Electric field therapy for pancreatic cancer

Abstract

Devices, systems, and techniques are disclosed for delivering electric field therapy to a pancreas of a subject. In one example, system can include an implantable structure comprising a plurality of electrodes, at least a portion of the implantable structure configured to be implanted within a pancreas. The system can also include an implantable medical device comprising stimulation circuitry configured to generate a plurality of electric fields deliverable to at least a portion of the pancreas via one or more electrodes of the plurality of electrodes.

Description

Docket No.: A0009895WO01 / 1123-783WO01 ELECTRIC FIELD THERAPY FOR PANCREATIC CANCER

[0001] This application is a PCT application claiming priority to, and the benefit of, U.S. Provisional Patent Application No.63 / 625,800, filed January 26, 2024, the entire contents of which is incorporated herein by reference. TECHNICAL FIELD

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

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

[0004] In general, the disclosure describes devices, systems, and techniques related to delivering electric and magnetic stimulation therapy, which includes electrical field therapy and / or detecting electrical signals for treating conditions associated with the pancreas. 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 that can be delivered to all or some of the pancreas of a patient. Other types of electric and magnetic stimulation therapy are described herein in various examples and combinations. For example, an implantable medical device (IMD) may be coupled to one or more leads carrying an array of electrodes. The leads may include an implantable structure configured for implantation at least partially within the pancreas in order to position one or more electrodes within a target portion of the pancreas. 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. In some examples, the target portionDocket No.: A0009895WO01 / 1123-783WO01 of the target tissue may be determined based on one or more factors such as: the size of the tumor(s), the shape of the tumor(s), the dispersity of the tumor / tumor cells, the resectability of the tumor (according to the stage of progression of the cancer and / or the location of the tumor relative to nearby anatomical features), anchoring the implantable device, or avoiding structures during surgery (e.g., blood vessels, critical structures, etc.).

[0005] The one or more leads may be configured to position the array of electrodes with respect to target tissue, such as target regions (before or after tissue resection) that is intended to receive the electrical field modulation. For example, the leads may include one or more structures configured to dispose the electrodes at a desired location with respect to a target tissue and / or tissue associated with a tissue resection region of the pancreas. These structures may be curved, flexible, formable, inflatable, and / or extendable from the lead housing in order to dispose the electrodes at locations to deliver electrical field modulation to target tissue which may be associated with the tissue resection region. The tissue resection region may be a region within the anatomy of the patient where tissue was removed, such tissue that included tumor cells, e.g., pancreatic cancer cells, 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 or tumorous cells, such as pancreatic cancer cells, or the reduction in growth or proliferation or directional migration of non-tumorous cells within the body. These cells may also be located outside of the pancreas and still be treated as described herein. 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.

[0006] In one example, a system includes an implantable structure comprising a plurality of electrodes, at least a portion of the implantable structure configured to be implanted within a pancreas; and an implantable medical device comprising stimulation circuitry configured to generate a plurality of electric fields deliverable to at least a portion of the pancreas via one or more electrodes of the plurality of electrodes.

[0007] In another example, a method includes generating, by stimulation circuitry of an implantable medical device, a plurality of electric fields deliverable to at least a portion of a pancreas via one or more electrodes of a plurality of electrodes, wherein an implantableDocket No.: A0009895WO01 / 1123-783WO01 structure comprises the plurality of electrodes, and wherein at least a portion of the implantable structure is configured to be implanted within the pancreas.

[0008] In another example, an implantable lead includes an implantable structure comprising a plurality of electrodes, at least a portion of the implantable structure configured to be implanted within a pancreas, one or more conductors disposed within an elongated housing coupled to the implantable structure, the one or more conductors configured to electrically couple to respective electrodes of the plurality of electrodes, and one or more proximal connectors configured to couple the plurality of electrodes to stimulation circuitry of an implantable medical device via the one or more conductors, wherein the plurality of electrodes are configured to deliver, via the stimulation circuitry of the implantable medical device, a plurality of electric fields to the pancreas.

[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 pancreas of 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.

[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.Docket No.: A0009895WO01 / 1123-783WO01

[0017] FIG.7 is a conceptual diagram illustrating an example expandable structure comprising electrodes and configured to deliver alternating magnetic field (AEF) therapy to a pancreas.

[0018] FIG.8 is a conceptual diagram illustrating an example electrode structure with tines to anchor the electrode structure within a pancreas.

[0019] FIGS.9A and 9B are conceptual diagrams illustrating an example expandable system configured to deploy electrodes into target tissue.

[0020] FIG.10 is a conceptual diagram illustrating an example shape memory expandable lead for deploying electrodes to a target tissue.

[0021] FIG.11 is a conceptual diagram illustrating example paddle leads for deploying electrodes to a target tissue.

[0022] FIG.12A is a conceptual diagram illustrating an example flexible electrode array.

[0023] FIG.12B is a schematic diagram illustrating components of the flexible electrode array of FIG.19B.

[0024] FIG.13 is conceptual diagram illustrating an example flexible electrode array configured for delivering alternating electric field (AEF) therapy to a pancreas of a patient.

[0025] FIG.14 is a flowchart illustrating an example technique for implanting a flexible electrode array on pancreatic tissue of a patient.

[0026] FIG.15 is conceptual diagram illustrating an example flexible electrode array together with tack electrodes configured for delivering alternating electric field (AEF) therapy to a pancreas of a patient.

[0027] FIG.16 is a conceptual diagram of example tack electrodes configured to be implanted within the surface of or a resection cavity of a pancreas of a patient.

[0028] FIG.17 is a flowchart illustrating an example technique for implanting multiple tack electrodes within a resection cavity of a pancreas or a patient. DETAILED DESCRIPTION

[0029] This disclosure describes various devices, systems, and techniques for delivering modulated electrical field therapy (which may include the example of AEF therapy) to a pancreas of 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 pancreas, or a region at risk for cancer or previously associated with cancer, which may disrupt cellular division for rapidly-dividing cancer cells. In some examples, AEF therapy canDocket No.: A0009895WO01 / 1123-783WO01 include electric fields having a frequency and / or intensity range selective to a certain type of cell, such as cancer cells instead of healthy 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 electrodes be placed in contact with the skin. Skin placed electrodes can result in irritation, interruption of treatment, short term tolerance requiring repositioning, or other issues with long term placement. 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, it can be difficult to direct the AEF therapy to treat target tissue within the patient, such as to a pancreas of the patient that is positioned deep within the patient and adjacent several other organs, such as the liver, small intestine, and stomach. This difficulty may be due to changing electric field propagation through different tissue types such as changing dielectric properties (e.g., conductivity). Moreover, applying the AEF therapy to a larger volume of tissue that includes healthy organs may provide undesirable side effects for the patient. Moreover, other cancer treatments for the pancreas, such as chemotherapy or external radiation therapy, can cause damage to other healthy tissue within the region effected by these other treatments.

[0030] As described herein, a system may include one or more leads (e.g., an electrode carrying structure) configured to deliver electric field therapy (also referred to as AEF therapy in some examples) from implanted electrodes at a location and strength local to the pancreas. This AEF therapy to the pancreas may include electrodes placed in contact with the exterior surface of the pancreas and / or electrodes placed within the pancreas. In some examples, placement within the pancreas may refer to placement within pancreatic tissue, within the parenchyma of the pancreas, one or more pancreatic ducts, and / or vasculature of the pancreas. 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 within the pancreas, such as a pancreatic tumor or other cancerous cells within the pancreas. The implanted electrodes may be selected to target tissue identified as including cancerous cellsDocket No.: A0009895WO01 / 1123-783WO01 or tissue around a resection area (e.g., a tissue resection region) where a previous tumor was removed. For example, a medical lead may include one or more implantable 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 of the pancreas. 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 either before and / or after resection. A computing device may be used for planning implantation of electrodes and / or selection of stimulation parameters based on imaging data obtained for the patient used to generate a model of patient tissue. The system may adjust the one or more stimulation parameters based on various feedback variables, such as impedance tomography, histological analysis, patient activity, sensed temperature, an indication of pancreatic fluid (e.g., pH of surrounding fluid), and the like. In this manner, the IMD may operate in a closed-loop manner based on one or more feedback variables obtained from the patient. The AEF therapy described herein may facilitate patient-specific AEF therapy directed to target tissue of the pancreas. Using implanted electrodes may enable the system to operate over larger periods of time without impacting other non-target tissues and / or during most patient daily activities. In addition, leads using deployable (e.g., extendable and / or expandable) structures to place electrodes within the patient may reduce tissue damage during implantation and / or reduce the surgical time needed for a clinician to implant the lead within the patient. In some examples, the implantable structures may be configured to be delivered via a catheter or biopsy needle, endoscope, laparoscope, or other surgical instrument. Alternating electric fields may thus be configured to treat pancreatic cancer or other cancer cells within the pancreas, by, for example, preventing further cancer cell growth, prevent metastasis of existing cancer cells, shrink existing tumors, and / or prevent new tumor growth. These and other advantages may be realized by the systems and examples described herein.

[0031] Although this disclosure is directed to delivery of AEF therapy to the pancreas for the purpose of treating pancreatic cancer, 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, target tissue may include regions of expected metastatic elements, such as lymph nodes, to reduce the spread of cells from a different tumor cite. Moreover, a human patient is described for example purposes herein, but similar systems, devices, and techniques may be used for other animals in other examples.Docket No.: A0009895WO01 / 1123-783WO01

[0032] Delivery of AEF therapy using an implanted system may offer several advantages related to energy required to deliver the fields, dosing schedule and continuity of dosing, therapy compliance, and efficacy in killing cancer / tumor cells. With the fields originating from electrodes positioned on and / or in the cancerous tissue or tumor bed of the pancreas, for example, the intensity of the electric fields can be maintained over a more focused or smaller distance. In other examples, voltage delivered could be increased to achieve efficacious intensity over a larger region, and / or the power source could be connected to multiple sets of electrodes.

[0033] 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.

[0034] FIG.1 is a conceptual diagram illustrating an example system that includes an implantable medical device (IMD) 106 configured to deliver alternating electric field (AEF) therapy to pancreas 126 of a patient 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, connector 108, lead 113, and implantable structures 114A and 114B with respective sets of electrodes (e.g., electrodes 116 and 118 of FIG.2). In the example shown in FIG.1, electrodes 116, 118 of implantable structures 114A, 114B are positioned to deliver electrical stimulation to a tissue site within pancreas 126, such as target tissue 128 within a portion of pancreas 126. In other words, implantable structures 114A, 144B are inserted through an opening 130 of pancreas 126 and to the target position within pancreas 126. Pancreas 126 is generally located adjacent to small intestine 124, stomach 122, and liver 120. Delivering electric fields between two or more of electrodes 116, 118 may reduce the effect of the electric fields of other healthy tissues, such as small intestine 124, stomach 122, and liver 120.

[0035] In some examples, delivery of electric fields (e.g., electrical stimulation) to one or more regions 128 of pancreas 126, such as a region that contains a tumor such as a tumor pancreatic tumor cells, or region from which a tumor was resected (removed). This locationDocket No.: A0009895WO01 / 1123-783WO01 where the tumor was removed, e.g., the tumor bed, may be or be part of the target tissue 128 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 electric signals within pancreas 126. In some examples, some of electrodes 116, 118 may be configured to sense conductive signals, impedance, etc., and some or all of electrodes 116, 118 may be configured to deliver electrical stimulation to pancreas 126 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 pancreas 126. Implantable structures 114A, 114B are merely examples, as any other structures or lead configurations described herein may be configured to position respective electrodes within and / or around pancreas 126 to deliver AEF therapy to patient 122.

[0036] IMD 106 includes a therapy module (e.g., which may include processing circuitry, signal generation circuitry or other electrical circuitry configured to perform the functions attributed to IMD 106) that includes a stimulation generator configured to generate and deliver electrical stimulation therapy (e.g., AEF therapy) to patient 112 via a subset of electrodes 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 (e.g., anode or cathode) 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 128 (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.

[0037] 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 electricalDocket No.: A0009895WO01 / 1123-783WO01 current that changes the polarities of cellular components to disrupt cell division. Although two implantable structures 114 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. Implantable structures 114 are shown as extending from a single lead 113, but in other examples, each of implantable structures 114 may be coupled to different respective leads that are separately connected to IMD 106. In any example, the combination of leads may provide an overall array of electrodes that can be programmed to deliver alternating electrical fields to a target tissue. In some examples, patient imaging (e.g., with or without contrast) may be used to help guide implantation of electrodes to reduce possible tissue damage. 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.

[0038] In some examples, IMD 106 or other devices of system 100 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.

[0039] The system 100 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 pancreas 126 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 electrical signals. In other examples, the same electrodes may be used to deliver electrical stimulation and sense electrical signals. However, this configuration of using theDocket No.: A0009895WO01 / 1123-783WO01 same electrodes could require the system to switch between stimulation generation and sensing circuitry and may reduce the time the system can sense electrical 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.

[0040] 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.

[0041] IMD 106 may be implanted within a subcutaneous pocket above the clavicle or at any other suitable site within patient 112 such as a lower abdominal or high buttock location.Docket No.: A0009895WO01 / 1123-783WO01 Other configurations might include IMD 106 implanted at multiple locations, such as near a site of tumor occurrence and remote sites of likely tumor transmission or spread. Generally, IMD 106 is constructed of a biocompatible material that resists corrosion and degradation from bodily fluids. IMD 106 may comprise a hermetic housing to substantially enclose components, such as a processor, therapy module, and memory.

[0042] As shown in FIG.1, lead 113 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 113 traverses from the implant site of IMD 106 through the abdomen and to pancreas 126. In the example shown in FIG.1, implantable structures 114A and 114B (collectively “implantable structures 114”) are implanted adjacent to target tissue 128, respectively, of patient 112 in order deliver AEF therapy to one or more regions of pancreas 126, 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 113 and IMD 106 implant sites are contemplated. Although implantable structures 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.

[0043] Implantable structures 114 illustrate an example lead set that include axial leads carrying ring electrodes disposed at different axial positions (or longitudinal positions). In other examples, implantable structures may be referred to as “paddle” leads or implantable structures 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 implantable structures. For example, an implantable structure 114 may include or extend from 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. Implantable structures 114 may also include a plurality of electrodes disposed on the one or more structures and configured to deliver electrical fields to tissue. These one or more structures may be configured to position the plurality of electrodes with respect to a tissue resection region or other target tissue that is intended to receive the electrical fields (e.g., AEF therapy). For example, the one or more structures may beDocket No.: A0009895WO01 / 1123-783WO01 extendable prongs, curved members, expandable structures configured to expand in a radial direction, flexible mesh grids, tacks, or other structures configured to dispose the electrodes in a spatial configuration to deliver the electrical fields to tissue. In this manner, implantable structures 114 may be configured to be implanted within a patient comprising the tissue resection region.

[0044] Although implantable structures 114 are shown in FIG.1 as being coupled to a lead 113, in other examples, lead 113 may be coupled to IMD 106 via one or more lead extensions or directly to connector 108. Implantable structures 114 may be positioned to deliver electrical stimulation to one or more target tissue sites within pancreas 126. Implantable structures 114 may be implanted to position electrodes 116, 118 at desired locations of pancreas 126. Implantable structures 114 may be placed at any location within pancreas 126 such that electrodes 116, 118 are capable of providing electrical stimulation to target tissue 128 within pancreas 126 during treatment. For example, electrodes 116, 118 may be surgically implanted using a biopsy needle or catheter, and electrically coupled to IMD 106 via one or more leads 113.

[0045] In the example shown in FIG.1, electrodes 116, 118 of implantable structures 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 insulated portion. In some examples, fewer electrodes may be used to generate smaller electrical fields specifically selected to affect target tissue during the AEF delivery while avoiding subjecting other tissues to the electric fields. In some examples, a housing of IMD 106 may include one or more stimulation and / or sensing electrodes. In alternative examples,Docket No.: A0009895WO01 / 1123-783WO01 implantable structures 114 may have shapes other than elongated cylinders as shown in FIG. 1. For example, implantable structures 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.

[0046] 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 conformable grids, volumetric “balloons,” multiple small electrodes placed individually within the void, anchorable electrodes, spring formed structures (nitinol or other compliant material) to expand to fill the volume, tack electrodes, rotationally deployed electrodes, and hybrid arrays with paddle and / or grid elements to cover void surface and penetration elements to extend field perpendicular to the tissue surface.

[0047] 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 deliver AEF therapy to lymphatic channels, the spleen, thymus, or other anatomical location within the patient to modulate the proliferation of lymphocytes or leukocytes.

[0048] External programmer 104 wirelessly communicates with IMD 106 as needed to provide or retrieve therapy information. Programmer 104 is an external computing device that the user, e.g., a clinician and / or patient 112, may use to communicate with IMD 106. For example, programmer 104 may be a clinician programmer that the clinician uses to communicate with IMD 106 and program one or more therapy programs for IMD 106. Alternatively, programmer 104 may be a patient programmer that allows patient 112 to select programs and / or view and modify therapy parameters. The clinician programmer may include more programming features than the patient programmer. In other words, more complex or sensitive tasks may only be allowed by the clinician programmer to prevent an untrained patient from making undesirable changes to IMD 106. IMD 106 may also transmitDocket No.: A0009895WO01 / 1123-783WO01 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.

[0049] 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 implantable structures 114 and the electrode arrangement, the position of implantable structures 114 within pancreas 126, 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.

[0050] 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. For example, programmer 104 may present that “AEF therapy has been delivered for 85% of the time during the last week” or “AEF therapy has been delivered during 6 of the last 7 days.” In addition, programmer 104 may present remaining therapy time available before recharge is required when IMD 106 operates using a rechargeable power source. In some examples, the user interface may present a map of the pancreas with the electrode configuration representedDocket No.: A0009895WO01 / 1123-783WO01 and one or more zones of tissue that receive a specified therapeutic parameter (such as V / cm). In some examples, the user interface may be configured to receive user input manipulating the orientation of the field and / or adjustment of other stimulation parameter values.

[0051] 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.

[0052] 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, implantable structures 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.

[0053] 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.

[0054] 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 electrodeDocket No.: A0009895WO01 / 1123-783WO01 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.

[0055] In one example in which IMD 106 utilizes 4 different implantable leads (or 4 structures extending from a single lead), the first electrode combination includes a first set of anodes carried by a first lead, the second electrode combination includes a first set of cathodes carried by a second lead different than the first lead, the third electrode combination includes a second set of anodes carried by a third lead different than the first lead and the second lead, and the fourth electrode combination includes a second set of cathodes carried by a fourth lead different than the first lead, the second lead, and the third lead. The first and second electrical fields may generally be orthogonal or oblique to each other. In another example in which two leads are used to deliver AEF therapy, the first electrode combination includes a first set of anodes carried by a first lead, the second electrode combination includes a first set of cathodes carried by a second lead different than the first lead, the third electrode combination comprises a second set of anodes carried by the second lead, and the fourth electrode combination comprises a second set of cathodes carried by the first lead. In some examples, the AEF therapy may include alternating or switching between the first electrode combination and the second electrode combination, where some or all of electrodes of the first lead switch between operating as anodes in the first electrode combination and operating as cathodes in the second electrode combination, and electrodes of the second lead switch between operating as cathodes in the first electrode combination and operating as anodes in the second electrode combination. In other examples, the first and second electrode combinations may utilize completely different electrodes for each anodes and cathodes. In other examples, each electrode combination may utilize one lead for anodes and a different lead for cathodes. The different electrode combinations used to alternate electric fields may share leads or utilize separate leads for each electrode combination. These are only some of the different methods for generating alternating electric fields from an array of implanted electrodes, as other examples are also contemplated. For example, IMD 106 may instead alternate, or sweep through, three or more different electrical fields generated from respective electrode combinations. These larger number of electrical fields may effectively treat a larger number of cells depending on the location of the cells within respect to the location of the implanted electrodes.

[0056] 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. ForDocket No.: A0009895WO01 / 1123-783WO01 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.

[0057] In some examples, IMD 106 is configured to cycle the AEF therapy on and off according to a predetermined schedule. This predetermined cycle may be set according to the speed of tumor cell division in order to cycle the AEF therapy at a rate that enables the tumor cells are guaranteed to experience a relevant field at least once per cell divisional time to inhibit the division of the cells. In other examples, IMD 106 may be configured to receive temperature data indicative of a temperature of tissue that receives the AEF therapy, determine that the temperature exceeds a threshold temperature, responsive to determining that the temperature exceeds the threshold temperature, terminate delivery of the AEF therapy. This temperature monitoring may reduce the risk of tissue damage due to electrical field induced tissue heating.

[0058] 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.Docket No.: A0009895WO01 / 1123-783WO01

[0059] 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, Cm is the membrane capacitance, and σi and σe are the conductivity of the cytoplasm and external medium respectively. Given σi andare nearly identical, this equation can be simplified to:Given that within an individual cell the values for r and Cmwill remain approximately constant within an example frequency range for AEF therapy (e.g., 100kHz – 1MHz, or 100kHz – 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 fmaxis 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 * mm / S / nm, σi is 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. In some examples for pancreatic cancer, which possesses a cancer cell diameter of 18-22mm (for the purposes of this example, 20mm), 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,Docket No.: A0009895WO01 / 1123-783WO01 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.

[0060] 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 optimal frequency for maximal efficacy of AEF therapy if cell size dependent (as above), the system may deliver a sweep of different frequencies such as an interleaved or continuously sweeping protocol ranging between 100kHz to 250kHz would provide an optimal treatment for the diverse cell population of the tumor

[0061] 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 pancreatic cancer 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 exposure 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.

[0062] 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 104Docket No.: A0009895WO01 / 1123-783WO01 and / or IMD 106 may adjust one or more stimulation parameters that at least partially defines the AEF therapy based on histological data obtained from a sample of tissue affected by the AEF therapy. In another example, programmer 104 and / or IMD 106 may determine target tissue for AEF therapy based on water content data obtained from magnetic resonance imaging (MRI) data, and determine, based on the target tissue, the first electrode combination and the second electrode combination for delivery of the AEF therapy. In some examples, determining the electrode combinations may include determining the location, e.g., based on predictive computational models of electric field intensity in tissue, at which one or more leads should be located in order to deliver AEF therapy to the target tissue. As another example, programmer 104 and / or IMD 106 may determine target tissue for AEF therapy based on impedance tomography data obtained from sensed electrical potentials sensed from two or more of the implanted electrodes (and / or external electrodes disposed to record electric fields), and determine, based on the target tissue, at least the first electrode combination and the second electrode combination to deliver the AEF therapy. For example, impedance may be indicative of malignant cells with respect to healthy cells, and the system can direct implantation or electric fields to impedance indicated target tissue. 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.

[0063] 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 AEFDocket No.: A0009895WO01 / 1123-783WO01 therapy, the electrode near or within the non-target tissue could be paired to the local stimulating electrodes in a 180oor p 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 0p radians phase shifting configuration between the local electrode and the remote stimulating electrode. By conducting the stimulation in this manner, there is less permissible of differential established in the peak-to- peak voltage experienced by the local tissue and therefore a reduction in the resulting electric field.

[0064] In another example, the electrode combinations may be selected from a cube configuration where the selectable electrodes for each electrode combination form the eight vertices of a cube. In this example, the first electrode combination includes a first set of electrodes defined as cathodes and a second set of electrodes defined as anodes in a first paired configuration from the cube configuration, and the second electrode combination includes the first set of electrodes defined as anodes and the second set of electrodes defined as cathodes in a second paired configuration from the cube configuration.

[0065] 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 pancreas 126 and / or electrodes disposed on the outer surface of pancreas 126 or near pancreas 126.

[0066] Generally, AEF therapy is described herein as a treatment to already present tumors, such as pancreatic cancer. 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 prevent additional metastatic spread of tumor within the pancreas from current metastatic dissemination.

[0067] An AEF delivery implant (e.g., IMD 106 and implantable structures 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 implantable structures 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 axillaryDocket No.: A0009895WO01 / 1123-783WO01 lymph nodes in the setting of a newly diagnosed pancreatic 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. In some examples, the implantation strategies may be customized to the specific diagnosed tumor location (e.g., head or tail of pancreas to then focus on the liver, stomach, or lungs) or whether resection of the tumor and / or pancreas has occurred.

[0068] 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.

[0069] 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 or within pancreas 126 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.

[0070] As described herein, system 100 may include one or more implantable structure 114 comprising a plurality of electrodes 116 and / or 118. At least a portion of the implantable structure 114 may be configured to be implanted within pancreas 126. System 100 may also include implantable medical device 106 including stimulation circuitry configured to generate a plurality of electric fields deliverable to at least a portion of the pancreas via one or more electrodes of the plurality of electrodes. In some examples, all electrodes of the plurality of electrodes of implantable structure 114 are configured to be disposed within the pancreas. In some examples, at least a first electrode of the plurality of electrodes of implantable structureDocket No.: A0009895WO01 / 1123-783WO01 114 is configured to remain outside of pancreas 126 with at least a second electrode of the plurality of electrodes of implantable structure 114 being configured to be disposed within the pancreas. In some examples, implantable structure 114 is configured to be implanted one of percutaneously or subcutaneously. Implantable structures 114 may be configured to be delivered non-invasively, such as via a catheter or inserted through a needle such as a biopsy needle or other minimally invasive surgical instrument such as through trocar or using a camera to locate the target tissue. In some examples, more invasive open surgical techniques may be used alternatively or additionally.

[0071] In some examples, system 100 may include one or more (same and / or different) sensors that are configured to sense a particular physiological condition, and system 100 may utilize signals from one or more of these sensors to perform various functions such as determine the location of electrodes 114 during or after implantation, determine electrode migration, determine efficacy of AEF therapy, identify one or more side effects, or otherwise obtain feedback regarding therapy using system 100. In one example, one or more of implantable structures 114 may include one or more pH sensors configured to sense a physiological condition indicative of fluids from the pancreas 126. For example, the pH within pancreas 126 (typically between 8.3 and 8.6) may be different than surround tissues such as interstitial tissue or within a different organ. System 100 can use this pH to help identify the target tissue 128 or track pancreas 126 function during therapy for purposes of adjusting one or more parameters that define AEF therapy from electrodes 114. System 100 may thus be equipped with one or more sensors configured to aid in targeting / differentiating tumor tissue from non-tumor tissue for positioning electrodes, monitoring effect / progression of treatment, etc. For example, when equipped with pH sensor, the pH of cancerous pancreatic tissue is expected to be measured around 6.98 whereas the pH of noncancerous pancreatic tissue is expected to be around 7.54. These values can be used to determine proper placement and / or progression of disease. In some examples, the measurement of pH could also be used by the system to differentiate cancerous and noncancerous tissues to inform the localized focus of the AEFs and / or defining the boundary of the region requiring the relative maximum field strength.

[0072] Other physiological characteristics may also be identified or monitored by system 100. In some examples, IMD 106 or another device of system 100 may include sensing circuity and processing circuitry, wherein the processing circuity is configured to control the sensing circuitry to measure an impedance of tissue. This impedance measurement may also include delivery of a signal via one or more electrodes 114. System 100 may determine thatDocket No.: A0009895WO01 / 1123-783WO01 the impedance is out of range and generate an alert, for delivery to a user, indicating a change with the tissue adjacent at least a portion of the implantable structure. For example, IMD 106 may transmit this alert to programmer 104, and programmer 104 may present the alert to the user, such as the clinician or patient.

[0073] In the example of FIG.1, implantable structures 114 are in the form of cylindrical leads that carry curved electrodes around the circumference of each lead. Implantable structures 114 and the electrodes carried thereon may take different forms in different examples, such as paddle structures with electrodes on one or both sides of the paddle or needle electrodes. In any of the different example implantable structures and / or electrode configurations described herein may be used alone or in combination with one or more other types of implantable structures or electrode configurations.

[0074] In one example, an implantable structure may be an expandable stent including a plurality of interconnected struts, and wherein the expandable stent carries the plurality of electrodes. The implantable structure may have different dimensions to facilitate desired location of electrodes 114 within pancreas 126. For example, the implantable structure may include a structure body carrying the plurality of electrodes and having a first cross-sectional dimension (such as a diameter or cross-sectional area) and one or more tines configures to anchor the implantable structure within the pancreas. The one or more times are disposed distally of the plurality of electrodes in some examples, but may be located proximal to one or more electrodes in other examples. The implantable structure may include a proximal stop portion proximal of the plurality of electrodes, wherein the proximal stop portion defines a second cross-sectional dimension (e.g., diameter or area) larger than the first cross-sectional dimension. In this manner, the proximal stop portion may resist further insertion of the implantable structure within the pancreas. The proximal stop portion may include one or more electrodes that can contact an external surface of the pancreas in some examples.

[0075] In some examples, the implantable structure is shaped like a tack and may be referred to as a tack electrode although the tack may include more than one electrode. The tack may include a housing comprising a non-conductive cap and a post coupled to the non- conductive cap and configured to carry the plurality of electrodes at different axial positions along the post. The cross-sectional area of the post may be smaller than a cross-sectional area of the non-conductive cap in order for the cap to limit the tack from proceeding deeper into the pancreas. In some examples, the post is configured to be inserted into tissue to a depth limited by a length of the post extending from a distal surface of the non-conductive cap.Docket No.: A0009895WO01 / 1123-783WO01

[0076] In some examples, the implantable structure may include a flexible mesh carrying electrodes such that the flexible mesh and the at least some electrodes are configured to contact an external surface of the pancreas. These electrodes of the flexible mesh outside of the pancreas may deliver AEF therapy alone or between one or more electrodes also inserted within pancreas 126.

[0077] In some examples, the implantable structure may have one or more moving parts that enable deployment of electrodes into the tissue once inserted to a desired location adjacent to, or within, the pancreas. For example, the implantable structure may include an external housing and an internal housing (e.g., FIGS.9A and 9B), where the external housing can rotate circumferentially about a common axis with the internal housing. The external housing may include a plurality of openings, each opening of the plurality of openings being configured to allow a respective electrode of the plurality of electrodes to pass. In some examples, the electrode may be a wire or be carried by a wire that can pass through the respective opening. Rotation of the external housing with respect to the internal housing causes the plurality of electrodes to extend radially out from the respective openings of the external housing. For example, the user may twist a handle coupled to either the internal or external housing such that electrodes coupled to the internal housing can extent radially outward through the respective openings in the external housing in response to rotation of the inner housing with respect to the outer housing.

[0078] As described herein, a variety of different implantable structures, electrodes, or combination thereof, may be configured specifically for directing AEF therapy to the pancreas of the patient. One or more of these implantable structures and / or electrodes may be selected based on tumor size, tumor location, stage of cancer, and / or whether the tumor(s) have not been resected or have been resected. In some examples, the tumor may be operable and removed, but some cancer cells may still remain in the tumor bed for treatment as described herein. These situations may include bile duct removal, post-Whipple resections, and / or post-distal pancreatectomy. In other examples, the tumor may not be resectable, but implanting one or more implantable structures and electrodes described herein may provide treatment to the non-resectable tumor or other cancerous cells of the pancreas. In some examples, electrodes may be implanted within the pancreas, on a surface of the pancreas, within the stomach, within the liver, within one or more blood vessels, within one or more bile ducts, within one or more lymph ducts, within a spleen, or within the abdominal cavity and direct AEF therapy to the pancreas or treat pancreatic cancer cells.Docket No.: A0009895WO01 / 1123-783WO01

[0079] Other tissues may also be targeted for implantation of structures, electrodes, or combinations thereof. Example ligaments of relevance based on local proximity to target tissues may include the omentum, gastrocolic ligament (atop the pancreas and may be too thin for an anchor but a device could penetrate through this), peritoneum, or gastroheaptic ligament. In some cases it may be advantageous to place components in the foramen of winslow, the lesser sac (a potential space between the abdomen), transverse mesocolon, mesenteric vessels (artery and vein that occur where the duoenum bends, ligament of trite, pancreatic duct, sphincter of odi (where a device can be left behind in the duct), or the inferior vena cava at the level of the umbilicus. In some cases, implantation of electrodes and / or the structure can include cutting through fascia to access the posterior side of the pancreas, or wires could go along the paraspinal muscles in the back, and then bring out cephalad or posterior to colon (between colon and liver) and out the abdominal wall (to avoid bowel obstruction). If structures are not sutured into the organ (to avoid a fibrotic reaction that could occur in examples such as mesh on the surface eliciting fibrosis), structures could be held in position by contact from the other organs (e.g., by the stomach on top of the pancreas). For laparoscopic implantation, the clinician can pull the colon down, dissect under the inferior border of the pancreas, and put electrodes underneath such as where the tail of the pancreas is present.

[0080] FIG.2 is a block diagram of the example IMD 106 of FIG.1 for delivering AEF therapy according to an example of the techniques of the disclosure. 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.Docket No.: A0009895WO01 / 1123-783WO01

[0081] 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 therapy program 214 defines a particular set of electrical stimulation parameters (e.g., a therapy parameter set), such as a stimulation electrode combination, electrode polarity, current or voltage amplitude, pulse width, and pulse rate. In some examples, individual therapy programs may be stored as a therapy group, which defines a set of therapy programs with which stimulation may be generated.

[0082] 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.

[0083] 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.

[0084] Stimulation generator 202, under the control of processing circuitry 210, generates stimulation signals for delivery to patient 112 via selected combinations of electrodes 116,Docket No.: A0009895WO01 / 1123-783WO01 118. An example range of electrical stimulation parameters believed to be effective in AEF therapy to manage cellular activity include: 1. Frequency (e.g., waveform frequency or pulse rate): between approximately 50 kHz and approximately 500 kHz, such as between approximately 100 kHz to 300 kHz, or such as approximately 150 kHz or 200 kHz. 2. In the case of a voltage controlled system, Voltage Amplitude: between approximately 0.1 volts and approximately 50 volts, such as between approximately 2 volts and approximately 10 volts. 3. In the alternative case of a current controlled system, Current Amplitude: between approximately 0.2 milliamps to approximately 100 milliamps, such as between approximately 1.3 milliamps and approximately 2.0 milliamps. 4. Pulse Width: between approximately 1 microseconds and approximately 10 microseconds, such as between approximately 1 microseconds and approximately 5 microseconds, or between approximately 2 microseconds and approximately 10 microseconds. 5. Cycle time (e.g., communication time), which is the time a waveform remains consistent before switching off or switching to a new waveform or phase. 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.

[0085] 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).

[0086] 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 processingDocket No.: A0009895WO01 / 1123-783WO01 circuitry 210 herein may be embodied as firmware, hardware, software or any combination thereof. Processing circuitry 210 may control stimulation generator 202 according to therapy programs 214 stored in memory 211 to apply particular stimulation parameter values specified by one or more of programs, such as voltage amplitude or current amplitude, pulse width, or pulse rate.

[0087] 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 electrical 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).

[0088] 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.

[0089] 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 electrodesDocket No.: A0009895WO01 / 1123-783WO01 at each longitudinal location along the length of the lead, such as multiple electrodes at different perimeter locations around the perimeter of the lead at each of the locations A, B, C, and D. On one example, the electrodes may be electrically coupled to switch module 206 via respective wires that are straight or coiled within the housing or the lead and run to a connector at the proximal end of the lead. In another example, each of the electrodes of the lead may be electrodes deposited on a thin film. The thin film may include an electrically conductive trace for each electrode that runs the length of the thin film to a proximal end connector. The thin film may then be wrapped (e.g., a helical wrap) around an internal member to form the lead 114. These and other constructions may be used to create a lead with a complex electrode geometry.

[0090] 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 electrical signals that may be sensed include muscle potentials, local field potentials (LFPs), evoked compound action potentials (ECAPs), or any other signals near or within the pancreas or nerves intervening the pancreas. 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. IMD 106 may conduct sensed signals in real-time in an interleaved manner to permit ongoing stimulation with periodic analysis.

[0091] 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), pH, or any other physiological activity. 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).

[0092] 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,Docket No.: A0009895WO01 / 1123-783WO01 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.

[0093] Power source 220 delivers operating power to various components of IMD 106. Power source 220 may include a small rechargeable or non-rechargeable battery and a power generation circuit to produce the operating power. Recharging may be accomplished through proximal inductive interaction between an external charger and an inductive charging coil within IMD 220. In some examples, power requirements may be small enough to allow IMD 220 to utilize patient motion and implement a kinetic energy-scavenging device to trickle charge a rechargeable battery. In other examples, traditional batteries may be used for a limited period of time. In other examples, IMD 106 may include a power receiving antenna an corresponding circuitry to continually receive external power that enables IMD 106 to deliver electric field therapy indefinitely without possible internal power source drain.

[0094] 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.

[0095] 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 oneDocket No.: A0009895WO01 / 1123-783WO01 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.

[0096] FIG.3 is a block diagram of the external programmer 104 of FIG.1 for controlling delivery of AEF therapy 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.

[0097] 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.Docket No.: A0009895WO01 / 1123-783WO01

[0098] 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.

[0099] 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.

[0100] 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.

[0101] 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 toDocket No.: A0009895WO01 / 1123-783WO01 transmit a spatial electrode movement pattern or other stimulation parameter values to IMD 106 for delivery of stimulation therapy.

[0102] FIG.4 is a block diagram illustrating an example system 354 that includes an external device, such as a server 360, and one or more computing devices 362A-362N, that are coupled to IMD 106 and external programmer 104 shown in FIG.1 via a network 352. 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 350 via a second wireless connection.

[0103] In the example of FIG.4, access point 350, external programmer 104, server 360, and computing devices 362A-362N are interconnected, and able to communicate with each other, through network 352. In some cases, one or more of access point 350, external programmer 104, server 360, and computing devices 362A-362N may be coupled to network 352 through one or more wireless connections. In some examples, computing device 362N (or any other computing devices) may be configured to communicate directly to programmer 104 over communication link 356 (e.g., via short range wireless communication such as Bluetooth) such that programmer 104 can relay commands or data between IMD 106 and computing device 362N. IMD 106, external programmer 104, server 360, and computing devices 362A-362N 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.

[0104] Access point 350 may comprise a device, such as a home monitoring device, that connects to network 352 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 350 may be coupled to network 352 through different forms of connections, including wired or wireless connections.

[0105] 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 externalDocket No.: A0009895WO01 / 1123-783WO01 programmer 104 and / or server 360, either wirelessly or via access point 350 and network 352, for remote processing and analysis.

[0106] 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 352 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 362A. Alternatively, processing, trending and evaluation functions may be distributed to other devices such as external programmer 104 or server 360, which are coupled to network 352. In addition, AEF therapy data may be archived by any of such devices, e.g., for later retrieval and analysis by a clinician.

[0107] In some cases, server 360 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 352 may comprise a local area network, wide area network, or global network, such as the Internet. In other cases, external programmer 104 or server 360 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 362A-362N. System 354 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.

[0108] Although some examples of the disclosure may involve AEF therapy information and data, system 354 may be employed to distribute any information relating to the treatment of patient 112 and the operation of any device associated therewith. For example, system 354 may allow therapy errors or device errors to be immediately reported to the clinician. In addition, system 354 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 354 to monitor multiple patients and share data with other clinicians in an effort to coordinate rapid evolution of effective treatment of patients.

[0109] 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 the pancreas or other associated structure to a target position within the pancreas or at other locations in associationDocket No.: A0009895WO01 / 1123-783WO01 with the pancreas. In some examples, external electrodes may be used instead of, or in addition to, leads such as lead 400.

[0110] Lead 400 can be implanted within the pancreas 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.

[0111] Lead housing 402 may include a radiopaque stripe or other one or more radiopaque marker (not shown) along the outside of the lead housing. The radiopaque stripe corresponds to a certain circumferential location that allows lead 400 to be imaged and reliably localized when implanted in patient 112. Using the images of patient 112, the clinician can use the radiopaque stripe as a marker for the exact orientation of lead 400 within the pancreas 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 andDocket No.: A0009895WO01 / 1123-783WO01 relative to target tissue. In other examples, a lead housing or structure may include visibility materials or features that may facilitate different imaging modalities such as sonographic or echogenic features on the lead or structure. These features may facilitate visibility of the structure or lead during navigation of implantation and / or orientation with respect to anatomical structures.

[0112] 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 an opening in the exterior surface of pancreas 126 to a target location within the pancreas. 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.

[0113] 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.

[0114] 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 tissue 128 within pancreas 126. 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.Docket No.: A0009895WO01 / 1123-783WO01

[0115] 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.

[0116] FIGS.5C, 5D, 5E, and 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.

[0117] FIG.5D shows electrode level 510 which includes two electrodes 512 and 514. Each electrode 512 and 514 wraps approximately 170 degrees around the circumference of electrode level 510. Spaces of approximately 10 degrees are located between electrodes 512 and 514 to prevent inadvertent coupling of electrical current between the electrodes. Smaller or larger spaces between electrodes (e.g., between 10 degrees and 30 degrees) may be provided in other examples. Each electrode 512 and 514 may be programmed to act as an anode or cathode.

[0118] 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.Docket No.: A0009895WO01 / 1123-783WO01

[0119] 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.

[0120] Also, the insulation space, or non-electrode surface area, may be of any size. Generally, the insulation space is between approximately 1 degree and approximately 20 degrees. More specifically, the insulation space may be between approximately 5 and approximately 15 degrees. In other examples, insulation space may be between approximately 10 degrees and 30 degrees or larger. Smaller insulation spaces may allow a greater volume of tissue to be stimulated. In alternative embodiments, electrode size may be varied around the circumference of an electrode level. In addition, insulation spaces may vary in size as well. Such asymmetrical electrode levels may be used in leads implanted at tissues needing certain shaped stimulation fields. In some examples, the insulation region of the lead may include a projection that extends radially outward from the lead body. Although not shown, any lead or electrode array may include one or more fixation elements (e.g., tines, screws, electrode shapes, adhesives, etc.) that enable the lead or electrodes to be relatively fixed in position with respect to surrounding tissue.

[0121] FIG.6 is a flowchart illustrating an example technique for delivering AEF therapy to the pancreas of 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.

[0122] 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 104Docket No.: A0009895WO01 / 1123-783WO01 or a pre-programmed delivery schedule. Processing circuitry 210 then determines therapy parameter values for AEF therapy delivery to the pancreas (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. In some examples, processing circuitry 210 may analyze sensed data to determine spatial distances between implanted electrodes, where the electrodes are within the pancreas (e.g., via pH sensor and / or impedance measurements) and select parameters based on this information.

[0123] 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 to the target region of the pancreas (606). In some examples, the first and second electrical fields may be phase shifted so as to not overlap. In other examples, the first and second electrical fields may be phase shifted so as to partially overlap in time. In some examples, the first and second electrical fields may be temporally interleaved to be fully non- overlapping or partially overlapping. Although the first and second electrical fields may be delivered with the same amplitude and frequency, the first and second electrical fields may be defined by different amplitudes and / or different frequencies (e.g., 150 kHz and 200 kHz). The first and second electrode combinations may use completely different electrodes or partially different electrodes, for example. The first and second electrode combinations may be selected to generate respective electrical fields that are orthogonal to each other or oblique, in some examples. Although all electrodes of the first and second electrode combinations may be implanted in some examples, one or more of the electrodes may be external electrodes in other examples. In general, processing circuitry 210 may determine the frequency of electrical field alternation based on the number of electrical combinations used to alternate the electrical fields for therapy. No interphase period may be required between the delivery of each electric field, although processing circuitry 210 may provide an interphase period in some examples.

[0124] 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 orDocket No.: A0009895WO01 / 1123-783WO01 otherwise paused, processing circuitry 210 stops delivering the AEF therapy to the pancreas (610).

[0125] FIG.7 is a conceptual diagram illustrating an example expandable structure 702 comprising electrodes (not shown) and configured to deliver alternating magnetic field (AEF) therapy to a pancreas. As shown in the example of FIG.7, system 700 includes IMD 106 couped to lead 704 connected to IMD 106 that is now shown in FIG.7. System 700 may be an example of system 100 described herein, and expandable structure 702 may be an example of an implantable structure 114.

[0126] Expandable structure 702 may be similar to a stent or be referred to as a “stent- like” structure. Expandable structure 702 may be constructed with a plurality of repeating struts 730 or other structural elements that can collapsed on each other in order for expandable structure 702 to be deployed to the target area with a small cross-section and then transformed into the expanded configuration. A series of struts 730 can be connected to other series of struts via connector elements 732. These repeating elements may be constructed of a metal or metal alloy (e.g., nitinol) or a polymer than may be a shape memory material. Expandable structure 702 may be flexible to conform within the target location and to prevent breakage when used in soft tissues such as pancreas 126. Before being expanded, expandable structure 702 may have a compact configuration that enables expandable structure 702, and lead 704 in some examples, to be inserted into position through a catheter or needle, such as a biopsy needle. Expandable structure 702 may be constructed with various different lengths or diameters to fit with target tissue.

[0127] In some examples, expandable structure itself 702 may be electrically conductive and used as a one or more electrodes itself. In some examples, portions of expandable structure 702 may be covered in an insulating material to provide discontinuous electrically conductive areas that can shape the electric field produced. In other examples, one or more electrodes 734 may be attached to expandable structure 702. System 700 may include one expandable structure 702 or multiple expandable structures 702 wherein electrical fields may be generated therebetween. In some examples, lead 704 may carry additional electrodes or have other implantable structures attached to lead 704 that may carry one or more additional electrodes. These additional electrodes may be configured to be disposed within the pancreas or contact an external surface of the pancreas, for example.

[0128] In some examples, expandable structure 702 may be configured to be positioned within various locations of pancreas 126. These locations may include within tissue of the pancreas, within an internal duct of the pancreas or nearby structure (e.g., a pancreatic duct orDocket No.: A0009895WO01 / 1123-783WO01 a bile duct), or an anterior or posterior pancreaticoduodenal artery (or inferior or superior branches thereof). In this manner, expandable structure 702 may be configured to be located within the pancreas or other organs without damaging other tissues. In some examples, expandable structure 702 may be placed within the resection cavity of pancreas 126 after the tumor is removed. Expandable structure 702 may expand to a diameter to substantially fill the resection cavity and / or contact the surface of the resection cavity. Expandable structure 702 may be expanded via an expandable balloon within expandable structure 702, or expandable structure 702 may self-expand as a result of the increased temperature of the patient.

[0129] FIG.8 is a conceptual diagram illustrating an example implantable structure 800 with tines 808 configured to anchor implantable structure 800 within a pancreas or within adjacent ligaments or other connective tissue that may have stiffness favorable for the intended target tissue. Implantable structure 800 may be attached to, or a part of, a lead or elongated housing that couples electrodes 804 to an implantable medical device, such as IMD 106. Implantable structure 800 may be configured to be at least partially implanted within the pancreas, such as directly within the pancreatic tissue or within a pancreatic duct.

[0130] Implantable structure 800 may include several components, and implantable structure 800 can be fully or partially implanted within a pancreas. For example, implantable structure 800 may include a structure body 802 that carries the plurality of electrodes 804. Although four electrodes 804 are shown, as few as one electrode may be provided or more than 4 may be provided in other examples. The electrode configuration may be similar to any other cylindrical or segmented electrodes as described herein, such as in FIGS.4A-5F. Structure body 802 is shown as a cylinder, but other shapes may be used in other examples, such as elongated rectangular structures, flat structures, etc.

[0131] Implantable structure 800 may also include a proximal stop portion, such as proximal plug 810 that is attached to structure body 802. Proximal plug 810 may have a conical shape including a proximal surface 812, a distal surface 814, and a curved surface 816. The larger diameter of proximal surface 812 than the smaller diameter of distal surface 814 may form a wedge with curved surface 816 that prevents implantable structure 800 from being pushed further into the pancreas or another space. In this manner, distal surface 814 and / or curved surface 816 may be configured to contact tissue of the pancreas, while proximal surface 812 remains external of the pancreas. In some examples, curved surface 816 and / or distal surface 814 may carry one or more electrodes. In general, at least one cross-sectional dimension of the proximal stop portion may be larger than the cross-sectionalDocket No.: A0009895WO01 / 1123-783WO01 dimension of structure body 802 in order to enable insertion of structure body 802 into desired target tissue while providing a stopping point for insertion.

[0132] Near distal end 806 of implantable structure 800, one or more tines 808 are disposed to prevent migration of implantable structure 800 within the desired tissue location. Tines 808 are shown with four tines, but as few as one or more than four tines may be provided in other examples. Tines 808 may be rigid such that the tines do not deform under normal tissue stress conditions, but tines 808 may provide some flexibility under normal tissue stress to prevent tissue damage while also not allowing implantable structure 800 to move. Although tines 808 are shown to have elongated members extending at an acute angle towards the proximal direction, other configurations may be used in other examples. For example, other tines may be protrusions that extend in a distal direction or in an orthogonal direction from the longitudinal axis of structure body 802. Tines 808 may be straight or curved in some examples. Tines may be equally spaced about the circumference of structure body 802 or may be placed on certain sides in other examples depending where implantable structure 800 is intended to be implanted. In some examples, tines 808 may be disposed at the proximal end of implantable structure 800.

[0133] FIGS.9A and 9B are conceptual diagrams illustrating an example expandable system 900 configured to deploy electrodes 912 into target tissue. As shown in the example of FIG.9A, a perspective view of a portion expandable system 900 is shown. System 900 may be substantially longer and / or include a proximal portion that can be extended out of the patient in order to control the rotation of housings and extend the electrodes into target tissue. Expandable system 900 may be configured to expand or deploy electrodes out from the system in a radial direction. System 900 may be or include an implantable structure configured for deploying the electrodes.

[0134] For example, system 900 may be inserted into a portion of the pancreas, through a duct of the pancreas or other organ, a blood vessel, or into any other passage with the electrodes contained within external housing 902. External housing 902 may define one or more openings 904 at different axial and / or circumferential positions that run in a generally radially direction into external housing 902. Internal housing 906 may be disposed radially inward from the inner surface of external housing 902. The outer surface of internal housing 906 may have a diameter slightly less than the diameter of the inner surface of the external housing 902 to facilitate movement of the internal housing 906 with respect to external housing 902. In some examples, internal housing 906 may define a channel 908. Channel 908 may be configured to accept a stylet to facilitate implantation of system 900, aDocket No.: A0009895WO01 / 1123-783WO01 deployment structure configured to contact the inner surface of internal housing 906 to cause rotation of internal housing 906, and / or be suitable to deliver or remove a fluid to or from the patient.

[0135] As shown in FIG.9B, system 900 thus may be an example implantable structure that includes external housing 902 and internal housing 906. External housing 902 may define a plurality of openings 904, where each opening 902 may be configured allow a respective electrode of the plurality of electrodes 912 to pass through the outer surface of exterior housing 902. Multiple wires 910 may be coupled to internal housing 906 at different circumferential and / or different axial locations of internal housing 906. In the example of FIG.9B, each wire 910 carries two electrodes 912 that may operate together or independently to deliver electrical fields. In other examples, each wire 910 may carry a single electrode or operate as an electrode itself, or each wire 910 may carry three or more electrodes. Electrodes 912 may be coupled to conductors, which may be wires 910 or adjacent to respective wires 910 for a least a portion of system 900. The conductors may be disposed within the length of system 900, such as travel through the proximal portion of the lead of system 900 and back to connectors of IMD 16, for example.

[0136] Each of wires 910 are shows as being configured to travel through a respective curved shape of opening 904 through external housing 902. This curve of openings 904 may facilitate passage of respective wires 910. In other examples, openings 904 may have a different shape or be straight. Although each opening 904 may be orthogonal on the longitudinal, or axial, axis passing through the middle of channel 908, in other examples, openings 904 may be disposed to start and end at different axial locations of system 900. The example of FIG.9B illustrates that openings 904 and corresponding wires 910 are equally spaced around the circumference of external housing 902. Wires 910 and openings 904 are shown at the same axial position of system 900, but one or more wires 910 and openings 904 may be disposed at different axial positions along the length of system 900 in other examples. In other examples, wires 910 may be disposed unequally around the circumference as desired to deliver a the target electrical fields to the patient once electrodes 912 are deployed. For example, wires 910 may be disposed on one side (e.g., within about 180 degrees or half of the circumference) in order to treat a target tissue located to once side of the position of system 900 within the patient. In some examples, all of wires 910 and openings 904 may be located at the same circumferential position and different axial locations along the length of system 900. In some examples, the user may selectively remove or add desired wires (and corresponding electrodes) and / or deploy selective wires while other wires are not deployed.Docket No.: A0009895WO01 / 1123-783WO01

[0137] As described herein, rotation of external housing 902 with respect to internal housing 906 causes the plurality of electrodes 912 and the wires they are carried upon to extend radially out from the respective openings 904 of external housing 902. The user may rotate a handle or other control external from the patient to perform this rotation. In other examples, a spring or other mechanical device may be pre-loaded (or biased) and connected between internal housing 906 and external housing 902. The user may press a control that releases a catch on the spring, for example, which releases the stored energy can causes internal housing 906 to rotate with respect to external housing 902 and deploy wires 910 and electrodes 912. In some examples, a clinician may be able to cause rotation the opposite direction to retract wires 910 and remove system 900 from the patient. Although all wires 910 may generally carry one or more electrodes, one or more wires may not carry an electrode in other examples. These non-electrode carrying wires may carry one or more different sensors and / or only be used to anchor system 900 without having another functional purpose.

[0138] Although the example of system 900 is described using nested cylinders and rotation to deploy electrodes 912, other structures may be used to perform similar rotational deployment of electrodes into a desired tissue. In one example, a stent-like frame or balloon (example implantable structures) may be expanded to fill a tumor bed, duct, or other space of pancreas 126 or other organ. This expansion may cause the outer surface of the implanted structure to contact adjacent tissue. Twisting or rotational motion of a control with respect to the stent-like frame or balloon may cause the undeployed electrodes to extend radially outward from the stent-like frame or balloon. In some examples, these implanted structures, such as a stent-like structure or balloon, may be cylindrical in shape similar to external housing 902 and internal housing 906. In other examples, cross-sections similar to curved partial cylinders (e.g., structures having a “C” shape) that are about or less than 180 degrees or about 180 degrees or more may be used in other examples. In any of these examples, some or all of the implanted structures (e.g., housings 902, 906, the stent-like frame, or balloon) may remain with the patient after electrode deployment. In other examples, after electrode deployment, some or all of the implanted structures may be withdrawn from the patient and not remain within tissue during therapy.

[0139] FIG.10 is a conceptual diagram illustrating an example lead 1000 that includes an implantable structure 1002 having a shape memory material that is expandable for deploying electrodes to a target tissue. As shown in the example of FIG.10, lead 1000 includes housing 1004 (which may be an elongated member defining one or more channels) from whichDocket No.: A0009895WO01 / 1123-783WO01 implantable structure 1002 extends. Implantable structure 1002 may be or include a shape memory metal (e.g., nitinol) or some other shape memory material that is configured to be contained in a generally straight shape of housing 1004. When extended out the distal end of housing 1004, implantable structure 1002 can assume the pre-formed shape with one or more curves, such as the complex shape shown in the example of FIG.10. For example, the pre- formed shape of implantable structure 1002 shown in the illustration of FIG.10 includes various different curves and spaces that may be configured to enable implantable structure 1002 to fill a cavity or duct within the pancreas or other organ. For example, implantable structure 1002 in the deployed or expanded configuration may define multiple circles 1006, narrow gaps 1008, and elongated gaps 1010. The dimensions of these circles and gaps may be selected according to the cavities (such as a resection cavity) of the pancreas or another void.

[0140] In some examples the material that defines implantable structure 1002 may be conductive to deliver electrical fields directly from the material. In some examples, an electrically insulating material may cover portions of implantable structure 1002 in order for the electrical fields to propagate from the exposed portions of implantable structure 1002. In some examples, implantable structure 1002 may carry one or more electrodes are respective locations of implantable structure 1002 that are configured to deliver electrical fields to the target tissue. The shape-memory material of implantable structure 1002 may be configured to conduct electrical signals from IMD 106 to the electrodes. In other examples, one or more conductors that transmit electrical signals from IMD 106 to the carried electrodes may be disposed within a channel within the shape-memory material of implantable structure 1002 or may be disposed adjacent to the shape memory material and within housing 1004. In any case, the electrodes may be configured to generate and deliver electrical fields for AEF therapy to the tissue in or around implantable structure 1002.

[0141] FIG.11 is a conceptual diagram illustrating example paddle leads 1102A and 1102B for deploying electrodes to a target tissue. Paddle leads 1102A and 11020B (collectively “paddle leads 1102”) implantable to treat a target tissue of a pancreas or other organ for AEF therapy. Paddle leads 1102 are example implantable structures that can be implanted within a pancreas or placed on an external surface of the pancreas to provide electrical fields via the electrodes of the paddle lead. One or more of paddle leads 1102. In some examples, one or more of leads 1102 may be implanted around the periphery of a resection bed of a pancreas. In other examples, paddle leads 1102 may be placed within the resection bed such that electrodes carried by paddle leads 1102 may be placed against theDocket No.: A0009895WO01 / 1123-783WO01 tissue surface of the resection bed. Paddle leads 1102 may include any array of electrodes 1108 that can be placed near the boundary of the tumor resection, within the pancreas, or at any tissue surface of the pancreas. This close placement of paddle leads 1102 may reduce complexity during or after resection of the tumor and may provide a larger surface area to cover the tissue within and / or near the resection bed.

[0142] Electrodes 1108 may be positioned in a grid configuration on substrate 1006. Conductors electrically coupled to respective electrodes 1108 may travel through substrate 1106 and through the proximal lead portion 1104 towards IMD 106. Paddle lead 1102A includes a 4 x 4 grid of electrodes 1108, and paddle lead 1102B includes a 2 x 6 grid of electrodes 1108. Other numbers of electrodes in each row and column may be used, or electrodes 1108 may be placed at non-symmetrical or various positions that do not have regular spacing, as desired to deliver electric fields.

[0143] FIG.19A is a conceptual diagram illustrating an example flexible electrode array 1200. As shown in FIG.19A, flexible electrode array 1200 is an example implantable structure (which may be attached to a lead) in which the structure carrying electrodes 1204 and 1206 is flexible and configured to conform to a tissue surface, such as the exterior surface of a pancreas or the surface of a resection cavity within the pancreas. For example, flexible structure 1202 carries electrodes 1204 and 1206. Conductors 1210 may be electrically coupled to electrodes 1206 and conductors 1208 may be electrically coupled to electrodes 1204. Conductors 1208 and 1210 may be housed within a lead housing (not shown) that houses the conductors used to couple to IMD 106, for example.

[0144] FIG.12B is a schematic diagram illustrating components of flexible electrode array 1200 of FIG.12B. Flexible structure 1202 may be constructed of several layers that make up this multi-layered pad. In this manner, flexible structure 1202 may include first flexible layer 1220 and second flexible layer 1222. The first flexible layer 1220 and second flexible layer 1222 may form the outer surfaces of flexible structure 1202 and constructed of a flexible polymer such as silicone or other biocompatible polymer or composite material. Electrodes 1204 are a first subset of electrodes that are disposed between first flexible layer 1220 and second flexible layer 1222, and electrodes 1206 are a second subset of electrodes disposed between first flexible layer 1220 and second flexible layer 1222. Electrodes 1204 and 1206 may be separated by a gel electrolyte that is retained within a polymer (e.g., silicone) spacer around the perimeter of the gel electrolyte. In some examples, electrodes 1204 and 1206 may be constructed using different materials, such as copper and aluminum, respectively. Electrodes 1204 may be sandwiched between polyimide layers, and electrodesDocket No.: A0009895WO01 / 1123-783WO01 1206 may also be sandwiched between respective polyimide layers. In some examples, an anode slurry is provided between the gel electrolyte and electrodes 1204 and a cathode slurry is provided between the gel electrolyte and electrodes 1206. In other examples, electrodes 1204 and 1206 may be constructed of the same material.

[0145] Electrodes 1204 and 1206 may be provided in a grid array in which electrodes 1204 and 1206 are completely overlapping each other (e.g., occupy the same x- and y- axis position within array 1200. In other examples, electrodes 1204 and 1206 may only be partially overlapping or completely non-overlapping. Electrodes 1204 and 1206 may have the same dimensions (e.g., the same total area) or different dimensions (e.g., different total area) from each other in other examples. Electrode array 1200 may include four or more sets of electrodes, eight or more sets electrodes, ten or more sets of electrodes, or 20 or more sets of electrodes. In the example of electrode array 1200 includes 100 sets of electrodes (e.g., 100 electrodes 1204 and 100 electrodes 1206). The construction of electrode array 1200 enables array 1200 to be flexible and confirm to a tissue surface, such as the external surface of a pancreas, or a surface of a resection cavity within a pancreas.

[0146] FIG.13 is conceptual diagram illustrating an example flexible electrode array 1304 configured for delivering alternating electric field (AEF) therapy to pancreas 126 of a patient. System 1300 include flexible electrode array 1304 and lead 1310. Flexible electrode array 1304 may be or include an example implantable structure and may be similar to electrode array 1200 of FIGS.12A and 12B in some examples.

[0147] Flexible electrode array 1304 may include a plurality of electrodes 1304 one or both surfaces of the body of the array. Electrodes 1304 may be positioned as a grid in electrode array 1304 or positioned in an irregular configuration. Each electrode may be connected to its own or share one of conductors 1308 that travels from electrodes 1306 and through lead 1310 back to be connected to IMD 16. Although nine electrodes 1306 are shown in the example of FIG.13, fewer or greater numbers of electrodes may be carried by flexible array 1304, such as twelve electrodes in other examples. Electrode array 1304 may have a width and height on the order of 2 to 10 cm each in some examples. In one example, a length of may be approximately 6 cm and the height may be approximately 3 to 4 cm. In this manner, flexible array 1304 may have a square shape, rectangular shape, triangular shape, or an irregular shape. Flexible array 1304 may have various contours or even slits that facilitate the array being shaped around the exterior of pancreas 126 or within a resection cavity.

[0148] As shown in the example of FIG.13, flexible electrode array 1304 may be positioned on an external surface of pancreas 126 such that electrical fields may be deliveredDocket No.: A0009895WO01 / 1123-783WO01 to target tissue 1302 of pancreas 126 via some or all of electrodes 1306. Target tissue 1302 may be an anterior tumor aspect, local lymph nodes, or any other target tissue. This external surface of pancreas 126 may not have been surgically altered, such as cancer cells may not have been removed. In other examples, flexible electrode array 1304 may be configured to be disposed within a resection cavity after the tumor is removed from pancreas 126.

[0149] FIG.14 is a flowchart illustrating an example technique for implanting a flexible electrode array 1200 or 1304 on pancreatic tissue of a patient. The method of FIG.21 will be described with respect to flexible electrode array 1304, but the technique may be used to implant and lead that includes other flexible arrays such as flexible electrode array 1200.

[0150] As shown in the example of FIG.14, a clinician can access the target surface of tissue and / or resect tissue of the pancreas (1400). Access can be achieved by inserting flexible electrode array 1304 through an access port during a minimally invasive procedure or via a biopsy needle or insertion catheter. In some examples, the clinician may remove a tumor which creates a resection cavity in the pancreas (or other organ associated with the pancreatic cancer). Then, the clinician can insert flexible electrode array 1304 against the tissue surface of the target tissue (1402). Once flexible electrode array 1304 is in position in against surface of the target tissue, the clinician may couple the proximal end of the lead housing of flexible electrode array 1304 (such as the proximal end of lead 1310) to a medical device such as IMD 106 (1404).

[0151] In some examples, the flexible electrode array 1304 can be inserted through a trocar of a laparoscopic surgery during which insufflation of the abdominal cavity can facilitate visualization and access to complex placement in and around the pancreas. Wires and components of the device or system can be inserted or exited as part of existing treatments applied to the pancreas. In some examples, various tools or sensors can be inserted during placement of the electrodes and may be placed based on mechanical stiffness or impedance of the target tissue. Various visualization modalities can be used to assist in implantation, such as ultrasound, and echogenic features on implanted devices or implantation tools may assist with visualization.

[0152] FIG.15 is conceptual diagram illustrating an example flexible electrode array 1504 together with tack electrodes 1520 configured for delivering alternating electric field (AEF) therapy to pancreas 126 of a patient. Flexible electrode array 1504 may be similar to flexible electrode array of FIG.13. For example, flexible electrode array 1504 includes a flexible material that carries a plurality of electrodes 1506 and conductors coupled to electrodes 1506 and disposed proximally through lead 1510. In addition, one or more tackDocket No.: A0009895WO01 / 1123-783WO01 electrodes 1520 can be inserted through the flexible substrate of flexible electrode array 1504. The substrate of flexible electrode array 1504 may define a plurality of openings sized to accept a portion of one tack electrode 1520. In this manner, a clinician may insert each tack electrode 1520 through a respective opening in the substrate of flexible electrode array 1504. Instead of, or in addition to, openings sized to accept a tack electrode 1520, the substrate may include perforations and / or slits that can be separated by insertion of the distal end of a tack electrode through the slit. In other examples, the substrate of flexible electrode array 1504 may be constructed of a gel or polymer of low strength such that the clinician can force the distal end of tack electrode 1520 through the substrate of flexible electrode array 1504 at a desired location. In his manner, flexible electrode array 1504 may be configured to enable placement of tack electrodes 1520 at a variety of locations within pancreas 126 and with respect to electrodes 1506 of flexible electrode array 1504. Electric fields may be generated between electrodes of tack electrodes 1520, electrodes 1506, or any combination thereof.

[0153] Each tack electrode 1520 (an example implantable structure) may include components such as non-conductive cap 1534 coupled to one or more structures that may include post 1536. Post 1536 is configured to carry one or more electrodes, such as electrodes 1538 and 1540. Each of electrodes 1538 and 1540 may be disposed at different axial positions along post 1536. Different tack electrodes 1520 may be configured with different length posts 1536 and / or a different number of electrodes. The cross-sectional area of post 1536 is smaller than a cross-sectional area of non-conductive cap 1534. In this manner, post 1536 is configured to be inserted into tissue of pancreas 126, for example, to a depth limited by a length of post 1536 extending from a distal surface of non-conductive cap 1534. In other words, non-conductive cap 1534 may be configured to be a depth stop for insertion of post 1536. Each of tack electrodes 1520 may be coupled to a conductor 1508 (or different conductor separate from flexible electrode array 1504) extending proximal from non-conductive cap 1534 in order to carry one or more conductors to IMD 106, for example. In some examples, the non-conductive cap 1534 may carry one or more electrodes in addition to, or instead of, electrodes 1538 and 1540. For example, non-conductive cap 1534 may include one or more electrodes on the surface configured to contact a surface the tissue of pancreas 126. The length of post 1536 may be selected for insertion into pancreas 126. For example, the length of post 1536 may be from 1 cm to 6 cm. In one example, the length of post 1536 may be approximately 3 cm.

[0154] In some examples, the combination of tack electrodes 1520 and flexible electrode array 1504 may be referred to as a “pinned blanked.” Tack electrodes 1520 may provideDocket No.: A0009895WO01 / 1123-783WO01 mechanical anchoring of electrode array 1504 to tissue in addition to electrodes for electrical field delivery. The addition of one or more tack electrodes 1540 may enable the system to deliver AEF therapy, for example, to cover a posterior tumor aspect or even the spread of cancer cells into or near vasculature. Three tack electrodes 1520 are shown in the example of FIG.15, but fewer or greater number of tack electrodes may be used in other example. Part of the structures for delivery and / or initial positioning of array 1504 and / or tack electrodes 1520 may be resorbable or implanted in narrow strips to avoid an extensive fibrotic response for the tissue.

[0155] FIG.16 is a conceptual diagram of example tack electrodes 1520 configured to be implanted within the surface 1606 of a resection cavity 1604 of a patient. In some examples, tack electrodes 1520 may be used separately from flexible electrode array 1504, either within resection cavity 1604 or at any other surface of the pancreas or other tissue. As shown in FIG.16, five tack electrodes 1520 are included within lead system 1600. Lead system 1600 can be implanted within tissue 1602, which may be a portion of the pancreas of the patient. Surface 1606 may be the inner surface of resection cavity 1604 (e.g., a tissue resection region). Although lead 1600 includes five tack electrodes 1520 in this example, other examples of system 1600 may include as few as one tack electrode, two or more tack electrodes, or five or more electrodes. Tack electrodes 1520 may be positioned at any position around surface 1606, which may create a planar or three-dimensional electrode array.

[0156] In some examples, lead system 1600 may facilitate implantation of a large variety of numbers of tack electrodes 1520, such as only one tack electrode 1520, or a large number of tack electrodes distributed around surface 1606 of resection cavity 1604. In this manner, the clinician may select the number of tack electrodes 1520 needed to achieve appropriate coverage for AEF therapy or other therapy, or even mix and match different types of tack electrodes 1520 (e.g., different lengths of post 1536, different number of electrodes 1538 and 1540, etc.).

[0157] FIG.17 is a flowchart illustrating an example technique for implanting multiple tack electrodes 1520 within a resection cavity 1604 of a pancreas of a patient. The method of FIG.17 will be described with respect to lead system 1600 of FIG.16, but the technique may be used to implant other types of individual electrodes or electrode structures. In other examples, similar techniques may be used to implant tack electrodes to other portions of the pancreas or other target tissue.Docket No.: A0009895WO01 / 1123-783WO01

[0158] As shown in the example of FIG.17, a clinician creates a resection by removing target tissue (1700). The removed tissue may be identified as including a tumor or other undesirable tissue. Then, the clinician can insert one tack electrode 1520 through the surface 1606 of tissue 1602 around resection cavity 1604 at the desired location (1702). The position of tack electrode 1520 may be chosen as part of a larger spatial electrical field target using multiple tack electrodes 1520. If another tack electrode 1520 needs to be implanted (“YES” branch of block 1704), the clinician inserts another tack electrode at the desired location (1702). If no further tack electrodes are needed to be implanted (“NO” branch of block 1704), the clinician then couples the proximal end of lead housings of each tack electrode 1520 to a medical device such as IMD 106 (1706). In this manner, IMD 106 may be configured to generate electrical field modulation, such as AEF, to the target tissue resection region using some or all of the electrodes of the implanted tack electrodes 1520.

[0159] The following examples are described herein.

[0160] Example 1. A system comprising: an implantable structure comprising a plurality of electrodes, at least a portion of the implantable structure configured to be implanted within a pancreas; and an implantable medical device comprising stimulation circuitry configured to generate a plurality of electric fields deliverable to at least a portion of the pancreas via one or more electrodes of the plurality of electrodes.

[0161] Example 2. The system of example 1, wherein all electrodes of the plurality of electrodes are configured to be disposed within the pancreas.

[0162] Example 3. The system of example 1, wherein at least a first electrode of the plurality of electrodes is configured to remain outside the pancreas with at least a second electrode of the plurality of electrodes being configured to be disposed within the pancreas.

[0163] Example 4. The system of example 1, wherein the implantable structure is configured to be implanted one of percutaneously or subcutaneously.

[0164] Example 5. The system of any of examples 1 through 4, wherein the implantable structure is configured to be inserted through a biopsy needle.

[0165] Example 6. The system of any of examples 1 through 5, wherein the implantable structure comprises a pH sensor configured to sense a physiological condition indicative of fluids from the pancreas.

[0166] Example 7. The system of any of examples 1 through 6, further comprising sensing circuity and processing circuitry, wherein the processing circuity is configured to: control the sensing circuitry to measure an impedance of tissue; determine that the impedanceDocket No.: A0009895WO01 / 1123-783WO01 is out of range; and generate an alert, for delivery to a user, indicating a change with the tissue adjacent at least a portion of the implantable structure.

[0167] Example 8. The system of any of examples 1 through 7, wherein the stimulation circuitry is configured to generate the plurality of electric fields at a frequency from about 150k Hz to about 200 kHz.

[0168] Example 9. The system of any of examples 1 through 8, wherein the implantable structure comprises an expandable stent comprising a plurality of interconnected struts, and wherein the expandable stent carries the plurality of electrodes.

[0169] Example 10. The system of any of examples 1 through 8, wherein the implantable structure comprises: a structure body carrying the plurality of electrodes and having a first cross-sectional dimension; one or more tines configures to anchor the implantable structure within the pancreas, wherein the one or more times are disposed distally of the plurality of electrodes; and a proximal stop portion proximal of the plurality of electrodes, wherein the proximal stop portion defines a second cross-sectional dimension larger than the first cross- sectional dimension.

[0170] Example 11. The system of any of examples 1 through 8, wherein the implantable structure comprises: a housing comprising a non-conductive cap; and a post coupled to the non-conductive cap and configured to carry the plurality of electrodes at different axial positions along the post, and wherein a cross-sectional area of the post is smaller than a cross- sectional area of the non-conductive cap.

[0171] Example 12. The system of example 11, wherein the post is configured to be inserted into tissue to a depth limited by a length of the post extending from a distal surface of the non-conductive cap.

[0172] Example 13. The system of any of examples 1 through 12, wherein the plurality of electrodes is a first plurality of electrodes, and wherein the system further comprises a flexible mesh carrying a second plurality of electrodes, the flexible mesh and the at least some electrodes configured to contact a surface of the pancreas, wherein the implantable medical device is configured to generate one or more electric fields of the plurality of electric fields via the second plurality of electrodes.

[0173] Example 14. The system of any of examples 1 through 8, wherein: the implantable structure comprises an external housing and an internal housing; the external housing device defining a plurality of openings, each opening of the plurality of openings is configured allow a respective electrode of the plurality of electrodes to pass; and rotation ofDocket No.: A0009895WO01 / 1123-783WO01 the external housing with respect to the internal housing causes the plurality of electrodes to extend radially out from the respective openings of the external housing.

[0174] Example 15. The system any of examples 1 through 14, further comprising: one or more conductors disposed within an elongated housing coupled to the implantable structure, the one or more conductors configured to electrically couple to respective electrodes of the plurality of electrodes; and one or more proximal connectors configured to couple the plurality of electrodes to stimulation circuitry of the implantable medical device via the one or more conductors.

[0175] Example 16. A method comprising: generating, by stimulation circuitry of an implantable medical device, a plurality of electric fields deliverable to at least a portion of a pancreas via one or more electrodes of a plurality of electrodes, wherein an implantable structure comprises the plurality of electrodes, and wherein at least a portion of the implantable structure is configured to be implanted within the pancreas.

[0176] Example 17. The method of example 15, wherein all electrodes of the plurality of electrodes are configured to be disposed within the pancreas, and wherein the implantable medical device is configured to deliver the plurality of electric fields from within the pancreas.

[0177] Example 18. The method of example 15, wherein at least a first electrode of the plurality of electrodes is configured to remain outside the pancreas with at least a second electrode of the plurality of electrodes is configured to be disposed within the pancreas, and wherein the implantable medical device is configured to deliver the plurality of electric fields between at least the first electrode outside the pancreas and at least the second electrode within the pancreas.

[0178] Example 19. The method of any of examples 15 through 17, further comprising inserting the implantable structure through a biopsy needle to the pancreas.

[0179] Example 20. The method of any of examples 15 through 18, wherein the implantable structure comprises a pH sensor configured to sense a physiological condition indicative of fluids from the pancreas, and wherein the implantable medical device is configured to detect the physiological condition based on a signal from the pH sensor.

[0180] Example 21. The method of any of examples 15 through 19, further comprising: controlling, by the processing circuitry, sensing circuitry to measure an impedance of tissue; determining that the impedance is out of range; and generating an alert, for delivery to a user, indicating a change with the tissue adjacent at least a portion of the implantable structure.Docket No.: A0009895WO01 / 1123-783WO01

[0181] Example 22. The method of any of examples 15 through 20, wherein generating the plurality of electric fields comprises generating the plurality of electric fields at a frequency from about 150k Hz to about 200 kHz.

[0182] Example 23. The method of any of examples 15 through 21, wherein generating the plurality of electric fields comprises generating the plurality of electric fields via the plurality of electrodes carried by the implantable structure comprising an expandable stent comprising a plurality of interconnected struts.

[0183] Example 24. The method of any of examples 15 through 21, wherein the implantable structure comprises: a housing comprising a non-conductive cap; and a post coupled to the non-conductive cap and configured to carry the plurality of electrodes at different axial positions along the post, and wherein a cross-sectional area of the post is smaller than a cross-sectional area of the non-conductive cap.

[0184] Example 25. The method of any of examples 15 through 23, wherein the plurality of electrodes is a first plurality of electrodes, and wherein a flexible mesh carries a second plurality of electrodes, the flexible mesh and the at least some electrodes configured to contact a surface of the pancreas, and wherein generating the plurality of electric fields comprises generating one or more electric fields of the plurality of electric fields via the second plurality of electrodes.

[0185] Example 26. The method of any of examples 15 through 21, wherein: the implantable structure comprises an external housing and an internal housing; the external housing device defining a plurality of openings, each opening of the plurality of openings is configured allow a respective electrode of the plurality of electrodes to pass; and the method further comprises deploying the plurality of electrodes into the pancreas by at least rotating the external housing with respect to the internal housing causes the plurality of electrodes to extend radially out from the respective openings of the external housing.

[0186] Example 27. The method of any of examples 15 through 25, wherein the portion of the pancreas comprises a remaining portion of the pancreas, and wherein the method further comprises: resecting a first portion of the pancreas to expose a tumor bed surface of the pancreas; and implanting at least one electrode of the plurality of electrodes in at least one of the tumor bed surface or the remaining portion of the pancreas, wherein generating the plurality of electric fields comprises generating the plurality of electric fields via the at least one electrode implanted in at least one of the tumor bed surface or the remaining portion of the pancreas.Docket No.: A0009895WO01 / 1123-783WO01

[0187] Example 28. An implantable lead comprising: an implantable structure comprising a plurality of electrodes, at least a portion of the implantable structure configured to be implanted within a pancreas, one or more conductors disposed within an elongated housing coupled to the implantable structure, the one or more conductors configured to electrically couple to respective electrodes of the plurality of electrodes; and one or more proximal connectors configured to couple the plurality of electrodes to stimulation circuitry of an implantable medical device via the one or more conductors, wherein the plurality of electrodes are configured to deliver, via the stimulation circuitry of the implantable medical device, a plurality of electric fields to the pancreas.

[0188] Example 29. The implantable lead of example 27, wherein the implantable structure is configured to be inserted through a biopsy needle.

[0189] Example 30. The implantable lead of any of examples 27 or 28, wherein the implantable structure comprises a pH sensor configured to sense a physiological condition indicative of fluids from the pancreas.

[0190] Example 31. The implantable lead of any of examples 27 through 29, wherein the implantable structure comprises an expandable stent comprising a plurality of interconnected struts, and wherein the expandable stent carries the plurality of electrodes.

[0191] Example 32. The implantable lead of any of examples 27 through 29, wherein the implantable structure comprises: a structure body carrying the plurality of electrodes and having a first cross-sectional dimension; one or more tines configures to anchor the implantable structure within the pancreas, wherein the one or more times are disposed distally of the plurality of electrodes; and a proximal stop portion proximal of the plurality of electrodes, wherein the proximal stop portion defines a second cross-sectional dimension larger than the first cross-sectional dimension.

[0192] Example 33. The implantable lead of any of examples 27 through 30, wherein the implantable structure comprises: a housing comprising a non-conductive cap; and a post coupled to the non-conductive cap and configured to carry the plurality of electrodes at different axial positions along the post, wherein a cross-sectional area of the post is smaller than a cross-sectional area of the non-conductive cap, and wherein the post is configured to be inserted into tissue to a depth limited by a length of the post extending from a distal surface of the non-conductive cap.

[0193] Example 34. The implantable lead of any of examples 27 through 32, wherein the plurality of electrodes is a first plurality of electrodes, and wherein the system further comprises a flexible mesh carrying a second plurality of electrodes, the flexible mesh and theDocket No.: A0009895WO01 / 1123-783WO01 at least some electrodes configured to contact a surface of the pancreas, wherein the implantable medical device is configured to generate one or more electric fields of the plurality of electric fields via the second plurality of electrodes.

[0194] Example 35. The implantable lead of any of examples 27 through 30, wherein: the implantable structure comprises an external housing and an internal housing; the external housing device defining a plurality of openings, each opening of the plurality of openings is configured allow a respective electrode of the plurality of electrodes to pass; and rotation of the external housing with respect to the internal housing causes the plurality of electrodes to extend radially out from the respective openings of the external housing.

[0195] Example 36. Any device, system, method, or computer-readable medium described or otherwise supported in the specification herein.

[0196] 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.

[0197] The techniques described in this disclosure may be implemented, at least in part, in hardware, software, firmware or any combination thereof. For example, various aspects of the described techniques may be implemented within one or more processors, such as fixed function processing circuitry and / or programmable processing circuitry, including one or more microprocessors, digital signal processors (DSPs), application specific integrated circuits (ASICs), field programmable gate arrays (FPGAs), or any other equivalent integrated or discrete logic circuitry, as well as any combinations of such components. The term “processor” or “processing circuitry” may generally refer to any of the foregoing logic circuitry, alone or in combination with other logic circuitry, or any other equivalent circuitry.Docket No.: A0009895WO01 / 1123-783WO01 A control unit comprising hardware may also perform one or more of the techniques of this disclosure.

[0198] 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.

[0199] 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.

[0200] Various examples have been described. These and other examples are within the scope of the following claims.

Claims

Docket No.: A0009895WO01 / 1123-783WO01 WHAT IS CLAIMED IS:

1. A system comprising: an implantable structure comprising a plurality of electrodes, at least a portion of the implantable structure configured to be implanted within a pancreas; and an implantable medical device comprising stimulation circuitry configured to generate a plurality of electric fields deliverable to at least a portion of the pancreas via one or more electrodes of the plurality of electrodes.

2. The system of claim 1, wherein all electrodes of the plurality of electrodes are configured to be disposed within the pancreas.

3. The system of claim 1, wherein at least a first electrode of the plurality of electrodes is configured to remain outside the pancreas with at least a second electrode of the plurality of electrodes being configured to be disposed within the pancreas.

4. The system of claim 1, wherein the implantable structure is configured to be implanted one of percutaneously or subcutaneously.

5. The system of any of claims 1 through 4, wherein the implantable structure is configured to be inserted through a biopsy needle.

6. The system of any of claims 1 through 5, wherein the implantable structure comprises a pH sensor configured to sense a physiological condition indicative of fluids from the pancreas.

7. The system of any of claims 1 through 6, further comprising sensing circuity and processing circuitry, wherein the processing circuity is configured to: control the sensing circuitry to measure an impedance of tissue; determine that the impedance is out of range; and generate an alert, for delivery to a user, indicating a change with the tissue adjacent at least a portion of the implantable structure.Docket No.: A0009895WO01 / 1123-783WO01 8. The system of any of claims 1 through 7, wherein the stimulation circuitry is configured to generate the plurality of electric fields at a frequency from about 150k Hz to about 200 kHz.

9. The system of any of claims 1 through 8, wherein the implantable structure comprises an expandable stent comprising a plurality of interconnected struts, and wherein the expandable stent carries the plurality of electrodes.

10. The system of any of claims 1 through 8, wherein the implantable structure comprises: a structure body carrying the plurality of electrodes and having a first cross-sectional dimension; one or more tines configures to anchor the implantable structure within the pancreas, wherein the one or more times are disposed distally of the plurality of electrodes; and a proximal stop portion proximal of the plurality of electrodes, wherein the proximal stop portion defines a second cross-sectional dimension larger than the first cross-sectional dimension.

11. The system of any of claims 1 through 8, wherein the implantable structure comprises: a housing comprising a non-conductive cap; and a post coupled to the non-conductive cap and configured to carry the plurality of electrodes at different axial positions along the post, and wherein a cross-sectional area of the post is smaller than a cross-sectional area of the non-conductive cap.

12. The system of claim 11, wherein the post is configured to be inserted into tissue to a depth limited by a length of the post extending from a distal surface of the non-conductive cap.

13. The system of any of claims 1 through 12, wherein the plurality of electrodes is a first plurality of electrodes, and wherein the system further comprises a flexible mesh carrying a second plurality of electrodes, the flexible mesh and the at least some electrodes configured to contact a surface of the pancreas, wherein the implantable medical device is configured toDocket No.: A0009895WO01 / 1123-783WO01 generate one or more electric fields of the plurality of electric fields via the second plurality of electrodes.

14. The system of any of claims 1 through 8, wherein: the implantable structure comprises an external housing and an internal housing; the external housing device defining a plurality of openings, each opening of the plurality of openings is configured allow a respective electrode of the plurality of electrodes to pass; and rotation of the external housing with respect to the internal housing causes the plurality of electrodes to extend radially out from the respective openings of the external housing.

15. The system any of claims 1 through 14, further comprising: one or more conductors disposed within an elongated housing coupled to the implantable structure, the one or more conductors configured to electrically couple to respective electrodes of the plurality of electrodes; and one or more proximal connectors configured to couple the plurality of electrodes to stimulation circuitry of the implantable medical device via the one or more conductors.

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