Patent Description:
Embodiments herein relate to medical devices and exemplary methods for using the same to treat cancerous tumors within a bodily tissue.

According to the American Cancer Society, cancer accounts for nearly <NUM>% of the deaths that occur in the United States each year. The current standard of care for cancerous tumors can include first-line therapies such as surgery, radiation therapy, and chemotherapy. Additional second-line therapies can include radioactive seeding, cryotherapy, hormone or biologics therapy, ablation, and the like. Combinations of first-line therapies and second-line therapies can also be a benefit to patients if one particular therapy on its own is not effective.

Cancerous tumors can form if one normal cell in any part of the body mutates and then begins to grow and multiply too much and too quickly. Cancerous tumors can be a result of a genetic mutation to the cellular DNA or RNA that arises during cell division, an external stimulus such as ionizing or non-ionizing radiation, exposure to a carcinogen, or a result of a hereditary gene mutation. Regardless of the etiology, many cancerous tumors are the result of unchecked rapid cellular division.

<CIT> discloses medical device systems including electric field shaping elements for use in treating cancerous tumors within a bodily tissue. A method for treating a cancerous tumor is provided. The method can include implanting one or more electrodes within a patient and measuring the impedance of tissue within the patient along a vector passing through or near a cancerous tumor. The method can also include administering an electric field to the cancerous tumor of the patient based on the measured impedance.

<CIT> discloses iMDs and methods for electroporation treatment of subcutaneous tumors. IMDs may store and introduce chemotherapy drugs into the body prior to electroporation therapy. High frequency stimulation of tissue in or around the tumor may also be provided to increase tissue temperature prior to electroporation therapy. Still further, delivery of the electroporation therapy may be synchronized with cardiac qRs complex. Algorithms to suspend therapy in the event of edema may also be incorporated.

<CIT> discloses cells that are in the process division being vulnerable to damage by AC electric fields that have specific frequency and field strength characteristics. The selective destruction of rapidly dividing cells can therefore be accomplished by imposing an AC electric field in a target region for extended periods of time at particular frequencies with particular filed strengths.

<CIT> discloses a method for a localized tissue heating of tumors. Localized radio frequency current fields are produced with specific electrode configurations. Several electrode configurations are disclosed, enabling variations in electrical and thermal properties of tissues to be exploited.

<CIT> discloses high-frequency ablation of tissue in the body using a cooled high-frequency electrode connected to a high frequency generator including a computer graphic control system and an automatic controller for control the signal output from the generator, and adapted to display on a real time graphic display a measured parameter related to the ablation process and visually monitor the variation of the parameter of the signal output that is controlled by the controller during the ablation process. One or more measured parameters may be displayed simultaneously to visually interpret the relation of their variation and values. The displayed one or more parameters can be taken from the list of measured voltage, current, power, impedance, electrode temperature, and tissue temperature related to the ablation process.

<CIT> discloses ablation of cardiac tissue being carried out by inserting a probe having an ablation electrode and a plurality of microelectrodes into a body of a living subject to establish contact between two of the microelectrodes and target tissue, and energizing the ablation electrode. While the ablation electrode is energized impedances are measured between the microelectrodes, and the power level of the ablation electrode adjusted according to the impedances.

Methods described hereinafter are not part of the present invention and are presented for understanding the present invention.

Several aspects of the present disclosure will be described hereinafter.

In a first aspect, a medical device system is included having an electric field generating circuit configured to generate one or more electric fields and a control circuit in communication with the electric field generating circuit. The control circuit can be configured to control delivery of the one or more electric fields from the electric field generating circuit. The system can include two or more electrodes to deliver the electric fields to a site of a cancerous tumor within a patient and a temperature sensor to measure the temperature of tissue at the site of the cancerous tumor, the temperature sensor in electronic communication with the control circuit. The control circuit can cause the electric field generating circuit to generate one or more electric fields at frequencies selected from a range of between <NUM> to <NUM>.

In a second aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the system can include a first lead providing electrical communication between the control circuit and at least one electrode; wherein the temperature sensor is disposed on the first lead.

In a third aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the first lead can include at least one of a transcutaneous lead and a fully implanted lead.

In a fourth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, at least two electrodes are configured to be implanted.

In a fifth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the electric fields are delivered across at least one vector defined by an electrode pair.

In a sixth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the temperature sensor is positioned between the electrode pair.

In a seventh aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the temperature sensor is adapted to be inserted into the cancerous tumor.

In an eighth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the electric fields are delivered across at least two vectors, wherein a first vector is defined by a first pair of electrodes and a second vector is defined by a second pair of electrodes.

In a ninth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, wherein the electric fields along the at least two vectors are spatially and/or directionally separated from one another.

In a tenth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the system can include at least two electric field generating circuits, wherein a first electric field generating circuit is implanted and a second electric field generating circuit is external.

In an eleventh aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the system can further include an implanted housing, the implanted housing defining an interior volume into which the electric field generating circuit and the control circuit are disposed.

In a twelfth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the temperature sensor is selected from the group consisting of a thermistor, a resistance thermometer, a thermocouple, and a semi-conductor based sensor.

In a thirteenth aspect, a medical device system is included having an electric field generating circuit configured to generate one or more electric fields and a control circuit in communication with the electric field generating circuit, the control circuit configured to control delivery of the one or more electric fields from the electric field generating circuit. The system can include two or more electrodes forming at least one electrode pair to deliver the electric fields to a site of a cancerous tumor within a patient. The control circuit can cause the electric field generating circuit to generate one or more electric fields at frequencies selected from a range of between <NUM> to <NUM>. The control circuit can calculate a power output of the electric field and estimate a temperature of tissue within the electric field based on the power output and a distance between the electrodes of the electrode pair.

In a fourteenth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the medical device system is configured to receive data regarding the distance between the electrodes of the electrode pair.

In a fifteenth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the medical device system is configured to estimate the distance between the electrodes of the electrode pair based on impedance data.

In a sixteenth aspect, a medical device system is included having an electric field generating circuit configured to generate one or more electric fields and a control circuit in communication with the electric field generating circuit, the control circuit configured to control delivery of the one or more electric fields from the electric field generating circuit. The system can further include two or more electrodes forming at least one electrode pair to deliver the electric fields to a site of a cancerous tumor within a patient and wherein the control circuit causes the electric field generating circuit to generate one or more electric fields at frequencies selected from a range of between <NUM> to <NUM>. The control circuit can estimate a temperature of tissue within the electric field based on an impedance measurement.

In a seventeenth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the control circuit estimates a temperature of tissue within the electric field based on an impedance measurement and a distance between the electrodes of the electrode pair.

In an eighteenth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the medical device system is configured to receive data regarding the distance between the electrodes of the electrode pair.

In a nineteenth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the control circuit estimates changes in temperature of tissue within the electric field based on changes in measured impedance.

In a twentieth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the system can further include a heating element, wherein the control circuit causes the heating element to generate heat.

This summary is an overview of some of the teachings of the present disclosure and is not intended to be an exclusive or exhaustive treatment of the present subject matter. Further details are found in the detailed description and appended claims. Other aspects will be apparent to persons skilled in the art upon reading and understanding the following detailed description and viewing the drawings that form a part thereof, each of which is not to be taken in a limiting sense.

While embodiments are susceptible to various modifications and alternative forms, specifics thereof have been shown by way of example and drawings, and will be described in detail. It should be understood, however, that the scope of the present invention is defined by the appended claims.

As referenced above, many cancerous tumors can result from unchecked rapid cellular division. Some traditional first-line therapies to treat cancerous tumors can include surgery, radiation therapy, and chemotherapy. However, many first-line therapies have undesirable concomitant side effects, such as fatigue, hair loss, immunosuppression, and long surgical recovery times, to name a few.

While not intending to be bound by theory, it is believed that electric fields can disrupt mitosis within a cancerous tumor, such as by interfering with the dipole alignment of key proteins involved in cellular division; tubulin and septin in particular. The polymerization of tubulin proteins that form microtubule spindle fibers can be disrupted, thus preventing the formation of spindle fibers required for chromosome separation. This can halt cellular division at the metaphase stage of mitosis. In some instances, an electric field can halt polymerization of already growing spindle fibers, leading to incomplete spindles and unequal chromosome separation during anaphase, should the cell survive that long. In each case, halting microtubule spindle formation and unequal chromosome separation during anaphase caused by incomplete polymerization of microtubules, can result in apoptosis (i.e., programmed cell death). It is also believed that alternating electric fields can lead to increased electric field density near the cleavage furrow of the dividing cells during telophase. An increased electric field density in the region of the cleavage furrow can result in dielectrophoresis of charged macromolecules, such as proteins and nucleic acids, toward the high electric field density at the furrow. The unequal concentration of key macromolecules required for cellular division at the site of the cleavage furrow can disrupt the final separation of the sister cells during telophase and eventually lead to apoptosis.

Temperature can be in important parameter to measure during the administration of an electrical field. In some cases, it may be desirable to limit and/or prevent thermal destruction of tissues. As such, the temperature of tissue can be monitored (directly or indirectly) in order to prevent the temperature from rising to a level where the thermal destruction of tissue may occur. However, in some embodiments, a degree of heating in combination with the application of an electrical field may be therapeutic. Thus, in some embodiments, it may be desirable to apply heat to tissue.

As such, various embodiments disclosed herein include a medical device system that can generate an electric field for treatment of cancer that can include, or can control, at least one electrode, and/or at least one temperature sensor or at least one heating element. In various embodiments, an electric field can be generated, and heat can be applied, such as via a heating element, to treat a tumor. In various embodiments, a temperature sensor can be used to monitor the temperature of tissue near or around an electric field or a heating element, such as to observe changes to tissue during heating or electric field generation. In various embodiments, the medical device can be configured to turn off or stop the therapy if the temperature of the tissue exceed a threshold.

Referring now to <FIG>, a schematic view is shown of a medical device <NUM> in accordance with various embodiments herein. The medical device <NUM> can be implanted entirely within the body of a patient <NUM> at or near the site of a cancerous tumor <NUM> located within a bodily tissue. Various implant sites can be used including areas such as in the limbs, the upper torso, the abdominal area, the head, and the like.

Referring now to <FIG>, another schematic view is shown of a medical device <NUM> in accordance with various embodiments herein. The medical device <NUM> can be external but can be connected to a component, such as leads, that are at least partially implanted within the body of a patient <NUM>. In some embodiments, the medical device <NUM> can be partially implanted and partially external to the body of a patient. In some embodiments, the medical device <NUM> can include a transcutaneous connection between components disposed internal to the body and external to the body. In various embodiments, the medical device system described herein can include an implanted medical device <NUM> and an external medical device <NUM>. In other embodiments, the medical device system described herein can include a partially implanted medical device.

An implanted portion of a medical device system, such as an implanted medical device <NUM> or portion thereof, can wirelessly communicate patient identification data, diagnostic information, electric field data, physiological parameters, software updates, and the like with a fully or partially external portion of a medical device <NUM> over a wireless connection. Implanted medical device <NUM> can also wirelessly communicate with an external device configured to wirelessly charge the medical device utilizing inductance, radio frequency, and acoustic energy transfer techniques, and the like.

In some embodiments, a portion of a medical device or system can be entirely implanted, and a portion of the medical device can be entirely external. For example, in some embodiments, one or more electrodes or leads can be entirely implanted within the body, whereas the portion of the medical device that generates an electric field, such as an electric field generator, can be entirely external to the body. It will be appreciated that in some embodiments described herein, the electric field generators described can include many of the same components as and can be configured to perform many of the same functions as a pulse generator. In embodiments where a portion of a medical device is entirely implanted, and a portion of the medical device is entirely external, the portion of the medical device that is entirely external can communicate wirelessly with the portion of the medical device that is entirely internal. However, in other embodiments a wired connection can be used for the implanted portion to communication with the external portion.

The implanted medical device <NUM> and/or the medical device <NUM> can include a housing <NUM> and a header <NUM> coupled to the housing <NUM>. Various materials can be used to form the housing <NUM>. In some embodiments, the housing <NUM> can be formed of a material such as a metal, ceramic, polymer, composite, or the like. In some embodiments, the housing <NUM>, or one or more portions thereof, can be formed of titanium. The header <NUM> can be formed of various materials, but in some embodiments the header <NUM> can be formed of a translucent polymer such as an epoxy material. In some embodiments the header <NUM> can be hollow. In other embodiments the header <NUM> can be filled with components and/or structural materials such as epoxy or another material such that it is non-hollow.

In some embodiments where a portion of the medical device <NUM> or <NUM> is partially external, the header <NUM> and housing <NUM> can be surrounded by a protective casing made of durable polymeric material. In other embodiments, where a portion of a device is partially external, the header <NUM> and housing <NUM> can be surrounded by a protective casing made of one or more of a polymeric material, metallic material, and/or glass material.

The header <NUM> can be coupled to one or more leads <NUM>. The header <NUM> can serve to provide fixation of the proximal end of one or more leads <NUM> and electrically couple the one or more leads <NUM> to one or more components within the housing <NUM>. The one or more leads <NUM> can include one or more electrodes <NUM> disposed along the length of the electrical leads <NUM>. In some embodiments, electrodes <NUM> can include electric field generating electrodes and in other embodiments electrodes <NUM> can include electric field sensing electrodes. In some embodiments, leads <NUM> can include both electric field generating and electric field sensing electrodes. In other embodiments, leads <NUM> can include any number of electrodes that are both electric field sensing and electric field generating. The leads <NUM> can include one or more conductors therein, such as metal wires, to provide electrical communication between the electrodes and a proximal end (or plug) of the lead. The wires can exist as single strands or fibers or can be multifibrillar such as a cable. The leads <NUM> can include a shaft, typically formed of a polymeric material or another non-conductive material, within which the conductors therein can pass. The proximal end of the leads <NUM> can be inserted into the header <NUM>, thereby providing electrical communication between the electrodes <NUM> and the components inside the housing <NUM>. It will be appreciated that while many embodiments of medical devices herein are designed to function with leads, leadless medical devices that generate electrical fields are also contemplated herein.

In various embodiments, the electrodes <NUM> can be positioned around or adjacent to a tumor <NUM>, such as a cancerous tumor. The tumor <NUM> can be positioned within an electric field generated by the electrodes <NUM>.

The electric fields generated by the implanted medical device <NUM> and/or the medical device <NUM> can vary. In some embodiments, the implanted medical device <NUM> and/or the medical device <NUM> can generate one or more electric fields at frequencies selected from a range of between <NUM> to <NUM>.

In some embodiments, an electric field can be applied to the site of a cancerous tumor at a specific frequency or constant frequency range. However, in some embodiments, an electric field can be applied to the site of a cancerous tumor by sweeping through a range of frequencies. As one example, referring now to <FIG>, exemplary plot <NUM> shows an alternating electric field, delivered by the electrodes <NUM>, where the frequency increases over time. Similarly, <FIG> shows the change in frequency as a function of time in exemplary plot <NUM> during a programmed therapy parameter. In some embodiments, a frequency sweep can include sweeping from a minimum frequency up to a maximum frequency. In some embodiments, a frequency sweep can include sweeping from a maximum frequency down to a minimum frequency. In other embodiments, sweeping from a minimum frequency up to a maximum frequency and sweeping from the maximum frequency down to the minimum frequency can be repeated as many times as desired throughout the duration of the delivery of the electric field from the electric field generating circuit.

As therapy progresses during a frequency sweep, it may be desired to alternate between frequency ranges so that as the cells within a population change in size and number in response to therapy, more cells can be targeted. For example, in some embodiments, a frequency sweep can include alternating between a first frequency sweep covering a range of about <NUM> to <NUM> and a second frequency sweep covering a range about <NUM> to <NUM>. It will be appreciated that sweeping through a first and second frequency range as described can be performed indefinitely throughout the course of the therapy. In some embodiments, the second frequency sweep (range) can be at higher frequencies than the first frequency sweep (range). In some embodiments, the first frequency sweep (range) can be at higher frequencies than the second frequency sweep (range).

Frequency ranges for the first and second frequency ranges can be any range including specific frequencies recited above or below, provided that the lower end of each range is a value less than the upper end of each range. At times, it may be beneficial to have some amount of overlap between the frequency range of the first and second frequency sweep.

In reference now to <FIG>, a schematic view of a medical device <NUM> is shown in accordance with various embodiments herein. In various embodiments, the medical device <NUM> can include at least one electric field generating circuit configured to generate one or more electric fields. The electric field generating circuit can be disposed within the housing <NUM>. The medical device <NUM> can further include control circuity that can be in communication with the electric field generating circuit. The control circuity can be configured to control delivery of the one or more electric fields from the electric field generating circuit. In various embodiments, the control circuitry causes the electric field generating circuit to generate one or more electric fields at frequencies selected from a range of between <NUM> to <NUM>. In various embodiments, the medical device <NUM> can include an implanted housing <NUM>. The implanted housing <NUM> can define an interior volume into which the electric field generating circuit and the first control circuit are disposed.

In some embodiments, the medical device <NUM> can include one or more leads <NUM>, such as two leads <NUM> (although embodiments with three, four, five, six or more leads are also directly contemplated herein). In some embodiments, at least one of the leads <NUM> can be fully implanted or fully beneath the patient's skin <NUM>, such as shown in <FIG>. In some embodiments, a plurality of leads <NUM> are fully implanted, such as two leads <NUM>, three leads <NUM>, four leads <NUM>, five leads <NUM>, or six leads <NUM>. In some embodiments, at least two electrodes <NUM> are implanted and disposed on a fully implanted lead <NUM>. In various embodiments, the lead <NUM> can be a transcutaneous lead that extends across the patient's skin <NUM>, such as shown in <FIG>.

In various embodiments, the medical device <NUM> can include two or more electrodes <NUM>. The electrodes <NUM> can be configured to deliver the electric fields to the site of a cancerous tumor <NUM>. In various embodiments, a lead <NUM> can provide electrical communication between the control circuitry and at least one electrode <NUM>. In various embodiments, an electric field can be delivered across at least one vector <NUM> defined by a pair of electrodes <NUM> formed by two or more electrodes <NUM>. In some embodiments, the electric fields can be delivered across at least two vectors. In some embodiments, a first vector can be defined by a first pair of electrodes and a second vector can be defined by a second pair of electrodes.

In some embodiments, the medical device can include at least one temperature sensor <NUM>. The temperature sensor <NUM> can be configured to measure the temperature of tissue at the site of the tumor <NUM>, such as to monitor temperature changes that could be a result of electric field generation or changes that could be a result of heating with a heating element. The temperature sensor <NUM> can be in electronic communication with the control circuitry. In some embodiments, the medical device can include at least one temperature sensor <NUM> which is disposed in tissue which is not within the region being treated, such as within healthy tissue. The temperature sensor <NUM>, which is remote from the treatment region, can be used along with temperature sensors <NUM> to determine changes in temperature that are a result of the therapy.

Many different types of sensors can be used as a temperature sensor herein. In some embodiments, the temperature sensor <NUM> can be selected from the group consisting of a thermistor, a resistance thermometer, a thermocouple, a semi-conductor based sensor, a bimetallic device, a thermometer, a change-of-state sensor, an optical temperature sensor (such as an infrared sensor), and the like.

In some embodiments, the temperature sensor <NUM> can be disposed on a lead <NUM>. In some embodiments, a plurality of temperature sensors <NUM> can be disposed on a single lead <NUM>. In some embodiments, at least one temperature sensor <NUM> is disposed on each of the leads <NUM>. In some embodiments with multiple leads <NUM>, at least two of the leads <NUM> can have a temperature sensor <NUM> disposed on the lead <NUM>.

In some embodiments herein, a temperature sensor can be chronically implanted. In some embodiments, a temperature sensor can be implanted for greater than <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> or more weeks, or an amount falling within a range between any of the foregoing. However, in some embodiments, a temperature sensor can be transitorily implanted. In some embodiments, a temperature sensor can be implanted for less than <NUM> days, <NUM> day, <NUM> hours, <NUM> hours, <NUM> hours, or <NUM> hour, or an amount falling within a range between any of the foregoing. In some embodiments, a temperature sensor <NUM> can be removable, such that it can be removed after confirmation that the medical device is delivering therapy in a safe or expected manner. In various embodiments, during implanting of the electrodes <NUM>, a removeable temperature sensor can be implanted. The removeable temperature sensor can be configured to measure the temperature of tissue near one or more electrodes, such as during implanting the of the electrodes. The removeable temperature sensor can be mounted on a transitorily inserted lead, introducer sheath, guide wire, delivery catheter, other type of catheter, or other type of surgical or implant instrument.

In some embodiments, a patient can undergo a thermal scan, such as after a medical device has been implanted. The thermal scan can be conducted by an external device or component. The thermal scan can determine temperatures of tissues in the patient's body, such as tissues near the electrodes. The thermal scan can allow for a less intrusive manner to monitor the temperature of various tissues within the patient's body, such as during therapy by a medical device.

It will be appreciated that a thermal scan can be performed in various ways. For example, a thermal scan can be performed using infrared thermography (IRT), an infrared thermometer, thermal imaging, thermal video, indium antimonide (InSb) devices, mercury cadmium telluride (MCT) devices, and the like.

In some embodiments, the control circuitry can be configured to calculate the power output of the electric field. The control circuit can also be configured to estimate a temperature of tissue within the electric field, such as based on the power output and the distance between the electrodes <NUM> of the electrode pair. Power (in Watts) is related to current and resistance/impedance as follows Pavg = I<NUM>rms*R. <NUM> watt is equivalent to <NUM> joule/second. Heat transferred can be determined as q = mCpΔT or ΔT = q/mCp, wherein q is energy in kilojoules, m is the mass, Cp is the specific heat capacity of the tissue, and ΔT is the change in temperature. Thus, ΔT can be approximated as I<NUM>rms*R/mCp. In some embodiments, the distance (D) between electrodes can be used as a proxy for mass. Thus, in some embodiments, ΔT can be approximated as I<NUM>rms*R/DCp. The specific heat capacity of the tissue can be about <NUM> to <NUM> kJ kg-<NUM> K-<NUM>.

In some embodiments, the control circuit can be configured to estimate a power output based on a change in temperature. Specifically, the equations above can be reconfigured to solve for Pavg based on ΔT.

In some embodiments, the medical device <NUM> can be configured to receive data regarding the distance between two electrodes <NUM> in an electrode pair, such as to estimate the temperature of the tissue within the electric field. In some embodiments, the medical device <NUM> can receive data regarding the distance between two electrodes from a user. As an example, a user can enter the distance during a programming phase. In some embodiments, a user, such as a physician, can use an imaging device, such as a fluoroscope or ultrasound imaging device, to determine the distance between two electrodes <NUM>. The data can then be entered into the medical device <NUM>. In further embodiments, the medical device <NUM> can be configured to estimate the distance between the electrodes <NUM> of an electrode pair, such as based on impedance data between the two electrodes <NUM>.

In some embodiments, the control circuitry can be configured to estimate the temperature of tissue within the electric field, such as based on an impedance measurement. In some embodiments, the control circuitry can be configured to estimate the temperature of tissue within the electric field, such as based on an impedance measurement and the distance between the electrodes <NUM> of the electrode pair. The medical device <NUM> can be configured to receive data regarding the distance between the electrodes <NUM> of the electrode pair. In further embodiments, the control circuitry can be configured to estimate changes in temperature of tissue within the electric field, such as based on changes in measured impedance.

In various embodiments, the impedance of tissue can change as the temperature of the tissue changes. These changes in impedance can be characterized and compared to known data for the therapy device. Afterwards, the impedance measurements can be correlated to a temperature estimate of the tissue.

In reference now to <FIG>, a schematic view of a medical device <NUM> is shown in accordance with various embodiments herein. In some embodiments, the medical device <NUM> can include a temperature sensor <NUM> positioned between a pair of electrodes <NUM>. In some embodiments, the temperature sensor <NUM> can be adapted to be inserted into the tumor <NUM>.

In some embodiments, the lead <NUM> which the temperature sensor <NUM> is disposed on does not include an electrode. In some embodiments, the lead <NUM> can include a plurality of temperature sensors <NUM>.

In some embodiments, the therapy delivered by the medical device <NUM> can include generating an electric field and generating heat at the tumor <NUM>. <FIG> is a schematic view of a medical device <NUM> in accordance with various embodiments herein. In some embodiments, the medical device <NUM> can include a heating element <NUM>. The heating element <NUM> can be configured to generate heat. In various embodiments, the heating element <NUM> can generate heat simultaneously with the electrodes generating an electric field.

The heating element <NUM> can generate heat and cause tissue to be heated through various means. In some embodiments, the heating element <NUM> may operate to heat tissue through conduction. For example, the heating element <NUM> may itself heat up through joule heating (also known as Ohmic or resistive heating) which can be performed by passing an electric current through a component with electrical resistance. For example, a nichrome (nickel/chromium <NUM>/<NUM>) wire, ribbon, or strip either directly exposed or embedded within another material can be used as a heating element <NUM> and as it is heated it can heat the surrounding tissue through thermal conduction. Various other materials can also be used as a heating element. In some embodiments, the heating element <NUM> may emit electromagnetic radiation that is then absorbed by the surrounding tissue causing it to heat up. For example, the heating element <NUM> can include an infrared light emitter which generates electromagnetic radiation that can be absorbed the surrounding tissue raising its temperature, which can serve as an example of radiant heating. In some embodiments, the heating element <NUM> can provide heat to tissue both through conduction and radiation.

In some embodiments, the control circuitry causes the heating element <NUM> to generate heat. In some embodiments, the control circuity estimates the temperature of tissue within the electric field based on an impedance measurement. In some embodiments, the control circuitry estimates the temperature of the tissue within the electric field based on a power measurement.

In various embodiments, one or more heating elements <NUM> can be disposed on a lead <NUM>. In some embodiments, a lead <NUM> which includes a heating element <NUM> does not include an electrode <NUM>.

In some embodiments, a lead <NUM> can include at least one heating element <NUM> and at least one electrode <NUM>, such as shown in <FIG> shows a schematic view of a medical device <NUM> in accordance with various embodiments herein. The medical device <NUM> can include a housing <NUM> (which can be an external housing in this example) and one or more leads <NUM>.

The medical device <NUM> can include one or more transcutaneous leads <NUM>, such as a lead <NUM> that passes through or across the patient's skin <NUM>. In various embodiments, at least two electrodes <NUM> are implanted and disposed on a transcutaneous lead <NUM>. In various embodiments, at least two electrodes <NUM> are implanted and disposed on transcutaneous leads <NUM>, such as at least one electrode <NUM> on two different transcutaneous leads <NUM>.

In some cases, device operations herein may consume a significant amount of electrical power. By way of example, joule heating may consume a significant amount of electrical power. The power capacity of fully implanted components may be somewhat limited (e.g., there are finite limits to the total power capacity provided by implanted batteries). As such, in some embodiments, the system may be configured to deliver power to an internal (implanted) component from an external power source.

<FIG> show a schematic view of a medical device <NUM> in accordance with various embodiments herein. The medical device <NUM> can include an implanted housing <NUM> and one or more fully implanted leads <NUM>. The implanted leads <NUM> can include electrodes <NUM>. The medical device <NUM> can include an external housing <NUM>. In some embodiments, an external power supply can be disposed within the external housing <NUM>. In various embodiments, the implanted housing <NUM> can be in wireless communication with the external housing <NUM>, such as exchange data or information regarding therapy delivery.

In some embodiments, control circuity can be disposed in one of the implanted housing <NUM> or the external housing <NUM>. In some embodiments, control circuitry can be disposed at least partially in the implanted housing <NUM> and the external housing <NUM>.

In some embodiments, a transcutaneous lead <NUM> can include a wireless power transfer connection <NUM>. The wireless power transfer connection <NUM> can be established transcutaneously between the external housing <NUM>, such as a power supply within an external housing <NUM>, and an implanted lead <NUM>. In some embodiments, the medical device <NUM> can include an inductive power transfer link, including paired internal <NUM> and external <NUM> inductors to transfer power form outside of the body to an implanted component of the system. The inductive power transfer link can allow for a transfer of power from an external power supply to an internal component, which in turn can cause an electrical field to be generated or heat to be generated without puncturing the skin <NUM> or otherwise requiring a maintained opening or tunnel through the patient's skin <NUM>.

In various embodiments, the fully implanted leads <NUM> can include electrodes <NUM> and can be free of heating elements <NUM>, and the transcutaneous lead <NUM> can include one or more heating elements <NUM>. In some embodiments, the external housing <NUM> can include a power source, such as to power the heating elements <NUM>.

In reference now to <FIG> a schematic view of a medical device <NUM> is shown in accordance with various embodiments herein. In some embodiments, the electric fields can be delivered across at least two vectors <NUM>, <NUM>. The first vector <NUM> can be defined by a first pair of electrodes <NUM>, and the second vector <NUM> can be defined by a second pair of electrodes <NUM>. In various embodiments, the first vector <NUM> and the second vector <NUM> can be substantially orthogonal to one another.

In some embodiments, the medical device <NUM> can include at least two electric field generating circuits. In various embodiments, a first electric field generating circuit can be implanted, such as within the housing <NUM>, and a second electric field generating circuit can be external, such as within the housing <NUM>.

Referring now to <FIG>, a schematic cross-sectional view of medical device <NUM> is shown in accordance with various embodiments herein. The housing <NUM> can define an interior volume <NUM> that can be hollow and that in some embodiments is hermetically sealed off from the area <NUM> outside of medical device <NUM>. In other embodiments the housing <NUM> can be filled with components and/or structural materials such that it is non-hollow. The medical device <NUM> can include control circuitry <NUM>, which can include various components <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, and <NUM> disposed within housing <NUM>. In some embodiments, these components can be integrated and in other embodiments these components can be separate. In yet other embodiments, there can be a combination of both integrated and separate components. The medical device <NUM> can also include an antenna <NUM>, to allow for unidirectional or bidirectional wireless data communication, such as with an external device or an external power supply. In some embodiments, the components of medical device <NUM> can include an inductive energy receiver coil (not shown) communicatively coupled or attached thereto to facilitate transcutaneous recharging of the medical device via recharging circuitry.

The various components <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, and <NUM> of control circuitry <NUM> can include, but are not limited to, a microprocessor, memory circuit (such as random access memory (RAM) and/or read only memory (ROM)), recorder circuitry, controller circuit, a telemetry circuit, a power supply circuit (such as a battery), a timing circuit, and an application specific integrated circuit (ASIC), a recharging circuit, amongst others. Control circuitry <NUM> can be in communication with an electric field generating circuit <NUM> that can be configured to generate electric current to create one or more fields. The electric field generating circuit <NUM> can be integrated with the control circuitry <NUM> or can be a separate component from control circuitry <NUM>. Control circuitry <NUM> can be configured to control delivery of electric current from the electric field generating circuit <NUM>. In some embodiments, the electric field generating circuit <NUM> can be present in a portion of the medical device that is external to the body.

In some embodiments, the control circuitry <NUM> can be configured to direct the electric field generating circuit <NUM> to deliver an electric field via leads <NUM> to the site of a cancerous tumor located within a bodily tissue. In other embodiments, the control circuitry <NUM> can be configured to direct the electric field generating circuit <NUM> to deliver an electric field via the housing <NUM> of medical device <NUM> to the site of a cancerous tumor located within a bodily tissue. In other embodiments, the control circuitry <NUM> can be configured to direct the electric field generating circuit <NUM> to deliver an electric field between leads <NUM> and the housing <NUM> of medical device <NUM>. In some embodiments, one or more leads <NUM> can be in electrical communication with the electric field generating circuit <NUM>.

In some embodiments, various components within medical device <NUM> can include an electric field sensing circuit <NUM> configured to generate a signal corresponding to sensed electric fields. Electric field sensing circuit <NUM> can be integrated with control circuitry <NUM> or it can be separate from control circuitry <NUM>.

Sensing electrodes can be disposed on or adjacent to the housing of the medical device, on one or more leads connected to the housing, on a separate device implanted near or in the tumor, or any combination of these locations. In some embodiments, the electric field sensing circuit <NUM> can include a first sensing electrode <NUM> and a second sensing electrode <NUM>. In other embodiments, the housing <NUM> itself can serve as a sensing electrode for the electric field sensing circuit <NUM>. The electrodes <NUM> and <NUM> can be in communication with the electric field sensing circuit <NUM>. The electric field sensing circuit <NUM> can measure the electrical potential difference (voltage) between the first electrode <NUM> and the second electrode <NUM>. In some embodiments, the electric field sensing circuit <NUM> can measure the electrical potential difference (voltage) between the first electrode <NUM> or second electrode <NUM>, and an electrode disposed along the length of one or more leads <NUM>. In some embodiments, the electric field sensing circuit can be configured to measure sensed electric fields and to record electric field strength in V/cm.

It will be appreciated that the electric field sensing circuit <NUM> can additionally measure an electrical potential difference between the first electrode <NUM> or the second electrode <NUM> and the housing <NUM> itself. In other embodiments, the medical device can include a third electrode <NUM>, which can be an electric field sensing electrode or an electric field generating electrode. In some embodiments, one or more sensing electrodes can be disposed along lead <NUM> and can serve as additional locations for sensing an electric field. Many combinations can be imagined for measuring electrical potential difference between electrodes disposed along the length of one or more leads <NUM> and the housing <NUM> in accordance with the embodiments herein.

In some embodiments, the one or more leads <NUM> can be in electrical communication with the electric field generating circuit <NUM>. The one or more leads <NUM> can include one or more electrodes <NUM>, as shown in <FIG>. In some embodiments, various electrical conductors, such as electrical conductors <NUM> and <NUM>, can pass from the header <NUM> through a feed-through structure <NUM> and into the interior volume <NUM> of medical device <NUM>. As such, the electrical conductors <NUM> and <NUM> can serve to provide electrical communication between the one or more leads <NUM> and control circuitry <NUM> disposed within the interior volume <NUM> of the housing <NUM>.

In some embodiments, recorder circuitry can be configured to record the data produced by the electric field sensing circuit <NUM> and record time stamps regarding the same. In some embodiments, the control circuitry <NUM> can be hardwired to execute various functions, while in other embodiments the control circuitry <NUM> can be directed to implement instructions executing on a microprocessor or other external computation device. A telemetry circuit can also be provided for communicating with external computation devices such as a programmer, a home-based unit, and/or a mobile unit (e.g. a cellular phone, personal computer, smart phone, tablet computer, and the like).

Elements of various embodiments of the medical devices described herein are shown in <FIG>. However, it will be appreciated that some embodiments can include additional elements beyond those shown in <FIG>. In addition, some embodiments may lack some elements shown in <FIG>. The medical devices as embodied herein can gather information through one or more sensing channels and can output information through one or more field generating channels. A microprocessor <NUM> can communicate with a memory <NUM> via a bidirectional data bus. The memory <NUM> can include read only memory (ROM) or random-access memory (RAM) for program storage and RAM for data storage. The microprocessor <NUM> can also be connected to a telemetry interface <NUM> for communicating with external devices such as a programmer, a home-based unit and/or a mobile unit (e.g. a cellular phone, personal computer, smart phone, tablet computer, and the like) or directly to the cloud or another communication network as facilitated by a cellular or other data communication network. The medical device can include a power supply circuit <NUM>. In some embodiments, the medical device can include an inductive energy receiver coil interface (not shown) communicatively coupled or attached thereto to facilitate transcutaneous recharging of the medical device.

The medical device can include one or more electric field sensing electrodes <NUM> and one or more electric field sensor channel interfaces <NUM> that can communicate with a port of microprocessor <NUM>. The medical device can also include one or more electric field generating circuits <NUM>, one or more electric field generating electrodes <NUM>, and one or more electric field generating channel interfaces <NUM> that can communicate with a port of microprocessor <NUM>. The medical device can also include one or more temperature sensors <NUM> and one or more temperature sensor channel interfaces <NUM> that can communicate with a port of microprocessor <NUM>. The channel interfaces <NUM>, <NUM>, and <NUM> can include various components such as analog-to-digital converters for digitizing signal inputs, sensing amplifiers, registers which can be written to by the control circuitry in order to adjust the gain and threshold values for the sensing amplifiers, source drivers, modulators, demodulators, multiplexers, and the like.

Although the temperature sensors <NUM> are shown as part of a medical device in <FIG>, it is realized that in some embodiments one or more of the temperature sensors could be physically separate from the medical device. In various embodiments, one or more of the temperature sensors can be within another implanted medical device communicatively coupled to a medical device via telemetry interface <NUM>. In yet other embodiments, one or more of the temperature sensors can be external to the body and coupled to a medical device via telemetry interface <NUM>.

Many different exemplary methods are contemplated herein, including, but not limited to, methods of making, methods of using, and the like. Aspects of system/device operation described elsewhere herein can be performed as operations of one or more methods in accordance with various examples herein.

In an example, a method of treating a cancerous tumor is included. The exemplary can include implanting at least two electrodes inside a body of a patient with the cancerous tumor, implanting a temperature sensor inside the body of the patent, generating an electrical field between at least one pair of electrodes, the electric field having frequencies within a range of between <NUM> to <NUM>, and sensing the temperature with the temperature sensor.

<FIG> shows a flowchart depicting an exemplary method <NUM> in accordance with various examples herein. The method <NUM> can be a method for treating a cancerous tumor. The method <NUM> can include implanting at least two electrodes inside a body of a patient with the cancerous tumor, step <NUM>. The method <NUM> can further include implanting a temperature sensor inside the body of the patent, step <NUM>, such as near or within the cancerous tumor. The method <NUM> can also include generating an electrical field between at least one pair of electrodes, step <NUM>. In various embodiments, the electric field can have frequencies within a range of between <NUM> to <NUM>.

In some examples, the method <NUM> can include sensing the temperature with the temperature sensor, step <NUM>, such as the temperature of the tissue near the tumor or the temperature of the tumor. In some examples, the method <NUM> can include estimating the temperature of tissue within the electric field, such as based on the power output and the distance between the electrodes. In some examples, the method <NUM> can include estimating the distance between electrodes of an electrode pair, such as based on impedance data.

In various embodiments, systems or device herein (or components thereof, such as control circuitry) can be configured to direct an electric field generating circuit to deliver an electric field using one or more frequencies selected from a range of between <NUM> to <NUM>. In some embodiments, the control circuitry can be configured to direct the electric field generating circuit to deliver an electric field at one or more frequencies selected from a range of between <NUM> to <NUM>. In some embodiments, the control circuitry can be configured to direct the electric field generating circuit to deliver an electric field at one or more frequencies selected from a range of between <NUM> to <NUM>. In some embodiments, the control circuitry can be configured to direct the electric field generating circuit to periodically deliver an electric field using one or more frequencies greater than <NUM>.

In some embodiments, the electric field can be effective in disrupting cellular mitosis in cancerous cells. The electric field can be delivered to the site of a cancerous tumor along more than one vector. In some examples, the electric field can be delivered along at least one vector, including at least one of the lead electrodes. In some embodiments, at least two vectors with spatial diversity between the two vectors can be used. The vectors can be spatially and/or directionally separated (e.g., the vectors can be disposed at an angle with respect to one another) by at least about <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> or <NUM> degrees.

A desired electric field strength can be achieved by delivering an electric current between two electrodes. The specific current and voltage at which the electric field is delivered can vary and can be adjusted to achieve the desired electric field strength at the site of the tissue to be treated. In some embodiments, the control circuitry can be configured to direct the electric field generating circuit to deliver an electric field using currents ranging from <NUM> mAmp to <NUM> mAmp to the site of a cancerous tumor. In some embodiments, the control circuitry can be configured to direct the electric field generating circuit to deliver an electric field using currents ranging from <NUM> mAmp to <NUM> mAmp to the site of a cancerous tumor. In some embodiments, the control circuitry can be configured to direct the electric field generating circuit to deliver an electric field using currents ranging from <NUM> mAmp to <NUM> mAmp to the site of a cancerous tumor.

In some embodiments, the control circuitry can be configured to direct the electric field generating circuit to deliver an electric field using currents including <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp , <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, <NUM> mAmp, or <NUM> mAmp. It will be appreciated that the control circuitry can be configured to direct the electric field generating circuit to deliver an electric field at a current falling within a range, wherein any of the forgoing currents can serve as the lower or upper bound of the range, provided that the lower bound of the range is a value less than the upper bound of the range.

In some embodiments, the control circuitry can be configured to direct the electric field generating circuit to deliver an electric field using voltages ranging from <NUM> Vrms to <NUM> Vrms to the site of a cancerous tumor. In some embodiments, the control circuitry can be configured to direct the electric field generating circuit to deliver an electric field using voltages ranging from <NUM> Vrms to <NUM> Vrms to the site of a cancerous tumor. In some embodiments, the control circuitry can be configured to direct the electric field generating circuit to deliver an electric field using voltages ranging from <NUM> Vrms to <NUM> Vrms to the site of a cancerous tumor.

In some embodiments, the control circuitry can be configured to direct the electric field generating circuit to deliver an electric field using one or more voltages including <NUM> Vrms, <NUM> Vrms, <NUM> Vrms, <NUM> Vrms, <NUM> Vrms, <NUM> Vrms, <NUM> Vrms, <NUM> Vrms, <NUM> Vrms, <NUM> Vrms, <NUM> Vrms, <NUM> Vrms, <NUM> Vrms, <NUM> Vrms, <NUM> Vrms, <NUM> Vrms, <NUM> Vrms, or <NUM> Vrms. It will be appreciated that the control circuitry can be configured to direct the electric field generating circuit to deliver an electric field using a voltage falling within a range, wherein any of the forgoing voltages can serve as the lower or upper bound of the range, provided that the lower bound of the range is a value less than the upper bound of the range.

In some embodiments, the control circuitry can be configured to direct the electric field generating circuit to deliver and electric field using one or more frequencies including <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>. It will be appreciated that the electric field generating circuit can deliver an electric field using a frequency falling within a range, wherein any of the foregoing frequencies can serve as the upper or lower bound of the range, provided that the upper bound is greater than the lower bound.

In some embodiments, the control circuitry can be configured to direct the electric field generating circuit to generate one or more applied electric field strengths selected from a range of between <NUM> V/cm to <NUM> V/cm. In some embodiments, the control circuitry can be configured to direct the electric field generating circuit to generate one or more applied electric field strengths of greater than <NUM> V/cm. In some embodiments, the control circuitry can be configured to direct the electric field generating circuit to generate one or more applied electric field strengths selected from a range of between <NUM> V/cm to <NUM> V/cm. In some embodiments, the control circuitry can be configured to direct the electric field generating circuit to generate one or more applied electric field strengths selected from a range of between <NUM> V/cm to <NUM> V/cm.

In other embodiments, the control circuitry can be configured to direct the electric field generating circuit to generate one or more applied electric field strengths including <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm, <NUM> V/cm. It will be appreciated that the electric field generating circuit can generate an electric field having a field strength at a treatment site falling within a range, wherein any of the foregoing field strengths can serve as the upper or lower bound of the range, provided that the upper bound is greater than the lower bound.

It should be noted that, as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the content clearly dictates otherwise. It should also be noted that the term "or" is generally employed in its sense including "and/or" unless the content clearly dictates otherwise.

All publications and patent applications in this specification are indicative of the level of ordinary skill in the art to which this invention pertains.

As used herein, the recitation of numerical ranges by endpoints shall include all numbers subsumed within that range (e.g., <NUM> to <NUM> includes <NUM>, <NUM>, <NUM>, <NUM>, etc.).

Claim 1:
A medical device system comprising:
an electric field generating circuit (<NUM>) configured to generate one or more electric fields; and
a control circuit (<NUM>) in communication with the electric field generating circuit (<NUM>), the control circuit (<NUM>) configured to control delivery of the one or more electric fields from the electric field generating circuit (<NUM>);
two or more electrodes (<NUM>) to deliver the electric fields to a site of a cancerous tumor within a patient;
a heating element (<NUM>) disposed on a lead (<NUM>), wherein the control circuit (<NUM>) is configured to cause the heating element (<NUM>) to generate heat and heat a surrounding of the heating element (<NUM>) through thermal conduction; and
a temperature sensor (<NUM>) to measure the temperature of tissue at the site of the cancerous tumor, the temperature sensor (<NUM>) in electronic communication with the control circuit (<NUM>);
wherein the control circuit (<NUM>) causes the electric field generating circuit (<NUM>) to generate one or more electric fields at frequencies selected from a range of between <NUM> to <NUM>.