Controlled flushing for neuromodulation systems and associated methods

Abstract

Disclosed herein are neuromodulation catheter systems with controlled irrigation capabilities and methods for using such systems. One such method includes, for example, positioning an irrigated neuromodulation catheter at a treatment site within a renal vessel of a human patient, delivering neuromodulation energy at the treatment site, and delivering an irrigation fluid having a property coordinated with the delivered energy to the treatment site. As power is increased, the property may be adjusted to maintain the energy delivery element and / or tissue of the vessel at a constant temperature. The method may further include monitoring at least one parameter of the tissue and / or energy delivery element, and adjusting a property of the neuromodulation energy and / or irrigation fluid if the at least one parameter falls outside a therapeutic range of values.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This disclosure claims the benefit of U.S. Patent Application No. 15 / 959,043, filed on April 20, 2018, and U.S. Provisional Patent Application No. 62 / 621,359, filed on January 24, 2018, both of which are incorporated herein by reference in their entireties. Technical Field

[0003] The present technology relates to irrigated neuromodulation systems and associated methods. In particular, various embodiments of the present technology relate to neuromodulation catheter systems with controlled irrigation capabilities and methods for using such systems. Background Art

[0004] The sympathetic nervous system (SNS) is the main involuntary body control system usually associated with stress response. The fibers of SNS extend through the tissues in almost every organ system of human body and can affect characteristics such as pupil diameter, intestinal motility and urine output. This regulation can be adaptively used to maintain homeostasis or prepare the body to respond quickly to environmental factors. However, the chronic overactivation of SNS is a common maladaptive reaction that can drive the evolution of many disease states. In particular, the overactivation of kidney SNS has been experimentally and in humans identified as a possible contributor to the complex pathophysiology of arrhythmia, hypertension, volume overload (such as, heart failure) and progressive nephropathy.

[0005] The sympathetic nerves of the kidney terminate in the renal blood vessels, juxtaglomerular apparatus, and renal tubules and other structures. Stimulation of the renal sympathetic nerves can cause, for example, increased renin release, increased sodium reabsorption, and reduced renal blood flow (blood flow). These and other neural regulatory components of renal function are significantly stimulated in disease states characterized by elevated sympathetic tone. For example, as a result of renal sympathetic nerve efferent stimulation, reduced renal blood flow and glomerular filtration rate are likely to be the basis for renal function loss in cardiorenal syndrome (i.e., renal insufficiency as a progressive complication of chronic heart failure). Pharmacological strategies for hindering the results of renal sympathetic nerve stimulation include centrally acting sympathetic drugs, beta blockers (e.g., to reduce renin release), angiotensin converting enzyme inhibitors and receptor blockers (e.g., to prevent the effect of angiotensin II after renin release and aldosterone activation) and diuretics (e.g., to counteract sodium and water retention (retention) mediated by renal sympathetic nerves). However, these pharmacological strategies have significant limitations, including limited efficacy, compliance issues, side effects, and others. BRIEF DESCRIPTION OF THE DRAWINGS

[0006] Figure 1is a partially schematic perspective view illustrating a renal neuromodulation system including an irrigation therapy device configured in accordance with an embodiment of the present technology.

[0007] Figure 2A is a partial schematic side view of a neuromodulation catheter with a distal portion of a guidewire positioned within a blood vessel of a human patient and configured in accordance with an embodiment of the present technology.

[0008] Figure 2B and Figure 2C yes Figure 2A A partial schematic side view of a neuromodulation catheter is shown with an irrigation therapy assembly in a first state and a second state, respectively, within a blood vessel of a human patient.

[0009] Figure 2D is Figure 2C is a front view of the irrigation therapy assembly in a second state, shown in , looking proximally down the longitudinal axis of a blood vessel of a human patient.

[0010] Figure 3 is a partially schematic side elevational view of a neuromodulation catheter having an irrigation therapy assembly in a deployed state within a blood vessel of a human patient and configured in accordance with an embodiment of the present technology.

[0011] Figure 4 is a partially schematic side elevational view of a neuromodulation catheter having an irrigation therapy assembly in a deployed state within a blood vessel of a human patient and configured in accordance with an embodiment of the present technology.

[0012] Figure 5 is a diagram depicting an energy delivery algorithm that may be used in conjunction with a neuromodulation system configured in accordance with embodiments of the present technology.

[0013] Figure 6 is a flow chart of a process or method for treating a patient using a neuromodulation system configured in accordance with embodiments of the present technology.

[0014] Figure 7 The present invention is shown using an embodiment according to the present technology Figure 1 systems to modulate renal nerves and / or evaluate neuromodulation therapies.

[0015] Figure 8 A conceptual diagram of the sympathetic nervous system (SNS) and how the brain communicates with the body via the SNS.

[0016] Fig. 9 is an enlarged anatomical illustration of the nerves innervating the left kidney to form the renal plexus surrounding the left renal artery.

[0017] Fig.10 and Fig.11Anatomical and conceptual views of the human body depicting efferent and afferent neural communications between the brain and kidneys, respectively.

[0018] Fig.12 and Fig.13 These are anatomical diagrams of the human arterial and venous vascular systems, respectively. DETAILED DESCRIPTION

[0019] The following disclosure describes a neuromodulation catheter system with controlled irrigation capabilities and methods of using such a system. More specifically, a neuromodulation system configured in accordance with embodiments of the present technology utilizes a neuromodulation catheter with an irrigation treatment component. The disclosed neuromodulation system is configured to deliver coordinated neuromodulation energy and irrigation fluid to an irrigation treatment component at a treatment site within a patient's blood vessel (e.g., a renal blood vessel). The disclosed system is configured to adjust / modify one or more parameters of energy delivery and irrigation throughout the treatment process based on, for example, patient tissue characteristics at the treatment site, treatment component component characteristics, irrigation fluid characteristics, the power at which energy is currently being applied, and parameters related thereto.

[0020] Using conventional neuromodulation systems and methods, the depth of injury can be increased at a target site in a patient's body by increasing the power at which energy is delivered to the tissue. However, the temperature of one or more electrodes used to deliver this energy also increases as the power increases. In some cases, the increased electrode temperature can cause blood coagulation and charring of vascular tissue. This tissue damage can in turn lead to other adverse effects, including downstream infarction or other undesirable tissue damage. For this reason, some conventional systems incorporate flushing to provide cooling at the treatment site and avoid some of the adverse effects experienced by non-flushed catheters. However, flushing ablation systems have been shown to produce undesirable greater damage compared to non-flushed catheters, and several adverse effects associated with tissue damage have been documented after using these flushing catheters, including renal artery stenosis, arterial access site problems, and / or significant eGFR decline.

[0021] There are many reasons why the adverse effects associated with the use of conventional irrigation catheters persist. For example, the irrigation fluid in these conventional systems is often applied in an uncontrolled manner, with limited control over the flow rate and timing of delivery, and limited control over the temperature of the infusate. These practices can bias the temperature measurements obtained by the neuromodulation system during treatment. In particular, the irrigation fluid can cause these conventional systems to report electrode temperatures that are between the temperature of the irrigation fluid (e.g., room temperature) and the patient's body temperature, which becomes increasingly inaccurate as treatment progresses (especially as power increases). Therefore, in many cases, any electrode temperature information transmitted back to the system's generator after the use of the irrigation fluid cannot be reliably used as a measure of ablation progress. As a result, these conventional irrigation systems inaccurately track the size of the lesion created and the condition of the tissue being treated. Although this problem is less of a concern when ablating certain anatomical structures (e.g., cardiac tissue), this lack of control is particularly prominent when ablating near electrically fragile, thin-walled or other arterial structures. For example, the renal anatomy is generally more complex than cardiac tissue in terms of local heterogeneity of the anatomy. Therefore, more control and care is required when performing renal denervation than can be provided with conventional irrigation systems.

[0022] Compared to conventional systems and techniques, neuromodulation systems and methods according to embodiments of the present technology are configured to deliver coordinated neuromodulation energy and irrigation fluid to a treatment site. In some embodiments, these systems and methods are configured to actively monitor characteristics of tissue and / or neuromodulation element(s) at the treatment site (e.g., temperature, impedance, etc.). The systems and methods can use this diagnostic information to monitor treatment progress and / or adjust (i) the characteristics of the neuromodulation energy applied to the treatment site in relation to the control algorithm of the neuromodulation procedure (e.g., type, power level, duration, frequency, etc.) and / or (ii) the characteristics of the irrigation fluid delivered to the treatment site (e.g., volume, temperature, type, duration, rate, etc.). Therefore, it is expected that systems configured according to the present technology achieve greater control over injury characteristics during neuromodulation procedures and increase the likelihood that neuromodulation procedures will be successful, particularly in vessels with damaged blood vessels and / or low blood flow. For example, it is expected that systems and methods according to embodiments of the present technology achieve greater injury depths without the adverse effects noted in patients after using conventional systems and methods.

[0023] References in this article Figure 1A-13 describes specific details of several embodiments of the present technology. Although many embodiments are described with respect to devices, systems, and methods for intravascular renal neuromodulation, other applications and other embodiments other than those described herein are also within the scope of the present technology. For example, at least some embodiments of the present technology may be used for intracavitary neuromodulation, extravascular neuromodulation, non-renal neuromodulation, and / or for treatments other than neuromodulation. It should be noted that other embodiments other than those disclosed herein are within the scope of the present technology. In addition, embodiments of the present technology may have configurations, components, and / or procedures that are different from the configurations, components, and / or procedures shown or described herein. In addition, a person of ordinary skill in the art will understand that embodiments of the present technology may have configurations, components, and / or procedures other than those shown or described herein, and these and other embodiments may not have some of the configurations, components, and / or procedures shown or described herein without departing from the present technology.

[0024] As used herein, the terms "distal" and "proximal" define a position or direction relative to a clinician or clinician's control device (e.g., a handle of a neuromodulation catheter). The terms "distal" and "distally" refer to a position along the length of the device away from the clinician or clinician's control device or in a direction away from the clinician or clinician's control device. The terms "proximal" and "proximally" refer to a position along the length of the device close to the clinician or clinician's control device or in a direction toward the clinician or clinician's control device. The headings provided herein are for convenience only and should not be construed as limiting the disclosed subject matter.

[0025] A. Selected Embodiments of Neuromodulation Catheters and Systems

[0026] Figure 1 1 is a partial schematic diagram illustrating a neuromodulation system 100 configured in accordance with an embodiment of the present technology. The system 100 may include a treatment device 110 (e.g., an irrigation catheter) operably coupled to a console 102 via a connector 101 (e.g., a cable). The system 100 further includes an irrigation pump 104 that is integrated with the console 102 to facilitate simultaneous and / or coordinated delivery of neuromodulation energy and irrigation fluid during treatment. Figure 1As shown, the treatment device 110 may include: an elongated shaft 112 having a proximal portion 114, a handle assembly 111 at a proximal region of the proximal portion 114, and a distal portion 116 extending distally relative to the proximal portion 114. The elongated shaft 112 may be configured to position the distal portion 116 at a treatment location within a blood vessel (e.g., within a renal artery) or within another suitable body cavity (e.g., within a ureter). The treatment device 110 may further include a treatment assembly 120 carried by or secured to the distal portion 116 of the elongated shaft 112. The treatment assembly 120 may include one or more neuromodulatory elements 126 ( Figure 1 ), the neuromodulator 126 is configured to deliver therapeutic energy or compound to a nerve located at least proximate to a wall of a body cavity. In some embodiments, the handle 111 may include an actuator 113 to convert the therapeutic assembly 120 between a delivery state and a deployed state via a guidewire (not shown) and remote actuation of the actuator 113.

[0027] The console 102 may be configured to control, monitor, supply, or otherwise support the operation of the treatment device 110. For example, the console 102 may include an energy generator operably connected to the neuromodulation element(s) 126 and configured to generate therapeutic neuromodulation energy (e.g., radiofrequency energy ("RF"), pulsed energy, microwave energy, light energy, direct thermal energy, or other suitable type of energy) of a selected form and amplitude for delivery to a treatment site via the neuromodulation element(s) 126 to alter, damage, or destroy nerves.

[0028] In some embodiments, the console 102 can be configured to store an irrigation fluid (e.g., saline, distilled water, etc.) and / or to transmit the irrigation fluid to the treatment assembly 120 (via the connector 101 and / or the elongated shaft 112). As previously described, for example, the console 102 includes an irrigation pump 104 to transfer the irrigation fluid from the console 102 to the treatment assembly 120 of the treatment device 110. In other embodiments, the system 100 can include a neuromodulation console (not shown) and a separate irrigation console (not shown) that includes the irrigation pump 104 and / or a storage container (not shown) for storing irrigation fluid. In these embodiments, the neuromodulation console can be communicatively coupled to the irrigation console. As described in more detail below, the system 100 can facilitate simultaneous and / or coordinated delivery of neuromodulation energy and irrigation fluid to the treatment assembly 120. In order to reduce the possibility of tissue damage and / or associated adverse effects, the irrigation fluid can be used to cool (i) tissue at the treatment site and / or (ii) components of the treatment assembly 120.

[0029] The console 102 can be electrically coupled to the treatment device 110 via a connector 101 (e.g., a cable). One or more power cords (not shown) can be passed along the elongated shaft 112 or through a lumen in the elongated shaft 112 to the neuromodulation element(s) 126 to deliver neuromodulation energy to the neuromodulation element(s) 126. Additionally, one or more fluid supply lumens (not shown) can be passed along the elongated shaft 112 or through a lumen in the elongated shaft 112 to the treatment assembly 120. The fluid supply lumen(s) can deliver irrigation fluid to one or more irrigation outlets (not shown) in the treatment assembly 120.

[0030] The console 102 may also be configured to deliver neuromodulation energy and / or irrigation fluid to the treatment assembly 120 according to an automatic control algorithm 150 and / or under the control of a clinician. The control algorithm 150 may be executed on a processor (not shown) of the system 100. One or more sensors (e.g., pressure, temperature, impedance, flow, chemical, ultrasonic, electromagnetic, etc.) of the treatment assembly 120 and / or the treatment device 110 may generate diagnostic information / measurements related to the patient tissue at the treatment site and / or related to the components of the treatment assembly 120. The diagnostic information may be used as feedback to the control algorithm 150 and may allow the system 100 to adjust the control algorithm 150 (e.g., based on a comparison of the diagnostic information to a predetermined parameter profile range). In particular, the system 100 may adjust the characteristics of the neuromodulation energy delivered to the neuromodulation element(s) 126 (e.g., type, power level, duration, frequency, etc.) and / or the characteristics of the irrigation fluid delivered to the treatment assembly 120 (e.g., volume, temperature, type, rate, duration, etc.). The diagnostic information can also provide feedback to the clinician, such as via an indicator 105 (e.g., a display, a user interface, one or more LEDs, etc.) associated with the console 102 and / or system 100. For example, the console 102 may include a user interface that can receive user input and / or provide diagnostic information to the user. Feedback from the diagnostic information can allow the clinician to determine the effectiveness of the energy applied during treatment and / or shortly after treatment (e.g., while the patient is still catheterized). Similarly, while the patient is still catheterized, the clinician can decide to repeat, pause, and / or terminate treatment (e.g., to avoid tissue damage) based on feedback from the diagnostic information. Therefore, this feedback can be useful in helping the clinician increase the likelihood of success of a current or subsequent treatment and / or avoid adverse effects of treatment(s). Refer to the following Figure 5 Further details regarding a suitable control algorithm 150 are described.

[0031] The system 100 may include a controller 106 having, for example, a memory (not shown), a storage device (e.g., a disk drive), one or more output devices (e.g., a display), one or more input devices (e.g., a keyboard, a touch screen, etc.), and / or a processing circuit system (not shown). The controller 106 may be configured to execute, adjust, and / or modify the control algorithm 150. For example, the output device may be configured to communicate with the treatment device 110 (e.g., via the connector 101) to control power to the neuromodulation element(s) 126 and / or control the supply of irrigation fluid to the treatment assembly 120. In some embodiments, the output device may be further configured to obtain signals from the neuromodulation element(s) 126 and / or any associated sensors. The display device may be configured to provide an indication of the power level or sensor data, such as an audio, visual, or other indication, and / or the display device may be configured to convey the information to another device.

[0032] In some embodiments, the controller 106 may be part of the console 102, such as Figure 1 As shown. Additionally or alternatively, the controller 106 can be a personal computer (multiple), a server computer (multiple), a handheld or laptop device (multiple), a multiprocessor system (multiple), a microprocessor-based system (multiple), a programmable consumer electronic device (multiple), a digital camera (multiple), a network PC (multiple), a minicomputer (multiple), a mainframe computer (multiple), a tablet computer, and / or any suitable computing environment. Memory and storage devices are computer-readable storage media that can be encoded with non-transient computer-executable instructions (e.g., control algorithm 150, feedback algorithm, etc.). In addition, instructions, data structures, and message structures can be stored or transmitted via data transmission media (such as signals on a communication link) and can be encrypted. Various communication links can be used, such as the Internet, a local area network, a wide area network, a point-to-point dial-up connection, a mobile phone network, Bluetooth, RFID, and other suitable communication channels. The system 100 can be described in the general context of computer-executable instructions (such as program modules) executed by one or more computers or other devices. In general, program modules include routines, programs, objects, components, data structures, etc. that perform specific tasks or implement specific abstract data types. Typically the functionality of the program modules may be combined or distributed as desired in various embodiments.

[0033] The neuromodulation element(s) 126 of the therapeutic assembly 120 can be configured to modulate one or more nerves (e.g., renal nerves) within the tissue at or at least proximate to the vessel or lumen wall. As described in more detail below, the neuromodulation element(s) 126 can include one or more energy delivery elements (e.g., electrodes; Figure 2A-4) and / or one or more sensors (e.g., to monitor the energy delivery element and / or tissue at the treatment site). For example, in some embodiments, the neuromodulation element(s) 126 may include a single energy delivery element located at the distal portion 116 of the treatment device 110. In other embodiments, the neuromodulation element(s) 126 may include two or more energy delivery elements. The energy delivery elements may be separate band electrodes spaced apart from each other along a portion of the length of the shaft 112. The electrodes may be adhesively bonded to the support structure at different locations along the length of the shaft 112. In some embodiments, the energy delivery element may be formed of a suitable conductive material (e.g., a metal such as gold, platinum, an alloy of platinum and iridium, etc.). The number, arrangement, shape (e.g., spiral and / or coil electrodes) and / or composition of the energy delivery elements may vary. The individual energy delivery elements of the neuromodulation element(s) 126 may be electrically connected to the handle assembly 111 and / or the console 102 by a conductor or double-stranded wire extending through the lumen of the shaft 112.

[0034] In embodiments having multiple energy delivery elements, the energy delivery elements can deliver power independently (i.e., can be used in a monopolar manner) simultaneously, selectively, or sequentially, and / or can deliver power between any desired combination of elements (i.e., can be used in a bipolar manner). In addition, the clinician can optionally be allowed to select which energy delivery element(s) to use for power delivery in order to form highly customized lesions(s) within a blood vessel (e.g., a renal artery) or other body cavity (e.g., a ureter) as desired. In some embodiments, the system 100 can be configured to provide delivery of a monopolar electric field via the neuromodulatory element(s) 126. In such embodiments, a neutral or dispersive electrode 109 can be electrically connected to the console 102 and attached to the exterior of the patient.

[0035] Figures 2A-2C is a neuromodulation catheter 210 (e.g., Figure 1 A partial schematic side view of the treatment device 110 shown. Figures 2A-2C 2 shows a neuromodulation catheter 210 in different arrangements when positioned at a treatment site within a blood vessel V (e.g., a renal artery) of a human patient. The neuromodulation catheter 210 includes a guide wire 215 (only in Figure 2A226) and an irrigation therapy assembly 220 that can be advanced over the guidewire 215 to a treatment site within the blood vessel V. The irrigation therapy assembly 220 is configured to perform neuromodulation therapy at the treatment site, for example to ablate nerves proximate to the wall of the blood vessel V. As discussed in more detail below, the irrigation therapy assembly 220 can be configured to monitor the tissue of the blood vessel V at the treatment site and components of the irrigation therapy assembly 220 (e.g., the neuromodulation element(s) 226). For example, one or more sensors (not shown) of the irrigation therapy assembly 220 are configured to collect diagnostic information and measurements related to the temperature of the tissue and / or the neuromodulation element(s) 226 during neuromodulation therapy of the tissue. The diagnostic information can be used as feedback to adjust the characteristics of the neuromodulation energy delivery and / or the characteristics of the irrigation fluid delivered to the irrigation therapy assembly 220.

[0036] The guidewire 215 includes an elongated member 218 having a distal portion 218a configured to be positioned at a treatment site within a blood vessel V and a proximal portion (not visible) extending outside the patient's body to a handle (e.g., Figure 1 111) or other feature(s) that allows an operator to manipulate distal portion 218a to a desired position / orientation (e.g., using Figure 1 13). The elongated member 218 can be sized to be slidably positioned within the lumen of the neuromodulation catheter 210. In other embodiments, the elongated member 218 includes other suitable components (e.g., sensor(s)) and / or configurations. Additionally, the elongated member 218 can have a uniform stiffness along its length, or can have a varying stiffness along its length.

[0037] like Figure 2B As best shown, the elongated shaft 112 of the neuromodulation catheter 210 is configured to be slidably delivered over a guidewire 215. The elongated shaft 112 has a distal portion 116 configured to be intravascularly positioned at a treatment site within a blood vessel V and a proximal portion 114 extending outside the patient's body to a handle (e.g., Figure 1 The handle 111 shown in FIG. 10 is a handle 111 of FIG. 10 ) or other features that allow an operator to manipulate the distal portion 116 of the elongated shaft 112 (e.g., using Figure 1 The actuator 113 shown in FIG. Figure 2B and Figure 2CAs shown, for example, the irrigation treatment assembly 220 of the neuromodulation catheter 210 is convertible between a first state or arrangement in which the distal portion 116 of the elongated shaft 112 is at least generally straight and a second (e.g., deployed, expanded, etc.) state or arrangement. Figure 2B ), in which the distal portion 116 is transformed or otherwise deployed into a helical / spiral shape ( Figure 2C In some embodiments, the therapeutic assembly 220 may have a shape memory corresponding to the second state, and the guide wire 215 ( Figure 2A ) can maintain the therapeutic assembly 220 in the first state until the guidewire 215 is at least partially removed (e.g., retracted). The distal portion 116 of the elongated shaft 112 (e.g., Figure 2C The dimensions (e.g., outer diameter and length) of the distal portion 116 (the portion in the second state shown as being spirally shaped) can be selected to accommodate a blood vessel or other body cavity in which the distal portion 116 is designed to be delivered. For example, when in the second state, the axial length of the distal portion 116 of the elongated shaft 112 can be selected to be no longer than a patient's renal artery (e.g., typically less than 7 cm) and to have a diameter that accommodates the inner diameter of a typical renal artery (e.g., approximately 2-10 mm). In other embodiments, the distal portion 116 of the elongated shaft 112 can have other dimensions depending on the body cavity in which the distal portion 116 of the elongated shaft 112 is configured to be deployed. In other embodiments, the distal portion 116 of the elongated shaft 112 may have other suitable shapes (e.g., semicircular, curved, straight, etc.), sizes, and / or configurations. Other suitable devices and techniques are described, for example, in U.S. Pat. No. 8,777,942; U.S. Pat. No. 9,084,610; U.S. Pat. No. 9,060,755; U.S. Pat. No. 8,998,894; PCT Application No. PCT / US2011 / 057754 filed on October 25, 2011; and U.S. Pat. No. 8,888,773. All of the above applications are incorporated herein by reference in their entirety. Non-limiting examples of devices and systems include Symplicity Spyral TM Multi-electrode RF ablation catheter and Arctic Front Advance TM Cardiac Cryoablation System.

[0038] Reference together Figure 2B and Figure 2C, the irrigation treatment assembly 220 includes four neuromodulation elements 226 spaced apart along the distal portion 116 of the elongated shaft 112. However, in other embodiments, the irrigation treatment assembly 220 may include one, two, three, or more than four neuromodulation elements (plurality) 226 and / or may include a plurality of support members configured to carry one or more neuromodulation elements 226. Each neuromodulation element 226 in the illustrated embodiment includes an electrode 224 (identified as first to fourth electrodes 224a-224d, respectively). In other embodiments, the neuromodulation elements 226 may include a greater and / or lesser number of electrodes 224. In some embodiments, the neuromodulation elements 226 may include one or more sensors configured to monitor tissue at a treatment site and / or components of the treatment assembly 220 (e.g., electrodes 224a-224d).

[0039] When the flushing treatment component 220 is in Figure 2C In the second state shown, the electrodes 224a-224d are configured to deliver neuromodulation energy (e.g., RF energy) to tissue at or at least proximate to the vessel wall V at the treatment site to modulate one or more nerves (e.g., renal nerves) within the tissue. In this state, the distal portion 116 of the elongated shaft 112 can be designed to apply a desired outward radial force to the vessel V to place one or more of the electrodes 224a-224d in contact with the vessel wall. In these and other embodiments, the irrigation treatment assembly 220 can include electrodes, transducers, or other elements to deliver other suitable neuromodulation modalities, such as pulsed electrical energy, microwave energy, light energy, ultrasound energy (e.g., intravascularly delivered ultrasound and / or high intensity focused ultrasound (HIFU)), direct thermal energy, radiation (e.g., infrared, visible, and / or gamma radiation), and / or other suitable types of energy to alter, damage, or destroy nerves.

[0040] As described above, one or more of the neuromodulatory elements 226 and / or the treatment assembly 220 may include one or more sensors (not shown) configured to monitor characteristics (such as temperature) of tissue and / or components of the treatment assembly 220 (e.g., electrodes 224a-224d and / or neuromodulatory element(s) 226) at the treatment site. In some embodiments, one or more sensors may be incorporated directly into the neuromodulatory element(s) 226 of the irrigation treatment assembly (e.g., incorporated into and / or adjacent to electrodes 224a-224d). In these and other embodiments, one or more sensors may be positioned at various locations along the elongated shaft 112 of the neuromodulatory catheter 210 and / or separate from the neuromodulatory element(s) 226 of the irrigation treatment assembly 220. The one or more sensors may be configured to measure and / or generate diagnostic information related to tissue of the vessel V and / or components of the neuromodulatory element(s) 226 of the irrigation treatment assembly 220. For example, one or more sensors may continuously and / or periodically measure temperature, pressure, time, impedance, power, flow rate, volumetric flow rate, blood pressure, heart rate, parameters of returned energy, or other parameters of the neuromodulation catheter 210 and / or patient tissue at the treatment site. From these measurements, the one or more sensors generate diagnostic information that may be reported back to the one or more controllers 106 of the system 100, as described in more detail below.

[0041] like Figure 2B and Figure 2C As best shown, the irrigation treatment assembly 220 can include one or more irrigation outlets 222 at the distal portion 216 of the elongated shaft 112. The irrigation outlets 222 can be connected to one or more fluid supply lumens (not shown) that extend along the elongated shaft 112 (or through a lumen in the elongated shaft 112) to an irrigation pump (e.g., Figure 1 ) and / or a storage container (not shown). As described above, an irrigation fluid (e.g., saline, distilled water, etc.) can be delivered to the treatment assembly 220 via the fluid supply lumen and can be released at the treatment site via the irrigation outlet 222. In this manner, the neuromodulation catheter 210 can cool components of the irrigation treatment assembly 220 (e.g., the neuromodulation element(s) 226) and / or tissue at the treatment site (e.g., during neuromodulation therapy).

[0042] The irrigation outlets 222 may be disposed at various points around the circumference of the elongated shaft 112 (eg, Figure 2B ), such that when the treatment assembly 220 is in the second state ( Figure 2CWhen the flushing outlets 222 are positioned in a desired orientation, the flushing outlets 222 are positioned in a desired orientation. For example, the flushing outlets 222 can be arranged so that they direct the flushing fluid distally along or approximately along the longitudinal axis L of the blood vessel V (e.g., Figure 2C and Figure 2D In other embodiments, when the treatment assembly 220 is in the second state, the irrigation outlet 222 can be oriented to face one or more different directions (e.g., facing the direction opposite to the treatment assembly 220). Figure 2C and Figure 2D In operation, the system 100 can release irrigation fluid via the irrigation outlet 222 near the wall of the vessel V and / or near the electrodes 224a-224d. Thus, the irrigation fluid released from the irrigation outlet 222 can provide cooling to (i) tissue of the vessel wall and / or (ii) components of the treatment assembly 220 proximate to the irrigation outlet 222. In addition, the irrigation fluid released from the irrigation outlet 222 can be carried along the vessel wall by blood flowing through the vessel V. Thus, the irrigation fluid released from the irrigation outlet 222 can also provide cooling to (i) tissue of the vessel wall, (ii) components of the treatment assembly 220, and / or (iii) components of the neuromodulation catheter 210 located downstream of the irrigation outlet 222.

[0043] Despite Figures 2A-2D The irrigation outlets 222 shown in FIG. 2 are positioned near the electrodes 224a-224d of the treatment assembly 220, but in other embodiments of the present technology, one or more of the irrigation outlets 222 may be positioned at other locations and / or in a different arrangement. For example, Figure 3 and Figure 4 3 and 4 are partial schematic side views of neuromodulation catheters 310 and 410, respectively, configured in accordance with other embodiments of the present technology. Figure 3 As shown, the neuromodulation catheter 310 includes an irrigation treatment assembly 320 that is arranged along the elongated shaft 112. Figures 2A-2D The flushing outlet 222 shown in FIG. 1 has a flushing outlet 322 (eg, Figures 2A-2D The irrigation outlets 322 are positioned around the circumference of the elongated shaft 112 and are configured to release irrigation fluid radially outward from the elongated shaft 112. Additionally or alternatively, the irrigation outlets 322 may be formed within the elongated shaft 112 and / or a fluid supply lumen coupled to the irrigation outlet(s) 322 may be oriented within the elongated shaft 112 so that irrigation fluid is output from the irrigation outlets 322 in a desired direction away from the irrigation outlets 322.

[0044] In other embodiments and as Figure 4As shown, the neuromodulation catheter 410 can include an irrigation therapy assembly 420 having an irrigation ring / donut element 430 with one or more irrigation outlets 422. The irrigation ring element 430 is configured to expand radially outward from the elongated shaft 112 so that the irrigation ring 430 surrounds the elongated shaft 112 and is proximate to or engages the inner vessel wall. As shown, one or more fluid supply lumens 434 can extend (e.g., from the elongated shaft 112) into the irrigation ring element 430. The irrigation outlets 422 and / or fluid supply lumens 434 can (i) be oriented to direct irrigation fluid downward along the longitudinal axis L of the vessel V, (ii) be oriented to face the vessel wall and / or another direction, (iii) be configured to direct irrigation toward the vessel wall, and / or (iv) be shaped and / or oriented within the irrigation ring element 430 so that irrigation fluid is output from the irrigation ring element 430 in a desired direction away from the irrigation outlets 422.

[0045] As discussed above, neuromodulation catheters 210, 310, and 410 configured in accordance with embodiments of the present technology may be communicatively coupled to a console 102 (eg, a control console 102) via a wired or wireless communication link. Figure 1 ) of one or more controllers 106. In some embodiments, one or more controllers 106 may be separate from the console, for example, Figure 1 In the illustrated embodiment, the irrigation pump 104 is separate from the console 102. The controller(s) 106 can be configured to initiate, terminate, and / or adjust the operation of one or more components (e.g., electrodes 224a-224d) of the therapeutic assemblies 220, 320, and 420, directly and / or via the console 102. For example, the controller(s) 106 can be configured to continuously or intermittently monitor the tissue of the vessel wall and / or components of the therapeutic assemblies 220, 320, and 420 using diagnostic information from one or more sensors (not shown) of the therapeutic assemblies 220, 320, and 420. More specifically, the controller 106 can use the diagnostic information to adjust (i) the characteristics of the neuromodulation energy and / or (ii) (e.g., in accordance with a control algorithm) the characteristics of the irrigation fluid delivered to the therapeutic assemblies 220, 320, and 420. Thus, controller 106(s) can be configured to control, monitor, supply, adjust and / or otherwise support the operation of neuromodulation catheters 210, 310, and 410 based at least in part on diagnostic information generated by one or more sensors of therapeutic components 220, 320, and 420.

[0046] B. Control of applied energy and flushing characteristics

[0047] As discussed above, a neuromodulation system (e.g., Figure 1The system 100 shown in FIG. 1 ) can be configured to deliver coordinated neuromodulation energy (eg, RF energy) and irrigation fluid to therapeutic components of a therapeutic device according to an automated control algorithm 150 and / or under the control of a clinician. Figure 5 106 (eg, Figure 1-4 106) is an embodiment of an automatic control algorithm 150 implemented by the controller 106 shown in FIG. Figure 5 As shown, when the clinician initiates treatment, the control algorithm 150 may include instructions that cause the console (e.g., Figure 1 The console 102 shown in FIG. 1 gradually adjusts the power of the energy applied to the treatment site to a first power level P1 (e.g., 5 watts) over a first time period t1 (e.g., 15 seconds). During the first time period, the power can generally increase linearly. As a result, the console can increase its power output at a substantially constant rate of P1 / t1. Alternatively, the power can increase nonlinearly (e.g., exponentially or parabolically) at a variable rate of increase.

[0048] Additionally or alternatively, the control algorithm 150 may include instructions for coordinating the delivery of irrigation fluid to the treatment site before, during, and / or after neuromodulation energy is applied to the treatment site, adjusted, and / or modified. For example, the control algorithm 150 may include instructions for directing the system (e.g., the console and / or the irrigation pump) to deliver irrigation fluid with characteristics corresponding to an increase in power to a first power level P1. In some embodiments, the instructions may direct the system to deliver a specific type (e.g., saline, distilled water, etc.) and / or a certain volume of irrigation fluid to the treatment site. In these and other embodiments, the instructions may direct the system to deliver irrigation fluid (i) at a specified temperature (e.g., room temperature, body temperature, or another temperature above or below room temperature), (ii) at a specified flow rate, and / or (ii) for a specified duration. In these and yet other embodiments, the instructions may direct the system to adjust (e.g., increase, decrease, change, and / or terminate) any of these irrigation fluid characteristics when the power is adjusted (e.g., increased, decreased, and / or held constant). In yet other embodiments, the control algorithm 150 may include instructions for avoiding delivery of irrigation fluid until a specified power level is reached, avoiding delivery of irrigation fluid until a specified electrode temperature is reached, and / or avoiding delivery of irrigation fluid for a specified period of time.

[0049] Once P1 and t1 are reached, the control algorithm 150 may remain at P1 for a predetermined time period t2-t1 (e.g., 3 seconds) until a new time t2. The control algorithm 150 may similarly maintain the irrigation fluid properties constant until t2 and / or may adjust the irrigation fluid properties (e.g., based on monitored parameters of the tissue at the treatment site and / or components of the treatment device, as described in more detail below). At t2, the power is increased to P2 in predetermined increments (e.g., 1 Watt) over a predetermined time period t3-t2 (e.g., 1 second). The control algorithm 150 may include instructions directing the system to adjust the irrigation fluid properties in accordance with the power increase. The power ramp in predetermined increments of approximately 1 Watt over a predetermined time period may continue until a maximum power P is reached. MAX Or until some other condition is met (e.g., a maximum irrigation flow rate / volume and / or a minimum irrigation fluid temperature is reached). Optionally, the power may be maintained at a maximum power P MAX In some embodiments, the controller may continuously change the irrigation fluid characteristics based on, for example, (i) monitored parameters of tissue at the treatment site and / or components of the treatment device and / or (ii) the progress of the neuromodulation procedure.

[0050] In addition and before, during, and / or after the neuromodulation procedure, the controller may monitor (e.g., using one or more sensors of the treatment assembly) one or more parameters corresponding to tissue at the treatment site, to the patient, to the irrigation fluid, and / or to components of the treatment device (e.g., a neuromodulation element). For example, the controller may continuously or periodically monitor temperature, time, impedance, power, flow rate, volumetric flow rate, blood pressure, heart rate, parameters of returned energy, and / or other parameters. The controller may use diagnostic information / measurements of the parameters as feedback related to the progress of the neuromodulation procedure, the status of components of the treatment device (e.g., temperature), and / or the condition of tissue at the treatment site. In some embodiments, the controller (i) may check the monitored parameters against a predetermined parameter distribution to determine whether each parameter, individually or in combination, falls within a range set by the predetermined parameter distribution, and (ii) may correspondingly coordinate and / or adjust the characteristics of the neuromodulation energy and / or irrigation fluid delivered to the treatment site. For example, given certain neuromodulation energy characteristics and / or irrigation fluid characteristics, the controller may check whether the monitored parameters fall within a range set by the predetermined parameter distribution. If the monitored parameter falls within the range, then treatment may continue according to the control algorithm 150. However, if the monitored parameter falls outside of the range, then the controller may adjust the control algorithm 150 accordingly.

[0051] For example, if a temperature measurement associated with tissue at the treatment site and / or with a component of the treatment device (e.g., a neuromodulatory element) is too high for the currently applied power level, the controller may adjust and / or modify the control algorithm 150 (e.g., until the parameter is within the parameter distribution range(s)). In some embodiments, the controller may reduce, pause, and / or terminate the applied power; may extend or shorten t1, t2, t3, etc. of the control algorithm 150; and / or may modify the duty cycle, frequency, or other parameters of the control algorithm 150. Additionally or alternatively, the controller may change the characteristics of the irrigation fluid delivered to the treatment site. For example, the controller may increase and / or decrease the flow rate, volume, and / or temperature of the irrigation fluid delivered to the treatment site. In these and other embodiments, the controller may change the type of irrigation fluid released at the treatment site and / or the duration for which the irrigation fluid is applied to the treatment site. Those skilled in the art will appreciate that the controller may adjust (e.g., increase, decrease, change, adjust, and / or otherwise alter) the control algorithm 150 or maintain the control algorithm 150 constant in response to other events indicated by the control algorithm 150. For example, the controller may appropriately adjust the control algorithm 150 in response to: (i) one or more parameters outside of (e.g., above and / or below) a predetermined parameter distribution range(s); and / or (ii) sudden, unexpected, and / or undesirable changes in measured parameters / characteristics of tissue and / or components of the treatment device (e.g., even if the parameters / characteristics fall within the parameter distribution range(s)). The system may also be equipped with various audible and visual alarms to allow the controller to alert the operator to certain conditions.

[0052] In some embodiments, the system may include one or more safety thresholds that prevent the controller from adjusting the characteristics of the energy and / or irrigation fluid above and / or below the threshold. For example, when the neuromodulation energy is applied at or above a specified power level and / or is applied for longer than a specified duration, the system may prevent the controller from (i) reducing the flow rate below a specified threshold and / or (ii) increasing the temperature of the irrigation fluid above a specified threshold. In other embodiments, to prevent the system (e.g., one or more sensors on a neuromodulation element of a therapeutic device) from reporting inaccurate (e.g., temperature) measurements related to components of the therapeutic device and / or tissue at a treatment site, the system may prevent the controller from (i) increasing the flow rate of the irrigation fluid above a specified threshold and / or (ii) reducing the temperature of the irrigation fluid below a specified threshold. In yet other embodiments, the system may prevent the controller from increasing the power level of the neuromodulation energy above a specified threshold (e.g., when a maximum flow rate and / or volume of irrigation fluid supplied to the treatment site is reached and / or when a minimum temperature of the irrigation fluid is reached).

[0053] In this manner, the controller can deliver coordinated neuromodulatory energy and irrigation fluid to the treatment site. As a result, the controller can maintain the temperature of the neuromodulatory element constant and / or within a desired range by controlling the use and / or continued use of an irrigation fluid having desired characteristics. This allows the neuromodulatory system to achieve greater depths of injury by increasing the power of the neuromodulatory energy applied to the vessel without causing blood clotting or charring of vascular tissue associated with elevated electrode temperatures during treatment. Thus, the maximum power that can be safely delivered to the patient during treatment can be increased. In particular, a neuromodulatory system configured in accordance with the present technology allows for safe increases in power until a maximum power level of the energy generator is reached, until a maximum irrigation flow rate / volume is reached, until a minimum irrigation fluid temperature is reached, and / or until the system otherwise prevents the controller from further increasing power (e.g., according to a preset safety threshold). In some embodiments, the maximum irrigation flow rate and / or volume may be determined by: (i) irrigation pump capacity; (ii) the patient's blood dilution limit (ensuring adequate blood supply to the end organ); (iii) safety factors determined from preclinical models, general human anatomical knowledge, specific patient anatomy and / or ablation location; and / or (v) achievement of a specific lesion depth. In addition, because the irrigation fluid is applied in a controlled manner (e.g., only when needed, with desired characteristics and / or at a flow rate that is typically less than that of conventional irrigation systems) throughout the neuromodulation procedure, diagnostic information reported to the controller regarding the progress of the neuromodulation procedure, the condition of tissue at the treatment site, and / or the condition of components of the treatment device remains meaningful and accurate. As a result, the neuromodulation systems of the present technology are better able to avoid tissue damage and adverse effects of neuromodulation therapy that typically occur after use of conventional neuromodulation systems.

[0054] Figure 6 670 is a flow chart illustrating a routine 670 for a method of treating a patient configured in accordance with embodiments of the present technology. Routine 670 may be performed, for example, by various components of a neuromodulation system (e.g., a console, a controller, a control algorithm, an irrigation pump, and / or a treatment device) and / or a clinician operating the neuromodulation system. Routine 670 may be initiated at box 671 by positioning a treatment component of a treatment device within a blood vessel (e.g., within a renal artery) or within another suitable body cavity within a patient (e.g., within a ureter). Routine 670 may further include deploying the treatment component at a treatment site within the patient (e.g., by retracting a guidewire).

[0055] At box 672, routine 670 may include delivering neuromodulatory energy to tissue at a treatment site via a neuromodulatory element of the treatment assembly (e.g., according to a control algorithm of the neuromodulatory system). At box 673, routine 670 may additionally or alternatively include delivering an irrigation fluid having desired characteristics via an irrigation outlet in the treatment assembly. The delivery of the irrigation fluid may be controlled, for example, according to a control algorithm. For example, routine 670 may (i) deliver neuromodulatory energy at a first power level after a first time period and / or during a first time period and / or (ii) deliver an irrigation fluid of a first type having desired characteristics corresponding to a ramping of power (e.g., at a first volume, temperature, and / or flow rate). In some embodiments, routine 670 may deliver an irrigation fluid having specified characteristics to maintain a temperature of a neuromodulatory element on the treatment assembly within a desired temperature range. In these and other embodiments, routine 670 may refrain from delivering irrigation fluid to the treatment site until the neuromodulatory energy reaches a specified power level and / or until the neuromodulatory element and / or tissue at the treatment site reaches a specified temperature.

[0056] In some embodiments, routine 670 may continue to increase the power of the neuromodulation energy and / or modify the characteristics of the irrigation fluid delivered to the treatment site in accordance with the control algorithm. For example, routine 670 may increase the power of the neuromodulation energy to a second power level (e.g., after a second time period) and apply the neuromodulation energy to the tissue at the treatment site at the second power level (box 672). Additionally, routine 670 may adjust and / or modify the characteristics of the irrigation fluid delivered to the treatment site in accordance with the power increase. For example, routine 670 may increase the volume and / or flow rate of the irrigation fluid delivered to the treatment site as the power of the neuromodulation energy increases (box 673). In these and other embodiments, routine 670 may reduce the temperature at which the irrigation fluid is supplied to the treatment site and / or may change the type of irrigation fluid supplied to the treatment site (box 673). In other embodiments, routine 670 may (i) maintain the irrigation fluid properties constant, (ii) cease delivering irrigation fluid to the treatment site, and / or (iii) wait to adjust and / or modify the properties of the irrigation fluid supplied to the treatment site until a second power level is reached and / or until the neuromodulatory element reaches a specified temperature (box 673).

[0057] In some embodiments, routine 670 may continue to deliver neuromodulation energy and / or irrigation fluid according to the control algorithm until a maximum power value and / or other safety threshold of the neuromodulation system is reached (blocks 672 and 673). At this point, routine 670 may prevent an increase in power if a maximum volume and / or flow rate of the irrigation fluid is reached. Additionally or alternatively, routine 670 may prevent an increase in power if a minimum temperature of the irrigation fluid is reached and / or a maximum temperature of the neuromodulation element is reached.

[0058] At any time before, during, and / or after positioning and / or deploying the treatment assembly, routine 670 may monitor (e.g., continuously and / or simultaneously) one or more parameters related to the patient and / or to components of the neuromodulation system (e.g., neuromodulation elements and / or electrodes) (block 674). For example, routine 670 may use one or more sensors located on or near the neuromodulation elements of the treatment device to measure temperature, impedance, duration, power, flow rate, volumetric flow rate, blood pressure, heart rate, parameters of returned energy, and / or other parameters of the tissue at the treatment site, the patient, the irrigation fluid, and / or the neuromodulation elements of the treatment device. Routine 670 may use this diagnostic information as feedback related to the progress of the neuromodulation procedure (e.g., the size and / or depth of lesions formed during treatment), the condition of the tissue at the treatment site, and / or the condition of components of the neuromodulation system.

[0059] In some embodiments, routine 670 may determine whether to adjust and / or modify one or more characteristics of the neuromodulation energy applied to the treatment site and / or one or more characteristics of the irrigation fluid supplied to the treatment site, respectively, based at least in part on the diagnostic information. For example, routine 670 may compare the diagnostic information to predetermined parameter distribution ranges to determine whether one or more parameters are outside of those range(s). If a particular parameter and / or a predetermined number of parameters fall within the parameter distribution ranges, routine 670 may continue to apply neuromodulation energy and / or irrigation fluid according to the control algorithm (blocks 672 and / or 673).

[0060] On the other hand, if one or more of the parameters fall outside of the predetermined parameter distribution range (e.g., above and / or below the predetermined parameter distribution range), the routine 670 may decide to adjust and / or modify one or more characteristics of the neuromodulation energy applied to the treatment site (block 675) and / or one or more characteristics of the irrigation fluid applied to the treatment site (block 676). For example, if the routine 670 determines that the temperature of the tissue at the treatment site and / or the temperature of the neuromodulation element is above the predetermined temperature distribution range (e.g., given the current energy characteristics, the current stage in the neuromodulation procedure, the current irrigation fluid characteristics, and / or the safety threshold(s)), the routine 670 may change and / or modify the control algorithm to change and / or modify the power level of the neuromodulation energy (block 675). In some embodiments, the routine 670 may reduce the power at which the neuromodulation energy is applied. In other embodiments, the routine 670 may maintain the power level constant and / or may increase the power level at a slower rate. Additionally or alternatively, the routine 670 may change and / or modify the control algorithm to change and / or modify the irrigation fluid characteristics (e.g., block 676). For example, routine 670 may (i) increase the volume and / or flow rate of irrigation fluid applied at the treatment site, (ii) decrease the temperature at which irrigation fluid is applied at the treatment site, and / or (iii) change the type of irrigation fluid applied to the treatment site. In some embodiments, routine 670 may (i) increase the power of neuromodulation energy applied to the treatment site and / or the temperature of irrigation fluid applied to the treatment site and / or (ii) decrease the volume and / or flow rate of irrigation fluid only after one or more parameters move back within a predetermined parameter distribution range(s).

[0061] Although the steps of routine 670 are discussed and illustrated in a particular order, the method illustrated in routine 670 is not limited thereto. In other embodiments, the method may be performed in a different order. For example, prior to delivering energy and / or irrigation fluid to the treatment site, one or more sensors of the neuromodulation system may monitor parameters of the neuromodulation system and / or the patient. In other embodiments, irrigation fluid may be applied to the treatment site prior to applying neuromodulation energy to the treatment site and / or adjusting the neuromodulation energy. In these and other embodiments, the neuromodulation system may require that an increase in power applied to the treatment site be performed after or concurrently with: (i) an increase in the volume and / or flow rate of irrigation fluid applied to the treatment site and / or (ii) a decrease in the temperature of the irrigation fluid. Additionally, for completeness, boxes 671-676 are shown. Those skilled in the art will readily recognize that the method illustrated may be varied and still remain within these and other embodiments of the present technology. For example, in some embodiments, the method illustrated may be omitted and / or repeated. Figure 6 One or more steps of the method shown.

[0062] C. Selected Examples of Neuromodulation Devices and Related Systems

[0063] Figure 7 (See also Figure 1 ) shows a schematic diagram of a system 100 ( Figure 1 ) embodiments modulate renal nerves. The neuromodulation device 110 provides access to the renal plexus RP through an intravascular pathway P, such as a percutaneous access site in the femoral artery (shown), brachial artery, radial artery, or axillary artery to a target treatment site within a corresponding renal artery RA. By manipulating the proximal portion 114 of the elongated shaft 112 from outside the intravascular pathway P, the clinician can advance the elongated shaft 112 through the sometimes tortuous intravascular pathway P and remotely manipulate the distal portion 116 of the elongated shaft 112 ( Figure 1 ).exist Figure 7 In the illustrated embodiment, the neuromodulation assembly 120 is delivered intravascularly to the treatment site using a guidewire 715 in the OTW technique. At the treatment site, the guidewire 715 can be at least partially retracted or removed, and the neuromodulation assembly 120 can be converted or otherwise moved into a deployed arrangement for recording neural activity and / or delivering energy at the treatment site. In other embodiments, the neuromodulation assembly 120 can be delivered to the treatment site within a guide sheath (not shown) with or without the use of the guidewire 715. When the neuromodulation assembly 120 is at the target site, the guide sheath can be at least partially retracted or retracted, and the neuromodulation assembly 120 can be converted into a deployed arrangement. In other embodiments, the elongated shaft 112 itself can be maneuverable so that the neuromodulation assembly 120 can be delivered to the treatment site without the assistance of the guidewire 715 and / or the guide sheath.

[0064] Image guidance (e.g., computed tomography (CT), fluoroscopy, intravascular ultrasound (IVUS), optical coherence tomography (OCT), intracardiac echocardiography (ICE), or other suitable guidance modalities or combinations thereof) may be used to assist the clinician in positioning and manipulating the neuromodulation assembly 120. For example, a fluoroscopic system (e.g., including a flat panel detector, x-ray, or c-arm) may be rotated to accurately visualize and identify a target treatment site. In other embodiments, the treatment site may be determined prior to delivery of the neuromodulation assembly 120 using IVUS, OCT, and / or other suitable image mapping modalities that may associate the target treatment site with identifiable anatomical structures (e.g., spinal features) and / or opaque scales (e.g., located beneath or on the patient). Further, in some embodiments, an image guidance component (e.g., IVUS, OCT) may be integrated with the neuromodulation device 110 and / or run in parallel with the neuromodulation device 110 to provide image guidance during positioning of the neuromodulation assembly 120. For example, an image guidance component (eg, IVUS or OCT) can be coupled to the neuromodulation assembly 120 to provide a three-dimensional image of the vasculature proximal to the treatment site to facilitate positioning or deployment of the multi-electrode assembly within the target renal vasculature.

[0065] Energy from the neuromodulatory element 126 may then be applied to the target tissue to induce one or more desired neuromodulatory effects on a local region of the renal artery RA and an adjacent region of the renal plexus RP, which is located closely within the adventitia of the renal artery RA, adjacent to the adventitia of the renal artery RA, or in close proximity to the adventitia of the renal artery RA. . The purposeful application of energy may achieve neuromodulation along all or at least a portion of the renal plexus RP. The neuromodulatory effect is generally at least in part a function of power, time, contact between the energy delivery element and the vessel wall, and blood flow through the vessel. The neuromodulatory effect may include denervation, thermal ablation, and / or non-ablative thermal change or damage (e.g., via continuous heating and / or resistive heating). The desired thermal heating effect may include raising the temperature of the target nerve fibers above a desired threshold to achieve non-ablative thermal change, or to a higher temperature to achieve ablative thermal change. For example, the target temperature may be higher than body temperature (e.g., approximately 37° C.) but less than approximately 45° C. for non-ablative thermal change, or the target temperature may be approximately 45° C. or higher for ablative thermal change. Desired non-thermal neuromodulation effects may include altering electrical signals transmitted in nerves.

[0066] The cryogenic effect can also provide neuromodulation. For example, a cryotherapy applicator can be used to cool tissue at the treatment site to provide therapeutically effective direct cell damage (e.g., necrosis), vascular damage (e.g., by destroying the supplying blood vessels so that the cells die of lack of nutrients) and sublethal hypothermia with subsequent apoptosis. Exposure to cryogenic cooling may result in acute cell death (e.g., death immediately after exposure) and / or delayed cell death (e.g., death during tissue thawing and subsequent overperfusion). Several embodiments of the present technology may include cooling a structure at or near the inner surface of the renal artery wall so that the approaching (e.g., adjacent) tissue is effectively cooled to the depth where the renal sympathetic nerves reside. For example, the cooling structure is cooled to the extent that it causes therapeutically effective low-temperature renal neuromodulation. It is expected that sufficient cooling of at least a portion of the renal sympathetic nerves will slow or possibly block the conduction of nerve signals to produce a long-term or permanent reduction in renal sympathetic nerve activity.

[0067] D. Renal neuromodulation

[0068] Renal neuromodulation is the partial or complete incapacitation or other effective destruction of renal nerves (e.g., nerves terminating in the kidney or in structures closely associated with the kidney). In particular, renal neuromodulation can include inhibiting, reducing, and / or blocking neural communication along the nerve fibers (e.g., efferent and / or afferent nerve fibers) of the kidney. Such incapacitation can be long-term (e.g., permanent or for a period of months, years, or decades) or short-term (e.g., for a period of minutes, hours, days, or weeks). It is expected that renal neuromodulation contributes to the systemic reduction of sympathetic tone or impulses and / or benefits at least some specific organs and / or other body structures innervated by the sympathetic nerves. Therefore, it is expected that renal neuromodulation can be used to treat clinical conditions associated with systemic sympathetic overactivity or hyperactivity, particularly conditions associated with central sympathetic overstimulation. For example, renal neuromodulation is expected to be effective in treating conditions such as hypertension, heart failure, acute myocardial infarction, metabolic syndrome, insulin resistance, diabetes, left ventricular hypertrophy, chronic and end-stage renal disease, inappropriate fluid retention in heart failure, cardio-renal syndrome, polycystic kidney disease, polycystic ovary syndrome, osteoporosis, erectile dysfunction, and sudden death.

[0069] During the treatment process, renal neuromodulation can be induced electrically, thermally, chemically, or in other suitable ways or combinations at one or more suitable treatment sites. The treatment site can be located within or otherwise close to the renal lumen (e.g., renal artery, ureter, renal pelvis, renal calyces, renal calyces, or other suitable structures) and the treated tissue can include tissue at least close to the renal lumen wall. For example, with respect to the renal artery, the treatment process can include regulating nerves in the renal plexus, which are closely located within or adjacent to the adventitia of the renal artery.

[0070] Renal neuromodulation can include cryotherapy alone or in combination with another treatment modality. Cryotherapy can include cooling tissue at the treatment site in a manner that regulates neural function. For example, sufficient cooling of at least a portion of the renal sympathetic nerves can slow or possibly block the conduction of nerve signals to produce a long-term or permanent reduction in renal sympathetic nerve activity. This effect can occur due to cryotherapy tissue damage, which can include, for example, direct cell damage (e.g., necrosis), vascular or luminal damage (e.g., by destroying the supplying blood vessels so that cells die of lack of nutrients), and / or sublethal hypothermia with subsequent apoptosis. Exposure to cryocooling may result in acute cell death (e.g., death immediately after exposure) and / or delayed cell death (e.g., death during tissue thawing and subsequent overperfusion). Neuromodulation using cryotherapy according to embodiments of the present technology can include cooling structures close to the inner surface of the body cavity wall so that the tissue is effectively cooled to the depth where the renal sympathetic nerves reside. For example, in some embodiments, the cooling component of the cryotherapy device can be cooled to the extent that it causes therapeutically effective low-temperature renal neuromodulation. In other embodiments, the cryotherapy modality may include cooling that is configured not to cause neuromodulation. For example, the cooling may be at or above certain cryogenic temperatures and may be used to control neuromodulation (e.g., to protect tissue from neuromodulation energy) via another treatment modality.

[0071] Renal neuromodulation can include electrode-based or transducer-based treatment modalities alone or in combination with another treatment modality. Electrode-based or transducer-based treatment can include delivering electricity and / or another form of energy to the tissue at the treatment location so as to stimulate and / or heat the tissue in a manner that regulates neural function. For example, sufficient stimulation and / or heating of at least a portion of the renal sympathetic nerves can slow down or possibly block the conduction of nerve signals to produce a long-term or permanent reduction in renal sympathetic nerve activity. Various suitable types of energy can be used to stimulate and / or heat the tissue at the treatment location. For example, neuromodulation according to an embodiment of the present technology can include delivering RF energy, pulsed energy, microwave energy, light energy, focused ultrasound energy (e.g., high-intensity focused ultrasound energy), or another suitable type of energy, alone or in combination. Electrodes or transducers for transmitting this energy can be used alone or in combination with other electrodes or transducers in a multi-electrode or multi-transducer array. In addition, energy can be applied from within the body (e.g., in the vascular system or other body cavity in a catheter-based approach) and / or from outside the body (e.g., via an applicator located outside the body). Furthermore, when target tissue adjacent to non-target tissue is subjected to neuromodulatory cooling, energy may be used to reduce damage to the non-target tissue.

[0072] Neuromodulation using focused ultrasound energy (e.g., high-intensity focused ultrasound energy) may be beneficial relative to neuromodulation using other treatment modalities. Focused ultrasound is an example of a transducer-based treatment modality that can be delivered from outside the body. Focused ultrasound therapy can be performed in close association with imaging (e.g., magnetic resonance, computed tomography, fluoroscopy, ultrasound (e.g., intravascular or intracavitary), optical coherence tomography, or another suitable imaging modality). For example, imaging can be used to identify the anatomical location of the treatment location (e.g., as a set of coordinates relative to a reference point). The coordinates can then enter a focused ultrasound device that is configured to change power, angle, phase, or other suitable parameters to generate an ultrasound focus zone at a location corresponding to the coordinates. The focus zone can be small enough to confine therapeutically effective heating to the treatment location while partially or completely avoiding potential harmful damage to nearby structures. In order to generate a focus zone, the ultrasound device can be configured to pass the ultrasound energy through a lens, and / or the ultrasound energy can be generated by a curved transducer or by multiple transducers in a (curved or straight) phased array.

[0073] The heating effect of electrode-based or transducer-based treatment can include ablation, and / or non-ablative changes or damage (e.g., via continuous heating and / or resistive heating). For example, the treatment process can include raising the temperature of the target nerve fiber to a target temperature above a first threshold to achieve non-ablative changes, or above a higher second threshold to achieve ablation. For non-ablative changes, the target temperature can be above about body temperature (e.g., about 37°C) but below about 45°C, and for ablation, the target temperature can be above about 45°C. Heating the tissue to a temperature between about body temperature and about 45°C can cause non-ablative changes, for example, via moderate heating of the target nerve fiber or the vascular or luminal structure that perfuses the target nerve fiber. In the case where the vascular structure is affected, the target nerve fiber can refuse perfusion, resulting in necrosis of the neural tissue. Heating the tissue to a target temperature above about 45°C (e.g., above about 60°C) can cause ablation, for example, via substantial heating of the target nerve fiber or the vascular or luminal structure that perfuses the target fiber. In some patients, it may be desirable to heat the tissue to a temperature sufficient to ablate target neural fibers or vascular or luminal structures, but below about 90°C (eg, below about 85°C, below about 80°C, or below about 75°C).

[0074] Renal neuromodulation can include chemical-based treatment modalities alone or in combination with another treatment modality. Neuromodulation using chemical-based treatments can include delivering one or more chemicals (e.g., drugs or other agents) to tissue at the treatment location in a manner that modulates neural function. For example, chemicals can be selected to generally affect the treatment location or selectively affect some structures at the treatment location rather than other structures. For example, the chemical can be guanethidine, ethanol, phenol, neurotoxin, or other suitable agents selected for changing, damaging or destroying nerves. Chemicals can be delivered to tissue at the treatment location using various suitable techniques. For example, chemicals can be delivered via one or more needles from outside the body or delivered in the vascular system or other body cavities. In an intravascular example, a catheter can be used to position a treatment element including multiple needles (e.g., microneedles) within a blood vessel, which can be retracted or otherwise blocked before deployment. In other embodiments, chemicals can be introduced into tissue at the treatment location via simple diffusion through the wall of the body cavity, electrophoresis, or another suitable mechanism. Similar techniques can be used to introduce chemicals that are configured not to cause neuromodulation but to promote neuromodulation via another treatment modality.

[0075] E. Related anatomy and physiology

[0076] As previously noted, the sympathetic nervous system (SNS) is a branch of the autonomic nervous system, along with the enteric nervous system and the parasympathetic nervous system. It is always active at a basal level (called sympathetic tone) and becomes more active when stressed. Like the rest of the nervous system, the sympathetic nervous system operates through a series of interconnected neurons. Although many sympathetic neurons are located in the central nervous system (CNS), sympathetic neurons are often considered to be part of the peripheral nervous system (PNS). The sympathetic neurons of the spinal cord (which is part of the CNS) communicate with peripheral sympathetic neurons via a series of sympathetic ganglia. Within the ganglia, spinal sympathetic neurons connect to peripheral sympathetic neurons through synapses. Therefore, spinal sympathetic neurons are referred to as presynaptic (or preganglionic) neurons, and peripheral neurons are referred to as postsynaptic (or postganglionic) neurons.

[0077] At synapses within the sympathetic ganglia, preganglionic sympathetic neurons release acetylcholine, a chemical messenger that binds to and activates nicotinic acetylcholine receptors on postganglionic neurons. In response to this stimulation, postganglionic neurons primarily release noradrenaline (norepinephrine). Prolonged activation can cause the release of epinephrine from the adrenal medulla.

[0078] Once released, norepinephrine and epinephrine bind to adrenergic receptors on peripheral tissues. Binding to adrenergic receptors results in neural and hormonal responses. Physiological clinical manifestations include pupil dilation, increased heart rate, occasional vomiting, and increased blood pressure. Increased sweating due to binding to cholinergic receptors of sweat glands has also been seen.

[0079] The sympathetic nervous system is responsible for the multi-stable mechanisms in the organism of up-regulation and down-regulation. Fibers from the SNS innervate tissues in almost every organ system, thereby providing at least some regulatory functions to physiological features as diverse as pupil diameter, intestinal motility, and urine output. This reaction is also referred to as the sympathetic adrenal response of the body, because the preganglionic sympathetic nerve fibers (and all other sympathetic nerve fibers) that terminate in the adrenal medulla secrete acetylcholine, which activates the secretion of adrenaline (epinephrine) and norepinephrine (noradrenaline) to a lesser extent. Therefore, the reaction that mainly acts on the cardiovascular system is mediated directly via the pulsation transmitted by the sympathetic nervous system and indirectly via the catecholamines secreted from the adrenal medulla.

[0080] Science generally views the SNS as an autoregulatory system, i.e., a system that operates without the intervention of conscious thought. Since the sympathetic nervous system is responsible for priming the body for action, some evolutionary theorists have proposed that the sympathetic nervous system operated in early organisms to maintain survival. An example of such priming is the moment before arousal, when sympathetic outflow spontaneously increases in preparation for action.

[0081] 1. Sympathetic chain

[0082] like Figure 8 As shown, SNS provides a neural network that allows the brain to communicate with the body. Sympathetic nerves originate in the spine, towards the middle of the spinal cord in the middle lateral cell column (or lateral angle), which begins in the first thoracic segment of the spinal cord and is considered to extend to the second or third lumbar segment. Because its cells begin in the thoracic and lumbar regions of the spinal cord, it can be considered that SNS has thoracolumbar outflow. The axons of these nerves leave the spinal cord by the anterior root / root. They pass near the spinal column (sensory) ganglion, where they enter the anterior ramus of the spinal nerve. However, unlike somatic innervation, they are soon separated by white branch connectors, which are connected to the paravertebral (near the spine) or prevertebral (near the aortic branch) ganglia extending beside the spine.

[0083] In order to reach the target organs and glands, axons should travel long distances in the body, and, to accomplish this, many axons relay their message to a second cell through synaptic transmission. The tip of the axon connects to the dendrites of the second cell across a space (synapse). The first cell (presynaptic cell) sends a neurotransmitter across the synaptic cleft, where it activates the second cell (postsynaptic cell). The message is then carried to the final destination.

[0084] In the SNS and other components of the peripheral nervous system, these synapses are generated at sites called ganglia (discussed above). The cells that send their fibers are called preganglionic cells, and the cells whose fibers leave the ganglia are called postganglionic cells. As mentioned above, the preganglionic cells of the SNS are located between the first thoracic (T1) segment and the third lumbar (L3) segment of the spinal cord. Postganglionic cells have their cell bodies in the ganglia and send their axons to target organs or glands.

[0085] The ganglia include not only the sympathetic trunks but also the cervical ganglia (superior, middle, and inferior) which send sympathetic nerve fibers to the organs of the head and chest, and the celiac and mesenteric ganglia (which send sympathetic nerve fibers to the intestines).

[0086] a. Innervation of the kidneys

[0087] like Fig. 9As shown in Figure 1, kidney is dominated by the renal plexus (RP) closely associated with the renal artery. The renal plexus (RP) is an autonomic plexus surrounding the renal artery and embedded in the adventitia of the renal artery. The renal plexus (RP) extends along the renal artery until it reaches the substance of the kidney. The fibers that contribute to the renal plexus (RP) are produced by the celiac ganglion, superior mesenteric ganglion, aortic renal ganglion and aortic plexus. The renal plexus (RP) (also known as renal nerve) is mainly composed of sympathetic components. There is no (or at least very little) parasympathetic innervation of the kidney.

[0088] Preganglionic neuron cell bodies are located in the intermediolateral cell columns of the spinal cord. Preganglionic axons pass through the paravertebral ganglia (they do not synapse) to become the lesser splanchnic nerve, the smallest splanchnic nerve, the first lumbar splanchnic nerve, the second lumbar splanchnic nerve, and travel to the celiac ganglion, the superior mesenteric ganglion, and the aortic renal ganglion. Postganglionic neuron cell bodies exit the celiac ganglion, the superior mesenteric ganglion, and the aortic renal ganglion to the renal plexus (RP) and are distributed to the renal vascular system.

[0089] b. Renal sympathetic nerve activity

[0090] Messages travel through SNS in a two-way flow. Outgoing messages can trigger changes in different parts of the body simultaneously. For example, the sympathetic nervous system can increase heart rate; dilate bronchial passages; reduce motility (movement) of the large intestine; constrict blood vessels; increase esophageal motility; cause pupil dilation, piloerection (goose bumps), and perspiration (sweating); and raise blood pressure. Incoming messages carry information from various organs and sensory receptors in the body to other organs, especially the brain.

[0091] Hypertension, heart failure, and chronic kidney disease are some of the many disease states caused by chronic activation of the SNS (particularly the renal sympathetic nervous system). Chronic activation of the SNS is a maladaptive response that drives the progression of these disease states. Drug management of the renin-angiotensin-aldosterone system (RAAS) has been a long-standing method for reducing the overactivity of the SNS, but some are inefficient.

[0092] As mentioned above, the renal sympathetic nervous system has been identified experimentally and in humans as a major contributor to the complex pathophysiology of hypertension, states of volume overload (such as heart failure), and progressive renal disease. Studies using radiotracer dilution methods to measure norepinephrine flowing from the kidneys to plasma show that the increased renal norepinephrine (NE) overflow rate (which is consistent with the increased NE overflow from the heart) in patients with essential hypertension (especially in young hypertensive patients) is consistent with the hemodynamic distribution commonly seen in early hypertension and is characterized by increased heart rate, cardiac output, and renal vascular resistance. It is now known that essential hypertension is usually neurological, often accompanied by significant sympathetic nervous system overactivity.

[0093] Activation of cardiorenal sympathetic nerve activity is even more pronounced in heart failure, as evidenced by an exaggerated increase in NE spillover from the heart and kidneys to plasma in this patient population. Consistent with this concept is the recent demonstration of a strong negative predictive value of renal sympathetic nerve activation for all-cause mortality and cardiac transplantation in patients with congestive heart failure, independent of overall sympathetic nerve activity, glomerular filtration rate, and left ventricular ejection fraction. These findings support the concept that treatment regimens designed to reduce renal sympathetic nerve stimulation have the potential to improve survival in patients with heart failure.

[0094] Chronic and end-stage renal disease are characterized by elevated sympathetic activation. In patients with chronic and end-stage renal disease, plasma levels of norepinephrine above the median have been shown to be a precursor to all-cause mortality and cardiovascular death. This is also true for patients with diabetes or contrast-induced nephropathy. There is convincing evidence that sensory afferent signals originating from the diseased kidneys are the main cause of initiation and maintenance of elevated central sympathetic outflow in this patient population; this promotes the well-known adverse consequences of chronic sympathetic overactivity, such as hypertension, left ventricular hypertrophy, ventricular arrhythmias, sudden cardiac death, insulin resistance, diabetes, and metabolic syndrome.

[0095] i Renal sympathetic nerve outflow activity

[0096] Sympathetic nerves to the kidneys terminate in blood vessels, juxtaglomerular apparatus, and renal tubules. Stimulation of renal sympathetic nerves results in the release of renin, increased sodium (Na + ) reabsorption, and the reduction of renal blood flow. These components of the neural regulation of renal function are greatly stimulated in the disease state characterized by the increased sympathetic tone and clearly promoting the increase in blood pressure in hypertensive patients. The reduction of renal blood flow and glomerular filtration rate caused by the stimulation of renal sympathetic nerve efferent may be the basis of the loss of renal function in cardiorenal syndrome (which is the renal insufficiency caused by the progressive complications of chronic heart failure), with a clinical course that fluctuates with the clinical state and treatment of the patient. The pharmacological strategy for hindering the results of renal efferent sympathetic nerve stimulation includes centrally acting sympathetic drugs, beta blockers (intended to reduce renin release), angiotensin converting enzyme inhibitors and receptor blockers (intended to prevent angiotensin II and aldosterone activation caused by renin release) and diuretics (intended to counteract sodium and water retention mediated by renal sympathetic nerves). However, current pharmacological strategies have significant limitations, including limited efficacy, compliance issues, side effects and others.

[0097] ii Renal sensory afferent nerve activity

[0098] The kidneys communicate with structures throughout the central nervous system via renal sensory afferent nerves. Several forms of "renal injury" can cause activation of sensory afferent signals. For example, renal ischemia, a decrease in stroke volume or renal blood flow, or high levels of adenosine can trigger activation of afferent nerve communication. Fig.10 and Fig.11 As shown in , this incoming communication can be from the kidney to the brain or from one kidney to another kidney (via the central nervous system). These incoming signals are all centrally integrated and may result in increased sympathetic outflow. The sympathetic impulses are directed toward the kidneys, thereby activating the RAAS and inducing increased renin secretion, sodium retention, volume retention, and vasoconstriction. Central sympathetic overactivity also affects other organs and body structures (such as the heart and peripheral vasculature) that are innervated by the sympathetic nerves, resulting in the adverse effects of the described sympathetic activation, some aspects of which also contribute to increased blood pressure.

[0099] Thus, physiology suggests that (i) modulation of tissues with efferent sympathetic nerves will reduce inappropriate renin release, sodium retention, and decrease renal blood flow, and (ii) modulation of tissues with afferent sensory nerves will reduce systemic contributions to hypertension and other disease states associated with central sympathetic tone through its direct effects on the posterior hypothalamus and contralateral kidney. In addition to the central hypotensive effects of denervation of the afferent kidney, a desired reduction in central sympathetic outflow to various other sympathetically innervated organs, such as the heart and blood vessels, is contemplated.

[0100] 2. Additional clinical benefits of renal denervation

[0101] As described above, renal denervation may be valuable in the treatment of several clinical conditions characterized by increased global and specific renal sympathetic nerve activity, such as hypertension, metabolic syndrome, insulin resistance, diabetes, left ventricular hypertrophy, chronic and end-stage renal disease, inappropriate fluid retention in heart failure, cardiorenal syndrome, and sudden death. Because the reduction in afferent nerve signals contributes to a systemic reduction in sympathetic tone / impulsivity, renal denervation may also be beneficial in the treatment of other conditions associated with systemic sympathetic hyperactivity. Thus, renal denervation may also benefit other organs and body structures innervated by sympathetic nerves, including in Figure 8 For example, as previously discussed, reduction of central sympathetic nerve impulses may reduce insulin resistance that afflicts people with metabolic syndrome and type II diabetes. In addition, patients with osteoporosis are also sympathetically activated and may also benefit from downregulation of sympathetic nerve impulses that accompanies renal denervation.

[0102] 3. Achieving intravascular access to the renal artery

[0103] According to the present technology, neuromodulation of the left and / or right renal plexus (RP) closely associated with the left and / or right renal arteries can be achieved via intravascular access. Fig.12 As shown in FIG. 1 , the aorta carries blood moved by the contraction of the heart from the left ventricle of the heart. The aorta descends through the chest and branches into the left and right renal arteries. Below the renal arteries, the aorta branches at the left and right common iliac arteries. The left and right common iliac arteries descend through the left and right legs, respectively, and connect to the left and right femoral arteries.

[0104] like Fig.13 As shown, blood collects in the veins and enters the iliac veins through the femoral veins and into the inferior vena cava, returning to the heart. The inferior vena cava branches into the left and right renal veins. Above the renal veins, the inferior vena cava ascends to deliver blood to the right atrium of the heart. From the right atrium, blood is pumped through the right ventricle into the lungs, where the blood is oxygenated. From the lungs, oxygenated blood is delivered to the left atrium. From the left atrium, oxygenated blood is delivered through the left ventricle back to the aorta.

[0105] As will be described in more detail later, the femoral artery can be accessed and cannulated only at the base of the femoral triangle below the midpoint of the inguinal ligament. A catheter can be inserted percutaneously through this access site into the femoral artery, through the iliac artery and aorta, and placed in the left or right renal artery. This includes an intravascular route that provides minimally invasive access to the respective renal artery and / or other renal vessels.

[0106] The wrist, upper arm, and shoulder areas provide other locations for introducing catheters into the arterial system. For example, catheterization of the radial, brachial, or axillary arteries may be used in selected cases. The catheter introduced via these entry points may be passed through the subclavian artery on the left side (or via the subclavian and brachiocephalic arteries on the right side), through the aortic arch, down along the descending aorta, and into the renal arteries using standard angiographic techniques.

[0107] 4. Properties and characteristics of renal blood vessels

[0108] Since neuromodulation of the left and / or right renal plexus (RP) can be achieved through intravascular access according to the present technology, the properties and characteristics of the renal vasculature can impose constraints on and / or inform the design of devices, systems and methods for achieving such renal neuromodulation. Some of these properties and characteristics may vary across patient populations and / or vary over time within a particular patient, as well as in response to disease states such as hypertension, chronic kidney disease, vascular disease, end-stage renal disease, insulin resistance, diabetes, metabolic syndrome, etc. As explained herein, these properties and characteristics may be related to the efficacy of the procedure and the specific design of the intravascular device. Properties of interest may include, for example, material / mechanical, spatial, fluid / hemodynamic, and / or thermodynamic properties.

[0109] As discussed above, the catheter can be percutaneously advanced into the left or right renal artery via a minimally invasive intravascular path. However, minimally invasive renal artery access may be challenging, for example, because compared with some other arteries that are routinely accessed using a catheter, the renal artery is often extremely tortuous, can be a relatively small diameter, and / or can be a relatively short length. In addition, renal artery atherosclerosis is common in many patients, particularly those patients with cardiovascular disease. Renal artery anatomy can also be significantly different from patient to patient, which further complicates minimally invasive access. For example, significant patient-to-patient variation can be seen in relative tortuosity, diameter, length and / or atherosclerotic plaque load and the take-off angle of the renal artery from the aortic branch. These and other aspects of renal artery anatomy and its variation across patient populations should be considered for devices, systems and methods for realizing renal neuromodulation via intravascular access when minimally invasively accessing the renal artery.

[0110] In addition to complicating access to the renal artery, details of the renal anatomy also complicate establishing stable contact between the neuromodulator and the luminal surface or wall of the renal artery. For example, the narrow space within the renal artery and the tortuosity of the artery may hinder navigation. In addition, establishing consistent contact may be complicated by patient movement, respiration, and / or the cardiac cycle, as these factors may cause significant movement of the renal artery relative to the aorta, and the cardiac cycle may transiently dilate the renal artery (i.e., cause the wall of the artery to pulsate).

[0111] Even after entering the renal artery and facilitating stable contact between the neuromodulator and the luminal surface of the artery, the nerves in and around the adventitia of the artery should still be safely regulated via the neuromodulator. Given the potential clinical complications associated with thermal therapy, it is not trivial to effectively apply thermal therapy to the renal artery. For example, the intima and media of the renal artery are easily damaged by thermal damage. As discussed in more detail below, the thickness of the intima medium separating the vascular cavity from its adventitia indicates that the target renal nerve can be several millimeters away from the luminal surface of the artery. Sufficient energy should be delivered to the target renal nerve or heat should be removed from the target renal nerve to regulate the target renal nerve without excessively cooling or heating the vascular wall to the extent of freezing the wall, the extent of drying, or otherwise not potentially affecting the undesirable extent. A potential clinical complication associated with overheating is thrombosis caused by coagulation of blood flowing through the artery. Assuming that such thrombus may cause renal infarction, thereby causing irreversible damage to the kidney, thermal therapy in the renal artery should be applied with caution. Therefore, the complex fluid dynamics and thermodynamic conditions that exist in the renal artery during treatment (particularly those conditions that may affect the dynamics of heat transfer at the treatment site) may be important in applying energy (e.g., heating thermal energy) and / or removing heat from tissue within the renal artery (e.g., cooling thermal conditions).

[0112] Since the location of treatment may also affect clinical efficacy, the neuromodulator should also be configured to allow the energy delivery element to be adjustably positioned and repositioned within the renal artery. For example, assuming that the renal nerves can be spaced axially around the renal artery, it may be attractive to apply full-circumferential treatment within the renal artery. In some cases, full-circumferential damage that may be caused by continuous circumferential treatment may potentially be related to renal artery stenosis. Therefore, the formation of more complex damage along the longitudinal dimension of the renal artery and / or the repositioning of the neuromodulator to multiple treatment positions may be desirable. However, it should be noted that the benefits of creating circumferential ablation may outweigh the risks of renal artery stenosis, or certain embodiments may be used or the risk may be mitigated in certain patients, and creating circumferential ablation may be the goal. In addition, variable positioning and repositioning of the neuromodulator may prove useful in cases where the renal artery is particularly tortuous or there are proximal branch vessels that detach from the main renal artery vessels, resulting in challenging treatment in certain positions. The manipulation of the device in the renal artery should also take into account the mechanical damage imposed by the device on the renal artery. Movement of the device within the artery, for example by insertion, manipulation, unblocking bends, etc., can result in dissection, perforation, intimal denudation, or disruption of the internal elastic lamina.

[0113] Blood flow through the renal artery may be temporarily occluded for a short period of time with little or no complications. However, occlusion for extended periods of time should be avoided to prevent damage to the kidney, such as ischemia. It may be beneficial to avoid occlusion altogether, or to limit the duration of occlusion to, for example, 2-5 minutes when occlusion is beneficial for certain embodiments.

[0114] Based on the challenges described above of: (1) renal artery access; (2) maintaining consistent and stable placement of therapeutic elements against the vessel wall; (3) effective delivery of therapy across the vessel wall; (4) positioning and potentially repositioning the therapeutic device to allow for multiple treatment locations; and (5) avoiding or limiting the duration of blood flow obstruction, various independent and dependent attributes of the renal vasculature that may be of interest include, for example, (a) vessel diameter, vessel length, intima-media thickness, and (a) the properties of the renal artery and / or the aorta. The properties of the renal artery include: (i) the thickness, friction coefficient, and tortuosity of the aorta; (b) the expansibility, stiffness, and elastic modulus of the vessel wall; (c) the peak systolic and end-diastolic blood flow velocities, as well as the average systolic-diastolic peak blood flow velocities, and the average / maximum volumetric blood flow rates; (d) the specific heat capacity of the blood and / or the vessel wall, the thermal conductivity of the blood and / or the vessel wall, and / or the thermal convection and / or radiative heat transfer of the blood flowing through the vessel wall treatment site; (e) the movement of the renal artery relative to the aorta caused by breathing, patient movement, and / or blood flow pulsatility; and (f) the take-off angle of the renal artery relative to the aorta. These properties will be discussed in more detail in conjunction with the renal artery. However, depending on the device, system, and method used to achieve renal neuromodulation, such properties of the renal artery may also guide and / or constrain design characteristics.

[0115] As noted above, the device positioned in the renal artery should conform to the geometry of the artery. Renal artery tube diameter DRA is generally in the range of about 2-10mm, wherein the DRA of most patient populations is about 4mm to about 8mm, and an average of about 6mm. The renal artery tube length LRA between the renal artery orifice at the aorta / renal artery junction and the distal branch of the renal artery is generally in the range of about 5-70mm, and a large part of the patient population is in the range of about 20-50mm. Because the target renal plexus is embedded in the adventitia of the renal artery, the composite intima-media thickness IMT (i.e., the radially outward distance from the arterial cavity surface to the adventitia containing the target neural structure) is noteworthy, and is generally in the range of about 0.5-2.5mm, wherein an average of about 1.5mm. Although a certain treatment depth is important for reaching the target neural fibers, treatment should not be too deep (e.g., from the inner wall of the renal artery>5mm), to avoid non-target tissues and anatomical structures, such as the renal vein.

[0116] An additional property of the renal arteries that may be of interest is the degree of renal motion relative to the aorta due to respiration and / or blood flow pulsatility. A patient's kidneys, located at the distal end of the renal arteries, may move cranially as much as 4" with respiratory excursions. This can cause significant motion of the renal arteries connecting the aorta and kidneys, necessitating a unique balance of rigidity and flexibility from the neuromodulatory device to maintain contact between the energy delivery elements and the vessel wall during the respiratory cycle. Furthermore, the take-off angle between the renal arteries and the aorta may vary significantly between patients, and may also vary dynamically within a patient, for example due to renal motion. The take-off angle may typically be in the range of approximately 30°-135°.

[0117] F: Additional Examples

[0118] Several aspects of the present technology are illustrated in the following examples.

[0119] 1. A neuromodulation system, comprising:

[0120] A catheter comprising—

[0121] an elongated shaft having a distal portion configured to be positioned intravascularly at a treatment site within a renal vessel of a human patient;

[0122] a plurality of electrodes spaced apart along a distal portion of the shaft, wherein the electrodes are configured to deliver neuromodulation energy to a target nerve at or adjacent to the treatment site; and

[0123] a flushing outlet proximate the electrode; and

[0124] a controller configured to be communicatively coupled to the neuromodulation element, wherein the controller is further configured to monitor a parameter of at least one of the electrode and tissue at or adjacent to the treatment site,

[0125] Wherein the irrigation outlet is configured to direct the irrigation fluid in a first direction based at least in part on instructions from the controller corresponding to the monitored parameter.

[0126] 2. The neuromodulation system of Example 1, wherein the first direction is parallel to the longitudinal axis of the renal blood vessel.

[0127] 3. The neuromodulation system of Example 1, further comprising—

[0128] an energy generator external to the patient and electrically coupled to the plurality of electrodes and the controller; and

[0129] a flush pump operably coupled to the flush outlet and the controller,

[0130] Wherein the controller is further configured to: cause the energy generator to deliver neuromodulation energy via the electrodes, and cause the irrigation pump to deliver irrigation fluid via the irrigation outlet.

[0131] 4. The neuromodulation system of Example 3, wherein the controller is further configured to—

[0132] comparing the parameter to a predetermined parameter distribution range;

[0133] causing the energy generator to deliver neuromodulation energy at a power level according to a control algorithm when the parameter is within the range;

[0134] When the parameters are within the range, causing the energy generator to deliver irrigation fluid at a temperature and flow rate according to a control algorithm; and

[0135] When the parameter is outside the range, the control algorithm is modified to adjust a characteristic of at least one of the energy and the irrigation fluid.

[0136] 5. The neuromodulation system of Example 4, wherein the parameter is the temperature of one of the electrodes, wherein the characteristic is the power level at which the energy is delivered, and wherein the controller is configured to reduce the power level when the temperature of the electrode is outside the range.

[0137] 6. The neuromodulation system of Example 4, wherein the parameter is the temperature of one of the electrodes, wherein the characteristic is the power level at which energy is delivered, and wherein the controller is configured to: maintain the power level constant or reduce the power level when the temperature of the electrode is outside the range.

[0138] 7. The neuromodulation system of Example 4 or 6, wherein the parameter is the temperature of one of the electrodes, wherein the characteristic is the flow rate or temperature at which the irrigation fluid is delivered, and wherein the controller is configured to increase the flow rate at which the irrigation fluid is delivered or decrease the temperature at which the irrigation fluid is delivered when the temperature of the electrode is outside the range.

[0139] 8. A system comprising:

[0140] A neuromodulation catheter comprising—

[0141] an elongated shaft having a distal portion sized and shaped to be positioned intravascularly at a treatment site within a blood vessel of a human patient;

[0142] an electrode configured to deliver radio frequency (RF) energy to a target nerve at or adjacent to the treatment site, wherein the electrode is configured to deliver the RF energy according to a control algorithm; and

[0143] a plurality of irrigation outlets positioned to release irrigation fluid according to a control algorithm;

[0144] an irrigation pump coupled to the plurality of irrigation outlets, the irrigation pump configured to deliver irrigation fluid to the treatment site via the plurality of irrigation outlets;

[0145] an energy generator external to the patient and coupled to the electrodes and the irrigation pump, wherein the energy generator is configured to deliver RF energy to the target nerve via the electrodes; and

[0146] A controller is communicatively coupled to the electrodes, the energy generator, and the irrigation pump, wherein the controller is further configured to monitor a parameter of at least one of the electrodes and tissue at or adjacent to the treatment site.

[0147] 9. The system of example 8, wherein a first subset of the plurality of irrigation outlets is positioned proximate the electrode, and wherein each of the first subset of irrigation outlets is oriented to direct irrigation fluid in a first direction.

[0148] 10. The system of Example 9, wherein the electrode is a first electrode, wherein the system further includes a second electrode spaced apart from the first electrode on the elongated shaft, wherein the second electrode is positioned between the first electrode and a distal end of the elongated shaft, and wherein the first subset is configured to release irrigation fluid so that the irrigation fluid cools the second electrode.

[0149] 11. The system of example 8 wherein a plurality of irrigation outlets are positioned on the elongated shaft between the electrode and a proximal portion of the elongated shaft.

[0150] 12. The system of example 10, wherein each of the plurality of irrigation outlets is oriented to direct irrigation fluid radially outward from the elongated shaft.

[0151] 13. The system of Example 8, wherein the neuromodulation catheter further comprises an irrigation ring, and wherein the plurality of irrigation outlets are positioned on the irrigation ring.

[0152] 14. The system of Example 8, wherein the parameter is the temperature of the electrode, and wherein the controller is further configured to increase the power level of the energy generator at which the neuromodulatory energy is delivered while maintaining the temperature of the electrode within a predetermined temperature distribution range.

[0153] 15. The system of example 14, wherein when the controller increases the power level, the controller is further configured to (i) maintain or increase the flow rate and / or (ii) maintain or decrease the temperature of the irrigation fluid delivered by the irrigation pump.

[0154] 16. The system of example 15, wherein the controller is configured to increase the power level only if the flow rate increases and / or only if the temperature of the irrigation fluid decreases.

[0155] 17. The system of Example 8, wherein the controller is configured to prevent the energy generator from increasing a power level at which the energy generator delivers neuromodulatory energy when an irrigation fluid delivered by the irrigation pump reaches a maximum flow rate and / or a minimum temperature.

[0156] 18. A method comprising:

[0157] positioning a neuromodulation catheter at a treatment site within a renal blood vessel of a human patient, wherein the neuromodulation catheter comprises a treatment assembly having one or more electrodes and one or more irrigation outlets;

[0158] deploying the treatment assembly so that the one or more electrodes contact a blood vessel at a treatment site;

[0159] delivering neuromodulatory energy via one or more electrodes in accordance with a control algorithm;

[0160] monitoring the temperature of one or more electrodes and / or the temperature of tissue of a vessel at or near the treatment site; and

[0161] An irrigation fluid corresponding at least in part to the neuromodulation energy and the monitored temperature is delivered via the one or more irrigation outlets.

[0162] 19. The method of Example 18, wherein delivering neuromodulatory energy according to a control algorithm comprises: increasing a power level of the neuromodulatory energy, and wherein delivering an irrigation fluid comprises: delivering the irrigation fluid at an increased flow rate and / or decreased temperature corresponding to the increased power level.

[0163] 20. The method of example 19, further comprising: maintaining the temperature of one or more electrodes constant and / or within an acceptable temperature range while increasing the power level.

[0164] 21. The method of example 18, further comprising: comparing the temperature of the one or more electrodes and / or the temperature of the tissue to a predetermined temperature distribution range, and wherein delivering the neuromodulatory energy according to the control algorithm comprises—

[0165] When the temperature of one or more electrodes and / or the temperature of the tissue is outside the range, maintaining or reducing the power level of the neuromodulation energy; and / or

[0166] When the temperature of one or more electrodes and / or the temperature of the tissue is outside of this range, the power level is increased at a slower rate.

[0167] 22. The method of Example 18, further comprising: comparing the temperature of one or more electrodes and / or the temperature of the tissue with a predetermined temperature distribution range, and wherein delivering the irrigation fluid comprises: delivering the irrigation fluid at an increased flow rate and / or decreased temperature when the temperature of one or more electrodes and / or the temperature of the tissue is outside the range.

[0168] 23. The method of Example 18, further comprising:

[0169] comparing the temperature of the one or more electrodes and / or the temperature of the tissue to a predetermined temperature distribution range;

[0170] delivering irrigation fluid to the treatment site via the one or more irrigation outlets when the temperature of the one or more electrodes and / or the temperature of the tissue is outside the range; and

[0171] When the temperature of one or more electrodes and / or the temperature of the tissue is within the range, the power level at which the neuromodulation energy is delivered is increased.

[0172] Conclusion

[0173] The above detailed description of the embodiments of the technology is not intended to be exhaustive or to limit the technology to the precise form disclosed above. Although specific embodiments and examples of the present technology are described above for illustrative purposes, various equivalent modifications are possible within the scope of the present technology as will be appreciated by those skilled in the relevant art. For example, although the steps are presented in a given order, alternative embodiments may perform the steps in a different order. In addition, the various embodiments described herein may also be combined to provide further embodiments.

[0174] As can be understood from the foregoing, the specific embodiments of the present technology have been described herein for the purpose of illustration, but the known structures and functions are not shown or described in detail to avoid unnecessary ambiguity in the description of the embodiments of the present technology. Where the context permits, singular or plural terms may also include plural or singular terms, respectively. In addition, when quoting a list with two or more items, unless the word "or" is explicitly limited to represent only a single item and does not include other items, the use of "or" in such a list will be interpreted as including (a) any single item in the list, (b) all items in the list, or (c) any combination of items in the list. Where the context permits, singular or plural terms may also include plural or singular terms, respectively. In addition, the terms "including", "having / with" are used throughout the text to represent at least including the recorded feature (multiple), so as not to exclude any more number of the same features and / or other types of other features.

[0175] Based on the foregoing, it will also be understood that various modifications may be made without departing from the present technology. For example, the various components of the present technology may be further divided into subcomponents, or the various components and functions of the present technology may be combined and / or integrated. In addition, although the advantages associated with those embodiments have been described in the context of certain embodiments of the technology, other embodiments may also exhibit such advantages, and not all embodiments need to exhibit these advantages to fall within the scope of the present technology. Therefore, the present disclosure and associated technology may encompass other embodiments not explicitly shown or described herein.

Claims

1. A neuromodulation system, comprising: A catheter, the catheter comprising: an elongated shaft having a distal portion configured to be positioned intravascularly at a treatment site within a renal vessel of a human patient; a plurality of electrodes spaced apart along the distal portion of the elongated shaft, wherein the plurality of electrodes are configured to deliver neuromodulation energy to a target nerve at or adjacent to the treatment site; and an irrigation outlet proximate an electrode of the plurality of electrodes and configured to output an irrigation fluid; and a controller configured to be communicatively coupled to the plurality of electrodes, wherein the controller is configured to: monitoring a temperature of at least one of the plurality of electrodes or a temperature of tissue at or adjacent to the treatment site or a power level of at least one of the plurality of electrodes; When the monitored temperature of at least one of the plurality of electrodes or the temperature of tissue at or adjacent to the treatment site or the monitored power level of at least one of the plurality of electrodes increases, performing one or more of the following: increasing the flow rate at which the irrigation fluid is delivered, or decreasing the temperature of the irrigation fluid to be output from the irrigation outlet; and To prevent the neuromodulation system from determining an inaccurate measure of ablation progress, the flow rate of the irrigation fluid is prevented from increasing above a flow rate threshold and the temperature of the irrigation fluid is prevented from decreasing below a temperature threshold.

2. The neuromodulation system according to claim 1, wherein: The irrigation outlet is further configured to direct the irrigation fluid in a first direction parallel to a longitudinal axis of the renal blood vessel.

3. The neuromodulation system according to claim 1, wherein: Further including: an energy generator external to the human patient and electrically coupled to the plurality of electrodes and the controller; as well as a flush pump operably coupled to the flush outlet and the controller, Wherein the controller is further configured to: cause the energy generator to deliver the neuromodulation energy via the plurality of electrodes, and cause the irrigation pump to deliver the irrigation fluid via the irrigation outlet.

4. The neuromodulation system according to claim 3, characterized in that: The controller is further configured to: comparing the monitored temperature or the monitored power level to a predetermined parameter distribution range; When the monitored temperature or the monitored power level is within the predetermined parameter distribution range, causing the energy generator to deliver the neuromodulation energy at a power level according to a control algorithm; causing the energy generator to deliver the irrigation fluid at a temperature and flow rate according to the control algorithm when the monitored temperature or the monitored power level is within the predetermined parameter distribution range; and When the monitored temperature or the monitored power level is outside of the predetermined parameter distribution range, the control algorithm is modified to adjust a characteristic of at least one of the neuromodulation energy or the irrigation fluid.

5. The neuromodulation system according to claim 4, characterized in that: The monitored temperature is the temperature of one of the plurality of electrodes, wherein the characteristic is the power level at which the neuromodulation energy is delivered, and wherein the controller is configured to reduce the power level at which the neuromodulation energy is delivered when the temperature of the one of the plurality of electrodes is outside the predetermined parameter distribution range.

6. The neuromodulation system according to claim 4, characterized in that The monitored temperature is the temperature of one of the plurality of electrodes, wherein the characteristic is the power level at which the neuromodulation energy is delivered, and wherein the controller is configured to maintain the power level at which the neuromodulation energy is delivered constant or to reduce the power level at which the neuromodulation energy is delivered when the temperature of the one of the plurality of electrodes is outside the predetermined parameter distribution range.

7. The neuromodulation system according to claim 4, characterized in that: The monitored temperature is a temperature of one of the plurality of electrodes, wherein the characteristic is the temperature of the irrigation fluid to be output from the irrigation outlet or the flow rate at which the irrigation fluid is delivered, and wherein the controller is configured to increase the flow rate at which the irrigation fluid is delivered or decrease the temperature at which the irrigation fluid is delivered when the temperature of the one of the plurality of electrodes is outside the predetermined parameter distribution range.

8. A system comprising: A neuromodulation catheter, the neuromodulation catheter comprising: an elongated shaft having a distal portion sized and shaped to be positioned intravascularly at a treatment site within a blood vessel of a human patient; an electrode configured to deliver radio frequency (RF) energy to a target nerve at or adjacent to the treatment site, wherein the electrode is configured to deliver the RF energy according to a control algorithm; and a plurality of irrigation outlets positioned to release irrigation fluid according to the control algorithm; an irrigation pump coupled to the plurality of irrigation outlets, the irrigation pump configured to deliver the irrigation fluid to the treatment site via the plurality of irrigation outlets; an energy generator external to the human patient and coupled to the electrode and the irrigation pump, wherein the energy generator is configured to deliver the RF energy to the target nerve via the electrode; and a controller communicatively coupled to the electrode, the energy generator, and the irrigation pump, wherein the controller is further configured to: monitoring at least one of a temperature of the electrode or a temperature of tissue at or adjacent to the treatment site or a power level of the electrode; When at least one of the monitored temperature of the electrode or the temperature of tissue at or adjacent to the treatment site or the monitored power level of the electrode increases, one or more of: increasing the flow rate at which the irrigation fluid is delivered, or decreasing the temperature of the irrigation fluid to be output from the irrigation outlet; and To prevent the system from determining an inaccurate measure of ablation progress, the flow rate of the irrigation fluid is prevented from increasing above a flow rate threshold, and the temperature of the irrigation fluid is prevented from decreasing below a temperature threshold.

9. The system according to claim 8, characterized in that A first subset of the plurality of irrigation outlets is positioned proximate the electrode, and wherein each of the first subset of irrigation outlets is oriented to direct irrigation fluid in a first direction parallel to a longitudinal axis of the blood vessel.

10. The system according to claim 9, characterized in that The electrode is a first electrode, wherein the system further includes a second electrode spaced apart from the first electrode on the elongated shaft, wherein the second electrode is positioned between the first electrode and a distal end of the elongated shaft, and wherein the first subset is configured to release the irrigation fluid such that the irrigation fluid cools the second electrode.

11. The system according to claim 8, characterized in that The plurality of irrigation outlets are positioned on the elongated shaft between the electrode and a proximal portion of the elongated shaft.

12. The system according to claim 10, characterized in that Each of the plurality of irrigation outlets is oriented to direct irrigation fluid radially outward from the elongated shaft.

13. The system of claim 8, wherein: The neuromodulation catheter further comprises an irrigation ring, and wherein the plurality of irrigation outlets are positioned on the irrigation ring.

14. The system of claim 8, wherein: The monitored temperature is a temperature of the electrode, and wherein the controller is further configured to increase a power level at which the energy generator delivers the RF energy while maintaining the temperature of the electrode within a predetermined temperature profile.

15. The system of claim 14, wherein: When the controller increases the power level at which the energy generator delivers the RF energy, the controller is further configured to (i) maintain or increase the flow rate or (ii) maintain or decrease the temperature at which the irrigation fluid is delivered by the irrigation pump.

16. The system of claim 8, wherein: The controller is configured to increase only the flow rate or decrease only the temperature of the irrigation fluid to be output from the irrigation outlet when the power level of the electrode increases.

17. The system of claim 8, wherein: The controller is configured to prevent the energy generator from increasing a power level at which the energy generator delivers the RF energy when the irrigation fluid delivered by the irrigation pump reaches a maximum flow rate or a minimum temperature.

18. A non-transitory computer readable storage medium comprising instructions for causing a controller to: delivering neuromodulation energy via one or more electrodes in accordance with a control algorithm, wherein a neuromodulation catheter includes a treatment assembly having the one or more electrodes and one or more irrigation outlets, the neuromodulation catheter is positioned at a treatment site within a renal blood vessel of a human patient, and the treatment assembly is deployed such that the one or more electrodes contact the blood vessel at the treatment site; monitoring the temperature of the one or more electrodes and / or the temperature of tissue of the vessel at or near the treatment site or the power level of at least one of the one or more electrodes; delivering, via the one or more irrigation outlets, an irrigation fluid corresponding at least in part to the neuromodulation energy and the monitored temperature; When the monitored temperature of the one or more electrodes and / or the temperature of the tissue of the blood vessel at or near the treatment site or the monitored power level of at least one of the one or more electrodes increases, performing one or more of the following: increasing the flow rate at which the irrigation fluid is delivered, or decreasing the temperature of the irrigation fluid to be output from the irrigation outlet; and To prevent an inaccurate measure of ablation progress from being determined, the flow rate of the irrigation fluid is prevented from increasing above a flow rate threshold and the temperature of the irrigation fluid to be output from the irrigation outlet is prevented from decreasing below a temperature threshold.

19. The non-transitory computer-readable storage medium of claim 18, wherein: Delivering the neuromodulation energy according to the control algorithm includes increasing a power level of the neuromodulation energy, and wherein delivering the irrigation fluid includes delivering the irrigation fluid at an increased flow rate and / or decreased temperature corresponding to the increased power level.

20. The non-transitory computer-readable storage medium of claim 19, wherein: The non-transitory computer-readable storage medium further includes instructions for causing a controller to maintain the temperature of the one or more electrodes constant and / or within an acceptable temperature range while increasing the power level.

21. The non-transitory computer-readable storage medium of claim 18, wherein: The non-transitory computer readable storage medium further comprises instructions for causing a controller to: compare the temperature of the one or more electrodes and / or the temperature of the tissue to a predetermined temperature distribution range, and wherein delivering the neuromodulation energy according to the control algorithm comprises: maintaining or reducing the power level of the neuromodulation energy when the temperature of the one or more electrodes and / or the temperature of the tissue is outside of the range; and / or When the temperature of the one or more electrodes and / or the temperature of the tissue is outside of the range, the power level is increased at a slower rate.

22. The non-transitory computer-readable storage medium of claim 18, wherein: The non-transitory computer-readable storage medium further comprises instructions for causing a controller to perform the following operations: comparing the temperature of the one or more electrodes and / or the temperature of the tissue to a predetermined temperature distribution range, and wherein delivering the irrigation fluid comprises: delivering the irrigation fluid at an increased flow rate and / or decreased temperature when the temperature of the one or more electrodes and / or the temperature of the tissue is outside of the range.

23. The non-transitory computer-readable storage medium of claim 18, wherein: The non-transitory computer readable storage medium further includes instructions for causing the controller to: comparing the temperature of the one or more electrodes and / or the temperature of the tissue to a predetermined temperature distribution range; delivering irrigation fluid to the treatment site via the one or more irrigation outlets when the temperature of the one or more electrodes and / or the temperature of the tissue is outside of the range; as well as When the temperature of the one or more electrodes and / or the temperature of the tissue is within the range, the power level at which the neuromodulation energy is delivered is increased.

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