 50A / 50P / 50L / 50R are positioned on the subject's body (e.g., placed on the subject's skin) in front, behind, left and right of the tumor, respectively.

[0050] The system includes an AC voltage generator 21 which generates an AC power source between its two output terminals. One phase of the AC voltage generator's output is provided to a bank of switches 25A and 25R, and the other phase of the AC voltage generator's output is provided to a bank of switches 25P and 25L. In the illustrated embodiment, each bank of switches includes nine individual switches, each corresponding to a respective element on one of the transducer arrays 50A / 50P / 50L / 50R. The number of switches in each bank corresponds to the number of electrode elements in each array. Thus, for example, in an embodiment having four electrode elements in each array, each bank includes four switches.

[0051] The switches in banks 25R and 25A are arranged to pass or block a first phase of the AC voltage generator output to corresponding elements on transducer arrays 50R and 50A depending on the state of each individual switch. The switches in banks 25P and 25L are arranged to pass or block the other phase of the AC voltage generator output to corresponding elements on transducer arrays 50P and 50L depending on the state of each individual switch.

[0052] Controller 30 controls the state of each switch within each of banks 25A / 25P / 25L / 25R by issuing appropriate control signals to the bank of switches. For example, controller 30 may output 36 control bits, one bit for each switch, such that if the control bit for any given switch is 1, the switch is closed and if the control bit for any given switch is 0, the switch is open.

[0053] In this arrangement, when the controller 30 issues a control signal to close all nine switches in bank 25R and all nine switches in bank 25L, one phase of the output of the AC voltage generator 21 is routed to all of the electrode elements R1-R9 in the first transducer array 50R, and the other phase of the output of the AC voltage generator is routed to all of the electrode elements L1-L9 in the second transducer array 50L. As the arrays 50L and 50R are positioned on the subject's skin to the left and right of the tumor, respectively, the AC voltages on these transducer arrays 50L and 50R induce an electric field through the subject's body, whose field lines generally run from right to left and left to right, as shown diagrammatically in FIG. 4A by dashed lines. Note that in reality, the electric field lines are not straight lines. However, straight dashed lines are nevertheless used in FIGS. 4A-5D to show the general direction of the field lines.

[0054] Similarly, if controller 30 issues a control signal to close all nine switches in bank 25A and all nine switches in bank 25P, then one phase of the output of AC voltage generator 21 is routed to all of the electrode elements A1-A9 in the third transducer array 50A and the other phase of the AC voltage generator output is routed to all of the electrode elements P1-P9 in the fourth transducer array 50P. As arrays 50A and 50P are positioned on the subject's skin anteriorly and posteriorly relative to the tumor, respectively, the AC voltages on these transducer arrays 50A and 50P induce electric fields through the subject's body whose field lines generally run from anterior to posterior and posterior to front, as shown diagrammatically by dashed lines in FIG.

[0055] By periodically (e.g., every second) switching back and forth between the two states described in the previous paragraph (i.e., one state with all switches in banks 25R and 25L closed, and another state with all switches in banks 25A and 25P closed), the controller causes the system to induce an electric field through the tumor that switches direction every second. The electric field resulting from this control sequence is equivalent to the electric field induced in a subject's body using a prior art Optune® system (in which all of the electrode elements in any given transducer array are wired together in parallel) and therefore can be used to treat tumors in a target volume.

[0056] Notably, in addition to replicating the sequence of electric fields provided by the prior art Optune® system, the embodiment of FIG. 3 provides an important additional capability, since the very same hardware that induces TTFields in the subject's body (as described above) can also be used to perform impedance tomography of the portion of the subject's body that is between transducer arrays 50A / 50P / 50L / 50R. In alternative embodiments, separate sets of electrode elements are used to perform TTFields and to perform impedance tomography. When separate sets of electrode elements are used for these two functions, these separate sets of electrode elements are compatible with each other in some embodiments. Optionally, the set of electrode elements used to perform impedance tomography measurements may be integrated into a tight-fitting cap, vest, or other garment.

[0057] More specifically, if the controller 30 closes a single selected switch from bank 25R and also closes a single selected switch from bank 25L, the output of the AC voltage generator 21 is applied between a single electrode element 52 from the first array 50R and a single electrode element 52 from the second array 50L. By measuring the voltage and current of the AC voltage generator 21, the impedance of the path including the two selected electrode elements can be determined. Referring now to FIG. 5A, if the controller 30 closes switch #1 of the first bank 50R and also closes switch #1 in the second bank 50L and measures the voltage and current of the AC voltage generator 21, the impedance of the path including elements R1 and L1 (shown diagrammatically by the dashed line between these two elements) can be determined. Similarly, if the controller 30 closes switch #1 in the first bank 50R and also closes switch #2 in the second bank 50L and measures the voltage and current of the AC voltage generator 21, the impedance of the path including these elements R1 and L2 (schematically shown by the dashed line between these two elements) can be determined. Note that FIG. 5A only shows four paths (using dashed lines) for simplicity. However, if the left and right arrays each include nine elements, there are a total of 9×9=81 paths / combinations. The controller 30 preferably successively closes a single switch in the first bank 50R and a single switch in the second bank 50L corresponding to each of these 81 combinations, measures the voltage and current of the AC voltage generator 21 for each combination, and determines the impedance of the circuit including each of these 81 paths based on the voltage and current measurements.

[0058] Similarly, referring now to FIG. 5B, if the controller 30 closes switch #1 in the third bank 50A and also closes switch #1 in the fourth bank 50P and measures the voltage and current of the AC voltage generator 21, it can determine the impedance of the path including elements A1 and P1 (shown diagrammatically by the dashed line between these two elements). Although only four paths are shown (using dashed lines), the front and rear arrays each include nine elements, so there are a total of 9×9=81 paths / combinations. The controller 30 preferably successively closes a single switch in the third bank 50A and a single switch in the fourth bank 50P corresponding to each of these 81 combinations, and determines the impedance of the circuit including each of these 81 paths, as described above in connection with FIG. 5A.

[0059] These 81+81=162 measurements are then fed into a conventional backpropagation algorithm to determine the impedance at each voxel in the set of voxels positioned in the subject's body between transducer arrays 50A / 50P / 50L / 50R. (If the number of electrode elements in each array is greater than nine, the number of measurements will be greater; if the number of electrode elements in each array is less than nine, the number of measurements will be smaller.) Notably, the resolution of these voxels need not be high, and relatively large voxels (e.g., approximately 1 cm) can be used for the purposes described herein. 3 voxels) is appropriate. In one example, a volume measuring 3 cm x 3 cm x 3 cm can be divided into a 3 x 3 x 3 array of voxels, meaning there are 27 voxels. Similarly, a volume measuring 4 cm x 4 cm x 4 cm can be divided into a 4 x 4 x 4 array of voxels, meaning there are 64 voxels.

[0060] Optionally, additional impedance measurements of the volume between the transducer arrays may be obtained and used to refine the calculation of the impedance at each voxel in the target volume. More specifically, referring now to FIG. 5C, if the controller 30 closes switch #1 in the second bank 50L and also closes switch #1 in the third bank 50A and measures the voltage and current of the AC voltage generator 21, the impedance of the path including elements L1 and A1 (shown diagrammatically by dashed lines between these two elements) can be determined. Although only four paths are shown (using dashed lines), there are a total of 9×9=81 paths / combinations. Thus, the controller 30 can successively close a single switch in the second bank 50L and a single switch in the third bank 50A corresponding to each of these 81 combinations and determine the impedance of the circuit including each of these 81 paths as described above. Similarly, referring now to FIG. 5D, if the controller 30 closes switch #1 in the first bank 50R and also closes switch #1 in the fourth bank 50P and measures the voltage and current of the AC voltage generator 21, the impedance of the path including elements A1 and R1 (shown diagrammatically by a dashed line between these two elements) can be determined. Although only four paths are shown (using dashed lines), there are a total of 9×9=81 paths / combinations. Thus, the controller 30 can successively close a single switch in the first bank 50R and a single switch in the fourth bank 50P that correspond to each of these 81 combinations and determine the impedance of the circuit including each of these 81 paths, as described above in connection with FIG. 5A.

[0061] When the optional additional impedance measurements described in the previous paragraph are obtained, these impedance measurements are fed into a back-propagation algorithm that determines the impedance at each voxel in the target volume to improve the accuracy of the obtained impedance tomography image.

[0062] If the impedance of each voxel in the region between the transducer arrays is known, these impedances are used to create a model of the body part (e.g., the head). The electric field strength (or power density) to be delivered to the tumor can then be calculated by applying model voltages to model electrodes positioned on the model of the body part and calculating what the electric field strength (or power density) will be in the tumor when a given AC voltage is applied to the model electrodes. This information can be used to generate a plan for treating the target region with TTFields.

[0063] In particular, unlike the prior art described in the background section, when the impedance at each voxel is generated using impedance tomography as described above, the results do not depend on assumptions about the electrical characteristics (e.g., conductivity) of the tissue between the electrodes. More specifically, because this technique uses impedance values ​​for each voxel obtained by performing measurements on the particular subject about to be treated using TTFields, this technique can provide improved accuracy over the prior art. Moreover, the techniques described herein with actual impedance measurements advantageously eliminate tedious and computationally intensive infinite element simulations.

[0064]

[0031] Figure 6 illustrates a method of using sets of electrodes positioned on a subject's body to generate a plan for treating a target region within the subject's body using TTFields. Looking at Figure 6 in conjunction with Figure 3, in step S20, N electrode elements of a first set 50R are positioned on the subject's body on a first side (e.g., right side) of the target region, and M electrode elements of a second set 50L are positioned on the subject's body on a second side (e.g., left side) of the target region that is opposite the first side. Both N and M are at least 4, and in the illustrated embodiment, N=9 and M=9.

[0065] In step S30, the system sequentially measures the respective impedances between each of the N electrode elements in the first set 50R and each of the M electrode elements in the second set 50L during a first time window. This may be accomplished, for example, by sequentially closing combinations of switches in the first bank 25R and the second bank 25L (as described above), such that an AC voltage is sequentially applied between combinations of electrode elements R1-R9 and L1-L9. While an AC voltage is applied to each pair, current and voltage are measured, and impedance is calculated from these measurements. The first time window should be long enough to obtain all necessary impedance measurements, and is typically less than 30 minutes (e.g., less than 1 minute).

[0066] Next, in step S40, the impedance at each of the voxels (e.g., at least 27 voxels or at least 64 voxels corresponding to the target region) in the impedance tomography image is calculated (e.g., using a back-propagation algorithm as described above). In step S60, a plan for treating the target region with TTFields is generated based on the calculated impedance of the voxels. The plan can include, for example, recommendations of where to position electrode elements (used to apply TTFields) on the subject's body.

[0067] Although it is possible to implement a system that only positions electrode elements on the first and second sides of the target area, improved results are obtained in embodiments that use an optional additional set of electrodes positioned on the subject's body. More specifically, as described in connection with FIG. 3, X electrode elements of a third set 50A are positioned on the subject's body on a third side (e.g., anterior) of the target area, and Y electrode elements of a fourth set 50P are positioned on the subject's body on a fourth side (e.g., posterior) of the target area that is opposite the third side. X and Y are both at least 4, and in the illustrated embodiment, X=9 and Y=9. The system continuously measures the respective impedances between each of the X electrode elements in the third set 50A and each of the Y electrode elements in the fourth set 50P during the first time window. The calculation of the impedance at each voxel in step S40 is also based on the measured impedances between the electrode elements in the third set and the electrode elements in the fourth set (in addition to the measured impedances between the electrode elements in the first set and the electrode elements in the second set).

[0068] Optionally, after a plan for treating the target area with an AC electric field has been generated, in step S70 an AC voltage is applied between a majority (e.g., all) of the electrode elements R1-R9 in the first set 50R and a majority (e.g., all) of the electrode elements L1-L9 in the second set 50L to induce an electric field in one direction in the target area, and an AC voltage is applied between a majority (e.g., all) of the electrode elements A1-A9 in the third set 50A and a majority (e.g., all) of the electrode elements P1-P9 in the fourth set 50P to induce an electric field in another direction in the target area.

[0069] A plan for treating a target area with an alternating electric field may include generating recommendations for moving at least one set of 50A / 50P / 50L / 50R electrode elements to different locations on the subject's body.

[0070] FIG. 7 illustrates a method of using both an MRI and a set of electrodes positioned on a subject's body to generate a plan for treating a target region in the subject's body using TTFields. First, in step S110, an MRI is obtained. Then, in steps S120-S140, an impedance tomography image is obtained as described above in connection with S20-S40 of FIG. 6. The impedance tomography image should be obtained within 30 days of the MRI, and more preferably within 7 days or within 1 day of the MRI, to facilitate registration of the two images. In step S150, the impedance tomography voxels are registered to the MRI (e.g., using conventional image registration algorithms) and the registration is stored in memory. In this embodiment, a plan for treating the target region using TTFields may be generated in step S160 based on both the MRI and the impedance tomography images. The plan may include, for example, recommendations of where to position electrode elements (used to apply TTFields) on the subject's body. Finally, treatment of the target region using TTFields occurs in step S170. The MRI obtained in step S110 and the impedance voxels obtained in step S140 serve as a baseline for future comparisons.

[0071] After the registration that occurs in step S150, changes in the tumor can be tracked using only the impedance tomography images (e.g., obtained by repeating steps S20-S40 of FIG. 6), because if the tumor grows or shrinks, the impedance of a voxel in the impedance tomography image will change. Thus, in some embodiments, the plan for treating the target region with an alternating electric field considers a comparison between the recent impedance and the baseline impedance. For example, tumors can be detected by impedance tomography, since tumors typically have a different impedance than the surrounding tissue, and changes in tumor size can be tracked by the impedance changes in the region of the tumor. For example, an increase in the impedance of a voxel around a tumor previously identified in the baseline MRI may indicate that the portion of the tumor in that voxel has grown if the tumor impedance is higher than the surrounding tissue.

[0072] Based on any detected growth, shrinkage, or movement of the tumor, it may be desirable to reposition the electrode elements (used to apply the TTFields) to a position that provides increased electric field strength at the new location of the tumor. Determining the new position for the electrode elements may be performed using conventional software for that purpose (e.g., Novotal™). By comparing the impedance tomography images with previous impedance tomography images, the need for repeat MRIs may be reduced, or the time interval between repeat MRIs may at least be extended.

[0073] Optionally, new impedance tomography images may be generated at periodic intervals (e.g., by repeating steps S20-S40 of FIG. 6, e.g., once a day) or each time a new set of transducer arrays is positioned on the subject's body, and each new impedance tomography image is compared to one or more previous impedance tomography images (optionally to a baseline MRI previously registered to the original impedance tomography images). Optionally, the conditions under which all of the impedance tomography images are obtained may be standardized to the extent possible (e.g., using a new transducer array positioned on freshly shaved skin, standardizing the temperature and humidity at the time the impedance tomography images are captured, and / or standardizing the subject's resting heart rate).

[0074] Optionally, when a new transducer array is first positioned on the subject's body, an impedance tomography image is captured and the impedance tomography image is compared to the previous impedance tomography image. This comparison can determine whether the new transducer array is positioned at the same location on the subject's skin, or whether the new transducer array is positioned at an offset location. In the latter situation, the system can output instructions asking the subject (or practitioner) to move one of the new transducer arrays to a new location (e.g., move the right transducer array up 1 cm).

[0075] It should be noted that although the above embodiments describe obtaining impedance measurements, a similar result can be arrived at by replacing the impedance measurements with conductance measurements. The nature of the change required to switch from impedance to conductance will be apparent to one skilled in the art.

[0076] Also, while the above embodiments describe obtaining impedance measurements using a transducer array positioned on the subject's body, it should be noted that impedance measurements can also be obtained using a transducer array positioned within the subject's body (e.g., by implanting a transducer array under the subject's skin).

[0077] Referring now only to FIG. 3, a temperature sensor (e.g., a thermistor (not shown)) may optionally be incorporated into the array 50 to measure the temperature of the electrode elements, and hardware for sensing the temperature at each electrode element may be incorporated into the system.

[0078] Unless otherwise indicated herein or clearly contradicted by content, embodiments illustrated under any heading or in any part of the disclosure may be combined with embodiments illustrated under the same or any other heading or in any other part of the disclosure.

[0079] Although the present invention has been disclosed with reference to specific embodiments, many changes, modifications, and variations to the described embodiments are possible without departing from the sphere and scope of the invention, as defined in the appended claims. Accordingly, the present invention is not intended to be limited to the described embodiments, but rather to have the full scope defined by the language of the following claims, and equivalents thereof. [Explanation of symbols]

[0080] 21 AC Generator 30 Controller 50 Transducer Array 52 Electrode element 57 Connector 59 Support structure

Claims

1. 1. An apparatus for planning treatment of a target area within a subject's body using an alternating electric field, comprising: a first set of N electrode elements positioned on or within the subject's body on a first side of the target area, where N is at least 4; a second set of M electrode elements positioned on or within the subject's body on a second side of the target area, where M is at least 4, and the second side is opposite the first side; and 1. A processor comprising: sequentially measuring, during a first time window, a respective impedance or conductance between each of the N electrode elements in the first set and each of the M electrode elements in the second set; calculating a first impedance or conductance in each of at least 27 voxels corresponding to the target region based on the impedance or conductance measurements; generating a plan for treating the target area with an alternating electric field based on the first impedance or conductance of the voxels; A processor programmed to execute 13. An apparatus comprising:

2. a third set of X electrode elements positioned on or within the subject's body on a third side of the target area, where X is at least 4; a fourth set of Y electrode elements positioned on or within the subject's body on a fourth side of the target area, where Y is at least four and the fourth side is opposite the third side; a processor programmed to perform the steps of: continuously measuring, during the first time window, a respective impedance or conductance between each of the X electrode elements in the third set and each of the Y electrode elements in the fourth set; Further comprising:

2. The apparatus of claim 1, wherein the calculation of the first impedance or conductance at each of the at least 27 voxels is also based on the measured impedance or conductance between the electrode elements in the third set and the electrode elements in the fourth set.

3. 3. The apparatus of claim 2, further comprising, after the step of generating the plan, the steps of: (a) applying an alternating voltage between a majority of the electrode elements in the first set and a majority of the electrode elements in the second set to induce an electric field in the target area; and (b) applying an alternating voltage between a majority of the electrode elements in the third set and a majority of the electrode elements in the fourth set to induce an electric field in the target area.

4. The apparatus of claim 2 , wherein the planning includes generating recommendations for moving at least one set of electrode elements to different locations on or within the subject's body.

5. 5. The apparatus of claim 4, further comprising, prior to said step of generating said plan, the steps of: (a) obtaining an MRI; and (b) registering said voxels to said MRI, and wherein said recommendation to move at least one set of electrode elements to a different position is also based on said MRI.

6. 3. The apparatus of claim 2, wherein N is at least 9, M is at least 9, X is at least 9, and Y is at least 9.

7. The processor, obtaining a baseline MRI of the target region at a baseline time prior to the first time window; calculating a baseline impedance or conductance in each of at least 27 voxels corresponding to the target region based on baseline impedance or conductance measurements obtained within 30 days of the baseline time; registering the baseline impedance or conductance of the voxels to the baseline MRI; and further programmed to execute 10. The apparatus of claim 1, wherein the plan for treating the target area with an alternating electric field is further based on a comparison between the first impedance or conductance and the baseline impedance or conductance.

8. 1. An apparatus for planning treatment of a target area within a subject's body using an alternating electric field, comprising: a first set of N electrode elements positioned on or within the subject's body on a first side of the target area, where N is at least 4; a second set of M electrode elements positioned on or within the subject's body on a second side of the target area, where M is at least 4, and the second side is opposite the first side; and 1. A processor comprising: determining a first impedance or conductance in each of at least 27 voxels corresponding to the target region based on a plurality of impedance or conductance measurements obtained during a first time window; generating a plan for treating the target area with an alternating electric field based on the first impedance or conductance of the voxels; A processor programmed to execute 13. An apparatus comprising:

9. 9. The apparatus of claim 8, wherein the plurality of impedance or conductance measurements are obtained by positioning at least ten electrode elements on or within the subject's body and applying a plurality of electrical signals to the electrode elements.

10. 10. The apparatus of claim 8, further comprising the step of treating a tumor in the target region by applying an alternating voltage between a plurality of the electrode elements to induce an electric field in the target region.

11. obtaining a baseline MRI of the target region at a baseline time prior to the first time window; calculating a baseline impedance or conductance in each of at least 27 voxels corresponding to the target region based on baseline impedance or conductance measurements obtained within 30 days of the baseline time; registering the baseline impedance or conductance of the voxel to the baseline MRI; 10. The apparatus of claim 8, wherein the plan for treating the target area with an alternating electric field is further based on a comparison between the first impedance or conductance and the baseline impedance or conductance.

12. 1. A method of adaptively treating a cancer patient by administering an alternating electric field to a target area within the patient's body combined with in situ measurement of cancer progression or regression or redistribution within said target area, comprising: a first set of N electrode elements positioned on or within the patient's body on a first side of the target area, where N is at least 4; a second set of M electrode elements positioned on or within the patient's body on a second side of the target area, where M is at least 4, the second side being opposite the first side; and 1. A processor comprising: applying a plurality of electrical signals sequentially to the electrode elements in the first set and to the electrode elements in the second set during a first period of time; determining a first impedance or conductance in each of at least 27 voxels corresponding to the target region based on the applied electrical signal; Cancer targets, i.e. (i) a tumor or residual tumor, (ii) a cancer cell population; (iii) cancer cells, (iv) The border region between cancer cells and healthy tissue determining a first target position of at least one first target selected from; delivering an alternating electric field therapy to the first target at the first target location within the patient's body; monitoring changes in the electrical impedance or conductance of the voxels over a second time period using electrical impedance or conductance measurements, at least a portion of the second time period including a time during which the patient is receiving alternating electric field therapy; administering an alternating electric field to at least one second target within said target region using altered electric field strength or altered positioning, or both, for at least one set of electrode elements in response to an observed change in said electrical impedance or conductance of said voxels, and optionally repeating one or more steps one or more times; A processor programmed to execute 13. An apparatus comprising:

13. a third set of X electrode elements positioned on or within the patient's body on a third side of the target area, where X is at least 4; a fourth set of Y electrode elements positioned on or within the patient's body on a fourth side of the target area, where Y is at least four and the fourth side is opposite the third side; a processor further programmed to sequentially apply a plurality of electrical signals to the electrode elements in the third set and the electrode elements in the fourth set during the first period of time; Further comprising:

13. The apparatus of claim 12, wherein the step of determining the first impedance or conductance in each of the at least 27 voxels is also based on the plurality of electrical signals applied to the electrode elements in the third set and the electrode elements in the fourth set.

14. 14. The apparatus of claim 13, wherein the step of delivering an alternating current electric field therapy to the first target at the first target location within the patient's body comprises: (a) applying an alternating current voltage between a majority of the electrode elements in the first set and a majority of the electrode elements in the second set to induce an electric field in the target area; and (b) applying an alternating current voltage between a majority of the electrode elements in the third set and a majority of the electrode elements in the fourth set to induce an electric field in the target area.

15. 14. The apparatus of claim 13, wherein N is at least 9, M is at least 9, X is at least 9, and Y is at least 9.

16. 13. The apparatus of claim 12, further comprising the steps of generating a baseline tomographic image of the target region based on the first impedance or conductance in each of the voxels corresponding to the target region prior to the step of determining a first target location of at least one first target and prior to the step of delivering an alternating electric field therapy to the first target.

17. 17. The apparatus of claim 16, further comprising the steps of: (a) obtaining a baseline MRI of the target region; and (b) registering the first impedance or conductance at each of the voxels to the baseline MRI or registering the baseline tomographic image of the target region based on the first impedance or conductance at each of the voxels to the baseline MRI prior to the step of determining a first target location of at least one first target and prior to the step of delivering an alternating electric field therapy to the first target, wherein the step of determining the first target location of the at least one first target is also based on the baseline MRI.

18. 13. The apparatus of claim 12, wherein the step of monitoring the change in the electrical impedance or conductance of the voxel over a second period of time is used to assess progression or regression of cancer occurring at the first target location or the growth of new cancer away from the first target location.

19. 13. The apparatus of claim 12, wherein monitoring the change in the electrical impedance or conductance of the voxel over a second period of time comprises measuring the electrical impedance or conductance of the voxel simultaneously with administering an alternating electric field to the target region.

20. 13. The apparatus of claim 12, further comprising an iterative process of performing one or more steps of the method performed over a third time period to identify one or more additional cancer targets at one or more new locations of cancer growth away from the first target location and administering an alternating electric field to at least one of the additional cancer targets.

21. 13. The apparatus of claim 12, further comprising an iterative process of performing one or more steps of the method over a fourth time period to predict a new location of cancer growth away from the first target location and administering an alternating electric field to the new location.

22. 1. An apparatus for planning treatment of a target area within a subject's body using an alternating electric field, comprising: a first set of at least four electrode elements disposed on or within the subject's body on a first side of the target area; a second set of four electrode elements positioned on or within the subject's body on a second side of the target area, the second side being opposite the first side; and 1. A processor comprising: applying a plurality of first electrical signals to the electrode elements in the first set and to the electrode elements in the second set during a first time window; determining a plurality of first electrical characteristics of the target area while the plurality of first electrical signals are being applied; generating a first tomographic image of the target area based on the determined plurality of first electrical characteristics; generating a plan based on the first tomographic image for treating the target area with an alternating electric field; A processor programmed to execute 13. An apparatus comprising:

23. 23. The apparatus of claim 22, further comprising, after the step of generating the plan, applying an alternating voltage between a majority of the electrode elements in the first set and a majority of the electrode elements in the second set to induce an electric field in the target area.

24. 23. The apparatus of claim 22, wherein the planning includes generating a recommendation for moving at least one set of electrode elements to a different location on the subject's body prior to initiation of the treatment.

25. 23. The apparatus of claim 22, wherein the plan comprises selecting a plurality of first electrode elements from the first set and selecting a plurality of second electrode elements from the second set.

26. 26. The apparatus of claim 25, further comprising, after the step of generating the plan, applying an alternating voltage between the first plurality of electrode elements and the second plurality of electrode elements to induce an electric field in the target area.

27. 23. The apparatus of claim 22, further comprising, prior to said step of generating said plan, the steps of: (a) obtaining an MRI; and (b) registering said first tomographic image to said MRI, said plan also being based on said MRI.

28. 23. The apparatus of claim 22, wherein each set of electrode elements includes at least nine electrode elements and the first tomographic image includes at least 64 voxels.

29. obtaining a baseline MRI of the target region at a baseline time prior to the first time window; generating a baseline tomographic image of the target area based on baseline impedance or conductance measurements obtained within 30 days of the baseline time; and registering the baseline tomographic image to the baseline MRI.

23. The apparatus of claim 22, wherein the plan for treating the target area with an alternating electric field is further based on a comparison between the first tomographic image and the baseline tomographic image.

30. a third set of at least four electrode elements positioned on or within the subject's body on a third side of the target area; a fourth set of at least four electrode elements disposed on or within the subject's body on a fourth side of the target area, the fourth side being opposite the third side; and 1. A processor comprising: applying a plurality of second electrical signals to the electrode elements in the third set and to the electrode elements in the fourth set; determining a plurality of second electrical characteristics of the target area while the plurality of second electrical signals are being applied; A processor programmed to execute Further comprising:

23. The apparatus of claim 22, wherein the first tomographic image of the target area is also based on the determined plurality of second electrical characteristics.

31. 31. The apparatus of claim 30, further comprising, after the step of generating the plan, the steps of: (a) applying an alternating voltage between a majority of the electrode elements in the first set and a majority of the electrode elements in the second set to induce an electric field in the target area; and (b) applying an alternating voltage between a majority of the electrode elements in the third set and a majority of the electrode elements in the fourth set to induce an electric field in the target area.

32. 32. The apparatus of claim 31, wherein each of the sets of electrode elements includes at least nine electrode elements and the first tomographic image includes at least 64 voxels.

33. 1. An apparatus for generating output identifying positions for one or more electrode arrays to apply an alternating electric field to a target area within a subject's body using a first set of at least four electrode elements positioned on or within the subject's body on a first side of the target area within the body and a second set of at least four electrode elements positioned on or within the subject's body on a second side of the target area opposite the first side, comprising: Successively measuring a respective first impedance or conductance between each of the electrode elements in the first set and each of the electrode elements in the second set during a first time window; calculating a first impedance or conductance in each of at least 27 voxels corresponding to the target region based on the first impedance or conductance measurements; generating a first output identifying a location for the electrode array based on the first impedance or conductance of the voxels to apply an alternating electric field to a first target within the target region; The apparatus includes a processor programmed to:

34. The processor further comprises: acquiring a baseline MRI of the target region at a baseline time prior to the first time window; calculating a baseline impedance or conductance in each of at least 27 voxels corresponding to the target region based on a baseline impedance or conductance measurement obtained within 30 days of the baseline time; registering the baseline impedance or conductance of the voxels to the baseline MRI; It is programmed to 34. The apparatus of claim 33, wherein the first output identifying a location for the electrode array to apply an alternating electric field to the first target within the target area is further based on a comparison between the first impedance or conductance and the baseline impedance or conductance.

35. The processor further comprises: during the first time window, using a third set of at least four electrode elements positioned on or within the subject's body on a third side of the target area and a fourth set of at least four electrode elements positioned on or within the subject's body on a fourth side of the target area opposite the third side, continuously measuring a respective first impedance or conductance between each of the electrode elements in the third set and each of the electrode elements in the fourth set; calculating the first impedance or conductance in each of the at least 27 voxels also based on the measured impedance or conductance between the electrode elements in the third set and the electrode elements in the fourth set.

34. The apparatus of claim 33, programmed to:

36. The processor further comprises: re-measuring continuously during a second time window, for at least a portion of the second time window that includes a time during which an alternating electric field is applied to the target area, and a second impedance or conductance between each of the electrode elements in the first set and each of the electrode elements in the second set, and between each of the electrode elements in the third set and each of the electrode elements in the fourth set, respectively; recalculating a second impedance or conductance in each of the at least 27 voxels corresponding to the target region based on the impedance or conductance measurements; calculating a difference between the second impedance or conductance and the first impedance or conductance in each of the at least 27 voxels corresponding to the target region; generating a second output that identifies a modified position for one or more of the electrode arrays based on the difference between the second impedance or conductance and the first impedance or conductance in each of the at least 27 voxels to apply an alternating electric field to a new target within the target region.

36. The apparatus of claim 35, programmed to:

37. 1. An apparatus for generating output identifying positions for one or more electrode arrays to apply an alternating electric field to a target area within a subject's body using a first set of at least four electrode elements positioned on or within the subject's body on a first side of the target area within the body and a second set of at least four electrode elements positioned on or within the subject's body on a second side of the target area opposite the first side, comprising: applying a plurality of first electrical signals to the electrode elements in the first set and to the electrode elements in the second set during a first time window; determining a plurality of first electrical characteristics of the target area while the plurality of first electrical signals are being applied; generating a first tomographic image of the target area based on the determined plurality of first electrical characteristics; generating an output identifying a location for the electrode array based on the first tomographic image to apply an alternating electric field to the target region; The apparatus includes a processor programmed to:

38. The processor further comprises: inputting a baseline MRI of the target region at a baseline time prior to the first time window; generating a baseline tomographic image of the target area based on baseline impedance or conductance measurements obtained within 30 days of the baseline time; registering the baseline tomographic image to the baseline MRI; It is programmed to 40. The apparatus of claim 37, wherein the output identifying a location for the electrode array to apply an alternating electric field to the target area is further based on a comparison between the first tomographic image and the baseline tomographic image.

Images