Patent Publication Number: US-10314651-B2

Title: Device and methods for renal nerve modulation monitoring

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of and claims priority to U.S. application Ser. No. 15/664,120, filed Jul. 31, 2017, which is a continuation of and claims priority to U.S. application Ser. No. 14/837,562, filed Aug. 27, 2015, now U.S. Pat. No. 9,861,435, which is a divisional of and claims priority to U.S. application Ser. No. 13/678,306, filed Nov. 15, 2012, now U.S. Pat. No. 9,119,600, which claims the benefit of priority under 35 U.S.C. § 119 to U.S. Provisional Application Ser. No. 61/560,026, filed Nov. 15, 2011, the disclosures of which are herein incorporated herein by reference in their entireties. 
    
    
     TECHNICAL FIELD 
     The present invention relates to methods and apparatuses for nerve modulation techniques such as ablation of nerve tissue or other destructive modulation technique through the walls of blood vessels and monitoring thereof. 
     BACKGROUND 
     Certain treatments require the temporary or permanent interruption or modification of select nerve function. One example treatment is renal nerve ablation which is sometimes used to treat hypertension and other conditions related to hypertension and 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 of the nerves running to the kidneys may reduce or eliminate this sympathetic function, which may provide 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 thus can be accessed intravascularly through the walls of the blood vessels. In some instances, it may be desirable to ablate perivascular renal nerves using a radio frequency (RF) electrode in an off-wall configuration. However, the electrode and/or temperature sensors associated with the device may not be able to detect tissue changes in the target region because the electrode is not in contact with the wall. Sensing electrodes may allow the use of impedance measuring to monitor tissue changes. It is therefore desirable to provide for alternative systems and methods for intravascular nerve modulation. 
     SUMMARY 
     The disclosure is directed to several alternative designs, materials and methods of manufacturing medical device structures and assemblies for performing and monitoring tissue changes. 
     Accordingly, one illustrative embodiment is a system for nerve modulation that may include an elongate shaft having a proximal end region and a distal end region. An ablation electrode and a first sensing electrode may be disposed on the elongate shaft adjacent to distal end region. The system may further include a ground pad. The ablation electrode, sensing electrode, and ground pad may be electrically connected to a control unit. 
     Another illustrative embodiment is a method for detecting tissue changes during tissue modulation. A tissue modulation system including an elongate shaft having a proximal end region and a distal end region may be provided. The modulation system may further include a first electrode disposed adjacent the distal end region and a second electrode disposed adjacent to the distal end region and spaced a distance from the first electrode. The modulation system may be advanced through a lumen such that the distal end region is adjacent to a target region. Voltage may be applied to the modulation system to impart a current between the first and second electrodes and an impedance of the target region may be calculated from the current. Voltage may be applied to at least one of the first or second electrodes to effect tissue modulation on the target region. The current between the first and second electrodes may be monitored for changes in the impedance of the target region. 
     The above summary of some example embodiments is not intended to describe each disclosed embodiment or every implementation of the invention. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The invention 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 schematic view illustrating a renal nerve modulation system in situ. 
         FIG. 2  illustrates a distal end of an illustrative renal nerve modulation system. 
         FIG. 3  illustrates a distal end of another illustrative renal nerve modulation system. 
         FIG. 4  illustrates a distal end of another illustrative renal nerve modulation system. 
         FIG. 5  illustrates a distal end of another illustrative renal nerve modulation system. 
         FIG. 6  is another illustrative view of the renal nerve modulation system of  FIG. 5 . 
         FIG. 7  illustrates a distal end of another illustrative renal nerve modulation system. 
     
    
    
     While the invention is amenable to various modifications and alternative forms, specifics thereof have been shown by way of example in the drawings and will be described in detail. It should be understood, however, that the intention is not to limit aspects of the invention 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 invention. 
     DETAILED DESCRIPTION 
     For the following defined terms, these definitions shall be applied, unless a different definition is given in the claims or elsewhere in this 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 dimensions, 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 may 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 invention. 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, it is contemplated that the devices and methods may be used in other applications where nerve modulation and/or ablation are desired. For example, the devices and methods described herein may also be used for prostate ablation, tumor ablation, and/or other therapies requiring heating or ablation of target tissue. In some instances, it may be desirable to ablate perivascular renal nerves with deep target tissue heating. As energy passes from a modulation element to the desired treatment region the energy may heat both the tissue and the intervening fluid (e.g. blood) as it passes. As more energy is used, higher temperatures in the desired treatment region may be achieved thus resulting in a deeper lesion. Monitoring tissue properties may, for example, verify effective ablation, improve safety, and optimize treatment time. 
     In some instances, ablation is performed with the modulation element in direct contact with the vessel or chamber wall. The modulation element may contain a thermistor or thermocouple which facilitates monitoring of the ablation progress by providing a real-time temperature signal. However, in some instances, it may be advantageous to move the modulation element away from the vessel wall in an off-the-wall configuration, such as when circumferential ablation is desired. During circumferential ablation, the modulation element may be positioned at the center of the lumen. However, when the modulation element does not contact the vessel wall it may be difficult to detect tissue changes during and/or after the ablation process. When provided in an off-the-wall configuration, the modulation element, and thus any temperature sensing means provided on or adjacent to the ablation electrode, may be cooled by the blood flow surrounding the modulation element. As such, thermal feedback may not be useful to provide monitoring as the ablation is performed, resulting in a “blind” ablation scenario. Although the ability to monitor the tissue properties during circumferential ablation may be reduced or require additional sensing elements, off-the-wall ablation may allow for free flow of blood across the vessel surface minimizing heat damage to the vessel wall due to the ablation process. 
     In some instances, impedance monitoring may be used to detect changes in target tissues as ablation progresses. Sensing electrodes may be provided in addition to the modulation element. In some instances, the impedance may not be directly measured, but may be a function of the current distribution between the sensing electrodes. In general, the resistance of the surrounding tissue may decrease as the temperature of the tissue increases until a point where the tissue begins to denature or irreversibly change, for example, at approximately 50-60° C. Once the tissue has begun to denature the resistance of the tissue may increase. As the target tissue is ablated, the change in impedance may be analyzed to determine how much tissue has been ablated. The power level and duration of the ablation may be adjusted accordingly based on the impedance of the tissue. 
       FIG. 1  is a schematic view of an illustrative renal nerve modulation system  10  in situ. System  10  may include an element  12  for providing power to a nerve modulation element disposed about and/or within a central elongate shaft  14  and, optionally, within a sheath or guide catheter  16 . A proximal end of element  12  may be connected to a control and power element  18 , which supplies the necessary electrical energy to activate the one or more modulation elements at or near a distal end of the element  12 . In some instances, return electrode patches  20  may be supplied on the legs or at another conventional location on the patient&#39;s body to complete the circuit. The control and power element  18  may include monitoring elements to monitor parameters such as power, temperature, voltage, pulse size, and/or shape and other suitable parameters as well as suitable controls for performing the desired procedure. In some instances, the power element  18  may control a radio frequency (RF) ablation electrode and/or one or more sensing electrodes. It is contemplated that more than one power element  18  may be provided. In some instances, the ablation electrode and the sensing electrode may be connected to separate power elements  18 . The ablation electrode may be configured to operate at a frequency of approximately 460 kHz. It is contemplated that any desired frequency in the RF range may be used, for example, from 100-500 kHz. However, it is contemplated that different types of energy outside the RF spectrum may be used as desired, for example, but not limited to ultrasound, microwave, and laser to perform the ablation. While the term ablation electrode is used herein, it is contemplated that the modulation element and modulation frequency may be selected according to the energy used to perform the ablation. For example, when ultrasound energy is used, an ultrasonic transducer may be selected as the modulation element and modulation frequencies may be in the MHz range. The sensing electrodes may be configured to operate over frequency ranges which are different from the frequency range at which the ablation is being performed. It is contemplated that the sensing electrodes may be operated over a range of frequencies for improved impedance measuring. 
       FIG. 2  is an illustrative embodiment of a distal end of a renal nerve modulation system  100  disposed within a body lumen  102  having a vessel wall  104 . The vessel wall  104  may be surrounded by additional body tissue  106 . A portion of the tissue  106  may be the desired treatment region  118 ,  120 , as will be discussed in more detail below. The system  100  may include an elongate shaft  108  having a distal end region  110 . The elongate shaft  108  may extend proximally from the distal end region  110  to a proximal end configured to remain outside of a patient&#39;s body. The proximal end of the elongate shaft  108  may include a hub attached thereto for connecting other treatment devices or providing a port for facilitating other treatments. It is contemplated that the stiffness of the elongate shaft  108  may be modified to form a modulation system  100  for use in various vessel diameters and various locations within the vascular tree. The elongate shaft  108  may further include one or more lumens extending therethrough. For example, the elongate shaft  108  may include a guidewire lumen and/or one or more auxiliary lumens. The lumens may be configured in any way known in the art. For example, the guidewire lumen may extend the entire length of the elongate shaft  108  such as in an over-the-wire catheter or may extend only along a distal portion of the elongate shaft  108  such as in a single operator exchange (SOE) catheter. These examples are not intended to be limiting, but rather examples of some possible configurations. While not explicitly shown, the modulation system  100  may further include temperature sensors/wire, an infusion lumen, radiopaque marker bands, fixed guidewire tip, a guidewire lumen, external sheath and/or other components to facilitate the use and advancement of the system  100  within the vasculature. 
     The system  100  may further include one or more ablation electrodes  112  disposed on the outer surface of the elongate shaft  108  adjacent the distal end region  110 . However, the ablation electrode  112  may be placed at any longitudinal location along the elongate shaft desired. While the system  100  is illustrated as including one ablation electrode  112 , it is contemplated that the modulation system  100  may include any number of ablation electrodes  112  desired, such as, but not limited to, two, three, four, or more. If multiple ablation electrodes  112  are provided, the ablation electrodes  112  may be longitudinally, radially and/or circumferentially spaced as desired. In some instances, the ablation electrode  112  may be a circumferential electrode extending around the outer perimeter of the elongate shaft  108 . A circumferential electrode  112  may allow for circumferential ablation while reducing and/or eliminating the need for circumferential repositioning of the electrode  112  and/or elongate shaft  108 . In some embodiments, the ablation electrode  112  may not extend all the way around the perimeter of the elongate shaft  108 . It is contemplated that multiple ablation electrodes  112  may be circumferentially positioned around the perimeter of the elongate shaft  108  to reduce and/or eliminate the need to circumferentially reposition the elongate shaft  108  to perform 360° ablation. 
     In some embodiments, the ablation electrode  112  may be formed of a separate structure and attached to the elongate shaft  108 . For example, the ablation electrode  112  may be machined or stamped from a monolithic piece of material and subsequently bonded or otherwise attached to the elongate shaft  108 . In other embodiments, the ablation electrode  112  may be formed directly on the surface of the elongate shaft  108 . For example, the ablation electrode  112  may be plated, printed, or otherwise deposited on the surface. In some instances, the ablation electrode  112  may sufficiently radiopaque so that it also functions as a radiopaque marker. The ablation electrode  112  may be formed from any suitable material such as, but not limited to, platinum, gold, stainless steel, cobalt alloys, or other non-oxidizing materials. In some instances, titanium, tantalum, or tungsten may be used. It is contemplated that the ablation electrode  112  may take any shape desired, such as, but not limited to, square, rectangular, circular, elliptical, etc. In some embodiments, the ablation electrode  112  may have rounded edges in order to reduce the affects of sharp edges on current density. The size of the ablation electrode  112  may be chosen to optimize the current density without increasing the profile of the modulation system  100 . For example, an ablation electrode  112  that is too small may generate high local current densities resulting in greater heat transfer to the blood and surrounding tissues. An ablation electrode  112  that is too large may require a larger elongate shaft  108  to carry it. In some instances, the ablation electrode  112  may have an aspect ratio of 2:1 (length to width) or greater. Such an elongated structure may provide the ablation electrode  112  with more surface area without increasing the profile of the modulation system  100 . 
     During the ablation procedure, the ablation electrode  112  may be positioned away from the vessel wall  104  in an off-the-wall configuration. While not explicitly shown, modulation system  100  may further include structure to maintain the ablation electrode  112  in the off-the-wall configuration. For example, in some instances, the elongate shaft may further include a positioning basket configured to expand and engage the vessel wall  104  to center the electrode  112 . In other embodiments, elongate shaft  108  may further include a partially occlusive balloon which may be used to position the ablation electrode  112  and/or to increase the blood velocity near the ablation electrode  112  to provide better vessel wall  104  cooling. It is further contemplated that the ablation electrode  112  and/or sensing electrodes  114 ,  116  may be positioned on a positioning basket and/or balloon. 
     The modulation system  100  may further include a proximal sensing electrode  114  and a distal sensing electrode  116 . The proximal sensing electrode  114  may be located proximal of the ablation electrode  112  and the distal sensing electrode  116  may be located distal of the ablation electrode  112 . In some embodiments, the distal sensing electrode  116  may be located proximal of the distal end  124  of the elongate shaft  108 . In other embodiments, the distal sensing electrode  116  may be adjacent to the distal end  124  of the elongate shaft  108 . While the system is illustrated as including two sensing electrodes  114 ,  116 , it is contemplated that fewer than or more than two sensing electrodes  114 ,  116  may be provided to improve or provide additional impedance information. In some embodiments, the sensing electrodes may be high-impedance sensing electrodes. This may minimize the field distortion during the measurement. However, in some instances, low-impedance sensing electrodes may be used. 
     The sensing electrodes  114 ,  116  may be used to monitor the impedance of the tissue separating them. Impedance sensing current  122  may pass between the proximal  114  and distal  116  sensing electrodes. For clarity, not all of the potential current paths  122  have been illustrated or numbered. For example, it is contemplated that some current may pass through the bloodstream between the sensing electrodes  114 ,  116 . As ablation of the target region  118 ,  120  progresses, the impedance properties of the surrounding tissue  118 ,  120  may change thus changing the impedance calculated between the proximal sensing electrode  114  and the distal sensing electrode  116 . The sensing electrodes  114 ,  116  may be symmetrically placed about the ablation electrode  112  such that they can easily track the change which occurs to the tissue impedance in the ablation zone  118 ,  120  located between them. This may provide improved signal-to-noise ratio for better real-time monitoring of the ablation progress. However, the sensing electrodes  114 ,  116  may be arranged in any orientation desired and need not be symmetrical about the ablation electrode  112 . While the sensing electrodes  114 ,  116  are illustrated in a non-contact ablation system  100  it is contemplated that the sensing electrodes  114 ,  116  may be used in systems where the ablation electrode  112  contacts the vessel wall  104 . 
     In some embodiments, the sensing electrodes  114 ,  116  may be formed of a separate structure and attached to the elongate shaft  108 . For example, the sensing electrodes  114 ,  116  may be machined or stamped from a monolithic piece of material and subsequently bonded or otherwise attached to the elongate shaft  108 . In other embodiments, sensing electrodes  114 ,  116  may be formed directly on the surface of the elongate shaft  108 . For example, the sensing electrodes  114 ,  116  may be plated, printed, or otherwise deposited on the surface. In some instances, the sensing electrodes  114 ,  116  may also function as radiopaque marker bands. The sensing electrodes  114 ,  116  may be formed from any suitable material such as, but not limited to, platinum, gold, stainless steel, cobalt alloys, or other non-oxidizing materials. In some instances, titanium, tantalum, or tungsten may be used. It is contemplated that the sensing electrodes  114 ,  116  may take any shape desired, such as, but not limited to, square, rectangular, circular, oblong, etc. The size of the sensing electrodes  114 ,  116  may be chosen to optimize the current density without increasing the profile of the modulation system  100 . 
     While not explicitly shown, the sensing electrodes  114 ,  116  may be connected to the control unit (such as control unit  18  in  FIG. 1 ) by electrical conductors. In some embodiments the sensing electrodes  114 ,  116  may be on a separate electrical circuit from the ablation electrode  112  and from each other. The sensing electrodes  114 ,  116  may be operated at a different frequency than the ablation electrode  112 . For example, the frequency, duty cycle, and shape of the excitation waveform of the sensing electrodes  114 ,  116  can be adapted to yield an optimized signal-to-noise ratio for each of the tissue parameters monitored. In some instances, the sensing electrodes  114 ,  116  may be operated simultaneously with the ablation electrode  112  to provide real-time feedback of the ablation progress. In other embodiments, the sensing electrodes  114 ,  116  may be operated in an alternating fashion (e.g. an ablation/sensing duty cycle) with the ablation electrode  112  such that the sensing electrodes  114 ,  116  and the ablation electrode  112  are not simultaneously active. 
     While not explicitly shown, the ablation electrode  112  may be connected to a control unit (such as control unit  18  in  FIG. 1 ) by electrical conductors. Once the modulation system  100  has been advanced to the treatment region, energy may be supplied to the ablation electrode  112 . The amount of energy delivered to the ablation electrode  112  may be determined by the desired treatment as well as the feedback obtained from the sensing electrodes  114 ,  116 . As discussed above, once the target tissue  118 ,  120  has begun to denature the resistance of the tissue may increase. The target region  118  nearest the ablation electrode  112  may receive more energy than the target region  120  positioned further away from the ablation electrode  112  and thus may begin to denature more quickly. As the target tissue  118 ,  120  is ablated, the change in impedance in the tissue  118 ,  120  may be analyzed to determine how much tissue has been ablated and/or the degree of denaturing. The power level and duration of the ablation may be adjusted accordingly based on the impedance of the tissue. For example, more energy may result in a larger, deeper lesion. 
     The modulation system  100  may be advanced through the vasculature in any manner known in the art. For example, system  100  may include a guidewire lumen to allow the system  100  to be advanced over a previously located guidewire. In some embodiments, the modulation system  100  may be advanced, or partially advanced, within a guide sheath such as the sheath  16  shown in  FIG. 1 . Once the ablation electrode  112  of the modulation system  100  has been placed adjacent to the desired treatment area, positioning mechanisms may be deployed, if so provided. While not explicitly shown, the ablation electrode  112  and the sensing electrodes  114 ,  116  may be connected to a single control unit or to separate control units (such as control unit  18  in  FIG. 1 ) by electrical conductors. Once the modulation system  100  has been advanced to the treatment region, energy may be supplied to the ablation electrode  112  and the sensing electrodes  114 ,  116 . As discussed above, the energy may be supplied to both the ablation electrode  112  and sensing electrodes  114 ,  116  simultaneously or in an alternating fashion at desired. The amount of energy delivered to the ablation electrode  112  may be determined by the desired treatment as well as the feedback provided by the sensing electrodes  114 ,  116 . 
     It is contemplated if an ablation electrode  112  is provided that does not extend around the entire circumference of the elongate shaft  108 , the elongate shaft  108  may need to be circumferentially repositioned and energy may once again be delivered to the ablation electrode  112  and the sensing electrodes  114 ,  116  to adequately ablate the target tissue. The number of times the elongate shaft  108  is rotated at a given longitudinal location may be determined by the number and size of the ablation electrode(s)  112  on the elongate shaft  108 . Once a particular location has been ablated, it may be desirable to perform further ablation procedures at different longitudinal locations. Once the elongate shaft  108  has been longitudinally repositioned, energy may once again be delivered to the ablation electrode  112 , and the sensing electrodes  114 ,  116 . If necessary, the elongate shaft  108  may be circumferentially repositioned at each longitudinal location. This process may be repeated at any number of longitudinal locations desired. It is contemplated that in some embodiments, the system  100  may include ablation electrodes  112  at various positions along the length of the modulation system  100  such that a larger region may be treated without longitudinal displacement of the elongate shaft  108 . 
     While  FIG. 2  illustrates the sensing electrodes  114 ,  116  in an off-the-wall configuration, is contemplated that one or both of the sensing electrodes  114 ,  116  may be placed in direct contact with the vessel wall  104 . As the sensing electrodes  114 ,  116  may be operated at a frequency and amplitude which does not result in tissue ablation, placing the sensing electrodes  114 ,  116  against the vessel wall  104  will not cause the vessel damage. In instances where direct contact ablation is acceptable, the ablation electrode  112  may also be placed in contact with the vessel wall  104 . It is contemplated that the elongate shaft  108  may further include an infusion lumen configured to perfuse the vessel lumen  102  with saline or other conductive fluid during the ablation procedure. In some instances, the perfused fluid may be provided at room temperature or cooler. 
       FIG. 3  is an illustrative embodiment of a distal end of a renal nerve modulation system  200  that may be similar in form and function to other systems disclosed herein. The modulation system may be disposed within a body lumen  202  having a vessel wall  204 . The vessel wall  204  may be surrounded by additional body tissues  206   a - f . There may be several different tissue types  206   a - f  surrounding the vessel wall  204 . For example, the tissues  206   a - f  may comprise adventitia and connective tissues, nerves, fat, fluid, etc. in addition to the muscular vessel wall  204 . It is contemplated that some of the body tissues  206   a - f  may be the same type of tissue or may be all different types of tissue. The body tissues  206   a - f  shown in  FIG. 3  is not intended to fully represent the tissue composition surrounding a vessel wall  204 , but rather illustrate that different tissue types and sizes may surround the vessel wall  204 . It is to be further understood that while  FIG. 3  illustrated the body tissues  206   a - f  on a single side of the vessel wall, the body tissues  206   a - f  may surround the perimeter of the vessel wall  204  and is not limited to one side. 
     Each of the different types of tissue  206   a - f  may have different electrical properties (e.g. impedance, permittivity, conductivity, etc.) and may also have different changes in those properties due to thermal ablation. Variation in local tissue types  206   a - f  and impedance may cause unpredictable variation in the ablation effect on the target tissue and in local artery wall heating. It may be desirable to characterize local tissues and monitor tissue changes in order to control the energy delivery for proper target tissue ablation. The nerve modulation system  200  may include two or more sensing electrodes  214 ,  216  to determine one or more impedance values over a range of frequencies. It is contemplated that tissue impedance may be monitored during RF, ultrasound, laser, microwave, or other ablation. The frequency at which the sensing electrodes  214 ,  216  are operated may be chosen according to the tissue material present or expected to be present. The impedance may be used to evaluate which type(s) of tissue are adjacent to the ablation region and to monitor changes which occur by thermal ablation of that tissue(s). 
     The system  200  may include an elongate shaft  208  having a distal end region  210  and a distal end  220 . The elongate shaft  208  may extend proximally from the distal end  220  to a proximal end configured to remain outside of a patient&#39;s body. The proximal end of the elongate shaft  208  may include a hub attached thereto for connecting other treatment devices or providing a port for facilitating other treatments. It is contemplated that the stiffness of the elongate shaft  208  may be modified to form modulation system  200  for use in various vessel diameters. The elongate shaft  208  may further include one or more lumens extending therethrough. For example, the elongate shaft  208  may include a guide wire lumen and/or one or more auxiliary lumens. The lumens may be configured in any suitable way such as those ways commonly used for medical devices. While not explicitly shown, the modulation system  200  may further include temperature sensors/wire, an infusion lumen, radiopaque marker bands, fixed guidewire tip, external sheath and/or other components to facilitate the use and advancement of the system  200  within the vasculature. 
     The system  200  may further include one or more ablation electrodes  212  disposed on the outer surface of the elongate shaft  208 . While the system  200  is illustrated as including a single ablation electrode  212 , it is contemplated that the modulation system  200  may include any number of ablation electrodes  212  desired, such as, but not limited to, two, three, four, or more. If multiple ablation electrodes  212  are provided, the ablation electrodes  212  may be longitudinally and/or radially spaced as desired. The ablation electrode  212  may include similar features and may function in a similar manner to the ablation electrode discussed with respect to  FIG. 2 . 
     During the ablation procedure, the ablation electrode  212  may be positioned away from the vessel wall  204  in an off-the-wall configuration. While not explicitly shown, the modulation system  200  may further include structure to maintain the ablation electrode  212  in the off-the-wall configuration. For example, in some instances the elongate shaft may further include a positioning basket configured to expand and engage the vessel wall  204  to center the electrode  212 . In other embodiments elongate shaft  208  may further include a partially occlusive balloon which may be used to position the ablation electrode  212  and/or to increase the blood velocity near the ablation electrode  212  to provide better vessel wall cooling. It is further contemplated that the ablation electrode  212  and/or sensing electrodes  214 ,  216  may be positioned on a positioning basket and/or balloon. 
     The modulation system  200  may further include a proximal sensing electrode  214  and a distal sensing electrode  216 . It is contemplated that the modulation system  200  may include more than two sensing electrodes  214 ,  216  to further refine the tissue evaluation. The sensing electrodes  214 ,  216  may include similar features and may function in a similar manner to the sensing electrodes discussed with respect to  FIG. 2 . In some instances, high impedance sensing electrodes  214 ,  216  may be used in order to avoid significant distortion of the electric field and to avoid bipolar ablation between the ablation electrode  212  and the sensing electrodes  214 ,  216 . The proximal sensing electrode  214  may be located proximal of the ablation electrode  212  and the distal sensing electrode  216  may be located distal of the ablation electrode  212 . In some embodiments, the distal sensing electrode  216  may be located adjacent to the distal end  220  of the elongate shaft  208 . In other embodiments, the distal sensing electrode  216  may be proximal of the distal end  220  of the elongate shaft  208 . 
     The sensing electrodes  214 ,  216  may be used to monitor the impedance of the tissue separating them. While not explicitly shown, the sensing electrodes  214 ,  216  may be connected through separate insulated conductors to a control unit (such as control unit  18  illustrated in  FIG. 1 ). In some embodiments the sensing electrodes  214 ,  216  may be on a separate electrical circuit from the ablation electrode  212 . The sensing electrodes  214 ,  216  may be operated at a different frequency than the ablation electrode  212 . For example, the frequency, duty cycle, and shape of the excitation waveform of the sensing electrodes  214 ,  216  can be adapted to yield an optimized signal-to-noise ratio for each of the tissue parameters monitored. When voltage is applied across the sensing electrodes  214 ,  216 , a small current  218  may flow through the tissues  206   a - f . For clarity, not all of the potential current paths  218  have been illustrated or numbered. For example, it is contemplated that some current may pass through the bloodstream in lumen  202 . The current  218  may be monitored by the control unit and used to determine the local tissue impedance in the vicinity of the sensing electrodes  214 ,  216 . Various frequencies may be used to determine one or more impedance values, or a simpler calculation of resistance at low frequently can be utilized. Tissue impedance may vary at different temperatures and may also be affected by protein changes, perfusion changes, and fluid changes as a result of thermal ablation. The different tissues have different electrical properties and also react differently to thermal ablation. The impedance measurements may be used to determine which tissues are in the local ablation region, and to monitor changes which occur by ablation of those tissues. The use of various frequencies may allow for better discrimination between tissue types and monitoring of ablative changes. Accordingly, ongoing impedance monitoring may be used to evaluate whether the modulation system  200  and positioned appropriately treat target tissue and determine when ablation has been completed. It is contemplated that undesired changes, such as ablative changes to the muscular vessel wall  204 , can also be detected. 
     Tissue impedance may be monitored during simultaneous RF ablation (e.g. energy is applied simultaneously to the ablation electrode  212  and the sensing electrodes  214 ,  216 ). In such a case, most of the current may flow between the ablation electrode  212  and a skin contact ground pad (such as ground contact pad  20  in  FIG. 1 ) and through the perivascular target tissues to be ablated, while a small amount of current may flow between the ablation electrode  212  and at least one higher impedance sensing electrode  214 ,  216 . In this instance, it is contemplated that body impedance between the ablation electrode  212  and skin contact ground pad may also be measured. It is further contemplated that tissue impedance may be monitored during ablation/sensing duty cycle which may be used alternate between ablation and impedance measurement. As ablation of the target region progresses, the impedance properties of the surrounding tissues  206   a - f  may change thus changing the impedance calculated between the proximal sensing electrode  214  and the distal sensing electrode  216 , between the ablation electrode  212  and the contact ground pad, and/or between the ablation electrode  212  and one or more sensing electrodes  214 ,  216 . 
     While not explicitly shown, the ablation electrode  212  may be connected to a control unit (such as control unit  18  in  FIG. 1 ) by electrical conductors. Once the modulation system  200  has been advanced to the treatment region, energy may be supplied to the ablation electrode  212 . The amount of energy delivered to the ablation electrode  212  may be determined by the desired treatment as well as the feedback obtained from the sensing electrodes  214 ,  216 . As discussed above, once the target tissue has begun to denature the electrical properties of the tissue may begin to change. As the target tissue is ablated, the change in impedance may be analyzed to determine how much tissue has been ablated. The power level and duration of the ablation may be adjusted accordingly based on the impedance of the tissue. In some instances, the modulation system  200  may monitor impedance values of the surrounding tissues  206   a - f  prior to beginning the ablation procedure and adjust the ablation parameters accordingly. It is further contemplated that other electrical properties of the tissues  206   a - f  such as permittivity and/or conductivity may be used to set the current and/or power for RF or other ablation energy to target tissues. 
     The modulation system  200  may be advanced through the vasculature in any manner known in the art. For example, system  200  may include a guidewire lumen to allow the system  200  to be advanced over a previously located guidewire. In some embodiments, the modulation system  200  may be advanced, or partially advanced, within a guide sheath such as the sheath  16  shown in  FIG. 1 . Once the ablation electrode  212  of the modulation system  200  has been placed adjacent to the desired treatment area, positioning mechanisms may be deployed, if so provided. While not explicitly shown, the ablation electrode  212  and the sensing electrodes  214 ,  216  may be connected to a single control unit or to separate control units (such as control unit  18  in  FIG. 1 ) by electrical conductors. Once the modulation system  200  has been advanced to the treatment region, energy may be supplied to the ablation electrode  212  and the sensing electrodes  214 ,  216 . As discussed above, the energy may be supplied to both the ablation electrode  212  in sensing electrodes  214 ,  216  simultaneously or in an alternating duty cycle at desired. The amount of energy delivered to the ablation electrode  212  may be determined by the desired treatment as well as the feedback provided by the sensing electrodes  214 ,  216 . 
     It is contemplated if an ablation electrode  212  is provided that does not extend around the entire circumference of the elongate shaft  208 , the elongate shaft  208  may need to be circumferentially repositioned and energy may once again be delivered to the ablation electrode  212  and the sensing electrodes  214 ,  216  to adequately ablate the target tissue ablation. The number of times the elongate shaft  208  is rotated at a given longitudinal location may be determined by the number and size of the ablation electrode(s)  212  on the elongate shaft  208 . Once a particular location has been ablated, it may be desirable to perform further ablation at different longitudinal locations. Once the elongate shaft  208  has been longitudinally repositioned, energy may once again be delivered to the ablation electrode  212 , and the sensing electrodes  214 ,  216 . If necessary, the elongate shaft  208  may be circumferentially repositioned at each longitudinal location. This process may be repeated at any number of longitudinal locations desired. 
     It is contemplated that in some embodiments, the system  200  may include ablation electrodes  212  at various positions along the length of the modulation system  200  such that a larger region may be treated without longitudinal displacement of the elongate shaft  208 . 
     While  FIG. 3  illustrates the sensing electrodes  214 ,  216  in an off-the-wall configuration, it is contemplated that one or both of the sensing electrodes  214 ,  216  may be placed in direct contact with the vessel wall  204 . As the sensing electrodes  214 ,  216  may be operated at a frequency and amplitude which does not result in tissue ablation, placing the sensing electrodes  214 ,  216  against the vessel wall  204  will not cause the vessel damage. In instances where direct contact ablation is acceptable, the ablation electrode  212  may also be placed in contact with the vessel wall  204 . It is contemplated that the elongate shaft  208  may further include an infusion lumen configured to perfuse the vessel lumen  202  with saline or other conductive fluid during the ablation procedure. In some instances, the perfused fluid may be provided at room temperature or cooler. 
       FIG. 4  is an illustrative embodiment of a distal end of a renal nerve modulation system  300  that may be similar in form and function to other systems disclosed herein. The modulation system  300  may be disposed within a body lumen  302  having a vessel wall  304 . The vessel wall  304  may be surrounded by local target tissue  306 . It may be desirable to determine local tissue impedance and monitor tissue changes in order to control the energy delivery for proper target tissue ablation. The nerve modulation system  300  may include a high-impedance sensing electrode  314  to determine local impedance. It is contemplated that tissue impedance may be monitored during RF, ultrasound, laser, microwave, or other ablation methods. 
     The system  300  may include an elongate shaft  308  having a distal end  310 . The elongate shaft  308  may extend proximally from the distal end  310  to a proximal end configured to remain outside of a patient&#39;s body. The proximal end of the elongate shaft  308  may include a hub attached thereto for connecting other treatment devices or providing a port for facilitating other treatments. It is contemplated that the stiffness of the elongate shaft  308  may be modified to form modulation system  300  for use in various vessel diameters. The elongate shaft  308  may further include one or more lumens extending therethrough. For example, the elongate shaft  308  may include a guide wire lumen and/or one or more auxiliary lumens. The lumens may be configured in any suitable way such as those ways commonly used for medical devices. While not explicitly shown, the modulation system  300  may further include temperature sensors/wires, an infusion lumen, radiopaque marker bands, fixed guidewire tip, external sheath and/or other components to facilitate the use and advancement of the system  300  within the vasculature. 
     The system  300  may further include one or more ablation electrodes  312  disposed on the outer surface of the elongate shaft  308 . While the system  300  is illustrated as including one ablation electrode  312 , it is contemplated that the modulation system  300  may include any number of ablation electrodes  312  desired, such as, but not limited to, two, three, four, or more. If multiple ablation electrodes  312  are provided, the ablation electrodes  312  may be longitudinally and/or radially and/or circumferentially spaced as desired. The ablation electrode  312  may include similar features and may function in a similar manner to the ablation electrode discussed with respect to  FIG. 2 . In some embodiments, the ablation electrode  312  may be positioned adjacent to the distal end  310  of the elongate shaft  308 . In other embodiments, the ablation electrode  312  may be positioned proximal of the distal end  310 . 
     The modulation system  300  may further include a sensing electrode  314 . It is contemplated that the modulation system  300  may include more than one sensing electrode  314  to further refine the tissue evaluation. The sensing electrode  314  may include similar features and may function in a similar manner to the sensing electrode discussed with respect  FIG. 2 . In some instances, a high impedance sensing electrode  314  may be used in order to avoid significant distortion of the electric field and to avoid bipolar ablation between the ablation electrode  312  and the sensing electrode  314 . In some embodiments, the sensing electrode  314  may be located proximal of the ablation electrode  312 . In other embodiments, the sensing electrode  314  may be located distal of the ablation electrode  312 . 
     The ablation electrode  312  and the sensing electrode  314  may be used to monitor the impedance of the local tissue  306 . While not explicitly shown, the ablation electrode  312  and the sensing electrode  314  may be connected through separate insulated conductors to a control unit (such as control unit  18  in  FIG. 1 ). A skin-contact ground pad  320  may also be connected through an electrical conductor  324  to the control unit. As voltage is applied to the ablation electrode  312 , current  322  may pass through the local tissue  306  and additional body tissue  318  to the ground pad  320 . During ablation, the sensing electrode  314  may be used as a reference electrode and measure the local voltage at a known location in the local tissue  306 , which may be monitored by the control unit. The local voltage may be used to determine the local tissue impedance between the ablation electrode  312  and the sensing electrode  314 . Various frequencies may be used to determine one or more impedance values, or a simpler calculation of resistance at low frequency can be utilized. 
     Tissue impedance may be monitored during simultaneous RF ablation (e.g. energy is applied simultaneously to the ablation electrode  312  and the sensing electrodes  314 ). In such a case, most of the current  322  may flow between the ablation electrode  312  and the skin-contact ground pad  320  and through the perivascular target tissues to be ablated, while a small amount of current  316  may flow between the ablation electrode  312  and the high impedance sensing electrode  314 . In this instance, the body impedance resulting from body tissue  318  outside of the target tissue region  306  between the ablation electrode  312  and skin contact ground pad  320  may also be measured. Tissue distribution and make-up may vary from patient to patient. For example, in some instances, a large portion of the power applied to the system  300  (e.g. approximately 80% in some cases) may be distributed locally, or within approximately two to three radii of in the ablation electrode  312 , while the remaining portion (e.g. approximately 20%) is distributed throughout the remainder of the body (e.g across the skin, subcutaneous fat, and/or other tissue not in the local target tissue  306 ). As the body composition may vary from person to person, the power distribution may also vary. The modulation system  300  may be configured to normalize the voltage supplied to the ablation electrode  312  to account for variations in impedance of the patient&#39;s body. It is contemplated that the local voltage (e.g. the difference between the voltage at the ablation electrode  312  and the voltage at the sensing electrode  314 ) may be used to determine the local power density (e.g. the power density adjacent to the ablation electrode  312 ). For example, the local power density may be determined by the Equation 1:
 
 P   loc   =IΔV   (1)
 
where P loc  is the local power density, I is the current, and ΔV is the difference between the voltage at the ablation electrode  312  and the voltage at the sensing electrode  314 . The local power density may then be used to adjust the power delivery of the system  300  to achieve the desired tissue modulation.
 
     It is further contemplated that tissue impedance may be monitored during an ablation/sensing duty cycle which may be used alternate between ablation and impedance measurements. As ablation of the target region progresses, the impedance properties of the local tissue  306  may change thus changing the impedance calculated between the ablation electrode  312  and the contact ground pad  320  and/or between the ablation electrode  312  and the sensing electrode  314 . It is contemplated that poor ground pad  320  contact may also be detected during the ablation process. 
     While not explicitly shown, the ablation electrode  312  may be connected to a control unit (such as control unit  18  in  FIG. 1 ) by electrical conductors. Once the modulation system  300  has been advanced to the treatment region, energy may be supplied to the ablation electrode  312 . The amount of energy delivered to the ablation electrode  312  may be determined by the desired treatment as well as the feedback obtained from the sensing electrodes  314 . Once the target tissue has begun to rise in temperature, and/or denature, the electrical properties of the tissue may begin to change. As the target tissue is ablated, the change in impedance may be analyzed to determine how much tissue has been ablated. The power level and duration of the ablation may be adjusted accordingly based on the impedance of the tissue. In some instances, the modulation system  300  may monitor impedance values of the surrounding tissue  306  prior to beginning the ablation procedure and adjust the ablation parameters accordingly. It is further contemplated that other electrical properties of the local tissue  306  such as permittivity and/or conductivity may be used to set the current and/or power for RF or other sources of ablation energy to target tissues. 
     The modulation system  300  may be advanced through the vasculature in any manner known in the art. For example, system  300  may include a guidewire lumen to allow the system  300  to be advanced over a previously located guidewire. In some embodiments, the modulation system  300  may be advanced, or partially advanced, within a guide sheath such as the sheath  16  shown in  FIG. 1 . Once the ablation electrode  312  of the modulation system  300  has been placed adjacent to the desired treatment area, positioning mechanisms may be deployed, if so provided. For example, in some embodiments, the elongate shaft  308  may include push and/or pull wires to deflect a distal end region of the elongate shaft  308 . For example, a push and/or pull wire may be attached adjacent to the distal end  310  of the elongate shaft  308  and then extend along an outer surface of the elongate shaft  308  or along an interior passageway formed in the shaft  308  to a position where it is accessible to a user. In other embodiments, the elongate shaft  308  may incorporate a planar deflection mechanism, such as a rib and spine mechanism. However, it is contemplated that the elongate shaft  308  may be deflected in any desired manner. The ablation electrode  312  and the sensing electrode  314  may be positioned adjacent to the deflectable region of the elongate shaft  308 . Deflection of the elongate shaft  308  may position the ablation electrode  312  adjacent a first target region and the sensing electrode  314  adjacent a second target region. 
     As discussed above, the ablation electrode  312  and the sensing electrode  314  may be connected to a control unit (such as control unit  18  in  FIG. 1 ) by insulated electrical conductors. Once the modulation system  300  has been advanced to the treatment region, energy may be supplied to the ablation electrode  312 . As discussed above, the energy may be supplied to both the ablation electrode  312  and/or the sensing electrode  314  simultaneously or in an alternating duty cycle as desired. The amount of energy delivered to the ablation electrode  312  may be determined by the desired treatment as well as the feedback provided by the sensing electrode  314 . 
     It is contemplated if an ablation electrode  312  is provided that does not extend around the entire circumference of the elongate shaft  308 , the elongate shaft  308  may need to be circumferentially repositioned and energy may once again be delivered to the ablation electrode  312  to adequately ablate the target tissue. The number of times the elongate shaft  308  is rotated at a given longitudinal location may be determined by the number and size of the ablation electrode(s)  312  on the elongate shaft  308 . Once a particular location has been ablated, it may be desirable to perform further ablation at different longitudinal locations. Once the elongate shaft  308  has been longitudinally repositioned, energy may once again be delivered to the ablation electrode  312 . If necessary, the elongate shaft  308  may be circumferentially repositioned at each longitudinal location. This process may be repeated at any number of longitudinal locations desired. It is contemplated that in some embodiments, the system  300  may include ablation electrodes  312  at various positions along the length of the modulation system  300  such that a larger region may be treated without longitudinal displacement of the elongate shaft  308 . 
     While  FIG. 4  illustrates the ablation electrode  312  and the sensing electrode  314  in direct contact with the vessel wall, it is contemplated that the ablation electrode  312  and/or the sensing electrode  314  may be positioned away from the vessel wall  304  in an off-the-wall configuration. While not explicitly shown, the modulation system  300  may further include structure to maintain the ablation electrode  312  in the off-the-wall configuration. For example, in some instances the elongate shaft may further include a positioning basket configured to expand and engage the vessel wall  304  to center the electrode  312 . In other embodiments elongate shaft  308  may further include a partially occlusive balloon which may be used to position the ablation electrode  312  and/or to increase the blood velocity near the ablation electrode  312  to provide better vessel wall cooling. It is contemplated that the elongate shaft  308  may further include an infusion lumen configured to perfuse the vessel lumen  302  with saline or other conductive fluid during the ablation procedure. In some instances, the perfused fluid may be provided at room temperature or cooler. 
       FIG. 5  is another illustrative embodiment of a distal end of a renal nerve modulation system  400  that may be similar in form and function to other systems disclosed herein. The modulation system  400  may be disposed within a body lumen  402  having a vessel wall  404 . The vessel wall  404  may be surrounded by local target tissue. It may be desirable to determine local tissue impedance and monitor tissue changes in order to control energy delivery for proper target tissue ablation. The nerve modulation system  400  may include a high-impedance or low-impedance sensing electrode  414  to determine local impedance in the target tissue and surrounding blood. It is contemplated that tissue impedance may be monitored during RF, ultrasound, laser, microwave, or other ablation methods. 
     The system  400  may include an elongate member  406  having an expandable framework  408  disposed adjacent the distal end region  410 . In some instances, the modulation system  400  may include an expandable balloon in place of the expandable framework  408 . It is further contemplated that the modulation system  400  may not include an expandable portion. The elongate member  406  may extend proximally from the distal end region  410  to a proximal end configured to remain outside of a patient&#39;s body. The proximal end of the elongate member  406  may include a hub attached thereto for connecting other treatment devices or providing a port for facilitating other treatments. It is contemplated that the stiffness of the elongate member  406  may be modified to form modulation system  400  for use in various vessel diameters. In some instances, the elongate member  406  may be a wire having a generally solid cross-section. In other embodiments, the elongate member  406  may include one or more lumens extending therethrough. For example, the elongate member  406  may include a guide wire lumen and/or one or more auxiliary lumens. The lumens may be configured in any suitable way such as those ways commonly used for medical devices. While not explicitly shown, the modulation system  400  may further include temperature sensors/wires, an infusion lumen, radiopaque marker bands, fixed guidewire tip, external sheath and/or other components to facilitate the use and advancement of the system  400  within the vasculature. 
     The system  400  may further include one or more ablation electrodes  412  disposed on the expandable framework  408 . The ablation electrodes  412  may be positioned on separate struts  432  of the expandable framework  408  such that the when the framework  408  is expanded the ablation electrodes  412  are positioned adjacent to opposite sides of the vessel wall  404 . While the system  400  is illustrated as including two ablation electrodes  412 , it is contemplated that the modulation system  400  may include any number of ablation electrodes  412  desired, such as, but not limited to, one, three, four, or more. If multiple ablation electrodes  412  are provided, the ablation electrodes  412  may be longitudinally and/or radially and/or circumferentially spaced as desired. In some instances, the ablation electrodes  412  may be positioned to be adjacent to opposite sides of the vessel  404 . The ablation electrodes  412  may include similar features and may function in a similar manner to the ablation electrode discussed with respect to  FIG. 2 . In some embodiments, the ablation electrodes  412  may be positioned proximal of the distal end region  410  of the elongate member  406 . In other embodiments, the ablation electrodes  412  may be positioned adjacent to the distal end region  410 . It is further contemplated that the ablation electrodes  412  may function as both ablation and sensing electrodes. 
     The modulation system  400  may further include a sensing electrode  414 . It is contemplated that the modulation system  400  may include more than one sensing electrode  414  to further refine the tissue evaluation. The sensing electrode  414  may include similar features and may function in a similar manner to the sensing electrode discussed with respect  FIG. 2 . In some instances, a high impedance sensing electrode  414  may be used in order to avoid significant distortion of the electric field and to avoid bipolar ablation between the ablation electrode  412  and the sensing electrode  414 . In other instances, a low-impedance sensing electrode  414  may be used. In some embodiments, the sensing electrode  414  may be located distal of the ablation electrodes  412  and adjacent to the distal end region  410 . In other embodiments, the sensing electrode  414  may be located proximal of the ablation electrodes  412 . 
     The ablation electrodes  412  and the sensing electrode  414  may be used to monitor the impedance of the local tissue. While not explicitly shown, the ablation electrode  412  and the sensing electrode  414  may be connected through separate insulated conductors to a control unit (such as control unit  18  in  FIG. 1 ). In some instances, the ablation electrodes  412  may be used as sensing electrodes to determine local tissue impedance. The ablation electrodes  412  may be spaced a distance from the sensing electrode  414  such that voltage applied to the electrodes  412 ,  414  may cause current to flow between the electrodes  412 ,  414  through the blood and nearby tissues. Measurement of the current may allow the resistance or complex impedance of the blood and tissue to be calculated. Various frequencies may be used to determine one or more impedance values, or a simpler calculation of resistance at low frequency can be utilized. 
     In some instances, it may be desirable to calculate the impedance of the blood or other fluid within the body lumen  402 . The modulation system may include a catheter shaft  416  including a lumen for perfusing saline or other fluid  418  with known conductivity into the body lumen  402 . In some instances, the perfused fluid  418  may be provided at room temperature or cooler. It is contemplated that multiple fluids and/or concentrations with known conductivity may be used. The impedance may be determined while the fluid  418  is being perfused. The difference between the impedance calculated with blood and the impedance calculated with the perfused fluid may be used to calculate the impedance of the blood. Referring to  FIG. 6 , which illustrates the current paths between various electrodes and ground pads, skin-contact ground pads  420  may also be connected through an electrical conductor to the control unit. As voltage is applied to the ablation electrodes  412 , current  430  may pass through the local tissue  422  and additional body tissue  428  to the ground pads  420 . Analysis of the impedance measurements between the ablation electrodes  412  and the sensing electrode  414  and between the ablation electrodes  412  and the ground pads  420  and/or between the sensing electrode  414  and the ground pads  420  may determine the tissue impedance in the local tissue  422  (e.g. target region) adjacent the electrodes  412 ,  414 . 
     Tissue impedance may be monitored during simultaneous RF ablation (e.g. energy is applied simultaneously to the ablation electrode  412  and the sensing electrodes  414 ). In such a case, most of the current  430  may flow between the ablation electrode  412  and the skin-contact ground pads  420  and through the perivascular target tissues to be ablated, while a small amount of current  424 ,  426  may flow between the ablation electrodes  412  and the sensing electrode  414 . As noted above, some of the current  424  will pass through the local tissue  422  while some of the current  426  will pass through the fluid in the body lumen  402  (e.g. blood or perfused fluid). The body impedance resulting from body tissue  428  outside of the local tissue  422  region between the ablation electrode  412  and skin contact ground pad  420  may also be measured. The impedance of the blood, local tissue  422 , and body tissue  428  may be used to properly adjust the RF energy applied for ablation of the target tissue. It is further contemplated that impedance of the blood, local tissue  422 , and body tissue  428  may be monitored during an ablation/sensing duty cycle which may be used alternate between ablation and impedance measurements. As ablation of the target region progresses, the impedance properties of the local tissue may change thus changing the impedance calculated between the ablation electrode  412  and the contact ground pad  420  and/or between the ablation electrodes  412  and the sensing electrode  414 . Multiple measurements between the electrodes  412 ,  414  and/or the ground pads  420  (with blood or perfused fluid  418 ) may account for the location of the system  400  and vessel geometry effects. It is contemplated that poor ground pad  420  contact may also be detected during the ablation process. 
     While not explicitly shown, the ablation electrodes  412  may be connected to a control unit (such as control unit  18  in  FIG. 1 ) by electrical conductors. Once the modulation system  400  has been advanced to the treatment region, energy may be supplied to the ablation electrodes  412 . The amount of energy delivered to the ablation electrodes  412  may be determined by the desired treatment as well as the feedback obtained from the impedance calculations. It is contemplated that the impedance of the blood, local tissue  422 , and body tissue  428  may be determined prior to and/or during the ablation procedure. Once the target tissue has begun to rise in temperature, and/or denature, the electrical properties of the tissue may begin to change. As the target tissue is ablated, the change in impedance may be analyzed to determine how much tissue has been ablated. The power level and duration of the ablation may be adjusted accordingly based on the impedance of the tissue. In some instances, the modulation system  400  may monitor impedance values of the surrounding tissue prior to beginning the ablation procedure and adjust the ablation parameters accordingly. It is further contemplated that other electrical properties of the local tissue such as permittivity and/or conductivity may be used to set the current and/or power for RF or other sources of ablation energy to target tissues. 
     The modulation system  400  may be advanced through the vasculature in any manner known in the art. For example, system  400  may include a guidewire lumen to allow the system  400  to be advanced over a previously located guidewire. In some embodiments, the modulation system  400  may be advanced, or partially advanced, within a guide sheath such as the sheath  16  shown in  FIG. 1 . Once the ablation electrodes  412  of the modulation system  400  have been placed adjacent to the desired treatment area, positioning mechanisms may be deployed, if so provided. For example, once the distal end region  410  has been placed adjacent to the target region, the catheter shaft  416  may be retracted and the framework  408  allowed to expand. It is contemplated that other known mechanisms may be used to deploy the framework  408 . For example, a stent or expandable balloon may be used to expand the framework  408 . It is further contemplated that the framework  408  may be formed of a shape-memory material, such as nitinol, such that additional structure is not necessary to expand the framework  408 . Expansion of the framework  408  may place the ablation electrodes  412  adjacent to the desired treatment region. 
     As discussed above, the ablation electrodes  412  and the sensing electrode  414  may be connected to a control unit (such as control unit  18  in  FIG. 1 ) by insulated electrical conductors. Once the modulation system  400  has been advanced to the treatment region, energy may be supplied to the ablation electrodes  412 . As discussed above, the energy may be supplied to both the ablation electrodes  412  and/or the sensing electrode  414  simultaneously or in an alternating duty cycle as desired. The amount of energy delivered to the ablation electrodes  412  may be determined by the desired treatment as well as the feedback provided by the sensing electrode  414 . 
     It is contemplated if an ablation electrode  412  is provided that does not extend around the entire circumference of the elongate member  406 , the elongate member  406  may need to be circumferentially and/or radially repositioned and energy may once again be delivered to the ablation electrodes  412  to adequately ablate the target tissue. The number of times the elongate member  406  is repositioned at a given longitudinal location may be determined by the number and size of the ablation electrodes  412  on the elongate member  406 . Once a particular location has been ablated, it may be desirable to perform further ablation at different longitudinal locations. Once the elongate member  406  has been longitudinally repositioned, energy may once again be delivered to the ablation electrodes  412 . If necessary, the elongate member  406  may be radially repositioned at each longitudinal location. This process may be repeated at any number of longitudinal locations desired. It is contemplated that in some embodiments, the system  400  may include ablation electrodes  412  at various positions along the length of the modulation system  400  such that a larger region may be treated without longitudinal displacement of the elongate member  406 . 
     While  FIG. 5  illustrates the sensing electrodes  414  in an off-the-wall configuration, it is contemplated that the sensing electrodes  414  may be in direct contact with the vessel wall  404 . As the sensing electrodes  414  may be operated at a frequency which does not result in tissue ablation, placing the sensing electrodes  414  against the vessel wall  404  will not cause vessel damage. In instances where direct contact ablation is acceptable, the ablation electrodes  412  may also be placed in contact with the vessel wall  404 . 
       FIG. 7  is another illustrative embodiment of a distal end of a renal nerve modulation system  500  that may be similar in form and function to other systems disclosed herein. The modulation system  500  may be disposed within a body lumen  502  having a vessel wall  504 . The vessel wall  504  may be surrounded by local target tissue. It may be desirable to determine local tissue impedance and monitor tissue changes in order to control energy delivery for proper target tissue ablation. The nerve modulation system  500  may include one or more high-impedance or low-impedance sensing electrodes  514 ,  516  to determine local impedance in the target tissue and surrounding blood. It is contemplated that tissue impedance may be monitored during unipolar or bipolar RF, ultrasound, laser, microwave, or other ablation methods. 
     The system  500  may include an elongate member  506  having an expandable framework  508  disposed adjacent the distal end region  510  may include similar features and may function in a similar manner to the expandable framework described with respect to  FIG. 5 . The elongate member  506  may extend proximally from the distal end region  510  to a proximal end configured to remain outside of a patient&#39;s body. The proximal end of the elongate member  506  may include a hub attached thereto for connecting other treatment devices or providing a port for facilitating other treatments. It is contemplated that the stiffness of the elongate member  506  may be modified to form modulation system  500  for use in various vessel diameters. In some instances, the elongate member  506  may be a wire having a generally solid cross-section. In other embodiments, the elongate member  506  may include one or more lumens extending therethrough. For example, the elongate member  506  may include a guide wire lumen and/or one or more auxiliary lumens. The lumens may be configured in any suitable way such as those ways commonly used for medical devices. While not explicitly shown, the modulation system  500  may further include temperature sensors/wires, an infusion lumen, radiopaque marker bands, fixed guidewire tip, external sheath and/or other components to facilitate the use and advancement of the system  500  within the vasculature. 
     The system  500  may further include one or more ablation electrodes  512  disposed on the expandable framework  508 . The ablation electrodes  512  may be positioned on separate struts  522  of the expandable framework  508  such that the when the framework  508  is expanded the ablation electrodes  512  are positioned adjacent to opposite sides of the vessel wall  504 . While the system  500  is illustrated as including two ablation electrodes  512 , it is contemplated that the modulation system  500  may include any number of ablation electrodes  512  desired, such as, but not limited to, one, three, four, or more. If multiple ablation electrodes  512  are provided, the ablation electrodes  512  may be longitudinally and/or radially and/or circumferentially spaced as desired. In some instances, the ablation electrodes  512  may be positioned to be adjacent to opposite sides of the vessel  504 . The ablation electrodes  512  may include similar features and may function in a similar manner to the ablation electrode discussed with respect to  FIG. 2 . In some embodiments, the ablation electrodes  512  may be positioned proximal of the distal end region  510  of the elongate member  506 . In other embodiments, the ablation electrodes  512  may be positioned adjacent to the distal end region  510 . It is further contemplated that the ablation electrodes  512  may function as both ablation and sensing electrodes. 
     The modulation system  500  may further include a pair of proximal sensing electrodes  514  and a pair of distal sensing electrodes  516 . It is contemplated that the modulation system  500  may include fewer than or more than four sensing electrodes  514 ,  516  to further refine the tissue evaluation. The sensing electrodes  514 ,  516  may include similar features and may function in a similar manner to the sensing electrodes discussed with respect  FIG. 2 . In some instances, high-impedance sensing electrodes  514 ,  516  may be used in order to avoid significant distortion of the electric field and to avoid bipolar ablation between the ablation electrodes  512  and the sensing electrodes  514 ,  516 . In other instances, low-impedance sensing electrodes  514 ,  516  may be used. The sensing electrodes  514 ,  516  may be symmetrically placed about the ablation electrodes  512  such that they can easily track the change which occurs to the tissue impedance in the ablation zone located between them. However, the sensing electrodes  514 ,  516  may be arranged in any orientation desired. The sensing electrodes  514 ,  516  may be in direct contact with the vessel wall  504 . As the sensing electrode  414  may be operated at a frequency which does not result in tissue ablation, placing the sensing electrodes  514 ,  516  against the vessel wall  504  will not cause vessel damage. In instances where direct contact ablation is acceptable, the ablation electrodes  512  may also be placed in contact with the vessel wall  504 . While  FIG. 7  illustrates the sensing electrodes  514 ,  516  in direct contact with the vessel wall, it is contemplated that the sensing electrodes  514 ,  516  may be positioned away from the vessel wall  504  in an off-the-wall configuration. 
     The ablation electrodes  512  and the sensing electrodes  514 ,  516  may be used to monitor the impedance of the local tissue. While not explicitly shown, the ablation electrodes  512  and the sensing electrodes  514 ,  516  may be connected through separate insulated conductors to a control unit (such as control unit  18  in  FIG. 1 ). The sensing electrodes  514 ,  516  may be spaced a distance from one another such that voltage applied to the sensing electrodes  514 ,  516  may cause current to flow between the sensing electrodes  514 ,  516  through the blood and nearby tissues. Measurement of the current may allow the resistance or complex impedance of the blood and tissue to be calculated. Various frequencies may be used to determine one or more impedance values, or a simpler calculation of resistance at low frequency can be utilized. 
     In some instances, it may be desirable to calculate the impedance of the blood or other fluid within the body lumen  502 . The modulation system may include a catheter shaft  518  including a lumen for perfusing saline  520  or other fluid with known conductivity into the body lumen  502 . In some instances, the perfused fluid  520  may be provided at room temperature or cooler. It is contemplated that multiple fluids and/or concentrations with known conductivity may be used. The impedance may be determined while the fluid  520  is being perfused. The difference between the impedance calculated with blood and the impedance calculated with the perfused fluid may be used to calculate the impedance of the blood. 
     While not explicitly shown, skin-contact ground pads may also be connected through an electrical conductor to the control unit. As voltage is applied to the ablation electrodes  512 , current may pass through the local tissue and additional body tissue to the ground pads. Analysis of the impedance measurements between the ablation electrodes  512  and the sensing electrodes  514 ,  516  and between the ablation electrodes  512  and the ground pads and/or between the sensing electrodes  514 ,  516  and the ground pads may determine the tissue impedance in the local tissue (e.g. target region) adjacent the electrodes  512 ,  514 ,  516 . 
     Tissue impedance may be monitored during simultaneous RF ablation (e.g. energy is applied simultaneously to the ablation electrodes  512  and the sensing electrodes  514 ,  516 ) or during an ablation/sensing duty cycle which may be used alternate between ablation and impedance measurements. The tissue impedance may be determined in a similar manner to that discussed with respect to other modulation systems described herein. As ablation of the target region progresses, the impedance properties of the local tissue may change thus changing the impedance calculated between the ablation electrodes  512  and the contact ground pad and/or between the ablation electrodes  512  and the sensing electrodes  514 ,  516 . Multiple measurements between the electrodes  512 ,  514 ,  516  and/or the ground pads (with blood or perfused fluid  520 ) may account for the location of the system  500  and vessel geometry effects. It is contemplated that poor ground pad contact may also be detected during the ablation process. 
     While not explicitly shown, the ablation electrodes  512  may be connected to a control unit (such as control unit  18  in  FIG. 1 ) by electrical conductors. Once the modulation system  500  has been advanced to the treatment region, energy may be supplied to the ablation electrodes  512 . The amount of energy delivered to the ablation electrodes  512  may be determined by the desired treatment as well as the feedback obtained from the impedance calculations. It is contemplated that the impedance of the blood, local tissue, and body tissue may be determined prior to and/or during the ablation procedure. Once the target tissue has begun to rise in temperature, and/or denature, the electrical properties of the tissue may begin to change. As the target tissue is ablated, the change in impedance may be analyzed to determine how much tissue has been ablated. The power level and duration of the ablation may be adjusted accordingly based on the impedance of the tissue. In some instances, the modulation system  500  may monitor impedance values of the surrounding tissue prior to beginning the ablation procedure and adjust the ablation parameters accordingly. It is further contemplated that other electrical properties of the local tissue such as permittivity and/or conductivity may be used to set the current and/or power for RF or other sources of ablation energy to target tissues. The modulation system  500  may be advanced through the vasculature in any manner known in the art such, but not limited to, those methods discussed with respect to other modulation systems described herein. Once the ablation electrodes  512  of the modulation system  500  have been placed adjacent to the desired treatment area, positioning mechanisms may be deployed, if so provided. For example, once the distal end region  510  has been placed adjacent to the target region, the catheter shaft  518  may be retracted and the framework  508  allowed to expand in similar manners to those discussed with respect to modulation system  400 . 
     As discussed above, the ablation electrodes  512  and the sensing electrodes  514 ,  516  may be connected to a control unit (such as control unit  18  in  FIG. 1 ) by insulated electrical conductors. Once the modulation system  500  has been advanced to the treatment region, energy may be supplied to the ablation electrodes  512 . As discussed above, the energy may be supplied to both the ablation electrodes  512  and/or the sensing electrodes  514 ,  516  simultaneously or in an alternating duty cycle as desired. The amount of energy delivered to the ablation electrodes  512  may be determined by the desired treatment as well as the feedback provided by the sensing electrodes  514 ,  516 . The modulation system  500  may be radially, longitudinally, and/or circumferentially repositioned and energy subsequently applied as many times as necessary to complete the desired ablation. The number of times the modulation system  500  is repositioned may be determined by the number and size of the ablation electrodes  512  on the elongate member  506 . 
     Those skilled in the art will recognize that the present invention 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 invention as described in the appended claims.