Systems and methods for performing denervation procedures and determining their effectiveness - Patents.com

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

[0002] [Technical field] SUMMARY OF THE DISCLOSURE Embodiments of the present technology relate generally to techniques, and associated systems and methods, for performing denervation procedures and determining the effectiveness of denervation procedures. [Background technology]

[0003] The nervous system of the human body includes both the somatic nervous system, which provides sensing of the environment (e.g., vision, skin sensation) and regulation of skeletal muscles and is largely under voluntary control, and the autonomic nervous system, which serves primarily to regulate the activity of the internal organs and adapt them to the body's current needs and is largely not under voluntary control. The autonomic nervous system involves both afferent or sensory nerve fibers that can sense the state of the organs mechanically and chemically, and efferent fibers that convey the response of the central nervous system to the sensed state information (sometimes called a reflex arc). In some cases the somatic nervous system is also affected, such as by inducing vomiting or coughing in response to the sensed state.

[0004] Thus, the regulation of the organs of the human body can be characterized and controlled in part by monitoring and influencing the neural reflex arcs that cause organ activity.For example, the renal nerves leading to the kidneys often cause greater than desired reflex responses and can contribute significantly to hypertension.Thus, measurement of neural activity near the kidneys and subsequent ablation of the renal nerves can be used to control the nervous system's overstimulation of the kidneys, improving the operation of the kidneys and the entire body.

[0005] Therefore, because proper operation of the nervous system is a critical part of proper organ function, it is desirable to be able to monitor and alter nervous system function in the human body and to be able to characterize and modify nervous system regulation of human internal organs.

[0006] The aim of new medical therapies, which involve inserting catheters into the body at predefined anatomical locations and transmitting destructive means to nerves through the catheter (or probe) to irreversibly damage tissue in neighboring areas, is to regulate (e.g., abolish) the neural function of the specified anatomical location, so that the abnormally functioning physiological process is terminated or can be brought back to normal range. Unfortunately, such medical therapies are not always successful, as it is not possible to assess whether the neural activity has been successfully abolished. An alternative aim may be to increase or regulate the physiological process to an abnormal range.

[0007] One example is renal nerve ablation, known as renal denervation, 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 vasculature of a hypertensive patient and advanced to the renal artery. The renal nerve is located within the arterial wall and / or in the area adjacent to the artery. A destructive agent is delivered in close proximity to the renal artery wall to the extent intended to cause destruction of renal nerve activity. Destructive agents include energy such as radio frequency (RF), microwave, cryotherapy, ultrasound, optical, laser, or chemical agents. The goal is to abolish renal nerve activity. Such nerve activity is a key component in the generation and / or maintenance of hypertension, and abolishing nerve activity reduces blood pressure and drug burden.

[0008] Unfortunately, not all patients respond favorably to this therapy. Renal nerve ablation procedures are often ineffective, potentially due to a poor probe / tissue interface. Thus, an insufficient amount of destructive means is delivered to the nerve fibers traveling along the renal artery. One reason is that the delivery of destructive means to the arterial wall has no feedback mechanism to evaluate the effectiveness of the destruction of neural activity. As a result, an insufficient amount of destructive means is delivered and neural activity is not abolished. Thus, clinicians would benefit from improved methods of monitoring the integrity of the nerve fibers passing through the arterial wall to confirm the destruction of neural activity before terminating the therapy. Current techniques for the destruction of neural activity do not provide the practitioner with a feedback mechanism to detect when the desired destruction of neural activity has been achieved. Neurodestructive means are applied empirically without knowing that the desired effect has been achieved.

[0009] It is known that ablation of renal nerves with sufficient energy can effectively reduce both systolic and diastolic blood pressure. Current methods are said to be open loop from an engineering point of view, i.e., the methods used to effectively denervate the kidney do not employ any method to measure the results of the applied ablation energy in an acute clinical setting. Only after application of such energy and for a certain period of time (3-12 months) is the effectiveness of the procedure known. Summary of the Invention

[0010] Certain embodiments of the present technology relate to a system for performing a denervation procedure and determining its effectiveness. According to certain embodiments, such a system comprises a catheter including an element or first and second elements configured to selectively deliver an ablation therapy and one or more sensing electrodes configured to selectively sense neural activity. The system also comprises an excitation source configured to selectively energize the element or first and second elements of the catheter, thereby causing the element or first and second elements to deliver an ablation therapy. Additionally, the system comprises a sensing subsystem electrically coupled to at least one sensing electrode. The system further comprises a controller communicatively coupled to the catheter, the excitation source, and the sensing subsystem. According to certain embodiments, the controller is configured such that the excitation source energizes the element or first element, thereby causing a first ablation therapy to be delivered, while the element or first element is located at a first longitudinal location along the biological lumen. The controller is configured such that the excitation source energizes the element or the second element to thereby deliver a second ablation therapy, while the element or the second element is located at a second longitudinal location along the biological lumen longitudinally spaced from the first longitudinal location, and the controller is further configured such that the sensing subsystem senses neural activity from a third longitudinal location, using at least one of the one or more sensing electrodes, to determine the effectiveness of at least one of the first or second ablation therapies.

[0011] Certain embodiments of the present technology relate to a method of performing a denervation procedure and determining its effectiveness, the method including delivering a first ablation therapy from a first longitudinal location along a biological lumen and delivering an ablation therapy from a second longitudinal location along the biological lumen spaced longitudinally from the first longitudinal location, the method further including sensing neural activity from a third longitudinal location longitudinally located between the first longitudinal location and the second longitudinal location, where the first or second ablation therapy has been delivered, respectively, and determining the effectiveness of at least one of the first or second ablation therapies.

[0012] According to certain embodiments, the method includes delivering a first ablation therapy from a first longitudinal location along the biological lumen, delivering a second ablation therapy from a second longitudinal location along the biological lumen that is longitudinally spaced from the first longitudinal location, and delivering stimulation energy using an electrode located at a third longitudinal location along the biological lumen, the third longitudinal location being one of proximal or distal to both the first and second longitudinal locations. The method also includes sensing an evoked neural response to the stimulation energy using an additional electrode located at a fourth longitudinal location along the biological lumen, the fourth longitudinal location being the other of proximal or distal to both the first and second longitudinal locations. The method further includes determining whether an additional ablation therapy needs to be delivered from a location along the longitudinal length of the biological lumen based on the sensed evoked neural response.

[0013] This summary is not intended to be a complete description of the embodiments of the present technology. Other features and advantages of the embodiments of the present technology will appear from the following description, in conjunction with the accompanying drawings and claims, in which preferred embodiments are set forth in detail. [Brief description of the drawings]

[0014] [Figure 1]Illustrates the kidneys, which receive blood via the abdominal aorta, the renal arteries, and branching vessels.

[0015] [Diagram 2] A cross section of a renal artery, used to illustrate the various layers and nerves of the renal artery wall.

[0016] [Diagram 3] It illustrates how a transducer in the renal artery can be used to deliver ablation therapy to a treatment area as part of a denervation procedure and is used to explain why it is difficult to determine the effectiveness of such a denervation procedure.

[0017] [Figure 4] 1 illustrates an improved technique for determining the effectiveness of a denervation procedure that involves performing nerve destruction at two longitudinal locations along the renal artery and sensing an intrinsic or evoked nerve response at a longitudinal location between the two nerve destruction sites.

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

[0019] [Figure 6] FIG. 1 is a high-level flow diagram used to summarize a method for performing a denervation procedure and determining its effectiveness, according to one particular embodiment of the current technology.

[0020] [Figure 7A] 1 illustrates an exemplary catheter having two selectively deployable electrodes in a non-deployed position.

[0021] [Figure 7B] 7B shows a catheter having two selectively deployable electrodes in their deployed positions as introduced in FIG. 7A.

[0022] [Figure 8] 1 is a schematic diagram of an exemplary system for interfacing with a patient's arterial nerve in accordance with an embodiment of the present technology.

[0023] [Figure 9A] 7A and 7B illustrate an example cross-section of a portion of the shaft of the catheter shown in FIG. [Figure 9B] 7A and 7B illustrate an example cross-section of a portion of the shaft of the catheter shown in FIG.

[0024] [Figure 10] 9 illustrates example details of the fluid supply subsystem introduced in FIG. 8.

[0025] [Figure 11A] 7A and 7B illustrate longitudinal and radial cross-sectional views, respectively, of an exemplary catheter transducer shown in FIG. [Figure 11B] 7A and 7B illustrate longitudinal and radial cross-sectional views, respectively, of an exemplary catheter transducer shown in FIG. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0026] In the following detailed description of the exemplary embodiments, reference is made to certain exemplary embodiments using drawings or illustrations. These examples are described in sufficient detail to enable those skilled in the art to practice what is described, and serve to illustrate how the elements of these examples are applied to various purposes or embodiments. Other embodiments exist, and logical, mechanical, electrical, and other changes may be made. The features or limitations of the various embodiments described herein are material to the exemplary embodiments in which they are incorporated, but do not limit other embodiments, and references to the elements, operations, and applications of the examples serve only to define these exemplary embodiments. The features or elements shown in the various examples described herein may be combined in ways other than those shown in the examples, and such combinations are expressly considered to be within the scope of the examples shown herein. Therefore, the following detailed description is not intended to limit the scope of what is claimed.

[0027] Modulation of the nervous system manipulation to characterize neural signals includes, in some instances, the introduction of a catheter (also referred to as a probe) into the body to a specific anatomical location and the partial destruction or ablation of a nerve using the probe to destroy neural tissue in an area near the probe. By reducing neural function in a selected location, abnormally functioning physiological processes can often be regulated back to normal ranges. It may also be possible to modulate neural function to intentionally induce abnormally functioning physiological processes that are beneficial to the patient.

[0028] Unfortunately, it is typically very difficult to estimate the extent to which neural activity has decreased, making it difficult to perform procedures in which it is desirable to remove all of the nerves, or to ablate some, but not all, of the nerves to restore the neural response to a desired range without completely destroying the neural response. Denervation procedures can be used, for example, to perform renal nerve ablation to treat hypertension.

[0029] As illustrated in FIG. 1 , the kidney 102 receives blood via the abdominal aorta 106, the renal artery 104, and the branching vessels 108. The renal sympathetic nerve, also called the sympathetic renal nerve, generally runs along the abdominal aorta 106 and the renal artery 104 and allows communication between the brain and the kidney 102. The renal sympathetic nerve includes both the afferent sensory renal nerve, which carries nerve impulses from the kidney 102 to the brain, and the efferent sympathetic renal nerve, which carries nerve impulses from the brain to the kidney 102. In other words, the efferent renal nerve 104 following the renal artery carries impulses from the brain to the kidney 102. In contrast, the afferent renal nerve following the renal artery carries impulses from the kidney 102 to the brain.

[0030] As illustrated in FIG. 2, which is a cross-section of a renal artery 104, the renal artery wall is made up of multiple layers, including the tunica intima 203, which contains an inner single layer of endothelial cells, the tunica media 205 in the middle of the arterial wall, and the tunica adventitia 204, which is an outer surface layer. Also shown are renal nerves 208 within the tunica adventitia 204, on the surface of the renal artery 104, and adjacent to the renal artery 104. The renal nerves 208 surround the renal artery 104. Different individuals have renal nerves 208 at different sites around the renal artery 104. Thus, the renal nerves 208 may be at different radial distances R from the central axis A of the renal artery 104 and may be in different locations around the renal artery 104. It is not practical to locate the renal nerves by reference 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 referred to as renal denervation) can be used to treat hypertension. Various studies have confirmed that renal nerve activity is associated with hypertension and that ablation of the renal nerve can improve renal function and reduce hypertension. In a typical procedure, a catheter (also referred to as a probe) is introduced into the arterial vasculature of a hypertensive patient and advanced into the renal artery 104. In a renal nerve denervation procedure, the renal nerve 208 located in the arterial wall and the area adjacent to the renal artery 104 is ablated by destructive means such as radio frequency (RF) energy, microwave energy, ultrasound energy, pulsed field energy, cryotherapy, laser or chemical agents to limit renal nerve activity and thereby reduce the patient's hypertension. The destructive means used to perform such a renal denervation procedure can be a transducer located on a distal portion of a catheter inserted into the renal artery 104. In much of the remaining discussion, the transducer is assumed to be an ultrasound transducer that can be operated to deliver unfocused ultrasound energy radially outward to suitably heat and treat tissue within the target anatomical region surrounding the renal artery 104. Such a transducer can be operated at a frequency, duration, and energy level suitable for treating the target tissue. In one non-limiting example, the unfocused ultrasound energy generated by the transducer can target selected neural tissue of a subject and heat such tissue in a manner to neuromodulate the neural tissue (e.g., completely or partially ablate, necrotize, or stimulate). Those skilled in the art will recognize that other mechanisms can be used to denervate the neural 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] Reference is now made to Figure 3, which is similar to Figure 1 in showing the kidney 102 receiving blood via the abdominal aorta 106, the renal artery 104, and the branch vessels 108, labeled the same in Figure 3 as in Figure 1. Figure 3 also shows a catheter 302 with a transducer 311 located on a 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 a balloon, an example of which is described in detail below with reference to Figures 7A and 7B. In Figure 3, the dashed cylindrical region labeled 312 indicates an exemplary denervation treatment region, with the portion of the renal artery 104 labeled A being proximal or upstream to the treatment region 312 and the portion of the renal artery labeled B being distal or downstream to the treatment region 312. The actual denervation treatment area may differ from the dashed cylindrical area labeled 312.

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

[0034] Prior to performing such a denervation procedure, the same catheter 302 or a separate catheter may be used to sense pre-denervation neural activity (also referred to as baseline neural activity) and compare the pre-denervation neural activity to post-denervation neural activity to determine whether the denervation procedure was successful and whether the denervation procedure can be terminated or whether additional ablation energy (or other type of ablation therapy) needs to be delivered. Furthermore, even if pre-denervation neural activity (also referred to as baseline neural activity) is not sensed, it may still be useful to sense post-denervation neural activity for purposes of determining whether the denervation procedure was successful and therefore whether it can be terminated or whether additional ablation energy (or other type of ablation therapy) needs to be delivered. The neural activity may be sensed using electrodes on the catheter, which may be the same catheter 302 or a separate catheter. Such electrodes may be positioned within the treatment region 312, upstream of the treatment region 312, or downstream of the treatment region 312. The neural activity sensed using such electrodes is intrinsic neural activity, which may alternatively be referred to as spontaneous neural activity. Alternatively, or in addition, the neural activity sensed using such electrodes may be an evoked neural response in response to stimulation energy delivered using an additional electrode on a catheter inserted into the renal artery 104.

[0035] After ablation energy (or other type of ablation therapy) is delivered to the treatment region 312, if one or more electrodes used to sense neural activity are positioned in region A of FIG. 3 proximal to (i.e., upstream of) the treatment region 312 in the renal artery 104, it may be difficult to determine the effectiveness of the denervation procedure because even if the target renal nerve in the treatment region 312 is sufficiently destroyed, neural activity of the efferent renal nerve attempting to carry nerve impulses from the brain to the kidney 102 may be detected by electrodes proximal to (i.e., upstream of) the treatment region 312. 3, i.e., distal to (i.e., downstream of) the treatment region 312 in the renal artery 104, it may also be difficult to determine the effectiveness of the denervation procedure because even if the target renal nerve in the treatment region 312 is sufficiently destroyed, neural activity of the afferent renal nerve attempting to carry a nerve impulse from the kidney 102 toward the brain may be detected by electrodes distal to (i.e., downstream of) the treatment region 312. More generally, the discussion of FIG. 3 is used to explain why, when one wishes to destroy nerves in a particular length or segment of a biological lumen (e.g., the renal artery) as part of a denervation procedure, it is often difficult to know whether the nerve destruction has been sufficient so that the denervation procedure can be considered complete.

[0036] As described below with reference to FIG. 4, in accordance with certain embodiments of the present technology, 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 neural responses at a longitudinal location between the two nerve destruction sites to improve the ability to determine the effectiveness of a denervation procedure.

[0037] More specifically, according to certain embodiments of the present technology, if one wishes to destroy nerves within a particular length or segment of a biological lumen (e.g., a renal artery), a catheter (302 in FIG. 3) is used to deliver ablation energy (or another type of ablation therapy) to a first longitudinal location (e.g., a distal end of the particular length or segment of the biological lumen) and then deliver ablation energy (or another type of ablation therapy) to a second longitudinal location (e.g., a proximal end of the particular length or segment of the biological lumen), or vice versa. The same catheter or separate catheters are then used to sense the intrinsic and / or evoked neural response between the first and second longitudinal locations of the biological lumen (i.e., between the two nerve destruction sites) to determine whether sufficient nerve destruction has been performed. If the intrinsic and / or evoked neural response are below a respective specified threshold, it can be determined that sufficient nerve destruction has been performed. On the other hand, if the intrinsic and / or evoked neural response are above a respective specified threshold, it can be determined that sufficient nerve destruction has not been performed. If sufficient nerve destruction has not been achieved, additional ablation energy (or another type of ablation therapy) can be applied to the first and / or second longitudinal locations. Additionally or alternatively, additional ablation energy (or another type of ablation therapy) can be delivered at one or more longitudinal locations between the first and second longitudinal locations. Additionally or alternatively, additional ablation energy (or another type of ablation therapy) can be delivered at a longitudinal location proximal (upstream of) the first and second longitudinal locations and / or at one or more longitudinal locations distal (downstream of) the first and second longitudinal locations.

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

[0039] 4, the dashed cylindrical region labeled 414 illustrates an exemplary first denervation treatment region, and the dashed cylindrical region labeled 416 illustrates an exemplary second denervation treatment region, with treatment regions 414 and 416 spaced apart longitudinally from one another along the renal artery 104. With further reference to FIG. 4, the portion of the renal artery 104 labeled A is proximal or upstream to both treatment regions 414 and 416, the portion of the renal artery 104 labeled B is distal or downstream to both treatment regions 414 and 416, and the portion of the renal artery 104 labeled C is between treatment regions 414 and 416. In accordance with certain embodiments of the present technology, one or more sensing electrodes are positioned within the portion of the renal artery 104 labeled C (i.e., between treatment regions 414 and 416) for purposes of determining the effectiveness of ablation energy delivered to treatment regions 414 and 416.

[0040] In such an embodiment, substantially no neural activity is detected between the two ablation locations (i.e., between treatment regions 414 and 416) indicating that both efferent and afferent traffic has been severed. In other words, if the ablations performed at both treatment regions 414 and 416 are successful, substantially no neural activity should be detected between treatment regions 414 and 416. More specifically, after ablation energy is delivered to treatment regions 414 and 416, if the ablation energy successfully denervates the renal nerve at both treatment regions 414 and 416, the ablation energy delivered to treatment region 414 should prevent the renal nerve's efferent impulses (traveling from the brain toward the kidney 102) from reaching region C, and the ablation energy delivered to treatment region 416 should prevent the renal nerve's afferent impulses (traveling from the kidney 102 toward the brain) from reaching region C. Thus, if the ablation performed in both treatment regions 414 and 416 is successful, one or more electrodes positioned within region C (FIG. 4) of the renal artery 104 will not detect substantially any renal nerve activity, i.e., the detected renal nerve activity will be below a specified threshold.

[0041] FIG. 5 illustrates expected sensed nerve activity in three regions, labeled A, B, and C in FIG. 4, following the denervation procedure described with reference to FIG. 4. Referring to FIG. 5, graph 502 illustrates expected nerve activity that may be sensed proximal (i.e., upstream) of treatment regions 414 and 416 in FIG. 4, indicating that the efferent renal nerve is inflamed. Graph 504 illustrates expected nerve activity that may be sensed in region B in FIG. 4, distal (i.e., downstream) of both treatment regions 414 and 416, thus indicating that the afferent renal nerve is inflamed. With further reference to FIG. 5, graph 506 illustrates expected nerve activity that may be sensed in region C, longitudinally between treatment regions 414 and 416, if the ablation energy delivered to each treatment region 414 and 416 successfully ablates the renal nerve therein. Thus, graph 506 illustrates that there is substantially no sensed nerve activity within region C.

[0042] Using the high level flow diagram of Figure 6, a method for performing a denervation procedure and determining its effectiveness is described, which may be implemented using a system (e.g., 800) that includes or may be electrically coupled to a catheter (e.g., 302, 702) in accordance with certain embodiments of the present technology. With reference to Figure 6 (as well as Figures 3, 4, 7, and 8), step 602 involves delivering a first ablation therapy from a first longitudinal location along the biological lumen (such as a renal artery). Step 604 involves delivering a second ablation therapy longitudinally from a second longitudinal location spaced apart 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) positioned longitudinally within the renal artery 104 such that ablation occurs in the treatment region 414, and step 604 can be performed by delivering a second ablation therapy from a transducer (e.g., 311, 711 or another transducer) positioned longitudinally within the renal artery 104 such that ablation occurs in the treatment region 416. Alternatively, step 602 can be performed by delivering a first ablation therapy from a transducer (e.g., 311, 711) positioned longitudinally within the renal artery 104 such that ablation occurs in the treatment region 416, and step 604 can be performed by delivering a second ablation therapy from a transducer (e.g., 311, 711 or another transducer) positioned longitudinally within the renal artery 104 such that ablation occurs in the treatment region 414. In other words, the first ablation therapy can be delivered proximally (downstream) than the second ablation therapy, depending on the particular implementation. In the above example, the transducer (311, 711, etc.) is positioned at a first location (such as the renal artery 104) within the biological lumen, step 602 is performed, and then the transducer (311, 711, etc.) is repositioned to a second location (such as the renal artery 104) either upstream or downstream of the first location within the biological lumen.Alternatively, two longitudinally separated transducers may be used to deliver ablation therapy at first and second locations within a biological lumen (such as the renal arteries 104).

[0043] According to certain embodiments, the same transducer (e.g., 311, 711) can be used to perform both steps 602 and 604 by first manipulating the catheter (e.g., 302, 702) containing the transducer (e.g., 311, 711) so that the transducer (e.g., 311, 711) is positioned at a first location and performing step 602 while the transducer 311, 711 is positioned at the first location, and then manipulating the catheter (e.g., 302, 702) containing the transducer (e.g., 311, 711) so that the transducer (e.g., 311, 711) is positioned at a second location and performing step 604 while the transducer (e.g., 311, 711) is positioned at the second location. More generally, the same therapy delivery element (e.g., 311, 711) can be used to perform both steps 602 and 604 by 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 and performing step 602 while the therapy delivery element (e.g., 311, 711) is positioned at the first location, and then 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 second location and performing step 604 while the therapy delivery element (e.g., 311, 711) is positioned at the second location.

[0044] In other embodiments, a catheter (e.g., 302, 702) includes two transducers (or other types of therapy delivery elements) that are longitudinally spaced apart from one another along a 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, a catheter (e.g., 302, 702) including two transducers (or other types of therapy delivery elements) is manipulated such that one of the transducers (or other types of therapy delivery elements) is positioned at a first location and the other of the transducers (or other types of therapy delivery elements) is positioned at a second location. Steps 602 and 604 may be performed simultaneously by energizing the two transducers simultaneously. Alternatively, step 602 can be performed by first energizing one of the transducers positioned at a first location, and then step 604 can be performed by energizing another of the transducers positioned at a second location, or vice versa. An example of a catheter including two longitudinally separated transducers is disclosed in U.S. Patent Publication No. 2023 / 0021354. Other catheters including two longitudinally separated transducers (or other types of therapy delivery elements) can also be used 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 in no balloon. Examples of other types of therapy delivery elements that may be spaced longitudinally apart from one another along the shaft (e.g., 722) of the catheter (e.g., 302, 702) and that may be used to perform 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 may also be referred to herein as elements configured to selectively deliver ablation therapy.

[0045] According to certain embodiments, the ablation therapy delivered at an instance of step 602 may include performing multiple ablations from a first longitudinal location. For example, multiple circumferential ablations may be performed from the same first longitudinal location simultaneously or sequentially in a time-multiplexed manner. This may be accomplished, for example, by performing multiple separate focal ablations from the first longitudinal location. In a more specific example, multiple (e.g., four) RF electrodes may be distributed around a portion of the circumference of the catheter (e.g., 302, 702). Such multiple RF electrodes may be used to emit ablation energy from the same longitudinal location in different radial directions simultaneously or in a time-multiplexed manner. Similarly, the ablation therapy delivered at step 604 may include performing multiple ablations from a second longitudinal location. Additionally, further ablations performed at an instance of step 608 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 located longitudinally between the first and second longitudinal locations, to which the first and second ablation therapies have been delivered (steps 602 and 604), respectively, thereby quantifying the extent to which nerves surrounding the biological lumen and adjacent 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, and referring briefly back to Figure 4, the sensing of step 606 may be performed from a location within region C shown in Figure 4. Additional details of how to perform step 606 are provided below.

[0047] Referring again to FIG. 6, optional but desirable step 608 involves determining whether further ablation therapy needs to be delivered from locations along the longitudinal length of the biological lumen based on the sensed neural activity (sensed in step 606). More specifically, the measure of neural activity sensed in step 606 may be compared to a corresponding threshold in step 608, and if the measure of neural energy is less than the threshold, then there may be a determination in step 608 that the denervation procedure was successful and no further denervation of the biological lumen is required. In contrast, if the measure of neural energy exceeds the corresponding threshold, then there may be a determination in step 608 that the denervation procedure was not successful and further denervation of the biological lumen is still required. If further denervation of the biological lumen is still required, then in optional but desirable step 610, further ablation therapy may 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 measure of the sensed neural activity 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 indicative of neural activity, an average or median amplitude can be determined, and that average or median amplitude can be the measure of the neural activity that is compared to the threshold. Alternatively, a curve can be fitted to a portion of the sensed signal indicative of neural activity, and the area under the curve can be the measure of the neural activity that is compared to the threshold. Other variations are possible and are within the scope of the embodiments described herein. The particular threshold to which the measure of neural activity is compared depends on how the particular measure of neural activity is determined.

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

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

[0050] According to certain embodiments, the neural activity sensed from the third longitudinal location in step 606 is intrinsic (also referred to as spontaneous) neural activity. According to other embodiments, the neural activity sensed from the third longitudinal location includes an evoked neural response to a delivered stimulus. Such a stimulus that induces a neural response can be delivered from at least one electrode (e.g., 726, 727) positioned in the biological lumen proximal (upstream) of both the first and second longitudinal locations, or at least one electrode (e.g., 726, 727) positioned in the biological lumen distal (downstream) of both the first and second longitudinal locations. Regardless of whether the neural activity sensed in step 606 is intrinsic (also referred to as spontaneous) neural activity or evoked neural activity, the neural activity sensed in step 606 can be sensed by electrodes (e.g., 726, 727) and additional electrodes positioned between the first and second longitudinal locations. In certain embodiments, additional electrodes are also positioned within the biological lumen between the first and second longitudinal locations, where both of the electrodes (e.g., 726, 727) used to sense intrinsic (aka spontaneous) neural activity are positioned between the first and second longitudinal locations. For example, briefly referring back to FIG. 4, assuming that ablation therapy is delivered to each of treatment regions 414 and 416, in certain embodiments, a pair of electrodes (e.g., 726, 727) both positioned in region C (between treatment regions 414 and 416) are used to sense intrinsic and evoked neural activity 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 may be referred to herein as sensing electrodes (e.g., 726, 727). In just the above embodiment, two sensing electrodes (e.g., 726, 727) were described as both being positioned within a biological lumen (e.g., a renal artery) between a first longitudinal location and a second longitudinal location to which the respective first and second ablation therapies were 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 the first and second longitudinal locations to which the first and second ablation therapies were delivered in steps 602 and 604, respectively, and the second (or further) sensing electrode is an external skin electrode.

[0052] In another alternative embodiment, a first sensing electrode is positioned in the biological lumen (e.g., the renal artery) between the first and second longitudinal locations to which the first and second ablation therapies were delivered in steps 602 and 604, respectively, and a second (which may be said another) sensing electrode is positioned proximal to (i.e., upstream of) the first and second longitudinal locations to which the ablation therapies were delivered in steps 602 and 604. For example, briefly referring back to FIG. 4 , assuming that an ablation therapy is delivered to each of treatment regions 414 and 416, in one particular embodiment, a first sensing electrode is positioned in region C (between treatment regions 414 and 416) and a second sensing electrode is positioned in region A (proximal or upstream of both treatment regions). Both the first and second sensing electrodes can be located on a catheter used to sense neural activity, which may or may not be the same catheter that includes the transducer (e.g., 311) and / or other ablative means, 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 catheter 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 catheters can be swapped between steps 604 and 606. In certain embodiments, the first sensing electrode is located on a catheter (which may or may not be the same catheter that includes a transducer, e.g., 311, used to deliver the ablation therapy in steps 602 and 604) and is positioned within the biological lumen (e.g., the renal artery) between the first and second longitudinal locations to which the ablation therapy is delivered in steps 602 and 604, while the second sensing electrode is located on a distal end of an introducer sheath used to insert the catheter including the first sensing electrode into the biological lumen (e.g., the renal artery).

[0053] In another embodiment, a first sensing electrode is positioned in the biological lumen (such as the renal artery) between the first and second longitudinal locations to which the ablation therapy was delivered in steps 602 and 604, and a second (which may be said another) sensing electrode is located distal to (i.e., downstream of) the first and second longitudinal locations to which the ablation therapy was delivered in steps 602 and 604. For example, briefly referring back to FIG. 4, assuming that an ablation therapy is delivered to each of treatment regions 414 and 416, in one particular embodiment, a first sensing electrode is positioned in region C (between treatment regions 414 and 416) and a second sensing electrode is positioned in region B (proximal or downstream of both treatment regions). The first and second sensing electrodes can both be located on the same catheter, which may or may not be the same catheter that contains the transducer (e.g., 311) or other ablation means and is used to deliver the ablation therapy in steps 602 and 604. The second sensing electrode can also be separate from the catheter, for example, located on the distal end of a guidewire that is used to guide the catheter containing the first sensing electrode into the biological lumen (such as the renal artery).

[0054] As mentioned above, in certain embodiments, the neural activity sensed in step 606 may be an evoked neural response to stimulation energy delivered using one or more electrodes (e.g., 724, 725) of a catheter (e.g., 302, 702) inserted into a biological lumen that also includes at least one of the sensing electrodes (e.g., 726, 727) used in step 60, which 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. As used herein, the pair of electrodes (e.g., 724, 725) used to deliver the stimulation that elicits the neural response may be referred to as the first and second stimulation 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 and second longitudinal locations to which ablation therapy was delivered in steps 602 and 604. For example, and referring briefly back to FIG. 4 , assuming that ablation therapy is delivered to each of treatment regions 414 and 416, the first and second stimulating electrodes (e.g., 724, 725) may be positioned within region C (between treatment regions 414 and 416).

[0055] In other embodiments, only the first stimulating electrode is positioned in the biological lumen (e.g., renal artery 104) between the first and second longitudinal locations to which the ablation therapy was delivered in steps 602 and 604, while the second stimulating electrode is located on the same catheter as the first stimulating electrode, but is located either proximal to (which may be translated as upstream of) both the first and second longitudinal locations or distal to (which may be translated as downstream of) both the first and second longitudinal locations. For example, briefly referring back to FIG. 4 , assuming that the ablation therapy is delivered to each of treatment regions 414 and 416, in certain embodiments, the first stimulating electrode is positioned in region C (between treatment regions 414 and 416) and the second stimulating electrode is positioned in region A (proximal or upstream of the treatment region) or region B (distal or downstream of the treatment region). One of the first and second stimulating electrodes should be configured as a stimulating anode and the other as a stimulating cathode.

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

[0057] Alternatively, stimulation can be delivered to the most proximal ablation site and evoked responsive neural activity can be sensed distal to the most distal ablation site. In other words, stimulation to evoke a neural response can be delivered via one or more stimulation electrodes located proximal (i.e., upstream) of the first and second longitudinal locations and sensed using one or more sensing electrodes located distal (i.e., downstream) of the first and second longitudinal locations. For example, referring back briefly to FIG. 4, assuming that ablation therapy is delivered to each of treatment regions 414 and 416, in certain embodiments, stimulation can be delivered from one or more electrodes in region A and evoked neural responses can be sensed using one or more sensing electrodes in region B.

[0058] Another alternative is to deliver distal stimulation to the most distal ablation site and sense the evoked neural response proximal to the most proximal ablation site. In other words, the stimulation to evoke a neural response can be delivered via one or more stimulation electrodes located distal to (i.e., downstream of) the first and second longitudinal locations and sensed using one or more sensing electrodes located proximal to (i.e., upstream of) the first and second longitudinal locations. For example, referring back briefly to FIG. 4, assuming that an ablation therapy is delivered to each of treatment regions 414 and 416, in certain embodiments, stimulation can be delivered from one or more electrodes in region A and the evoked neural response can be sensed using one or more sensing electrodes in region B.

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

[0060] The embodiments of the present technology may be implemented using a variety of different catheter implementations and are therefore not limited to the use of any particular catheter and / or catheter-containing system. Nevertheless, for completeness, exemplary catheters and systems that can be used to implement the embodiments of the present technology are described below. More specifically, Figures 7A-11B are used to describe exemplary catheters and systems that can be used to implement the embodiments of the present technology described above. Such systems may also be referred to herein as devices.

[0061] [Example Catheter] 7A shows the catheter 702 with its selectively deployable electrodes 724 and 726 in an undeployed position. The catheter 702 includes a catheter handle 712 and a catheter shaft 722. In addition to including the selectively deployable electrodes 724 and 726, the catheter shaft 722 is also shown to include a non-deployed electrode 725 proximal to the selectively deployable electrode 724 and a non-deployed electrode 727 distal to the selectively deployable electrode 726. The selectively deployable electrode 724 may also be referred to as a proximal selectively deployable electrode 724, more simply as a proximal electrode 724, or even more simply as an electrode 724. The selectively deployable electrode 726 may also be referred to as a distal selectively deployable electrode 726, more simply as a distal electrode 726, or even more simply as an electrode 726. The catheter shaft 722 may also be referred to herein more simply as a shaft 722. Catheter 702 may be a particular implementation of catheter 302 shown and described above with reference to FIG.

[0062] The catheter 702 is also shown to include a balloon 713 positioned longitudinally between the electrodes 724 and 726, the balloon 713 being selectively inflatable and deflatable. The balloon 713 may also be referred to as a selectively inflatable balloon 713, a selectively deployable balloon 713, or more simply, a balloon 713. When the balloon 713 is deflated, it may also be referred to as being in an uninflated or undeployed position. When the balloon 713 is inflated, it may also be referred to as being in a deployed position. As described in more detail below, the balloon 713 may be selectively inflated by injecting fluid into the balloon 713, and may be selectively deflated by removing fluid from the balloon 713. The balloon 713 may be made of an electrically insulating material, such as polyamide, polyethylene terephthalate, or a 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™), pellethan, isothan, or other suitable polymers, or any combination thereof.

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

[0064] Fluid (e.g., ejected from a pressure syringe) can enter a fluid lumen (in the catheter shaft 722) via a fluid inlet port 734a of the catheter 702 and at least partially fill the balloon 713. Fluid can be withdrawn from the balloon 713 (e.g., using a vacuum syringe) through another fluid lumen (in the catheter shaft 722) and out of a fluid outlet port 734b of the catheter 702. In this manner, 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 liquid through the balloon 713.

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

[0066] 7A, the transducer 711 is shown within the balloon 713. The transducer 711 is an example of an ablation element (i.e., an element configured to selectively deliver an ablation therapy) included in the shaft 722 and configured to ablate nerve tissue using ultrasonic energy. In other embodiments, the transducer and balloon may be replaced by a helical structure carrying multiple electrodes configured to deliver RF and / or pulsed field RF energy. In other embodiments, the transducer and balloon may be replaced by a microwave transparent element, which may or may not be within the expandable centering element. In other embodiments, the transducer may be replaced by a cryotherapy applicator. In other embodiments, the transducer and balloon may be replaced by an injection needle configured to deliver an ablative chemical to the renal nerve. The shaft 722 may also include two longitudinally spaced transducers, for example, as disclosed in U.S. Patent Publication No. 2023 / 0021354, which is incorporated herein by reference above.

[0067] If the transducer 711 is in the balloon 713, the fluid circulating in the balloon 713 can be referred to as a cooling fluid used to cool the transducer 711 and / or to cool a portion of the biological lumen in which the balloon 713 is located and / or to cool the biological tissue surrounding the lumen. It is also possible that the catheter 702 lacks the transducer 711 or other ablative means and a separate catheter including the transducer or other ablative means is used to deliver the ablation therapy (e.g., steps 602 and 604 of FIG. 6). If the catheter 702 lacks the transducer 711 or other ablative means, one or more electrodes (e.g., 726, 727) of the catheter 702 can be used to sense intrinsic neural activity. One or more electrodes (e.g., 724, 725) of the catheter 702 can be used to deliver stimulation energy and one or more additional electrodes (e.g., 726, 727) of the catheter 702 can be used to sense an evoked neural response to the stimulation 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 it is the proximal end of the catheter 702 (more specifically, the handle 712) that is used to manipulate the catheter 702. In the embodiment shown in Figures 7A and 7B, the electrode 726 is located closer to the distal end of the catheter 702 than the proximal end of the catheter 702, and is therefore also referred to as 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 the distal end of the catheter 702, and is therefore also referred to as the proximal selectively deployable electrode 724 as described above. For similar reasons, the electrode 725 is referred to as the proximal non-deployable electrode 725, and the electrode 727 is referred to as the distal non-deployable electrode 727.

[0069] FIGURE 7B illustrates the catheter 702 with the electrodes 724 and 726 in their deployed (also referred to as extended) positions. In certain embodiments, the proximal selectively deployable electrode 724 is configured to be deployed (also referred to as extended) in response to the actuator 714 sliding in a proximal direction indicated by the arrow 744 in FIGURE 7B. In such embodiments, the proximal electrode 724 may be returned to an undeployed (also referred to as unextended or retracted) position in response to the actuator 714 sliding in a distal direction opposite the arrow 744 in FIGURE 7B. More generally, the actuator 714 is used to selectively expand and retract the electrodes 724.

[0070] According to certain embodiments, the longitudinal distance between the distal electrode 726 and the proximal electrode 724 can be reduced by sliding the actuator 718 in a proximal direction as indicated by the arrow 748 in FIG. 7B. Then, if desired, the longitudinal distance between the distal electrode 726 and the proximal electrode 724 can be increased by sliding the actuator 718 in a distal direction opposite the arrow 748 in FIG. 7B. More generally, the actuator 718 is used to adjust the longitudinal distance between the electrodes 724 and 726. The longitudinal distance 724, 726 between the proximal and distal electrodes can be any distance between a maximum longitudinal distance and a minimum longitudinal distance controlled by a user using the actuator 718. According to certain embodiments, the electrode 724 is configured to be deployed in response to the actuator 714 sliding in a proximal direction as indicated by the arrow 744 in FIG. 7B. According to certain embodiments, the electrode 726 is configured to be deployed in response to the actuator 716 sliding in a proximal direction as indicated by the arrow 746 in FIG. 7B. In such embodiments, the proximal electrodes 726 may be returned to an undeployed position in response to the actuator 716 sliding distally opposite the arrow 746 in Figure 7B. More generally, the actuator 716 is used to selectively expand and retract the electrodes 726. Other variations are possible and are within the scope of the embodiments described herein.

[0071] Each of the selectively deployable electrodes 724, 726 can be made, for example, from a unitary nitinol tube that is laser cut to include apertures or openings having a pre-determined pattern. In Figures 7A and 7B, each of the electrodes 724, 726 has a laser cut spiral aperture between a proximal portion and a distal portion of each of the electrodes 724, 726. The spiral aperture 724, 726 of each of the electrodes enables each of the electrodes to selectively transition between their undeployed and deployed positions. The apertures cut in the electrodes 724, 726 can have shapes other than spiral, so long as the electrodes are enabled to transition between their undeployed and deployed positions. The selectively deployable electrodes 724, 726 can alternatively be mesh electrodes or spiral electrodes made from one or more conductive wires, optionally with portions insulated. Other variations are 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, at a location near a body organ, such as a kidney. The catheter 702 can be advanced to a desired catheter location in the biological lumen and then introduced through an introducer sheath that is sufficiently retracted until the shaft 722 is exposed to the biological lumen (e.g., the renal artery 104). Once the shaft 722 is within the biological lumen of the organism, one of the electrodes 724, 726 can be deployed (also referred to as 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 the electrodes 724 and 726 can then be adjusted using the actuator 718 as needed. The other one of the electrodes 724, 726 can be deployed (also referred to as expanded) to contact another portion of the circumferential inner wall of the biological lumen.

[0073] For example, if a catheter (e.g., 702) is inserted into a renal artery (e.g., 104) close to the kidney, the electrodes (e.g., 724, 726) can be positioned near the nerve bundle that connects the kidney to the central nervous system because the nerve bundle tends to follow the artery closely at the end of the artery close to the kidney, while spreading out somewhat as the artery expands away from the kidney. As a result, in some instances, it is desirable for the catheter shaft 722 to be small enough to be introduced relatively close to the kidney or other organ, since the closer the organ, the closer the nerves and arteries are likely to be to each other.

[0074] Once the catheter 702 is in place, the practitioner can stimulate one or more nerves using instrumentation (e.g., ECU 802) coupled to electrodes (e.g., 724, 725) and monitor evoked neural response signals that are used to characterize the nervous system's response to a particular stimulus. The transducer 711 and / or other ablative means are configured to ablate neural tissue using ultrasound, RF, pulsed field RF, microwave, cryotherapy, or other energy or chemical means, etc. Additionally, the catheter 702 can actively stimulate one or more nerves during application of ablation therapy via the transducer 711 and sense the resulting neural signals, allowing for more precise control of the extent and effectiveness of neural ablation. In another example, the catheter 702 lacking a transducer or other ablative means can be removed through a sheath, an ablation probe (also referred to as a catheter) can be inserted, the ablation probe can be removed and the catheter 702 can be reinserted, and the effectiveness of the ablation probe can be verified and characterized.

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

[0076] In most of the following description, the transducer 711 is assumed to be an ultrasound transducer that can be operated to deliver unfocused ultrasound energy radially outward to suitably heat and treat tissue in a target anatomical region. The 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 ultrasound energy generated by the transducer 711 can be targeted to selected neural tissue of a subject and can heat such tissue in a manner to neuromodulate the neural tissue (e.g., completely or partially ablate, necrotize, or stimulate). The transducer 711 can be the same transducer 311 discussed above in Figures 3 and 4.

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

[0078] In certain embodiments, the transducer 711 is an ultrasound 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 to an average depth of up to 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 may be covered with an electrical insulator to inhibit (and preferably prevent) short circuits from occurring between the inner and outer electrodes when the ultrasound 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, a parylene conformal coating. An excitation source (e.g., 826 in FIG. 8) can be electrically coupled to the inner and outer electrodes of the transducer 711 and can activate the transducer 711 by applying a voltage between the inner and outer electrodes (or other pair of electrodes) to cause the piezoelectric material of the piezoelectric transducer body to generate unfocused ultrasonic waves that radiate radially outward.

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

[0080] 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 electrical signals (including stimulation pulses) having a particular voltage, amperage, duration, duty cycle, and / or application frequency that causes activation of neural cells. For example, electrode 724 can be connected as a stimulation anode and electrode 725 can be connected as a stimulation cathode, or vice versa. In another example, electrode 725 can be connected as a stimulation anode and electrode 726 can be connected as a stimulation cathode, or vice versa. Switches, not specifically shown, can be used to selectively control how the various electrodes (e.g., 724, 725, 726, 727) are coupled to various nodes of the ECU 802, such as input terminals of the amplifier 812 or output terminals of the stimulator 806.

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

[0082] Stimulation of the nerve can be performed to induce an elicited electrical potential, which can cause such electrical potential to propagate in all directions along the nerve fiber. More generally, to induce a neural response, the STIM subsystem 805 can be used to deliver electrical stimulation via a selected pair of electrodes (e.g., 724, 725), and the SENS subsystem 804 can be used to sense the evoked neural response.

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

[0084] Additionally or alternatively, the ECU 802 may include a head stage and / or amplifier 812 to perform offsetting, filtering, and amplification of the signal received from the catheter 702. In some examples, the head stage applies a DC offset to the signal and performs a filtering step. In some such systems, the filtering may include applying a notch and / or band pass filter 814 to suppress certain undesired signals having certain frequency content and to pass desired signals having certain frequency content. The amplifier 812 may be used to uniformly amplify the entire signal or may be used 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, which may change the frequency dependence of the signal pickup and amplification. In some embodiments, the characteristics of the amplifier 812, such as the capacitance, may be adjusted to change the 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 that includes a non-inverting (+) input terminal, an inverting (-) input terminal, a power supply input terminal, and a ground or reference terminal. As can be seen in 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 supply input terminal is electrically coupled to a voltage source (e.g., a reference voltage generator), and the ground or reference terminal is electrically coupled to a ground reference electrode, which may be located on the catheter 702, may be located on the distal end of the introducer sheath, or may be located on the patient's skin, but is not limited to this.

[0086] In some embodiments, the ECU 802 can include a switching network configured to swap which electrodes (e.g., 724, 725, 726, 727) of the catheter (e.g., 702) are coupled to which portions of the ECU 802. In some such embodiments, a user can manually switch which input receives a connection to which electrode (e.g., 724, 725, 726, 727) of the catheter 702. Such configurability allows a system operator to adjust the propagation direction of the elicited potential as needed. For example, a switching network, or more generally a switch, can be used to connect electrodes 724 and 725 to the stimulator 806 during periods when stimulation pulses are emitted by the catheter 702, and a switch can be used to connect electrodes 726 and 726 to the amplifier 812 for sensing the elicited response to the stimulation pulse. Additionally or alternatively, a controller (e.g., 822) can autonomously control such a switching network.

[0087] The amplifier 812 may include any suitable amplifier for amplifying a desired signal or attenuating an undesired signal. In some examples, the amplifier 812 has a high common mode rejection ratio (CMRR) to remove or substantially attenuate undesired 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 attribute of the amplifier.

[0088] In the example system 800 of FIG. 8, the ECU 802 further includes a filter 814 to enhance a desired signal in a 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 to isolate the desired signal from noise artifacts in the received signal. In some embodiments, various characteristics of the filter 814 may be adjusted to manipulate its filtering characteristics. For example, the filter may include an adjustable capacitance or other parameter to adjust the frequency response.

[0089] At least one of amplifying and filtering the sensed signal (e.g., received at electrodes 726 and 727) can enable extraction of the desired signal at 816. In some embodiments, extraction 816 includes at least one additional processing step to isolate the desired signal from the signal sensed using the electrodes, such as preparing the signal for output at 818. In some embodiments, the functionality of any combination of amplifier 812, filter 814, and extraction 816 can be integrated into a single entity. For example, amplifier 812 can act to filter undesired frequency components from the signal without requiring additional filtering with 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 a permanent or temporary memory 820. The ECU 802 may include such a memory 820 or may otherwise be in communication with an external memory (not shown). Thus, the ECU 802 can be configured to emit stimulation pulses to the electrodes (e.g., 724, 725) of the catheter (e.g., 702), record such pulses in memory, receive signals from the catheter (e.g., 702), and also record such received signal data. The memory 820 within or associated with the ECU 802 can be internal or external to any portion of the ECU 802 or to the ECU 802 itself.

[0091] The ECU 802 or a separate external processor may further perform calculations on the stored data to determine characteristics of either the emitted or received signals via the catheter. For example, in various embodiments, the ECU 802 may determine either the amplitude, duration, or timing of occurrence of the received or emitted signals. The ECU 802 may further determine relationships, such as temporal relationships, between the received signals and the emitted stimulation signals. In some embodiments, the ECU 802 performs signal averaging of the signal data received from the catheter. Such averaging may act to reduce random temporal noise in the data while enhancing data corresponding to the elicited potentials received by the catheter.

[0092] Such averaging may result in a signal where the noise that is random in time is generally averaged out and the signals present in each recorded data set, such as the elicited potentials, remain high. In some embodiments, each iteration of the process may include a synchronization step, and each acquired data set may be temporally registered to facilitate data averaging. That is, events that occur consistently at the same time during each iteration may be detected, and temporally random artifacts (e.g., noise) may be reduced. In general, the signal-to-noise ratio (SNR) resulting from such averaging is improved by the square root of the number of samples averaged to create the averaged data set.

[0093] The ECU 802 may present information regarding some or all of the applied stimuli, signals, and any computation results to a user of the system, such as via an output 818. For example, the ECU 802 may generate a graphical display providing one or more graphs of signal strength versus time representative of the stimuli and / or received signals.

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

[0095] An exemplary electronic 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 a user. In some embodiments, the ECU 802 can include separate modules for emitting, receiving, calculating, and providing the results of the calculations. Additionally or alternatively, the functionality of the controller 822 can be integrated into the ECU 802 as shown, or can be in separate communication with the ECU 802.

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

[0097] [Cross-sectional view of an exemplary catheter shaft portion] An exemplary cross-section of a portion of shaft 722 is shown in Figures 9A and 9B. With reference to Figure 9A, the cross-section is shown as including a main lumen 902 having a circular cross-section and smaller lumens 904a, 904b. To effectuate fluid circulation through balloon 713, lumen 904a is fluidly coupled to fluid inlet port 734a (shown in Figure 7) to effectuate fluid (e.g., discharged from a pressure syringe) being supplied to and at least partially filling balloon 713, and lumen 904b is fluidly coupled to fluid outlet port 734b (shown in Figure 7) to effectuate fluid being withdrawn from 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 of which may be a cable lumen used to hold an electrical cable electrically coupled to a transducer (e.g., 711). Other variations are possible and are within the scope of the embodiments described herein.

[0098] [Example Fluid Delivery Subsystem] Exemplary details of the fluid delivery subsystem 828 introduced in the discussion of Figure 8 are described below with reference to Figure 10. With reference to Figure 10, the fluid delivery subsystem 828 is shown as including a cartridge 1030 and a reservoir 1010. The reservoir 1010 is shown implemented as a fluid bag, which may be the same as or similar to an intravenous (IV) bag in that it may 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 fluidly 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 of which is used 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 hubs 1048a, 1048b of each of the syringes 1042a, 1042b are coupled to a respective fluid conduit or hose. 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 FIG. 10, syringe pump 1040 includes one or more gears, stepper motors, or the like, controlled by controller 822 (FIG. 8) to selectively operate plungers 1046 of pressure syringe 1042a and vacuum syringe 1042b. Alternatively, gears and / or stepper motors can be used to control syringe pump 1040.

[0100] To at least partially fill the barrel of pressure syringe 1042a with a portion of the fluid stored in reservoir 1010, pinch valves V1 and V2 are closed, pinch valve V3 is opened, and plunger 1046a of pressure syringe 1042a is pulled to draw fluid 1013 into barrel 1044a of pressure syringe 1042a. Pinch valve V3 is then closed, pinch valves V1 and V2 are opened, and plunger 1046a of pressure syringe 1042a is then pushed to expel fluid from barrel 1044a of pressure syringe 1042a through a fluid conduit attached to hub 1048a of pressure syringe 1042a. Fluid ejected from the pressure syringe 1042a can enter the fluid lumen via the fluid inlet port 734a of the catheter 702 (e.g., 904a in the catheter shaft 722) and at least partially fill the balloon 713. At the same time, pulling on the plunger 1046b of the vacuum syringe 1042b can draw fluid from the balloon 713 into the fluid lumen (e.g., 904b of the catheter shaft 722), through the fluid outlet port 734b of the catheter 702, and then through a fluid tube attached to the hub 1048b of the vacuum syringe 1042b and into the barrel 1044b of the vacuum syringe 1042b. In this manner, 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 the balloon. One or more of pressure sensors P1, P2, and P3 can be used to monitor the pressure within the balloon 713 to achieve a target balloon pressure, such as, but not limited to, 70 pounds per square inch (psi). Once the balloon 713 is inflated to the target pressure, such as 70 psi and / or to a size thereof, fluid can be circulated through the balloon 713 without increasing or decreasing the amount of fluid within the balloon, such that the amount of fluid removed from the balloon 713 is the same as the amount of fluid supplied to the balloon 713. Also, once the target balloon pressure is reached, the ultrasonic transducer 711 can be excited to emit ultrasonic energy to treat tissue surrounding the balloon 713 and the portion of the biological lumen into which the transducer 711 is inserted (e.g., a portion of the renal artery).When the ultrasonic transducer 711 is emitting ultrasonic energy, which can also be said to be performing sonication or that sonication is occurring, coolant must be circulated 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 during sonication.

[0101] Once sonication is complete and balloon 713 has been deflated to allow catheter 702 to be removed from the biological lumen, the coolant must be returned from barrel 1044b of vacuum syringe 1042b to reservoir 1010. To return coolant from 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, expelling 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 cartridge 1030, and these pressure measurements can be provided to controller 822 as feedback for use in other purposes, such as, but not limited to, controlling syringe pump 1040 and / or determining fluid pressure within balloon 713. Additionally, flow sensors F1 and F2 can be used to monitor the flow rate of fluid being infused (also referred to as pushed, provided, or delivered) into balloon 713 and the flow rate of fluid being withdrawn (also referred to as pulled or removed) from balloon 713, respectively. Pressure measurements obtained from pressure sensors P1, P2, P3 can be provided to controller 822 so that controller 822 can monitor balloon pressure. Additionally, flow measurements obtained from flow sensors F1 and F2 can be provided to controller 822 so that controller 822 can monitor the flow rate of fluid being pushed into and withdrawn from balloon 713. Also, one or more pressure and / or flow sensors may be located at additional or alternative locations along the fluid path providing fluid to and from the balloon 713.

[0103] [Example Transducer] 11A and 11B illustrate longitudinal and radial cross-sectional views, respectively, of an exemplary transducer 711 that may be physically coupled to one of the tubes (e.g., the third tube 733) of the catheter 702 introduced above in the discussion of FIGS. 7A and 7B, according to certain embodiments of the present technology. The transducer 711, which in the embodiment shown in FIGS. 11A and 11B is an ultrasound transducer, includes a piezoelectric transducer body 1101 that includes a hollow tube of piezoelectric material having an inner surface and an outer surface, with an inner electrode 1102 disposed on the inner surface of the hollow tube of piezoelectric material and an outer electrode 1103 disposed 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 in shape and has a circular radial cross-section. However, in alternative embodiments, the transducer body 1101 may have other shapes besides being cylindrical and having a radial cross-sectional area. The inner electrode 1102 is covered with an electrical insulator 1104 and the outer electrode 1103 is covered with an electrical insulator 1105. It is also possible that only one of the electrodes 1102, 1103 is covered with an electrical insulator, or that neither of the electrodes 1102, 1103 is covered with an electrical insulator. Other variations 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 a catheter 302, 702 including an element 311, 711 or a first and second element 311, 711 configured to selectively deliver an ablation therapy, and one or more sensing electrodes 726, 727 configured to selectively sense neural activity. The system 800 also includes an excitation source 826 configured to selectively energize the element 311, 711 or the first and second elements 311, 711 of the catheter 302, 702, thereby causing the element 311, 711 or the first and second elements 311, 711 to deliver an ablation therapy. The system 800 further includes a sensing subsystem 804 electrically coupled to at least one sensing electrode 726, 727. The system 800 additionally comprises a controller 822, an excitation source 826, and a sensing subsystem 804 communicatively coupled to the catheter 302, 702. The controller 822 is configured to cause the excitation source 826 to energize the element 311, 711 or the first element 311, 711 while the element 311, 711 or the first element 311, 711 is located at 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 energize the element 311, 711 or the second element 311, 711 while the element 311, 711 or the second element 311, 711 is located at a second longitudinal location along the biological lumen 104 that is longitudinally spaced from the first longitudinal location, thereby delivering a second ablation therapy. The controller 822 is further configured to cause the sensing subsystem 804 to sense neural activity from a third longitudinal location using at least one of the one or more sensing electrodes 726, 727, thereby quantifying the extent to which nerves surrounding the biological lumen 104 and adjacent at least one of the first and second longitudinal locations have been 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 executable by one or more processors of the controller 822 that cause the excitation source 826 to energize the element 311, 711 or the 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 intrinsic neural activity.

[0107] In one embodiment, the system 800 further comprises one or more stimulation electrodes 724, 725 located on the catheter 302, 702 and a stimulator 806 electrically coupled to the one or more stimulation electrodes 724, 725 and communicatively coupled to the controller 822. In this embodiment, 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, thereby eliciting a neural response. The neural activity sensed by the sensing subsystem 804 from the third longitudinal location comprises an evoked neural response to the one or more stimulation pulses.

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

[0109] In one embodiment, at least one of the one or more stimulation electrodes 724, 725 used to deliver the one or more stimulation pulses is located at a longitudinal location that is proximal to both the first longitudinal location and the second longitudinal location. In one embodiment, a third location is a location where an evoked neural response is sensed using at least one of the 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 the one or more stimulation electrodes 724, 725 used to deliver the one or more stimulation pulses is located at a longitudinal location that is proximal to both the first longitudinal location and the second longitudinal location. In one embodiment, a third location is a location where an evoked neural response is sensed using at least one of the 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, the element 311,711 includes a transducer 311,711.

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

[0113] In one embodiment, the catheter 302, 702 comprises first and second transducers 311, 711 spaced longitudinally along a shaft 722 of the catheter 302, 702. In one embodiment, the controller 822 is configured to cause the excitation source 826 to energize the first transducer 311, 711 to deliver a first ablation therapy from a first longitudinal location along the biological lumen 104 and to energize the second transducer 311, 711 to deliver a second ablation therapy from a second longitudinal location spaced apart from the first longitudinal location along the biological lumen 104.

[0114] In one embodiment, the system 800 further comprises one or more stimulation electrodes 724, 725 located on the catheter 302, 702 and a stimulator 806 electrically coupled to the one or more stimulation electrodes 724, 725 and communicatively coupled to the controller 822. In one embodiment, 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 either proximal or distal to both the first longitudinal location and the second longitudinal location, thereby eliciting a neural response. Neural activity sensed by the sensing subsystem 804 from a third longitudinal location comprises an evoked neural response to the one or more stimulation pulses, the third longitudinal location being the other of proximal or distal to both the first longitudinal location and the second longitudinal location.

[0115] In one embodiment, the element 311, 711 or the first and second elements 311, 711 comprise one or more electrodes.

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

[0117] In one embodiment, the controller 822 is configured to compare the measured values ​​of the sensed neural activity to corresponding thresholds. In this embodiment, the controller 822 is also configured to determine that further ablation therapy needs to be delivered if the measured values ​​of the sensed neural activity exceed the corresponding thresholds. In one embodiment, the controller 822 is also configured to determine that the ablation therapy is complete if the measured values ​​of the sensed neural activity are below the corresponding thresholds.

[0118] In one embodiment, the controller 822 is configured to compare the measure of sensed neural activity to multiple thresholds, such as at least a first threshold and a second threshold, In one embodiment, the controller 822 determines that 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 of the measured neural activity to 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, the ablation was successful, incomplete, or otherwise 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 controller 822 determines that ablation has failed, user interface 824 may prompt the user to move to a different location, and / or user interface 824 may display a message indicating that ablation is incomplete, and / or user interface 824 may prompt the user to continue ablation at the same location.

[0123] In one embodiment, controller 822 is configured to compare the number of complete ablations to a preprogrammed number of complete ablations to determine whether the procedure is complete and no further ablations are required. For example, the preprogrammed number of complete ablations may be two or three ablations per main renal artery, and controller 822 may determine that the procedure is complete when the controller determines that there have been two or three complete ablations per main renal artery.

[0124] In one embodiment, the controller 822 is configured to, in response to the controller 822 determining that further ablation therapy needs to be delivered, cause the excitation source 826 to energize the element 311, 711 or the first element or the second element 311, 711, thereby delivering further ablation therapy, while the element 311, 711 or the first element or the second element 311, 711 is located at a location along the longitudinal length of the biological lumen 104.

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

[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 an ablation therapy and one or more sensing electrodes configured to selectively sense neural activity; an excitation source configured to selectively energize at least one of the one or more elements of the catheter to thereby deliver an 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 selectively energizes at least one of the elements to deliver an ablation therapy to at least one of the one or more elements. and a controller configured to energize at least one of the elements to deliver a first ablation therapy at a first longitudinal location along the biological lumen, the excitation source to energize at least one of the elements to deliver a second ablation therapy at a second longitudinal location along the biological lumen that is longitudinally spaced from the first longitudinal location, and a sensing subsystem to sense neural activity from a third longitudinal location using at least one of the one or more sensing electrodes to determine effectiveness of at least one of the first or second ablation therapies.

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

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

[0129] Example 4. The system of Example 1, further comprising one or more stimulation electrodes located on the catheter, and a stimulation device electrically coupled to the one or more stimulation electrodes and communicatively coupled to a controller, wherein the controller is further configured to cause the stimulation device to generate one or more stimulation pulses delivered via at least one of the one or more stimulation electrodes, thereby eliciting a neural response, and wherein the neural activity sensed by the sensing subsystem from a third longitudinal location comprises an evoked neural response to the one or more stimulation pulses.

[0130] Example 5. The system of Example 4, wherein a third longitudinal location, at which an evoked neural response is sensed and at which the first and second ablation therapies have been delivered, respectively, is located longitudinally between the first longitudinal location and the second longitudinal location.

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

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

[0133] Example 8. The system of any one of Examples 1-7, wherein one or more elements comprises a transducer.

[0134] Example 9. The system of Example 8, wherein the controller is configured to cause the excitation source to energize the transducer to deliver a first ablation therapy from a first longitudinal location along the biological lumen and, after being moved from the first longitudinal location to a second longitudinal location, to energize the transducer to deliver a second ablation therapy from a second longitudinal location longitudinally spaced from the first longitudinal location along the biological lumen.

[0135] Example 10. A system as described in any one of Examples 1 to 7, wherein the one or more elements include a first transducer and a second transducer longitudinally spaced from the first transducer, and the controller is configured to cause the excitation source to energize the first transducer to deliver a first ablation therapy from a first longitudinal location along the biological lumen and to energize the second transducer to deliver a second ablation therapy from a second longitudinal location spaced from the first longitudinal location along the biological lumen.

[0136] Example 11. The system of Example 1, further comprising one or more stimulation electrodes located on the catheter, and a stimulation device electrically coupled to the one or more stimulation electrodes and communicatively coupled to a controller, wherein the controller is further configured to cause the stimulation device to generate one or more stimulation pulses delivered via at least one of the one or more stimulation electrodes at a longitudinal location that is either proximal or distal to both the first and second longitudinal locations, thereby eliciting a neural response, and wherein the neural activity sensed from a third longitudinal location by the sensing subsystem comprises an induced neural response to the one or more stimulation pulses, the third longitudinal location being the other of proximal or distal to both the first and second longitudinal locations.

[0137] Example 12. A system described in 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 described in Example 12, wherein the controller is configured to compare a measure of sensed neural activity with a corresponding threshold, and determine that further ablation therapy needs to be delivered when the measure of sensed neural activity exceeds the corresponding threshold.

[0139] Example 14. The system of Example 13, wherein the controller is configured to, in response to the controller determining that additional ablation therapy needs to be delivered while at least one of the one or more elements is located at a location along the longitudinal length of the biological lumen, cause an excitation source to energize the one or more elements, thereby delivering the additional ablation therapy.

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

[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 along the biological lumen that is longitudinally spaced from the first longitudinal location; and sensing neural activity from a third longitudinal location longitudinally located between the first longitudinal location and the second longitudinal location, where the first and second ablation therapies have each been delivered, to determine the effectiveness of at least one of the first and second ablation therapies.

[0142] Example 17. The method of Example 16, wherein the method is performed using a catheter including an element configured to selectively deliver an ablation therapy, the method further comprising: inserting a distal portion of the catheter into the biological lumen such that the element is located at a first longitudinal location along the biological lumen, wherein delivering the first ablation therapy using the element is 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 spaced from the first longitudinal location along the biological lumen, wherein delivering the second ablation therapy using the element is 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 comprises a transducer.

[0144] Example 19. The method of example 17, wherein the element comprises one or more electrodes.

[0145] Example 20. The method of Example 16, wherein the method is performed using a catheter including first and second transducers spaced apart longitudinally from one another along a shaft of the catheter, and wherein delivering a first ablation therapy from a first longitudinal location along the biological lumen is performed using the first transducer, and delivering a second ablation therapy from a second longitudinal location longitudinally spaced apart from the first longitudinal location along the biological lumen is performed using the second transducer.

[0146] Example 21. The method of any one of Examples 16 to 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 of Example 21, wherein determining whether further ablation therapy needs to be delivered based on the sensed neural activity from a third longitudinal location includes comparing a measure of the sensed neural activity with a corresponding threshold, and determining that further ablation therapy needs to be delivered if the measure of the sensed neural activity exceeds the corresponding threshold.

[0148] Example 23. The method of example 22, further comprising delivering an additional ablation therapy in response to said determining that an additional ablation therapy needs to be delivered.

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

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

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

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

[0153] Example 28. The method of example 27, wherein the evoked neural response is also sensed using a further electrode, the further electrode being positioned either within the biological lumen or external to the skin.

[0154] Example 29. The method of any one of Examples 16-28, wherein the biological lumen comprises a renal artery.

[0155] Example 30. The method of 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, ultrasound energy, pulsed electric field energy, light energy, laser light, cryotherapy, or a chemical agent using a catheter including 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 along the biological lumen that is longitudinally spaced from the first longitudinal location; delivering stimulation energy using an electrode located at a third longitudinal location along the biological lumen, the third longitudinal location being one of proximal or distal to both the first and second longitudinal locations; sensing an evoked neural response to the stimulation energy using a further electrode located at a fourth longitudinal location along the biological lumen, the fourth longitudinal location being the other of proximal or distal to both the first and second longitudinal locations; and determining whether a further ablation therapy needs to be delivered based on the sensed evoked neural response.

[0157] Example 32. The method of 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 of 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 of any one of Examples 31 to 33, wherein delivering the first ablation therapy from a first longitudinal location is performed using a transducer in a distal portion of a catheter inserted into the biological lumen such that the transducer is positioned at the first longitudinal location, and delivering the second ablation therapy from a second longitudinal location is performed using a transducer in a distal portion of a catheter inserted into the 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 of any one of Examples 31 to 33, wherein delivering a first ablation therapy from a first longitudinal location is performed by emitting first radio frequency (RF) energy using one or more electrodes of a distal portion of a catheter inserted into the biological lumen such that the one or more electrodes are positioned at the first longitudinal location, and delivering a second ablation therapy from a second longitudinal location is performed by emitting second RF energy using one or more electrodes of a distal portion of a catheter inserted into the biological lumen after the 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 of any one of Examples 31 to 35, wherein determining whether further ablation therapy needs to be delivered based on the sensed induced neural response includes comparing a measured value of the sensed induced neural response to a corresponding threshold value, and determining that further ablation therapy needs to be delivered if the measured value of the sensed neural response exceeds the corresponding threshold value, and further including delivering the further ablation therapy in response to determining that further ablation therapy needs to be delivered.

[0162] Example 37. The method of 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 of energy: radio frequency (RF) energy, microwave energy, ultrasound energy, pulsed electric field energy, light energy, laser light, cryotherapy, or a chemical agent using a catheter including a shaft inserted into a biological lumen.

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

[0164] Example 39. The method of any one of Examples 16 to 37, further comprising displaying a message on a 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. A system described in any one of Examples 1 to 15, wherein the neural activity sensed using the sensing subsystem includes intrinsic neural activity.

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

[0167] Although several embodiments and examples are disclosed herein, the present application extends beyond the specifically disclosed embodiments to other alternative embodiments and / or uses of the invention, as well as modifications and equivalents thereof. It is also contemplated that various combinations or subcombinations of the specific features and aspects of the embodiments may be made and still fall within the scope of the invention. It should therefore be understood that various features and aspects of the disclosed embodiments can be combined with or substituted for one another to form various modes of the disclosed invention. It is therefore intended that the scope of the invention disclosed herein should not be limited by the specific embodiments disclosed above, but should be determined solely by a fair reading of the following claims.

[0168] While the invention is susceptible to various modifications and alternative forms, specific examples thereof have been shown in the drawings and are described in detail herein. It should be understood, however, that the invention is not limited to the particular forms or methods disclosed, but rather, the invention is intended to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the various embodiments described and the appended claims. The methods disclosed herein need not be performed in the order described.

Claims

1. 1. A system for performing a denervation procedure and determining the effectiveness thereof, comprising: a catheter including one or more elements configured to selectively deliver ablation therapy and one or more sensing electrodes configured to selectively sense neural activity; an excitation source configured to selectively energize at least one of the one or more elements of the catheter to thereby cause the at least one of the one or more elements to deliver the ablation therapy; a sensing subsystem electrically coupled to at least one of the one or more sensing electrodes; a controller communicatively coupled to the catheter, the excitation source, and the sensing subsystem, causing the excitation source to energize at least one of the one or more elements to thereby deliver a first ablation therapy at a first longitudinal location along the biological lumen; causing the excitation source to energize at least one of the one or more elements to thereby deliver a second ablation therapy at a second longitudinal location along the biological lumen that is longitudinally spaced from the first longitudinal location; and a controller, wherein the sensing subsystem is configured to sense neural activity from a third longitudinal location using at least one of the one or more sensing electrodes to determine the effectiveness of at least one of the first or second ablation therapies.

2. 2. The system of claim 1, wherein the third longitudinal location is located longitudinally between the first longitudinal location and the second longitudinal location, and the first and second ablation therapies are delivered from the third longitudinal location, respectively.

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

4. one or more stimulation electrodes located on the catheter; a stimulator electrically coupled to the one or more stimulation electrodes and communicatively coupled to the controller, the controller is further configured to cause the stimulator to generate one or more stimulation pulses delivered via at least one of the one or more stimulation electrodes to thereby elicit a neural response; The system of claim 1 , wherein the neural activity sensed by the sensing subsystem from the third longitudinal location comprises an evoked neural response to the one or more stimulation pulses.

5. 5. The system of claim 4, wherein the third longitudinal location at which the evoked neural response is sensed is located longitudinally between the first longitudinal location and the second longitudinal location, and from which the first and second ablation therapies, respectively, have been delivered.

6. at least one of the one or more stimulation electrodes used to deliver the one or more stimulation pulses is located at a longitudinal location that is proximal to both the first and second longitudinal locations; 5. The system of claim 4, wherein the third location at which the evoked neural response is sensed using at least one of the one or more sensing electrodes is distal to both the first and second longitudinal locations.

7. at least one of the one or more stimulation electrodes used to deliver the one or more stimulation pulses is located at a longitudinal location that is distal to both the first and second longitudinal locations; 5. The system of claim 4, wherein the third location at which the evoked neural response is sensed using at least one of the one or more sensing electrodes is proximal to both the first and second longitudinal locations.

8. The system of any one of claims 1 to 7, wherein the one or more elements include a transducer.

9. 10. The system of claim 8, wherein the controller is configured to cause the excitation source to energize the transducer to deliver the first ablation therapy from the first longitudinal location along the biological lumen and to energize the transducer to deliver the second ablation therapy from the second longitudinal location longitudinally spaced from the first longitudinal location along the biological lumen after the transducer is moved from the first longitudinal location to the second longitudinal location.

10. the one or more elements include a first transducer and a second transducer longitudinally spaced from the first transducer; 8. The system of claim 1, wherein the controller is configured to cause the excitation source to energize the first transducer to deliver the first ablation therapy from the first longitudinal location along the biological lumen and to energize the second transducer to deliver the second ablation therapy from the second longitudinal location spaced from the first longitudinal location along the biological lumen.

11. one or more stimulation electrodes located on the catheter; a stimulator electrically coupled to the one or more stimulation electrodes and communicatively coupled to the controller, the controller is further configured to cause the stimulator to generate one or more stimulation pulses delivered via at least one of the one or more stimulation electrodes at a longitudinal location that is either proximal or distal to both the first and second longitudinal locations, thereby eliciting a neural response; 2. The system of claim 1, wherein the neural activity sensed by the sensing subsystem from a third longitudinal location includes an evoked neural response to the one or more stimulation pulses, the third longitudinal location being the other of proximal or distal to both the first and second longitudinal locations.

12. 12. The system of claim 1, wherein the controller is configured to determine whether further ablation therapy needs to be delivered based on the neural activity sensed from the third longitudinal location.

13. The controller: comparing the sensed neural activity measure to a corresponding threshold; and determining that further ablation therapy needs to be delivered if the measure of the sensed neural activity exceeds the corresponding threshold.

14. 14. The system of claim 13, wherein the controller is configured, in response to the controller determining that additional ablation therapy needs to be delivered while the at least one of the one or more elements is located at a location along the longitudinal length of the biological lumen, to cause an excitation source to energize the at least one element to thereby deliver additional ablation therapy.

15. Each of the one or more elements comprises: Radio Frequency (RF) energy, Microwave energy, Ultrasonic energy, Pulsed electric field energy, Light energy, Laser light, Cryotherapy, or The method of any one of claims 1 to 7 or 11 to 14, wherein the method is configured to deliver one of the following types of agents:

16. 1. A method for performing and determining the effectiveness of a denervation procedure, comprising: delivering a first ablation therapy from a first longitudinal location along the biological lumen; delivering a second ablation therapy from a second longitudinal location along the biological lumen that is longitudinally spaced from the first longitudinal location; sensing neural activity from the third longitudinal location, the third longitudinal location being longitudinally located between the first longitudinal location and the second longitudinal location, and determining the effectiveness of at least one of the first and second ablation therapies from the third longitudinal location from which the first and second ablation therapies have been delivered, respectively.

17. The method is carried out using a catheter including an element configured to selectively deliver an ablation therapy, the method comprising: inserting a distal portion of the catheter into the biological lumen such that the element is located at the first longitudinal location along the biological lumen, wherein the delivering of the first ablation therapy using the element is performed while the element is located at the first longitudinal location along the biological lumen; 17. The method of claim 16, further comprising manipulating the catheter such that the element is located at a second longitudinal location along the biological lumen that is longitudinally spaced from the first longitudinal location, wherein the delivering of the second ablation therapy using the element is performed while the element is located at the second longitudinal location along the biological lumen.

18. The method of claim 17 , wherein the element comprises a transducer.

19. The method of claim 17 , wherein the element comprises one or more electrodes.

20. the method being carried out using a catheter including first and second transducers spaced apart longitudinally along a shaft of the catheter; the delivering of the first ablation therapy from the first longitudinal location along the biological lumen is performed using the first transducer; 17. The method of claim 16, wherein the delivering of the second ablation therapy from the second longitudinal location longitudinally spaced from the first longitudinal location along the biological lumen is performed using the second transducer.

21. 21. The method of any one of claims 16-20, further comprising determining whether further ablation therapy needs to be delivered based on the neural activity sensed from the third longitudinal location.

22. determining whether the further ablation therapy needs to be delivered based on the neural activity sensed from the third longitudinal location; comparing the sensed neural activity measure to a corresponding threshold; and determining that the further ablation therapy needs to be delivered if the measure of the sensed neural activity exceeds the corresponding threshold.

23. 23. The method of claim 22, further comprising, in response to the determination that the additional ablation therapy needs to be delivered, delivering the additional ablation therapy.

24. the sensing of the neural activity from the third longitudinal location is performed using an electrode positioned at the third longitudinal location longitudinally located between the first longitudinal location and the second longitudinal location; 17. The method of claim 16, wherein the electrodes used for the sensing of the neural activity from the third longitudinal location are included in a distal portion of a catheter, which may be the same or a different catheter as the catheter used to deliver the first and second ablation therapies.

25. the neural activity sensed from the third longitudinal location comprises intrinsic neural activity sensed using the electrode positioned at the third longitudinal location; The intrinsic neural activity is also sensed using a further electrode; 25. The method of claim 24, wherein the further electrode is positioned either within the biological lumen or external to the skin.

26. 26. The method of claim 25, wherein the additional electrode is positioned within the biological lumen between the first longitudinal location and the second longitudinal location.

27. 17. The method of claim 16, wherein the neural activity sensed from the third longitudinal location comprises an evoked neural response to a stimulus delivered from an electrode positioned within the biological lumen.

28. The evoked neural response is also sensed using a further electrode; 28. The method of claim 27, wherein the further electrode is positioned either within the biological lumen or external to the skin.

29. The method of any one of claims 16 to 28, wherein the biological lumen comprises a renal artery.

30. each of the first and second ablation therapies using a catheter including a shaft inserted into the biological lumen; Radio Frequency (RF) energy, Microwave energy, Ultrasonic energy, Pulsed electric field energy, Light energy, Laser light, Cryotherapy, or 30. The method of any one of claims 16, 17 or 21-29, wherein the method is performed by delivering one of:

31. 1. A method for performing and determining the effectiveness of a denervation procedure, comprising: delivering a first ablation therapy from a first longitudinal location along the biological lumen; delivering a second ablation therapy from a second longitudinal location along the biological lumen that is longitudinally spaced from the first longitudinal location; delivering stimulation energy using an electrode located at a third longitudinal location along the biological lumen, the third longitudinal location being one of proximal and distal to both the first and second longitudinal locations; sensing an evoked neural response to the stimulation energy using a further electrode located at a fourth longitudinal location along the biological lumen, the fourth longitudinal location being the other of proximal or distal to both the first and second longitudinal locations; and determining whether further ablation therapy needs to be delivered based on the sensed evoked neural response.

32. the third longitudinal location is proximal to both the first and second longitudinal locations; 32. The method of claim 31, wherein the fourth longitudinal location is distal to both the first and second longitudinal locations.

33. the third longitudinal location is distal to both the first and second longitudinal locations; 32. The method of claim 31, wherein the fourth longitudinal location is proximal to both the first and second longitudinal locations.

34. delivering the first ablation therapy from the first longitudinal location using a transducer in a distal portion of a catheter inserted into the biological lumen such that the transducer is positioned at the first longitudinal location; 34. The method of any one of claims 31 to 33, wherein the delivering of the second ablation therapy from the second longitudinal location is performed using the transducer of the distal portion of the catheter inserted into the biological lumen after the transducer has been moved from being positioned at the first longitudinal location to being positioned at the second longitudinal location.

35. delivering the first ablation therapy from the first longitudinal location by emitting first radio frequency (RF) energy using one or more electrodes in a distal portion of a catheter inserted into the biological lumen such that the one or more electrodes are positioned at the first longitudinal location; 34. The method of any one of claims 31-33, wherein the delivering of the second ablation therapy from the second longitudinal location is performed by emitting second RF energy using the one or more electrodes of the distal portion of the catheter inserted into the biological lumen after the one or more electrodes have been moved from being positioned at the first longitudinal location to being positioned at the second longitudinal location.

36. determining whether the further ablation therapy needs to be delivered based on the sensed evoked neural response; comparing the sensed measurements of the evoked neural responses to corresponding thresholds; determining that the further ablation therapy needs to be delivered when the measured value of the sensed neural response exceeds the corresponding threshold value; The method of any one of claims 31 to 35, further comprising, in response to the determination that the further ablation therapy needs to be delivered, delivering the further ablation therapy.

37. each of the first and second ablation therapies using a catheter including a shaft inserted into the biological lumen; Radio Frequency (RF) energy, Microwave energy, Ultrasonic energy, Pulsed electric field energy, Light energy, Laser light, Cryotherapy, or 37. The method of any one of claims 31 to 33 or 36, wherein the method is performed by delivering one of: a.

38. 38. The method of any one of claims 16-37, further comprising quantifying to what extent nerves surrounding the biological lumen and adjacent at least one of the first longitudinal location and the second longitudinal location are affected by the delivery of the first and second ablation therapies based on the neural activity sensed from the third longitudinal location.

39. 38. The method of any one of claims 16-37, further comprising displaying a message to a user on a user interface that at least one of the first or second ablation therapies was successful, incomplete, and / or failed based on the neural activity sensed from the third longitudinal location.

40. The system of claim 1 , wherein the neural activity sensed using the sensing subsystem comprises intrinsic neural activity.

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

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