WO2010107947A1 - Paramètres de champ électrique à impulsions nanosecondes destinés à détruire des tumeurs par un traitement unique - Google Patents

Paramètres de champ électrique à impulsions nanosecondes destinés à détruire des tumeurs par un traitement unique Download PDF

Info

Publication number
WO2010107947A1
WO2010107947A1 PCT/US2010/027708 US2010027708W WO2010107947A1 WO 2010107947 A1 WO2010107947 A1 WO 2010107947A1 US 2010027708 W US2010027708 W US 2010027708W WO 2010107947 A1 WO2010107947 A1 WO 2010107947A1
Authority
WO
WIPO (PCT)
Prior art keywords
tumor
electric field
applying
pulsed electric
pulse
Prior art date
Application number
PCT/US2010/027708
Other languages
English (en)
Inventor
Richard Lee Nuccitelli
Pamela Nuccitelli
Saleh Sheikh
Mark Kreis
Kevin Tran
Brian Athos
Original Assignee
Bioelectromed Corp.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bioelectromed Corp. filed Critical Bioelectromed Corp.
Publication of WO2010107947A1 publication Critical patent/WO2010107947A1/fr

Links

Classifications

    • 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
    • A61B18/1492—Probes or electrodes therefor having a flexible, catheter-like structure, e.g. for heart 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
    • 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
    • A61B2018/00053—Mechanical features of the instrument of device
    • A61B2018/00214—Expandable means emitting energy, e.g. by elements carried thereon
    • 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
    • A61B2018/00898—Alarms or notifications created in response to an abnormal condition
    • 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
    • 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
    • A61B2018/143—Needle multiple needles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/36—Image-producing devices or illumination devices not otherwise provided for
    • A61B90/37—Surgical systems with images on a monitor during operation
    • A61B2090/378—Surgical systems with images on a monitor during operation using ultrasound

Definitions

  • This application is directed to systems and methods for treating tumors on internal organs that have been identified using endoscopic ultrasound by precisely positioning a pulsed field delivery device on or in the tumor guided by ultrasound imaging.
  • Endoscopic ultrasound combines endoscopy and ultrasound in order to obtain images and information about the digestive tract and the surrounding tissue and organs.
  • Endoscopy refers to the procedure of inserting a long flexible tube via the mouth or the rectum to visualize the digestive tract
  • ultrasound uses high-frequency sound waves to produce images of the organs and structures inside the body such as ovaries, uterus, liver, gallbladder, pancreas, aorta, etc.
  • a small ultrasound transducer is installed on the tip of the endoscope.
  • the ultrasound transducer By inserting the endoscope through the esophagus into the stomach, the ultrasound transducer can be placed against the inner surface of the stomach or gastrointestinal tract so that sound waves can be beamed through the stomach wall to obtain high quality ultrasound images of the organs on the other side of the stomach wall such as the kidney, pancreas and liver.
  • the images obtained are frequently more accurate and more detailed than the ones obtained by traditional ultrasound where the transducer in placed on the skin.
  • Tumors on internal organs have ultrasound reflection properties that are different from the organ so that they can be easily detected with EUS.
  • EUS An example of EUS is shown and described in U.S. Pat. 7,318,806, which is incorporated herein by reference in its entirety.
  • Some of these ultrasound imaging endoscopes have been designed with an open channel down the center into which a fine needle aspirator or other instruments can be inserted to allow the sampling of tumor tissue by poking through the stomach wall and into the tumor tissue for aspiration. The aspirated tissue sample can then be stained and observed by a pathologist to obtain an immediate diagnosis of malignancy.
  • Nanosecond pulsed electric fields nsPEF have been found to trigger both necrosis and apoptosis in skin tumors.
  • nsPEF Treatment with nsPEF independently initiates the process of apoptosis within the tumor cells themselves causing the tumor to slowly self- destruct without requiring toxic drugs or permanent p ⁇ rmeabi ⁇ ization.
  • nanosecond pulsed electric fields halt blood flow in the capillaries feeding it which in turn reduces blood flow to the tumor and activation of apoptosis pathways causing the tumor to slowly shrink and disappear within an average of 47 days.
  • nsPEF An example of nsPEF is shown and described in U.S. Pat. 6,326,177, which is incorporated herein by reference in its entirety.
  • Various devices utilizing ElTS are known yet they are generally insufficient to treat tumors accessible via endoscopic access utilizing nsPEF. Accordingly, there exists a need for methods and devices which are efficacious and safe in facilitating the treatment of tumors in patients.
  • nsPEF nanosecond pulsed electric fields
  • an electrode assembly designed to draw tissue into a recessed cavity in order to immobilize the tissue and position the electrodes firmly against or within the tissue.
  • the recessed cavity may be varied in its size to match a size of any particular rumor to be treated such that the treated tumor may be received within the cavity in close proximity or in direct contact against the electrodes.
  • the electrode assembly may be configured into a variety of configurations for delivering electrotherapy and may also utilize suction to fix in place the tissue being treated.
  • the electrode assembly may comprise a support member having a pair of "U"-shaped planar electrodes disposed on the periphery of the recessed cavity.
  • Other variations may include a pair of spaced apart parallel plate electrodes while other variations may include a plurality of needle electrodes which are mounted at the base of a back plate to control the penetration depth of the tissue as it it> sucked into the recessed cavity.
  • each recessed cavity may have multiple apertures, such as on the order of 100 ⁇ m in diameter.
  • An air pump e.g., an oscillating diaphragm air pump or other suction source, is then coupled to the support member on the side of the base w all support opposite the recessed cavity and is used to generate a mild suction that pulls the tissue to be treated into the cup-like volume.
  • the support member may Miction or draw in tissue to be treated from various regions of the body into the recessed cavity into contact or proximity to the electrodes. Drawing in the tissue may further facilitate tissue treatment by clearly defining the treatment area to be treated for the operator.
  • nsPEF When nsPEF is applied to a tissue region such as a tumor, if a ⁇ arge resistance between the electrode and the tumor restricts current flow (such as the presence of the stratum corneitm in skin), the field may not pass into the tumor effectively.
  • a minimum current of 20 A (although lower currents may be applied if so desired) that may pass through the tumor during nsPEF application to have a desired effect of triggering tumor apoptosis.
  • the nsPEF therapy may be applied at a pulse frequency that will not heat the tissue above, e.g.. 40 0 C (the minimum temperature for hyperthermia effects). Therapy ⁇ ith nsPEF treatment is thus able to initiate apoptosis within the tumor cells without raising the temperature more than a few degrees so as to prevent harm to surrounding tissues from heat transfer.
  • the frequency of the applied pulses is desirably 7 pulses per second (Hz) or lower to prevent damage to surrounding tissues.
  • one or all of the following parameters may be adjusted to provide optimal treatment of tissue to effect tumor apoptosis: ( 1) pulse amplitude (kV'cm); (2) pulse duration (ns); (3) pulse application frequency (Hz); and/or (4) pulse number applied. [0014] Because the value of these parameters may vary widely over a number of ranges, it has been determined that particular ranges may be applied for effecting optimal tissue treatment which may effect tumor apoptosis in as few as a single treatment. In varying pulse amplitude, an applied amplitude as low as, e.g., 20 kV/ ' cm, may be sufficient for initiating an apoptotic response in the treated tissue.
  • the pulse amplitude may, of course, be increased from 20 kV/cm, e.g., up to 40 kV/'cm or greater. However, an applied amplitude of at least, e.g., 30 kV/cm or greater, may be applied for optimal response in the treated tissue, In varying pulse duration, durations in the range of. e.g., 50-900 ns, may be highly effective although shorter durations may be applied if the number of pulses is increased exponentially. In varying pulse application frequency, frequencies up to 7 Hz may be applied with 100 ns pulses without heating surrounding tissues to hyperthermic levels.
  • tissue heating may be dependent on pulse width multiplied by the frequency of application, shorter pulses may be applied at proportionately higher frequencies with similar heat generation.
  • the pulse number determines the total energy applied to the tissue region. Generally, applying a minimum pulse number of 600 pulses may result in complete remission of tumors.
  • nsPEF therapy having a pulse duration of 100 ns may be applied over a range of, e.g., 1000-2000 pulses, to effectively treat the tissue region.
  • N minimum number of pulses to cause tumor apoptosis with a single treatment
  • t pulse duration (in nanoseconds)
  • an elongate instrument which may be delivered via or through an endoscopic device may utilize any one or more of the nsPEF parameters described herein for tumor treatment.
  • the endoscopic device particularly an EUS device. may be used to image or locate a tissue region to be treated. Ultrasound imaging may be particularly useful in locating one or more tumors for treatment although conventional endoscopic imaging may also be utilized.
  • the nsPEF instrument With the targeted tissue region located within the body, the nsPEF instrument may be positioned or advanced within one or more working channels in the endoscope until a tapered piercing end of the nsPEF instrument is projected from a distal end of the endoscope.
  • the nsPEF instrument may also have an expandable or re configurable bipolar electrode assembly that may extend or reposition itself into a deployed profile. With the electrode assembly deployed, the piercing tip may be penetrated into or through the tissue to be treated (such as the tumor) while under the guidance of ultrasound imaging from the endoscope for desirably positioning the instrument.
  • the outer reference electrodes may be actuated by the operator to reconfigure the electrodes for pulse delivery and/or to retract them for insertion and/ or withdrawal from the patient.
  • the electrodes may be coupled via an electrical cable having at least two conductors which may also extend through the endoscope or electrode assembly to conduct the pulsed electric fields to the distal end effector.
  • the electrode assembly may be advanced into the tissue to be treated until the deployed outer electrodes are positioned on or against a surface of the tumor or tissue region.
  • the deployed outer electrodes may be spread or reconfigured into a variety of shapes, e.g.. hemi -circular plate configuration.
  • suction may be applied through, e.g., a working channel either through the endoscope, electrode assembly, or both for drawing the tumor into apposition against the electrode assembly.
  • Other mechanisms such as tissue graspers may also be used.
  • the electrode assembly may be configured to project distally from the shaft of the nsPEF instrument to surround the tissue to be treated, such as a tumor.
  • Various numbers of conductive needles may be utilized such that the tumor to be treated is surrounded by the needle array and the electric field created between the needles may be uniformly applied to the tumor.
  • These instruments may utilize any of the nsPEF parameters as described herein to effectively treat the tissue with, e.g., a single treatment of nsPEF therapy.
  • the treatment instrument may be withdrawn from the tumor and the outer electrodes may be reconfigured back to their original low profile configuration for retraction back into the endoscope.
  • Fig. 1 illustrates a schematic diagram of an apparatus for generating a nanosecond pulsed electric field (nsPEF) for treating tumors.
  • Figs. 2A to 2F illustrate perspective views of variations of electrode assemblies which may be used to apply the nsPEF upon tissue adhered via a retaining mechanism, such as a suction mechanism.
  • Figs- 3 A and 3B show side and perspective views, respectively, of an exemplar ⁇ ' suction electrode assembly having a plurality of needle electrodes projecting into a recessed cavity.
  • FIGs. 4A and 4B show side and perspective views, respectively, of another variation of the suction electrode assembly having two apposed electrodes positioned on either side of the recessed cavity.
  • FIGs. 5 A and 5B show side and perspective views, respectively, of yet another variation of the suction electrode assembly having at least six circumferentially positioned electrodes around the recessed cavity.
  • Figs. 6A to 6D illustrate side views of various tissue regions drawn into the recessed cavity for tissue treatment via nsPEF application.
  • FIG. 7 shows a perspective view of an example of a portable nsPEF treatment assembly readied for transportation or shipping.
  • Fig. 8 shows a graph of the applied pulse voltage with a rise time of, e.g., 15 ns and the current waveform delivered to the treated tissue.
  • Fig. 9 shows a graph illustrating the correlation for a given pulse duration or width and number of applied pulses to eliminate tumors in, e.g., a single treatment.
  • Fig. 10 illustrates a chart of the Optimum Pulse Number where a majority of tumors were successfully treated with no signs of resurgence after a single treatment when pulsed with at least 1500 to 2000 pulses.
  • Fig. 1 1 illustrates a chart of the Percent Efficacy after one treatment where the efficacy is shown to increase from 1500 pulses and higher.
  • Fig. 12 illustrates a chart of the Optimum Amplitude of the pulses where the number of tumors successfully treated after a single treatment increases at higher amplitudes.
  • Fig. 13 shows a chart recording tumor detection via GFP detection under fluorescent microscopy for tissue treated via nsPEF therapy with various electrode assemblies.
  • Fig. 14 s a chart recording transillumination and reflected light images adjacent to one another of the treated tissues (melanomas) corresponding to the various electrode assemblies.
  • Fig. 15 shows a chart with the measured change in GFP signal area normalized on a logarithmic scale over a period of time following nsPEF treatment with various electrode assemblies.
  • Fig. 16 shows a chart with the measured change in tumor area normalized on a logarithmic scale over a period of days following nsPEF treatment with various electrode assemblies.
  • Fig. 17 show s histological sections of both the treated tumors as w ell as skin immediately adjacent to the suction electrode location taken at different times after nsPEF treatment.
  • Fig. 18 show s a chart indicative of the number of tumors treated along w ith the number eliminated (e.g., by 1, 2, or 3 treatments) relative to the number of pulses applied during nsPEF treatment.
  • Fig. 19 shows a chart indicative of the number of tumors treated along with the number eliminated (e.g.. bj L 2, or 3 treatments) relative to the pulse amplitude applied during nsPEF treatment.
  • Fig. 20 shows a chart indicative of the number of tumors treated along with the number eliminated (e.g., by 1, 2. or 3 treatments) relativ e to the pulse frequency applied during nsPEF treatment.
  • Fig. 21 shows a chart recording tumor detection via GFP detection under fluorescent microscopy for tissue treated via nsPEF at various amplitudes.
  • Fig. 22 shows a chart recording trans-illumination images of treated tissue at various amplitudes.
  • Fig. 23 shows a chart recording reflected light images of treated tissue at various amplitudes.
  • Fig. 24 show s a chart recording the temperature increase within a tumor over a period of several minutes during nsPEF treatment.
  • Fig. 25 shows a chart recording the reflected light images of different nsPEF-treated tumors for various electrode assembly configurations.
  • Fig. 26 shows a chart of number of tumors treated and the percentage of tumor regrowth recorded over the range of pulses applied during a single treatment for a pulse duration of 25 ns at 30 kV/cm and with 20-25 Hz pulse frequency.
  • Fig. 27 shows a chart of number of tumors treated and the percentage of tumor regrowth recorded over the range of pulses applied during a single treatment for a pulse duration of 50 ns at 30 kV/cm and a pulse frequency of 20 Hz.
  • Figs. 28-30 show perspective views of a nsPEF instrument having a plurality of reference electrodes which are reconfigurable between a low-profile delivery shape and an extended deployed shape.
  • Fig. 31 shows a perspective view of a nsPEF instrument deployed from an
  • Fig. 32 shows a perspective view of a nsPEF instrument advanced into an organ and/or tumor under guidance of ultrasound imaging from the endoscope.
  • Fig. 33 shows a perspective view of a nsPEF instrument having one or more openings for drawing a suction to adhere tissue to be treated to the instrument.
  • FIGs. 34A and 34B show perspective views of another variation of a nsPEF instrument having a four-needle array projecting from a shaft for tissue treatment.
  • Fig. 34C shows an example of the electric field distribution formed by the four-needle array during nsPEF therapy.
  • Figs. 35A and 35B show perspective views of another variation of a nsPEF instrument having a six-needle array projecting from a shaft for tissue treatment.
  • Fig. 35C shows an example of the electric field distribution formed by the six-needle array during nsPEF therapy.
  • FIGs. 36A and 36B show perspective views of yet another variation of a nsPEF instrument having an eight-needle array projecting from a shaft and piercing length for tissue treatment.
  • Fig. 36C shows an example of the electric field distribution formed by the eight-needle array during nsPEF therapy.
  • an apparatus 10 (as described below) is illustrated schematically for intracellular electro-manipulation which includes a power supply 12 (a high voltage power supply, e.g., 20 kV or higher) and a delivery system 14 may be adapted to direct the electric pulse, particularly a nanosecond pulsed electric field (nsPEF), output to a load 16 such as target cells positioned in proximity to the delivery system 14.
  • the pulse generator may include a pulse forming network 18 and a high voltage switch 20, such as a spark gap.
  • the pulse forming network 18 may be a high voltage cable., a strip-line., or a pulse forming network constructed of individual capacitors and inductors in a transmission line arrangement with a matching network 22.
  • the high voltage switch 20 can suitably be a gaseous, liquid or solid state switch, e.g., a spark gap.
  • the energy in the pulse forming network 18 may be stored capacitively, which utilizes a closing switch 20 to release a pulse, or inductively, which requires an opening switch to release a pulse.
  • an electrical pulse is delivered through the delivery system 14 and launched into the load 16, e.g., the target cells in suspension or tissue form.
  • the switch 20 can be triggered by a variety of common methods, e.g., optically or electrically.
  • the power supply 12 may utilize a high voltage DC power supply (e.g.,
  • Matsusada RB3O-3OP to charge up, e.g., a coaxial cable (such as through a current limiting resistor), to a high voltage creating a capacitor on the coaxial cable between the inner conductor and its outer conductive shielding.
  • a coaxial cable such as through a current limiting resistor
  • a corresponding pulse of high voltage with, e.g., 5-15 ns rise and fall times, is generated across the load.
  • the duration of this pulse may be determined by the length of cable used, and the amplitude may be determined by the voltage at which the coaxial cable was charged.
  • a coaxial cable having a length of. e.g..
  • the generator 10 itself (including all components) may be sufficiently portable to fit into a rolling suitcase.
  • a microcontroller such as a digital programmable logic device (e.g.. Microchip PIC16F887) may be incorporated into the assembly to control the pulse delivery.
  • the user may input information to the microcontroller-based system via, e.g., a keypad, and a liquid crystal display (LCD) may be implemented to display information to the user.
  • the circuit may be battery-powered.
  • the 'ioad " ' 16 which includes the target cells in tissue or suspended in a medium, is placed between two or more electrodes. These electrodes may be solid material (in any of a number of suitable shapes, e.g., planar, cylindrical, spherical, etc), wires or meshes or combinations thereof.
  • One (set of) electrode(s) is connected to the high voltage connection of the pulse generator, and a second (set of) electrode(s) is connected to the ground connection of the pulse generator in a suitable manner, e.g., via a second stripline or high voltage cable.
  • the electrode material is a conductor, most commonly metal.
  • an electrode assembly may be utilized.
  • An example of some electrode assemblies which may be utilized are shown and described in further detail in U.S. Prov. Pat. App.
  • a medical instrument for delivering electrotherapy illustratively comprises an outer support member having an open distal end and a base wall portion within the support member arranged to form a cup-like open volume in the distal end of the support member. At least one aperture is formed in the cup- like volume for applying a suction mechanism to the cup-like region. At least a first and a second electrode have at least a portion extending into the cup-like region.
  • a system for delivering electrotherapy comprises a medical instrument having a suction mechanism for providing a source of suction within the cup-like volume to hold a tissue portion to be treated, and a power supply coupled to the first and second electrodes for applying electrical signals to provide electrotherapy to the tissue.
  • the tumor When the tissue or tumor to be treated is adhered to the instrument by the suction mechanism, the tumor may be positioned in apposition to the electrode assembly for effectively delivering the pulses.
  • a variety of pulse generators can be used. However, the pulse generator is desirably capable of delivering high voltage pulses (e.g., in the i-900 ns range) which are imposed across a pair of spaced apart electrodes, to generate electrical fields on the order of, e.g., 20 to 100 kV''cm.
  • the electrode assembly may be designed to draw tissue into the recessed cup-like volume in order to immobilize the tissue and position the electrodes firmly against or within the tissue. This allows for desirable targeted treatment of the tissue.
  • Fig s - 2A to 2D show variations of electrode assemblies for delivering electrotherapy using suction electrodes.
  • the electrode assemblies may utilize stainless steel electrodes which are electropolished to eliminate any sharp edges that can lead to corona formation at high voltages and are then embedded in a dielectric material, such as a plastic.
  • Very small holes 38 may be formed or drilled into the base of the recessed cavity 39 and during use a suction may be applied through the holes to draw the tissue to be treated into the recessed cavity 39, e.g., cup-like volume having an inner diameter of about 4 mm and a depth of about 2 mm. for electric field application.
  • the dimensions of recessed cavity 39 are intended to be illustrative and not limiting. Accordingly, recessed cavity 39 may be varied in its size to match a size of any particular tumor to be treated such that the treated tumor may be receh ed ⁇ ithin the cavity in close proximity or in direct contact against the electrodes. Fig.
  • FIG. 2A shows an example of an electrode assembly
  • a support member 30 having a cylindrical cross section having, e.g., six (6) spaced apart planar electrodes 32, positioned circumferentially about the recessed cavity 39.
  • the electrodes 32 are electrically isolated from one another by a dielectric material 34. such as plastic upon which the electrodes can be, e.g., partially embedded.
  • the electrodes 32 have one exposed side (without plastic) along the wall of the cavity 39 to allow direct contact to the skin.
  • the opposite sides of the electrode 32 may be coated with plastic.
  • electrodes in apposition from one another form bias pairs.
  • FIG. 2B shows another variation of the electrode assembly comprising support member 30 having a cylindrical cross section and having a pair of "U" -shaped planar electrodes 40 and 42 disposed on the periphery of the recessed cavity 39.
  • the electrodes 40, 42 may be electrically isolated from one another by a dielectric material, such as plastic 44 upon ⁇ hich the electrodes can be embedded.
  • Fig. 2C shows another variation comprising a support member 30 having a rectangular cross section and having a pair of spaced apart parallel plate electrodes 46 and 48.
  • the back plate 50 having a plurality of apertures 52 therein may be formed from a dielectric material.
  • Fig. 2D shows another variation comprising a support member 30 having a plurality of needle electrodes 54 which are mounted at the base of the back plate 56 to control the penetration depth of the tissue as it is sucked into the cup-shaped volume. The distance between the center needle and each of the four outer needles may vary but is shown in this example as about 2 mm.
  • Fig s - 2E and 2F show perspective and end views., respectively, of yet another variation of an electrode assembly.
  • support member 30 may also define the recessed cavity 39 and the plurality of apertures 38 defined over the back plate 36.
  • a plurality of needle electrodes 54 may project into the cavity 39 from the back plate 36 with the needle electrodes 54 arranged in a parallel array.
  • a linear arrangement of three (3) needle electrodes 54 may be aligned in parallel with an adjacent linear arrangement of three (3) needle electrodes 54, as shown, with the apertures 38 positioned about the electrode array.
  • each electrode is electrically isolated from one another, electrodes can be connected to separate electrically conductive (e.g. copper) wires, such as wires that end on a connector projecting out of the side of the plastic cylinder. This allows each electrode to be connected to a different pulse generator and biased differently for maximum versatility, if so desired.
  • electrically conductive e.g. copper
  • the back plate of each recessed cavity may have multiple apertures, such as on the order of 100 ⁇ m in diameter.
  • An air pump e.g., an oscillating diaphragm air pump or other suction source, is then coupled to the support member on the side of the base wall support opposite the recessed cavity and is used to generate a mild suction that pulls the tissue to be treated into the cup-like volume.
  • the electrodes may comprise an electrical conductor that is resistant to corrosion such as, for example, stainless steel.
  • the electrodes portioned at the distal end are preferably el ⁇ ctropolished or otherwise p ⁇ anarized. Electropolishing removes comers and sharp edges to minimize undesirable corona discharge when large voltages associated with generating nsPEF are applied to the electrodes.
  • the parameters in above-described U.S. Pat. 6,326,177 are generally insufficient in effectively treating such tumors.
  • the disclosed number of pulses, i.e., 20 pulses, at 100 us is insufficient; rather, 2000 pulses at 100 ns instead would be optimal for treating such tumors.
  • FIG. 3 A, 4 A, and 5 A side views of exemplary suction electrodes developed for use and experimentation are show n.
  • FIGs. 3B, 4B. and 5B show corresponding perspective views of the electrode treatment distal end effectors.
  • Each support member 60 may be seen having a recessed cavity 39 for contacting and receiving the tissue to be treated.
  • Fig. 3B illustrates the recessed cavity 39 of support member 60 having a plurality of needle electrodes 62, as previously described.
  • FIG. 4B illustrates the recessed cavity 39 having at least tw o electrodes 64 positioned in apposition on either end of the cavity 39 for treating the tissue region positioned therebetween and
  • Fig, 5B illustrates a variation having at least six electrodes 66 electrically isolated from one another and positioned about a circumference of recessed cavity 39. as previously described.
  • Figs. 6A to 6D show side view s of the support member 60 suctioning or drawing in tissue to be treated from various regions of the body to illustrate how the tissue may be drawn into the recessed cavity 39 into contact or proximity to the electrodes. Drawing in the tissue may further facilitate tissue treatment by clearly defining the treatment area to be treated for the operator. As shown in Fig.
  • a region of tissue 70 from a subject ' s face may be readily drawn into recessed cavity 39.
  • Fig. 6B illustrates a region of tissue 72 from a subject's arm.
  • Fig. 6C illustrates a region of tissue 74 from a subject's stomach, and
  • Fig. ⁇ D likewise illustrates a region of tissue 76 to be treated from the subject ' s leg.
  • the assembly may be stored or housed in a housing 80 for ready shipping or transportation, as shown in Fig. 7.
  • An example is shown in the graph of Fig. 8 of the applied pulse voltage 90 having a rise time of. e.g., 15 ns in this particular example, and the resulting current waveform 92 delivered to the tissue region, e.g., tumor, when utilizing an electrode treatment assembly having a six-electrode configuration, as previously described.
  • nsPEF When nsPEF is applied to a tissue region such as a tumor, if a large resistance between the electrode and the tumor restricts current flow (such as the presence of the stratum cornemn in skin), the field may not pass into the tumor effectively.
  • nsPEF therapy may be applied at a pulse frequency that will not heat the tissue above, e.g.. 40 0 C (the minimum temperature for hyperthermia effects). Therapy with nsPEF treatment is thus able to initiate apoptosis within the tumor cells without raising the temperature more than a few degrees so as to prevent harm to surrounding tissues from heat transfer.
  • the frequency of the applied pulses is desirably 7 pulses per second (Hz) or lower to prevent damage to surrounding tissues.
  • treatment of tissue regions such as skin tumors may be effected by applying nsPEF ⁇ hile specifying various parameters. For instance, one or all of the following parameters may be adjusted to provide optimal treatment of tissue to effect tumor apoptosis: ( 1) pulse amplitude (kV/cm); (2) pulse duration (ns); (3) pulse application frequency (Hz): and/or (4) pulse number applied.
  • nsPEF ⁇ hile specifying various parameters. For instance, one or all of the following parameters may be adjusted to provide optimal treatment of tissue to effect tumor apoptosis: ( 1) pulse amplitude (kV/cm); (2) pulse duration (ns); (3) pulse application frequency (Hz): and/or (4) pulse number applied.
  • an applied amplitude as low as, e.g.. 20 kV/cm may be sufficient for initiating an apoptosis response in the treated tissue.
  • the pulse amplitude may, of course, be increased from 20 kV/em. e.g., up to 40 kV'cm or greater.
  • an applied amplitude of at least, e.g., 30 kV/cm or greater may be applied for optimal response in the treated tissue.
  • durations in the range of, e.g.. 50-900 ns may be highly effective although shorter durations may be applied if the number of pulses is increased exponentially.
  • pulse application frequency frequencies up to 7 Hz may be applied with 100 ns pulses without heating surrounding tissues to hyperthermic levels. Because tissue heating may be dependent on pulse width multiplied by the frequency of application, shorter pulses may be applied at proportionately higher frequencies with similar heat generation.
  • the pulse number determines the total energy applied to the tissue region. Generally, applying a minimum pulse number of 600 pulses may result in complete remission of tumors.
  • nsPEF therapy having a pulse duration of 100 ns may be applied over a range of, e.g., 1000-2000 pulses, to effectively treat the tissue region.
  • N minimum number of pulses to cause tumor apoptosis with a single treatment
  • t pulse duration (in nanoseconds)
  • tumors such as melanoma tumors
  • nsPEF when exposed to 100 ns long pulses having a 15 ns rise time where the minimum number of pulses range from, e.g., 1500 to 2000 pulses, as illustrated in the chart of Fig. 10 which SIIO ⁇ VS the Optimum Pulse Number where a majority of tumors were successfully treated after a single treatment when pulsed with at least 1500 to 2000 pulses. Accordingly, as shown in the graph of Fig. 11 , the Percent Efficacy after one treatment is shown to increase from 1500 pulses and higher. [0085] As also indicated in the chart of Fig. 12 which illustrates Optimum
  • Amplitude of the pulses the number of tumors successfully treated after a single treatment begins to rise at higher amplitudes, e.g., from 25 kV/cm.
  • the minimum pulse amplitude observed is 30 kV/cm in this example ⁇ hile the optimum pulse amplitude is 40 kV/cm or greater in this example for effectively treating tumors such as melanoma tumors.
  • another parameter is pulse frequency. It has been determined that the optimum pulse frequency is 7 Hz as higher frequencies may result in excessive heat applied to the tissue, as previously described.
  • the treatment time to optimally treat a tumor would be at least 4 to 5 minutes at about, e.g., 4.76 minutes.
  • a treated tumor may be effectively eliminated within a week or two following a single application of the nsPEF. Additional treatments of the tumor or tumors may be effected if necessary or desired.
  • EXAMPLE 2 [0087] In this particular example, Murine B16-F10 melanoma cells transfected with enhanced green fluorescent protein (eGFP) were obtained and stored in liquid nitrogen until use. These cells were cultured and injected into 4-6 week old female Nu/Nu mice (immunodeficient, hairless, albino) using standard procedures at four injection sites each. Tumors were detected visually by the bulges they produced and by GFP detection under fluorescent microscopy.
  • eGFP enhanced green fluorescent protein
  • Electrodes 110. 112, and 114 each had a recessed cavity ⁇ ith an inner diameter of about 4 mm and a depth of about 2 mm w hile the electrode assembly 116 utilized an array of needles positioned within the recessed cavity where a distance between the center needle and each of the outer needles was about 2 mm.
  • one or more electrodes 118 were used to discharge the energy into the treated tissue while the remaining electrodes functioned as return electrodes.
  • a suction was drawn (e.g., 500 mm Hg) within the recessed cavity to pull the tumor therein and nsPEF therapy was applied with 100 ns pulse widths while either the pulse number, amplitude, or frequency was varied.
  • a typical treatment applied 2700 pulses with a pulse width of 100 ns at 30 kV'cm and a frequency of 5-7 Hz.
  • the suction electrode assembly was rotated 45° every 500 pulses to ensure uniform field distribution across the tumor.
  • GFP fluorescence changes following nsPEF application using the electrode pictured at the top of each column were noted at 0 min, 5 mm. 1 hr. 2 hr, 3 hr. and 4 hr.
  • FIG. 13 show s the resulting tumor activity for each of the electrode assemblies 110, 112, 114. and 116. Tumors that showed signs of regrowth, generally indicated by renew ed GFP production, were retreated using the same parameters as the first treatment. Tumors were considered eliminated ⁇ vhen no resro ⁇ vth was detected within two w eeks after the last treatment. [0091] Fig.
  • FIG. 14 also shows trans-illumination and reflected light images adjacent to one another of the treated tissues (melanomas) corresponding to the various electrode assemblies 110, 112, 114, and 116.
  • the images were recorded on the days indicated in the upper left corner of each pair of figures, e.g., 0, 3, 7, etc., where nsPEF treatment (if applied) occurred on day 0. [0092] Fig.
  • FIG. 15 shows the measured change in GFP signal area normalized on a logarithmic scale over a period of time in hours following nsPEF treatment with the indicated suction electrode type, i.e., the 6-pole dual plot correlates to electrode assembly 110, the 6-pole plot correlates to electrode assembly 112, the 2-pole plot correlates to electrode assembly 114, and the needle plot correlates to electrode assembly 116.
  • histological sections of the treated tumors and skin immediately adjacent to suction electrode location were taken at different times after treatment with 2000 pulses at 30 kV ' cm and a frequency of 7 Hz. Images in the three left columns were taken from skin (melanoma, epidermis, and blood cells) with tumors before (i.e., 0 hr) and several times after nsPEF treatment (i.e.. at 1 hr. 6 hrs, 24 hrs. and 48 hrs).
  • a minimum amplitude of 30 kV/cm has shown desirable elimination of tumors, although the amplitude may be lowered or increased if so desired, as indicated in the chart of Fig. 19.
  • pulse frequency it is generally desirable to use the highest pulse application frequency possible without damaging the surrounding tissue given the temperature rise in the tissue, as indicated in the chart of Fig. 20.
  • nsPEF at i Hz at 30 kV'cm and 20 A to tissue may increase the tumor temperature by 2 0 C whereas 5 Hz increased the tumor temperature by 6-7 0 C.
  • Applying a frequency of 7 Hz may limit the temperature rise of the treated tissue to 37 ° C which is below the hyperthermia threshold of 41° C.
  • applying pulses at 5 Hz or higher was more effective than using lower frequencies.
  • Typical melanoma responses to nsPEF therapy in the 10-25 kV'cm range were recorded where four melanomas on one mouse ⁇ ere treated with either 10, 15, 20 or 25 kV'cm nsPEF (2000 pulses, 100 ns, 7 Hz).
  • the GFP fluorescence at each respective pulse amplitude over a period of 0, 1, 6. and 8 days were recorded, as shown in Fig. 21. as were the trans-illumination, as shown in Fig. 22. and reflected light images, as shown in Fig. 23.
  • the temperature increase inside a tumor over a period of several minutes during nsPEF application were also recorded, as shown in Fig. 24.
  • a pulse amplitude of 30 kV'cm ⁇ ith 100 ns long pulses were applied beginning at the indicated frequency 120 with frequency of 1 Hz and 5 Hz. Pulsing was stopped at the indicated frequency 122 for 5 Hz and at 124 for 1 Hz. The 1 Hz pulse application increased tumor temperature bj. 2° C while the 5 Hz pulse application increased the temperature by 7° C.
  • nsPEF-treated skin on the indicated day following nsPEF therapy is shown in Fig. 25 in reflected light images of 20 different nsPEF-treated tumors.
  • the electrode configuration 110. 112, 114, and 116 used is shown with respect to each column.
  • EXAMPLE 4 [0098] A number of tumors were treated ⁇ ith nsPEF therapy over a range of pulses.
  • Fig. 26 With a pulse duration of 25 ns at 30 kV-'cm and with 20-25 Hz pulse frequency, the number of tumors treated and the percentage of tumor regrowth were recorded over the range of pulses applied during a single treatment, as shown in the chart of Fig. 26.
  • the chart illustrates how tumor elimination may be effected when at least 15.000 pulses w ere applied. Although the percentage of tumors eliminated was less than 100% at 15,000 pulses, complete tumor regrowth elimination may be potentially effected by treatment at a greater number of pulses when applied at these particular parameters.
  • Fig. 27 likew ise illustrates the number of tumors treated and the percentage of tumor regrowth over the number of pulses applied.
  • the optimal pulse number applied for a single treatment may completely eliminate tumor regrowth at 8000 pulses.
  • a number greater than 8000 pulses may also be potentially applied to effectuate complete tumor elimination.
  • an elongate instrument which may be delivered via or through an endoscopic device may utilize any one or more of the nsPEF parameters described herein for tumor treatment.
  • the endoscopic device particularly an EUS device, may be used to image or locate a tissue region to be treated. Ultrasound imaging may be particularly useful in locating one or more tumors for treatment although conventional endoscopic imaging may also be utilized.
  • the nsPEF instrument 140 With the targeted tissue region located within the body, the nsPEF instrument 140 may be positioned or advanced within one or more working channels in the endoscope until a tapered piercing end of the nsPEF instrument is projected from a distal end of the endoscope to deliver a highly localized treatment.
  • the nsPEF instrument 140 may be configured either as a bipolar or monopolar electrode configuration.
  • the nsPEF instrument 140 may be positioned upon the distal end of an elongate shaft 130 (such as an insulated conducting cable disposed within a flexible stainless steel tubing) which is sufficiently flexible for advancement through the endoscopic working lumen, as shown in the perspective view of Fig. 28.
  • the piercing tip 132 which may also function as a conducting electrode may project distally from the shaft 130 for piercing directly into the tissue to be treated or through a tissue region and/or for delivery and/or retraction through the endoscopic working lumen or patient body. Because the nsPEF instrument 140 as well as shaft 130 is designed to be advanced through the working lumen of an endoscopic device.
  • the nsPEF instrument 140 and/or shaft 130 may have a diameter of, e.g., around 3 mm, for advancement through a working lumen having a diameter of, e.g., 3.7 mm, with a working length of, e.g., about 125 cm.
  • One or more reference electrodes 134 may be positioned proximal to the piercing tip 132 in a low-profile configuration where the one or more reference electrodes 134 are placed against the conducting electrode.
  • each reference electrode 134 may be pivotably connected to the elongate shaft 130 such that when the one or more electrodes 134 are actuated to reconfigure, each electrode 134 may rotate about its pivot to extend into a radial pattern.
  • the piercing tip 132 and one or more reference electrodes 134 may be in connected in electrical communication with a pulse generator (as described herein) through corresponding conductors passed through elongate shaft 130.
  • the nsPEF therapy may be applied through nsPEF instrument 140 with the parameters as described herein.
  • Fig. 29 shows a perspective view of the one or more reference electrodes
  • each electrode 134 being partially extended or reconfigured about its proximal pivot into its deployed configuration.
  • the electrodes 134 may be actuated by the operator using a mechanism for deploying the electrodes 134 into their deployed configuration.
  • one or more corresponding cables or wires 136 attached to each electrode 134 may extend through openings 138 into and through the shaft 130 to an actuator positioned at or along a proximal end of shaft 130.
  • the piercing tip 132 may be penetrated into or through the tissue to be treated (such as the tumor) while under the guidance of ultrasound imaging from the endoscope for desirably positioning the instrument.
  • the one or more reference electrodes 134 are shown in their deployed configuration where each electrode 134 may extend radially from shaft 130. Although six electrodes 134 are illustrated circumferentially positioned and radially extending about shaft 130 in this embodiment, other variations may utilize different numbers of electrodes which are spread or configured into a variety of different shapes, e.g., a hemi-circular plate configuration.
  • a single treatment via nsPEF instrument 140 with the parameters described herein may stop blood flow to the tumor and initiate apoptosis and/ or necrosis resulting in tumor shrinkage.
  • the one or more reference electrodes 134 may be deployed, as shown in Fig. 31.
  • the piercing tip 132 may be advanced into a tissue region to be treated, such as a tumor located on or within an organ 162 until the one or more reference electrodes 134 are positioned on or against a surface 164 of the organ or tumor.
  • the endoscope 150 may be manipulated to position its distal end into proximity to the organ 162 and'or tumor while under guidance from an ultrasound transducer 154 positioned within the distal end of the endoscope 150.
  • the operator may utilize the captured ultrasound images from the transducer 154 to also guide the deployment of the nsPEF instrument 140 from endoscope 150 and insertion of the instrument into and/or against the organ 162 and into proximity to the tumor for nsPEF treatment, as shown in Fig, 32 and as described above.
  • suction may be applied through, e.g., an irrigation and/or suction lumen 156 either through the endoscope 150, through one or more openings 166 defined along the nsPEF instrument 140 (as shown in Fig. 33), or both for drawing the tumor into apposition against the electrode assembly.
  • Other mechanisms such as tissue graspers 160 advanced through an adjacent working lumen 158 through endoscope 150 may also be used (as shown in Fig. 32) to draw the tumor or organ into apposition with the nsPEF instrument 140.
  • the treatment instrument 140 may be withdrawn from the tumor and the outer reference electrodes 134 may be reconfigured back to their original low-profile configuration for retraction back into the working lumen 152 of endoscope 150.
  • nsPEF instrument 140 may be withdrawn from a first location within the organ and/or tumor and repositioned under the guidance of EUS to a second location for additional treatment. This procedure may be repeated as many times as desired by relocating the nsPEF instrument 140 until the entire tumor is treated by nsPEF therapy.
  • the nsPEF instrument 140 may penetrate through various tissue regions within the subject's body, such as through a gastrointestinal w all for treating various tissue regions such as the pancreas, liver, lymph nodes, and other surrounding structures.
  • One exemplary treatment which the nsPEF instrument 140 is suitable for treating may involve minimally invasive treatment of pancreatic carcinoma. Because typical carcinoma sizes may range from 1 -2 cm and are usually found within the pancreas 1 -2 cm from the outer edge of the organ, the instrument 140 having a piercing tip with a length of about 1-2 cm may be particularly suitable for treating the tumor or tumors.
  • FIGs. 34 A and 34B show perspective ⁇ iews of a nsPEF instrument which may utilize any one or more of the nsPEF parameters described herein for tumor treatment.
  • the nsPEF instrument as well as shaft 170 is designed to be anced through the working lumen of an endoscopic device, the nsPEF instrument and/or shaft 170 may have a diameter of, e.g., around 3 mm.
  • a piercing tip 172 may project from shaft 170 and further define four openings (in this particular example) proximal to the piercing tip 172 through which a corresponding needle array may be deployed. As shown in Fig. 34A, the piercing tip 172 may be advanced from the endoscope lumen and/or pierced through a tissue wall (such as a gastrointestinal wall) or in proximity to an organ to be treated (such as a pancreas) into proximity with a tumor 176 to be treated.
  • the ultrasound transducer 154 positioned w ithin the distal end of the endoscope 150 may be utilized to locate and image a position of tumor 176 such that the nsPEF instrument may be guided into proximity to the tumor 176, as shown.
  • piercing tip 172 may be advanced distally. e.g.. 1-2 cm, from shaft 170 through their corresponding openings 174 such that the array of needles extend to span a distance of, e.g., about 1 cm or more between the needles, sufficient to surround the tumor, as shown in Fig. 34B.
  • the conductive needles may be optionally configured into bipolar needle electrode pairs for forming the pulsed electric field therebetween.
  • a nsPEF having any of the parameters described herein may be applied through the needle array to generate an electric field pattern that may uniformly expose the carcinoma cells.
  • Fig. 34C illustrates an example of the electric field distribution created between the needle array (e.g., a nanosecond pulsed electric field of 40 kV/cm) for exposing and treating the tumor 176 between the needle array.
  • FIG. 35A and 35B illustrate a nsPEF instrument similar to the previous variation but having a six- electrode array 190. 192, 194. 196, 198. 200 positioned uniformly about piercing tip 172 and advanced through a corresponding opening 174.
  • each needle array may project distally and extend at an angle to allow the needle array to surround the tumor 176. as above.
  • a nsPEF treatment may be effected to treat the tissue enclosed w ithin the array, as shown by the electric field distribution in Fig. 35C.
  • Figs- 36A and 36B show perspective views of yet another variation which illustrates an eight-needle array.
  • the shaft 210 may comprise a piercing length 212, e.g., 1-2 cm or more, having a piercing tip 214 where the piercing length 212 is narrower in diameter relative to the shaft 210.
  • the piercing length 212 may be advanced from the endoscope lumen and pierced directly through the tumor 176, as shown in Fig.
  • one or more conductive needles may be advanced from the shaft 210 through openings 216 located proximally of tumor 176 as well as from piercing length 212 through openings 218 located distally of tumor 176.
  • the proximally located needle array 220 and distally located needle array 222 may extend radially from the instrument to completely surround the tumor 176 to be treated. Although four radially extending needles are illustrated in the proximal needle array 220 and four radially extending needles are illustrated in the distal needle array 222. the number of needles in either or both arrays may be varied.
  • the nsPEF therapy may be applied to treat the tumor 176 located bettt een the needle arrays, as shown by the electric field distribution in Fig. 36C. where 40 kV'cm is applied.
  • the applications of the devices and methods discussed above are not limited to treatment of melanoma tumors but may include any number of further treatment applications. Moreover, such devices and methods may be applied to other treatment sites within the body. Modification of the above-described assemblies and methods for carrying out the invention, combinations between different variations as practicable, and variations of aspects of the invention that are obvious to those of skill in the art are intended to be within the scope of the claims.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Surgery (AREA)
  • Engineering & Computer Science (AREA)
  • Plasma & Fusion (AREA)
  • Medical Informatics (AREA)
  • Otolaryngology (AREA)
  • Physics & Mathematics (AREA)
  • Cardiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Molecular Biology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Surgical Instruments (AREA)

Abstract

La présente invention concerne des paramètres de champ électrique à impulsions nanosecondes (nsPEF) destinés à détruire des tumeurs par un traitement unique. Un générateur de nsPEF peut être utilisé avec un ensemble électrode afin d'appliquer les impulsions à une ou plusieurs tumeurs, les paramètres pour le nsPEF étant optimisés pour le traitement de telles tumeurs. Ce système peut également être utilisé pour traiter des tumeurs sur ou dans des organes internes au moyen d'un ensemble électrode bipolaire extensible. Ledit ensemble électrique peut être imagé par ultrasons, pénétrer par exemple dans l'estomac, les intestins ou la paroi intestinale etc., et être positionné dans ou autour de la tumeur sur un organe interne, tout en étant guidé par un opérateur visualisant sa position avec une imagerie par ultrasons. Ledit système utilise un ensemble électrode qui s'étend vers le bas d'une cavité interne dans l'endoscope, pour permettre à l'opérateur d'étendre les électrodes afin de fournir des impulsions d'un champ électrique à impulsions nanosecondes (nsPEF) à la tumeur.
PCT/US2010/027708 2009-03-17 2010-03-17 Paramètres de champ électrique à impulsions nanosecondes destinés à détruire des tumeurs par un traitement unique WO2010107947A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US16104309P 2009-03-17 2009-03-17
US61/161,043 2009-03-17
US18679809P 2009-06-12 2009-06-12
US61/186,798 2009-06-12

Publications (1)

Publication Number Publication Date
WO2010107947A1 true WO2010107947A1 (fr) 2010-09-23

Family

ID=42739980

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2010/027708 WO2010107947A1 (fr) 2009-03-17 2010-03-17 Paramètres de champ électrique à impulsions nanosecondes destinés à détruire des tumeurs par un traitement unique

Country Status (1)

Country Link
WO (1) WO2010107947A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104056349A (zh) * 2014-05-28 2014-09-24 杭州睿笛生物科技有限公司 一种阴极外置阳极内置式纳秒脉冲电场荷载电极
CN109715096A (zh) * 2016-09-19 2019-05-03 脉冲生物科学有限公司 用于脉冲发生器的高压连接器和电极
US11571569B2 (en) 2019-02-15 2023-02-07 Pulse Biosciences, Inc. High-voltage catheters for sub-microsecond pulsing
WO2023235150A1 (fr) * 2022-06-02 2023-12-07 Boston Scientific Scimed, Inc. Générateur biphasique de pfa à pont a pour l'électroporation à l'aide d'un transfert d'énergie finie
US11938317B2 (en) 2017-12-26 2024-03-26 Galvanize Therapeutics, Inc. Optimization of energy delivery for various applications

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4323056A (en) * 1980-05-19 1982-04-06 Corning Glass Works Radio frequency induced hyperthermia for tumor therapy
US6423058B1 (en) * 1998-02-19 2002-07-23 Curon Medical, Inc. Assemblies to visualize and treat sphincters and adjoining tissue regions
US20020193784A1 (en) * 2001-03-07 2002-12-19 Mchale Anthony Patrick Ultrasound therapy for selective cell ablation
US20040254572A1 (en) * 2003-04-25 2004-12-16 Mcintyre Jon T. Self anchoring radio frequency ablation array
WO2007100727A2 (fr) * 2006-02-24 2007-09-07 Eastern Virginia Medical School Des champs électriques pulsés en nanoseconde causent l'autodestruction de mélanomes
WO2008131306A1 (fr) * 2007-04-19 2008-10-30 The Foundry, Inc. Systèmes et procédés pour créer un effet en utilisant une énergie micro-onde sur un tissu spécifié
WO2008141221A1 (fr) * 2007-05-09 2008-11-20 Old Dominion University Research Foundation Instrument medical a electrodes d'aspiration et systeme d'electrotherapie comprenant ledit instrument
US20080312712A1 (en) * 2007-06-13 2008-12-18 E-Pacing, Inc. Implantable Devices and Methods for Stimulation of Cardiac or Other Tissues

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4323056A (en) * 1980-05-19 1982-04-06 Corning Glass Works Radio frequency induced hyperthermia for tumor therapy
US6423058B1 (en) * 1998-02-19 2002-07-23 Curon Medical, Inc. Assemblies to visualize and treat sphincters and adjoining tissue regions
US20020193784A1 (en) * 2001-03-07 2002-12-19 Mchale Anthony Patrick Ultrasound therapy for selective cell ablation
US20040254572A1 (en) * 2003-04-25 2004-12-16 Mcintyre Jon T. Self anchoring radio frequency ablation array
WO2007100727A2 (fr) * 2006-02-24 2007-09-07 Eastern Virginia Medical School Des champs électriques pulsés en nanoseconde causent l'autodestruction de mélanomes
WO2008131306A1 (fr) * 2007-04-19 2008-10-30 The Foundry, Inc. Systèmes et procédés pour créer un effet en utilisant une énergie micro-onde sur un tissu spécifié
WO2008141221A1 (fr) * 2007-05-09 2008-11-20 Old Dominion University Research Foundation Instrument medical a electrodes d'aspiration et systeme d'electrotherapie comprenant ledit instrument
US20080312712A1 (en) * 2007-06-13 2008-12-18 E-Pacing, Inc. Implantable Devices and Methods for Stimulation of Cardiac or Other Tissues

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104056349A (zh) * 2014-05-28 2014-09-24 杭州睿笛生物科技有限公司 一种阴极外置阳极内置式纳秒脉冲电场荷载电极
CN109715096A (zh) * 2016-09-19 2019-05-03 脉冲生物科学有限公司 用于脉冲发生器的高压连接器和电极
CN109715096B (zh) * 2016-09-19 2022-07-26 脉冲生物科学有限公司 用于脉冲发生器的高压连接器和电极
US11938317B2 (en) 2017-12-26 2024-03-26 Galvanize Therapeutics, Inc. Optimization of energy delivery for various applications
US11571569B2 (en) 2019-02-15 2023-02-07 Pulse Biosciences, Inc. High-voltage catheters for sub-microsecond pulsing
US11931570B2 (en) 2019-02-15 2024-03-19 Pulse Biosciences, Inc. Treating tissue pulsed energy using high-voltage catheters
WO2023235150A1 (fr) * 2022-06-02 2023-12-07 Boston Scientific Scimed, Inc. Générateur biphasique de pfa à pont a pour l'électroporation à l'aide d'un transfert d'énergie finie

Similar Documents

Publication Publication Date Title
US20100240995A1 (en) System and method for treating tumors
US20180303541A1 (en) Surgical instrument comprising an electrode
US10478248B2 (en) Electroporation ablation apparatus, system, and method
US8506564B2 (en) Surgical instrument comprising an electrode
US20170119465A1 (en) Electrical ablation devices comprising an injector catheter electrode
US10779882B2 (en) Electrical ablation devices
US9788888B2 (en) Endoscopic cap electrode and method for using the same
US10278761B2 (en) Electrical ablation devices and methods
US8512334B2 (en) Nanosecond pulsed electric field parameters for destroying tumors with a single treatment
US9005198B2 (en) Surgical instrument comprising an electrode
US6958064B2 (en) Systems and methods for performing simultaneous ablation
US20110190764A1 (en) Surgical instrument comprising an electrode
EP2051650A2 (fr) Dispositif d'ablation de tissu
WO2010107947A1 (fr) Paramètres de champ électrique à impulsions nanosecondes destinés à détruire des tumeurs par un traitement unique

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 10754079

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 10754079

Country of ref document: EP

Kind code of ref document: A1