Implantable leads for electric field therapy

Abstract

Devices, systems, and techniques are disclosed for delivering electric field therapy to tissue of a subject. In one example, medical lead includes a housing that has a main portion and a distal portion, wherein the main portion comprises a fixation structure and defines a first cross-sectional dimension, and wherein the distal portion defines a tapered tip and extends distally from the main portion. The medical lead may also include one or more electrodes carried by the housing, and a proximal tether comprising at least one conductor electrically coupled to the one or more electrodes, wherein the proximal tether extends proximal from the housing and defines a second cross-sectional dimension smaller than the first cross-sectional dimension.

Description

Docket No.: A0008663WO01 IMPLANTABLE LEADS FOR ELECTRIC FIELD THERAPY CROSS-RELATED REFERENCES

[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No.63 / 639,388, filed April 26, 2024, the entire content of which is incorporated herein by reference. TECHNICAL FIELD

[0001] This disclosure generally relates to electrode configurations for alternating electric fields. BACKGROUND

[0002] 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

[0003] 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 one or more electrodes to establish 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.

[0004] 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 atDocket No.: A0008663WO01 a desired location with respect to a target tissue and / or tissue associated with a tissue resection region. These structures may be curved, flexible, include tapered tips, inflatable, and / or extendable from the lead housing in order to implant and then retain the electrodes at locations to deliver electrical field modulation to target tissue which may be associated with the tissue resection region.

[0005] 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 medical lead includes: a housing comprising a main portion and a distal portion, wherein the main portion comprises a fixation structure and defines a first cross-sectional dimension, and wherein the distal portion defines a tapered tip and extends distally from the main portion; one or more electrodes carried by the housing; and a proximal tether comprising at least one conductor electrically coupled to the one or more electrodes, wherein the proximal tether extends proximal from the housing and defines a second cross- sectional dimension smaller than the first cross-sectional dimension.

[0007] In another example, a method includes implanting one or more medical leads within a target tissue of a patient, wherein each medical lead of the one or more medical leads comprises: a housing comprising a main portion and a distal portion, wherein the main portion comprises a fixation structure and defines a first cross-sectional dimension, and wherein the distal portion defines a tapered tip and extends distally from the main portion;Docket No.: A0008663WO01 one or more electrodes carried by the housing; and a proximal tether comprising at least one conductor electrically coupled to the one or more electrodes, wherein the proximal tether extends proximal from the housing and defines a second cross-sectional dimension smaller than the first cross-sectional dimension, and delivering alternating electrical field therapy to the tissue via electrodes of the one or more medical leads implanted within the target tissue of the patient.

[0008] In another example, a system includes: one or more medical leads, each medical lead of the one or more medical leads comprising: a housing comprising a main portion and a distal portion, wherein the main portion comprises a fixation structure and defines a first cross-sectional dimension, and wherein the distal portion defines a tapered tip and extends distally from the main portion; one or more electrodes carried by the housing; and a proximal tether comprising at least one conductor electrically coupled to the one or more electrodes, wherein the proximal tether extends proximal from the housing and defines a second cross- sectional dimension smaller than the first cross-sectional dimension; and an implantable medical device comprising stimulation circuitry, the implantable medical device being configured to: couple with the at least one conductor of each medical lead of the one or more medical leads; and control the stimulation circuitry to generate one or more electrical signals deliverable via the one or more electrodes of the one or more medical leads.

[0009] The details of one or more examples of the techniques of this disclosure are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the techniques will be apparent from the description and drawings, and from the claims. BRIEF DESCRIPTION OF DRAWINGS

[0010] 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.

[0011] 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.

[0012] FIG.3 is a block diagram of the external programmer of FIG.1 for controlling delivery of AEF therapy according to an example of the techniques of the disclosure.

[0013] 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.Docket No.: A0008663WO01

[0014] FIGS.5A and 5B are conceptual diagrams of example leads with respective electrodes carried by the lead.

[0015] FIGS.5C, 5D, 5E, and 5F are conceptual diagrams of example electrodes disposed around a perimeter of a lead at a particular longitudinal location.

[0016] FIG.6 is a flowchart illustrating an example technique for delivering AEF therapy to a patient.

[0017] FIGS.7 and 8 are conceptual diagrams of example post electrodes configured to be implanted within the surface of a resection cavity of a patient.

[0018] FIG.9 is a conceptual diagram of an example medical lead with tapered tip and implantation tool.

[0019] FIGS.10A, 10B, 11A, 11B, and 11C are conceptual diagrams of example medical leads and fixation structures.

[0020] FIGS.12A and 12B are conceptual diagrams of example medical leads with adjustable depth fixation structures.

[0021] FIGS.13A, 13B, 14A, and 14B are conceptual diagrams of example implantation tools for implanting example medical leads.

[0022] FIG.15A is a cross-sectional view of an example implantation tool.

[0023] FIG.15B is a conceptual drawing of the example implantation tool of FIG.15A.

[0024] FIG.16 is a conceptual diagram of an example medical lead and associated implantation tool.

[0025] FIGS.17A and 17B are conceptual diagrams of an example medical lead having a plurality of tapered tip sections configured to open to retain the medical lead in tissue.

[0026] FIG.18 is a conceptual diagram of an example medical lead having an array of flexible electrode segments.

[0027] FIG.19 is a flowchart illustrating an example technique for implanting the medical lead of FIG.18 within a resection cavity of a patient.

[0028] FIG.20 is a conceptual diagram of a medical lead comprising an array of implantable strut fixation structures.

[0029] FIGS.21A and 21B are conceptual diagrams of an example medical lead with a plurality of flexible arms carrying one or more electrodes.

[0030] FIGS.22A and 22B are conceptual diagrams of an example medical lead with a plurality of flexible arms carrying one or more electrodes and a central depth post carrying one or more electrodes.Docket No.: A0008663WO01

[0031] FIGS.23A and 23B are conceptual diagrams of an example medical lead with a plurality of shapable arms comprising overmolded coils.

[0032] FIG.24 is a conceptual diagram illustrating a medical lead having a plurality of flexible conductors carrying respective electrodes.

[0033] FIGS.25A and 25B are conceptual diagrams of an example medical lead with a plurality of deformable arms carrying one or more electrodes and a central depth post carrying one or more electrodes.

[0034] FIGS.26A and 26B are conceptual diagrams of an example medical lead having a shape memory distal end for a deployed shape.

[0035] FIGS.27A and 27B are conceptual diagrams of an example medical lead with a plurality of deformable wings configured to bias respective electrodes against tissue surfaces.

[0036] FIGS.28A and 28B are conceptual diagrams of an example medical lead having a plurality of expandable fixation structures for retaining the medical lead within tissue.

[0037] FIGS.29A and 29B are conceptual diagrams of example medical leads configured to form coils of electrodes. DETAILED DESCRIPTION

[0038] 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.Docket No.: A0008663WO01

[0039] As described herein, a system may include one or more medical 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. Each lead may include one or more electrodes, and multiple leads may be coupled to an IMD. 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.

[0040] In some examples, a medical lead may include distal structures, such as a tapered tip, that facilitate insertion of the medical lead through tissue. In some examples, 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 or fix the medical lead at a desired position with respect to 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. 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 and / or fix the leads to tissue 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.

[0041] 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 isDocket No.: A0008663WO01 described for example purposes herein, but similar systems, devices, and techniques may be used for other animals in other examples.

[0042] 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 (AEF) 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.

[0043] 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 1 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 122.

[0044] IMD 106 includes a therapy module (e.g., which may include processing circuitry, signal generation circuitry or other electrical circuitry configured to perform the functionsDocket No.: A0008663WO01 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 116, 118 of leads 114A and 114B, respectively. The subset of electrodes 116, 118 that are used to deliver electrical stimulation to patient 112, 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 112 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.

[0045] 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 this 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.Docket No.: A0008663WO01

[0046] 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.

[0047] 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 switchDocket No.: A0008663WO01 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.

[0048] 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 112 for AEF therapy via 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 supra-perception threshold intensity. In this manner, IMD 106 may use sensed electrical stimulation and / or sensed physiological responses in a closed-loop manner to modulate delivered electrical stimulation, such as AEF therapy.

[0049] IMD 106 may be implanted within a subcutaneous pocket above the clavicle, or, alternatively, on or within cranium 122 or at any other suitable site within patient 112 such as a lower abdominal or high buttock location. Other configurations might include IMD 106Docket No.: A0008663WO01 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 lower back, shoulder, neck, abdomen, or any other location.

[0050] 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.1, 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.5A and 5B.

[0051] 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 moreDocket No.: A0008663WO01 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, individual leads with tapered tips, 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 may be configured to be implanted within a patient comprising the tissue resection region.

[0052] Although leads 114 are shown in FIG.1 as being coupled to a common lead extension 110, in 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.

[0053] 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 114 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 insulatedDocket No.: A0008663WO01 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.

[0054] In this 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 one or more leads each having one or more electrodes, leads with multiple flexible conductors coupled to respective electrodes, individually anchorable leads, adjustable depth electrodes, leads with multiple conformable arms, shape memory leads, or any other leads that include elements configured to dispose electrodes on tissue surface or electrodes within the tissue.

[0055] 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.

[0056] 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 selectDocket No.: A0008663WO01 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 delivery 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.

[0057] 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 120, 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.

[0058] 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 112 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.Docket No.: A0008663WO01

[0059] 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.

[0060] 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 112 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.

[0061] 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 delivery to target cells, enhancing the bioavailability of serologically available pharmaceuticals, enhancing theDocket No.: A0008663WO01 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.

[0062] 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.

[0063] 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. A set of one or more cathode and one or more anode used to deliver electrical stimulation may all be located on the same lead. In other examples, the set of cathode and one or more anode for delivering electrical stimulation may be carried by two or more leads.

[0064] 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 combinationDocket No.: A0008663WO01 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.

[0065] 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.

[0066] 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 tumorDocket No.: A0008663WO01 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.

[0067] 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.

[0068] In some examples, the stimulation frequency at which the maximum force (fmax) can be imparted on a spherical particle housed within a dividing cell is inversely related to the relaxation time (τ) possessed by the membrane charging voltage. The relaxation time (τ) can be described by this equation:The terms within the above formula are as follows: (τ) is the relaxation time of the membrane charging voltage, r is the radius of the cell, Cmis the membrane capacitance, and σiand are the conductivity of the cytoplasm and external medium respectively. Given σi and σeare nearly identical, this equation can be simplified to:Docket No.: A0008663WO01 Given that within an individual cell the values for r and Cmwill 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 (τ), it can be said that fmax is directly related to the cytoplasmic conductivity σi. With that relationship in mind, simulation results are indicative of a relationship between the radius of the cell (r ) and fmax 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, α represents a constant which was calculated from simulation results within the literature equivalent to 2155 kHz * m * µm / S / nm, σiis the cytoplasmic conductivity, r is the radius of the dividing cell, and d 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 17µm (or a radius of 8.5µm), cell membrane thickness is somewhat variable but is reported anywhere between 4 to 10nm (7nm for the purposes of this example), and the cytoplasmic conductivity extrapolated from data attained within a melanoma cancer cell, 0.1S / m. With those values and the value for α 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 18-22µm (for the purposes of this example, 20µm), 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 151kHz (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.

[0069] Given that AEF therapy has been demonstrated to impart an increase in cell volume within those cancer cells experiencing the therapy, in part due to the enhanced proportion of cells that occupy the G0 / G1 phase of the cell cycle, and that the optimalDocket No.: A0008663WO01 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

[0070] 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 indicative 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.

[0071] 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 combinationDocket No.: A0008663WO01 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.

[0072] 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 180oor π 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 0oor 0π radians phase shiftingDocket No.: A0008663WO01 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.

[0073] 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.

[0074] 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.

[0075] 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 114 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.Docket No.: A0008663WO01

[0076] 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.

[0077] 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.

[0078] FIG.2 is a block diagram of the example IMD 106 of FIG.1 configured 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, switch 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 211 may include any volatile or non-volatile media, such as a random-access memory (RAM), read only memory (ROM), non-volatile 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.

[0079] In the example shown in FIG.2, memory 211 stores therapy programs 214 that include respective stimulation parameter sets that define AEF therapy. Each stored therapyDocket No.: A0008663WO01 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.

[0080] 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 transmitting 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.

[0081] 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 all 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 AEF therapy.

[0082] Stimulation generator 202, under the control of processing circuitry 210, generates stimulation signals for delivery to patient 112 via selected combinations of electrodes 116, 118. An example range of electrical stimulation parameters believed to be effective in AEF therapy to manage cellular activity include:Docket No.: A0008663WO01 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.

[0083] 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 112. 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 elicit 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).

[0084] 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 therapyDocket No.: A0008663WO01 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.

[0085] In the example shown in FIG.2, the set of electrodes 116 includes electrodes 116A, 116B, 116C, and 116D, and the set of electrodes 118 includes electrodes 118A, 118B, 118C, and 118D. Processing circuitry 210 also controls switch module 206 to apply the stimulation signals generated by stimulation generator 202 to selected 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. Switch module 206 may be a switch array, switch 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 switch module 206 and conductors within leads 114. In some examples, however, IMD 106 does not include switch module 206, such as if each electrode is assigned a respective current and sink (e.g., independent current source).

[0086] 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.

[0087] 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,Docket No.: A0008663WO01 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.

[0088] 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 wired or wireless 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 28. 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 tumorDocket No.: A0008663WO01 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.

[0089] 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).

[0090] 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, telemetry module 208 may send information to external programmer 104 on a continuous basis, at periodic intervals, or upon request from IMD 106 or programmer 104.

[0091] 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 antennaDocket No.: A0008663WO01 an corresponding circuitry to continually receive external power that enables IMD 106 to deliver electric field therapy indefinitely without possible internal power source drain.

[0092] 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.

[0093] 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.

[0094] 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.Docket No.: A0008663WO01

[0095] 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.

[0096] Memory 311 (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 IMD 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.

[0097] 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.Docket No.: A0008663WO01

[0098] 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.

[0099] 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.

[0100] 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.

[0101] 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 wireless 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.Docket No.: A0008663WO01

[0102] 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.

[0103] 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.

[0104] 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 132A. 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.

[0105] 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 IMD 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. System 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, MN.

[0106] 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 treatmentDocket No.: A0008663WO01 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 112. 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..

[0107] FIGS.5A 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.

[0108] 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, two, 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 semi-circular electrodes that may or may not be circumferentially aligned between electrode levels.

[0109] 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, theDocket No.: A0008663WO01 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.

[0110] 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.

[0111] 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.Docket No.: A0008663WO01

[0112] 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.

[0113] 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. Example leads 400 and 410 represent electrodes that can be disposed at different perimeter, or circumferential, locations along a housing of a lead. This perimeter or circumferential positioning of different electrodes may also apply to any other leads described herein.

[0114] 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.

[0115] 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. SmallerDocket No.: A0008663WO01 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.

[0116] 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.

[0117] 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.

[0118] 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,Docket No.: A0008663WO01 screws, electrode shapes, adhesives, etc.) that enable the lead or electrodes to be relatively fixed in position with respect to surrounding tissue.

[0119] 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.

[0120] 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.

[0121] 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 deliveryDocket No.: A0008663WO01 of each electric field, although processing circuitry 210 may provide an interphase period in some examples.

[0122] 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).

[0123] FIGS.7 and 8 are conceptual diagrams of example post electrodes 710 configured to be implanted within the surface 706 of resection cavity 704 of a patient. As shown in FIG. 7, 5 post electrodes 710 are included within lead system 700. Lead system 700 can be implanted within tissue 702, which may be a portion of the brain of the patient or other tissue that may be associated with a tumor or tissue mass to be treated. Surface 706 may be the inner surface of resection cavity 704 (e.g., a tissue resection region). Although lead system 700 includes five post electrodes 710 in this example, other examples of system 700 may include as few as one post electrode, two or more post electrodes, or five or more post electrodes. In other examples, system 700 may include eight post electrodes 710 or more. Each post electrode 710 may include a single electrode or two or more electrodes on a single post 716. Post electrodes 710 may be positioned at any position around surface 706, which may create a planar or three-dimensional electrode array.

[0124] Each post electrode 710 may include components such as post 716 which may be a housing or other structure that is configured to be inserted into tissue. Post 716 is configured to carry one or more electrodes, such as electrodes 718 and 720. Each of electrodes 718 and 720 may be disposed at different axial positions along post 716. Different post electrodes 710 may be configured with different length posts 710 and / or a different number of electrodes. The cross-sectional area of post 710 may also be different at different axial positions on the post, such as a tapered shape. Post 710 is configured to be inserted into tissue 702 to a target depth that may be when post 710 is fully implanted within tissue or up to a structure or marking on post 710. Each of post electrodes 710 may include conductor 712 extending proximal from the proximal end of post 716. Each conductor 712 may include an electrically conductive material covered by an insulating material, such as one or more polymers. Conductors 712 may be flexible to enable the respective post electrode 710 to reach the desired target location.Docket No.: A0008663WO01

[0125] The proximal ends of conductors 712 can be coupled to lead body 730. Lead body 730 may include proximal housing 732 that extends proximally to a proximal end connector that is configured to be coupled to an IMD. Distal housing 734 may define a plurality of openings 736 that are each configured to accept a respective conductor 712 and post electrode 710. In this manner, lead body 730 can contain all of conductors 712 and manage conductors 712 extending out from resection cavity 704. In some examples, lead body 730 may define a lumen that is configured to accept a stylet that can steer lead body 730 into the target area, such as resection cavity 704. A clinician may manually insert each post electrode 710 into the target position of tissue 710 using a gloved hand and / or a tool such as a forceps. In other examples, each post electrode 710 may initially be stored within a respective opening 736, and the distal end of distal housing 734 can be pressed against surface 706. The clinician may then activate a trigger or extender that forces the post electrode out of opening 736 and at least partially into tissue 702. The clinician can then reposition distal housing 734 to the next location on surface 706 to inject the next post electrode 710.

[0126] In some examples, lead system 700 may facilitate implantation of a large variety of numbers of post electrodes 710, such as only one post electrode 710, or a large number of post electrodes distributed around surface 706 of resection cavity 704. In this manner, the clinician may select the number of post electrodes 710 needed to achieve appropriate coverage for AEF therapy or other therapy, or even mix and match different types of post electrodes 710 (e.g., different lengths of post 716, different number of electrodes 718 and 720, etc.).

[0127] As shown in the example of FIG.8, an expandable structure 802 may be configured to force post electrodes 710 of system 700 of FIG.7 into tissue 702. The technique and system of FIG.8 will be described with respect to lead system 700 of FIG.7, but the technique may be used to implant other types of individual electrodes or electrode structures.

[0128] As shown in the example of FIG.8, a clinician first creates a resection by removing target tissue. The removed tissue may be identified as including a tumor or other undesirable tissue. Then, the clinician can insert a plurality of post electrodes 710 through the surface 706 of tissue 702 around resection cavity 704 at the desired locations. The clinician can do this by inserting expandable structure 802 which includes post electrodes 710 coupled to respective locations around structure surface 804 of expandable structure 802. For example, the proximal end of each of post electrodes 710 may be adhered to fixed to theDocket No.: A0008663WO01 respective location of surface 804 and carried in the collapsed state of expandable structure 802 to be inserted into resection cavity 704. Expandable structure 802 may be a flexible bladder that can expand by adding fluid (e.g., saline or other biocompatible fluid) through inlet 806 and increasing the pressure to expand surface 804. The clinician may use a syringe or pump connected to inlet 806 in order to add fluid to expandable structure 802. This expansion of expandable structure 802 caused by increasing internal fluid pressure may force each post electrode 710 into tissue 702 through surface 706. Expandable structure 802 may form to the contours of surface 706. Once expandable structure 802 has inserted all of post electrodes 710 into tissue, the clinician may remove fluid from expandable structure 802 to promote collapsing of expandable structure 802. Since post electrodes 710 are attached to surface 804, expandable structure 802 may remain within resection cavity 704 in the collapsed state. In other examples, expandable structure 802 may be configured to detach from post electrodes 710 and be removed from resection cavity 704 and from the patient. The IMD, such as IMD 106, may then 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 post electrodes 710.

[0129] Alternative to having post electrodes 710 being coupled to expandable structure 802, post electrodes may be individually inserted by the clinician into tissue. Then, the clinician may insert expandable structure 802 into resection cavity 704 and expand the expandable structure 802 to fully seat, or insert, post electrodes 710 into tissue. The clinician can then collapse expandable structure 802 and remove expandable structure 802 to complete implantation.

[0130] FIG.9 is a conceptual diagram of a system 900 that includes example medical lead 902 with tapered tip 904 and implantation tool 920. System 900 can include implantation tool 920 and lead 902. As shown in the example of FIG.9, lead 902 includes several components, or features, that can facilitate implantation and delivered of an electrical signal. Lead 902 may include a housing that can includes several portions, such as a main portion and distal portion. The distal portion of the housing may include tapered tip 904. Tapered tip 904 may have a conical shape, a rounded tip shape, or any other shape that can facilitate insertion of lead 902 into tissue. Although tapered tip 904 may have a circumferentially symmetrical shape as shown in FIG.9, tapered tip 904 may have a wedge shape or any other shapes that include some taper at some point. Tapered tip 904 may have a very sharp end, rounded end, or other shape. In some examples, tapered tip 904 may carry or be constructed as one or more electrodes.Docket No.: A0008663WO01

[0131] The main portion of the housing of lead 902 may include one or more segments, such as portion 906, recessed portion 910, and portion 908. Portions 906 and 908 may define an external diameter or perimeter of the housing of lead 902. In some examples, one or both of portions 906 and 908 may carry or be a respective electrode. In some examples, lead 902 may include multiple electrodes, such as one or more electrodes carried by tapered tip 904 and one or more electrodes carried by portions 906 and / or 908 of the main housing. Recessed portion 910 may have a recessed channel that extends partially or fully around the perimeter (or circumference) of the main housing of lead 902. Recessed portion 910 may be configured to promote fixation with the tissue, such as tissue filling into recessed portion 910 between portions 906 and 908. Although portions 906 and 908 are shown with the same diameter, in some examples, one of portions 906 and 908 may have a larger diameter than another one of portions 906 and 908. In general, the main portion of the housing defines recessed channel 910 around a perimeter of the main portion, where recessed channel 910 defines a cross-sectional dimension less than the a cross-section dimension of other sections of the main housing, such as portions 906 and 908. Lead 902 also includes proximal tether 912 that includes at least one conductor (e.g., a wire) electrically coupled to the one or more electrodes carried by the housing. Proximal tether 912 extends proximal from the housing and defines a cross-sectional dimension that may be smaller than the cross-sectional dimensions of portions 906 and 908 and the cross-sectional dimension of recessed channel 910.

[0132] Implantation tool 920 may be configured to insert, or implant, lead 902 into tissue. Implantation tool 920 may include a distal portion that is configured to retain a portion of lead 902 for implantation and a proximal portion that can be manipulated by a hand or hands of the clinician. Although only distal end 924 of implantation tool 920 is shown in FIG.9, shaft 922 may extend proximately to the proximal end of implantation tool 920 and include a handle or other structure to be handled by the user. In some examples, shaft 922 may include one or more lumens (not shown) that are configured to accept a stylet or other structure that can create curves in shaft 922 or other shapes that can direct lead 902 to the target tissue.

[0133] Distal end 924 may include cradle 926 that defines chamber 932 configured to retain at least a portion of the housing of lead 902. Cradle 926 may be shaped similar to a half cylinder that ends at walls 928A and 928B around the sides of cradle 926. The distal end of cradle 926 may be partially enclosed by flange 934. Flange 934 may define a rounded slot 930 that is configured to mate with recessed portion 910 of lead 902. In this manner, recessed channel 910 of lead 902 is configured to mate to flange 934 such that a portion ofDocket No.: A0008663WO01 the main housing of lead 920 fits within rounded slot 930. When lead 902 is retained by flange 934 within cradle 926, flange 934 contacts the inner walls of portion 906 and portion 908 which prevents lead 902 from moving axially with respect to implantation tool 920 during insertion of lead 902 into tissue. Tether 912 may remain outside of cradle 926 when lead 902 is captured by cradle 926. In other examples, tether 912 may be disposed within a lumen of shaft 922 during implantation.

[0134] Implantation tool 920 may be configured to apply an axial force to lead 902 in order to create a tunnel through adjacent tissue via tapered tip 904. Implantation tool 920 can also be used to continue to apply pressure to tissue with tapered tip 904 until lead 902 is in the appropriate target tissue. Once lead 902 is positioned in tissue, such as with tapered tip 904 and portion 906 embedded within tissue, implantation tool 920 can be removed from lead 902. For example, cradle 926 may be moved laterally with respect to lead 902 to disengage flange 934 from recessed channel 910. Once cradle 926 has been separated from lead 902, the user may remove implantation tool 920 from the patient, and lead 902 is left behind within the patient at the target tissue.

[0135] FIGS.10A, 10B, 11A, 11B, and 11C are conceptual diagrams of example medical leads and fixation structures. As shown in the example of FIG.10A, lead 1002 may be similar to lead 902 of FIG.9. However, lead 1002 may include a fixation structure 1004 that is retained within recessed channel 910. Side walls of portions 906 and 908 of lead 902 may this retain fixation structure 1004 within recessed channel 910. For example, fixation structure 1004 may define an opening with a diameter that is larger than the cross-sectional area of recessed channel 910 and less than the cross-sectional area of portions 906 and 908. In some examples, fixation structure 1004 may be installed onto the main housing at recessed channel by stretching over tapered tip 904 and portion 906 until seated at recessed channel 910.

[0136] Fixation structure 1004 may be constructed and configured to intact with tissue and retain lead 902 at a target tissue location. Fixation structure 1004 may be constructed with any different types of outer dimensions and shapes, such as disc shaped, amorphous shaped, or even one or more “fingers” of material that extend radially from recessed channel 910. Fixation structure 1004 may be constructed of a flexible mesh material. A mesh material may facilitate tissue ingrowth over time. If fixation structure 1004 is flexible, the opening defined by fixation structure 1004 may be smaller in diameter than the recessed channel 910 but may stretch to remain in contact with recessed channel 910. The flexibleDocket No.: A0008663WO01 mesh material may be constructed of one or more types of polymer, a metal wire mesh, or any other biocompatible material.

[0137] As shown in the example of FIG.10B, lead 1020 may be similar to lead 1002 of FIG.10A and lead 902 of FIG.9. However, lead 1020 may include a fixation structure 1022 that is retained within recessed channel 910, where fixation structure 1022 may include a solid material in a disk shape or other such shape. The thickness of fixation structure 1022 may be similar to, or less than, the width of recessed channel 910. Side walls of portions 906 and 908 of lead 902 may this retain fixation structure 1022 within recessed channel 910. For example, fixation structure 1022 may define an opening with a diameter that is larger than the cross-sectional area of recessed channel 910 and less than the cross-sectional area of portions 906 and 908. In some examples, fixation structure 1022 may be installed onto the main housing at recessed channel by stretching over tapered tip 904 and portion 906 until seated at recessed channel 910.

[0138] Fixation structure 1022 may be constructed and configured to intact with tissue and retain lead 902 at a target tissue location. Fixation structure 1022 may be constructed with any different types of outer dimensions and shapes, such as disc shaped, amorphous shaped, or even one or more “fingers” of material that extend radially from recessed channel 910. If fixation structure 1004 is flexible, the opening defined by fixation structure 1004 may be smaller in diameter than the recessed channel 910 but may stretch to remain in contact with recessed channel 910. Flexible material 1022 may be constructed of one or more types of polymer, metal alloy, or any other biocompatible material.

[0139] With respect to leads 902, 1002, 1020, portion 906 that is distal from recessed channel 910 may include one or more features that may promote retention of lead 902 within tissue. For example, portion 906 of the main housing of lead 902 may have disposed on the surface an adhesive (or elute the adhesive from one or more pores within the housing) that may bond the tissue with portion 906. In some examples, portion 906 may include a texturized surface or one or more pores that promote tissue ingress and attachment to portion 906 of the main housing. In other examples, portion 906 may have one or more tines or other mechanical structure that extend from portion 906 to retain the lead in place with the target tissue.

[0140] As shown in the example of FIG.11A, lead 1100 may be similar to lead 902 of FIG.9. However, lead 1100 may include fixation portion 1102 of the main housing, between portions 906 and 908, from which fixation structure 1104 extends radially from the main housing. Fixation structure 1104 may be a single structure at one circumferential positionDocket No.: A0008663WO01 around the circumference of fixation portion 1102 of the housing of lead 1100, and fixation structure 1104 may be configured to be embedded within tissue in order to prevent lead 1100 from being removed from tissue. In other examples, two or more fixation structures 1104 may be disposed at respective circumferential locations around fixation portion 1102. Fixation structure 1104 may be cylindrical or angular. Fixation structure 1104 is shown as being extended in the proximal direction of lead 1100 such that an angle between fixation structure 1104 may be an acute angle. Fixation structure 1104 may be rigid or flexible, and may be constructed of one or more types of polymer, for example.

[0141] The example of FIG.11B shows lead 1120 that may be similar to lead 902 of FIG. 9. However, lead 1120 may include fixation portion 1122 of the main housing, between portions 906 and 908, from which fixation structures 1124 extends radially from the main housing. Fixation structure 1124 may be a single structure at one circumferential position around the circumference of fixation portion 1122 of the housing of lead 1100, and another similar fixation structure is located at an opposing circumferential side of fixation portion 122. Fixation structure 1124 may have a paddle shape which has a length and width that is greater than the depth along the axial direction of lead 1120. Fixation structure 1124 may be configured to be embedded within tissue in order to prevent lead 1120 from being removed from tissue. In other examples, three or more fixation structures may be disposed at respective circumferential locations around fixation portion 1122. Fixation structure 1124 is shown as being extended in the proximal direction of lead 1120 such that an angle between fixation structure 1124 may be an acute angle. Fixation structure 1124 may be rigid or flexible, and may be constructed of one or more types of polymer, for example. In some examples, fixation structure 1124 and other fixation structures around the circumference of fixation portion 1122.

[0142] As shown in the example of FIG.11C, lead 1140 may be similar to lead 902 of FIG.9. However, lead 1140 may include fixation portion 1142 of the main housing, between portions 906 and 908, from which fixation structure 1144 extends radially from the main housing and proximal in an angled direction. Fixation structure 1144 may encompass the full circumference of the main portion and may be configured to extend away from the main portion, similar to a “cone” or “skirt” shape. Fixation structure 1144 may thus create a space or volume between the fixation structure 1144 and the housing. In this examples, fixation structure 1144 may represent a flexible skirt that extends around at least half of a perimeter of the main portion (e.g., fixation portion 1142) of the main portion of the housing of lead 1140. In some examples, lead 1140 may include two or more different fixation structures 1144 thatDocket No.: A0008663WO01 are positioned at different circumferential locations and / or different axial locations of the housing. Fixation structure 1124 may be configured to be embedded within tissue in order to prevent lead 1120 from being removed from tissue. Fixation structure 1124 is shown as being extended in the proximal direction of lead 1120 such that an angle between fixation structure 1124 may be an acute angle. Fixation structure 1124 may be rigid or flexible, and may be constructed of one or more types of polymer, for example.

[0143] FIGS.12A and 12B are conceptual diagrams of example medical leads 1200 and 1220 with adjustable depth fixation structures 1210 and 1230, respectively. Leads 1200 and 1220 ma be similar to lead 902 of FIG.9. As shown in the example of FIG.12A, lead 1200 includes housing 1202 which includes tapered tip 1204 at a distal end and one or more electrodes carried at one or more locations on housing 1202. Lead 1200 also includes tether 1206 which may include one or more conductors that are electrically coupled to respective electrodes carried on housing 1202. The conductor(s) within tether 1206 may be coupled to one or more connectors at the proximal end of tether 1206 to couple with an IMD.

[0144] A main portion of housing 1202 may define or be attached to a plurality of posts 1208 positioned at a same circumferential position and at different respective axial positions along a length of the main portion of housing 1202. Although three posts 1208 are shown, more posts may be provided in other examples. Posts 1208 may be positioned at a spacing that accepts fixation structure 1210 between consecutive posts. Posts 1208 may have a rounded top surface that may or may not match the curvature of housing 1202. Fixation structure 1210 also defines a central opening configured to accept the main portion of housing 1202, wherein the central opening also includes keyed void 1212. Keyed void 1212 may be shaped and configured to pass over any of posts 1208. In this manner, a user can move fixation structure 1210 along the length the main portion of housing 1202 and between different posts 1208 when keyed void 1212 is circumferentially aligned with the same circumferential position of the plurality of posts 1208. Fixation structure 1210 can be rotated about a central axis of fixation structure 1210 and / or housing 1202 in order to align posts to keyed structure 1212 and / or lock fixation structure 1210 between consecutive posts 1208. Fixation structure 1210 may function as a depth stop and / or for tissue engagement. Fixation structure 1210 may be circular in shape or define other shapes, such as triangle, square, hexagon, an amorphous shape, or any other shapes.

[0145] As shown in the example of FIG.12B, lead 1220 may be similar to lead 1200 of FIG.12A. Lead 1220 includes housing 1122 which includes tapered tip 1224 at a distal end and one or more electrodes carried at one or more locations on housing 1222. Lead 1220 alsoDocket No.: A0008663WO01 includes tether 1226 which may include one or more conductors that are electrically coupled to respective electrodes carried on housing 1222. The conductor(s) within tether 1226 may be coupled to one or more connectors at the proximal end of tether 1226 to couple with an IMD.

[0146] A main portion of housing 1222 may define or be attached to a plurality of posts 1228 positioned at a same circumferential position and at different respective axial positions along a length of the main portion of housing 1222. Although three posts 1228 are shown, more posts may be provided in other examples. Posts 1228 may be positioned at a spacing that accepts fixation structure 1230 between consecutive posts. Posts 1228 may have a flat top surface and a rectangular or square cross-section. Fixation structure 1220 also defines a central opening configured to accept the main portion of housing 1222, wherein the central opening also includes keyed void 1232. Keyed void 1232 may be shaped and configured to pass over any of posts 1228. In this manner, a user can move fixation structure 1230 along the length the main portion of housing 1222 and between different posts 1228 when keyed void 1232 is circumferentially aligned with the same circumferential position of the plurality of posts 1228. Fixation structure 1230 can be rotated about a central axis of fixation structure 1230 and / or housing 1222 in order to align posts to keyed structure 1232 and / or lock fixation structure 1230 between consecutive posts 1228. Fixation structure 1230 may function as a depth stop and / or for tissue engagement. Fixation structure 1230 may be circular in shape or define other shapes, such as triangle, square, hexagon, an amorphous shape, or any other shapes.

[0147] FIGS.13A, 13B, 14A, and 14B are conceptual diagrams of example implantation tools for implanting example medical leads. As shown in the example of FIGS.13A and 13B, system 1300 that includes example medical lead 1302 with tapered tip and implantation tool 1310. System 1300 may be similar to system 900 such that lead 1302 may be similar to lead 902 (or lead 1120 with fixation structures 1124) and implantation tool 1310 may be similar to implantation tool 920. As shown in the example of FIG.13A, lead 1302 may be similar to other leads herein such as lead 902, but lead 1302 may include other features that facilitate implantation with implantation tool 1310. For example, lead 1302 may include housing 1303 that carries or forms projection 1304 that extends radially outward from the main portion of housing 1303. Projection 1304 may be disposed partially around a perimeter or circumference of housing 1303, but in other examples, projection 1304 may be disposed around a full perimeter of housing 1303 or multiple projections may be present on housing 1303.Docket No.: A0008663WO01

[0148] Projection 1304 may function to prevent lead 1302 from moving proximally with respect to implantation tool 1310. Implantation tool 1310 may define a proximal lumen 1324 that may, in some examples, accept a stylet 1326 that can be moved axially within proximal lumen 1324 to push lead 1302 out of implantation tool 1310 and into tissue. The distal end of implantation tool 1310 may include a conical shoulder 1312 that defines distal opening 1314 configured to accept the proximal end of lead 1302. Conical shoulder 1312 may be the distal end of wall 1316 that forms a partial cylinder defining axial slot 1318. Interior surface 1320 forms cavity 1322 that is configured to accept a proximal portion of lead 1302. Tether 1306 may extend out from slot 1306.

[0149] Implantation tool 1310 may support implantation of lead 1302 within tissue by enabling a user to push the tip of lead 1302 into tissue with force transferring from implantation tool 1310 to projection 1304. Once conical shoulder 1312 is pressed up against tissue, the user may extend stylet 1326 distally out of lumen 1324 and against the proximal end of lead 1302. The user may continued to extend stylet 1326 which can push lead 1302 out of distal opening 1314 and fully into tissue. The user may then couple tether 1306 to an IMD.

[0150] As shown in the example of FIGS.14A and 14B, system 1400 that includes example medical lead 1402 with tapered tip and implantation tool 1410 may be substantially similar to system 1300, lead 1302, and implantation tool 1310. As shown in the example of FIG.14A, lead 1402 may be similar to other leads herein such as lead 1302, but lead 1402 may not include a projection. Instead housing 1403 of lead 1402 may be cylindrical to be accepted within distal opening 1314. However, to keep the distal end of lead 1402 at least partially extended out from distal opening 1314, implantation tool 1410 may include bumper 1404 which may be configured to extend radially inward into cavity 1322 from interior surface 1320.

[0151] Implantation tool 1410 may support implantation of lead 1402 within tissue by enabling a user to push the tip of lead 1402 into tissue with force transferring from implantation tool 1410 to bumper 1404 which contacts the proximal end of lead 1402. Once conical shoulder 1312 is pressed up against tissue, the user may extend stylet 1326 distally out of lumen 1324, past bumper 1404, and against the proximal end of lead 1402. The user may continue to extend stylet 1326 which can push lead 1402 out of distal opening 1314 and fully into tissue. The user may then couple tether 1306 to an IMD.

[0152] FIGS.15A include a cross-sectional view of an example depth-stop 1500 that can be used with implantation tool 1502 shown in FIG.15B. As shown in FIGS.15A and 15B,Docket No.: A0008663WO01 implantation tool 1502 may be similar to implantation tool 1410. However, implantation tool 1502 may be configured to be coupled to depth-stop 1500 that can prevent implantation tool 1502 from being extended into tissue deeper than the position of depth-stop 1500. Implantation tool 1502 may include elongated housing 1510 that that includes bumper 1404 within the cavity to prevent lead 1402 from being pushed proximally into elongated housing 1510. The outer surface of elongated housing 1510 may form, or carry, a plurality of notches 1504 that extend radially outward from the surface of elongated housing 1510. Depth-stop 1500 may be a partial ring that may have a circumference greater than 180 degrees and less than 360 degrees to stay attached to elongated housing 1510. This partial ring of depth-stop 1500 may enable a user to slide depth-stop 1500 axially to different axial positions between respective notches 1504 in order to set the desired implantation depth of lead 1402 into tissue.

[0153] As shown in FIG.15B, depth-stop 1500 can be set to match the position of bumper 1404 in order for the proximal end of lead 1402 to be flush with tissue. Depth-stop 1500 can be moved distally or proximally of that location in order to set lead 1402 deeper or shallower based on the desired location of electrodes within tissue. In some examples, elongated housing 1510 may include numbers or other text indicating the tissue depth that would correspond to depth-stop 1500 being attached at that location of elongated housing 1510.

[0154] FIG.16 is a conceptual diagram of an example medical lead 1602 and associated implantation tool 1600. As shown in the example of FIG 16, system 1600 includes example medical lead 1602 with tapered tip and implantation tool 1610. System 1600 may be similar to system 900 such that lead 1602 may be similar to lead 902 (or lead 1120 with fixation structures 1124) and implantation tool 1610 may be similar to implantation tool 920. As shown in the example of FIG.16, lead 1602 may be similar to other leads herein such as lead 902, but lead 1302 may include other features that facilitate implantation with implantation tool 1610. For example, lead 1602 may include housing 1603 that forms internal channel 1604 within housing 1603 to accept the distal end of implantation tool 1600. Lead 1602 may also include tether 1605 which may be similar to tether 912.

[0155] Implantation tool 1610 may be configured to hold lead 1602 and insert lead 1602 into tissue before releasing lead 1602. Implantation tool may include a control shaft 1612 that runs to the proximal end of the tool. Control shaft 1612 may be split at the distal end into distal tine 1614 and distal tine 1616. Distal tines 1614 and 1616 may form an expandable distal end and biased in an open configuration as shown in FIG.16 such that distal tines 1614 and 1616 apply pressure to the internal surface of internal channel 1604.Docket No.: A0008663WO01 This pressure causes a friction fit between distal tines 1614 and 1616 and the internal surface of internal channel 1604. Once lead 1602 is in place, the user may disengage distal tines 1614 and 1616 from internal channel 1604 of lead 1602 by sliding collar 1618 (along axial direction 1620) distally to force distal tines closer together. The user can then remove implantation tool 1600 from the patient.

[0156] FIGS.17A and 17B are conceptual diagrams of an example medical lead 1702 having a plurality of tapered tip sections 1706A and 1706B (collectively “tapered tip sections 1706”) configured to open to retain the medical lead 1702 in tissue. Lead 1702 may be similar to lead 902 or other leads described herein, but lead 1702 includes tapered tip sections 1706 that form the tapered distal tip of lead 1702. These tapered tip sections 1706 can be configured to be separated, or opened, to retain lead 1702 within tissue. Although two tapered tip sections 1706 are shown in the example of FIGS.17A and 17B, three or more sections may form the tapered tip of lead 1702 in other examples. In some examples, one or more of tapered tip sections 1706 may carry or be electrodes.

[0157] Lead 1702 can include a housing that can include portion 908 which may be or carry one or more electrodes, and recessed channel 910 both proximal from tapered tip sections 1706. Tether 912 may extend proximally from portion 908. Recessed channel 910 may be configured to be captured by an implantation tool such as implantation tool 920. After tapered tip sections 1706 are inserted into tissue, tapered tip sections 1706 may be configured to separate or open within the tissue. In some examples, implantation tool 920 may be configured to force tapered tip sections 1706 open using a stylet or lever than opens the tips. In other examples, lead 1702 may include one or more springs or other mechanisms that, in response to removing implantation tool 920, tapered tip sections 1706 expand and open within tissue.

[0158] FIG.18 is a conceptual diagram of an example medical lead 1820 having an array of flexible electrode segments 1828. As shown in the example of FIG.18, system 1800 may include connector 1802 that includes contacts 1806 at different axial locations along elongated housing 1804. A proximal end of elongated housing 1804 (not shown) may include additional contacts for coupling with an IMD. Contacts 1806 may be configured to be inserted through opening 1824 in lead housing 1822 and into channel 1826. Although not shown, channel 1826 may include additional contacts configured to electrically couple with respective contacts of contacts 1806 of connector 1802.

[0159] Lead housing 1822 may also carry a plurality of electrodes. These electrodes may be in the form of flexible electrode segments 1828 that extend from lead housing 1822 atDocket No.: A0008663WO01 different locations. Lead housing 1822 may be implanted at an anatomical location, such as a skull of the patient, and flexible electrode segments 1828 can be disposed into various tissue locations (e.g., at different locations of tissue around a resection cavity in a brain). In some examples, the entire length of each flexible electrode segments 1828 can be electrically conductive. In other examples, some portion of flexible electrode segments 1828 may be covered in an electrical insulation that only enables current from entering or leaving each flexible electrode segment 1828 at the exposed portion devoid of the insulation. In other examples, flexible electrode segments 1828 may carry one or more discrete electrodes. Although five flexible electrode segments 1828 are shown in the example of FIG.18, fewer or more segments may be provided in other examples. In addition, flexible electrode segments 1828 may have the same or different lengths as needed for the patient.

[0160] FIG.19 is a flowchart illustrating an example technique for implanting the medical lead of FIG.18 within a resection cavity of a patient. The method of FIG.19 may apply to any leads described herein that may be placed at a desired location in a resection cavity. As shown in FIG.19, a clinician may create the resection by removing target tissue from the patient (1902). The clinician may then insert one or more electrodes (or leads) to a desired location through the resection surface and anchor the electrode (or lead) into tissue (1904). If there is another electrode to implant (“YES” branch of block 1906), the clinician can insert another electrode or lead (1904). If there is no further electrode to implant (“NO” branch of block 1906), the clinician can couple the implanted electrodes (or leads) to a medical device for sensing or delivery of therapy (1908).

[0161] FIG.20 is a conceptual diagram of a medical lead 2000 comprising an array of implantable strut fixation structures 2010 that each include one or more electrodes. As shown in FIG.20, 5 strut fixation structures 2010 are included within lead 200. Lead 2000 can be implanted within tissue 702, which may be a portion of the brain of the patient or other tissue that may be associated with a tumor or tissue mass to be treated. Surface 706 may be the inner surface of resection cavity 704 (e.g., a tissue resection region). Although lead 2000 includes five strut fixation structures 2010 in this example, other examples of lead 2000 may include as few as one strut fixation structure, two or more strut fixation structures, or five or more strut fixation structures. In other examples, lead 2000 may include eight strut fixation structures 2010 or more. Each strut fixation structure 2010 may include a single electrode or two or more electrodes (such as electrodes 2022 and 2020) on a single strut fixation structure 2010.Docket No.: A0008663WO01

[0162] Each of strut fixation structures 2010 may include struts 2018 which can be constructed of metal, polymer, or other material that can hold shape within tissue to retain strut fixation structures 2010 within tissue 702. Struts 2018 are shown to have a double diamond configuration, but any configuration of a collection of connected struts may be used to define a shape that can retain strut fixation structures 2010 within tissue. Generally, struts 2018 may be constructed of a more rigid or stiff material and / or shape than the conductor 2012 which may be flexible and attached to structs 2018 and electrodes 2020 and 2022. Electrodes 2020 and 2022 may be “dot” electrodes or “button” electrodes in some examples. Electrodes 2020 and 2022 may be coupled to respective locations on struts 2018 such that struts 2018 can retain a desired distance between electrodes 2020 and 2022. Strut fixation structures 2010 may be positioned at any position around surface 706, which may create a planar or three-dimensional electrode array. Different strut fixation structures 2010 may be configured with different lengths and / or shapes of struts 2018 and / or different number of electrodes. Conductor 2012 for each strut fixation structure 2010 may electrically couple to both electrodes 2020 and 2022 or conductor 2012 may include respective electrical conductors for each of electrodes 2020 and 2022 in order to individually control each electrode. Wire 2016 may extend from conductor 2012 to electrode 2020. Each conductor 2012 may include an electrically conductive material covered by an insulating material, such as one or more polymers. Conductors 2012 may be flexible to enable the respective strut fixation structure 2010 to reach the desired target location.

[0163] The proximal ends of conductors 2012 can be coupled to lead body 730. Lead body 730 may include proximal housing 732 that extends proximally to a proximal end connector that is configured to be coupled to an IMD. Distal housing 734 may define a plurality of openings 736 that are each configured to accept a respective conductor 2012 and strut fixation structures 2010. In this manner, lead body 730 can contain all of conductors 2012 and manage conductors 2012 extending out from resection cavity 704. In some examples, lead body 730 may define a lumen that is configured to accept a stylet that can steer lead body 730 into the target area, such as resection cavity 704. A clinician may manually insert each strut fixation structures 2010 into the target position of tissue 702 using a gloved hand and / or a tool such as a forceps. In other examples, each strut fixation structure 2010 may initially be stored within a respective opening 736, and the distal end of distal housing 734 can be pressed against surface 706. The clinician may then activate a trigger or extender that forces the strut fixation structures 2010 out of openings 736 and at leastDocket No.: A0008663WO01 partially into tissue 702. The clinician can then reposition distal housing 734 to the next location on surface 706 to inject the next strut fixation structure.

[0164] In some examples, lead 2000 may facilitate implantation of a large variety of numbers of strut fixation structures 2010, such as only one strut fixation structure 2010, or a large number of strut fixation structures 2010 distributed around surface 706 of resection cavity 704. In this manner, the clinician may select the number of strut fixation structures 2010 needed to achieve appropriate coverage for AEF therapy or other therapy, or even mix and match different types of strut fixation structures 2010 (e.g., different lengths of struts 2018, different number of electrodes 2020 and 2022, etc.). In some examples, one or more wireless stimulation devices may be positioned within tissue 702, on surface 706, or even outside of this area and remote from other electrodes, such as subcutaneously or even externally on the scalp. This wireless stimulation device (or more than one) may include one or more electrodes that may supplement the other electrodes of lead 2000, for example. The one or more electrodes of the wireless stimulation device may be used to shape the electric field delivered to tissue 702 by using the wireless stimulation device. Alternatively, or additionally, the wireless stimulation device may be configured to provide an additional electric field to reach additional tissue that lead 2000 may not be able to reach without further tissue tunneling and damage. Wireless stimulation devices may be used with any leads or lead systems described herein.

[0165] FIGS.21A and 21B are conceptual diagrams of an example medical lead 2100 with a plurality of flexible arms 2104 carrying one or more electrodes 2106. As shown in the example of FIG.21A, lead 2100 includes four flexible arms 2104 that each include two respective electrodes 2106. Each of electrodes 2106 within lead 2100 may be coupled to respective conductors for independent control of each electrode. In other examples, two or more electrodes within lead 2100 may be electrically coupled so that they operate together. Coupled electrodes may be located on the same arm 2104 and / or different arms 2104. Flexible arms 2104 can be connected to a central hub 2102. Electrodes 2106 are shown as having a rounded rectangle shape, but the electrodes may have other shapes and sizes (e.g., circular or oval electrodes). All of electrodes 2106 may have the same shape or different shapes. The number of electrodes 2106 may be different on different flexible arms 2104.

[0166] As shown in FIG.21B, a side view of lead 2100 shows that each of arms 2104 can be flexible and bent to conform to the surface of tissue 2122 that defines resection cavity 2120. Lead housing 2108 is coupled to flexible arms 2104 and can carry one or more electrical conductors for electrodes 2106 back to an IMD. Electrodes 2106 may then be inDocket No.: A0008663WO01 contact with the surface of tissue 2122. However, in some examples, it may be desirable to also dispose one or more electrodes within tissue 2122. Depth lead 2130 includes electrodes 2132 that can be inserted into tissue 2122, and one or more electrodes 2132 can provide an electric field that extends further into tissue.

[0167] Although lead 2100 is shown such that flexible arms 2104 can bend proximally to confirm to the surface of a resection cavity 2120, lead 2100 can be used for other tissues. For example, flexible arms 2104 may be configured to bend distally to bend around a solid tumor or other mass of tissue such that electrodes 2106 are in contact with the surface of the solid tumor. Lead 2130 may then also be inserted into the solid tumor such that electrodes 2132 are disposed within the solid tumor, in some examples.

[0168] Electrodes 2106 are shows as relatively flush with the surface of flexible arms 2104. However, in some examples, one or more of electrodes 2106 may extend from flexible arms 2104 in order to pierce into tissue 2122 instead of just remaining on the surface of the tissue. For example, the electrodes that are at the distal ends of each flexible arm 2104 may be carried at a distal end of a respective post that extends away from the respective flexible arm 2104. The post can thus facilitate insertion of the electrode(s) into tissue.

[0169] FIGS.22A and 22B are conceptual diagrams of an example medical lead 2200 with a plurality of flexible arms 2104 carrying one or more electrodes 2104 and a central depth post 2202 carrying one or more electrodes 2204. Lead 2200 may be substantially similar to lead 2100 of FIG.21A, but lead 2200 may also include central depth post 2202 that is configured to be inserted into tissues. As discussed above, electrodes 2104 can be disposed on flexible arms 2104. As shown in the side view of FIG.22B, central depth post 2202 can extend distally from flexible arms 2104. Central depth post 2202 may be more rigid than flexible arms 2104 to support insertion of the distal end of central depth post 2202 into tissue. Two electrodes 2204 are shown, but only one electrode, or three or more electrodes may be used in other examples. Electrodes 2204 may be cylindrical electrodes, but in other examples, one or more of electrodes 2204 may be disposed at different circumferential positions and the same axial position such that the electrodes can focus the electrical field to that circumferential direction. Lead housing 2208 may extend proximally from flexible arms 2104 and carry one or more conductors that are electrically coupled to one or more of electrodes 2106 and 2204.

[0170] In some examples, flexible arms 2104 may be continually flexible along the length of each arm. In other examples, some portions of arms 2104 may be more rigid (such as portions that include an electrode of electrodes 2106, and other portions of arms 2104 mayDocket No.: A0008663WO01 be more flexible to support bending at that location. These more flexible portions of arms 2104 may be constructed of a different and more flexible material and / or shaped with a smaller thickness that enables easier bending at that location. These more flexible locations may be referred to as “flex points” and may be configured to correspond to desired flexing that matches an implantation site and target tissue for disposition of electrodes 2106 at target tissue.

[0171] FIGS.23A and 23B are conceptual diagrams of an example medical lead 2300 with a plurality of shapable arms 2304 comprising overmolded coils 2312. Lead 2300 may be substantially similar to lead 2100 of FIG.21A, but lead 2300 may be configured to have shapable arms 2304 can be bent to different shapes that retain that shape. Each shapeable arm 2304 can include a main body 2303 that is connected to central post 2302. Main body 2303 may support one or more electrodes 2306, and a coil 2312 may include many turns of a metal that is wrapped around at least one surface of main body 2303. Coil 2312 may be constructed of a metal or metal alloy, such as titanium or nitinol, that can retain a shape after being deformed. Overmold 2310 may then be formed over coil 2312 and main body 2303 to separate coil 2312 from fluids of the body. A portion of electrode 2306 can still be exposed from overmold 2310. Overmold may be constructed of one or more polymers and may be flowed or otherwise wrapped around main body 2303 and coil 2312. In other examples, shapable arms 2304 may not include an overmold.

[0172] As shown in the side view of FIG.23B, shapable arms 2304 may be positioned in a single plane, or may be deformed in any number of different configurations or shapes that may be desired to conform to target tissue and / or deliver the desired electrical fields. Central post 2302 may be a lead body that contains one or more conductors that are electrically coupled to one or more respective electrodes 2306 carried by conformable arms 2304. In some examples, lead 2300 may also include one or more depth electrodes that extend from one or more shapable arms 2304 and / or a depth post that extends distally from central post 2302. In this manner, lead 2300 may be configured to include at least one electrode that can be disposed within tissue instead of, or in addition to, electrodes that reside on the surface of tissue.

[0173] FIG.24 is a conceptual diagram illustrating a medical lead 2406 having a plurality of flexible conductors 2404 carrying respective electrodes 2406. As shown in the example of FIG.24, lead 2400 includes lead body 2402 which extends proximally to the proximal end of lead 2402. The proximal end of lead body 2402 may include connectors for coupling with an IMD. Extending out distally from lead body 2402 is flexible conductors 2404. AlthoughDocket No.: A0008663WO01 four flexible conductors 2404 are shown, fewer or more flexible conductors may be provided in other examples. Each flexible conductor 2404 may include one or more electrodes 2406. Each of the one or more electrodes 2406 may be disposed within or on the surface of target tissue for generating electrical fields between at least some of electrodes 2406. Flexible conductors 2404 may include an external insulative cover (e.g., a polymer jacket or overmold) that protects and insulates electrically conductive wire(s) within the insulative cover. Flexible conductors 2404 may be manipulated by a user to be disposed at any target tissue.

[0174] FIGS.25A and 25B are conceptual diagrams of an example medical lead 2500 with a plurality of deformable arms 2504 carrying one or more electrodes 2506 and a central depth post 2502 carrying one or more electrodes 2532. Lead 2500 may be substantially similar to lead 2100 of FIG.21A and lead 2300 of FIG.23A, but lead 2500 may be configured to have deformable arms 2504 can have relatively large surface area for resting on tissue. Each deformable arm 2504 can be connected to lead body 2508 and central post 2502. Each deformable arm 2504 may define a plurality of slits that allow different portions of each deformable arm 2504 to deflect in different directions or at different angles based on the shape of the target tissue. Each slit may include a rounded termination to reduce the likelihood of tearing the material. Deformable arms 2504 are shapes as ovals, but other shapes may be used in other examples. Each deformable arm 2504 includes two electrodes 2506, but fewer or more electrodes may be carried by any of the deformable arms. Deformable arms 2504 may be constructed of one or more polymers or other flexible materials.

[0175] As shown in the side view of FIG.23B, conformable arms 2504 may be positioned in a single plane, or may be deformed in any number of different configurations or shapes that may be desired to conform to target tissue (e.g., tissue 2522 that forms resection cavity 2520) and / or deliver the desired electrical fields. Lead body 2508 may be a lead body that contains one or more conductors that are electrically coupled to one or more respective electrodes 2506 carried by conformable arms 2504. In some examples, lead 2500 may also include one or more depth electrodes that extend from one or more conformable arms 2504 and / or depth post 2502 that extends distally from lead body 2508. In this manner, lead 2500 may be configured to include at least one electrode that can be disposed within tissue instead of, or in addition to, electrodes that reside on the surface of tissue.

[0176] FIGS.26A and 26B are conceptual diagrams of an example medical lead 2602 having a shape memory distal end 2610 for a deployed shape. As shown in FIG.26A, systemDocket No.: A0008663WO01 2600 may include lead 2602 and sheath 2606. Sheath 2606 may retain distal end 2610 in a straight undeployed configuration that can facilitate implantation. Electrodes 2604 are carried on the end of lead 2602, distal from shape memory distal end 2610. Once lead 2602 has been implanted and electrodes 2604 are positioned in the target tissue, the user may move sheath 2606 proximally in order to enable shape memory distal end 2610 to change to the deployed configuration which may include one or more bends. The deployed configuration of shape memory distal end 2610 may be configured to facilitate implantation, anchor lead 2602 to tissue, avoid one or more anatomical structures (e.g., nerves or blood vessels), and / or reach a desired tissue area. Shape memory distal end 2610 may include one or more shape memory materials embedded within a portion of lead 2602. In some examples, one or more electrodes 2604 may be disposed on or on either side of bends in the shape memory distal end 2610.

[0177] In some examples, lead 2602 may utilize additional anchoring to tissue once shape memory distal end 2610 is in the deployed configuration. For example, a user may apply biocompatible glue or adhesive to a portion of lead 2602. In another example, one or more anchoring mechanisms (threads, bumps, protrusions, tines, etc.) may be disposed on or near shape memory distal end 2610 such that the deployed configuration can assist in fixing the anchoring mechanism within tissue.

[0178] FIGS.27A and 27B are conceptual diagrams of an example medical lead 2700 with a plurality of deformable wings 2704 configured to bias respective electrodes 2706 against tissue surfaces. Lead 2700 may be substantially similar to lead 2100 of FIG.21A, but lead 2700 may be configured to have biasing arms 2704 that can be configured to apply a bias force against adjacent tissue in order to maintain contact between respective one or more electrodes 2706 to adjacent tissue. In this manner, biasing arms 2704 may be “spring like” with and wave-like shape in both the radial plane and the axial plane as shown in FIG.27B. The distal end of each of biasing arms 2704 are shown to include one electrode that be placed in contact with tissue, but multiple electrodes may be used on any of biasing arms 2704. A conductor may be disposed on the surface or, or within, each of biasing arms 2704 in order to couple respective electrodes 2706 to a connector at a proximal end of lead housing 2702.

[0179] As shown in FIGS.27A and 27B. each of biasing arms 2704 may be coupled to and extend radially from lead housing 2702. Although 3 biasing arms 2704 are shown, two biasing arms or four or more biasing arms may extend from lead housing 2702 in other examples. When implanted, the tissue 2722 can push back against each of biasing arms 2704 so that all of biasing arms 2704 are biased to retain electrodes 2706 against tissue 2722. LeadDocket No.: A0008663WO01 housing 2702 can extend distally from biasing arms 2704 in order to form central post 2302. Central post may include one or more electrodes 2712 that can be placed on the surface of tissue 2722 or inserted into tissue as shown in the example of FIG.27B. In this manner, lead 2700 may support electrical field generation between any of electrodes 2706 and 2712 in some examples.

[0180] FIGS.28A and 28B are conceptual diagrams of an example medical lead 2800 having a plurality of expandable fixation structures 2808 for retaining the medical lead 2800 within tissue. As shown in the example of FIG.28A, lead 2800 includes lead housing 2802 to which fixation structures 2808 and electrode 2804 are attached. A single electrode 2804 is shown near the distal end of lead housing 2802 in this example, but two or more electrodes may be carried by lead housing 2802 in other examples. Generally, all of the electrodes are disposed distally of fixation structures 2808, but in other examples, one or more electrodes may be disposed proximally, or in between, fixation structures 2808.

[0181] Fixation structures 2808 may be indirectly attached to lead housing 2808 via collars 2806. In some examples, one of collars 2806 is fixed to lead housing 2808 and other collars are free to “float” along the length of lead housing 2808. In other examples, all of collars 2806 are free to float along the length of lead housing 2808. Fixation structures 2808 may be coupled to two adjacent collars 2806. In the undeployed state, fixation structures 2808 may be generally parallel with lead housing 2808 and lie close to lead housing 2808. In this undeployed configuration, lead 2800 can be inserted into tissue. Although four collars 2806 with three sets of fixation structures 2808 disposed in between, fewer or greater numbers of fixation structures and / or collars may be used in other examples.

[0182] As shown in FIG.28B, collars 2806 can be collapsed together by moving the proximal collars towards the distal collar in the direction of arrow 2820. This collapsing of collars can force fixation structures 2808 into the deployed configuration in which fixation structures 2808 bend radially outward from lead housing 2802. Because fixation structures 2808 extend outward from lead housing 2802, fixation structures 2808 may press against, or into, adjacent tissue to hold lead 2800 in position with respect to tissue.

[0183] FIGS.29A and 29B are conceptual diagrams of example medical leads configured to form coils of electrodes. As shown in FIG.29A, lead 2900 includes lead housing 2902 and coil electrode 2904. Coil electrode 2904 may be a continuous electrode that is formed to include several loops 2906. A conductor (not shown) may electrically couple coil electrode 2904 to a proximal connector (not shown) that is configured to couple to an IMD. In other examples, coil electrode 2904 may have insulation at one or more portions of coil electrodeDocket No.: A0008663WO01 2904 that only enables electrical fields from being created from the exposed portions of coil electrode 2904. In other examples, one or more electrodes may be disposed on the coil to provide electrical field delivery. In some examples, loops 2906 may have a diameter and pitch configured to fill a resection cavity or spiral around a tumor or other volume of tissue.

[0184] As shown in FIG.29B, lead 2940 includes lead housing 2942 and electrodes 2944. Electrodes 2944 are disposed at different axial locations along coil 2946. Each of electrodes 2944 may be carried at different locations along lead housing 2942, and respective conductors may be disposed within housing 2942 and carried proximally to a connector for an IMD (not shown). Coil electrode 2904 may be a continuous electrode that is formed to include several loops 2906. A conductor (not shown) may electrically couple coil electrode 2904 to a proximal connector (not shown) that is configured to couple to an IMD. In some examples, coil 2946 may have a diameter and pitch (if multiple loops) configured to fill a resection cavity or spiral around a tumor or other volume of tissue.

[0185] The following examples are described herein.

[0186] Example 1. A medical lead including a housing comprising a main portion and a distal portion, wherein the main portion comprises a fixation structure and defines a first cross-sectional dimension, and wherein the distal portion defines a tapered tip and extends distally from the main portion; one or more electrodes carried by the housing; and a proximal tether comprising at least one conductor electrically coupled to the one or more electrodes, wherein the proximal tether extends proximal from the housing and defines a second cross- sectional dimension smaller than the first cross-sectional dimension.

[0187] Example 2. The medical lead of example 1, wherein the tapered tip comprises a conical shape.

[0188] Example 3. The medical lead of any of examples 1 and 2, wherein the tapered tip comprises at least one electrode of the one or more electrodes.

[0189] Example 4. The medical lead of any of examples 1 through 3, wherein the tapered tip comprises a first electrode of the one or more electrodes, and wherein the main portion of the housing carries a second electrode of the one or more electrodes.

[0190] Example 5. The medical lead of any of examples 1 through 4, wherein the tapered tip is formed by two or more tip portions, and wherein distal ends of the two or more tip portions are configured to be separated to retain the medical lead to tissue.

[0191] Example 6. The medical lead of any of examples 1 through 5, wherein the main portion of the housing defines a recessed channel around a perimeter of the main portion,Docket No.: A0008663WO01 wherein the recessed channel defines a third cross-sectional dimension less than the first cross-section dimension.

[0192] Example 7. The medical lead of example 6, wherein the recessed channel is configured to mate to a flange that is dimensioned to fit within a portion of the recessed channel, and wherein an implantation tool comprises the flange and a cradle that is configured to at least partially surround main portion of the housing.

[0193] Example 8. The medical lead of example 6, wherein the recessed channel is configured to retain a fixation structure configured to retain the housing within tissue of a patient, and wherein the fixation structure defines an opening sized less than the first cross- sectional dimension.

[0194] Example 9. The medical lead of example 8, wherein the fixation structure is constructed of a flexible mesh material.

[0195] Example 10. The medical lead of any of examples 8 or 9, wherein the fixation structure has a disk shape.

[0196] Example 11. The medical lead of any of examples 1 through 10, further comprising at least one fixation structure attached to the main portion of the housing, wherein the at least one fixation structure is configured to extend away from the main portion of the housing in a proximal direction.

[0197] Example 12. The medical lead of example 11, wherein the at least one fixation structure comprises a flexible skirt extending around at least half of a perimeter of the main portion.

[0198] Example 13. The medical lead of example 11, wherein the main portion of the housing defines a plurality of posts positioned at a same circumferential position and at different respective axial positions along a length of the main portion, and wherein the fixation structure defines a central opening including a keyed void, wherein the fixation structure is configured to be moved along the length the main portion and between different posts of the plurality of posts when the keyed void is circumferentially aligned with the same circumferential position of the plurality of posts.

[0199] Example 14. The medical lead of any of examples 1 through 13, wherein the main portion of the housing defines an internal channel having an opening at a proximal end of the main portion, and wherein the internal channel is sized to accept an introducer tool with an expandable distal end configured to expand within the internal channel to deliver the medical lead to a target tissue location.Docket No.: A0008663WO01

[0200] Example 15. The medical lead of any of examples 1 through 14, wherein the at least one conductor is electrically coupled to a connector configured to be coupled to an implantable medical device, the implantable medical device configured to deliver alternating electrical field therapy to a patient via the one or more electrodes.

[0201] Example 16. A method comprising implanting one or more medical leads within a target tissue of a patient, wherein each medical lead of the one or more medical leads comprises: a housing comprising a main portion and a distal portion, wherein the main portion comprises a fixation structure and defines a first cross-sectional dimension, and wherein the distal portion defines a tapered tip and extends distally from the main portion; one or more electrodes carried by the housing; and a proximal tether comprising at least one conductor electrically coupled to the one or more electrodes, wherein the proximal tether extends proximal from the housing and defines a second cross-sectional dimension smaller than the first cross-sectional dimension, and delivering alternating electrical field therapy to the tissue via electrodes of the one or more medical leads implanted within the target tissue of the patient.

[0202] Example 17. The method of example 16, wherein inserting the one or more medical leads comprises creating a tunnel through adjacent tissue via the tapered tip.

[0203] Example 18. The method of any of example 16 or 17, wherein the tapered tip is formed by two or more tip portions, and wherein the method further comprises separating distal ends of the two or more tip portions to retain the medical lead at the target tissue.

[0204] Example 19. The method of any of examples 16 through 18, wherein: the main portion of the housing defines a recessed channel around a perimeter of the main portion, the recessed channel defines a third cross-sectional dimension less than the first cross-section dimension, the recessed channel is configured to mate to a flange of an implantation tool when the main portion of the housing is configured to be at last partially surrounded by a cradle of the implantation tool, the flange being dimensioned to fit within a portion of the recessed channel, and implanting the one or more medical leads comprises inserting the implantation tool coupled to the main portion of the housing at least partially surrounded by the cradle.

[0205] Example 20. The method of example 19, wherein the recessed channel is configured to retain a fixation structure configured to expand out from the cradle of the implantation tool, and wherein the fixation structure defines an opening sized less than the first cross-sectional dimension.Docket No.: A0008663WO01

[0206] Example 21. The method of any of examples 16 through 20, wherein the at least one conductor is electrically coupled to a connector configured to be coupled to an implantable medical device, and wherein delivering the alternating electrical field therapy comprises delivering, by the implantable medical device, the alternating electrical field therapy to a patient via the one or more electrodes.

[0207] Example 22. A system including: one or more medical leads, each medical lead of the one or more medical leads comprising: a housing comprising a main portion and a distal portion, wherein the main portion comprises a fixation structure and defines a first cross- sectional dimension, and wherein the distal portion defines a tapered tip and extends distally from the main portion; one or more electrodes carried by the housing; and a proximal tether comprising at least one conductor electrically coupled to the one or more electrodes, wherein the proximal tether extends proximal from the housing and defines a second cross-sectional dimension smaller than the first cross-sectional dimension; and an implantable medical device comprising stimulation circuitry, the implantable medical device being configured to: couple with the at least one conductor of each medical lead of the one or more medical leads; and control the stimulation circuitry to generate one or more electrical signals deliverable via the one or more electrodes of the one or more medical leads.

[0208] Example 23. Any device, system, method, or computer-readable medium described or otherwise supported in the specification herein.

[0209] 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.

[0210] 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 theDocket No.: A0008663WO01 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.

[0211] 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 by separate hardware or software components, or integrated within common or separate hardware or software components.

[0212] 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.

[0213] Various examples have been described. These and other examples are within the scope of the following claims.

Claims

Docket No.: A0008663WO01 WHAT IS CLAIMED IS:

1. A medical lead comprising: a housing comprising a main portion and a distal portion, wherein the main portion comprises a fixation structure and defines a first cross-sectional dimension, and wherein the distal portion defines a tapered tip and extends distally from the main portion; one or more electrodes carried by the housing; and a proximal tether comprising at least one conductor electrically coupled to the one or more electrodes, wherein the proximal tether extends proximal from the housing and defines a second cross-sectional dimension smaller than the first cross-sectional dimension.

2. The medical lead of claim 1, wherein the tapered tip comprises a conical shape.

3. The medical lead of any of claims 1 and 2, wherein the tapered tip comprises at least one electrode of the one or more electrodes.

4. The medical lead of any of claims 1 through 3, wherein the tapered tip comprises a first electrode of the one or more electrodes, and wherein the main portion of the housing carries a second electrode of the one or more electrodes.

5. The medical lead of any of claims 1 through 4, wherein the tapered tip is formed by two or more tip portions, and wherein distal ends of the two or more tip portions are configured to be separated to retain the medical lead to tissue.

6. The medical lead of any of claims 1 through 5, wherein the main portion of the housing defines a recessed channel around a perimeter of the main portion, wherein the recessed channel defines a third cross-sectional dimension less than the first cross-section dimension.

7. The medical lead of claim 6, wherein the recessed channel is configured to mate to a flange that is dimensioned to fit within a portion of the recessed channel, and wherein an implantation tool comprises the flange and a cradle that is configured to at least partially surround main portion of the housing.Docket No.: A0008663WO01 8. The medical lead of claim 6, wherein the recessed channel is configured to retain a fixation structure configured to retain the housing within tissue of a patient, and wherein the fixation structure defines an opening sized less than the first cross-sectional dimension.

9. The medical lead of claim 8, wherein the fixation structure is constructed of a flexible mesh material.

10. The medical lead of any of claims 8 or 9, wherein the fixation structure has a disk shape.

11. The medical lead of any of claims 1 through 10, further comprising at least one fixation structure attached to the main portion of the housing, wherein the at least one fixation structure is configured to extend away from the main portion of the housing in a proximal direction.

12. The medical lead of claim 11, wherein the at least one fixation structure comprises a flexible skirt extending around at least half of a perimeter of the main portion.

13. The medical lead of claim 11, wherein the main portion of the housing defines a plurality of posts positioned at a same circumferential position and at different respective axial positions along a length of the main portion, and wherein the fixation structure defines a central opening including a keyed void, wherein the fixation structure is configured to be moved along the length the main portion and between different posts of the plurality of posts when the keyed void is circumferentially aligned with the same circumferential position of the plurality of posts.

14. The medical lead of any of claims 1 through 13, wherein the main portion of the housing defines an internal channel having an opening at a proximal end of the main portion, and wherein the internal channel is sized to accept an introducer tool with an expandable distal end configured to expand within the internal channel to deliver the medical lead to a target tissue location.

15. The medical lead of any of claims 1 through 14, wherein the at least one conductor is electrically coupled to a connector configured to be coupled to an implantable medicalDocket No.: A0008663WO01 device, the implantable medical device configured to deliver alternating electrical field therapy to a patient via the one or more electrodes.

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