Patent Application
20230329541
The current disclosure relates to systems, devices, and methods for medical treatment, particular by the ablation of tissue such as with radiofrequency (RF) energy.
RF ablation within body organs has been extensively described previously and is well known in the art. Where elongated or extensive lesions with large surface areas are desired, the two main technologies utilizing RF energy are monopolar ablation and bipolar ablation.
In monopolar ablation, a treating electrode is placed where a lesion is created, and the current flows through the tissues to a dispersive electrode. The dispersive electrode has a large surface area compared to the treating electrode, so that current density over this dispersive electrode is low enough to prevent any lesion from forming. This dispersive, or “patient”, or “ground” electrode is usually placed on the patient's skin in a location such as the thighs or flanks.
Examples of internal organ ablation applications employing monopolar ablation include pulmonary vein isolation for atrial fibrillation and ablation of tumors in soft tissue such as in the liver.
Problems with this technology include situations in which contact between the dispersive electrode and the skin is suboptimal, in which case, current density increases and a skin lesion might form, in some cases associated with serious burns and injury. Worse yet, complete disconnection of the ground electrode might cause current to flow through a different route, which might endanger vital organs. Another disadvantage of monopolar ablation is the tendency of lesions to be more pronounced at the edge of the electrode (“edge effect”). This effect can be minimized by using relatively short electrodes, however this necessitates more wires.
In bipolar ablation, both electrodes are considered “treating” electrodes and are usually approximately identical in dimensions and electrical properties and placed very close to each other, usually less than 1 cm apart. The current flows between the two electrodes through the tissues; and, as the electrodes are identical and proximate, the tissues between them are more or less homogenously ablated. In this configuration, in order to achieve a linear lesion, two adjacent electrodes are needed, with two separate wires (“railway” like configuration).
Examples of internal organ ablation applications employing bipolar ablation include esophageal ablation with the Barrx device available from Medtronic PLC of Dublin, Ireland.
An advantage of this technology is the ability to control lesion depth with high accuracy. Problems with this technology are mainly associated with the limited area that can be treated by such electrodes, so that if a large ablation area is desired, a large number of electrodes must be used, resulting with many wires leading to them, which increased the diameter of elements in the device.
There remains a need for a technology that enables ablation within hollow organs in a manner that allows safe, easy, and quick creation of homogenous lesions having large areas, preferably elongated but optionally having a large surface area such as circular or oblong shaped, while using a simple device having few electrical wires running through it, and a low profile of insertion.
To solve the need outlined above, the current disclosure describes a technique herein called “Far-Field-Bipolar” ablation, as well as specific device embodiments which may employ this technique.
The far field bipolar technique may utilize bipolar electrodes having substantially equal surface areas, positioned at a relatively large distance from each other within the target organ, such that they may produce lesions similar to those produced with monopolar electrodes.
The device embodiments described in this disclosure may comprise an expandable element which may appose the electrodes to the target organ wall, and typically may be capable of stretching the electrodes to facilitate their collapse and removal from the patient's body.
An aspect of the present disclosure provides devices for treating a disorder in a hollow body organ. An exemplary device may comprise a shaft having a distal tip, at least one set of bipolar electrodes, and an expandable member configured to radially expand the at least one set of bipolar electrodes from a folded or compressed position to a deployed position. Each set of bipolar electrodes may comprise at least one first polarity electrode and at least one second polarity electrode. In the deployed position, each first polarity electrode may be configured to be positioned in a location within the hollow body organ substantially opposite each second polarity electrode. In the deployed position, the distance between each electrode pair may be at least 10 times the width of each of the electrodes.
A total tissue contact area of the at least one first polarity electrode of each set of bipolar electrodes may be substantially equal to a total surface area of the at least one second polarity electrode of the same set of bipolar electrodes.
The device may be configured for creating a predetermined pattern of electrically isolated tissue regions having reduced electrical propagation in an inner wall of the hollow body organ such that electrical propagation through the hollow body organ as a whole is reduced. Each electrode may comprise an elongate conductor.
The at least one set of bipolar electrodes may comprise four sets of bipolar electrodes. Two sets of bipolar electrodes may be longitudinal electrode sets which are configured to be substantially parallel to the longitudinal axis of the shaft in the deployed position. Two sets of bipolar electrodes may be two circumferential electrode sets which are configured to be substantially transverse to the longitudinal axis of the shaft in the deployed position. The predetermined pattern of electrically isolated tissue regions having reduced electrical propagation may comprise eight longitudinal splines and a circumferential line. Each set of longitudinal electrodes may comprise four distal electrode segments arranged in a “cross” pattern around the distal tip of the shaft, and four proximal electrode segments may be arranged to be positioned equidistantly between the four distal electrode segments and at a more proximal position. Each set of circumferential electrodes may comprise a first pair of circumferential electrode segments arranged opposite each other in a circumferential line around the expandable element in the deployed position, and a second pair of circumferential electrode segments may be arranged opposite each other in the gaps between the first pair of circumferential electrodes. Each set of longitudinal electrodes may comprise four distal electrode segments arranged in a “flattened x” pattern around the distal tip of the shaft, and four proximal electrode segments arranged such that two of the four proximal electrode segments may be positioned between the four distal electrode segments and at a more proximal position, and each set of circumferential electrodes may comprise a first pair of circumferential electrode segments arranged adjacent each other in a circumferential line around the expandable element in the deployed position and a second pair of circumferential electrode segments may be arranged adjacent each other opposite said first pair of circumferential electrode segments in a circumferential line around the expandable element in the deployed position.
The electrodes may comprise a flexible printed circuit material. The longitudinal electrodes may comprise a flexible printed circuit material, and the circumferential electrodes may comprise a wire or braid. All first polarity electrode segments of each set and all second polarity electrode segments of each set may be connected to each other but not to any other electrode segments via a printed circuit board located at the distal tip of the shaft. The tissue contact area of each electrode set is between 1 mm2 and 50 mm2.
The device may further comprise one or more wires configured to deliver power to a PCB pass via the shaft.
The device may further comprise an atraumatic cap at the distal tip of the shaft.
The expandable member may comprise a balloon or bladder.
The distance between the electrode pairs may be at least 10 mm.
The at least one set of bipolar electrodes may be printed on the expandable member.
The expandable member may be made of a non-compliant material or a compliant material.
The electrodes create a pattern that is asymmetrical. The pattern may be configured to spare an area of the hollow organ. The at least one first polarity electrode may comprise at least one positive electrode. The at least one second polarity electrode may comprise at least one negative electrode.
The hollow organ may be any of a urinary bladder, uterus, rectum, large or small bowel, stomach, pulmonary artery, cardiac atrium, cardiac ventricle, and the disorder is any of overactive bladder, Detrusor-sphincter dyssynergia, irritable uterus, menorrhagia, irritable bowel, obesity, asthma, atrial fibrillation, ventricular tachycardia.
The at least one set of bipolar electrodes may comprise a conductive flexible or gelatinous material layer on surfaces thereof.
The expandable member may comprise a plurality of parts welded together in a manner such that the expandable member has no outward protruding seam. The plurality of parts may be comprise flanges that are welded together using one or more of forceps, rollers, or clamps.
The at least one set of bipolar electrodes may be configured to protrude from the expandable member when the expandable member is expanded.
The at least one first polarity electrode and the at least one second polarity electrodes may have different surface areas to localize treatment to one of the at least one first polarity or at least one second polarity electrode.
Another aspect of the present disclosure provides devices for treating a disorder in a hollow body organ. An exemplary device may comprise: a handle having a distal end, a proximal end, and a slot; an inner shaft having a distal tip, a proximal end, a stopper and at least one opening; an outer shaft slideably positioned over the inner shaft and having a distal tip, a proximal end, a seal, and an outer shaft base; an outer sheath slideably positioned over the outer shaft and having a distal end, a proximal end, and a valve; at least one set of electrodes each having a distal end and a proximal end and comprising at least one electrode segment; and a balloon having a distal leg and a proximal leg. The proximal end of the inner shaft may be connected to the handle. The outer shaft base may further comprise a retraction knob which slideably protrudes through the slot of the handle. An inflation tube and wires may enter the handle and may be sealed to the inner shaft. The distal leg of the balloon may be connected to the inner shaft proximate the distal tip of the inner shaft and the proximal leg of the balloon may be connected to the outer shaft proximal the distal tip of the outer shaft. The wires may pass through the inner shaft and out of the distal tip of the shaft and connect to the at least one set of electrodes. The proximal end of the at least one electrodes may be connected as a ring slideably positioned over the outer shaft proximal to the proximal leg of the balloon.
The device may have a folded or compressed position and a deployed position and further comprises an atraumatic cap connected to the inner shaft distal tip. The atraumatic cap may be configured to either partially or completely cover the outer sheath distal end when in the folded or compressed position. The outer sheath may be configured to expose the electrodes when pulled proximally. The balloon may be configured to radially expand the electrodes when inflated. The electrodes may be configured to deliver energy to the hollow organ. The outer shaft may be configured to stretch the balloon and collapse the electrodes when pulled proximally by the retraction knob.
The at least one set of electrodes may comprise longitudinal and circumferential electrodes. The longitudinal electrodes may comprise a flexible printed circuit material. The circumferential electrodes may comprise a flexible printed circuit material. The circumferential electrodes may be foldable. The circumferential electrodes may have at least one joint. The at least one joint may comprises a hinge. The joint may comprise an area of the circumferential electrodes with longitudinal zig-zag cuts. A wire may be used to unfold the circumferential electrodes. A conductor of the circumferential electrodes may be on the back side of a printed circuit board (PCB).
The electrodes may create a pattern that is asymmetrical. The pattern may be configured to spare an area of the hollow organ.
The stopper may be positioned distally on the inner shaft such that when the handle is pushed distally, the balloon is configured to further expand radially and expand the electrodes further radially. The balloon may be made of a compliant material or a non-compliant material.
The hollow organ may be any of a urinary bladder, uterus, rectum, large or small bowel, stomach, pulmonary artery, cardiac atrium, cardiac ventricle, and the disorder is any of overactive bladder, Detrusor-sphincter dyssynergia, irritable uterus, menorrhagia, irritable bowel, obesity, asthma, atrial fibrillation, ventricular tachycardia.
The at least one set of bipolar electrodes may comprise a conductive flexible or gelatinous material layer on surfaces thereof. The at least one set of bipolar electrodes may be configured to protrude from the expandable member when expanded.
Another aspect of the present disclosure provides methods for treating a disorder in a hollow body organ. An expandable member may be positioned in the hollow body organ. The expandable member may be expanded in the hollow body organ to expand at least one set of bipolar electrodes from a folded or compressed position to a deployed position in the hollow body organ. The at least one set of bipolar electrodes may comprise at least one first polarity electrode and at least one second polarity electrode. Each first polarity electrode may be positioned in a location within the hollow body organ substantially opposite each second polarity electrode when the at least one set of bipolar electrodes is the deployed position in the hollow body organ. In the deployed position, the distance between each first polarity electrode and the second polarity electrode opposite of said first polarity electrode may be at least 10 times the width of each of the first polarity and second polarity electrodes.
With the at least one set of bipolar electrodes, a predetermined pattern of electrically isolated tissue regions having reduced electrical propagation may be created in an inner wall of the hollow body organ such that electrical propagation through the hollow body organ as a whole is reduced. The predetermined pattern may comprise at least one longitudinal splice and at least one circumferential line. The predetermined pattern may comprise a “cross” pattern or a “flattened x” pattern. The tissue contact area of each electrode set is between 1 mm2 and 50 mm2. The distance between the at least one first polarity electrode and the at least one second polarity electrode may be at least 10 mm.
The hollow organ may be any of a urinary bladder, uterus, rectum, large or small bowel, stomach, pulmonary artery, cardiac atrium, cardiac ventricle, and the disorder is any of overactive bladder, Detrusor-sphincter dyssynergia, irritable uterus, menorrhagia, irritable bowel, obesity, asthma, atrial fibrillation, ventricular tachycardia.
The expandable member may comprise a balloon, and the expandable member may be expanded by inflating the balloon.
The at least one set of bipolar electrodes may be energized via at least one longitudinal connector connected to and delivering power to the at least one set of bipolar electrodes.
An atraumatic sheath tip may cover a distal end of the expandable member.
Fluid around the expandable member may be removed after the expandable member is expanded in the hollow body organ.
The expandable member in the hollow body organ may be expanded so that the at least one set of bipolar electrodes conform to an inner surface of the hollow body organ. The at least one set of bipolar electrodes may comprise a conductive flexible or gelatinous material layer on surfaces thereof.
The expandable member may comprise a plurality of parts welded together in a manner such that the expandable member has no outward protruding seam. The plurality of parts may comprise flanges that are welded together using one or more of forceps, rollers, or clamps.
Expanding the expandable member in the hollow body organ may cause the at least one set of bipolar electrodes to protrude from the expandable member.
The at least one first polarity electrode and the at least one second polarity electrodes may have different surface areas to localize treatment to one of the at least one first polarity or at least one second polarity electrode. The at least one first polarity electrode may comprise at least one positive electrode. The at least one first polarity electrode may comprise at least one negative electrode.
Another aspect of the present disclosure provides devices treating a disorder in a hollow body organ. An exemplary device may comprise a shaft having a distal tip, an expandable member disposed on the shaft configured to radially expand within the hollow body organ, and a light source within the expandable member. At least the portion of the expandable member may be translucent or transparent to allow light generated from the light source to project from the expandable member to one or more of illuminate or ablate an inner surface of the hollow body organ.
Another aspect of the present disclosure may provide methods for treating a disorder in a hollow body organ. An expandable member may be positioned in the hollow body organ. The expandable member may be expanded in the hollow body organ. Light may be projected from within the expandable member through at least a portion of the expandable member that is translucent to one or more of illuminate or ablate an inner surface of the hollow body organ.
Various improvements and modifications to the above, intended for improving and monitoring surface contact of the electrodes, automation of procedure stages, as well as various other embodiments, are also described.
All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.
An understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:
Far Field Bipolar Technique.
To solve the need outlined above, the current disclosure describes a technique herein called “Far-Field-Bipolar” ablation.
This technique is based on use of bipolar electrodes or electrode sets having substantially equal, and relatively large surface areas, that may be positioned at a large distance from each other, relative to the size of the electrodes, and in an almost opposing location within the treated organ. Thus, current flowing from one set of electrodes to the other, may create identical lesions over both electrode sets, similar to monopolar lesions, while sparing the tissue between the electrodes.
To produce the desired effect, the distance between the electrodes should preferably be at least 10 times the relevant dimension of the electrodes, which in the case of elongate electrodes, may typically be the width of the electrode (or its diameter in case of a wire electrode). In the applications described herein, the distance may typically be 1-10 cm.
Since several electrodes can be connected together to form a set of electrodes, as long as the total surface area of each set of electrodes is no larger than approximately 20 mm2. This can allow for a relatively small number of wires to be used, while eliminating the need for a dispersive “patient” electrode, as well as the risks and hassle associated with use of such electrodes. An additional important aspect of this technology may be that total ablation time can be significantly reduced (more lesions are created at the same time). The short ablation time can be significant in increasing the appeal of the treatment (to both doctors and patients) and in reducing the pain or discomfort that might be associated with such treatment under local or regional anesthesia.
While this technology may be compatible with use in any body organ, it will be described herein in the context of the urinary bladder, where it may be used for performing Transurethral Bladder Partitioning (“TBP”) for treatment of overactive bladder or other micturition disorders, for performing bladder auto-augmentation by ablating certain layers of the bladder wall, or for any other therapy necessitating extensive or homogenous ablative treatment within the bladder.
TBP is a treatment wherein a transurethral device is used for creating a predetermined pattern of isolated tissue regions in the urinary bladder, such that electrical propagation through the organ as a whole is reduced, thereby treating any number of urinary disorders.
Specific Electrode Energy Coupling Combinations.
The far field bipolar technique described above, as well as any of the devices and methods in the current disclosure, may be used for creation of various ablation patterns in different body organs.
In the current bladder application, a target ablation pattern may be shaped as eight longitudinal splines and a circumferential equatorial line on the upper hemisphere of the bladder as shown in
More particularly,
Within bladder 1 is seen a schematic side view of an ablation pattern 10, in this embodiment comprising an equatorial circumferential line 11, and eight longitudinal splines 12 spanning from apex 9 to circumferential line 11, dividing it into 8 equal segments. One such segment is labeled C.
Within bladder 1 is seen a schematic bottom view of ablation pattern 10, comprising circumferential line 11, and eight longitudinal splines 12 spanning from apex 9 to circumferential line 11, dividing it into 8 equal segments. One such segment is labeled C.
This pattern may be configured to limit the free conductance (or communication) of electrical, neural, or other activity between adjacent bladder zones. In particular, this lesion pattern can limit the conduction or communication of excitatory signals traveling in directions other than along the long axis of the bladder. This configuration can be desirable since it may allow the normal conductance associated with micturition (preliminary along the long axis) to occur, while limiting the pathological, disorganized conductance associated with overactive bladder syndromes. For example, a signal originating at a certain point along the bladder wall (above the mid bladder line) may need to traverse 8 lines (all the longitudinal splines) to make a full circle around the bladder perimeter, while crossing only two lines (crossing the circumferential line twice) to make a full circle along the long axis of the bladder.
The ablation patterns described herein are shown on the surface of the bladder; however, their depth can be another important aspect. The depth of ablation may typically include any or all of the layers of the bladder, namely the mucosa and submucosa 6, detrusor 7, and adventitia or serosa 8.
Mucosa 6 typically further comprises an inner-most layer of the mucosa called the urothelium, and the lamina propria., and detrusor 7 typically further comprises an inner longitudinal muscle layer, a middle circumferential muscle layer, and an outer longitudinal muscle layer. Ablation may target any one of the above layers, part of a layer, or a combination of layers.
More particularly,
In many embodiments, expandable element 30 may be an elastic compliant balloon, or a noncompliant balloon, either referred to herein as a “balloon”. Other spherical expandable elements including cages or similar structures are within the scope of this disclosure.
Of note, a compliant balloon, made for example of silicone, latex, or low durometer polyurethane, may have the advantage of being more easily folded or compressed into a small diameter, as it may be stretched, which reduces its wall thickness.
In contrast, although more difficult to fit into a small diameter sheath, a non-compliant or semi-compliant balloon, for example made of PET, PEBAX, cross linked polyurethane, Nylon, Mylar, polyester, polyurethane, and other polymers in a crosslinked or non-crosslinked form etc., may be advantageous as it may create better wall apposition between the electrodes and organ wall. When inflated to a high pressure, a non-compliant balloon may become rigid, thus preventing bulging of the balloon between the electrodes, or “sinking” of the electrodes into the balloon. Instead, a non-compliant balloon inflated to a rigid state may force the electrodes to slightly bulge out into the target tissue.
In structure 40, all electrode segments 41, 42, and 43 may have substantially the same length, which may be approximately ⅛th of the sphere's circumference. In a human bladder inflated to ˜170 cc, this would typically correspond to a length of ˜27 mm. In some embodiments, the circumferential electrode segments may be longer than the longitudinal electrode segments, allowing the balloon to inflate more than the above mentioned volume. When inflated to a higher volume, the circumferential electrodes may move up the balloon, to encircle the balloon at a higher latitude (above the equator line).
Shown in
In
Various combinations of electrode energy coupling and electrode activation sequences can be used with this structure.
Two such electrode activation sequences employing far field bipolar ablation are shown in
Each of
More particularly,
Each of
It is important to note that although in the embodiment described herein pattern 10 is created using 24 electrode segments powered in four separate phases, far-field bipolar may be used to create basically any pattern, using any number of electrode segments and powering phases. As an example, for creating the current ablation pattern 10, using a greater number of segments (for example 48 instead of 24), powered in a larger number of phases (for example 8 instead of 4) is possible. This may be provide the advantage of increasing control and consistency of the lesions created by each individual segment, but this may come in the price of increased complexity of the device, generator, manufacturing, and overall cost.
The far field bipolar technology described above, may be implemented using various methods and devices. Some such embodiments are described in
Flexcircuit Design.
From distal to proximal,
More particularly, inner shaft 66 may be fixed to handle 90 via base 102, and to flexcircuit plate 54 via tip plug 58. Wires 104 may run through the length of inner shaft 66, entering it through base 102, and exiting through tip plug 58, where wires 104 connect to flexcircuit plate 54. Wires 104 may be connected to electric plug 106 at their proximal end.
Inflation tube 108 may connect to the lumen of inner shaft 66 via base 102. Base 102 may be sealed around the entry points of wires 104 and inflation tube 108 using glue or sealant, as known in the art. The distal end of inner tube 66 may be sealed by tip plug 58, and glue or sealant as known in the art, while allowing passage of wires 104 to connect with flexcircuit plate 54. In this embodiment, Wires 104 may be fixed at their passage points into and out of inner shaft 66 lumen, making sealing around these points easy to achieve.
Inner shaft 66 may further comprise proximal openings 130 and distal openings 132 allowing inflation of balloon 60. Stopper 70 may be located proximal to openings 130 and 132, and may limit movement of outer shaft 74 over inner shaft 66.
Outer shaft 74 may be fixed to outer shaft base 96. Retraction knob 100 may protrude out of housing 92 via slot 94. Outer shaft 74 may be slideaby positioned around inner shaft 66, and may slideably pass out of housing 92 via the distal end of handle 90. Outer shaft seal 98 may allow sliding of outer shaft base 96 around inner shaft 66, while preventing leakage between them.
In some embodiments, a certain degree of leakage through outer shaft seal 98 may be permitted, so as to enable smooth movement of outer shaft 74 over inner shaft 66, as long as this leakage when balloon 60 is fully inflated, remains insignificant, e.g., up to ˜2cc per minute.
Proximal ring 72 may be fixed to the distal end of outer shaft 74. Proximal balloon neck 64 may be fixedly connected to proximal ring 72, and distal balloon neck 62 may be fixedly connected to distal ring 68 of inner shaft 66. Both balloon necks may be sealed around these attachments.
Thus, pulling on retraction knob 100 may cause outer shaft 74 to move proximally in relation to inner shaft 66, resulting with longitudinal stretching of balloon 60, which may straighten it out, and reduce its outer diameter, enabling insertion at a small outer diameter. When base 96 passes tooth 124 of locking mechanism 120, tooth 124 may prevent distal movement of base 96, thus locking outer shaft 74 in this position.
Pressing release button 126 may cause lever 122 to rotate around hinge 128, releasing tooth 124 of locking mechanism 120 and allowing distal movement of outer shaft 74. This may typically be done prior to balloon inflation.
Following release of locking mechanism 120, outer shaft 74 may again be free to slide over inner shaft 66. Balloon 60 may then be inflated via the lumens of stopcock 110, inflation tube 108, inner shaft 66, and openings 130 and 132. Inflation of balloon 60 may cause it to expand, shorten, and pull outer shaft 74 distally as it inflates.
The distal ends of flexcircuit arms 56 may be fixedly attached to the distal end of inner shaft 66 as they may be continuous with flexcircuit plate 54, which may in turn be connected to tip plug 58, which may be connected and sealed to the distal end of inner shaft 66.
In contrast, the proximal ends of flexcircuit arms 56 may be connected together at flexcircuit arms proximal ring 76, which may be slideably positioned around outer shaft 74. Although in the current embodiment, device 50 may typically be configured to be used with a balloon inflation volume of ˜170 cc, the length of longitudinal flexcircuit arms 56 from flexcircuit plate 54 to proximal ring 76 may optionally be made sufficiently long to allow them to radially expand around a balloon inflated to any reasonable volume. For example, if balloon 60 were inflated to ˜400 cc (which may be considered a very high volume for this application), the length of longitudinal flexcircuit arms 56 from flexcircuit plate 54 to proximal ring 76 may be at least ˜14.4 cm, whereas for a 170 cc balloon volume, a length of ˜10.8 cm would suffice.
The structure described above may allow flexcircuit arms 56 to freely slide over outer shaft 74. Pulling retraction knob 100 proximally to stretch balloon 60, may cause proximal ring 72 of outer shaft 74 to pull flexcircuit arms proximal ring 76 in the same direction, thus also stretching and flattening out the longitudinal electrode structure formed by flexcircuit arms 56.
During inflation of balloon 60, flexcircuit arms proximal ring 76 may be free to slide along outer shaft 74 as it is pulled distally by the expansion of balloon 60, allowing flexcircuit arms 56 to expand radially, separately from balloon 60. This is especially important in case balloon 60 is made of a compliant material, whereas flexcircuit arms are made of a non-compliant material, which might create a different degree of stretch for each of them at various points along their circumference.
In case balloon 60 is made of a non-compliant or semi compliant material, separate expansion of the balloon and flexcircuit arms 56 may still be advantageous, as folding of balloon 60 may require it to assume a configuration that cannot be achieved if connected to flexcircuit arms 56. Alternatively or in combination, focal connections between balloon 60 and flexcircuit arms 56 at specific locations, may be desirable.
As described above, inner shaft 66 may be fixedly connected to handle 90, and outer shaft 74 may be slideable over inner shaft 66, but may be fixedly connected to retraction knob 100 which may slide within slot 94 of handle 90, thus preventing rotation of outer shaft 74. Therefore, both inner shaft 66, and outer shaft 74, maintain a constant orientation in relation to each other and handle 90. This can be important as it prevents unintentional twisting of the electrode structure which could interfere with retraction of the device. In addition, this arrangement allows the user to control the orientation of the electrodes, which is of significance in designs where there is asymmetry of the ablation pattern, as will be further described below.
In some embodiments, rotation of the flexcircuit arms proximal ring 76 may further be prevented, for example by making outer shaft 74 and flexcircuit arms proximal ring 76 include a directional feature such as a non-circular cross section, as known in the art. This is a further measure preventing twisting of electrodes.
Alternatively, a similar result may be achieved by providing a longitudinal slot along inner tube 66, and a protrusion from outer tube 74 which may slide inside said slot. Such an arrangement may require creating a seal between outer shaft 74 and inner shaft 66 distal to said slot to prevent leakage, for example by moving outer shaft seal 98 to the distal end of outer shaft 74.
Sheath 78 may be slideably positioned over outer shaft 74, with valve 80 creating a seal between them. Valve 80 may be any suitable valve which can allow both a good seal and sliding between the elements, as known in the art, for example a Tuohy-Borst valve. Sheath 78 can be moved distally to cover flexcircuit longitudinal arms 56, balloon 60 and inner shaft 66, in the folded or compressed position of device 50. In the fully folded or compressed state, the distal end of sheath 78 may be flush with the proximal end of atraumatic cap 52.
Atraumatic cap 52 may typically comprise a rounded structure, with smooth edges. Although it may be dome shaped, it may typically be rather flat, having a thickness of approximately 3-5 mm or less so as to prevent pushing of the tissue away from the electrodes. Its edges may optionally extend laterally to cover a part of or the entire distal tip of outer sheath 78. It may be made of plastic, rubber, metal, or any other biocompatible material, and may be glued, welded, screwed, or otherwise attached to the distal end of ablation device 50. In some embodiments, atraumatic cap 52 may merely comprise a layer of adhesive or other type of coating applied to the distal end of ablation device 50, typically to flexcircuit plate 54. In yet other embodiments, atraumatic cap 52 may be comprised of flexcircuit plate 54 alone. In yet other embodiments, atraumatic tip 52 may be made of gel, which may optionally dissolve following insertion into the body or following contact with fluid.
Sliding stopper 86 may comprise an element which can be easily slid along sheath 78 and locked at any position as desired by the user, to limit the depth of insertion into the body to the pre-measured urethral depth or desired deployment depth.
More particularly,
In the interest of clarity, only some of the insulated tracks and circumferential electrodes are shown. It should be understood however, that typically all flexcircuit arms may have electrode segments 41 and 42 on them, and circumferential electrode segments 43 between them, with connections as needed made by insulated tracks 147, which may run in different layers of the PCB.
It should also be noted that the length of circumferential electrode segments 43 may typically be shorter than appears in
Returning to the PCB, flexcircuit plate 54 may serve as the base for electrode structure 40 of the current embodiment, and wires 104, which may run through inner shaft 66 and may be connected to it, typically by soldering wires 104 to distal connectors 144.
Flexcircuit longitudinal arms 56 extend radially from flexcircuit plate 54. Typically, there may be eight arms 56 but this number can vary from 1 to approximately 20.
As shown in
For example, to drive the longitudinal electrodes as shown in
Continuing the same example, to drive the circumferential electrode segments as shown in
When fabricating the above described embodiment of device 50, wires 104 passing out of inner shaft 66 distal end, may be soldered to distal connectors 144 of flexcircuit plate 54, which may thereafter be connected to the distal tip of inner shaft 66, optionally using tip plug 58. Flexcircuit arms 56 may be bent parallel to the longitudinal axis of inner shaft 66, and flexcircuit proximal ends 142 may all be connected to each other at flexcircuit arms proximal ring 76, around outer shaft 74.
Circumferential electrode segments 43 may be soldered to proximal connectors 146, creating “bridges” between adjacent flexcircuit arms 56.
More particularly,
From distal to proximal are seen: atraumatic tip 52, flexcircuit legs 56 and circumferential electrode segments 43 in their collapsed state, overlying deflated balloon 60, outer sheath 78 with sliding valve 80 and sheath port 82, and sliding stopper 86, outer shaft 74, inner shaft 66, handle 90 comprising housing 92, locking mechanism 120, release button 126, retraction knob 100, and inflation tube 108.
Circumferential electrode segments 43 are seen bent at their middle, both halves of each segment becoming parallel to the longitudinal axis of inner shaft 66, allowing the structure to fit inside sheath 78.
Locking mechanism 120 is shown holding outer shaft 74 in a proximal position, longitudinally stretching balloon 60. Balloon 60 with the electrode structure are shown collapsed and covered by outer sheath 78.
From distal to proximal are seen: atraumatic tip 52, flexcircuit legs 56 and circumferential electrode segments 43 in their expanded state, overlying inflated balloon 60, outer sheath 78 with sliding valve 80 and sheath port 82, and sliding stopper 86, outer shaft 74, inner shaft 66, handle 90 comprising housing 92, locking mechanism 120, release button 126, retraction knob 100, and inflation tube 108.
Locking mechanism 120 is shown in its released state, outer shaft 74 is now shown in a distal position, having been pulled distally by balloon 60. Outer sheath 74 is shown drawn proximally, with balloon 60 fully inflated and the electrodes structure expanded. Circumferential electrode segments 43 are seen straightened out almost completely, enabling creation of an ablation line around the equator of the bladder.
The longitudinal electrode segments 41 and 42 in the above embodiment may typically be made of exposed tracks of PCB material, typically measuring approximately 0.5 mm*25 mm, and made of copper or other electrically conductive material. Dimensions may typically vary between 0.2 mm*10 mm to 1 mm*50 mm.
The circumferential electrode segments 43 in the above described embodiment may be made of bare wire, copper or another electrically conductive material of 30 AWG (American Wire Gauge), i.e., approximately 0.25 mm in diameter, which may be soldered to the proximal connectors 146. Wires or braided cables made of different materials may be used for these segments, such as stainless steel, silver etc. or for example copper with gold or other plating. Wires of different gauges can also be used, typically this will be in the range of 28-32 gauge.
Use of device 50 to perform TBP is described below, referring to
After appropriate cleansing and draping, the urethral length, or desired deployment depth may first be measured using a Foley catheter, and local anesthetic may be instilled into the bladder. Sliding stopper 86 may be locked over outer sheath 78 at the corresponding distance from atraumatic tip 52. Valve 80 may be locked to prevent unintentional deployment of the device.
Folded or compressed device 50, as seen in
While keeping sheath 78 in place so it does not move relative to the patient's body, handle 90 may be pushed forward, thus deploying the device, i.e. passing it out of outer sheath 78.
Release button 126 may be pressed to release locking mechanism 120. Balloon 60 may be inflated with fluid via inflation tube 108, causing outer shaft 74 to slide distally out of handle 90, and longitudinal flexcircuit arms 56 and circumferential electrode segments 43 to expand radially around balloon 60, as shown in
The bladder may be drained around the electrodes and balloon 60 through sheath port 82.
Measurement of impedances between the electrode sets may be performed, followed by energizing of the electrodes with an RF generator utilizing the far field bipolar technology, as described above, for ablation of the desired isolation lines pattern on the bladder wall.
Fluid may be instilled in the bladder around the balloon and electrodes via sheath port 82, optionally by transferring fluid from the balloon to the bladder, such that the bladder volume may be kept substantially stable during balloon deflation. This method may prevent interference with collapse of the balloon and electrode structure and removal of the device.
Retraction knob 100 may be pulled proximally to retract outer shaft 74, stretch balloon 60, and collapse longitudinal flexcircuit arms 56 and circumferential electrode segments 43. Once pulled sufficiently proximally, locking mechanism 120 may lock, and handle 90 may be pulled while holding sheath 78 in place, to retract balloon 60 with the electrode structure into sheath 78.
Handle 90 may then be pulled further proximally to remove device 50 from the patient's body.
Various modifications of the above described embodiments may be advantageous.
In some embodiments, the distal tip of outer sheath 78 may be modified to make it atraumatic.
For example, the distal tip of outer sheath 78 may be filed or otherwise processed using heat or other methods as known in the art so as to be extremely rounded and smooth, to prevent any damage to tissue during its insertion to a patient's body.
The distal tip of outer sheath 78 may additionally or alternatively be made soft, using similar processes. The transition from a more rigid to a softer consistency may occur gradually over a certain distance, typically along 2-20 mm.
Another possible embodiment of outer sheath distal tip 79 is shown in
Outer sheath distal tip 79 may additionally be made narrower than the more proximal part of outer sheath 78, so that in the folded or compressed state shown in
In
In some embodiments, power to circumferential electrode segments 43 may be delivered through only four of the flexcircuit arms 56, so that there may be a “powered” flexcircuit arm 56 between each two “dead” flexcircuit arms 56.
As can be seen, each pair of circumferential electrode segments 43 may receive power from one “powered” flexcircuit arms “p” between them, and each circumferential electrode segment 43 may connect to a separate adjacent “dead” flexcircuit arm “d”. Such an arrangement may simplify the PCB.
Use of copper wires for the circumferential electrode segments may provide the advantage of high conductivity, low cost, and ease of use.
However, these wires are malleable and tend to maintain the device in its open position even when the balloon is deflated, requiring pulling on the outer shaft, and retraction into sheath 78 to cause collapse of the electrode structure.
In addition, these wires are prone to breakage due to fatigue as a result of repeated bending at the same points. For disposable devices this is typically sufficient, however for a more durable design, any of the following modifications may be utilized.
A possible modification may include use of a braided cable or wire. A braid may be less easily fatigued, and depending on its material, may be non-malleable. For example, a stainless steel cable can be used, and if its conductivity is deemed too low, a silver wire or other highly conductive material can be incorporated in it to increase conductivity.
Connecting such a braid to proximal connectors 146 may require laser welding, as braided cables tend to act as wicks when soldered, resulting in hardened, fragile segments.
Typically, such soldering or welding to a “powered” proximal connector 146 may result with a durable attachment, as the electrical lead embedded within the PCB provides a good anchor. However, when connecting to a “dead” proximal connector 146, the attachment may be prone to detachment if the connector is a superficial solder pad on an outer layer of the PCB. This may be solved for example by providing proximal connectors 146 which may have a long enough extension embedded within the PCB, even though this lead may not connect to a power source (it is “dead”).
Alternatively, as shown in
Several possible modifications may utilize the same flexcircuit as described above for longitudinal electrode segments 41 and 42, instead of wires, for circumferential electrode segments 43.
The radius of the bifurcation marked R, may be configured to facilitate entry of the circumferential segment 34 into the sheath when pulled into it during crimping.
Note that the above described device 50 can be made with an asymmetrical electrode structure that, for example being slanted anteriorly, sparing the posterior aspect of the bladder from ablation as described above, while still using the far field bipolar technology, as long as equal lengths of opposing electrodes are used.
More particularly,
Upper circumferential electrode segments 160 and lower circumferential electrode segments 162 may be at the same distance from the equator line of spherical expandable element 30, and therefore may be of the same length, making them appropriate for use as bipolar pair. Diagonal electrode segments 168 are located one at each side of structure 40, and may also be a good bipolar pair.
Various combinations of parts of anterior longitudinal electrode segments 164 and posterior longitudinal electrode segments 166 may also be used as bipolar pairs, to enable creating this pattern using the far field bipolar technique.
In other embodiments, the far field bipolar may be used with opposing electrodes of unequal length. Rather, an equal degree of ablation at each electrode may be achieved by making the surface area of the electrodes equal (the shorter electrode being wider in an equal proportion).
In other embodiments, the far field technology may be used with a deliberate asymmetry between the two electrodes. This configuration may be useful when one electrode (or set of electrodes) is applied to a different surface, or at a different pressure. One example of this configuration may be coupling a relatively longer segment, apposed to the bladder dome, with a relatively shorter segment, apposed to the lateral wall of the bladder. This configuration may be useful for example when the contact pressure at the dome exceeds the contact pressure at the lateral walls (e.g., due to manual pressure applied along the long axis of the device, or other causes). Thus, the increased contact pressure at the dome may be offset by the decreased current density (due to the increased electrode length), and the resulting ablation may still be symmetrical though the electrode lengths and surface areas are different.
In other embodiments, the far field bipolar technology may be used with asymmetrical electrodes, with the intention to induce asymmetrical lesions. This configuration may be useful when different anatomical zones are ablated with coupled electrodes. An example of this configuration includes coupling longer distal (closer to the tip of the device) electrodes with shorter circumferential electrodes, with the intention to have increased current density and increased lesion depth at the circumferential electrodes. This configuration may be useful in creating shallower lesions in the anatomical regions of the bladder that are intraperitoneal, and deeper lesions in the regions that are not in direct contact with the peritoneal cavity. Another example may be coupling longer posterior lines with shorter anterior lines, in order to create differentially shallower lesions at the posterior side of the bladder, that is adjacent to sensitive organs such as the vagina (in women) and the seminal vesicles in men.
Yet another example may include a situation where the goal is creation of a significant lesion at one pole, and no lesion, or an insignificant lesion at the other, for example when localized treatment at a specific region is desired, as will be elaborated below.
Further Improvements and Variations.
Deployment Controls.
A useful modification of device 50 involves preventing the possibility of mistakenly inflating balloon 60 before locking mechanism 120 was released. Such inflation prior to releasing the locking mechanism could damage the balloon and/or electrodes.
Preventing inflation before release of the locking mechanism can easily be achieved for example by incorporating a safety valve near the proximal end of inner shaft 66, which closes when compressed by outer shaft base 96 when at its locked position, such that the lumen of inner shaft 66 remains closed as long as locking mechanism 120 is locked. Release of locking mechanism 120 may allow outer shaft base 96 to move distally, releasing this safety valve, and allowing inflation to be undertaken.
Another useful modification involves preventing the possibility of retracting the balloon and electrodes into sheath 78 before flexcircuit longitudinal arms 56 are pulled taut using retraction knob 100. Such retraction prior to the longitudinal flexcircuit arms being drawn taut might cause their compression by sheath 78, with a resulting outward protrusion which might interfere with device removal.
Preventing retraction before the longitudinal arms are drawn taut can easily be achieved for example by incorporating into handle 90 a lever that locks sheath 78 in place, until outer shaft base 96 reaches the locked position of locking mechanism 120.
Axial Force Application.
Application of axial force along the longitudinal axis of the device 50 during ablation may aid in improving the contact between the electrodes and bladder wall and achieving a more homogenous ablation pattern. This force may typically be 1-20 N, preferably 2-10 N.
Application of such axial force may be performed manually by the user.
Control over the force may be provided for example by incorporating a spring based gauge into the handle, optionally with an alarm that would set go off if excessive force were applied.
Another way for applying this axial force, is shown in
With this device, as shown in
Contact Force Measurement.
Measurement of the actual contact force between the electrodes and bladder wall may be beneficial, and may, for example, be performed by placing a miniature sensor adjacent to, or on at least one or more of the electrodes.
Miniature sensors that could be used for this include for example force sensing resistors such as the 400 series made by Interlink Electronics of Camarillo, CA 93012, USA.
Pressure sensors such as the FISO-LS series Fiber Optic Micro-catheter Pressure Transducers made by Harvard Apparatus of Holliston, MA 01746, USA, may also be used for estimation of the contact force.
The current disclosure further describes another method to assess the electrode-bladder contact pressure. According to this method, the volume in the balloon may be continuously monitored, as well as the pressure in the balloon (preferably measured at the balloon itself). The volume/pressure graph achieved in clinical practice (“measured pressure”) is compared to the bench tests of the same balloon (“expected pressure”). For any given volume in the balloon, the difference between the measured balloon pressure and the expected balloon pressure—is the balloon-bladder contact pressure.
The balloon may be inflated, pushed or deformed, until the desired contact pressure is achieved.
Pre-Choice of Optimal Balloon Volume.
In some embodiments described previously, the longitudinal flexcircuit arms 56 may be of variable length, and the balloon can be inflated to various volumes. The length of the circumferential electrodes may be variable as well (as previously described), or fixed to be long enough to accommodate the entire range of balloon inflation (being somewhat folded when the balloon is not fully inflated). In some embodiments, prior to insertion of the device, the bladder volume and pressures may be measured (as in urodynamic studies), and the volume of the bladder that achieves the desired contact pressure can be noted. Optimal contact pressure may typically be in the range of 5 cm H2O to 100 cm H2O, preferably 10 cm H2O to 40 cm H2O. Once this volume is noted, the device may then be inflated to this volume, to achieve the desired contact pressure.
Additionally, the volume of the balloon may need to be measured and correlated with the volume defined by the deployed geometry of the longitudinal and circumferential electrodes so that the balloon will better fit within this deployed geometry without placing added stress against the electrode elements or leaving void spaces without the desired pressure/force pressing the electrodes against the tissue.
Pre-Choice of Optimal Deployment Position.
In some embodiments, the balloon may have a fixed inflation volume. In these embodiments, the position of the balloon within the bladder (the displacement forward from the bladder neck) may affect the electrode-bladder contact pressure. In some embodiments, the optimal displacement may be predefined according to imaging of the bladder when filled with a fluid. When the optimal bladder pressure is reached, the long axis of the bladder may be measured, and the device may then be deployed in a position that will force the bladder to assume the same measured length. For example: a bladder may be filled with fluid, until a pressure of 40 cm H2O is reached. The bladder's long axis may then be measured (for the purpose of this example it will be assumed to be 12 cm). Then, the device may be introduced and deployed so that the tip of the device (once inflated) may be 12 cm from the bladder neck. In some embodiments, clear markings on the device shaft may allow the user to clearly see how far in the device is.
Another advantage of choosing the optimal deployment position may be to make sure the trigone area is avoided. If the bladder size allows (as assessed by imaging, urodynamic study or cystoscopy) a deployment position can be chosen to make sure the trigone and the intradetrusor segment of the ureters are spared of ablation.
Automatic Controls
Further modifications of device 50 may involve automatic control of many of its functions and controls. This automatic control may possibly and preferably be executed by the controller/generator unit.
The controlled phases and actions may include any or all of the following as well as additional features that are not listed herein:
Automatic deployment (moving shaft out of sheath)—can be implemented using a linear or other electric motor that may be operated by the controller following insertion of the probe into a patient's urethra, and pushing a button, or activating a footswitch, by the user. This motor could for example push handle 90 distally relative to sheath 78. The controller may measure the force applied by the motor to ensure excessive force is not exerted on patient's tissues.
Automatic Release of Retraction Knob.
This may be achieved mechanically as described above, or electronically once a sensor detects full deployment was reached.
Automatic inflation of balloon—may be performed by the controller by activating an electronic pump, or opening an electronic valve to allow flow of fluid or gas at a known pressure. Pressure, rate of flow and total volume delivered may be monitored and controlled. In some embodiments, rapid balloon filling may be applied, to rapidly stretch the bladder and thus increase the contact pressure (before the bladder has sufficient time to relax into the new increased volume).
Automatic Application of Axial Force.
Axial force may be applied to the inner shaft 66 as described above, with the difference that this force may be applied automatically by the controller. For this purpose, the position of handle 90 relative to the patient may need to be controlled by the controller.
Alternatively or in combination, axial force may be applied to the outer shaft 74 of device 50 as described above, with the difference that this force may be applied automatically by the controller. For this purpose, the position of handle 90 relative to the patient may need to be controlled by the controller, by the user, or it may be fixed in space, while the controller may operate a motor that may push retraction knob 100 distally on handle 90. The force may be monitored and controlled by the controller by adjusting operation of the motor to keep the force within the desired range.
Automatic adjustments according to measurement of contact force—measurement of the electrodes-bladder wall contact force may be performed as described above, and monitored by the controller. These data as well as additional data such as impedance measurement may be used separately or together, to adjust the axial force, inflation volume or pressure, or ablation power, time, or other parameters affecting ablation results.
Such adjustments may optionally be performed based on comparison of the above measurements with a database containing historical data and appropriate treatment settings associated with them.
Automatic Balloon Deflation by Transfer of Fluid from Balloon to Bladder.
Operation of an electronic pump by the controller, optionally the same pump used for balloon inflation, can be automatically initiated to perform this fluid transfer. Alternatively or in combination, the tube leading to the bladder and the tube leading to the balloon may be connected to the same port, and a clearly marked valve may display and enable choosing the currently open path (balloon or bladder).
Automatic Collapse of Balloon and Electrodes.
Pulling the retraction knob proximally may be performed by a controller activated electric motor.
Automatic Retraction of Shaft.
Pulling handle 90 proximally relative to sheath 78 may be performed by a controller activated electric motor, optionally and preferably, the same motor used for automatic deployment.
Automatic Cessation of Ablation if Peak Temperature is Exceeded.
In some embodiments, the device may not have temperature sensors to allow control over ablation heat, and limiting the ablation temperature may be achieved by the balloon itself. In some embodiments, the balloon material and wall width is selected so that the balloon tears when in contact with heat beyond a certain temperature threshold. Rupture of the balloon may immediately and automatically reduce the ablation at that point by reducing the contact pressure and by flushing with fluid from the balloon. Additionally or alternatively, a pressure sensor may sense the reduction in balloon pressure (or the loss of balloon volume) and automatically abort ablation. In some embodiments the balloon material is polyurethane, and the wall thickness at the target volume is 0.02-0.005 mm, intentionally making the balloon likely to rupture when heated above 70 degrees Centigrade, thus aborting the procedure.
Means for Improving Electrode-Tissue Contact
Ensuring good mechanical and electrical contact between the electrodes and tissue may be crucial for achieving satisfactory ablation results. Various optional aspects of the device intended to improve this contact are described:
Fluid Removal
Following deployment and expansion of expandable element 30, excess fluid between the electrodes and the organ wall may be removed to improve electrode-tissue contact. This may be done by applying suction to the space between the electrodes and organ wall. Such suction may be applied using any one (or a combination) of the following means, shown in
Alternatively, open channels, strips of an absorbant biocompatible cloth, or any other material, feature, or element capable of transmitting the suction may be used in place of miniature tubes 204.
Once adequate seal is ensured, aspiration of the fluids and gases inside the bladder may cause the pressure within the bladder to be less than the normal hemostatic pressure in the bladder and less than the pressure in the balloon when inflated, which may improve contact against the electrode elements.
Intentional Increase of Intra-Abdominal Pressure.
In some embodiments, electrode-tissue contact may be improved by increasing intra-abdominal pressure. This may be a transient increase prior to, or during the procedure, or both, or a longer lasting increase which may be applied for at least the duration of the procedure.
Such an increase in intra-abdominal pressure may be induced in many ways.
For example, in a conscious patient, it may be achieved by having the patient cough or perform a Valsalva maneuver.
In a ventilated patient under generalized anesthesia, this may be achieved for example by modifying ventilation parameters, such as increasing ventilation volume or positive end expiratory airway pressure.
A user, typically the treating physician, may increase the patient's intra-abdominal pressure by applying manual pressure on the patient's abdomen.
In some embodiments, a combination of the above may be used.
In some embodiments, intra-abdominal pressure may be monitored, for example using a rectal pressure probe, and a feedback indication may be provided to the physician and/or patient, to control the amount of pressure.
In some embodiments, the measured intra-abdominal pressure may be used to ensure that ablation may only be performed while the pressure is within a specific range, and may be automatically aborted if higher or lower than this range.
Micro-Conforming Electrodes.
In some situations, despite overall good contact between the electrodes and organ wall, and even following the measures described above, there may still be small gaps remaining between the electrodes and tissue, in at least some points along the electrodes. As shown in
In order to ensure creation of continuous lesions along the electrodes despite such gaps, various modifications to the electrodes may be used that may improve contact in these situations.
For example, as shown in
An example of a possible material 212 may be a poly (3,4-ethylenedioxythiophene)/polyurethane-hydrogel hybrid described by Sasaki et al. (Highly conductive stretchable and biocompatible electrode-hydrogel hybrids for advanced tissue engineering. Adv Healthc Mater. 2014 November; 3(11):1919-27).
Such a material may optionally be applied to the electrodes during PCB manufacturing, or manually during preparation of the probe just before the procedure.
Other materials or structures that may provide the same function as the above hydrogel by micro-conforming to the tissue surface may be used.
For example, a conductive fabric made of microfibers that constitute the electrodes or protrude from the electrode surface, may also provide this function. Such microfibers may be soft and conform to the tissue surface in a manner resembling the hydrogel described above. Alternatively, microfibers may possess sufficient sharpness and axial rigidity so as to penetrate the tissue, typically to a shallow depth limited to no more than 1 mm.
Semi-Conductive Medium.
Yet another embodiment intended to solve the problem of small gaps between the electrodes and the tissue relates to the medium used between the electrodes and organ wall. Typically such medium may be a fluid. Previous disclosures have discussed use of media that are either conductive such as saline or non-conductive such as glycine.
A highly conductive medium such as normal saline or hypertonic saline, may have the advantage of improving electrical coupling between the electrodes and tissue however it may run the risk of creating a “short” between the bipolar electrodes, if a thick enough layer of fluid is left between the electrodes and organ wall. In addition, it reduces the ability of the user to identify the existence of such excessive fluid layer, as it will not cause a noticeable change in impedance measurement between the electrodes.
A non-conductive medium such as glycine or sorbitol may have the advantage that if mechanical electrode-tissue contact is suboptimal, it may create a significant increase in measured impedance between the bipolar electrode pairs, so that the user may identify and fix the situation, for example by any of the above described methods.
The current invention includes optional use of a medium that may have a conductivity between that of the treated tissue and a complete insulator. For example, for a treatment in the urinary bladder, such a medium may be 0.1% saline, which may have a specific conductivity of approximately 0.1 Siemens/m. This conductivity is lower than that of the urothelium, which is described in various sources as having a conductivity between 0.2-1.9 S/m, yet it does not constitute a complete insulator. Thus, if a thin layer of this fluid remains between the electrodes and bladder wall, no “short circuiting” or “bypassing” of current flow through the tissue will occur, and an increase in impedance measurement may be detected, indicating the need for removal of fluid. On the other hand, fluid filling small scale or microscopic gaps within tissue folds or rugae along the electrodes may not act as an insulator, and may actually allow current flow, resulting with a more continuous lesion.
In some embodiments, a pressure sensor measuring balloon inflation pressure may be used during the procedure to detect various conditions, including leakage from the balloon. Typically, if measured proximal to inner shaft 66 or inflation tube 108, pressure may rise steeply during inflation due to resistance of the fluid pathways. Pressure may then decrease within a few seconds and stabilize at a pressure reflecting the fluid volume within the balloon, balloon size and elasticity, and bladder (or other treated organ) size and compliance.
Increases in pressure during bolus inflation to significantly more than ˜400 mmHg may typically indicate a problem such as inflation while the balloon is not fully deployed, a stuck electrode structure, a small or non-compliant bladder, or clogging of the fluid pathways. The user may choose to abort or change the procedure due to the above.
As mentioned previously, the pressure for the inflated device outside the body at a specific volume, may be pre-measured (“expected pressure”).
In case the equilibrated inflation pressure during the procedure is significantly higher (typically>˜20 mmHg higher) than the “expected pressure”, the user may conclude that the bladder is excessively small, contracted, or has very low compliance, and may choose to abort the procedure.
In case the measured inflation pressure does not equilibrate, or equilibrates to a level much lower than the pre-measured “expected pressure”, balloon leakage may be suspected, and the user may choose to replace the device.
It is important to note that this is only one of many possible inflation profiles. For example one that goes from flat pressure vs. volume, then monotonically increases in pressure with volume is possible as well.
Some embodiments may involve electrodes that may be printed over the expandable element.
The main advantage of such embodiments may be simplicity of manufacturing.
Disadvantages may include the following:
Non-Compliant Balloons and Methods of Manufacturing Thereof.
A non-compliant balloon appropriate for the device of the invention, may optionally be manufactured using blow molding, RF welding, or any other methods known in the art. Since the balloon of some of the embodiments may have an inflated diameter much larger than its proximal and distal neck diameters, standard blow-molding techniques may be less appropriate for manufacturing it as the initial tube will either need to be very thick, leaving very thick balloon necks, or it will not contain sufficient material for achieving a balloon wall of reasonable thickness in the inflated state.
In such cases, RF welding (or laser, or ultrasound welding, or other form of connecting balloon parts) of a balloon made of at least two parts (typically two halves of the balloon) may be a suitable solution. A common result of such manufacturing method may be the production of a welded balloon 220 with an outwards facing seam 222 along the welding/connecting lines, as shown in
Welded Balloon with Inward Facing Seam.
In some embodiments, a welded balloon 220′ may be manufactured which may have an inward facing seam 224.
Alternatively, the balloon may be manufactured with an outward facing seam in inverted upon itself resulting in the seam facing inwards.
Balloon part 228′ may be manufactured by compression molding, injection molding, dipping, blow molding of a polymer sheet, or any other method known in the art.
Balloon parts may be brought together so that their “flanges” are adjacent each other. This may optionally be done inside a mold or jig to help approximate the parts.
Specialized “forceps” 232 or “rollers” 234 may be provided that may be passed through the balloon necks, and may clamp adjacent “flanges” together. In the following descriptions, forceps 232 and rollers 234 are used interchangeably.
Forceps 232 are shown in
Rollers 234 have basically the same structure as forceps 232, with the addition of small wheels 235 on apposing elements 233.
These are just examples of possible tools, as any structure of a low profile that is capable of clamping together two balloon flanges and delivering the energy for welding them may be used. RF energy or other appropriate form of energy may be delivered between the two apposing elements 233 of “forceps” 232, or between an energy source positioned external to welded balloon 220 and “forceps” 232. Such energy may be RF energy, light (e.g. laser), ultrasound, heat, or any other energy as known in the art.
In the embodiment depicted in
In some embodiments, a single pair of “forceps” 232 (or rollers 234) may be used. In some embodiments, at least two pairs of “forceps” may be used in parallel (e.g. for a balloon made of two halves, one pair may be used for each seam on either side of the balloon, preferably moving along the seams in parallel so that the balloon's symmetry is preserved. Additional pairs of “forceps” may be used, for example four pairs, two inserted and removed from either neck of the balloon.
Of note, balloon 220′ shown in
In some embodiments, instead of facing inwards, “flange” 230′ may be at any angle to the balloon part wall, e.g. tangent, facing outwards, or any other angle. In such embodiments, the “forceps” 232 may also invert the “flange” 230 so as to cause it to face the opposite flange of the adjacent balloon part, just prior to welding.
In some embodiments, the balloon parts' “flanges” 230′ may be brought together from the inner side of the balloon by “clamps” 236 that may be designed to hold together the whole seam at once, and optionally to weld it all at once.
Typically, at least two clamps 236 will be used for each seam, one above and one underneath each “flange” 230′. Optionally, each clamp 236 may comprise at least two parts, to facilitate insertion into the balloon and removal therefrom.
Welded Balloon with No Protruding Seam.
In some embodiments, such as examples shown in
Needle Electrodes.
In some embodiments shown in
Needles 250 may be manufactured as an integral part of flexible PCB 140. Alternatively they may be manufactured as separate elements that may be welded or otherwise connected to PCB 140. For example needles 250 may be made by laser cutting strips of nitinol.
In some embodiments, needles 250 may be fixed, i.e., protrude from the surface to a constant distance without change during the procedure.
Alternatively, needles 250 may change the degree of their protrusion from segment 42 (or any other surface) during the procedure. Typically in such embodiments, needles 250 would protrude less in the folded or compressed state of device 50, and protrude more during the deployed state.
In some embodiments, needles 250 may be self-deploying, i.e., they may possess the innate tendency to protrude radially from electrode segment 42. This may for example be achieved by heat treatment of the needle structure fixing the needles with an outward angle as shown in
In other embodiments, needles 250 may be made of a shape memory alloy such as nitinol and may be heat treated in a way such as to assume a collapsed position when cold, and protrude radially when exposed to body temperature. Thus, needles 250 may be easily folded or compressed in the folded or compressed state of device 50, and may only protrude when inserted into the patient's body.
In yet other embodiments shown in
As seen in
The above are examples, other designs and methods known in the art may be used for causing needles 250 to be collapsed in the folded or compressed state of device 50 and assume a protruding position during deployed or expanded state.
The extent of protrusion of needles 250 may be predetermined and limited by design, depending on the treated organ and target tissue. For example, typically, for treatment in the urinary bladder, needles 250 may protrude between 0.1 mm to 1.5 mm from the surface of segment 42 (or any other surface). This distance is measured perpendicular to the surface, in other words, if at an angle as in
Typically, needles 250 may be used in combination with far field bipolar technology. However, needles 250 may also be used with other ablation technologies/modalities, for ablation in general and for TBP in particular.
Use of needles 250 in combination with the various above described methods of suction applied around the balloon may be of particular benefit.
The advantage of using needles 250 may be both in ensuring good tissue electrode-contact and in cases where it may be desirable to avoid ablation of superficial layers. In such cases, needles 250 may be insulated all over apart from at their tips.
Localized Treatment.
Although described above in the context of whole organ treatment, or treatment that targets a large area of an organ with a repetitive pattern (such as TBP for the bladder), in some embodiments, far field bipolar technology may be used for targeted treatment of localized, relatively small areas in an organ.
In some embodiments this may be achieved by the two poles of each set of electrodes having different surface areas, as mentioned above. For example, the pole at the target region may comprise electrodes with a small total surface area, while the electrodes at the other pole, where a lesion is not desired, may have a large total surface area. In such case, the large surface area pole serves a role similar to the “dispersive” electrode of monopolar ablation, despite being used here as bipolar.
The difference in surface areas between the “treating” and “dispersive” electrodes may typically be in a ratio of between 1:2 to 1:20, preferably between 1:5 to 1:10.
For the procedure that is the subject of this application, using “far-field bipolar” energy coupling, the “treating” and “dispersive” electrodes, which form the bipolar pair, are intended to have approximately the same surface area.
For example, in the bladder, the trigone may be specifically targeted. This may be done for example with the purpose of denervating the bladder. Alternatively this may be done for disrupting signal propagation within the bladder wall in the area of the trigone only, or for isolation of the trigone area.
As an example,
As seen in
In some embodiments, the bladder neck may be targeted, for example for inducing mechanical changes, for treating stress incontinence.
A localized area in the bladder dome may be treated for example for isolating that area following identification of an aberrant focus of activity there. Alternatively treatment for a localized area of the bladder using far field bipolar may be undertaken for treatment of a superficial tumor, bleeding, or any other bladder condition.
In some embodiments, the devices of the invention are further adapted to deliver therapeutic substances to the treated regions. This may for example be achieved by coating the treating electrodes with the drug that is to be delivered. Ablation of the tissue may increase its permeability and absorption of the drug. Release of the drug from the electrodes may be a result of the current flowing through the electrodes, a result of the increase in temperature, or both.
As an example, conditions that may be treated in this manner in the urinary bladder may include overactive bladder, bladder-detrusor dyssynergia, pelvic pain syndrome, hypoactive bladder, neoplastic disease.
Substances that may be delivered in this manner may for example include but are not limited to botulinum toxin, anticholinergics, and Glivec, to name a few.
Yet another embodiment may involve using a balloon which may be mirror like or opaque, except in specific lines where the ablation is desired, along which it may be at least partially transparent.
Shown in
Most of the surface area of balloon 274 may reflective or opaque to light coming from its interior (areas marked 278) while specific areas 280 of the balloon, may be transparent or semi-transparent. Areas 280 may have a linear shape or any other shape as necessary for creating the desired target ablation lesion.
The above may for example be achieved by application of a reflective or opaque coating to the interior or exterior of a transparent balloon, by manufacturing the balloon from reflective and transparent strips, or any other method.
A high intensity light source 282, for example an infrared light source, may be used to illuminate the inside of the balloon. Such light source may for example be an optic fiber transmitting laser light from an external source, or a small, yet powerful laser diode.
The light may illuminate the organ wall 272 only at the areas where the balloon is penetrable to light, thus producing ablation as determined by the transparent areas.
Optionally, different wavelengths can be used to target a specific layer or tissue type of the bladder wall.
Although described in the context of urinary bladder ablation for treatment of overactive bladder, it is clear that the devices and methods provided herein may be used in various other body organs and medical conditions.
These may include but are not limited to treating a urinary bladder for other micturition disorders such as detrusor-sphincter dyssynergia or pelvic pain syndrome, treating a uterus for irritable uterus or menorrhagia, treating a rectum, a large or a small bowel, for irritable bowel, treating a stomach for obesity, bronchi for asthma, a pulmonary artery or a cardiac atrium for atrial fibrillation, or a cardiac ventricle for ventricular tachycardia, uterus, pulmonary artery, cardiac atrium, cardiac ventricle, and the disorder is any of overactive bladder, obesity, asthma, atrial fibrillation, ventricular tachycardia.
Treatment of Underactive Bladder.
In some embodiments, the methods and devices described may be used to treat patients suffering from underactive bladder syndromes.
Detrusor underactivity, or underactive bladder (UAB), is defined as a contraction of reduced strength and/or duration resulting in prolonged bladder emptying and/or a failure to achieve complete bladder emptying within a normal time span. UAB can be observed in many neurologic conditions and myogenic failure. Diabetic cystopathy is the most important and inevitable disease developing from UAB, and can occur silently and early in the disease course. Careful neurologic and urodynamic examinations are necessary for the diagnosis of UAB. Proper management is focused on prevention of upper tract damage, avoidance of over distension, and reduction of residual urine. Scheduled voiding, double voiding, alpha blockers, and intermittent self-catheterization are the typical conservative treatment options. Sacral nerve stimulation may be an effective treatment option for UAB. New concepts such as stem cell therapy and neurotrophic gene therapy are being explored. Other new agents for UAB that act on prostaglandin E2 and EP2 receptors are currently under development.
For these embodiments, the device and methods described in the current invention may be adapted to achieve one or more of the desired effects: reduce the post voiding residual volume, decrease bladder compliance, induce (temporary) inflammation of the bladder wall, increase the afferent nerve signaling from the bladder, augment bladder contraction reflexes and/or awareness of bladder fullness, and/or cause partial denervation of the bladder.
Such treatment may be useful in treating patients who suffer from increased post voiding residual volume, and/or recurrent urinary tract infections, and/or difficulty with weaning from an indwelling urinary bladder catheter.
To achieve the desired effects and treat the listed clinical presentations, ablation device 50 may be adapted to create thermal effects in the bladder wall, with the intention of inducing various results, such as transient inflammation of the bladder wall. The treatment may be further adapted to temporarily damage the Urothelial layer only, enabling contact of urine with the underlying bladder wall layers—inducing inflammation and increased afferent nerve activity. Although the Urothelial layer is expected to quickly repair and return to normal, the underlying inflammation and the late effects of such inflammation (scarring, remodeling), are expected to be long lasting.
In some embodiments, only the dome of the bladder may be targeted. In some embodiments, the ablation may be applied to cause thermal damage through the entire bladder wall thickness, inducing inflammation of also the serosa covering the peritoneal parts of the bladder. In some embodiments, the ablation may be applied to damage the nerves supplying the bladder, effectively inducing a state of “neurogenic bladder” hyperactivity and increased bladder tone.
Generally, the ablation energy (duration times power) per bladder thickness for these indications may typically be 25% to 125% greater than the ablation energy applied to treat overactive bladder syndromes. When the bladder wall of an underactive bladder patient is thinner than the bladder wall of the average overactive bladder patient, the same power settings may be used, effectively achieving higher power settings per bladder thickness.
In some embodiments, the treatment of underactive bladder may be achieved by the eventual scarring and contraction of the ablation areas. For these embodiments, symmetric and continuous ablation lines may be preferred. The use of symmetric ablation patterns may allow uniform contraction of the bladder.
In some embodiments, the ablation may be applied with the bladder filled to a volume of 150 cc to 250 cc, and the bladder may subsequently be allowed to heal for two weeks or more, while the bladder may be kept at lower volumes (completely empty using an indwelling urinary catheter, or by frequent intermittent catheterizations and/or scheduled urinations). Using this method, the healing (with associated scarring and remodeling) of the ablations may somewhat affix the bladder at the empty state, reducing the volume of the bladder and bladder compliance, effectively increasing the micturition activities of the bladder.
While the exact mechanisms involved in causing bladder underactivity are still under much debate, most researchers agree that bladders that exhibit underactivity actually exhibit increased responsiveness to electrical field stimulation. (Yoshimura N.-Recent advances in understanding the biology of diabetes associated bladder complications. BJU Int. 2005 April; 95(6):733-8). These findings may suggest that bladder underactivity is caused or mediated, at least in part, by propagation of electrical fields within the bladder wall. Thus, in some embodiments of the current invention, bladder partitioning may be applied to treat underactive bladder syndromes. Partitioning of the bladder may be applied to block (limit) dissemination of relaxation signals throughout the bladder. As opposed to the common belief that bladder underactivity is caused by a lack of electrical and/or mechanical activity, the inventors believe that the pan-bladder underactivity may be caused and/or aggravated by electrical signaling through the bladder wall (much as in bladder over-activity). Thus, bladder partitioning to limit the conduction of electrical signals in the bladder as a whole is anticipated to alleviate the exaggerated bladder relaxation at the root of bladder underactivity.
In some embodiments, the partitioning of the bladder may be used to isolate sections of the bladder from efferent nerve activity (denervation). While complete denervation of the bladder may be substantially impossible from within the bladder (unless causing excessive damage to the bladder wall and surrounding tissues), isolation of bladder segments by creation of ablation lines around the entire periphery of a bladder zone may maximize the chances of complete denervation of at least certain zones of the bladder. It is believed that achieving substantially complete denervation of even a few bladder zones may induce increased tone and activity in such zones, effectively alleviating the bladder underactivity.
In some embodiments of the current invention, the pattern of ablation used to treat bladder underactivity may comprise a circumferential ablation line approximately at mid bladder height, with eight splines crossing the bladder dome (much like a sliced pizza would look like from above). This pattern may ensure the ureteral orifices and the trigone are spared, and may target the bladder dome which is most prone to over stretching and flaccidity (the lower parts of the bladder are limited by the pelvic organs).
A larger total ablation surface area may be expected to result with a greater reduction in post voiding residual volume, and may be more effective in treating underactive bladder. Thus, alternative patterns of bladder partitioning having a larger total ablation surface area may be preferable for treating underactive bladder. These patterns may include, but are not limited to, a pattern similar to that described above, having a greater number of longitudinal lines e.g., sixteen instead of eight, and/or a greater number of circumferential lines e.g. two instead of one.
In some embodiments of the current invention, the devices and techniques described may be used in conjunction with chemical agents that may be applied to the bladder following the ablations. In these embodiments, the ablation serves to remove the urothelial barrier over ablation lines, thus effectively targeting and facilitating the passage of chemical agents to the specific bladder wall areas beneath the ablations. In some embodiments, the chemical agent is botulinum toxin, and the end effect is reduced bladder activity (treating overactive bladder). In some embodiments, the chemical agent is Talc or a similar agent known to induce fibrosis, and the end effect is reduction in bladder volume and increase in bladder activity (treating underactive bladder). In some embodiments, the chemical agent is an inflammation inducing agent (biological foreign material or other irritative materials), to induce scarring. In some embodiments, the chemical agent applied is an acid or base, effectively thinning the bladder wall at the targeted (exposed) areas, to encourage the development of bladder diverticuli, to increase bladder compliance to treat overactive bladder.
In some embodiments of the current invention, the pattern of ablation described above (circumferential line and eight longitudinal splines) may be used to affix the bladder dome to the peritoneal cavity floor, effectively “capping” the bladder dome with thickened contracted tissue. This technique may be used to treat cystocele and/or to reduce symptoms of stress incontinence and/or reduce reflux of urine back to the ureters. The same effect may also be useful in the treatment of underactive bladders, by limiting the maximal volume of the bladder and increasing bladder tone (reducing bladder compliance).
In some embodiments, a mesh placed over the peritoneal part of the bladder may be used to achieve the same effect, using ablation, or optionally without using ablation at all. The mesh may be completely flat, or somewhat dome shaped to allow some flexibility of the bladder dome.
While preferred embodiments of the current disclosure have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the scope of the present disclosure. It should be understood that various alternatives to the embodiments described herein may be employed. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.
This application is a continuation of U.S. application Ser. No. 16/210,990, filed Dec. 5, 2018; which is a continuation of PCT Application No. PCT/US17/36212, filed Jun. 6, 2017; which claims the benefit of U.S. Provisional Application No. 62/346,095, filed Jun. 6, 2016; which applications are incorporated herein by reference in their entirety. The subject matter of this application is related to that of the following co-pending patent applications: PCT Application No. PCT/IB2016/000953, filed Jun. 10, 2016, and U.S. patent application Ser. No. 15/179,623, filed Jun. 10, 2016 both of which claim priority to U.S. Provisional Patent Application No. 62/174,296, filed Jun. 11, 2015, which applications are incorporated herein by reference. The subject matter of this application is also related to that of the following co-pending patent applications: PCT Application No. PCT/IB2014/003083, filed Nov. 25, 2014, which claims the benefit of U.S. patent application Ser. No. 14/519,933, filed Oct. 21, 2014, which is a continuation-in-part application of PCT Application Serial No. PCT/IB2013/001203, filed Apr. 19, 2013, which claims the benefit of U.S. Provisional Application Nos. 61/636,686, filed Apr. 22, 2012, and 61/649,334, filed May 20, 2012, and PCT Application No. PCT/IB2014/003083 also claims the benefit of U.S. Provisional Applications Nos. 61/908,748, filed Nov. 26, 2013, and 61/972,441, filed Mar. 31, 2014, which applications are incorporated herein by reference; and U.S. patent application Ser. No. 14/602,493, filed Jan. 22, 2015, which is a continuation of U.S. patent application Ser. No. 14/519,933, which applications are incorporated herein by reference.
| Number | Date | Country | |
|---|---|---|---|
| 62346095 | Jun 2016 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 16210990 | Dec 2018 | US |
| Child | 17953152 | US | |
| Parent | PCT/US17/36212 | Jan 0001 | US |
| Child | 16210990 | US |
