USRE42016E1 - Apparatus and method for the treatment of benign prostatic hyperplasia - Google Patents

Apparatus and method for the treatment of benign prostatic hyperplasia Download PDF

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USRE42016E1
USRE42016E1 US12/572,047 US57204709A USRE42016E US RE42016 E1 USRE42016 E1 US RE42016E1 US 57204709 A US57204709 A US 57204709A US RE42016 E USRE42016 E US RE42016E
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probe
probe portion
electrode
urethra
applicator
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Victor I. Chornenky
Ali Jaafar
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Angiodynamics Inc
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Angiodynamics Inc
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Priority claimed from US10/217,749 external-priority patent/US6994706B2/en
Priority claimed from US10/668,775 external-priority patent/US7130697B2/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/32Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/325Applying electric currents by contact electrodes alternating or intermittent currents for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12Surgical 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
    • A61B18/14Probes or electrodes therefor
    • A61B18/1477Needle-like probes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12Surgical 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
    • A61B18/14Probes or electrodes therefor
    • A61B18/1485Probes or electrodes therefor having a short rigid shaft for accessing the inner body through natural openings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/00234Surgical instruments, devices or methods, e.g. tourniquets for minimally invasive surgery
    • A61B2017/00238Type of minimally invasive operation
    • A61B2017/00274Prostate operation, e.g. prostatectomy, turp, bhp treatment
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00315Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for treatment of particular body parts
    • A61B2018/00547Prostate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12Surgical 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
    • A61B18/14Probes or electrodes therefor
    • A61B2018/1405Electrodes having a specific shape
    • A61B2018/1425Needle

Definitions

  • the present invention relates generally to methods and apparatus for the electroporation of tissues and more specifically to such methods and apparatus for the treatment of benign prostatic hyperplasia.
  • the present invention provides apparatus and methods of providing treatment for the undesirable proliferation of cells in the prostate by killing the cells with electric field pulses of selected duration and strength to take advantage of a cellular event known as “electroporation.”
  • electroporation refers to the use of electric field pulses to induce microscopic pores—“electropores”—in the lipid cell membranes.
  • electroporated cell can survive the pulsing or die.
  • the cause of death of an electroporated cell is believed to be a chemical imbalance in the cell, resulting from the fluid communication with the extra-cellular environment through the pores.
  • the number of electropores—and their size created in the cell by the applied electric field pulses depends on both the amplitude E of the electric field pulses and the duration t of the pulses.
  • an electroporated cell can survive the pulsing and restore its viability thereafter. Above the upper limit the pore diameters and number of induced pores become too large for a cell to survive. The irreversibly chemically imbalanced cell cannot repair itself by any spontaneous or biological process and dies.
  • a potential in the range of 2 to 4 V should be applied along the cell.
  • the cell killing by electroporation is a probabilistic process. That is, increasing the number of applied pulses of duration t leads to an increased probability of cell killing, a probability increase that is approximately equal to the percentage increase in the total time duration of the applied electric pulses.
  • the prostate gland forms part of the male reproductive system.
  • the prostate gland is located between the bladder and the rectum and wraps around the urethra, the tube that carries urine out from the bladder through the penis.
  • the gland consists a dense fibrous capsule enclosing several lobes or regions.
  • the prostate gland is generally composed of smooth muscles and glandular epithelial tissue.
  • the glandular epithelial tissue produces prostatic fluid.
  • the smooth muscles contract during sexual climax and squeeze the prostatic fluid into the urethra as the sperm passes through the ejaculatory ducts and urethra.
  • Prostatic fluid secreted by the prostate gland provides nutrition for ejaculated spermatozoids increasing their mobility and improves the spermatozoids chances for survival after ejaculation by making the environment in the vaginal canal less acidic.
  • the prostate gland is usually described as including three glandular zones: the central, peripheral and transitional zones.
  • the transitional zone is located right behind the place where the seminal vesicles merge with the urethra. This transitional zone tends to be predisposed to benign enlargement in later life.
  • the prostate reaches its normal size and weight (about 20 grams) soon after puberty.
  • the size and weight of the prostate typically remain stable until the individual reaches his mid-forties.
  • the prostate gland typically in the transitional zone—begins to enlarge through a process of excessive cell proliferation known as benign prostatic hyperplasia (BPH).
  • BPH benign prostatic hyperplasia
  • Benign prostate hyperplasia can cause distressing urination symptoms. As the disease progresses the dense capsule surrounding the enlarging prostate prevents it from further expansion outward and forces the prostate to press against the urethra, partially obstructing the urine flow. The tension in the smooth muscles of the prostate also increases which causes further compression of the urethra and reduction of the urine flow.
  • Some symptoms of BPH stem from the gradual loss of bladder function leading to an incomplete emptying of the bladder. The symptoms can include straining to urinate, a weak or intermittent stream, an increased frequency of urination, pain during urination, and incontinence—the involuntary loss of urine following an uncontrollable sense of urgency. These symptoms alone can negatively affect the quality of life of affected men. Left untreated, BPH can cause even more severe complications, such as urinary tract infection, acute urinary retention, and uremia.
  • Benign prostatic hyperplasia is the most common non-cancerous form of cell growth in men. About 14 million men in US have BPH, and about 375,000 new patients are diagnosed every year.
  • Finasteride inhibits production of hormone DHT.
  • DHT is one of the hormones that have been found to be involved in prostate enlargement. Treatment with Finasteride has been shown to shrink the prostate in some men.
  • Terazosin, doxazosin, and tamsulosin belong to the class of drugs known as alpha-blockers.
  • Alpha-blockers act by relaxing the smooth muscle of the prostate and bladder to improve urine flow and reduce bladder outlet obstruction. In men with severe symptoms, though, these medications are palliative only. They can delay but not prevent the eventual need for surgery.
  • transurethral microwave thermal therapy a Foley-type catheter containing a microwave antenna is placed within the urethra.
  • the microwave antenna is positioned adjacent to the transitional zone of the prostate, where BPH occurs, and allows selective heating of the prostate. Maintaining the temperature of the BPH tissue above 45 degrees C. during about a one hour session leads to necrosis of the tissues and subsequent reabsorption of necrotic tissue by the body.
  • TUNA transurethral needle ablation
  • RF radio frequency
  • the microwave and RF therapies are relatively long procedures. Also, because of the poor temperature control of the heated volume, the volume of removed tissue is often not sufficient for the long term relief of the symptoms and/or the healthy tissue of the urethra is damaged. A damaged urethra is capable of restoring itself, but the healing is a long morbid process accompanied by sloughing of the necrotic tissue into urethra and excretion of it during urination.
  • the present invention provides apparatus and methods for the treatment of benign prostate hyperplasia and the alleviation of the symptoms associated therewith.
  • An apparatus in accord with the present invention has a probe portion and a handle portion.
  • the probe portion is preferably entirely or partially hollow.
  • the probe is a hollow body having proximal, transitional, and distal probe portions.
  • the proximal probe portion is a substantially straight, hollow, elongate tube attached at its proximal end to the handle portion.
  • the proximal probe section is configured to be received within the penile section of the urethra and extend to the urogenital diaphragm, an anatomical structure separating the distal end of the penis from the prostate gland.
  • the distal probe portion is a substantially straight, hollow, elongate tube configured to be received within the prostatic segment of the urethra.
  • the transitional probe portion is a curved, hollow, tube extending between the proximal and distal probe portions to form therewith a continuous, hollow probe capable of being received by the urethra and extending from the penile opening to within the prostate.
  • the hollow probe portion provides access for a plurality of electrodes and other desirable instrumentation to the prostate gland.
  • a pair of needle electrodes and an flexible fiber optic endoscope can be housed within the probe portion.
  • separate passages or channels can be provided for the electrodes and the endoscope.
  • the endoscope will preferably extend the length of the probe, from the probe proximal end to the probe distal end.
  • the endoscope may be provided to enable the visualization of the urethra distally to the probe to enable safe placement and manipulation of the inventive apparatus during therapy procedures.
  • the needle electrodes are slidably disposed within the probe to enable their extension and retraction relative to the probe and into and out of the BPH tissue.
  • the aforementioned channels or passages will facilitate their extension and retraction.
  • the distal ends of the needles In their retracted position, the distal ends of the needles will be positioned within and near or at the distal end of the proximal probe portion. When the probe is properly positioned relative to the prostate gland, advancing the needles will advance them into the BPH tissue of the prostate gland. Only the distal needle ends should be exposed; that is, the proximal portions of the needle electrodes should be insulated to insulate the needle electrodes from the probe body as well as each other.
  • the proximal ends of the needles may be secured to a finger activated lever forming part of the handle portion.
  • the lever is positioned and adapted to advance the needles relative to the probe to pierce the urethra and thus position them in the body of the prostate gland; more specifically, advancing the needles during a procedure will result in the placement of the uninsulated needle ends being disposed substantially within the transition zone where BPH occurs.
  • the curved probe portion serves to displace the proximal and distal portions from each other. In turn, this displacement displaces the prostatic urethral segment and the penile urethral segments from each other.
  • the electrode needles can thus be advanced substantially parallel to the longitudinal axis of the proximal portion, and thus the penile urethral segment, into the prostate gland.
  • this displacement facilitates ready and proper positioning of the needle electrodes into the prostate gland without the necessity of bending needles about 90 into the prostate gland and without the associated complicated structures found in the prior art.
  • This probe geometry enables the needles to be placed into the prostate gland substantially parallel to the urethra, which in turn enables the use of fewer treatment positions and shorter treatments.
  • the entirety of the inventive apparatus is covered with a insulating biocompatible material.
  • That uninsulated distal probe portion may serve as a third, urethral electrode. All of the electrodes will be electrically insulated from each other and will be electrically connected to a generator producing the electroporation pulses.
  • the amplitude and duration of the pulses will be selected to provide and electric field in the prostatic tissue that exceeds the upper electroporation limit of the BPH fibromuscular and nerve tissues.
  • the duration of the pulses may be selected to range from about 10 microseconds to about 500 milliseconds. As stated, the amplitude, duration, and number of pulses will be preselected to cause necrosis of the fibromuscular and nerve cells constituting the benign prostatic hyperplasia tissues.
  • the entire probe will be insulated and only the needle electrodes will be utilized for providing electroporation therapy. In this embodiment, no electric pulses will be applied to the probe itself. It is anticipated that this embodiment of the present invention will be used for cases of moderate enlargement of the prostate gland.
  • the probe portion may have at least three sections, wherein the first and third sections take on a substantially tubular form with differing sizes, each of the first and third sections defining a substantially longitudinal axis, with the first and third sections' longitudinal axes lying parallel but not coaxial, and the second section is a transition section between the first and third sections.
  • the third section is desirably sized to be safely, comfortably, and appropriately received within the prostatic segment of the urethra.
  • the first section is desirably sized to be safely, comfortably, and appropriately configured to be received within the urethra and extend from urethral opening through the penis approximately to the urogenital diaphragm.
  • the second or transitional section is desirably sized to be safely, comfortably, and appropriately extend through the urogenital diaphragm.
  • the probe can be manufactured as integral unit or in separate sections that are joined using known manufacturing processes.
  • the first and third probe sections each define a longitudinal axis, with the two axes being non-parallel.
  • the needle electrodes may be curved.
  • the needle electrodes may be bent in one location.
  • a probe having at least first and second probe portions, with the first and second probe portions each defining an axis and the first and second probe portion axes not being collinear, is inserted into the urethra and maneuvered until the distal end of the probe lies within the prostatic urethral segment.
  • the distal or second probe portion displaces the prostate gland sideways relative to the axis of the proximal or first probe portion.
  • Needle electrodes electrically connected to a power source are extended from the first probe portion and inserted into the BPH tissue of the prostate. Electric field pulses of selected amplitude and duration are applied to the BPH tissue. In a preferred embodiment, the electric field is directed radially and thus along the longer dimension of the fibromuscular cells forming benign prostate hyperplasia as well as the nerve cells contained therein.
  • the present invention while described below with respect to electroporation, can also be utilized with radio frequency energies alone or in conjunction with electroporation.
  • FIG. 1 illustrates an embodiment of the present invention in a partial cross sectional view disposed in an operating position within a human penis and prostate gland.
  • FIG. 2 shows a cross-sectional view of the present invention taken along viewing plane 2 — 2 of FIG. 1 .
  • FIG. 3 shows a cross-sectional view of the present invention taken along viewing plane 3 — 3 of FIG. 1 .
  • FIG. 4 depicts an alternative embodiment of an apparatus in accord with the present invention.
  • FIG. 5 illustrates an alternative embodiment of an apparatus in accord with the present invention.
  • FIG. 6 shows an alternative embodiment of an apparatus in accord with the present invention.
  • Cells are not, generally speaking, spherical bodies. Rather, they come in a variety of sizes and geometries. For example, for cells similar to muscle fiber cells the length to width ratio of the cell can be as great as 20-30 to 1. Nerve cells can have even greater length to width ratios.
  • Cell vulnerability to electroporation is different for different directions of the applied electric field. That vulnerability depends on the size of the cell in the direction of the applied field.
  • the effect of electroporation on tissue can be modulated by selecting a field direction relative to a cell's geometry. Stated otherwise, an elongated cell can be killed with significantly lower electric field strength if the field is applied along the cell. If the field is applied across such a cell, the cell is capable of surviving much higher amplitudes of the electric field.
  • the current invention provides relief of the symptoms of BPH by providing electroporation treatment to the BPH treatment to create a necrotic zone in the BPH tissue around the urethra.
  • Control of the volume of the necrotic zone, its shape, and its location relative to healthy prostate tissue is provided by the present invention, including a system of electrodes that generate an electric field in the area of benign enlargement of the prostate gland.
  • Application of multiple pulses of the electric field having the appropriate voltage and duration leads to necrosis of the prostatic tissue around the urethra.
  • the predominant direction of fibers in the fibro-muscular glandular tissue of BPH is radial to the urethra.
  • the preferred direction of the applied electric field is also radial to the urethra, coinciding with the predominant direction of the BPH tissue.
  • Application of the electroporating pulses along the muscular fibers and nerves that anatomically follow them selectively kills both types of fibers.
  • two intermediate benefits of the present therapy are achieved with selective application of electroporation pulses to BPH tissue.
  • a significant volume of necrotic BPH tissue around the urethra is created by the therapy.
  • the nerves that cause elevation in tension of the muscle fibers are destroyed.
  • necrotic tissue including both the killed BPH tissue and nerves, are removed by macrophages. Removal of the necrotic BPH tissue reduces the total volume of BPH and pressure on the urethra while removal of the destroyed nerves results in relaxation of the prostate. Both effects contribute to the improvement of the urethra and bladder functions after treatment.
  • sphincters located on the urethra anterior and posterior to the prostate gland, consist of smooth muscle cells wrapped circumferentially around the urethra. These urethral sphincters control shutting down the flow of urine from the bladder and should be preserved during a therapy treatment.
  • the electrodes disposed within the urethra during therapy should not be positioned too closely to them.
  • the amplitude of the electric field during treatment applied to the urethra area should be selected not to exceed the upper electroporation limit of the sphincter muscles in the transverse direction.
  • FIG. 1 illustrates a BPH therapy applicator 10 comprising a handle 12 and a probe 14 .
  • Probe 14 includes at least first and second, or proximal and distal sections, 16 and 18 , respectively.
  • probe 14 also includes a third or transitional section 20 .
  • the applicator 10 is shown relative to a penis 22 in position for the application of an electroporation treatment to a patient experiencing BPH.
  • the probe 10 is shown inserted into the urethra 24 through the urethral opening 26 at the proximal end of the penis 22 .
  • probe proximal portion 16 is disposed within the penile urethral segment 30
  • probe distal portion 18 is disposed within the prostatic urethral segment 32
  • probe transitional portion 20 extends between the proximal and distal probe portions 16 and 18 and is disposed substantially through the urogenital diaphragm 34 .
  • Probe 14 has a substantially hollow configuration, to provide an interior passage 40 .
  • Passage 40 provides access for a flexible fiber optic endoscope 42 and at least one needle 44 .
  • two needles, 44 and 46 are shown.
  • One or more of the endoscope 42 and needles 44 and 46 may be enclosed within their own individual channels if desired.
  • the endoscope 42 extends to an eye piece 48 at its proximal end 50 .
  • a light source 52 which is connected to the endoscope 42 by a fiber optic cable 54 , enables visualization of the urethra during placement and manipulation of the applicator 10 in operation position and during a BPH electroporation treatment.
  • Needles 44 and 46 have insulating sheathes 60 on their surfaces that electrically separate or isolate them from the handle 12 and probe 14 as well as each other. Needles 44 and 46 are attached to a finger-activated lever 62 at their proximal ends in any known, appropriate manner. As seen in the Figure, lever 62 has been moved from its non-operational position seen in phantom to an operational position as indicated by the double-headed arrow 64 . Movement of the lever 62 between the two positions will cause the needles to extend from their non-operational position to an operational position as seen in the Figure and to retract into their non-operational position as desired by the lever operator.
  • both the lengths and the operating positions of the distal end of the distal end 80 of the probe 14 and the needle electrodes 44 and 46 are selected to avoid reaching the bladder 82 to reduce the likelihood of damage thereto during a procedure.
  • the sharp tips 84 and 86 of needles 44 and 46 should not penetrate the bladder 82 .
  • Electrodes 74 , 76 , and 88 are electrically insulated from each other and are connected via an appropriate connector 90 to a generator 92 that produces high voltage electrical pulses.
  • the amplitude and duration of the electric pulses applied between the electrodes will be selected to provide an electric field in the prostatic tissue exceeding the upper electroporation limit of the BPH tissue, including the nerve cells contained therein.
  • the pulse duration may be selected to be within the range of about 10 microseconds to about 500 milliseconds.
  • the amplitude and number of applied pulses are selected to cause necrosis of the BPH tissue, including the nerves and muscle cells.
  • proximal and distal probe sections 16 and 18 define longitudinal axes 96 and 98 respectively. As shown, axes 96 and 98 are not co-linear. They may, if desired, lie parallel to each other, however.
  • Proximal section 16 has a larger cross-sectional area than the distal section 18 , which does not need to carry the needles 44 and 46 therein, thus aiding to increase patient comfort during a procedure.
  • Probe section 20 transitions between the larger cross-sectional area proximal section 16 and smaller cross-sectional area section 18 . Additionally, the angled or curved nature of the section 20 serves to offset the proximal and distal sections 16 and 18 , respectively, from each other. In doing so, the prostate gland 78 is displaced sideways relative to the axis 96 of the proximal section 16 . This sideways displacement facilitates proper positioning of the needle electrodes in the BPH tissue.
  • FIG. 2 a cross-section of the prostate gland 78 is shown taken along viewing plane 2 — 2 of FIG. 1 with the applicator 10 in its operating position.
  • the electric field generated between the electrodes indicated generally by field lines 100 , causes necrosis of the BPH tissue.
  • the needles can be retracted within probe 14 and the probe can be rotated a selected angle to a new position for treatment. The needles will be advanced into the operating position and the electric pulses applied once again. A plurality of such needle advancements and treatments are indicated in the Figure by the open circles 102 .
  • the proximal probe section 16 preferably has a substantially elliptical configuration with a ratio of the axes in the range of about 1:3 to about 1:4.
  • the maximal diameter of the ellipse should generally not exceed about 12 to about 16 mm and minimal diameter should generally not be less than about 3 to about 4 mm.
  • the fiber bundle 42 of the endoscope and the tow needles 44 and 46 are positioned in line along the longer axis of the probe section 16 . As seen in the Figure, needles 44 and 46 are disposed, if desired, within channels or tubes 104 .
  • FIGS. 4-6 show alternative embodiments of the present invention.
  • probe 110 includes proximal and distal segments 112 and 114 , respectively. Segments 112 and 114 each define an axis 116 and 118 , respectively. As indicated, axes 116 and 118 do not lie parallel to each other, but are separated by an angle a lying in the range of about 10° to about 45°. Also as shown, the needles 44 and 46 can, if desired, be angularly disposed relative to each other. As seen in the Figure, needles 44 and 46 diverge by an angle ⁇ lying in the range of about 0° to about 30°. In this embodiment, the proximal segment 112 can be made smaller, thus increasing patient comfort.
  • FIG. 5 illustrates an embodiment 130 of the present invention wherein curved needles 132 and 134 having radii of curvature R 1 and R 2 , respectively, are used rather than the straight needles 44 and 46 previously illustrated and discussed. Where such curved needles are utilized, the radius of curvature of the needles are in the range of about 2 cm to about 5 cm.
  • FIG. 6 depicts another embodiment of the present invention.
  • probe 140 includes needles 142 and 142 that are bent at one location; as shown, the needles 142 and 144 are bent at the end of the insulating sheath 60 .
  • the probe of the present invention will be introduced into a patient's urethra under endoscopic guidance until the distal end is positioned in the prostatic segment of the patient's urethra.
  • the needle electrodes will then be advanced into the BPH tissue surrounding the urethra and a plurality of electric pulses will be applied.
  • the electroporation therapy will terminate when a significant and stable drop in the electrical resistance of the treated tissue occurs.
  • the resistance drop indicates a profound electroporation damage to the fibromuscular cells, which later leads to their necrosis and dissolution by macrophages.
  • Overall treatment of one site may take about ten pulses and several seconds to several tens of seconds in time depending on the repetition rate of the high voltage pulse generator.
  • the needle electrodes will be withdrawn and repositioned in another treatment site. Consecutive treatments are performed in light of patient comfort and safety and until the operator determines that a sufficient volume of BPH tissue has been treated.

Abstract

An apparatus and method for treatment of benign prostatic hyperplasia is disclosed wherein the apparatus includes an applicator having a probe having proximal and distal probe sections wherein the proximal and distal probe sections each define an axis and wherein the axes are not collinear.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS
The present application claims priority to U.S. Provisional Application No. 60/412,705 entitled “Apparatus and method for treatment of benign prostatic hyperplasia by electroporation”, which was filed Sep. 23, 2002. This application is a continuation-in-part of U.S. patent application Ser. No. 10/217,749 entitled “Apparatus and method for treatment of benign prostatic hyperplasia by electroporation”, which was filed Aug. 13, 2002 (U.S. Patent Application Publication 2003/0060856, published Mar. 27, 2003) now U.S. Pat. No. 6,994,706, which claims the benefit of U.S. Provisional Application Ser. No. 60/325,994 filed Oct. 1, 2001 and U.S. Provisional Application Ser. No. 60/311,792, filed Aug. 13, 2001.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to methods and apparatus for the electroporation of tissues and more specifically to such methods and apparatus for the treatment of benign prostatic hyperplasia.
2. Description of the Related Art
Though greater detail will follow in the discussion below, succinctly stated, the present invention provides apparatus and methods of providing treatment for the undesirable proliferation of cells in the prostate by killing the cells with electric field pulses of selected duration and strength to take advantage of a cellular event known as “electroporation.”
Electroporation
The biophysical phenomenon known as electroporation refers to the use of electric field pulses to induce microscopic pores—“electropores”—in the lipid cell membranes. Depending on the parameters of the electric pulses, an electroporated cell can survive the pulsing or die. The cause of death of an electroporated cell is believed to be a chemical imbalance in the cell, resulting from the fluid communication with the extra-cellular environment through the pores. For a given cell size, geometry, and orientation, the number of electropores—and their size created in the cell by the applied electric field pulses depends on both the amplitude E of the electric field pulses and the duration t of the pulses. That is, for a given pulse duration t, no pores will be induced in the cell until the amplitude E reaches a certain lower limit. This limit is different for different cells, particularly, for cells of different sizes. The smaller the size of a cell, the higher the electric field required to induce pores and thus the higher the lower limit is. Above the lower amplitude E limit the number of pores and their effective diameter increases proportionally with both increasing field amplitude E and pulse duration t. Electroporation is observed for pulse durations in the range from tens of microseconds to hundreds of milliseconds.
Until the upper limit of electroporation is achieved, an electroporated cell can survive the pulsing and restore its viability thereafter. Above the upper limit the pore diameters and number of induced pores become too large for a cell to survive. The irreversibly chemically imbalanced cell cannot repair itself by any spontaneous or biological process and dies. To kill a cell a potential in the range of 2 to 4 V should be applied along the cell. The cell killing by electroporation is a probabilistic process. That is, increasing the number of applied pulses of duration t leads to an increased probability of cell killing, a probability increase that is approximately equal to the percentage increase in the total time duration of the applied electric pulses.
The survivability of electroporated cells depends significantly on their temperature. At higher temperature cells are more vulnerable to cell death by electroporation. Thus, the amplitude and duration of the electric pulses required for cell killing are lower. It is believed that this observation is explained by two underlying phenomena: at higher temperatures cells are less stable biochemically because of more intense metabolic activity; and, secondly, at elevated temperatures the strength of lipid membranes decreases, which facilitates creating larger pores or irreversible rupture of the cell membrane. At lower temperatures (about 10 to about 20 degrees Celsius) cells are more resistant to electroporation and can survive two to three times higher voltages than they can at body temperature.
The Prostate Gland and Benign Prostatic Hyperplasia
The prostate gland forms part of the male reproductive system. The prostate gland is located between the bladder and the rectum and wraps around the urethra, the tube that carries urine out from the bladder through the penis. The gland consists a dense fibrous capsule enclosing several lobes or regions. The prostate gland is generally composed of smooth muscles and glandular epithelial tissue. The glandular epithelial tissue produces prostatic fluid. The smooth muscles contract during sexual climax and squeeze the prostatic fluid into the urethra as the sperm passes through the ejaculatory ducts and urethra. Prostatic fluid secreted by the prostate gland provides nutrition for ejaculated spermatozoids increasing their mobility and improves the spermatozoids chances for survival after ejaculation by making the environment in the vaginal canal less acidic.
Anatomically, the prostate gland is usually described as including three glandular zones: the central, peripheral and transitional zones. The transitional zone is located right behind the place where the seminal vesicles merge with the urethra. This transitional zone tends to be predisposed to benign enlargement in later life.
The prostate reaches its normal size and weight (about 20 grams) soon after puberty. The size and weight of the prostate typically remain stable until the individual reaches his mid-forties. At this age, the prostate gland—typically in the transitional zone—begins to enlarge through a process of excessive cell proliferation known as benign prostatic hyperplasia (BPH). This overgrowth can occur in both smooth muscle and glandular epithelial tissues and has been attributed to a number of different causes, including hormones and growth factors as well as generally to the aging process.
Benign prostate hyperplasia can cause distressing urination symptoms. As the disease progresses the dense capsule surrounding the enlarging prostate prevents it from further expansion outward and forces the prostate to press against the urethra, partially obstructing the urine flow. The tension in the smooth muscles of the prostate also increases which causes further compression of the urethra and reduction of the urine flow. Some symptoms of BPH stem from the gradual loss of bladder function leading to an incomplete emptying of the bladder. The symptoms can include straining to urinate, a weak or intermittent stream, an increased frequency of urination, pain during urination, and incontinence—the involuntary loss of urine following an uncontrollable sense of urgency. These symptoms alone can negatively affect the quality of life of affected men. Left untreated, BPH can cause even more severe complications, such as urinary tract infection, acute urinary retention, and uremia.
Before age 40, only 10% of men have benign prostatic hyperplasia; but by age 80, about 80% have signs of this condition. Benign prostatic hyperplasia is the most common non-cancerous form of cell growth in men. About 14 million men in US have BPH, and about 375,000 new patients are diagnosed every year.
For many years, researchers have tried to find medications to shrink the prostate or at least stop its growth. Between 1992 and 1997, the FDA approved four drugs for treatment of BPH: finasteride, terazosin, tamsulosin, and doxazosin.
Finasteride inhibits production of hormone DHT. DHT is one of the hormones that have been found to be involved in prostate enlargement. Treatment with Finasteride has been shown to shrink the prostate in some men.
Terazosin, doxazosin, and tamsulosin belong to the class of drugs known as alpha-blockers. Alpha-blockers act by relaxing the smooth muscle of the prostate and bladder to improve urine flow and reduce bladder outlet obstruction. In men with severe symptoms, though, these medications are palliative only. They can delay but not prevent the eventual need for surgery.
Regardless of the efficacy of any drug treatment, the long term exposure to xenobiotic compounds may produce additional unwanted side effects that are not realized until years after treatment. Accordingly, a need exists for an apparatus and method for the treatment of BPH that does not require the introduction of xenobiotic compounds.
For men with the most severe symptoms, surgery is generally considered to be the best long-term solution. There are several surgical procedures that have been developed for relieving symptoms of BPH. Each of these procedures, however, suffers from one or more of the following deficiencies: high morbidity, long hospital stays, the use of general anesthesia, significant side effects such as impotence, and possible complications such as infection and inflammation.
In recent years, a number of procedures have been introduced that are less invasive than surgery. One such procedure is transurethral microwave thermal therapy. In transurethral microwave thermal therapy, a Foley-type catheter containing a microwave antenna is placed within the urethra. The microwave antenna is positioned adjacent to the transitional zone of the prostate, where BPH occurs, and allows selective heating of the prostate. Maintaining the temperature of the BPH tissue above 45 degrees C. during about a one hour session leads to necrosis of the tissues and subsequent reabsorption of necrotic tissue by the body.
Another recently developed non-invasive technique is transurethral needle ablation (TUNA). TUNA uses low level radio frequency (RF) energy to heat the prostate. Using TUNA, two separate needles are inserted into prostate through the urethra. Several watts of RF energy is applied to each needle to cause thermal necrosis of the prostate cells around the needles. Application of this treatment to several sites of the prostate typically results in sufficient necrosis to relieve symptoms of the BPH.
While generally successful, the microwave and RF therapies are relatively long procedures. Also, because of the poor temperature control of the heated volume, the volume of removed tissue is often not sufficient for the long term relief of the symptoms and/or the healthy tissue of the urethra is damaged. A damaged urethra is capable of restoring itself, but the healing is a long morbid process accompanied by sloughing of the necrotic tissue into urethra and excretion of it during urination.
Therefore, a need exists for a minimally invasive therapy for treatment of BPH that requires shorter treatment times and is less morbid than existing therapies.
BRIEF DESCRIPTION OF THE INVENTION
The present invention provides apparatus and methods for the treatment of benign prostate hyperplasia and the alleviation of the symptoms associated therewith. An apparatus in accord with the present invention has a probe portion and a handle portion. The probe portion is preferably entirely or partially hollow.
In an embodiment of the present invention, the probe is a hollow body having proximal, transitional, and distal probe portions. The proximal probe portion is a substantially straight, hollow, elongate tube attached at its proximal end to the handle portion. The proximal probe section is configured to be received within the penile section of the urethra and extend to the urogenital diaphragm, an anatomical structure separating the distal end of the penis from the prostate gland. The distal probe portion is a substantially straight, hollow, elongate tube configured to be received within the prostatic segment of the urethra. The transitional probe portion is a curved, hollow, tube extending between the proximal and distal probe portions to form therewith a continuous, hollow probe capable of being received by the urethra and extending from the penile opening to within the prostate.
The hollow probe portion provides access for a plurality of electrodes and other desirable instrumentation to the prostate gland. For example, a pair of needle electrodes and an flexible fiber optic endoscope can be housed within the probe portion. If desired, separate passages or channels can be provided for the electrodes and the endoscope. The endoscope will preferably extend the length of the probe, from the probe proximal end to the probe distal end. The endoscope may be provided to enable the visualization of the urethra distally to the probe to enable safe placement and manipulation of the inventive apparatus during therapy procedures.
The needle electrodes are slidably disposed within the probe to enable their extension and retraction relative to the probe and into and out of the BPH tissue. The aforementioned channels or passages will facilitate their extension and retraction. In their retracted position, the distal ends of the needles will be positioned within and near or at the distal end of the proximal probe portion. When the probe is properly positioned relative to the prostate gland, advancing the needles will advance them into the BPH tissue of the prostate gland. Only the distal needle ends should be exposed; that is, the proximal portions of the needle electrodes should be insulated to insulate the needle electrodes from the probe body as well as each other. The proximal ends of the needles may be secured to a finger activated lever forming part of the handle portion. The lever is positioned and adapted to advance the needles relative to the probe to pierce the urethra and thus position them in the body of the prostate gland; more specifically, advancing the needles during a procedure will result in the placement of the uninsulated needle ends being disposed substantially within the transition zone where BPH occurs.
The curved probe portion serves to displace the proximal and distal portions from each other. In turn, this displacement displaces the prostatic urethral segment and the penile urethral segments from each other. The electrode needles can thus be advanced substantially parallel to the longitudinal axis of the proximal portion, and thus the penile urethral segment, into the prostate gland. Thus, this displacement facilitates ready and proper positioning of the needle electrodes into the prostate gland without the necessity of bending needles about 90 into the prostate gland and without the associated complicated structures found in the prior art. This probe geometry enables the needles to be placed into the prostate gland substantially parallel to the urethra, which in turn enables the use of fewer treatment positions and shorter treatments.
Preferably, the entirety of the inventive apparatus, save that portion of the distal probe portion that will be disposed within the prostatic urethra, is covered with a insulating biocompatible material. That uninsulated distal probe portion may serve as a third, urethral electrode. All of the electrodes will be electrically insulated from each other and will be electrically connected to a generator producing the electroporation pulses. The amplitude and duration of the pulses will be selected to provide and electric field in the prostatic tissue that exceeds the upper electroporation limit of the BPH fibromuscular and nerve tissues. The duration of the pulses may be selected to range from about 10 microseconds to about 500 milliseconds. As stated, the amplitude, duration, and number of pulses will be preselected to cause necrosis of the fibromuscular and nerve cells constituting the benign prostatic hyperplasia tissues.
In another embodiment of the present invention, the entire probe will be insulated and only the needle electrodes will be utilized for providing electroporation therapy. In this embodiment, no electric pulses will be applied to the probe itself. It is anticipated that this embodiment of the present invention will be used for cases of moderate enlargement of the prostate gland.
Stated alternatively, according to one aspect of the present invention, the probe portion may have at least three sections, wherein the first and third sections take on a substantially tubular form with differing sizes, each of the first and third sections defining a substantially longitudinal axis, with the first and third sections' longitudinal axes lying parallel but not coaxial, and the second section is a transition section between the first and third sections. The third section is desirably sized to be safely, comfortably, and appropriately received within the prostatic segment of the urethra. The first section is desirably sized to be safely, comfortably, and appropriately configured to be received within the urethra and extend from urethral opening through the penis approximately to the urogenital diaphragm. The second or transitional section is desirably sized to be safely, comfortably, and appropriately extend through the urogenital diaphragm. The probe can be manufactured as integral unit or in separate sections that are joined using known manufacturing processes.
In another aspect of the present invention, the first and third probe sections each define a longitudinal axis, with the two axes being non-parallel.
In yet another aspect of the present invention, the needle electrodes may be curved.
In still yet another aspect of the present invention, the needle electrodes may be bent in one location.
In a method in accord with the present invention, a probe having at least first and second probe portions, with the first and second probe portions each defining an axis and the first and second probe portion axes not being collinear, is inserted into the urethra and maneuvered until the distal end of the probe lies within the prostatic urethral segment. The distal or second probe portion displaces the prostate gland sideways relative to the axis of the proximal or first probe portion. Needle electrodes electrically connected to a power source are extended from the first probe portion and inserted into the BPH tissue of the prostate. Electric field pulses of selected amplitude and duration are applied to the BPH tissue. In a preferred embodiment, the electric field is directed radially and thus along the longer dimension of the fibromuscular cells forming benign prostate hyperplasia as well as the nerve cells contained therein.
The present invention, while described below with respect to electroporation, can also be utilized with radio frequency energies alone or in conjunction with electroporation.
The present invention, as well as its various features and advantages, will become evident to those skilled in the art when the following description of the invention is read in conjunction with the accompanying drawings as briefly described below and the appended claims. Throughout the drawings, like numerals refer to similar or identical parts.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 illustrates an embodiment of the present invention in a partial cross sectional view disposed in an operating position within a human penis and prostate gland.
FIG. 2 shows a cross-sectional view of the present invention taken along viewing plane 22 of FIG. 1.
FIG. 3 shows a cross-sectional view of the present invention taken along viewing plane 33 of FIG. 1.
FIG. 4 depicts an alternative embodiment of an apparatus in accord with the present invention.
FIG. 5 illustrates an alternative embodiment of an apparatus in accord with the present invention.
FIG. 6 shows an alternative embodiment of an apparatus in accord with the present invention.
DETAILED DESCRIPTION OF THE INVENTION
Cells are not, generally speaking, spherical bodies. Rather, they come in a variety of sizes and geometries. For example, for cells similar to muscle fiber cells the length to width ratio of the cell can be as great as 20-30 to 1. Nerve cells can have even greater length to width ratios. Cell vulnerability to electroporation, as noted earlier, is different for different directions of the applied electric field. That vulnerability depends on the size of the cell in the direction of the applied field. Thus, the effect of electroporation on tissue can be modulated by selecting a field direction relative to a cell's geometry. Stated otherwise, an elongated cell can be killed with significantly lower electric field strength if the field is applied along the cell. If the field is applied across such a cell, the cell is capable of surviving much higher amplitudes of the electric field.
The current invention provides relief of the symptoms of BPH by providing electroporation treatment to the BPH treatment to create a necrotic zone in the BPH tissue around the urethra. Control of the volume of the necrotic zone, its shape, and its location relative to healthy prostate tissue is provided by the present invention, including a system of electrodes that generate an electric field in the area of benign enlargement of the prostate gland. Application of multiple pulses of the electric field having the appropriate voltage and duration leads to necrosis of the prostatic tissue around the urethra.
Anatomically, the predominant direction of fibers in the fibro-muscular glandular tissue of BPH is radial to the urethra. In the present invention, the preferred direction of the applied electric field is also radial to the urethra, coinciding with the predominant direction of the BPH tissue. Application of the electroporating pulses along the muscular fibers and nerves that anatomically follow them selectively kills both types of fibers. Thus, two intermediate benefits of the present therapy are achieved with selective application of electroporation pulses to BPH tissue. First, a significant volume of necrotic BPH tissue around the urethra is created by the therapy. Second, the nerves that cause elevation in tension of the muscle fibers are destroyed. Subsequently, the necrotic tissue, including both the killed BPH tissue and nerves, are removed by macrophages. Removal of the necrotic BPH tissue reduces the total volume of BPH and pressure on the urethra while removal of the destroyed nerves results in relaxation of the prostate. Both effects contribute to the improvement of the urethra and bladder functions after treatment.
While the aforementioned therapy alleviates the symptoms of BPH, care must be taken to avoid damaging or destroying other tissue in the vicinity of the applied electroporation pulses. For example, sphincters, located on the urethra anterior and posterior to the prostate gland, consist of smooth muscle cells wrapped circumferentially around the urethra. These urethral sphincters control shutting down the flow of urine from the bladder and should be preserved during a therapy treatment. An electroporation field applied radially to the prostate—that is, coincident with the elongate fibromuscular and nerve cells of the BPH—results in the field being transverse to the sphincter muscle cells, thus making them relatively resistant to the electroporation pulsing. Thus, by selectively directing the electric field, damage to these muscles, whose health and function are important to quality of life for affected individuals, can be reduced or avoided. Nevertheless, to reduce the potential of damage to the sphincter muscles further, the electrodes disposed within the urethra during therapy should not be positioned too closely to them. Additionally, the amplitude of the electric field during treatment applied to the urethra area should be selected not to exceed the upper electroporation limit of the sphincter muscles in the transverse direction.
The foregoing therapeutic benefits are obtained by providing electroporation treatment to BPH by apparatus and methods in accord with the present invention.
A BPH therapy applicator and methods of providing BPT treatment in accord with the present invention are described below with reference to FIGS. 1-3. Referring specifically to FIG. 1, this Figure illustrates a BPH therapy applicator 10 comprising a handle 12 and a probe 14. Probe 14 includes at least first and second, or proximal and distal sections, 16 and 18, respectively. In the embodiment shown, probe 14 also includes a third or transitional section 20. The applicator 10 is shown relative to a penis 22 in position for the application of an electroporation treatment to a patient experiencing BPH. Thus, the probe 10 is shown inserted into the urethra 24 through the urethral opening 26 at the proximal end of the penis 22. As shown in its operational position, probe proximal portion 16 is disposed within the penile urethral segment 30, probe distal portion 18 is disposed within the prostatic urethral segment 32, and probe transitional portion 20 extends between the proximal and distal probe portions 16 and 18 and is disposed substantially through the urogenital diaphragm 34.
Probe 14 has a substantially hollow configuration, to provide an interior passage 40. Passage 40 provides access for a flexible fiber optic endoscope 42 and at least one needle 44. In the embodiment shown in FIG. 1, two needles, 44 and 46, are shown. One or more of the endoscope 42 and needles 44 and 46 may be enclosed within their own individual channels if desired. The endoscope 42 extends to an eye piece 48 at its proximal end 50. A light source 52, which is connected to the endoscope 42 by a fiber optic cable 54, enables visualization of the urethra during placement and manipulation of the applicator 10 in operation position and during a BPH electroporation treatment.
Needles 44 and 46 have insulating sheathes 60 on their surfaces that electrically separate or isolate them from the handle 12 and probe 14 as well as each other. Needles 44 and 46 are attached to a finger-activated lever 62 at their proximal ends in any known, appropriate manner. As seen in the Figure, lever 62 has been moved from its non-operational position seen in phantom to an operational position as indicated by the double-headed arrow 64. Movement of the lever 62 between the two positions will cause the needles to extend from their non-operational position to an operational position as seen in the Figure and to retract into their non-operational position as desired by the lever operator. Thus, movement of the lever to the operational position shown will cause the needles to extend or advance through holes 66 and 68 in the distal end 70 of the first or proximal probe section 16. The advancement of the needles 66 and 68 out of the probe 14 causes the needles to pierce the urethra 24 and the urogenital diaphragm 36 and disposes the uninsulated needle ends 74 and 76 of needles 44 and 46, respectively, which form a pair of electrodes, in the body of the prostate gland 78. Preferably, both the lengths and the operating positions of the distal end of the distal end 80 of the probe 14 and the needle electrodes 44 and 46 are selected to avoid reaching the bladder 82 to reduce the likelihood of damage thereto during a procedure. In particular, the sharp tips 84 and 86 of needles 44 and 46, respectively, should not penetrate the bladder 82.
The entirety of the surface of the applicator 10, save for a small portion 88 of the distal probe section 18 is covered with an insulating, biocompatible layer of any known or hereafter discovered, appropriate material. Uninsulated distal probe section portion 88 is therefore exposed to the surrounding tissue and can comprise a third, urethral electrode of the applicator 10. Electrodes 74, 76, and 88 are electrically insulated from each other and are connected via an appropriate connector 90 to a generator 92 that produces high voltage electrical pulses. As noted previously, the amplitude and duration of the electric pulses applied between the electrodes will be selected to provide an electric field in the prostatic tissue exceeding the upper electroporation limit of the BPH tissue, including the nerve cells contained therein. The pulse duration may be selected to be within the range of about 10 microseconds to about 500 milliseconds. The amplitude and number of applied pulses are selected to cause necrosis of the BPH tissue, including the nerves and muscle cells.
It will be observed that the proximal and distal probe sections 16 and 18 define longitudinal axes 96 and 98 respectively. As shown, axes 96 and 98 are not co-linear. They may, if desired, lie parallel to each other, however. Proximal section 16 has a larger cross-sectional area than the distal section 18, which does not need to carry the needles 44 and 46 therein, thus aiding to increase patient comfort during a procedure. Probe section 20 transitions between the larger cross-sectional area proximal section 16 and smaller cross-sectional area section 18. Additionally, the angled or curved nature of the section 20 serves to offset the proximal and distal sections 16 and 18, respectively, from each other. In doing so, the prostate gland 78 is displaced sideways relative to the axis 96 of the proximal section 16. This sideways displacement facilitates proper positioning of the needle electrodes in the BPH tissue.
Referring now specifically to FIG. 2, a cross-section of the prostate gland 78 is shown taken along viewing plane 22 of FIG. 1 with the applicator 10 in its operating position. When electric pulses are applied between the urethral electrode 88 and needle electrodes 74 and 79, the electric field generated between the electrodes, indicated generally by field lines 100, causes necrosis of the BPH tissue. After an electroporation treatment in one site of the prostate gland is completed, the needles can be retracted within probe 14 and the probe can be rotated a selected angle to a new position for treatment. The needles will be advanced into the operating position and the electric pulses applied once again. A plurality of such needle advancements and treatments are indicated in the Figure by the open circles 102.
Referring now specifically to FIG. 3, a cross-section of the prostate gland 78 is shown taken along viewing plane 33 of FIG. 1 with the applicator 10 in its operating position. As shown, the proximal probe section 16 preferably has a substantially elliptical configuration with a ratio of the axes in the range of about 1:3 to about 1:4. The maximal diameter of the ellipse should generally not exceed about 12 to about 16 mm and minimal diameter should generally not be less than about 3 to about 4 mm. The fiber bundle 42 of the endoscope and the tow needles 44 and 46 are positioned in line along the longer axis of the probe section 16. As seen in the Figure, needles 44 and 46 are disposed, if desired, within channels or tubes 104.
FIGS. 4-6 show alternative embodiments of the present invention. In FIG. 4, probe 110 includes proximal and distal segments 112 and 114, respectively. Segments 112 and 114 each define an axis 116 and 118, respectively. As indicated, axes 116 and 118 do not lie parallel to each other, but are separated by an angle a lying in the range of about 10° to about 45°. Also as shown, the needles 44 and 46 can, if desired, be angularly disposed relative to each other. As seen in the Figure, needles 44 and 46 diverge by an angle β lying in the range of about 0° to about 30°. In this embodiment, the proximal segment 112 can be made smaller, thus increasing patient comfort.
FIG. 5 illustrates an embodiment 130 of the present invention wherein curved needles 132 and 134 having radii of curvature R1 and R2, respectively, are used rather than the straight needles 44 and 46 previously illustrated and discussed. Where such curved needles are utilized, the radius of curvature of the needles are in the range of about 2 cm to about 5 cm.
FIG. 6 depicts another embodiment of the present invention. In this embodiment, probe 140 includes needles 142 and 142 that are bent at one location; as shown, the needles 142 and 144 are bent at the end of the insulating sheath 60.
Operatively, the probe of the present invention will be introduced into a patient's urethra under endoscopic guidance until the distal end is positioned in the prostatic segment of the patient's urethra. The needle electrodes will then be advanced into the BPH tissue surrounding the urethra and a plurality of electric pulses will be applied. The electroporation therapy will terminate when a significant and stable drop in the electrical resistance of the treated tissue occurs. The resistance drop indicates a profound electroporation damage to the fibromuscular cells, which later leads to their necrosis and dissolution by macrophages. Overall treatment of one site may take about ten pulses and several seconds to several tens of seconds in time depending on the repetition rate of the high voltage pulse generator. After each treatment the needle electrodes will be withdrawn and repositioned in another treatment site. Consecutive treatments are performed in light of patient comfort and safety and until the operator determines that a sufficient volume of BPH tissue has been treated.
It will be obvious to those skilled in the art that many modifications may be made within the scope of the present invention without departing from the spirit of thereof, and the invention includes all such modifications.

Claims (16)

1. An apparatus for providing electroporation therapy for benign prostatic hyperplasia, said apparatus comprising:
a urethral applicator configured for insertion into a urethra, said applicator including:
a substantially hollow probe, said probe portion including first, second and third probe portions, said first probe portion being configured for insertion into the penile urethral segment and said third probe portion being configured for insertion into the prostatic urethral segment, said first and third probe portions defining first and second probe portion longitudinal axes, wherein said axes are not collinear with each other and wherein said second probe portion lies between said first and third probe portion;
a handle, said handle being attached to said probe;
a plurality of needle electrodes, said electrodes being mounted within said first probe portion for reciprocal movement into and out of said first probe portion substantially parallel to the urethra, said electrodes being provided for connection to an electric pulse generator;
wherein when said applicator is disposed in operating position, said needle electrodes may be advanced into benign prostatic hyperplasia tissue for electroporation therapy.
2. The apparatus of claim 1 wherein said first and second probe portion longitudinal axes are parallel.
3. The apparatus of claim 1 wherein said first and second probe portion longitudinal axes are non-parallel.
4. The apparatus of claim 1 wherein said third probe portion is uninsulated and is provided for electrical connection to a pulse generator.
5. The apparatus of claim 1 wherein said first probe portion has a greater cross-sectional area than said third probe portion.
6. The apparatus of claim 1 wherein said needle electrodes are curved.
7. The apparatus of claim 1 wherein said needle electrodes are bent.
8. The apparatus of claim 1 and further including a flexible fiber optic endoscope.
9. The apparatus of claim 1 and further including an electric pulse generator.
10. The apparatus of claim 9 wherein said third probe portion is uninsulated and is electrically connected to a said electric pulse generator.
11. The apparatus of claim 1 wherein said first and third probe portions are longitudinally offset relative to each other.
12. The apparatus of claim 1 wherein said first and third probe portions are angularly off-set relative to each other.
13. The apparatus of claim 1 wherein said needle electrodes are electrically insulated from each other and said applicator.
14. The apparatus of claim 1 wherein said handle includes a lever engaged with said needle electrodes to enable the operator to selectively advance and retract said needle electrodes.
15. A method of providing electroporation therapy for benign prostatic hyperplasia comprising:
providing an applicator including a probe having a proximal probe portion and a distal probe electrode portion, said portions each defining non-collinear longitudinal axes, said probe including at least one electrode for electroporation therapy;
inserting the applicator into a patient's urethra to dispose the distal probe portion in the prostatic urethral segment and the proximal probe portion in the penile urethral segment and to displace the patient's prostate gland sideways relative to the proximal probe portion;
advancing at least a first electrode into the benign prostatic hyperplasia tissue; and
applying electric pulses to the distal probe electrode portion and the at least first electrode to generate electroporating electric fields.
16. The method of claim 15 and further including:
retracting the at least first electrode following the completion of electroporation therapy at a first site
rotating the probe a preselected amount;
advancing the at least first electrode into the benign prostatic hyperplasia tissue at a new location in the tissue; and
applying electric pulses to the distal probe electrode portion and the at least first electrode to generate electroporating electric fields.
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Cited By (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100262067A1 (en) * 2001-08-13 2010-10-14 Chornenky Victor I Method for Treatment of Neoplastic Cells in the Prostate of a Patient
US9598691B2 (en) 2008-04-29 2017-03-21 Virginia Tech Intellectual Properties, Inc. Irreversible electroporation to create tissue scaffolds
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
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
US10154874B2 (en) 2008-04-29 2018-12-18 Virginia Tech Intellectual Properties, Inc. Immunotherapeutic methods using irreversible electroporation
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
US10245105B2 (en) 2008-04-29 2019-04-02 Virginia Tech Intellectual Properties, Inc. Electroporation with cooling to treat tissue
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
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
US10471254B2 (en) 2014-05-12 2019-11-12 Virginia Tech Intellectual Properties, Inc. Selective modulation of intracellular effects of cells using pulsed electric fields
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
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
US10702337B2 (en) 2016-06-27 2020-07-07 Galary, Inc. Methods, apparatuses, and systems for the treatment of pulmonary disorders
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
US11311329B2 (en) 2018-03-13 2022-04-26 Virginia Tech Intellectual Properties, Inc. Treatment planning for immunotherapy based treatments using non-thermal ablation techniques
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
US11453873B2 (en) 2008-04-29 2022-09-27 Virginia Tech Intellectual Properties, Inc. Methods for delivery of biphasic electrical pulses for non-thermal ablation
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
US11707629B2 (en) 2009-05-28 2023-07-25 Angiodynamics, Inc. System and method for synchronizing energy delivery to the cardiac rhythm
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) 2019-09-18 2024-03-12 Virginia Tech Intellectual Properties, Inc. Treatment planning system for immunotherapy enhancement via non-thermal ablation

Citations (128)

* 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 (en) 1951-07-03 1953-01-15 Walter Hallegger Instrument for transcutaneous and subcutaneous heating and iontophoresis and method of its use
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
US4226246A (en) 1977-05-27 1980-10-07 Carba Societe Anonyme Apparatus for maintaining the negative potential of human, animal, and plant cells
US4262672A (en) 1978-01-02 1981-04-21 Horst Kief Acupuncture instrument
US4407943A (en) 1976-12-16 1983-10-04 Millipore Corporation Immobilized antibody or antigen for immunoassay
US4810963A (en) 1984-04-03 1989-03-07 Public Health Laboratory Service Board Method for investigating the condition of a bacterial suspension through frequency profile of electrical admittance
US4907601A (en) 1988-06-15 1990-03-13 Etama Ag Electrotherapy arrangement
US4946793A (en) 1986-05-09 1990-08-07 Electropore, Inc. Impedance matching for instrumentation which electrically alters vesicle membranes
US5019034A (en) 1988-01-21 1991-05-28 Massachusetts Institute Of Technology Control of transport of molecules across tissue using electroporation
DE4000893A1 (en) 1990-01-15 1991-07-18 Bosch Gmbh Robert Multichannel appts. for electro-simulation - provides several current circuits for patient with electrodes applying pulse signals
US5052391A (en) 1990-10-22 1991-10-01 R.F.P., Inc. High frequency high intensity transcutaneous electrical nerve stimulator and method of treatment
US5058605A (en) 1989-02-22 1991-10-22 Ceske Vysoke Uceni Technicke Method and device for the controlled local, non-invasive application of dc pulses to human and animal tissues
US5098843A (en) 1987-06-04 1992-03-24 Calvin Noel M Apparatus for the high efficiency transformation of living cells
US5134070A (en) 1990-06-04 1992-07-28 Casnig Dael R Method and device for cell cultivation on electrodes
US5173158A (en) 1991-07-22 1992-12-22 Schmukler Robert E Apparatus and methods for electroporation and electrofusion
US5193537A (en) 1990-06-12 1993-03-16 Zmd Corporation Method and apparatus for transcutaneous electrical cardiac pacing
US5273525A (en) 1992-08-13 1993-12-28 Btx Inc. Injection and electroporation apparatus for drug and gene delivery
US5318563A (en) 1992-06-04 1994-06-07 Valley Forge Scientific Corporation Bipolar RF generator
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
US5389069A (en) 1988-01-21 1995-02-14 Massachusetts Institute Of Technology Method and apparatus for in vivo electroporation of remote cells and tissue
US5403311A (en) 1993-03-29 1995-04-04 Boston Scientific Corporation Electro-coagulation and ablation and other electrotherapeutic treatments of body tissue
US5425752A (en) 1991-11-25 1995-06-20 Vu'nguyen; Dung D. Method of direct electrical myostimulation using acupuncture needles
US5439440A (en) 1993-04-01 1995-08-08 Genetronics, Inc. Electroporation system with voltage control feedback for clinical applications
US5458625A (en) 1994-05-04 1995-10-17 Kendall; Donald E. Transcutaneous nerve stimulation device and method for using same
US5533999A (en) 1993-08-23 1996-07-09 Refractec, Inc. Method and apparatus for modifications of visual acuity by thermal means
US5536240A (en) 1992-08-12 1996-07-16 Vidamed, Inc. Medical probe device and method
US5575811A (en) 1993-07-08 1996-11-19 Urologix, Inc. Benign prostatic hyperplasia treatment catheter with urethral cooling
EP0378132B1 (en) 1989-01-09 1996-11-27 Cit Ionofor, S.L. A device for the administration of medication by iontopheresis for local - regional treatment.
US5626146A (en) 1992-12-18 1997-05-06 British Technology Group Limited Electrical impedance tomography
US5634899A (en) 1993-08-20 1997-06-03 Cortrak Medical, Inc. Simultaneous cardiac pacing and local drug delivery method
US5674267A (en) 1993-03-30 1997-10-07 Centre National De La Recherche Scientifique Electric pulse applicator using pairs of needle electrodes for the treatment of biological tissue
US5702359A (en) 1995-06-06 1997-12-30 Genetronics, Inc. Needle electrodes for mediated delivery of drugs and genes
US5720921A (en) 1995-03-10 1998-02-24 Entremed, Inc. Flow electroporation chamber and method
US5778894A (en) 1996-04-18 1998-07-14 Elizabeth Arden Co. Method for reducing human body cellulite by treatment with pulsed electromagnetic energy
US5782882A (en) 1995-11-30 1998-07-21 Hewlett-Packard Company System and method for administering transcutaneous cardiac pacing with transcutaneous electrical nerve stimulation
US5810762A (en) 1995-04-10 1998-09-22 Genetronics, Inc. Electroporation system with voltage control feedback for clinical applications
US5836905A (en) 1994-06-20 1998-11-17 Lemelson; Jerome H. Apparatus and methods for gene therapy
US5843026A (en) * 1992-08-12 1998-12-01 Vidamed, Inc. BPH ablation method and apparatus
US5873849A (en) 1997-04-24 1999-02-23 Ichor Medical Systems, Inc. Electrodes and electrode arrays for generating electroporation inducing electrical fields
US5919142A (en) 1995-06-22 1999-07-06 Btg International Limited Electrical impedance tomography method and apparatus
US5947889A (en) 1995-01-17 1999-09-07 Hehrlein; Christoph Balloon catheter used to prevent re-stenosis after angioplasty and process for producing a balloon catheter
US5983131A (en) 1995-08-11 1999-11-09 Massachusetts Institute Of Technology Apparatus and method for electroporation 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
US5999847A (en) 1997-10-21 1999-12-07 Elstrom; John A. Apparatus and method for delivery of surgical and therapeutic agents
US6009347A (en) 1998-01-27 1999-12-28 Genetronics, Inc. Electroporation apparatus with connective electrode template
US6010613A (en) 1995-12-08 2000-01-04 Cyto Pulse Sciences, Inc. Method of treating materials with pulsed electrical fields
US6016452A (en) 1996-03-19 2000-01-18 Kasevich; Raymond S. Dynamic heating method and radio frequency thermal treatment
US6041252A (en) 1995-06-07 2000-03-21 Ichor Medical Systems Inc. Drug delivery system and method
US6055453A (en) 1997-08-01 2000-04-25 Genetronics, Inc. Apparatus for addressing needle array electrodes for electroporation therapy
US6085115A (en) 1997-05-22 2000-07-04 Massachusetts Institite Of Technology Biopotential measurement including electroporation of tissue surface
US6090106A (en) 1996-01-09 2000-07-18 Gyrus Medical Limited Electrosurgical instrument
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
US6109270A (en) 1997-02-04 2000-08-29 The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration Multimodality instrument for tissue characterization
US6122599A (en) 1998-02-13 2000-09-19 Mehta; Shailesh Apparatus and method for analyzing particles
US6132419A (en) 1992-05-22 2000-10-17 Genetronics, Inc. Electroporetic gene and drug therapy
US6159163A (en) 1998-05-07 2000-12-12 Cedars-Sinai Medical Center System for attenuating pain during bone marrow aspiration and method
US6208893B1 (en) * 1998-01-27 2001-03-27 Genetronics, Inc. Electroporation apparatus with connective electrode template
US6212433B1 (en) 1998-07-28 2001-04-03 Radiotherapeutics Corporation Method for treating tumors near the surface of an organ
US6210402B1 (en) 1995-11-22 2001-04-03 Arthrocare Corporation Methods for electrosurgical dermatological treatment
US6216034B1 (en) 1997-08-01 2001-04-10 Genetronics, Inc. Method of programming an array of needle electrodes for electroporation therapy of tissue
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
US6241702B1 (en) 1992-08-12 2001-06-05 Vidamed, Inc. Radio frequency ablation device for treatment of the prostate
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
US6300108B1 (en) 1999-07-21 2001-10-09 The Regents Of The University Of California Controlled electroporation and mass transfer across cell membranes
US20010044596A1 (en) 2000-05-10 2001-11-22 Ali Jaafar Apparatus and method for treatment of vascular restenosis by electroporation
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
US20020010491A1 (en) 1999-08-04 2002-01-24 Schoenbach Karl H. Method and apparatus for intracellular electro-manipulation
US6347247B1 (en) 1998-05-08 2002-02-12 Genetronics Inc. Electrically induced vessel vasodilation
US6349233B1 (en) 1993-02-22 2002-02-19 Angeion Corporation Neuro-stimulation to control pain during cardioversion defibrillation
US6351674B2 (en) 1998-11-23 2002-02-26 Synaptic Corporation Method for inducing electroanesthesia using high frequency, high intensity transcutaneous electrical nerve stimulation
US20020055731A1 (en) 1997-10-24 2002-05-09 Anthony Atala Methods for promoting cell transfection in vivo
US6387671B1 (en) 1999-07-21 2002-05-14 The Regents Of The University Of California Electrical impedance tomography to control electroporation
US6403348B1 (en) 1999-07-21 2002-06-11 The Regents Of The University Of California Controlled electroporation and mass transfer across cell membranes
US20020077676A1 (en) 1999-04-09 2002-06-20 Schroeppel Edward A. Implantable device and method for the electrical treatment of cancer
US20020099323A1 (en) 1998-07-13 2002-07-25 Nagendu B. Dev Skin and muscle-targeted gene therapy by pulsed electrical field
US20020138117A1 (en) 2000-06-21 2002-09-26 Son Young Tae Apparatus and method for selectively removing a body fat mass in human body
US6470211B1 (en) 1997-06-03 2002-10-22 Uab Research Foundation Method and apparatus for treating cardiac arrhythmia
US6493592B1 (en) 1999-12-01 2002-12-10 Vertis Neuroscience, Inc. Percutaneous electrical therapy system with electrode position maintenance
US20020193831A1 (en) 2001-04-26 2002-12-19 Smith Edward Dewey Method and apparatus for the treatment of cosmetic skin conditions
US6500173B2 (en) 1992-01-07 2002-12-31 Ronald A. Underwood Methods for electrosurgical spine surgery
US20030009110A1 (en) 2001-07-06 2003-01-09 Hosheng Tu Device for tumor diagnosis and methods thereof
US6526320B2 (en) 1998-11-16 2003-02-25 United States Surgical Corporation Apparatus for thermal treatment of tissue
US20030060856A1 (en) 2001-08-13 2003-03-27 Victor Chornenky Apparatus and method for treatment of benign prostatic hyperplasia
US20030088199A1 (en) 1999-10-01 2003-05-08 Toshikuni Kawaji Analgesic and anti-inflammatory patches for external use containing 4-biphenylylylacetic acid
US20030130711A1 (en) 2001-09-28 2003-07-10 Pearson Robert M. Impedance controlled tissue ablation apparatus and method
US6607529B1 (en) * 1995-06-19 2003-08-19 Medtronic Vidamed, Inc. Electrosurgical device
US6611706B2 (en) 1998-11-09 2003-08-26 Transpharma Ltd. Monopolar and bipolar current application for transdermal drug delivery and analyte extraction
US6613211B1 (en) 1999-08-27 2003-09-02 Aclara Biosciences, Inc. Capillary electrokinesis based cellular assays
US20030170898A1 (en) 2001-12-04 2003-09-11 Gundersen Martin A. Method for intracellular modifications within living cells using pulsed electric fields
US6627421B1 (en) 1999-04-13 2003-09-30 Imarx Therapeutics, Inc. Methods and systems for applying multi-mode energy to biological samples
US20030208200A1 (en) 2002-05-03 2003-11-06 Palanker Daniel V. Method and apparatus for plasma-mediated thermo-electrical ablation
US6653091B1 (en) 1998-09-30 2003-11-25 Cyngnus, Inc. Method and device for predicting physiological values
US20030225360A1 (en) 2002-03-11 2003-12-04 Jonathan Eppstein Transdermal drug delivery patch system, method of making same and method of using same
US6669691B1 (en) 2000-07-18 2003-12-30 Scimed Life Systems, Inc. Epicardial myocardial revascularization and denervation methods and apparatus
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
US6692493B2 (en) * 1998-02-11 2004-02-17 Cosman Company, Inc. Method for performing intraurethral radio-frequency urethral enlargement
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
US6702808B1 (en) 2000-09-28 2004-03-09 Syneron Medical Ltd. Device and method for treating skin
US20040059389A1 (en) 2002-08-13 2004-03-25 Chornenky Victor I. Apparatus and method for the treatment of benign prostatic hyperplasia
US20040146877A1 (en) 2001-04-12 2004-07-29 Diss James K.J. Diagnosis and treatment of cancer:I
US20040153057A1 (en) 1998-11-20 2004-08-05 Arthrocare Corporation Electrosurgical apparatus and methods for ablating tissue
US6795728B2 (en) 2001-08-17 2004-09-21 Minnesota Medical Physics, Llc Apparatus and method for reducing subcutaneous fat deposits by electroporation
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
US20040243107A1 (en) 2001-10-01 2004-12-02 Macoviak John A Methods and devices for treating atrial fibrilation
US20040267189A1 (en) 2001-10-24 2004-12-30 Daniela Mavor Device and method for controlled delivery of active substance into the skin
WO2004037341A3 (en) 2002-05-07 2005-01-27 Edward A Schroeppel Method and device for treating concer with electrical therapy in conjunction with chemotherapeutic agents and radiation therapy
US20050043726A1 (en) 2001-03-07 2005-02-24 Mchale Anthony Patrick Device II
US20050049541A1 (en) 2001-10-12 2005-03-03 Francine Behar Device for medicine delivery by intraocular iontophoresis or electroporation
EP0935482B1 (en) 1996-07-18 2005-05-04 Radinvent AB An apparatus for treating tumoral diseases (cancer)
US6912417B1 (en) 2002-04-05 2005-06-28 Ichor Medical Systmes, Inc. Method and apparatus for delivery of therapeutic agents
US20050165393A1 (en) 1996-12-31 2005-07-28 Eppstein Jonathan A. Microporation of tissue for delivery of bioactive agents
US20050171523A1 (en) 2003-12-24 2005-08-04 The Regents Of The University Of California Irreversible electroporation to control bleeding
US6927049B2 (en) 1999-07-21 2005-08-09 The Regents Of The University Of California Cell viability detection using electrical measurements
US6962587B2 (en) 2000-07-25 2005-11-08 Rita Medical Systems, Inc. Method for detecting and treating tumors using localized impedance measurement
US20050261672A1 (en) 2004-05-18 2005-11-24 Mark Deem Systems and methods for selective denervation of heart dysrhythmias
US6972014B2 (en) 2003-01-04 2005-12-06 Endocare, Inc. Open system heat exchange catheters and methods of use
US20050288730A1 (en) 2002-04-08 2005-12-29 Mark Deem Methods and apparatus for renal neuromodulation
US20060015147A1 (en) 1998-03-31 2006-01-19 Aditus Medical Ab. Apparatus for controlling the generation of electric fields
US20060025760A1 (en) 2002-05-06 2006-02-02 Podhajsky Ronald J Blood detector for controlling anesu and method therefor
US20060079883A1 (en) * 2004-10-13 2006-04-13 Ahmed Elmouelhi Transurethral needle ablation system
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
US7063698B2 (en) 2002-06-14 2006-06-20 Ncontact Surgical, Inc. Vacuum coagulation probes
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
US7211083B2 (en) 2003-03-17 2007-05-01 Minnesota Medical Physics, Llc Apparatus and method for hair removal by electroporation
US20080052786A1 (en) 2006-08-24 2008-02-28 Pei-Cheng Lin Animal Model of Prostate Cancer and Use Thereof

Patent Citations (147)

* 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 (en) 1951-07-03 1953-01-15 Walter Hallegger Instrument for transcutaneous and subcutaneous heating and iontophoresis and method of its use
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
US4226246A (en) 1977-05-27 1980-10-07 Carba Societe Anonyme Apparatus for maintaining the negative potential of human, animal, and plant cells
US4262672A (en) 1978-01-02 1981-04-21 Horst Kief Acupuncture instrument
US4810963A (en) 1984-04-03 1989-03-07 Public Health Laboratory Service Board Method for investigating the condition of a bacterial suspension through frequency profile of electrical admittance
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
US5019034A (en) 1988-01-21 1991-05-28 Massachusetts Institute Of Technology Control of transport of molecules across tissue using electroporation
US5389069A (en) 1988-01-21 1995-02-14 Massachusetts Institute Of Technology Method and apparatus for in vivo electroporation of remote cells and tissue
US5019034B1 (en) 1988-01-21 1995-08-15 Massachusetts Inst Technology Control of transport of molecules across tissue using electroporation
US4907601A (en) 1988-06-15 1990-03-13 Etama Ag Electrotherapy arrangement
EP0378132B1 (en) 1989-01-09 1996-11-27 Cit Ionofor, S.L. A device for the administration of medication by iontopheresis for local - regional treatment.
US5058605A (en) 1989-02-22 1991-10-22 Ceske Vysoke Uceni Technicke Method and device for the controlled local, non-invasive application of dc pulses to human and animal tissues
DE4000893A1 (en) 1990-01-15 1991-07-18 Bosch Gmbh Robert Multichannel appts. for electro-simulation - provides several current circuits for patient with electrodes applying pulse signals
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
US5283194A (en) 1991-07-22 1994-02-01 Schmukler Robert E Apparatus and methods for electroporation and electrofusion
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
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
US6241702B1 (en) 1992-08-12 2001-06-05 Vidamed, Inc. Radio frequency ablation device for treatment of the prostate
US5536240A (en) 1992-08-12 1996-07-16 Vidamed, Inc. Medical probe device and method
US5843026A (en) * 1992-08-12 1998-12-01 Vidamed, Inc. BPH ablation method and apparatus
US5800378A (en) 1992-08-12 1998-09-01 Vidamed, Inc. Medical probe device and method
US5273525A (en) 1992-08-13 1993-12-28 Btx Inc. Injection and electroporation apparatus for drug and gene delivery
US5626146A (en) 1992-12-18 1997-05-06 British Technology Group Limited Electrical impedance tomography
US6349233B1 (en) 1993-02-22 2002-02-19 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
US5674267A (en) 1993-03-30 1997-10-07 Centre National De La Recherche Scientifique Electric pulse applicator using pairs of needle electrodes for the treatment of biological tissue
US5439440A (en) 1993-04-01 1995-08-08 Genetronics, Inc. Electroporation system with voltage control feedback for clinical applications
US5575811A (en) 1993-07-08 1996-11-19 Urologix, Inc. Benign prostatic hyperplasia treatment catheter with urethral cooling
US5634899A (en) 1993-08-20 1997-06-03 Cortrak Medical, Inc. Simultaneous cardiac pacing and local drug delivery method
US5533999A (en) 1993-08-23 1996-07-09 Refractec, Inc. Method and apparatus for modifications of visual acuity by thermal means
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
US5947889A (en) 1995-01-17 1999-09-07 Hehrlein; Christoph Balloon catheter used to prevent re-stenosis after angioplasty and process for producing a balloon catheter
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
US5702359A (en) 1995-06-06 1997-12-30 Genetronics, Inc. Needle electrodes for mediated delivery of drugs and genes
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
US6210402B1 (en) 1995-11-22 2001-04-03 Arthrocare Corporation Methods for electrosurgical dermatological treatment
US5782882A (en) 1995-11-30 1998-07-21 Hewlett-Packard Company System and method for administering transcutaneous cardiac pacing with transcutaneous electrical nerve stimulation
US6010613A (en) 1995-12-08 2000-01-04 Cyto Pulse Sciences, Inc. Method of treating materials with pulsed electrical fields
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
EP0935482B1 (en) 1996-07-18 2005-05-04 Radinvent AB An apparatus for treating tumoral diseases (cancer)
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
US20050165393A1 (en) 1996-12-31 2005-07-28 Eppstein Jonathan A. Microporation of tissue for delivery of bioactive agents
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
US6109270A (en) 1997-02-04 2000-08-29 The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration Multimodality instrument for tissue characterization
US6278895B1 (en) 1997-04-24 2001-08-21 Ichor Medical Systems, Inc. Electrodes and electrode arrays for generating electroporation inducing electrical fields
US5873849A (en) 1997-04-24 1999-02-23 Ichor Medical Systems, Inc. Electrodes and electrode arrays for generating electroporation inducing electrical fields
US6085115A (en) 1997-05-22 2000-07-04 Massachusetts Institite Of Technology Biopotential measurement including electroporation of tissue surface
US6470211B1 (en) 1997-06-03 2002-10-22 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
US6068650A (en) 1997-08-01 2000-05-30 Gentronics Inc. Method of Selectively applying needle array configurations
US6216034B1 (en) 1997-08-01 2001-04-10 Genetronics, Inc. Method of programming an array of needle electrodes for electroporation therapy of tissue
US5999847A (en) 1997-10-21 1999-12-07 Elstrom; John A. Apparatus and method for delivery of surgical and therapeutic agents
US20020055731A1 (en) 1997-10-24 2002-05-09 Anthony Atala 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
US6692493B2 (en) * 1998-02-11 2004-02-17 Cosman Company, Inc. Method for performing intraurethral radio-frequency urethral enlargement
US6122599A (en) 1998-02-13 2000-09-19 Mehta; Shailesh Apparatus and method for analyzing particles
US20060015147A1 (en) 1998-03-31 2006-01-19 Aditus Medical Ab. Apparatus for controlling the generation of electric fields
US20070118069A1 (en) 1998-03-31 2007-05-24 Aditus Medical Ab Apparatus for controlling the generation of electric fields
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
US6347247B1 (en) 1998-05-08 2002-02-12 Genetronics Inc. Electrically induced vessel vasodilation
US6865416B2 (en) 1998-05-08 2005-03-08 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
US20020099323A1 (en) 1998-07-13 2002-07-25 Nagendu B. Dev 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
US6653091B1 (en) 1998-09-30 2003-11-25 Cyngnus, Inc. Method and device for predicting physiological values
US6611706B2 (en) 1998-11-09 2003-08-26 Transpharma Ltd. Monopolar and bipolar current application for transdermal drug delivery and analyte extraction
US6526320B2 (en) 1998-11-16 2003-02-25 United States Surgical Corporation Apparatus for thermal treatment of tissue
US20040153057A1 (en) 1998-11-20 2004-08-05 Arthrocare Corporation Electrosurgical apparatus and methods for ablating tissue
US6351674B2 (en) 1998-11-23 2002-02-26 Synaptic Corporation Method for inducing electroanesthesia using high frequency, high intensity transcutaneous electrical nerve stimulation
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
US20020077676A1 (en) 1999-04-09 2002-06-20 Schroeppel Edward A. Implantable device and method for the electrical treatment of cancer
US6627421B1 (en) 1999-04-13 2003-09-30 Imarx Therapeutics, Inc. Methods and systems for applying multi-mode energy to biological samples
US6387671B1 (en) 1999-07-21 2002-05-14 The Regents Of The University Of California Electrical impedance tomography to control electroporation
US6562604B2 (en) 1999-07-21 2003-05-13 The Regents Of The University Of California Controlled electroporation and mass transfer across cell membranes
US20060121610A1 (en) 1999-07-21 2006-06-08 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
US6927049B2 (en) 1999-07-21 2005-08-09 The Regents Of The University Of California Cell viability detection using electrical measurements
US6403348B1 (en) 1999-07-21 2002-06-11 The Regents Of The University Of California Controlled electroporation and mass transfer across cell membranes
US6300108B1 (en) 1999-07-21 2001-10-09 The Regents Of The University Of California Controlled electroporation and mass transfer across cell membranes
US6482619B1 (en) 1999-07-21 2002-11-19 The Regents Of The University Of California Cell/tissue analysis via controlled electroporation
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
US6613211B1 (en) 1999-08-27 2003-09-02 Aclara Biosciences, Inc. Capillary electrokinesis based cellular assays
US20030088199A1 (en) 1999-10-01 2003-05-08 Toshikuni Kawaji Analgesic and anti-inflammatory patches for external use containing 4-biphenylylylacetic acid
US6493592B1 (en) 1999-12-01 2002-12-10 Vertis Neuroscience, Inc. Percutaneous electrical therapy system with electrode position maintenance
US20010044596A1 (en) 2000-05-10 2001-11-22 Ali Jaafar Apparatus and method for treatment of vascular restenosis by electroporation
US20020138117A1 (en) 2000-06-21 2002-09-26 Son Young Tae Apparatus and method for selectively removing a body fat mass in human body
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
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
US6702808B1 (en) 2000-09-28 2004-03-09 Syneron Medical Ltd. Device and method for treating skin
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
US6892099B2 (en) 2001-02-08 2005-05-10 Minnesota Medical Physics, Llc Apparatus and method for reducing subcutaneous fat deposits, virtual face lift and body sculpturing by electroporation
US20050043726A1 (en) 2001-03-07 2005-02-24 Mchale Anthony Patrick Device II
US20040146877A1 (en) 2001-04-12 2004-07-29 Diss James K.J. Diagnosis and treatment of cancer:I
US20020193831A1 (en) 2001-04-26 2002-12-19 Smith Edward Dewey Method and apparatus for the treatment of cosmetic skin conditions
US20030009110A1 (en) 2001-07-06 2003-01-09 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
US20060217703A1 (en) 2001-08-13 2006-09-28 Chornenky Victor I Apparatus and method for treatment of benign prostatic hyperplasia
US20030060856A1 (en) 2001-08-13 2003-03-27 Victor Chornenky Apparatus and method for treatment of benign prostatic hyperplasia
US6795728B2 (en) 2001-08-17 2004-09-21 Minnesota Medical Physics, Llc Apparatus and method for reducing subcutaneous fat deposits 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
US20030130711A1 (en) 2001-09-28 2003-07-10 Pearson Robert M. 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
US20050049541A1 (en) 2001-10-12 2005-03-03 Francine Behar Device for medicine delivery by intraocular iontophoresis or electroporation
US20040267189A1 (en) 2001-10-24 2004-12-30 Daniela Mavor Device and method for controlled delivery of active substance into the skin
US20030170898A1 (en) 2001-12-04 2003-09-11 Gundersen Martin A. Method for intracellular modifications within living cells using pulsed electric fields
US20030225360A1 (en) 2002-03-11 2003-12-04 Jonathan Eppstein Transdermal drug delivery patch system, method of making same and method of using same
US6912417B1 (en) 2002-04-05 2005-06-28 Ichor Medical Systmes, Inc. Method and apparatus for delivery of therapeutic agents
US20050288730A1 (en) 2002-04-08 2005-12-29 Mark Deem Methods and apparatus for renal neuromodulation
US20060212078A1 (en) 2002-04-08 2006-09-21 Ardian, Inc. Methods and apparatus for treating congestive heart failure
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
US20030208200A1 (en) 2002-05-03 2003-11-06 Palanker Daniel V. Method and apparatus for plasma-mediated thermo-electrical ablation
US20060025760A1 (en) 2002-05-06 2006-02-02 Podhajsky Ronald J Blood detector for controlling anesu and method therefor
WO2004037341A3 (en) 2002-05-07 2005-01-27 Edward A Schroeppel Method and device for treating concer with electrical therapy in conjunction with chemotherapeutic agents and radiation therapy
US7063698B2 (en) 2002-06-14 2006-06-20 Ncontact Surgical, Inc. Vacuum coagulation probes
US20040059389A1 (en) 2002-08-13 2004-03-25 Chornenky Victor I. Apparatus and method for the 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
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
US7267676B2 (en) 2003-03-17 2007-09-11 Minnesota Medical Physics Llc Method for hair removal by electroporation
US20050171574A1 (en) 2003-12-24 2005-08-04 The Regents Of The University Of California Electroporation to interrupt blood flow
US20070043345A1 (en) 2003-12-24 2007-02-22 Rafael Davalos Tissue ablation with irreversible electroporation
US20050171523A1 (en) 2003-12-24 2005-08-04 The Regents Of The University Of California Irreversible electroporation to control bleeding
US20050261672A1 (en) 2004-05-18 2005-11-24 Mark Deem Systems and methods for selective denervation of heart dysrhythmias
US20060079883A1 (en) * 2004-10-13 2006-04-13 Ahmed Elmouelhi 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
US20080052786A1 (en) 2006-08-24 2008-02-28 Pei-Cheng Lin Animal Model of Prostate Cancer and Use Thereof

Non-Patent Citations (87)

* Cited by examiner, † Cited by third party
Title
Amasha, et al., Quantitative Assessment of Impedance Tomography for Temperature Measurements in Microwave Hyperthermia, Clin. Phys. Physiol. Meas., 1998, Suppl. A, 49-53.
Andreason, Electroporation as a Technique for the Transfer of Macromolecules into Mammalian Cell Lines, J. Tiss. Cult. Meth., 15:56-62, 1993.
Baker, et al., Calcium-Dependent Exocytosis in Bovine Adrenal Medullary Cells with Leaky Plasma Membranes, Nature, vol. 276, pp. 620-622, 1978.
Barber, Electrical Impedance Tomography Applied Potential Tomography, Advances in Biomedical Engineering, Beneken and Thevenin, eds., IOS Press, 1993.
Beebe, S.J., et al., Nanosecond pulsed electric field (nsPEF) effects on cells and tissues: apoptosis induction and tumor growth inhibition. PPPS-2001 Pulsed Power Plasma Science 2001, 28th IEEE International Conference on Plasma Science and 13th IEEE International Pulsed Power Conference, Digest of Technical Papers (Cat. No. 01CH37251). IEEE, Part vol. 1, 2001, pp. 211-215, vol. I, Piscataway, NJ, USA.
Blad, et al., Impedance Spectra of Tumour Tissue in Comparison with Normal Tissue; a Possible Clinical Application for Electrical Impedance Tomography, Physiol. Meas. 17 (1996) A105-A115.
Bown, S.G., Phototherapy of tumors. World J. Surgery, 1983. 7: p. 700-9.
BPH Management Strategies: Improving Patient Satisfaction, Urology Times, May 2001, vol. 29, Supplement 1.
Brown, et al., Blood Flow Imaging Using Electrical Impedance Tomography, Clin. Phys. Physiol. Meas., 1992, vol. 13, Suppl. A, 175-179.
Chandrasekar, et al., Transurethral Needle Ablation of the Prostate (TUNA)-a Propsective Study, Six Year Follow Up, (Abstract), Presented at 2001 National Meeting, Anaheim, CA, Jun. 5, 2001.
Chandrasekar, et al., Transurethral Needle Ablation of the Prostate (TUNA)—a Propsective Study, Six Year Follow Up, (Abstract), Presented at 2001 National Meeting, Anaheim, CA, Jun. 5, 2001.
Coates, C.W.,et al., "The Electrical Discharge of the Electric Eel, Electrophorous Electricus," Zoologica, 1937, 22(1), pp. 1-32.
Cook, et al., ACT3: A High-Speed, High-Precision Electrical Impedance Tomograph, IEEE Transactions on Biomedical Engineering, vol. 41, No. 8, Aug. 1994.
Cowley, Good News for Boomers, Newsweek, Dec. 30, 1996/Jan. 6, 1997.
Cox, et al., Surgical Treatment of Atrial Fibrillation: A Review, Europace (2004) 5, S20-S-29.
Crowley, Electrical Breakdown of Biomolecular Lipid Membranes as an Electromechanical Instability, Biophysical Journal, vol. 13, pp. 711-724, 1973.
Davalos, et al., A Feasibility Study for Electrical Impedance Tomography as a Means to Monitor T issue Electroporation for Molecular Medicine, IEEE Transactions on Biomedical Engineering, vol. 49, No. 4, Apr. 2002.
Davalos, et al., Theoretical Analysis of the Thermal Effects During In Vivo Tissue Electroporation, Bioelectrochemistry, vol. 61, pp. 99-107, 2003.
Davalos, et al., Tissue Ablation with Irreversible Electroporation, Annals of Biomedical Engineering, vol. 33, No. 2, Feb. 2005.
Davalos, Real-Time Imaging for Molecular Medicine through Electrical Impedance Tomography of Electroporation, Dissertation for Ph.D. in Engineering-Mechanical Engineering, Graduate Division of University of California, Berkeley, 2002.
Dean, Nonviral Gene Transfer to Skeletal, Smooth, and Cardiac Muscle in Living Animals, Am J. Physiol Cell Physiol 289: 233-245, 2005.
Dev, et al., Medical Applications of Electroporation, IEEE Transactions of Plasma Science, vol. 28, No. 1, pp. 206-223, Feb. 2000.
Dev, et al., Sustained Local Delivery of Heparin to the Rabbit Arterial Wall with an Electroporation Catheter, Catheterization and Cardiovascular Diagnosis, Nov. 1998, vol. 45, No. 3, pp. 337-343.
Duraiswami, et al., Boundary Element Techniques for Efficient 2-D and 3-D Electrical Impedance Tomography, Chemical Engineering Science, vol. 52, No. 13, pp. 2185-2196, 1997.
Duraiswami, et al., Efficient 2D and 3D Electrical Impedance Tomography Using Dual Reciprocity Boundary Element Techniques, Engineering Analysis with Boundary Elements22, (1998) 13-31.
Duraiswami, et al., Solution of Electrical Impedance Tomography Equations Using Boundary Element Methods, Boundary Element Technology XII, 1997, pp. 226-237.
Edd, J., et al., In-Vivo Results of a New Focal Tissue Ablation Technique: Irreversible Electroporation, IEEE Trans. Biomed. Eng. 53 (2006) p. 1409-1415.
Erez, et al., Controlled Destruction and Temperature Distributions in Biological Tissues Subjected to Monoactive Electrocoagulation, Transactions of the ASME: Journal of Mechanical Design, vol. 102, Feb. 1980.
Foster, R.S., et al., High-intensity focused ultrasound in the treatment of prostactic disease. Eur. Urol., 1993. 23: 44-7).
Fox, et al., Sampling Conductivity Images via MCMC, Mathematics Department, Auckland University, New Zealand, May 1997.
Gauger, et al., A Study of Dielectric Membrane Breakdown in the Fucus Egg, J. Membrane Biol., vol. 48, No. 3, pp. 249-264, 1979.
Gehl, et al., In Vivo Electroporation of Skeletal Muscle: Threshold, Efficacy and Relation to Electric Field Distribution, Biochimica et Biphysica Acta 1428, 1999, pp. 233-240.
Gençer, et al., Electrical Impedance Tomography: Induced-Current Imaging Achieved with a Multiple Coil System, IEEE Transactions on Biomedical Engineering, vol. 43, No. 2, Feb. 1996.
Gilbert, et al., Novel Electrode Designs for Electrochemotheraphy, Biochimica et Biophysica Acta 1334, 1997, pp. 9-14.
Gilbert, et al., The Use of Ultrasound Imaging for Monitoring Cryosurgery, Proceedings 6th Annual Conference, IEEE Engineering in Medicine and Biology, 107-111, 1984.
Glidewell, et al., The Use of Magnetic Resonance Imaging Data and the Inclusion of Anisotropic Regions in Electrical Impedance Tomography, Biomed, Sci. Instrum. 1993; 29: 251-7.
Gothelf, et al., Electrochemotherapy: Results of Cancer Treatment Using Enhanced Delivery of Bleomycin by Electroporation, Cancer Treatment Reviews 2003: 29: 371-387.
Griffiths, et al., A Dual-Frequency Electrical Impedance Tomography System, Phys. Med. Biol., 1989, vol. 34, No. 10, pp. 1465-1476.
Griffiths, The Importance of Phase Measurement in Electrical Impedance Tomography, Phys. Med. Biol., 1987, vol. 32, No. 11, pp. 1435-1444.
Griffiths, Tissue Spectroscopy with Electrical Impedance Tomography: Computer Simulations, IEEE Transactions on Biomedical Engineering, vol. 42, No. 9, Sep. 1995.
Gumerov, et al., The Dipole Approximation Method and Its Coupling with the Regular Boundary Element Method for Efficient Electrical Impedance Tomography, Boundary Element Technology XIII, 1999.
Hapala, Breaking the Barrier: Methods for Reversible Permeabilization of Cellular Membranes, Critical Reviews in Biotechnology, 17(2): 105-122, 1997.
Heller, et al., Clinical Applications of Electrochemotherapy, Advanced Drug Delivery Reviews, vol. 35, pp. 119-129, 1999.
Ho, et al., Electroporation of Cell Membranes: A Review, Critical Reviews in Biotechnology, 16(4): 349-362, 1996.
Holder, et al., Assessment and Calibration of a Low-Frequency System for Electrical Impedance Tomography (EIT), Optimized for Use in Imaging Brain Function in Ambulant Human Subjects, Annals of the New York Academy of Science, vol. 873, Issue 1, Electrical BI, pp. 512-519, 1999.
Huang, et al., Micro-Electroporation: Improving the Efficiency and Understanding of Electrical Permeabilization of Cells, Biomedical Microdevices, vol. 2, pp. 145-150, 1999.
Hughes, et al., An Analysis of Studies Comparing Electrical Impedance Tomography with X-Ray Videofluoroscopy in the Assessment of Swallowing, Physiol. Meas. 15, 1994, pp. A199-A209.
Issa, et al., The TUNA Procedure for BPH: Review of the Technology: The TUNA Procedure for BPH: Basic Procedure and Clinical Results, Reprinted from Infections in Urology, Jul./Aug. 1998 and Sep./Oct. 1998.
Ivanu{hacek over (s)}a, et al., MRI Macromolecular Contrast Agents as Indicators of Changed Tumor Blood Flow, Radiol. Oncol. 2001; 35(2): 139-47.
Jaroszeski, et al., In Vivo Gene Delivery by Electroporation, Advanced Drug Delivery Review, vol. 35, pp. 131-137, 1999.
Kinosita, et al., Hemolysis of Human Erythrocytes by a Transient Electric Field, Proc. Natl. Acad. Sci. USA, vol. 74, No. 5, pp. 1923-1927, 1977.
Liu, et al., Measurement of Pharyngeal Transit Time by Electrical Impedance Tomography, Clin. Phys. Physiol. Meas., 1992, vol. 13, Suppl. A, pp. 197-200.
Lundqvist, et al., Altering the Biochemical State of Individual Cultured Cells and Organelles with Ultramicroelectrodes, Proc. Natl. Acad. Sci. USA, vol. 95, pp. 10356-10360, Sep. 1998.
Lurquin, Gene Transfer by Electroporation, Molecular Biotechnology, vol. 7, 1997.
Lynn, et al., A New Method for the Generation and Use of Focused Ultrasound in Experimental Biology, The Journal of General Physiology, vol. 26, 179-193, 1942.
Miklav{hacek over (c)}i{hacek over (c)}, et al., A Validated Model of an in Vivo Electric Field Distribution in Tissues for Electrochemotherapy and for DNA Electrotransfer for Gene Therapy, Biochimica et Biophysica Acta 1523 (2000), pp. 73-83.
Miklav{hacek over (c)}i{hacek over (c)}, et al., The Importance of Electric Field Distribution for Effective in Vivo Electroporation of Tissues, Biophysical Journal, vol. 74, May 1998, pp. 2152-2158.
Miller, L., et al., Cancer cells ablation with irreversible electroporation, Technology in Cancer Research and Treatment 4 (2005) 699-706.
Mir, et al., Effective Treatment of Cutaneous and Subcutaneous Malignant Tumours by Electrochemotherapy, British Journal of Cancer, vol. 77, No. 12, pp. 2336-2342, 1998.
Mir, et al., Electrochemotherapy Potentiation of Antitumour Effect of Bleomycin by Local Electric Pulses, European Journal of Cancer, vol. 27, No. 1, pp. 68-72, 1991.
Mir, et al., Electrochemotherapy, a Novel Antitumor Treatment: First Clinical Trial, C.R. Acad. Sci. Paris, Ser. III, vol. 313, pp. 613-618, 1991.
Mir, L.M. and Orlowski, S., 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.
Mir, L.M., et al., Electric Pulse-Mediated Gene Delivery to Various Animal Tissues, in Advances in Genetics, Academic Press, 2005, p. 83-114.
Mir, Therapeutic Perspectives of In Vivo Cell Electropermeabilization, Bioelectrochemistry, vol. 53, pp. 1-10, 2000.
Narayan, et al., Establishment and Characterization of a Human Primary Prostatic Adenocarcinoma Cell Line (ND-1), The Journal of Urology, vol. 148, 1600-1604, Nov. 1992.
Naslund, Cost-Effectiveness of Minimally Invasive Treatments and Transurethral Resection (TURP) in Benign Prostatic Hyperplasia (BPH), (Abstract), Presented at 2001 AUA National Meeting,, Anaheim, CA, Jun. 5, 2001.
Naslund, Michael J., Transurethral Needle Ablation of the Prostate, Urology, vol. 50, No. 2, Aug. 1997.
Neumann, et al., Gene Transfer into Mouse Lyoma Cells by Electroporation in High Electric Fields, J. Embo., vol. 1, No. 7, pp. 841-845, 1982.
Neumann, et al., Permeability Changes Induced by Electric Impulses in Vesicular Membranes, J. Membrane Biol., vol. 10, pp. 279-290, 1972.
Okino, et al., Effects of High-Voltage Electrical Impulse and an Anticancer Drug on In Vivo Growing Tumors, Japanese Journal of Cancer Research, vol. 78, pp. 1319-1321, 1987.
Onik, et al., Sonographic Monitoring of Hepatic Cryosurgery in an Experimental Animal Model, AJR American J. of Roentgenology, vol. 144, pp. 1043-1047, May 1985.
Onik, et al., Ultrasonic Characteristics of Frozen Liver, Cryobiology, vol. 21, pp. 321-328, 1984.
Organ, L.W., Electrophysiological principles of radiofrequency lesion making, Apply. Neurophysiol.,1976. 39: p. 69-76.
Piñero, et al., Apoptotic and Necrotic Cell Death Are Both Induced by Electroporation in HL60 Human Promyeloid Leukaemia Cells, Apoptosis, vol. 2, No. 3, 330-336, Aug. 1997.
Rols, M.P., et al., Highly Efficient Transfection of Mammalian Cells by Electric Field Pulses: Application to Large Volumes of Cell Culture by Using a Flow System, Eur. J. Biochem. 1992, 206, pp. 115-121.
Rubinsky, B., ed, Cryosurgery. Annu Rev. Biomed. Eng. vol. 2 2000. 157-187.
Sersa, et al., Reduced Blood Flow and Oxygenation in SA-1 Tumours after Electrochemotherapy with Cisplatin, British Journal of Cancer, 87, 1047-1054, 2002.
Sersa, et al., Tumour Blood Flow Modifying Effects of Electrochemotherapy: a Potential Vascular Targeted Mechanism, Radiol. Oncol., 37(1): 43-8, 2003.
Sharma, et al., Poloxamer 188 Decreases Susceptibility of Artificial Lipid Membranes to Electroporation, Biophysical Journal, vol. 71, No. 6, pp. 3229-3241, Dec. 1996.
Shiina, S., et al, Percutaneous ethanol injection therapy for hepatocellular carcinoma: results in 146 patients. AJR, 1993, 160: p. 1023-8.
Thompson, et al., To determine whether the temperature of 2% lignocaine gel affects the initial discomfort which may be associated with its instillation into the male urethra, BJU International (1999), 84, 1035-1037.
Weaver, Electroporation: A General Phenomenon for Manipulating Cells and Tissues, Journal of Cellular Biochemistry, 51: 426-435, 1993.
Weaver, et al., Theory of Electroporation: A Review, Bioelectrochemistry and Bioenergetics, vol. 41, pp. 136-160, 1996.
Zimmermann, et al., Dielectric Breakdown of Cell Membranes, Biophysical Journal, vol. 14, No. 11, pp. 881-899, 1974.
Zlotta, et al., Long-Term Evaluation of Transurethral Needle Ablation of the Prostate (TUNA) for Treatment of Benign Prostatic Hyperplasia (BPH): Clinical Outcome After 5 Years. (Abstract) Presented at 2001 AUA National Meeting, Anaheim, CA-Jun. 5, 2001.
Zlotta, et al., Long-Term Evaluation of Transurethral Needle Ablation of the Prostate (TUNA) for Treatment of Benign Prostatic Hyperplasia (BPH): Clinical Outcome After 5 Years. (Abstract) Presented at 2001 AUA National Meeting, Anaheim, CA—Jun. 5, 2001.
Zlotta, et al., Possible Mechanisms of Action of Transurethral Needle Ablation of the Prostate on Benign Prostatic Hyperplasia Symptoms: a Neurohistochemical Study, Reprinted from Journal of Urology, vol. 157, No. 3, Mar. 1997, pp. 894-899.

Cited By (45)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100262067A1 (en) * 2001-08-13 2010-10-14 Chornenky Victor I Method for Treatment of Neoplastic Cells in the Prostate of a Patient
US8634929B2 (en) * 2001-08-13 2014-01-21 Angiodynamics, Inc. Method for treatment of neoplastic cells in the prostate of a patient
US20140107643A1 (en) * 2001-08-13 2014-04-17 Angiodynamics, Inc. Method for Relaxing Muscle Tension on a Tubular Anatomical Structure
US8958888B2 (en) * 2001-08-13 2015-02-17 Angiodynamics, Inc. Method for relaxing muscle tension on a tubular anatomical structure
US11453873B2 (en) 2008-04-29 2022-09-27 Virginia Tech Intellectual Properties, Inc. Methods for delivery of biphasic electrical pulses for non-thermal ablation
US11737810B2 (en) 2008-04-29 2023-08-29 Virginia Tech Intellectual Properties, Inc. Immunotherapeutic methods using electroporation
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
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US9598691B2 (en) 2008-04-29 2017-03-21 Virginia Tech Intellectual Properties, Inc. Irreversible electroporation to create tissue scaffolds
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
US10828085B2 (en) 2008-04-29 2020-11-10 Virginia Tech Intellectual Properties, Inc. Immunotherapeutic methods using irreversible electroporation
US10154874B2 (en) 2008-04-29 2018-12-18 Virginia Tech Intellectual Properties, Inc. Immunotherapeutic methods using irreversible electroporation
US10292755B2 (en) 2009-04-09 2019-05-21 Virginia Tech Intellectual Properties, Inc. High frequency electroporation for cancer therapy
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
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
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
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
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
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
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
US11369433B2 (en) 2016-06-27 2022-06-28 Galvanize Therapeutics, Inc. Methods, apparatuses, and systems for the treatment of pulmonary disorders
US10702337B2 (en) 2016-06-27 2020-07-07 Galary, Inc. Methods, apparatuses, and systems for the treatment of pulmonary disorders
US10939958B2 (en) 2016-06-27 2021-03-09 Galary, 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
US11607537B2 (en) 2017-12-05 2023-03-21 Virginia Tech Intellectual Properties, Inc. Method for treating neurological disorders, including tumors, with electroporation
US11311329B2 (en) 2018-03-13 2022-04-26 Virginia Tech Intellectual Properties, Inc. Treatment planning for immunotherapy based treatments using non-thermal ablation techniques
US11925405B2 (en) 2019-09-18 2024-03-12 Virginia Tech Intellectual Properties, Inc. Treatment planning system for immunotherapy enhancement via non-thermal ablation

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