Patent Publication Number: US-2021169567-A1

Title: Irreversible-electroporation (ire) balloon catheter with membrane-insulated high-voltage balloon wires

Description:
FIELD OF THE INVENTION 
     The present invention relates generally to the invasive medical probes, and particularly to balloon catheters for irreversible electroporation. 
     BACKGROUND OF THE INVENTION 
     Delivery of irreversible electroporation (IRE) energy to tissue was previously proposed in the patent literature. For example, U.S. Patent Application Publication 2019/0030328 describes a medical device configured to electroporate an area of tissue, the medical device including a balloon having a distal portion and a proximal portion, and a plurality of electrodes disposed on the distal portion of the balloon, each of the plurality of electrodes being configured to deliver electroporation energy to the area of tissue. 
     As another example, U.S. Pat. No. 10,285,755 describes a catheter having a distal expandable element coupled to the catheter body with a mesh or array of longitudinal splines substantially surrounding the expandable element, where at least a portion of the mesh or splines being electrically conductive. In an embodiment, an electrically insulated portion is disposed between two conductive portions of the mesh. The conductive portions may be operated in a bipolar manner to conduct current around the insulated portion and through tissue along pathways substantially parallel to a longitudinal axis of the expandable element between adjacent or otherwise spaced conductive portion of the mesh. 
     PCT International Publication WO 2019/055512 describes systems, devices, and methods for electroporation ablation therapy, including an endocardial ablation device that includes an inflatable member, such as a balloon, and at least one electrode for focal ablation by pulse delivery to tissue. In an embodiment, the ablation device includes a set of electrodes disposed on the balloon. The electrodes may be formed on a surface of a distal end of the balloon and be useful for forming lesions on endocardial surfaces via focal ablation. During use, the electrodes may be disposed in a chamber of the heart in order to deliver a pulse waveform to ablate tissue. The electrodes may each couple to a respective insulated electrical lead, with each lead having sufficient electrical insulation to sustain an electrical potential difference across its thickness without dielectric breakdown. 
     SUMMARY OF THE INVENTION 
     An exemplary embodiment of the present invention provides a medical probe including a shaft and an expandable balloon. The shaft is configured for insertion into an organ of a patient. The expandable balloon is coupled to a distal end of the shaft, with the expandable balloon including: (a) an expandable membrane having an outer surface and an inner surface, wherein the expandable membrane is configured to be expanded from a collapsed shape to a balloon shaped member, (b) a plurality of electrodes disposed on the outer surface of the expandable membrane, (c) one or more wires connected to the plurality of electrodes, the wires extending from the distal end to the electrode, (d) and an expandable cover that encapsulates the wires between the expandable cover and the expandable membrane so that the wires are constrained between the cover and the expandable membrane but the electrodes are exposed to ambient environment. 
     In some exemplary embodiments, the medical probe further includes a seal that runs over a distal edge of the cover membrane and is configured to seal the cover to the expandable membrane. In other exemplary embodiments, the seal covers a proximal edge of each of the electrodes. 
     In an exemplary embodiment, the electrodes are disposed equiangularly about a longitudinal axis of the expandable membrane. In another exemplary embodiment, each of the electrodes is coupled to the outer surface of the expandable membrane via a substrate. 
     In some exemplary embodiments, at least one of the electrodes includes a radiopaque marker having a configuration different from other radiopaque markers on the other electrodes. 
     In some exemplary embodiments, the plurality of electrodes is disposed over a distal hemisphere portion of the expendable membrane. 
     There is also provided, in accordance with an exemplary embodiment of the present invention, a method of manufacturing a medical probe, the method including assembling an expandable balloon by assembling an expandable membrane having an outer surface and an inner surface, wherein the expandable membrane is configured to be expanded from a collapsed shape to a balloon shaped member. A plurality of electrodes is disposed on the outer surface of the expandable membrane. Wires are connected to the plurality of electrodes, and using an expandable cover, the wires between the cover and the expandable membrane are encapsulated so that the wires are constrained between the cover and the expandable membrane but the electrodes are exposed to ambient environment. The expandable balloon is coupled to a distal end of a shaft. 
     In some exemplary embodiments, the method further includes sealing the cover against the expendable membrane using a seal running over a distal edge of the cover. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The present invention will be more fully understood from the following detailed description of the embodiments thereof, taken together with the drawings in which: 
         FIG. 1  is a schematic, pictorial illustration of a catheter-based irreversible electroporation (IRE) system, in accordance with an exemplary embodiment of the present invention; 
         FIG. 2  is an exploded perspective view of the irreversible electroporation (IRE) balloon catheter of  FIG. 1 , in accordance with an exemplary embodiment of the present invention; and 
         FIG. 3  is a side view of the assembled irreversible electroporation (IRE) balloon catheter of  FIG. 2 , in accordance with an exemplary embodiment of the present invention. 
     
    
    
     DETAILED DESCRIPTION OF EMBODIMENTS 
     Overview Irreversible electroporation (IRE), which is used as an invasive therapeutic modality, kills tissue cells by subjecting tissue to high-voltage pulses. A medical probe, such as a balloon catheter, may be used to apply high voltage pulses to tissue using a plurality of electrodes disposed on the balloon. For a wire used to conduct high voltage electrical signals to an electrode on the balloon, it would be detrimental to expose the wire to the ambient biological tissue environment (e.g., biological tissues or blood), as well as to the interior of the balloon. Therefore, the wiring to the balloon electrodes has to be sufficiently electrically insulated to prevent dielectric breakdown. 
     Exemplary embodiments of the present invention provide an IRE balloon catheter comprising insulated electrical wires. However, while the wires have their own insulation, this insulation may not be sufficient in an environment with high moisture content. Thus, the wires are disposed on an outer surface of an expandable membrane of the balloon catheter, so the wires are well separated from, for example, electrically conducting saline solution that is typically used for inflating the expandable membrane. 
     To achieve sufficient electrical insulation from the ambient environment, such as blood that is also electrically conducting, the wires are disposed between the expandable membrane and an encapsulating cover membrane, with the two membranes attached to each other in such a way that the wires are captured between the two membranes and only the electrodes connected to the wires are exposed to the ambient environment. 
     The disclosed IRE balloon catheter is coupled to a distal end of a hollow shaft for insertion into an organ of a patient. The expandable membrane is disposed about a longitudinal axis of the distal end of the shaft and is coupled at its distal end to an elongation rod. When pulled proximally into the hollow shaft, the elongation rod causes the expandable membrane to expand from an elongated, collapsed shape, to a balloon shaped member. 
     Each of the plurality of electrodes is connected to an output of an IRE pulse generator via one or more of the aforementioned wires disposed between the two membranes, where these highly insulated wires are coupled at a proximal end of the balloon catheter to supply wires that run inside the hollow shaft. 
     In some exemplary embodiments the cover membrane is sealed against the expendable membrane using a seal running over a distal edge of the cover membrane. Additionally or alternatively, the cover membrane is adhered to the outer surface of the expendable membrane, by, for example, gluing the cover membrane over its entire area to the outer surface of the expendable membrane. 
     The IRE balloon catheter is also configured to have the following features, which can be combined into various combinations or permutations, for example, each of the plurality of electrodes defining a shape optimized for IRE; each electrode disposed on the outer surface of the expandable membrane via a substrate; each electrode including a radiopaque marker having a configuration different from other radiopaque markers on the other electrodes; the expandable membrane including a generally spheroidal member and the expandable cover membrane including a hemi-spherical member. 
     The disclosed IRE balloon catheter enables application of IRE treatments in an electrically safe manner, and may thus improve the clinical outcome of invasive IRE treatments, such as of an IRE treatment of cardiac arrhythmia. 
     System Description 
       FIG. 1  is a schematic, pictorial illustration of a catheter-based irreversible electroporation (IRE) system  20 , in accordance with an exemplary embodiment of the present invention. System  20  comprises a catheter  21 , wherein a shaft  22  of the catheter is inserted into a heart  26  of a patient  28  through a sheath  23 . The proximal end of catheter  21  is connected to a console  24 . 
     Console  24  comprises an IRE generator  38  for applying IRE pulses via catheter  21  to irreversibly electroporate ostium tissue of a pulmonary vein in a left atrium  45  of the heart  26 . In the exemplary embodiment described herein, catheter  21  may be used for any other suitable therapeutic and/or diagnostic purposes, such as electrical sensing and/or irreversibly electroporating other tissue of the heart  26 . 
     A physician  30  inserts shaft  22  through the vascular system of patient  28 . As seen in inset  25 , an expandable balloon catheter  40  that is fitted at a distal end  22   a  of shaft  22  comprises a high-voltage insulation cover membrane  50  in a form of a hemisphere, further described in  FIG. 2 . During the insertion of shaft  22 , balloon  40  is maintained in a collapsed configuration inside sheath  23 . By containing balloon  40  in a collapsed configuration, sheath  23  also serves to minimize vascular trauma along the way to target location. Physician  30  navigates the distal end of shaft  22  to a target location in heart  26 . 
     Once distal end  22   a  of shaft  22  has reached the target location, physician  30  retracts sheath  23 , and expands balloon  40 , among other means by pumping saline into an internal volume defined by the aforementioned expandable membrane. Physician  30  then manipulates shaft  22  to have electrodes  55  disposed on balloon catheter  40  engage an interior wall of the ostium, and operates console  24  to apply high-voltage IRE pulses via electrodes  55  to the ostium tissue. 
     Console  24  comprises a processor  41 , typically a general-purpose computer, with suitable front end and interface circuits  37  for receiving signals from catheter  21  and from external-electrodes  49 , which are typically placed around the chest of patient  26 . For this purpose, processor  41  is connected to external-electrodes  49  by wires running through a cable  39 . 
     Processor  41  is typically programmed (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  20  and the methods described herein may alternatively be applied in controlling ablation using other sorts of multi-electrode ablation devices, such as multi-arm ablation catheters. 
     IRE Balloon Catheter with Membrane-Insulated High Voltage Balloon Wires 
       FIG. 2  is an exploded perspective view of irreversible electroporation (IRE) balloon catheter  40  of  FIG. 1 , in accordance with an exemplary embodiment of the present invention. 
     An expandable membrane  44  of balloon catheter  40  is attached to distal end  22   a  of shaft  22  at a proximal membrane portion  46  of membrane  44 . Membrane  44  is disposed about a longitudinal axis  42  and has an outer surface  44   a  and an inner surface  44   b . Outer surface  44   a  is exposed to the ambient environment while inner surface  44   b  is exposed to an internal volume of the balloon defined by membrane  44 . 
     Expandable membrane  44  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  55  are disposed on outer surface  44   a  of the expandable membrane  44 . Electrodes  55  are arranged equidistantly over a distal hemisphere portion of membrane  44 . In the illustrated exemplary embodiment, each of electrodes  55  is connected to an insulated electrical wire  60 , which is electrically connected to conduct high voltage to the electrode. Each wire  60  comprises an electrically conductive core surrounded by an electrically insulating sleeve. Electrical wires  60  are coupled to the output of IRE generator  24  by wiring (not shown) that run via hollow shaft  22  to console  24 . 
     The underside surface of each electrode  55  is the electrode surface that is not exposed to the ambient environment and is typically bonded to outer surface  44   a  of membrane  44 . 
     An expandable cover membrane  50 , having a border  52 , encapsulates wires  60  between cover membrane  50  and expandable membrane  44  so that wires  60  are constrained between membrane  44  and cover membrane  50 . Expandable cover membrane  50  is also referred to herein simply as “cover, “cover membrane” or “expandable cover,” for brevity and for avoiding confusion with membrane  44 . In this way, wires  60  are resilient to dielectric breakdown due to high voltage electrical signals that they conduct during an IRE procedure. In other words, the total electrical insulation between the cores of wires  60  and the ambient environment comprises both the insulation of the insulating sleeves of wires  60 , and the insulation of cover membrane  50 . In an exemplary embodiment, cover membrane  50  is secured to the expandable balloon with an adhesive (not shown). 
       FIG. 3  is a side view of the assembled irreversible electroporation (IRE) balloon catheter  40  of  FIG. 2 , in accordance with an exemplary embodiment of the present invention. As seen, each of the plurality of electrodes  55  defines an area not covered by expandable cover membrane  50  to allow the electrodes to be exposed to the ambient environment. 
     The plurality of electrodes  55  is disposed equiangularly about longitudinal axis  42  such that cover membrane  50  encapsulates a proximal edge of each electrode  55 . A seal  54  runs over border  52  (i.e., over the proximal edge of electrodes  55 ) of cover membrane  50  and may extend by up to few millimeters over a proximal portion of the outer surface of electrodes  55  while allowing the electrodes to be exposed to the ambient environment. In an embodiment, seal  54  can be provided in a form of a polyurethane or epoxy seal. 
     Typically, each electrode  55  is coupled to the outer surface of expandable membrane  44  via a substrate  53  which itself is connected, or bonded, to the outer surface of membrane  44 . 
     As can be seen in  FIG. 3 , each wire  60  on membrane  44  extends from distal end  22   a  to a respective electrode  55  such that each wire follows the topographic outer surface of membrane  44 . 
     As each wire  60  may be used to conduct high voltage electrical signals, it would be detrimental to expose wires to the ambient biological tissue environment (e.g., biological tissues or blood). While each wire  60  has its own insulating sleeve, this insulation may not be sufficient in a high humidity environment, especially in view of the high voltages involved. As such, expandable cover membrane  50  eliminates potential electrical breakdown between a wire and the ambient environment. The electrodes remain exposed to biological tissue so that the electrodes can perform their intended purposes. Moreover, as wires  60  are constrained or captured between the two membranes, there is virtually no likelihood of the wires being entangled or mis-connected to the wrong electrode during assembly. 
     The exterior wall of membranes  44  and  50  is typically made of a bio-compatible material, for example, formed from a plastic (e.g., polymer) such as polyethylene terephthalate (PET), polyurethane or PEBAX®. These plastics provide sufficient electrical insulation against dielectric breakdown under the strong electric fields occurring with IRE pulses. 
     Any of the examples or exemplary embodiments described herein may include various other features in addition to or in lieu of those described above. In particular, the exemplary configurations shown in  FIGS. 2 and 3  are chosen purely for the sake of conceptual clarity. For example, cover membrane  50  may be glued over its internal surface to the outer surface of the expendable membrane  44 . 
     Although the exemplary embodiments described herein mainly address IRE procedures, the disclosed techniques can be used for other suitable applications, such as for electrophysiological (EP) sensing. Examples of EP catheters are described, for example, in U.S. Provisional Patent Application 62/769,424, filed Nov. 19, 2018, which is assigned to the assignee of the present patent application and whose disclosure is incorporated herein by reference. 
     Although the exemplary 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, otolaryngology, and general surgical procedures. 
     It will thus be appreciated that the embodiments described above are cited by way of example, and that the present invention is not limited to what has been particularly shown and described hereinabove. Rather, the scope of the present invention includes both combinations and sub-combinations of the various features described hereinabove, as well as variations and modifications thereof which would occur to persons skilled in the art upon reading the foregoing description and which are not disclosed in the prior art. Documents incorporated by reference in the present patent application are to be considered an integral part of the application except that to the extent any terms are defined in these incorporated documents in a manner that conflicts with the definitions made explicitly or implicitly in the present specification, only the definitions in the present specification should be considered.