A system and method for performing denervation procedures and determining their effectiveness.

Abstract

Described herein are systems and methods for performing and determining the effectiveness of a denervation procedure. Such systems include an excitation source, a controller, and a catheter including elements for delivering a first ablation therapy from a first longitudinal location along a biological lumen and for delivering a second ablation therapy from a second longitudinal location longitudinally spaced from the first longitudinal location. A sensing subsystem of the system senses neural activity from a third longitudinal location along the biological lumen and determines the effectiveness of at least one of the first or second ablation therapies.

Description

Technical Field

[0001] [Claiming Priority] This application claims priority to U.S. Provisional Patent Application No. 63 / 319,912, filed on March 15, 2022, entitled "METHODS AND SYSTEMS FOR MEASURING NEURAL ACTIVITY BETWEEN PAIR OF ABLATION SITES TO DETERMINE EFFICACY OF DENERVATION PROCEDURE", which is incorporated herein by reference.

[0002] [Technical Field] Embodiments of the present technology generally relate to techniques for performing denervation procedures and determining the efficacy of denervation procedures, and related systems and methods.

Background Art

[0003] The human nervous system provides sensing of the environment (vision, skin sensation, etc.) and regulation of skeletal muscles, and includes both the somatic nervous system, which is largely under voluntary control, and the autonomic nervous system, which primarily regulates the activity of internal organs, functions to adapt the body to current needs, and is largely not under voluntary control. The autonomic nervous system involves both afferent or sensory nerve fibers that can mechanically and chemically sense organ conditions, and efferent fibers that transmit the response of the central nervous system (sometimes referred to as a reflex arc) to the sensed condition information. In some cases, the somatic nervous system is also affected, such as triggering vomiting or coughing in response to sensed conditions.

[0004] Accordingly, regulation of organs in the human body can be somewhat characterized and controlled by monitoring and influencing the neural reflex arcs that drive organ activity. For example, renal nerves leading to the kidneys often trigger larger reflex responses than desired, which can contribute significantly to hypertension. Therefore, measurement of nerve activity near the kidneys, followed by ablation of renal nerves, can be used to control overstimulation of the nervous system to the kidneys, and improve the function of the kidneys and the entire body.

[0005] Therefore, since the proper functioning of the nervous system is a crucial part of proper organ function, it is desirable to be able to monitor and alter the function of the human nervous system, and to characterize and modify the nervous system regulation of human viscera.

[0006] A new medical therapy is being practiced that involves inserting a catheter into the body at a predetermined anatomical location and transmitting destructive means to the nerves via the catheter (which can be rephrased as a probe) to irreversibly damage the surrounding tissue. The goal is to modulate (e.g., abolish) the nerve function at the specified anatomical location. As a result, abnormally functioning physiological processes can be terminated or returned to normal. Unfortunately, such medical therapies are not always successful because it is not possible to assess whether nerve activity has been successfully abolished. Alternative objectives may include increasing or adjusting physiological processes to abnormal ranges.

[0007] One example is renal nerve ablation, also known as renal denervation, used to reduce hypertension. Various studies have confirmed the relationship between renal nerve activity and blood pressure regulation. In various renal ablation procedures, a catheter is introduced into the arterial vascular system of a hypertensive patient and advanced into the renal artery. Renal nerves are located within the arterial wall and / or in the region adjacent to the artery. Destructive means are delivered close to the renal artery wall to the extent intended to cause destruction of renal nerve activity. Destructive means include energy such as radiofrequency (RF), microwave, cryotherapy, ultrasound, optics, lasers, or chemicals. The goal is to eliminate renal nerve activity. Such nerve activity is an important factor in the development and / or maintenance of hypertension, and eliminating nerve activity reduces the burden on blood pressure and medication.

[0008] Unfortunately, not all patients respond favorably to this therapy. Renal nerve ablation procedures are often ineffective due to potentially insufficient probe / tissue interface. Consequently, an insufficient amount of destructive agent is delivered to nerve fibers transmitted along the renal artery. One reason is that the delivery of the destructive agent to the arterial wall lacks a feedback mechanism for evaluating the effectiveness of the destruction of nerve activity. As a result, an insufficient amount of destructive agent is delivered, and nerve activity is not eliminated. Therefore, it is beneficial for clinicians to have an improved method of monitoring the integrity of nerve fibers passing through the arterial wall to confirm the destruction of nerve activity before discontinuing the therapy. Current techniques for the destruction of nerve activity do not provide practitioners with a feedback mechanism to detect when the desired destruction of nerve activity has been achieved. Neurodestructive agents are applied empirically without knowing that the desired effect has been achieved.

[0009] It is known that renal nerve ablation with sufficient energy can effectively lower both systolic and diastolic blood pressure. Current methods are considered open-loop from an engineering standpoint; that is, methods used to effectively denervate the kidneys do not employ any method for measuring the results of the applied ablation energy in an acute clinical setting. The effects of the procedure are only known after such energy application and a certain period of time (3-12 months). [Overview of the project]

[0010] A particular embodiment of this technology relates to a system for performing a denervation procedure and determining its effectiveness. According to a particular embodiment, such a system comprises a catheter including an element or first and second elements configured to selectively deliver ablation therapy, and one or more sensing electrodes configured to selectively sense nerve activity. The system also comprises an excitation source configured to selectively supply energy to the element or the first and second elements of the catheter, thereby delivering ablation therapy to the element or the first and second elements. Additionally, the system comprises a sensing subsystem electrically coupled to at least one sensing electrode. The system further includes a controller communicatively coupled to the catheter, the excitation source, and the sensing subsystem. According to a particular embodiment, the controller is configured such that the excitation source supplies energy to the element or first element, thereby delivering a first ablation therapy, while the element or first element is located in a first longitudinal location along a biological lumen. The controller is configured such that an excitation source supplies energy to an element or a second element, thereby delivering a second ablation therapy, while the element or second element is located at a second longitudinal location along a biological lumen longitudinally separated from a first longitudinal location. The controller is further configured such that a sensing subsystem senses neural activity from a third longitudinal location, and uses at least one of one or more sensing electrodes to determine the effectiveness of at least one of the first or second ablation therapies.

[0011] A particular embodiment of the present technology relates to a method for performing a denervation procedure and determining its effectiveness. Such a method may include delivering a first ablation therapy from a first longitudinal location along a biological lumen, and delivering a second ablation therapy from a second longitudinal location longitudinally separated from the first longitudinal location along the biological lumen. The method further includes sensing neural activity from a third longitudinal location longitudinally located between the first and second longitudinal locations, where the first or second ablation therapy has been delivered, and determining the effectiveness of at least one of the first or second ablation therapy.

[0012] According to a particular embodiment, the method includes delivering a first ablation therapy from a first longitudinal location along a biological lumen, delivering a second ablation therapy from a second longitudinal location longitudinally separated from the first longitudinal location along a biological lumen, and delivering stimulating energy using electrodes located at a third longitudinal location along a biological lumen, the third longitudinal location being one of those that are proximal or distal to both the first and second longitudinal locations. The method also includes sensing an evoked neuronal response to the stimulating energy using further electrodes located at a fourth longitudinal location along a biological lumen, the fourth longitudinal location being one of the other that is proximal or distal to both the first and second longitudinal locations. The method further includes determining, based on the sensed evoked neuronal response, whether further ablation therapy needs to be delivered from a location along the longitudinal length of the biological lumen.

[0013] This abstract is not intended to provide a complete description of the embodiments of the Art. Other features and advantages of the embodiments of the Art will appear in the following description, in conjunction with the accompanying drawings and claims, in which preferred embodiments are shown in detail. [Brief explanation of the drawing]

[0014] [Figure 1]This figure illustrates a kidney receiving blood via the abdominal aorta, the renal artery, and branching vessels.

[0015] [Figure 2] This is a cross-section of the renal artery, which is used to explain the various layers of the renal artery wall and nerves.

[0016] [Figure 3] This figure illustrates a method of delivering ablation therapy to a treatment area as part of a denervation procedure using a transducer inside the renal artery, and is used to explain why it is difficult to determine the efficacy of such a denervation procedure.

[0017] [Figure 4] This figure illustrates an improved technique for determining the efficacy of a denervation procedure, which involves performing neurolysis at two longitudinal locations along the renal artery and sensing intrinsic or evoked neural responses at a longitudinal location between the two neurolysis sites.

[0018] [Figure 5] This figure illustrates expected sensed neural activity in the three regions (labeled A, B, and C in FIG. 4) after the denervation procedure described with reference to FIG. 4.

[0019] [Figure 6] This is a high-level flow diagram used to summarize a method of performing a denervation procedure and determining its efficacy in accordance with certain embodiments of the present technology.

[0020] [Figure 7A] This shows an exemplary catheter having two selectively deployable electrodes in an undeployed position.

[0021] [Figure 7B] This shows the catheter with two selectively deployable electrodes in their deployed positions introduced in FIG. 7A.

[0022] [Figure 8] It is a schematic diagram of an exemplary system according to an embodiment of the present technology for interfacing with a patient's arterial nerve.

[0023] [Figure 9A] It illustrates exemplary cross-sections of a portion of the shaft of the catheter shown in FIGS. 7A and 7B. [Figure 9B] It illustrates exemplary cross-sections of a portion of the shaft of the catheter shown in FIGS. 7A and 7B.

[0024] [Figure 10] It illustrates exemplary details of the fluid supply subsystem introduced in FIG. 8.

[0025] [Figure 11A] It respectively illustrates a longitudinal cross-sectional view and a radial cross-sectional view of the transducer of the exemplary catheter shown in FIGS. 7A and 7B. [Figure 11B] It respectively illustrates a longitudinal cross-sectional view and a radial cross-sectional view of the transducer of the exemplary catheter shown in FIGS. 7A and 7B. DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

[0026] The following detailed description of exemplary embodiments refers to specific exemplary embodiments with reference to drawings or illustrations. These embodiments are described in sufficient detail to enable a skilled in the art to practice what is described and to illustrate how elements of these examples apply to various purposes or embodiments. Other embodiments exist and logical, mechanical, electrical, and other modifications may be made. Features or limitations of the various embodiments described herein are important to the exemplary embodiments in which they are incorporated, but do not limit other embodiments, and references to elements, operations, and applications of the examples are for the sole purpose of defining these exemplary embodiments. Features or elements shown in the various embodiments described herein may be combined in ways other than those shown in the embodiments, and such combinations are expressly considered to be within the scope of the embodiments shown herein. Accordingly, the following detailed description does not limit the scope of the claims.

[0027] Modification of the manipulation of the nervous system to characterize nerve signals may, in some cases, involve introducing a catheter (which can be rephrased as a probe) into the body at a specific anatomical site, and using the probe to destroy nerve tissue in an area near the probe, resulting in partial destruction or resection of nerves. By reducing nerve function at a selected site, abnormally functioning physiological processes can often be modulated back to a normal range. It may also be possible to modulate nerve function to intentionally induce abnormally functioning physiological processes that are beneficial to the patient.

[0028] Unfortunately, estimating the degree of nerve activity reduction is typically very difficult, and performing procedures where it is desirable to remove all nerves, or to remove some but not all nerves to restore the nervous system's response to the desired range without completely destroying it, is challenging. Denervation procedures can be used, for example, to perform renal nerve ablation to treat hypertension.

[0029] As illustrated in Figure 1, the kidney 102 receives blood via the abdominal aorta 106, the renal artery 104, and the branching vessels 108. The renal sympathetic nerves, also called sympathetic renal nerves, generally run along the abdominal aorta 106 and the renal artery 104, enabling transmission between the brain and the kidney 102. The renal sympathetic nerves include both afferent sensory renal nerves that carry nerve impulses from the kidney 102 to the brain, and efferent sympathetic renal nerves that transmit nerve impulses from the brain to the kidney 102. In other words, the efferent renal nerves 104 following the renal artery carry impulses from the brain to the kidney 102. In contrast, the afferent renal nerves following the renal artery carry impulses from the kidney 102 to the brain.

[0030] As illustrated in Figure 2, a cross-section of the renal artery 104, the renal artery wall is composed of multiple layers, including the intima 203 containing an inner monolayer of endothelial cells, the media 205 in the center of the arterial wall, and the adventitia 204, which is the outer layer. The renal nerves 208 within the adventitia 204, on the surface of the renal artery 104, and adjacent to the renal artery 104 are also shown. The renal nerves 208 surround the renal artery 104. Different individuals have renal nerves 208 in different locations around the renal artery 104. Therefore, the renal nerves 208 can be at different radial distances R from the central axis A of the renal artery 104, and can also be in different locations around the renal artery 104. It is not practical to locate the renal nerves by referring to anatomical landmarks. Furthermore, it is difficult or impossible to locate individual renal nerves 208 using common in vivo imaging techniques.

[0031] As explained in the background above, renal nerve ablation (also known as renal denervation) can be used to treat hypertension. Various studies have confirmed that renal nerve activity is associated with hypertension and that renal nerve ablation can improve renal function and lower hypertension. In a typical procedure, a catheter (also known as a probe) is introduced into the arterial vascular system of a hypertensive patient and advanced into the renal artery 104. In renal nerve denervation, the renal nerve 208 located in the arterial wall and the region adjacent to the renal artery 104 is resected by destructive means such as radiofrequency (RF) energy, microwave energy, ultrasound energy, pulsed electric field energy, cryotherapy, laser, or chemicals to limit renal nerve activity and thereby lower the patient's hypertension. The destructive means used to perform such renal denervation may be a transducer located on the distal portion of the catheter inserted into the renal artery 104. Much of the remaining discussion assumes that the transducer is an ultrasonic transducer capable of operating to deliver unfocused ultrasonic energy radially outward to suitably heat and treat tissue within a target anatomical region surrounding the renal artery 104. Such a transducer can operate at a frequency, duration, and energy level suitable for treating the target tissue. In one non-limiting example, the unfocused ultrasonic energy generated by the transducer may target selected nerve tissue of the subject and heat such tissue in a manner that neuromodulates the nerve tissue (e.g., by complete or partial excision, necrosis, or stimulation). Those skilled in the art will recognize that other mechanisms may be used to denervate nerve tissue. Non-limiting examples of other mechanisms used to perform renal denervation procedures include, but are not limited to, RF energy, microwave energy, pulsed electric field energy, chemicals, light energy, lasers, and / or cryotherapy.

[0032] Referring now to Figure 3, this is similar to Figure 1 in that it shows the abdominal aorta 106, the renal artery 104, and the kidney 102 receiving blood via the branching vessels 108, with the same labels used in Figure 3 as in Figure 1. Figure 3 also shows a catheter 302 with a transducer 311 located on the distal portion of the catheter 302, the distal portion of the catheter 302 including the transducer 311 being inserted into the renal artery 104. Although not shown in Figure 3, the transducer 311 may (or may not) be located within the balloon, and details of such examples are described below with reference to Figures 7A and 7B. In Figure 3, the dashed cylindrical region labeled 312 indicates an exemplary denervation area, where the portion of the renal artery 104 labeled A is proximal or upstream of the treatment area 312, and the portion of the renal artery labeled B is distal or downstream of the treatment area 312. The actual denervation area may differ from the dashed cylindrical area labeled 312.

[0033] Denervation can be performed by using transducer 311 to perform ablation therapy and emitting ultrasonic ablation energy into the treatment area 312. Alternatively or additionally, other means for performing ablation therapy of denervation can be used, such as emitting RF energy, pulsed electric field energy, or microwave ablation energy, but not limited to these. Alternatively or additionally, denervation can be performed using other means for providing ablation therapy, such as chemical, optical, laser, and / or cryotherapy. After such a denervation, it would be useful to determine the effectiveness of the denervation to determine whether the denervation was successful and can therefore be completed, and also to determine, for example, whether further ablation therapy needs to be delivered because the denervation was unsuccessful or incomplete.

[0034] Before performing such a denervation procedure, pre-dermal nerve activity (rephrased as baseline nerve activity) can be sensed using the same catheter 302 or a separate catheter. By comparing this pre-dermal activity with post-dermal activity, it is possible to determine whether the denervation procedure was successful, whether the procedure can be completed, or whether additional ablation energy (or other types of ablation therapy) needs to be delivered. Furthermore, even if pre-dermal nerve activity (rephrased as baseline nerve activity) is not sensed, sensing post-dermal activity may still be useful for determining whether the denervation procedure was successful, and therefore can be completed, or whether additional ablation energy (or other types of ablation therapy) needs to be delivered. Nerve activity can be sensed using electrodes on a catheter, which may be the same catheter 302 or a separate catheter. Such electrodes can be positioned within the treatment area 312, upstream of the treatment area 312, or downstream of the treatment area 312. Nerve activity sensed using such electrodes is intrinsic nerve activity, and is sometimes alternatively referred to as spontaneous nerve activity. Alternatively, or additionally, the neural activity sensed using such electrodes may be an evoked neural response in response to stimulating energy delivered using additional electrodes of a catheter inserted into the renal artery 104.

[0035] If, after the ablation energy (or other type of ablation therapy) has been delivered to the treatment area 312, one or more electrodes used to sense nerve activity are positioned in area A of Figure 3, which is proximal (i.e., upstream) of the treatment area 312 within the renal artery 104, it may be difficult to determine the effectiveness of the denervation procedure because, even if the target renal nerve within the treatment area 312 is sufficiently destroyed, nerve activity from efferent renal nerves attempting to carry nerve impulses from the brain to the kidney 102 may be detected by the electrodes located proximal (i.e., upstream) of the treatment area 312. If one or more electrodes used to sense nerve activity are instead positioned in region B in Figure 3, i.e., distal (i.e., downstream) of the treatment area 312 within the renal artery 104, it may become difficult to determine the effectiveness of the denervation procedure because, even if the target renal nerve within the treatment area 312 is sufficiently destroyed, nerve activity from afferent renal nerves attempting to carry nerve impulses from the kidney 102 towards the brain may be detected by the electrodes located distal (i.e., downstream) of the treatment area 312. More generally, the discussion in Figure 3 is used to explain why, when you want to destroy nerves within a specific length or segment of a biological lumen (e.g., a renal artery) as part of a denervation procedure, it is often difficult to know whether the nerve destruction was sufficient for the denervation procedure to be considered complete.

[0036] As described below with reference to Figure 4, according to a particular embodiment of the present technology, in order to improve the ability to determine the effectiveness of a denervation procedure, nerve destruction is performed at two different longitudinally separated locations along a biological lumen (e.g., a renal artery), and electrodes are used to sense intrinsic or evoked nerve responses at a longitudinal location between the two nerve destruction sites.

[0037] More specifically, according to a particular embodiment of this technology, when it is desired to destroy nerves within a specific length or segment of a biological lumen (e.g., a renal artery), a catheter (302 in Figure 3) is used to deliver ablation energy (or another type of ablation therapy) to a first longitudinal location (e.g., the distal end of a specific length or segment of the biological lumen), then to a second longitudinal location (e.g., the proximal end of a specific length or segment of the biological lumen), or vice versa. Subsequently, using the same catheter or a separate catheter, intrinsic and / or induced nerve responses between the first and second longitudinal locations of the biological lumen (i.e., between the two nerve destruction sites) are sensed to determine whether sufficient nerve destruction has been achieved. If the intrinsic and / or induced nerve responses fall below a specified threshold, it can be determined that sufficient nerve destruction has been achieved. On the other hand, if the intrinsic and / or induced nerve responses exceed a specified threshold, it can be determined that sufficient nerve destruction has not been achieved. If sufficient nerve destruction has not been achieved, additional ablation energy (or another type of ablation therapy) may be applied to the first and / or second longitudinal locations. Additionally or alternatively, additional ablation energy (or another type of ablation therapy) may be delivered to one or more longitudinal locations between the first and second longitudinal locations. Additionally or alternatively, additional ablation energy (or another type of ablation therapy) may be delivered to longitudinal locations proximal (upstream) to the aforementioned first and second longitudinal locations, and / or to one or more longitudinal locations distal (downstream) to the aforementioned first and second longitudinal locations.

[0038] In this specification, denervation procedures are often described as being performed by delivering ablation energy, such as by delivering ultrasonic energy, RF energy, pulsed electric field energy, or microwave energy using an appropriate transducer in a catheter. However, it should be understood from the description herein that other types of ablation therapies may be used alternatively or additionally within the scope of the embodiments described herein. Such other types of ablation therapies include, but are not limited to, cryotherapy, chemicals (e.g., drugs or other agents), laser light or optical energy, magnetic energy, direct thermal energy, radiation (e.g., infrared, visible light, gamma rays), or combinations thereof.

[0039] Referring here to Figure 4, the dashed cylindrical region labeled 414 illustrates an exemplary first denervation treatment area, and the dashed cylindrical region labeled 416 illustrates an exemplary second denervation treatment area, with treatment areas 414 and 416 longitudinally separated from each other along the renal artery 104. Further referring to Figure 4, the portion of the renal artery 104 labeled A is proximal or upstream of both treatment areas 414 and 416, the portion of the renal artery 104 labeled B is distal or downstream of both treatment areas 414 and 416, and the portion of the renal artery 104 labeled C is between treatment areas 414 and 416. According to a particular embodiment of the art, one or more sensing electrodes are positioned within the portion of the renal artery 104 labeled C (i.e., between treatment areas 414 and 416) for the purpose of determining the effectiveness of the ablation energy delivered to treatment areas 414 and 416.

[0040] In such embodiments, the fact that substantially no neural activity is detected between the two ablation sites (i.e., between treatment areas 414 and 416) indicates that both efferent and afferent traffic are severed. In other words, if ablation performed in both treatment areas 414 and 416 is successful, substantially no neural activity should be detected between treatment areas 414 and 416. More specifically, if the ablation energy is delivered to treatment areas 414 and 416 and the ablation energy successfully denervates the renal nerves in both treatment areas 414 and 416, the ablation energy delivered to treatment area 414 should prevent efferent impulses from the renal nerves (traveling from the brain towards the kidney 102) from reaching area C, and the ablation energy delivered to treatment area 416 should prevent afferent impulses from the renal nerves (traveling from the kidney 102 towards the brain) from reaching area C. Therefore, if the ablation performed in both treatment areas 414 and 416 is successful, one or more electrodes positioned within area C (Figure 4) of the renal artery 104 should not detect any renal nerve activity, meaning that any detected renal nerve activity should be below the specified threshold.

[0041] Figure 5 illustrates the expected perceived nerve activity in three regions after the denervation procedure described with reference to Figure 4, labeled A, B, and C in Figure 4. Referring to Figure 5, graph 502 illustrates the expected nerve activity that may be perceived proximal (i.e., upstream) to treatment regions 414 and 416 in Figure 4, which indicates inflammation of the efferent renal nerves. Graph 504 illustrates the expected nerve activity that may be perceived in region B in Figure 4, distal (i.e., downstream) to both treatment regions 414 and 416, thus indicating inflammation of the afferent renal nerves. Further referring to Figure 5, graph 506 shows the expected nerve activity that may be perceived in region C, located longitudinally between treatment regions 414 and 416, assuming that the ablation energy delivered to each treatment region 414 and 416 successfully ablates the renal nerves within them. Thus, graph 506 indicates that virtually no nerve activity is perceived within region C.

[0042] Using the high-level flow chart in Figure 6, a method for performing a denervation procedure and a method for determining its effectiveness are illustrated, which may be implemented according to certain embodiments of the present art, including a catheter (e.g., 302, 702) or a system (e.g., 800) that can be electrically coupled to a catheter. Referring to Figure 6 (and Figures 3, 4, 7, and 8), step 602 involves delivering a first ablation therapy from a first longitudinal location along a biological lumen (e.g., a renal artery). Step 604 involves delivering a second ablation therapy longitudinally from a second longitudinal location separated from the first longitudinal location along the biological lumen. Alternatively, step 602 can be performed by delivering a first ablation therapy from a transducer (e.g., 311, 711) longitudinally positioned within the renal artery 104 so that ablation occurs within the treatment area 414, and step 604 can be performed by delivering a second ablation therapy from a transducer (e.g., 311, 711 or another transducer) longitudinally positioned within the renal artery 104 so that ablation occurs within the treatment area 416. Alternatively, step 602 can be performed by delivering a first ablation therapy from a transducer (e.g., 311, 711) longitudinally positioned within the renal artery 104 so that ablation occurs within the treatment area 416, and step 604 can be performed by delivering a second ablation therapy from a transducer (e.g., 311, 711 or another transducer) longitudinally positioned within the renal artery 104 so that ablation occurs within the treatment area 414. In other words, the first ablation therapy can be delivered more proximal (downstream) than the second ablation therapy, depending on the specific implementation. In the example above, the transducer (311, 711, etc.) is positioned at a first location in the biological lumen (e.g., renal artery 104), and after performing step 602, the transducer (311, 711, etc.) is repositioned at a second location (e.g., renal artery 104) either upstream or downstream of the first location in the biological lumen.Alternatively, ablation therapy can be delivered at first and second locations within the biological lumen (such as renal artery 104) using two longitudinally separated transducers.

[0043] According to a particular embodiment, using the same transducers (e.g., 311, 711), step 602 and 604 can be performed by first manipulating a catheter (e.g., 302, 702) containing the transducers (e.g., 311, 711) so that the transducers (e.g., 311, 711) are positioned in a first location, and performing step 602 while the transducers 311, 711 are positioned in the first location; and then manipulating the catheter (e.g., 302, 702) containing the transducers (e.g., 311, 711) so that the transducers (e.g., 311, 711) are positioned in a second location, and performing step 604 while the transducers (e.g., 311, 711) are positioned in the second location. More generally, steps 602 and 604 can be performed by using the same therapy delivery element (e.g., 311, 711) and first manipulating a catheter (e.g., 302, 702) containing the therapy delivery element (e.g., 311, 711) so that the therapy delivery element (e.g., 311, 711) is positioned at a first location, performing step 602 while the therapy delivery element (e.g., 311, 711) is positioned at the first location, and then manipulating the catheter (e.g., 302, 702) containing the therapy delivery element (e.g., 311, 711) so that the therapy delivery element (e.g., 311, 711) is positioned at a second location, performing step 604 while the therapy delivery element (e.g., 311, 711) is positioned at the second location.

[0044] In other embodiments, the catheter (e.g., 302, 702) contains two transducers (or other type of therapy delivery element) that are longitudinally separated from each other along the shaft (e.g., 722) of the catheter (e.g., 302, 702), thereby enabling steps 602 and 604 to be performed without the need to reposition the catheter (e.g., 302, 702) between steps 602 and 604. More specifically, the catheter (e.g., 302, 702) containing two transducers (or other type of therapy delivery element) is operated such that one of the transducers (or other type of therapy delivery element) is positioned at a first location and the other transducer (or other type of therapy delivery element) is positioned at a second location. Steps 602 and 604 can be performed simultaneously by simultaneously supplying energy to the two transducers. Alternatively, step 602 may be carried out by first supplying energy to one of the transducers positioned at the first location, and then step 604 may be carried out by supplying energy to the other transducer positioned at the second location, or vice versa. An example of a catheter containing two longitudinally separated transducers is disclosed in U.S. Patent Publication No. 2023 / 0021354. Other catheters containing two longitudinally separated transducers (or other types of therapy delivery elements) are also available and are within the scope of the embodiments described herein. The two transducers may or may not be located in one or more balloons (e.g., 713). More specifically, the two transducers may be located in the same balloon (e.g., 713), in separate balloons (e.g., 713), or not in any balloon. Other types of therapy delivery elements that can be separated longitudinally from one another along the shaft (e.g., 722) of a catheter (e.g., 302, 702) and used to carry out steps 602 and 604 include, but are not limited to, cryotherapy delivery elements, chemical delivery elements, and lasers. The above therapy delivery elements may also be referred to herein as ablation mechanisms.Such therapy delivery elements can also be referred to here as elements configured to selectively deliver ablation therapy.

[0045] According to a particular embodiment, the ablation therapy delivered in an instance of step 602 may include performing multiple ablations from a first longitudinal location. For example, multiple circumferential ablations may be performed simultaneously or sequentially in a time-multiplexed manner from the same first longitudinal location. This can be achieved, for example, by performing multiple distinct focal ablations from a first longitudinal location. In a more specific example, multiple (e.g., four) RF electrodes may be distributed on a portion of the circumference of a catheter (e.g., 302, 702). Using such multiple RF electrodes, ablation energy can be released simultaneously or in a time-multiplexed manner in different radial directions from the same location in the same longitudinal direction. Similarly, the ablation therapy delivered in step 604 may include performing multiple ablations from a second longitudinal location. Additionally, further ablations performed in instance step 608, as described below, may similarly involve performing multiple ablations from the same longitudinal location.

[0046] Referring again to Figure 6, step 606 involves sensing neural activity from a third longitudinal location, preferably longitudinally located between the first and second longitudinal locations, where the first and second ablation therapies have been delivered, respectively (steps 602 and 604), thereby quantifying the extent to which nerves surrounding the biological lumen and adjacent to at least one of the first and second longitudinal locations have been affected by the delivery of the first and second ablation therapies. For example, returning briefly to Figure 4 again, the sensing in step 606 can be performed from a location within region C shown in Figure 4. Additional details on how to perform step 606 are provided below.

[0047] Referring again to Figure 6, an optional but desirable step 608 involves determining, based on the sensed nerve activity (sensed in step 606), whether further ablation therapy needs to be delivered from locations along the longitudinal length of the biological lumen. More specifically, the measured nerve activity in step 606 can be compared to the corresponding threshold in step 608. If the nerve energy measure is less than the threshold, it may be determined in step 608 that the denervation procedure was successful and no further denervation of the biological lumen is necessary. In contrast, if the nerve energy measure exceeds the corresponding threshold, it may be determined in step 608 that the denervation procedure was unsuccessful and further denervation of the biological lumen is still necessary. If further denervation of the biological lumen is still needed, in an optional but desirable step 610, further ablation therapy can be delivered to the first longitudinal location referenced in step 602, the second longitudinal location referenced in step 604, and / or between the first and second longitudinal locations. Alternatively, or additionally, in step 610, further ablation therapy can be delivered proximal to both the first and second longitudinal locations and / or distal to both the first and second longitudinal locations. The measured value of neural activity sensed in step 606 is, for example, the maximum peak amplitude of the sensed neural activity. Alternatively, if there are multiple peaks in the sensed signal indicating neural activity, the mean or median amplitude can be determined, and that mean or median amplitude may be the measured value of neural activity compared to a threshold. Alternatively, the curve can be fitted to a portion of the sensed signal indicating neural activity, and the area under the curve may be the measured value of neural activity compared to a threshold. Other modifications are also possible and are within the scope of the embodiments described herein. The specific threshold to which the measured value of neural activity is compared depends on how the specific measured value of neural activity is determined.

[0048] According to a particular embodiment, step 602 is performed using a transducer (e.g., 311, 711) located on the distal portion of a catheter (e.g., 302, 711) inserted into a biological lumen to position a transducer (e.g., 311, 711) at a first longitudinal location, and step 604 is performed using a transducer (e.g., 311, 711) on the distal portion of a catheter (e.g., 302, 711) inserted into a biological lumen, after the transducer (e.g., 311, 711) has been moved from being positioned at the first longitudinal location to being positioned at the second longitudinal location. According to one particular embodiment, the transducer (e.g., 311, 711) is an ultrasonic transducer, in which case step 602 may be carried out by emitting a first ultrasonic energy from the ultrasonic transducer (e.g., 311, 711) while positioning the ultrasonic transducer (e.g., 311, 711) at a first longitudinal location, and step 604 may be carried out by emitting a second ultrasonic energy from the ultrasonic transducer (e.g., 311, 711) while positioning the ultrasonic transducer (e.g., 311, 711) at a second longitudinal location. According to another embodiment, step 602 may be carried out by emitting a first RF energy using one or more electrodes positioned at a first longitudinal location, and step 604 may be carried out by emitting a second RF energy using one or more electrodes positioned at a second longitudinal location. As described above, other types of ablation mechanisms can be used to carry out steps 602 and 604, including, but not limited to, microwave energy, cryotherapy, chemicals, light energy, laser and / or pulsed field ablation.

[0049] According to a particular embodiment, step 606 is carried out using electrodes (e.g., 726, 727) positioned at a third longitudinal location, preferably longitudinally located between a first longitudinal location and a second longitudinal location. Such electrodes (e.g., 726, 727), used to sense neural activity from the third longitudinal location, may be included in the distal portion of a catheter (e.g., 302, 702), which may be the same catheter as the one containing the transducer (e.g., 311, 711) and / or other resectable means, or it may be a different catheter.

[0050] According to one particular embodiment, the neural activity sensed from the third longitudinal location in step 606 is intrinsic (or spontaneous) neural activity. According to another embodiment, the neural activity sensed from the third longitudinal location includes an evoked neural response to a delivered stimulus. Such a stimulus that elicits a neural response can be delivered from at least one electrode (e.g., 726, 727) positioned in the proximal (upstream) biological lumen of both the first and second longitudinal locations, or from at least one electrode (e.g., 726, 727) positioned in the distal (downstream) biological lumen of both the first and second longitudinal locations. Regardless of whether the neural activity sensed in step 606 is intrinsic (or spontaneous) neural activity or evoked neural activity, the neural activity sensed in step 606 may be sensed by an electrode (e.g., 726, 727) positioned between the first and second longitudinal locations and further electrodes. In certain embodiments, additional electrodes are also positioned within the biological lumen between a first longitudinal location and a second longitudinal location, in which case both electrodes (e.g., 726, 727) used to sense intrinsic (or spontaneous, to put it another way) neural activity are positioned between the first longitudinal location and the second longitudinal location. For example, returning to Figure 4 for brief reference, assuming that the ablation therapy is delivered to each of the treatment areas 414 and 416, in certain embodiments, a pair of electrodes (e.g., 726, 727) both positioned in area C (between treatment areas 414 and 416) are used to sense intrinsic and evoked neural activity so as to determine the effectiveness of the denervation procedure based on that in step 608. The electrodes (e.g., 726, 727) used to sense neural activity can here be referred to as sensing electrodes (e.g., 726, 727). In the embodiments described above, both sensing electrodes (e.g., 726, 727) are positioned within a biological lumen (e.g., renal artery) between a first longitudinal location and a second longitudinal location where the respective first and second ablation therapies are delivered in steps 602 and 604.

[0051] In an alternative embodiment, the first sensing electrode is positioned within a biological lumen (e.g., a renal artery) between a first longitudinal location and a second longitudinal location where the first and second ablation therapies are delivered in steps 602 and 604, respectively, and the second (further, to put it another way) sensing electrode is an external skin electrode.

[0052] In another alternative embodiment, the first sensing electrode is positioned within a biological lumen (e.g., a renal artery) between a first longitudinal location and a second longitudinal location where the first and second ablation therapies are delivered in steps 602 and 604, respectively, and the second (further, to put it another way) sensing electrode is positioned proximal (i.e., upstream) of the first and second longitudinal locations where the ablation therapy is delivered in steps 602 and 604. For example, returning to and briefly referring back to Figure 4, assuming that the ablation therapy is delivered to each of the treatment areas 414 and 416, in a particular embodiment, the first sensing electrode is positioned within area C (between treatment areas 414 and 416) and the second sensing electrode is positioned within area A (proximal or upstream of both treatment areas). Both the first and second sensing electrodes may be located on a catheter used to sense nerve activity, which may include a transducer (e.g., 311) and / or other resectable means, and may be the same catheter used to deliver the ablation therapy in steps 602 and 604. If the first and second sensing electrodes are located on a different catheter than the one used to deliver the ablation therapy in steps 602 and 604, the catheter used to perform steps 602 and 604 is removed after step 604, and a different catheter is inserted into the biological lumen between steps 604 and 606. In other words, the catheter may be swapped between steps 604 and 606. In a particular embodiment, the first sensing electrode is located on a catheter (which may or may not be the same catheter used to deliver the ablation therapy in steps 602 and 604, and which includes a transducer, e.g., 311) and is positioned within a biological lumen (e.g., renal artery) between a first longitudinal location and a second longitudinal location where the ablation therapy was delivered in steps 602 and 604, while the second sensing electrode is located on the distal end of an introducer sheath used to insert the catheter containing the first sensing electrode into the biological lumen (e.g., renal artery).

[0053] In another embodiment, the first sensing electrode is positioned within a biological lumen (such as a renal artery) between a first longitudinal location and a second longitudinal location where the ablation therapy is delivered in steps 602 and 604, and the second (further, to put it another way) sensing electrode is positioned distal to (i.e., downstream of) the first and second longitudinal locations where the ablation therapy is delivered in steps 602 and 604. For example, returning to Figure 4 for a brief reference, assuming that the ablation therapy is delivered to treatment areas 414 and 416 respectively, in a particular embodiment, the first sensing electrode is positioned within area C (between treatment areas 414 and 416) and the second sensing electrode is positioned within area B (proximal or downstream of both treatment areas). The first and second sensing electrodes may both be located on the same catheter, which may or may not be the same catheter used to deliver the ablation therapy in steps 602 and 604, and which includes a transducer (e.g., 311) or other ablation means. The second sensing electrode may also be separated from the catheter, for example, by positioning it on the distal end of a guidewire used to guide the catheter containing the first sensing electrode into a biological lumen (such as a renal artery).

[0054] As described above, in certain embodiments, the neural activity sensed in step 606 may be an evoked neural response to stimulatory energy delivered using one or more electrodes (e.g., 724, 725) of a catheter (e.g., 302, 702) inserted into a biological lumen, the catheter (e.g., 302, 702) also includes at least one of the sensing electrodes (e.g., 726, 727) used in step 60, and the catheter (e.g., 302, 702) may or may not be the same catheter used to deliver the ablation therapy in steps 602 and 604, depending on the particular implementation. For the purposes of this specification, a pair of electrodes (e.g., 724, 725) used to deliver stimuli that induce a neural response may be referred to as the first and second stimulatory electrodes (e.g., 724, 725). In certain embodiments, both the first and second stimulating electrodes (e.g., 724, 725) are positioned within the biological lumen (e.g., renal artery 104) between the first longitudinal location and the second longitudinal location where the ablation therapy is delivered in steps 602 and 604. For example, referring back briefly to Figure 4, assuming that the ablation therapy is delivered to treatment areas 414 and 416 respectively, the first and second stimulating electrodes (e.g., 724, 725) may be positioned within area C (between treatment areas 414 and 416).

[0055] In other embodiments, only the first stimulating electrode is positioned within the biological lumen (e.g., renal artery 104) between the first and second longitudinal locations where the ablation therapy is delivered in steps 602 and 604, while the second stimulating electrode is located on the same catheter as the first stimulating electrode, but either proximal (or upstream) to both the first and second longitudinal locations, or distal (or downstream) to both the first and second longitudinal locations. For example, returning to Figure 4 for a brief reference, assuming that the ablation therapy is delivered to treatment areas 414 and 416, in a particular embodiment, the first stimulating electrode is positioned within area C (between treatment areas 414 and 416), and the second stimulating electrode is positioned within area A (proximal or upstream of the treatment area) or area B (distal or downstream of the treatment area). One of the first and second stimulating electrodes must be configured as the stimulating anode, and the other as the stimulating cathode.

[0056] In yet another embodiment, the second stimulating electrode (used as a return electrode) is located not on the same catheter as the first stimulating electrode, but on the distal end of the introducer sheath used to insert the catheter containing the first stimulating electrode into the biological lumen, or on the distal end of the guidewire used to guide the catheter containing the first stimulating electrode into the biological lumen. In yet another embodiment, the second stimulating electrode (used as a return electrode) is an external skin electrode, rather than being located on the same catheter as the first stimulating electrode.

[0057] Alternatively, the stimulus can be delivered to the most proximal ablation site, and the evoked response neuronal activity can be sensed distal to the most distal ablation site. In other words, the stimulus that elicits a neuronal response can be delivered via one or more stimulating electrodes located proximal (i.e., upstream) to the first and second longitudinal locations, and can be sensed using one or more sensing electrodes located distal (i.e., downstream) to the first and second longitudinal locations. For example, referring back briefly to Figure 4, assuming that ablation therapy is delivered to treatment areas 414 and 416, in a particular embodiment, the stimulus may be delivered from one or more electrodes in area A, and the evoked neuronal response may be sensed using one or more sensing electrodes in area B.

[0058] Another alternative is to deliver distal stimuli to the most distal ablation site and sense the evoked neuronal response adjacent to the most proximal ablation site. In other words, the stimuli that elicit a neuronal response can be delivered via one or more stimulating electrodes located distal (i.e., downstream) to the first and second longitudinal locations and sensed using one or more sensing electrodes located proximal (i.e., upstream) to the first and second longitudinal locations. For example, referring back briefly to Figure 4, assuming that ablation therapy is delivered to treatment areas 414 and 416 respectively, in a particular embodiment, the stimuli may be delivered from one or more electrodes in area A, and the evoked neuronal response may be sensed using one or more sensing electrodes in area B.

[0059] As described above, the same catheters (e.g., 302, 702) used to perform steps 602 and 604 can also be used to perform step 606, regardless of whether the neural activity sensed in step 606 is intrinsic (or spontaneous) neural activity or an evoked response to a stimulus delivered via one or more electrodes (e.g., 724, 725) of the catheter (e.g., 302, 702). Alternatively, as described above, step 606 can be performed using a different catheter than the one used to perform steps 602 and 604, regardless of whether the neural activity sensed in step 606 is intrinsic (or spontaneous) neural activity or an evoked response to a stimulus delivered via a different catheter, in which case the catheters would need to be exchanged between steps 604 and 606.

[0060] Embodiments of this technology can be implemented using various different catheter configurations and are therefore not limited to the use of any specific catheter and / or system containing a catheter. Nevertheless, for completeness, exemplary catheters and systems that can be used to implement embodiments of this technology are described below. More specifically, Figures 7A to 711B are used to illustrate exemplary catheters and systems that can be used to implement the embodiments of this technology described above. Such systems may also be referred to as devices herein.

[0061] [Example catheter] Figure 7A shows catheter 702 in a position where its selectively deployable electrodes 724 and 726 are not deployed. Catheter 702 includes a catheter handle 712 and a catheter shaft 722. In addition to including selectively deployable electrodes 724 and 726, it is shown that the catheter shaft 722 also includes an undeployed electrode 725 proximal to the selectively deployable electrode 724 and an undeployed electrode 727 distal to the selectively deployable electrode 726. The selectively deployable electrode 724 may also be called the proximal selectively deployable electrode 724, more simply the proximal electrode 724, or even more simply the electrode 724. The selectively deployable electrode 726 may also be called the distal selectively deployable electrode 726, more simply the distal electrode 726, or even more simply the electrode 726. The catheter shaft 722 may also be more simply referred to as the shaft 722 in this specification. Catheter 702 may be a specific implementation of catheter 302 as shown and described above, with reference to Figure 3.

[0062] The catheter 702 is also shown to include a balloon 713 positioned longitudinally between electrodes 724 and 726, the balloon 713 being selectively inflatable and deflated. The balloon 713 is also called the selectively inflatable balloon 713, the selectively deployable balloon 713, or more simply, the balloon 713. When the balloon 713 is deflated, it is sometimes referred to as being in the uninflated or undeployed position. When the balloon 713 is inflated, it is sometimes referred to as being in the deployed position. As will be described in more detail below, the balloon 713 can be selectively inflated by injecting fluid into it, and the balloon 713 can be selectively deflated by removing fluid from it. The balloon 713 can be made of an electrically insulating material such as polyamide, polyethylene terephthalate, or thermoplastic elastomer. In certain embodiments, the balloon 713 is made from, but is not limited to, nylon, polyimide film, thermoplastic elastomer (such as those marked with the trademark PEBAX®), medical-grade thermoplastic polyurethane elastomer (such as those sold under the trademark PELLETHANE®), pelletan, isotan, or other suitable polymers, or any combination thereof.

[0063] The catheter handle 712, also more simply called the handle 712, includes actuators 714, 716, and 718, which can be used to selectively deploy electrodes 724 and 726, as well as to adjust the longitudinal distance between electrodes 724 and 726, which will be described in detail later. Actuators 714, 716, and 718 are also called sliders, as they are slidable within slots 715, 717, and 719 of the handle 712, respectively. The catheter handle 712 is also shown to include a fluid inlet port 734a and a fluid outlet let port 734b.

[0064] Fluid (e.g., discharged from a pressure syringe) can enter the fluid lumen (inside the catheter shaft 722) via the fluid inlet port 734a of the catheter 702 and at least partially fill the balloon 713. Fluid can be withdrawn from the balloon 713 through another fluid lumen (inside the catheter shaft 722) (e.g., using a vacuum syringe) and out through the fluid outlet port 734b of the catheter 702. In this way, the fluid can be used to selectively inflate and selectively deflate the balloon 713. In certain embodiments, liquid can be injected into and removed from the balloon 713, thereby circulating the liquid through the balloon 713.

[0065] The catheter 702 is also called the intraluminal micro-nerve recording probe 702, or more simply, the probe 702. A cable 704 extending from the proximal portion of the handle 712 provides an electrical connection between the catheter 702 (more specifically, its electrodes) and an electrical control unit (ECU), an example of which is described below with reference to Figure 8.

[0066] Referring further to Figure 7A, the transducer 711 is shown to be located within the balloon 713. The transducer 711 is an example of an ablation element (or, to put it another way, an element configured to selectively deliver ablation therapy) contained within the shaft 722 and configured to excise nerve tissue using ultrasonic energy. In other embodiments, the transducer and balloon may be replaced with a helical structure carrying multiple electrodes configured to deliver RF and / or pulsed electric field RF energy. In other embodiments, the transducer and balloon may be replaced with a microwave-transmitting element, which may or may not be located within an expandable centering element. In other embodiments, the transducer may be replaced with a cryotherapy applicator. In other embodiments, the transducer and balloon may be replaced with an injection needle configured to deliver excisive chemicals to the renal nerve. The shaft 722 may also include, for example, two longitudinally spaced transducers, as disclosed in U.S. Patent Publication 2023 / 0021354, which is incorporated herein by reference above.

[0067] If the transducer 711 is located within the balloon 713, the fluid circulating within the balloon 713 can be called a cooling fluid used to cool the transducer 711 and / or the portion of the biological lumen in which the balloon 713 is located and / or the biological tissue surrounding the lumen. It is also possible that the catheter 702 lacks the transducer 711 or other resectable means, and a separate catheter containing the transducer or other resectable means is used to deliver the ablation therapy (e.g., steps 602 and 604 in Figure 6). If the catheter 702 lacks the transducer 711 or other resectable means, one or more electrodes of the catheter 702 (e.g., 726, 727) can be used to sense intrinsic nerve activity. One or more electrodes of the catheter 702 (e.g., 724, 725) can be used to deliver stimulating energy, and one or more additional electrodes of the catheter 702 (e.g., 726, 727) can be used to sense the evoked nerve response to the stimulating energy.

[0068] When the catheter 702 is inserted into a biological lumen such as an artery, vein, or other blood vessel, it is the distal portion of the catheter 702 (more specifically the shaft 722) that is inserted into the biological lumen, and the proximal end of the catheter 702 (more specifically the handle 712) that is used to manipulate the catheter 702. In the embodiments shown in Figures 7A and 7B, the electrode 726 is located closer to the distal end of the catheter 702 than to the proximal end of the catheter 702, and is therefore also called the distal selectively deployable electrode 726 as described above, and the electrode 724 is located closer to the proximal end of the catheter 702 than to the distal end of the catheter 702, and is therefore also called the proximal selectively deployable electrode 724 as described above. For similar reasons, the electrode 725 is called the proximal non-deployable electrode 725, and the electrode 727 is called the distal non-deployable electrode 727.

[0069] Figure 7B shows a catheter 702 having electrodes 724 and 726 in their deployed (or extended) positions. In certain embodiments, the proximal selectively deployable electrode 724 is deployed (or extended) in response to an actuator 714 sliding proximally, as indicated by arrow 744 in Figure 7B. In such embodiments, the proximal electrode 724 can be returned to its undeployed (or unextended or retractable) position in response to the actuator 714 sliding distally to the opposite side of arrow 744 in Figure 7B. More generally, the actuator 714 is used to selectively extend and retract the electrode 724.

[0070] According to a particular embodiment, the longitudinal distance between the distal electrode 726 and the proximal electrode 724 can be reduced by sliding the actuator 718 in the proximal direction indicated by arrow 748 in Figure 7B. Then, if necessary, the longitudinal distance between the distal electrode 726 and the proximal electrode 724 can be increased by sliding the actuator 718 in the distal direction opposite to arrow 748 in Figure 7B. More generally, the actuator 718 is used to adjust the longitudinal distance between electrodes 724 and 726. The longitudinal distances 724, 726 between the proximal and distal electrodes can be any distance between the maximum and minimum longitudinal distances controlled by the user using the actuator 718. According to a particular embodiment, electrode 724 is configured to unfold in response to actuator 714 sliding in the proximal direction indicated by arrow 744 in Figure 7B. According to a particular embodiment, electrode 726 is configured to unfold in response to actuator 716 sliding in the proximal direction indicated by arrow 746 in Figure 7B. In such embodiments, the actuator 716 can be returned to a non-extended position in response to distal sliding of the actuator 716 to the opposite side of arrow 746 in Figure 7B. More generally, the actuator 716 is used to selectively extend and retract the electrode 726. Other modifications are also possible and are within the scope of the embodiments described herein.

[0071] Each of the selectively deployable electrodes 724, 726 can be fabricated, for example, from a unital linitinol tube laser-cut to include an aperture or opening having a predetermined pattern. In Figures 7A and 7B, each of the electrodes 724, 726 has a laser-cut helical aperture between the proximal and distal portions of each electrode 724, 726. The helical apertures 724, 726 of each electrode enable each electrode to selectively transition between their undeployed and deployed positions. The apertures cut into electrodes 724, 726 can have shapes other than helical, as long as it enables the electrode to transition between the undeployed and deployed positions. The selectively deployable electrodes 724, 726 are alternatively mesh electrodes or helical electrodes fabricated from one or more conductive wires, which can optionally be partially insulated. Other modifications are also possible and are within the scope of the embodiments described herein.

[0072] The catheter 702 can be configured to be introduced into a biological lumen, such as an artery, located near a body organ, such as the kidney. The catheter 702 can advance to the desired catheter site in the biological lumen and then be introduced via an introducer sheath that is fully retracted until the shaft 722 is exposed to the biological lumen (e.g., the renal artery 104). Once the shaft 722 is inside the biological lumen of the organism, one of the electrodes 724, 726 can be deployed (or expanded) using one of the actuators 714, 716 to contact a portion of the circumferential inner wall of the biological lumen of the organism. The longitudinal distance between electrodes 724 and 726 can then be adjusted as needed using actuator 718. The other electrode 724, 726 can be deployed (or expanded) to contact another portion of the circumferential inner wall of the biological lumen.

[0073] For example, when a catheter (e.g., 702) is inserted into a renal artery (e.g., 104) near the kidney, the electrodes (e.g., 724, 726) can be positioned close to the nerve bundles connecting the kidney to the central nervous system, because nerve bundles tend to closely follow the arteries that connect to most body organs. Nerve bundles tend to closely follow the arteries at the ends of the arteries near the kidney, while spreading somewhat as the arteries expand away from the kidney. As a result, in some cases, the distance between nerves and arteries is likely to decrease as one approaches the organ, so it is desirable that the catheter shaft 722 be small enough to be introduced relatively close to the kidney or other organ.

[0074] Once catheter 702 is positioned, the practitioner can use measuring instruments (e.g., ECU 802) coupled to electrodes (e.g., 724, 725) to stimulate one or more nerves and monitor the evoked nerve response signals used to characterize the nervous system's response to a particular stimulus. The transducer 711 and / or other resecting means are configured to resect nerve tissue using ultrasound, RF, pulsed electric field RF, microwave, cryotherapy, or other energy or chemical means. Additionally, catheter 702 can be used to actively stimulate one or more nerves during the application of ablation therapy via transducer 711 and sense the resulting nerve signals, thereby allowing for more precise control of the degree and effect of nerve ablation. In other examples, catheter 702 lacking a transducer or other resecting means can be removed through the sheath, an ablation probe (rephrased as catheter) can be inserted, the ablation probe can be removed, and catheter 702 can be reinserted to verify and characterize the effect of the ablation probe.

[0075] Any one or more electrodes of catheter 702 (e.g., 724, 725) can be selectively used to deliver stimulating energy to nerves surrounding the biological lumen. Similarly, any one or more electrodes of catheter 702 (e.g., 726, 727) can be selectively used to sense nerve activity in nerves surrounding the biological lumen, which may be spontaneous or evoked nerve activity.

[0076] For the most part of the following description, transducer 711 is assumed to be an ultrasonic transducer capable of suitably heating and treating tissue within a target anatomical region by operating to deliver unfocused ultrasonic energy radially outward. Transducer 711 can be operated at a frequency, duration, and energy level suitable for treating the target tissue. In one non-limiting example, the unfocused ultrasonic energy generated by transducer 711 may target selected nerve tissue of a subject and heat such tissue in a manner that neuromodulates the nerve tissue (e.g., by complete or partial excision, necrosis, or stimulation). Transducer 711 may be the same transducer 311 discussed above, as shown in Figures 3 and 4.

[0077] According to a particular embodiment, the transducer 711 includes a piezoelectric transducer body comprising a hollow tube of piezoelectric material having an inner surface and an outer surface, wherein an inner electrode is disposed on the inner surface of the hollow tube of piezoelectric material and an outer electrode is disposed on the outer surface of the hollow tube of piezoelectric material. In such embodiments, the hollow tube of piezoelectric material is an example of the piezoelectric transducer body. The hollow tube of piezoelectric material, or more generally the piezoelectric transducer body, may be cylindrical and have a circular radial cross-section. However, in alternative embodiments, the hollow tube of piezoelectric material may have shapes other than being cylindrical with a circular radial cross-section. Other cross-sectional shapes of the hollow tube of piezoelectric material, or more generally the piezoelectric transducer body, include, but are not limited to, elliptical or oblong cross-sections, square or rectangular cross-sections, pentagonal cross-sections, hexagonal cross-sections, heptagonal cross-sections, octagonal cross-sections, and the like. The hollow tube of the piezoelectric material, more generally the piezoelectric transducer body, may be made from a variety of piezoelectric materials, including, but is not limited to, lead zirconate titanate (PZT), polyvinylidene fluoride (PVDF), or other piezoelectric ceramic materials currently available or to be developed in the future. In other embodiments, the transducer 711 may be made from other materials and / or may have other shapes.

[0078] In certain embodiments, transducer 711 is an ultrasonic transducer configured to deliver acoustic energy in the frequency range of 8.5–9.5 MHz. In certain embodiments, the transducer is configured to deliver acoustic energy in the frequency range of 8.7–9.3 MHz or 8.695–9.304 MHz. Transducers delivering acoustic energy in the frequency range of 8.7–9.3 MHz have been shown to produce ablation up to an average depth of 6 mm. The piezoelectric transducer body is configured to generate ultrasound when a voltage is applied between the inner and outer electrodes. One or both of the inner and outer electrodes can be covered with an electrical insulator to suppress (and preferably prevent) a short circuit between the inner and outer electrodes when the ultrasonic transducer is placed in a conductive fluid and a voltage is applied between the inner and outer electrodes. Such an electrical insulator may be, but is not limited to, parylene, more specifically parylene conformal coating. An excitation source (e.g., 826 in Figure 8) is electrically coupled to the inner and outer electrodes of the transducer 711, and by applying a voltage between the inner and outer electrodes (or another pair of electrodes), the transducer 711 can be activated to generate unfocused ultrasonic waves that are radially emitted outward from the piezoelectric material of the piezoelectric transducer body.

[0079] [Exemplary Electrical Control Unit (ECU)] Figure 8 is a high-level block diagram of an electrical control unit (ECU) 802 configured to electrically communicate with a catheter such as the catheter 702 described above. The ECU 802 and the catheter (e.g., 702) to which the ECU 802 is electrically coupled via a cable (e.g., 704) are more commonly referred to as system 800. The ECU 802 can process received signals to generate output signals and can present information including information about the output signals, received signals, or processed information. Such system 800 can be used, for example, in diagnostic procedures to assess the state of nerve activity in a patient adjacent to a biological lumen such as a vein or artery, e.g., a renal artery, or other type of blood vessel. Such system 800 can be additionally or alternatively used to select preferred pre-denervation parameters for use in denervation procedures. The same catheter (e.g., 702) used to assess the state of nerve activity in a patient and / or select preferred denervation parameters can also be used to perform denervation procedures, as will be described in more detail below. Alternatively, the catheter used to perform the denervation procedure may differ from the catheter used to assess the state of the patient's nerve activity as it approaches the biological lumen, in which case different catheters may be swapped in and out of the biological lumen during the procedure.

[0080] Referring further to Figure 8, the ECU 802 includes a stimulator 806 electrically coupled to a selected pair of electrodes (e.g., 724, 725) of the catheter 702. The stimulator 806, which is part of the STIM circuit or subsystem 804, can selectively emit an electrical signal (including a stimulation pulse) having a specific voltage, amperage, duration, duty cycle, and / or applicable frequency that causes activation of nerve cells. For example, electrode 724 can be connected as the stimulation anode and electrode 725 as the stimulation cathode, or vice versa. In another example, electrode 725 can be connected as the stimulation anode and electrode 726 as the stimulation cathode, or vice versa. Switches not specifically shown can be used to selectively control how various electrodes (e.g., 724, 725, 726, 727) are coupled to various nodes of the ECU 802, such as the input terminals of amplifier 812 or the output terminals of stimulator 806.

[0081] Upon receiving a stimulation signal generated by the stimulator 806, the electrodes of the catheter 702 connected as stimulating electrodes (e.g., 724, 725) can apply electrical energy to the patient's nerves through the biological lumen wall based on the received signal. Such stimulation can have, but is not limited to, various known waveforms such as sine waves, square waves, and triangular waves. In various examples, stimulation can be applied for durations ranging from approximately 0.05 milliseconds (msec) to approximately 8 milliseconds.

[0082] Nerve stimulation can be performed to induce an elicited electrical potential, which can cause such a potential to propagate in any direction along the nerve fiber. More generally, to elicit a nerve response, electrical stimulation can be delivered via a selected pair of electrodes (e.g., 724, 725) using the STIM subsystem 805, and the elicited nerve response can be sensed using the SENS subsystem 804.

[0083] In some embodiments, the ECU 802 can receive electrical signals from the catheter 702 by digitally sampling the sensed signals using a pair of electrodes (e.g., 726, 727). In alternative embodiments, the signals can be recorded as analog signals. Upon receiving electrical signals from the electrodes of the catheter 702 (e.g., 726, 727), the ECU 802 can perform filtering and other processing steps on the signals. Generally, such steps can be performed to distinguish the signal of interest sensed by the catheter (e.g., 702) from background noise in the patient's blood vessels, such that the resulting output is primarily a signal from nerve cell activation. In some cases, the ECU 802 can modulate the electrical impedance of the signal receiving portion to correspond to the electrical characteristics and spatial isolation of electrodes attached to the catheter in a manner that achieves the highest fidelity, selectivity, and resolution for the received signals. For example, the size, isolation, and conductivity characteristics of the electrodes can affect the electric field strength at the electrode / tissue interface.

[0084] Additionally, or alternatively, the ECU 802 may be equipped with a headstage and / or amplifier 812 to perform offsetting, filtering, and amplification of the signal received from the catheter 702. In some examples, the headstage applies a DC offset to the signal and performs a filtering step. In some such systems, filtering may include applying a notch and / or bandpass filter 814 to suppress certain undesirable signals having certain frequency components and to allow desired signals having certain frequency components to pass through. The amplifier 812 may be used to amplify the entire signal uniformly or to amplify certain parts of the signal more than others. For example, in some configurations, the amplifier 812 may be configured to provide an adjustable capacitance of the recording electrode, thereby changing the frequency dependence of signal pickup and amplification. In some embodiments, characteristics of the amplifier 812, such as capacitance, can be tuned to change amplification characteristics, such as the resonant frequency of the amplifier.

[0085] In the embodiment illustrated in Figure 8, the ECU 802 includes an amplifier 812 which includes a non-inverting (+) input terminal, an inverting (-) input terminal, a power input terminal, and a ground or reference terminal. As can be seen from Figure 8, the non-inverting (+) input terminal may be coupled to electrode 726, the inverting (-) input terminal may be electrically coupled to electrode 727, the power input terminal may be electrically coupled to a voltage source (e.g., a reference voltage generator), and the ground or reference terminal may be electrically coupled to a ground reference electrode which may be located on catheter 702, on the distal end of the introduction sheath, or on the patient's skin.

[0086] In some embodiments, the ECU 802 may include a switching network configured to change which electrodes (e.g., 724, 725, 726, 727) of a catheter (e.g., 702) are coupled to which part of the ECU 802. In some such embodiments, a user can manually switch which input receives the connection to which electrodes (e.g., 724, 725, 726, 727) of the catheter 702. Such configurability allows a system operator to adjust the direction of propagation of the drawn potential as needed. For example, a switching network, or more generally a switch, could be used to connect electrodes 724 and 725 to the stimulator 806 during the period when the catheter 702 emits a stimulation pulse, and the switch could be used to connect electrodes 726 and 726 to an amplifier 812 to sense the drawn response to the stimulation pulse. Additionally or alternatively, a controller (e.g., 822) may autonomously control such a switching network.

[0087] The amplifier 812 may include any suitable amplifier for amplifying a desired signal or attenuating an undesirable signal. In some examples, the amplifier 812 has a high common-mode rejection ratio (CMRR) to remove or substantially attenuate undesirable signals present at each of the respective sensing electrodes (e.g., 726, 727). In some embodiments, the amplifier 812 may be tuned, for example, via an adjustable capacitance or other attributes of the amplifier.

[0088] In the exemplary system 800 of Figure 8, the ECU 802 further includes a filter 814 for enhancing a desired signal in the signal received via a pair of electrodes (e.g., 726, 727). The filter 814 may include a bandpass filter, a notch filter, or other suitable filter for isolating the desired signal from noise artifacts in the received signal. In some embodiments, various characteristics of the filter 814 may be tuned to manipulate its filtering characteristics. For example, the filter may include tunable capacitances or other parameters to adjust the frequency response.

[0089] At least one of amplification and filtering of the sensed signal (e.g., received by electrodes 726 and 727) can enable the extraction of the desired signal at 816. In some embodiments, the extraction at 816 includes at least one additional processing step for isolating the desired signal from the signal sensed using the electrodes, such as preparing the signal for output at 818. In some embodiments, the functions of any combination of the amplifier at 812, the filter at 814, and the extraction at 816 can be integrated into a single entity. For example, the amplifier at 812 may act to filter out undesirable frequency components from the signal without requiring additional filtering by a separate filter.

[0090] In some embodiments, the ECU 802 can record emitted stimuli and / or received signals. Such data can then be stored in permanent or temporary memory 820. The ECU 802 may include such memory 820 or otherwise communicate with external memory (not shown). Thus, the ECU 802 can be configured to emit stimuli pulses to electrodes (e.g., 724, 725) of a catheter (e.g., 702), record such pulses in memory, receive signals from the catheter (e.g., 702), and also record such received signal data. Memory 820 within or associated with the ECU 802 may be located in any part of the ECU 802 or inside or outside the ECU 802 itself.

[0091] The ECU802 or a separate external processor can further perform calculations on the stored data to determine the characteristics of either the signals emitted or received through the catheter. For example, in various embodiments, the ECU802 can determine the amplitude, duration, or timing of the occurrence of the received or emitted signals. The ECU802 can further determine relationships, such as the temporal relationship between the received signal and the emitted stimulus signal. In some embodiments, the ECU802 performs signal averaging of the signal data received from the catheter. Such averaging can act to reduce random temporal noise in the data while enhancing the data corresponding to the extracted potentials received by the catheter.

[0092] Such averaging can result in signals where time-random noise is generally averaged out, and signals present in each recorded dataset, such as extracted potentials, remain high. In some embodiments, each iteration of the process may include a synchronization step, and each acquired dataset may be temporarily registered to facilitate data averaging. That is, events occurring simultaneously and consistently during each iteration can be detected, temporarily reducing random artifacts (e.g., noise). Generally, the signal-to-noise ratio (SNR) resulting from such averaging is improved by the square root of the averaged number of samples to create an averaged dataset.

[0093] The ECU 802 can present information about the applied stimulus, signal, and some or all of the calculation results to the system user, for example, via output 818. For example, the ECU 802 may generate a graphic display that provides one or more graphs of signal intensity and time representing the stimulus and / or received signal.

[0094] In some embodiments, the ECU 802 may include a controller 822 that communicates with one or both of the stimulator 806 and the SENS subsystem 804. The controller 822 may be configured so that the stimulator 806 applies a stimulation signal to a catheter, e.g., catheter 702. Additionally or alternatively, the controller 822 may be configured to analyze signals received and / or output by the SENS subsystem 804. In some embodiments, the controller 822 may act to control the timing of applying the stimulation signal from the stimulator 806 and the timing of receiving signals from the SENS subsystem 804. The controller 822 may be implemented using, for example, one or more processors, field-programmable gate arrays (FPGAs), state machines, and / or application-specific integrated circuits (ASICs), but is not limited to these.

[0095] An exemplary electrical control unit is described. In various embodiments, the ECU 802 can emit stimulation pulses to the catheter 702, receive signals from the catheter 702, perform calculations on the emitted and / or received signals, and present the signals and / or results of such calculations to the user. In some embodiments, the ECU 802 may include separate modules for emitting, receiving, calculating, and providing calculation results. Additionally or alternatively, the functions of the controller 822 may be integrated into the ECU 802 as shown, or communicate separately from the ECU 802.

[0096] The controller 822 can also control a fluid supply subsystem 828, which may include a cartridge and reservoir (described later with reference to Figure 10), but may also include an alternative type of fluid pump. The fluid supply subsystem 828 is fluidically coupled to one or more fluid lumens within the catheter shaft 722 (e.g., 904a and 904b in Figures 9A and 9B), which are sequentially fluidically coupled to the balloon 713. The fluid supply subsystem 828 can be configured to circulate coolant through the catheter 702 to the transducer 711 in the balloon 713.

[0097] [Cross-sectional view of the shaft portion of an exemplary catheter] Exemplary cross-sections of parts of shaft 722 are shown in Figures 9A and 9B. Referring to Figure 9A, the cross-section is shown to include a main lumen 902 having a circular cross-section and smaller lumens 904a and 904b. To enable fluid circulation through balloon 713, lumen 904a is fluidically coupled to a fluid inlet port 734a (shown in Figure 7) to enable fluid (e.g., discharged from a pressure syringe) to be supplied to and at least partially filled with balloon 713, and lumen 904b is fluidically coupled to a fluid outlet port 734b (shown in Figure 7) to enable fluid to be drawn out of balloon 713 (e.g., using a vacuum syringe). Figure 9B shows alternative cross-sections for lumens 902, 904b, and 904c. The main lumen 902 may function as a guidewire lumen, or the main lumen may be subdivided into additional lumens, one of which may be a guidewire lumen and another may be a cable lumen used to hold an electrical cable electrically coupled to a transducer (e.g., 711). Other modifications are also possible and are within the scope of the embodiments described herein.

[0098] [Exemplary fluid supply subsystem] Exemplary details of the fluid supply subsystem 828, introduced in the discussion of Figure 8, are described below with reference to Figure 10. Referring to Figure 10, the fluid supply subsystem 828 is shown to include a cartridge 1030 and a reservoir 1010. The reservoir 1010 is shown as being implemented as a fluid bag and may be the same as or similar to an intravenous (IV) bag in that it can be suspended from a hook or the like. The reservoir 1010 and cartridge 1030 may be disposable and replaceable items.

[0099] The reservoir 1010 is fluidically coupled to the cartridge 1030 via a pair of fluid paths, one of which is used as a fluid outlet path (supplying fluid from the reservoir to the cartridge) and the other as a fluid inlet path (returning fluid from the cartridge to the reservoir). The cartridge 1030 is shown to include a syringe pump 1040, which includes a pressure syringe 1042a and a vacuum syringe 1042b. The pressure syringe 1042a includes a barrel 1044a, a plunger 1046a, and a hub 1048a. Similarly, the vacuum syringe 1042b includes a barrel 1044b, a plunger 1046b, and a hub 1048b. The respective hubs 1048a and 1048b of syringes 1042a and 1042b are coupled to their respective fluid tubes or hoses. Cartridge 1030 is also shown to include pinch valves V1, V2, V3, pressure sensors P1, P2, P3, and check valve CV. Although not specifically shown in Figure 10, the syringe pump 1040 includes one or more gears and stepping motors, etc., controlled by controller 822 (Figure 8) to selectively operate the plungers 1046 of pressure syringes 1042a and vacuum syringes 1042b. Alternatively, the syringe pump 1040 can be controlled using gears and / or stepping motors.

[0100] To at least partially fill the barrel of the pressure syringe 1042a with some of the fluid stored in the reservoir 1010, pinch valves V1 and V2 are closed, pinch valve V3 is opened, and the plunger 1046a of the pressure syringe 1042a is pulled to draw the fluid 1013 into the barrel 1044a of the pressure syringe 1042a. Next, pinch valve V3 is closed, pinch valves V1 and V2 are opened, and then the plunger 1046a of the pressure syringe 1042a is pushed, causing the fluid to be discharged from the barrel 1044a of the pressure syringe 1042a through the fluid tube attached to the hub 1048a of the pressure syringe 1042a. The fluid discharged from the pressure syringe 1042a enters the fluid lumen of the catheter 702 via the fluid inlet port 734a (e.g., 904a in the catheter shaft 722) and can at least partially fill the balloon 713. Simultaneously, when the plunger 1046b of the vacuum syringe 1042b is pulled, the fluid is drawn from the balloon 713 into the fluid lumen (e.g., 904b in the catheter shaft 722), through the fluid outlet port 734b of the catheter 702, and then through the fluid tube attached to the hub 1048b of the vacuum syringe 1042b to the barrel 1044b of the vacuum syringe 1042b. In this manner, the liquid can be circulated through the balloon 713. The balloon 713 can be inflated by supplying more fluid to the balloon than is removed from it. One or more of the pressure sensors P1, P2, and P3 can be used to monitor the pressure inside balloon 713 to achieve a target balloon pressure, for example, 70 pounds per square inch (psi). Once balloon 713 is inflated to the target pressure, for example, 70 psi and / or its size, the fluid can be circulated through balloon 713 without increasing or decreasing the amount of fluid inside the balloon, by ensuring that the amount of fluid removed from balloon 713 is equal to the amount of fluid supplied to balloon 713. Also, once the target balloon pressure is reached, the ultrasonic transducer 711 can be excited to release ultrasonic energy to treat the tissue surrounding balloon 713 and the portion of the biological lumen into which transducer 711 is inserted (for example, a portion of a renal artery).When the ultrasonic transducer 711 is emitting ultrasonic energy, this can be said to mean that the ultrasonic transducer 711 is performing ultrasonic treatment, or that ultrasonic treatment is occurring. During ultrasonic treatment, it is necessary to circulate the coolant through the balloon 713 by continuously pushing the plunger 1046a of the pressure syringe 1042a and continuously pulling the plunger 1046b of the vacuum syringe 1042b.

[0101] After sonication is complete and balloon 713 has been deflated to allow catheter 702 to be removed from the biological lumen, the coolant needs to be returned from the barrel 1044b of vacuum syringe 1042b to reservoir 1010. To return the coolant from the barrel 1044b of vacuum syringe 1042b to reservoir 1010, pinch valves V1, V2, and V3 are all closed, and the plunger of vacuum syringe 1042b is pushed to discharge the coolant from the barrel of vacuum syringe 1042b, through check valve CV, and into reservoir 1010.

[0102] Pressure sensors P1, P2, and P3 can be used to monitor fluid pressure at various points along various fluid paths within the cartridge 1030, and these pressure readings can be provided to the controller 822 as feedback for use in controlling the syringe pump 1040 and / or determining the fluid pressure in the balloon 713, and for other purposes, but are not limited to these. Additionally, flow sensors F1 and F2 can be used to monitor the flow rate of fluid being injected into (or supplied to, pushed into, or supplied to) the balloon 713, and to monitor the flow rate of fluid being withdrawn (or pulled out or removed from) the balloon 713, respectively. Pressure readings obtained from pressure sensors P1, P2, and P3 can be provided to the controller 822 so that it can monitor the balloon pressure. Additionally, flow readings obtained from flow sensors F1 and F2 can be provided to the controller 822 so that it can monitor the flow rate of fluid being pushed into or withdrawn from the balloon 713. Furthermore, one or more pressure sensors and / or flow sensors may be positioned at additional or alternative locations along the fluid path to and from the balloon 713.

[0103] [Example transducer] Figures 11A and 11B illustrate longitudinal and radial cross-sectional views, respectively, of an exemplary transducer 711 that can be physically coupled to one of the tubes of the catheter 702 described above in the discussion of Figures 7A and 7B, respectively, according to a particular embodiment of the present technology. In the embodiments shown in Figures 11A and 11B, the transducer 711, which is an ultrasonic transducer, includes a piezoelectric transducer body 1101 comprising a hollow tube of piezoelectric material having an inner surface and an outer surface, with an inner electrode 1102 positioned on the inner surface of the hollow tube of piezoelectric material and an outer electrode 1103 positioned on the outer surface of the hollow tube of piezoelectric material. The hollow tube of piezoelectric material, or more generally the piezoelectric transducer body 1101, is cylindrical and has a circular radial cross-section. However, in alternative embodiments, the transducer body 1101 may have other shapes besides being cylindrical with a radial cross-section. The inner electrode 1102 is covered with an electrical insulator 1104, and the outer electrode 1103 is covered with an electrical insulator 1105. Alternatively, only one of electrodes 1102 or 1103 may be covered with an electrical insulator, or neither electrode 1102 nor 1103 may be covered with an electrical insulator. Other modifications are possible and are within the scope of the embodiments described herein.

[0104] [system] One aspect of the present invention relates to a system 800 for performing a denervation procedure and determining its effectiveness. The system 800 includes catheters 302, 702 comprising elements 311, 711 or first and second elements 311, 711 configured to selectively deliver ablation therapy, and one or more sensing electrodes 726, 727 configured to selectively sense nerve activity. The system 800 also includes an excitation source 826 configured to selectively supply energy to elements 311, 711 or the first and second elements 311, 711 of the catheters 302, 702, thereby delivering ablation therapy to the elements 311, 711 or the first and second elements 311, 711. The system 800 further comprises a sensing subsystem 804 electrically coupled to at least one sensing electrode 726, 727. The system 800 further comprises a controller 822, an excitation source 826, and a sensing subsystem 804, all of which are communicatively coupled to the catheters 302, 702. The controller 822 is configured to cause the excitation source 826 to supply energy to the element 311, 711 or the first element 311, 711 while the element 311, 711 or the first element 311, 711 is located in a first longitudinal location along the biological lumen, thereby delivering a first ablation therapy. The controller 822 is configured to cause the excitation source 826 to supply energy to the element 311, 711 or the second element 311, 711 while the element 311, 711 or the second element 311, 711 is located in a second longitudinal location along the biological lumen 104 longitudinally separated from the first longitudinal location, thereby delivering a second ablation therapy. The controller 822 is further configured such that the sensing subsystem 804 senses neural activity from a third longitudinal location using at least one of one or more sensing electrodes 726, 727, thereby quantifying the extent to which nerves surrounding the biological lumen 104 and adjacent to at least one of the first and second longitudinal locations were affected by the delivery of the first and second ablation therapies.

[0105] In one embodiment, the system 800 also includes a memory 820 configured to store instructions that can be executed by one or more processors of the controller 822, which cause the excitation source 826 to supply energy to elements 311, 711 or first and second elements 311, 711, and the sensing subsystem 814 to sense neural activity.

[0106] In one embodiment, the neural activity sensed using the sensing subsystem 804 includes unique neural activity.

[0107] In one embodiment, the system 800 further comprises one or more stimulating electrodes 724, 725 located on catheters 302, 702, and a stimulator 806 electrically coupled to one or more stimulating electrodes 724, 725 and communicatively coupled to a controller 822. In this embodiment, the controller 822 is further configured to cause the stimulator 806 to generate one or more stimulating pulses delivered via at least one of the one or more stimulating electrodes 724, 725, thereby inducing a neural response. The neural activity sensed by the sensing subsystem 804 from a third longitudinal location includes the induced neural response to one or more stimulating pulses.

[0108] In one embodiment, a third longitudinal location where neural activity is sensed and the first and second ablation therapies have been delivered, respectively, is longitudinally located between the first and second longitudinal locations.

[0109] In one embodiment, at least one of one or more stimulating electrodes 724, 725 used to deliver one or more stimulation pulses is located in a longitudinal location that is proximal to both a first longitudinal location and a second longitudinal location. In one embodiment, a third location is where an evoked neuronal response is sensed using at least one of one or more sensing electrodes 726, 727, and is distal to both the first longitudinal location and the second longitudinal location.

[0110] In one embodiment, at least one of one or more stimulating electrodes 724, 725 used to deliver one or more stimulation pulses is located in a longitudinal location that is proximal to both a first longitudinal location and a second longitudinal location. In one embodiment, a third location is where an evoked neuronal response is sensed using at least one of one or more sensing electrodes 726, 727, and is proximal to both the first longitudinal location and the second longitudinal location.

[0111] In one embodiment, elements 311 and 711 include transducers 311 and 711.

[0112] In one embodiment, the controller 822 is configured to cause the excitation source 826 to energy the transducers 311 and 711 to deliver a first ablation therapy from a first longitudinal location along the biological lumen 104, and then, after the transducers 311 and 711 have moved from the first longitudinal location to a second longitudinal location, to energy the transducers 311 and 711 to deliver a second ablation therapy from a second longitudinal location longitudinally separated from the first longitudinal location along the biological lumen 104.

[0113] In one embodiment, the catheters 302, 702 include first and second transducers 311, 711 separated longitudinally along the shaft 722 of the catheters 302, 702. In one embodiment, the controller 822 is configured to supply energy from an excitation source 826 to the first transducers 311, 711 to deliver a first ablation therapy from a first longitudinal location along the biological lumen 104, and to supply energy from the second transducers 311, 711 to deliver a second ablation therapy from a second longitudinal location separated from the first longitudinal location along the biological lumen 104.

[0114] In one embodiment, the system 800 further comprises one or more stimulating electrodes 724, 725 located on catheters 302, 702, and a stimulator 806 electrically coupled to one or more stimulating electrodes 724, 725 and communicatively coupled to a controller 822. In one embodiment, the controller 822 is further configured to cause the stimulator 806 to generate one or more stimulating pulses delivered via at least one of the one or more stimulating electrodes 724, 725 at one of the longitudinal locations which is proximal or distal to both the first and second longitudinal locations, thereby inducing a neural response. The neural activity sensed from a third longitudinal location by the sensing subsystem 804 includes an induced neural response to one or more stimulating pulses, where the third longitudinal location is the other which is proximal or distal to both the first and second longitudinal locations.

[0115] In one embodiment, elements 311, 711 or the first and second elements 311, 711 are provided with one or more electrodes.

[0116] In one embodiment, the controller 822 is configured to determine, based on neural activity sensed from a third longitudinal location, whether further ablation therapy needs to be delivered from a location along the longitudinal length of the biological lumen 104.

[0117] In one embodiment, the controller 822 is configured to compare the measured value of the sensed neural activity with a corresponding threshold. In this embodiment, the controller 822 is also configured to determine that further ablation therapy is needed if the measured value of the sensed neural activity exceeds the corresponding threshold. In another embodiment, the controller 822 is also configured to determine that the ablation therapy is complete if the measured value of the sensed neural activity is below the corresponding threshold.

[0118] In one embodiment, the controller 822 is configured to compare the measured value of the sensed neural activity with a plurality of thresholds, for example, at least a first threshold and a second threshold. In one embodiment, the controller 822 determines that the ablation is incomplete when the neural activity is less than the first threshold but greater than the second threshold.

[0119] In one embodiment, the user interface 824 may be used to display a comparison between measured neural activity and a threshold value.

[0120] In one embodiment, the user interface 824 may be used to display a message to the user that, based on the determination of the controller 822, is either successful, incomplete, or failed.

[0121] In one embodiment, after the controller 822 determines that the ablation is successful, the user interface 824 may prompt the user to move to a different location.

[0122] In one embodiment, after the controller 822 determines that the ablation has failed, the user interface 824 may prompt the user to move to a different location, and / or the user interface 824 may display a message indicating that the ablation is incomplete, and / or the user interface 824 may prompt the user to continue excision at the same location.

[0123] In one embodiment, the controller 822 is configured to compare the number of complete ablations with a pre-programmed number of complete ablations to determine whether the procedure is complete and whether further ablations are necessary. For example, the pre-programmed number of complete ablations may be two or three ablations per main renal artery, and the controller 822 may determine that the procedure is complete when it determines that there have been two or three complete ablations per main renal artery.

[0124] In one embodiment, the controller 822 is configured to react to the controller 822 determining that it is necessary to deliver further ablation therapy by causing the excitation source 826 to supply energy to elements 311, 711 or the first or second elements 311, 711, thereby delivering further ablation therapy, while elements 311, 711 or the first or second elements 311, 711 are located along the longitudinal length of the biological lumen 104.

[0125] In one embodiment, elements 311, 711 or the first or second element 311, 711 are configured to deliver one of the following types of ablation therapy: radio frequency (RF) energy, microwave energy, ultrasonic energy, pulsed electric field energy, light energy, laser light, cryotherapy, or chemical ablation therapy.

[0126] [Exemplary Systems and Methods] Example 1. A system for performing a denervation procedure and determining its effectiveness, comprising: a catheter including one or more elements configured to selectively deliver ablation therapy and one or more sensing electrodes configured to selectively sense nerve activity; an excitation source configured to selectively supply energy to at least one of the one or more elements of the catheter, thereby delivering ablation therapy to at least one of the one or more elements; a sensing subsystem electrically coupled to at least one of the one or more sensing electrodes; and a controller communicatively coupled to the catheter, the excitation source and the sensing subsystem, wherein the excitation source is connected to the element A system comprising: a controller configured to supply energy to at least one of the elements thereby delivering a first ablation therapy at a first longitudinal location along a biological lumen; an excitation source configured to supply energy to at least one of the elements thereby delivering a second ablation therapy at a second longitudinal location along a biological lumen longitudinally separated from the first longitudinal location; and a sensing subsystem configured to determine the effectiveness of at least one of the first or second ablation therapies by sensing neural activity from a third longitudinal location using at least one of one or more sensing electrodes.

[0127] Example 2. The system according to Example 1, wherein a third longitudinal location is longitudinally located between the first longitudinal location and the second longitudinal location, and the first and second ablation therapies are delivered thereto, respectively.

[0128] Example 3. The system according to Example 1 or 2, wherein the controller is configured to quantify, based on neural activity sensed from a third longitudinal location, the extent to which nerves surrounding the biological lumen and adjacent to at least one of the first and second longitudinal locations were affected by the delivery of the first and second ablation therapies.

[0129] Example 4. The system according to Example 1, further comprising one or more stimulating electrodes located in a catheter, and a stimulator electrically coupled to one or more stimulating electrodes and communicably coupled to a controller, wherein the controller is further configured to cause the stimulator to generate one or more stimulating pulses delivered via at least one of the one or more stimulating electrodes, thereby inducing a neuronal response, and the neuronal activity sensed by a sensing subsystem from a third longitudinal location includes the induced neuronal response to one or more stimulating pulses.

[0130] Example 5. The system according to Example 4, wherein a third longitudinal location, where an induced neuronal response is detected and the first and second ablation therapies have been delivered, is longitudinally located between the first and second longitudinal locations.

[0131] Example 6. The system according to Example 4, wherein at least one of one or more stimulating electrodes used to deliver one or more stimulating pulses is located in a longitudinal location that is proximal to both first and second longitudinal locations, and a third location where the evoked nerve response is sensed using at least one of one or more sensing electrodes is distal to both first and second longitudinal locations.

[0132] Example 7. The system according to Example 4, wherein at least one of one or more stimulating electrodes used to deliver one or more stimulating pulses is located in a longitudinal location that is proximal to both first and second longitudinal locations, and a third location where the evoked nerve response is sensed using at least one of one or more sensing electrodes is distal to both first and second longitudinal locations.

[0133] Example 8. The system according to any one of Examples 1 to 7, wherein one or more elements comprise transducers.

[0134] Example 9. The system according to Example 8, wherein the controller is configured to power an excitation source to energy a transducer to deliver a first ablation therapy from a first longitudinal location along the biological lumen, and after the transducer has moved from the first longitudinal location to a second longitudinal location, it powers the transducer to deliver a second ablation therapy from a second longitudinal location longitudinally separated from the first longitudinal location along the biological lumen.

[0135] Example 10. The system according to any one of Examples 1 to 7, wherein one or more elements comprise a first transducer and a second transducer longitudinally separated from the first transducer, and the controller is configured to cause an excitation source to energy supply the first transducer to deliver a first ablation therapy from a first longitudinal location along the biological lumen, and to energy supply the second transducer to deliver a second ablation therapy from a second longitudinal location separated from the first longitudinal location along the biological lumen.

[0136] Example 11. The system according to Example 1, further comprising one or more stimulating electrodes located in a catheter, and a stimulator electrically coupled to one or more stimulating electrodes and communicably coupled to a controller, wherein the controller is further configured to cause the stimulator to generate one or more stimulating pulses delivered via at least one of the one or more stimulating electrodes at one of the longitudinal locations which is proximal or distal to both first and second longitudinal locations, thereby inducing a neuronal response, wherein neuronal activity sensed from a third longitudinal location by a sensing subsystem includes an induced neuronal response to one or more stimulating pulses, the third longitudinal location being the other of proximal or distal to both first and second longitudinal locations.

[0137] Example 12. The system according to any one of Examples 1 to 11, wherein the controller is configured to determine whether further ablation therapy needs to be delivered based on neural activity sensed from a third longitudinal location.

[0138] Example 13. The system according to Example 12, wherein the controller is configured to compare a measured value of sensed neural activity with a corresponding threshold and to determine if further ablation therapy needs to be delivered if the measured value of sensed neural activity exceeds the corresponding threshold.

[0139] Example 14. The system according to Example 13, wherein the controller is configured to deliver further ablation therapy in response to the controller determining that further ablation therapy needs to be delivered while at least one of the elements is located along the longitudinal length of the biological lumen, by causing the excitation source to supply energy to at least one of the elements, thereby delivering further ablation therapy.

[0140] Example 15. The method according to any one of Examples 1-7 or 11-14, wherein each of one or more elements is configured to deliver one of the following types of ablation therapy: radio frequency (RF) energy, microwave energy, ultrasonic energy, pulsed electric field energy, light energy, laser light, cryotherapy, or chemicals.

[0141] Example 16. A method for performing a denervation procedure and determining its effectiveness, comprising: delivering a first ablation therapy from a first longitudinal location along a biological lumen; delivering a second ablation therapy from a second longitudinal location longitudinally separated from the first longitudinal location along a biological lumen; and sensing nerve activity from a third longitudinal location longitudinally located between the first and second longitudinal locations, where the first and second ablation therapies have been delivered, and determining the effectiveness of at least one of the first and second ablation therapies.

[0142] Example 17. The method of Example 16, further comprising: inserting the distal portion of the catheter into a biological lumen such that the element is located at a first longitudinal location along the biological lumen, the method of delivering a first ablation therapy using the element being performed while the element is located at the first longitudinal location along the biological lumen; and manipulating the catheter such that the element is located at a second longitudinal location longitudinally separated from the first longitudinal location along the biological lumen, the method of delivering a second ablation therapy using the element being performed while the element is located at the second longitudinal location along the biological lumen.

[0143] Example 18. The method of Example 17, wherein the element includes a transducer.

[0144] Example 19. The method according to Example 17, wherein the element includes one or more electrodes.

[0145] Example 20. The method according to Example 16, wherein the method is performed using a catheter comprising first and second transducers longitudinally separated from each other along the shaft of the catheter, wherein the first ablation therapy is delivered from a first longitudinal location along the biological lumen using the first transducer, and the second ablation therapy is delivered from a second longitudinal location longitudinally separated from the first longitudinal location along the biological lumen using the second transducer.

[0146] Example 21. The method according to any one of Examples 16-20, further comprising determining whether further ablation therapy needs to be delivered based on neural activity sensed from a third longitudinal location.

[0147] Example 22. The method according to Example 21, wherein determining whether further ablation therapy is necessary based on neural activity sensed from a third longitudinal location includes comparing a measured value of the sensed neural activity with a corresponding threshold, and determining that further ablation therapy is necessary if the measured value of the sensed neural activity exceeds the corresponding threshold.

[0148] Example 23. The method of Example 22, further comprising delivering further ablation therapy in response to the determination that further ablation therapy is necessary.

[0149] Example 24. The method of Example 16, wherein sensing nerve activity from a third longitudinal location is performed using an electrode positioned at a third longitudinal location longitudinally located between the first and second longitudinal locations, and the electrode used to sense nerve activity from the third longitudinal location is included in the distal portion of a catheter, which may be the same as or a different catheter used to deliver the first and second ablation therapies.

[0150] Example 25. The method according to Example 24, wherein the neural activity sensed from a third longitudinal location includes intrinsic neural activity sensed using an electrode positioned at the third longitudinal location, the intrinsic neural activity is also sensed using a further electrode, the further electrode being positioned either within a biological lumen or outside the skin.

[0151] Example 26. The method of Example 25, wherein an additional electrode is positioned within a biological lumen between a first longitudinal location and a second longitudinal location.

[0152] Example 27. The method of Example 16, wherein neural activity sensed from a third longitudinal location includes an evoked neural response to a stimulus delivered from an electrode positioned within a biological lumen.

[0153] Example 28. The method of Example 27, wherein the induced nerve response is also sensed using additional electrodes, the additional electrodes being positioned either within a biological lumen or outside the skin.

[0154] Example 29. The method according to any one of Examples 16 to 28, wherein the biological lumen includes the renal artery.

[0155] Example 30. The method according to any one of Examples 16, 17, or 21-29, wherein each of the first and second ablation therapies is performed by delivering one of the following types of energy: radio frequency (RF) energy, microwave energy, ultrasonic energy, pulsed electric field energy, light energy, laser light, cryotherapy, or chemicals, using a catheter that includes a shaft inserted into a biological lumen.

[0156] Example 31. A method for performing a denervation procedure and determining its effectiveness, comprising: delivering a first ablation therapy from a first longitudinal location along a biological lumen; delivering a second ablation therapy from a second longitudinal location longitudinally separated from the first longitudinal location along a biological lumen; delivering stimulating energy using electrodes located at a third longitudinal location along a biological lumen, wherein the third longitudinal location is either proximal or distal to both the first and second longitudinal locations; sensing an evoked nerve response to the stimulating energy using further electrodes located at a fourth longitudinal location along a biological lumen, wherein the fourth longitudinal location is either proximal or distal to both the first and second longitudinal locations; and determining, based on the sensed evoked nerve response, whether further ablation therapy needs to be delivered.

[0157] Example 32. The method according to Example 31, wherein the third longitudinal location is proximal to both the first and second longitudinal locations, and the fourth longitudinal location is distal to both the first and second longitudinal locations.

[0158] Example 33. The method according to Example 31, wherein the third longitudinal location is proximal to both the first and second longitudinal locations, and the fourth longitudinal location is distal to both the first and second longitudinal locations.

[0159] Example 34. The method according to any one of Examples 31 to 33, wherein the first ablation therapy is delivered from a first longitudinal location by using a transducer on the distal portion of a catheter inserted into a biological lumen so that the transducer is positioned at the first longitudinal location, and the second ablation therapy is delivered from a second longitudinal location by using a transducer on the distal portion of a catheter inserted into a biological lumen after the transducer has been moved from being positioned at the first longitudinal location to being positioned at the second longitudinal location.

[0160] Example 35. The method according to any one of Examples 31 to 33, wherein the first ablation therapy is delivered from a first longitudinal location by emitting first radio frequency (RF) energy using one or more electrodes on the distal portion of a catheter inserted into a biological lumen so that one or more electrodes are positioned at the first longitudinal location, and the second ablation therapy is delivered from a second longitudinal location by emitting second RF energy using one or more electrodes on the distal portion of a catheter inserted into a biological lumen after one or more electrodes have been moved from being positioned at the first longitudinal location to being positioned at the second longitudinal location.

[0161] Example 36. The method according to any one of Examples 31 to 35, wherein determining whether further ablation therapy needs to be delivered based on a sensed evoked nerve response includes comparing a measured value of the sensed evoked nerve response with a corresponding threshold, and determining that further ablation therapy needs to be delivered if the measured value of the sensed nerve response exceeds the corresponding threshold, and further comprising delivering further ablation therapy in response to the determination that further ablation therapy needs to be delivered.

[0162] Example 37. The method according to any one of Examples 31-33 or 36, wherein each of the first and second ablation therapies is performed by delivering one of the following types: radio frequency (RF) energy, microwave energy, ultrasonic energy, pulsed electric field energy, light energy, laser light, cryotherapy, or chemicals, using a catheter including a shaft inserted into a biological lumen.

[0163] Example 38. The method according to any one of Examples 16 to 37, further comprising quantifying the extent to which nerves surrounding a biological lumen and adjacent to at least one of a first longitudinal location and a second longitudinal location were affected by the delivery of the first and second ablation therapies based on nerve activity sensed from a third longitudinal location.

[0164] Example 39. The method according to any one of Examples 16 to 37, further comprising displaying a message on the user interface indicating whether at least one of the first or second ablation therapies was successful, incomplete, and / or failed, based on neural activity sensed from a third longitudinal location.

[0165] Example 40. The system according to any one of Examples 1 to 15, wherein the neural activity sensed using the sensing subsystem includes intrinsic neural activity.

[0166] Example 41. The system according to any one of Examples 1 to 15, further comprising a user interface configured to display a message to the user indicating whether the ablation was successful, incomplete, and / or failed, based on neural activity sensed from a third longitudinal location.

[0167] While several embodiments and examples are disclosed herein, this application extends beyond the specifically disclosed embodiments to other alternative embodiments and / or uses of the Invention, as well as their modifications and equivalents. Furthermore, various combinations or subcombinations of specific features and aspects of the embodiments are still considered to fall within the scope of the Invention. Accordingly, it should be understood that the various features and aspects of the disclosed embodiments can be combined with or substituted for each other to form various modes of the disclosed Invention. Therefore, the scope of the Invention disclosed herein is not intended to be limited by the specific embodiments disclosed above, but should be determined solely by a fair reading of the subsequent claims.

[0168] While various modifications and alternative forms of the present invention are possible, specific examples are shown in the drawings and described in detail herein. However, it should be understood that the present invention is not limited to any particular form or method disclosed, but rather encompasses all modifications, equivalents, and alternatives that fall within the spirit and scope of the various embodiments described and the appended claims. The methods disclosed herein do not need to be carried out in the order mentioned.

Claims

1. A system for performing denervation procedures and determining their effectiveness, A catheter (302, 702) comprising one or more elements (311, 711) configured to selectively deliver ablation therapy, and one or more sensing electrodes (726, 727) configured to selectively sense nerve activity, An excitation source (826) is configured to selectively supply energy to at least one of the one or more elements (311, 711) of the catheter (302, 702), thereby delivering the ablation therapy to at least one of the one or more elements (311, 711), A sensing subsystem (804) electrically coupled to at least one of the one or more sensing electrodes (726, 727), A controller (822) that is communicatively coupled to the catheters (302, 702), the excitation source (826), and the sensing subsystem (804), The excitation source (826) supplies energy to at least one of the one or more elements (311, 711), thereby delivering the first ablation therapy at a first longitudinal location along the biological lumen. The excitation source (826) supplies energy to at least one of the one or more elements (311, 711), thereby delivering a second ablation therapy at a second longitudinal location along the biological lumen, which is longitudinally separated from the first longitudinal location. The sensing subsystem (804) is configured to sense neural activity from a third longitudinal location using at least one of the one or more sensing electrodes (726, 727), and the controller (822) is configured to determine that both the first and second ablation therapies were effective when the sensing subsystem does not substantially detect neural activity at the third longitudinal location. The system (800) wherein the third longitudinal location is longitudinally located between the first longitudinal location and the second longitudinal location, and the first and second ablation therapies are delivered from the first and second longitudinal locations, respectively.

2. The system (800) according to claim 1, wherein the controller (822) is configured to quantify, based on the nerve activity sensed from the third longitudinal location, the extent to which nerves surrounding the biological lumen and adjacent to at least one of the first and second longitudinal locations have been affected by the delivery of the first and second ablation therapies.

3. One or more stimulating electrodes (724, 725) located on the catheter (302, 702), The system further comprises a stimulator (806) electrically coupled to one or more stimulator electrodes (724, 725) and communicatively coupled to the controller (822), The controller (822) is further configured to cause the stimulator (806) to generate one or more stimulation pulses that are delivered via at least one of the one or more stimulation electrodes (724, 725), thereby inducing a neuronal response. The system (800) according to claim 1, wherein the neural activity sensed by the sensing subsystem (804) from the third longitudinal location includes an evoked neural response to one or more stimulation pulses.

4. The system (800) according to claim 3, wherein the third longitudinal location where the induced nerve response is sensed is longitudinally located between the first longitudinal location and the second longitudinal location, and the first and second ablation therapies have been delivered from the third longitudinal location, respectively.

5. At least one of the one or more stimulating electrodes (724, 725) used to deliver the one or more stimulating pulses is located in a longitudinal position that is proximal to both the first and second longitudinal locations, The system (800) according to claim 3, wherein the third location where the induced nerve response is sensed using at least one of the one or more sensing electrodes (726, 727) is distal to both the first and second longitudinal locations.

6. At least one of the one or more stimulating electrodes (724, 725) used to deliver the one or more stimulating pulses is located in a longitudinal position distal to both the first and second longitudinal positions, The system (800) according to claim 3, wherein the third location where the induced neural response is sensed using at least one of the one or more sensing electrodes (726, 727) is proximal to both the first and second longitudinal locations.

7. The system (800) according to claim 1, wherein one or more of the elements (311, 711) include transducers (311, 711).

8. The system (800) according to claim 7, wherein the controller (822) is configured to cause the excitation source (826) to supply energy to the transducers (311, 711) to deliver the first ablation therapy from a first longitudinal location along the biological lumen, and the transducers (311, 711) are moved from the first longitudinal location to a second longitudinal location, and then the transducers (311, 711) are configured to supply energy to deliver the second ablation therapy from a second longitudinal location longitudinally separated from the first longitudinal location along the biological lumen.

9. The one or more elements (311, 711) include a first transducer (311, 711) and a second transducer (311, 711) longitudinally separated from the first transducer (311, 711), The system (800) according to claim 1, wherein the controller (822) is configured to supply energy from the excitation source (826) to the first transducer (311, 711) to deliver the first ablation therapy from a first longitudinal location along the biological lumen, and to supply energy from the second transducer (311, 711) to deliver the second ablation therapy from a second longitudinal location separated from the first longitudinal location along the biological lumen.

10. One or more stimulating electrodes (724, 725) located on the catheter (302, 702), The system further comprises a stimulator (806) electrically coupled to one or more stimulator electrodes (724, 725) and communicatively coupled to the controller (822), The controller (822) is further configured to cause the stimulator (806) to generate one or more stimulation pulses delivered via at least one of the one or more stimulation electrodes (724, 725) at a longitudinal location that is proximal or distal to both the first and second longitudinal locations, thereby inducing a neuronal response. The system (800) according to claim 1, wherein the neural activity sensed by the sensing subsystem (804) from a third longitudinal location includes an evoked neural response to one or more stimulation pulses, and the third longitudinal location is either proximal or distal to both the first and second longitudinal locations.

11. The system (800) according to claim 1, wherein the controller (822) is configured to determine whether further ablation therapy needs to be delivered based on the neural activity sensed from the third longitudinal location.

12. The controller (822) Comparing the measured value of the perceived neural activity with the corresponding threshold, The system (800) according to claim 11, configured to determine that further ablation therapy needs to be delivered when the measured value of the sensed neural activity exceeds the corresponding threshold.

13. The system (800) according to claim 12, wherein the controller (822) is configured to respond to the controller (822) determining that it is necessary to deliver further ablation therapy while at least one of the one or more elements (311, 711) is located along the longitudinal length of the biological lumen, by causing an excitation source (826) to supply energy to at least one of the one or more elements (311, 711), thereby delivering further ablation therapy.

14. Each of the one or more elements (311, 711) is a part of ablation therapy. Radio frequency (RF) energy, microwave energy, Ultrasonic energy, Pulse electric field energy, Light energy, Laser light, Cryotherapy, or The system (800) according to claim 1, configured to deliver one of the types of chemicals.

15. The system (800) according to claim 1, wherein the neural activity sensed using the sensing subsystem (804) includes intrinsic neural activity.

16. The system (800) according to claim 1, further comprising a user interface (824) configured to display a message to the user indicating whether the ablation was successful, incomplete, and / or failed, based on neural activity sensed from a third longitudinal location.

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