Patent Publication Number: US-2013231658-A1

Title: Expandable ablation device and methods for nerve modulation

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims priority under 35 U.S.C. §119 to U.S. Provisional Application Ser. No. 61/605,583, filed Mar. 1, 2012, the entirety of which is incorporated herein by reference. 
    
    
     TECHNICAL FIELD 
     The present disclosure relates to methods and apparatuses for modulating nerves through the walls of blood vessels. Such modulation may include ablation of nerve tissue or other modulation technique. 
     BACKGROUND 
     Certain treatments require temporary or permanent interruption or modification of select nerve functions. One example treatment is renal nerve ablation, which is sometimes used to treat conditions related to congestive heart failure. The kidneys produce a sympathetic response to congestive heart failure, which among other effects, increases the undesired retention of water and/or sodium. Ablating some nerves running to the kidneys may reduce or eliminate this sympathetic function, providing a corresponding reduction in the associated undesired symptoms. 
     Many nerves (and nervous tissue such as brain tissue), including renal nerves, run along the walls of or in close proximity to blood vessels and these nerves can be accessed intravascularly through the blood vessel walls. In some instances, it may be desirable to ablate perivascular renal nerves using a radio frequency (RF) electrode. Such treatment, however, may result in thermal injury to the vessel at the electrode and other undesirable side effects such as, but not limited to, blood damage, clotting, and/or protein fouling of the electrode. To prevent such undesirable side effects, some techniques attempt to increase the distance between the vessel walls and the electrode. In these systems, however, the electrode may inadvertently contact the vessel walls, causing irreparable damage. 
     Therefore, there remains room for improvement and/or alternatives in providing systems and methods for intravascular nerve modulation. 
     SUMMARY 
     The disclosure is directed to several alternative designs and methods of using medical device structures and assemblies. 
     Accordingly, some embodiments pertain to a medical device for nerve modulation through the wall of a blood vessel. The medical device includes an elongate member having a proximal end and a distal end. Further, a hollow ablation member is disposed at the distal end of the elongate member. The ablation member includes a number of electrodes positioned on its outer surface. In addition, the ablation member is configured to switch between a collapsed state and an expanded state such that that a portion of the ablation member may be brought into contact with a wall of a blood vessel. The ablation member may be self-expandable or expanded by an actuating means. For example, the ablation member may be implemented as a stent. The ablation member may further include an insulated section. The insulated section may cover the outer surface of the ablation member or may partially surround the electrodes. Alternatively, the ablation member may be made of a non-conductive material. The medical device may further include one or more sensors and the electrodes may be coupled to one or more conductors. 
     Some other embodiments pertain to a system for nerve modulation through the wall of a blood vessel. The system includes a sheath having a proximal end, a distal end, and a lumen extending from the proximal to distal end. An elongate member extends along a central elongate axis within the lumen of the sheath, the elongate member having a proximal end and a distal end. The system further includes an expandable hollow ablation member coupled to the distal end of the elongate member. The ablation member may include an insulating section, and a number of electrodes disposed on its outer surface. The ablation member may be configured to switch between a collapsed state, and an expanded state in which the ablation member extends out of the distal end of the sheath such that that a portion of the ablation member contacts the walls of the blood vessel. The ablation member is self-expandable or expanded by an actuating means. In one aspect, the ablation member may be a stent, or other hollow tubular member. In addition, the insulated section may cover the outer surface of the ablation member or partially surround the electrodes. Alternatively, the ablation member may be made of a non-conductive material. Also, the system may include one or more sensors. 
     Some embodiments pertain to a method for ablating a renal nerve through a blood vessel. The method includes advancing a medical device proximate to a desired location in a vessel lumen. The medical device includes an elongate member having a proximal end and a distal end. Further, a hollow ablation member is disposed at the distal end of the elongate member. The ablation member includes a number of electrodes positioned on its outer surface. In addition, the ablation member is configured to switch between a collapsed state, and an expanded state such that that a portion of the ablation member contacts the walls of the blood vessel. The method further includes deploying the expandable ablation member by reconfiguring the ablation member to its expanded state in the vessel lumen, and activating one or more electrodes to ablate at least a portion of the nerve tissue. 
     The summary of some example embodiments is not intended to describe each disclosed embodiment or every implementation of the disclosure. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The present disclosure may be more completely understood in consideration of the following detailed description of various embodiments in connection with the accompanying drawings, in which: 
         FIG. 1  is a cross-sectional side view of one embodiment of a renal nerve modulation system. 
         FIG. 2  is a sectional side view of one embodiment of an electrode used in the renal nerve modulation system. 
         FIG. 3  is a three dimensional view of an embodiment of a renal nerve modulation system with a stent having insulation on the stent. 
         FIG. 4A  is a three dimensional view of the renal nerve modulation system shown in  FIG. 1 , in an expanded state. 
         FIG. 4B  is a three dimensional view of the renal nerve modulation system shown in  FIG. 1 , in a collapsed state. 
         FIG. 5  illustrates an embodiment of the renal nerve modulation system shown in  FIG. 1 , disposed within a blood vessel in its expanded state. 
         FIG. 6  illustrates the distal portion of an embodiment of a renal nerve modulation system in its expanded state. 
     
    
    
     While specific embodiments of the present disclosure have been shown in the drawings and are discussed in detail below, the implementation of the disclosure is amenable to various modifications and alternative forms. It should therefore be understood that the intention is not to limit aspects of the disclosure to the particular embodiments described. On the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present disclosure. 
     DETAILED DESCRIPTION 
     For the following defined terms, these definitions shall be applied, unless a different definition is given in the claims or elsewhere in the specification. 
     All numeric values are herein assumed to be modified by the term “about,” whether or not explicitly indicated. The term “about” generally refers to a range of numbers that one of skill in the art would consider equivalent to the recited value (i.e., having the same function or result). In many instances, the term “about” may be indicative as including numbers that are rounded to the nearest significant figure. 
     The recitation of numerical ranges by endpoints includes all numbers within that range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, and 5). 
     Although some suitable dimension ranges and/or values pertaining to various components, features, and/or specifications are disclosed, one of skill in the art, incited by the present disclosure, would understand desired dimensions, ranges and/or values many of which will deviate from those expressly disclosed. 
     As used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the content clearly dictates otherwise. As used in this specification and the appended claims, the term “or” is generally employed in its sense including “and/or” unless the content clearly dictates otherwise. 
     The following detailed description should be read with reference to the drawings in which similar elements in different drawings are numbered the same. The detailed description and the drawings, which are not necessarily to scale, depict illustrative embodiments and are not intended to limit the scope of the disclosure. The illustrative embodiments depicted are intended only as exemplary. Selected features of any illustrative embodiment may be incorporated into an additional embodiment unless clearly stated to the contrary. 
     While the devices and methods described herein are discussed relative to renal nerve modulation for treatment of hypertension, it is contemplated that the devices and methods may be used in other applications where nerve modulation and/or ablation are desired. 
     The present disclosure provides methods and systems to ablate a renal nerve. To this end, the system may employ an expandable stent-like structure having electrodes on its outer surface. In general, the stent-like structure has a cylindrical shape and assumes a collapsed state during insertion and retrieval, and once deployed, the stent expands to contact the blood vessel walls. Electrodes may be positioned on the surface of the stent in a suitable manner, as desired. The self-expanding stent described in the present disclosure provides substantially uniform contact between the electrodes and the vessel wall. The term stent is used herein to indicate a tubular expandable structure that may be self-expanding or may be expanded by other means (e.g. a balloon) to a larger diameter; the term stent is not intended to reference the structures of the same name that may be implanted during angioplasty procedures and like procedures to expand an occluded blood vessel. 
       FIG. 1  is a cross-sectional view of an exemplary renal nerve modulation system  100  that includes an ablation member configured as a stent  102  and an elongate member  104 . The stent  102  includes a distal end  106 , a proximal end  108 , and a lumen  109  extending between the distal and proximal ends  106 ,  108 . Further, the elongate member  104  includes a proximal end  110 , and a distal end  112 , which is connected to the proximal end  108  of the stent  102 . For ablation purposes, one or more electrodes  114  may be mounted on the exterior surface of the stent  102 . 
     In general, the elongate member  104  may be a tubular member extending proximally from the proximal end of the stent  102 , the proximal end  110  of the elongate member  104  being configured to remain outside a patient&#39;s body. The proximal end of the elongate member  104  may include mechanisms for controlling the electrodes  114  or for facilitating various treatments. 
     The elongate member  104  may be made of any suitable biocompatible material such as polyurethane, plastic, or any other such material. Moreover, the elongate member  104  may be flexible along its entire length or adapted for flexure along portions of its length. Alternatively, the elongate member&#39;s distal end may be more flexible while the remaining member may be stiffer. Flexibility allows the elongate member  104  to maneuver in the circuitous vasculature, while stiffness allows the required force to be transmitted to urge the elongate member  104  forward. The diameter of the elongate member  104  may vary according to the desired application, but it is generally smaller than the typical diameter of a patient&#39;s vasculature. 
     The stent  102  along with the elongate member  104  may be configured to be advanced into a body lumen such as a renal artery to ablate body tissue (e.g., renal nerves or ganglia). The stent  102  is implemented as a hollow, elongate tube with cross-sectional configuration adapted according to a desired body lumen. In the illustrated embodiment, the stent  102  is generally circular, with a generally circular hollow interior lumen  109 . The interior lumen  109  may have an open distal end and/or an open proximal end. In some embodiments, the stent  102  has an open proximal end and an open distal end to allow for blood flow through the stent  102  when it is in an expanded state. In some embodiments the interior lumen  109  has a generally uniform cross-sectional area along the length of the stent. In one embodiment of the present disclosure, the stent  102  may have a diamond lattice or any suitable pattern. Further, stent  102  may have a uniform diameter along its length, or may be tapered at the distal end to allow convenient insertion within the body. Depending upon the particular implementation and intended use, the length of the stent  102  may vary. The diameter of the stent  102  may be tailored to the diameter of the body lumen. Similarly, depending upon the particular implementation and intended use, the stent  102  can be rigid along its entire length, flexible along a portion of its length, or configured for flexure at only certain specified locations. 
     The stent  102  may be implemented as an expandable device made of a smooth material that is sufficiently flexible to conform to the body lumen while at the same time being sufficiently rigid to position the electrodes  114  against the vessel wall with a uniform and gentle pressure. Once appropriately deployed, the stent  102  expands to conform to the blood vessel shape, facilitating appropriate positioning. The stent  102  may be self-expanding or may expand by known mechanisms. These expansion mechanisms are discussed in detail in the following section in connection with  FIGS. 4A and 4B . 
     The stent  102  may be made of any suitable material that is compatible with living tissue or a living system, non-toxic or non-injurious, and does not cause immunological reaction or rejection. Such materials may include, for example, polymers, nitinol, ePTFE, fabric, and suitable nickel and titanium alloys. For example, stent  102  can be made from polyurethane that is non-electrically conductive and biocompatible. In general, stent  102  may be formed of a material that is sufficiently flexible to conform to the bodily location in which it is employed, yet sufficiently rigid to maintain the integrity of lumen  109 . 
     One or more electrodes  114  may be attached to the outer surface of the stent  102 . In the illustrated embodiment, the electrodes  114  are an electrode (e.g., radio frequency electrode) configured as a cube or a cuboidal member having regular or irregularly outer surface. In other embodiments, the electrodes have a circular or oblong shape. In one embodiment, the stent  102  may be formed with recesses within which the electrodes  114  may be mounted. It should be understood that each of the electrodes  114  can be configured as a disc, a plate, a strut, a ring, or other suitable configuration, as desired. 
     The electrodes  114  may be disposed on the stent in any desired manner. For example, the electrodes  114  may be arranged in a staggered configuration or aligned around a circumference of the stent  102 . In addition, the number of electrodes may vary depending on the target area, and the condition being treated. For example, there may be two, three or more electrodes. As will be recognized, other number of electrodes  114  may also be contemplated. Further, electrodes  114  can be formed using any conductive, biocompatible material. Examples of suitable material include metals, alloys, conductive polymers, and conductive carbon. In one example arrangement of electrodes  114 , the electrodes are arranged to treat the vessel wall such that any longitudinally extending line drawn along the vessel wall in the area treated passes through the ablative zone of at least one electrode, and the plurality of electrodes  114  are also spaced from each other such that there are gaps between the ablative zones of the electrodes  114 . Such an arrangement may ensure that the generally longitudinally extending nerves along the renal artery are treated while avoiding undue weakening of the vessel wall. 
     In addition, a control and power element (not shown), located at the proximal end of the system  100 , may be coupled to the electrodes  114  through connectors  116  to provide the necessary electrical energy to activate the electrodes  114 . The connectors  116  may be conductive wires, for example. The electrodes  114  may be configured to operate at a frequency of approximately 460 kHz. It is contemplated that any desired frequency may be used, for example, in the RF range, from 450-500 kHz. However, it is also contemplated that different types of energy outside the RF spectrum may be used as desired, for example, but not limited to ultrasound, microwave, laser, and thermal energy. 
     Arrangement of electrodes  114  on the surface of the stent  102  may be optimized to produce the desired therapeutic ablative effect. Thus, the size, spacing, and placement of electrodes  114  will vary based on the application of RF energy to surrounding tissues. In one embodiment, electrodes  114  may be arranged to preclude overlap among the RF fields produced by the individual electrodes. That arrangement ensures a relatively uniform application of energy to the perivascular nerve tissues. 
     The electrodes  114  conduct electrical current pulses to stimulate nerve fibers, muscle fibers, or other body tissues. In one embodiment, the control element may control the activation, timing and electrical characteristics of the modulation system  100 . For example, the control element can, if desired, control one or more of the timing, frequency, strength, duration, and waveform of the pulses. In addition, the control element can selectively activate one or more electrodes  114  for stimulation. 
     In at least some embodiments, one or more sensors (depicted in  FIG. 1  by reference numeral  120 ) may be located on the outer surface of the stent  102  or proximate the electrodes  114 . These sensors may be connected to the control element or other monitoring device to monitor one or more conditions (e.g., pressure, temperature, or impedance) surrounding the stent  102 , the electrodes  114 , or the blood and/or luminal surface of the blood vessel proximate the site of ablation. 
     The embodiments of the present disclosure ensure that only target tissues are ablated and surrounding tissues are protected from thermal energy and provide thermal protection for blood. Different techniques may be employed by different embodiments of the present disclosure to achieve this purpose. In one embodiment of the present disclosure the stent  102  may be made of a non-conductive material that ensures that ablation energy is transferred only to tissue proximate the electrodes  114 . Suitable non-conductive materials may be used for manufacturing the stent  102 . For example, known polymers may be used such as polyurethane that is non-electrically conductive and biocompatible. 
     In another embodiment of the present disclosure, each electrode  114  may include an insulation layer between the electrode and the stent  102 .  FIG. 2  is a side cross-sectional view of an electrode  114  having an insulation layer  202 . As shown, the insulation layer  202  surrounds the electrode  114  to electrically isolate the electrode  114  from the stent  102  while leaving an exposed surface to allow the energy provided through the electrode  114  to ablate. An electrode  114  as shown in this figure will generally be mounted on a stent  102  with the exposed surface of the electrode  114  facing outwardly and such an electrode will also preferably be mounted so that the exposed surface can be positioned against the vessel wall in the treatment zone. 
       FIG. 3  illustrates an alternative embodiment of the renal nerve modulation system  300 . Here, the entire outer surface of the stent  102  may include an insulation layer  302 . In each of the embodiments shown in  FIGS. 2 and 3 , insulation may be provided by mechanisms known to those skilled in the art. Suitable material to manufacture the insulation layer  202 ,  302  may include Teflon, or other known polymers. The electrodes  114  are mounted on the insulation layer over the stent  102 . In this embodiment, the stent may be made from a conductive material such as stainless steel or nitinol and yet be kept electrically isolated from the electrodes  114 . 
     Another aspect of the present disclosure is that in some embodiments the element providing ablation is expandable in nature.  FIG. 4A  is a distal end of the renal nerve modulation system  100  in an expanded state, while  FIG. 4B  is a distal end of the system  100  in a collapsed or compressed state. For state change purposes, the embodiments of the present disclosure employ a sheath  402  for enclosing the stent  102 . 
     The sheath  402  may define a substantially circular hollow lumen, having a proximal end  406  and a distal end  404 , adapted to deploy the stent  102  within a patient&#39;s body. The sheath  402  exerts a radially inwardly directed pressure on the stent  102  keeping it in the compressed state, as shown in  FIG. 4B . Once the stent  102  exits the sheath  402 ; however, the pressure is released, and the stent  102  expands, as shown in 
       FIG. 4A . It will be understood that in such situations, the material and thickness of the sheath  402  is selected such that it is capable of withstanding a greater force than the force exerted by the stent  102  on the sheath  402 . If the sheath  402  material is too thin or too elastic, it may not be sufficient to hold the stent  102  in the compressed state and the stent  102  may expand within the sheath  402 . Alternatively, if the sheath  402  is too rigid or thick, it may not be able to traverse the circuitous vasculature path, causing injury to the vessel walls. Therefore a suitable material is preferably chosen with a thickness keeping both aspects in mind. 
     In another embodiment, one or more pull wires (not shown) are used to expand or collapse the stent. Pull wires may be attached to the stent&#39;s outer surface at one or more positions. In one embodiment, when a pull wire is pulled or pushed it exerts a force on the stent  102  in to keep the stent in a compressed state. When the pull string is released, the force is released allowing the stent  102  to expand. Moreover, means to pull, push, or release the pull wire may be provided at the proximal end of the system  100  allowing operators to easily expand or compress the stent  102 , as required. In addition, the amount of expansion and compression may also be controlled. 
     Various mechanisms to change the state of the stent  102  may be contemplated. In one embodiment, the stent  102  may be made from a self-expandable material. For example, such members may be formed of shape memory alloys such as Nitinol or any other self-expandable material commonly known in the art. 
     Alternative expansion mechanisms may be applied without departing from the scope of the present disclosure. The stent  102  may, for example, be expanded by an inflation mechanism that exerts an outward radial force on the stent  102  to expand it. Such inflating mechanism (not shown) may include one or more balloons inflated by fluids, or dilators. Other such inflating means may include springs, or levers. 
     The expansion of the stent  102  should be such that is does not damage the artery by exerting too large a force on the vessel walls. For example, each of the electrodes  114  may exert approximately 5-10 grams of force on the vessel wall, avoiding vessel damage. In some embodiments, the stent  102  may include visualization devices such as a camera. The stent  102  may be provided with a fluorescent dye to make it easier to visualize the extent of expansion. Further, the stent  102  may include a force or expansion-limiting component that prevents the stent  102  from expanding beyond a certain limit. For example, the diameter of the stent  102  may be maintained below 6-7 mm. Often, the expansion limit may be set during manufacture of the stent  102 . In general, operators may know the average size of renal arteries, and they may ensure that the stent  102  does not expand beyond the average artery size. 
     The expansion of the stent  102  may also assist in pushing the electrodes  114  against the vessel walls to provide effective ablation. For example, the diameter of the stent  102  may be sized such that when the stent  102  is fully expanded within the lumen of the vessel, the stent  102  exerts a force on the vessel wall to ensure generally uniform circumferential contact of the vessel wall, and thus urge the electrodes  114  against the luminal surface of the vessel wall. In other embodiments, the stent may be sized such that expansion of the stent  102  positions the electrodes  114  at a predetermined distance from the vessel wall to maintain the electrodes in spaced relationship with the vessel wall. 
     It should be noted that the stent  102  is designed for retraction from the patient&#39;s body after the treatment is concluded. To that end, the stent  102  reverses the procedure set out above, by first collapsing the stent body and then retracting it into sheath  402 , employing control wires or other suitable conventional means. 
       FIG. 6  illustrates the distal portion of an example embodiment of a renal nerve modulation system  600 . A stent  602  may include mounts  604  for affixed electrodes  606  thereon. The stent  602  may have a lattice-work pattern of interconnected struts  608  as shown or another suitable self-expanding pattern as is known in the art. The stent  602  may be biased to the expanded position shown and may be made from a resilient material such as described above. The stent  602 , particularly if electrically conductive, may be electrically isolated from the electrodes  606 . The mounts may be located at selected interstices of the struts  608  or may be located along an individual strut. The mounts may be annular as shown or may have another suitable shape to provide geometry for an electrode to be securely fixed thereto. In some contemplated embodiments, the stent  602  lacks mounts and the electrodes  606  are shaped to be fixed securely to the stent  602 . For example, an electrode may be provided with a Y-shaped groove to allow it to be securely fixed to an interstice of the illustrated stent  602 . Electrodes  606  are shown as having a circular pad  610  which contacts the vessel wall and a mounting portion  618 . Electrode  606  can be described as a smaller disc (pad  610 ) centered on a larger disc (mounting portion  618 ). It can be appreciated that pads of various sizes and shapes are contemplated. For example, electrodes may be provided that have oblong or oval shaped pads. Four electrodes  606  are shown. It can be appreciated that more or fewer electrodes may be included. For example, 3, 4, 5, 6, 7, 8, 9, 10 or more pads may be includes in various embodiments. The electrodes are preferably spaced from each other and distributed to provide good circumferential coverage. Each electrode may be connected to a power source by a conductor  612  such as a wire. The stent  602  may be provided with features such as slots  614  to allow the conductors  612  to be securely attached. The proximal end of the stent  602  is preferably securely attached to an elongate member  616  (the distal end of which is illustrated). In this embodiment, elongate member  616  is a tube having a lumen and the proximal ends of the stent  602  are fixed within the lumen and the conductors  612  extend through the lumen. The lumen may also include sufficient room for a guidewire. 
       FIG. 5  illustrates a method of ablating tissue using the renal nerve modulation system  100 , shown in  FIG. 1 . The system  100  may be introduced percutaneously as is conventional in the intravascular medicinal device arts. For example, a guidewire may be introduced percutaneously through a femoral artery and navigated to a renal artery using standard radiographic techniques. In the present method the sheath  402  is first introduced over the guide wire, after which the guide wire is withdrawn. Subsequently, the stent  102  is introduced into the sheath  402 . Alternatively, the sheath  402  carrying the stent  102  in the compressed state may be introduced over the guide wires. 
     Once the sheath  402  reaches the desired location proximate a vessel wall  502  where ablation is required, the sheath  402  may be retracted proximally to allow the stent  102  to expand or the stent  102  may be urged distally to extend beyond the distal end of the sheath  402 . In the shown embodiment the stent  102  expands to circumferentially contact the luminal surface of the vessel wall  502 . 
     The electrodes  114  may then be activated to ablate the desired nerve tissue. To allow ablation of only the target tissue while protecting surrounding tissue from thermal energy, the stent  102  may include varying configurations and may include means for selectively activating some of the electrodes. The electrodes  114  may be activated sequentially, simultaneously, or selectively, as desired. During this procedure, the system  100  may continuously monitor the temperature or impedance at the electrodes  114  and the vessel wall  502 . Known radiography techniques may be utilized to monitor the tissue being ablated. Once the tissue is sufficiently ablated, the sheath  402  may be advanced or the stent  102  retracted to compress the stent  102  within the sheath  402 , and subsequently the sheath  402  may be retrieved from the patient&#39;s body. 
     Those skilled in the art will recognize that the present disclosure may be manifested in a variety of forms other than the specific embodiments described and contemplated herein. Accordingly, departure in form and detail may be made without departing from the scope and spirit of the present disclosure as described in the appended claims.