[0001 ] This application is a PCT application that claims priority to U.S. Provisional Patent Application No. 63/316,243, filed March 3, 2022, the entire contents of which is incorporated herein by reference.

TECHNICAL FIELD

[0002] This disclosure generally relates to electrode configurations for alternating electric fields.

BACKGROUND

[0003] Alternating electric field (AEF) therapy, is a type of electric field therapy which uses low-intensity electrical fields to treat brain tumors; glioblastoma in particular. Conventional cancer treatments include chemotherapy and radiation, which are associated with treatment- related toxicity' and high rates of tumor recurrence. AEF uses an alternating electric field to disrupt cell division in cancer cells, thereby inhibiting cellular replication and initiating apoptosis (cell death). AEF therapy is typically delivered via electrodes located external to the patient.

SUMMARY

[0004] In general, the disclosure describes devices, systems, and techniques related to delivering electric and magnetic stimulation therapy, which includes electrical field therapy and/or detecting electrical signals. Electric field therapy may include modulated electrical field therapy which may include types of electrical field modulation, such as alternating current stimulation which includes alternating electrical field (AEF) therapy and is discussed herein as one example of therapy. Other types of electric and magnetic stimulation therapy are described herein in various examples and combinations. For example, an implantable medical device (IMD) may be coupled to one or more leads carrying an array of electrodes. The IMD may alternate delivery of electrical fields from respective different electrode combinations utilizing some or all of the implanted electrodes carried on the one or more leads.

[0005] The one or more leads may be configured to position the array of electrodes with respect to target tissue that is intended to receive the electrical field modulation. For example, the leads may include one or more structures configured to dispose the electrodes at a desired location with respect to a target tissue and/or tissue associated with a tissue resection region. These structures may be curved, inflatable, and/or extendable from the lead housing in order to dispose the electrodes at locations to deliver electrical field modulation to target tissue which may be associated with the tissue resection region. The tissue resection region may be a region within the anatomy of the patient where tissue was removed, such tissue that included tumor cells, e.g., glioblastomas or other types of tumor or cancer cells. The remaining cells in or near the tissue resection region may thus be treated by the electrical field modulation via the electrodes of the leads. For example, AEF therapy may be used for various reasons, such as reducing or preventing the growth of tumor cells, such as glioblastomas, or the reduction in growth or proliferation or directional migration of non-tumorous cells within the body. Examples of cells may be within the following tissues: skin, muscle, pulmonary, laryngeal, nasopharyngeal, liver, gastric, splenic, renal, intestinal, pancreatic, or prostate. These manipulations of normal cells could be conducted to address pathological processes or to enhance efficiency of normal cellular functions, such as secretory, migratory, or differentiational activities, AEF therapy has been demonstrated to impact the microstructural elements within cells (e.g., microtubules and/or actin filaments) such that a system can precisely deliver AEF therapy to a subpopulation of cells in a targeted manner to direct or restrict cell migratory' activities. In some examples, AEF therapy may be delivered to a patient to modulate fibroblasts and their role in scar tissue formation or modulate the proliferation of lymphocytes or leukocytes for patients with an auto-immune condition.

[0006] In one example, a system includes medical lead comprising: a housing; one or more structures coupled to the housing; and a plurality of electrodes disposed on the one or more structures and configured to deliver electrical fields, wherein the one or more structures are configured to position the plurality of electrodes with respect to a tissue resection region.

[0007] In another example, system includes an implantable medical device comprising stimulation circuitry configured to generate one or more electrical signals; and a medical lead comprising: a housing; one or more structures coupled to the housing; and a plurality of electrodes disposed on the one or more structures and configured to deliver electrical fields resulting from the one or more electrical signals applied to a subset of the plurality of the electrodes, wherein the one or more structures are configured to position the plurality of electrodes with respect to a tissue resection region.

[0008] The details of one or more examples of the techniques of this disclosure are set forth m the accompanying drawings and the description below. Other features, objects, and advantages of the techniques wall be apparent from the description and drawings, and from the claims.

BRIEF DESCRIPTION OF DRAWINGS

[0009] FIG. 1 is a conceptual diagram illustrating an example system that includes an implantable medical device (IMD) configured to deliver alternating electric field (AEF) therapy to a patient according to an example of the techniques of the disclosure.

[0010] FIG. 2 is a block diagram of the example IMD of FIG. 1 for delivering AEF therapy according to an example of the techniques of the disclosure.

[0011] FIG. 3 is a block diagram of the external programmer of FIG. I for controlling deliver}' of AEF therapy according to an example of the techniques of the disclosure.

[0012] FIG 4 is a block diagram illustrating an example system that includes an external device, such as a server, and one or more computing devices that are coupled to an implantable medical device and external programmer shown in FIG. 1 via a network.

[0013] FIGS. 5A and 5B are conceptual diagrams of example leads with respective electrodes carried by the lead.

[0014] FIGS. 5C, 5D, 5E, and 5F are conceptual diagrams of example electrodes disposed around a perimeter of a lead at a particular longitudinal location.

[0015] FIG. 6 is a flowchart illustrating an example technique for delivering AEF therapy to a patient.

[0016] FIG. 7 is a conceptual diagram illustrating an example multiple pronged lead configured to deliver alternating magnetic field (AEF) therapy.

[0017] FIG. 8A-8F are conceptual diagrams illustrating example configurations of multiple pronged lead.

[0018] FIG. 9 is a cross-sectional view of an example lead including multiple prongs.

[0019] FIG. 10 is a conceptual diagram illustrating an expandable cone electrode configuration. [0020] FIG. 11 is a flowchart illustrating an example technique for implanting an expandable electrode configuration to a patient.

[0021] FIG. 12 is a conceptual diagram illustrating an expandable multiple filar lead.

[0022] FIG. 13 is a conceptual diagram illustrating a balloon lead.

[0023] FIG. 14 is a conceptual diagram illustrating an expandable bell lead.

[0024] FIG. 15 is a flowchart illustrating an example technique for implanting an expandable balloon lead to a patient.

[0025] FIG. 16 is a conceptual diagram of an example configuration of multiple paddle leads implantable to treat a target tissue of a patient for AEF therapy.

[0026] FIG. 17 is a conceptual diagram illustrating a paddle lead including a coil electrode.

[0027] FIG. 18 is a conceptual diagram illustrating a paddle lead including an electrode array.

[0028] FIG. 19A is a conceptual diagram illustrating an example flexible electrode array.

[0029] FIG. 19B is a schematic diagram illustrating components of the flexible electrode array of FIG, 19B.

[0030] FIG. 20 is a conceptual diagram of implantation position of a flexible electrode array within a resection ca vity of a patient,

[0031] FIG. 21 is a flowchart illustrating an example technique for implanting a flexible electrode array within a resection cavity of a patient.

[0032] FIG. 22 is a conceptual diagram of example tack electrodes configured to be implanted within the surface of a resection cavity of a patient.

[0033] FIG. 23 is a flowchart illustrating an example technique for implanting multiple tack electrodes within a resection cavity of a patient.

DETAILED DESCRIPTION

[0034] This disclosure describes various devices, systems, and techniques for delivering modulated electrical field therapy (which may include the example of AEF therapy) to a patient via implanted electrodes. Alternating electric field application is a cancer treatment type with the potential to reduce treatment related toxicity . In alternating electric field application, an alternating electric field is applied to a cancerous region of the brain, which may disrupt cellular division for rapidly-dividing cancer cells. To administer alternating electric field treatment to a patient, an external system can be applied near the anatomy of interest, such as around the cranium of the patient, in order to deliver the alternating electric field to the patient. However, there are various challenges to external delivery of AEF therapy. For example, external AEF therapy requires that hair be removed from the scalp of the patient. As another example, electrical fields delivered from the external electrodes for extended periods of time required for AEF therapy may cause increased tissue heating and potential burns on the skin of the patient. In addition, external electrodes may prevent localized treatment of tumors within the brain. For implanted electrodes, it may be difficult to implant electrodes carried by traditional cylindrical leads at desired locations of tumor cells, such as tumor cells that may remain after tissue resection.

[0035] As described herein, a system may include one or more leads configured to deliver electric field therapy (also referred to as AEF therapy in some examples) from implanted electrodes at a location and strength specific for the patient. Electric field therapy may generally refer to therapy in which electrical fields are modulated to provide some therapeutic response. For example, alternating electric field therapy described herein includes a system that modulates electric fields by alternating between different electrode combinations, different field directions, and/or other parameters that define the electric field therapy). This internal AEF therapy may act to inhibit cellular division and/or initiate apoptosis of cancer cells at the targeted treatment location. The implanted electrodes may be selected to target tissue identified as including cancerous cells or tissue around a resection area (e.g., a tissue resection region) where a previous tumor was removed. For example, a medical lead may include one or more structures configured to extend from a lead housing and/or expand in order to deploy the electrodes to an appropriate position that enables delivery of AEF or other electrical field modulation to the target tissue. In this manner, the system may operate to deliver AEF therapy to reduce cancerous cells in the patient and/or prevent or reduce the reoccurrence of cancer after resection. A computing device may be used for planning implantation of electrodes and/or selection of stimulation parameters based on imaging data obtained for the patient used to generate a model of patient tissue. The sy stem may adjust the one or more stimulation parameters based on various feedback variables, such as impedance tomography, histological analysis, patient activity, sensed temperature, and the tike. In this manner, the IMD may operate in a closed-loop manner based on one or more feedback variables obtained from the patient. The AEF therapy described herein may facilitate patient-specific AEF therapy directed to specific target tissue. Using implanted electrodes may enable the system to operate over larger periods of time without impacting most patient daily activities. In addition, leads using deployable (e.g., extendable and/or expandable) structures to place electrodes within the patient may reduce tissue damage during implantation and/or reduce the surgical time needed for a clinician to implant the lead within the patient. These and other advantages may be realized by the systems and examples described herein.

[0036] Although this disclosure is directed to delivery of AEF therapy to the brain for the purpose of treating glioblastoma, the systems, devices, and techniques described herein may similarly operate to deliver AEF therapy or similar electric-field therapies to other tissue areas and/or to treat different types of cancer. For example, a system may be implanted to treat and/or prevent cancer in the spine, pelvis, abdomen, or any other location. Some examples of target tissue may include regions of expected metastatic elements, such as lymph nodes, to reduce the spread of cells from a different tumor cite. Moreover, a human patient is described for example purposes herein, but similar systems, devices, and techniques may be used for other animals in other examples.

[0037] Electric field therapy described herein may include several different types of therapy in which different electric fields are delivered to a patient. These therapies may include modified electric field therapy, modulated electric field therapy, alternating electric field (AEE) therapy, or other therapies in which different electric fields are delivered to a patient. In some examples, these different electric fields change over time in a symmetric, non-symmetric, continuous, and/or non-continuous manner. While reference is primarily made to AEF in the examples described herein, other types of electric field therapy can be applied in the various example devices, systems, and techniques described herein.

[0038] FIG. 1 is a conceptual diagram illustrating an example system 100 that includes an implantable medical device (IMD) 106 configured to deliver therapy to patient 112 according to an example of the techniques of the disclosure. This therapy may be AEF therapy or another therapy based on applied electrical fields. As shown in the example of FIG. 1, example system 100 includes medical device programmer 104, implantable medical device (IMD) 106, lead extension 110, and leads 114A and 114B with respective sets of electrodes 116, 118. In the example shown in FIG. 1, electrodes 116, 118 of leads 114A, 114B are positioned to deliver electrical stimulation to a tissue site within brain 120, such as a deep brain site under the dura mater of brain 120 of patient 112. In some examples, delivery of electric fields (e.g., electrical stimulation) to one or more regions of brain 120, such as a region that contains a tumor such as glioblastoma, or region from which a glioblastoma was resected (removed). This location where the tumor was removed, e.g., the tumor bed, may be or be part of the target tissue for AEF therapy. The tumor bed may be of various sizes, but may be between approximately I mm to 3 mm in diameter in some examples. Some or all of electrodes 116, 118 also may be positioned to sense neurological brain signals within brain 120 of patient 112. In some examples, some of electrodes 116, 118 may be configured to sense neurological brain signals, impedance, etc., and some or all of electrodes 116, 118 may be configured to deliver electrical stimulation to brain 120 in the form of AEF therapy. In other examples, all of electrodes 116, 118 are configured to both sense electrical signals and deliver electrical stimulation to brain 120. Leads 114A, 114B are merely examples, as any other leads or lead configurations described herein may be configured to position respective electrodes within brain 120 to deliver AEF therapy to patient j99

[0039] IMD 106 includes a therapy module (e.g., which may include processing circuitry, signal generation circuitry or other electrical circuitry configured to perform the functions attributed to IMD 106) that includes a stimulation generator configured to generate and deliver electrical stimulation therapy (e.g. , AEF therapy) to patient 112 via a subset of electrodes 1 16, 1 18 of leads 114A and 114B, respectively. The subset of electrodes 116, 118 that are used to deliver electrical stimulation to patient 1 12, and, in some cases, the polarity of the subset of electrodes 116, 118, may be referred to as a stimulation electrode combination. As described in further detail below, the stimulation electrode combination can be selected for a particular patient 1 12 and target tissue site (e.g., selected based on the patient condition or based on the determined location of a tumor or other tissue of interest). The group of electrodes 116, 118 includes at. least one electrode and can include a plurality of electrodes.

[0040] In some examples, the plurality of electrodes 116 and/or 118 may have a complex electrode geometry such that two or more electrodes of the lead are located at different positions around the perimeter of the respective lead (e.g., different positions around a longitudinal axis of the lead). In other examples, the electrodes at different positions around the perimeter of the lead may be disposed on different structures of the lead. In tins manner, electrodes at different perimeter locations may be used to generate different electrical fields. For example, anodes on a first side of a first lead and cathodes on a second side of a second lead, wherein the first sides and second side face opposing directions, may be used to generate a first electric field. The second electric field may be generated with cathodes on the second side of the first lead and anodes on the first side of the second lead. In this manner, alternating between the first and second electric fields may generate electrical current that changes the polarities of cellular components to disrupt cell division. Although two leads 14 are shown in the example of FIG. 1, a single lead, three leads, four leads, five leads, or more leads may be implanted in different examples. In some examples, a single lead may include two or more structures extending from the lead housing, where each structure carries one or more electrodes (e.g., curved prongs 704 in FIG. 7). In any case, the combination of leads may provide an overall array of electrodes that can be programmed to deliver alternating electrical fields to a target tissue. These complex electrode geometries can also enable directional sensing that can measure the orientation of electric fields generated in tissue. For example, the system may measure electrical potentials between electrodes at different locations on a lead or between different leads to determine a gradient of electrical potentials and a gradient of the delivered electrical field. The system can then determine electric field spread and configure the electric fields and/or calibrate a predictive model of field spread based on the sensed gradient of electrical potentials.

[0041] In some examples, the neurological signals (e.g., an example type of electrical signals) sensed within brain 120 may reflect changes in electrical current produced by the sum of electrical potential differences across brain tissue. Examples of neurological brain signals include, but are not limited to, electrical signals generated from local field potentials (LFP) sensed within one or more regions of brain 120, electroencephalogram (EEG) signals, or electrocorticogram (ECoG) signals. Any of these sensed signals may be intrinsic signals generated by physiological neural activity and/or evoked signals generated in response to a delivered stimulus (e.g., a delivered electrical stimulation signal). It is noted that modulated electric field therapy (e.g., AEF therapy) may not evoke neuron propagation or affect other normal neurological function. However, the system may deliver signals intended to affect neurological processes in order to sense signals that may be indicative of physiological states or the response to modulated electric field therapy. In some examples, the system may utilize any electrode combinations to directly sense the electrical field (e.g., field strengths, field locations, or other characteristics) delivered by other electrode combinations. In this manner, the system may confirm expected electrical field strengths, adjust one or more stimulation parameters that define the electrical fields to effect target tissue (e.g., to match a desired stimulation model), and/or adjust the model of stimulation to reflect the reality of tissue characteristics. In some examples, the system may adjust the stimulation parameters defining the electrical fields to accommodate for tissue changes over time and/or lead movement within the patient after surgery or over time. The system may adjust any of these parameters in response to reviewing previously stored data and/or in real-time as sensed data is received or generated.

[0042] In some examples, the neurological brain signals that are used to select a stimulation electrode combination may be sensed within the same region of brain 120 as the target tissue site for the electrical stimulation and/or from a region different (e.g., adjacent to or outside of) than the target tissue site. The system may be configured to compute or predict the electrical field at the target tissue based on the signals sensed within the target tissue and/or at a region different than the target tissue. The specific target tissue sites and/or regions within brain 120 may be selected based on the patient condition or location, size, depth, and/or volume of a tumor or resection bed. Thus, due to these differences in target locations, in some examples, the electrodes used for delivering electrical stimulation may be different than the electrodes used for sensing neurological brain signals. In other examples, the same electrodes may be used to deliver electrical stimulation and sense brain signals. However, this configuration of using the same electrodes could require the system to switch between stimulation generation and sensing circuitry and may reduce the time the system can sense brain signals. In some examples, the system may be configured to deliver electrical signals to generate the electrical fields from the same electrode configurations (or using at least some of the same electrodes) in an at least partially interleaved basis.

[0043] Electrical stimulation generated by IMD 106 may be configured to manage a variety of disorders and conditions. In some examples, the stimulation generator of IMD 106 is configured to generate and deliver electrical stimulation pulses to patient 1 12 for AEF therapyvia electrodes of a selected stimulation electrode combination. However, in other examples, the stimulation generator of IMD 106 may be configured to generate and deliver a continuous wave signal, e.g., a sine wave or triangle wave of specified amplitude (peak to peak) and frequency as part of the electrical fields of the AEF therapy. Generally, modulated electric field therapy (e.g., AEF therapy) may include the delivery of the continuous wave signal(s), but the waveforms may be symmetric, asymmetric, non-continuous, continuous, cycled, interleaved between different combinations, constant, or otherwise changing over time at random or predetermined sequences. In either case, a stimulation generator within IMD 106 may generate the AEF therapy according to a therapy program that is selected at that given time in therapy. In examples in which IMD 106 delivers electrical stimulation in the form of stimulation pulses, a therapy program may include a set of therapy parameter values (e.g., stimulation parameters), such as a stimulation electrode combination for delivering different electrical fields to patient 112, pulse frequency, pulse width, and a current or voltage amplitude of the pulses or continuous signals. As previously indicated, the electrode combination may indicate the specific electrodes 116, 118 that are selected to deliver stimulation signals to tissue of patient 112. and the respective polarities of the selected electrodes. IMD 106 may deliver electrical stimulation intended to contribute to a therapeutic effect. In some examples, IMD 106 may also, or alternatively, deliver electrical stimulation intended to be sensed by other electrodes and/or elicit a physiological response, such as an evoked compound action potential (ECAP), that can be sensed by electrodes. The delivered stimulation may have a sub-perception threshold intensity or supraperception threshold intensity. In this manner, IMD 106 may used sensed electrical stimulation and/or sensed physiological responses in a closed-loop manner to modulate delivered electrical stimulation, such as AEF therapy,

[0044] IMD 106 may be implanted withm a subcutaneous pocket above the clavicle, or, alternatively, on or within cranium 122 or at any other suitable site withm patient 112 such as a lower abdominal or high buttock location. Other configurations might include IMD 106 implanted at multiple locations, such as near a site of tumor occurrence and remote sites of likely tumor transmission or spread. Generally, IMD 106 is constructed of a biocompatible material that resists corrosion and degradation from bodily fluids. IMD 106 may comprise a hermetic housing to substantially enclose components, such as a processor, therapy module, and memory. Other implant locations for IMD 106 may be utilized for treatment of the brain or other tissues. Example alternative implantation sites for IMD 106 may include the lov/er back, shoulder, neck, abdomen, or any other location.

[0045] As shown in FIG. 1, implanted lead extension 110 is coupled to IMD 106 via connector 108 (also referred to as a connector block or a header of IMD 106). In the example of FIG. I , lead extension 110 traverses from the implant site of IMD 106 and along the neck of patient 112 to cranium 122 of patient 112 to access brain 120. In the example shown in FIG. 1, leads 114A and 114B (collectively “leads 114”) are implanted within the right and left hemispheres, respectively, of patient 112 in order deliver AEF therapy to one or more regions of brain 120, which may be selected based on the patient condition or disorder controlled by therapy system 100. The specific target tissue site and the stimulation electrodes used to deliver stimulation to the target tissue site, however, may be selected, e.g., according to the locations of a tumor or resection bed and/or other sensed patient parameters. Other lead 114 and IMD 106 implant sites are contemplated. For example, IMD 106 may be implanted on or within cranium 122, in some examples. Or leads 114 may be implanted within the same hemisphere or IMD 106 may be coupled to a single lead implanted in a single hemisphere. Although leads 114 may have ring electrodes at different longitudinal positions as shown in FIG. 1, leads 114 may have electrodes disposed at different positions around the perimeter of the lead (e.g., different circumferential positions for a cylindrical shaped lead) as shown in the examples of FIGS. 5 A and 5B.

[0046] Leads 114 illustrate an example lead set that include axial leads carrying ring electrodes disposed at different axial positions (or longitudinal positions). In other examples, leads may be referred to as “paddle” leads carrying planar arrays of electrodes on one side of the lead structure or a “grid” of electrodes that enable the placement of electrical elements at a variety of locations around the tissue. In addition, as described herein, complex lead array geometries may be used in which electrodes are disposed at different respective longitudinal positions and different positions around the perimeter of the lead. For example, a lead 114 may include a lead housing (e.g., a structure configured to housing conductors that travel from a proximal end to a distal end of the lead) and one or more structures coupled to the housing. Lead 114 may also include a plurality of electrodes disposed on the one or more structures and configured to deliver electrical fields to tissue. These one or more structures may be configured to position the plurality of electrodes with respect to a tissue resection region or other target tissue that is intended to receive the electrical fields (e.g., AEF therapy). For example, the one or more structures may be extendable curved prongs, curved members, expandable structures configured to expand in a radial direction, or other structures configured to dispose the electrodes in a spatial configuration to deliver the electrical fields to tissue. In this manner, lead 114 maybe configured to be implanted within a patient comprising the tissue resection region. [0047] Although leads 114 are shown in FIG. 1 as being coupled to a common lead extension 110, m other examples, leads 114 may be coupled to IMD 106 via separate lead extensions or directly to connector 108. Leads 114 may be positioned to deliver electrical stimulation to one or more target tissue sites within brain 120. Leads 114 may be implanted to position electrodes 116, 118 at desired locations of brain 120 through respective holes, or a common hole, in cranium 122. Leads 114 may be placed at any location within brain 120 such that electrodes 116, 118 are capable of providing electrical stimulation to target tissue sites within brain 120 during treatment. For example, electrodes 116, 118 may be surgically implanted under the dura mater of brain 120 or within the cerebral cortex of brain 120 via a burr hole in cranium 122 of patient 112, and electrically coupled to IMD 106 via one or more leads 114.

[0048] In the example shown in FIG. 1 , electrodes 116, 118 of leads 114 are shown as ring electrodes. Ring electrodes may be used in AEF therapy applications because they are relatively simple to program and are capable of delivering an electrical field to any tissue adjacent to electrodes 116, 118. In other examples, electrodes 116, 118 may have different configurations. For example, in some examples, at least some of the electrodes 116, 118 of leads 114 may have a complex electrode array geometry? that is capable of producing electrical fields of various shapes and electrical fields directed to different directions with respect to the lead, such as in the various medical leads described herein. The complex electrode array geometry may include multiple electrodes (e.g,, partial ring or segmented electrodes) around the outer perimeter of each lead 114, rather than one ring electrode, such as shown in FIGS. 5A and 5B. In this manner, electrical stimulation may be directed in a specific direction, such as alternating directions for alternating electrical fields, from leads 114 to provide AEF therapy. In some examples, one or more leads 1 14 may include insulation on a portion of the lead that may enable electrical field directionality such that the electrical current is directed to certain circumferential locations other than the insulated portion. In some examples, fewer electrodes may be used to generate smaller electrical fields specifically selected to affect target tissue during the AEF delivery while avoiding subjecting other tissues to the electric fields. In some examples, a housing of IMD 106 may include one or more stimulation and/or sensing electrodes. In alternative examples, leads 114 may have shapes other than elongated cylinders as shown in FIG. 1. For example, leads 114 may be paddle leads, spherical leads, bendable leads, leads having one or more structures that extend and/or expand from a lead housing, or any other type of shape that positions electrodes to be effective in treating patient 112 and/or minimizing invasiveness of leads 114.

[0049] In tins manner, any electrode arrays may be designed to be placed surgically in a tumor void or bed and deliver electric fields to cover the interior volume of the debulked void therein. These electrode arrays may include conformable grids, volumetric “balloons,” multiple small electrodes placed individually within the void, surface anchorable electrodes applied with sutures or glue to the inside surface of the void, very long linear array s wrapped around the circumference of the void or spiraled within, spring formed structures (nitinol or other compliant material) to expand to fill the volume, and hybrid arrays with paddle and/or grid elements to cover void surface and penetration elements to extend field perpendicular to the tissue surface. [0050] In the example shown in FIG. 1, IMD 106 includes a memory to store a plurality of therapy programs that each define a set of therapy parameter values. In some examples, IMD 106 may select a therapy program from the memory based on various parameters, such as sensed patient parameters and the identified patient behaviors. IMD 106 may generate electrical or magnetic stimulation based on the selected therapy program to deliver effective AEF therapy that reduces or prevents cancerous cell division , enhances apoptosis of cancer cells, facilitates immune-mediated cell death, or modulates other cellular functions, such as cell differentiation or de-differentiation, or secretory vesicle release. In other examples, AEF therapy may be delivered for additional or alternative benefits. For example, the system may target AEF therapy to fibroblasts in order to inhibit scar formation within a wound. For a patient with an auto-immune disease, the system may deliver AEF therapy to lymphatic channels, the spleen, thymus, or other anatomical location within the patient to modulate the proliferation of lymphocytes or leukocytes.

[0051] External programmer 104 wirelessly communicates with IMD 106 as needed to provide or retrieve therapy information. Programmer 104 is an external computing device that the user, e.g., a clinician and/or patient 112, may use to communicate with IMD 106. For example, programmer 104 may be a clinician programmer that the clinician uses to communicate with IMD 106 and program one or more therapy programs for IMD 106. Alternatively, programmer 104 may be a patient programmer that allows patient 112 to select programs and/or view and modify therapy parameters. The clinician programmer may include more programming features than the patient programmer. In other words, more complex or sensitive tasks may only be allowed by the clinician programmer to prevent an untrained patient from making undesirable changes to IMD 106. IMD 106 may also transmit notifications to programmer 104 for deliver}' to a user in response to detecting one or more problems with stimulation and/or detection of one or more trigger events for patient 112. Programmer 104 may enter a new programming session for the user to select new stimulation parameters for subsequent therapy. External programmer 104 may display estimated locations of target tissue locations and/or suggested stimulation parameter values for delivering electrical stimulation that affects the target tissue location.

[0052] When programmer 104 is configured for use by the clinician, programmer 104 may be used to transmit initial programming information to IMD 106. This initial information may include hardware information, such as the type of leads 114 and the electrode arrangement, the position of leads 114 within brain 12.0, the configuration of electrode array 116, 118, initial programs defining therapy parameter values, and any other information the clinician desires to program into IMD 106. Programmer 104 may also be capable of completing functional tests (e.g., measuring the impedance of electrodes 116, 118 of leads 114 or the electric field strength at a strategic location on one of leads 114). In some examples, programmer 104 may receive sensed signals or representative information and perform the same techniques and functions attributed to IMD 106 herein. In other examples, a remote server (e.g., a standalone server or part of a cloud service as shown in FIG. 4) may perform the functions attributed to IMD 106, programmer 104, or any other devices described herein.

[0053] Programmer 104 may also be configured for use by patient 112, When configured as a patient programmer, programmer 104 may have limited functionality (compared to a clinician programmer) in order to prevent patient. 1 12 from altering critical functions of IMD 106 or applications that may be detrimental to patient 112. In this manner, programmer 104 may only allow patient 112 to adjust values for certain therapy parameters or set an available range of values for a particular therapy parameter. In one example, a patient programmer may only allow for functions such as turning AEF therapy on or off and/or decreasing stimulation intensity. In some examples, programmer 104 may present an indication of delivery time for the patient, such as a screen that indicates the amount of time that the therapy is delivered and/or time the therapy has been off for each day, week, month, etc. For example, programmer 104 may present that “AEF therapy has been delivered for 85% of the time during the last week” or “AEF therapy has been delivered during 6 of the last 7 days.” In addition, programmer 104 may present remaining therapy time available before recharge is required when IMD 106 operates using a rechargeable power source. In some examples, the user interface may present a map of the cranium with the electrode configuration represented and one or more zones of tissue that receive a specified therapeutic parameter (such as V/cm). In some examples, the user interface may be configured to receive user input manipulating the orientation of the field and/or adjustment of other stimulation parameter values.

[0054] Programmer 104 may also provide an indication to patient 112 when therapy is being delivered, when patient input has triggered a change in therapy or when the power source within programmer 104 or IMD 106 needs to be replaced or recharged. For example, programmer 112. may include an alert LED, may flash a message to patient 112 via a programmer display, generate an audible sound or somatosensory cue to confirm patient input was received, e.g., to indicate a patient state or to manually modify a therapy parameter.

[0055] Therapy system 100 may be implemented to provide chronic stimulation therapy to patient 112 over the course of several months or years. However, system 100 may also be employed on a trial basis to evaluate therapy before committing to full implantation. For example, leads 114 may be configured to be implanted for a relatively short time (e.g., a few weeks or months) or for longer periods of years for chronic use. If implemented temporarily, some components of system 100 may not be implanted within patient 112. For example, patient 1 12 may be fitted with an external medical device, such as a trial stimulator, rather than IMD 106. The external medical device may be coupled to percutaneous leads or to implanted leads via a percutaneous extension. If the trial stimulator indicates AEF system 100 provides effective treatment to patient 112, the clinician may implant a chronic stimulator within patient 112 for relatively long-term treatment with AEF therapy.

[0056] Although IMD 106 is described as delivering electrical stimulation therapy to brain 120, IMD 106 may be configured to direct electrical stimulation to other anatomical regions of patient 112 in other examples. In other examples, system 100 may include an implantable drug pump in addition to, or in place of, IMD 106. Further, an IMD may provide other electrical stimulation such as spinal cord stimulation to treat other types of cancer or other diseases or disorders. In some embodiments, the therapy delivered by IMD 106 is designed to enhance the ability of particular drugs to pass through the blood-brain barrier, or is designed to enable particular drugs to pass through the blood-brain barrier, through for example, delivering therapy at a specific parameter set such as a frequency of 100kHz. The therapy may function by either specification of opening diameter within the blood brain barrier or by the transcriptomic manipulation of the cells composing the blood brain barrier to impact the cellular receptors within the region adjacent to the blood brain barrier. Example drugs or substances may include viral vectors or contrast agents (e.g., substances that my facilitate imaging or intraoperative visualization). In other embodiments, the therapy delivered by IMD 106 is designed to enhance and/or enable cell membrane permeabilization for the purpose of mediating cell transfection by enhancing viral deliver}' to target cells, enhancing the bioavailability of serologically available pharmaceuticals, enhancing the delivery of tumor-specific marker agents, such as 5- aminolevulinic acid (5-ALA), or for combinatorial efficacy with additional therapy modalities through imparting cellular stress on those cells selectively vulnerable to permeabilization. By being designed to achieve these goals, IMD 106 may be configured (via specific stimulation parameter values) to deliver electrical field therapy that increases blood-brain barrier permeabilization and/or enhances cell membrane permeabilization.

[0057] According to the techniques of the disclosure, system 100 may include processing circuitry' configured to receive a request to deliver alternating electric field (AEF) therapy, determine therapy parameter values that define the AEF therapy, wherein the AEF therapy comprises delivery' of a first electric field and a second electric field, control IMD 106 to deliver the first electric field from a first electrode combination of implanted electrodes, and control IMD 106 to deliver, alternating with the first electric field, the second electric field from a second electrode combination of implanted electrodes different than the first electrode combination. The request may be via user input and/or an automated system request to start AEF therapy delivery'-.

[0058] The electrical fields that IMD 106 alternates over time to produce the AEF therapy may involve different electrode combinations and/or different methods for alternating the electrical fields between different electrode combinations (e.g., different electrodes and/or different polarities of the same or different electrodes). In one example, the first electrode combination includes a first set of electrodes defined as cathodes and a second set of electrodes defined as anodes, and the second electrode combination includes the first set of electrodes defined as anodes and the second set of electrodes defined as cathodes. [0059] In one example in which IMD 106 utilizes 4 different implantable leads (or 4 structures extending from a single lead), the first electrode combination includes a first set of anodes carried by a first lead, the second electrode combination includes a first set of cathodes carried by a second lead different than the first lead, the third electrode combination includes a second set of anodes carried by a third lead different than the first lead and the second lead, and the fourth electrode combination includes a second set of cathodes carried by a fourth lead different than the first lead, the second lead, and the third lead. The first and second electrical fields may generally be orthogonal or oblique to each other. In another example in which two leads are used to deliver AEF therapy, the first electrode combination includes a first set of anodes carried by a first lead, the second electrode combination includes a first set of cathodes carried by a second lead different than the first lead, the third electrode combination comprises a second set of anodes carried by the second lead, and the fourth electrode combination comprises a second set of cathodes carried by the first lead. In some examples, the AEF therapy may include alternating or switching between the first electrode combination and the second electrode combination, where some or all of electrodes of the first lead switch between operating as anodes in the first electrode combination and operating as cathodes in the second electrode combination, and electrodes of the second lead switch between operating as cathodes in the first electrode combination and operating as anodes in the second electrode combination. In other examples, the first and second electrode combinations may utilize completely different electrodes for each anodes and cathodes. In other examples, each electrode combination may utilize one lead for anodes and a different lead for cathodes. The different electrode combinations used to alternate electric fields may share leads or utilize separate leads for each electrode combination. These are only some of the different methods for generating alternating electric fields from an array of implanted electrodes, as other examples are also contemplated. For example, IMD 106 may instead alternate, or sweep through, three or more different electrical fields generated from respective electrode combinations. These larger number of electrical fields may effectively treat a larger number of cells depending on the location of the cells within respect to the location of the implanted electrodes.

[0060] Although alternating electric field therapy is generally described as delivering two different electric fields, three or more electric fields may be delivered in other examples. For example, IMD 106 may be configured to deliver three electric fields that are all orthogonal to each other. In other examples, four or more different electric fields may be delivered to the cells in order to affect cells oriented in a variety of different directions. In this manner, IMD 106 may deliver tens or hundreds of different electric fields having different vectors (limited only by the available electrode combinations for delivering the electric fields) by sweeping through a sequence of these electric fields or otherwise delivering these different electric fields in order to affect cells having different orientations. Three electric fields with all different directional vectors may enable three dimensional electrical field treatment of the target tissue.

[0061] In some examples, IMD 106 is configured to cycle the AEF therapy on and off according to a predetermined schedule. This predetermined cycle may be set according to the speed of tumor cell division in order to cycle the AEF therapy at a rate that enables the tumor cells are guaranteed to experience a relevant field at least once per cell divisional time to inhibit the division of the cells. In other examples, IMD 106 may be configured to receive temperature data indicative of a temperature of tissue that receives the AEF therapy, determine that the temperature exceeds a threshold temperature, responsive to determining that the temperature exceeds the threshold temperature, terminate delivery of the AEF therapy. This temperature monitoring may reduce the risk of tissue damage due to electrical field induced tissue heating. [0062] IMD 106 may generally use the same pulse or signal frequency for generating the first and second electrical fields of the AEF therapy. In one example, the frequency may be approximately 150 kHz, In another example, the frequency may be approximately 200 kHz. In general, the frequency may be selected from a range of approximately 100 kHz through 300 kHz, but frequencies higher or lower than this range may be used in other examples. In some examples, the frequencies employed by IMD 106 are selected based on the types of cells targeted for treatment. For example, if targeting cancer cells of a certain size (e.g., 13 micrometers in diameter), the IMD 106 delivers therapy with a frequency (e.g., 200kHz) at which therapy will be more effective for that cell size. In some examples, the frequency or range of frequencies at which the electrical fields are delivered may be selected based on a workup of a patient biopsy or based on a lookup table according to the tumor type and associated distributions of cell sizes. In some examples, the minimum or maximum frequencies may be selected in order to avoid affecting sizes of healthy cells within the electric fields that may differ from the size of the tumor cells. [0063] In some examples, the stimulation frequency at which the maximum force (/max) can be imparted on a spherical particle housed within a dividing cell is inversely related to the relaxation time (T) possessed by the membrane charging voltage. The relaxation time (T) can be described by this equation:

The terms within the above formula are as follows: (T) is foe relaxation time of the membrane

Given that within an individual cell the values for rand G#vill remain approximately constant within an example frequency range for AEF therapy (100-500kHz), and again keeping in mind that the frequency at which a maximum force (fmax) is imparted on particles within the dividing cell is inversely related to the relaxation time (T), it can be said that/war is directly related to the cytoplasmic conductivity m# With that relationship in mind, simulation results are indicative of a relationship between as follows:

The terms within this above formula are as follows '. fmax is the frequency at which maximum force is imparted on a spherical particle within a dividing cell, a represents a constant which was calculated from simulation results within the literature equivalent to 2155 kHz * m * um/S/nm, m#s foe cytoplasmic conductivity, r is foe radius of foe dividing cell, and o is the membrane thickness represented in nanometers. With this relationship between the frequency for imparting maximal force and cell radius in mind, it can then be determined that with an increase in the cell size, the frequency for affecting the cell will decrease. As in the example of glioblastoma, the standardized cell lines possess an average diameter of approximately 17pm (or a radius of mentioned above the resulting optimal frequency to achieve a maximal force on cytoplasmic particles would be 177 kHz (or approximately 200kHz). This can be compared with a larger cancer cell such as pancreatic cancer which possesses a diameter of 18-22um (for the purposes of this example, 20pm), with all other variables remaining constant, and solving for the equation above the resulting optimal electric field frequency to achieve the maximal force on intracytoplasmic particles would be 151 kHz (or approximately 150kHz). Both these frequencies are shown to be effective, suggesting validity to the relationship between the variables highlighted above. Therefore, if a particular cell type can be selectively impacted by a specific TTF therapy (or .AEF therapy) frequency, it is feasible for a system to selectively avoid the impact on normal cell types that possess differing values of cell radius or cytoplasmic conductivity.

[0064] Given that AEF therapy has been demonstrated to impart an increase in cell volume within those cancer cells experiencing the therapy, m part due to the enhanced proportion of ceils that occupy the Go/Gi phase of the cell cycle, and that the optimal frequency for maximal efficacy of AEF therapy if cell size dependent (as above), the system may deliver a sweep of different frequencies such as an interleaved or continuously sweeping protocol ranging between 100kHz to 250kHz would provide an optimal treatment for the diverse cell population of the tumor .

[0065] In some examples, system 100 may be configured to determine, or recommend for user approval, one or more stimulation parameters that at least partially define the AEF therapy. For example, programmer 104 may include a. user interface configured to receive user input indicative of target tissue to receive AEF therapy. Programmer 104 may be configured to determine, based on the user input, the first electrode combination and the second electrode combination. In this manner, system 100 can achieve therapy of desired tissue, such as a glioblastoma tumor or other tissue of concern. Alternatively, or in addition, programmer 104 may include a user interface configured to receive user input indicati ve of tissue to avoid receiving AEF therapy. Since programmer 104 may be a patient or clinician programmer, the user interface may be configured to receive input from a clinician or a patient. However, in some examples, the user interface may provide additional options or expanded customizability for clinicians when compared to patients. In some embodiments, the IMD 106 is configured, to determine, e.g., using signals sensed by the electrodes, that electric fields are reaching a particular tissue structure. In some examples, one or more of the electrodes may be located in or near a non- target tissue to indicate the presence of electric fields at the non-target tissue (e.g., a specific recording electrode(s)). The IMD 106 (either alone or in combination with external devices) can adjust the applied therapy to reduce or eliminate the applied electric fields (or the effects of the applied electric fields) at that particular tissue structure. Programmer 104 may then determine, based on the user input, the first electrode combination and the second electrode combination. System 100 can then attempt to reduce the effect of AEF therapy on non-target tissues. In some examples, system 100 may receive user input indicative of target tissue and/or tissue to avoid from a remote device over a network to support remote programmer options for system 100.

[0066] System 100 may also determine stimulation parameters based on feedback regarding the state of patient 112 and/or tissue of the patient. For example, programmer 104 and/or IMD 106 may adjust one or more stimulation parameters that at least partially defines the AEF therapy based on histological data obtained from a sample of tissue affected by the AEF therapy. In another example, programmer 104 and/or IMD 106 may determine target tissue for AEF therapy based on water content data obtained from magnetic resonance imaging (MRI) data, and determine, based on the target tissue, the first electrode combination and the second electrode combination for delivery of the AEF therapy. In some examples, determining the electrode combinations may include determining the location, e.g., based on predictive computational models of electric field intensity in tissue, at which one or more leads should be located in order to deliver AEF therapy to the target tissue. As another example, programmer 104 and/or IMD 106 may determine target tissue for AEF therapy based on impedance tomography data obtained from sensed electrical potentials sensed from two or more of the implanted electrodes (and/or external electrodes disposed to record electric fields), and determine, based on the target tissue, at least the first electrode combination and the second electrode combination to deliver the AEF therapy. System 100 may also map AEF features to anatomy to inform AEF therapy planning and/or adjustments over time. For example, programmer 104 may be configured to generate an AEF dosimetry metric for anatomy that receives the AEF therapy and map the AEF dosimetry across target tissue of the anatomy . This AEF dosimetry map may inform which tissues within the anatomy are receiving different strengths of the electrical fields. Programmer 104 may also display the map of the AEF dosimetry with respect to the anatomy. [0067] IMD 106 may alternate the electrical fields in AEF therapy by delivering the electrical fields from different electrodes and/or electrodes with different polarities. In one example, IMD 106 may continually shift the polarities of the electrodes in one direction with respect to the electrode array. The first electrode combination may include a first set of electrodes defined as cathodes and a second set of electrodes defined as anodes, the second electrode combination may include a third set of electrodes defined as anodes and a fourth set of electrodes defined as cathodes, where the third set of electrodes are adjacent to the first set of electrodes in one direction on a first lead, and the fourth set of electrodes are adjacent to the second set of electrodes in the one direction on a second lead. In some examples, electrode combinations adjacent each other may be 180 degrees out of phase with each other in order to provide a maximum amount of change in voltage between the tissue separating the adjacent electrode contacts. In some examples, to accomplish the enhancement of AEF therapy, the electrode near or within the non-target tissue could be paired to the local stimulating electrodes in a 180° or n radians phase shifted configuration along the stimulation sinusoidal waveform. In doing so, the resulting electric field magnitude experienced by the non-target tissue may be higher due to the larger peak-to-peak differential in voltage between the two electrodes. To accomplish a reduction or elimination of AEF therapy within the non-target tissue region, the system may implement a 0° or Ox radians phase shifting configuration between the local electrode and the remote stimulating electrode. By conducting the stimulation in this manner, there is less permissible of differential established in the peak-to-peak voltage experienced by the local tissue and therefore a reduction in the resulting electric field.

[0068] In another example, the electrode combinations may be selected from a cube configuration where the selectable electrodes for each electrode combination form the eight vertices of a cube. In this example, the first electrode combination includes a first set of electrodes defined as cathodes and a second set of electrodes defined as anodes in a first paired configuration from the cube configuration, and the second electrode combination includes the first set of electrodes defined as anodes and the second set of electrodes defined as cathodes in a second paired configuration from the cube configuration.

[0069] As shown in FIG. 1, the electrodes (e.g., at least two electrodes) used to deliver the AEF therapy are carried by an electrode array positioned adjacent a resection bed of tissue (e.g., a tissue resection region). In some examples, system 100 may generate the electrical field modulation, such as AEF, using one or more electrodes implanted within the skull, outside of the skull and under the skin (e.g., subcutaneous), and/or external to the skin of patient 122.

[0070] Generally, AEF therapy is described herein as a treatment to already present tumors, such as glioblastomas. In other examples, the application of AEF therapy can reduce the extent of metastatic tumor burden and seeding of tumors from a remote tumor source. Therefore, AEF treatment could be delivered to protect tissue regions from metastatic spread. For example, AEF could be utilized to provide global brain protection in the setting of a known malignant tumor within the body, particularly those that have a propensity for cerebral dissemination (e.g., Melanoma). AEF could be delivered to prevent additional metastatic spread of tumor within the organ system of current metastatic dissemination. In addition, AEF implant planning could be provided for the protection of certain neurological function (e.g., motor function), such that the implant system 100 would be focused on treatment to the pre-central gyrus and/or corticospinal tract to preserve its function and avoid seeding.

[0071] An AEF delivery implant (e.g., IMD 106 and leads 114) could be utilized to prophylactically treat a body region that is expected to have a high risk for metastatic dissemination (e.g., a presumed location where tumor would progress next). The one or more leads 1 14 may be configured to implant electrodes at positions to deliver the electrical field modulation to the target tissue. An example of this is the axillary lymph nodes in the setting of a newly diagnosed breast cancer. Lymphatic channels have predictable flow and are common highways for metastatic dissemination. Therefore, implantation strategies that focus on the systematic treatment of these highways could meaningfully impact the propensity and capability for tumors to metastatically spread. AEF delivery could also utilize electrodes within arteries to permit wider control of metastatic spread. Put another way, AEF delivery could reduce the likelihood of metastatic tumor cells to exit the blood stream and seed other regions within the body.

[0072] The architecture of system 100 illustrated in FIG. 1 is shown as an example. The techniques as set forth in this disclosure may be implemented in the example system 100 of FIG. 1, as well as other types of systems not described specifically herein. Nothing in this disclosure should be construed so as to limit the techniques of this disclosure to the example architecture illustrated by FIG. 1. [0073] System 100 is generally described as including IMD 106 and external programmer 104. However, in other examples, an external medical device may be configured to perform any of the techniques described herein or described with respect to IMD 106. The external medical device may be coupled to percutaneous leads or other devices that pass through the skin in order to dispose implanted electrodes at various locations within patient for at least partially delivering electric field therapy and/or sensing signals as described herein. Additionally, or alternatively, the external device may be coupled to external electrodes configured to at least partially deliver electric field therapy and/or sense signals as described herein. The external medical device may be configured to communicate with programmer 104 and/or partially or fully incorporate structures to perform the various functionality described with respect to programmer 104.

[0074] FIG. 2 is a block diagram of the example IMD 106 of FIG. 1 for delivering AEF therapy. In the example shown in FIG. 2, IMD 106 includes processing circuitry 210, memory 211, stimulation generator 202, sensing module 204, switch module 206, telemetry module 208, sensor 212, and power source 220. Each of these modules may be or include electrical circuitry configured to perform the functions attributed to each respective module. For example, processing circuitry 210 may include processing circuitry, swatch module 206 may include switch circuitry', sensing module 204 may include sensing circuitry, and telemetry' module 208 may include telemetry circuitry. Switch module 206 may not be used for multiple current source and sink configurations, but one or more switches may still be used to disconnect sensing module 204 from the source and sinks in such a configuration. Memory 21 1 may include any volatile or non-volatile media, such as a random-access memory (RAM), read only memory (ROM), nonvolatile RAM (NVRAM), electrically erasable programmable ROM (EEPROM), flash memory, and the like. Memory 211 may store computer-readable instructions that, when executed by processing circuitry 210, cause IMD 106 to perform various functions. Memory 211 may be a storage device or other non-transitory medium.

[0075] In the example shown in FIG. 2, memory 21 1 stores therapy programs 214 that include respective stimulation parameter sets that define AEF therapy. Each stored therapy program 214 defines a particular set of electrical stimulation parameters (e.g., a therapy parameter set), such as a stimulation electrode combination, electrode polarity , current or voltage amplitude, pulse width, and pulse rate. In some examples, individual therapy programs may be stored as a therapy group, which defines a set of therapy programs with which stimulation may be generated.

[0076] Memory 211 may also include parameter selection instructions 217 and notification instructions 218. Parameter selection instructions 217 may include instructions that control processing circuitry 210 selecting different stimulation parameter values such as electrode combinations, amplitudes, pulse frequencies, or other parameter values for compensating for various locations of target tissue or feedback related to changes in patient condition or tissue state. Parameter selection instructions 217 may include instructions for processing circuitry 210 to select parameter values based on various feedback variables. Notification instructions 218 may define instructions that control processing circuitry 210 actions such as transmiting an alert or other notification to an external device, such as programmer 104, that therapy is on or off, or if changes to AEF therapy have been made or are recommended.

[0077] In some examples, the sense and stimulation electrode combinations may include the same subset of electrodes 116, 118, a housing of IMD 106 functioning as an electrode, or may include different subsets or combinations of such electrodes. Thus, memory 211 can store a plurality' of sense electrode combinations and, for each sense electrode combination, store information identifying the stimulation electrode combination that is associated with the respective sense electrode combination. The associations between sense and stimulation electrode combinations can be determined, e.g., by a clinician or automatically by processing circuitry 210. In some examples, corresponding sense and stimulation electrode combinations may comprise some or all of the same electrodes. In other examples, however, some or ah of the electrodes in corresponding sense and stimulation electrode combinations may be different. For example, a stimulation electrode combination may include more electrodes than the corresponding sense electrode combination in order to increase the efficacy of the A EF therapy. [0078] Stimulation generator 202, under the control of processing circuitry 210, generates stimulation signals for delivery to patient 112 via selected combinations of electrodes 1 16, 1 18. An example range of electrical stimulation parameters believed to be effective in AEF therapy to manage cellular activity include:

1. Frequency (e.g., waveform frequency or pulse rate): between approximately 50 kHz and approximately 500 kHz, such as between approximately 100 kHz to 300 kHz, or such as approximately 150 kHz or 200 kHz. 2. In the case of a voltage controlled system. Voltage Amplitude: between approximately 0.1 volts and approximately 50 volts, such as between approximately 2 volts and approximately 10 volts.

3. In the alternative case of a current controlled system. Current Amplitude: between approximately 0.2 milliamps to approximately 100 milliamps, such as between approximately 1.3 milliamps and approximately 2.0 milliamps.

4. Pulse Width: between approximately 1 microseconds and approximately 10 microseconds, such as between approximately 1 microseconds and approximately 5 microseconds, or between approximately 2. microseconds and approximately 10 microseconds.

5. Cycle time (e.g., communication time), which is the time a waveform remains consistent before switching off or switching to a new waveform. The cycle time may be selected from a range of 30 seconds and 30 minutes, or within a range from 1 minute to 10 minutes. Shorter and longer cycle times may be used in other examples.

[0079] Accordingly, in some examples, stimulation generator 202 generates electrical stimulation signals in accordance with the electrical stimulation parameters noted above. Other ranges of therapy parameter values may also be useful , and may depend on the target stimulation site within patient 1 12. While stimulation pulses are described, stimulation signals may be of any form, such as continuous-time signals (e.g., sine waves) or the like. Stimulation signals configured to el icit ECAPs or other evoked physiological signals may be similar or different from the above parameter value ranges. In addition, sensing circuitry 204 may be configured to sense signals via one or more electrode combinations on one or more leads 114 (e.g., the same or different electrodes may deliver stimulation and sense electrical signals).

[0080] Processing circuitry 210 may include fixed function processing circuitry and/or programmable processing circuitry, and may comprise, for example, any one or more of a microprocessor, a controller, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field-programmable gate array (FPGA), discrete logic circuitry, or any other processing circuitry configured to provide the functions attributed to processing circuitry 210 herein may be embodied as firmware, hardware, software or any combination thereof. Processing circuitry 210 may control stimulation generator 202 according to therapy programs 214 stored in memory 211 to apply particular stimulation parameter values specified by one or more of programs, such as voltage amplitude or current amplitude, pulse width, or pulse rate. [0081] In the example shown in FIG. 2, the set of electrodes 116 includes eiectrodes 116A, 116B, 116C, and 116D, and the set of eiectrodes 118 includes electrodes 118A, 118B, I I 8C, and 118D. Processing circuitry 210 also controls switch module 206 to apply the stimulation signals generated by stimulation generator 202 to seiected combinations of electrodes 116, 118. In particular, switch module 204 may couple stimulation signals to selected conductors within leads 114, which, in turn, deliver the stimulation signals across selected electrodes 116, 118. Swatch module 206 may be a swatch array, swatch matrix, multiplexer, or any other type of switching module configured to selectively couple stimulation energy to selected electrodes 116, 118 and to selectively sense neurological brain signals with selected electrodes 116, 118. Hence, stimulation generator 202 is coupled to electrodes 116, 118 via swatch module 206 and conductors within leads 114. In some examples, however, IMD 106 does not include swdtch module 206, such as if each electrode is assigned a respective current and sink (e.g., independent current source).

[0082] Stimulation generator 202 may be a single channel or multi-channel stimulation generator. In particular, stimulation generator 202 may be capable of delivering a single stimulation pulse, multiple stimulation pulses, or a continuous signal at a given time via a single electrode combination or multiple stimulation pulses at a given time via multiple electrode combinations. In some examples, however, stimulation generator 202 and switch module 206 may be configured to deliver multiple channels on a time-interleaved basis. For example, switch module 206 may serve to time divide the output of stimulation generator 202 across different electrode combinations at different times to deliver multiple programs or channels of stimulation energy to patient 112 (e.g., cycling between regimes of stimulation on a fixed or variable sequence). Alternatively, stimulation generator 202 may comprise multiple voltage or current sources and sinks that are coupled to respective electrodes to drive the electrodes as cathodes or anodes. In this example, IMD 106 may not require the functionality of switch module 206 for time-interleaved multiplexing of stimulation via different electrodes.

[0083] Electrodes 116, 118 on respective leads 114 may be constructed of a variety of different designs. For example, one or both of leads 114 may include two or more electrodes at each longitudinal location along the length of the lead, such as multiple electrodes at different perimeter locations around the perimeter of the lead at each of the locations A, B, C, and D. On one example, the electrodes may be electrically coupled to switch module 206 via respective wires that are straight or coiled within the housing or the lead and run to a connector at the proximal end of the lead. In another example, each of the electrodes of the lead may be electrodes deposited on a thin film. The thin film may include an electrically conductive trace for each electrode that runs the length of the thin film to a proximal end connector. The thin film may then be wrapped (e.g., a helical wrap) around an internal member to form the lead 114. These and other constructions may be used to create a lead with a complex electrode geometry. [0084] Although sensing module 204 is incorporated into a common housing with stimulation generator 202 and processing circuitry 210 in FIG. 2, in other examples, sensing module 204 may be in a separate housing from IMD 106 and may communicate with processing circuitry’ 210 via wared or wareless communication techniques. Example neurological brain signals include, but are not limited to, a signal generated from local field potentials (LFPs) within one or more regions of brain 2.8. EEG and ECoG signals are examples of other types of electrical signals that may be measured within brain 120 and/or outside of brain 120. Other examples include sensed signals representative of electric field or voltage gradients caused by a remote electrode as recorded by a proximal electrode or electrode pair. Instead of, or in addition to, LFPs, IMD 106 may be configured to detect patterns of single- unit activity and/or multi- unit activity'. IMD 106 may sample this activity' at rates above 1,000 Hz, and in some examples within a frequency range of 6,000 Hz to 500,000 Hz. IMD 106 may identify the wave-shape of single units and/or an envelope of unit modulation that may be features used to differentiate or rank electrodes. In some examples, this technique may include phase-amplitude coupling to the envelope or to specific frequency bands in the LFPs sensed from the same or different electrodes. In some examples, the sampling technique may be set to identify the electric field strength at any location. For example, IMD 106 may include a peak following circuitry that holds the amplitude of a field of a specific frequency for later sampling. Alternatively, the response of a resonant circuit may be tuned to the AEF frequency might sampled to infer the field strength of the desired signal. In some examples, IMD 106 may be configured to detect a geometric response within the network of 114 electrodes in response to a single-pulse electrical stimulation generated within the system. The utilization of a basis profile curve algorithm to analyze this geometric response as sensed within the multitude of 114 electrodes within the system can permit diagnostics, such as demonstration of patters indicative of depression, anxiety, or tumor progression within the cerebral environment. IMD 106 may conduct this real-time diagnostic modality in an interleaved manner to permit ongoing stimulation with periodic analysis.

[0085] Sensor 212 may include one or more sensing elements that sense values of a respective patient parameter, such as patient activity (e.g., movement and/or sleep). For example, sensor 212 may include one or more accelerometers, optical sensors, chemical sensors, temperature sensors, pressure sensors, or any other types of sensors. Sensor 212 may output patient parameter values that may be used as feedback to control delivery of AEF therapy. IMD 106 may include additional sensors within the housing of IMD 106 and/or coupled via one of leads 114 or other leads. In addition, IMD 106 may receive sensor signals wirelessly from remote sensors via telemetry’ module 208, for example. In some examples, one or more of these remote sensors may be external to patient (e.g., carried on the external surface of the skin, attached to clothing, or otherwise positioned external to the patient).

[0086] Telemetry module 208 supports wireless communication between IMD 106 and an external programmer 104 or another computing device under the control of processing circuitry 210. Processing circuitry 210 of IMD 106 may receive, as updates to programs, values for various stimulation parameters such as magnitude and electrode combination, from programmer 104 via telemetry module 208. The updates to the therapy programs may be stored within therapy programs 214 portion of memory 211 . In addition, processing circuitry’ 210 may control telemetry' module 208 to transmit alerts or other information to programmer 104 that indicate a lead moved with respect to tissue. Telemetry module 208 in IMD 106, as well as telemetry' modules in other devices and systems described herein, such as programmer 104, may accomplish communication by radiofrequency (RF) communication techniques. In addition, telemetry module 208 may communicate with external medical device programmer 104 via proximal inductive interaction of IMD 106 with programmer 104. Accordingly, telemetrymodule 208 may send information to external programmer 104 on a continuous basis, at periodic intervals, or upon request from IMD 106 or programmer 104.

[0087] Power source 220 delivers operating power to various components of IMD 106. Power source 220 may include a small rechargeable or non-rechargeable battery and a power generation circuit to produce the operating power. Recharging may be accomplished through proximal inductive interaction between an external charger and an inductive charging coil within IMD 220. In some examples, power requirements may be small enough to allow IMD 220 to utilize patient motion and implement a kinetic energy-scavenging device to trickle charge a rechargeable battery. In other examples, traditional batteries may be used for a limited period of time. In other examples, IMD 106 may include a power receiving antenna an corresponding circuitry to continually receive external power that enables IMD 106 to deliver electric field therapy indefinitely without possible internal power source dram.

[0088] According to the techniques of the disclosure, processing circuitry 210 of IMD 106 delivers, electrodes 116, 118 interposed along leads 114 (and optionally switch module 206), electrical stimulation therapy to patient 112. The AEF therapy is defined by one or more therapy programs 214 having one or more parameters stored within memory 211. For example, the one or more parameters include a current amplitude (for a current-controlled system) or a voltage amplitude (for a voltage-controlled system), a pulse rate or frequency, and a pulse width, or quantity of pulses per cycle. In examples where the electrical stimulation is delivered according to a “burst” of pulses, or a series of electrical pulses defined by an “on-time” and an “off-time,” the one or more parameters may further define one or more of a number of pulses per burst, an on-time, and an off-time,

[0089] In some examples, the plurality of electrode combinations includes at least one electrode combination comprising electrodes disposed at different positions around a perimeter, or circumference, of the longitudinal axis lead. In some examples, at least one electrode combination includes electrodes disposed at different positions along a longitudinal axis of the lead implanted in the patient. These electrodes may be placed at the same or different radial positions with respect to the longitudinal axis.

[0090] FIG. 3 is a block diagram of the external programmer 104 of FIG. 1 for planning and/or controlling delivery of AEF therapy using available electrodes according to an example of the techniques of the disclosure. Although programmer 104 may generally be described as a hand-held device, programmer 104 may be a larger portable device or a more stationary device. In some examples, programmer 104 may be referred to as a tablet computing device or a smart phone computing device. In addition, in other examples, programmer 104 may be included as part of a bed-side monitor, an external charging device or include the functionality of an external charging device. As illustrated in FIG. 3, programmer 104 may include a processing circuitry 310, memory 311, user interface 302, telemetry module 308, and power source 320. Memory 311 may store instructions that, when executed by processing circuitry 310, cause processing circuitry 310 and external programmer 104 to provide the functionality ascribed to external programmer 104 throughout this disclosure. Each of these components, or modules, may include electrical circuitry that is configured to perform some or all of the functionality described herein. For example, processing circuitry 310 may include processing circuitry configured to perform the processes discussed with respect to processing circuitry 310.

[0091] In general, programmer 104 comprises any suitable arrangement of hardware, alone or in combination with software and/or firmware, to perform the techniques attributed to programmer 104, and processing circuitry 310, user interface 302, and telemetry’ module 308 of programmer 104. In various examples, programmer 104 may include one or more processors, which may include fixed function processing circuitry and/or programmable processing circuitry, as formed by, for example, one or more microprocessors, DSPs, ASICs, FPGAs, or any other equivalent integrated or discrete logic circuitry, as well as any combinations of such components. Programmer 104 also, in various examples, may include a memory 311, such as RAM, ROM, PROM, EPROM, EEPROM, flash memory, a hard disk, a CD-ROM, comprising executable instructions for causing the one or more processors to perform the actions attributed to them. Moreover, although processing circuitry 310 and telemetry module 308 are described as separate modules, in some examples, processing circuitry 310 and telemetry module 308 may be functionally integrated with one another. In some examples, processing circuitry’ 310 and telemetry module 308 correspond to individual hardware units, such as ASICs, DSPs, FPGAs, or other hardware units.

[0092] Memory 31 1 (e.g., a storage device) may store instructions that, when executed by processing circuitry 310, cause processing circuitry 310 and programmer 104 to provide the functionality ascribed to programmer 104 throughout this disclosure. For example, memory 311 may include instructions that cause processing circuitry 310 to obtain a parameter set from memory, present a model of patient anatomy for predicting electrical field strengths, provide an interface that recommends or otherwise facilitates parameter value selection, or receive a user input and send a corresponding command to 1MD 106, or instructions for any other functionality. In addition, memory 311 may include a plurality of programs, where each program includes a parameter set that defines stimulation therapy.

[0093] User interface 302 may include a button or keypad, lights, a speaker for voice commands, a display, such as a liquid crystal (LCD), light-emitting diode (LED), or organic light-emitting diode (OLED). In some examples the display may be a presence-sensitive screen, such as a touch screen. User interface 302 may be configured to display any information related to the delivery of stimulation therapy , detected trigger events, progression of therapy, suggested stimulation parameter values, sensed patient parameter values, or any other such information. User interface 302 may also receive user input via user interface 302. The input may be, for example, in the form of pressing a button on a keypad or selecting an icon from a touch screen. [0094] Telemetry module 308 may support wireless communication between IMD 106 and programmer 104 under the control of processing circuitry 310. Telemetry module 308 may also be configured to communicate with another computing device via wireless communication techniques, or direct communication through a wired connection. In some examples, telemetry module 308 provides wireless communication via an RF or proximal inductive medium. In some examples, telemetry module 308 includes an antenna, which may take on a variety of forms, such as an internal or external antenna. In some examples, IMD 106 and/or programmer 104 may communicate with remote servers via one or more cloud-services in order to deliver and/or receive information between a clinic and/or programmer,

[0095] Examples of local wireless communication techniques that may be employed to facilitate communication between programmer 104 and IMD 106 include RF communication according to the 802.11 or Bluetooth specification sets or other standard or proprietary' telemetry protocols. Security protocols and encryption techniques may be applied to enhance the security of the communication techniques. In addition, other external devices may be capable of communicating with programmer 104 without needing to establish a secure wireless connection. As described herein, telemetry module 308 may be configured to transmit a spatial electrode movement pattern or other stimulation parameter values to IMD 106 for delivery of stimulation therapy.

[0096] FIG. 4 is a block diagram illustrating an example system 124 that includes an external device, such as a server 130, and one or more computing devices 132A-132N, that are coupled to IMD 106 and external programmer 104 shown in FIG. 1 via a network 126. In this example, IMD 106 may use its telemetry circuit to communicate with external programmer 104 via a first wireless connection, and to communication with an access point 128 via a second wireless connection. [0097] In the example of FIG. 4, access point 128, external programmer 104, server 130, and computing devices 132A-132N are interconnected, and able to communicate with each other, through network 126. In some cases, one or more of access point 128, external programmer 104, server 130, and computing devices 132A-132N may be coupled to network 126 through one or more war el ess connections. IMD 106, external programmer 104, server 130, and computing devices 132A-132N may each comprise one or more processors, such as one or more microprocessors, digital signal processors (DSPs), application specific integrated circuits (ASICs), field programmable gate arrays (FPGAs), programmable logic circuitry, or the like, that may perform various functions and operations, such as those described in this disclosure.

[0098] Access point 128 may comprise a device, such as a home monitoring device, that connects to network 126 via any of a variety of connections, such as telephone dial-up, digital subscriber line (DSL), or cable modem connections. In other embodiments, access point 128 may be coupled to network 126 through different forms of connections, including wired or wireless connections.

[0099] During operation, IMD 106 may collect and store various forms of data. For example, IMD 106 may collect sensed posture state information during therapy that indicate how patient 112 moves throughout each day. IMD 106 may store usage statistics (e.g., delivery times in hours per day, percentage of on time, compliance to the dosing schedule, etc.) for later presentation to a user or otherwise evaluating therapy and/or patient compliance. In some cases, IMD 106 may directly analyze the collected data to evaluate the status of the patient and the delivery of AEF therapy or any other aspects of the patient. In other cases, however, IMD 106 may send stored data relating to AEF therapy to external programmer 104 and/or server 130, either wirelessly or via access point 128 and network 126, for remote processing and analysis. [0100] For example, IMD 106 may sense, process, trend and evaluate sensed data and/or AEF therapy information. This communication may occur in real time, and network 126 may allow a remote clinician to review the data representative of AEF therapy by receiving a presentation of the data on a remote display, e.g., computing device 132 A. Alternatively, processing, trending and evaluation functions may be distributed to other devices such as external programmer 104 or server 130, which are coupled to network 126. In addition, AEF therapy data may be archived by any of such devices, e.g., for later retrieval and analysis by a clinician. [0101] In some cases, server 130 may be configured to provide a secure storage site for archival of AEF therapy information that has been collected from I.MD 106 and/or external programmer 104. Network 126 may comprise a local area network, wide area network, or global network, such as the Internet. In other cases, external programmer 104 or server 130 may assemble AEF therapy information in web pages or other documents for viewing by trained professionals, such as clinicians, via viewing terminals associated with computing devices 132A- 132N. Sy stem 124 may be implemented, in some aspects, with general network technology and functionality similar to that provided by the Medtronic CareLink® Network developed by Medtronic, Inc., of Minneapolis, AIN.

[0102] Although some examples of the disclosure may involve AEF therapy information and data, system 124 may be employed to distribute any information relating to the treatment of patient 112 and the operation of any device associated therewith. For example, system 124 may allow therapy errors or device errors to be immediately reported to the clinician. In addition, system 124 may allow the clinician to remotely intervene in the therapy and reprogram IMD 106, patient programmer 104, or communicate with patient 1 12. In an additional example, the clinician may utilize system 124 to monitor multiple patients and share data with other clinicians in an effort to coordinate rapid evolution of effective treatment of patients..

[0103] FIGS. 5 A and 5B are conceptual diagrams of example leads 400 and 410, respectively, with respective electrodes carried by the lead. As shown in FIGS. 5A and 5B, leads 400 and 410 are embodiments of leads 114 shown in FIG. 1 . As shown in FIG. 5A, lead 400 includes four electrode levels 404 (includes levels 404A-404D) mounted at various lengths of lead housing 402. Lead 400 is inserted into through cranium 122 to a target position within brain 18. In some examples, external electrodes may be used instead of, or in addition to, leads such as lead 400.

[0104] Lead 400 is implanted within brain 120 at a location determined by the clinician that may be near an anatomical region to receive AEF therapy, such as a tumor location or resection bed. Electrode levels 404A, 404B, 404C, and 404D are equally spaced along the axial length of lead housing 402 at different axial positions. Each electrode level 404 may have one, tw'O, three, or more electrodes located at different angular positions around the circumference (e.g., around the perimeter) of lead housing 402. As shown in FIG. 5A, electrode level 404A and 404D include a single respective ring electrode, and electrode levels 404B and 404C each include three electrodes at different circumferential positions. This electrode pattern may be referred to as a 1 - 3-3-1 lead in reference to the number of electrodes from the proximal end to the distal end of lead 400. Electrodes of one circumferential location may be lined up on an axis parallel to the longitudinal axis of lead 400. Alternatively, electrodes of different electrode levels may be staggered around the circumference of lead housing 402. In addition, lead 400 or 410 may include asymmetrical electrode locations around the circumference, or perimeter, of each lead or electrodes of the same level that have different sizes. These electrodes may include semicircular electrodes that may or may not be circumferentially aligned between electrode levels. [0105] Lead housing 402 may include a radiopaque stripe or other one or more radiopaque marker (not shown) along the outside of the lead housing. The radiopaque stripe corresponds to a certain circumferential location that allows lead 400 to be imaged and reliably localized when implanted in patient 112. Using the images of patient 112, the clinician can use the radiopaque stripe as a marker for the exact orientation of lead 400 within the brain of patient 112.

Orientation of lead 400 may be needed to easily program the stimulation parameters by generating the correct electrode configuration to match the stimulation field defined by the clinician. In other embodiments, a marking mechanism other than a radiopaque stripe may be used to identify the orientation of lead 400, These marking mechanisms may include something similar to a tab, detent, or other structure on the outside of lead housing 402. In some embodiments, the clinician may note the position of markings along a lead wire during implantation to determine the orientation of lead 400 within patient 112, In some examples, programmer 104 may update the orientation of lead 400 in visualizations based on the movement of lead 400 from sensed signals. Any mechanical or radiopaque markers may be provided in any leads and/or lead structures described herein in order to identify locations of the leads and/or electrodes implanted within the patient and relative to target tissue.

[0106] FIG. 5B illustrates lead 410 that includes multiple electrodes at different respective circumferential positions at each of levels 414A-414D. Similar to lead 400, lead 410 is inserted through a burr hole, craniostomy, or craniotomy in cranium 122 to a target location within brain 120. Lead 410 includes lead housing 412, Four electrode levels 414 (414A-414D) are located at the distal end of lead 410. Each electrode level 414 is evenly spaced from the adjacent electrode level and includes two or more electrodes. In one embodiment, each electrode level 414 includes three, four, or more electrodes distributed around the circumference of lead housing 412. Therefore, lead 410 includes 414 electrodes in a preferred embodiment. Each electrode may be substantially rectangular in shape. Alternatively, the individual electrodes may have alternative shapes, e.g., circular, oval, triangular, rounded rectangles, or the like.

[0107] In alternative embodiments, electrode levels 404 or 414 are not evenly spaced along the longitudinal axis of the respective leads 400 and 410. For example, electrode levels 404C and 404D may be spaced approximately 3 millimeters (mm) apart while electrodes 404A and 404B are 10 mm apart. Variable spaced electrode levels may be useful in reaching target anatomical regions deep within brain 120 while avoiding potentially undesirable anatomical regions. The variable spacing may also be utilized to enhance the resulting AEF therapy generated between a pair of electrodes carried on any of leads 400 or 410. Further, the electrodes in adjacent levels need not be aligned in the direction as the longitudinal axis of the lead, and instead may be oriented diagonally with respect to the longitudinal axis.

[0108] Leads 400 and 410 are substantially rigid to prevent the implanted lead from varying from the expected lead shape. Leads 400 or 410 may be substantially cylindrical in shape. In other embodiments, leads 400 or 410 may be shaped differently than a cylinder. For example, the leads may include one or more curves to reach target anatomical regions of brain 120. In some embodiments, leads 400 or 410 may be similar to a flat paddle lead or a conformable lead shaped for patient 112. Also, in other embodiments, leads 400 and 410 may any of a variety of different polygonal cross sections (e.g., triangle, square, rectangle, octagonal, etc.) taken transverse to the longitudinal axis of the lead.

[0109] As shown in the example of lead 400, the plurality of electrodes of lead 400 includes a first set of three electrodes disposed at different respective positions around the longitudinal axis of the lead and at a first longitudinal position along the lead (e.g., electrode level 404B), a second set of three electrodes disposed at a second longitudinal position along the lead different than the first longitudinal position (e.g., electrode level 404C), and at least one ring electrode disposed at a third longitudinal position along the lead different than the first longitudinal position and the second longitudinal position (e.g., electrode level 404A and/or electrode level 404D). In some examples, electrode level 404D may be a bullet tip or cone shaped electrode that covers the distal end of lead 402.

[0110] FIGS. 5C-5F are transverse cross-sections of example stimulation leads having one or more electrodes around the circumference of the lead. As shown in FIGS. 5C-5F, one electrode level, such as one of electrode levels 404 and 414 of leads 400 and 410, are illustrated to show electrode placement around the perimeter, or around the longitudinal axis, of the lead. FIG. 5C shows electrode level 500 that includes circumferential electrode 502. Circumferential electrode 502 encircles the entire circumference of electrode level 500 and may be referred to as a ring electrode in some examples. Circumferential electrode 502 may be utilized as a cathode or anode as configured by the user interface. Any of the electrodes of FIGS. 5A-5F may be configured to act as a sensing electrode, or as part of a sensing electrode combination, within a tissue environment.

[0111] FIG. 5D shows electrode level 510 which includes two electrodes 512 and 514. Each electrode 512 and 514 wraps approximately 170 degrees around the circumference of electrode level 510. Spaces of approximately 10 degrees are located between electrodes 512 and 514 to prevent inadvertent coupling of electrical current between the electrodes. Smaller or larger spaces between electrodes (e.g., between 10 degrees and 30 degrees) may be provided in other examples. Each electrode 512 and 514 may be programmed to act as an anode or cathode.

[0112] FIG. 5E shows electrode level 520 which includes three equally sized electrodes 522, 524 and 526. Each electrode 522, 524 and 526 encompass approximately 110 degrees of the circumference of electrode level 520. Similar to electrode level 510, spaces of approximately 10 degrees separate electrodes 522, 524 and 526. Smaller or larger spaces between electrodes (e.g., between 10 degrees and 30 degrees) may be provided in other examples. Electrodes 522, 524 and 526 may be independently programmed as an anode or cathode for stimulation.

[0113] FIG. 5F shows electrode level 530 which includes four electrodes 532, 534, 536 and 538. Each electrode 532, 534, 536 and 538 covers approximately 80 degrees of the circumference with approximately 10 degrees of insulation space between adjacent electrodes. Smaller or larger spaces between electrodes (e.g., between 10 degrees and 30 degrees) may be provided in other examples. In other embodiments, up to ten or more electrodes may be included within an electrode level. In alternative embodiments, consecutive electrode levels of lead 114 may include a variety of electrode levels 500, 510, 520, and 530. For example, lead 114 (or any other lead described herein) may include electrode levels that alternate between electrode levels 510 and 530 depicted in FIGS. 5D and 5F. In this manner, various stimulation field shapes may be produced within brain 120 of patient 112. Further the above-described sizes of electrodes within an electrode level are merely examples, and the invention is not limited to the example electrode sizes.

[0114] Also, the insulation space, or non-electrode surface area, may be of any size. Generally, the insulation space is between approximately 1 degree and approximately 20 degrees. More specifically, the insulation space may be between approximately 5 and approximately 15 degrees. In other examples, insulation space may be between approximately 10 degrees and 30 degrees or larger. Smaller insulation spaces may allow a greater volume of tissue to be stimulated. In alternative embodiments, electrode size may be varied around the circumference of an electrode level. In addition, insulation spaces may vary in size as well. Such asymmetrical electrode levels may be used in leads implanted at tissues needing certain shaped stimulation fields. In some examples, the insulation region of the lead may include a projection that extends radially outward from the lead body. Although not shown, any lead or electrode array may include one or more fixation elements (e.g., tines, screws, electrode shapes, adhesives, etc.) that enable the lead or electrodes to be relatively fixed in position with respect to surrounding tissue.

[0115] FIG. 6 is a flowchart illustrating an example technique for delivering AEF therapy to a patient. The technique of FIG. 6 will be described with respect to processing circuitry 210 of IMD 106 in FIG. 2. However, other processors, devices, or combinations thereof, such as processing circuitry' 310 of programmer 104 or some combination of devices or processors, may perform the techniques of FIG. 6 in other examples. The technique of FIG 6 may apply to therapies other than AEF therapy in a similar manner.

[0116] As shown in the example of FIG. 6, processing circuitry 210 receives a request to deliver alternating electric field (AEF) therapy (600), such as from external programmer 104 or a pre-programmed delivery schedule. Processing circuitry 210 then determines therapy parameter values for AEF therapy (602). This determination may be retrieval of parameter values from memory or determining one or more parameter values based on a delivery schedule, sensed data, or any other information. For example, the parameter values may be based on the spatial location of electrodes carried by the lead, such as lead 114 or any leads described herein.

[0117] Processing circuitry 210 then delivers the AEF therapy by delivering a first electric field from a first electrode combination (604) alternating with delivery of a second electric field from a second electrode combination different than the first electrode combination (606). In some examples, the first and second electrical fields may be phase shifted so as to not overlap. In other examples, the first and second electrical fields may be phase shifted so as to partially overlap in time. In some examples, the first and second electrical fields may be temporally interleaved to be fully non-overlapping or partially overlapping. Although the first and second electrical fields may be delivered with the same amplitude and frequency, the first and second electrical fields may be defined by different amplitudes and/or different frequencies (e.g., 150 kHz and 200 kHz). The first and second electrode combinations may use completely different electrodes or partially different electrodes, for example. The first and second electrode combinations may be selected to generate respective electrical fields that are orthogonal to each other or oblique, in some examples. Although all electrodes of the first and second electrode combinations may be implanted in some examples, one or more of the electrodes may be external electrodes in other examples. In general, processing circuitry’ 210 may determine the frequency of electrical field alternation based on the number of electrical combinations used to alternate the electrical fields for therapy. No interphase period may be required between the delivery of each electric field, although processing circuitry’ 210 may provide an interphase period in some examples.

[01 IS] Processing circuitry 210 then determines whether to terminate the AEF therapy (608).

If processing circuitry’ 210 determines that AEF therapy is not to be terminated, processing circuitry' 210 continues to deliver the first and second electric fields (604 and 606). If processing circuitry 210 determines that AEF therapy is to be terminated or otherwise paused, processing circuitry 210 stops delivering the AEF therapy to the patient (610).

[0119] FIG. 7 is a conceptual diagram illustrating an example multiple pronged lead configured to deliver alternating electric field (AEF) therapy. As shown in the example of FIG.

7, system 700 includes IMD 106 couped to lead 702 via lead extension 110. System 700 may be an example of system 100 described herein, and lead 702 may be an example of one of leads 114 described herein. Lead 702 includes a housing from which curved prongs 704 extend out from the distal end of the housing. Curved prongs 704 are each structures that carry one or more respective electrodes. Curved prongs 704 may be configured to position the respective electrodes within or around tissue resection region 706. The electrodes carried by curved prongs 704 may be configured to produce an electric field in response to IMD 106 driving electrical current through the respective electrodes. In some examples, electrodes of curved prongs from two or more different leads may be used to deliver AEF therapy or some other electrical field modulation therapy. The electric fields from each electrode may be alternating in time in order to produce an effect similar to AEF therapy described herein in order to provide various treatments, such as reducing or preventing cell division for treating glioblastoma.

[0120] In the example of FIG. 7, lead 702 includes three curved prongs 704 that extend out from the distal end of the housing of lead 702. In other examples, lead 702 may include two curved prongs, four curved prongs, or more than four curved prongs. In some examples, curved prongs 704 may be equally spaced around a perimeter or circumference of the housing of lead 702, but in other examples, curved prongs may have different circumferential spacing between each curved prong. In some examples, each curved prong may have an electrically conductive portion configured to function as an electrode. In other examples, each curved prong may cany one or more electrodes coupled to the structure of the respective curved prong. Although curved prongs 704 are illustrated has assuming a curved shape when extended out from the housing of lead 702, prongs 704 may be straight, or include curved and straight portions, in other examples. [0121] FIG. 8A-8F are conceptual diagrams illustrating example configurations of a multiple pronged lead 710. Lead 710 is an example of lead 702 of FIG. 7. Lead 710 includes housing 802, and curved prongs 804, 806, and 808 surrounding straight prong 810. All curved and straight prongs are configured to be housed within a lumen of housing 802 in a retracted or collapsed configuration and configured to be extended di stally from the distal end of housing 802 in the extended or expanded configuration. As shown in FIG. 8A, housing 802 retains curved prongs 804, 806, and 808 within the lumen of housing 802. In this collapsed or retracted configuration, lead 702 may be inserted into the body tissue of interest during an implanted procedure. Curved prongs 804, 806, and 808 and straight prong 810 may be constructed of a flexible material which may include a polymer, a shape memory metal (e.g., nitmol), or any other material configured to maintain a curved prong or straight prong as appropriate.

[0122] As shown in FIG. 8B, curved prongs 804, 806, and 808 are in the collapsed configuration and surround straight prong 810 in the axial view. In this example, straight prong 810 is disposed at the center of housing 802 and radially inward of all curved prongs 804, 806, and 808. Straight prong 810 is shown as a cylindrical structure, but the cross-section of each of curved prongs 804, 806, and 808 has a concave shape to create a lumen in which straight prong 810 can reside in the collapsed configuration. In other examples, straight prong 810 may have a non-circuiar cross-section and/or the curved prongs may have circular, oval, rectangular, or other non-concaved shape. In some examples, lead 710 may not include straight prong 810 at the center of curved prongs 804, 806, and 808. In some examples, lead 710 may include two, four, or more than four curved prongs.

[0123 ] As shown in FIG. 8C, once the distal end of housing 802 is inserted to the appropriate location, the clinician may deploy curved prongs 804, 806, and 808 and straight prong 810 distally out of the distal end of housing 802. For example, the clinician may pull housing 802 proximally with respect to the prongs. Each of curved prongs 804, 806, and 808 and straight prong 810 may include three electrodes. However, in other examples, the prongs may carry fewer, greater, or a different number of electrodes on each prong. Each electrode on each prong may be separated from each other. The distal tip of each prong may include an electrode or the most distal electrode may be proximal from the distal end of the respective prong. In some examples, one, some, or all of the electrodes carried on each prong may be disposed around the entire perimeter of the cross-section of the prong. In other examples, electrodes may be located on an inner surface of each prong (e.g., facing a central axis of lead 710) and/or located on an outer surface of each prong (e.g., facing away from the central axis of lead 710). FIG. 8D provides the axial view of a partially deployed curved prongs 804, 806, and 808. As shown in FIG. 8E, curved prongs 804, 806, and 808 and straight prong 810 are fully deployed, or extended, from the distal end of housing 802. In this extended or deployed configuration, the distal ends of curved prongs 804, 806, and 808 may be disposed at a maximum distance between each other. FIG. 8F illustrates the axial view of the fully deployed curved prongs 804, 806, and 808 and straight prong 810.

[0124] In this manner, lead 710 includes a plurality of structures in the form of curved prongs 804, 806, and 808. Each of the curved prongs include one or more electrodes of a plurality of electrodes, and each prong of the plurality of curved prongs 804, 806, and 808 include a distal end that curves in a radial direction away from a longitudinal axis of housing 802. The longitudinal axis of housing 802 may run through the middle of the lumen of housing 802. In the extended or deployed configuration, curved prongs 804, 806, and 808 are extended out from the distal end of housing 802. In the collapsed configuration curved prongs 804, 806, and 808 are straightened and disposed within the lumen of housing 802, In some examples, lead 710 includes a structure that is center straight prong 810 that also includes one or more electrodes. Center straight prong 810 may be disposed radially inward from each prong of the plurality of curved prongs 804, 806, and 808.

[0125] FIG. 9 is a cross-sectional view of an example lead 902 including multiple prongs 904, 906, and 910. Lead 902 may be similar to lead 702 and 710. The cross-section in FIG. 9 illustrates one example of how prongs 904 and 906 may be deployed from housing 918. Prongs 904 and 906 may be curved prongs similar to curved prongs 804, 806, and 808 of lead 710. [0126] As show'll in FIG. 9, lead 902 includes housing 918 and inner filler 916 that resides generally radially inward from outer filler 914 represented by outer filler portion 914A and outer filler portion 914B. Prongs 904 and 906 may be flexible and configured to be moved through the curved channels defined by inner filler 916 and outer filler 914. These curved channels can cause bends 912A and 912B of prongs 904 and 906, respectively, in order for prongs 904 and 906 to be forced out from distal end 908 of housing 918. Programs 904 and 906 may extend our from distal end 908 of housing 918 at an angle A with respect to a longitudinal axis of lead 902, which may be the same or different for each prong. Inner filler 916 may also define a center channel through which center prong 910 may be extended through housing 918. Prong 910 may be shaped and function similar to prongs 904 and 906 in some examples.

[0127] FIG. 10 is a conceptual diagram illustrating an expandable cone electrode lead 1002. Expandable cone electrode lead 1002 may be an example of lead 114. As shown in the example of FIG, 10, expandable cone electrode lead 1002 includes housing 1004 and flexible frame 1010 extending from a distal end of housing 1004. In this manner, expandable cone electrode lead 1002 may include one or more structures that include flexible frame 1010 that defines a conical shape. For example, flexible frame 1010 may be constructed of a patern of struts or other components using a shape memory material such as ni tinol or a flexible polymer. For example, flexible frame 1010 may include a plurality of flanges disposed at different circumferential locations around the longitudinal axis of housing 1004. Flexible frame 1010 may include a wider end configured to be distal from the distal end of housing 1004 and a narrow end configured to be proximal to the distal end of housing 1004. Lead 1002 may include electrode 1006 disposed within the narrow end of flexible frame 1010. In this manner, electrode 1006 may be disposed at a center of flexible frame 1010 and housing 1004.

[0128] Lead 1002 also includes a conical covering 1008 that is configured to cover at least a portion of flexible frame 1010. Conical covering 1008 may be constructed of a polymer or other material configured to encase flexible frame 1010. In some examples, lead 1002 may include a plurality of electrodes disposed an a radially outward surface of flexible frame 1010 and/or a radially inward surface of flexible frame 1010. These electrodes carried by flexible frame 1010 may be in addition to or instead of electrode 1006. Flexible frame 1010 may also be configured to be retracted and extended out from housing 1004. In this manner, lead 1002 can be inserted within the patient when flexible frame 1010 is in the collapsed or retracted configuration at least partially within housing 1004 and then deployed out of the distal end of housing 1004 into the conical shape as shown in FIG. 10.

[0129] FIG. 11 is a flowchart illustrating an example technique for implanting an expandable electrode configuration to a patient. The method of FIG. 11 will be described with respect to lead 710, but the technique may be used to implant and lead that includes expandable or deployable structures such as lead 702, 902, or 1002.

[0130] As shown in the example of FIG. 11, a clinician can insert the distal end of lead 710 into patient 122 when the electrodes and structures, such as prongs 804, 806, and 808 are in the collapsed configuration (1102). The clinician can then position the distal end of housing 802 proximate the edge of the target tissue (1104). For example, the clinician may be positioned such that the electrodes can be deployed adjacent to the tissue resection region from which tumor cells have already been removed.

[0131] Once the distal end of housing 802 is in position, the clinician may extend the electrode segments, such as the structures in the form of curved prongs 804, 806, and 808 and straight prong 810 distally from the distal end of lead housing 802 and into the expanded configuration of lead 710 (1106). In the expanded configuration, prongs 804, 806, 808, and 810 may be disposed within or adjacent to the target tissue resection region. Once lead 710 is implanted, the clinician may couple the proximal end of lead 710 to a medical device such as IMD 106 (1108).

[0132] FIG. 12 is a conceptual diagram illustrating an expandable multiple filar lead 1200. As shown in the example of FIG. 12, multiple filar lead 1200 includes housing 1202 from which curved members 1204 extend. Curved members 1204 are filars or structures that carry respecti ve electrodes 1206 of the plurality of electrodes of lead 1200. In this manner, each curved member of curved members 1204 may include two or more electrodes 1206. Electrodes 1206 may be spaced from each other along the respective curved member 1204 such that each electrode can operate separately from, or together with, each other. Each curved member 1204 may be configured to curve in a radial direction away from a longitudinal axis of housing 1202. Each curved member 1204 also includes a distal end that meets distal ends of other curved members 1204. In the example of FIG. 12, the distal ends of curved members 1204 may be coupled to distal joint 1208.

[0133] The configuration of lead 1200 in FIG. 12 is the extended configuration in which curved members 1204 are extended out from the distal end of housing 1202. Prior to being in the extended configuration, curved members 1204 are configured to be in a collapsed configuration in which curved members 1204 are straightened and disposed within housing 1202. In the collapsed configuration, lead 1200 may be inserted within the tissue of the patient. Then, once implanted to the desired target tissue, the clinician may extend curved members 1204 out from the distal end of housing 1202 and into the curved members 1204 as shown. In the extended configuration, curved members 1204 may have a shape similar to an eggbeater.

[0134] FIG. 13 is a conceptual diagram illustrating a balloon lead 1302. As shown in the example of FIG, 13, balloon lead 1302 includes housing 1304 from which radially flexible member 1306 extends in a distal direction. In this manner, lead 1302 may include one or more structures that include radially flexible member 1306 (e.g., a balloon or other expandable structure). Radially flexible member 1306 may be configured to be expanded via fluid pressure within radially flexible member 1306. For example, housing 1304 may define a lumen through which fluid may be pumped into radially flexible member 1306 to increase the pressure of fluid and cause radially flexible member 1306 to expand from a collapsed configuration (to facilitate insertion of lead 1302 into the patient) to an expanded configuration (to position electrodes 1310 within a tissue resection region, for example). The fluid may be saline, a gas, or any other fluid. Radially flexible member 1306 may carry or include electrodes 1310 disposed at different, circumferential positions around the longitudinal axis of housing 1304 and around radially flexible member 1306.

[0135] Each electrode of electrodes 1310 may include an electrode structure configured to conform to a surface of radially flexible member 1306. Electrodes 1310 may be disposed on an interior surface of flexible member 1306, an exterior surface of flexible member 1306, or even within the material of flexible member 1306. Each electrode may have a plurality of flanges that extend from a central region in order to facilitate electrode flexibility while also increasing the surface area of each electrode. In some examples, radially flexible member 1306 may be configured to be expanded into a spherical shape in the expanded configuration, an ovoid configuration, or any other shape. Radially flexible member 1306 may also include electrically conductive struts 1308 configured to transmit electrical signals to and/or from electrodes 1310 and conductors disposed within housing 1304.

[0136] FIG. 14 is a conceptual diagram illustrating an expandable bell lead 1400. As shown in the example of FIG. 14, expandable bell lead 1400 includes housing 1402 from which radially flexible member 1404 extends in a distal direction. In this manner, lead 1400 may include one or more structures that include radially flexible member 1404 (e.g., a balloon or other expandable structure). Radially flexible member 1404 may be similar to radially flexible member 1306. Radially flexible member 1404 may be configured to form a bell shape in an expanded configuration. The bell shape may include a larger radius at a distal location than the radius at a proximal location of radially flexible member 1404. In this manner, radially flexible member 1404 may be configured to have a larger diameter at the distal location than a proximal portion of radially flexible member 1404, Lead 1400 may also include two or more electrodes 1406A and 1406B disposed at different circumferential positions are disposed on a distal portion of radially flexible member 1404. Each of electrodes 1406A and 1406B may be electrically coupled to respective conductor 1408A or 1408B.

[0137] Radially flexible member 1404 may be configured to be expanded via fluid pressure within radially flexible member 1404. For example, housing 1402 may define a lumen through which fluid may be pumped into radially flexible member 1404 to increase the pressure of fluid and cause radially flexible member 1404 to expand from a collapsed configuration (to facilitate insertion of lead 1400 into the patient) to an expanded configuration (to position electrodes 1406A and 1406B (collectively “electrodes 1406”) within a tissue resection region, for example). The fluid may be saline, a gas, or any other fluid. Radially flexible member 1404 may carry or include electrodes 1406 disposed at different circumferential positions around the longitudinal axis of housing 1402 and around radially flexible member 1404. In the expanded configuration, electrodes 1406 may be biased by radially flexible member 1404 against tissue of the tissue resection region. In some examples, electrodes 1406 may be rigid such that electrodes 1406 retain their shape due to the bias from radially flexible member 1404. In other examples, electrodes 1404 may be constructed of an electrode structure configured to conform to a surface of radially flexible member 1404.

[0138] FIG. 15 is a flowchart illustrating an example technique for implanting expandable balloon lead 1302 or other radially flexible member to a patient. The method of FIG. 15 will be described with respect to lead 1302, but the technique may be used to implant and lead that includes expandable or deployable balloons such as lead 1400.

[0139] As shown in the example of FIG. 15, a clinician can insert the distal end of lead 1302 into patient 122 when the balloon, such as radially flexible member 1306 is in the collapsed configuration (e.g., within housing 1304) (1502). The clinician can then position the distal end of housing 1304 proximate the edge of the target tissue ( 1504). For example, the clinician may be positioned such that electrodes 1310 carried by radially flexible member 1306 can be deployed adjacent to the tissue resection region from which tumor cells have already been removed.

[0140] Once the distal end of housing 1304 is in position, the clinician may cause fluid to be injected through the lumen of housing 1304 such that fluid pressure increases the volume of radially flexible member 1306 and expands radially flexible member 1306 distally from the distal end of housing 1304 and into the expanded configuration of lead 1302 (1506). In the expanded configuration, radially flexible member 1306 may dispose electrodes 1310 against tissue of the target tissue resection region. Once lead 1302 is implanted, the clinician may couple the proximal end of lead 1302 to a medical device such as IMD 106 (1508).

[0141] FIG. 16 is a conceptual diagram of an example configuration of multiple paddle leads 1610A and 1610B (collectively “paddle leads 161 O’ ¹ ) implantable to treat a target tissue 1606 of a patient for AEF therapy. As shown in FIG. 16, spatial volume 1602 indicates a three- dimensional representation of various elements associated with AEF therapy. Brain 1604 is shown together with paddle leads 1610. Resection bed 1606 indicates the location of the area from which a glioblastoma tumor was removed. Resection bed 1606 is shown as a solid shape for purposes of illustration, but any resection bed is actually the inner surfaces of tissue that remains after a tumor is removed. In other words, resection bed 1606 may be the tissue surrounding the void at which the tumor used to be located. Resection bed 1606 may alternatively be referred to as tissue resection region 1606. Initially, imaging data may be used to identify the location, size, and shape of resection bed 1606 with respect to other tissues or structures (not shown) identified within brain 1604 in order to assist the clinician to place two or more paddles 1610 adjacent to resection bed 1606. In some examples, a single paddle lead may be effective for delivering AEF therapy to the cells associated with resection bed 1606.

[0142] As shown in FIG. 16, leads 1610 may be disposed around the periphery of resection bed 1606. In other examples, leads 1610 may be placed within resection bed 1606 such that electrodes carried by paddle leads 1610 may be placed against the tissue surface of resection bed 1606. Paddle leads 1610 may include any array of electrodes that can be placed near the boundary of the tumor resection. This close placement of paddle lead 1610 may reduce complexity during or after resection of the tumor and may provide a larger surface area to cover the tissue within and/or near resection bed 1606. Instead of paddle lead 1610, any electrode strips or electrode coils may be used to provide a similar coverage effect.

[0143] In any effect, it may be desirable to deliver AEF therapy near resection bed 1606 because the resection bed 1606 is generally a place conducive to tumor regrowth. In some examples, the clinician may use a bio-compatible adhesive agent (such as DuraSeal) to affix electrodes at desired locations along the surface of the target organ or resection bed 1606. Additional electrodes or leads may include 3D printable electrode structures configured to match patient-specific resection bed 1606, other tissues, or optimize therapy placement for the specific patient.

[0144] FIG. 17 is a conceptual diagram illustrating paddle lead 1700 including a coil electrode 1706. Paddle lead 1700 is one example of paddle leads 1610 of FIG. 16. As shown in FIG. 17, paddle lead 1700 includes a structure that is paddle housing 1704 configured to carrycoil electrode 1706. Paddle housing 1704 may be coupled to lead housing 1702, where lead housing 1702 includes conductors electrically coupled to coil electrode 1706. Paddle housing 1704 defines a diameter or cross-sectional width that is the dimension in a plane of the coil electrode 1706. The diameter or cross-sectional width of paddle housing 1704 may generally be larger than a thickness that is the dimension into the page of FIG. 17. In some examples, multiple paddle leads 1700 may be placed within the tissue resection region and/or against tissue surrounding the tissue resection region in order to generate electrical field modulation, such as AEF therapy, as described herein.

[0145] In some examples, paddle lead 1700 may include two or more coil electrodes 1706. In some examples, the two or more coil electrodes may be co-planar within paddle housing 1704. In other examples, the two or more coil electrodes may be stacked in different planes within paddle housing 1704. In other examples, two or more coil electrodes may be disposed at different regions within paddle housing 1704 that are in different planes and/or non-overlapping with each other. These different configurations of coil electrodes may transfer an electrical current that can generate different electrical field shapes that may be used to deliver AEF, for example.

[0146] FIG. 18 is a conceptual diagram illustrating another paddle lead 1800 including an electrode array 1804. Paddle lead 1800 may be similar to paddle lead 1700 from FIG. 17. However, paddle lead 1800 includes electrode array 1804 that is made up of a plurality of electrodes at different locations across a surface of paddle housing 1802. Paddle housing 1802 may define a first surface having a first diameter and a second surface defining a second diameter opposing a second surface. In this manner, paddle housing 1802 may be shaped like a disk. However in other examples, the first and second surfaces may define an oval, rectangle, or any other shape. The distance between the first surface and the second surface defines a thickness of paddle housing 102. In some examples, paddle housing 1802 is configured to be rigid so that paddle housing 1802 does not conform within the patient. In other examples, paddle housing 1802 may be configured to be flexible and conform to a tissue surface, such as a curved surface of a tissue resection region. In some examples, paddle housing 1802 may be constructed of silicone rubber (or other flexible polymer) and Dacron mesh,

[0147] Each electrode of electrode array 1804 may be disposed on the first surface of paddle housing 1802. In other examples, electrodes of electrode array 1804 may be disposed on both opposing surfaces (e.g., the first surface and the second surface) of paddle housing 1802, The electrodes of electrode array 1804 may define a pattern shaped as a circle, concentric circles, one or more rectangles, one or more triangles, patient-specific patterns to target one or more areas associated with a tissue resection region, random spacing, or any other patterns. In the example of FIG. 18, electrode array 1804 includes 13 electrodes, but in some examples, electrode array 1804 may include four or more electrodes, eight or more electrodes, ten or more electrodes, or even 20 or more electrodes. In some examples, each electrode of electrode array 1804 may be independently programmable as a cathode or an anode. In other examples, the electrodes of electrode array 1804 may be pre-configured as either anodes or cathodes. These anodes or cathodes may be ganged together any operated together. Electrode array 1804 may have an equal number of anodes and cathodes or a different number of anodes from cathodes in order to achieve a desired electrical field or current concentration at specific locations with respect to paddle housing 1802. The electrodes of electrode array 1804 may be constructed of an electrically conductive material such as platinum-iridium.

[0148] Lead housing 1806A and 1806B extend proximally from lead housing 1802 and carry one or more conductors electrically coupled to electrode array 1804. In some examples, lead housing 1806A and 1806B may be configured to be flexible and provide strain relief from movements of the brain within the cranium during use. This flexibility may reduce the possibility that paddle housing 1802 moves within the brain. In some examples, lead housings 1806A and 1806B may be constructed of wire (e.g., copper or other electrical conductive material) encased in a polymer (e.g., 55D urethane). In some examples, lead housings 1806A and 1806B include an s-shaped bend, or other shape, configured to provide strain relief between the lead and paddle housing 1802. This strain relief shape may be selected to support the angle or position of the lead with respect to the paddle housing 1802 when implanted at the desired location, such as to transition from the dura matter to the outside of the skull.

[0149] FIG. 19A is a conceptual diagram illustrating an example flexible electrode array 1900. As shown in FIG, 19A, flexible electrode array 1900 is an example lead in which the structure carrying electrodes 1904 and 1906 is flexible and configured to conform to a tissue surface. For example, flexible structure 1902 carries electrodes 1904 and 1906. Conductors 1910 may be electrically coupled to electrodes 1906 and conductors 1908 may be electrically coupled to electrodes 1904. Conductors 1908 and 1910 may be housed within a lead housing (not. shown) that houses the conductors used to couple to IMD 106, for example.

[0150] FIG. 19B is a schematic diagram illustrating components of flexible electrode array- 1900 of FIG. 19B. Flexible structure 1902 may be constructed of several layers that make up this multi-layered pad. In this manner, flexible structure 1902 may include first flexible layer 1920 and second flexible layer 1922, The first flexible layer 1920 and second flexible layer 1922 may form the outer surfaces of flexible structure 1902 and constructed of a flexible polymer such as silicone or other biocompatible polymer or composite material. Electrodes 1904 are a first subset of electrodes that are disposed between first flexible layer 1920 and second flexible layer 1922, and electrodes 1906 are a second subset of electrodes disposed between first flexible layer 1920 and second flexible layer 1922. Electrodes 1904 and 1906 may be separated by a gel electrolyte that is retained within a polymer (e.g., silicone) spacer around the perimeter of the gel electrolyte. In some examples, electrodes 1904 and 1906 may be constructed using different materials, such as copper and aluminum, respectively. Electrodes 1904 may be sandwiched between poly imide layers, and electrodes 1906 may also be sandwiched between respective polyimide layers. In some examples, an anode slurry is provided between the gel electrolyte and electrodes 1904 and a cathode slurry is provided between the gel electrolyte and electrodes 1906. In other examples, electrodes 1904 and 1906 may be constructed of the same material.

[0151] Electrodes 1904 and 1906 may be provided in a grid array in which electrodes 1904 and 1906 are completely overlapping each other (e.g., occupy the same x- and y- axis position within array 1900. In other examples, electrodes 1904 and 1906 may only be partially overlapping or completely non-overlapping. Electrodes 1904 and 1906 may have the same dimensions (e.g., the same total area) or different dimensions (e.g., different total area) from each other in other examples. Electrode array 1900 may include four or more sets of electrodes, eight or more sets electrodes, ten or more sets of electrodes, or 20 or more sets of electrodes. In the example of electrode array 1900 includes 100 sets of electrodes (e.g., 100 electrodes 1904 and 100 electrodes 1906). The construction of electrode array 1900 enables array 1900 to be flexible and confirm to a tissue surface.

[0152] FIG. 20 is a conceptual diagram of implantation position of a flexible electrode array 2006 within a resection cavity 2002 of a patient. As shown in FIG. 20, brain 2012 is located within cranium 2010. Resection cavity 2002 may be formed by removing a tumor, for example. Resection cavity 2002 may also be described as or part of a tissue resection region at which electrodes can be implanted. Flexible electrode array 2006 may be an example of an implantable lead and flexible arrays 1800 or 1900. Flexible electrode array 2006 may be an example of a lead that can conform to the tissue surface 2004. One or more lead housing 2008 may be coupled to flexible electrode array 2006 and exit cranium 2010 towards IMD 106 or other medical device. Although flexible electrode array 2006 is shown as fully conforming to tissue surface 2004, flexible electrode array 2006 may contact one or more locations of tissue surface 2004 and also reside further within resection cavity 2002 in some examples.

[0153] FIG. 21 is a flowchart illustrating an example technique for implanting a flexible electrode array within a resection cavity of a patient. The method of FIG. 21 will be described with respect to flexible electrode array 2006, but the technique may be used to implant and lead that includes other flexible arrays such as flexible electrode arrays 1800 or 1900.

[0154] As shown in the example of FIG. 21, a clinician creates a resection by removing target tissue (2102). The removed tissue may be identified as including a tumor or other undesirable tissue. Then, the clinician can insert flexible electrode array 2006 against the tissue surface of the resection (2104). Once flexible electrode array 2006 is in position in against surface of the resection, the clinician may couple the proximal end of the lead housing of flexible electrode array 2006 to a medical device such as IMD 106 (2106).

[0155] FIG. 22 is a conceptual diagram of example tack electrodes 22.10 configured to be implanted within the surface 22.06 of a resection cavity’ 2204 of a patient. As shown in FIG. 22, five tack electrodes 2210 are included within lead system 2200. Lead system 200 can be implanted within tissue 2022, which may be a portion of the brain of the patient. Surface 2206 may be the inner surface of resection cavity 2204 (e.g., a tissue resection region). Although lead system 2200 includes five tack electrodes 2210 in this example, other examples of system 2.200 may include as few as one tack electrode, two or more tack electrodes, or five or more electrodes. Tack electrodes 2210 may be positioned at any position around surface 2206, which may create a planar or three-dimensional electrode array.

[0156] Each tack electrode 2210 may include components such as non-conductive cap 2214 coupled to one or more structures that may include post 2216. Post 2216 is configured to carry' one or more electrodes, such as electrodes 2218 and 2220. Each of electrodes 2218 and 2220 may be disposed at different axial positions along post 2216. Different tack electrodes 2210 may be configured with different length posts 2216 and/or a different number of electrodes. The cross-sectional area of post 2216 is smaller than a cross-sectional area of non-conductive cap 2214. In this manner, post 2216 is configured to be inserted into tissue 2202 to a depth limited by a length of post. 2216 extending from a distal surface of non-conductive cap 2214. In other words, non-conductive cap 2214 may be configured to be a depth stop for insertion of post 2216. Each of tack electrodes 2210 may include lead housing 2212 extending proximal from non- conductive cap 2214 in order to carry one or more conductors to IMD 106, for example. The proximal ends of lead housing 2212 can then be coupled to IMD 106. In some examples, the non-conductive cap may carry one or more electrodes in addition to, or instead of, electrodes 2118 and 2220. For example, non-conductive cap 2214 may include one or more electrodes on the surface configured to contact surface 2206 of the tissue defining resection cavity 2204.

[0157] In some examples, lead system 2200 may facilitate implantation of a large variety of numbers of tack electrodes 2210, such as only one tack electrode 2210, or a large number of tack electrodes distributed around surface 2206 of resection cavity 2204. In this manner, the clinician may select the number of tack electrodes 2210 needed to achieve appropriate coverage for AEF therapy or other therapy, or even mix and match different types of tack electrodes 2210 (e.g., different lengths of post 2216, different number of electrodes 2218 and 2220, etc.).

[0158] FIG. 23 is a flowchart illustrating an example technique for implanting multiple tack electrodes 2210 within a resection cavity 2204 of a patient. The method of FIG. 23 will be described with respect to lead system 2200 of FIG. 22, but the technique may be used to implant other types of individual electrodes or electrode structures.

[0159] As shown in the example of FIG. 23, a clinician creates a resection by removing target tissue (2302). The removed tissue may be identified as including a tumor or other undesirable tissue. Then, the clinician can insert one tack electrode 2210 through the surface 2206 of tissue 2202 around resection cavity 2204 at the desired location (2304). The position of tack electrode 2210 may be chosen as part of a larger spatial electrical field target using multiple tack electrodes 2210, If another tack electrode 2210 needs to be implanted (“YES” branch of block 2306), the clinician inserts another tack electrode at the desired location (2304), If no further tack electrodes are needed to be implanted (“NO” branch of block 2306), the clinician then couples the proximal end of lead housings 2212 of each tack electrode 2210 to a medical device such as IMD 106 (2308). In this manner, IMD 106 may be configured to generate electrical field modulation, such as AEF, to the target tissue resection region using some or all of the electrodes of the implanted tack electrodes 2210.

[0160] The following examples are described herein.

[0161] Example 1 : A medical lead includes a housing; one or more structures coupled to the housing; and a plurality of electrodes disposed on the one or more structures and configured to deliver electrical fields, wherein the one or more structures are configured to position the plurality of electrodes with respect to a tissue resection region.

[0162] Example 2: The medical lead of example 1, wherein the one or more structures comprise a plurality of curved prongs, wherein each prong of the plurality of curved prongs comprises one or more electrodes of the plurality of electrodes, and wherein each prong of the plurality of curved prongs comprises a distal end that curves in a radial direction away from a longitudinal axis of the housing.

[0163] Example 3: The medical lead of example 2, wherein the medical lead comprises an extended configuration in which the plurality of curved prongs are extended out from a distal end of the housing and a collapsed configuration in which the plurality of curved prongs are straightened and disposed within the housing.

[0164] Example 4: The medical lead of any of examples 2 or 3, wherein the one or more structures comprises a center straight prong comprising one or more electrodes of the plurality of electrodes, wherein the center straight prong is disposed radially inward from each prong of the plurality of curved prongs.

[0165] Example 5: The medical lead of example 1, wherein: the one or more structures comprises a flexible frame comprising a conical shape; the flexible frame comprises a wider end configured to be distal from a distal end of the housing; and the plurality of electrodes comprises one or more electrodes disposed within a narrow end of the flexible frame proximal to the distal end of the housing.

[0166] Example 6: The medical lead of example 5, further comprising a conical covering configured to cover at least a portion of the flexible frame.

[0167] Example 7: The medical lead of any of examples 5 and 6, wherein the plurality of electrodes comprises one or more electrodes disposed an a radially outward surface of the flexible frame.

[0168] Example 8: The medical lead of example 1, wherein the one or more structures comprise a plurality of curved members, wherein each member of the plurality of curved members comprises two or more electrodes of the plurality of electrodes, curves in a radial direction away from a longitudinal axis of the housing, and comprises a distal end that meets distal ends of other curved members.

[0169] Example 9: The medical lead of example 8, wherein the medical lead comprises an extended configuration in which the plurality of curved members are extended out from a distal end of the housing and a collapsed configuration in which the plurality of curved members are straightened and disposed within the housing. [0170] Example 10: The medical lead of example 1, wherein the one or more structures comprises a radially flexible member configured to be expanded via fluid pressure within the radially flexible member, and wherein the radially flexible member comprises the plurality of electrodes, and wherein at least some electrodes of the plurality of electrodes are disposed at different circumferential positions around the radially flexible member.

[0171] Example 11: The medical lead of example 10, wherein one or more electrodes of the plurality of electrodes comprises an electrode structure configured to conform to a surface of the radially flexible member.

[0172] Example 12: The medical lead of any of examples 10 or 11, wherein the radially flexible member is configured to form a spherical shape in an expanded configuration.

[0173] Example 13: The medical lead of any of examples 10 or 11, wherein the radially flexible member is configured to form a bell shape in an expanded configuration.

[0174] Example 14: The medical lead of example 13, wherein the at least some electrodes disposed at different circumferential positions are disposed on a distal portion of the radially flexible member configured to have a larger diameter than a proximal portion of the radially flexible member.

[0175] Example 15: The medical lead of example 1, wherein the one or more structures comprises a paddle having a diameter that is larger than a thickness of the paddle, and wherein the plurality of electrodes comprises two or more coil electrodes disposed within the paddle. [0176] Example 16: The medical lead of example 1, wherein the one or more structures comprises a paddle defining a first surface having a first diameter and a second surface defining a second diameter opposing a second surface, wherein a distance between the first surface and the second surface defines a thickness of the paddle, and wherein the plurality of electrodes are disposed on the first surface.

[0177] Example 17: The medical lead of example 16, wherein the paddle is configured to be flexible and conform to a tissue surface.

[0178] Example 18: The medical lead of any of examples 16 or 17, wherein the plurality of electrodes comprises eight or more electrodes.

[0179] Example 19: The medical lead of example 1, wherein the one or more structures comprises a multi-layered pad comprising a first flexible layer and a second flexible layer. wherein the plurality of electrodes comprises a first subset of electrodes disposed between the second flexible layer and the gel electrolyte.

[0180] Example 20: The medical lead of example 18, wherein the multi-layered pad is configured to be flexible and conform to a tissue surface.

[0181] Example 21 : The medical lead of any of examples 19 or 20, wherein the plurality of electrodes comprises eight or more electrodes.

[0182] Example 22: The medical lead of example 1, wherein the housing comprises a non- conductive cap, wherein the one or more structures comprises a post coupled to the non- conductive cap and configured to cany the plurality of electrodes at different axial positions along the post, and wherein a cross-sectional area of the post is smaller than a cross-sectional area of the non-conductive cap.

[0183] Example 23: The medical lead of example 22, wherein the post is configured to be inserted into tissue to a depth limited by a length of the post extending from a distal surface of the non-conductive cap.

[0184] Example 24: The medical lead of any of example 1 through 23, wherein the medical lead is configured to be implanted within a patient comprising the tissue resection region.

[0185] Example 25: The medical lead of any of example 1 through 24, further comprising one or more conductors disposed within the housing and configured to electrically couple to respective electrodes of the plurality of electrodes.

[0186] Example 26: The medical lead of any of examples 1 through 25, wherein the medical lead comprises one or more proximal connectors configured to couple the plurality of electrodes to stimulation circuitry of an implantable medical device.

[0187] Example 27: A system includes an implantable medical device includes a housing, one or more structures coupled to the housing, and a plurality of electrodes disposed on the one or more structures and configured to deliver electrical fields resulting from the one or more electrical signals applied to a subset of the plurality of the electrodes, wherein the one or more structures are configured to position the plurality of electrodes with respect to a tissue resection region.

[0188] Example 28: The system of example 27, further comprising processing circuitry configured to control the stimulation circuitry to generate the one or more electrical signals. [0189] Example 29: The system of any of examples 27 or 28, wherein the medical lead is a first medical lead and the plurality of electrodes comprise a first plurality of electrodes, and wherein the system further comprises a second medical lead comprising a second plurality of electrodes.

[0190] Example 30. Any device, system, method, or computer-readable medium described or otherwise supported in the specification herein.

[0191] A variety of different therapies are described herein that are related to each other, but some are slightly different. Generally, electric and magnetic stimulation therapy covers all of the therapies described herein. This includes, for example, direct current stimulation (DCS).

Electric field therapy includes alternating current stimulation, which also includes alternating electric field (AEF) therapy, which includes tumor treating field (TTF) therapy (e.g., AEF therapy within a range of 100kHz to 500kHz). Electric field therapy also includes pulse electric fields, which includes nanosecond pulsed electric fields (or nanopulse stimulation), which includes both irreversible electroporation and reversible electroporation. Electric and magnetic stimulation therapy also includes magnetic field therapy, which includes examples such as alternating magnetic field (AMF) therapy, oscillating magnetic field (OMF) therapy, and extremely low frequency electromagnetic field (ELF-EMF) therapy. Other types of therapy may also be included within any of these example categories of therapies.

[0192] The techniques described in this disclosure may be implemented, at least in part, in hardware, software, firmware or any combination thereof. For example, various aspects of the described techniques may be implemented within one or more processors, such as fixed function processing circuitry and/or programmable processing circuitry, including one or more microprocessors, digital signal processors (DSPs), application specific integrated circuits (ASICs), field programmable gate arrays (FPGAs), or any other equivalent integrated or discrete logic circuitry, as well as any combinations of such components. The term “processor” or “processing circuitry” may generally refer to any of the foregoing logic circuitry, alone or in combination with other logic circuitry, or any other equivalent circuitry . A control unit comprising hardware may also perform one or more of the techniques of this disclosure.

[0193] Such hardware, software, and firmware may be implemented within the same device or within separate devices to support the various operations and functions described in this disclosure. In addition, any of the described units, modules or components may be implemented together or separately as discrete but interoperable logic devices. Depiction of different features as modules or units is intended to highlight different functional aspects and does not necessarily imply that such modules or units must be realized by separate hardware or software components. Rather, functionality associated with one or more modules or units may be performed byseparate hardware or software components, or integrated within common or separate hardware or software components.

[0194] The techniques described in this disclosure may also be embodied or encoded in a computer-readable medium, such as a computer-readable storage medium, containing instructions. Instructions embedded or encoded in a computer-readable storage medium may cause a programmable processor, or other processor, to perform the method, e.g., when the instructions are executed. Computer readable storage media may include random access memory (RAM), read only memory (ROM), programmable read only memory (PROM), erasable programmable read only memory' (EPROM), electronically erasable programmable read only memory (EEPROM), flash memory', a hard disk, a CD-ROM, a floppy disk, a cassette, magnetic media, optical media, or other computer readable media.

[0195] Various examples have been described. These and other examples are within the scope of the following claims.