Systems, devices and methods for evaluating the efficacy of renal neuromodulation therapy

Abstract

Disclosed herein are systems and methods for performing, evaluating, and adjusting neuromodulation therapy. A method for evaluating the possible efficacy of a neuromodulation therapy includes positioning a neuromodulation catheter at a target site within a renal vessel of a human patient, and obtaining measurements related to a diameter of the renal vessel via the neuromodulation catheter. The method may further include determining a diameter of the renal vessel at or near the target site based on the measurements. In some embodiments, (i) one or more parameters of the neuromodulation energy to be delivered to the renal vessel may be adjusted based on the determined diameter and / or (ii) the neuromodulation catheter may be repositioned within the renal vessel.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATION(S)

[0002] This disclosure claims the benefit of U.S. Patent Application No. 15 / 960,333, filed on April 23, 2018, and U.S. Provisional Patent Application No. 62 / 621,304, filed on January 24, 2018, both of which are incorporated herein by reference in their entireties. Technical Field

[0003] The present technology relates to neuromodulation. In particular, various embodiments of the present technology relate to systems and methods for measuring the diameter of a blood vessel and modifying parameters of a neuromodulation therapy performed in the blood vessel based on the measured vessel diameter. 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 1Ais a partially schematic side view of a neuromodulation system in accordance with an embodiment of the present technology, wherein a distal portion of a guidewire is positioned within a blood vessel of a human patient.

[0007] Figure 1B and Figure 1C According to an embodiment of the present technology Figure 1A A partial schematic side view of a neuromodulation system shown in FIG. , wherein a distal portion of a neuromodulation catheter is in a first state and a second state, respectively, within a blood vessel of a human patient.

[0008] Figure 2 is configured according to an embodiment of the present technology Figure 1C A partial schematic side view of a neuromodulation system with a distance sensor shown in FIG.

[0009] Figure 3 yes Figure 1C is a front view of a neuromodulation catheter shown in looking proximally down the longitudinal axis of a blood vessel of a human patient.

[0010] Figure 4 is a flow chart of a process or method for evaluating the likely efficacy of a neuromodulation therapy and / or modifying one or more parameters of the neuromodulation therapy in accordance with an embodiment of the present technology.

[0011] Figure 5 is a graph illustrating a neuromodulatory energy delivery profile in accordance with an embodiment of the present technology.

[0012] Figure 6 is a partial schematic diagram of a neuromodulation system configured according to another embodiment of the present technology.

[0013] Figure 7 The present invention is shown using an embodiment according to the present technology Figure 6 systems to modulate renal nerves and / or evaluate neuromodulation therapies.

[0014] Figure 8 A conceptual diagram of the sympathetic nervous system (SNS) and how the brain communicates with the body via the SNS.

[0015] Fig. 9 is an enlarged anatomical illustration of the nerves innervating the left kidney to form the renal plexus surrounding the left renal artery.

[0016] Fig.10 and Fig.11 Anatomical and conceptual views of the human body depicting efferent and afferent neural communications between the brain and kidneys, respectively.

[0017] Fig.12 and Fig.13 These are anatomical diagrams of the human arterial and venous vascular systems, respectively. DETAILED DESCRIPTION

[0018] Systems and methods according to embodiments of the present technology involve obtaining measurements related to the size of renal blood vessels prior to a neuromodulation procedure, such as a renal denervation procedure, to periprocedurally assess the likely efficacy of the neuromodulation procedure. The disclosed technology can, for example, be used to assess the likelihood that a particular patient will gain a therapeutic benefit from the delivered neuromodulation energy.

[0019] Recent studies have shown that the diameter of a renal vessel can be related to the efficacy of a subsequent renal denervation procedure performed in the renal vessel (e.g., the resulting decrease in blood pressure, the reduced risk associated with cardiovascular disease, the improvement in heart failure status, the reduction in arrhythmias, etc.). More specifically, renal denervation may be more effective in renal vessels with relatively smaller diameters. The reason for the improved efficacy may be due to many factors. For example, in renal vessels with larger diameters, the renal nerves tend to be away from the vessel wall, whereas in renal vessels with smaller diameters, the renal nerves tend to be closer to the vessel wall. In addition, smaller tubes may allow for greater applanation pressure of the neuromodulation catheter, resulting in better contact between the neuromodulation electrodes on the catheter and the vessel wall. In addition, in smaller tubes, the net proportion of the tube circumference affected by a single injury from a single neuromodulation electrode may be greater. Regardless of the specific reason for the improved efficacy, measuring the diameter (or related value) of the renal vessel before performing a neuromodulation procedure in a particular renal vessel is expected to provide periprocedural information related to the possible success (or failure) of the neuromodulation procedure. Furthermore, such information may be used to modify or adjust parameters of a neuromodulation procedure (such as power, timing, location, and / or other characteristics of energy delivered during the neuromodulation procedure) to increase the likelihood of success of the neuromodulation procedure.

[0020] Currently, professionals performing neuromodulation procedures have only limited means available to know whether and / or where the procedure is likely to be successful. Furthermore, current techniques for measuring renal vessel diameter (e.g., quantitative angiography and intravascular ultrasound) require additional equipment and procedures, and can be slow, expensive, and relatively inaccurate.

[0021] In contrast to conventional techniques, in several embodiments described below, a neuromodulation system may include a neuromodulation catheter configured to both: (i) detect one or more measurements related to the size of a renal vessel at or near a target site in the renal vasculature and (ii) deliver therapeutic neuromodulation at the target site. A controller may receive the one or more measurements and accurately estimate the diameter of the renal vessel at or near the target site. Based at least in part on the diameter, an operator and / or controller of the neuromodulation system may (i) assess the likely efficacy of delivering therapeutic neuromodulation at the target site, (ii) adjust one or more parameters of the therapeutic neuromodulation to be delivered at the target site, and / or (iii) reposition the neuromodulation catheter to a new target site. Thus, by detecting simple pre-neuromodulation measurements of the renal vessel where neuromodulation is to be performed, a system configured in accordance with the present technology is expected to improve the efficacy of a neuromodulation procedure without requiring costly and untimely additional measurements using a separate conventional measurement system.

[0022] References in this article Figure 1A-13 Specific details of several embodiments of the present technology are described. 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 extravascular neuromodulation, intravascular 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.

[0023] 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.

[0024] I. Selected Embodiments of Neuromodulation Catheters and Systems

[0025] Figures 1A-1C 1 is a partially schematic side view of a neuromodulation system 100 ("system 100") configured in accordance with an embodiment of the present technology and shown in different arrangements when positioned at a target site within a blood vessel V (e.g., a renal artery) of a human patient. System 100 includes a guidewire 101 (only in Figure 1A ) and a neuromodulation catheter 102 that can be advanced over a guidewire 101 to a target site within a blood vessel V. In other embodiments, the neuromodulation catheter 102 can be configured for delivery to a target site via other methods (e.g., via a guide catheter, retracted through a sheath, via a pull wire, etc.).

[0026] The neuromodulation catheter 102 is configured to perform neuromodulation therapy at a target site, for example, to ablate a nerve proximate to a wall of a blood vessel V. As discussed in more detail below, the neuromodulation catheter 102 is further configured to detect one or more measurements related to the dimensions (e.g., diameter, cross-sectional area, circumference, segmented volume, etc.) of the blood vessel V prior to the neuromodulation therapy to assess the potential efficacy of a subsequent neuromodulation therapy performed at the target site. The system 100 further includes one or more controllers 104 communicatively coupled to the neuromodulation catheter 102 via a wired or wireless communication link.

[0027] Reference Figure 1A , the guidewire 101 includes a slender member 103, the slender member 103 having a distal portion 103a and a proximal portion (not visible), the distal portion 103a is configured to be positioned at a target site within a blood vessel V, and the proximal portion extends outside the patient's body to a handle (not shown) or to other features (multiple) that allow an operator to manipulate the distal portion 103a to a desired position / orientation. The size of the slender member 103 can be designed to be slidably positioned within the cavity of the neuromodulation catheter 102. Additionally, the slender member 103 may have a uniform stiffness along its length, or may have a varying stiffness along its length. In other embodiments, the slender member 103 may include other suitable components and / or configurations.

[0028] like Figure 1B As best shown, the neuromodulation catheter 102 includes an elongated shaft 106 configured to be slidably delivered over the guidewire 101. The elongated shaft 106 has a distal portion 106a configured to be intravascularly positioned at a target site within a blood vessel V and a proximal portion 106b extending outside the patient's body, to a handle (not shown), or to other features of the distal portion 106a that allow an operator to manipulate the elongated shaft 106. Figure 1B and Figure 1CAs shown, for example, the neuromodulation catheter 102 is convertible between a first state or arrangement in which the distal portion 106a of the elongated shaft 106 is at least generally straight and in a low-profile delivery arrangement (e.g., deployed, expanded, etc.) and a second (e.g., deployed, expanded, etc.) state or arrangement. Figure 1B ), in which the distal portion 106a is transformed or otherwise deployed into a helical / spiral shape ( Figure 1C ).

[0029] Reference together Figure 1B and Figure 1C , the neuromodulation catheter 102 includes a plurality of energy delivery elements, such as electrodes 110, spaced apart along the distal portion 106a of the elongated shaft 106, and a distal tip 108 (e.g., an atraumatic tip). In the illustrated embodiment, the neuromodulation catheter 102 includes four electrodes 110 (individually identified as first to fourth electrodes 110a-110d, respectively). However, in other embodiments, the neuromodulation catheter 102 may include one, two, three, or more than four electrodes 110, and / or may include different energy delivery elements. The electrodes 110 are configured to deliver neuromodulation energy to a target site to modulate or ablate nerves (e.g., renal nerves) proximal to the target site. In other embodiments, the neuromodulation catheter 102 may include electrodes, transducers, or other elements to deliver energy for modulating nerves using 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. In certain embodiments, the neuromodulation catheter 102 may be configured for cryotherapy, and cryogenic cooling may be applied to the blood vessel V using a refrigerant (e.g., via a balloon catheter that circulates the refrigerant).

[0030] The distal portion 106a of the elongated shaft 106 (e.g., Figure 1CThe dimensions (e.g., outer diameter and length) of the distal portion 106a (the portion in the helical / spiral shape in the second state shown) can be selected to accommodate a blood vessel or other body cavity in which the distal portion 106a is designed to be delivered. For example, when in the second state, the axial length of the distal portion 106a of the elongated shaft 106 can be selected to be no longer than a patient's renal artery (e.g., typically less than 7 cm) and 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 106a of the elongated shaft 106 can have other dimensions depending on the body cavity in which the distal portion 106a of the elongated shaft 112 is configured to be deployed. Regardless of the selected dimensions of the distal portion 106a, in some embodiments, one or more dimensions of the distal portion 106a are known prior to performing a neuromodulation procedure with the neuromodulation catheter 102. As described in more detail below, in some embodiments, the known dimensions may be used to calculate other (e.g., variable, unknown, non-constant, etc.) dimensions of the distal portion 106a, such as the diameter of the distal portion 106a in the helical / spiral second state. In further embodiments, the distal portion 106a of the elongated shaft 106 may have other suitable shapes (e.g., semicircular, curved, straight, etc.), and / or the neuromodulation catheter 102 may include a plurality of support members configured to carry one or more electrodes 110. The distal portion 106a of the elongated shaft 106 may also be designed to apply a desired outward radial force to the tube when deployed into the helical / spiral second state to place one or more of the electrodes 110 in contact with the tube wall.

[0031] In some embodiments, the system 100 includes a console (not shown). The controller 104 may be separate from the console or may be integrated with the console. The controller 104 may be configured to initiate, terminate and / or adjust the operation of one or more components (e.g., electrodes 110) of the neuromodulation catheter 102 directly and / or via the console. For example, as described in more detail below, the controller 104 may be configured to continuously or intermittently monitor the impedance between each of the electrodes 110. The console may be configured to communicate with the neuromodulation catheter 102 via a wireless and / or wired communication link. For example, in some embodiments, the console may include an entry port for receiving a wired connection of the neuromodulation catheter 102. The console may be configured to control, monitor, supply and / or otherwise support the operation of the neuromodulation catheter 102. The console may be further configured to generate energy of a selected form and / or energy of a selected amplitude for delivery to the tissue at the target site via the electrode 110, and therefore, the console may have different configurations depending on the treatment modality of the neuromodulation catheter 102. For example, the console may include an energy generator (not shown) configured to generate RF energy. Furthermore, the console may be configured to provide feedback to the operator before, during, and / or after a neuromodulation procedure, such as, for example, a determined diameter of the vessel V and / or the likely efficacy of the neuromodulation procedure performed at the target site.

[0032] although Figures 1A-1C The embodiment of the neuromodulation catheter 102 shown in has a spiral / helical configuration, but in other embodiments, the neuromodulation catheter 102 can have other suitable shapes, sizes, and / or configurations. Other suitable devices and techniques are described in, for example, U.S. Patent No. 8,777,942; U.S. Patent No. 9,084,610; U.S. Patent No. 9,060,755; U.S. Patent No. 8,998,894; PCT Application No. PCT / US2011 / 057754 filed on October 25, 2011; and U.S. Patent No. 8,888,773. All of the above applications are incorporated herein by reference in their entirety. Another non-limiting example of a device includes the Symplicity Spyral TM Multi-electrode RF ablation catheter.

[0033] II. Selected embodiments of a neuromodulation catheter having a measurement element for determining the size of a blood vessel

[0034] As described above, neuromodulation therapy is expected to be more likely to be successful or effective (e.g., causing a desired degree of target nerve ablation and / or ablating a sufficient volume of target nerves) when performed in a vessel having a smaller diameter or in a relatively smaller portion of the same vessel. Therefore, it may be advantageous to measure the size (e.g., diameter) of a patient's vessel in order to relevantly determine the likely efficacy of neuromodulation therapy performed in the vessel and / or to modify one or more parameters of the neuromodulation therapy. Generally, as described in detail below, system 100 of the present technology includes at least one measurement element that is configured to detect (e.g., obtain, perform, etc.) one or more measurements related to the size of the vessel prior to delivery of neuromodulation energy.

[0035] For example, in some embodiments, the measuring element may include one or more of the electrodes 110 at the distal portion 106a of the elongated shaft 106 of the neuromodulation catheter 102. In such embodiments, the system 100 can be configured to measure the impedance between two or more of the electrodes 110 prior to delivering neuromodulation energy via the electrodes 110. The detected impedance measurements can be transmitted to the controller 104 and / or another device outside the patient's body. The controller 104 can be configured to receive and store the detected impedance measurements, and determine the size (e.g., diameter) of the blood vessel V based at least in part on one or more of the detected impedance measurements.

[0036] More specifically, in some embodiments, a signal (e.g., a low-power electrical signal) may be sent between one or more pairs of electrodes in the electrodes 110 to measure the impedance between the electrodes 110. In some embodiments, the impedance between two different combinations of electrodes may be measured. For example, a signal may be sent between (i) the first electrode 110a and the second electrode 110b, (ii) the first electrode 110a and the third electrode 110c, (iii) the first electrode 110a and the fourth electrode 110d, (iv) the second electrode 110b and the third electrode 110c, (v) the second electrode 110b and the fourth electrode 110d, and (vi) the third electrode 110c and the fourth electrode 110d. In some embodiments, an impedance measurement for each combination of less than each pair of electrodes 110 may be obtained (e.g., a single impedance measurement between the first electrode 110a and the fourth electrode 110d).

[0037] Regardless of the combination(s) of electrodes 110 used to measure impedance, the impedance measurements obtained may be stored at the controller 104 and processed to determine the size of the blood vessel V near the electrodes 110 (e.g., near the target site). For example, in some embodiments, the size of the blood vessel V may be estimated using the cylinder equation:

[0038]

[0039] As is known in the art, the cylinder equation (1) states that the cross-sectional area A of a relatively constant diameter cylinder filled with a material of constant resistivity p is proportional to the impedance R measured over a distance L. The resistivity p of the blood in the blood vessel V can be measured directly or estimated by applying one or more predetermined correction coefficients to the cylinder equation (1). Therefore, based on the known longitudinal distance L between the selected electrodes 110, the cross-sectional area A (and therefore the diameter of the blood vessel V) can be estimated.

[0040] Typically, impedance measurements and / or related values ​​(e.g., corresponding longitudinal distances between electrodes, corresponding diameters of a vessel, etc.) may be averaged and / or otherwise combined to provide a relatively accurate estimate of the diameter or another dimension (e.g., circumference) of the vessel V. In some embodiments, impedance measurements detected by electrodes 110 may be used to determine an actual (e.g., absolute) size of the vessel V, while in other embodiments, impedance measurements may be compared to a baseline measurement to determine a relative difference in the size of the vessel V (e.g., from a first location to a second location within the vessel).

[0041] One advantage of using electrodes 110 to detect measurements related to the size of a vessel V is that no physical modification needs to be made to the neuromodulation catheter 102. That is, if the resistivity of the blood in the vessel V is known or can be estimated, the same electrodes 110 that deliver neuromodulation energy can be used to determine the diameter of the target vessel V.

[0042] In certain embodiments, the measurement element of system 100 may include a separate component positioned at the distal portion of neuromodulation catheter 102. For example, Figure 2 yes Figure 1CA partial schematic side view of a neuromodulation system (e.g., in a second state) is shown and includes a distance sensor (e.g., a proximity sensor). The distance sensor can be configured to detect a distance between a first portion of the neuromodulation catheter 102 (such as the distal tip 108) and a second, more proximal portion of the neuromodulation catheter 102. For example, in the illustrated embodiment, the distance sensor includes a first sensing component 223 and a second sensing component 224, the first sensing component 223 being on the distal tip 108 and the second sensing component 224 being on the distal portion of the neuromodulation catheter 102 and positioned proximal to the fourth electrode 110d. In some embodiments, the distance sensor is a capacitive distance sensor, a Hall effect distance sensor, a piezoelectric distance sensor, a magnetic distance sensor, and / or another type of distance sensor configured to measure the distance between the first sensing component 223 and the second sensing component 224 ("sensing components 223, 224"). The detected distance between the sensing components 223, 224 can be used to determine the size (e.g., diameter) of the blood vessel V based on the known size of the neuromodulation catheter 102.

[0043] Specifically, since, for example, the longitudinal distance between the sensing components will vary in accordance with the diameter of the blood vessel V (e.g., the longitudinal distance will be greater when the blood vessel V has a smaller diameter and the distal portion of the neuromodulation catheter 102 is not fully radially deployed), the detected distance between the sensing components 223, 224 can be used to determine the diameter of the blood vessel V. More specifically, in some embodiments, when the neuromodulation catheter 102 is in the second (deployed) state, the longitudinal distance between the sensing components 223, 224 can be used to determine the rotation angle of the distal portion of the neuromodulation catheter 102. Based on the known dimensions of the neuromodulation catheter 102, the rotation angle can be used to calculate the diameter of the distal portion of the neuromodulation catheter 102 that is apposed to the inner wall of the blood vessel V. Therefore, the determined diameter of the distal portion of the neuromodulation catheter 102 can be used to estimate the diameter of the blood vessel V.

[0044] In other embodiments, the sensing components 223, 224 can be positioned differently relative to the neuromodulation catheter 102. For example, the second sensing component 224 can be positioned more distally or more proximally relative to the neuromodulation catheter 102 (e.g., adjacent one of the electrodes 110) and / or the first sensing component 223 can be positioned proximal to the distal tip 108. In the illustrated embodiment, the sensing components 223, 224 are positioned outside the neuromodulation catheter 102. However, in other embodiments, the sensing components 223, 224 can be positioned completely within the neuromodulation catheter 102 (i.e., inside the neuromodulation catheter 102) or partially within the neuromodulation catheter 102. In certain embodiments, the system 100 can include more than one distance sensor and / or one or more distance measurements can be averaged or otherwise combined to estimate the size of the blood vessel V. In addition, the sensing components 223, 224 can be coupled to the controller 104 and / or other components of the system 100 via one or more wires extending through the neuromodulation catheter 102, or the sensing components 223, 224 can be wirelessly coupled to the controller 104 and / or other components of the system 100.

[0045] Figure 3 Another embodiment of a measurement element positioned at the distal portion of the neuromodulation catheter 102 is shown. Specifically, Figure 3 is in Figure 1C The second state shown and in the proximal direction from the longitudinal axis L of the blood vessel V ( Figure 1C ) is a front view of the distal portion of the neuromodulation catheter 102 looking downward. Figure 3 As shown, the system 100 can include a distance sensor 322 positioned at the distal tip 108 of the neuromodulation catheter. In other embodiments, the distance sensor 322 can be positioned at other locations on the distal portion of the neuromodulation catheter 102. The distance sensor 322 can be an odometer-type sensor (e.g., a wheel, a trackball, other rotatable component, etc.) configured to measure the circumference (or other dimension) of the blood vessel V when the distal portion of the neuromodulation catheter 102 rotates within the blood vessel V. For example, the system 100 can be configured to automatically rotate the distal portion of the neuromodulation catheter 102 in the direction of arrow C (e.g., via a motor outside the patient's body) so that the distance sensor 322 passes completely around the circumference of the blood vessel V (e.g., one full circle). The detected circumference of the blood vessel V can be easily used to determine the diameter of the blood vessel V.

[0046] In other embodiments, the measurement element of the system 100 may include other components suitable for detecting measurements related to the size of the blood vessel V. For example, in some embodiments, a balloon or other expandable component may be at least partially positioned at the distal portion of the neuromodulation catheter 102. For example, the balloon may (i) be positioned on the exterior of the neuromodulation catheter 102, (ii) have at least one fixed dimension (e.g., a fixed longitudinal length), and (iii) may be inflated with a measured (e.g., known) volume or inflation pressure. Thus, once the balloon is inflated to contact the inner wall of the blood vessel V, the diameter of the blood vessel V may be estimated. In some embodiments, the balloon may have one or more electrodes configured to detect when the balloon contacts the inner wall of the blood vessel V. In some such embodiments, the electrodes on the balloon may also be configured to deliver neuromodulation energy. In other embodiments, the pressure inside the balloon may be measured and used to detect when the balloon contacts the inner wall of the blood vessel V. For example, a sudden increase in balloon pressure may indicate that the balloon is in apposition to the inner wall of the blood vessel V.

[0047] In other embodiments, the measuring element of the system 100 may include one or more wires or other electrical elements that are positioned at the distal portion of the neuromodulation catheter 102 and have a variable resistance that changes based on how much the electrical element is bent. In some such embodiments, for example, the resistance of the electrical element can be used to determine the diameter of the distal portion of the neuromodulation catheter 102 (e.g., can be correlated to the diameter of the distal portion of the neuromodulation catheter 102). Specifically, the change in resistance can be directly related to the curvature of the neuromodulation catheter 102, which can be used to determine the diameter of the blood vessel V, as described above. Therefore, the diameter of the blood vessel V can be estimated based on the resistance of the electrical element.

[0048] In yet other embodiments, the measuring element 100 may include standard imaging systems and / or components used in well-known imaging techniques such as, for example, fluoroscopy, magnetic resonance imaging (MRI), intravascular ultrasound (IVUS), and the like.

[0049] Each of the described embodiments is expected to facilitate making measurement(s) related to the size of a vessel V via a neuromodulation catheter 102. Such measurements can be used to determine or estimate the diameter of the vessel V near a target site in the vessel V, and relatedly, determine or estimate the likely efficacy of a neuromodulation treatment subsequently performed at the target site. Thus, embodiments of the present technology are expected to quickly and inexpensively determine the likely efficacy of a neuromodulation treatment because the same device can be used to both measure the size of a target vessel and deliver neuromodulation energy to a target nerve adjacent to the same vessel. As described in further detail below, the present technology is also expected to improve the efficacy of neuromodulation treatments by allowing (i) customization of neuromodulation energy delivery profiles and / or (ii) improved target site selection.

[0050] III. One or more parameters for evaluating the potential efficacy of a neuromodulation therapy and / or modifying a neuromodulation therapy How to select the number

[0051] Figure 4 is a flow chart of a method or process 400 for evaluating the potential efficacy of a neuromodulation therapy and / or modifying one or more parameters of a neuromodulation therapy in accordance with an embodiment of the present technology. Figure 1A-3 The method 400 may be implemented using the system 100 described herein and / or other suitable systems. For example, the neuromodulation catheter 102 and / or the controller 104 may be used to perform the various steps of the method 400. Therefore, for the sake of illustration, the method 400 will be described in detail below. Figure 1A-3 Some features of method 400 are described in the context of the illustrated embodiment.

[0052] Beginning at block 402, method 400 includes positioning a neuromodulation catheter 102 at a target site within a blood vessel V of a human patient. In some embodiments, positioning the neuromodulation catheter 102 includes (i) positioning a guidewire 101 along a portion of the blood vessel V proximal to the target site; Figure 1A ), (ii) advancing the neuromodulation catheter 102 over the guide wire 101 to the target site ( Figure 1B ), and (iii) converting or otherwise deploying the distal portion of the neuromodulation catheter 102 into a helical / spiral shape in which the electrode 110 contacts the wall of the blood vessel V ( Figure 1C ).

[0053] At box 404, method 400 includes obtaining one or more measurements related to or corresponding to the size (e.g., diameter, circumference, etc.) of blood vessel V near the target site by, for example, using a measuring element of the neuromodulation catheter 102. For example, as described above, the measurement may include one or more of the following: impedance measurement(s) between two or more of the electrodes 110; the distance between spaced-apart portions of the neuromodulation catheter 102; the distance between two or more of the electrodes 110; the rotation angle of the distal portion of the neuromodulation catheter 102; the volume of the inflatable balloon; and the like. More specifically, in certain embodiments where the measuring element includes electrodes 110, the controller 104 may be configured to (i) control the electrodes 110 to generate and detect one or more signals propagating through the blood vessel V, and (ii) determine one or more impedance values ​​between two or more of the electrodes 110 related to the size of the blood vessel V. In other embodiments, where the measuring element includes a distance sensor ( Figure 2 and Figure 3 ), the controller 104 can be configured to control the distance sensor to obtain a distance measurement related to the size of the blood vessel V.

[0054] In addition, one or more measurements may be a single measurement, or a composite or average of several different measurements. For example, the measurements may be an average of several measurements taken over a period of several seconds (e.g., about 0.5 seconds, about 1 second, about 2 seconds, less than about 5 seconds, etc.) to account for changes in the size of the blood vessel V during the cardiac cycle (e.g., to account for different vessel diameters during systole and diastole). In some embodiments, the measurements obtained may be transmitted and stored in a memory of the controller 104 and / or another component of the system 100.

[0055] At box 406, the method 400 includes determining the diameter of the blood vessel V at or near the target site based on one or more measurements obtained via the measuring element of the neuromodulation catheter 102. For example, as described in detail above, the controller 104 or another component of the system 100 can process the one or more measurements to determine the diameter of the blood vessel V (e.g., based on known properties of the neuromodulation catheter 102). Based on the determined diameter of the blood vessel V, the controller 104 and / or the operator of the system 100 can evaluate the possible efficacy of performing the neuromodulation therapy at the target site by, for example, correlating the diameter with an expected result of the neuromodulation therapy (e.g., an expected drop in blood pressure at a certain point after the renal denervation procedure). For example, if the diameter of the blood vessel V is less than the baseline value, the controller 104 and / or the operator can determine that the neuromodulation therapy is more likely to be effective. In some embodiments, the baseline value can be a diameter measurement at a different location (e.g., a different target site) within the same blood vessel V, or a diameter measurement of a different blood vessel in the patient's body. In some embodiments, the baseline measurement can be an average vessel size (e.g., for patients with similar characteristics) or another value that is not specific to the patient.

[0056] In some embodiments, at block 408, method 400 may include repositioning neuromodulation catheter 102 to a different target site, for example, within blood vessel V. For example, in certain embodiments, a measurement element of neuromodulation catheter 102 may be used to estimate the diameter of blood vessel V at multiple locations within blood vessel V (e.g., as neuromodulation catheter 102 is moved within blood vessel V) to determine a minimum diameter portion of blood vessel V. In some embodiments, the estimated diameter may be displayed to an operator of system 100 (e.g., on a console in real time or near real time), and the operator may view the display and manipulate neuromodulation catheter 102 within the patient in order to identify the minimum diameter portion of blood vessel V.

[0057] In some embodiments, at block 410, method 400 may include adjusting one or more parameters of the neuromodulation therapy to be delivered at the target site. Figure 5 is a graph showing a suitable neuromodulatory energy delivery curve according to an embodiment of the present technology. Figure 5As shown, the neuromodulation therapy may include an initial power ramp phase, in which the power of the delivered neuromodulation energy is ramped to power P1 within time T1. Power P1 may then be maintained for time T2 before a first ramp phase, in which the power of the delivered neuromodulation energy is ramped to power P2 within time T3. Power P2 may then be maintained for time T4 before a second ramp phase, in which the power of the delivered neuromodulation energy is ramped to power P5 within time T5. The power may then (i) step down to power P4 and maintain for time T6, and then (ii) step down to power P3 and maintain for time T7. In other embodiments, the neuromodulation energy delivery curve may have other configurations and / or parameters.

[0058] In some embodiments, the powers P1-P5 and / or the delivery times T1-T7 are standard or baseline values ​​that can be adjusted manually by an operator of the system 100 and / or automatically by the controller 104 based on the estimated diameter of the tube. That is, the energy delivery curve can be modified to target renal nerves at varying depths from the wall of the vessel V, as opposed to conventional systems in which the energy delivery curve targets a uniform ablation depth via a fixed power output (e.g., a fixed maximum sustained power output). For example, in some embodiments, if the diameter of the tube is measured to be relatively large, the delivery time (e.g., any one or all of T1-T7) can be increased and / or the amount of power delivered (e.g., any one or all of P1-P5) can be increased to ensure that target nerves near the target site receive sufficient neuromodulation energy to be denervated. Therefore, regardless of the diameter of the renal blood vessel, the present technology can achieve more uniform neuromodulation treatment of the target renal nerves.

[0059] In some embodiments, a menu on a console of system 100 may include two or more selectable options for tube diameter, each option providing a different combination of neuromodulation parameters. In some such embodiments, the options may include, for example, a main tube option (e.g., for a tube having a relatively larger diameter) and a branch option (e.g., for a tube having a relatively smaller diameter). Such embodiments are based on the assumption that the diameter of the branch tube is relatively smaller than the diameter of the corresponding main tube. In some embodiments, the menu may include more specific options, such as, for example, a branch tube option having more vasculature around it (e.g., thereby increasing heat transfer away from the target site) and a branch tube option having less vasculature around it. In some embodiments, method 400 may determine that no parameters of the neuromodulation energy delivery curve need to be adjusted, and method 400 may proceed directly to box 412.

[0060] Once a suitable target site and parameters for the neuromodulation therapy are selected, the method 400 proceeds to block 412 and neuromodulation energy is delivered at the target site in the vessel V to ablate nerves proximate to the wall of the vessel V. For example, the method 400 may include applying RF energy (e.g., via the electrode 110), pulsed electrical energy, microwave energy, light energy, ultrasound energy (e.g., intravascularly delivered ultrasound and / or HIFU), direct thermal energy, radiation, cryogenic cooling, chemical-based therapy, and / or another suitable type of neuromodulation energy.

[0061] As described above, studies have shown that there is a strong correlation between the diameter of the renal blood vessels in which neuromodulation therapy is performed and the ultimate efficacy of the neuromodulation procedure (e.g., the ultimate reduction in blood pressure). Therefore, determining the diameter of the renal blood vessels prior to delivering neuromodulation energy and subsequently adjusting the position of the neuromodulation catheter and / or the parameters of the neuromodulation energy to be delivered is expected to increase the efficacy of the neuromodulation procedure. Therefore, system 100 can facilitate efficient and effective neuromodulation therapy.

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

[0063] Figure 6 6 is a partial schematic diagram of a therapeutic system 600 ("system 600") configured in accordance with an embodiment of the present technology. System 600 may include a device similar to that described above with reference to Figure 1A-3 The various features of the neuromodulation system 100 described herein. In addition, the system 600 can be used to implement any of the methods described herein. Figure 6 As shown, system 600 includes a neuromodulation catheter 602, a console 614, and a cable 606 extending therebetween. Neuromodulation catheter 602 may include an elongated shaft 608 having a proximal portion 608b, a distal portion 608a, and a handle 611 operably connected to elongated shaft 608 at proximal portion 608b. Elongated shaft 608 may be 2, 3, 4, 5, 6, or 7 French or another suitable size. Figure 6 As shown, one or more electrodes 610 can be spaced apart along the distal portion 608a of the elongated shaft 608. The electrodes 610 can be configured to apply electrical stimulation (e.g., radio frequency (RF) energy) to a target site at or near the tube in the patient's body, temporarily stun a nerve, deliver neuromodulation energy to the target site, and / or detect tube impedance. In various embodiments, certain electrodes 610 can be dedicated to applying stimulation and / or detecting impedance, and the neuromodulation catheter 602 can include other types of therapeutic elements that provide neuromodulation therapy using various modalities (e.g., cryotherapeutic cooling, ultrasound energy, etc.).

[0064] The console 614 may be configured to control, monitor, supply, and / or otherwise support the operation of the neuromodulation catheter 602. Additionally, the console 614 may be configured to provide feedback to the operator before, during, and / or after the treatment procedure via the evaluation / feedback algorithm 616. The console 614 may be further configured to generate a selected form of energy and / or a selected amplitude of energy for delivery to tissue at a treatment site via the electrodes 610, and thus, the console 614 may have different configurations depending on the treatment modality of the neuromodulation catheter 602. For example, when the neuromodulation catheter 602 is configured for electrode-based therapy, thermal element-based therapy, or transducer-based therapy, the console 614 may include an energy generator 670 (shown schematically) configured to generate RF energy (e.g., monopolar and / or bipolar RF energy), pulsed 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 light, and / or gamma radiation), and / or another suitable type of energy. In this configuration, the console 614 may also include an evaluation / feedback algorithm 616 for controlling the electrodes 610. In selected embodiments, the energy generator 670 may be configured to deliver a monopolar electric field via one or more of the electrodes 610. In such embodiments, a neutral or dispersive electrode 660 may be electrically coupled to the energy generator 670 and attached to the exterior of the patient. When the neuromodulation catheter 602 is configured for cryotherapy, the console 614 may include a refrigerant reservoir (not shown) and may be configured to supply refrigerant to the neuromodulation catheter 602. Similarly, when the neuromodulation catheter 602 is configured for chemical-based therapy (e.g., drug infusion), the console 614 may include a chemical reservoir (not shown) and may be configured to supply one or more chemicals to the neuromodulation catheter 602.

[0065] In various embodiments, the system 600 may further include a controller 604 communicatively coupled to the neuromodulation catheter 602. The controller 604 may be configured to initiate, terminate, and / or adjust the operation of one or more components (e.g., electrodes 610) of the neuromodulation catheter 602 directly and / or via a console 614 and / or via a wired or wireless communication link. In various embodiments, the system 600 may include multiple controllers. In other embodiments, the neuromodulation catheter 602 is communicatively coupled to a single controller 604. The controller (s) 604 may be integrated with the console 614 or a handle 611 located outside the patient's body and used to operate the system 600. In other embodiments, the controller 604 may be omitted or have other suitable locations (e.g., within the handle 611, along the cable 606, etc.). The controller 604 may include computer-implemented instructions to initiate, terminate, and / or adjust the operation of one or more components of the neuromodulation catheter 602 directly and / or via another aspect of the system (e.g., the console 614 and / or the handle 611). For example, the controller 604 can further provide instructions to the neuromodulation catheter 602 to apply neuromodulation energy to the treatment site (e.g., applying RF energy via the electrode 610). The controller 604 can be configured to execute automatic control algorithms and / or receive control instructions from an operator. In addition, the controller 604 can include or be linked to an evaluation / feedback algorithm 616 that can provide feedback to the operator via a console, monitor, and / or other user interface before, during, and / or after the treatment procedure.

[0066] Figure 7 (See also Figure 6 ) shows modulation of renal nerves according to an embodiment of the system 600. The neuromodulation catheter 602 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 608b of the elongated shaft 608 from outside of the intravascular pathway P, the clinician can advance the elongated shaft 608 through the sometimes tortuous intravascular pathway P and remotely manipulate the distal portion 608b of the elongated shaft 608. Figure 7In the illustrated embodiment, the distal portion 608a of the elongated shaft 608 is intravascularly delivered to the treatment site using a guidewire 601 in an OTW technique. The distal end of the neuromodulation catheter 602 can define a channel for accommodating the guidewire 601 for delivering the neuromodulation catheter 602 using an OTW or RX technique. At the treatment site, the guidewire 601 can be at least partially retracted or removed, and the distal portion of the neuromodulation catheter 602 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 catheter 602 can be delivered to the treatment site within a guide sheath (not shown) with or without the use of the guidewire 601. When the neuromodulation catheter 602 is at the target site, the guide sheath can be at least partially retracted or withdrawn, and the distal portion of the neuromodulation catheter 602 can be converted into a deployed arrangement. In yet other embodiments, the elongated shaft 608 itself may be steerable such that the neuromodulation catheter 602 may be delivered to a treatment site without the aid of a guidewire 601 and / or a guide sheath.

[0067] 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 maneuvering the neuromodulation catheter 602. 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 the target treatment site. In other embodiments, the treatment site may be determined prior to delivery of the neuromodulation catheter 602 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 catheter 602 and / or run in parallel with the neuromodulation catheter 602 to provide image guidance during positioning of the neuromodulation catheter 602. For example, an image guidance component (eg, IVUS or OCT) may be coupled to the neuromodulation catheter 602 to provide a three-dimensional image of the vasculature proximate to the target site to facilitate positioning or deployment of a multi-electrode assembly within the target renal vessel.

[0068] Then the light from electrode 610 ( Figure 6) and / or other energy delivery elements are applied to the target tissue to induce one or more desired neuromodulatory effects on a local area of ​​the renal artery RA and an adjacent area of ​​the renal plexus RP, which is closely located within the adventitia of the renal artery RA, adjacent to the adventitia of the renal artery RA, or closely adjacent to the adventitia of the renal artery RA. . The purposeful application of energy can achieve neuromodulation along all or at least a portion of the renal plexus RP. The neuromodulatory effect is generally at least partially a function of power, time, contact between the energy delivery element and the vessel wall, and blood flow through the blood 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.

[0069] V. Renal neuromodulation

[0070] 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.

[0071] 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.

[0072] 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.

[0073] 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., HIFU 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 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.

[0074] Neuromodulation using focused ultrasound energy (e.g., HIFU 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, 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.

[0075] 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).

[0076] 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.

[0077] VI. Related anatomy and physiology

[0078] 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.

[0079] 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.

[0080] 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.

[0081] 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.

[0082] 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.

[0083] A. Sympathetic chain

[0084] 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.

[0085] 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.

[0086] 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.

[0087] 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).

[0088] 1. Innervation of the kidneys

[0089] 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.

[0090] 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.

[0091] 2. Renal sympathetic nerve activity

[0092] 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.

[0093] 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.

[0094] 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.

[0095] 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.

[0096] 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.

[0097] (i) Renal sympathetic nerve outflow activity

[0098] 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.

[0099] (ii) Renal sensory afferent nerve activity

[0100] 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.

[0101] 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.

[0102] B. Additional clinical benefits of renal denervation

[0103] 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.

[0104] C. Achieving intravascular access to the renal artery

[0105] 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.

[0106] 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.

[0107] 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.

[0108] 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.

[0109] D. Properties and characteristics of renal blood vessels

[0110] 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.

[0111] 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.

[0112] 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).

[0113] 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).

[0114] 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.

[0115] 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.

[0116] 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, coefficient of friction, 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 rate; (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.

[0117] 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.

[0118] 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, requiring 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. In addition, 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°.

[0119] VII. Example

[0120] 1. A system comprising:

[0121] A neuromodulation catheter comprising—

[0122] an elongated shaft having a distal portion configured to be positioned intravascularly at a target site within a renal vessel of a human patient, and

[0123] a plurality of electrodes spaced apart along a distal portion of the shaft, the plurality of electrodes comprising a first electrode and a second electrode, wherein the electrodes are configured to deliver neuromodulatory energy to a target renal nerve at or adjacent to a target site; and

[0124] a controller configured to be communicatively coupled to the electrode, wherein the controller is further configured to—

[0125] obtaining an impedance measurement between the first electrode and the second electrode; and

[0126] Based on the impedance measurements, the diameter of a renal blood vessel at or near the target site is determined.

[0127] 2. The system of Example 1 further includes an energy generator outside the patient's body and coupled to the plurality of electrodes and the controller, wherein the controller is configured to: cause the energy generator to deliver neuromodulatory energy via the first and second electrodes based on the determined diameter of the renal blood vessel.

[0128] 3. The system of Example 2, wherein the controller is further configured to—

[0129] If the diameter of the renal blood vessel is a first value, delivering neuromodulatory energy having a first set of parameters; and

[0130] If the diameter of the renal blood vessel is a second value different from the first value, delivering neuromodulatory energy having a second set of parameters,

[0131] At least one parameter in the second set of parameters is different from a corresponding parameter in the first set of parameters.

[0132] 4. The system of example 3, wherein at least one parameter is the amount of neuromodulatory energy.

[0133] 5. The system of Example 3, wherein at least one parameter is a delivery time of the neuromodulatory energy.

[0134] 6. The system of any of Examples 1-5, wherein the impedance measurement is an average measurement over a period of less than about 5 seconds.

[0135] 7. A system comprising:

[0136] A neuromodulation catheter comprising—

[0137] an elongated shaft having a distal portion configured to be positioned intravascularly at a target site within a blood vessel of a human patient,

[0138] wherein the distal portion is convertible between a low-profile delivery configuration and an expanded treatment configuration at a target site within a blood vessel;

[0139] a plurality of electrodes spaced apart along a distal portion of the shaft, wherein when the distal portion is in the deployed treatment configuration, the plurality of electrodes are positioned in juxtaposition with an inner wall of the blood vessel and are configured to deliver neuromodulation energy to a target nerve at or adjacent to the target site; and

[0140] a distance sensor at a distal portion of the elongated shaft, the distance sensor configured to detect a distance measurement corresponding to a distance between a first portion of the elongated shaft and a second portion of the elongated shaft; and

[0141] a controller configured to be communicatively coupled to the distance sensor, wherein the controller is further configured to—

[0142] obtaining a distance measurement from a distance sensor; and

[0143] Based on the distance measurement, the diameter of the blood vessel at or near the target site is determined.

[0144] 8. The system of example 7, further comprising an energy generator located outside the patient's body and operably coupled to the electrode and the controller, wherein the controller is configured to—

[0145] If the diameter of the blood vessel is a first value, instructing the energy generator to deliver neuromodulation energy having a first set of parameters via the electrode; and

[0146] instructing the energy generator to deliver neuromodulatory energy having a second set of parameters via the electrode if the diameter of the blood vessel is a second value;

[0147] At least one parameter in the first set of parameters is different from a corresponding parameter in the second set of parameters.

[0148] 9. The system of Example 8, wherein at least one parameter is the amount of neuromodulatory energy and the time of delivery of the neuromodulatory energy.

[0149] 10. The system of any of examples 7-9, wherein determining the diameter of the blood vessel is based at least in part on a known size of the neuromodulation catheter.

[0150] 11. A method comprising:

[0151] positioning a neuromodulation catheter having one or more electrodes at a target site within a renal blood vessel of a human patient;

[0152] obtaining measurements related to renal blood vessel diameter via a neuromodulation catheter; and

[0153] Based on the measurement, the diameter of the renal blood vessel at or near the target site is determined.

[0154] 12. The method of Example 11, further comprising: adjusting parameters of the neuromodulatory energy to be delivered to the renal blood vessel at the target site based on the diameter of the renal blood vessel.

[0155] 13. The method of Example 12, further comprising: delivering neuromodulation energy to the renal nerves at the target site via one or more electrodes of the neuromodulation catheter.

[0156] 14. The method of Example 12 or Example 13, wherein the parameter of the neuromodulation energy is at least one of the amount of the neuromodulation energy and the delivery time of the neuromodulation energy.

[0157] 15. The method of any one of Examples 11-14, further comprising:

[0158] comparing the determined diameter of the renal blood vessel to a baseline value; and

[0159] Based on this comparison, the likely efficacy of the neuromodulatory energy to be delivered to the renal vessels at the target site is assessed.

[0160] 16. The method of any one of Examples 11-15, further comprising:

[0161] comparing the determined diameter of the renal blood vessel to a baseline value; and

[0162] When the determined diameter is greater than the baseline value, the neuromodulation catheter is repositioned to a different target site within the renal vessel.

[0163] 17. The method of any of Examples 11-16, wherein obtaining a measurement related to a size of a renal blood vessel comprises detecting impedance between at least two of one or more electrodes of a neuromodulation catheter.

[0164] 18. The method of any of Examples 11-16, wherein obtaining a measurement related to a size of a renal blood vessel comprises detecting impedance between each pair of one or more electrodes of a neuromodulation catheter.

[0165] 19. The method of any of Examples 11-16, wherein obtaining a measurement related to a size of the renal blood vessel comprises detecting a distance measurement corresponding to a distance between a first portion and a second portion of the neuromodulation catheter.

[0166] 20. The method of any of examples 11-16, wherein obtaining a measurement related to a size of a renal blood vessel comprises—

[0167] inflating a balloon coupled to the neuromodulation catheter; and

[0168] Determine when the balloon contacts the inner wall of the renal blood vessel.

[0169] Conclusion

[0170] 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, as will be appreciated by those skilled in the relevant art, various equivalent modifications are possible within the scope of the present technology. 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. References herein to "one embodiment," "embodiment," or similar expressions refer to specific features, structures, operations, or characteristics described in conjunction with the embodiment that may be included in at least one embodiment of the present technology. Therefore, the appearance of these phrases or expressions herein do not necessarily all refer to the same embodiment.

[0171] Some aspects of the present technology can take the form of computer executable instructions, including routines performed by controllers or other data processors. In certain embodiments, controllers or other data processors are specially programmed, configured, and / or constructed to perform one or more instructions in these computer executable instructions. In addition, some aspects of the present technology can take the form of data (e.g., non-transient data) stored or distributed on a computer-readable medium, and the computer-readable medium includes magnetic or optically readable and / or removable computer disks and electronically distributed media through a network. Therefore, data structures and data transmissions specific to various aspects of the present technology are included in the scope of the present technology. The present technology also encompasses methods in which computer-readable media are programmed to perform both specific steps and execution steps.

[0172] Similarly, when referencing a list with two or more items, unless the word "or" is explicitly limited to represent only a single item and not including 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 term "include" is used throughout the text to indicate that at least the recorded feature (s) is included, so that any greater number of the same features and / or other types of other features are not excluded. Directional terms such as "upper", "lower", "front", "back", "vertical" and "horizontal" may be used herein to express and clarify the relationship between the elements. It should be understood that such terms do not represent absolute orientation. In addition, although the advantages associated with those embodiments of the technology have been described in the context of certain embodiments, 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 cover other embodiments not explicitly shown or described herein.

Claims

1. A neuromodulation system, comprising: A neuromodulation catheter, the neuromodulation catheter comprising: an elongated shaft having a distal portion configured to be positioned intravascularly at a target site within a renal vessel of a human patient; and a plurality of electrodes spaced apart along the distal portion of the shaft, the plurality of electrodes comprising a first electrode and a second electrode, wherein the electrodes are configured to deliver neuromodulatory energy to a target renal nerve at or adjacent to the target site; and a controller configured to be communicatively coupled to the electrode, wherein the controller is further configured to: obtaining an impedance measurement between the first electrode and the second electrode; determining a diameter of the renal blood vessel at or near the target site based on the impedance measurement; If the diameter of the renal blood vessel is a first value, delivering neuromodulatory energy having a first set of parameters; and delivering neuromodulatory energy having a second set of parameters if the diameter of the renal blood vessel is a second value different than the first value, Wherein, at least one parameter in the second set of parameters is different from a corresponding parameter in the first set of parameters.

2. The system according to claim 1, characterized in that The system further includes an energy generator external to the patient and coupled to the plurality of electrodes and the controller, and wherein the controller is configured to cause the energy generator to deliver neuromodulatory energy via the first and second electrodes based on the determined diameter of the renal blood vessel.

3. The system according to claim 1, characterized in that The at least one parameter is the amount of neuromodulatory energy.

4. The system according to claim 1, characterized in that The at least one parameter is a delivery time of the neuromodulation energy.

5. The system according to claim 1, wherein: The impedance measurements are average measurements over a period of less than 5 seconds.

6. A neuromodulation system comprising: A neuromodulation catheter, the neuromodulation catheter comprising: an elongated shaft having a distal portion configured to be positioned intravascularly at a target site within a blood vessel of a human patient, wherein the distal portion is convertible between a low-profile delivery configuration and an expanded treatment configuration at the target site within the blood vessel; a plurality of electrodes spaced apart along the distal portion of the shaft, wherein, when the distal portion is in the deployed treatment configuration, the plurality of electrodes are positioned in juxtaposition with an inner wall of the blood vessel and are configured to deliver neuromodulation energy to a target nerve at or adjacent to the target site; and a distance sensor at the distal portion of the elongated shaft, the distance sensor configured to detect a distance measurement corresponding to a distance between a first portion of the elongated shaft and a second portion of the elongated shaft; and a controller configured to be communicatively coupled to the distance sensor, wherein the controller is further configured to: obtaining the distance measurement from the distance sensor; determining a diameter of the blood vessel at or near the target site based on the distance measurement; If the diameter of the blood vessel is a first value, delivering neuromodulatory energy having a first set of parameters; and delivering neuromodulatory energy having a second set of parameters if the diameter of the blood vessel is a second value; Wherein, at least one parameter in the first set of parameters is different from a corresponding parameter in the second set of parameters.

7. The system according to claim 6, characterized in that Further comprising an energy generator external to the patient and operably coupled to the electrode and the controller, and wherein the controller is configured to cause the energy generator to deliver neuromodulatory energy via the electrode based on the determined diameter of the blood vessel.

8. The system according to claim 6, characterized in that The at least one parameter is the amount of neuromodulation energy and the time of delivery of the neuromodulation energy.

9. The system according to claim 6, characterized in that Determining the diameter of the blood vessel is based at least in part on a known size of the neuromodulation catheter.

Images