Patent Grant
10258406
Electrical ablation therapy has been used in medicine for the treatment of undesirable tissue, such as, for example, diseased tissue, cancer, malignant and benign tumors, masses, lesions, and other abnormal tissue growths. Apparatuses, systems, and methods for conventional ablation therapies may include electrical ablation therapies, such as, for example, high temperature thermal therapies including, focused ultrasound ablation, radiofrequency (RF) ablation, and interstitial laser coagulation, chemical therapies in which chemical agents are injected into the undesirable tissue to cause ablation, surgical excision, cryotherapy, radiation, photodynamic therapy, Moh's micrographic surgery, topical treatments with 5-fluorouracil, and laser ablation. Conventional electrical ablation therapies may suffer from some of the following limitations: cost, length of recovery, and extraordinary pain inflicted on the patient. In particular, one drawback of conventional electrical ablation therapies may be any permanent damage to healthy tissue surrounding the undesirable tissue due to detrimental thermal effects resulting from exposing the tissue to thermal energy generated by the electrical ablation device. For example, permanent damage to surrounding healthy tissue may occur when using high temperature thermal therapies to expose undesirable tissue to electric potentials sufficient to cause cell necrosis.
Additionally, conventional electrical ablation therapies to treat large masses of undesirable tissue may comprise treating a first portion of the tissue treatment region, repositioning the electrical ablation device, and treating the remaining portion of the tissue treatment region. Conventional electrical ablation therapies to treat large masses of undesirable tissue may suffer from some of the following additional limitations: small tissue treatment regions, repositioning the ablation apparatus, and multiple procedures. In particular, the surgeon or clinician may need to reposition the electrical ablation apparatus within the tissue treatment region and begin the process anew to treat large masses of undesirable tissue. Accordingly, more efficient electrical ablation apparatuses, systems, and methods for the treatment of undesirable tissue having reduced or no detrimental thermal effects to surrounding healthy tissue are desirable.
The various embodiments of electrical ablation devices and methods thereof described herein may be better understood by considering the following description in conjunction with the accompanying drawings.
Various embodiments are directed to electrical ablation apparatuses, systems, and methods for the treatment of undesirable tissue having reduced or no detrimental thermal effects to surrounding healthy tissue.
This disclosure describes various elements, features, aspects, and advantages of various embodiments of electrical ablation devices and methods thereof. It is to be understood that certain descriptions of the various embodiments have been simplified to illustrate only those elements, features and aspects that are relevant to a more clear understanding of the disclosed embodiments, while eliminating, for purposes of brevity or clarity, other elements, features and aspects. Any references to “various embodiments,” “some embodiments,” “one embodiment,” or “an embodiment” generally means that a particular element, feature and/or aspect described in the embodiment is included in at least one embodiment. The phrases “in various embodiments,” “in some embodiments,” “in one embodiment,” or “in an embodiment” may not refer to the same embodiment. Persons having ordinary skill in the art, upon considering the description herein, will recognize that various combinations or sub-combinations of the various embodiments and other elements, features, and aspects may be desirable in particular implementations or applications. However, because such other elements, features, and aspects may be readily ascertained by persons having ordinary skill in the art upon considering the description herein, and are not necessary for a complete understanding of the disclosed embodiments, a description of such elements, features, and aspects may not be provided. As such, it is to be understood that the description set forth herein is merely exemplary and illustrative of the disclosed embodiments and is not intended to limit the scope of the invention as defined solely by the claims.
All numerical quantities stated herein are approximate unless stated otherwise, meaning that the term “about” may be inferred when not expressly stated. The numerical quantities disclosed herein are to be understood as not being strictly limited to the exact numerical values recited. Instead, unless stated otherwise, each numerical value is intended to mean both the recited value and a functionally equivalent range surrounding that value. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding the approximations of numerical quantities stated herein, the numerical quantities described in specific examples of actual measured values are reported as precisely as possible.
All numerical ranges stated herein include all sub-ranges subsumed therein. For example, a range of “1 to 10” is intended to include all sub-ranges between and including the recited minimum value of 1 and the recited maximum value of 10. Any maximum numerical limitation recited herein is intended to include all lower numerical limitations. Any minimum numerical limitation recited herein is intended to include all higher numerical limitations.
As generally used herein, the terms “proximal” and “distal” generally refer to a clinician manipulating one end of an instrument used to treat a patient. The term “proximal” generally refers to the portion of the instrument closest to the clinician. The term “distal” generally refers to the portion located furthest from the clinician. It will be further appreciated that for conciseness and clarity, spatial terms such as “vertical,” “horizontal,” “up,” and “down” may be used herein with respect to the illustrated embodiments. However, surgical instruments may be used in many orientations and positions, and these terms are not intended to be limiting and absolute.
According to certain embodiments, an ablation apparatus may generally comprise first and second electrodes coupled to an energy source operative to generate and deliver a first sequence of electrical pulses and a second sequence of electrical pulses to tissue having a necrotic threshold, wherein the first sequence of electrical pulses delivers a first energy dose that is less than the necrotic threshold to induce thermal heating in the tissue and the second sequence of electrical pulses delivers a second energy dose equal to or greater than the necrotic threshold to induce cell necrosis in the tissue by irreversible electroporation. The necrotic threshold generally refers the electric field strength that induces cell necrosis by irreversible electroporation. The necrotic threshold may relate to at least the following parameters: cell type, temperature, electrical conductivity, pH and tissue perfusion. Table 1 illustrates the necrotic threshold for several cell types.
In certain embodiments, electrical ablation devices may generally comprise one or more electrodes configured to be positioned into or proximal to undesirable tissue in a tissue treatment region (e.g., a target site or a worksite). The tissue treatment region may have evidence of abnormal tissue growth. In general, the electrodes may comprise an electrically conductive portion (e.g., medical grade stainless steel, gold plated, etc.) and may be configured to electrically couple to an energy source. Once the electrodes are positioned into or proximal to the undesirable tissue, an energizing potential may be applied to the electrodes to create an electric field to which the undesirable tissue is exposed. The energizing potential (and the resulting electric field) may be characterized by various parameters, such as, for example, frequency, amplitude, pulse width (duration of a pulse or pulse length), and/or polarity. Depending on the diagnostic or therapeutic treatment to be rendered, a particular electrode may be configured either as an anode or a cathode, or a plurality of electrodes may be configured with at least one electrode configured as an anode and at least one other electrode configured as a cathode. Regardless of the initial polarity configuration, the polarity of the electrodes may be reversed by reversing the polarity of the output of the energy source.
In certain embodiments, a suitable energy source may comprise an electrical waveform generator. The electrical waveform generator may be configured to create an electric field that is suitable to induce thermal heating in the tissue without inducing cell necrosis in the tissue by irreversible electroporation at various electric field amplitudes and durations. The electrical waveform generator may be configured to create an electric field that is suitable to create irreversible electroporation in undesirable tissue at various electric field amplitudes and durations. The energy source may be configured to deliver electrical pulses in the form of direct-current (DC) and/or alternating-current (AC) voltage potentials (e.g., time-varying voltage potentials) to the electrodes. The energy source may also be configured to reverse the potential between the electrodes. The electrical pulses may be characterized by various parameters, such as, for example, frequency, amplitude, pulse width, polarity, total number of pulses, delay between pulses bursts, total number of pulses at a lower voltage, and total number of pulses at high voltage. The undesirable tissue may be heated by exposure to the electric potential difference across the electrodes. The undesirable tissue may be ablated by exposure to the electric potential difference across the electrodes.
In certain embodiments, the apparatuses, systems, and methods may be configured for minimally invasive ablation treatment of undesirable tissue through the use of irreversible electroporation. Minimally invasive ablation treatment of undesirable tissue may be characterized by the ability to ablate undesirable tissue in a controlled and focused manner having reduced or no thermally damaging effects to the surrounding healthy tissue. The apparatuses, systems, and methods may be configured to ablate undesirable tissue through the use of electroporation or electropermeabilization. Electroporation refers to the application of electric pulses to a cell membrane to cause an increase in the permeabilization of the cell membrane. The external electric field (i.e., electric potential/per unit length) applied to the cell may significantly increase the electrical conductivity and permeability of the plasma in the cell membrane.
More specifically, the apparatuses, systems, and methods may be configured to ablate undesirable tissue through the use of irreversible electroporation. Irreversible electroporation refers to the application of an electric field of a specific magnitude and duration to a cell membrane such that the permeabilization of the cell membrane cannot be reversed. One of the primary parameters affecting the transmembrane potential is the potential difference across the cell membrane. The destabilizing potential may form pores in the cell membrane when the potential across the cell membrane exceeds its dielectric strength causing the cell to die under a process known as apoptosis and/or necrosis. Irreversible electroporation may induce localized heating of the tissue surrounding the electrodes. Irreversible electroporation may lead to cell death without inducing a significant amount of heat in the cell membrane.
The application of irreversible electroporation pulses to cells may be an effective way for ablating large volumes of undesirable tissue with no or minimal detrimental thermal effects to the surrounding healthy tissue. Without wishing to be bound to any particular theory, it is believed that irreversible electroporation destroys cells with no or minimal heat, and thus, may not destroy the cellular support structure or regional vasculature. A destabilizing irreversible electroporation pulse, suitable to cause cell death without inducing a significant amount of thermal damage to the surrounding healthy tissue, may have amplitude in the range of several hundred to several thousand volts and may be generally applied across biological membranes over a distance of several millimeters, for example, for a relatively long duration of 1 μs to 100 ms. Thus, the undesirable tissue may be ablated in-vivo through the delivery of destabilizing electric fields by quickly causing cell necrosis.
The apparatuses, systems, and methods for electrical ablation therapy may be adapted for use in minimally invasive surgical procedures to access the tissue treatment region in various anatomic locations, such as, for example, the brain, lungs, breast, liver, gall bladder, pancreas, prostate gland, and various internal body lumen defined by the esophagus, stomach, intestine, colon, arteries, veins, anus, vagina, cervix, fallopian tubes, and the peritoneal cavity. Minimally invasive electrical ablation devices may be introduced to the tissue treatment region though a small opening formed in the patient's body using a trocar or through a natural body orifice such as the mouth, anus, or vagina using translumenal access techniques known as Natural Orifice Translumenal Endoscopic Surgery (NOTES)™. Once the electrical ablation devices (e.g., electrodes) are located into or proximal to the undesirable tissue in the treatment region, electric field potentials may be applied by the energy source to the undesirable tissue. The electrical ablation devices may comprise portions that may be inserted into the tissue treatment region percutaneously (e.g., where access to inner organs or other tissue is done via needle-puncture of the skin). Other portions of the electrical ablation devices may be introduced into the tissue treatment region endoscopically (e.g., laparoscopically and/or thoracoscopically) through trocars or channels of the endoscope, through small incisions, or transcutaneously (e.g., where electric pulses are delivered to the tissue treatment region through the skin). An electrical ablation device is described in commonly owned U.S. patent application Ser. No. 12/352,375, filed Jan. 12, 2009, entitled, “ELECTRICAL ABLATION DEVICES”, now U.S. Pat. No. 8,361,066.
Once positioned into or proximate the tissue treatment region, the electrical ablation system 10 may be actuated (e.g., energized) to ablate the undesirable tissue. In one embodiment, the electrical ablation system 10 may be configured to treat diseased tissue in the gastrointestinal tract, esophagus, lung, and/or stomach that may be accessed orally. In another embodiment, the electrical ablation system 10 may be adapted to treat undesirable tissue in the liver or other organs that may be accessible using translumenal access techniques, such as, for example, NOTES™ techniques where the electrical ablation devices may be initially introduced through a natural body orifice and then advanced to the tissue treatment site by puncturing the walls of internal body lumen. In various embodiments, the electrical ablation system 10 may be adapted to treat undesirable tissue in the brain, lung, breast, liver, gall bladder, pancreas, or prostate gland, using one or more electrodes positioned percutaneously, transcutaneously, translumenally, minimally invasively, and/or through open surgical techniques, or any combination thereof.
In one embodiment, the electrical ablation system 10 may be employed in conjunction with a flexible endoscope 12, as well as a rigid endoscope, laparoscope, or thoracoscope, such as the GIF-100 model available from Olympus Corporation. In one embodiment, the endoscope 12 may be introduced to the tissue treatment region trans-anally through the colon, trans-orally through the esophagus and stomach, trans-vaginally through the cervix, transcutaneously, or via an external incision or keyhole formed in the abdomen in conjunction with a trocar. The electrical ablation system 10 may be inserted and guided into or proximate the tissue treatment region using the endoscope 12. In other embodiments, the endoscope 12 is not utilized, and instead other techniques, such as, for example, ultrasound or a computerized tomography (CT) scan, may be used to determine proper instrument placement during the procedure.
In the embodiment illustrated in
In one embodiment, one or more electrodes (e.g., needle electrodes, balloon electrodes), such as first and second electrodes 24a,b may extend out from the distal end of the electrical ablation device 20. In one embodiment, the first electrode 24a may be configured as the positive electrode and the second electrode 24b may be configured as the negative electrode. The first electrode 24a may be electrically connected to a first electrical conductor 18a, or similar electrically conductive lead or wire, which may be coupled to the positive terminal of the energy source 14 through the activation switch 62. The second electrode 24b may be electrically connected to a second electrical conductor 18b, or similar electrically conductive lead or wire, which may be coupled to the negative terminal of the energy source 14 through the activation switch 62. The electrical conductors 18a,b may be electrically insulated from each other and surrounding structures, except for the electrical connections to the respective electrodes 24a,b.
In certain embodiments, the electrical ablation device 20 may be configured to be introduced into or proximate the tissue treatment region using the endoscope 12 (laparoscope or thoracoscope), open surgical procedures, and/or external and non-invasive medical procedures. The electrodes 24a,b may be referred to herein as endoscopic or laparoscopic electrodes, although variations thereof may be inserted transcutaneously or percutaneously. In various embodiments, one or both electrodes 24a,b may be adapted and configured to slideably move in and out of a cannula, lumen, or channel defined within the flexible shaft 22.
When the electrodes 24a,b are positioned at the desired location into or proximate the tissue treatment region, the electrodes 24a,b may be connected to or disconnected from the energy source 14 by actuating or de-actuating the activation switch 62 on the hand piece 16. The activation switch 62 may be operated manually or may be mounted on a foot switch (not shown), for example. The electrodes 24a,b may deliver electric field pulses to the undesirable tissue. The electric field pulses may be characterized by various parameters, such as, for example, pulse shape, amplitude, frequency, pulse width, polarity, total number of pulses and duration. The electric field pulses may be sufficient to induce thermal heating in the undesirable tissue without inducing irreversible electroporation in the undesirable tissue. The electric field pulses may be sufficient to induce irreversible electroporation in the undesirable tissue. The induced potential may depend on a variety of conditions, such as, for example, tissue type, cell size, and electrical field pulse parameters. The transmembrane potential of a specific tissue type may primarily depend on the amplitude of the electric field and pulse width.
In certain embodiments, a protective sleeve or sheath 26 may be slidably disposed over the flexible shaft 22 and within a handle 28. In another embodiment, the sheath 26 may be slidably disposed within the flexible shaft 22 and the handle 28. The sheath 26 may be slideable and may be located over the electrodes 24a,b to protect the trocar and prevent accidental piercing when the electrical ablation device 20 is advanced therethrough. One or both of the electrodes 24a,b may be adapted and configured to slideably move in and out of a cannula, lumen, or channel formed within the flexible shaft 22. One or both of the electrodes 24a,b may be fixed in place. One of the electrodes 24a,b may provide a pivot about which the other electrode may be moved in an arc to other points in the tissue treatment region to treat larger portions of the diseased tissue that cannot be treated by fixing both of the electrodes 24a,b in one location. In one embodiment, one or both of the electrodes 24a,b may be adapted and configured to slideably move in and out of a working channel formed within a flexible shaft 32 of the endoscope 12 or may be located independently of the endoscope 12.
In one embodiment, the first and second electrical conductors 18a,b may be provided through the handle 28. The first electrode 24a may be slideably moved in and out of the distal end of the flexible shaft 22 using a slide member 30 to retract and/or advance the first electrode 24a. The second electrode 24b may be slideably moved in and out of the distal end of the flexible shaft 22 using the slide member 30 or a different slide member to retract and/or advance the second electrode 24b. One or both electrodes 24a,b may be coupled to the slide member 30, or additional slide members, to advance and retract the electrodes 24a,b and position the electrodes 24a,b. In this manner, the first and second electrodes 24a,b, which may be slidably movable within the cannula, lumen, or channel defined within the flexible shaft 22, may be advanced and retracted with the slide member 30. As shown in
In various other embodiments, transducers or sensors 29 may be located in the handle 28 (or other suitable location) of the electrical ablation device 20 to sense the force with which the electrodes 24a,b penetrate the tissue in the tissue treatment region. This feedback information may be useful to determine whether one or both of the electrodes 24a,b have been properly inserted in the tissue treatment region. As is particularly well known, cancerous tumor tissue tends to be denser than healthy tissue, and thus greater force may be typically required to insert the electrodes 24a,b therein. The transducers or sensors 29 may provide feedback to the operator, surgeon, or clinician to physically sense when the electrodes 24a,b are placed within the cancerous tumor. The feedback information provided by the transducers or sensors 29 may be processed and displayed by circuits located either internally or externally to the energy source 14. The sensor 29 readings may be employed to determine whether the electrodes 24a,b have been properly located within the cancerous tumor thereby assuring that a suitable margin of error has been achieved in locating the electrodes 24a,b. The sensor 29 readings may also be employed to determine whether the pulse parameters need to be adjusted to achieve a desired result, such as, for example, reducing the intensity of muscular contractions in the patient.
Referring to
Referring to
In certain embodiments, the temperature sensor and/or pressure sensor may be separate from the electrical ablation system 10. The electrical ablation device 20 may include the temperature sensor 25 and the pressure sensor may be separate from the electrical ablation system 10. The electrical ablation device 20 may include the pressure sensor 27 and the temperature sensor may be separate from the electrical ablation system 10.
According to certain embodiments, the temperature sensor may measure the temperature of the tissue treatment region. The temperature sensor may measure the temperature of the undesirable tissue. The temperature sensor may measure the temperature of the tissue surrounding the electrodes. The temperature sensor may measure the temperature before, during, and/or after treatment. The temperature sensor may measure the temperature before the first sequence of electrical pulses is delivered to the tissue. The temperature sensor may measure the temperature after the first sequence of electrical pulses is delivered to the tissue. The temperature sensor may measure the temperature before the second sequence of electrical pulses is delivered to the tissue. The temperature sensor may measure the temperature after the second sequence of electrical pulses is delivered to the tissue.
According to certain embodiments, the pressure sensor may measure the pressure of the tissue treatment region. The pressure sensor may measure the pressure of the space between the electrodes. The pressure sensor may measure the pressure surrounding the electrodes. The pressure sensor may measure the pressure before, during, and/or after treatment. The pressure sensor may measure the pressure before the first sequence of electrical pulses is delivered to the tissue. The pressure sensor may measure the pressure after the first sequence of electrical pulses is delivered to the tissue. The pressure sensor may measure the pressure before the second sequence of electrical pulses is delivered to the tissue. The pressure sensor may measure the pressure after the second sequence of electrical pulses is delivered to the tissue.
The temperature sensor and pressure sensor may provide feedback to the operator, surgeon, or clinician to apply an electric field pulse to the undesirable tissue. The pressure and/or temperature information may be useful to determine whether the undesirable tissue may be treated having reduced or no detrimental thermal effects to surrounding healthy tissue. The feedback information provided by the transducers or sensors 29 may be processed and displayed by circuits located either internally or externally to the energy source 14.
In one embodiment, the input to the energy source 14 may be connected to a commercial power supply by way of a plug (not shown). The output of the energy source 14 is coupled to the electrodes 24a,b, which may be energized using the activation switch 62 on the hand piece 16, or an activation switch mounted on a foot activated pedal (not shown). The energy source 14 may be configured to produce electrical energy suitable for thermal heating and/or electrical ablation.
In one embodiment, the electrodes 24a,b may be adapted and configured to electrically couple to the energy source 14 (e.g., generator, waveform generator). Once electrical energy is coupled to the electrodes 24a,b, an electric field may be formed at a distal end of the electrodes 24a,b. The energy source 14 may be configured to generate electric pulses at a predetermined frequency, amplitude, pulse width, and/or polarity that are suitable to induce thermal heating in the undesirable tissue in the treatment region. The energy source 14 may be configured to generate electric pulses at a predetermined frequency, amplitude, pulse width, and/or polarity that are suitable to induce irreversible electroporation to ablate substantial volumes of undesirable tissue in the treatment region. For example, the energy source 14 may be configured to deliver DC electric pulses having a predetermined frequency, amplitude, pulse width, and/or polarity suitable to induce thermal heating in the undesirable tissue in the treatment region. For example, the energy source 14 may be configured to deliver DC electric pulses having a predetermined frequency, amplitude, pulse width, and/or polarity suitable to induce irreversible electroporation to ablate substantial volumes of undesirable tissue in the treatment region. The DC pulses may be positive or negative relative to a particular reference polarity. The polarity of the DC pulses may be reversed or inverted from positive-to-negative or negative-to-positive a predetermined number of times to induce irreversible electroporation to ablate substantial volumes of undesirable tissue in the treatment region.
In one embodiment, a timing circuit may be coupled to the output of the energy source 14 to generate electric pulses. The timing circuit may comprise one or more suitable switching elements to produce the electric pulses. For example, the energy source 14 may produce a series of m electric pulses (where m is any positive integer) of sufficient amplitude and duration less than the necrotic threshold to induce thermal heating in the undesirable tissue when the m electric pulses are applied to the electrodes 24a,b and a series of n electric pulses (where n is any positive integer) of sufficient amplitude and duration to induce irreversible electroporation suitable for tissue ablation when the n electric pulses are applied to the electrodes 24a,b. In one embodiment, the electric pulses may have a fixed or variable pulse width, amplitude, and/or frequency.
The electrical ablation device 20 may be operated either in bipolar mode, i.e., monophasic, or monopolar mode, i.e., biphasic. In monopolar mode, the surface area of the electrodes may be different, and a dispersive pad (i.e., a ground pad) may be positioned relatively far from the “active” electrode. In bipolar mode, the surface area of the electrodes may be similar, and electrodes may be positioned relatively close together.
In one embodiment, the energy source 14 may be configured to produce RF waveforms at predetermined frequencies, amplitudes, pulse widths, and/or polarities suitable for thermal heating and/or electrical ablation of cells in the tissue treatment region. One example of a suitable RF energy source may be a commercially available conventional, bipolar/monopolar electrosurgical RF generator, such as Model Number ICC 350, available from Erbe, GmbH. In one embodiment, the energy source may comprise a microwave energy source configured to produce microwave waveforms at predetermined frequencies, amplitudes, pulse widths, and/or polarities suitable for thermal heating and/or electrical ablation of cells in the tissue treatment region. The microwave power source, such as MicroThermx, available from Boston Scientific Corp., may be coupled to a microwave antenna providing microwave energy in the frequency range from 915 MHz to 2.45 GHz.
In one embodiment, the energy source 14 may be configured to produce destabilizing electrical potentials (e.g., fields) suitable to induce thermal heating and/or irreversible electroporation. The destabilizing electrical potentials may be in the form of biphasic/monophasic DC electric pulses suitable for inducing thermal heating and/or irreversible electroporation to ablate tissue undesirable tissue with the electrical ablation device 20. A commercially available energy source suitable for generating thermal heating and/or irreversible electroporation electric field pulses in bipolar or monopolar mode is a pulsed DC generator such as Model Number ECM 830, available from BTX Molecular Delivery Systems Boston, Mass. In bipolar mode, the first electrode 24a may be electrically coupled to a first polarity and the second electrode 25 may be electrically coupled to a second (e.g., opposite) polarity of the energy source 14. Biphasic/monophasic electric pulses may be generated at a variety of frequencies, amplitudes, pulse widths, and/or polarities. Unlike RF ablation systems, which may require high power and energy levels delivered into the tissue to heat and thermally destroy the tissue, irreversible electroporation may require very little energy applied to the tissue to heat and kill the cells of the undesirable tissue using electric field potentials rather than heat. Accordingly, irreversible electroporation systems may avoid the detrimental thermal effects caused by RF ablation systems.
In certain embodiments, the energy source may comprise a wireless transmitter to deliver energy to the electrodes using wireless energy transfer techniques via one or more remotely positioned antennas. Those skilled in the art will appreciate that wireless energy transfer or wireless power transmission refers to the process of transmitting electrical energy from an energy source to an electrical load without interconnecting wires. In one embodiment, the energy source 14 may be coupled to the first and second electrodes 24a,b by a wired or a wireless connection. In a wired connection, the energy source 14 may be coupled to the electrodes 24a,b by way of the electrical conductors 18a,b, as shown. In a wireless connection, the electrical conductors 18a,b may be replaced with a first antenna (not shown) coupled the energy source 14 and a second antenna (not shown) coupled to the electrodes 24a,b, wherein the second antenna may be remotely located from the first antenna. In one embodiment, the energy source may comprise a wireless transmitter to deliver energy to the electrodes using wireless energy transfer techniques via one or more remotely positioned antennas. As previously discussed, wireless energy transfer or wireless power transmission is the process of transmitting electrical energy from the energy source 14 to an electrical load, e.g., the abnormal cells in the tissue treatment region, without using the interconnecting electrical conductors 18a,b. An electrical transformer is the simplest example of wireless energy transfer. The primary and secondary circuits of a transformer may not be directly connected and the transfer of energy may take place by electromagnetic coupling through a process known as mutual induction. Power also may be transferred wirelessly using RF energy.
In one embodiment, the energy source 14 may be configured to generate DC electric pulses at frequencies in the range of about 1 Hz to about 10,000 Hz, amplitudes in the range of about ±100 VDC to about ±6,000 VDC, and pulse width in the range of about 1 μs to about 100 ms. The polarity of the electric potentials coupled to the electrodes 24a,b may be reversed during thermal heating and/or electrical ablation therapy. For example, initially, the electric pulses may have a positive polarity and an amplitude in the range of about +100 VDC to about +6,000 VDC. Subsequently, the polarity of the DC electric pulses may be reversed such that the amplitude is in the range of about −100 VDC to about −6,000 VDC. In one embodiment, the undesirable cells in the tissue treatment region may be electrically ablated with DC pulses suitable to induce irreversible electroporation at frequencies of about 10 Hz to about 100 Hz, amplitudes in the range of about +700 VDC to about +3,000 VDC, and pulse widths of about 10 μs to about 50 μs. In another embodiment, the abnormal cells in the tissue treatment region may be electrically ablated with an electrical waveform having an amplitude of about +500 VDC and pulse duration of about 20 μs delivered at a pulse period T or repetition rate, frequency f=1/T, of about 10 Hz. Without wishing to be bound to any particular theory, it is believed that an electric field strength of about 800 V/cm to 1,000 V/cm is suitable for destroying living tissue by inducing irreversible electroporation.
The electrodes 24a,b may have a diameter or radius from 0.5 mm to 1.5 mm, such as, for example, 0.5 mm, 0.75 mm, 1 mm, and 1.5 mm. In various embodiments, the diameter of the first electrode 24a may by different from the diameter of the second electrode 24b. The electrode spacing may be from 0.5 cm to 3 cm. In various embodiments, the distance from the first electrode 24a to the second electrode 24b may be from 0.5 cm to 3 cm, such as, for example, 1 cm, 1.5 cm, 2.0 cm, and 3 cm. In one embodiment, the electrical ablation device 20 may comprise multiple needle electrodes.
According to certain embodiments, the electrical ablation device 20 may be introduced into the tissue treatment region through a trocar, for example, or inserted to a tissue treatment region transcutaneously, percutaneously, or other suitable techniques. In one embodiment, the cannula, lumen, or channel defined within the flexible shaft 22 may comprise a cutting edge, such as a bevel or other sharp edge, to aid in the puncturing/piercing of tissue.
According to certain embodiments, a method of treating tissue may generally comprise obtaining an ablation apparatus comprising first and second electrodes coupled to an energy source operative to generate and deliver a first sequence of electrical pulses and a second sequence of electrical pulses to tissue having a necrotic threshold, wherein the first sequence of electrical pulses deliver a first energy dose that is less than the necrotic threshold to induce thermal heating in the tissue and the second sequence of electrical pulses deliver a second energy dose equal to or greater than the necrotic threshold to induce cell necrosis in the tissue by irreversible electroporation, inserting the first electrode into a mass of tissue having a necrotic threshold, applying a first sequence of electrical pulses to the first electrode less than the necrotic threshold to induce thermal heating, applying a second sequence of electrical pulses to the first electrode to induce cell necrosis by irreversible electroporation, and applying a ground potential to the second electrode, wherein the ablation apparatus is operative to reduce the necrotic threshold of the tissue relative to a corresponding ablation apparatus having an energy source configured to deliver a first sequence of electrical pulses to induce cell necrosis by irreversible electroporation.
In certain embodiments, the ablation apparatus may reduce the necrotic threshold of the cell membrane by 0-500 mV, such as, for example, 50-400 mV, 100-300 mV, and 150-250 mV relative to a corresponding ablation apparatus having an energy source configured to deliver a first sequence of electrical pulses to induce cell necrosis by irreversible electroporation. The ablation apparatus may reduce the necrotic threshold by 0-50%, such as, for example, 10%, 20%, 30%, and 40%, relative to a corresponding ablation apparatus having an energy source configured to deliver a first sequence of electrical pulses to induce cell necrosis by irreversible electroporation.
According to certain embodiments, a method of treating tissue may generally comprise applying a first sequence of electrical pulses to undesirable tissue to induce thermal heating and applying a second sequence of electrical pulses to undesirable tissue to induce cell necrosis by irreversible electroporation. The first energy dose may be less than the necrotic threshold, less than the critical membrane voltage, less than the threshold for muscle contraction, and/or less than the threshold for ventricular arrhythmia. The first energy dose may reduce the necrotic threshold of the tissue. The first energy dose may reduce the necrotic threshold of the cell membrane by 0-500 mV, such as, for example, 50-400 mV, 100-300 mV, and 150-250 mV. The first energy dose may reduce the necrotic threshold by 0-50%, such as, for example, 10%, 20%, 30%, and 40%. The first energy dose and/or second energy dose may be synchronized with the patient's cardiac cycle to prevent ventricular arrhythmia. According to certain embodiments, the ablation apparatus may reduce the risk of ventricular arrhythmia relative to a similar ablation apparatus comprising a first sequence of electrical pulses to induce cell necrosis in the tissue by irreversible electroporation.
In certain embodiments, a method of treating tissue may generally comprise inserting the first electrode into a mass of tissue having a membrane potential and a necrotic threshold, applying a first sequence of electrical pulses to the first electrode less than the necrotic threshold to induce thermal heating, applying a second sequence of electrical pulses to the first electrode to induce cell necrosis by irreversible electroporation, and applying a ground potential to the second electrode. In one embodiment, the method may comprise re-applying the sequence of electrical pulses to the first electrode. In one embodiment, the energy source may be operative to generate and deliver a sequence interval between the first sequence and second sequence. The first sequence of electrical pulses may comprise a series of first pulse trains each having a first pulse train amplitude, a first pulse train pulse width, and a first pulse train frequency, and the second sequence of electrical pulses may comprise a series of second pulse trains each comprising a second pulse train amplitude, a second pulse train pulse width, and a second pulse train frequency. The first pulse trains may comprise a plurality of first pulses each having a first amplitude, a first pulse width, and a first frequency, and each of the second pulse trains may comprise a plurality of second pulses each having a second amplitude, a second pulse width, and a second frequency. Each of the first pulses and the second pulses may independently have amplitudes in the range of about ±100 VDC to about ±10,000 VDC, pulse widths in the range of about 1 μs to about 100 ms, and frequencies in the range of about 1 Hz to about 10,000 Hz.
In certain embodiments, at least one of the first pulse train amplitude V1, the first pulse train pulse width Tw1, and the first pulse train frequency F1 may be greater than or equal to the second pulse train amplitude V2, the second pulse train pulse width Tw2, and the second pulse train frequency F2. The first pulse train amplitude V1 may be less than or equal to the second pulse train amplitude V2. The first pulse train pulse width Tw1 may be less than, greater than, or equal to the second pulse train pulse width Tw2. The first pulse train frequency F1 may be greater than or equal to the second pulse train frequency F2. The first sequence duration D1 may be greater than or equal to the second sequence duration D2. The total number of first pulse trains may be 70 may be greater than or equal to the total number of second pulse trains 72. In one embodiment, the first pulse train amplitude may be less than the second pulse train amplitude, the first pulse train pulse width may be equal to the second pulse train pulse width, and the first pulse train frequency may be greater than the second pulse train frequency. The energy source may operative to generate and deliver a sequence interval S1 between the first sequence and second sequence. The sequence interval may be from 0 to 10 seconds, 1 second to 10 seconds, such as, for example, 0.5 seconds, 1 second, and 2 seconds.
In one embodiment, a first pulse train 70 comprising high-voltage DC electrical pulses having a first pulse train amplitude V1 of 500 VDC and a first pulse train pulse width Tw1 of 50 μs may be applied to the first and second electrodes 24a,b by the energy source 14 to induce thermal heating in the tissue. A second pulse train 72 comprising higher high-voltage DC electrical pulses having a second pulse train amplitude V2 of 1000 V and a second pulse train pulse width Tw2 of 50 μs may be applied to the first and second electrodes 24a,b by the energy source 14 to induce cell necrosis in the tissue by irreversible electroporation. In one embodiment, the polarity of at least one of the first pulse train 70 and the second pulse train 72 may be inverted or reversed by the energy source 14 during the thermal heating and/or ablation processes.
In one embodiment, the series of first pulses 70 may comprises a single pulse 70a or multiple pulses having a first amplitude v1 of 500 VDC, a first pulse width tw1 of 10 μs to 15 μs, and a period t1 of about 100 ms (f1=10 Hz) sufficient to induce thermal heating in the tissue proximate the electrode-tissue-interface immediately surrounding the respective electrodes 24a,b. In one embodiment, the series of second pulses 72 may comprise 20 to 40 electric pulses 72a having a second amplitude v2 of 1000 VDC, a second pulse width tw2 of 10 μs to 15 μs, and a period t2 of 100 μs (f2=10,000 Hz) sufficient to induce irreversible electroporation. In one embodiment, the series of second pulses 72 may comprise multiple electrical pulses, for example, 20 to 40 electric pulses, having a second amplitude v2 of 1500 to 3000 VDC, a second pulse width tw2 of 10 μs to 50 μs, and a period t2 of 10 μs. In one embodiment, the undesirable cells in the tissue treatment region may be electrically ablated with DC pulses suitable to induce irreversible electroporation at frequencies of about 10 Hz to about 100 Hz, amplitudes in the range of about +700 VDC to about +1500 VDC, and pulse widths of about 10 μs to about 50 μs. In another embodiment, the abnormal cells in the tissue treatment region may be heated with an electrical waveform having an amplitude of about +500 VDC and pulse duration of about 20 ms delivered at a pulse period or repetition rate, frequency f=1/T, of about 10 Hz.
In certain embodiments, a total dose average power may comprise the average power of the first sequence of electrical pulses, the average power of the second sequence of electrical pulses, and the sequence interval. The first energy dose may have an average power from 5 Watts to 10 Watts. The second first energy dose may have an average power from 10 Watts to 15 Watts. The total dose average power may be 1 Watt to 5 Watts. In one embodiment, a total dose average power from 5 Watts to 10 Watts may cause thermal coagulation. The first and second sequences of electrical pulses may be configured to reduce or eliminate thermal coagulation at the electrode/tissue interface.
In certain embodiments, the polarity of the electric potentials coupled to the electrodes 24a,b may be reversed during the electrical ablation therapy. As shown in
As shown in
In one embodiment, the energy source 14 may be configured to generate and deliver DC first pulses and the second pulses at frequencies in the range of 1 Hz to 10,000 Hz, amplitudes in the range of ±100 VDC to ±3000 VDC, and pulse width in the range of about 1 μs to about 100 ms. In one embodiment, the first pulse trains may comprise a plurality of DC first pulses having a positive polarity and an amplitude in the range of about +100 VDC to about +6000 VDC and a negative polarity and an amplitude in the range of about −100 VDC to about −6000 VDC, the second pulse trains may comprise a plurality of second pulses having a positive polarity and an amplitude in the range of about +100 VDC to about +6000 VDC and a negative polarity and an amplitude in the range of about −100 VDC to about −6000 VDC. In one embodiment, the method may comprise applying a sequence of electrical pulses having a first polarity to induce cell thermal heating and applying a sequence of electrical pulses having an opposite polarity to induce cell necrosis by irreversible electroporation.
Without wishing to be bound to any particular theory, it is believed that biphasic pulses may reduce the skeletal muscle contractions by reducing or eliminating the action potential caused by a positive monophasic pulse. Biphasic pulses may reduce or eliminate skeletal muscle contractions and cardiac events. A person skilled in the art will understand that poration of the cell membrane occurs when the pulse increases the membrane voltage. A person skilled in the art may expect the poration to be reversed by a negative going pulse. Without wishing to be bound to any particular theory, however, it is believed that hyperpolarization occurs on each side of the cell. For example, the opposite side of the cell membrane may be hyperpolarized when the electric field switches orientation due to a negative-going pulse. In other words, the polarization of the cell may be dependent on the orientation of the electric field.
According to certain embodiments, the method of treating tissue may comprise heating the tissue by applying an electric field that is less than the necrotic threshold to lower the necrotic threshold before inducing cell necrosis. The method may comprise lowering the necrotic threshold by heating the tissue by applying an electric field that is less than about 700 V/cm, such as, for example, less than about 500 V/cm and less than about 300 V/cm. The method may comprise lowering the necrotic threshold by 30% by heating the tissue by applying an electric field that is less than about 700 V/cm. The method may comprise heating the tissue by applying an electric field that is less than the necrotic threshold to lower the necrotic threshold and inducing cell necrosis by irreversible electroporation by applying an electric filed that is greater than or equal to the necrotic threshold. The method may comprise heating the tissue by applying an electric field that is less than 700 V/cm to lower the necrotic threshold and inducing cell necrosis by irreversible electroporation by applying an electric filed that is greater than about 700 V/cm.
According to certain embodiment, the method of treating tissue may comprise applying a sequence of electrical pulses to increase a membrane potential to less than the necrotic threshold and applying a sequence of electrical pulses to increase a membrane potential to greater than or equal to the necrotic threshold. The method may comprise applying a sequence of electrical pulses to increase a membrane potential from less than zero to greater than zero, applying a sequence of electrical pulses to increase a membrane potential from greater than zero to less than the necrotic threshold, and applying a sequence of electrical pulses to increase a membrane potential from less than the necrotic threshold to the necrotic threshold. The method may comprise applying a sequence of electrical pulses to increase a membrane potential from less than zero to 100 mV, applying a sequence of electrical pulses to increase a membrane potential from 100 mV to 500 mV, and applying a sequence of electrical pulses to increase a membrane potential from 500 mV to the necrotic threshold.
In one embodiment, the first sequence of electrical pulses may have a pulse width of 50 μm or less and subsequent pulses may have higher voltages and pulse widths less than 50 μm. The pulses may increase the membrane potential from −70 mV to +100 mV, the next sequence of pulses may increase the membrane potential from 100 mV to 500 mV, and the final sequence of pulses may have pulse width of 1 μs to increase the membrane potential to cause cell necrosis. Without wishing to be bound to any particular theory, it is believed that the synergistic effect of applying the first sequence of pulses to induce thermal heating and applying the second sequence of pulses to induce cell necrosis by irreversible electroporation may decrease the membrane threshold from 1 V to 0.7 V.
According to certain embodiments, the method may comprise forming a pre-heated zone in the undesirable tissue by applying an electric field that is less than the necrotic threshold. The method may comprise forming a pre-heated zone in the undesirable tissue by applying an electric field that is less than the necrotic threshold and forming a necrotic zone by applying an electric field that is equal to or greater than the necrotic threshold to induce cell necrosis by irreversible electroporation. The method may comprise forming a pre-heated zone by applying an electric field that is less than about 700 V/cm and forming a necrotic zone by applying an electric filed that is equal to or greater than about 700 V/cm.
In one embodiment, a pre-heated thermal zone may be formed in the tissue immediately surrounding the electrodes 24a,b at the tissue-electrode-interface by applying an electric field less than the necrotic threshold. Without wishing to be bound to any particular theory, it is believed that increasing the temperature of the tissue may reduce the electric field necessary to cause cell necrosis in the undesirable tissue 48. Thus, the method of treating tissue may comprise applying a combination of a series of first electrical pulses 70 having substantially lower voltage (in the range of 1000 V to 2000 V) and a series of second electrical pulses 72 having a higher voltage to induce cell necrosis. In one embodiment, a first series of pulses 70 may be applied to create a pre-heated thermal zone to increase the temperature of the tissue and then a second series of pulses 72 to induce cell necrosis at a lower voltage then otherwise would be necessary without the thermal heating of the tissue before inducing irreversible electroporation. In one embodiment, the method of treating tissue may comprise applying a combination of a series of first electrical pulses 70 having substantially lower voltage to increase the size of the pre-heated thermal zone at the same voltage.
Once positioned by the user, the electrodes may be energized to form a pre-heated zone having a first shape in the tissue treatment region. The shape of the pre-heated zone may be dependent on the position of the first and second electrodes. When the electrodes are re-energized, a necrotic zone having a second shape may be formed in the tissue treatment region. The size of the pre-heated zone may be less than or equal to the size of the necrotic zone. This process may be repeated as often as necessary to create any number of necrotic zones using the electrical ablation apparatus. Various parameters, such as, for example, pressure, temperature, and duration, may be altered or adjusted according to the type of tissue in the tissue treatment region and the desired size of the pre-heated zone and/or necrotic zone. In one embodiment, the ablation apparatus may increase the size of the necrotic zone relative to a similar ablation apparatus comprising a first sequence of electrical pulses to induce cell necrosis in the tissue by irreversible electroporation. At anytime, the surgeon or clinician may reposition the electrical ablation apparatus within the tissue treatment region and begin the process anew.
According to certain embodiments, the method of treating tissue may comprise applying a first sequence of electrical pulses to induce thermal heating and applying a second sequence of electrical pulses to induce cell necrosis by irreversible electroporation, wherein the first and second sequences of electrical pulses create a ratio of thermal volume to non-thermal volume of 5 to 1. The thermal volume may comprise the volume of the pre-heated zone. In one embodiment, at least one of the first sequence of electrical pulses, the second sequence of electrical pulses, and sequence interval may be configured to create a ratio of thermal volume to non-thermal volume of 2 to 1. In one embodiment, at least one of the first sequence of electrical pulses, the second sequence of electrical pulses, and sequence interval may be configured to create a ratio of thermal zone volume to necrotic zone volume of 1 to 1.
According to certain embodiments, the method may comprise measuring at least one of temperature and pressure of the tissue treatment region. The method may comprise measuring at least one of temperature and pressure of the undesirable tissue. The method may comprise measuring at least one of temperature and pressure adjacent at least one of the first and second electrodes. The method may comprise measuring at least one of temperature and pressure adjacent at least one of the first and second electrodes and applying a sequence of electrical pulses when at least one of a predetermined temperature and a predetermined pressure is achieved. The method may comprise measuring at least one of temperature and pressure adjacent at least one of the first and second electrodes and stopping a sequence of electrical pulses when at least one of a predetermined temperature and a predetermined pressure is achieved. The method may comprise measuring at least one of temperature and pressure adjacent at least one of the first and second electrodes and applying a sequence of electrical pulses to achieve at least one of a predetermined temperature and a predetermined pressure.
Without wishing to be bound to any particular theory, it is believed that the critical membrane voltage of a cell is inversely proportional to the cell's temperature. In other words, the cell's critical membrane voltage may decrease as the cell's temperature increases. As a result, a lower electric field may be applied to pre-heated undesirable tissue to induce cell necrosis by irreversible electroporation than to the same undesirable tissue without pre-heating. The predetermined temperature may be 40° C. to 50° C. For example, an electrical pulse or sequence of electrical pulses may be applied when the temperature of the tissue falls below 50° C. The method may comprise stopping a sequence of electrical pulses when at least one of a predetermined temperature and a predetermined pressure is achieved. For example, an electrical pulse or sequence of electrical pulses may be stopped when the temperature of the tissue reaches 60° C. In one embodiment, the first and second sequences of electrical pulses may be configured to maintain the tissue at a temperature sufficient to induce thermal coagulation. For example, the first and second sequences of electrical pulses may be configured to maintain the tissue at a temperature between 50-60° C. The predetermined pressure may be atmospheric pressure.
According to certain embodiments, the ablation apparatus may reduce the risk of an electrical arc relative to a similar ablation apparatus comprising a first sequence of electrical pulses to induce cell necrosis in the tissue by irreversible electroporation. Under certain conditions, an arc may form between the two electrodes. For example, high voltage may cause a breakdown in air in the space between the un-insulated conductive portions of the electrodes that are not fully embedded in the tissue. An electrical arc at high voltages (>10 k VDC) may occur when the un-insulated conductive portions of the two electrodes are not fully embedded into the tissue or the tissue moves away from the electrode tip and the high voltage causes an electrical breakdown of the gas surrounding the electrode tip. The first and second sequences of electrical pulses may be configured to reduce or eliminate the creation of an arc. As described in commonly owned U.S. patent application Ser. No. 12/651,181, filed Dec. 31, 2009, entitled “ELECTRICAL ABLATION DEVICES”, now U.S. Patent Application Publication No. 2011/0160514, a gel may be continuously supplied to the space to displace the air in the space and prevent an arc from forming. The gel may be any water-based, water-soluble lubricant, such as, for example, KY® Jelly available from Johnson & Johnson.
Once the electrical ablation device 20 has been suitably introduced into or proximate the undesirable tissue 48, the sheath 26 may be retracted to expose the electrodes 24a,b to treat the undesirable tissue 48. The treat the undesirable tissue 48, the operator initially may locate the first electrode 24a at a first position and the second electrode 24b at a second position using endoscopic visualization and maintaining the undesirable tissue 48 within the field of view of the flexible endoscope 12. The first position may be near a perimeter edge of the undesirable tissue 48. Once the electrodes 24a,b are located into or proximate the undesirable tissue 48, the electrodes 24a,b may be energized with a first sequence of electrical pulses to deliver a first energy dose that is less than the necrotic threshold to induce thermal heating in the tissue surrounding the electrode/tissue interface. Once the temperature and/or pressure of the undesirable tissue 48 achieves a predetermined threshold, the electrodes 24a,b may be energized with a second sequence of electrical pulses to deliver a second energy dose equal to or greater than the necrotic threshold to induce cell necrosis in the tissue by irreversible electroporation to create a necrotic zone 65. For example, once the first and second electrodes 24a,b are located in the desired positions, the undesirable tissue 48 may be exposed to an electric field generated by energizing the first and second electrodes 24a,b with the energy source 14.
The electric field created by the first sequence of electrical pulses may have a magnitude, frequency, pulse width suitable to increase the temperature of the undesirable tissue to a predetermined threshold. The electric field created by the second sequence of electrical pulses may have a magnitude, frequency, and pulse width suitable to induce irreversible electroporation in the undesirable tissue 48 within the necrotic zone 65. Without wishing to be bound to any particular theory, it is believed that increasing the temperature of the undesirable tissue to a predetermined threshold may reduce the magnitude, frequency, and/or pulse width of the electric field suitable to induce irreversible electroporation in the undesirable tissue 48. The size of the necrotic zone may be substantially dependent on the size and separation of the electrodes 24a,b. The treatment time may be defined as the time that the electrodes 24a,b are activated or energized to generate the electric pulses suitable for inducing thermal heating and/or irreversible electroporation in the undesirable tissue 48.
This procedure may be repeated to destroy relatively larger portions of the undesirable tissue 48. At anytime, the surgeon or clinician may reposition the first and second electrodes 24a,b and begin the process anew. In other embodiments, the electrical ablation device may comprise multiple needle electrodes that may be employed to treat the undesirable tissue 48. Those skilled in the art will appreciate that similar techniques may be employed to ablate any other undesirable tissues that may be accessible trans-anally through the colon, and/or orally through the esophagus and the stomach using translumenal access techniques.
The embodiments of the electrical ablation devices described herein may be introduced inside a patient using minimally invasive or open surgical techniques. In some instances it may be advantageous to introduce the electrical ablation devices inside the patient using a combination of minimally invasive and open surgical techniques. Minimally invasive techniques may provide more accurate and effective access to the treatment region for diagnostic and treatment procedures. To reach internal treatment regions within the patient, the electrical ablation devices described herein may be inserted through natural openings of the body such as the mouth, anus, and/or vagina, for example. Minimally invasive procedures performed by the introduction of various medical devices into the patient through a natural opening of the patient are known in the art as NOTES™ procedures. Surgical devices, such as an electrical ablation devices, may be introduced to the treatment region through the channels of the endoscope to perform key surgical activities (KSA), including, for example, electrical ablation of tissues using irreversible electroporation energy. Some portions of the electrical ablation devices may be introduced to the tissue treatment region percutaneously or through small—keyhole—incisions.
Endoscopic minimally invasive surgical and diagnostic medical procedures are used to evaluate and treat internal organs by inserting a small tube into the body. The endoscope may have a rigid or a flexible tube. A flexible endoscope may be introduced either through a natural body opening (e.g., mouth, anus, and/or vagina). A rigid endoscope may be introduced via trocar through a relatively small—keyhole—incision incisions (usually 0.5 cm to 1.5 cm). The endoscope can be used to observe surface conditions of internal organs, including abnormal or diseased tissue such as lesions and other surface conditions and capture images for visual inspection and photography. The endoscope may be adapted and configured with channels for introducing medical instruments to the treatment region for taking biopsies, retrieving foreign objects, and/or performing surgical procedures.
Once an electrical ablation device is inserted in the human body internal organs may be reached using trans-organ or translumenal surgical procedures. The electrical ablation device may be advanced to the treatment site using endoscopic translumenal access techniques to perforate a lumen, and then, advance the electrical ablation device and the endoscope into the peritoneal cavity. Translumenal access procedures for perforating a lumen wall, inserting, and advancing an endoscope therethrough, and pneumoperitoneum devices for insufflating the peritoneal cavity and closing or suturing the perforated lumen wall are well known. During a translumenal access procedure, a puncture must be formed in the stomach wall or in the gastrointestinal tract to access the peritoneal cavity. One device often used to form such a puncture is a needle knife which is inserted through the channel of the endoscope, and which utilizes energy to penetrate through the tissue. A guidewire is then feed through the endoscope and is passed through the puncture in the stomach wall and into the peritoneal cavity. The needle knife is removed, leaving the guidewire as a placeholder. A balloon catheter is then passed over the guidewire and through the channel of the endoscope to position the balloon within the opening in the stomach wall. The balloon can then be inflated to increase the size of the opening, thereby enabling the endoscope to push against the rear of the balloon and to be feed through the opening and into the peritoneal cavity. Once the endoscope is positioned within the peritoneal cavity, numerous procedures can be performed through the channel of the endoscope.
The endoscope may be connected to a video camera (single chip or multiple chips) and may be attached to a fiber-optic cable system connected to a “cold” light source (halogen or xenon), to illuminate the operative field. The video camera provides a direct line-of-sight view of the treatment region. If working in the abdomen, the abdomen may be insufflated with carbon dioxide (CO2) gas to create a working and viewing space. The abdomen is essentially blown up like a balloon (insufflated), elevating the abdominal wall above the internal organs like a dome. CO2 gas is used because it is common to the human body and can be removed by the respiratory system if it is absorbed through tissue.
Once the electrical ablation devices are located at the target site, the diseased tissue may be electrically ablated or destroyed using the various embodiments of electrodes discussed herein. The placement and location of the electrodes can be important for effective and efficient electrical ablation therapy. For example, the electrodes may be positioned proximal to a treatment region (e.g., target site or worksite) either endoscopically or transcutaneously (percutaneously). In some implementations, it may be necessary to introduce the electrodes inside the patient using a combination of endoscopic, transcutaneous, and/or open techniques. The electrodes may be introduced to the tissue treatment region through a channel of the endoscope, an overtube, or a trocar and, in some implementations, may be introduced through percutaneously or through small—keyhole—incisions.
Preferably, the various embodiments of the devices described herein will be processed before surgery. First, a new or used instrument is obtained and if necessary cleaned. The instrument can then be sterilized. In one sterilization technique, the instrument is placed in a closed and sealed container, such as a plastic or TYVEK® bag. The container and instrument are then placed in a field of radiation that can penetrate the container, such as gamma radiation, x-rays, or high-energy electrons. The radiation kills bacteria on the instrument and in the container. The sterilized instrument can then be stored in the sterile container. The sealed container keeps the instrument sterile until it is opened in the medical facility.
It is preferred that the device is sterilized prior to use. This can be done by any number of ways known to those skilled in the art including beta or gamma radiation, ethylene oxide, steam.
The various embodiments described herein may be better understood when read in conjunction with the following representative examples. The following examples are included for purposes of illustration and not limitation.
An ablation apparatus comprising two electrodes coupled to a energy source and a temperature sensor according to certain embodiments was used to deliver a series of electrical pulses ex vivo to healthy porcine liver to induce irreversible electroporation (Dose 1). In one embodiment, the Dose 1 pulse parameters may include a 3,000 V amplitude, a 10 μs pulse width, 10 total number of pulses per burst, a frequency of 200 Hz, 6 total number of bursts, and a 3 s delay between each burst. Dose 1 is generally characterized by low energy and high voltage. Dose 1 was not suitable for synchronizing to a patient's cardiac cycle.
An ablation apparatus comprising two electrodes coupled to a energy source and a temperature sensor according to certain embodiments was used to deliver a series of electrical pulses ex vivo to healthy porcine liver to induce irreversible electroporation (Dose 2). In one embodiment, the Dose 2 parameters may include a first series of bursts including a 1000 V amplitude, a 5 μs pulse width, 500 total number of pulses per burst, a total of 30 first series bursts, a 0.1 s delay between each burst followed by a second series of bursts pulses including a 1500 V amplitude, a 5 μs pulse width, 500 total number of pulses per burst, a total of 20 second bursts, a 0.1 s delay between each burst followed by a third series of bursts including a 3000 V amplitude, a 10 μs pulse width, 10 total number of pulses per burst, a total of 10 third series bursts, a 3 s delay between each burst. The frequency may be 200 Hz. Dose 2 is generally characterized by a multi-train dose at a higher energy than Dose 1. Dose 2 was not suitable for synchronizing to a patient's cardiac cycle. As shown in
The size and area of the necrotic zone of Dose 1 was compared to the size and area of the necrotic zone of Dose 2.
The size and proportion of the necrosis zone may be also related to electrode spacing.
According to certain embodiments, the electrical ablation system may be configured to treat larger masses of tissue. As described above, the ablation apparatus may generally comprise a one or more electrodes, such as, for example, two, three, four, and five electrodes, configured to be positioned into or proximal to undesirable tissue in a tissue treatment region. The ablation apparatus may comprise a central electrode and an electrode array comprising a plurality of electrodes. The electrodes may be coupled to an energy source operative to independently generate and deliver a first sequence of electrical pulses to the electrode array and a second sequence of electrical pulses to the central electrode. The first sequence of electrical pulses to the electrode array may deliver a first energy dose that is less than the necrotic threshold to induce thermal heating in the tissue. The second sequence of electrical pulses to the central electrode may deliver a second energy dose equal to or greater than the necrotic threshold to induce cell necrosis in the tissue. In certain embodiments, the electrode array and central electrode may induce thermal heating and/or cell necrosis in larger masses of tissue relative to conventional electrical ablation therapies.
In various embodiments, the electrode array and central electrode may reduce the pain, trauma, and/or hemorrhaging associated with treating larger masses of undesirable tissue relative to conventional electrical ablation therapies. For example, in various embodiments, the electrode array may spread the heating more rapidly than conventional electrical ablation therapies by creating multiple heat sources. The surgeon or clinician may not need to reposition the electrical ablation apparatus within the tissue treatment region to treat large masses of undesirable tissue. Further, the relative positions and orientations of electrode array and central electrode may induce thermal heating and/or cell necrosis in larger masses of tissue of various shapes and sizes relative to conventional electrical ablation therapies.
In certain embodiments, an electrical ablation system may comprise an electrical ablation device comprising a relatively flexible member or shaft that may be introduced to the tissue treatment region using any of the techniques discussed above, such as, for example, an open incision and a trocar, through one or more of the channels of an endoscope, percutaneously, or transcuteously. The electrical ablation system may comprise an electrical ablation device comprising a central electrode and an electrode array. Referring to
When the electrode array and/or central electrode is positioned at the desired location into or proximate the tissue treatment region, the electrodes may be connected to or disconnected from the energy source by actuating or de-actuating an activation switch on the hand piece. The electrode array and central electrode may deliver electric field pulses to the undesirable tissue. As described above, the electrical field pulses may be characterized by various parameters, such as, for example, pulse shape, amplitude, frequency, pulse width, polarity, total number of pulses and duration. The electric field pulses delivered by the electrode array may be sufficient to induce thermal heating in the undesirable tissue without inducing irreversible electroporation in the undesirable tissue. The electric field pulses delivered by the central electrode may be sufficient to induce irreversible electroporation in the undesirable tissue. A ground pad may be positioned proximal to the tissue. A ground pad may be positioned adjacent to the tissue. The ground pad may serve as a return path for current from the generator through the electrodes.
In certain embodiments, the ablation system may comprise an energy source, as discussed above. The electrode array and central electrode may be coupled to the energy source. Once the energy source is coupled the electrode array and central electrode, an electric field may be independently formed at a distal end of one or more of the electrodes. The energy source may be configured to produce electrical energy suitable for thermal heating and/or electrical ablation. The energy source may be configured to independently produce electrical waveforms, such as, for example, RF waveforms, microwave waveforms, and/or ultrasonic waveforms, at predetermined frequencies, amplitudes, pulse widths and/or polarities suitable for thermal heating by the electrode array and electrical ablation by the central electrode. The energy source may be configured to produce destabilizing electrical potentials (e.g., fields) suitable to induce thermal heating by the electrode array and electrical ablation by the central electrode. The energy source may be configured to deliver electrical pulses in the form of DC and/or AC voltage potentials to the electrodes. As described above, a timing circuit may be coupled to the output of the energy source to generate electric pulses. As discussed above, the energy source may be configured to operate in either biphasic mode or monophasic mode. The energy source may comprise the controller.
In certain embodiments, the ablation system may comprise at least one controller configured to concurrently or sequentially operate the energy source. The controller may comprise a processor (e.g., a microprocessor), a central processing unit (CPU), a digital signal processor (DSP), an application-specific integrated circuit (ASIC), a field programmable gate array (FPGA) and any combinations thereof. The controller may comprise digital and/or analog circuit elements and electronics. In one embodiment, the controller may be configured to automatically control at least one parameter associated with the delivery of the electrical pulse. In one embodiment, the controller may be operably coupled to the energy source and configured to control at least one parameter associated with the delivery of the electrical pulse.
Referring to
Referring to
Referring to
In various embodiments, the controller and components thereof, such as the processor and memory, may comprise more than one separate functional element, such as various modules and/or blocks. Although certain modules and/or blocks may be described by way of example, it will be appreciated that a greater or lesser number of modules and/or blocks may be used and still fall within the scope of the embodiments. Further, although various embodiments may be described in terms of modules and/or blocks to facilitate the desired function, such modules and/or blocks may be implemented by one or more hardware components, e.g., processor, Complex Programmable Logic Device (CPLD), Digital Signal Processor (DSP), Programmable Logic Devices (PLD), Application Specific Integrated Circuit (ASIC), circuits, registers and/or software components, e.g., programs, subroutines, logic and/or combinations of hardware and software components.
In certain embodiments, an electrical ablation system may comprise one or more memories that, for example, store instructions or data, for example, volatile memory (e.g., Random Access Memory (RAM), Dynamic Random Access Memory (DRAM), or the like), non-volatile memory (e.g., Read-Only Memory (ROM), Electrically Erasable Programmable Read-Only Memory (EEPROM), Compact Disc Read-Only Memory (CD-ROM), or the like), persistent memory, or the like. Further non-limiting examples of one or more memories include Erasable Programmable Read-Only Memory (EPROM), flash memory, and the like. The one or more memories may be coupled to, for example, one or more controllers by one or more instruction, data, or power buses.
According to certain embodiments, a computer-implemented system for delivering energy to tissue having a necrotic threshold may generally comprise an electrode array comprising a plurality of electrodes, a central electrode, a ground pad, a processor, and a memory coupled to the processor and storing instructions to be executed by the processor to apply a first sequence of electrical pulses to the electrode array less than the necrotic threshold to induce thermal heating in the tissue, apply a second sequence of electrical pulses to the central electrode equal to or greater than the necrotic threshold to induce cell necrosis in the tissue by irreversible electroporation, and apply a ground potential to the ground pad. The ground pad may be adjacent to the tissue. The ground pad me be proximal to the tissue.
In certain embodiments, the system may comprise an energy source coupled to the electrode array and the central electrode operative to generate and deliver the first sequence of electrical pulses and the second sequence of electrical pulses to tissue having a necrotic threshold. The electrode array and the central electrode may be independently adapted and configured to electrically couple to the energy source (e.g., generator, waveform generator). The energy source may comprise any of the energy sources described herein. The energy source may be configured to generate DC electric pulses at frequencies in the range of about 1 Hz to about 10,000 Hz, amplitudes in the range of about ±100 VDC to about ±6,000 VDC, and pulse width in the range of about 1 μs to about 100 ms. The energy source may be configured to generate electric pulses suitable to induce thermal heating and irreversible electroporation in the tissue. The energy source may be operated in biphasic mode and monophasic mode.
In certain embodiments, the system may comprise a controller, such as, for example, any of the controllers illustrated in
In certain embodiments, the system may comprise instructions to be executed by the processor to deliver a first sequence of electrical pulses sufficient to create a thermal zone in a first portion of the tissue induced by thermal heating in an area near an electrode-tissue-interface of each of the plurality of electrodes of the electrode array, and a second sequence of electrical pulses sufficient to create a necrotic zone in a second portion of tissue induced by irreversible electroporation in an area surrounding both the central electrode and the plurality of electrodes of the electrode array. Referring to
As shown in
In certain embodiments, the volume of the necrotic zone may be greater than or equal to the volume of the thermal zone.
In certain embodiments, the system may comprise instructions to be executed by the processor to form a pre-heated zone by applying an electric field that is less than about 800 V/cm by the first sequence of electrical pulses, and form a necrotic zone by applying an electric field that is greater than about 800 V/cm by the second sequence of electrical pulses. The system may comprise instructions to form a pre-heated zone by applying an electric field that is less than about 700 V/cm by the first sequence of electrical pulses, and form a necrotic zone by applying an electric filed that is equal to or greater than about 700 V/cm by the second sequence of electrical pulses. As discussed above, the shape of the pre-heated zone may be dependent on the position of the electrode array and ground pad. The pre-heated zone may be similar to the thermal zone discussed above. The shape of the necrotic zone may be dependent on the position of the central electrode and ground pad. The size of the pre-heated zone may be less than or equal to the size of the necrotic zone.
The shape and size of the thermal zone and/or necrotic zone may be controlled by the configuration and/or position of the central electrode, electrode array, the geometry of the electrodes, e.g., the length and width of each electrode, and the electrical pulses applied to the electrodes, and/or ground pad. For example, the size and shape of the thermal zone and/or necrotic zone may be changed by retracting or advancing the length of each electrode. In certain embodiments, the geometry of the central electrode and/or each of the plurality of electrodes may be one of parallel and non-parallel. The central electrode and electrode array may be configured to induce thermal heating and/or induce cell necrosis in large masses of tissue of various shapes and sizes by employing multiple electrodes.
In certain embodiments, the system may comprise instructions to be executed by the processor to heat the mass of tissue by applying an electric field that is less than about 800V/cm by the first sequence of electrical pulses to lower the necrotic threshold, and induce cell necrosis by irreversible electroporation by applying an electric filed that is greater than about 800 V/cm by the second sequence of electrical pulses. In one embodiment, the system may comprise instructions to be executed by the processor to heat the mass of tissue by applying an electric field that is less than about 700V/cm by the first sequence of electrical pulses to lower the necrotic threshold, and induce cell necrosis by irreversible electroporation by applying an electric filed that is greater than about 700 V/cm by the second sequence of electrical pulses.
In certain embodiments, the system may comprise instructions to be executed by the processor to apply a combination of a series of first electrical pulses having substantially lower voltage (in the range of 1000 V to 2000 V) to the electrode array to induce thermal heating, and a series of second electrical pulses having a higher voltage to the central electrode to induce cell necrosis. In one embodiment, a first series of pulses may be applied to create thermal zone to increase the temperature of the tissue and then a second series of pulses to induce cell necrosis at a lower voltage then otherwise would be necessary without the thermal heating of the tissue before inducing irreversible electroporation. In one embodiment, the system may comprise instructions to apply a combination of a series of first electrical pulses having substantially lower voltage to the electrode array to increase the size of the thermal zone at the same voltage.
In certain embodiments, the system may comprise instructions to be executed by the processor to apply a first sequence of electrical pulses to the electrode array less than the necrotic threshold to lower the necrotic threshold, and apply a second sequence of electrical pulses to the central electrode to induce cell necrosis by irreversible electroporation. In one embodiment, the system may comprise instructions to be executed by the processor to apply a first sequence of electrical pulses to the central electrode less than the necrotic threshold to lower the necrotic threshold when the first sequence of electrical pulses is applied to the electrode array. In one embodiment, the system may comprise instructions to be executed by the processor to not apply a second sequence of electrical pulses to the electrode array to induce cell necrosis by irreversible electroporation when the second sequence of electrical pulses is applied to the central electrode.
In certain embodiments, the system may comprise instructions to be executed by the processor to deliver a first energy dose that is less than the necrotic threshold to induce thermal heating by the first sequence of electrical pulses, and deliver a second energy dose equal to or greater than the necrotic threshold to induce cell necrosis in the tissue by irreversible electroporation by the second sequence of electrical pulses. As discussed above,
In certain embodiments, the system may comprise at least one of a temperature sensor and a pressure sensor adjacent at least one of the electrode array and central electrode. The temperature sensor may measure the temperature of the tissue surrounding one or more of the plurality of electrodes of the electrode array and/or central electrode. The pressure sensor may measure the pressure surrounding one or more of the plurality of electrodes of the electrode array and/or central electrode. In one embodiment, the apparatus may comprise at least one of a temperature sensor and a pressure sensor adjacent at least one of the electrode array and the central electrode. In one embodiment, the temperature sensor and/or pressure sensor may be located within one or more of the plurality of electrodes of the electrode array and/or central electrode. As discussed above, the pressure sensor may be adjacent to at least one of the vents in the shaft. In one embodiment, the pressure sensor may be adjacent at least one of the vents and the temperature sensor may be located at the distal end of the flexible shaft of the electrode array and/or central electrode. The energy source may be operative to generate and deliver the second sequence of electrical pulses to the central electrode when at least one of a predetermined temperature and a predetermined pressure is achieved.
In certain embodiments, the system may comprise instructions to be executed by the processor to apply a sequence of electrical pulses to the electrode array, the sequence of electrical pulses having amplitudes in the range of about ±100 VDC to about ±10,000 VDC, pulse widths in the range of about 1 μs to about 100 ms, and frequencies in the range of about 1 Hz to about 10,000 Hz, and re-apply the sequence of electrical pulses to the central electrode. In one embodiment, the energy source may be configured to generate and deliver DC first pulses and the second pulses at having amplitudes in the range of about ±100 VDC to about ±3,000 VDC, pulse widths in the range of about 1 μs to about 100 ms, and frequencies in the range of about 1 Hz to about 10,000 Hz. The sequence of electrical pulses may comprise a series of pulse trains each having a pulse train amplitude, a pulse train pulse width, and a pulse train frequency. The pulse trains may comprise a plurality of pulses each having an amplitude, a pulse width, and a frequency. The first sequence of electrical pulses may comprise a series of first pulse trains each having a first pulse train amplitude, a first pulse train pulse width, and a first pulse train frequency, and the second sequence of electrical pulses may comprise a series of second pulse trains each comprising a second pulse train amplitude, a second pulse train pulse width, and a second pulse train frequency.
Referring to
In certain embodiments, the method may comprise positioning each of the plurality of electrodes spaced apart from the other of the plurality of electrodes, and positioning the central electrode intermediate the plurality of electrodes. The user may position the electrode array and central array depending on the clinical conditions and/or clinical application. The user may consider the number of electrodes and the position of the electrodes relative to each other. The method may comprise independently positioning each of the plurality of electrodes of the electrode array at a first position, depth, and angle in the tissue, and positioning the central electrode at a second position, depth, and angle in the tissue. The first position, depth, and/or angle may be the same or different from the second position, depth, and/or angle. The method may comprise positioning one of the plurality of electrodes at the same or different position, depth, and/or angle of one or more of the other plurality of electrodes. The method may comprise positioning the plurality of electrodes spaced apart from the other of the plurality of electrodes. The method may comprise positioning the central electrode intermediate the plurality of electrodes. In one embodiment, the method may comprise positioning each of the electrodes of the electrode array as an outer electrode and positioning the central electrode as an inner electrode.
In certain embodiments, the method may generally comprise coupling the electrode array and the central electrode to an energy source operative to generate the first sequence of electrical pulses and the second sequence of electrical pulses. In various embodiments, the first sequence of electrical pulses may be sufficient to create at least one thermal zone in a portion of the tissue induced by thermal heating in an area near an electrode-tissue-interface of each of the plurality of electrodes, and the second sequence of electrical pulses may be sufficient to create a necrotic zone in a portion of tissue induced by irreversible electroporation in an area surrounding each of the plurality of electrodes and the central electrode. The thermal zone of one of the plurality of electrodes may contact the thermal zone of one or more of the other of the plurality of electrodes. The thermal zone of at least one of the plurality of electrodes may contact the central electrode. The thermal zone of each of the plurality of electrodes may contact the central electrode. The thermal zone of each of the plurality of electrodes may not contact the central electrode. The central electrode may be positioned within the thermal zone of each of the plurality of electrodes. The central electrode may be positioned outside the thermal zone of each of the plurality of electrodes. The volume of the necrotic zone may be greater than or equal to the volume of the thermal zone.
In certain embodiments, the method may generally comprise forming a pre-heated zone by applying an electric field that is less than about 800 V/cm by the first sequence of electrical pulses, and forming a necrotic zone by applying an electric filed that is greater than about 800 V/cm by the second sequence of electrical pulses. The method may comprise forming a pre-heated zone by applying an electric field that is less than about 700 V/cm by the first sequence of electrical pulses, and forming a necrotic zone by applying an electric filed that is greater than about 700 V/cm by the second sequence of electrical pulses. The electrode array and central electrode may be independently activated by the generator. In certain embodiments, the volume and/or geometry of the thermal zone and/or necrotic zone may be tailored to the clinical application. The relative positions and orientations of the electrodes may enable different shapes and sizes of volumes of the pre-heated zone and/or necrotic zone. The shape and size of the volume of pre-heated zone and/or necrotic zone may be controlled by the configuration and/or position of the electrode array and/or central electrode, the geometry of the electrodes, and parameters associated with the delivery of the electrical pulse. The size of the pre-heated zone may be less than or equal to the size of the necrotic zone.
In certain embodiments, the method may generally comprise heating the tissue by applying an electric field that is less than about 800V/cm by the first sequence of electrical pulses to lower the necrotic threshold, and inducing cell necrosis by irreversible electroporation by applying an electric filed that is greater than about 800 V/cm by the second sequence of electrical pulses. The method may comprise heating the tissue by applying an electric field that is less than about 700V/cm by the first sequence of electrical pulses to lower the necrotic threshold, and inducing cell necrosis by irreversible electroporation by applying an electric filed that is greater than about 700 V/cm by the second sequence of electrical pulses.
In certain embodiments, the method may generally comprise applying a first sequence of electrical pulses to the electrode array less than the necrotic threshold to lower the necrotic threshold, and applying a second sequence of electrical pulses to the central electrode to induce cell necrosis by irreversible electroporation. The method may comprise applying the first sequence of electrical pulses to the central electrode when the first sequence of electrical pulses is applied to the electrode array. The method may comprise applying the second sequence of electrical pulses to the electrode array when the second sequence of electrical pulses is applied to the central electrode. The method may comprise not applying the second sequence of electrical pulses to the electrode array when the second sequence of electrical pulses is applied to the central electrode.
In certain embodiments, the method may generally comprise delivering a first energy dose to the tissue that is less than the necrotic threshold to induce thermal heating by the first sequence of electrical pulses, and delivering a second energy dose to the tissue equal to or greater than the necrotic threshold to induce cell necrosis in the tissue by irreversible electroporation by the second sequence of electrical pulses. The first energy dose may be delivered by the electrode array and/or central electrode. The first energy dose may not be delivered by the central electrode. The second energy dose may be delivered by the central electrode. In one embodiment, the first energy dose may be delivered by the electrode array and the second energy dose may be delivered by the central electrode.
In certain embodiments, the method may generally comprise measuring at least one of temperature and pressure adjacent at least one of the electrode array and central electrode, applying a first sequence of electrical pulses to the electrode array to achieve at least one of a predetermined temperature and a predetermined pressure, and applying a second sequence of electrical pulses to the central electrode when the at least one of a predetermined temperature and a predetermined pressure is achieved. The predetermined temperature may be body temperature, about 37° C., and greater than 37° C., such as, for example, 40° C. to 60° C., 40° C. to 50° C., 40° C. to 55° C. and up to 60° C. The temperature of the tissue after the first sequence electrical pulses may be greater that body temperature, such as, for example, 37° C. The temperature of the tissue after the first sequence of electrical pulses may be about 55° C. The first and second sequences of electrical pulses may be configured to maintain the tissue at a temperature between 50-60° C. The predetermined pressure may be atmospheric pressure.
In certain embodiments, the method may generally comprise applying a sequence of electrical pulses to the electrode array, the sequence of electrical pulses having amplitudes in the range of about ±100 VDC to about ±10,000 VDC, pulse widths in the range of about 1 μs to about 100 ms, and frequencies in the range of about 1 Hz to about 10,000 Hz, and re-applying the sequence of electrical pulses to the central electrode. Each of the pulses may independently have amplitudes in the range of about ±100 VDC to about ±10,000 VDC, pulse widths in the range of about 1 μs to about 100 ms, and frequencies in the range of about 1 Hz to about 10,000 Hz. In one embodiment, the method may generally comprise applying a sequence of electrical pulses having amplitudes in the range of about ±100 VDC to about ±3,000 VDC, pulse widths in the range of about 1 μs to about 100 ms, and frequencies in the range of about 1 Hz to about 10,000 Hz. The sequence of electrical pulses may comprise a series of pulse trains each having a pulse train amplitude, a pulse train pulse width, and a pulse train frequency. The pulse trains may comprise a plurality of pulses each having an amplitude, a pulse width, and a frequency. As discussed above, the first sequence of electrical pulses may comprise a series of first pulse trains each having a first pulse train amplitude, a first pulse train pulse width, and a first pulse train frequency, and the second sequence of electrical pulses may comprise a series of second pulse trains each comprising a second pulse train amplitude, a second pulse train pulse width, and a second pulse train frequency.
In certain embodiments, the method may generally comprise lowering the necrotic threshold by heating the tissue by applying an electric field that is less than about 800 V/cm by the first sequence of electrical pulses. The method may comprise lowering the necrotic threshold by 30% by heating the tissue by applying an electric field that is less than about 800 V/cm. The method may comprise lowering the necrotic threshold by heating the tissue by applying an electric field that is less than about 700 V/cm by the first sequence of electrical pulses.
Once positioned by the user, at least one of the plurality of electrodes in the electrode array may be energized to form a pre-heated zone having a first shape in the tissue treatment region. The electrode array may be inserted into a tissue treatment region to create a plurality of pre-heated zones having a plurality of shapes by retracting the at least one of the plurality of electrodes in the electrode array, rotating at least one of the plurality of electrodes in the electrode array to a new location, advancing or retracting at least one of the plurality of electrodes in the electrode array into the tissue treatment region, and/or energizing or de-energizing at least one of the plurality of electrodes in the electrode array. For example, the shape of the pre-heated zone may be dependent on the position of the plurality of electrodes in the electrode array. When the central electrode is energized, a necrotic zone having a second shape may be formed in the tissue treatment region. This process may be repeated as often as necessary to create any number of necrotic zones using the electrical ablation apparatus.
Various parameters, such as, for example, pressure, temperature, and duration, may be altered or adjusted according to the type of tissue in the tissue treatment region and the desired size of the pre-heated zone and/or necrotic zone. The size of the pre-heated zone may be less than or equal to the size of the necrotic zone. In one embodiment, the ablation apparatus may increase the size of the necrotic zone relative to a similar ablation apparatus comprising a first sequence of electrical pulses to induce cell necrosis in the tissue by irreversible electroporation. At anytime, the surgeon or clinician may reposition the electrical ablation apparatus within the tissue treatment region and begin the process anew.
According to certain embodiments, the method may comprise applying a first sequence of electrical pulses to the electrode array to induce thermal heating and applying a second sequence of electrical pulses to the central electrode to induce cell necrosis by irreversible electroporation, wherein the first and second sequences of electrical pulses create a ratio of thermal volume to non-thermal volume of 5 to 1. The thermal volume may comprise the volume of the pre-heated zone. In one embodiment, at least one of the first sequence of electrical pulses, the second sequence of electrical pulses, and sequence interval may be configured to create a ratio of thermal volume to non-thermal volume of 2 to 1. In one embodiment, at least one of the first sequence of electrical pulses, the second sequence of electrical pulses, and sequence interval may be configured to create a ratio of thermal zone volume to necrotic zone volume of 1 to 1.
According to certain embodiments, the method may comprise measuring at least one of temperature and pressure of the tissue treatment region. The method may comprise measuring at least one of temperature and pressure of the undesirable tissue. The method may comprise measuring at least one of temperature and pressure adjacent at least one of the plurality of electrodes of the electrode array and the central electrode. The method may comprise measuring at least one of temperature and pressure adjacent at least one of the plurality of electrodes of the electrode array and the central electrode and applying a sequence of electrical pulses when at least one of a predetermined temperature and a predetermined pressure is achieved. The method may comprise measuring at least one of temperature and pressure adjacent at least one of the plurality of electrodes of the electrode array and the central electrode and stopping a sequence of electrical pulses when at least one of a predetermined temperature and a predetermined pressure is achieved. The method may comprise measuring at least one of temperature and pressure adjacent at least one of the plurality of electrodes of the electrode array and the central electrode and applying a sequence of electrical pulses to achieve at least one of a predetermined temperature and a predetermined pressure.
In one embodiment, the electrical ablation system comprising an electrode array and a central electrode may be used to deliver energy to tissue, such as, for example, undesirable tissue located on the surface of the liver. In use, the electrical ablation device may be introduced into or proximate the tissue treatment region through a port of a trocar. The trocar may be introduced into the patient via a small incision formed in the skin. The endoscope may be introduced into the patient trans-anally through the colon, trans-orally down the esophagus and through the stomach using translumenal techniques, or through a small incision or keyhole formed through the patient's abdominal wall (e.g., the peritoneal wall). The endoscope may be employed to guide and locate the distal end of the electrical ablation device into or proximate the undesirable tissue. Prior to introducing the flexible shaft through the trocar, the sheath may be slid over the flexible shaft in a direction toward the distal end thereof to cover each of the electrodes of the electrode array and central electrode until the distal end of the electrical ablation device reaches the undesirable tissue.
Once the electrical ablation device has been suitably introduced into or proximate the undesirable tissue, the sheath may be retracted to expose the at least one of the plurality of electrodes of the electrode array and/or central electrode to deliver energy to the undesirable tissue. To deliver the energy to the undesirable tissue, the operator initially may locate the each of the electrodes of the electrode array at a first position and the central electrode at a second position using endoscopic visualization and maintaining the undesirable tissue within the field of view of the flexible endoscope. The first position may be near a perimeter edge of the undesirable tissue. Once the electrodes are located into or proximate the undesirable tissue, the electrode array may be energized with a first sequence of electrical pulses to deliver a first energy dose that is less than the necrotic threshold to induce thermal heating in the tissue surrounding the electrode/tissue interface. Once the temperature and/or pressure of the undesirable tissue achieves a predetermined threshold, the central electrode may be energized with a second sequence of electrical pulses to deliver a second energy dose equal to or greater than the necrotic threshold to induce cell necrosis in the tissue by irreversible electroporation to create a necrotic zone. For example, once the electrode array and central electrode are located in the desired positions, the undesirable tissue may be exposed to an electric field generated by independently energizing the electrodes with the energy source.
According to certain embodiments, an ablation apparatus for delivering energy to tissue having a necrotic threshold may generally comprise an electrode array comprising a plurality of electrodes and a central electrode coupled to an energy source operative to generate and deliver a first sequence of electrical pulses to the electrode array and a second sequences of electrical pulses to the electrode array, wherein the first sequence of electrical pulses delivers a first energy dose to the tissue that is less than the necrotic threshold to induce thermal heating in the tissue and the second sequence of electrical pulses delivers a second energy dose to the tissue equal to or greater than the necrotic threshold to induce cell necrosis in the tissue by irreversible electroporation. The ablation apparatus may comprise a ground pad. The ground pad may be positioned proximal to or adjacent the tissue. The ablation apparatus may comprise a controller, including any of the controllers discussed herein. The controller may be coupled to the energy source and configured to control at least one parameter associated with the delivery of the electrical pulses. In various embodiments, each of the plurality of electrodes may comprise outer electrodes spaced apart from the other of the plurality of electrodes, and the central electrode may comprise an inner electrode intermediate the plurality of electrodes.
According to certain embodiments, an ablation apparatus may comprise an energy source configured to generate and deliver DC first pulses and the second pulses at frequencies in the range of 1 Hz to 10,000 Hz, amplitudes in the range of ±100 VDC to ±3000 VDC, and pulse width in the range of about 1 μs to about 100 ms. The first sequence of electrical pulses may be sufficient to create a thermal zone in a first portion of the tissue induced by thermal heating in an area near an electrode-tissue-interface of each of the plurality of electrodes, and the second sequence of electrical pulses may be sufficient to create a necrotic zone in a second portion of tissue induced by irreversible electroporation in an area surrounding each of the plurality of electrodes and the central electrode.
According to certain embodiments, a method of treating tissue may generally comprise obtaining an ablation apparatus comprising a central electrode and an electrode array coupled to an energy source operative to generate and deliver a first sequence of electrical pulses and a second sequence of electrical pulses to tissue having a necrotic threshold, wherein the first sequence of electrical pulses deliver a first energy dose that is less than the necrotic threshold to induce thermal heating in the tissue and the second sequence of electrical pulses deliver a second energy dose equal to or greater than the necrotic threshold to induce cell necrosis in the tissue by irreversible electroporation, inserting the electrode array into a mass of tissue having a necrotic threshold, applying a first sequence of electrical pulses to the electrode array less than the necrotic threshold to induce thermal heating, applying a second sequence of electrical pulses to the central electrode to induce cell necrosis by irreversible electroporation, and applying a ground potential to a ground pad, wherein the ablation apparatus is operative to reduce the necrotic threshold of the tissue relative to a corresponding ablation apparatus having an energy source configured to deliver a sequence of electrical pulses to induce cell necrosis by irreversible electroporation.
According to certain embodiments, a method of treating tissue may generally comprise inserting a central electrode and an electrode array comprising a plurality of electrodes into a mass of tissue having a membrane potential and a necrotic threshold, applying a first sequence of electrical pulses to the electrode array less than the necrotic threshold to induce thermal heating, applying a second sequence of electrical pulses to the central electrode to induce cell necrosis by irreversible electroporation, and applying a ground potential to a ground pad proximal to the tissue. In one embodiment, the method may comprise re-applying the sequence of electrical pulses to the central electrode. In one embodiment, an energy source may be operative to generate and deliver a sequence interval between the first sequence and second sequence. The first sequence of electrical pulses may comprise a series of first pulse trains each having a first pulse train amplitude, a first pulse train pulse width, and a first pulse train frequency, and the second sequence of electrical pulses may comprise a series of second pulse trains each comprising a second pulse train amplitude, a second pulse train pulse width, and a second pulse train frequency. The first pulse trains may comprise a plurality of first pulses each having a first amplitude, a first pulse width, and a first frequency, and each of the second pulse trains may comprise a plurality of second pulses each having a second amplitude, a second pulse width, and a second frequency. Each of the first pulses and the second pulses may independently have amplitudes in the range of about ±100 VDC to about ±10,000 VDC, pulse widths in the range of about 1 μs to about 100 ms, and frequencies in the range of about 1 Hz to about 10,000 Hz.
Although the various embodiments of the devices have been described herein in connection with certain disclosed embodiments, many modifications and variations to those embodiments may be implemented. For example, different types of end effectors may be employed. Also, where materials are disclosed for certain components, other materials may be used. The foregoing description and following claims are intended to cover all such modification and variations.
Any patent, publication, or other disclosure material, in whole or in part, that is said to be incorporated by reference herein is incorporated herein only to the extent that the incorporated materials does not conflict with existing definitions, statements, or other disclosure material set forth in this disclosure. As such, and to the extent necessary, the disclosure as explicitly set forth herein supersedes any conflicting material incorporated herein by reference. Any material, or portion thereof, that is said to be incorporated by reference herein, but which conflicts with existing definitions, statements, or other disclosure material set forth herein will only be incorporated to the extent that no conflict arises between that incorporated material and the existing disclosure material.
This application is a divisional application claiming priority under 35 U.S.C. § 121 to U.S. patent application Ser. No. 13/352,495, filed Jan. 18, 2012, now U.S. Pat. No. 9,314,620, entitled, ELECTRICAL, ABLATION DEVICES AND METHODS, which is a continuation-in-part application claiming priority under 35 U.S.C. § 120 to U.S. patent application Ser. No. 13/036,908, filed Feb. 28, 2011, now U.S. Pat. No. 9,233,241, entitled ELECTRICAL ABLATION DEVICES AND METHODS, the entire disclosures of which are hereby incorporated by reference herein.
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