US20050171574A1 - Electroporation to interrupt blood flow - Google Patents

Electroporation to interrupt blood flow Download PDF

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US20050171574A1
US20050171574A1 US11/022,310 US2231004A US2005171574A1 US 20050171574 A1 US20050171574 A1 US 20050171574A1 US 2231004 A US2231004 A US 2231004A US 2005171574 A1 US2005171574 A1 US 2005171574A1
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blood flow
voltage
electroporation
tissue
cells
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Boris Rubinsky
Jon Edd
Liana Horowitz
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University of California San Diego UCSD
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Assigned to THE REGENTS OF THE UNIVERSITY OF CALIFORNIA reassignment THE REGENTS OF THE UNIVERSITY OF CALIFORNIA ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: HOROWITZ, LIANA, RUBINSKY, BORIS, EDD, JON
Publication of US20050171574A1 publication Critical patent/US20050171574A1/en
Priority to US12/163,727 priority patent/US20080269586A1/en
Priority to US12/430,336 priority patent/US8298222B2/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/1206—Generators therefor
    • A61B18/1233—Generators therefor with circuits for assuring patient safety
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/0404—Electrodes for external use
    • A61N1/0408—Use-related aspects
    • A61N1/0412—Specially adapted for transcutaneous electroporation, e.g. including drug reservoirs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/14—Probes or electrodes therefor
    • A61B18/1477—Needle-like probes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00571—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for achieving a particular surgical effect
    • A61B2018/00577—Ablation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00571—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for achieving a particular surgical effect
    • A61B2018/00613—Irreversible electroporation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00636—Sensing and controlling the application of energy
    • A61B2018/00696—Controlled or regulated parameters
    • A61B2018/00714—Temperature
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00636—Sensing and controlling the application of energy
    • A61B2018/00696—Controlled or regulated parameters
    • A61B2018/00761—Duration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00636—Sensing and controlling the application of energy
    • A61B2018/00773—Sensed parameters
    • A61B2018/00827—Current
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/14—Probes or electrodes therefor
    • A61B2018/1405—Electrodes having a specific shape
    • A61B2018/1425—Needle
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/0404—Electrodes for external use
    • A61N1/0472—Structure-related aspects
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/327—Applying electric currents by contact electrodes alternating or intermittent currents for enhancing the absorption properties of tissue, e.g. by electroporation

Definitions

  • This invention relates to the field of electrode devices useful to disrupt blood flow in order to carry out treatments.
  • cryosurgery is a low temperature minimally invasive technique in which tissue is frozen on contact with a cryogen cooled probe inserted in the undesirable tissue (Rubinsky, B., ed. Cryosurgery . Annu. Rev. Biomed. Eng. Vol. 2. 2000. 157-187.).
  • Non-selective chemical ablation is a technique in which chemical agents such as ethanol are injected in the undesirable tissue to cause ablation (Shiina, S., et al., Percutaneous ethanol injection therapy for hepatocellular carcinoma: results in 146 patients . AJR, 1993. 160: p. 1023-8).
  • Non-selective chemical therapy is easy to apply.
  • the affected area cannot be controlled because of the local blood flow and transport of the chemical species. Elevated temperatures are also used to ablate tissue.
  • Focused ultrasound is a high temperature non-invasive technique in which the tissue is heated to coagulation using high-intensity ultrasound beams focused on the undesirable tissue (Lynn, J. G., et al., A new method for the generation of use of focused ultrasound in experimental biology . J. Gen Physiol., 1942. 26: p. 179-93; Foster, R. S., et al., High - intensity focused ultrasound in the treatment of prostatic disease . Eur. Urol., 1993. 23: p. 44-7). Electrical currents are also commonly used to heat tissue.
  • Radiofrequency ablation is a high temperature minimally invasive technique in which an active electrode is introduced in the undesirable tissue and a high frequency alternating current of up to 500 kHz is used to heat the tissue to coagulation (Organ, L. W., Electrophysiological principles of radiofrequency lesion making . Appl. Neurophysiol., 1976. 39: p. 69-76).
  • RF heating traditional Joule heating methods with electrodes inserted in tissue and dc or ac currents are also common, (Erez, A., Shitzer, A. ( Controlled destruction and temperature distribution in biological tissue subjected to monoactive electrocoagulation ) J. Biomech. Eng. 1980: 102(1): 42-9).
  • Interstitial laser coagulation is a high temperature thermal technique in which tumors are slowly heated to temperatures exceeding the threshold of protein denaturation using low power lasers delivered to the tumors by optical fibers (Bown, S. G., Phototherapy of tumors . World. J. Surgery, 1983. 7: p. 700-9).
  • High temperature thermal therapies have the advantage of ease of application.
  • the disadvantage is the extent of the treated area is difficult to control because blood circulation has a strong local effect on the temperature field that develops in the tissue.
  • the armamentarium of surgery is enhanced by the availability of the large number of minimally invasive surgical techniques in existence, each with their own advantages and disadvantages and particular applications.
  • This document discloses another minimally invasive surgical technique for tissue ablation, irreversible electroporation. We will describe the technique, evaluate its feasibility through mathematical modeling and demonstrate the feasibility with in vivo experimental studies.
  • Electroporation is defined as the phenomenon that makes cell membranes permeable by exposing them to certain electric pulses (Weaver, J. C. and Y. A. Chizmadzhev, Theory of electroporation: a review . Bioelectrochem. Bioenerg., 1996. 41: p. 135-60). Electroporation pulses are defined as those electrical pulses that through a specific combination of amplitude, shape, time length and number of repeats produce no other substantial effect on biological cells than the permeabilization of the cell membrane.
  • the range of electrical parameters that produce electroporation is bounded by: a) parameters that have no substantial effect on the cell and the cell membrane, b) parameters that cause substantial thermal effects (Joule heating) and c) parameters that affect the interior of the cell, e.g. the nucleus, without affecting the cell membrane. Joule heating, the thermal effect that electrical currents produce when applied to biological materials is known for centuries. It was noted in the previous paragraph that electrical thermal effects which elevate temperatures to values that damage cells are commonly used to ablate undesirable tissues. The pulse parameters that produce thermal effects are longer and/or have higher amplitudes than the electroporation pulses whose only substantial effect is to permeabilize the cell membrane.
  • thermal effects there are a variety of methods to electrically produce thermal effects that ablate tissue. These include RF, electrode heating, and induction heating. Electrical pulses that produce thermal effects are distinctly different from the pulses which produce electroporation. The distinction can be recognizing through their effect on cells and their utility. The effect of the thermal electrical pulses is primarily on the temperature of the biological material and their utility is in raising the temperature to induce tissue ablation through thermal effects.
  • nanosecond pulses The effect of the electroporation parameters is primarily on the cell membrane and their utility is in permeabilizing the cell membrane for various applications. Electrical parameters that only affect the interior of the cell, without affecting the cell membrane were also identified recently. They are normally referred to as “nanosecond pulses”. It has been shown that high amplitude, and short (substantially shorter than electroporation pulses—nanoseconds versus millisecond) length pulses can affect the interior of the cell and in particular the nucleus without affecting the membrane. Studies on nanosecond pulses show that they are “distinctly different than electroporation pulses” (Beebe S J. Fox P M. Rec L J. Somers K. Stark R H. Schoenbach K H.
  • Several applications have been identified for nano-second pulses. One of them is for tissue ablation through an effect on the nucleus (Schoenbach, K. H., Beebe, S. J., Buescher, K. S. Method and apparatus for intracellular electro-manipulation U.S. Patent Application Pub No.
  • Electroporation is known for over half a century. It was found that as a function of the electrical parameters, electroporation pulses can have two different effects on the permeability of the cell membrane.
  • the permeabilization of the membrane can be reversible or irreversible as a function of the electrical parameters used. In reversible electroporation the cell membrane reseals a certain time after the pulses cease and the cell survives. In irreversible electroporation the cell membrane does not reseal and the cell lyses.
  • FIG. 1 A schematic diagram showing the effect of electrical parameters on the cell membrane permeabilization (electroporation) and the separation between: no effect, reversible electroporation and irreversible electroporation is shown in FIG. 1 (Dev, S.
  • electroporation The mechanism of electroporation is not yet fully understood. It is thought that the electrical field changes the electrochemical potential around a cell membrane and induces instabilities in the polarized cell membrane lipid bilayer. The unstable membrane then alters its shape forming aqueous pathways that possibly are nano-scale pores through the membrane, hence the term “electroporation” (Chang, D. C., et al., Guide to Electroporation and Electrofusion. 1992, San Diego, Calif.: Academic Press, Inc.). Mass transfer can now occur through these channels under electrochemical control. Whatever the mechanism through which the cell membrane becomes permeabilized, electroporation has become an important method for enhanced mass transfer across the cell membrane.
  • the first important application of the cell membrane permeabilizing properties of electroporation is due to Neumann (Neumann, E., et al., Gene transfer into mouse lyoma cells by electroporation in high electric fields . J. EMBO, 1982. 1: p. 841-5). He has shown that by applying reversible electroporation to cells it is possible to sufficiently permeabilize the cell membrane so that genes, which are macromolecules that normally are too large to enter cells, can after electroporation enter the cell. Using reversible electroporation electrical parameters is crucial to the success of the procedure, since the goal of the procedure is to have a viable cell that incorporates the gene.
  • electroporation became commonly used to reversible permeabilize the cell membrane for various applications in medicine and biotechnology to introduce into cells or to extract from cells chemical species that normally do not pass, or have difficulty passing across the cell membrane, from small molecules such as fluorescent dyes, drugs and radioactive tracers to high molecular weight molecules such as antibodies, enzymes, nucleic acids, HMW dextrans and DNA. It is important to emphasize that in all these applications electroporation needs to be reversible since the outcome of the mass transport requires for the cells to be alive after the electroporation.
  • Tissue electroporation is now becoming an increasingly popular minimally invasive surgical technique for introducing small drugs and macromolecules into cells in specific areas of the body. This technique is accomplished by injecting drugs or macromolecules into the affected area and placing electrodes into or around the targeted tissue to generate reversible permeabilizing electric field in the tissue, thereby introducing the drugs or macromolecules into the cells of the affected area (Mir, L. M., Therapeutic perspectives of in vivo cell electropermeabilization . Bioelectrochemistry, 2001. 53: p. 1-10).
  • Basal cell carcinoma (32), malignant melanoma (142), adenocarcinoma (30) and head and neck squamous cell carcinoma (87) were treated for a total of 291 tumors (Mir, L. M., et al., Effective treatment of cutaneous and subcutaneous malignant tumours by electrochemotherapy . British Journal of Cancer, 1998. 77(12): p. 2336-2342).
  • Electrochemotherapy is a promising minimally invasive surgical technique to locally ablate tissue and treat tumors regardless of their histological type with minimal adverse side effects and a high response rate (Dev, S. B., et al., Medical Applications of Electroporation . IEEE Transactions on Plasma Science, 2000. 28(1): p. 206-223; Heller, R., R. Gilbert, and M. J. Jaroszeski, Clinical applications of electrochemotherapy . Advanced drug delivery reviews, 1999. 35: p. 119-129).
  • Electrochemotherapy which is performed through the insertion of electrodes into the undesirable tissue, the injection of cytotoxic dugs in the tissue and the application of reversible electroporation parameters, benefits from the ease of application of both high temperature treatment therapies and non-selective chemical therapies and results in outcomes comparable of both high temperature therapies and non-selective chemical therapies.
  • the control over the extent of the affected tissue by this mode of ablation does not depend on the blood flow as in thermal and non-selective chemical therapies.
  • electroporation protocols for ablation of tissue with drugs that are incorporated in the cell and function in the living cells it was important to employ reversible electroporation; because the drugs can only function in a living cell. Therefore, in designing protocols for electrochemotherapy the emphasize was on avoiding irreversible electroporation.
  • the focus of the entire field of electroporation for ablation of tissue was on using reversible pulses, while avoiding irreversible electroporation pulses, that can cause the incorporation of selective drugs in undesirable tissue to selectively destroy malignant cells.
  • Electrochemotherapy which employs reversible electroporation in combination with drugs, is beneficial due to its selectivity however, a disadvantage is that by its nature, it requires the combination of chemical agents with an electrical field and it depends on the successful incorporation of the chemical agent inside the cell.
  • Ivanusa et al have found using MRI that with certain electroporation pulses, which appear to be in the irreversible electroporation range, that the electroporation transiently but significantly reduced tumor blood flow (Ivanusa, T., Beravs, K., Cemazar, M, Jevtic, V., Demsar, F., Sersa, G. MRI macromolecular contrast agents as indicators of changed tumor blood flow, Radiol. Oncol. 2001; 35(2): 139-47). These findings are very different from those described here.
  • Sersa et al performed studies whose goal was to determine the effect of electrochemotherapy, reversible elctroporation with bleomycin or cisplatin, on tumor blood flow (Sersa, G., Sentjurc, M., Ivanusa, T., Beravs, K, Kotnik, V., Coer, A., Swartz, H. M., Cemazar, M Reduced blood flow and axygenation in SA -1 tumours after electrochemotherapy with cisplatin, Br. J. Cancer, 2002: 87(9): 1047-54) (Sersa, G., Cemazar, M, Miklavcic, D.
  • the present inventors have found through histological analysis of electroporated tissue that in regions of tissue which are irreversible electroporated the local blood flow completely ceases, whereas outside that area the blood flow is not affected. This has the effect of local blood flow cessation and the appearance of global blood flow reduction. The applications of local blood flow cessation with irreversible electroporation are disclosed and described here.
  • Irreversible electroporation has been considered detrimental to conventional electrochemotherapy.
  • the present invention shows that it can be used to disrupt blood flow. Once blood flow to an area is stopped the cells in that area die.
  • the method can be used in various treatments as described here.
  • the present invention comprises a method for disrupting blood flow, involving the placement of electrodes into or near the vicinity where the undesirable flow of blood is occurring and using the electrodes to provide electrical pulses.
  • the length of time of the electrical pulses, the voltage applied and the resulting membrane permeability are all controlled within defined ranges.
  • the invention may further comprise monitoring blood flow in a specific area and determining desired results have been achieved once the flow being monitored has been determined to have stopped flowing. Cells which have been deprived of blood flow die and may be left in situ and may be removed by natural processes such as the body's own immune system.
  • the invention may further comprise infusing a material such as a chemotherapeutic agent and/or a marker in blood prior to interrupting blood flow. Such may be timed to trap the material in a targeted cite and may be used to ablate tumor cells.
  • Irreversible electroporation is different from intracellular electro-manipulation which substantially only affects the interior of the cell and does not cause irreversible cell membrane damage.
  • Irreversible electroporation is not electrically induced thermal coagulation—which induces cell damage through thermal effects but rather a more benign method to destroy only the cell membrane of cells in the targeted tissue.
  • Irreversible electroporation which irreversible destroys the cell membrane is also different from electrochemotherapy in which reversible electroporation pulses are used to introduce drugs into the living cells and in which the drugs subsequently affect the living cell.
  • An electrical pulse can either have no effect on the cell membrane, effect internal cell components, reversibly open the cell membrane after which cells can survive, or irreversibly open the cell membrane.
  • the membrane of a cell is irreversibly opened the cell dies.
  • a sufficient number of cells in an area are killed (e.g. blood vessel cells) blood flow to that area is disrupted.
  • blood flow to other cells is disrupted those cells die.
  • Others have generally considered irreversible electroporation of tissue to be undesirable due to the possibility of instantaneous necrosis of the entire tissue affected by the electrical field, regardless of its diseased or healthy state.
  • Irreversible electroporation is detrimental in certain applications, such as gene therapy or electrochemotherapy, where the sole purpose of the electric pulses is to facilitate the introduction of the drug or gene into the cells of a tissue without killing the cell (Mir, L. M. and S. Orlowski, The basis of electrochemotherapy, in Electrochemotherapy, electrogenetherapy, and transdermal drug delivery: Electrically mediated delivery of molecules to cells , M. J. Jaroszeski, R. Heller, R. Gilbert, Editors, 2000, Humana Press, p. 99-118).
  • irreversible electroporation to disrupt blood flow can provide useful treatments.
  • the method is carried out using electrical pulses to serve as the active means for tissue destruction by a specific means, i.e. by fatally disrupting the cell membrane.
  • Electrochemotherapy may be selective, but it does require the combination of chemical agents with the electrical field.
  • Irreversible electroporation to disrupt blood flow although non-selective, may be used to stop bleeding or for the ablation of undesirable tissue (such as a tumor) as a minimally invasive surgical procedure with or without the use of adjuvant drugs. Its non-selective mode of tissue ablation is acceptable in the field of minimally invasive surgery and provides results which in some ways are comparable to cryosurgery, non-selective chemical ablation and high temperature thermal ablation.
  • An aspect of the invention is a method whereby blood flow is disrupted by applying pulses of very precisely determined length and voltage. This may be done while measuring and/or observing changes in electrical impedance in real time and noting decreases at the onset of electroporation and adjusting the current in real time to obtain irreversible cellular damage without thermal damage.
  • the monitoring of the impedance affords the user knowledge of the presence or absence of pores. This measurement can show the progress of the pore formation and indicate the occurrence of irreversible pore formation, leading to cell death and blood flow disruption.
  • An aspect of this invention is that the onset and extent of electroporation of cells in tissue can be correlated to changes in the electrical impedance (which term is used herein to mean the voltage over current) of the tissue.
  • the electroporation becomes irreversible.
  • a decrease in the resistivity of a group of biological cells occurs when membranes of the cells become permeable due to pore formation.
  • By monitoring the impedance of the biological cells in a tissue one can detect the average point in time in which pore formation of the cells occurs, as well as the relative degree of cell membrane permeability due to the pore formation.
  • By gradually increasing voltage and testing cells in a given tissue one can determine a point where irreversible electroporation occurs and at which blood flow is disrupted.
  • This information can then be used to establish that, on average, the cells of the tissue have, in fact, undergone irreversible electroporation and blood flow has been disrupted.
  • This information can also be used to control the electroporation process and thereby control blood flow by governing the selection of the voltage magnitude.
  • the invention provides the simultaneous irreversible electroporation of multitudes of cells providing a direct indication of the actual occurrence of electroporation and an indication of the degree of electroporation averaged over the multitude sufficient to disrupt blood flow.
  • the discovery is likewise useful in the irreversible electroporation of cells which make-up vessels and of cells in blood.
  • the benefits of this process include a high level of control over the beginning point of irreversible electroporation and the control of blood flow to and out of very specific areas.
  • a feature of the invention is that the magnitude of electrical current during electroporation of the tissue becomes dependent on the degree of electroporation so that current and pulse length are adjusted within a range predetermined to obtain irreversible electroporation of targeted cells of the blood and blood vessels while minimizing cellular damage to surrounding cells and tissue.
  • An aspect of the invention is that pulse length and current are precisely adjusted within ranges to provide more than mere intracellular electro-manipulation which results in cell death and less than that which would cause thermal damages to the surrounding tissues.
  • electroporation may be carried out with or without adding drugs or other materials of any sort to the blood.
  • Another aspect of the invention is monitoring blood flow into and/or out of an area and adjusting any or all of current, voltage, pulse length or number of pulses in real time to obtain a residual degree of blood flow restriction into or out of the area.
  • Another aspect of the invention comprises infusion of a drug and/or image marking agent into blood and then disrupting blood flow to a targeted area so that the drug and/or image marker are trapped in the targeted area.
  • Another aspect of the invention is measuring blood flow in real time provides an indirect indication of electroporation of a targeted area.
  • Another feature of the invention is that measuring current and/or blood flow (in real time) through a circuit gives a measurement of the average overall degree of electroporation obtained.
  • Another aspect of the invention is that the precise electrical resistance of the tissue is calculated from cross-time voltage measurement with probe electrodes and cross-current measurement with the circuit attached to electroporation electrodes.
  • Another aspect of the invention is that the precise electrical resistance of the tissue is calculated from cross-time voltage measurement with probe electrodes and cross-current measurement with the circuit attached to electroporation electrodes.
  • Another aspect of the invention is that electrical measurements of the tissue can be used to map the electroporation and blood flow distribution of the tissue.
  • Another aspect of the invention is treating cancer by infusing a chemotherapeutic agent into blood, and applying current pulses as described here to disrupt blood flow and thereby trap the chemotherapeutic agent in a target area.
  • Yet another aspect of the invention is infusing a higher than normal concentration of a chemotherapeutic agent into a blood vessel immediately upstream of a targeted area and applying current when the agent reached the targeted area to disrupt blood flow and trap the agent in the tumor.
  • Still another aspect of the invention is to infuse a marker molecule with a chemotherapeutic agent into a blood vessel upstream of a targeted area followed by current application sufficient to disrupt flow when the marker is determined to be at the targeted area.
  • an organ is flushed such as with normal saline solution, then fixed, and thereafter subjected to histology to examine the effects of prior irreversible electroporation on cells of that organ.
  • FIG. 1 is a graph showing a schematic relationship between field strength and pulselength applicable to the electroporation of cells.
  • FIGS. 2A, 2B and 2 C are each images of irreversibly electroporated areas for two-electrode configurations using 10 mm center-to-center spacing as following for FIGS. 2A , B and C: ( 2 A) 0.5 mm (857V); ( 2 B) 1.0 mm (1295V); ( 2 C) 1.5 mm (1575V) diameter electrodes with a 680V/cm threshold for irreversible electroporation.
  • FIGS. 3A, 3B , and 3 C are images showing irreversibly electroporated regions using a 680 V/cm threshold for a two-electrode confirmation with 1 mm diameter and 876V and 5 mm spacing for FIGS. 3A ; 1116V and 7.5 mm for FIG. 3B ; and 1295V and 10 mm spacing for FIG. 3C .
  • FIGS. 4A, 4B and 4 C are images showing the effect of electrode diameter for a 4-electrode configuration with 10 mm spacing wherein FIG. 4A is for 0.5 mm diameter and 940V; FIG. 4B is for 1.0 mm diameter and 1404V and FIG. 4C is for 1.5 mm and 1685V.
  • FIGS. 5A, 5B and 5 C are images showing the effect of electrode spacing for a 4-electrode configuration wherein the electrode is 1 mm in diameter and FIG. 5A shows results with a 5 mm and 910V; FIG. 5B 7.5 mm and 1175V and FIG. 5C 10 mm and 1404V.
  • FIG. 6 is an image showing the irreversible (1295V, 680V/cm threshold) as compared to the reversible region (1300V, 360V/cm threshold) using virtually the same electrical parameters.
  • 1300V is the most common voltage applied across two electrodes for ECT.
  • the most common voltage parameters are eight 100 ⁇ s pulses at a frequency of 1 Hz. Applying a single 800 ⁇ s pulse provides a conservative estimate of the heating associated with a procedure.
  • the one second space normally between pulses will enlarge an area amount of heat to be dissipated through the tissue.
  • FIG. 7 is an image showing reversible electroporation with 1 mm electrodes, 10 mm spacing. A voltage of 189V applied between the electrodes induces reversible electroporation without any irreversible electroporation by not surpassing the 680V/cm irreversible electroporation threshold anyone in the domain. The shaded area is greater than 360 V/cm.
  • FIGS. 8A and 8B show a comparison of the effect of blood flow and metabolism on the amount of irreversible electroporation.
  • FIG. 8A no blood flow or metabolism.
  • FIG. 9 is a schematic view of a liver between two cylindrical Ag/AgCl electrodes.
  • the distance between the electrodes was 4 mm and the radius of the electrodes is 10 mm.
  • the electrodes were clamped with special rig parallel and concentric to each other. The liver lobe was compressed between the electrodes to achieve good contact.
  • FIG. 10 is a photo of a view of a liver which was electroporated by irreversible electroporation with two cylindrical surface electrodes of 10 mm in diameter. Histology shows that the dark area is necrotic.
  • FIG. 11 is a photo of a cross section through an electroporated liver. Histology shows that the dark area is necrotic. The distance between the two A1 plates that hold the liver is exactly 4 mm. The electroporation electrodes were 10 mm in diameter and centered in the middle of the lesion.
  • FIG. 12 shows the liver of calculated temperature distribution (C), upper panel, and electrical potential gradient (electroporation gradient) (V/cm), lower panel, for the in vivo experiment.
  • C calculated temperature distribution
  • V/cm electrical potential gradient
  • FIG. 12 also shows conditions through a cross section of a liver slab through the center of the electroporated area. Height of the slab is 4 mm.
  • FIG. 13 combines FIGS. 11 and 12 to show a comparison between the extent of tissue necrosis (dark area) and the temperature and voltage gradient distribution in the electroporated tissue. It is evident that most of the dark area was at a temperature of about 42 C following the 40 milliseconds electroporation pulse. The edge of the dark area seems to correspond to the 300 V/cm electroporation gradient line.
  • FIG. 14 is a photo of a micrograph of the interface between irreversible electroporated liver and normal liver.
  • the left hand side shows normal hepatocytes with clear nucleus and nuclei, well defined cell membrane and clean (flushed) sinusoids.
  • the right hand side shows condensed nuclei, no evidence of cell membrane, expanded cell border with no evidence of sinusoids. Disintegrated red blood cells are in what could have been the spaces of the sinusoids. No effect of flushing.
  • reversible electroporation encompasses permeabilization of the cell membrane through the application of electrical pulses across the cell. In “reversible electroporation” the permeabilization of the cell membrane ceases after the application of the pulse and the cell membrane permeability reverts to normal. The cell survives “reversible electroporation.” It is used as a means for introducing chemicals, DNA, or other materials into cells.
  • the term “irreversible electroporation” also encompasses the permeabilization of the cell membrane through the application of electrical pulses across the cell. However, in “irreversible electroporation” the permeabilization of the cell membrane does not cease after the application of the pulse and the cell membrane permeability does not revert to normal. The cell does not survive “irreversible electroporation” and the cell death is caused by the disruption of the cell membrane and not merely by internal perturbation of cellular components. Openings in the cell membrane are created and/or expanded in size resulting in a fatal disruption in the normal controlled flow of material across the cell membrane. The cell membrane is highly specialized in its ability to regulate what leaves and enters the cell. Irreversible electroporation destroys that ability to regulate in a manner such that the cell can not compensate and as such the cell dies.
  • the present invention is a result of the new finding that: a) irreversible electroporation can cause permanent occlusion of certain blood vessels, b) it can cause disintegration and trapping of cells in the area that was irreversible electroporated and c) it can also cause trapping of any kind of compound present at that location at the instant of irreversible electroporation in the region that was electroporated.
  • Irreversible electroporation may be used to occlude blood flow and blood supply in an undesirable region of tissue so as to induce cell death by ischemia in the region that was irreversible electroporated. This is substantially different from other uses of electrical pulses for tissue ablation which are for the destruction of individual cells and which do not address blood vessels.
  • the advantage of using irreversible electroporation to occlude blood flow is that cell death by ischemia is absolute over the entire region in which blood ceases to flow—while cell destruction by electroporation needs to address each cell individually and may suffer from a statistical probability that some cells may survive. Occlusion of blood flow and induction of ischemia by chemical methods has been considered as a method for the treatment of cancer. Irreversible electroporation provides a very efficient method for occluding blood flow without the need for chemicals.
  • FIG. 14 shows that red blood cells have become trapped and disintegrated in the irreversible electroporation area.
  • drugs may be loaded in vesicles or liposomes (a standard method for drug delivery) and the irreversible electroporation can cause the vesicles to disintegrate in the electroporated region. This provides for the delivery of a drug directly to that region.
  • results provided here show that there is no blood flow in the irreversible electroporated region which shows that drugs which are injected systemically in the body blood flow circulation would be entrapped in the irreversible electroporation.
  • drugs could be designed to produce long term effects.
  • the drugs could be in controlled release formulations and be slowly delivered to the tissue surrounding the electroporated area as well as to cells in the electroporated area. Drugs trapped in this manner would not be washed out of the body through the kidneys or metabolized by the liver and therefore would have a long term effect.
  • the drugs could be for destruction of cancer and they could act on possible cancer cells that have survive in the electroporated zone or the area immediately surrounds this area.
  • drugs discussed here are substantially different from those used in rreversible electroporation. More specifically, drugs used in reversible electroporation are restricted to those that normally cannot easily penetrate the cell membrane and the reversible electroporation is used to introduce these drugs in the cells.
  • the typical drugs are bleomycin an Cis-platinum.
  • Using blood flow occlusion with irreversible electroporation allows any kind of drug to be employed because the mechanism for using the drugs is different. Here we do not promote the transport of the drug across the cell membrane but rather the retention of the drug in the irreversible electroporated area for long periods of time.
  • Another method to utilize the blood occlusion for delivery of drugs is to inject after the irreversible electroporation in the electroporated region the drug.
  • the blood occlusion will ensure that the drug is trapped in this area.
  • Imaging markers such as gadolinium for MRI or markers for ultrasound or CT. These markers are injected and used to image the area that was irreversible electroporated using any imaging technique relevant to the markers and/or area.
  • the invention provides a method and a system for blood flow disruption to a targeted area resulting in destruction (ablation) of undesirable tissue in the targeted area.
  • One embodiment of the invention involves the insertion (bringing) electroporation electrodes to the vicinity of the undesirable tissue and in good electrical contact with the tissue and the application of electrical pulses that cause irreversible electroporation of the cells throughout the entire area of the undesirable tissue.
  • a blood vessel or group of blood vessels are targeted at a point or points immediately upstream of a flow of blood to an area of undesired tissue.
  • the cells whose membrane was irreversible permeabilized as well as those whose blood supply has been disrupted may be left in situ (not removed) and as such may be gradually removed by the body's immune system. Cell death is produced by inducing the electrical parameters of irreversible electroporation in the undesirable area.
  • Electroporation protocols involve the generation of electrical fields in tissue and are affected by the Joule heating of the electrical pulses.
  • tissue electroporation protocols it is important to determine the appropriate electrical parameters that will maximize tissue permeabilization without inducing deleterious thermal effects. It has been shown that substantial volumes of tissue can be electroporated with reversible electroporation without inducing damaging thermal effects to cells and has quantified these volumes (Davalos, R. V., B. Rubinsky, and L. M. Mir, Theoretical analysis of the thermal effects during in vivo tissue electroporation . Bioelectrochemistry, 2003. Vol 61(1-2): p. 99-107).
  • unwanted thermal damage can be further reduced. This can be accomplished by applying current to a smaller area and disrupting blood flow to a larger area and thereby ablating tissue in the larger area which is deprived of blood flow.
  • the electrical pulses required to induce irreversible electroporation in tissue are larger in magnitude and duration from the electrical pulses required for reversible electroporation. Further, the duration and strength of the pulses required for irreversible electroporation are different from other methodologies using electrical pulses such as for intracellular electro-manipulation or thermal ablation. The methods are very different even when the intracellular (nano-seconds) electro-manipulation is used to cause cell death, e.g. ablate the tissue of a tumor or when the thermal effects produce damage to cells causing cell death.
  • Typical values for pulse length for irreversible electroporation are in a range of from about 5 microseconds to about 62,000 milliseconds or about 75 microseconds to about 20,000 milliseconds or about 100 microseconds ⁇ 10 microseconds. This is significantly longer than the pulse length generally used in intracellular (nano-seconds) electro-manipulation which is 1 microsecond or less—see published U.S. application 2002/0010491 published Jan. 24, 2002.
  • the pulse is at voltage of about 100 V/cm to 7,000 V/cm or 200 V/cm to 2000 V/cn or 300V/cm to 1000 V/cm about 600 V/cm ⁇ 10% for irreversible electroporation. This is substantially lower than that used for intracellular electro-manipulation which is about 10,000 V/cm, see U.S. application 2002/0010491 published Jan. 24, 2002.
  • the voltage expressed above is the voltage gradient (voltage per centimeter).
  • the electrodes may be different shapes and sizes and be positioned at different distances from each other.
  • the shape may be circular, oval, square, rectangular or irregular etc.
  • the distance of one electrode to another may be 0.5 to 10 cm., 1 to 5 cm., or 2-3 cm.
  • the electrode may have a surface area of 0.1-5 sq. cm. or 1-2 sq. cm.
  • the size, shape and distances of the electrodes can vary and such can change the voltage and pulse duration used. Those skilled in the art will adjust the parameters in accordance with this disclosure to obtain the desired degree of electroporation and avoid thermal damage to surrounding cells.
  • FIG. 1 is showing that irreversible electroporation pulses are longer and have higher amplitude than the reversible electroporation pulses.
  • irreversible electroporation pulses When using irreversible electroporation for tissue ablation, there may be concern that the irreversible electroporation pulses will be as large as to cause thermal damaging effects to the surrounding tissue and the extent of the tissue ablated by irreversible electroporation will not be significant relative to that ablated by thermal effects. Under such circumstances irreversible electroporation could not be considered as an effective tissue ablation modality as it will act in superposition with thermal ablation. To a degree, this problem is addressed via the present invention. Specifically, blood vessels supplying blood to a tumor can be targeted. When the flow is disrupted the tumor cells die even when the tumor cells themselves may not have been subjected to irreversible electroporation.
  • the present invention evaluates, through mathematical models and experiment, the maximal extent of tissue ablation that could be accomplished by irreversible electroporation prior to the onset of thermal effects.
  • the models focused on electroporation of liver tissue with two and four needle electrodes and on electroporation of liver tissue with two infinite parallel plates using available experimental data.
  • the experiment evaluates irreversible electroporation between two cylindrical electrodes, also in the liver. The liver was chosen because it is considered a potential candidate for irreversible electroporation ablation.
  • FIG. 14 is a photo of a micrograph. This micrograph is from the interface between irreversible electroporated liver and normal liver.
  • the left hand side shows normal hepatocytes with clear nucleus and nuclei.
  • the photo shows well defined cell membranes and clean (flushed) sinusoids.
  • the right hand side of FIG. 14 shows condensed nuclei, no evidence of cell membrane, expanded cell border with no evidence of sinusoids.
  • the disintegrated red blood cells shown in FIG. 14 are in what could have been the spaces of the sinusoids. Flushing is not believed to have had an effect on the results obtained on the right hand side of FIG. 14 .
  • EIT electrical impedance tomography
  • Irreversible electroporation therefore, has the advantage of a tissue ablation technique that is as easy to apply as high temperature ablation, without the need for adjuvant chemicals as electrochemotherapy and with real-time control of the affected area with electrical impedance tomography.
  • various types of imaging and monitoring technologies can be used to determine blood flow into and out of a specific area of targeted tissues. These monitoring technologies can be used with the present invention with or without the use of imaging agents which may be added to the blood.
  • the invention can be used with high volume procedures including uterine fibroid embolization (UFE) and targeted liver embolization (TLE).
  • UFE uterine fibroid embolization
  • TLE targeted liver embolization
  • Uterine fibroids are benign tumors which can cause symptoms such as excessive bleeding, pain and disfigurement. If left untreated, the symptoms can persist until menopause, which severely impacts the patient's quality of life. They afflict approximately 25 million women in the U.S. Industry sources indicate that 200,000-300,000 of the 600,000 hysterectomies performed in the U.S. each year are due to fibroids. Further, there is a large pool of approximately six million women in the U.S. who are symptomatic enough to see their doctor. Today, many of these women take drugs that are not curative and often have severe side effects such as osteoporosis, or they go untreated.
  • UFE is the occlusion of the blood supply to uterine fibroids to reduce their size and alleviate associated symptoms.
  • Uterine fibroids afflict approximately 25 million women in the U.S., cause mild to moderate symptoms in approximately 6 million, and over 200,000 to undergo surgical procedures.
  • the primary surgical procedures for uterine fibroids are hysterectomy and myomectomy, both of which often are accompanied by complications and long recovery periods.
  • the UFE market is projected to grow from 5,000 procedures and under $10 million in 1998 to more than 300,000 procedures and over $500 million by 2004.
  • TLE is the occlusion of the blood supply to liver tumors to deprive them of the nutrients they require to survive.
  • Over four million people in the U.S. are positive for Hepatitis C which is thought to be a precursor to liver cancer in 10 to 20 percent of these individuals.
  • the present invention can be used with imaging materials and material such as such as embosphere micro spheres can be used to block the flow of blood to liver tumors.
  • Embolization is also used in neurointerventions (in the brain and spinal cord) and other parts of the body to occlude the blood flow to hyper vascularized tumors. While not high volume, these are often intricate procedures, especially in the brain, that require an embolic material that can pass through a micro catheter easily and be targeted precisely as can be carried out with the present invention.
  • the methods of the present invention may be aided by the use of commercially available materials such as EmboGold® Micro spheres which bring visibility to the procedure.
  • EmboGold Micro spheres were first marketed in the U.S. in September, 2001 and are precisely calibrated, spherical, hydrophilic, micro-porous beads made of an acrylic co-polymer, which is then cross-linked with gelatin. They are colored to facilitate handling and procedural efficiency. They eliminate aggregation in the catheter, unwanted proximal embolization and unpredictable distal embolization due to particle fragmentation.
  • the mathematical model provided here shows that irreversible tissue ablation can affect substantial volumes of tissue, without inducing damaging thermal effects.
  • the present invention uses the Laplace equation to calculate the electrical potential distribution in tissue during typical electroporation pulses and a modified Pennes (bioheat), (Pennes, H. H., Analysis of tissue and arterial blood flow temperatures in the resting forearm . J of Appl. Physiology., 1948. 1: p. 93-122), equation to calculate the resulting temperature distribution.
  • bioheat Pennes
  • the analysis modeled conditions typical to tissue electroporation in the liver.
  • the liver was chosen because it is the organ that most minimally invasive ablation techniques treat since cancer in the liver can be resolved by extirpation of the diseased area while surgical resection is not possible in many cases for this organ (Onik, G., B. Rubinsky, and et al., Ultrasound - Guided Hepatic Cryosurgery in the Treatment of Metastatic Colon Carcinoma . Cancer, 1991. 67(4): p. 901-907).
  • the electroporation parameters i.e.
  • Equation (9) is a measure of thermal damage
  • ⁇ is the frequency factor
  • E a is the activation energy
  • R is the universal gas constant.
  • thermal damage is a complex function of time, temperature and all the parameters in Equation (9) above and that there are various degrees of thermal damage.
  • irreversible electroporation protocols that induce some degree of thermal damage, either in part of the electroporated region or at a reduced level throughout the electroporated region.
  • 50° C. as the target temperature for several reasons.
  • Thermal damage begins at temperatures higher than 42° C., but only for prolonged exposures. Damage is relatively low until 50° C. to 60° C. at which the rate of damage dramatically increases (Diller, K. R., Modeling of bioheat transfer processes at high and low temperatures , in Bioengineering heat transfer , Y. I.
  • 50 C will be a relatively low bound on the possible thermal effects during irreversible electroporation. It is anticipated that the electrical parameters chosen for irreversible electroporation without a thermal effect could be substantially longer and higher than those obtained from an evaluation for 50 C in this example. Furthermore, since the Laplace and bioheat equations are linear, the results provided here can be extrapolated and considered indicative of the overall thermal behavior.
  • the analyzed configurations have two needles or four needle electrodes embedded in a square model of the liver. Needle electrodes are commonly used in tissue electroporation and will be most likely also used in the liver (Somiari, S., et al., Theory and in vivo application of electroporative gene delivery . Molecular Therapy, 2000. 2(3): p. 178-187).
  • the square model of the liver was chosen large enough to avoid outer surface boundary effects and to produce an upper limit for the temperature, which develops during electroporation in the liver.
  • the surface of one electrode is assumed to have a prescribed voltage with the other electrode set to ground. The effect of the spacing between the electrodes was investigated by comparing distances of 5, 7.5 and 10 mm, which are typical.
  • the electrodes were also modeled with typical dimensions of 0.5, 1 and 1.5 mm in diameter.
  • the blood flow perfusion rate was taken to zero or 1.0 kg/m 3 s (Deng, Z. S. and J. Liu, Blood perfusion - based model for characterizing the temperature fluctuations in living tissue .
  • the metabolic heat was taken to be either zero or 33.8 kW/m 3 (Deng, Z. S. and J. Liu, Blood perfusion - based model for characterizing the temperature fluctuations in living tissue .
  • Phys A STAT Mech Appl, 2001. 300: p. 521-530 The metabolic heat was taken to be either zero or 33.8 kW/m 3 (Deng, Z. S. and J. Liu, Blood perfusion - based model for characterizing the temperature fluctuations in living tissue .
  • Phys A STAT Mech Appl, 2001. 300: p. 521-530 The metabolic heat was taken to be either zero or 33.8 kW/m 3 (Deng, Z. S. and J.
  • a transmembrane potential on the order of 1V is required to induce irreversible electroporation. This value is dependent on a variety of conditions such as tissue type, cell size and other external conditions and pulse parameters.
  • the primary electrical parameter affecting the transmembrane potential for a specific tissue type is the amplitude of the electric field to which the tissue is exposed.
  • the electric field thresholds used in estimating the extent of the region that was irreversibly electroporated were taken from the fundamental studies of Miklavcic, Mir and their colleagues performed with rabbit liver tissue (Miklavcic, D., et al., A validated model of in vivo electric field distribution in tissues for electrochemotherapy and for DNA electro transfer for gene therapy . Biochimica et Biophysica Acta, 2000.
  • FIGS. 2 and 3 examine the effect of the electrode size and spacing on the ablated area in a two-needle electroporation configuration. In obtaining these figures, we ignored the effect of the blood flow and metabolism in the heat transfer equation, which should give an upper limit for the estimated ablation area.
  • FIG. 2 compares the extent of the irreversible electroporated area for electroporation electrode sizes of 0.5, 1 and 1.5 mm in diameter and a distance between electrodes of 10 mm. The strong effect of the electrode size is evident. It is seen that for the smaller electrodes, the irreversibly electroporated area is not contiguous, while for a 1.5 mm electrode the area of potential tissue, ablation has an elliptical shape with dimensions of about 15 mm by 10 mm.
  • FIG. 3 evaluates the effect of the spacing between the electrodes. It is observed that in the tested range, the small dimension of the contiguous elliptical shape of the ablated lesion remains the same, while the larger dimension seems to scale with the distance between the electrodes.
  • FIGS. 2 and 3 demonstrate that the extent of tissue ablation with irreversible electroporation is comparable to that of other typical minimally invasive methods for tissue ablation, such as cryosurgery (Onik, G. M., B. Rubinsky, and et. al., Ultrasound - guided hepatic cryosurgery in the treatment of metastatic colon carcinoma . Cancer, 1991. 67(4): p. 901-907; Onik, G. M., et al., Transrectal ultrasound - guided percutaneous radical cryosurgical ablation of the prostate . Cancer, 1993. 72(4): p. 1291-99). It also shows that varying electrode size and spacing can control lesion size and shape.
  • the shape and size of the ablated lesion can be also controlled by varying the number of electrodes used. This is shown in FIGS. 4 and 5 , for a four-electrode configuration. These figures also compare the effect of probe size and spacing and the results were also obtained by ignoring the effect of blood flow and metabolism in the energy equation. Again, it is seen that larger electrodes have a substantial effect on the extent of the ablated region and that the extent of ablation scales with the spacing between the electrodes.
  • FIGS. 6 and 7 A comparison between reversible and irreversible electroporation protocols can be achieved from FIGS. 6 and 7 .
  • an 800 ⁇ s, 1295 V pulse was applied between two 1.5 mm diameter electrodes placed 10 mm apart. This produces a tissue temperature lower than 50° C.
  • the figure plots the margin of the irreversibly electroporated region, i.e. the 680 V/cm voltage-to-distance gradients and that of the reversible electroporated region, the 360 V/cm gradients.
  • FIG. 7 was obtained for two 1 mm electrodes placed 10 mm apart. In this figure, we produced an electroporated region that was only reversibly electroporated, i.e. with electric fields lower than 360 V/cm.
  • FIGS. 6 and 7 it is obvious that the extent of the ablated area possible through electrochemotherapy alone is substantially smaller than that through irreversible electroporation alone.
  • FIG. 8 The effect of blood flow and metabolism on the extent of irreversible electroporation is illustrated in FIG. 8 .
  • the figures compare a situation with metabolism and a relatively high blood flow rate to a situation without blood flow or metabolism. It is obvious that metabolism and blood perfusion have a negligible effect on the possible extent of irreversible tissue electroporation. This is because the effect of the Joule heating produced by the electroporation current is substantially larger than the effects of blood flow or metabolism.
  • tissue ablation by electroporation is produced through the use of cytotoxic drugs injected in tissue combined with reversible electroporation, a procedure known as electrochemotherapy.
  • the present invention shows that irreversible electroporation by itself produces substantial tissue ablation for the destruction of undesirable tissues in the body.
  • the concern was that higher voltages required for irreversible electroporation would cause Joule heating and would induce thermal tissue damage to a degree that would make irreversible electroporation a marginal effect in tissue ablation.
  • the present invention shows that the area ablated by irreversible tissue electroporation prior to the onset of thermal effects is substantial and comparable to that of other tissue ablation techniques such as cryosurgery.
  • Our earlier studies have shown that the extent of electroporation can be imaged in real time with electrical impedance tomography (Davalos, R. V., B. Rubinsky, and D. M. Otten, A feasibility study for electrical impedance tomography as a means to monitor tissue electroporation for molecular medicine . IEEE Transactions on Biomedical Engineering, 2002. 49(4): p. 400-403; Davalos, R.
  • Irreversible electroporation therefore, has the advantage of being a tissue ablation technique, which is as easy to apply as high temperature ablation, without the need for adjuvant chemicals as required in electrochemical ablation and electrochemotherapy.
  • a unique aspect of irreversible electroporation is that the affected area can be controlled in real time with electrical impedance tomography.
  • This example was developed to produce a correlation between electroporation pulses and thermal effects.
  • the system analyzed is an infinitesimally small control volume of tissue exposed to an electroporation voltage gradient of V (Volts/cm). The entire electrical energy is dissipated as heat and there is no conduction of heat from the system.
  • the calculations produce the increase in temperature with time during the application of the pulse and the results are a safe lower limit for how long a certain electroporation pulse can be administered until a certain temperature is reached.
  • the second column of Table 1 gives the amount of time it takes for the temperature of the liver to raise 1 C, when the tissue experiences the electroporation pulse in column 1.
  • the time for even a relatively high electroporation voltage of 1500V/cm is of the order of 1.33 millisecond for 1 C rise and 37.32 millisecond until a temperature of 65 C is reached.
  • equation (2-1) or Table 1 it is possible to evaluate the amount of time a certain pulse can be applied without inducing thermal effects. Considering the typical electroporation parameters reported so far there is no limitation in the electroporation length from thermal considerations.
  • Column 3 of Table 1 shows the time required to reach 65 C, which is where thermal damage may begin.
  • the calculations in this example give a lower limit for the extent of time in which a certain thermal effects will be induced by electroporation pulses. For more precise calculations it is possible to use the equation developed in this example with equation (9) or (10) from Example 1.
  • the goal of this experiment was to verify the ability of irreversible electroporation pulses to produce substantial tissue ablation in the non-thermal regime.
  • the electrodes had their flat surface parallel; they were concentric and the liver between the electrodes was compressed so that the lobes were separated by 4 mm.
  • a schematic of the electrodes and the liver is shown in FIG. 9 .
  • the liver was exposed to a single electroporation pulse of 40 milliseconds. One electrode was set to 400 V and the other grounded. The rest of the liver was not in contact with any media and therefore is considered electrically insulated.
  • electroporation the rat was maintained under controlled anesthesia for three hours. Following exsanguination the liver was flushed with physiological saline under pressure and fixed by perfusion with formaldehyde. The liver was resected through the center of the electroporated region and analyzed by histology.
  • FIG. 10 and 11 show the appearance of the liver. Histology has determined that the dark area corresponds to the region of tissue necrosis.
  • the electrical field in the electroporated liver and the temperature distribution were calculated using the equations in Example 1, subject to one electrode at a voltage of 400V and the other grounded, for 40 milliseconds.
  • the liver was modeled as an infinite slab of 4 mm thickness, with concentric cylindrical electrodes (see FIG. 9 ).
  • the results are shown in FIG. 12 .
  • FIG. 12 shows lines of constant voltage gradients (V/cm) and lines of constant temperature. It is evident that in the majority of the electroporated tissue the temperature is about 42 C immediately after the pulse. The highest temperature occurs near the edge of the cylindrical electrodes, where it is about 50 C.
  • FIG. 12 shows lines of constant voltage gradients (V/cm) and lines of constant temperature. It is evident that in the majority of the electroporated tissue the temperature is about 42 C immediately after the pulse. The highest temperature occurs near the edge of the cylindrical electrodes, where
  • FIGS. 11 and 12 were obtained by bringing together FIGS. 11 and 12 .
  • Superimposing the calculated results on the histological measurements reveals that the dark (necrotic) area margin corresponds to electroporation parameters of about 300 V/cm.
  • the results demonstrate that irreversible electroporation can induce substantial tissue necrosis without the need for chemical additives as in electrochemotherapy and without a thermal effect.
  • FIG. 14 is a photo of a micrograph. This micrograph is from the interface between irreversible electroporated liver and normal liver.
  • the left hand side shows normal hepatocytes with clear nucleus and nuclei.
  • the photo shows well defined cell membranes and clean (flushed) sinusoids.
  • the right hand side of FIG. 14 shows condensed nuclei, no evidence of cell membrane, expanded cell border with no evidence of sinusoids.
  • the disintegrated red blood cells shown in FIG. 14 are in what could have been the spaces of the sinusoids. Flushing is not believed to have had an effect on the results obtained on the right hand side of FIG. 14 .

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Cited By (137)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030060856A1 (en) * 2001-08-13 2003-03-27 Victor Chornenky Apparatus and method for treatment of benign prostatic hyperplasia
US20030149451A1 (en) * 2001-08-17 2003-08-07 Chomenky Victor I. Apparatus and method for reducing subcutaneous fat deposits by electroporation with improved comfort of patients
US20040059389A1 (en) * 2002-08-13 2004-03-25 Chornenky Victor I. Apparatus and method for the treatment of benign prostatic hyperplasia
US20050182462A1 (en) * 2000-08-17 2005-08-18 Chornenky Victor I. Apparatus and method for reducing subcutaneous fat deposits, virtual face lift and body sculpturing by electroporation
US20060121610A1 (en) * 1999-07-21 2006-06-08 The Regents Of The University Of California Controlled electroporation and mass transfer across cell membranes
US20060142801A1 (en) * 2002-04-08 2006-06-29 Ardian, Inc. Methods and apparatus for intravascularly-induced neuromodulation
US20060212078A1 (en) * 2002-04-08 2006-09-21 Ardian, Inc. Methods and apparatus for treating congestive heart failure
US20060264752A1 (en) * 2005-04-27 2006-11-23 The Regents Of The University Of California Electroporation controlled with real time imaging
US20060293725A1 (en) * 2005-06-24 2006-12-28 Boris Rubinsky Methods and systems for treating fatty tissue sites using electroporation
US20060293713A1 (en) * 2005-06-24 2006-12-28 Boris Rubinsky Methods and systems for treating BPH using electroporation
US7162303B2 (en) 2002-04-08 2007-01-09 Ardian, Inc. Renal nerve stimulation method and apparatus for treatment of patients
US20070043345A1 (en) * 2003-12-24 2007-02-22 Rafael Davalos Tissue ablation with irreversible electroporation
US20070156135A1 (en) * 2006-01-03 2007-07-05 Boris Rubinsky System and methods for treating atrial fibrillation using electroporation
US20080015571A1 (en) * 2005-06-24 2008-01-17 Boris Rubinsky Methods and systems for treating tumors using electroporation
US20080071264A1 (en) * 2006-09-14 2008-03-20 Larry Azure Ablation probe with deployable electrodes
US20080132884A1 (en) * 2006-12-01 2008-06-05 Boris Rubinsky Systems for treating tissue sites using electroporation
US20080241315A1 (en) * 2007-03-29 2008-10-02 Novozymes A/S Process for treating vegetable material with an enzyme
US20090076496A1 (en) * 2007-09-14 2009-03-19 Lazure Technologies Llc. Prostate cancer ablation
US20090076500A1 (en) * 2007-09-14 2009-03-19 Lazure Technologies, Llc Multi-tine probe and treatment by activation of opposing tines
US20090076499A1 (en) * 2007-09-14 2009-03-19 Lazure Technologies, Llc. Multi-layer electrode ablation probe and related methods
US20090247933A1 (en) * 2008-03-27 2009-10-01 The Regents Of The University Of California; Angiodynamics, Inc. Balloon catheter method for reducing restenosis via irreversible electroporation
US7617005B2 (en) 2002-04-08 2009-11-10 Ardian, Inc. Methods and apparatus for thermally-induced renal neuromodulation
US20090281477A1 (en) * 2008-05-09 2009-11-12 Angiodynamics, Inc. Electroporation device and method
US7620451B2 (en) 2005-12-29 2009-11-17 Ardian, Inc. Methods and apparatus for pulsed electric field neuromodulation via an intra-to-extravascular approach
WO2009151783A1 (en) * 2008-04-17 2009-12-17 The Neuro-Signaling Foundation System and method to elicit apoptosis in malignant tumor cells for medical treatment
US20090318905A1 (en) * 2008-06-23 2009-12-24 Angiodynamics, Inc. Treatment Devices and Methods
US20090318849A1 (en) * 2008-06-20 2009-12-24 Angiodynamics, Inc. Device and Method for the Ablation of Fibrin Sheath Formation on a Venous Catheter
US20090326436A1 (en) * 2003-12-24 2009-12-31 The Regents Of The University Of California Electroporation to deliver chemotherapeutics and enhance tumor regression
US7653438B2 (en) 2002-04-08 2010-01-26 Ardian, Inc. Methods and apparatus for renal neuromodulation
US20100023004A1 (en) * 2008-07-28 2010-01-28 David Francischelli Systems and methods for cardiac tissue electroporation ablation
US20100030211A1 (en) * 2008-04-29 2010-02-04 Rafael Davalos Irreversible electroporation to treat aberrant cell masses
US7674249B2 (en) 2006-10-16 2010-03-09 The Regents Of The University Of California Gels with predetermined conductivity used in electroporation of tissue
US20100100093A1 (en) * 2008-09-16 2010-04-22 Lazure Technologies, Llc. System and method for controlled tissue heating for destruction of cancerous cells
US20100152725A1 (en) * 2008-12-12 2010-06-17 Angiodynamics, Inc. Method and system for tissue treatment utilizing irreversible electroporation and thermal track coagulation
US20100204638A1 (en) * 2009-02-10 2010-08-12 Angiodynamics, Inc. Irreversible electroporation and tissue regeneration
US20100240995A1 (en) * 2009-03-17 2010-09-23 Bioelectromed Corp. System and method for treating tumors
ITTO20090353A1 (it) * 2009-05-04 2010-11-05 Igea S P A Dispositivo per elettroporazione reversibile atto ad indurre apoptosi cellulare
US7853333B2 (en) 2002-04-08 2010-12-14 Ardian, Inc. Methods and apparatus for multi-vessel renal neuromodulation
USRE42016E1 (en) 2001-08-13 2010-12-28 Angiodynamics, Inc. Apparatus and method for the treatment of benign prostatic hyperplasia
USD630321S1 (en) 2009-05-08 2011-01-04 Angio Dynamics, Inc. Probe handle
US20110004096A1 (en) * 2009-07-06 2011-01-06 California Institute Of Technology Electromagnetic cellular tomography
US20110009860A1 (en) * 2000-08-17 2011-01-13 Chornenky Victor I Apparatus and Method for Reducing Subcutaneous Fat Deposits, Virtual Face Lift and Body Sculpturing by Electroporation
US7937143B2 (en) 2004-11-02 2011-05-03 Ardian, Inc. Methods and apparatus for inducing controlled renal neuromodulation
USRE43009E1 (en) 2000-08-17 2011-12-06 Angiodynamics, Inc. Apparatus and method for reducing subcutaneous fat deposits by electroporation
US8131371B2 (en) 2002-04-08 2012-03-06 Ardian, Inc. Methods and apparatus for monopolar renal neuromodulation
US8145317B2 (en) 2002-04-08 2012-03-27 Ardian, Inc. Methods for renal neuromodulation
US8145316B2 (en) 2002-04-08 2012-03-27 Ardian, Inc. Methods and apparatus for renal neuromodulation
US8150519B2 (en) 2002-04-08 2012-04-03 Ardian, Inc. Methods and apparatus for bilateral renal neuromodulation
US8347891B2 (en) 2002-04-08 2013-01-08 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for performing a non-continuous circumferential treatment of a body lumen
US8603087B2 (en) 2005-06-24 2013-12-10 Angiodynamics, Inc. Methods and systems for treating restenosis using electroporation
US8620423B2 (en) 2002-04-08 2013-12-31 Medtronic Ardian Luxembourg S.A.R.L. Methods for thermal modulation of nerves contributing to renal function
US8626300B2 (en) 2002-04-08 2014-01-07 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for thermally-induced renal neuromodulation
US8728139B2 (en) 2009-04-16 2014-05-20 Lazure Technologies, Llc System and method for energy delivery to a tissue using an electrode array
US8753335B2 (en) 2009-01-23 2014-06-17 Angiodynamics, Inc. Therapeutic energy delivery device with rotational mechanism
US8774922B2 (en) 2002-04-08 2014-07-08 Medtronic Ardian Luxembourg S.A.R.L. Catheter apparatuses having expandable balloons for renal neuromodulation and associated systems and methods
US8774913B2 (en) 2002-04-08 2014-07-08 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for intravasculary-induced neuromodulation
US8771252B2 (en) 2002-04-08 2014-07-08 Medtronic Ardian Luxembourg S.A.R.L. Methods and devices for renal nerve blocking
US20140378963A1 (en) * 2013-06-20 2014-12-25 Gyrus Acmi, Inc., D.B.A. Olympus Surgical Technologies America Treatment of uterine fibroids by arterial ablation
US8926606B2 (en) 2009-04-09 2015-01-06 Virginia Tech Intellectual Properties, Inc. Integration of very short electric pulses for minimally to noninvasive electroporation
US9032964B2 (en) 2008-01-10 2015-05-19 Neuro Code Teen Holdings; LLC Method and system for processing cancer cell electrical signals for medical therapy
US9192715B2 (en) 2002-04-08 2015-11-24 Medtronic Ardian Luxembourg S.A.R.L. Methods for renal nerve blocking
US20150335380A1 (en) * 2014-05-22 2015-11-26 Uriel Hiram Chee Systems and methods for performing endometrial ablation
US9198733B2 (en) 2008-04-29 2015-12-01 Virginia Tech Intellectual Properties, Inc. Treatment planning for electroporation-based therapies
US9283051B2 (en) 2008-04-29 2016-03-15 Virginia Tech Intellectual Properties, Inc. System and method for estimating a treatment volume for administering electrical-energy based therapies
US9308044B2 (en) 2002-04-08 2016-04-12 Medtronic Ardian Luxembourg S.A.R.L. Methods for therapeutic renal neuromodulation
US9308043B2 (en) 2002-04-08 2016-04-12 Medtronic Ardian Luxembourg S.A.R.L. Methods for monopolar renal neuromodulation
US9327122B2 (en) 2002-04-08 2016-05-03 Medtronic Ardian Luxembourg S.A.R.L. Methods for catheter-based renal neuromodulation
US9414881B2 (en) 2012-02-08 2016-08-16 Angiodynamics, Inc. System and method for increasing a target zone for electrical ablation
US9439726B2 (en) 2002-04-08 2016-09-13 Medtronic Ardian Luxembourg S.A.R.L. Methods for therapeutic renal neuromodulation
US20160287313A1 (en) * 2009-11-19 2016-10-06 The Regents Of The University Of California Controlled irreversible electroporation
US9526911B1 (en) 2010-04-27 2016-12-27 Lazure Scientific, Inc. Immune mediated cancer cell destruction, systems and methods
US9598691B2 (en) 2008-04-29 2017-03-21 Virginia Tech Intellectual Properties, Inc. Irreversible electroporation to create tissue scaffolds
US9599591B2 (en) 2009-03-06 2017-03-21 California Institute Of Technology Low cost, portable sensor for molecular assays
US9662060B2 (en) 2011-10-07 2017-05-30 Aegea Medical Inc. Integrity testing method and apparatus for delivering vapor to the uterus
US9700368B2 (en) 2010-10-13 2017-07-11 Angiodynamics, Inc. System and method for electrically ablating tissue of a patient
US9707403B2 (en) 2007-12-12 2017-07-18 Neuro Code Tech Holdings, Llc Rapid destruction of malignant tumors by excitotoxicity and osmotic-shock medical tactics
US9743974B2 (en) 2010-11-09 2017-08-29 Aegea Medical Inc. Positioning method and apparatus for delivering vapor to the uterus
US9757196B2 (en) 2011-09-28 2017-09-12 Angiodynamics, Inc. Multiple treatment zone ablation probe
US9867652B2 (en) 2008-04-29 2018-01-16 Virginia Tech Intellectual Properties, Inc. Irreversible electroporation using tissue vasculature to treat aberrant cell masses or create tissue scaffolds
US9895189B2 (en) 2009-06-19 2018-02-20 Angiodynamics, Inc. Methods of sterilization and treating infection using irreversible electroporation
US9980766B1 (en) 2014-03-28 2018-05-29 Medtronic Ardian Luxembourg S.A.R.L. Methods and systems for renal neuromodulation
US10080864B2 (en) 2012-10-19 2018-09-25 Medtronic Ardian Luxembourg S.A.R.L. Packaging for catheter treatment devices and associated devices, systems, and methods
US10117707B2 (en) 2008-04-29 2018-11-06 Virginia Tech Intellectual Properties, Inc. System and method for estimating tissue heating of a target ablation zone for electrical-energy based therapies
US10131900B2 (en) 2010-12-15 2018-11-20 Old Dominion University Research Foundation Electroporation-induced electrosensitization
US10154874B2 (en) 2008-04-29 2018-12-18 Virginia Tech Intellectual Properties, Inc. Immunotherapeutic methods using irreversible electroporation
US10154871B2 (en) 2007-08-23 2018-12-18 Aegea Medical Inc. Uterine therapy device and method
US10166321B2 (en) 2014-01-09 2019-01-01 Angiodynamics, Inc. High-flow port and infusion needle systems
US10179020B2 (en) 2010-10-25 2019-01-15 Medtronic Ardian Luxembourg S.A.R.L. Devices, systems and methods for evaluation and feedback of neuromodulation treatment
US10179019B2 (en) 2014-05-22 2019-01-15 Aegea Medical Inc. Integrity testing method and apparatus for delivering vapor to the uterus
US10194980B1 (en) 2014-03-28 2019-02-05 Medtronic Ardian Luxembourg S.A.R.L. Methods for catheter-based renal neuromodulation
US10194979B1 (en) 2014-03-28 2019-02-05 Medtronic Ardian Luxembourg S.A.R.L. Methods for catheter-based renal neuromodulation
US10238447B2 (en) 2008-04-29 2019-03-26 Virginia Tech Intellectual Properties, Inc. System and method for ablating a tissue site by electroporation with real-time monitoring of treatment progress
US10271893B2 (en) 2014-12-15 2019-04-30 Medtronic Ablation Frontiers Llc Timed energy delivery
US10272178B2 (en) 2008-04-29 2019-04-30 Virginia Tech Intellectual Properties Inc. Methods for blood-brain barrier disruption using electrical energy
US10292755B2 (en) 2009-04-09 2019-05-21 Virginia Tech Intellectual Properties, Inc. High frequency electroporation for cancer therapy
US10471254B2 (en) 2014-05-12 2019-11-12 Virginia Tech Intellectual Properties, Inc. Selective modulation of intracellular effects of cells using pulsed electric fields
US10537385B2 (en) 2008-12-31 2020-01-21 Medtronic Ardian Luxembourg S.A.R.L. Intravascular, thermally-induced renal neuromodulation for treatment of polycystic ovary syndrome or infertility
US10694972B2 (en) 2014-12-15 2020-06-30 Virginia Tech Intellectual Properties, Inc. Devices, systems, and methods for real-time monitoring of electrophysical effects during tissue treatment
US10702337B2 (en) 2016-06-27 2020-07-07 Galary, Inc. Methods, apparatuses, and systems for the treatment of pulmonary disorders
US10702326B2 (en) 2011-07-15 2020-07-07 Virginia Tech Intellectual Properties, Inc. Device and method for electroporation based treatment of stenosis of a tubular body part
US10874455B2 (en) 2012-03-08 2020-12-29 Medtronic Ardian Luxembourg S.A.R.L. Ovarian neuromodulation and associated systems and methods
US11154238B2 (en) 2015-08-07 2021-10-26 Electroceuticals, Llc Systems, methods and apparatuses for providing bioelectronic neurocode-based therapies to mammals
US11207118B2 (en) 2007-07-06 2021-12-28 Tsunami Medtech, Llc Medical system and method of use
US11254926B2 (en) 2008-04-29 2022-02-22 Virginia Tech Intellectual Properties, Inc. Devices and methods for high frequency electroporation
US11272979B2 (en) 2008-04-29 2022-03-15 Virginia Tech Intellectual Properties, Inc. System and method for estimating tissue heating of a target ablation zone for electrical-energy based therapies
US11284931B2 (en) 2009-02-03 2022-03-29 Tsunami Medtech, Llc Medical systems and methods for ablating and absorbing tissue
US11311329B2 (en) 2018-03-13 2022-04-26 Virginia Tech Intellectual Properties, Inc. Treatment planning for immunotherapy based treatments using non-thermal ablation techniques
US11331037B2 (en) 2016-02-19 2022-05-17 Aegea Medical Inc. Methods and apparatus for determining the integrity of a bodily cavity
US11338140B2 (en) 2012-03-08 2022-05-24 Medtronic Ardian Luxembourg S.A.R.L. Monitoring of neuromodulation using biomarkers
US11382681B2 (en) 2009-04-09 2022-07-12 Virginia Tech Intellectual Properties, Inc. Device and methods for delivery of high frequency electrical pulses for non-thermal ablation
US11413086B2 (en) 2013-03-15 2022-08-16 Tsunami Medtech, Llc Medical system and method of use
US11607537B2 (en) 2017-12-05 2023-03-21 Virginia Tech Intellectual Properties, Inc. Method for treating neurological disorders, including tumors, with electroporation
US11638603B2 (en) 2009-04-09 2023-05-02 Virginia Tech Intellectual Properties, Inc. Selective modulation of intracellular effects of cells using pulsed electric fields
US11690999B2 (en) 2017-07-28 2023-07-04 Scandinavian Chemotech Ab Electrode device and a needle electrode for use in delivery of electrical pulses to a desired tissue of a mammal
US11707629B2 (en) 2009-05-28 2023-07-25 Angiodynamics, Inc. System and method for synchronizing energy delivery to the cardiac rhythm
US11717337B2 (en) * 2016-11-29 2023-08-08 St. Jude Medical, Cardiology Division, Inc. Electroporation systems and catheters for electroporation systems
US11723710B2 (en) 2016-11-17 2023-08-15 Angiodynamics, Inc. Techniques for irreversible electroporation using a single-pole tine-style internal device communicating with an external surface electrode
US11925405B2 (en) 2018-03-13 2024-03-12 Virginia Tech Intellectual Properties, Inc. Treatment planning system for immunotherapy enhancement via non-thermal ablation
US11938317B2 (en) 2017-12-26 2024-03-26 Galvanize Therapeutics, Inc. Optimization of energy delivery for various applications
US11950835B2 (en) 2019-06-28 2024-04-09 Virginia Tech Intellectual Properties, Inc. Cycled pulsing to mitigate thermal damage for multi-electrode irreversible electroporation therapy
US11998262B1 (en) 2020-04-09 2024-06-04 Neurent Medical Limited Systems and methods for improving sleep with therapeutic nasal treatment
US12114911B2 (en) 2014-08-28 2024-10-15 Angiodynamics, Inc. System and method for ablating a tissue site by electroporation with real-time pulse monitoring
US12201349B2 (en) 2009-04-03 2025-01-21 Angiodynamics, Inc. Congestive obstruction pulmonary disease (COPD)
US12214189B2 (en) 2019-07-24 2025-02-04 Virginia Tech Intellectual Properties, Inc. Fourier analysis spectroscopy for monitoring tissue impedance changes and treatment outcome during electroporation-based-therapies
US12268433B2 (en) 2015-05-12 2025-04-08 National University Of Ireland, Galway Devices for therapeutic nasal neuromodulation and associated methods and systems
US12279808B2 (en) 2018-12-11 2025-04-22 Neurent Medical Limited Systems and methods for therapeutic nasal neuromodulation
US12336750B2 (en) 2016-12-22 2025-06-24 Aerin Medical Inc. Soft palate treatment
US12357378B2 (en) 2011-06-14 2025-07-15 Aerin Medical Inc. Treating upper airway nerve tissue
US12357817B2 (en) 2021-04-06 2025-07-15 Aerin Medical Inc. Nasal neuromodulation devices and methods
US12364532B2 (en) 2011-06-14 2025-07-22 Aerin Medical Inc. Methods and devices to treat nasal airways
US12369963B1 (en) 2011-06-14 2025-07-29 Aerin Medical Inc. Methods and devices to treat nasal airways
US12390262B2 (en) 2018-03-13 2025-08-19 Virginia Tech Intellectual Properties, Inc. Treatment planning system for immunotherapy enhancement via non-thermal ablation
US12403305B2 (en) 2016-06-27 2025-09-02 Galvanize Therapeutics, Inc. Immunostimulation in the treatment of viral infection
US12433837B2 (en) 2005-07-22 2025-10-07 The Foundry, Llc Systems and methods for delivery of a therapeutic agent
US12458434B2 (en) 2019-07-16 2025-11-04 Galvanize Therapeutics, Inc. Treatment of the reproductive tract with pulsed electric fields
US12471978B2 (en) 2016-03-04 2025-11-18 Aerin Medical Inc. Eustachian tube modification
US12485279B2 (en) 2020-11-25 2025-12-02 Virginia Tech Intellectual Properties, Inc. Methods for modulating temporal infrastructure of pulsed electric fields

Families Citing this family (201)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6355425B1 (en) * 1999-03-26 2002-03-12 Billups-Rothenberg, Inc. Mutations associated with iron disorders
JP4443278B2 (ja) * 2004-03-26 2010-03-31 テルモ株式会社 拡張体付カテーテル
US7601149B2 (en) 2005-03-07 2009-10-13 Boston Scientific Scimed, Inc. Apparatus for switching nominal and attenuated power between ablation probes
US8214221B2 (en) * 2005-06-30 2012-07-03 Lg Electronics Inc. Method and apparatus for decoding an audio signal and identifying information included in the audio signal
DE602006014206D1 (de) * 2006-01-03 2010-06-17 Alcon Inc System zur spaltung und entfernung von proteinösem gewebe
WO2007100727A2 (en) * 2006-02-24 2007-09-07 Eastern Virginia Medical School Nanosecond pulsed electric fields cause melanomas to self-destruct
DE602007006342D1 (de) * 2006-12-08 2010-06-17 Philips Intellectual Property System, verfahren und computerlesbares medium sowie verwendung zur programmierung einer kombinationstherapie
US20080200911A1 (en) * 2007-02-15 2008-08-21 Long Gary L Electrical ablation apparatus, system, and method
US7655004B2 (en) 2007-02-15 2010-02-02 Ethicon Endo-Surgery, Inc. Electroporation ablation apparatus, system, and method
US20080200762A1 (en) * 2007-02-16 2008-08-21 Stokes Michael J Flexible endoscope shapelock
US7815662B2 (en) 2007-03-08 2010-10-19 Ethicon Endo-Surgery, Inc. Surgical suture anchors and deployment device
US8075572B2 (en) 2007-04-26 2011-12-13 Ethicon Endo-Surgery, Inc. Surgical suturing apparatus
US8100922B2 (en) 2007-04-27 2012-01-24 Ethicon Endo-Surgery, Inc. Curved needle suturing tool
US20090054728A1 (en) * 2007-08-21 2009-02-26 Trusty Robert M Manipulatable guide system and methods for natural orifice translumenal endoscopic surgery
US8262655B2 (en) 2007-11-21 2012-09-11 Ethicon Endo-Surgery, Inc. Bipolar forceps
US8673623B2 (en) * 2007-08-31 2014-03-18 Board Of Regents, The University Of Texas System Apparatus for performing magnetic electroporation
US8579897B2 (en) 2007-11-21 2013-11-12 Ethicon Endo-Surgery, Inc. Bipolar forceps
US8568410B2 (en) 2007-08-31 2013-10-29 Ethicon Endo-Surgery, Inc. Electrical ablation surgical instruments
US20160184006A1 (en) * 2007-09-14 2016-06-30 Lazure Scientific, Inc. Ablation probe with deployable electrodes
US20090087900A1 (en) * 2007-09-28 2009-04-02 Kent Davey Apparatus for Performing Electrodistention on Algae Cells
US8480657B2 (en) 2007-10-31 2013-07-09 Ethicon Endo-Surgery, Inc. Detachable distal overtube section and methods for forming a sealable opening in the wall of an organ
US20090112059A1 (en) 2007-10-31 2009-04-30 Nobis Rudolph H Apparatus and methods for closing a gastrotomy
US20090177219A1 (en) * 2008-01-03 2009-07-09 Conlon Sean P Flexible tissue-penetration instrument with blunt tip assembly and methods for penetrating tissue
US8262680B2 (en) 2008-03-10 2012-09-11 Ethicon Endo-Surgery, Inc. Anastomotic device
US20100004623A1 (en) * 2008-03-27 2010-01-07 Angiodynamics, Inc. Method for Treatment of Complications Associated with Arteriovenous Grafts and Fistulas Using Electroporation
WO2012071526A2 (en) * 2010-11-23 2012-05-31 Virginia Tech Intellectual Properties, Inc. Irreversible electroporation using tissue vasculature to treat aberrant cell masses or create tissue scaffolds
WO2009137609A2 (en) 2008-05-06 2009-11-12 Cellutions, Inc. Apparatus and systems for treating a human tissue condition
US20090281559A1 (en) * 2008-05-06 2009-11-12 Ethicon Endo-Surgery, Inc. Anastomosis patch
US8114072B2 (en) 2008-05-30 2012-02-14 Ethicon Endo-Surgery, Inc. Electrical ablation device
US8317806B2 (en) 2008-05-30 2012-11-27 Ethicon Endo-Surgery, Inc. Endoscopic suturing tension controlling and indication devices
US8070759B2 (en) 2008-05-30 2011-12-06 Ethicon Endo-Surgery, Inc. Surgical fastening device
US8771260B2 (en) 2008-05-30 2014-07-08 Ethicon Endo-Surgery, Inc. Actuating and articulating surgical device
US8652150B2 (en) 2008-05-30 2014-02-18 Ethicon Endo-Surgery, Inc. Multifunction surgical device
US8679003B2 (en) 2008-05-30 2014-03-25 Ethicon Endo-Surgery, Inc. Surgical device and endoscope including same
US8906035B2 (en) 2008-06-04 2014-12-09 Ethicon Endo-Surgery, Inc. Endoscopic drop off bag
US8403926B2 (en) 2008-06-05 2013-03-26 Ethicon Endo-Surgery, Inc. Manually articulating devices
US8361112B2 (en) 2008-06-27 2013-01-29 Ethicon Endo-Surgery, Inc. Surgical suture arrangement
US20100010294A1 (en) * 2008-07-10 2010-01-14 Ethicon Endo-Surgery, Inc. Temporarily positionable medical devices
US20100010298A1 (en) * 2008-07-14 2010-01-14 Ethicon Endo-Surgery, Inc. Endoscopic translumenal flexible overtube
US8262563B2 (en) 2008-07-14 2012-09-11 Ethicon Endo-Surgery, Inc. Endoscopic translumenal articulatable steerable overtube
US8888792B2 (en) 2008-07-14 2014-11-18 Ethicon Endo-Surgery, Inc. Tissue apposition clip application devices and methods
US8211125B2 (en) 2008-08-15 2012-07-03 Ethicon Endo-Surgery, Inc. Sterile appliance delivery device for endoscopic procedures
US8529563B2 (en) * 2008-08-25 2013-09-10 Ethicon Endo-Surgery, Inc. Electrical ablation devices
US8241204B2 (en) 2008-08-29 2012-08-14 Ethicon Endo-Surgery, Inc. Articulating end cap
US8480689B2 (en) 2008-09-02 2013-07-09 Ethicon Endo-Surgery, Inc. Suturing device
US20100056862A1 (en) * 2008-09-03 2010-03-04 Ethicon Endo-Surgery, Inc. Access needle for natural orifice translumenal endoscopic surgery
US8409200B2 (en) 2008-09-03 2013-04-02 Ethicon Endo-Surgery, Inc. Surgical grasping device
US8114119B2 (en) 2008-09-09 2012-02-14 Ethicon Endo-Surgery, Inc. Surgical grasping device
US8337394B2 (en) 2008-10-01 2012-12-25 Ethicon Endo-Surgery, Inc. Overtube with expandable tip
CA2738471A1 (en) * 2008-10-01 2010-04-08 Chad Steelberg On-site barcode advertising
US8157834B2 (en) 2008-11-25 2012-04-17 Ethicon Endo-Surgery, Inc. Rotational coupling device for surgical instrument with flexible actuators
US8172772B2 (en) 2008-12-11 2012-05-08 Ethicon Endo-Surgery, Inc. Specimen retrieval device
US8828031B2 (en) 2009-01-12 2014-09-09 Ethicon Endo-Surgery, Inc. Apparatus for forming an anastomosis
US8361066B2 (en) * 2009-01-12 2013-01-29 Ethicon Endo-Surgery, Inc. Electrical ablation devices
US8252057B2 (en) 2009-01-30 2012-08-28 Ethicon Endo-Surgery, Inc. Surgical access device
US9226772B2 (en) 2009-01-30 2016-01-05 Ethicon Endo-Surgery, Inc. Surgical device
US8037591B2 (en) 2009-02-02 2011-10-18 Ethicon Endo-Surgery, Inc. Surgical scissors
US20100198248A1 (en) * 2009-02-02 2010-08-05 Ethicon Endo-Surgery, Inc. Surgical dissector
US20100249700A1 (en) * 2009-03-27 2010-09-30 Ethicon Endo-Surgery, Inc. Surgical instruments for in vivo assembly
JP2012521863A (ja) * 2009-03-31 2012-09-20 アンジオダイナミツクス・インコーポレイテツド 治療装置の治療領域推定およびインタラクティブな患者治療計画のためのシステムおよび方法
US10022202B2 (en) 2013-03-15 2018-07-17 Triagenics, Llc Therapeutic tooth bud ablation
US9402693B2 (en) 2009-05-11 2016-08-02 Triagenics, Llc Therapeutic tooth bud ablation
WO2014143014A1 (en) 2013-03-15 2014-09-18 Triagenics, Llc Therapeutic tooth bud ablation
WO2011028937A1 (en) * 2009-09-04 2011-03-10 The Regents Of The University Of California Extracellular matrix material created using non-thermal irreversible electroporation
US20110065161A1 (en) * 2009-09-14 2011-03-17 Board Of Regents, The University Of Texas System Bipolar solid state marx generator
US9775664B2 (en) 2009-09-22 2017-10-03 Mederi Therapeutics, Inc. Systems and methods for treating tissue with radiofrequency energy
US10386990B2 (en) 2009-09-22 2019-08-20 Mederi Rf, Llc Systems and methods for treating tissue with radiofrequency energy
US9750563B2 (en) 2009-09-22 2017-09-05 Mederi Therapeutics, Inc. Systems and methods for treating tissue with radiofrequency energy
US9474565B2 (en) 2009-09-22 2016-10-25 Mederi Therapeutics, Inc. Systems and methods for treating tissue with radiofrequency energy
US20110093009A1 (en) * 2009-10-16 2011-04-21 Ethicon Endo-Surgery, Inc. Otomy closure device
US20110098704A1 (en) 2009-10-28 2011-04-28 Ethicon Endo-Surgery, Inc. Electrical ablation devices
US8608652B2 (en) 2009-11-05 2013-12-17 Ethicon Endo-Surgery, Inc. Vaginal entry surgical devices, kit, system, and method
US20110118729A1 (en) * 2009-11-13 2011-05-19 Alcon Research, Ltd High-intensity pulsed electric field vitrectomy apparatus with load detection
US20110118734A1 (en) * 2009-11-16 2011-05-19 Alcon Research, Ltd. Capsularhexis device using pulsed electric fields
US20110135626A1 (en) * 2009-12-08 2011-06-09 Alcon Research, Ltd. Localized Chemical Lysis of Ocular Tissue
US20110144562A1 (en) * 2009-12-14 2011-06-16 Alcon Research, Ltd. Localized Pharmacological Treatment of Ocular Tissue Using High-Intensity Pulsed Electrical Fields
WO2011081897A1 (en) * 2009-12-15 2011-07-07 Alcon Research, Ltd. High-intensity pulsed electric field vitrectomy apparatus
US8496574B2 (en) 2009-12-17 2013-07-30 Ethicon Endo-Surgery, Inc. Selectively positionable camera for surgical guide tube assembly
US8353487B2 (en) 2009-12-17 2013-01-15 Ethicon Endo-Surgery, Inc. User interface support devices for endoscopic surgical instruments
US9028483B2 (en) 2009-12-18 2015-05-12 Ethicon Endo-Surgery, Inc. Surgical instrument comprising an electrode
US8506564B2 (en) 2009-12-18 2013-08-13 Ethicon Endo-Surgery, Inc. Surgical instrument comprising an electrode
US9005198B2 (en) 2010-01-29 2015-04-14 Ethicon Endo-Surgery, Inc. Surgical instrument comprising an electrode
US20110202052A1 (en) * 2010-02-12 2011-08-18 Daniel Gelbart System for treating benign prostatic hyperplasia
KR20130108067A (ko) 2010-04-09 2013-10-02 베식스 바스큘라 인코포레이티드 조직 치료를 위한 발전 및 제어 장치
GB201006841D0 (en) * 2010-04-26 2010-06-09 Thomsen Lars Method, device and system for targetted cell lysis
US8546979B2 (en) 2010-08-11 2013-10-01 Alcon Research, Ltd. Self-matching pulse generator with adjustable pulse width and pulse frequency
US8652130B2 (en) * 2010-08-18 2014-02-18 Invasix Ltd. Method and device for soft tissue ablation
US10092291B2 (en) 2011-01-25 2018-10-09 Ethicon Endo-Surgery, Inc. Surgical instrument with selectively rigidizable features
US9233241B2 (en) 2011-02-28 2016-01-12 Ethicon Endo-Surgery, Inc. Electrical ablation devices and methods
US9254169B2 (en) 2011-02-28 2016-02-09 Ethicon Endo-Surgery, Inc. Electrical ablation devices and methods
US9314620B2 (en) 2011-02-28 2016-04-19 Ethicon Endo-Surgery, Inc. Electrical ablation devices and methods
US9049987B2 (en) 2011-03-17 2015-06-09 Ethicon Endo-Surgery, Inc. Hand held surgical device for manipulating an internal magnet assembly within a patient
US10813630B2 (en) 2011-08-09 2020-10-27 Corquest Medical, Inc. Closure system for atrial wall
US10307167B2 (en) 2012-12-14 2019-06-04 Corquest Medical, Inc. Assembly and method for left atrial appendage occlusion
US10314594B2 (en) 2012-12-14 2019-06-11 Corquest Medical, Inc. Assembly and method for left atrial appendage occlusion
US8986199B2 (en) 2012-02-17 2015-03-24 Ethicon Endo-Surgery, Inc. Apparatus and methods for cleaning the lens of an endoscope
WO2013167952A1 (en) * 2012-05-07 2013-11-14 The University Of Ottawa Method for controlling the size of solid-state nanopores
US9427255B2 (en) 2012-05-14 2016-08-30 Ethicon Endo-Surgery, Inc. Apparatus for introducing a steerable camera assembly into a patient
CA3158197A1 (en) 2012-05-29 2013-12-05 Autonomix Medical, Inc. Endoscopic sympathectomy systems and methods
US9078662B2 (en) 2012-07-03 2015-07-14 Ethicon Endo-Surgery, Inc. Endoscopic cap electrode and method for using the same
US9545290B2 (en) 2012-07-30 2017-01-17 Ethicon Endo-Surgery, Inc. Needle probe guide
US9572623B2 (en) 2012-08-02 2017-02-21 Ethicon Endo-Surgery, Inc. Reusable electrode and disposable sheath
US10314649B2 (en) 2012-08-02 2019-06-11 Ethicon Endo-Surgery, Inc. Flexible expandable electrode and method of intraluminal delivery of pulsed power
JP6301926B2 (ja) 2012-08-09 2018-03-28 ユニバーシティ オブ アイオワ リサーチ ファウンデーション カテーテル、カテーテルシステム、及び組織構造を刺通する方法
US9277957B2 (en) 2012-08-15 2016-03-08 Ethicon Endo-Surgery, Inc. Electrosurgical devices and methods
US9113911B2 (en) * 2012-09-06 2015-08-25 Medtronic Ablation Frontiers Llc Ablation device and method for electroporating tissue cells
US10080907B1 (en) 2012-10-26 2018-09-25 University Of South Florida Systems and methods for controlling the spatial distribution of an electromagnetic field
US20140142689A1 (en) 2012-11-21 2014-05-22 Didier De Canniere Device and method of treating heart valve malfunction
US10098527B2 (en) 2013-02-27 2018-10-16 Ethidcon Endo-Surgery, Inc. System for performing a minimally invasive surgical procedure
US9438264B1 (en) 2015-09-10 2016-09-06 Realtek Semiconductor Corp. High-speed capacitive digital-to-analog converter and method thereof
US10154869B2 (en) 2013-08-02 2018-12-18 Gary M. Onik System and method for creating radio-frequency energy electrical membrane breakdown for tissue ablation
US10709491B2 (en) 2013-08-06 2020-07-14 Memorial Sloan-Kettering Cancer Center System, method and computer-accessible medium for in-vivo tissue ablation and/or damage
WO2015073877A1 (en) 2013-11-14 2015-05-21 Paul Mikus Methods, systems, and apparatuses for delivery of electrolysis products
US9566443B2 (en) 2013-11-26 2017-02-14 Corquest Medical, Inc. System for treating heart valve malfunction including mitral regurgitation
JP6723153B2 (ja) 2013-12-05 2020-07-15 アールエフイーエムビー ホールディングス リミテッド ライアビリティ カンパニー 生体内の望ましくない軟部組織を切除するシステム
US10314648B2 (en) 2013-12-13 2019-06-11 The Trustees of the Universoty of Pennsylvania Coaxial ablation probe and method and system for real-time monitoring of ablation therapy
WO2015103574A1 (en) 2014-01-06 2015-07-09 Iowa Approach Inc. Apparatus and methods for renal denervation ablation
US20150289923A1 (en) * 2014-04-14 2015-10-15 Virginia Tech Intellectual Properties, Inc. Treatment planning for electrical-energy based therapies based on cell characteristics
EP4238521B1 (en) 2014-05-07 2025-10-15 Boston Scientific Scimed, Inc. Apparatus for selective tissue ablation
WO2015175944A1 (en) 2014-05-16 2015-11-19 Gary Long Methods and apparatus for multi-catheter tissue ablation
WO2015192018A1 (en) 2014-06-12 2015-12-17 Iowa Approach Inc. Method and apparatus for rapid and selective tissue ablation with cooling
WO2015192027A1 (en) 2014-06-12 2015-12-17 Iowa Approach Inc. Method and apparatus for rapid and selective transurethral tissue ablation
WO2016060983A1 (en) 2014-10-14 2016-04-21 Iowa Approach Inc. Method and apparatus for rapid and safe pulmonary vein cardiac ablation
US10835311B2 (en) 2014-10-24 2020-11-17 Northwestern University Electroporation apparatus and method of using same for ablation of an arbitrary volume
US10842626B2 (en) 2014-12-09 2020-11-24 Didier De Canniere Intracardiac device to correct mitral regurgitation
KR102128856B1 (ko) 2015-01-30 2020-07-02 알에프이엠비 홀딩스, 엘엘씨 고주파 전기적 막 파괴를 이용하여 생명체의 바람직하지 않은 연조직을 절제하는 시스템
US20180021084A1 (en) * 2015-02-04 2018-01-25 Rfemb Holdings, Llc Radio-frequency electrical membrane breakdown for reducing restenosis
WO2016130385A2 (en) * 2015-02-10 2016-08-18 George Mbella Ekema Tissue ablation by rapid and sustained alteration in membrane potential
EP3282953A4 (en) * 2015-04-10 2019-04-17 AngioDynamics, Inc. SYSTEM AND METHOD FOR IRREVERSIBLE ELECTROPORATION WITH THERMALLY CONTROLLED ELECTRODES
US10939949B2 (en) 2015-05-01 2021-03-09 Inter Science Gmbh Methods, systems, and apparatuses for tissue ablation using pulse shape designs
WO2016201264A1 (en) * 2015-06-11 2016-12-15 Massachusetts Institute Of Technology Methods for inducing electroporation and tissue ablation
CA3000878A1 (en) 2015-10-07 2017-04-13 Mayo Foundation For Medical Education And Research Electroporation for obesity or diabetes treatment
US20170189097A1 (en) 2016-01-05 2017-07-06 Iowa Approach Inc. Systems, apparatuses and methods for delivery of ablative energy to tissue
US10172673B2 (en) 2016-01-05 2019-01-08 Farapulse, Inc. Systems devices, and methods for delivery of pulsed electric field ablative energy to endocardial tissue
US10660702B2 (en) 2016-01-05 2020-05-26 Farapulse, Inc. Systems, devices, and methods for focal ablation
US12144541B2 (en) 2016-01-05 2024-11-19 Boston Scientific Scimed, Inc. Systems, apparatuses and methods for delivery of ablative energy to tissue
US10130423B1 (en) 2017-07-06 2018-11-20 Farapulse, Inc. Systems, devices, and methods for focal ablation
EP3402517B1 (en) 2016-01-15 2025-08-20 RFEMB Holdings, LLC Immunologic treatment of cancer by using a tumor ablation technic together with a combination of a ctla-4 inhibitor, a pd-1 inhibitor and gm-csf
EP3471631A4 (en) 2016-06-16 2020-03-04 Farapulse, Inc. Systems, apparatuses, and methods for guide wire delivery
JP7158820B2 (ja) * 2016-10-26 2022-10-24 ロレアル エレクトロポレーションデバイスおよびエレクトロポレーションデバイスを制御するための方法
US11432871B2 (en) 2017-04-10 2022-09-06 St. Jude Medical, Cardiology Division, Inc. Electroporation system and method of preconditioning tissue for electroporation therapy
US9987081B1 (en) 2017-04-27 2018-06-05 Iowa Approach, Inc. Systems, devices, and methods for signal generation
US10617867B2 (en) 2017-04-28 2020-04-14 Farapulse, Inc. Systems, devices, and methods for delivery of pulsed electric field ablative energy to esophageal tissue
EP3681391A1 (en) 2017-09-12 2020-07-22 Farapulse, Inc. Systems, apparatuses, and methods for ventricular focal ablation
US11045648B2 (en) 2017-11-14 2021-06-29 Boston Scientific Scimed, Inc. Irreversible electroporation through a combination of substance injection and electrical field application
WO2019147619A1 (en) 2018-01-23 2019-08-01 Boston Scientific Scimed, Inc. Enhanced needle array and therapies for tumor ablation
WO2019157359A1 (en) 2018-02-08 2019-08-15 Farapulse, Inc. Method and apparatus for controlled delivery of pulsed electric field ablative energy to tissue
JP7043317B2 (ja) * 2018-03-29 2022-03-29 富士フイルムヘルスケア株式会社 医療システム
US11007317B2 (en) 2018-05-02 2021-05-18 Cequr Sa Devices and methods for providing a bolus dose in a microfluidic circuit of a pump
US20190336198A1 (en) 2018-05-03 2019-11-07 Farapulse, Inc. Systems, devices, and methods for ablation using surgical clamps
EP3790486A1 (en) 2018-05-07 2021-03-17 Farapulse, Inc. Systems, apparatuses and methods for delivery of ablative energy to tissue
EP3790485B1 (en) 2018-05-07 2024-06-26 Boston Scientific Scimed, Inc. Epicardial ablation catheter
CN112118798B (zh) 2018-05-07 2024-09-20 波士顿科学医学有限公司 用于过滤由脉冲电场消融诱导的高压噪声的系统、设备和方法
CN108830017B (zh) * 2018-07-05 2022-06-24 上海美杰医疗科技有限公司 基于个体阻抗的射频加热温度场预测系统
EP3846724A4 (en) 2018-09-04 2022-05-11 Inter Science GmbH METHODS, SYSTEMS AND DEVICES FOR TISSUE ABLATION USING A MODULATED EXPONENTIAL OUTLET PULSE
EP3852661A1 (en) 2018-09-20 2021-07-28 Farapulse, Inc. Systems, apparatuses, and methods for delivery of pulsed electric field ablative energy to endocardial tissue
ES2949058T3 (es) 2018-11-05 2023-09-25 Region Hovedstaden V/Herlev Hospital Un conjunto de electrodos para mejorar la distribución del campo eléctrico
WO2020150255A1 (en) 2019-01-14 2020-07-23 Cryoelectric Science Ltd. Methods, systems, and apparatuses for cryosurgery, coldsurgery, and electrolysis
US20200277379A1 (en) 2019-03-01 2020-09-03 Rampart Health, L.L.C. Pharmaceutical composition combining immunologic and chemotherapeutic method for the treatment of cancer
CN113853174B (zh) 2019-03-15 2024-10-11 波士顿科学国际有限公司 用于选择性细胞消融的时间多路复用波形
JP7402889B2 (ja) * 2019-03-15 2023-12-21 ボストン サイエンティフィック サイムド，インコーポレイテッド 選択的細胞切除のための空間多重化波形
EP3937812B1 (en) 2019-03-15 2025-04-23 Boston Scientific Scimed, Inc. Waveform generator and control for selective cell ablation
EP3979938B1 (en) 2019-06-06 2024-07-24 TriAgenics, Inc. Ablation probe systems
US10625080B1 (en) 2019-09-17 2020-04-21 Farapulse, Inc. Systems, apparatuses, and methods for detecting ectopic electrocardiogram signals during pulsed electric field ablation
CN114945338A (zh) 2019-10-15 2022-08-26 波士顿科学国际有限公司 用于消融系统的控制系统和用户界面
CN114786605A (zh) 2019-10-21 2022-07-22 英杜基奈克斯公司 用于十二指肠脉冲电场治疗的装置、系统和方法
US11065047B2 (en) 2019-11-20 2021-07-20 Farapulse, Inc. Systems, apparatuses, and methods for protecting electronic components from high power noise induced by high voltage pulses
US11497541B2 (en) 2019-11-20 2022-11-15 Boston Scientific Scimed, Inc. Systems, apparatuses, and methods for protecting electronic components from high power noise induced by high voltage pulses
US10842572B1 (en) 2019-11-25 2020-11-24 Farapulse, Inc. Methods, systems, and apparatuses for tracking ablation devices and generating lesion lines
US11540877B2 (en) 2019-12-03 2023-01-03 Biosense Webster (Israel) Ltd. Pulse generator for irreversible electroporation
US12102374B2 (en) 2019-12-03 2024-10-01 Biosense Webster (Israel) Ltd. Pulse generator for irreversible electroporation with switchable pulse application
US11660135B2 (en) 2019-12-05 2023-05-30 Biosense Webster (Israel) Ltd. Generating and interleaving of irreversible-electroporation and radiofrequnecy ablation (IRE/RFA) waveforms
US12042216B2 (en) 2019-12-09 2024-07-23 Biosense Webster (Israel) Ltd. Irreversible-electroporation (IRE) balloon catheter with membrane-insulated high-voltage balloon wires
US11903638B2 (en) 2019-12-11 2024-02-20 Biosense Webster (Israel) Ltd. Regulating delivery of irreversible electroporation pulses according to transferred energy
US11707320B2 (en) 2019-12-24 2023-07-25 Biosense Webster (Israel) Ltd. Irreversible electroporation (IRE) based on field, contact force and time
US11583332B2 (en) 2019-12-24 2023-02-21 Biosense Webster (Israel) Ltd. Combined cardiac pacing and irreversible electroporation (IRE) treatment
US11992260B2 (en) 2020-03-31 2024-05-28 Boston Scientific Scimed, Inc. Smart probe identification for ablation modalities
US12285206B2 (en) 2020-06-01 2025-04-29 Biosense Webster (Israel) Ltd. Application of irreversible electroporation (IRE) ablation using catheter with electrode array
US11794004B2 (en) 2020-06-10 2023-10-24 Biosense Webster (Israel) Ltd. Electroporation with cooling
US12349962B2 (en) 2020-07-13 2025-07-08 Biosense Webster (Israel) Ltd. Sequential activation of electrode-pairs during irreversible electroporation (IRE)
CN116209406A (zh) 2020-07-24 2023-06-02 波士顿科学医学有限公司 不可逆电穿孔单次心脏消融的电场应用
US12310652B2 (en) 2020-07-24 2025-05-27 Boston Scientific Scimed, Inc. Hybrid electroporation ablation catheter
US11819265B2 (en) 2020-07-28 2023-11-21 Biosense Webster (Israel) Ltd. Cautious irreversible-electroporation (IRE) protocol for avoiding bubble generation
US12426944B2 (en) 2020-07-28 2025-09-30 Biosense Webster (Israel) Ltd. Automatically performing irreversible electroporation ablation during heart refractory period
US12076071B2 (en) 2020-08-14 2024-09-03 Kardium Inc. Systems and methods for treating tissue with pulsed field ablation
US11532082B2 (en) 2020-08-31 2022-12-20 Biosense Webster (Israel) Ltd. Real-time correction of anatomical maps
JP7617250B2 (ja) 2020-09-08 2025-01-17 ボストン サイエンティフィック サイムド，インコーポレイテッド パルス電界アブレーションのための輪郭成形電極、ならびにそのシステム、デバイス、および方法
WO2022072385A2 (en) 2020-09-30 2022-04-07 Boston Scientific Scimed Inc Pretreatment waveform for irreversible electroporation
US12290306B2 (en) 2020-10-19 2025-05-06 Biosense Webster (Israel) Ltd. Using unipolar configuration for irreversible-electroporation (IRE)
AU2020475251C1 (en) 2020-10-26 2024-09-19 TriAgenics, Inc. Ablation probe systems
US11911096B2 (en) 2020-12-17 2024-02-27 Biosense Webster (Israel) Ltd. Detecting contact and proximity between ablation electrodes by sensing changes in voltage morphology of non-activated electrodes
EP4284276A1 (en) 2021-01-27 2023-12-06 Boston Scientific Scimed, Inc. Voltage controlled pulse sequences for irreversible electroporation ablations
JP2024506914A (ja) 2021-02-12 2024-02-15 ランパート ヘルス リミテッド ライアビリティー カンパニー がんの処置のための多重免疫療法とがんワクチンとを組み合わせた治療用組成物及び方法
AU2022254861B2 (en) 2021-04-07 2024-01-18 Btl Medical Development A.S. Pulsed field ablation device and method
US20220361944A1 (en) 2021-05-17 2022-11-17 Boston Scientific Scimed, Inc. Energy Delivery System, Method and Device
HRP20250794T1 (hr) 2021-07-06 2025-08-29 Btl Medical Development A.S. Uređaj za ablaciju pulsnim poljem
EP4436506A1 (en) 2021-11-29 2024-10-02 Boston Scientific Scimed Inc. Bipolar needle with adjustable electrode for geometrically controlled thermal ablation of biological tissue
WO2023161796A1 (en) * 2022-02-23 2023-08-31 Cochlear Limited Adaptive electroporation
IT202200019635A1 (it) 2022-09-23 2024-03-23 Igea S P A Dispositivo per l'elettroporazione migliorato
EP4598461A1 (en) 2022-10-05 2025-08-13 BTL Medical Development A.S. Pulsed field ablation device and method
US12484963B2 (en) 2024-04-03 2025-12-02 Field Medical, Inc. Systems and methods for affecting a target tissue via a pulsed field

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6010613A (en) * 1995-12-08 2000-01-04 Cyto Pulse Sciences, Inc. Method of treating materials with pulsed electrical fields
US6278895B1 (en) * 1997-04-24 2001-08-21 Ichor Medical Systems, Inc. Electrodes and electrode arrays for generating electroporation inducing electrical fields
US6387671B1 (en) * 1999-07-21 2002-05-14 The Regents Of The University Of California Electrical impedance tomography to control electroporation
US20040019371A1 (en) * 2001-02-08 2004-01-29 Ali Jaafar Apparatus and method for reducing subcutaneous fat deposits, virtual face lift and body sculpturing by electroporation
US6697670B2 (en) * 2001-08-17 2004-02-24 Minnesota Medical Physics, Llc Apparatus and method for reducing subcutaneous fat deposits by electroporation with improved comfort of patients
US6795728B2 (en) * 2001-08-17 2004-09-21 Minnesota Medical Physics, Llc Apparatus and method for reducing subcutaneous fat deposits by electroporation
US20060025760A1 (en) * 2002-05-06 2006-02-02 Podhajsky Ronald J Blood detector for controlling anesu and method therefor

Family Cites Families (146)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1653819A (en) 1926-08-07 1927-12-27 Northcott Ephraim Electrotherapeutical apparatus
DE863111C (de) 1951-07-03 1953-01-15 Walter Hallegger Instrument zur transkutanen und subkutanen Erwaermung und Iontophorese und Verfahrenzu seiner Anwendung
US4016886A (en) 1974-11-26 1977-04-12 The United States Of America As Represented By The United States Energy Research And Development Administration Method for localizing heating in tumor tissue
US4407943A (en) 1976-12-16 1983-10-04 Millipore Corporation Immobilized antibody or antigen for immunoassay
CH617590A5 (enExample) 1977-05-27 1980-06-13 Carba Ag
DE2800039C2 (de) 1978-01-02 1984-06-20 Horst Dr.Med. 6700 Ludwigshafen Kief Akupunkturgerät
US5385544A (en) 1992-08-12 1995-01-31 Vidamed, Inc. BPH ablation method and apparatus
US5370675A (en) 1992-08-12 1994-12-06 Vidamed, Inc. Medical probe device and method
GB8408529D0 (en) 1984-04-03 1984-05-16 Health Lab Service Board Concentration of biological particles
US4946793A (en) 1986-05-09 1990-08-07 Electropore, Inc. Impedance matching for instrumentation which electrically alters vesicle membranes
US5098843A (en) 1987-06-04 1992-03-24 Calvin Noel M Apparatus for the high efficiency transformation of living cells
US5389069A (en) 1988-01-21 1995-02-14 Massachusetts Institute Of Technology Method and apparatus for in vivo electroporation of remote cells and tissue
DE68925030T2 (de) 1988-01-21 1996-07-25 Massachusetts Inst Technology Molekültransport durch gewebe mit der verwendung von elektroporation.
US5749847A (en) 1988-01-21 1998-05-12 Massachusetts Institute Of Technology Delivery of nucleotides into organisms by electroporation
EP0346513A1 (de) 1988-06-15 1989-12-20 Etama Ag Anordnung zur Elektrotherapie
ES2012944A6 (es) 1989-01-09 1990-04-16 Tomas Justribo Jose Ramon Procedimiento y su dispositivo para la admionistracion de farmacos mediante ionoforesis, para tratamiento loco-regionales.
CS275292B2 (en) 1989-02-22 1992-02-19 Cvut Fakulta Elektrotechnick Private rehabilitation apparatus with ion transcutaneous acceleration
DE4000893A1 (de) 1990-01-15 1991-07-18 Bosch Gmbh Robert Mehrkanaliges geraet zur elektrostimulation
US5134070A (en) 1990-06-04 1992-07-28 Casnig Dael R Method and device for cell cultivation on electrodes
US5193537A (en) 1990-06-12 1993-03-16 Zmd Corporation Method and apparatus for transcutaneous electrical cardiac pacing
US5052391A (en) 1990-10-22 1991-10-01 R.F.P., Inc. High frequency high intensity transcutaneous electrical nerve stimulator and method of treatment
US5990095A (en) 1991-07-03 1999-11-23 Hyal Pharmaceutical Corporation Use of hyaluronic acid and forms to prevent arterial restenosis
US5173158A (en) 1991-07-22 1992-12-22 Schmukler Robert E Apparatus and methods for electroporation and electrofusion
US5328451A (en) 1991-08-15 1994-07-12 Board Of Regents, The University Of Texas System Iontophoretic device and method for killing bacteria and other microbes
US5425752A (en) 1991-11-25 1995-06-20 Vu'nguyen; Dung D. Method of direct electrical myostimulation using acupuncture needles
US6210402B1 (en) 1995-11-22 2001-04-03 Arthrocare Corporation Methods for electrosurgical dermatological treatment
US6500173B2 (en) * 1992-01-07 2002-12-31 Ronald A. Underwood Methods for electrosurgical spine surgery
US6132419A (en) 1992-05-22 2000-10-17 Genetronics, Inc. Electroporetic gene and drug therapy
US5318563A (en) 1992-06-04 1994-06-07 Valley Forge Scientific Corporation Bipolar RF generator
US5549644A (en) 1992-08-12 1996-08-27 Vidamed, Inc. Transurethral needle ablation device with cystoscope and method for treatment of the prostate
US5273525A (en) 1992-08-13 1993-12-28 Btx Inc. Injection and electroporation apparatus for drug and gene delivery
US5634899A (en) 1993-08-20 1997-06-03 Cortrak Medical, Inc. Simultaneous cardiac pacing and local drug delivery method
US5807306A (en) 1992-11-09 1998-09-15 Cortrak Medical, Inc. Polymer matrix drug delivery apparatus
GB9226376D0 (en) 1992-12-18 1993-02-10 British Tech Group Tomography
US5792187A (en) 1993-02-22 1998-08-11 Angeion Corporation Neuro-stimulation to control pain during cardioversion defibrillation
US5403311A (en) 1993-03-29 1995-04-04 Boston Scientific Corporation Electro-coagulation and ablation and other electrotherapeutic treatments of body tissue
FR2703253B1 (fr) 1993-03-30 1995-06-23 Centre Nat Rech Scient Applicateur d'impulsions electriques pour traitement de tissus biologiques.
US5702359A (en) 1995-06-06 1997-12-30 Genetronics, Inc. Needle electrodes for mediated delivery of drugs and genes
US5439440A (en) 1993-04-01 1995-08-08 Genetronics, Inc. Electroporation system with voltage control feedback for clinical applications
US6832996B2 (en) 1995-06-07 2004-12-21 Arthrocare Corporation Electrosurgical systems and methods for treating tissue
US5464437A (en) 1993-07-08 1995-11-07 Urologix, Inc. Benign prostatic hyperplasia treatment catheter with urethral cooling
US5533999A (en) 1993-08-23 1996-07-09 Refractec, Inc. Method and apparatus for modifications of visual acuity by thermal means
JP3054319B2 (ja) * 1994-03-04 2000-06-19 矢崎総業株式会社 防水ゴム栓およびその製造方法
US5458625A (en) 1994-05-04 1995-10-17 Kendall; Donald E. Transcutaneous nerve stimulation device and method for using same
US5836905A (en) 1994-06-20 1998-11-17 Lemelson; Jerome H. Apparatus and methods for gene therapy
ATE182478T1 (de) 1995-01-17 1999-08-15 Christoph Hehrlein Ballon-katheter zur verhinderung der re-stenose nach angioplastie, und verfahren zum herstellen eines ballon-katheters
US5720921A (en) 1995-03-10 1998-02-24 Entremed, Inc. Flow electroporation chamber and method
US5810762A (en) 1995-04-10 1998-09-22 Genetronics, Inc. Electroporation system with voltage control feedback for clinical applications
US6041252A (en) 1995-06-07 2000-03-21 Ichor Medical Systems Inc. Drug delivery system and method
US6607529B1 (en) 1995-06-19 2003-08-19 Medtronic Vidamed, Inc. Electrosurgical device
US5919142A (en) 1995-06-22 1999-07-06 Btg International Limited Electrical impedance tomography method and apparatus
US5983131A (en) 1995-08-11 1999-11-09 Massachusetts Institute Of Technology Apparatus and method for electroporation of tissue
EP0776678A1 (en) 1995-11-30 1997-06-04 Hewlett-Packard Company System for administering transcutaneous cardiac pacing with transcutaneous electrical nerve stimuli
US5718246A (en) * 1996-01-03 1998-02-17 Preferential, Inc. Preferential induction of electrically mediated cell death from applied pulses
US6090106A (en) 1996-01-09 2000-07-18 Gyrus Medical Limited Electrosurgical instrument
US6016452A (en) 1996-03-19 2000-01-18 Kasevich; Raymond S. Dynamic heating method and radio frequency thermal treatment
US5778894A (en) 1996-04-18 1998-07-14 Elizabeth Arden Co. Method for reducing human body cellulite by treatment with pulsed electromagnetic energy
SE509241C2 (sv) 1996-07-18 1998-12-21 Radinvent Ab Anordningar för elektrodynamisk strålterapi av tumörsjukdomar
US6102885A (en) 1996-08-08 2000-08-15 Bass; Lawrence S. Device for suction-assisted lipectomy and method of using same
US6106521A (en) 1996-08-16 2000-08-22 United States Surgical Corporation Apparatus for thermal treatment of tissue
US5991697A (en) 1996-12-31 1999-11-23 The Regents Of The University Of California Method and apparatus for optical Doppler tomographic imaging of fluid flow velocity in highly scattering media
WO1998033451A1 (en) 1997-02-04 1998-08-06 National Aeronautics And Space Administration Multimodality instrument for tissue characterization
JPH10243947A (ja) * 1997-03-04 1998-09-14 Olympus Optical Co Ltd 高周波装置
US6085115A (en) 1997-05-22 2000-07-04 Massachusetts Institite Of Technology Biopotential measurement including electroporation of tissue surface
US5978704A (en) 1997-06-03 1999-11-02 Uab Research Foundation Method and apparatus for treating cardiac arrhythmia
US6055453A (en) 1997-08-01 2000-04-25 Genetronics, Inc. Apparatus for addressing needle array electrodes for electroporation therapy
US6216034B1 (en) 1997-08-01 2001-04-10 Genetronics, Inc. Method of programming an array of needle electrodes for electroporation therapy of tissue
US6043066A (en) * 1997-09-04 2000-03-28 Mangano; Joseph A. Cell separation using electric fields
US5999847A (en) 1997-10-21 1999-12-07 Elstrom; John A. Apparatus and method for delivery of surgical and therapeutic agents
AU1114699A (en) 1997-10-24 1999-05-17 Children's Medical Center Corporation Methods for promoting cell transfection (in vivo)
US6009347A (en) 1998-01-27 1999-12-28 Genetronics, Inc. Electroporation apparatus with connective electrode template
US6208893B1 (en) * 1998-01-27 2001-03-27 Genetronics, Inc. Electroporation apparatus with connective electrode template
US6440127B2 (en) 1998-02-11 2002-08-27 Cosman Company, Inc. Method for performing intraurethral radio-frequency urethral enlargement
CA2229528A1 (en) 1998-02-13 1999-08-13 Shailesh Mehta Apparatus and method for analyzing particles
SE513814C2 (sv) 1998-03-31 2000-11-06 Aditus Medical Ab Anordning för behandling av sjukdomar med elektriska fält
US6219577B1 (en) 1998-04-14 2001-04-17 Global Vascular Concepts, Inc. Iontophoresis, electroporation and combination catheters for local drug delivery to arteries and other body tissues
US6159163A (en) 1998-05-07 2000-12-12 Cedars-Sinai Medical Center System for attenuating pain during bone marrow aspiration and method
AU3973599A (en) 1998-05-08 1999-11-29 Genetronics, Inc. Electrically induced vessel vasodilation
US6697669B2 (en) 1998-07-13 2004-02-24 Genetronics, Inc. Skin and muscle-targeted gene therapy by pulsed electrical field
US6212433B1 (en) 1998-07-28 2001-04-03 Radiotherapeutics Corporation Method for treating tumors near the surface of an organ
CA2346055C (en) 1998-09-30 2004-06-29 Cygnus, Inc. Method and device for predicting physiological values
US6846668B1 (en) 1998-10-08 2005-01-25 Astrazeneca Ab Microfabricated cell injector
US6611706B2 (en) 1998-11-09 2003-08-26 Transpharma Ltd. Monopolar and bipolar current application for transdermal drug delivery and analyte extraction
DE69924750T2 (de) 1998-11-16 2006-03-02 United States Surgical Corp., Norwalk Gerät zur thermischen behandlung von gewebe
US6090016A (en) * 1998-11-18 2000-07-18 Kuo; Hai Pin Collapsible treader with enhanced stability
US6351674B2 (en) 1998-11-23 2002-02-26 Synaptic Corporation Method for inducing electroanesthesia using high frequency, high intensity transcutaneous electrical nerve stimulation
US6477410B1 (en) * 2000-05-31 2002-11-05 Biophoretic Therapeutic Systems, Llc Electrokinetic delivery of medicaments
US6261831B1 (en) 1999-03-26 2001-07-17 The United States Of America As Represented By The Secretary Of The Air Force Ultra-wide band RF-enhanced chemotherapy for cancer treatmeat
US6738663B2 (en) 1999-04-09 2004-05-18 Oncostim, A Minnesota Corporation Implantable device and method for the electrical treatment of cancer
US7412285B2 (en) 1999-04-09 2008-08-12 Oncostim, Inc. Method and device for treating cancer with electrical therapy in conjunction with chemotherapeutic agents and radiation therapy
US6627421B1 (en) 1999-04-13 2003-09-30 Imarx Therapeutics, Inc. Methods and systems for applying multi-mode energy to biological samples
US6403348B1 (en) 1999-07-21 2002-06-11 The Regents Of The University Of California Controlled electroporation and mass transfer across cell membranes
US7053063B2 (en) 1999-07-21 2006-05-30 The Regents Of The University Of California Controlled electroporation and mass transfer across cell membranes in tissue
US6300108B1 (en) 1999-07-21 2001-10-09 The Regents Of The University Of California Controlled electroporation and mass transfer across cell membranes
US6927049B2 (en) 1999-07-21 2005-08-09 The Regents Of The University Of California Cell viability detection using electrical measurements
US20020010491A1 (en) 1999-08-04 2002-01-24 Schoenbach Karl H. Method and apparatus for intracellular electro-manipulation
US6326177B1 (en) 1999-08-04 2001-12-04 Eastern Virginia Medical School Of The Medical College Of Hampton Roads Method and apparatus for intracellular electro-manipulation
US20030078499A1 (en) 1999-08-12 2003-04-24 Eppstein Jonathan A. Microporation of tissue for delivery of bioactive agents
US6613211B1 (en) 1999-08-27 2003-09-02 Aclara Biosciences, Inc. Capillary electrokinesis based cellular assays
JP4676042B2 (ja) * 1999-10-01 2011-04-27 帝國製薬株式会社 フェルビナク含有鎮痛・消炎外用貼付剤
US6493592B1 (en) 1999-12-01 2002-12-10 Vertis Neuroscience, Inc. Percutaneous electrical therapy system with electrode position maintenance
IT1320186B1 (it) 2000-04-21 2003-11-26 Igea Srl Dispositivo e metodo di elettro-porazione in cui l'ampiezzadell'impulso o degli impulsi viene stabilita in modo automatico in
US20010044596A1 (en) 2000-05-10 2001-11-22 Ali Jaafar Apparatus and method for treatment of vascular restenosis by electroporation
KR100375657B1 (ko) 2000-06-21 2003-03-15 주식회사 몸앤맘 체지방 제거장치 및 방법
US6669691B1 (en) 2000-07-18 2003-12-30 Scimed Life Systems, Inc. Epicardial myocardial revascularization and denervation methods and apparatus
US6962587B2 (en) 2000-07-25 2005-11-08 Rita Medical Systems, Inc. Method for detecting and treating tumors using localized impedance measurement
US6702808B1 (en) 2000-09-28 2004-03-09 Syneron Medical Ltd. Device and method for treating skin
US20020133324A1 (en) * 2000-11-03 2002-09-19 Weaver James C. Functional simulation method
WO2003099382A1 (en) * 2002-05-23 2003-12-04 Gendel Limited Ablation device
US20050043726A1 (en) 2001-03-07 2005-02-24 Mchale Anthony Patrick Device II
US20020177847A1 (en) * 2001-03-30 2002-11-28 Long Gary L. Endoscopic ablation system with flexible coupling
EP2341148A3 (en) 2001-04-12 2012-05-30 Imperial Innovations Limited Diagnosis and treatment of cancer
WO2002087692A1 (en) 2001-04-26 2002-11-07 The Procter & Gamble Company A method and apparatus for the treatment of cosmetic skin conditioins
CN100518685C (zh) * 2001-05-10 2009-07-29 脉管动力股份有限公司 组织消融设备
JP2002360712A (ja) * 2001-06-06 2002-12-17 Komatsu Powertron Kk 生体用誘導加熱方法及びその装置
US7127284B2 (en) * 2001-06-11 2006-10-24 Mercator Medsystems, Inc. Electroporation microneedle and methods for its use
US6832111B2 (en) 2001-07-06 2004-12-14 Hosheng Tu Device for tumor diagnosis and methods thereof
US6994706B2 (en) * 2001-08-13 2006-02-07 Minnesota Medical Physics, Llc Apparatus and method for treatment of benign prostatic hyperplasia
US7130697B2 (en) 2002-08-13 2006-10-31 Minnesota Medical Physics Llc Apparatus and method for the treatment of benign prostatic hyperplasia
AU2002327779B2 (en) * 2001-09-28 2008-06-26 Angiodynamics, Inc. Impedance controlled tissue ablation apparatus and method
US20040243107A1 (en) 2001-10-01 2004-12-02 Macoviak John A Methods and devices for treating atrial fibrilation
FR2830767B1 (fr) 2001-10-12 2004-03-12 Optis France Sa Dispositif de delivrance de medicaments par iontophorese ou electroporation introculaire
JP4394444B2 (ja) 2001-10-24 2010-01-06 パワー ペーパー リミティド 活性物質の制御された皮膚内デリバリーのためのデバイス及び方法
US6807444B2 (en) 2001-11-05 2004-10-19 Hosheng Tu Apparatus and methods for monitoring tissue impedance
WO2003047684A2 (en) * 2001-12-04 2003-06-12 University Of Southern California Method for intracellular modifications within living cells using pulsed electric fields
AU2003265226A1 (en) 2002-03-11 2003-12-19 Altea Therapeutics Corporation Transdermal drug delivery device, method and use
US6912417B1 (en) 2002-04-05 2005-06-28 Ichor Medical Systmes, Inc. Method and apparatus for delivery of therapeutic agents
US8551069B2 (en) 2002-04-08 2013-10-08 Medtronic Adrian Luxembourg S.a.r.l. Methods and apparatus for treating contrast nephropathy
US7653438B2 (en) 2002-04-08 2010-01-26 Ardian, Inc. Methods and apparatus for renal neuromodulation
US6801804B2 (en) 2002-05-03 2004-10-05 Aciont, Inc. Device and method for monitoring and controlling electrical resistance at a tissue site undergoing iontophoresis
US6780178B2 (en) 2002-05-03 2004-08-24 The Board Of Trustees Of The Leland Stanford Junior University Method and apparatus for plasma-mediated thermo-electrical ablation
US7063698B2 (en) 2002-06-14 2006-06-20 Ncontact Surgical, Inc. Vacuum coagulation probes
US6972014B2 (en) 2003-01-04 2005-12-06 Endocare, Inc. Open system heat exchange catheters and methods of use
US7211083B2 (en) 2003-03-17 2007-05-01 Minnesota Medical Physics, Llc Apparatus and method for hair removal by electroporation
AU2004311842C1 (en) 2003-12-24 2011-01-06 The Regents Of The University Of California Tissue ablation with irreversible electroporation
US20050261672A1 (en) 2004-05-18 2005-11-24 Mark Deem Systems and methods for selective denervation of heart dysrhythmias
US7261710B2 (en) 2004-10-13 2007-08-28 Medtronic, Inc. Transurethral needle ablation system
US20060264752A1 (en) 2005-04-27 2006-11-23 The Regents Of The University Of California Electroporation controlled with real time imaging
US8114070B2 (en) * 2005-06-24 2012-02-14 Angiodynamics, Inc. Methods and systems for treating BPH using electroporation
US20060293730A1 (en) 2005-06-24 2006-12-28 Boris Rubinsky Methods and systems for treating restenosis sites using electroporation
US20070156135A1 (en) * 2006-01-03 2007-07-05 Boris Rubinsky System and methods for treating atrial fibrillation using electroporation
US20080052786A1 (en) 2006-08-24 2008-02-28 Pei-Cheng Lin Animal Model of Prostate Cancer and Use Thereof
WO2008034103A2 (en) * 2006-09-14 2008-03-20 Lazure Technologies, Llc Device and method for destruction of cancer cells
US7655004B2 (en) * 2007-02-15 2010-02-02 Ethicon Endo-Surgery, Inc. Electroporation ablation apparatus, system, and method
WO2009121009A2 (en) * 2008-03-27 2009-10-01 The Regents Of The University Of California Irreversible electroporation device for use in attenuating neointimal
US10702326B2 (en) * 2011-07-15 2020-07-07 Virginia Tech Intellectual Properties, Inc. Device and method for electroporation based treatment of stenosis of a tubular body part

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6010613A (en) * 1995-12-08 2000-01-04 Cyto Pulse Sciences, Inc. Method of treating materials with pulsed electrical fields
US6278895B1 (en) * 1997-04-24 2001-08-21 Ichor Medical Systems, Inc. Electrodes and electrode arrays for generating electroporation inducing electrical fields
US6387671B1 (en) * 1999-07-21 2002-05-14 The Regents Of The University Of California Electrical impedance tomography to control electroporation
US20040019371A1 (en) * 2001-02-08 2004-01-29 Ali Jaafar Apparatus and method for reducing subcutaneous fat deposits, virtual face lift and body sculpturing by electroporation
US6697670B2 (en) * 2001-08-17 2004-02-24 Minnesota Medical Physics, Llc Apparatus and method for reducing subcutaneous fat deposits by electroporation with improved comfort of patients
US6795728B2 (en) * 2001-08-17 2004-09-21 Minnesota Medical Physics, Llc Apparatus and method for reducing subcutaneous fat deposits by electroporation
US20060025760A1 (en) * 2002-05-06 2006-02-02 Podhajsky Ronald J Blood detector for controlling anesu and method therefor

Cited By (332)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060121610A1 (en) * 1999-07-21 2006-06-08 The Regents Of The University Of California Controlled electroporation and mass transfer across cell membranes
US20100196984A1 (en) * 1999-07-21 2010-08-05 The Regents Of The University Of California Controlled electroporation and mass transfer across cell membranes
US7955827B2 (en) 1999-07-21 2011-06-07 The Regents Of The University Of California Controlled electroporation and mass transfer across cell membranes
US7718409B2 (en) 1999-07-21 2010-05-18 The Regents Of The University Of California Controlled electroporation and mass transfer across cell membranes
USRE43009E1 (en) 2000-08-17 2011-12-06 Angiodynamics, Inc. Apparatus and method for reducing subcutaneous fat deposits by electroporation
US8647338B2 (en) 2000-08-17 2014-02-11 Angiodynamics, Inc. Method of destroying tissue cells by electroporation
US8251986B2 (en) 2000-08-17 2012-08-28 Angiodynamics, Inc. Method of destroying tissue cells by eletroporation
US20050182462A1 (en) * 2000-08-17 2005-08-18 Chornenky Victor I. Apparatus and method for reducing subcutaneous fat deposits, virtual face lift and body sculpturing by electroporation
USRE42835E1 (en) 2000-08-17 2011-10-11 Angiodynamics, Inc. Apparatus and method for reducing subcutaneous fat deposits by electroporation with improved comfort of patients
US7938824B2 (en) 2000-08-17 2011-05-10 Angiodynamics, Inc. Apparatus and method for reducing subcutaneous fat deposits, virtual face lift and body sculpturing by electroporation
USRE42277E1 (en) 2000-08-17 2011-04-05 Angiodynamics, Inc. Apparatus and method for reducing subcutaneous fat deposits, virtual face lift and body sculpturing by electroporation
US20110009860A1 (en) * 2000-08-17 2011-01-13 Chornenky Victor I Apparatus and Method for Reducing Subcutaneous Fat Deposits, Virtual Face Lift and Body Sculpturing by Electroporation
US8634929B2 (en) 2001-08-13 2014-01-21 Angiodynamics, Inc. Method for treatment of neoplastic cells in the prostate of a patient
US20030060856A1 (en) * 2001-08-13 2003-03-27 Victor Chornenky Apparatus and method for treatment of benign prostatic hyperplasia
USRE42016E1 (en) 2001-08-13 2010-12-28 Angiodynamics, Inc. Apparatus and method for the treatment of benign prostatic hyperplasia
US7765010B2 (en) 2001-08-13 2010-07-27 Angiodynamics, Inc. Apparatus and method for treatment of benign prostatic hyperplasia
US20030149451A1 (en) * 2001-08-17 2003-08-07 Chomenky Victor I. Apparatus and method for reducing subcutaneous fat deposits by electroporation with improved comfort of patients
US8444640B2 (en) 2002-04-08 2013-05-21 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for performing a non-continuous circumferential treatment of a body lumen
US9131978B2 (en) 2002-04-08 2015-09-15 Medtronic Ardian Luxembourg S.A.R.L. Methods for bilateral renal neuromodulation
US9731132B2 (en) 2002-04-08 2017-08-15 Medtronic Ardian Luxembourg S.A.R.L. Methods for renal neuromodulation
US9707035B2 (en) 2002-04-08 2017-07-18 Medtronic Ardian Luxembourg S.A.R.L. Methods for catheter-based renal neuromodulation
US9743983B2 (en) 2002-04-08 2017-08-29 Medtronic Ardian Luxembourg S.A.R.L. Renal neuromodulation for treatment of patients
US9675413B2 (en) 2002-04-08 2017-06-13 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for renal neuromodulation
US11033328B2 (en) 2002-04-08 2021-06-15 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for renal neuromodulation
US9636174B2 (en) 2002-04-08 2017-05-02 Medtronic Ardian Luxembourg S.A.R.L. Methods for therapeutic renal neuromodulation
US9757192B2 (en) 2002-04-08 2017-09-12 Medtronic Ardian Luxembourg S.A.R.L. Renal neuromodulation for treatment of patients
US9757193B2 (en) 2002-04-08 2017-09-12 Medtronic Ardian Luxembourg S.A.R.L. Balloon catheter apparatus for renal neuromodulation
US9486270B2 (en) 2002-04-08 2016-11-08 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for bilateral renal neuromodulation
US9474563B2 (en) 2002-04-08 2016-10-25 Medtronic Ardian Luxembourg S.A.R.L. Methods for renal neuromodulation
US7617005B2 (en) 2002-04-08 2009-11-10 Ardian, Inc. Methods and apparatus for thermally-induced renal neuromodulation
US10376516B2 (en) 2002-04-08 2019-08-13 Medtronic Ardian Luxembourg S.A.R.L. Methods and devices for renal nerve blocking
US9468497B2 (en) 2002-04-08 2016-10-18 Medtronic Ardian Luxembourg S.A.R.L. Methods for monopolar renal neuromodulation
US10293190B2 (en) 2002-04-08 2019-05-21 Medtronic Ardian Luxembourg S.A.R.L. Thermally-induced renal neuromodulation and associated systems and methods
US10376311B2 (en) 2002-04-08 2019-08-13 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for intravascularly-induced neuromodulation
US10272246B2 (en) 2002-04-08 2019-04-30 Medtronic Adrian Luxembourg S.a.r.l Methods for extravascular renal neuromodulation
US9463066B2 (en) 2002-04-08 2016-10-11 Medtronic Ardian Luxembourg S.A.R.L. Methods for renal neuromodulation
US7647115B2 (en) 2002-04-08 2010-01-12 Ardian, Inc. Renal nerve stimulation method and apparatus for treatment of patients
US7653438B2 (en) 2002-04-08 2010-01-26 Ardian, Inc. Methods and apparatus for renal neuromodulation
US10420606B2 (en) 2002-04-08 2019-09-24 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for performing a non-continuous circumferential treatment of a body lumen
US10245429B2 (en) 2002-04-08 2019-04-02 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for renal neuromodulation
US10441356B2 (en) 2002-04-08 2019-10-15 Medtronic Ardian Luxembourg S.A.R.L. Methods for renal neuromodulation via neuromodulatory agents
US9814873B2 (en) 2002-04-08 2017-11-14 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for bilateral renal neuromodulation
US9456869B2 (en) 2002-04-08 2016-10-04 Medtronic Ardian Luxembourg S.A.R.L. Methods for bilateral renal neuromodulation
US9445867B1 (en) 2002-04-08 2016-09-20 Medtronic Ardian Luxembourg S.A.R.L. Methods for renal neuromodulation via catheters having expandable treatment members
US9439726B2 (en) 2002-04-08 2016-09-13 Medtronic Ardian Luxembourg S.A.R.L. Methods for therapeutic renal neuromodulation
US7717948B2 (en) 2002-04-08 2010-05-18 Ardian, Inc. Methods and apparatus for thermally-induced renal neuromodulation
US9827041B2 (en) 2002-04-08 2017-11-28 Medtronic Ardian Luxembourg S.A.R.L. Balloon catheter apparatuses for renal denervation
US10179028B2 (en) 2002-04-08 2019-01-15 Medtronic Ardian Luxembourg S.A.R.L. Methods for treating patients via renal neuromodulation
US9364280B2 (en) 2002-04-08 2016-06-14 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for pulsed electric field neuromodulation via an intra-to-extravascular approach
US7756583B2 (en) 2002-04-08 2010-07-13 Ardian, Inc. Methods and apparatus for intravascularly-induced neuromodulation
US9326817B2 (en) 2002-04-08 2016-05-03 Medtronic Ardian Luxembourg S.A.R.L. Methods for treating heart arrhythmia
US9327122B2 (en) 2002-04-08 2016-05-03 Medtronic Ardian Luxembourg S.A.R.L. Methods for catheter-based renal neuromodulation
US10179027B2 (en) 2002-04-08 2019-01-15 Medtronic Ardian Luxembourg S.A.R.L. Catheter apparatuses having expandable baskets for renal neuromodulation and associated systems and methods
US9320561B2 (en) 2002-04-08 2016-04-26 Medtronic Ardian Luxembourg S.A.R.L. Methods for bilateral renal neuromodulation
US10179235B2 (en) 2002-04-08 2019-01-15 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for bilateral renal neuromodulation
US9314630B2 (en) 2002-04-08 2016-04-19 Medtronic Ardian Luxembourg S.A.R.L. Renal neuromodulation for treatment of patients
US7853333B2 (en) 2002-04-08 2010-12-14 Ardian, Inc. Methods and apparatus for multi-vessel renal neuromodulation
US9308043B2 (en) 2002-04-08 2016-04-12 Medtronic Ardian Luxembourg S.A.R.L. Methods for monopolar renal neuromodulation
US9308044B2 (en) 2002-04-08 2016-04-12 Medtronic Ardian Luxembourg S.A.R.L. Methods for therapeutic renal neuromodulation
US10130792B2 (en) 2002-04-08 2018-11-20 Medtronic Ardian Luxembourg S.A.R.L. Methods for therapeutic renal neuromodulation using neuromodulatory agents or drugs
US9289255B2 (en) 2002-04-08 2016-03-22 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for renal neuromodulation
US10124195B2 (en) 2002-04-08 2018-11-13 Medtronic Ardian Luxembourg S.A.R.L. Methods for thermally-induced renal neuromodulation
US9827040B2 (en) 2002-04-08 2017-11-28 Medtronic Adrian Luxembourg S.a.r.l. Methods and apparatus for intravascularly-induced neuromodulation
US9265558B2 (en) 2002-04-08 2016-02-23 Medtronic Ardian Luxembourg S.A.R.L. Methods for bilateral renal neuromodulation
US9895195B2 (en) 2002-04-08 2018-02-20 Medtronic Ardian Luxembourg S.A.R.L. Methods for therapeutic renal neuromodulation
US9907611B2 (en) 2002-04-08 2018-03-06 Medtronic Ardian Luxembourg S.A.R.L. Renal neuromodulation for treatment of patients
US7162303B2 (en) 2002-04-08 2007-01-09 Ardian, Inc. Renal nerve stimulation method and apparatus for treatment of patients
US9192715B2 (en) 2002-04-08 2015-11-24 Medtronic Ardian Luxembourg S.A.R.L. Methods for renal nerve blocking
US9186198B2 (en) 2002-04-08 2015-11-17 Medtronic Ardian Luxembourg S.A.R.L. Ultrasound apparatuses for thermally-induced renal neuromodulation and associated systems and methods
US9186213B2 (en) 2002-04-08 2015-11-17 Medtronic Ardian Luxembourg S.A.R.L. Methods for renal neuromodulation
US9138281B2 (en) 2002-04-08 2015-09-22 Medtronic Ardian Luxembourg S.A.R.L. Methods for bilateral renal neuromodulation via catheter apparatuses having expandable baskets
US9125661B2 (en) 2002-04-08 2015-09-08 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for renal neuromodulation
US8131371B2 (en) 2002-04-08 2012-03-06 Ardian, Inc. Methods and apparatus for monopolar renal neuromodulation
US8131372B2 (en) 2002-04-08 2012-03-06 Ardian, Inc. Renal nerve stimulation method for treatment of patients
US8145317B2 (en) 2002-04-08 2012-03-27 Ardian, Inc. Methods for renal neuromodulation
US8145316B2 (en) 2002-04-08 2012-03-27 Ardian, Inc. Methods and apparatus for renal neuromodulation
US8150518B2 (en) 2002-04-08 2012-04-03 Ardian, Inc. Renal nerve stimulation method and apparatus for treatment of patients
US8150519B2 (en) 2002-04-08 2012-04-03 Ardian, Inc. Methods and apparatus for bilateral renal neuromodulation
US8150520B2 (en) 2002-04-08 2012-04-03 Ardian, Inc. Methods for catheter-based renal denervation
US9072527B2 (en) 2002-04-08 2015-07-07 Medtronic Ardian Luxembourg S.A.R.L. Apparatuses and methods for renal neuromodulation
US8175711B2 (en) 2002-04-08 2012-05-08 Ardian, Inc. Methods for treating a condition or disease associated with cardio-renal function
US9023037B2 (en) 2002-04-08 2015-05-05 Medtronic Ardian Luxembourg S.A.R.L. Balloon catheter apparatus for renal neuromodulation
US10111707B2 (en) 2002-04-08 2018-10-30 Medtronic Ardian Luxembourg S.A.R.L. Renal neuromodulation for treatment of human patients
US9956410B2 (en) 2002-04-08 2018-05-01 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for renal neuromodulation
US8986294B2 (en) 2002-04-08 2015-03-24 Medtronic Ardian Luxembourg S.a.rl. Apparatuses for thermally-induced renal neuromodulation
US8983595B2 (en) 2002-04-08 2015-03-17 Medtronic Ardian Luxembourg S.A.R.L. Renal neuromodulation for treatment of patients with chronic heart failure
US8958871B2 (en) 2002-04-08 2015-02-17 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for pulsed electric field neuromodulation via an intra-to-extravascular approach
US8347891B2 (en) 2002-04-08 2013-01-08 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for performing a non-continuous circumferential treatment of a body lumen
US8948865B2 (en) 2002-04-08 2015-02-03 Medtronic Ardian Luxembourg S.A.R.L. Methods for treating heart arrhythmia
US8934978B2 (en) 2002-04-08 2015-01-13 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for renal neuromodulation
US8454594B2 (en) 2002-04-08 2013-06-04 Medtronic Ardian Luxembourg S.A.R.L. Apparatus for performing a non-continuous circumferential treatment of a body lumen
US10105180B2 (en) 2002-04-08 2018-10-23 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for intravascularly-induced neuromodulation
US8548600B2 (en) 2002-04-08 2013-10-01 Medtronic Ardian Luxembourg S.A.R.L. Apparatuses for renal neuromodulation and associated systems and methods
US8551069B2 (en) 2002-04-08 2013-10-08 Medtronic Adrian Luxembourg S.a.r.l. Methods and apparatus for treating contrast nephropathy
US9968611B2 (en) 2002-04-08 2018-05-15 Medtronic Ardian Luxembourg S.A.R.L. Methods and devices for renal nerve blocking
US10850091B2 (en) 2002-04-08 2020-12-01 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for bilateral renal neuromodulation
US8626300B2 (en) 2002-04-08 2014-01-07 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for thermally-induced renal neuromodulation
US20060212078A1 (en) * 2002-04-08 2006-09-21 Ardian, Inc. Methods and apparatus for treating congestive heart failure
US8620423B2 (en) 2002-04-08 2013-12-31 Medtronic Ardian Luxembourg S.A.R.L. Methods for thermal modulation of nerves contributing to renal function
US20060142801A1 (en) * 2002-04-08 2006-06-29 Ardian, Inc. Methods and apparatus for intravascularly-induced neuromodulation
US8684998B2 (en) 2002-04-08 2014-04-01 Medtronic Ardian Luxembourg S.A.R.L. Methods for inhibiting renal nerve activity
US8721637B2 (en) 2002-04-08 2014-05-13 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for performing renal neuromodulation via catheter apparatuses having inflatable balloons
US8728137B2 (en) 2002-04-08 2014-05-20 Medtronic Ardian Luxembourg S.A.R.L. Methods for thermally-induced renal neuromodulation
US8728138B2 (en) 2002-04-08 2014-05-20 Medtronic Ardian Luxembourg S.A.R.L. Methods for thermally-induced renal neuromodulation
US10039596B2 (en) 2002-04-08 2018-08-07 Medtronic Ardian Luxembourg S.A.R.L. Apparatus for renal neuromodulation via an intra-to-extravascular approach
US8740896B2 (en) 2002-04-08 2014-06-03 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for performing renal neuromodulation via catheter apparatuses having inflatable balloons
US10034708B2 (en) 2002-04-08 2018-07-31 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for thermally-induced renal neuromodulation
US8768470B2 (en) 2002-04-08 2014-07-01 Medtronic Ardian Luxembourg S.A.R.L. Methods for monitoring renal neuromodulation
US8774922B2 (en) 2002-04-08 2014-07-08 Medtronic Ardian Luxembourg S.A.R.L. Catheter apparatuses having expandable balloons for renal neuromodulation and associated systems and methods
US8774913B2 (en) 2002-04-08 2014-07-08 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for intravasculary-induced neuromodulation
US8771252B2 (en) 2002-04-08 2014-07-08 Medtronic Ardian Luxembourg S.A.R.L. Methods and devices for renal nerve blocking
US8784463B2 (en) 2002-04-08 2014-07-22 Medtronic Ardian Luxembourg S.A.R.L. Methods for thermally-induced renal neuromodulation
US8880186B2 (en) 2002-04-08 2014-11-04 Medtronic Ardian Luxembourg S.A.R.L. Renal neuromodulation for treatment of patients with chronic heart failure
US8818514B2 (en) 2002-04-08 2014-08-26 Medtronic Ardian Luxembourg S.A.R.L. Methods for intravascularly-induced neuromodulation
US8852163B2 (en) 2002-04-08 2014-10-07 Medtronic Ardian Luxembourg S.A.R.L. Renal neuromodulation via drugs and neuromodulatory agents and associated systems and methods
US10376312B2 (en) 2002-04-08 2019-08-13 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for monopolar renal neuromodulation
US8845629B2 (en) 2002-04-08 2014-09-30 Medtronic Ardian Luxembourg S.A.R.L. Ultrasound apparatuses for thermally-induced renal neuromodulation
US20040059389A1 (en) * 2002-08-13 2004-03-25 Chornenky Victor I. Apparatus and method for the treatment of benign prostatic hyperplasia
US8282631B2 (en) 2003-12-24 2012-10-09 The Regents Of The University Of California Tissue ablation with irreversible electroporation
US20080269586A1 (en) * 2003-12-24 2008-10-30 The Regents Of The University Of California Electroporation to interrupt blood flow
US11033321B2 (en) 2003-12-24 2021-06-15 The Regents Of The University Of California Tissue ablation with irreversible electroporation
US20070043345A1 (en) * 2003-12-24 2007-02-22 Rafael Davalos Tissue ablation with irreversible electroporation
US8048067B2 (en) 2003-12-24 2011-11-01 The Regents Of The University Of California Tissue ablation with irreversible electroporation
US10117701B2 (en) 2003-12-24 2018-11-06 The Regents Of The University Of California Tissue ablation with irreversible electroporation
US9005189B2 (en) 2003-12-24 2015-04-14 The Regents Of The University Of California Tissue ablation with irreversible electroporation
US20090326436A1 (en) * 2003-12-24 2009-12-31 The Regents Of The University Of California Electroporation to deliver chemotherapeutics and enhance tumor regression
US8298222B2 (en) 2003-12-24 2012-10-30 The Regents Of The University Of California Electroporation to deliver chemotherapeutics and enhance tumor regression
US10537734B2 (en) 2004-10-05 2020-01-21 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for multi-vessel renal neuromodulation
US8433423B2 (en) 2004-10-05 2013-04-30 Ardian, Inc. Methods for multi-vessel renal neuromodulation
US8805545B2 (en) 2004-10-05 2014-08-12 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for multi-vessel renal neuromodulation
US9402992B2 (en) 2004-10-05 2016-08-02 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for multi-vessel renal neuromodulation
US9108040B2 (en) 2004-10-05 2015-08-18 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for multi-vessel renal neuromodulation
US9950161B2 (en) 2004-10-05 2018-04-24 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for multi-vessel renal neuromodulation
US7937143B2 (en) 2004-11-02 2011-05-03 Ardian, Inc. Methods and apparatus for inducing controlled renal neuromodulation
US20060264752A1 (en) * 2005-04-27 2006-11-23 The Regents Of The University Of California Electroporation controlled with real time imaging
US20080015571A1 (en) * 2005-06-24 2008-01-17 Boris Rubinsky Methods and systems for treating tumors using electroporation
US8114070B2 (en) 2005-06-24 2012-02-14 Angiodynamics, Inc. Methods and systems for treating BPH using electroporation
US20060293725A1 (en) * 2005-06-24 2006-12-28 Boris Rubinsky Methods and systems for treating fatty tissue sites using electroporation
US20060293713A1 (en) * 2005-06-24 2006-12-28 Boris Rubinsky Methods and systems for treating BPH using electroporation
US8603087B2 (en) 2005-06-24 2013-12-10 Angiodynamics, Inc. Methods and systems for treating restenosis using electroporation
US12433837B2 (en) 2005-07-22 2025-10-07 The Foundry, Llc Systems and methods for delivery of a therapeutic agent
US7620451B2 (en) 2005-12-29 2009-11-17 Ardian, Inc. Methods and apparatus for pulsed electric field neuromodulation via an intra-to-extravascular approach
WO2007079438A3 (en) * 2006-01-03 2008-02-21 Oncobionic Inc System and methods for treating atrial fibrillation using electroporation
EP1978882A4 (en) * 2006-01-03 2009-03-11 Angiodynamics SYSTEM AND METHOD FOR THE TREATMENT OF CARDIAC VENTILATORS WITH ELECTROPORATION
US20070156135A1 (en) * 2006-01-03 2007-07-05 Boris Rubinsky System and methods for treating atrial fibrillation using electroporation
US20110015630A1 (en) * 2006-09-14 2011-01-20 Lazure Technologies, Llc Device and method for destruction of cancer cells
US7722606B2 (en) 2006-09-14 2010-05-25 LaZúre Technologies, LLC Device and method for destruction of cancer cells
US9308039B2 (en) 2006-09-14 2016-04-12 Lazure Scientific, Inc. Ablation probe with deployable electrodes
US8109926B2 (en) 2006-09-14 2012-02-07 Lazure Scientific, Inc. Ablation probe with deployable electrodes
WO2008034103A3 (en) * 2006-09-14 2008-11-20 Lazure Technologies Llc Device and method for destruction of cancer cells
WO2008034107A3 (en) * 2006-09-14 2008-11-27 Lazure Technologies Llc Tissue ablation and removal
US8915911B2 (en) 2006-09-14 2014-12-23 Lazure Technologies, Llc Device and method for destruction of cancer cells
US20080071264A1 (en) * 2006-09-14 2008-03-20 Larry Azure Ablation probe with deployable electrodes
US20080071262A1 (en) * 2006-09-14 2008-03-20 Larry Azure Tissue ablation and removal
US7680543B2 (en) 2006-09-14 2010-03-16 Lazure Technologies, Llc Tissue ablation and removal
US20080071265A1 (en) * 2006-09-14 2008-03-20 Larry Azure Device and method for destruction of cancer cells
US7674249B2 (en) 2006-10-16 2010-03-09 The Regents Of The University Of California Gels with predetermined conductivity used in electroporation of tissue
US8162918B2 (en) 2006-10-16 2012-04-24 The Regents Of The University Of California Gels with predetermined conductivity used in electroporation of tissue
US20100160850A1 (en) * 2006-10-16 2010-06-24 The Regents Of The University Of California Gels with predetermined conductivity used in electroporation of tissue
US8348921B2 (en) 2006-10-16 2013-01-08 The Regents Of The University Of California Gels with predetermined conductivity used in electroporation of tissue
US20080132884A1 (en) * 2006-12-01 2008-06-05 Boris Rubinsky Systems for treating tissue sites using electroporation
US20080241315A1 (en) * 2007-03-29 2008-10-02 Novozymes A/S Process for treating vegetable material with an enzyme
US11207118B2 (en) 2007-07-06 2021-12-28 Tsunami Medtech, Llc Medical system and method of use
US10758292B2 (en) 2007-08-23 2020-09-01 Aegea Medical Inc. Uterine therapy device and method
US11213338B2 (en) 2007-08-23 2022-01-04 Aegea Medical Inc. Uterine therapy device and method
US10154871B2 (en) 2007-08-23 2018-12-18 Aegea Medical Inc. Uterine therapy device and method
US20090076496A1 (en) * 2007-09-14 2009-03-19 Lazure Technologies Llc. Prostate cancer ablation
US8562602B2 (en) 2007-09-14 2013-10-22 Lazure Technologies, Llc Multi-layer electrode ablation probe and related methods
US9603654B2 (en) 2007-09-14 2017-03-28 Lazure Technologies, Llc. Multi-layer electrode ablation probe and related methods
US20090076500A1 (en) * 2007-09-14 2009-03-19 Lazure Technologies, Llc Multi-tine probe and treatment by activation of opposing tines
US20090076499A1 (en) * 2007-09-14 2009-03-19 Lazure Technologies, Llc. Multi-layer electrode ablation probe and related methods
US8880195B2 (en) 2007-09-14 2014-11-04 Lazure Technologies, Llc Transurethral systems and methods for ablation treatment of prostate tissue
US9707403B2 (en) 2007-12-12 2017-07-18 Neuro Code Tech Holdings, Llc Rapid destruction of malignant tumors by excitotoxicity and osmotic-shock medical tactics
US9032964B2 (en) 2008-01-10 2015-05-19 Neuro Code Teen Holdings; LLC Method and system for processing cancer cell electrical signals for medical therapy
US20090248012A1 (en) * 2008-03-27 2009-10-01 The Regents Of The University Of California Irreversible electroporation device and method for attenuating neointimal
US10010666B2 (en) 2008-03-27 2018-07-03 Angiodynamics, Inc. Balloon catheter method for reducing restenosis via irreversible electroporation
US20090247933A1 (en) * 2008-03-27 2009-10-01 The Regents Of The University Of California; Angiodynamics, Inc. Balloon catheter method for reducing restenosis via irreversible electroporation
US8831738B2 (en) 2008-04-17 2014-09-09 Neuro Code Tech Holdings, Llc System and method to elicit apoptosis in malignant tumor cells for medical treatment
WO2009151783A1 (en) * 2008-04-17 2009-12-17 The Neuro-Signaling Foundation System and method to elicit apoptosis in malignant tumor cells for medical treatment
US8814860B2 (en) 2008-04-29 2014-08-26 Virginia Tech Intellectual Properties, Inc. Irreversible electroporation using nanoparticles
US11952568B2 (en) 2008-04-29 2024-04-09 Virginia Tech Intellectual Properties, Inc. Device and methods for delivery of biphasic electrical pulses for non-thermal ablation
US11272979B2 (en) 2008-04-29 2022-03-15 Virginia Tech Intellectual Properties, Inc. System and method for estimating tissue heating of a target ablation zone for electrical-energy based therapies
US11254926B2 (en) 2008-04-29 2022-02-22 Virginia Tech Intellectual Properties, Inc. Devices and methods for high frequency electroporation
US11453873B2 (en) 2008-04-29 2022-09-27 Virginia Tech Intellectual Properties, Inc. Methods for delivery of biphasic electrical pulses for non-thermal ablation
US9283051B2 (en) 2008-04-29 2016-03-15 Virginia Tech Intellectual Properties, Inc. System and method for estimating a treatment volume for administering electrical-energy based therapies
US9867652B2 (en) 2008-04-29 2018-01-16 Virginia Tech Intellectual Properties, Inc. Irreversible electroporation using tissue vasculature to treat aberrant cell masses or create tissue scaffolds
US9198733B2 (en) 2008-04-29 2015-12-01 Virginia Tech Intellectual Properties, Inc. Treatment planning for electroporation-based therapies
US10272178B2 (en) 2008-04-29 2019-04-30 Virginia Tech Intellectual Properties Inc. Methods for blood-brain barrier disruption using electrical energy
US11655466B2 (en) 2008-04-29 2023-05-23 Virginia Tech Intellectual Properties, Inc. Methods of reducing adverse effects of non-thermal ablation
US10286108B2 (en) 2008-04-29 2019-05-14 Virginia Tech Intellectual Properties, Inc. Irreversible electroporation to create tissue scaffolds
US8992517B2 (en) * 2008-04-29 2015-03-31 Virginia Tech Intellectual Properties Inc. Irreversible electroporation to treat aberrant cell masses
US11737810B2 (en) 2008-04-29 2023-08-29 Virginia Tech Intellectual Properties, Inc. Immunotherapeutic methods using electroporation
US10959772B2 (en) 2008-04-29 2021-03-30 Virginia Tech Intellectual Properties, Inc. Blood-brain barrier disruption using electrical energy
US9598691B2 (en) 2008-04-29 2017-03-21 Virginia Tech Intellectual Properties, Inc. Irreversible electroporation to create tissue scaffolds
US11890046B2 (en) 2008-04-29 2024-02-06 Virginia Tech Intellectual Properties, Inc. System and method for ablating a tissue site by electroporation with real-time monitoring of treatment progress
US11607271B2 (en) 2008-04-29 2023-03-21 Virginia Tech Intellectual Properties, Inc. System and method for estimating a treatment volume for administering electrical-energy based therapies
US10470822B2 (en) 2008-04-29 2019-11-12 Virginia Tech Intellectual Properties, Inc. System and method for estimating a treatment volume for administering electrical-energy based therapies
US10828085B2 (en) 2008-04-29 2020-11-10 Virginia Tech Intellectual Properties, Inc. Immunotherapeutic methods using irreversible electroporation
US8465484B2 (en) 2008-04-29 2013-06-18 Virginia Tech Intellectual Properties, Inc. Irreversible electroporation using nanoparticles
US10245105B2 (en) 2008-04-29 2019-04-02 Virginia Tech Intellectual Properties, Inc. Electroporation with cooling to treat tissue
US10117707B2 (en) 2008-04-29 2018-11-06 Virginia Tech Intellectual Properties, Inc. System and method for estimating tissue heating of a target ablation zone for electrical-energy based therapies
US20100030211A1 (en) * 2008-04-29 2010-02-04 Rafael Davalos Irreversible electroporation to treat aberrant cell masses
US10245098B2 (en) 2008-04-29 2019-04-02 Virginia Tech Intellectual Properties, Inc. Acute blood-brain barrier disruption using electrical energy based therapy
US10828086B2 (en) 2008-04-29 2020-11-10 Virginia Tech Intellectual Properties, Inc. Immunotherapeutic methods using irreversible electroporation
US11974800B2 (en) 2008-04-29 2024-05-07 Virginia Tech Intellectual Properties, Inc. Irreversible electroporation using tissue vasculature to treat aberrant cell masses or create tissue scaffolds
US12059197B2 (en) 2008-04-29 2024-08-13 Virginia Tech Intellectual Properties, Inc. Blood-brain barrier disruption using reversible or irreversible electroporation
US10154874B2 (en) 2008-04-29 2018-12-18 Virginia Tech Intellectual Properties, Inc. Immunotherapeutic methods using irreversible electroporation
US12173280B2 (en) 2008-04-29 2024-12-24 Virginia Tech Intellectual Properties, Inc. Methods of reducing adverse effects of non-thermal ablation
US10238447B2 (en) 2008-04-29 2019-03-26 Virginia Tech Intellectual Properties, Inc. System and method for ablating a tissue site by electroporation with real-time monitoring of treatment progress
US10537379B2 (en) 2008-04-29 2020-01-21 Virginia Tech Intellectual Properties, Inc. Irreversible electroporation using tissue vasculature to treat aberrant cell masses or create tissue scaffolds
US12390268B2 (en) 2008-04-29 2025-08-19 Virginia Tech Intellectual Properties, Inc. System and method for estimating tissue heating of a target ablation zone for electrical-energy based therapies
USD631154S1 (en) 2008-05-09 2011-01-18 Angiodynamics, Inc. Probe handle tip
US20090281477A1 (en) * 2008-05-09 2009-11-12 Angiodynamics, Inc. Electroporation device and method
US20090318849A1 (en) * 2008-06-20 2009-12-24 Angiodynamics, Inc. Device and Method for the Ablation of Fibrin Sheath Formation on a Venous Catheter
US9173704B2 (en) 2008-06-20 2015-11-03 Angiodynamics, Inc. Device and method for the ablation of fibrin sheath formation on a venous catheter
US20090318905A1 (en) * 2008-06-23 2009-12-24 Angiodynamics, Inc. Treatment Devices and Methods
US9681909B2 (en) 2008-06-23 2017-06-20 Angiodynamics, Inc. Treatment devices and methods
WO2010014480A1 (en) * 2008-07-28 2010-02-04 Medtronic, Inc. Systems and methods for cardiac tissue electroporation ablation
US8221411B2 (en) 2008-07-28 2012-07-17 Medtronic, Inc. Systems and methods for cardiac tissue electroporation ablation
US20100023004A1 (en) * 2008-07-28 2010-01-28 David Francischelli Systems and methods for cardiac tissue electroporation ablation
US20100100093A1 (en) * 2008-09-16 2010-04-22 Lazure Technologies, Llc. System and method for controlled tissue heating for destruction of cancerous cells
US20100152725A1 (en) * 2008-12-12 2010-06-17 Angiodynamics, Inc. Method and system for tissue treatment utilizing irreversible electroporation and thermal track coagulation
US10561460B2 (en) 2008-12-31 2020-02-18 Medtronic Ardian Luxembourg S.A.R.L. Neuromodulation systems and methods for treatment of sexual dysfunction
US10537385B2 (en) 2008-12-31 2020-01-21 Medtronic Ardian Luxembourg S.A.R.L. Intravascular, thermally-induced renal neuromodulation for treatment of polycystic ovary syndrome or infertility
US8753335B2 (en) 2009-01-23 2014-06-17 Angiodynamics, Inc. Therapeutic energy delivery device with rotational mechanism
US11284931B2 (en) 2009-02-03 2022-03-29 Tsunami Medtech, Llc Medical systems and methods for ablating and absorbing tissue
US8231603B2 (en) 2009-02-10 2012-07-31 Angiodynamics, Inc. Irreversible electroporation and tissue regeneration
US20100204638A1 (en) * 2009-02-10 2010-08-12 Angiodynamics, Inc. Irreversible electroporation and tissue regeneration
US9599591B2 (en) 2009-03-06 2017-03-21 California Institute Of Technology Low cost, portable sensor for molecular assays
US20100240995A1 (en) * 2009-03-17 2010-09-23 Bioelectromed Corp. System and method for treating tumors
US12201349B2 (en) 2009-04-03 2025-01-21 Angiodynamics, Inc. Congestive obstruction pulmonary disease (COPD)
US8926606B2 (en) 2009-04-09 2015-01-06 Virginia Tech Intellectual Properties, Inc. Integration of very short electric pulses for minimally to noninvasive electroporation
US10292755B2 (en) 2009-04-09 2019-05-21 Virginia Tech Intellectual Properties, Inc. High frequency electroporation for cancer therapy
US10448989B2 (en) 2009-04-09 2019-10-22 Virginia Tech Intellectual Properties, Inc. High-frequency electroporation for cancer therapy
US11638603B2 (en) 2009-04-09 2023-05-02 Virginia Tech Intellectual Properties, Inc. Selective modulation of intracellular effects of cells using pulsed electric fields
US11382681B2 (en) 2009-04-09 2022-07-12 Virginia Tech Intellectual Properties, Inc. Device and methods for delivery of high frequency electrical pulses for non-thermal ablation
US8728139B2 (en) 2009-04-16 2014-05-20 Lazure Technologies, Llc System and method for energy delivery to a tissue using an electrode array
WO2010128373A1 (en) * 2009-05-04 2010-11-11 Igea S.P.A. Reversible electroporation device for inducing cell apoptosis
ITTO20090353A1 (it) * 2009-05-04 2010-11-05 Igea S P A Dispositivo per elettroporazione reversibile atto ad indurre apoptosi cellulare
USD630321S1 (en) 2009-05-08 2011-01-04 Angio Dynamics, Inc. Probe handle
US11707629B2 (en) 2009-05-28 2023-07-25 Angiodynamics, Inc. System and method for synchronizing energy delivery to the cardiac rhythm
US9895189B2 (en) 2009-06-19 2018-02-20 Angiodynamics, Inc. Methods of sterilization and treating infection using irreversible electroporation
US20110004096A1 (en) * 2009-07-06 2011-01-06 California Institute Of Technology Electromagnetic cellular tomography
US10143512B2 (en) * 2009-11-19 2018-12-04 The Regents Of The University Of California Controlled irreversible electroporation
US20160287313A1 (en) * 2009-11-19 2016-10-06 The Regents Of The University Of California Controlled irreversible electroporation
US9526911B1 (en) 2010-04-27 2016-12-27 Lazure Scientific, Inc. Immune mediated cancer cell destruction, systems and methods
US11457969B2 (en) 2010-08-13 2022-10-04 Tsunami Medtech, Llc Medical system and method of use
US9700368B2 (en) 2010-10-13 2017-07-11 Angiodynamics, Inc. System and method for electrically ablating tissue of a patient
US10179020B2 (en) 2010-10-25 2019-01-15 Medtronic Ardian Luxembourg S.A.R.L. Devices, systems and methods for evaluation and feedback of neuromodulation treatment
US9743974B2 (en) 2010-11-09 2017-08-29 Aegea Medical Inc. Positioning method and apparatus for delivering vapor to the uterus
US11160597B2 (en) 2010-11-09 2021-11-02 Aegea Medical Inc. Positioning method and apparatus for delivering vapor to the uterus
US12279802B2 (en) 2010-11-09 2025-04-22 Coopersurgical, Inc. Positioning method and apparatus for delivering vapor to the uterus
US10238446B2 (en) 2010-11-09 2019-03-26 Aegea Medical Inc. Positioning method and apparatus for delivering vapor to the uterus
US10131900B2 (en) 2010-12-15 2018-11-20 Old Dominion University Research Foundation Electroporation-induced electrosensitization
US10982206B2 (en) 2010-12-15 2021-04-20 Old Dominion University Research Foundation Electroporation-induced electrosensitization
US11820976B2 (en) 2010-12-15 2023-11-21 Old Dominion University Research Foundation Electroporation-induced electrosensitization
US12357378B2 (en) 2011-06-14 2025-07-15 Aerin Medical Inc. Treating upper airway nerve tissue
US12369973B1 (en) 2011-06-14 2025-07-29 Aerin Medical Inc. Methods for reducing mucus production
US12369963B1 (en) 2011-06-14 2025-07-29 Aerin Medical Inc. Methods and devices to treat nasal airways
US12364532B2 (en) 2011-06-14 2025-07-22 Aerin Medical Inc. Methods and devices to treat nasal airways
US12369966B2 (en) 2011-06-14 2025-07-29 Aerin Medical Inc. Methods and devices to treat nasal airways
US12232792B2 (en) 2011-07-15 2025-02-25 Virginia Tech Intellectual Properties, Inc. Device and method for electroporation based treatment
US10702326B2 (en) 2011-07-15 2020-07-07 Virginia Tech Intellectual Properties, Inc. Device and method for electroporation based treatment of stenosis of a tubular body part
US11779395B2 (en) 2011-09-28 2023-10-10 Angiodynamics, Inc. Multiple treatment zone ablation probe
US9757196B2 (en) 2011-09-28 2017-09-12 Angiodynamics, Inc. Multiple treatment zone ablation probe
US9662060B2 (en) 2011-10-07 2017-05-30 Aegea Medical Inc. Integrity testing method and apparatus for delivering vapor to the uterus
US10881442B2 (en) 2011-10-07 2021-01-05 Aegea Medical Inc. Integrity testing method and apparatus for delivering vapor to the uterus
US12102376B2 (en) 2012-02-08 2024-10-01 Angiodynamics, Inc. System and method for increasing a target zone for electrical ablation
US9414881B2 (en) 2012-02-08 2016-08-16 Angiodynamics, Inc. System and method for increasing a target zone for electrical ablation
US11338140B2 (en) 2012-03-08 2022-05-24 Medtronic Ardian Luxembourg S.A.R.L. Monitoring of neuromodulation using biomarkers
US10874455B2 (en) 2012-03-08 2020-12-29 Medtronic Ardian Luxembourg S.A.R.L. Ovarian neuromodulation and associated systems and methods
US10080864B2 (en) 2012-10-19 2018-09-25 Medtronic Ardian Luxembourg S.A.R.L. Packaging for catheter treatment devices and associated devices, systems, and methods
US12114909B2 (en) 2013-03-15 2024-10-15 Tsunami Medtech, Llc Medical system and method of use
US11413086B2 (en) 2013-03-15 2022-08-16 Tsunami Medtech, Llc Medical system and method of use
US11672584B2 (en) 2013-03-15 2023-06-13 Tsunami Medtech, Llc Medical system and method of use
US11957405B2 (en) 2013-06-13 2024-04-16 Angiodynamics, Inc. Methods of sterilization and treating infection using irreversible electroporation
US20140378963A1 (en) * 2013-06-20 2014-12-25 Gyrus Acmi, Inc., D.B.A. Olympus Surgical Technologies America Treatment of uterine fibroids by arterial ablation
US10166321B2 (en) 2014-01-09 2019-01-01 Angiodynamics, Inc. High-flow port and infusion needle systems
US10194979B1 (en) 2014-03-28 2019-02-05 Medtronic Ardian Luxembourg S.A.R.L. Methods for catheter-based renal neuromodulation
US9980766B1 (en) 2014-03-28 2018-05-29 Medtronic Ardian Luxembourg S.A.R.L. Methods and systems for renal neuromodulation
US10194980B1 (en) 2014-03-28 2019-02-05 Medtronic Ardian Luxembourg S.A.R.L. Methods for catheter-based renal neuromodulation
US10471254B2 (en) 2014-05-12 2019-11-12 Virginia Tech Intellectual Properties, Inc. Selective modulation of intracellular effects of cells using pulsed electric fields
US11406820B2 (en) 2014-05-12 2022-08-09 Virginia Tech Intellectual Properties, Inc. Selective modulation of intracellular effects of cells using pulsed electric fields
US11219479B2 (en) 2014-05-22 2022-01-11 Aegea Medical Inc. Integrity testing method and apparatus for delivering vapor to the uterus
US10299856B2 (en) 2014-05-22 2019-05-28 Aegea Medical Inc. Systems and methods for performing endometrial ablation
US10179019B2 (en) 2014-05-22 2019-01-15 Aegea Medical Inc. Integrity testing method and apparatus for delivering vapor to the uterus
US20150335380A1 (en) * 2014-05-22 2015-11-26 Uriel Hiram Chee Systems and methods for performing endometrial ablation
US10575898B2 (en) 2014-05-22 2020-03-03 Aegea Medical Inc. Systems and methods for performing endometrial ablation
WO2015179666A1 (en) * 2014-05-22 2015-11-26 Aegea Medical Inc. Systems and methods for performing endometrial ablation
US9993290B2 (en) * 2014-05-22 2018-06-12 Aegea Medical Inc. Systems and methods for performing endometrial ablation
US12114911B2 (en) 2014-08-28 2024-10-15 Angiodynamics, Inc. System and method for ablating a tissue site by electroporation with real-time pulse monitoring
US10271893B2 (en) 2014-12-15 2019-04-30 Medtronic Ablation Frontiers Llc Timed energy delivery
US11903690B2 (en) 2014-12-15 2024-02-20 Virginia Tech Intellectual Properties, Inc. Devices, systems, and methods for real-time monitoring of electrophysical effects during tissue treatment
US11033329B2 (en) 2014-12-15 2021-06-15 Medtronic Ablation Frontiers Llc Timed energy delivery
US10694972B2 (en) 2014-12-15 2020-06-30 Virginia Tech Intellectual Properties, Inc. Devices, systems, and methods for real-time monitoring of electrophysical effects during tissue treatment
US12402942B2 (en) 2014-12-15 2025-09-02 Medtronic Ablation Frontiers Llc Timed energy delivery
US12048480B2 (en) 2014-12-15 2024-07-30 Medtronic Ablation Frontiers Llc Timed energy delivery
US12446953B1 (en) 2015-05-12 2025-10-21 Neurent Medical Limited Devices for therapeutic nasal neuromodulation and associated methods and systems
US12268433B2 (en) 2015-05-12 2025-04-08 National University Of Ireland, Galway Devices for therapeutic nasal neuromodulation and associated methods and systems
US12484957B2 (en) 2015-05-12 2025-12-02 National University Of Ireland, Galway Devices for therapeutic nasal neuromodulation and associated methods and systems
US11950923B2 (en) 2015-08-07 2024-04-09 Electroceuticals, Llc Systems, methods and apparatuses for providing bioelectronic neurocode-based therapies to mammals
US11154238B2 (en) 2015-08-07 2021-10-26 Electroceuticals, Llc Systems, methods and apparatuses for providing bioelectronic neurocode-based therapies to mammals
US12011283B2 (en) 2016-02-19 2024-06-18 Aegea Medical Inc. Methods and apparatus for determining the integrity of a bodily cavity
US11331037B2 (en) 2016-02-19 2022-05-17 Aegea Medical Inc. Methods and apparatus for determining the integrity of a bodily cavity
US12471978B2 (en) 2016-03-04 2025-11-18 Aerin Medical Inc. Eustachian tube modification
US10702337B2 (en) 2016-06-27 2020-07-07 Galary, Inc. Methods, apparatuses, and systems for the treatment of pulmonary disorders
US12349967B2 (en) 2016-06-27 2025-07-08 Galvanize Therapeutics, Inc. Methods, apparatuses, and systems for the treatment of pulmonary disorders
US12403305B2 (en) 2016-06-27 2025-09-02 Galvanize Therapeutics, Inc. Immunostimulation in the treatment of viral infection
US10939958B2 (en) 2016-06-27 2021-03-09 Galary, Inc. Methods, apparatuses, and systems for the treatment of pulmonary disorders
US11369433B2 (en) 2016-06-27 2022-06-28 Galvanize Therapeutics, Inc. Methods, apparatuses, and systems for the treatment of pulmonary disorders
US11723710B2 (en) 2016-11-17 2023-08-15 Angiodynamics, Inc. Techniques for irreversible electroporation using a single-pole tine-style internal device communicating with an external surface electrode
US11717337B2 (en) * 2016-11-29 2023-08-08 St. Jude Medical, Cardiology Division, Inc. Electroporation systems and catheters for electroporation systems
US12336750B2 (en) 2016-12-22 2025-06-24 Aerin Medical Inc. Soft palate treatment
US11690999B2 (en) 2017-07-28 2023-07-04 Scandinavian Chemotech Ab Electrode device and a needle electrode for use in delivery of electrical pulses to a desired tissue of a mammal
US11607537B2 (en) 2017-12-05 2023-03-21 Virginia Tech Intellectual Properties, Inc. Method for treating neurological disorders, including tumors, with electroporation
US11938317B2 (en) 2017-12-26 2024-03-26 Galvanize Therapeutics, Inc. Optimization of energy delivery for various applications
US11925405B2 (en) 2018-03-13 2024-03-12 Virginia Tech Intellectual Properties, Inc. Treatment planning system for immunotherapy enhancement via non-thermal ablation
US11311329B2 (en) 2018-03-13 2022-04-26 Virginia Tech Intellectual Properties, Inc. Treatment planning for immunotherapy based treatments using non-thermal ablation techniques
US12390262B2 (en) 2018-03-13 2025-08-19 Virginia Tech Intellectual Properties, Inc. Treatment planning system for immunotherapy enhancement via non-thermal ablation
US12279808B2 (en) 2018-12-11 2025-04-22 Neurent Medical Limited Systems and methods for therapeutic nasal neuromodulation
US11950835B2 (en) 2019-06-28 2024-04-09 Virginia Tech Intellectual Properties, Inc. Cycled pulsing to mitigate thermal damage for multi-electrode irreversible electroporation therapy
US12458434B2 (en) 2019-07-16 2025-11-04 Galvanize Therapeutics, Inc. Treatment of the reproductive tract with pulsed electric fields
US12214189B2 (en) 2019-07-24 2025-02-04 Virginia Tech Intellectual Properties, Inc. Fourier analysis spectroscopy for monitoring tissue impedance changes and treatment outcome during electroporation-based-therapies
US12102379B2 (en) 2020-04-09 2024-10-01 Neurent Medical Limited Systems and methods for therapeutic nasal treatment using handheld device
US12096973B1 (en) 2020-04-09 2024-09-24 Neurent Medical Limited Systems and methods for therapeutic nasal treatment using handheld device
US12096974B1 (en) 2020-04-09 2024-09-24 Neurent Medical Limited Systems and methods for therapeutic nasal treatment using handheld device
US12108979B2 (en) 2020-04-09 2024-10-08 Neurent Medical Limited Systems and methods for improving sleep with therapeutic nasal treatment
US12089889B2 (en) 2020-04-09 2024-09-17 Neurent Medial Limited Systems and methods for therapeutic nasal treatment using handheld device
US12245803B2 (en) 2020-04-09 2025-03-11 Neurent Medical Limited Systems and methods for therapeutic nasal treatment using handheld device
US11998262B1 (en) 2020-04-09 2024-06-04 Neurent Medical Limited Systems and methods for improving sleep with therapeutic nasal treatment
US12485279B2 (en) 2020-11-25 2025-12-02 Virginia Tech Intellectual Properties, Inc. Methods for modulating temporal infrastructure of pulsed electric fields
US12357817B2 (en) 2021-04-06 2025-07-15 Aerin Medical Inc. Nasal neuromodulation devices and methods

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