Method for operating an AC electric field generating device

Abstract

A method for operating a subdurally implanted AC electric field generating device is provided. [Solution] A method for operating an AC electric field generating device comprising: an electrode array including a plurality of subdural electrodes and a plurality of deep stimulation electrodes, which generates an AC electric field through the plurality of subdural electrodes and the plurality of deep stimulation electrodes; a waveform generator operable to generate and transmit a waveform representing the AC electric field to the electrode array; a processing unit operable to communicate a set of waveform parameters to the waveform generator; and a controller module operable to communicate with the electrode array, wherein the controller module operates the waveform generator to transmit the waveform to the electrode array via a plurality of conductive wires.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application is a PCT application claiming the benefit of U.S. Provisional Patent Application No. 62 / 699,146, filed July 17, 2018, which is incorporated by reference in its entirety.

[0002] FIELD OF THE DISCLOSURE The present disclosure relates generally to the treatment of carcinomas, and specifically to the treatment of brain carcinomas via electric field generation. [Background technology]

[0003] Alternating current electric field (AEF) therapy is a type of electromagnetic field therapy that uses low-intensity electric fields to treat brain cancer tumors (particularly glioblastoma). Traditional cancer treatments include chemotherapy and radiation, which are associated with treatment-related toxicity and a high rate of tumor recurrence. AEF uses alternating current electric fields to disrupt cell division within cancer cells, thereby inhibiting cell replication and initiating apoptosis (cell death). However, some topical AEF treatment methods are associated with skin inflammation and rashes, as well as the requirement for patients to maintain a shaved head and limited physical activity. Summary of the Invention

[0004] It is with these observations, among others, in mind that the various aspects of the present disclosure have been conceived and developed. [Brief explanation of the drawings]

[0005] [Figure 1] FIG. 1 shows the electrode array and controller module of the system, where the electrode array is implanted in the brain and the controller module with wires is operably connected to the electrode array. [Figure 2] FIG. 2 is an illustration of the system of FIG. 1 in relation to a patient's body. [Figure 3] FIG. 2 is an illustration showing how the electrode array arrangement of the system of FIG. 1 can surround a cancerous region of the brain. [Figure 4]FIG. 2 is a simplified block diagram showing how the controller module, external computer, and electrode array hardware of the system of FIG. 1 work together. [Figure 5] 2 is a flowchart illustrating a treatment and optimization process for a patient using the system of FIG. 1. DETAILED DESCRIPTION OF THE INVENTION

[0006] Corresponding reference characters indicate corresponding elements in the drawing figures. The headings used in the figures do not limit the scope of the claims.

[0007] The application of alternating current electric fields is a type of cancer treatment that has the potential to reduce treatment-related toxicity and is rapidly gaining research attention. In the application of alternating current electric fields, an alternating current electric field is applied to cancerous regions of the brain, thereby inhibiting cell division of rapidly dividing cancer cells. To administer alternating current electric field treatment to a patient, a system and method for an alternating current electric field generating device, referred to herein as "the present system," to generate an alternating current electric field of optimized strength at a desired location within the body to inhibit cell division and / or initiate apoptosis of cancer cells at the target treatment location is disclosed herein.

[0008] The present system provides, among other aspects, a system and method for subdural implantation, in which, through the use of subdural electrodes implanted subdurally and an array of deep stimulation electrodes implanted deep in brain tissue, a targeted alternating current electric field is generated for the treatment of rapidly dividing cancer cells. In one aspect, the array of stimulation electrodes is in operative communication with a controller module, which generates waveforms for creating the alternating current electric field and receives feedback from the array of stimulation electrodes. Referring to the drawings, an embodiment of the present system is generally shown as 100 in FIGS. 1-5.

[0009] 1 and 2, in some embodiments of the system 100, a primary array 101 including stimulation electrodes 103 and 104 is configured to be placed beneath the dura mater of a patient's brain. The primary array 101 is in operative communication with a controller module 120 via a wire array 110. The controller module 120 is operable to generate the AC electric field, receive feedback from the primary array 101, and communicate with an external computer 200 for receiving operating parameters as well as exporting operating data related to the strength of the AC electric field.

[0010] The primary array 101 may include not only a plurality of subdural electrodes 103 but also a plurality of deep stimulation electrodes 104, such that the subdural electrodes 103 and the deep stimulation electrodes 104 are operable to generate an alternating electric field applied to brain tissue. In one aspect, the alternating electric field is configured for appropriate strength and distribution to inhibit cancerous cells in contact with the alternating electric field from dividing. In some embodiments, one or more wires 102 each define a respective distal end, extend from a respective subdural electrode 103, and terminate in a conductive contact. In one possible application, each of the plurality of subdural electrodes 103 is positioned on the surface of the brain. In some embodiments, the subdural electrodes 103 can be thin enough to fit between the dura mater and the patient's brain, and in some embodiments, may be surrounded by a gel. Each subdural electrode 103 defines a proximal surface 105 and a distal surface (not shown), the proximal surface operably associated with the distal end of each wire 102, and the distal surface includes a transduction contact applied outside the brain. In some embodiments, the deep stimulation electrodes 104 have an elongated, rod-shaped member including segmented strips of conductive material. The deep stimulation electrodes 104 are implanted deep within the brain to facilitate penetration of the alternating electric field into brain tissue. In some embodiments, each of the deep stimulation electrodes 104 defines a distal end and a proximal end, the distal end of each of the deep stimulation electrodes 104 being implanted within brain tissue, and the proximal end of each of the deep stimulation electrodes 104 being operably associated with a respective wire 102. In some embodiments, the deep stimulation electrodes 104 are operable to measure aspects of the alternating electric field applied to various locations within the brain by the primary array 101 and communicate the measured aspects of the alternating electric field back to the controller module 120. In one aspect, each subdural electrode 103 and deep stimulation electrode 104 is operable to apply a current waveform to the tissue through wires 102. By applying waveforms to the brain from multiple sources, an alternating electric field is generated.

[0011] One visual example of the placement of the subdural electrodes 103 and deep stimulation electrodes 104 relative to a cancerous region of the brain is shown in Figure 3. The optimal placement and number of the subdural electrodes 103 and deep stimulation electrodes 104 may vary between patients. Therefore, various imaging platforms may be used to scan the brain and determine the optimal placement, type, and quantity of electrodes 103 and 104 to collectively create the array 101.

[0012] 4 , in some embodiments, the controller module 120 includes a waveform generator 124 and a processing unit 122, with the waveform generator 124 in operative communication with the array 101 over one or more wires 110. The waveform generator 124 of the controller module 120 is operable to receive a set of operating parameters from the processing unit 122 and output a waveform such that an alternating electric field is applied to brain tissue as the waveform is distributed across the array 101. The processing unit 122 of the controller module 120, such as a microprocessor or microcontroller, is operable to output the set of operating parameters to the waveform generator 124. The processing unit 122 is also operable to receive input from the array 101 regarding measured aspects of the alternating electric field, communicate the input to the external computer 200, update the set of operating parameters, and communicate the updated set of operating parameters to the waveform generator 124.

[0013] Empirical studies for TTF therapy recommend a standard 200 kHz waveform to generate the AC electric field, generated by the waveform generator 124. Ideal waveform modulation and intensity parameters are determined by the external computer 200 and delivered to the waveform generator 124 through the processing unit 122.

[0014] The controller module 120 may also include a wireless communication module 126 that enables communication between the processing unit 122 of the controller module 120 and the external computer 200. In this manner, the processing unit 122 of the controller module 120 is operable to wirelessly receive software updates and instructions from the external computer 200 as well as transmit measured aspects of the AC field to the external computer 200 for review and system optimization. The controller module 120 may also include an implantable battery (not shown) or other power source.

[0015] A method for treating carcinoma using the present system 100 is illustrated in FIG. 5. In step 300, the disease is discovered, and in step 302, one or more cranial mapping techniques are employed to determine optimal placement and placement for the electrode array 101. In step 304, the electrode array 101, wires 110, and controller module 120 are surgically attached or implanted. Referring back to FIG. 2, the electrode array 101 is implanted intracranially in the patient, the subdural electrodes 103 are placed under the dura on the surface of the brain, and the deep stimulation electrodes 104 are implanted deep within the brain. The controller module 120 may be surgically implanted or attached subclavianally or abdominally. In other cases, the controller module 120 may be attached outside the body, depending on the patient's anatomy.

[0016] 5 , once the electrode array 101, wires 102, and control module 120 are attached or implanted, in step 306, the AC electric field generated by the electrode array 101 is optimized using an initial set of parameters and the known location of each subdural electrode 103 and deep stimulation electrode 104 above or within the patient's brain. The optimization process is performed using an external computer 200, which runs a simulation environment application to determine optimal waveform operating parameters for the controller module 120. This simulation environment application may be embodied as a program or application and may be installed and operated on the external computer 200. If feedback information from the array 101 is available, that feedback is incorporated into the optimization step 306. In step 308, the optimal waveform operating parameters are communicated to the controller module 120, and then in step 310, the optimized AC electric field is applied to the patient's brain by the array 101. As the AC field is delivered, one or more of the deep stimulation electrodes 104 measure aspects of the AC field and communicate this data to the controller module 120. The controller module 120 records the information and / or transmits it to the external computer 200 in step 312. In this manner, the optimization process can be iteratively repeated using feedback regarding the measured aspects of the AC field and the precise position of each subdural electrode 103 and deep stimulation electrode 104 until the AC field is at its most effective applied strength.

[0017] In some embodiments of the present system 100, the simulation environment used in the optimization process using the external computer 200 is operable to receive as input the precise locations of the subdural electrodes 103 and deep stimulation electrodes 104, as well as information regarding the AC field strength measured by the deep stimulation electrodes 104. Furthermore, the simulation environment application is operable to allow a user to observe changes in the AC field delivered to the brain with changes in the waveform delivered to any given electrode 103 or 104. As changes in the delivered waveform are simulated, the simulation environment application is operable to optimize the AC field generation by calculating and displaying the distribution of AC field strength throughout the brain as a result of changes in the delivered waveform, the precise locations of the electrodes 103 and 104, and / or the unique anatomy of the patient's brain. This allows a user to determine the best configuration of electrode stimulation parameters for the electrodes 103 and 104 to optimize the AC field in the target region. Then, while real-time data is acquired by one or more of the deep stimulation electrodes 104 in the brain, given parameters can be initialized and altered within the patient to ensure that the appropriate AC field strength is achieved.

[0018] It should be understood from the foregoing that, while particular embodiments have been illustrated and described, it will be apparent to those skilled in the art that various modifications can be made to those embodiments without departing from the spirit and scope of the invention. Such changes and modifications are within the scope and teachings of the present invention as defined in the claims appended hereto.

Claims

1. a plurality of subdural electrodes; a plurality of deep stimulation electrodes; an electrode array including: an electrode array configured to generate an alternating electric field through the plurality of subdural electrodes and the plurality of deep stimulation electrodes; a waveform generator operable to generate and transmit to the electrode array a waveform representative of the alternating electric field; a processing unit operable to communicate a set of waveform parameters to the waveform generator; a controller module operable to communicate with the electrode array; A method for operating an AC electric field generating device, comprising: the controller module operates the waveform generator to transmit the waveform to the electrode array over a plurality of conductive wires; Method of operating an AC electric field generating device.

2. 2. The method of claim 1, wherein the processing unit is operable to receive the measured field strength of the alternating current electric field from one or more of the plurality of deep stimulation electrodes of the electrode array.

3. 3. The method of claim 2, wherein one or more of the plurality of conductive wires is operable to transmit the measured field strength of the AC electric field from the electrode array to the controller module.

4. one or more of the plurality of conductive wires is operable to transmit the waveform from the controller module to the electrode array; A method for operating the AC electric field generating device according to claim 1.

5. each of the plurality of deep stimulation electrodes defining a rod-shaped member; one or more conductive contacts disposed along the rod-shaped member; One end of each of the plurality of deep stimulation electrodes is connected to one or more of the plurality of conductive wires. A method for operating the AC electric field generating device according to claim 1.

6. each of the plurality of subdural electrodes defining opposing surfaces; one of the opposing surfaces includes a conductive contact; the plurality of subdural electrodes are operably connected to one or more conductive wires; A method for operating the AC electric field generating device according to claim 1.

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