Patent Description:
Delivery of high voltage irreversible electroporation (IRE) pulses to tissue was previously proposed in the patent literature. For example, <CIT> describes a system that improves urine flow by increasing the inside diameter of the urethra going through the prostate by eroding the urethral wall, rather than by reducing the prostate volume. This is done by a specially designed IRE electrode, which limits the penetration depth of the electric field to the urethral wall. In an embodiment, a catheter carrying the electrodes can be made hollow and irrigation holes can be added. Such holes can be used to deliver a saline solution for cooling as well as medication to assist the procedure such as for pain reduction.

As another example, <CIT> describes several devices and methods for treating obesity and diabetes by using electroporation to modulate the duodenal mucosa. In some embodiments, an endoscope is used that includes a lumen (e.g., an irrigation lumen) through which electrically conductive liquid can flow. When the electroporation device is in use, the electrically conductive liquid can flow through the lumen of the endoscope and thereafter reside in the duodenum between a proximal balloon and distal balloon inflated in the electroporation device. In this arrangement, energy from energized electrodes of the electroporation device can be conducted by the electrically conductive liquid to the duodenal mucosa, including within the crypts of the duodenal mucosa.

<CIT> describes an electrode catheter device with indifferent electrode for direct current tissue therapies. An example of the catheter device has a flexible tubing with at least one ablation electrode. The catheter device may also be used with a sheath for introducing the flexible tubing inside a patient's body. An indifferent electrode on the sheath can provide a ground for a direct current (DC) pulse to deliver electrical energy and create an electrical field adjacent tissue. Various other embodiments are also disclosed. In one embodiment, of an irrigated catheter, the tip electrode and/or other locations in the tip assembly may be formed with a plurality of openings, e.g., between two or more of the electrodes. A central lumen may be in fluid communication with a fluid fitting on one end, and with the ports at the other end. Thus, an electricity conductive fluid or gel may be injected through the inner tube and secreted from the ports to form a current path and facilitate conduction of an electrical current between the electrodes.

<CIT> discloses a cardiac tissue ablation catheter including an inflatable and flexible toroidal or spherically shaped balloon disposed at a distal region of an elongate member.

<CIT> discloses an irrigated balloon catheter, including balloon carrying contact electrodes.

<CIT> discloses a balloon catheter including a shaft, a balloon made of an expandable membrane, a flexible substrate, one or more electrodes, and one or more radiopaque flags.

<CIT> discloses a reverse irrigation device comprising at least one ablation electrode and at least one reverse irrigation port.

<CIT> discloses a medical instrument including a shaft, multiple electrodes, and a vibration generator.

The present invention provides a medical probe as defined in claim <NUM>.

In an embodiment, the irrigation channels are made of a thermally conducting material.

In another embodiment, the thermally conducting material comprises Nitinol.

There is additionally provided a system according to claim <NUM>.

Catheter-based irreversible electroporation (IRE) may be used to apply high-voltage bipolar pulses (e.g., between adjacent electrodes of the catheter) to achieve the high field strengths needed to destroy tissue cells to which the pulses are applied. For example, a medical probe, such as a balloon catheter, could be used to apply the high voltage pulses to tissue using a plurality of electrodes disposed on the balloon. Other types of catheters that carry electrodes, such as a basket catheter or a lasso catheter (made by Biosense-Webster, Irvine, California) may be used as well. However, the high voltages may cause arcing between electrodes applying the pulses, which causes drops in the electric field and may cause excessive heating.

Arcing may be generated when high-voltage pulses cause an electrode surface to heat and generate bubbles in blood in contact with electrodes, for example, by electrolysis. Due to the bubbles, the bipolar impedance increases and more gas may be formed around the electrode due to heating. The high voltage generates current through the high impedance gas, creating ionized plasma, and arcing occurs, usually at edges of the electrodes (e.g., edge locations over the perimeter of electrodes) where the current density is higher and temperature may locally peak.

Exemplary embodiments of the present disclosure that are described hereafter use irrigation to reduce the probability of arcing by locally cooling blood to suppress formation of gas bubbles. Since the arcing tends to occur on electrode edges, the irrigation is preferably concentrated in these regions.

Some exemplary embodiments provide a shaft for insertion into an organ of a patient, with a frame, where the frame can be an expandable frame or a fixed frame, coupled to a distal end of the shaft. The frame includes a plurality of electrodes disposed on an outer surface of the frame which are configured to apply IRE to tissue by applying voltage pulses. One or more irrigation channels are configured to flow irrigation fluid in a vicinity of the electrodes, to cool blood at edges of the electrodes.

In one exemplary embodiment, the irrigation is open (i.e., where the irrigation fluid, typically saline, is expelled from the IRE catheter into the patient) to remove heat from blood by heat convection. In another exemplary embodiment, the irrigation fluid runs in a closed circuit, where a cool fluid is recirculated from the catheter using tubing in thermal contact with the electrodes to remove heat from blood by heat conduction.

These irrigation methods, whether used separately or combined, significantly diminish heating of blood at electrode edges during application of IRE pulses to tissue, and by so doing prevent a buildup of conditions favorable to arcing.

Typically, a heat removal rate of few tens of milliwatts per second over the entire catheter should be sufficient. Due to the high heat capacity of water, heat removal by convection is readily achievable with an open irrigation that mixes cooler saline with blood at typical rates of at least several milliliters per minute. For example, irrigation can readily remove heat from radiofrequency balloon electrodes at a rate of several watts per electrode.

Thermal conduction, on the other hand, must be more carefully engineered, as heat removal rate by thermal conductivity of water is much lower, e.g., by about three orders of magnitude compared with convection. Still, proper design of the closed-circuit irrigation geometry and materials (e.g., avoiding plastic tubing in favor of materials, such as Nitinol, which have good thermal contact between tubing and electrode), as well as a lowered saline temperature to cool the tubes, can readily provide a sufficient rate of heat removal.

The disclosed open-circuit and closed-circuit irrigated IRE catheters enable the application of IRE treatment in a safe and electrically efficient manner, and may thus improve the clinical outcome of invasive IRE treatments, such as of an IRE treatment of cardiac arrhythmia.

<FIG> is a schematic, pictorial illustration of a catheter-based irreversible electroporation (IRE) system <NUM>, in accordance with an exemplary embodiment of the present disclosure. System <NUM> comprises a catheter <NUM>, wherein a shaft <NUM> of the catheter is inserted into a heart <NUM> of a patient <NUM> through a sheath <NUM>. The proximal end of catheter <NUM> is connected to a console <NUM>.

Console <NUM> comprises an IRE generator <NUM> for applying IRE pulses via catheter <NUM> to irreversibly electroporate an ostium tissue of a pulmonary vein in left atrium <NUM> of heart <NUM>. In the exemplary embodiment described herein, catheter <NUM> may be used for any other suitable therapeutic and/or diagnostic purpose, such as electrical sensing and/or irreversibly electroporating another tissue of heart <NUM>.

A physician <NUM> inserts shaft <NUM> through the vascular system of patient <NUM>. As seen in inset <NUM>, an expandable balloon catheter <NUM> that is fitted at a distal end 22a of shaft <NUM> comprises a high-voltage insulation cover membrane <NUM> in a form of a hemisphere and irrigation, further described in <FIG>. Cover membrane <NUM> is described in <CIT>, entitled "Irreversible-Electroporation (IRE) Balloon Catheter with Membrane-Insulated High-Voltage Balloon wires," which is assigned to the assignee of the present patent application, which document is incorporated by reference herein.

During the insertion of shaft <NUM>, balloon <NUM> is maintained in a collapsed configuration inside sheath <NUM>. By containing balloon <NUM> in a collapsed configuration, sheath <NUM> also serves to minimize vascular trauma. Physician <NUM> navigates the distal end of shaft <NUM> to a target location in heart <NUM>.

Once distal end 22a of shaft <NUM> has reached the target location, physician <NUM> retracts sheath <NUM> and expands balloon <NUM> by, for example, pumping saline into an internal volume defined by the aforementioned expendable membrane. Physician <NUM> then manipulates shaft <NUM> such that electrodes <NUM> disposed on balloon catheter <NUM> engage an interior wall of the ostium, and operates console <NUM> to apply high-voltage IRE pulses via electrodes <NUM> to the ostium tissue.

Console <NUM> comprises an irrigation pumping system <NUM> that pumps saline into balloon <NUM> via a pipe running inside shaft <NUM>. Irrigation fluid pours out of irrigation holes <NUM> on the edges of electrodes <NUM> to cool blood by convection to avoid conditions favorable for arcing.

Console <NUM> comprises a processor <NUM>, typically a general-purpose computer, with suitable front end and interface circuits <NUM> for receiving signals from catheter <NUM> and from external-electrodes <NUM>, which are typically placed around the chest of patient <NUM>. For this purpose, processor <NUM> is connected to external-electrodes <NUM> by wires running through a cable <NUM>.

Processor <NUM> is typically programmed in software to carry out the functions described herein. The software may be downloaded to the computer in electronic form, over a network, for example, or it may, alternatively or additionally, be provided and/or stored on non-transitory tangible media, such as magnetic, optical, or electronic memory.

Although the illustrated exemplary embodiment relates specifically to the use of a balloon for IRE of heart tissue, the elements of system <NUM> and the methods described herein may alternatively be applied in controlling ablation using other sorts of multi-electrode ablation devices, such as ablation catheters having an expandable frame, e.g., a basket catheter, and catheters having a fixed frame, e.g., a Lasso® catheter or a PentaRay® catheter.

<FIG> is an exploded perspective view of irreversible electroporation (IRE) balloon catheter <NUM> of <FIG>, in accordance with an exemplary embodiment of the present disclosure.

An expandable membrane <NUM> of balloon catheter <NUM> is attached to distal end 22a of shaft <NUM> at a proximal membrane portion <NUM> of membrane <NUM>. Membrane <NUM> is disposed about a longitudinal axis <NUM> and has an outer surface 44a and an inner surface 44b. Outer surface 44a is exposed to the ambient environment while inner surface 44b is exposed to an internal volume of the balloon defined by membrane <NUM>.

Expandable membrane <NUM> is configured to be expanded from a collapsed shape (generally an elongated tubular configuration) to a balloon (or generally spheroidal) shaped member. A plurality of electrodes <NUM> is disposed on outer surface 44a of the expandable membrane <NUM>. Electrodes <NUM> are arranged equidistantly over a distal hemisphere portion of membrane <NUM>. In the illustrated exemplary embodiment, each of electrodes <NUM> has an insulated electrical wire <NUM>, which is electrically connected to conduct high voltage to the electrode. Electrical wires <NUM> are coupled to the output of IRE generator <NUM> by wiring (not shown) that goes to console <NUM> via hollow shaft <NUM>.

The underside surface of each electrode <NUM> is not exposed to the ambient environment and is typically bonded to outer surface 44a of membrane <NUM>.

An expandable cover membrane <NUM>, having a border <NUM>, encapsulates wires <NUM> between cover membrane <NUM> and expandable membrane <NUM> so that wires <NUM> are constrained between membrane <NUM> and cover membrane <NUM>. In this way, wires <NUM> are resilient to dielectric breakdown due to high voltage electrical signals that they conduct during an IRE procedure.

Each electrode <NUM> has a tube <NUM> that feeds a circulation tube <NUM> encircling the electrode. In some exemplary embodiments, circulation tubes <NUM> are fitted with irrigation holes, as described in <FIG>, to cool electrode edges by convection. In other exemplary embodiments, circulation tubes <NUM> are made of a heat-conductive material, such as Nitinol, and each circulation tube <NUM> is thermally coupled to a respective electrode to cool the edges of the electrode by heat conduction.

<FIG> is a side view of the assembled irreversible electroporation (IRE) balloon catheter <NUM> of <FIG>, in accordance with an exemplary embodiment of the present disclosure. As seen, each of the plurality of electrodes <NUM> defines an area not covered by expandable cover membrane <NUM> to allow the electrodes to be exposed to the ambient environment.

The plurality of electrodes <NUM> is disposed equiangularly about longitudinal axis <NUM>, such that cover membrane <NUM> encapsulates a proximal edge of each electrode <NUM>. Typically, each electrode <NUM> is coupled to the outer surface of expandable membrane <NUM> via a substrate <NUM> which itself is connected, or bonded, to the outer surface of membrane <NUM>.

As can be seen in <FIG>, each tube <NUM> runs within the internal volume of balloon <NUM> (under membrane <NUM>) and extends from distal end 22a to a respective circulation tube <NUM> of electrode <NUM> such that each tube <NUM> substantially follows the topography of membrane <NUM>. In this way there is little or no risk of the tubes being entangled during the expansion and collapse of balloon <NUM>.

In the illustrated exemplary embodiment, further detailed in cross-sectional inset <NUM>, the irrigated fluid of each circulation tube <NUM> flows via irrigation holes <NUM> to the outside of balloon <NUM>, i.e., into the ambient environment, to cool the blood at the edge of electrode <NUM>.

The exterior wall of membrane <NUM> and tubes (<NUM>, <NUM>) are made of bio-compatible materials, for example, formed from a plastic (e.g., polymer) such as polyethylene terephthalate (PET), polyurethane, or PEBAX®.

Any of the examples or embodiments described herein may include various other features in addition to or in lieu of those described above. In particular, the simplified configurations shown in <FIG> and <FIG> are chosen purely for the sake of conceptual clarity and simplicity of presentation. For example, electrodes <NUM> may be disposed with temperature sensors.

Although the embodiments described herein mainly address cardiac applications, the methods and systems described herein can also be used in other medical applications, such as in neurology and otolaryngology.

Claim 1:
A medical probe for irreversible electroporation with irrigation, the medical probe comprising:
a shaft (<NUM>) for insertion into an organ of a patient; and
a frame coupled to a distal end of the shaft, the frame comprising:
a plurality of electrodes (<NUM>) disposed on an outer surface of the frame and configured to apply irreversible electroporation (IRE) to tissue by applying voltage pulses; and
one or more irrigation channels (<NUM>), configured to flow irrigation fluid in a vicinity of the electrodes, wherein the irrigation channels (<NUM>) are thermally coupled to the electrodes (<NUM>), and are configured to flow the irrigation fluid in a closed circuit to remove heat from edges of the electrodes.