Airbag transducer for ultrasonic nerve ablation and system using the airbag transducer - Patents.com

Abstract

An apparatus is provided that includes an ultrasonic transducer configured to emit ultrasonic waves. The ultrasonic transducer includes a hollow piezoelectric transducer body having a longitudinal axis and a radially inner surface. The apparatus further includes a tubular backing support member extending longitudinally through the piezoelectric transducer body and having a radially outer surface. The tubular backing support member has a first axial end and an opposite second axial end, the first axial end being defined between the radially inner surface of the piezoelectric transducer body and the radially outer surface of the tubular backing support member. Each of the ends is formed by a conductive component and a hermetic sealing layer of a metal solder material contacting a surface of the conductive component opposite the chamber.

Description

[Technical Field]

[0001] [Priority] This application claims priority to the following U.S. provisional patent applications, each of which is incorporated by reference herein: U.S. Provisional Patent Application No. 63 / 493,268 (PMD00095US) to Thirumalai et al., filed March 30, 2023; U.S. Provisional Patent Application No. 63 / / 371,638 (PMD00059US) to Thirumalai et al., filed August 16, 2022; and U.S. Provisional Patent Application No. 63 / / 371,635 (PMD00058US) to Zhai, filed August 16, 2022.

[0002] [Technical field] This application relates generally to minimally invasive devices, systems, and methods for providing energy delivery to targeted anatomical locations in a subject, and more particularly to catheter-based intraluminal devices and systems configured to deliver ultrasound energy to treat tissue, such as neural tissue. [Background technology]

[0003] High blood pressure, also known as hypertension, commonly affects adults. If left untreated, hypertension can lead to kidney disease, arrhythmias, and heart failure. Treatment of hypertension focuses on interventional approaches to inactivate the renal nerves surrounding the renal arteries. Autonomic nerves tend to follow blood vessels toward the organs they innervate. Intraluminal devices, such as catheters, can reach specific structures, such as renal nerves, that are proximal to the body cavity through which the catheter passes. Thus, catheter-based systems can deliver energy from within the body cavity to inactivate renal nerves within and / or around the vessel wall.

[0004] One approach to inactivating renal nerves is to use radiofrequency (RF) energy. RF energy is delivered to a catheter with multiple electrodes placed against the intima of the renal artery, generating an electric field in the vessel wall and surrounding tissue. The electric field results in resistive (ohmic) heating of the tissue, ablating (removing) the tissue and the renal nerves that pass through it. To treat the renal nerves surrounding the renal artery, the RF electrodes are repositioned around the inside of the renal artery several times.

[0005] Systems with ultrasound transducers that emit one or more therapeutic doses of unfocused ultrasound energy are superior to RF systems. The ultrasound transducer can be attached to the distal end of a catheter, and the unfocused ultrasound energy can heat tissue adjacent to the body cavity in which the catheter (and transducer) is located. Unfocused ultrasound energy systems can also include a balloon attached to the distal end of the catheter around the ultrasound transducer. During delivery of ultrasound energy, a coolant can be circulated through the balloon to cool the transducer and the body cavity. Such unfocused ultrasound energy systems can ablate targeted nerves surrounding a body cavity without damaging non-target tissue, such as the lining of the cavity or unintended organs outside the cavity. Such a design allows for the creation of one or more ablation zones sufficient to achieve long-term nerve deactivation at different locations around a blood vessel.

[0006] Catheters that output ultrasonic energy advantageously allow ablation energy to be distributed around the vessel wall at greater depths than is possible with radiofrequency ablation catheters. Ultrasound energy can be applied to nerves located around the vessel. For example, ultrasound energy can be applied to the renal nerves surrounding the renal arteries to deactivate these nerves. However, nerve locations may vary from patient to patient and may be in different locations around the vessel. Furthermore, blood vessels may be located near tissues and / or organs. As a result, it is desirable to be able to limit the application of ultrasound energy to target nerves so as to eliminate or reduce application of ultrasound energy to tissues and / or organs in order to optimize the effectiveness and safety of the procedure. Furthermore, blood vessels may contain features such as calcification or plaque. Depending on the situation, it may be desirable to apply ultrasound energy to or avoid these features. As a result, it is desirable to be able to control the application of ultrasound energy within a blood vessel. Summary of the Invention

[0007] An apparatus is provided that includes an ultrasonic transducer configured to emit ultrasonic waves, the ultrasonic transducer comprising: a hollow piezoelectric transducer body having a longitudinal axis and a radially inner surface; a tubular backing support member extending longitudinally through the piezoelectric transducer body and having a radially outer surface; and a chamber defined between the radially inner surface of the piezoelectric transducer body and the radially outer surface of the tubular backing support member, the chamber being defined between a first axial end and an opposite second axial end, each of the ends being formed by a conductive component and a hermetic sealing layer of metal solder material contacting a surface of the conductive component opposite the chamber.

[0008] An apparatus is provided that includes an ultrasound transducer configured to emit ultrasound waves, the ultrasound transducer comprising: a hollow piezoelectric transducer body comprising a tube of piezoelectric material, the tube having a radially inner surface and a radially outer surface; an inner electrode disposed on at least a portion of the inner surface of the tube of piezoelectric material; an outer electrode disposed on at least a portion of the outer surface of the tube of piezoelectric material; a tubular backing support member extending longitudinally through the piezoelectric transducer body and having a radially outer surface; and an airtight chamber defined between the radially inner surface of the piezoelectric transducer body and the radially outer surface of the tubular backing support member, the airtight chamber having a first end and a second axially opposite end, the piezoelectric transducer body / piezoelectric material being fabricated from Navy Type III (PZT-8) high-density lead zirconate titanate (PZT) piezoelectric material.

[0009] A method of using a catheter having an airbag ultrasound transducer in a distal portion is provided, the method comprising the steps of: inserting the distal portion of the catheter into a body cavity of a patient so that the airbag ultrasound transducer is positioned adjacent to a nerve surrounding the body cavity to be ablated; causing the airbag ultrasound transducer to emit ultrasound waves having a first power density for a first time period while the airbag ultrasound transducer is positioned adjacent to the nerve surrounding the body cavity to be ablated; and causing the airbag ultrasound transducer to emit ultrasound waves having a second power density for a second time period occurring after the first time period while the airbag ultrasound transducer is positioned adjacent to the nerve surrounding the body cavity to be ablated, the second power density being different from the first power density.

[0010] A tissue treatment device is provided, comprising: a catheter having a distal end; an ultrasound transducer positioned at the distal end of the catheter; and a backing support member, the ultrasound transducer having an inner surface and an outer surface, each of the inner surface and the outer surface having an electrode, the ultrasound transducer attached to the backing support member to define an air chamber adjacent the inner surface, the air chamber being insulated to prevent fluid from entering the air chamber during use, the backing support member having a distal end and a proximal end, the backing support member having at least one first standoff post at the distal end thereof and at least one second standoff post at the proximal end thereof; Each of the at least one first standoff post and the at least one second standoff post has an inner surface and an outer surface, the inner surface being inside the air chamber and the outer surface being outside the air chamber, the at least one first standoff post and the at least one second standoff post being soldered to the ultrasound transducer only at the outer surfaces of the at least one first standoff post and the at least one second standoff post, and the ultrasound transducer is configured to deliver sufficient acoustic energy during ultrasound treatment, such as to thermally induce modulation of nerve fibers surrounding a blood vessel to improve a measurable physiological parameter corresponding to a diagnosed patient condition.

[0011] An apparatus is provided, the apparatus comprising: an ultrasonic transducer configured to emit ultrasonic waves, the ultrasonic transducer having a hollow piezoelectric transducer body having a longitudinal axis and a radially inner surface; a tubular backing support member extending longitudinally through the piezoelectric transducer body and having a radially outer surface; a chamber defined between the radially inner surface of the piezoelectric transducer body and the radially outer surface of the tubular backing support member, the chamber being defined between a first axial end and an opposite second axial end; and a method of irradiating the ultrasonic transducer with an ultrasonic wave of 170 W / cm for a time period between 2 seconds and 4 seconds. 2 ~327W / cm2 and a controller configured to cause the ends to emit ultrasonic waves having a power density between

[0012] The above summary does not contain an exhaustive list of all features of the present invention. The present invention includes all systems and methods that may be practiced from all suitable combinations of the various features of the above summary, the various features disclosed in the detailed description below, and the various features particularly pointed out in the claims as filed. Such combinations have certain advantages not specifically recited in the above summary.

[0013] The novel features of the present disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which: [Brief explanation of the drawings]

[0014] [Figure 1A] FIG. 1A shows a side view of a catheter system, according to many embodiments.

[0015] [Figure 1B] FIG. 1B shows a side view of a hub of a catheter system, according to many embodiments.

[0016] [Figure 1C] FIG. 1C shows a cross-sectional view of the catheter shaft of FIG. 1B along line 1C, according to many embodiments.

[0017] [Figure 2A] FIG. 2A shows a backing support member for a water-backed transducer.

[0018] [Figure 2B]FIG. 2B illustrates a backing support member for an air-backed transducer, according to many embodiments.

[0019] [Figure 2C] FIG. 2C shows the design of the water-bag transducer assembly.

[0020] [Figure 2D] FIG. 2D illustrates an airbag transducer assembly design, according to many embodiments.

[0021] [Figure 2E] FIG. 2E shows a cross-sectional view of the water-bag transducer assembly design.

[0022] [Figure 2F] FIG. 2F shows a cross-sectional view of an airbag transducer assembly design with a step at the proximal end of the transducer, according to many embodiments.

[0023] [Figure 2G] FIG. 2G shows a cross-sectional view of an airbag-style transducer assembly design with a step at the proximal end of the transducer, according to many embodiments.

[0024] [Figure 2H] FIG. 2H shows a cross-sectional view of an airbag transducer assembly design with a step and an airbag transducer assembly design without a step, according to many embodiments.

[0025] [Figure 2IA] FIG. 2IA shows a side view of a water-bag backing support member.

[0026] [Figure 2IB] FIG. 2IB shows a side view of an airbag-style backing support member, according to many embodiments.

[0027] [Figure 2J] FIG. 2J shows a side view of an airbag-style backing support member having a cap at its distal end, according to many embodiments.

[0028] [Figure 2K] FIG. 2K shows a side view of a backing support member having a standoff post at its proximal end, according to many embodiments.

[0029] [Figure 2L] FIG. 2L shows a side view of a backing support member without a standoff post at its proximal end, according to many embodiments.

[0030] [Figure 2M] FIG. 2M illustrates a soldered design for the proximal end of a backing support member without standoff posts, according to many embodiments.

[0031] [Figure 2N] FIG. 2N shows a cover (also known as a collar) used on the proximal end of the backing support member, according to many embodiments.

[0032] [Figure 2O] FIG. 2O illustrates a soldered design for the proximal end of a backing support member with standoff posts, according to many embodiments.

[0033] [Figure 2P] FIG. 2P shows a washer used on the proximal end of the backing support member, according to many embodiments.

[0034] [Figure 2Q] FIG. 2Q shows a perspective view of a sloped cover (also known as a sloped collar) that may be used on both the proximal end of the backing support member and the distal end of the backing support member to provide an airbag-style transducer, according to certain embodiments.

[0035] [Figure 2R] FIG. 2R shows an example (cross-section) of a sloped cover (also known as a sloped collar) that may be used on both the proximal end of the backing support member and the distal end of the backing support member to provide an airbag-style transducer, according to certain embodiments.

[0036] [Figure 2S] FIG. 2S illustrates a soldered design for the proximal and distal ends of a backing support member with standoff posts, according to many embodiments.

[0037] [Figure 3A] FIG. 3A illustrates a water-bag transducer, according to many embodiments.

[0038] [Figure 3B] FIG. 3B illustrates an ID encapsulated transducer, according to many embodiments.

[0039] [Figure 3C] FIG. 3C illustrates an airbag-style saline compatible transducer, according to many embodiments.

[0040] [Figure 3D] FIG. 3D shows an airbag-style saline compatible transducer according to a further embodiment.

[0041] [Figure 4A] FIG. 4A shows a two-piece backing support member with dual steps on the transducer, according to many embodiments.

[0042] [Figure 4B] FIG. 4B shows a continuous backing support member with dual steps on the transducer, according to many embodiments.

[0043] [Figure 5A]5A and 5B illustrate uniform and circumferential energy delivery by an airbag-style transducer, according to many embodiments. [Figure 5B] 5A and 5B illustrate uniform and circumferential energy delivery by an airbag-style transducer, according to many embodiments.

[0044] [Figure 6A] 6A and 6B are graphs and data tables showing safety and effectiveness data for high frequency airbag-style transducers, according to many embodiments. [Figure 6B] 6A and 6B are graphs and data tables showing safety and effectiveness data for high frequency airbag-style transducers, according to many embodiments.

[0045] [Figure 7A] 7A, 7B, 7C, and 7D are graphs illustrating the results of destructive testing of water-bag and air-bag transducers, according to many embodiments. [Figure 7B] 7A, 7B, 7C, and 7D are graphs illustrating the results of destructive testing of water-bag and air-bag transducers, according to many embodiments. [Figure 7C] 7A, 7B, 7C, and 7D are graphs illustrating the results of destructive testing of water-bag and air-bag transducers, according to many embodiments. [Figure 7D] 7A, 7B, 7C, and 7D are graphs illustrating the results of destructive testing of water-bag and air-bag transducers, according to many embodiments.

[0046] [Figure 8A] FIG. 8A shows a target region for nerve ablation, according to many embodiments.

[0047] [Figure 8B]FIG. 8B illustrates the increased safety achieved by reducing the non-target area, according to many embodiments.

[0048] [Figure 8C] FIG. 8C shows partial circumferential delivery of energy.

[0049] [Figure 8D] FIG. 8D illustrates improved uniform and circumferential energy delivery, according to many embodiments.

[0050] [Figure 8E] FIG. 8E is a comparison table showing energy delivery between a 9 MHz transducer and a 15 MHz transducer, according to many embodiments.

[0051] [Figure 9A] 9A and 9B show a comparison between high frequency transducers, according to many embodiments. [Figure 9B] 9A and 9B show a comparison between high frequency transducers, according to many embodiments.

[0052] [Figure 10A] FIG. 10A is a graph illustrating lobe asymmetry without a dual step design, according to many embodiments.

[0053] [Figure 10B] FIG. 10A is a graph illustrating lobe symmetry with a dual step design, according to many embodiments.

[0054] [Figure 11A] FIG. 11A is a side view of a distal portion of a catheter of an ultrasound-based tissue treatment system including an airbag transducer, in accordance with certain embodiments of the present technology.

[0055] [Figure 11B]FIG. 11B is a perspective view of an airbag-style transducer in accordance with certain embodiments of the present technology.

[0056] [Figure 11C] FIG. 11C shows a longitudinal cross-sectional view of the airbag-style transducer introduced in FIGS. 11A and 11B.

[0057] [Figure 11D] FIG. 11D shows a radial cross-section of the airbag-style transducer introduced in FIGS. 11A and 11B.

[0058]

[0059] [Figure 12A] Figures 12A-12D show a catheter suitable for use in the catheter system of Figure 1 A. Figure 12A is a cross-sectional view of the distal end of the catheter along the longitudinal axis of the catheter.

[0060] [Figure 12B] Figures 12A-12D show catheters suitable for use in the catheter system of Figure 1 A. Figure 12B is a cross-sectional view of the catheter of Figure 12A taken along line B in Figure 12A.

[0061] [Figure 12C] Figures 12A-12D show catheters suitable for use in the catheter system of Figure IA. Figure 12C is a cross-sectional view of the catheter of Figure 12A taken along line C in Figure 12A.

[0062] [Figure 12D] Figures 12A-12D show catheters suitable for use in the catheter system of Figure 1 A. Figure 12D is a side view of the distal end of the catheter of Figure 12A.

[0063] [Figure 12E] FIG. 12E shows a cross section of the transducer from the catheter of FIG. 12C.

[0064] [Figure 13] FIG. 13 shows the transducer of FIG. 12E modified so that the outer electrode is split into multiple outer electrodes.

[0065] [Figure 14A] FIG. 14A shows the transducer of FIG. 12E modified to exclude regions of uniform thickness.

[0066] [Figure 14B] FIG. 14B shows the transducer of FIG. 14A modified so that the inner electrode is not positioned over and / or in contact with the transition region.

[0067] [Figure 15] FIG. 15 shows the balloon of the catheter positioned at a treatment site within a patient's body.

[0068] [Figure 16] FIG. 16 shows the catheter positioned at a treatment site within a patient.

[0069] [Figure 17] FIG. 17 is a high-level flowchart used to outline (summarize) a method in accordance with certain embodiments of the present technology.

[0070] [Figure 18] FIG. 18 is a high-level flowchart used to outline (summarize) a method in accordance with certain embodiments of the present technology.

[0071] [Figure 19] FIG. 19 is a schematic illustration of an exemplary system for interfacing with a patient's blood vessel, in accordance with certain embodiments of the present technology.

[0072] [Figure 20]FIG. 20 is a high-level flowchart used to outline (summarize) a method in accordance with a further embodiment of the present technology. DETAILED DESCRIPTION OF THE INVENTION

[0073] While various embodiments of the present disclosure have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided for illustrative purposes. Those skilled in the art will recognize that numerous variations, modifications, and substitutions may occur to them without departing from the present disclosure. It should be understood that various alternatives may be employed to the embodiments of the present disclosure described herein.

[0074] When the terms "at least," "greater than," or "equivalent to" are used in reference to two or more consecutive numbers (preceding the first number in the English language), the term "at least," "greater than," or "equivalent to" applies to (and is interpreted as) each number in the series. For example, "1, 2, or 3 or more" is equivalent to "1 or more, 2 or more, or 3 or more."

[0075] When the terms "no more than," "less than," or "equal to or less than" are used in connection with two or more consecutive numbers (preceding the first number in the English language), the terms "at least," "greater than," or "equal to or less than" apply to (and will be interpreted as) each such number in the series. For example, "equal to or less than 3, 2, or 1" is equivalent to "equal to or less than 3, 2, or 1."

[0076] As used herein, certain embodiments of the present invention contemplate numerical ranges. When a range is present, the range includes both endpoints. Furthermore, all subranges and values ​​within the range are intended to be disclosed (and interpreted as such) as if expressly written out. Terms such as "about" or "approximately" may mean within an acceptable error range for a particular value, which may depend in part on how the value is measured or determined, such as the limitations of the measurement system. For example, "about" may mean within one standard deviation or within more than one standard deviation, in accordance with the practice in the art. Alternatively, "about" may mean within a range of up to 20%, up to 10%, up to 5%, or up to 1% of a given value. When a specific value is described in the application (specification) and claims, unless otherwise specified, the term "about" may be assumed to mean within an acceptable error range for the particular value.

[0077] The terms back surface, inner surface, and inner diameter of the active element refer to the same area of ​​the active element of an airbag-style transducer.

[0078] Certain embodiments described herein are directed to an apparatus including an airbag ultrasound transducer, the airbag ultrasound transducer having a piezoelectric transducer body including a hollow cylindrical tube of piezoelectric material having an inner surface and an outer surface, an inner electrode disposed on at least a portion of the inner surface of the piezoelectric transducer body, an outer electrode disposed on at least a portion of the outer surface of the piezoelectric transducer body, and an inner and radially outer surface 209, the piezoelectric transducer body having a longitudinal opening extending longitudinally through the hollow cylindrical tube of piezoelectric material configured to receive a guidewire. The piezoelectric transducer body includes a backing support member including a hollow tube, and first and second standoff members extending between the radially outer surface 209 of the hollow tube of the backing support member 210 and the inner surface of the hollow cylindrical tube of piezoelectric material of the piezoelectric transducer body to define an air chamber therebetween, wherein the inner electrode is disposed within the air chamber, thereby isolating the piezoelectric transducer body from a fluid within which it is disposed, such as a fluid used to cool the outer electrode, and the piezoelectric transducer body is configured to generate ultrasonic waves in response to application of a voltage between the inner and outer electrodes. In certain such embodiments, the hollow cylindrical tube of piezoelectric material of the piezoelectric transducer body is fabricated by hot isostatic pressing (HIPing) Navy Type III (PZT-8) high-density lead zirconate titanate (PZT) piezoelectric material. In other words, the piezoelectric transducer body is made of hot isostatically pressed (HIPed) Navy Type III high-density PZT piezoelectric material. The pressures used in hot isostatic pressing (HIPing) can range from 10 MPa to 200 MPa at temperatures between 400°C and 2000°C. Hot isostatic pressing of Navy Type III high density PZT piezoelectric material advantageously reduces the porosity of the Navy Type III high density PZT piezoelectric material compared to non-hot isostatic pressing. Hot isostatic pressing of Navy Type III high density PZT piezoelectric material also provides a dissipation factor (DF) of less than 0.006.Here, DF is defined as the ratio of equivalent series resistance (ESR) to the magnitude of the capacitance reactance (Xc), and materials with lower DF make better resonators. In one such embodiment, the airbag ultrasound transducer provides 100 W / cm. 2 ~327W / cm 2 The ultrasonic transducer is configured to generate ultrasound waves having a power density in the range of

[0079] Certain embodiments described herein are directed to a method of using a catheter having an airbag ultrasound transducer in a distal portion, the method comprising: inserting the distal portion of the catheter into a body cavity of a patient so that the airbag ultrasound transducer is positioned adjacent to a nerve surrounding the body cavity to be ablated; causing the airbag ultrasound transducer to emit ultrasound waves having a first power density for a first time period while the airbag ultrasound transducer is positioned adjacent to the nerve surrounding the body cavity to be ablated; and causing the airbag ultrasound transducer to emit ultrasound waves having a second power density for a second time period occurring after the first time period while the airbag ultrasound transducer is positioned adjacent to the nerve surrounding the body cavity to be ablated, the second power density being different from the first power density. In certain such embodiments, the first period has a duration within a first range of 2 seconds to 4 seconds, and the second period has a duration within a second range of 2 seconds to 4 seconds. According to certain embodiments, the method further comprises causing the ultrasonic transducer to not emit ultrasonic waves during a third period between the first period and the second period, the third period having a duration within a third range of 2 seconds to 4 seconds. According to certain embodiments, one of the first power density and the second power density is 170 W / cm. 2 ~327W / cm 2 and the other of the first power density and the second power density is in the range of 50 W / cm 2 ~169W / cm 2is within the range.

[0080] In certain embodiments described herein, a tissue treatment device is provided comprising: a catheter having a distal end; an ultrasound transducer positioned at the distal end of the catheter; and a backing support member, wherein the ultrasound transducer has an inner (posterior) surface and an outer (anterior) surface, each of the inner and outer surfaces having an electrode; the ultrasound transducer is attached to the backing support member and defines an air chamber adjacent the inner surface, the air chamber being insulated to prevent fluid from entering the air chamber during use; the backing support member has a distal end and a proximal end; and the ultrasound transducer is configured to deliver sufficient acoustic energy during sonication, such as to thermally induce modulation of nerve fibers surrounding a blood vessel to improve a measurable physiological parameter corresponding to a diagnosed patient condition.

[0081] In certain embodiments described herein, a method of ablating target tissue is provided, the method comprising advancing a catheter including an ablation element through at least one internal vessel to a location at or near the target tissue, the ablation element including a piezoelectric component, a backing support member, and an air chamber therebetween, the method further comprising energizing the piezoelectric component of the ablation element to deliver energy to the target tissue, thereby ablating the target tissue, the target tissue including one or more sympathetic nerves or nerve branches.

[0082] In certain embodiments described herein, a system for ablating target tissue is provided, the system comprising: an ultrasonic energy generator; and a catheter coupled to the ultrasonic energy generator, the catheter configured to be advanceable through at least one body vessel to a location at or near the target tissue, the catheter comprising a catheter shaft and an ablation element at a distal end of the catheter, the ablation element including a piezoelectric element, a backing support member, and an air chamber therebetween, the ultrasonic energy generator operably coupled to the ablation element and supplying energy to the piezoelectric element to deliver energy to the target tissue, thereby ablating the target tissue, the target tissue including one or more sympathetic nerves or nerve branches.

[0083] In certain embodiments described herein, an ultrasound tissue treatment catheter is provided having a cylindrical ultrasound transducer having an outer diameter of approximately 1.3 mm and an operating frequency of 11-15 MHz, the ultrasound transducer configured to deliver sufficient acoustic energy during sonication, such as to thermally induce modulation of nerve fibers surrounding blood vessels to improve measurable physiological parameters corresponding to a diagnosed patient condition. In certain embodiments described herein, a tissue treatment device is provided comprising a catheter configured to be advanceable through at least one body vessel to a location at or near a target tissue, the catheter including a catheter shaft and an ablation element carried at a distal end of the catheter, the ablation element including a piezoelectric component having a first edge and a second edge, a backing support member having a cap at a distal end thereof, and an air chamber between the piezoelectric component and the backing support member, the air chamber being insulated to prevent fluid from entering the air chamber during use, and the piezoelectric component configured to deliver energy to the target tissue to ablate the target tissue.

[0084] 1A-1C illustrate an exemplary catheter system, according to many embodiments. The catheter system may include a catheter 10 having a proximal end and a distal end. The catheter 10 may include a catheter shaft 12, a balloon 14, and a tip member 15. The balloon 14 may be positioned between the catheter shaft 12 and the tip member 15. The balloon 14 may be or include a compliant, semi-compliant, or non-compliant medical balloon 14. Suitable materials for the balloon 14 may include, but are not limited to, nylon, polyimide film, thermoplastic elastomers such as those sold under the trademark PEBAX®, medical-grade thermoplastic polyurethane elastomers such as those sold under the trademark PELLETHANE®, pellethane, isotane, and other suitable polymers, or any combination thereof.

[0085] In one embodiment, a catheter system for ablating target tissue may include an ultrasonic energy generator (electronics) 22 and a catheter 10 coupled to the ultrasonic energy generator. The catheter 10 may be configured to be advanceable through at least one body vessel to a location at or near the target tissue. The catheter 10 may include a catheter shaft 12 and an ablation element disposed in a distal portion of the catheter 10. The ablation element may be comprised of a piezoelectric component, such as an ultrasonic transducer 200, a backing support member 210, and an air chamber 230 therebetween. The ultrasonic energy generator may be operatively coupled to the ablation element to supply energy to the ultrasonic transducer 200 to deliver energy to the target tissue and ablate it. The target tissue may include one or more nerves or nerve branches. In one embodiment, the target tissue may include a nerve or nerve branch that begins within the adventitia (i.e., beyond the intima-media thickness) and terminates within about 10 mm of the lumen of the blood vessel, e.g., less than 6 mm from the lumen. In certain embodiments, an imaging transducer is used to find the media-adventitial boundary, and ablation is initiated at a set distance, e.g., 0.1 mm, from the media-adventitial boundary. In certain embodiments, the target tissue may include a nerve or nerve branch beginning 0.3 mm to 10 mm from the lumen of a blood vessel, e.g., 0.5 mm to 6 mm or 1 mm to 6 mm from the lumen of one or more blood vessels, such as the renal artery, hepatic artery, and / or pulmonary artery. In one embodiment, the target tissue may include cardiac tissue, e.g., conductive cardiac tissue.

[0086] In one embodiment, the generator may be configured to energize a piezoelectric component, such as an ultrasonic transducer 200, at a frequency of 11 MHz to 15 MHz, or at both frequencies, for a duration of 5 to 20 seconds. In one embodiment, the generator may be configured to energize a piezoelectric component at a frequency of 12 MHz to 14 MHz, or at both frequencies, for a duration of 6 to 10 seconds. In one embodiment, the generator may be configured to energize a piezoelectric component at a frequency of approximately 13 MHz, or at both frequencies, for approximately 7 seconds. Energizing the piezoelectric component with the generator may raise the temperature of the piezoelectric component by up to 50°C. Energizing the piezoelectric component with the generator may raise the temperature of the piezoelectric component by up to 50°C, or at an average surface acoustic intensity of 20 W / cm. 2 ~150W / cm 2 of energy is delivered.

[0087] The catheter 10 may have a handle 16 at the proximal end of the catheter shaft 12. The handle 16 may include one or more electrical couplings 18 for connecting the catheter system to one or more external electrical conductors 20, each in electrical communication with electronics 22 (e.g., a generator). Suitable external electrical conductors 20 include, but are not limited to, wires, cables, and flexible printed circuits (FPCs).

[0088] The electronics 22 can control the catheter 10, sweep the operating frequency, control the duration of individual pulses and the total time of the series of pulses, control the temperature of the ablation region, and shape the lesion.

[0089] The catheter shaft 12 may include one or more electrical lumens 121. Each of the electrical lumens 121 may extend along the longitudinal length of the catheter shaft 12 from one or more electrical couplings 18 toward the distal end of the catheter shaft 12. Each of the electrical lumens may carry one or more electrical conductor carriers, each carrying one or more electrical conductors. The electrical conductors may be in electrical communication with the electronics 22 via the electrical couplings 18 and one or more external electrical conductors 20. Suitable electrical conductors include, but are not limited to, wire, insulated wire, cable, and flexible printed circuit (FPC). When the electrical conductor carrier carries multiple electrical conductors 20, a suitable electrical conductor carrier may be an electrically insulating jacket. When the electrical conductor carrier carries a single electrical conductor 20, electrical insulation on the electrical conductor may function as the electrical conductor carrier.

[0090] The handle 16 may include one or more fluid ports 24 for connecting the catheter to conduits 26. Suitable conduits 26 include, but are not limited to, tubing or hoses. The conduits 26 may provide fluid communication between the fluid ports 24 and a fluid source 28. Suitable fluid sources 28 include, but are not limited to, pumps, tanks, reservoirs, and containers. The catheter shaft 12 may include one or more fluid lumens 241. Each of the fluid lumens 241 extends along the length of the catheter shaft 12 toward the distal end of the catheter shaft 12 and may be in fluid communication with one of the fluid ports 24.

[0091] The handle 16 may include one or more guidewire ports 30 for receiving a guidewire 31. The catheter shaft 12 may include a guidewire lumen 301. The guidewire lumen 301 may extend along the longitudinal length of the catheter shaft 12 toward the distal end of the catheter shaft 12. The guidewire lumen may be in fluid communication with the guidewire port 30, such that a guidewire 31 inserted into the guidewire port 30 may be housed within the guidewire lumen.

[0092] In certain embodiments, the catheter 10 may include an imaging transducer 17, such as a single-element or array transducer, at the distal end of the catheter 10. The imaging transducer 17 may have a center frequency of 15-50 MHz, e.g., 20-30 MHz, and may be used to distinguish between target and non-target structures. The imaging transducer 17 may be positioned in front of or behind the balloon 14. The imaging transducer 17 may comprise a single ring or a ring array having multiple rings. The imaging depth may be up to approximately 12 mm and may be used to image vessel size, anatomical structures, pathology, lesion formation, temperature changes, heat sinks such as lymph nodes, vessel walls, plaque, calcification, tissue layers, and nerves. The imaging frequency may be approximately 20 MHz-35 MHz, the bandwidth may be 10 MHz or greater, and the array size may be, but is not limited to, 16-256 elements. The dimensions of the array elements can be 0.5 mm to 1.5 mm in length and 0.5 mm to two wavelengths in width. A multi-row cylindrical array can help reduce the thickness of the image slice, achieving better contrast resolution. The elements can be individually controlled for transmission and reception, for example by ASIC circuitry, to reduce the number of cables required.

[0093] In certain embodiments, the catheter system may additionally or alternatively include electrodes on the balloon 14 configured to sense neural activity and / or confirm the effectiveness of treatment, as disclosed in U.S. Patent Application Publication No. 2023 / 0021354 A1 to Zhai et al., which is incorporated by reference in its entirety.

[0094] In certain embodiments, the catheter system may additionally or alternatively include a neural sensing and / or therapy confirmation component as disclosed in U.S. Patent Application No. 63 / 320,103, filed March 15, 2022, by Barman et al., which is incorporated by reference in its entirety. As disclosed in further detail in U.S. Patent Application No. 63 / 320,103, the therapy confirmation component may be used to determine the type, size, function, and / or health of the fiber from which a neural response is being sensed by determining the latency of the sensed electrical impulse. The delay (also known as latency) may indicate the depth of the nerve surrounding the biological cavity (e.g., the renal artery) within which the catheter being used to measure the delay is located. According to certain embodiments of the present technology, the delay (also known as latency) may be utilized to select a frequency to use for ablation. Electronics 22 control catheter 10 to sweep operating frequencies and control individual and total durations to control the temperature of the ablation region and shape the lesion. Some transducers 200 activated at lower frequencies are used to target deeper regions when nerves are determined to be in those deeper regions. Some transducers 200 activated at higher frequencies are used to target closer regions when nerves are determined to be in those closer regions.

[0095] 2A-2IB illustrate various transducers, including water-backed transducers (FIGS. 2A, 2C, 2E, 2IA) and air-backed transducers (FIGS. 2B, 2D, 2F, 2G, 2H, 2IB, 2S), and / or components thereof. Air-backed transducers have an air layer on the inner surface of the transducer or piezoelectric component. The air layer can help direct all acoustic energy transmitted through the outer surface or diameter of the transducer. Air-backed transducer embodiments of the present invention can provide better uniformity and efficiency of energy delivery to the tissue site being treated, as well as safer treatments. Lesion uniformity can depend on the concentricity of the piezoelectric transducer and is less dependent on the support member being separated from the PZT member by the air layer. However, the airbag-type ultrasonic transducer 200 may not be concentric with the backing support member 210 and still function as intended. Therefore, in certain embodiments, the backing support member 210 is positioned non-concentrically with the piezoelectric transducer body 208. This reduces the transducer's dependency on the assembly process without sacrificing acoustic field uniformity. The air behind the transducer, next to the inner surface of the PZT element, can ensure that acoustic waves emanate from the outer diameter (OD) of the transducer. Therefore, structures such as posts and other assembly components that pass through a cylindrical transducer are separated from the PZT element by an air layer and have little or no effect on acoustic efficiency. This allows for open (possible, flexible) geometric design of the transducer and the various components that pass through it. As long as there is an air gap between the inner surface of the PZT element and the backing support member 210 or other assembly components, the OD profile can be scaled down or scaled to any size. The reduced size of the transducer allows for use with, for example, a 4Fr or 5Fr catheter, which allows the device to be advanced to a target site within a subject's or patient's blood vessels, such as the renal arteries, through the radial artery rather than a larger artery such as the femoral artery.Radial access for advancing a catheter equipped with an ultrasound transducer according to the present disclosure is disclosed in U.S. Provisional Patent Application No. 63 / 383,816, filed November 15, 2022 (Attorney Docket No. PMD00091US), to Mazzone et al., U.S. Provisional Patent Application No. 63 / 375,357, filed September 12, 2022 (Attorney Docket No. PMD00076US), to Mazzone et al. ), U.S. Provisional Patent Application No. 63 / 381,081 filed October 26, 2022 by Merino et al. (Attorney Docket No. PMD00085US), U.S. Provisional Patent Application No. 63 / 429,452 filed December 1, 2022 by Zhai (Attorney Docket No. PMD00093US), and U.S. Provisional Patent Application No. 63 / 387,056 filed December 1, 2022 by Marino et al. (Attorney Docket No. PMD00099US), all of which are incorporated by reference herein in their entireties. The specific inner diameter (ID) and outer diameter (OD) of the transducer may depend largely on the intended operating frequency. For example, for an airbag-style transducer operating at 9 MHz, the outer diameter may be 0.06 inches and the inner diameter may be 0.04 inches.

[0096] In many embodiments, the ultrasound transducers described herein are airbag-type, as shown in Figures 2B, 2D, 2F, 2G, 2H, 2IB, 2J-4B. According to some embodiments, a tissue treatment catheter 10 is provided with an ultrasound transducer 200 positioned at the distal end of the catheter 10. The ultrasonic transducer 200 includes a piezoelectric transducer body 208 comprising a hollow cylindrical tube of piezoelectric material having an inner surface 207 and an outer surface 206, each of which has an electrode. A backing support member 210 may extend through the ultrasonic transducer 200, and the backing support member 210 may have at least one first conductive component 212 (e.g., a first standoff post) at a distal end thereof and at least one second conductive component 212 (e.g., a second standoff post) at a proximal end thereof (FIGS. 2B, 2IB). Each standoff post 212 has an inner surface 212a and an outer surface 212b. Optionally, a step 250 may be provided at the proximal end of the ultrasonic transducer 200 (FIGS. 2F, 2G). Alternatively, a chamfer may be provided at the proximal end of the ultrasonic transducer 200 instead of the step 250. Alternatively, neither the step 250 nor the chamfer is provided (present) at the proximal end of the ultrasonic transducer 200. The ultrasonic transducer 200 may optionally be attached to at least first and second standoff posts 212 of the backing support member 210 and define an air chamber 230 adjacent the inner surface 207, the air chamber 230 being insulated to prevent fluid from entering the air chamber 230 during use, and the transducer 200 is configured during sonication to deliver sufficient acoustic energy, such as to thermally induce modulation of nerve fibers surrounding a blood vessel to improve a measurable physiological parameter corresponding to a diagnosed patient condition, to generate an ablation region, e.g., 3 mm to 6 mm wide, e.g., 5 mm wide, and 0.5 mm to 10 mm deep, e.g., 1 mm to 6 mm deep, from the lumen of the blood vessel.

[0097] The backing support member 210 may have a length ranging from approximately 0.250 inches to 0.400 inches (6.25 mm to 10.16 mm), for example, from approximately 0.300 inches to 0.350 inches (7.62 mm to 8.89 mm). The posts 212 may be made of a conductive material, such as stainless steel, e.g., electroless nickel-plated (ENIG) stainless steel, or unplated bronze, copper, brass, tungsten, or the like. It is often difficult to solder to stainless steel. Therefore, if the backing support member 210 is made of stainless steel, the outer surface of the backing support member 210 may be plated with a metal that is easily soldered, e.g., nickel and / or gold, to provide, for example, an ENIG-plated stainless steel backing support member 210. Similarly, the exterior and interior surfaces of the transducer body 208 may also be plated with a metal to which solder can be readily applied, such as nickel and / or gold, and thus the exterior and interior surfaces of the transducer body 208 may be referred to as plated surfaces 260. The ultrasonic transducer 200 may be attached to at least first and second standoff members 212 of the backing support member 210 and may define an air chamber 230 adjacent the interior surface 207, with the backing support member 210 extending a first length from the exterior surface 212b of the standoff post 212 and the transducer 200 extending a second, shorter length from the exterior surface 212b of the standoff post 212 to define an entrance or pocket 270 for establishing a circumferential solder seal (FIG. 2G) using a solder material 201. Such pockets 270 may be created at both the proximal and distal longitudinal ends of the transducer 200 and may provide areas where solder may be placed and used to provide an airtight seal for the air chamber 230. In certain embodiments, solder nuggets or solder balls may be used. For example, solder nuggets or solder balls and solder flux (e.g., liquid or cream flux) may be placed in the pocket 270, and a soldering iron may be used to heat the solder nuggets or solder balls, causing the solder balls and solder flux to melt and fill the pocket 270.The solder nuggets may be created by cutting solder wire into segments (also known as nuggets) that are about 0.01 inches to about 0.015 inches thick. In a particular embodiment, after solder is used to fill the pockets 270 at both the proximal and distal longitudinal ends of the transducer 200, the transducer 200 is placed in an ultrasonic cleaner containing about 70% isopropyl alcohol (IPA) for about five minutes and dried with compressed air. The solder joints are then visually inspected, for example, using a visual aid. If the solder joints are determined to be unacceptable, more flux is applied, the joints are resoldered, and the cleaning and inspection process is repeated until the solder joints are determined to be acceptable or the transducer is rejected. In certain embodiments, the outer diameter of the standoff post 212 may closely fit the inner diameter of the transducer 200, so that solder is only required on the outer surface 212b of the standoff post 212 and does not migrate into the air chamber 230, e.g., the inner diameter (ID) of the transducer, during use. The solder seal can also prevent adhesive migration, for example, during ultrasonic processing. Using a solder preform is another option to help prevent solder from penetrating into the air chamber 230. The solder preform can be, for example, a washer 203 or a washer-like element, such as a washer having a top-hat shaped side cross-section 202. Such a solder preform may be placed in a suitable location on the backing support member 210, for example adjacent the standoff post 212, and then heated to cause the solder preform to reflow and seal any gaps that exist between the standoff post 212 (or other type of standoff member) and the inner surface of the body of the ultrasonic transducer 200, providing an airtight seal for the air chamber 230. Alternatively or additionally, a ring of solder balls pre-coated with solder flux may be used to provide an airtight seal for the air chamber 230. In certain embodiments, the solder preform comprises a tin-lead alloy, such as a 63 / 37 tin-lead alloy.Alternatively or additionally, the solder preform comprises a non-lead alloy such as tin-silver-copper or tin-copper.

[0098] It is beneficial to prevent solder and adhesive from leaking (a.k.a., seeping in or migrating) into the air chamber 230 of the air-bag transducers described herein for at least the following reasons: If the solder and / or adhesive (e.g., resin) leaks into the air chamber 230, the solder and / or adhesive will act as a backing material, causing sound waves to pass through or bounce off the solder and / or adhesive layer (which has leaked into the air chamber). If the solder and / or adhesive is not applied in a controlled manner, i.e., if the solder and / or adhesive leaks into the air chamber, the acoustic output will be disrupted (disrupted) in the affected area of ​​the transducer (i.e., the area where the solder and / or adhesive has leaked into the air chamber 230). This can have two undesirable effects: 1) areas along the longitudinal length of the airbag transducer where solder or adhesive has leaked into the air chamber 230 may experience lower acoustic output due to a suboptimal thickness of the transducer body, potentially reducing the effective longitudinal length of the airbag transducer; and 2) because acoustic output uniformity is highly dependent on the transducer body being highly cylindrically symmetric (i.e., having a high degree of concentricity), solder and / or adhesive (e.g., resin) leaking into the air chamber 230 may adversely affect the acoustic output uniformity.

[0099] Additionally or alternatively, the backing support member 210 can have a first conductive component 212, e.g., a first standoff post, and a second conductive component 212, e.g., a second standoff post. The first standoff post 212 and the second standoff post 212 can be coupled to a piezoelectric component, e.g., the ultrasonic transducer 200, to define an air chamber 230 together with the piezoelectric component and the area of ​​the backing support member 210 between the first standoff post 212 and the second standoff post 212. One or more of the first standoff post 212 or the second standoff post 212 can be coupled to the ultrasonic transducer 200 by soldering. Additionally or alternatively, the ablation element can further include at least one spacing element positioned between one or more of the first standoff post 212 or the second standoff post 212 and the ultrasonic transducer 200. The at least one spacing element may be soldered to one or more of the first standoff post or the second standoff post and the piezoelectric component. The at least one spacing element may include at least one washer 203. The at least one spacing element may include a solder preform. The transducer may optionally be provided with a step and / or a chamfer at one or more of its longitudinal ends, i.e., at its proximal end and / or its distal end. The transducer may optionally be provided with no step or chamfer at one or more of its longitudinal ends.

[0100] FIG. 2J illustrates an embodiment that addresses the issue of solder penetration into the air chamber 230. The backing support member 210 may have a cap 214 at its distal end and a standoff post 212 at its proximal end. The cap 214 includes a step 250 for centering the backing support member 210 relative to the ultrasonic transducer 200. The plated surface 260 may be removed at the chamfered edge 216 of the ultrasonic transducer 200. The removal of the plated surface 260 may be accomplished by, for example, grinding. Additionally or alternatively, the removal of the plated surface may be accomplished before attaching the backing support member 210 to the ultrasonic transducer 200. A solder material 201 may be disposed at the interface between the cap 214 and the plated surface 260 of the inner surface 207. The solder material 201 may be disposed at the proximal end of the backing support member where the first standoff post abuts the plated surface 260 of the inner surface 207. By inserting the backing support member 210 from the distal end of the ultrasound transducer 200, easier positioning of the backing support member 210 may be achieved.

[0101] In some embodiments, the shape of the backing support member 210 or the standoff posts 212 may be modified to inhibit solder infiltration into the air chamber 230. For example, as shown in FIG. 2K, the backing support member 210 may be modified so that its distal end has a cap 214 with a stepped portion 250 and its proximal end has a standoff post 212 to prevent solder material 201 from infiltrating through the proximal end. Another embodiment is shown in FIG. 2L, in which the backing support member 210 may include a cap 214 with a stepped portion 250 at its distal end and no standoff post 212 at its proximal end.

[0102] At the proximal end of the transducer assembly, there may be many embodiments to prevent the solder material 201 from migrating into the air chamber 230. For example, as shown in FIG. 2M, the plated surface 260 may be removed from the chamfered edge 216 of the ultrasonic transducer 200. A backing support member 210 without standoff posts 212 may be used with a cover 202 to close the space between the backing support member 210 and the ultrasonic transducer 200. The cover 202 may also be referred to herein as a collar because it surrounds the backing support member 210. The solder material 201 may be disposed at the interface between the cover 202 and the plated surface 260 of the ultrasonic transducer 200 and at the interface between the cover 202 and the backing support member 210. FIG. 2N shows one embodiment of the cover 202. The cover 202 (also known as a collar) may be made of copper, brass, or other materials. 2N includes a first portion having a first outer diameter configured to fit within the space between the backing support member 210 and the ultrasonic transducer 200, and a second portion having a second outer diameter (larger than the first outer diameter of the first portion of the cover 202) configured to abut a longitudinal end of the transducer 200. Overall, the first and second portions of the cover 202 give the cover 202 a shape resembling a sideways top hat (top hat), with an abrupt transition between the first and second outer diameters.

[0103] Another embodiment for preventing the solder material 201 from migrating into the air chamber 230 is shown in FIG. 20 . A backing support member 210 having a standoff post 212 at its proximal end may be used with a washer 203. The washer 203 may be disposed on the outer surface of the standoff post 212. The solder material 201 may be disposed at the interface between the washer 203 and the backing support member 210 and at the interface between the washer 203 and a plated surface 260 of the ultrasonic transducer 200. The plated surface 260 may optionally be removed from the chamfered edge of the ultrasonic transducer 200. FIG. 2P shows one embodiment of the washer 203. The washer 203 may be made of a conductive material such as copper, brass, or a gold-plated polymer. In the embodiment shown in Figures 2J, 2M, and 2O, the plated surface 260 is removed to separate the outer diameter of the ultrasonic transducer 200 from the inner diameter, thereby preventing short circuits between the inner and outer electrodes (e.g., electrodes 204, 205 in Figures 11C and 11D).

[0104] 2M and 2N , the cover 202 (also known as the collar 202) shown in Figures 2Q and 2R may be used in place of the cover 202 (also known as the collar 202). The cover 282 includes a first portion 284 having a first outer diameter configured to fit within the space between the backing support member 210 and the ultrasonic transducer 200, and a second portion 288 having a tapered or sloped outer diameter that begins larger than the first outer diameter of the first portion 284 but ultimately tapers to a second portion 286 having the same outer diameter as the first portion 284, thereby allowing the cover 282 to be slid over the outer diameter of the backing support member 210 and providing an interference fit between the outer circumferential surface of the backing support member 210 and the inner circumferential surface of the transducer 200. In a manner similar to the manner in which solder 201 is applied in the embodiment of FIG. 2M, solder material 201 may be disposed at the interface between tilted cover 282 and backing support member 210. In the embodiment shown in FIG. 2R, examples of tilted cover 282 are included at both the proximal and distal ends of transducer 200, providing air chamber 230, thereby providing an air-bag transducer 200. The air chamber may contain a low acoustic impedance medium, including, but not limited to, air, helium, argon, or nitrogen. Alternatively, the air chamber may be evacuated, i.e., under a vacuum. Because air chamber 230 may contain gases other than air or may be evacuated, air chamber 230 may also be referred to as a gas chamber or vacuum chamber 230. For similar reasons, air-bag transducer 200 may also be referred to as a gas-bag or vacuum-bag transducer 200.

[0105] In one embodiment, the standoff posts 212 may be angled to prevent wicking of solder into the air chamber 230. This may advantageously allow the transducer 200 to withstand higher power than conventional airbag transducers. The standoff posts 212 may not be necessary in airbag transducer designs. In another embodiment, an interference-fit cover (also known as a collar) may be used to seal the air chamber 230 at both ends of the ultrasonic transducer 200, and a rod may be placed through the inner diameter of the ultrasonic transducer. That is, the seal design is not limited as long as the air chamber 230 is hermetically sealed. An advantage of not requiring standoff posts 212 in ultrasonic transducer designs is that it provides more design options for hermetically sealing the air chamber 230.

[0106] 2S, a small amount of conductive solder 201 may penetrate the air chamber 230 to provide an electrical connection between the inner diameter of the transducer 200 and the backing support member 210. A solder preform 203 may be placed in an appropriate location on the backing support member 210, such as adjacent both standoff posts 212, and then heated to cause the solder preform to reflow and flow into the air chamber 230 in a sufficient amount to electrically connect the inner diameter of the transducer 200 and the backing support member 210 and form a seal between the standoff posts 212 (or other type of standoff member) and the inner surface of the body of the ultrasonic transducer 200, providing an airtight seal for the air chamber 230.

[0107] In certain embodiments, the transducer 200 is configured to deliver a power level required to ablate a target tissue, e.g., a renal nerve, e.g., up to about 150 W / cm across the outer surface area of ​​the transducer 200. 2or greater, such that the transducer 200 is configured to deliver sufficient acoustic energy during ultrasound treatment to thermally induce modulation of nerve fibers surrounding a blood vessel, such that the thermally induced modulation is sufficient to improve a measurable physiological parameter corresponding to a diagnosed patient condition, while being small enough to fit into a renal artery and / or allow radial access using a 5F or smaller catheter.

[0108] In some embodiments, the transducer 200 has a stepped portion 250 at least at the proximal end where the electrical conductor 20 can connect to the external electrode of the transducer. Locating the connection between the electrical conductor 20 and the solder material 201 at the stepped portion 250 of the transducer 200 does not interfere with the acoustic output of the transducer 200 and provides an airbag transducer design that allows the transducer 200 to be attached to a cable while maintaining a smaller profile.

[0109] Referring to Figures 2A, 2C, 2E, and 2IA, a water-backed or liquid-backed transducer and its components are illustrated. Such water-backed transducers may have similar components to air-backed transducers. Water-backed or liquid-backed transducers have a water or liquid layer behind or adjacent to the inner surface of the PZT component. Often, water-backed or liquid-backed transducers have an additional solid backing or support member 211 that passes through the water or liquid layer. Carefully designed geometries can induce constructive acoustic interference at the outer surface of the water or liquid layer in combination with the solid backing member, maximizing acoustic transmission efficiency. In such cases, the distance between the inner diameter of the transducer or piezoelectric component and the outer diameter of the solid backing member (i.e., the height of the water or liquid layer) can be carefully controlled and manufactured to introduce constructive interference between ultrasound waves directed outward from the outer diameter of the transducer or piezoelectric component and those reflected from the solid backing member. By providing an air layer instead, the material behind the back surface has little or no effect on the acoustic energy transmitted from the front surface of the transducer. All energy is reflected from the back surface and transmitted from the front surface, improving transmission efficiency. The so-called "air layer" includes low acoustic impedance media such as, but not limited to, air, helium, argon, carbon dioxide, and / or nitrogen. The so-called "air layer" may alternatively be evacuated. Therefore, the "air layer" may also be referred to as a vacuum layer or a gas layer.

[0110] In water-backed or liquid-backed embodiments of the ultrasound transducer 200, a backing member 211 may extend through the ultrasound transducer 200 and may have multiple posts 213 at its distal end and multiple posts 213 at its proximal end (FIGS. 2A, 2C, and 2AI). The posts 213 leave openings between adjacent posts through which liquid or water may pass. The ultrasound transducer 200 may be attached to the posts 213 to define a water or liquid backing layer 231. The backing layer 231 may be open in fluid communication with the ultrasound transducer, allowing water or liquid to be circulated, for example, to cool the transducer. The transducer 200 may be configured to deliver sufficient acoustic energy during ultrasound treatment, such as to thermally induce modulation of nerve fibers surrounding blood vessels sufficient to improve measurable physiological parameters corresponding to a diagnosed patient condition.

[0111] Ultrasound ablation utilizes the phenomenon of attenuation to generate heat. As ultrasound energy or ultrasound propagates through soft tissue, acoustic energy is reduced and the lost acoustic energy is converted to heat. In one embodiment suitable for renal denervation, frequencies between 10 and 15 MHz may be used. More generally, in embodiments suitable for renal denervation, frequencies in the range of 1 MHz to 30 MHz may be used, optionally between 7 MHz and 15 MHz, optionally between 8 MHz and 13 MHz, optionally between 8.5 MHz and 9.5 MHz, or optionally between 8.7 MHz and 9.3 MHz.

[0112] In one embodiment suitable for renal denervation, the airbag transducer wall thickness may be, for example, 0.15 mm to 0.2 mm, e.g., 0.17 mm, and the operating frequency may be, for example, 12 to 15 MHz, e.g., 13 MHz. The outer diameter of the airbag transducer may be minimized for radial access (e.g., about 1.3 mm), and the inner diameter may be maximized for heat dissipation (e.g., about 1 mm), so that during sonication, sufficient acoustic energy may be delivered to thermally induce modulation of the renal nerves surrounding the renal vessels to improve a measurable physiological parameter, e.g., blood pressure, corresponding to a diagnosed condition in the patient, e.g., hypertension.

[0113] Those skilled in the art, after reading this application, will understand that the transducer geometry may be optimized for other applications, such as cardiac ablation and other tubular anatomies.

[0114] In certain embodiments, the transducer 200 includes a cylindrical hollow tube of piezoelectric material, which may be referred to as the piezoelectric transducer body 208. In other embodiments, the piezoelectric transducer body may have a variety of other shapes and need not be hollow. For example, in certain embodiments suitable for renal denervation, the piezoelectric material may be lead zirconate titanate 8 (PZT8), also known as Navy III piezoelectric material. The raw PZT transducer may be plated with layers of copper, nickel, and / or gold to create electrodes on the surfaces (e.g., inner and outer surfaces) of the piezoelectric transducer body 208, as disclosed, for example, in U.S. Pat. No. 10,230,041 to Taylor et al., which is incorporated by reference in its entirety. In certain embodiments, the PZT may be annealed or hot isostatically pressed (HIPed), as known in the art. More specifically, in certain embodiments, the piezoelectric transducer body 208 is fabricated by hot isostatic pressing Navy Type III high-density lead zirconate titanate (PZT) piezoelectric material. Prior to machining the PZT, a combination of high temperature and high pressure may be used to densify the PZT. This process may eliminate porosity in the PZT material, thereby leading to improved breakdown strength of the transducer. More specifically, by forming the HIPed piezoelectric transducer body 208 in this manner and defining the air chamber 230 to provide an air-bag ultrasonic transducer, such an ultrasonic transducer 200 can output significantly more output power than a water-bag ultrasonic transducer, as can be seen in part from the graphs of FIGS. 7A-7D described below.

[0115] The water-bag design of FIG. 3A shows that the transducer 200 has a step 250 at least at the proximal end where the electrical conductor 20 can connect to the transducer's external electrode. FIGS. 3B and 3C show that the inner diameter (ID) of the air-bag design transducer 200 is isolated from the fluid (i.e., the fluid within the balloon 14, or bodily fluids such as blood in balloon-less embodiments), allowing the catheter to be compatible with saline. Adhesives 303, 304 that can be used to maintain the seal intact can include adhesives (bonds) that bond to the backing support member material, which can be made of metal. The adhesive can be durable, as vibration can cause the adhesive to delaminate. One example of an applicable adhesive can be epoxy.

[0116] In certain embodiments, the proximal end of the ultrasound transducer 200 may include a stepped portion 250, while the distal end of the transducer 200 may or may not include a similar stepped portion, depending on the specific implementation. In certain embodiments, the axial length of the stepped portion 250 of the transducer 200 is approximately 0.4 mm, and the axial length of the non-stepped portion of the transducer 200 is approximately 6 mm. Other variations are possible and are within the scope of the embodiments described herein. In certain embodiments, the non-stepped portion of the transducer 200 is the main portion of the transducer that generates the majority of the ultrasonic energy delivered from the catheter 10. In certain embodiments, the stepped portion 250 has a different outer diameter than the non-stepped portion and behaves differently than the non-stepped portion.

[0117] According to certain embodiments, to improve the durability of the airbag-style transducer 200, a pair of standoff members 212 used to provide the air chamber 230 are attached (by soldering and / or adhesive) to proximal and distal portions of the piezoelectric transducer body 208, which are configured not to vibrate in response to application of a voltage between the inner electrode 204 and the outer electrode 205 of the airbag-style transducer 200. Between the proximal and distal portions of the piezoelectric transducer body 208 (which are configured not to vibrate when a voltage is applied between the inner electrode 204 and the outer electrode 205) is a central portion of the piezoelectric transducer body 208, which is configured to vibrate in response to application of a voltage between the inner electrode 204 and the outer electrode 205. Solder and / or adhesive are included between the piezoelectric transducer body 208 and the pair of standoff members 212 to provide an airtight seal and prevent fluid (in which the piezoelectric transducer body 208 may be disposed) from leaking into the air chamber 230. By attaching the standoff members 212 to proximal and distal portions of the piezoelectric transducer body, respectively, that are configured not to vibrate in response to application of a voltage between the inner and outer electrodes, the likelihood of the airtight seal provided by the solder and / or adhesive being breached and fluid leaking into the air chamber 230 is reduced compared to when at least one of the standoff members 230 is attached to a central portion of the piezoelectric transducer body that is configured to vibrate in response to application of a voltage between the inner and outer electrodes.

[0118] The generator 22 may be electrically connected to the transducer 200 by a coaxial cable, a parallel pair of solid / stranded conductors, a shielded parallel pair, a twisted pair, or a flex circuit.

[0119] In certain embodiments, two separate coaxial cables are electrically connected to the proximal portion of the ultrasound transducer 200. The two separate coaxial cables may collectively constitute an electrical cable. Each of these coaxial cables includes an inner conductor surrounded by a dielectric and an outer tubular conductive shield surrounding the inner conductor, all of which are surrounded by an insulating jacket. In certain embodiments, the distal ends of the inner conductors of the coaxial cables may be electrically coupled to outer electrodes (e.g., electrodes 205 in FIGS. 11C and 11D ) at the proximal end of the transducer 200 approximately 180 degrees apart. More specifically, each of the inner conductors of the coaxial cables is soldered to a stepped portion 250 at the proximal end of the transducer 200 approximately 180 degrees apart, such that current output from the electronics 22 flows from the inner conductors of the coaxial cables to the outer electrodes 205 of the transducer 200. The proximal ends of the inner conductors of the coaxial cables may be electrically coupled to each other, such as by soldering. When disposed within the cable lumen of the catheter shaft 12, the pair of coaxial cables will extend parallel to one another through the cable lumen.

[0120] Each of the outer conductors of the coaxial cables may have multiple wires that are bundled together and soldered to the backing support member 218, electrically coupling the inner electrode of the transducer 200 (e.g., electrode 204 in FIGS. 11C and 11D ) to the coaxial cable via the backing support member 210 (in embodiments where the backing member is conductive and electrically connected to the inner electrode 204). The proximal ends of the outer tubular conductive shields of the coaxial cables may similarly be bundled together and / or soldered.

[0121] The wires of the electrical cable soldered to the proximal end of the transducer 200, more specifically the inner electrode 204 and outer electrode 205 of the transducer 200, and even more specifically the stepped portion 250 and backing support member 210, may contain sharp edges that could damage the balloon 14 within which the transducer 200 is disposed. In balloon-less embodiments, such wires could damage the distal portion of the catheter 10 and the body cavity within which the transducer 200 is positioned.

[0122] Referring to FIG. 3D , according to certain embodiments, a dielectric tube 290 is disposed over the distal ends of the wires of the electrical cable that are soldered to the proximal end of the transducer 200 (e.g., its stepped portion 250) and over the distal end of the backing support member 210 to cover the sharp edges of the wires. Such a dielectric tube 290 may be fabricated from, but is not limited to, polyimide. A liquid resin 291 or other type of adhesive with a high dielectric breakdown threshold may be injected into at least a portion of the dielectric tube and then UV- or heat-cured to act as a potting compound for the wires. Similarly, an additional dielectric tube 292 may be disposed over the distal portion of the transducer 200 and the distal portion of the backing support member 210 and secured in place using a UV- or heat-cured liquid resin 293 or other type of adhesive with a high dielectric breakdown threshold. The dielectric strength of the dielectric tubes 290, 292 and resin or other type of adhesive 291, 293 should be at least 40 volts / mil (1 mil is 1 / 1000 inch) and can be in the range of 40 volts / mil to 400 volts / mil, but is not limited to this. In certain embodiments, adhesive-lined heat shrink tubing can be used to provide the dielectric tubes 290, 292 and resin or other type of adhesive 291, 293.

[0123] In certain embodiments, instead of providing a stepped portion 250 at the proximal end of transducer 200, transducer 200 has a flat portion at the proximal end, which is used as a location where the inner conductor of the coaxial cable is soldered to transducer 200 instead of stepped portion 250. The solder leaves the flat portion of transducer 200 as a dead section. In certain embodiments, the axial length of the flat portion of transducer 200 is about 0.4 mm, and the axial length of the non-flat portion of transducer 200 is about 6 mm.

[0124] Air-bag transducers have a design that provides an air layer on the inner surface of the active element. The interface between the air and the element is highly reflective because the acoustic impedance of air is much lower than that of ceramic. This interface can act as a backing interface and help direct acoustic vibrations through the outer surface of the tubular element, which acts as the front or radiating surface of the transducer.

[0125] Airbag transducers can offer good efficiency and can be compact, although the radiant power of such transducers can be limited by thermal considerations. Air and other gases can provide only limited cooling of the inner surface of the active element. To avoid overheating of the transducer, the power of the applied drive signal can be limited. This problem can be particularly acute for small transducers for applications such as ablation. In some embodiments, fluid within a balloon surrounding the transducer contributes to cooling and thermoregulation of the transducer. In some embodiments, the transducer can be cooled and / or thermoregulated by direct contact with blood (in balloon-less embodiments).

[0126] According to some embodiments, one challenge in designing transducers that deliver large powers (greater than about 10 acoustic watts per square centimeter of transducer surface) is preventing degradation of adhesives or other heat / vibration sensitive materials in close proximity to the transducer. If degradation occurs, the material below or above the transducer may delaminate, creating voids that can adversely affect the acoustic coupling and impedance of the transducer. If an air backing for the transducer is used, material degradation can result in liquid ingress into the air space, degrading the transducer's performance.

[0127] The use of adhesives / epoxies in current designs does not provide control over the amount of adhesive applied to the unit. This can result in adhesive seepage on the backside of the transducer, which can result in the transducer overheating and reduced performance of the transducer. Embodiments herein also provide efficiencies in manufacturing capabilities. The use of adhesives in airbags can be difficult to control and prevent degradation. The embodiments disclosed herein provide an improved method of sealing the transducer to prevent electrical shorts.

[0128] [Improved uniformity] In the case of air-backed devices, device uniformity is largely dependent on the concentricity of the piezoelectric transducer, rather than on the interaction between the transducer and the backing support. Ablation can therefore be more uniform. The dependency of device performance on the transducer assembly process can be significantly reduced. The average uniformity is improved, indicating a more uniform circumferential energy delivery is provided.

[0129] [Increased efficiency] Air behind the transducer can ensure that the acoustic waves emanate primarily from the outer diameter (OD) of the transducer.

[0130] [Saline compatibility] Because the inner diameter (ID) of the transducer is separated from the coolant, more options for saline compatibility may be available.

[0131] If the soldering process is imperfect, the adhesive seal can provide another air-bag-style barrier layer to prevent liquid ingress into the ID (inner diameter) space. Because the ID is completely isolated, selective insulation can be provided, which can enable saline compatibility. Coating all or substantially all exposed surfaces with parylene, with or without the adhesive seal, can also enable saline compatibility. The seal can be provided to withstand voltages in excess of 80 VDC per minute.

[0132] [Compactness] The OD (outer diameter) profile of the transducer can be reduced to allow for implementation of a 4F / 5F catheter. As used herein, a 4F catheter is a catheter compatible with a 4F guide catheter, and a 5F catheter is a catheter compatible with a 5F guide catheter. In contrast to liquid-backed or water-backed transducers, air-backed transducers do not need to be manufactured with tight tolerances between the transducer and the backing support, such as a quarter-wave design. Post-machining annealing to reduce residual stresses may also improve durability.

[0133] The airbag and electrically isolated configurations may allow the OD (outer diameter) of the device to be reduced to accommodate smaller catheter sizes. Arrays of transducers may be provided with varying thicknesses and / or operating frequencies on the same backing support. For example, in a 4F / 5F device, the ID (inner diameter) and OD (outer diameter) of the transducers may be reduced due to the airbag configuration. Asymmetries may also exist, such as rings of different OD (outer diameter) for the backing support (e.g., the distal end may be smaller than the proximal end for easier installation or to reduce plating loss during manufacturing and / or use).

[0134] 4A shows a two-piece backing support member 210 having backing support member elements positioned primarily distal and proximal to the transducer 200, according to some embodiments. Each backing support member element may include a standoff post 212 for coupling to the transducer 200. The body of the transducer 200 may be positioned between the proximal and distal standoff posts 212, above the air chamber 230 and above the catheter shaft 12 and / or hypotube. The two-piece backing member 210 may allow the backing support member 210 to be constructed around the transducer 200 without milling the inner diameter (ID) of the transducer 200.

[0135] FIG. 4B shows a continuous backing support member 210, according to some embodiments. Alternatively, or in combination with having a stepped portion 250 as shown in FIG. 4B, the transducer 200 can be chamfered at the end of the transducer 200. The chamfered end can be another way of providing a non-vibrating portion of the transducer 200. The chamfered end of the transducer 200 can be a non-vibrating portion, while the rest of the transducer 200 is free to vibrate. In this embodiment, there can be better symmetry of the acoustic energy distribution, as shown in FIG. 10B.

[0136] The transducer 200 of FIGS. 4A and 4B has a dual-step design with a step 250 at the proximal and distal portions of the transducer 200. Creating a transducer with a symmetrical geometry can provide symmetry in the acoustic energy distribution. Having a dual-step design can restrain the transducer 200 from vibrating at the step 250, allowing the body of the transducer 200 to vibrate. A coating or adhesive bonded to the non-vibrating step 250 of the transducer 200 can provide improved isolation. In some embodiments, the transducer 200 can have one step, two step, or no step. In some embodiments, there can also be a slot 252 for aligning the transducer 200. Additionally or alternatively, the acoustic performance of the ultrasound transducer 200 can be maintained even when constrained by approximately 0.01 inches at the distal / non-step end.

[0137] In some embodiments, multiple transducer assemblies may be positioned within one or more balloons on a single catheter.

[0138] Electrical conductors may be connected to the transducer assemblies. A first electrical conductor may connect to the backing support member 210. A second electrical conductor may connect to the outer electrode of the most proximal transducer assembly and connect the outer electrode to a generator via a cable system through the catheter shaft. A third electrical conductor may extend from the outer electrode of the distal transducer assembly through an opening to the lumen of the backing support member 210 and into the catheter shaft. The electrical conductor may connect the outer electrode of the transducer assembly to the generator via a cable system through the catheter shaft.

[0139] During operation of the transducer assemblies, the backing support member 210 may function as a common return for electrical energy applied to one or more transducer assemblies. As a result, the electronics can independently activate multiple transducer assemblies by applying a voltage between the external electrode of a selected transducer assembly and the backing support member 210. Alternative arrangements of electrical conductors can be used to allow independent operation of all or different selections of transducer assemblies.

[0140] The electrical conductors can be wires, but other electrical conductors can also be employed. For example, a conductive adhesive can function as one or more electrical conductors. The conductive adhesive can be used in combination with a substrate. For example, the conductive adhesive can have one or more characteristics selected from the group consisting of being on one side of the substrate, being on both sides of the substrate, being supported by the substrate, or being positioned with the substrate by mechanisms such as absorption or other impregnation. In one example, the conductive adhesive can be included in a layer on the tape, replacing the third electrical conductor. Suitable conductive adhesives include, but are not limited to, conductive epoxies, adhesive metal films, mixtures including epoxy and acrylates impregnated with silver-coated glass beads, etc. Suitable substrates include, but are not limited to, plastics such as polyethylene terephthalate (PET).

[0141] At least a portion of the bridge portion of the backing support member extending between adjacent transducer assemblies may include one or more regions of increased flexibility, which may be selected to increase the flexibility of the backing support member 210 and, correspondingly, the catheter. For example, a portion of the backing support member 210 having an increased flexibility region may be more flexible and / or flexible than one or more portions of the backing support member 210 that do not have an increased flexibility region.

[0142] Suitable regions of increased flexibility include, but are not limited to, a plurality of openings through the wall of the backing support member 210 arranged in a pattern, a backing support member 210 cut into a grid pattern, and the like.

[0143] The openings may be spiral around the longitudinal axis of the backing support member 210 for portions of the backing support member 210 located between adjacent transducer assemblies. As a result, at least one enhanced flexibility portion of the backing member 210 may have a helical or substantially helical configuration for a portion of the longitudinal length of the backing support member 210. In some cases, the enhanced flexibility region does not extend into any of the multiple transducer assemblies within the balloon.

[0144] The helical rate may be measured in degrees that the helical form rotates around the longitudinal axis of the backing support member per unit length of the longitudinal axis. The helical rate may determine the degree of flexibility of the enhanced flexibility portion of the backing support member 210. For example, increasing the helical rate may provide a more flexible backing support member 210, while decreasing the helical rate may provide a stiffer backing support member 210. Suitable helical rates (pitch numbers) include, but are not limited to, rates greater than 0° / mm, and may be greater than 360°, or greater than 720°.

[0145] Multiple transducer assemblies can be used within a single balloon, increasing the flexibility of the catheter. Increased flexibility can provide access to smaller diameter body lumens, such as the accessory renal arteries and renal artery branches (e.g., vessels with diameters less than 3 mm), aid in catheter manipulation within tortuous anatomical structures, and / or reduce transducer assembly misalignment due to placement of the transducer assembly at curves within a body lumen. When it becomes more desirable to treat smaller and / or more tortuous spaces, the transducer assembly can be split into multiple smaller transducer assemblies.

[0146] In some embodiments, the electrical connections can be arranged to provide the electronics with the ability to independently operate the transducer assemblies. In some embodiments, the electrical connections can be arranged for simultaneous operation of the transducer assemblies. For example, the transducer assemblies can be connected in parallel or in series.

[0147] In some embodiments, two transducer assemblies are provided, but a single catheter may include more transducer assemblies, such as, but not limited to, three, four, five, six, or more transducer assemblies, all of which may be connected in series by electrical conductors that may connect the outer electrodes of each pair of transducer assemblies to each other and ultimately connect the most proximal outer electrode of the most proximal transducer assembly to the generator via a cable system that extends through the catheter shaft to the generator.

[0148] 5A and 5B, the catheter system of the present disclosure can be used to uniformly and circumferentially deliver energy using airbag-style transducers. For example, as shown in FIG. 5A, multiple annular ablation regions (or lesions) 501 can be created around a patient's renal arteries, accessory arteries, or proximal side branches.

[0149] Certain embodiments described herein provide a method for ablating target tissue. A catheter 10 including an ablation element can be advanced through at least one body vessel to a location at or near the target tissue. The ablation element can have a piezoelectric component, such as an ultrasound transducer 200, a backing support member 210, and an air chamber 230 therebetween. The piezoelectric component of the ablation element can be energized to deliver energy to the target tissue, thereby ablating the target tissue. The target tissue can include one or more nerves or nerve branches. The catheter 10 can be advanced through at least the radial artery. In some embodiments, the target tissue includes one or more renal nerves or renal nerve branches, and the catheter 10 is advanced from at least the radial artery into one or more renal arteries. The catheter 10 can have a size of 5 French or less. The catheter 10 can be advanced through an introducer having a size of 5 French or less to access a body vessel. The catheter 10 may be sized to be advanceable through at least the radial artery. The target tissue may have one or more renal sympathetic nerves or renal sympathetic nerve branches, and the catheter 10 may be sized to be advanceable from the radial artery into one or more renal arteries. The catheter 10 may have a size of 5 Fr or less. The catheter 10 may be configured to be advanced through an introducer having a size of 5 Fr or less to access a blood vessel within the body.

[0150] In one embodiment, a piezoelectric component, e.g., an ultrasonic transducer 200, may be energized at a frequency of 11 MHz to 15 MHz, or both frequencies, for a period of 5 to 20 seconds. In one embodiment, a piezoelectric component may be energized at a frequency of 12 MHz to 14 MHz, or both frequencies, for a period of 6 to 10 seconds. In one embodiment, a piezoelectric component may be energized at a frequency of about 13 MHz, or both frequencies, for approximately 7 seconds. In one embodiment, energizing the piezoelectric component may increase the temperature of the piezoelectric component by a temperature of 50°C or less. In one embodiment, energizing the piezoelectric component may increase the temperature of the piezoelectric component by a temperature of 50°C or less. In one embodiment, energizing the piezoelectric component may increase the temperature of the piezoelectric component by a temperature of 50°C or less, for an average surface acoustic intensity of 20 W / cm. 2 ~150W / cm 2 of energy can be delivered.

[0151] [Experiments and Tests] Referring to Figures 6A and 6B, tests were conducted to evaluate the uniformity of ablation regions or lesions produced by airbag and waterbag ultrasound transducers. Figure 6A shows a graph of the uniformity ratio, or UR (the ratio of maximum energy release to minimum energy release across the energy-emitting surface of the transducer), of various ablation regions or lesions produced by airbag and waterbag transducers. As shown in the graph of Figure 6A, the use of airbag transducers resulted in improved average uniformity, indicating more uniform circumferential energy delivery. The average uniformity ratio for all 147 transducers tested was 0.757615, the average uniformity ratio for the 47 airbag transducers tested was 0.797581, and the average uniformity ratio for the 95 waterbag transducers tested was 0.737842. Further analytical data is shown in the table of Figure 6B. The manufacturing yield of ultrasound transducers that deliver energy with at least a particular uniformity challenge (e.g., 0.74) can be increased because a higher percentage of manufactured airbag ultrasound transducers have higher uniformity of energy delivery.

[0152] Referring to Figures 7A-7D, destructive testing was performed on various airbag and waterbag transducers. The transducers were supplied with powers ranging from 10 W to 100 W, and the acoustic output (in watts) was measured. The acoustic output (sound power) increases smoothly with increasing power until the transducer breaks, at which point it drops sharply and loses energy conversion efficiency. As shown in Figure 7A, 11 waterbag transducers were tested, with the first failure occurring near 45 W of power, further failures occurring between 50 W and 85 W, and only one transducer not failing at 90 W. As shown in Figure 7B, 11 airbag transducers were tested, with no failures occurring until near 60 W, further failures occurring between 70 W and 90 W (with three failures occurring between 80 W and 90 W), and five transducers not failing at 90 W. These results indicate that the airbag transducer is more durable than the waterbag transducer. Figures 7C and 7D show graphs combining the destructive test data for both transducer types.

[0153] (W / cm 2 The power density in units of Ω can be calculated using the following relationship: Power density (W / cm 2 )=Sound power(W) / (2*pi*r*h) where r is the radius of the transducer and h is the effective length of the transducer. If the radius of the transducer is 0.0762 cm and the effective length of the transducer is 0.575 cm, then the power density (W / cm) for an airbag transducer that will survive 90 W (i.e., will not fail at an acoustic power of 90 W) is: 2 )=Sound output (W) / (2*pi*r*h)=90W / (2*pi*0.0762cm*0.575cm)=372(W / cm 2 ), so they are about 372 (W / cm 2 ) power density.

[0154] FIG. 8A shows a diagram of the nerve distribution around the renal artery. The majority of nerves are within 6 mm of the inner wall of the renal artery. Therefore, directing the majority of the ablation energy within this 6 mm boundary can be desirable and energy-efficient. FIG. 8B shows a comparison of the cross-sections of an ultrasound transducer operating at 9 MHz, a smaller, thinner ultrasound transducer operating at 15 MHz, and a smaller ultrasound transducer configured for delivery through a 5 Fr or smaller introducer as described herein. FIG. 8C shows an image of an ablation region or lesion 801 created on test chicken breast tissue using a 9 MHz transducer. FIG. 8D shows an image of an ablation region or lesion 802 created on test chicken breast tissue using a 15 MHz transducer. At higher operating frequencies, the ablation region or lesion created can be more uniform and better controlled. Furthermore, as shown in Figure 8E, at 15 MHz, most of the delivered energy is delivered to distances of 6 mm or less (65% compared to 46% at 9 MHz), improving energy targeting specificity and safety.

[0155] Figures 9A and 9B show a comparison between high-frequency transducers. Figure 9A shows a comparison of ultrasound transducers set to operate at 9 MHz, 12 MHz, and 15 MHz. At 12 MHz, less than 43% of the remaining energy is transmitted beyond 6 mm. At 15 MHz, less than 35% of the remaining energy is transmitted beyond 6 mm. Figure 9B shows a graph of relative heating power versus distance from the transducer surface for a theoretical tissue model. From 0 to 2 mm, the tissue can be cooled by the inflated balloon surrounding the transducer (i.e., the "cooling zone"). From 2 to 6 mm, the delivered energy can create a lesion (damage) (i.e., the "lesion zone"). As shown in Figure 9B, comparing the heating power profiles of transducers operating at 12 MHz and 15 MHz, the 12 MHz transducer has higher heating power at distances less than approximately 6 mm and lower heating power at distances greater than approximately 6 mm.

[0156] Figures 10A and 10B illustrate how the intensity of acoustic energy may appear in three-dimensional space. Figures 10A and 10B illustrate normalized acoustic energy across the axial length of a transducer, measured from the axial center of the transducer. Figure 10A illustrates lobe asymmetry (e.g., acoustic energy distribution) without a dual step design, according to one embodiment. Instead, transducer 200 has steps 250 only at the proximal end of transducer 200. Figure 10B illustrates lobe symmetry with a dual step design, according to one embodiment. Steps 250 are located at the proximal and distal ends of transducer 200, making transducer 200 more symmetric. This symmetry of transducer 200 provides symmetry in the acoustic energy distribution. Alternatively, instead of providing stepped sections 250 at the proximal and distal ends of transducer 200, the inner conductor of the coaxial cable is soldered to transducer 200 in the inactive area of ​​the transducer created by an airbag solder seal. The solder seal can be located in a non-vibrating portion of the transducer. While the solder seal may create a dead section, because it is located in a non-vibrating portion of the transducer, it does not significantly affect the acoustic output, and the lobe symmetry is similar to the dual stepped section design shown in FIG. 10B without increasing the length of the transducer. In a specific embodiment, the axial length of the solder seal portion of transducer 200 is approximately 0.4 mm or less, and the axial length of the non-solder seal portion of transducer 200 is approximately 6 mm or less.

[0157] When the acoustic energy distribution is more symmetric, there can be a more uniform and circumferential delivery of acoustic energy at the ablation site.

[0158]

[0013] Figure 11A is a side view of a distal portion of a catheter (e.g., 10) of an ultrasound-based tissue treatment system including an airbag-type transducer 200 in accordance with certain embodiments of the present technology. The airbag-type transducer 200 may also be referred to simply as a transducer 200. Figure 11B is a perspective view of the transducer 200 in accordance with certain embodiments of the present technology. Figures 11C and 11D show longitudinal and radial cross-sectional views of the transducer 200, respectively.

[0159] In the embodiment of Figures 11A-11D, the piezoelectric transducer body 208 comprises a hollow tube of piezoelectric material having an inner surface and an outer surface, with an inner electrode 204 disposed on the inner surface of the hollow tube of piezoelectric material and an outer electrode 205 disposed on the outer surface of the hollow tube of piezoelectric material. In such an embodiment, the hollow tube of piezoelectric material is an example of a piezoelectric transducer body 208. In Figures 11A-11D, the hollow tube of piezoelectric material (more generally, the piezoelectric transducer body 208) is cylindrical and has a circular radial cross-section, as can be seen in Figure 11D. However, in alternative embodiments, the hollow tube of piezoelectric material can have other shapes besides a cylinder with a circular radial cross-section. Other cross-sectional shapes for the hollow tube of piezoelectric material (more generally, the piezoelectric transducer body 208) include, but are not limited to, an oval or elliptical cross-section, a square or rectangular cross-section, a pentagonal cross-section, a hexagonal cross-section, a heptagonal cross-section, an octagonal cross-section, etc.

[0160] The hollow tube of piezoelectric material, or more generally, the piezoelectric transducer body 208, can be fabricated from a variety of different types of piezoelectric materials, such as, but not limited to, lead zirconate titanate (PZT), polyvinylidene fluoride (PVDF), or other piezoelectric ceramic materials currently available or developed in the future. As shown in FIGS. 11A-11C, the transducer 200 can include a stepped portion 250, as described in U.S. Pat. No. 10,456,605, the entire contents of which are incorporated herein by reference. In certain embodiments, the stepped portion 250 at the proximal end of the transducer 200 allows for attachment of an electrical conductor 20 (of an electrical cable) that delivers energy to the transducer 200. In certain embodiments, such an electrical cable comprises a parallel coaxial cable having an overall impedance of approximately 50 ohms. Such a stepped portion 250 can be incorporated into any of the transducers described herein. It is also possible to include steps (identical or similar to 250) on both the proximal and distal ends of the transducer, and such an embodiment may be referred to as a dual step embodiment.

[0161] 11A, the backing support member 210 may have an insulating tube 219 along its inner surface to prevent or reduce the possibility of electrical conduction between the guidewire and the backing support member 210 and may be used in embodiments where such electrical conduction is undesirable. The insulating tube 219 may be formed of a non-conductive material (e.g., a polymer such as polyimide) and may also be referred to as an electrical insulator. The insulating tube 219 may extend from the catheter shaft 12 through the lumen of the backing support member 210 within the transducer 200 to the tip 215.

[0162] 11C, according to a specific embodiment suitable for renal denervation surgery, the outer diameter (OD) of the piezoelectric transducer body 208 is in the range of approximately 1.3 mm to 1.7 mm, and the inner diameter (ID) of the piezoelectric transducer body 208 is in the range of approximately 0.8 mm to 1.2 mm. In a specific embodiment, the OD is approximately 1.5 mm, and the ID is approximately 1 mm. According to a specific embodiment, the wall thickness (W-TH) between the inner diameter (ID) and the outer diameter (OD) of the piezoelectric material of the piezoelectric transducer body 208 is in the range of 0.2 mm to 1.0 mm. More specifically, the wall thickness (W-TH) can be in the range of 0.2 mm to 0.5 mm. Even more specifically, the wall thickness (W-TH) can be in the range of 0.24 mm to 0.26 mm (and even more specifically, 0.25 mm ± 0.01 mm), which can provide an ultrasound transducer that generates acoustic energy having a frequency of approximately 9 MHz. In certain embodiments, ultrasound transducers described herein (e.g., 200, 300, etc.) are configured to deliver acoustic energy in the 8.5-9.5 MHz frequency range. In certain embodiments, such transducers are configured to deliver acoustic energy in the 8.7-9.3 MHz or 8.695-9.304 MHz frequency range. Transducers delivering acoustic energy in the 8.7-9.3 MHz frequency range have been shown (proven) to produce ablations up to an average depth of 6 mm. The piezoelectric transducer body 208 and the inner and outer electrodes 204, 205 may be formed using any suitable method, such as that described in U.S. Pat. No. 10,140,041 to Taylor, the entire contents of which are incorporated herein by reference. The aforementioned dimensions and thicknesses are described with reference to the embodiment shown in FIGS. 11A-11D, but also apply to other embodiments described herein, including those described below.

[0163] The piezoelectric transducer body 208 is configured to generate ultrasound waves in response to a voltage applied between the inner electrode 204 and the outer electrode 205. Because the inner electrode is located within the air chamber 230, shorting between the inner electrode 204 and the outer electrode 205 is prevented, even if the ultrasound transducer 200 is placed in a conductive fluid and a voltage is applied between the inner electrode 204 and the outer electrode 205. More specifically, the electronics 22 may be electrically coupled to the inner electrode 204 and the outer electrode 205 via an electrical cable, and may activate the transducer 200 (or any other transducer described herein) by applying a voltage between the inner electrode 204 and the outer electrode 205 (or any other electrode pair described herein), causing the piezoelectric material of the piezoelectric transducer body 208 to generate unfocused ultrasound waves that radiate radially outward.

[0164] In certain embodiments, the ultrasound transducer 200 is disposed within a balloon (e.g., 14) at least partially filled with a cooling fluid, which is used to cool a portion of the body cavity BL within which the ultrasound transducer 200 may be positioned. In certain embodiments, the cooling fluid is a conductive fluid, such as, but not limited to, saline, non-pure water, sodium lactate solution, or combinations thereof. In alternative embodiments, which may be referred to as balloon-less embodiments, the ultrasound transducer 200 is directly exposed to the blood flowing through the body cavity BL within which the ultrasound transducer may be positioned, in which case the conductive fluid includes blood. In yet other embodiments, the airbag ultrasound transducer 200 is disposed within a balloon, but the cooling fluid is not circulated or flows through the balloon. Bench testing has shown that the lack of flow within the balloon can adversely affect the durability of waterbag ultrasound transducers and can reduce their acoustic output. Beneficially, bench testing has shown that the airbag transducers described herein can operate successfully under no-flow conditions. Use of the no-flow embodiment reduces the system footprint by eliminating the need for a cooling fluid cartridge and may also aid in the introduction of near-field lesions.

[0165] In the foregoing embodiments, with reference to the foregoing figures, the transducer 200 has been shown as having a generally uniform thickness along its longitudinal length, except for a step at one or both longitudinal ends of the transducer 200. According to certain embodiments described below, the transducer has different thicknesses at different locations on the transducer, and the variations in the transducer thickness can control and / or adjust the direction of acoustic signals away from the transducer, thereby directing the acoustic signals to a treatment site. This ability to direct acoustic signals allows the acoustic signals to be directed to desired targets, such as nerves, cancer cells, cardiac tissue, and / or features such as calcification and / or plaque. Furthermore, this ability to direct acoustic signals also allows the acoustic signals to be directed away from non-target tissue, such as lymph nodes, hypoaxial skeletal muscle with fibrous sheaths, peritoneum, periaorthenial vessels, calcifications, organs (e.g., ureters, intestines, liver, pancreas, urethra, renal pelvis, bladder, liver, pancreas, spleen, and kidneys), and / or features such as calcifications and / or plaque. Furthermore, varying the thickness of the transducer allows the catheter to more selectively ablate targets at long and / or short distances. Some transducers operating at lower frequencies can be used to target deeper regions. Some transducers operating at higher frequencies can be used to target closer regions. Transducers with varying thicknesses, described below, are referred to as transducers 300. A transducer 300 having a varying thickness may be used in place of a transducer 200 having a generally uniform thickness along its longitudinal length in any of the embodiments described above with reference to Figures 1A to 11.

[0166] Figure 12A is a cross-sectional view of the distal end of the catheter taken along the longitudinal axis of the catheter. Figure 12B is a cross-sectional view of the catheter shown in Figure 12A taken along line B in Figure 12A. Figure 12C is a cross-sectional view of the catheter shown in Figure 12A taken along line C in Figure 12A. Figure 12D is a side view of the distal end of the catheter shown in Figure 12A. The balloon 14 can be positioned between the catheter shaft 12 and the tip member 15. The balloon 14 can be secured along the exterior of the catheter shaft 12 and / or the exterior of the tip member 15. Suitable mechanisms for securing the balloon 14 to the exterior of the catheter shaft 12 and / or the exterior of the tip member 15 include, but are not limited to, friction fit; adhesive mechanisms such as glue, adhesive, or epoxy; mechanical attachment mechanisms such as retainers, locking rings, or clamps (e.g., ring clamps or hose clamps); welding, such as laser welding or heat welding; and combinations thereof.

[0167] In one embodiment, a transducer assembly 302 is positioned within the balloon 14. The transducer assembly 302 may include a transducer 300. The transducer may have an inner surface and an outer surface. An inner electrode 36 may contact the inner surface and extend along the length of the transducer 300. An outer electrode 38 may contact the outer surface and extend along the length of the transducer 300. Suitable materials for the transducer 300 include, but are not limited to, piezoelectric materials, including piezoelectric ceramics, piezoelectric crystals, and piezoelectric polymers, and acoustic microelectromechanical system (MEMS) transducers, such as piezoelectric micromachined ultrasound transducers (PMUTs) and capacitive micromachined ultrasound transducers (CMUTs). Examples of suitable piezoelectric materials include, but are not limited to, lead zirconate titanate (PZT), CMUTs, and PMUTs. In certain embodiments suitable for use in renal denervation, the transducer 300 material includes or is composed of lead zirconate titanate 8 (PZT8), also known as Navy III piezoelectric material. In certain embodiments, the PZT8 is hot isostatically pressed (HIP). The raw PZT transducer may be plated with layers of copper, nickel, and / or gold to create the inner electrode 36 and outer electrode 38. Additionally or alternatively, the transducer 300 may be an airbag-style transducer according to one embodiment described herein. Advantageously, using an airbag-style directional, non-concentric transducer allows for more compact and efficient tissue targeting without affecting acoustic efficiency, since the backing support member 42 can be non-concentric within the transducer assembly 302.

[0168] FIG. 12A shows a fluid lumen 40 within the catheter shaft 12. The lumen 40 includes a fluid port 41 that allows fluid to be exchanged between the fluid lumen 40 and the interior of the balloon 14. As a result, the fluid lumen 40 and the interior of the balloon 14 are in fluid communication. Thus, the fluid lumen 40 provides fluid communication between the interior of the balloon 14 and one of the conduits 26 disclosed in the context of FIG. 1 . The catheter system can be configured to pump fluid into the interior of the balloon 14 through the fluid lumen 40 and / or to withdraw fluid from the interior of the balloon 14 through the fluid lumen 40. As a result, the fluid can be used to inflate and deflate the balloon 14. Alternatively, the catheter shaft 12 can include multiple fluid lumens 40, each opening into the interior of the balloon 14. The catheter system can be configured to pump fluid into the interior of the balloon 14 through a first selection of the fluid lumens 40 and withdraw fluid from the interior of the balloon 14 through a second selection of the fluid lumens 40. The relative flow of fluid into and out of the balloon 14 can be varied to inflate the balloon 14, deflate the balloon 14, or maintain a steady level of inflation of the balloon 14.

[0169] In some cases, the fluid is a liquid. Fluid inside the balloon 14 may contact the transducer assembly 302. For example, the fluid may contact the transducer 300, the inner electrode 36, and / or the outer electrode 38. As a result, the fluid may provide cooling for the transducer assembly 302. In some cases, the fluid source 28 disclosed in the context of FIG. 1 is configured to pre-cool the fluid and / or store pre-cooled fluid. As a result, the fluid is cooled before entering the fluid lumen 40 and / or the interior of the balloon 14. Suitable temperatures for the pre-cooled fluid include, but are not limited to, temperatures from the freezing point of the fluid to room temperature, and / or temperatures above 0° C., 15° C., or 25° C. and / or below 20° C., 25° C., or 37° C. Examples of suitable fluids include, but are not limited to, sterile water, dextrose, saline, or other suitable cooling fluids.

[0170] A backing member 42 may be positioned within the acoustic transducer 300. In some cases, the backing member 42 is also positioned within the inner electrode 36. The inner electrode 36 and / or the transducer 300 may surround and / or define an opening or void within which the backing member 42 is positioned. As is apparent from FIG. 12A , the backing member 42 may extend beyond both ends of the transducer 300. The backing member 42 extends from the distal end of the catheter shaft 12 to the tip member 15. One end of the backing member 42 is received within a recess 44 in the distal end of the catheter shaft 12, and the opposite end of the backing member 42 is received within a recess 44 in the tip member 15.

[0171] A backing member lumen 46 extends longitudinally through the backing member 42. An electrical insulator 48 may be positioned within the backing member lumen 46. A second guidewire lumen 50 extends longitudinally through the backing member 42 and may be defined by the electrical insulator 48. The second guidewire lumen 50 is aligned with a guidewire lumen 51 extending longitudinally through the catheter shaft 12. The guidewire lumen 51 and the second guidewire lumen 50 are sized to receive (accommodate) a guidewire (not shown). The electrical insulator 48 is positioned to electrically insulate the backing member 42 from a guidewire received in the second guidewire lumen 50. Suitable materials for the electrical insulator 48 include, but are not limited to, polyimide, other polymeric or elastomeric materials, and other natural or synthetic materials. The backing member 42 may be constructed of an electrically conductive material. Suitable materials for the backing member 42 include, but are not limited to, tungsten, steel, and aluminum.

[0172] The second guidewire lumen 50 is aligned with the lumen of the tip member 15. The lumen of the tip member 15 is also sized to receive a guidewire (not shown). As a result, the catheter can be moved along a guidewire positioned within the guidewire lumen, the second guidewire lumen 50, and the lumen of the tip member 15.

[0173] One or more spacing elements 54 may be positioned between the backing member 42 and the transducer assembly 302. The spacing elements 54 may be configured to maintain a spacing between the backing member 42 and the transducer assembly 302. The spacing elements 54 may include a plurality of spacers 56 extending away from a spacer body 58. An opening may extend through the spacer body 58. The opening may be sized to accommodate the backing member 42, thereby allowing the spacer body 58 to surround the backing member 42.

[0174] The spacer 56 may contact the interior of the transducer assembly 302 at one or more contact locations. For example, the spacer 56 may contact the inner electrode 36 at one or more contact locations. The contact locations may be selected to allow fluid within the balloon 14 to flow into contact with the interior of the transducer assembly 302 and the exterior of the backing member 42 while maintaining the relative positions of the transducer 300 and backing member 42. In some cases, the contact locations are selected to maintain the backing member 42 concentric within the transducer assembly 302 and are configured to allow fluid within the balloon 14 to flow through the backing member 42 into contact with the interior of the transducer assembly 302 and / or from contact with the interior of the transducer assembly 302.

[0175] FIG. 12B illustrates a first set of contact locations at the same location along the length of the longitudinal axis (L). The contact locations in FIG. 12B are spaced apart from one another and positioned around the longitudinal axis of the backing member 42. The spacing between the contact locations is the result of openings between the spacers 56, which allow fluid to flow into the interior of the transducer assembly 302. FIG. 12B illustrates three spacers 56 spaced approximately equally apart at 120° from one another as measured from the longitudinal axis of the backing member 42. However, the quantity, shape, size, orientation, spacing, and / or other details of the spacers 56 may be varied as desired or required depending on the particular design or application.

[0176] One or more of the spacing pieces 54 may be electrically conductive. Suitable materials for the electrically conductive spacing pieces 54 include, but are not limited to, steel, copper, and aluminum.

[0177] 12A, the catheter system includes a second spacing element 54 spaced apart from the spacing element 54 of FIG. 12B along the longitudinal axis of the backing element 42. The spacing elements 54 may be positioned at or near opposite ends of the transducer assembly 302.

[0178] The catheter shaft 12 includes an electrical lumen 64. The illustrated electrical lumen 64 includes a conductor carrier 66. The conductor carrier 66 extends through the wall of the catheter shaft 12 to the interior of the balloon 14. The conductor carrier 66 includes a first electrical conductor 70 that can be connected to the backing member 42. The conductive backing member 42 and the conductive spacing element 54 provide electrical communication between the inner electrode 36 and the first electrical conductor 70. The first electrical conductor 70 is further in electrical communication with the electronics 22 (e.g., a generator) via the electrical coupling 18 and one of the external electrical conductors 20.

[0179] The conductor carrier 66 includes a second electrical conductor 72 that can be connected to the outer electrode 38 of the transducer assembly 302. Further, the second electrical conductor 72 is in electrical communication with the electronics 22 via the electrical coupling 18 and one of the outer electrical conductors 20. As a result, the outer electrode 38 of the transducer assembly 302 is in electrical communication with the electronics 22 via the second electrical conductor 72, the electrical coupling 18, and one of the outer electrical conductors 20.

[0180] The electronics 22 are in electrical communication with the inner and outer electrodes 36, 38 such that application of a voltage and alternating current across the inner and outer electrodes 36, 38 causes the transducer 300 to vibrate transversely to the longitudinal axis of the transducer 300 and emit a radial acoustic signal. In some cases, the transducer 300 is actuated so that the acoustic signal has a desired frequency level.

[0181] The thickness of the transducer 300 is labeled "T" in Figures 12B and 12C. The thickness varies, i.e., the thickness of the transducer 300 is different at different locations around the circumference of the transducer. For example, the thickness of the transducer 300 in Figures 12B and 12C varies smoothly as the location on the transducer moves around the inner surface of the transducer 300. The variation in thickness of the transducer 300 may be the result of the opening defined by the inner surface of the transducer 300 not being concentric with the opening defined by the outer surface of the transducer 300.

[0182] FIG. 12E shows the transducer 300 of FIG. 12C outside the balloon. As a result of the varying thickness of the transducer 300, the direction in which the acoustic signal travels away from the transducer 230 changes in response to changes in the frequency of the applied AC current. This change in direction results from the varying efficiency of the transducer 300 at different applied AC frequencies. Generally, the thickness of the portion of the transducer 300 that generates the acoustic signal is inversely proportional to the frequency of the AC current applied to the transducer 300. As a result, the frequency of the applied AC current can be adjusted to adjust the portion of the transducer 300 that generates the acoustic signal, and the direction in which the acoustic signal travels away from the transducer 300 can be adjusted accordingly. In certain embodiments, portions of the transducer 300 that activate at lower frequencies (thicker portions) are used to target deeper regions (e.g., 4 mm to 10 mm from the lumen of a blood vessel). A portion (thinner portion) of the transducer 300 that activates (operates) at a higher frequency is used to target a closer area (eg, 0.5 mm to 4 mm from the lumen of the blood vessel).

[0183] 12E shows an arrow A representing the direction in which the acoustic signal travels away from the transducer 300. The direction in which the acoustic signal travels away from the transducer 300 may be represented by an angle θ, where the angle θ is measured relative to a measurement line, such as measurement line S in FIG. 12E. Examples of suitable measurement lines include, but are not limited to, a line of symmetry of the outer surface of the transducer. In some cases, the measurement line extends through the center of the outer surface of the transducer, the center of gravity of the outer surface of the transducer, and / or the center of gravity of the transducer.

[0184] 12E includes a graph of an exemplary power distribution of acoustic signal A. The power distribution shows the power levels of acoustic signal A from angle θ denoted by R to angle θ denoted by Q. The angle θ (representative angle) associated with acoustic signal A may be selected to represent a direction in which acoustic signal A moves away from the transducer. For example, the representative angle associated with acoustic signal A may be located at the maximum of the power distribution, the average value of the power distribution over a range of angle θ, or a weighted average value of the power distribution weighted by power and obtained over an angle range of 30°, 90°, or 180°.

[0185] To illustrate the steerable nature of the acoustic signal, arrows B and C are also shown in FIG. 12E. Arrows A, B, and C each represent a different acoustic signal direction away from transducer 300. The acoustic signal represented by arrow A occurs when a higher AC frequency ("first frequency") is applied to transducer 300 compared to the acoustic signal represented by arrow B. Furthermore, the acoustic signal represented by arrow B occurs when a higher AC frequency ("second frequency") is applied to transducer 300 compared to the acoustic signal represented by arrow C. Furthermore, the acoustic signal represented by arrow C occurs when a lower AC frequency ("third frequency") is applied to transducer 300 compared to the acoustic signal represented by either arrow B or arrow A. Thus, different angles are associated with different AC frequency levels.

[0186] Measurement line S in FIG. 12E is a line of symmetry. In one embodiment, a first region of transducer 300 on one side of the line of symmetry has the same thickness as a second region of transducer 300 on the other side of the line of symmetry. As a result, transducer 300 can simultaneously output identical acoustic signals from both opposing regions of transducer 300. For example, the transducer of FIG. 12E can simultaneously output acoustic signals A and A' at a first frequency and with equal power, acoustic signals B and B' at a second frequency and with equal power, and acoustic signals C and C' at a third frequency and with equal power. As a result, a single AC frequency level can be associated with multiple angles θ.

[0187] The transducer 300 of FIG. 12E may be modified so that the region from which an acoustic signal is output can be selected when the transducer 300 has multiple different regions of the same thickness. For example, FIG. 13 shows an example where the transducer 300 of FIG. 12E has been modified so that the outer electrode 38 is divided into a first outer electrode 60 and a second outer electrode 62. The first outer electrode 60 and the second outer electrode 62 are positioned on opposite sides of a line of symmetry (S). The conductor carrier 66 (FIG. 12A) may include three different electrical conductors, including a first electrical conductor 70, a second electrical conductor 72, and a third electrical conductor (not shown). The electronics 22 may be in electrical communication with the inner electrode 36 via the first electrical conductor 70, as described above. The electronics 22 may be in electrical communication with the first outer electrode 60 via the second electrical conductor 72. The electronics 22 may be in electrical communication with the second outer electrode 62 via the third electrical conductor.

[0188] The acoustic signal output from the transducer 300 can be selected by selecting the combination of electrodes to which the AC current is applied. For example, acoustic signal A in FIG. 13 can be selected by applying an AC current between the inner electrode 36 and the first outer electrode 60. The direction of acoustic signal A in FIG. 13 can be adjusted by adjusting the frequency of the applied AC current. Acoustic signal A' in FIG. 13 can be selected by applying an AC current between the inner electrode 36 and the second outer electrode 62. The direction of acoustic signal A' in FIG. 13 can be adjusted by adjusting the frequency of the applied AC current.

[0189] 12E so that the outer electrode 38 is divided into a first outer electrode 60 and a second outer electrode 62, the inner electrode 36 may be divided into a first inner electrode (not shown) and a second inner electrode (not shown). The transducer assembly 302 may be configured such that the electronics are in electrical communication with each of the electrodes via a different conductor selected from the group consisting of a first electrical conductor 70, a second electrical conductor 72, and a third electrical conductor (not shown). As a result, the acoustic signal output from the transducer 300 may be selected by selecting the combination of electrodes to which the alternating current is applied.

[0190] The transducer 300 of FIG. 12E may also be modified to eliminate or reduce the presence of regions of the transducer 300 having uniform thickness. As an example, FIG. 14A shows the transducer 300 of FIG. 12E modified to eliminate regions of uniform thickness. For example, the thickness of the transducer 300 increases from a minimum thickness (Ti) to a maximum thickness (Ta), and then returns to the minimum thickness (Ti) upon reaching the transition region 68. The change from the minimum thickness (Ti) to the maximum thickness (Ta) may be smooth and may extend over an angular range greater than 340° or 355° to 360° or less. The transition region 68 may extend over an angular range θ greater than 0.0°, 30°, 90°, or 180°, and less than 90°, 180°, or 270°. The angle θ may be measured relative to a measurement line (M) extending through the center of the outer surface of the transducer, the centroid of the outer surface of the transducer, and / or the centroid of the transducer.

[0191] Although Figure 14A shows the inner electrode 36 spanning and / or contacting the transition region 68, the inner electrode 36 need not be positioned across and / or in contact with the transition region 68. By way of example, Figure 14B shows the transducer 300 of Figure 14A modified such that the inner electrode 36 is not positioned across and / or in contact with the transition region 68.

[0192] 14A and 14B depict the transducer assembly 302 and the outer electrode 38 as having a circular cross-section, the transducer assembly 302 and / or the outer electrode 38 need not be circular in cross-section. While FIGS. 12A through 13 depict the transducer assembly 302 and the outer electrode 38 as having an oval or substantially oval cross-section, the transducer assembly 302 and / or the outer electrode 38 need not be oval in cross-section. Suitable geometric shapes for the cross-section of one or more components selected from the group consisting of the transducer assembly 302, the transducer 300, the outer electrode 38, and the inner electrode 36 include, but are not limited to, a triangle or any shape.

[0193] The transducer 300 has a thickness extending from a minimum thickness (Ti) to a maximum thickness (Ta), as shown in Figures 12E and 14A. The minimum thickness (Ti) may be associated with a minimum thickness frequency, and the maximum thickness (Ta) may be associated with a maximum thickness frequency. The minimum thickness frequency may represent an alternating current frequency applied to the transducer 300 that causes an acoustic signal to be output from a region of the transducer 300 having the minimum thickness (Ti). For example, the minimum thickness frequency may represent an alternating current frequency applied to the transducer 300 that causes an acoustic signal to be directed away from the transducer 300 in a direction extending from the region of the transducer 300 having the minimum thickness (Ti). The maximum thickness frequency may represent an alternating current frequency applied to the transducer 300 that causes an acoustic signal to be output from a region of the transducer 300 having the maximum thickness (Ta). The maximum thickness frequency may represent the alternating current frequency applied to the transducer 300 that causes an acoustic signal to move away from the transducer 300 in a direction extending from the region of the transducer 300 having the maximum thickness (Ta).

[0194] Suitable minimum thicknesses (Ti) include, but are not limited to, greater than 0.1 mm, 0.5 mm, or 2 mm, and / or less than 5 mm, 3 mm, or 1 mm. Additionally or alternatively, suitable maximum thicknesses (Ta) include, but are not limited to, greater than 0.1 mm, 0.5 mm, or 2 mm, and / or less than 5 mm, 3 mm, or 1 mm. Additionally or alternatively, suitable frequencies of the alternating current applied to the transducer 300 include, but are not limited to, frequencies within a range extending from 1 MHz, 5 MHz, 9 MHz, 12-15 MHz, or frequencies above 20 MHz to frequencies below 20 MHz or below 10 MHz. In one example, the frequency of the alternating current applied to the transducer 300 is within a range extending from frequencies above 8 MHz to frequencies below 15 MHz.

[0195] Referring to the transducer cross-sections of FIGS. 14B and 12E, an angle θ (not shown) may be measured relative to an indicated measurement line M. The measurement line may extend through the apex of the angle at the center of the outer surface of the transducer, the centroid of the outer surface of the transducer, and / or the centroid of the transducer. The angle θ may be determined between the measurement line and a line extending from the outer surface of the transducer to the apex of the angle. While the transducers shown above show a continuous change in transducer thickness over an angle θ equal to or substantially equal to 360°, the transducer may have one or more regions where the transducer thickness does not change. In some cases, the transducer thickness varies continuously over an angle θ between 0° and 360°.

[0196] The transducer assembly 302 and / or the transducer 300 have a length (Lt in FIG. 12A ). In some cases, the transducer cross-section may represent the cross-section of the transducer over the entire length of the transducer 300. In some cases, the transducer assembly 302 and / or the transducer 300 have a length of 0.5 mm or more and / or 12 mm or less and / or a diameter of 3 French or more and / or 10 French or less. In one example suitable for renal denervation and other applications, the balloon-in-transducer assembly 302 and / or the balloon-in-transducer each have a length of 2 mm or more and / or 8 mm or less and a diameter of 3 French or more and / or 6 French or less.

[0197] Although the transducers are illustrated as having elliptical or circular inner and / or outer surfaces, the inner and / or outer surfaces may have other geometric shapes.

[0198] The distal end of the catheter is configured to be inserted into a body cavity of a subject. Examples of suitable body cavities include, but are not limited to, veins and / or arteries, such as the renal arteries. As an example, FIG. 15 is a cross-sectional view of a body cavity 75 having multiple nerves 73 in its adventitia. For example, the body cavity 75 in FIG. 15 may represent a blood vessel, such as a renal artery, having nerves 73 in its adventitia layer. As shown in FIG. 15, the balloon 14, the distal portion of the catheter shaft 12, and the tip member 15 are received within the body cavity 75. As shown in FIG. 15, a guidewire 31 may be used to assist in positioning the catheter within the body cavity 75.

[0199] Nerve 73, shown in Figure 15, is arranged in a bundle above body cavity 75. When it is desired to direct an acoustic signal to nerve 73, the frequency of the alternating current applied to transducer 300 can be selected so that transducer 300 outputs an acoustic signal that travels away from transducer 300 in a direction toward nerve 73. For example, the alternating current applied to transducer 300 can be selected so that the acoustic signal travels in the direction of arrow A in Figure 15. This ability to control the direction of the acoustic signal allows for targeting of nerve 73.

[0200] In some cases, the treatment site within the body cavity 75 may be positioned near a living body 74 that may be damaged by exposure to the acoustic signal. Figure 15 shows a living body 74 close enough to the transducer 300 to be exposed to the acoustic signal from the transducer 300. The ability to control the direction of the acoustic signal can prevent or reduce damage to the living body 74. Examples of living bodies include, but are not limited to, organs such as the intestine, kidney, ureter, renal pelvis, bladder, urethra, liver, pancreas, spleen, and tissues such as lymph nodes and muscle.

[0201] In some cases, it is desirable for the acoustic signal to be applied uniformly around the treatment area. In these cases, the AC frequency applied to the transducer may be swept from a minimum thickness frequency to a maximum thickness frequency. This frequency sweep may be continuous or may be repeated one or more times. The AC frequency applied to the transducer may be swept from a minimum thickness frequency to a maximum thickness frequency, and then back from the maximum thickness frequency to the minimum thickness frequency. This frequency sweep sequence may be repeated one or more times.

[0202] In some cases, the orientation of the transducer 300 within the body cavity 75 may be unknown at the time the transducer 300 is placed at the treatment site. It may be desirable to know the orientation of the transducer 300 in order to direct the acoustic signal to a desired target. One or more receivers may be used to identify the orientation of the transducer 300. As an example, FIG. 16 shows the balloon 14 of a catheter positioned at a treatment site within a patient's body 76. The treatment site includes a nerve bundle or ganglion to which the acoustic signal is to be delivered. A receiver is positioned outside the body 76 to receive the acoustic signal output from the transducer 300. Suitable receivers include, but are not limited to, ultrasound transducers, external magnetic detectors, etc.

[0203] The AC frequency applied to the transducer may be swept across a frequency range. In some cases, the frequency range extends from a minimum thickness frequency to a maximum thickness frequency. The AC frequency that provides the greatest acoustic signal power to a particular receiver 78 during the sweep may be identified. For example, the AC frequency that provides the greatest acoustic signal power to a receiver 78 labeled A during the sweep may be identified.

[0204] The angle associated with the identified frequency (θf) may also be identified and may indicate the angular orientation of the receiver 78 relative to the measurement line (labeled M). As a result of measurements obtained by the imaging device, the angular orientation of the receiver 78 relative to the nerve 73 (labeled θT) may be known. Suitable imaging devices include, but are not limited to, ultrasound imaging systems.

[0205] The value of the angle between the nerve 73 and the measurement line may be determined by adding the angle (θf) associated with the identified frequency and the angular orientation (θT) of the receiver 78 relative to the nerve 73. To apply an acoustic signal to the nerve 73, an alternating current may be applied to the transducer 300 at a frequency associated with the angle θT.

[0206] Although Figure 16 shows a single receiver 78, multiple receivers 78 may be used to verify the accuracy of the identified frequency and / or the accuracy of the angular orientation (θf) of the receiver 78 relative to the measurement line. As will be apparent from the description of Figure 16, the measurement line may serve as a reference line from which other measurements are taken.

[0207] Figure 8 is a side view of an alternative catheter system, which may include all of the components of Figure 16 plus an imaging transducer 17, such as a single element or array transducer, at the distal end of the catheter 10. The imaging transducer 17 may have a center frequency of 15-50 MHz, e.g., 20-30 MHz, and may be utilized to distinguish between target and non-target structures.

[0208] In certain embodiments, the catheter system may additionally or alternatively include electrodes on the balloon 14 configured to sense neural activity and / or confirm the effectiveness of treatment, as disclosed in U.S. Patent Application No. 17 / 813,311 to Zhai et al., filed July 19, 2022, claiming priority to U.S. Provisional Patent Application No. 63 / 306,496, both of which are incorporated by reference in their entireties.

[0209] In certain embodiments, the catheter system may additionally or alternatively include a neural sensing and / or therapy confirmation component as disclosed in U.S. Patent Application No. 18 / 182,821 (PMD00104US), filed March 13, 2023, claiming priority to U.S. Patent Application No. 63 / 320,103. Both of these applications are incorporated by reference in their entirety. As disclosed in further detail in U.S. Patent Application No. 18 / 182,821 and U.S. Patent Application No. 63 / 320,103, the therapy confirmation component may be used to determine the type, size, function, and / or health of the fiber from which the neural response is being sensed by determining the latency of the sensed electrical impulse. The delay (also known as latency) may indicate the depth of the nerve surrounding the biological cavity (e.g., the renal artery) within which the catheter being used to measure the delay is located. According to certain embodiments of the present technology, the aforementioned delay (also known as latency) can be used to select the frequency used for ablation. Electronics 22 control catheter 10 to sweep operating frequencies, controlling the individual and total durations to control the temperature of the ablation region and shape the lesion. Some of the transducers 300 activated at lower frequencies are used to target deeper regions when nerves are determined to be in deeper areas. Some of the transducers 300 activated at higher frequencies are used to target closer regions when nerves are determined to be in closer areas. The imaging transducer 17 can be positioned in front of or behind balloon 14. The imaging transducer 17 can consist of a single ring or a ring array with multiple rings. The imaging depth can be up to approximately 12 mm and can be used to image vessel size, anatomical structure, pathology, vessel wall, plaque, calcification, tissue layers, and nerves. The imaging frequency may be approximately 20 MHz to 35 MHz, the bandwidth may be 10 MHz or more, and the array size may be comprised of 16 to 256 elements, but is not limited to these.The dimensions of the array elements can be 0.5 mm to 1.5 mm in length and 0.5 mm to two wavelengths in width. A multi-row cylindrical array can help reduce the thickness of the image slice, achieving better contrast resolution. The elements can be individually controlled for transmission and reception, for example by ASIC circuitry, to reduce the number of cables required.

[0210] In some cases, a catheter constructed as disclosed in the context of Figures 1-8 has a catheter shaft with a diameter of 3 French or more and / or 9 French or less and / or a length of 75 cm or more and / or 175 cm or less. In one example suitable for renal denervation, the catheter has a catheter shaft with a diameter of 3 French or more and / or 6 French or less and / or a length of 85 cm or more and 155 cm or less.

[0211] Although the transducer 300 is disclosed as being positioned within the balloon 14, the transducer 300 may be positioned outside the balloon 14 and / or the catheter may exclude the balloon 14. For example, a catheter may be configured as disclosed in FIG. 12A without the use of a balloon 14. Thus, the transducer 300 may be coupled to the catheter shaft even when no balloon 14 is present on the catheter.

[0212] The balloon 14 may be a compliant or non-compliant balloon 14 configured to be inflated to a diameter between a first and a second inflated diameter using an inflation pressure between a first and a second inflation pressure, with the outer diameter directly correlated to the pressure of the balloon 14. In some cases, the balloon 14 is configured to be inflated from the first to the second inflated diameter using a constant inflation pressure. The relationship between the inflated diameter and the inflation pressure may change over time in response to multiple inflation and deflation cycles of the balloon. For example, an increased number of inflation and deflation cycles may require less pressure to maintain the balloon at the same diameter.

[0213] Suitable first inflated diameters include, but are not limited to, first inflated diameters of 1.5 mm, 2.0 mm, or 3.0 mm or more and / or 3.5 mm, 5.0 mm, or 8.0 mm or less. Suitable second inflated diameters include, but are not limited to, second inflated diameters of 3.5 mm, 4.0 mm, or 5.0 mm or more and / or 6.0 mm, 8.0 mm, or 10 mm or less. Suitable first inflated pressures include, but are not limited to, first inflated pressures of 2 psi, 5 psi, or 8 psi or more and / or 12 psi, 15 psi, or 30 psi or less. Suitable second inflated pressures include, but are not limited to, second inflated pressures of 2 psi, 5 psi, or 8 psi or more and / or 12 psi, 15 psi, or 30 psi or less. Suitable constant inflated pressures can be between or equal to the first and second inflated pressures. In one example, the first inflated diameter is greater than 1.5 mm and less than 5.0 mm, the second inflated diameter is greater than 3.5 mm and less than 8.0 mm, the first inflation pressure is greater than 5 psi and less than 25 psi, and the second inflation pressure is greater than 5 psi and less than 25 psi.

[0214] Inflating the balloon 14 to a second inflated diameter and / or a second inflation pressure may cause the balloon 14 to contact the inner surface of the body cavity. For example, inflating the balloon 14 to a second inflated diameter and / or a second inflation pressure may cause the balloon 14 to contact the inner surface of a renal artery. The portion of the surface of the balloon 14 configured to contact the inner surface of the body cavity (the contact portion of the surface of the balloon 14) has a length indicated as L in FIG. 12A . In some cases, the length of the contact portion of the surface of the balloon 14 is greater than 1 mm or 18 mm and / or less than 30 mm or 100 mm. In one example, the length of the contact portion of the surface of the balloon 14 is greater than 1 mm and less than 90 mm. Increasing the length of the contact portion of the surface of the balloon 14 may provide room for one or more external electrodes at the contact portion of the surface of the balloon 14.

[0215] The electronics 22 can activate the transducer assembly 302 to cause the transducer to output an acoustic signal before, during, and / or after the balloon 14 is inflated to the second inflated diameter and / or second inflation pressure. In some cases, the electronics 22 can activate the transducer assembly 302 to cause the transducer to output an acoustic signal having a frequency in the range of 1-20 MHz. For example, the transducer can be configured to output an acoustic signal having a frequency of approximately 9 MHz. In other examples, the transducer can output an acoustic signal having a frequency of 12-15 MHz. In other examples, the transducer can output an acoustic signal having a frequency less than 1 MHz. For example, the transducer can output an acoustic signal having a frequency greater than or equal to 0.1 MHz and less than 1 MHz. The frequency of the acoustic signal can vary depending on the particular application, function, or use of the catheter.

[0216] The power supplied to the transducer to generate the acoustic signal can be varied as desired or required. In some cases, the power supplied to the transducer to generate the acoustic signal is between 5 and 80 watts. The duration for which the acoustic signal is applied to the body cavity can vary due to various factors, including the treatment procedure, the power level of the transducer, the frequency of the emitted acoustic signal, the size of the body cavity or the type of tissue being treated, the age of the patient, the weight of the patient, and the gender of the patient. However, in some cases, the acoustic signal can be applied to the body cavity for a duration of at least 0.1 seconds and up to 20 minutes. In one embodiment, the acoustic signal is applied to the body cavity for a duration of 5 to 10 seconds. In one embodiment, the acoustic signal is applied to the body cavity for a duration of 7 seconds. In certain embodiments, the acoustic signal is applied for a duration of 3.5 to 9 seconds, more specifically, for a duration of 4 to 5 seconds.

[0217] The foregoing description of the operation of the catheter and / or internal catheter describes one or more movements of the catheter within the body lumen. These movements may include movement from one location to another within the body lumen and / or adjustment of the position of the catheter within the body lumen. Movement of the catheter within the body lumen may include deflating a balloon at a first location within the body lumen, followed by physical rotation and / or translation of the catheter, and then re-inflating one or more balloons of the catheter at a second location.

[0218] Suitable electronics 22 may include one or more components selected from the group consisting of analog electrical circuitry, digital electrical circuitry, a processor, a microprocessor, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a computer, a microcomputer, or any combination thereof suitable for performing the aforementioned operating, monitoring, and control functions. In some cases, electronics 22 includes an RF electrosurgical generator, such as an electrosurgical unit or ESU, for generating energy in electromagnetic signals output from all or a portion of a selection of one or more electrodes 76. In some cases, electronics 22 includes a user interface that allows an operator to provide input to and / or extract information and / or data from electronics 22. In some cases, electronics 22 includes memory that stores instructions to be executed by electronics 22 during the performance of operating, control, and monitoring functions. Although electronics 22 is shown as a single component in a single location, electronics 22 may include multiple different components that are separate and / or located in different locations.

[0219] Application of acoustic signals to renal nerves can be effective in treating hypertension, although catheters can also be used for a variety of other applications, such as applying acoustic signals to the renal arteries to treat chronic kidney disease, atrial fibrillation, arrhythmias, heart failure, chronic kidney disease, end-stage renal disease, myocardial infarction, anxiety, contrast nephropathy, diabetes, metabolic disorders, and insulin resistance, applying acoustic signals to the pulmonary arteries to treat pulmonary hypertension, applying acoustic signals to the hepatic artery to treat diabetes, applying acoustic signals to the splenic, celiac, superior, or inferior mesenteric arteries to treat autoimmune and / or inflammatory diseases such as rheumatoid arthritis, sepsis, Crohn's disease, ulcerative colitis, and / or gastrointestinal motility disorders, and applying acoustic signals to the cardiovascular system to treat atrial fibrillation.

[0220] The high-level flowchart of Figure 17 is used to outline (summarize) a method according to a particular embodiment of the present technology.

[0221] Referring to FIG. 17 , step 701 involves imaging blood vessels and / or surrounding anatomical structures using, for example, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography, ultrasound (US), radiology equipment, etc. Target structures (e.g., nerves, cancer cells, cardiac tissue, calcifications and / or plaque) and non-target structures (e.g., lymph nodes, subaxial skeletal muscle with fibrous sheath, peritoneum, periatrial vessels, organs, ureters, intestines, liver, pancreas, urethra, renal pelvis, bladder, liver, pancreas, spleen, kidneys, calcifications and / or plaque) and their relative locations are determined using the imaging step. Step 702 involves inserting a catheter into a biological body cavity (e.g., renal artery, hepatic artery, etc.). In certain embodiments, the imaging step is performed by an imaging transducer disposed on catheter 10, in which case step 702 may be performed before step 701.

[0222] 17, step 704 includes selecting an ablation power based on characteristics of the image. In one embodiment, the ablation power of transducer 300 may be selected by selecting the frequency of the applied alternating current generated by electronics 22 (which selectively activates one or more regions of the transducer to direct acoustic signals toward the target and / or away from non-targets). In one embodiment, electronics 22 determines the ablation power based on the image by selecting a combination of electrodes to which the alternating current is applied (which selectively activates one or more regions of the transducer to direct acoustic signals toward the target and / or away from non-targets).

[0223] In one embodiment, the selection is performed using electronics 22, which includes one or more processors, such as, for example, an electronic control unit (ECU). In certain embodiments, the ablation output is selected using one or more tables stored in memory (e.g., memory 1120 of FIG. 19) and accessed by at least one processor (e.g., controller 1122 of FIG. 19). In other embodiments, the ablation parameters are selected using machine learning models, or more generally, artificial intelligence, implemented by at least one of the one or more processors.

[0224] Step 706 includes performing an ablation procedure using the selected ablation power, thereby selectively ablating the target structure while avoiding the non-target structures.

[0225] According to certain embodiments, the ablation procedure performed in step 706 emits ultrasound energy using an ultrasound transducer in a catheter inserted into the biological body cavity. In certain such embodiments, the ablation parameters selected in step 704 and used in step 706 may specify the vector, amplitude, power, duration, frequency, and / or duty cycle of the ultrasound energy. In certain such embodiments, the ultrasound transducer is disposed within a balloon at least partially filled with a cooling fluid that is circulated within the balloon to cool at least a portion of the tissue surrounding the biological body cavity proximate the balloon. In certain such embodiments, the ablation parameters selected in step 704 and used in step 706 may specify the flow rate and / or temperature associated with the cooling fluid.

[0226] Referring to FIG. 18 , step 801 includes inserting a catheter into a biological body cavity (e.g., a renal artery), and step 804 includes sensing neural activity of nerves in tissue surrounding the biological body cavity, the sensing step being performed using at least one electrode of the catheter inserted into the biological body cavity. The electrode used to sense neural activity may be referred to herein as a sensing electrode. The neural activity sensed in step 804 may be native (also known as spontaneous) neural activity. Alternatively or additionally, the neural activity sensed in step 804 may be evoked neural activity evoked by electrical stimulation delivered using the same catheter used to sense the neural activity in step 804. More specifically, in certain embodiments, between steps 801 and 804, stimulation energy is emitted using one or more electrodes of the catheter (step 802, shown by dashed lines), which generates an evoked neural response that is sensed in step 804. One example of a catheter including multiple electrodes that can be used to perform steps 802 and 804 and that can be used to selectively emit stimulation energy to elicit a neural response in step 802 is described with reference to Figures 3A and 3B in U.S. patent application Ser. No. 18 / 182,821 (PMD00104US), filed March 13, 2023, to Barman et al., which claims priority to U.S. patent application Ser. No. 63 / 320,103, both of which are incorporated herein by reference. However, embodiments of the present technology are not limited to use with the exemplary catheter described with reference to Figures 3A and 3B of Barman et al.

[0227] With continued reference to FIG. 18, step 806 includes determining characteristics of the sensed neural activity of nerves within tissue surrounding the biological body cavity, where the characteristics are indicative of one or more of the size, type, function, or health of the nerve from which the neural activity is sensed, indicative of the proximity of the nerve to the sensing electrodes of the catheter, and / or indicative of the distribution / location of the nerve around the renal arteries.

[0228] Step 808 includes selecting a frequency of the alternating current applied to the transducer 300 and / or selecting a denervation electrode of the transducer 300 to selectively target nerves according to the distribution of the nerve around the body cavity based on characteristics of the sensed neural activity. The denervation parameters are used in performing a denervation procedure intended to denervate at least a portion of the nerve in which neural activity is sensed, and the selection is performed using, for example, one or more processors of an electronic control unit (ECU), an example of which is described below with reference to FIG. 19. In certain embodiments, the denervation frequency and / or electrode are selected using one or more tables stored in a memory (e.g., memory 1120 of FIG. 19) and accessed by at least one processor (e.g., controller 1122 of FIG. 19). In other embodiments, the denervation frequency and / or electrode are selected using a machine learning model implemented by at least one of the one or more processors, or more generally, using artificial intelligence. Higher frequencies can be used to activate thinner portions of the transducer located proximal to the nerve to selectively direct the acoustic signal to that nerve. Lower frequencies can be used to activate thicker portions of the transducer located proximal to the nerve to selectively direct the acoustic signal to that nerve. Additionally or alternatively, electrodes located proximal to the nerve can be selected to direct the acoustic signal to that nerve.

[0229] In addition to selecting the frequency of the alternating current applied to the transducer 300 and / or selecting the denervation electrodes of the transducer 300 based on characteristics of the sensed neural activity, as shown in FIG. 17, frequency and / or electrode selection may also be based on imaging of blood vessels. A processor (e.g., controller 1122 of FIG. 19) may consider both the nerve distribution and the location of structures (e.g., lymph nodes, hypoaxial skeletal muscle with fibrous sheaths, peritoneum, periaqueductal vessels, organs (e.g., ureters, intestines, liver, pancreas, urethra, renal pelvis, bladder, liver, pancreas, spleen, kidneys), and / or features (e.g., calcifications and / or plaques)) when selecting the frequency of the alternating current applied to the transducer 300 and / or when selecting the denervation electrodes of the transducer 300. The processor can use both characteristics of the image and characteristics of the sensed neural activity to more selectively target nerves while avoiding non-target structures.

[0230] Step 810 includes performing a denervation procedure using the selected denervation frequency, thereby denervating at least a portion of the nerve whose neural activity was sensed. Depending on the specific implementation, the denervation procedure may be performed in step 810 using the same catheter used to sense neural activity in step 804, or may be performed in step 810 using a different catheter inserted into the biological cavity after the catheter used to sense neural activity in step 804 is removed. In other words, in certain embodiments, one catheter may be replaced with another catheter during the time between when step 804 is performed and when step 810 is performed. The catheter described in U.S. Patent Application No. 18 / 182,821 (PMD00104US) to Barman et al., filed March 13, 2023, claiming priority to U.S. Patent Application No. 63 / 320,103, may be used. However, as described herein, transducers 300 may also be used that have different thicknesses at different locations on the transducer and / or have multiple electrode pairs that can be selectively selected to vary the depth and / or direction of the acoustic signal away from the transducer.

[0231] According to certain embodiments, the biological body lumen referred to in the flow diagram of Figure 18 is the renal artery and the nerve includes the renal nerve that innervates the kidney. The method may also include removing a catheter that has been inserted into the biological body lumen, such as the renal artery.

[0232] According to certain embodiments, the denervation procedure is performed in step 810 using an ultrasound transducer 300 having multiple electrode pairs with different thicknesses at different locations on the transducer and / or that can be selectively selected to vary the depth and / or direction of acoustic signals traveling away from the transducer, inserted into a biological body cavity and emitting ultrasound energy, as described above. In certain such embodiments, the denervation frequency and / or electrodes selected in step 808 and used in step 810 depend on the distribution of nerves around the artery and / or whether the nerves are located near and / or far. In certain such embodiments, the ultrasound transducer is disposed within a balloon at least partially filled with a cooling fluid that is circulated within the balloon to cool at least a portion of the tissue surrounding the biological body cavity proximate the balloon, as described above with reference to FIGS. 1-8 . In certain such embodiments, further denervation parameters can be selected in step 808 and used in step 810 based on characteristics of sensed neural activity. Such parameters include the amplitude, power, duration and / or duty cycle of the ultrasonic energy, and the flow rate and / or temperature associated with the cooling fluid.

[0233] Step 804 of FIG. 18 may be performed by using a pair of electrodes to sense a signal indicative of neural activity. At least one of the pair of electrodes is on the catheter inserted in step 801. The signal indicative of neural activity includes multiple peaks that are separated in time from one another. Electrodes used to sense neural activity (spontaneous or evoked) may be referred to herein as sensing electrodes, and electrodes used to deliver stimulation energy to elicit a neural response may be referred to herein as stimulating electrodes. Switches in the catheter and / or in an electronic control unit (ECU) to which the catheter is electrically connected may be used to selectively change particular electrodes from sensing electrodes to stimulating electrodes and / or vice versa at different times. According to certain embodiments, both electrodes of the pair of sensing electrodes are located on the catheter. In other embodiments, one sensing electrode of a pair of sensing electrodes is located on the catheter, and the other sensing electrode of the pair is located within the distal end of an introducer sheath (used to insert the catheter into the biological body cavity), on the distal end of a guidewire (used to guide the catheter into the biological body cavity), or is an external skin electrode placed on the patient's skin.

[0234] In certain embodiments, the characteristics of the sensed neural activity are determined in step 806 based on the amplitudes of the peaks and / or the time intervals between the peaks. For example, an average amplitude of the peaks may be determined, and the denervation parameter may be selected based on the average amplitude of the peaks. Alternatively or additionally, a median amplitude of the peaks may be determined, and the denervation parameter may be selected based on the median amplitude of the peaks. Alternatively or additionally, determining the characteristics of the sensed neural activity in step 806 may include fitting a curve to a portion of the signal indicative of neural activity to determine an area under the curve, and step 808 may include selecting the denervation parameter based on the area under the curve.

[0235] As previously described, in certain embodiments, a stimulus is delivered to elicit a neural response to the stimulus (step 802). This may be accomplished by delivering the stimulus using a first electrode (e.g., a first electrode of a first electrode pair) on the catheter shaft and sensing the evoked response with a second electrode (e.g., a second electrode of a second electrode pair) on the catheter that is a known distance from the first electrode. The electrode used to stimulate the nerve to elicit the neural response may be referred to herein as a stimulating electrode, as previously described. Also, as previously described, switches within the catheter and / or switches within an electronic control unit (ECU) to which the catheter is electrically connected may be used to selectively change a particular electrode from a sensing electrode to a stimulating electrode and / or vice versa at different times. According to certain embodiments, both electrodes of a pair of stimulating electrodes are located on the catheter. In other embodiments, one stimulation electrode of a pair of stimulation electrodes is located on the catheter, and the other stimulation electrode of the pair is located within the distal end of an introducer sheath (used to insert the catheter into the biological body cavity), on the distal end of a guidewire (used to guide the catheter into the biological body cavity), or is an external skin electrode placed on the patient's skin.

[0236] The delay (also known as latency) between when a stimulus is delivered and when an evoked neural response is detected can be determined, with the delay (also known as latency) indicating the conduction velocity of the nerve in response to the stimulus. Different nerve fibers can have different conduction velocities. Some electrical impulses travel faster than others. Larger nerve fibers tend to have very fast conduction velocities. In contrast, smaller nerve fibers tend to have relatively slower conduction velocities than larger nerve fibers. Thus, the latency of a sensed electrical impulse can be used to determine the type, size, function, and / or health of the fiber in which the neural response is being sensed. The delay (also known as latency) can indicate the depth of the nerve surrounding the biological body lumen (e.g., the renal artery) within which the catheter used to measure the delay is located. According to certain embodiments of the present technology, the aforementioned delay (also known as latency) is another example of a characteristic of sensed neural activity that may be determined in step 806 of FIG. 18 and used to select denervation parameters in step 808 of FIG. 18.

[0237] When nerve fibers are ablated during a denervation procedure, causing deterioration of the nerve fiber's health or destruction, the amplitude and shape of the sensed signal indicative of neural activity, its latency, and its synchronization change compared to such characteristics before the denervation procedure. In certain embodiments, one or more of various characteristics, such as amplitude, shape, latency, synchronization, etc., are used to quantify the nerve fiber's health.

[0238] According to certain embodiments, convolution is used to determine how far a nerve fiber is from a sensing electrode (or more generally, from a sensing site, which may also be called a recording site). Typically, the greater the amplitude of the sensed neural activity, the closer the nerve fiber is likely to be to the sensing site, and the smaller the amplitude of the sensed neural activity, the farther the nerve fiber is likely to be from the sensing site. For example, assume that neural activity of two different nerve fibers is sensed using a single sensing electrode on a single catheter, one of which is relatively far from the sensing site and the other of which is relatively close to the sensing site. Now, assume that both the relatively far nerve fiber and the relatively close nerve fiber fire simultaneously in response to stimulation energy intended to elicit a neural response. When a single catheter is used to sense such neural activity, the characteristics of both the relatively far nerve fiber and the relatively close nerve fiber can be distinguished from each other in the sensed signal, which may enable the system and / or physician to estimate how far the different nerve fibers are from the sensing site and the size of such fibers. These are examples of properties of sensed neural activity that may be determined in step 806 of FIG. 18:

[0239] According to certain embodiments, the characteristics of sensed neural activity identified in step 806 and used to select denervation parameters in step 108 include frequency and / or electrode pair selection that selectively activates portions of the transducer 300 to affect the direction and / or depth of acoustic signals away from the transducer 300, the minimum amount of energy delivered with a particular waveform to achieve an evoked response, and / or the amount of energy delivered with the particular waveform to achieve saturation of the evoked neural response. The evoked neural response may be considered saturated when increasing neural stimulation no longer increases the evoked neural response. These characteristics may be used to select the therapeutic dose delivered to the target region and / or nerve fiber for treatment to achieve complete neural capture and full effect. More generally, these characteristics may be used to select denervation parameters in step 808 of FIG. 18 .

[0240] In one embodiment, instead of or in addition to using electrical energy to perform stimulation to elicit a neural response, a neural response is elicited by heating the nerve to a temperature below that at which ablation occurs, and a baseline neural response is sensed before ablation and / or a neural response is sensed after ablation to determine whether the nerve ablation was successful or whether additional nerve ablation needs to be performed. The same transducer used for ablation may also be used to elicit a neural response prior to ablation by using the transducer to heat the artery to a temperature sufficient to elicit a neural response but not sufficient to cause ablation. This may eliminate the need for stimulation electrodes to elicit a neural response, reducing catheter complexity.

[0241] In one embodiment, in step 802, the frequency and / or electrode pair of the transducer 300 is used to activate a selected portion of the transducer to output an acoustic signal of sufficient power to heat the nerve below the temperature at which ablation occurs. This elicits a neural response, and a baseline neural response before ablation is sensed. In step 804, neural activity is sensed using at least one neural sensing electrode of the catheter. In one embodiment, steps 802 and 804 are repeated 360 degrees around the blood vessel. In step 806, characteristics of the sensed neural activity at a particular vector can be determined based on the characteristics of the sensed neural activity. In embodiments in which steps 802 and 804 are repeated 360 degrees around the blood vessel, a neural profile around that circumference can be determined. In step 808, electronics 22 can determine an optimal vector for ablation and select the corresponding nerve ablation frequency(ies) and / or electrode pair(s) of the transducer 300, as well as other nerve ablation parameters. The vector may also be determined based on imaging as described herein with reference to Figure 17. At step 810, a denervation procedure may be performed using the selected denervation parameters to denervate at least a portion of the target nerve in which neural activity is sensed.

[0242] In one embodiment, after ablation, the effectiveness of the ablation procedure may be verified in step 812. The frequency and / or electrode pairs of the transducer 300 may be selected to activate specific portions of the transducer to again output acoustic signals at specific vectors with sufficient power to heat the nerves along those vectors below the temperature at which ablation occurs, thereby eliciting a neural response and sensing the neural response after ablation. If the ablation is determined to be ineffective, ablation may be applied again, for example, at the specific vector around the blood vessel, and / or the catheter may be moved to another location along the blood vessel.

[0243] [Example Electrical Control Unit (ECU)] FIG. 19 is a high-level block diagram of an electronic control unit (ECU) 1102 configured to be in electrical communication with a catheter, such as the catheter 10 described above. The ECU 1102 and the catheter (e.g., catheter 10) to which the ECU 1102 is electrically coupled via a cable may be more generally referred to as a system 1100. The ECU 1102 may process received signals to generate output signals and may present information, including information about the output signals, the received signals, or the processed information. Such a system may be used, for example, in diagnostic procedures to determine the location of target and non-target structures or to evaluate the state of neural activity in a patient adjacent to a biological body lumen, such as a vein, artery (e.g., renal artery), or other type of blood vessel. Such a system may additionally or alternatively be used to select preferred ablation parameters, such as the frequency of the alternating current output by the electronics 22, for use in an ablation procedure. As disclosed in U.S. Patent Application No. 18 / 182,821 (PMD00104US) to Barman et al., filed March 13, 2023, claiming priority to U.S. Patent Application No. 63 / 320,103, the same catheter used to assess the state of a patient's neural activity and / or select preferred denervation parameters can also be used to perform the nerve ablation procedure. Both of these applications are incorporated herein by reference. Alternatively, the catheter used to perform the nerve ablation procedure can be different from the catheter used to assess the state of a patient's neural activity adjacent to the biological body cavity. In that case, different catheters can be exchanged in and out of the biological body cavity during the procedure.

[0244] 19 , the ECU 1102 includes a stimulator 1106 electrically coupled to selected pairs of neural stimulation electrodes of the catheter 10. The stimulator 1106, part of the STIM circuit or subsystem 1105, can selectively emit electrical signals (including stimulation pulses) having a particular voltage, amperage, duration, duty cycle, and / or application frequency that cause neural activation. For example, one neural stimulation electrode can be connected as a stimulation anode and another neural stimulation electrode can be connected as a stimulation cathode, or vice versa. Switches, not specifically shown, can be used to selectively control how the various neural stimulation electrodes are coupled to various nodes of the ECU 1102, such as the input terminals of the amplifier 1112 and the output terminals of the stimulator 1106. In this manner, the switches can be used to control which electrodes are configured as stimulation electrodes and which electrodes are configured as sensing electrodes.

[0245] Upon receiving the stimulation signal generated by the stimulator 1106, an electrode of the catheter 10 connected as a neural stimulation electrode may apply electrical energy to the patient's nerve through the wall of the biological body cavity based on the received signal. Such stimulation may have any of a variety of known waveforms, such as, but not limited to, a sine wave, a square wave, a triangular wave, etc. In various examples, stimulation may be applied for a duration between about 0.05 milliseconds (msec) and about 8 msec.

[0246] Stimulation of the nerve may be performed to induce evoked potentials, which may propagate in any direction along the nerve fiber. More generally, the STIM subsystem 1105 may be used to deliver electrical stimulation via selected electrode pairs to induce a neural response, and the SENS subsystem 1104 may be used to sense the evoked neural response.

[0247] In some embodiments, the ECU 1102 may digitally sample the sensed signal using an electrode pair to receive the electrical signal from the catheter 10. In another embodiment, the signal may be recorded as an analog signal. When receiving the electrical signal from the electrodes on the catheter 10, the ECU 1102 may perform filtering and / or other processing steps on the signal. Typically, such steps may be performed to distinguish the signal sensed by the catheter from any background noise in the patient's vasculature, so that the resulting output is primarily a signal from neuronal activation. In some cases, the ECU 1102 may adjust the electrical impedance of the signal receiving portion to accommodate the electrical characteristics and spatial separation of the electrodes attached to the catheter in a manner that achieves the highest fidelity, selectivity, and resolution of the received signal. For example, the size, spacing, and conductivity characteristics of the electrodes may affect the electric field strength at the electrode / tissue interface.

[0248] Additionally or alternatively, the ECU 1102 may include a headstage and / or amplifier to offset, filter, and / or amplify the signal received from the catheter. In some examples, the headstage applies a DC offset to the signal and performs filtering. In some such systems, the filtering may include applying a notch filter and / or a bandpass filter to suppress specific undesired signals with specific frequency content or pass desired signals with specific frequency content. An amplifier may be used to amplify the entire signal uniformly or to amplify certain portions of the signal more than others. For example, in some configurations, the amplifier may be configured to provide adjustable capacitance of the recording electrode to change the frequency dependence of signal pickup and amplification. In some embodiments, characteristics such as the amplifier's capacitance may be adjusted to change amplification characteristics such as the amplifier's resonant frequency.

[0249] 19, ECU 1102 includes amplifier 1112 including a non-inverting (+) input terminal, an inverting (-) input terminal, a power supply input terminal, and a ground or reference terminal. As can be seen from FIG. 19, the non-inverting (+) input terminal may be coupled to electrode 326, the inverting (-) input terminal may be electrically coupled to electrode 327, the power supply input terminal may be electrically coupled to a voltage source (e.g., a reference voltage generator), and the ground or reference terminal may be electrically coupled to a ground reference electrode. The ground reference electrode may be located on catheter 10, on the distal end of the introducer sheath, or on the patient's skin, but is not limited to this.

[0250] In some embodiments, the ECU 1102 may include a switching network configured to switch which electrodes of a catheter (e.g., catheter 10) are coupled to which portions of the ECU. In some such embodiments, a user can manually switch which inputs are connected to which electrodes of the catheter 10. Such configurability allows a system operator to adjust the propagation direction of evoked potentials as desired. For example, a switching network (or more generally, a switch) may be used to connect a neural stimulation electrode to the stimulator 1106 during the time that a stimulation pulse is to be emitted by the catheter 10, and the switch may be used to connect electrodes 326, 327 to the amplifier 312 for sensing responses evoked by the stimulation pulse. Additionally or alternatively, a controller (e.g., controller 1122) may autonomously control such a switching network.

[0251] The amplifier 1112 may include any suitable amplifier for amplifying desired signals and attenuating undesired signals. In some examples, the amplifier has a high common-mode rejection ratio (CMRR) to reject or significantly attenuate undesired signals present in each of the sensing electrodes. In some embodiments, the amplifier 1112 may be adjusted, for example, via an adjustable capacitance or other attribute of the amplifier.

[0252] 19 , the ECU 1102 further includes an amplifier 1114 for amplifying a desired signal within a signal received via the pair of electrodes. The amplifier 1114 may include a bandpass filter, a notch filter, or any other suitable filter to separate the desired signal from noise artifacts within the received signal. In some embodiments, various characteristics of the amplifier 1114 may be adjusted to manipulate its filtering characteristics. For example, the filter may include an adjustable capacitance or other parameter to adjust the frequency response.

[0253] Amplifying and / or filtering the sensed signal (e.g., the signal received at the neural stimulation electrode) may allow for extraction of the desired signal in step 1116. In some embodiments, extraction (step) 1116 includes at least one additional processing step to separate the desired signal from the signal sensed using the electrodes, such as preparing the signal for output in step 1118. In some embodiments, the functionality of any combination of amplifier (step) 1112, amplifier (step) 1114, and extraction (step) 1116 may be combined into a single entity. For example, amplifier 1112 may operate to filter undesired frequency content from the signal without requiring additional filtering with a separate filter.

[0254] In some embodiments, the ECU 1102 may record the emitted stimuli and / or received signals. Such data may then be stored in persistent or temporary memory 1120. The ECU 1102 may include such memory 1120 or may be in communication with an external memory (not shown). Thus, the ECU 1102 may be configured to emit stimulation pulses to electrodes of the catheter and record such pulses in memory, receive signals from the catheter, and also record such received signal data. The memory 1120 within or associated with the ECU 1102 may reside in any portion of the ECU 1102 or internal or external to the ECU 1102 itself.

[0255] The ECU 1102 or a separate external processor may perform further calculations on the stored data to determine characteristics of signals transmitted or received through the catheter. For example, in various embodiments, the ECU 1102 may determine any of the amplitude, duration, or timing of occurrence of the received or transmitted signals. The ECU 1102 may further determine the relationship between the received signal and the transmitted stimulus signal, such as the temporal relationship therebetween. In some embodiments, the ECU 1102 performs signal averaging on the signal data received from the catheter. Such averaging may serve to enhance the data corresponding to the evoked potentials received by the catheter while reducing random temporal noise in the data.

[0256] Such averaging may result in signals such that random noise in time is generally averaged out, while signals present in each recorded data set, such as evoked potentials, remain high. In some embodiments, each iteration of processing may include a synchronization step, whereby each acquired data set may be registered in time, facilitating data averaging. That is, events that consistently occur simultaneously during each iteration may be detected, and random artifacts in time (such as noise) may be reduced. Generally, the signal-to-noise ratio (SNR) resulting from such averaging improves with the square root of the number of samples averaged to create the averaged data set.

[0257] ECU 1102 may further present information regarding any or all of the applied stimuli, signals, and results of any calculations to a user of the system, such as via output 1118. For example, ECU 1102 may generate a graphical display providing one or more graphs of signal strength versus time representing the stimuli and / or received signals.

[0258] In some embodiments, the ECU 1102 may include a controller 1122 in communication with one or both of the stimulator 1106 and the SENS subsystem 1104. The controller 1122 may be configured to cause the stimulator 1106 to apply a stimulation signal to a catheter (e.g., catheter 10). Additionally or alternatively, the controller 1122 may be configured to analyze signals received and / or output by the SENS subsystem 1104. In some embodiments, the controller 1122 may operate to control the timing of application of the stimulation signal from the stimulator 1106 and the timing of reception of signals by the SENS subsystem 1104. The controller 1122 may be implemented using, for example, but not limited to, one or more processors, field programmable gate arrays (FPGAs), state machines, and / or application specific integrated circuits (ASICs).

[0259] An exemplary electrical control unit has been described. In various embodiments, the ECU 1102 may transmit stimulation pulses to the catheter 10, receive signals from the catheter 10, perform calculations on the transmitted and / or received signals, and present the signals and / or the results of such calculations to a user. In some embodiments, the ECU 1102 may include separate modules for transmitting, receiving, calculating, and providing the results of the calculations. Additionally or alternatively, the functionality of the controller 1122 may be integrated within the ECU 1102 as shown, or may be separate from and in communication with the ECU.

[0260] The controller 1122 may also control a fluid supply subsystem 1128, which may include a cartridge and reservoir (described below with reference to FIG. 1), but may also include alternative types of fluid pumps, etc. The fluid supply subsystem 1128 is fluidly coupled to one or more fluid lumens (not shown) in the catheter shaft 12, which are fluidly coupled to the balloon 14. The fluid supply subsystem 1128 may be configured to circulate a cooling fluid through the catheter 10 to the transducer 200 (or 300) in the balloon 14 to cool the transducer and protect the body cavity. The fluid supply subsystem 1128 is an example of the fluid source 28 described above with reference to FIG. 1A.

[0261] An ultrasonic excitation source 1126 may be electrically coupled to the inner and outer electrodes of the transducer 300 via electrical conductors 72 (FIG. 12A), and may activate the transducer 300 by applying a voltage between the inner and outer electrodes (or any other electrode pair), causing the piezoelectric material of the piezoelectric transducer body 208 to generate unfocused ultrasonic waves that radiate radially outward.

[0262] The controller 1122 may be configured to cause the ultrasonic excitation source 1126 to apply particular frequencies to the transducer 300 to direct the acoustic signal toward one or more targets and / or away from one or more non-target structures.

[0263] In some embodiments, the controller 1122 may operate to cause the ultrasonic excitation source 1126 to apply an alternating current between selected electrodes of the transducer 300 (e.g., between electrodes 36, 60 or between electrodes 36, 62 of FIG. 13 ) to direct acoustic signals toward one or more targets and / or away from one or more non-target structures.

[0264] Additionally or alternatively, the controller 1122 may be configured to analyze signals received and / or output by the SENS subsystem 1104. In certain embodiments, the controller 1122 may operate to cause the ultrasonic excitation source 1126 to apply an alternating current of a particular frequency to the transducer 300 to direct acoustic signals to near-field nerves. In some embodiments, the controller 1122 may operate to cause the ultrasonic excitation source 1126 to apply an alternating current of a particular frequency to the transducer 300 to direct acoustic signals to far-field nerves.

[0265] [Multiple-dose treatment] Because the airbag ultrasound transducers described herein can provide both low-power density and high-power density treatments without transducer failure, such airbag ultrasound transducers can be advantageously used to provide both low-power density and high-power density ultrasound treatments from the same longitudinal location within a body cavity (e.g., a renal artery). This can include, for example, delivering an ultrasound treatment having a low power density for a first period (also known as a first duration) while the airbag ultrasound transducer is positioned adjacent to a nerve (surrounding a body cavity) to be denervated, and then delivering an ultrasound treatment having a high power density for a second period (also known as a second duration) while the same airbag ultrasound transducer is positioned adjacent to the same nerve (surrounding a body cavity) to be denervated. In other words, low-power density and high-power density treatments can be delivered from the same airbag transducer without moving the transducer. A high-power-density treatment may be delivered before a low-power-density treatment. According to certain embodiments, the first duration is within a first range of 2 seconds to 4 seconds, and the second duration is within a second range of 2 seconds to 4 seconds. In certain embodiments, the airbag ultrasound transducer is controlled to refrain from emitting ultrasound waves for a third period (also known as a third duration) between the first and second periods (between the first and second durations). This third period may also have a duration within a third range of 2 seconds to 4 seconds. In certain embodiments, if the airbag ultrasound transducer is within a balloon through which a cooling fluid is circulated, the cooling fluid is circulated within the balloon during the third period between the first and second periods, thereby cooling the transducer and the tissue surrounding the transducer between the two sonication periods. Such an embodiment is described below with reference to FIG. 20, which is a high-level flow diagram illustrating a method of using a catheter including an airbag ultrasound transducer in a distal portion of the catheter, in accordance with certain embodiments of the present technology.

[0266] Referring to FIG. 20 , step 1202 includes inserting a distal portion of a catheter into a patient's body cavity such that an airbag ultrasound transducer is positioned adjacent to a nerve surrounding the body cavity to be denervated. Step 1204 includes causing the airbag ultrasound transducer to emit ultrasound waves having a first power density for a first period while the airbag ultrasound transducer is positioned adjacent to the nerve surrounding the body cavity to be denervated. Step 1206 includes causing the airbag ultrasound transducer to emit ultrasound waves having a second power density for a second period occurring after the first period while the airbag ultrasound transducer is positioned adjacent to the nerve surrounding the body cavity to be denervated. Here, the second power density is different from the first power density. According to certain embodiments, the first period has a duration within a first range of 2 seconds to 4 seconds, and the second period has a duration within a second range of 2 seconds to 4 seconds. According to certain embodiments, the method includes, in step 1205 (occurring between steps 1204 and 1206), causing the airbag ultrasound transducer to refrain from emitting ultrasound waves for a third time period between the first time period and the second time period. In certain embodiments, the third time period has a duration within a third range of 2 to 4 seconds. As previously mentioned, during this third time period, if the airbag ultrasound transducer is disposed within a balloon, a cooling fluid may be circulated through the balloon.

[0267] The advantage of using two different ultrasound power densities (one low and one high) to deliver ultrasound energy to the same treatment site using the embodiment outlined (summarized) with reference to Figure 20 is that it can help avoid deeper heating while trying to move the internal lesion area closer to the body cavity surface (e.g., the renal artery surface), and it can also help extend the lesion created axially, which can increase the likelihood of nerve ablation.

[0268] Continuing with reference to the embodiment described with reference to FIG. 20, in certain embodiments, one of the first power density and the second power density is 170 W / cm 2 ~327W / cm2 and the other of the first power density and the second power density is in the range of 50 W / cm 2 ~169W / cm 2 Other variations are possible and are within the scope of the embodiments described herein.

[0269] [Shortening of active treatment duration] When a catheter (e.g., 10) equipped with an ultrasound transducer (e.g., 200, 300) performs a denervation procedure (e.g., a renal denervation procedure), the longer it takes to perform the denervation procedure (i.e., active treatment duration), the longer the patient during which the procedure is performed may experience pain and / or discomfort. Certain embodiments of the present technology, as described below, can be used to reduce patient pain and / or discomfort by maximizing peak treatment temperature and minimizing active treatment duration (also known as active ablation duration).

[0270] Tissue coagulation is achieved by the deposition of a thermal dose. Above 43 degrees Celsius (°C), the thermal dose doubles within a given time interval for every degree Celsius increase in temperature. Above 65°C, tissue necrosis occurs instantaneously. Therefore, by more quickly raising the treatment temperature to the target temperature (i.e., a higher temperature), the active treatment time (also known as active ablation duration) can be significantly reduced while maintaining efficacy. Therefore, according to certain embodiments of the present technology, a maximum peak temperature method can be applied to deliver effective treatment with a minimum active treatment time (also known as minimum active ablation duration). In certain such embodiments, the total treatment power can be predetermined to be optimized based on the target tissue, transducer geometry, and acoustic parameters such as frequency and attenuation.

[0271] In some embodiments, the power delivered to the patient is programmed to continuously increase the temperature until ablation is complete at one target site, while in other embodiments, the power is programmed to increase the temperature as quickly as possible to a target peak temperature, and then the power is reduced to maintain that temperature until the denervation treatment is complete.

[0272] The location of the peak temperature in acoustic thermal ablation depends on various factors, such as transducer geometry, operating frequency, acoustic intensity, treatment duration, tissue properties, anatomical structure, etc. For a given denervation application, the location of the peak temperature relative to the transducer face can be predetermined or characterized based on bench models or thermal simulations. With this knowledge, the acoustic output (power) can be precisely programmed to achieve a target maximum temperature to enable effective treatment and achieve the shortest treatment time to minimize patient discomfort / pain. For example, in a renal denervation (RDN) application, the target peak temperature is first determined, which in one embodiment is just below the boiling point (e.g., 99°C) of the tissue to be treated. Next, the input power to the patient is programmed according to the size of the body cavity (e.g., renal artery) to achieve a target temperature in the ablation space surrounding the body cavity (e.g., renal artery). In such an embodiment, the active ablation duration is short (typically only a few seconds), minimizing the effects of heat conduction. Therefore, a strategy of providing constant acoustic energy can be used to balance power versus time. For example, for an 8 mm diameter blood vessel, non-focused ultrasound therapy can be delivered (administered) for 7 seconds with an acoustic energy of approximately 235 joules (J) at a maximum peak temperature of approximately 70°C. If the strategy of the present invention is applied and the target temperature is 99°C (instead of 70°C), an input power of 70 W can be applied at the same treatment frequency (assuming the power is constant during treatment) to shorten the treatment time to approximately 3.5 seconds. This is half the 7-second duration used when the target temperature is 70°C.

[0273] Alternatively or additionally, increasing the acoustic operating frequency can shorten the active treatment duration. Only a portion of the total transmitted acoustic energy is converted into heat within the target tissue. This portion increases with increasing acoustic frequency. Therefore, for the same total acoustic power, using higher frequency ultrasound generates more heat and the temperature rises more rapidly. For example, with the same transducer surface geometry and total power, a 15 MHz unfocused ultrasound signal generates approximately 40% more heat within the first 6 mm of the treated tissue compared to a 9 MHz unfocused ultrasound signal, which can help shorten the active treatment duration to less than 5 seconds.

[0274] In some embodiments, the acoustic power is set constant to continuously increase the temperature of the tissue until the end of treatment. In some other embodiments, a higher acoustic power is delivered initially to rapidly increase the temperature until the target temperature is reached. The generator then switches to a lower power to maintain that temperature until the end of treatment. In certain such embodiments, pulses with a predetermined duty cycle factor (on / off duration ratio) can be used to achieve the same effect of maintaining the temperature. Examples / Further Embodiments [Example / Embodiment 1] 1. An ultrasound transducer configured to emit ultrasound waves (optionally therapeutic ultrasound waves), the ultrasound transducer comprising: a hollow (optionally tubular) piezoelectric transducer body having a longitudinal axis and a radially inner surface; a tubular backing support member extending longitudinally through the piezoelectric transducer body and having a radially outer surface; and a chamber defined between the radially inner surface of the piezoelectric transducer body and the radially outer surface of the tubular backing support member, the chamber being defined between a first end in the axial (longitudinal) direction and an opposite second end, wherein each of the ends is formed by a conductive part (e.g., a ring-shaped metal part such as a standoff member of the tubular backing support member) and a hermetic sealing layer (optionally ring-shaped) of metal solder material contacting a surface (e.g., a side) of the conductive part (ring-shaped metal part) opposite the chamber (optionally the device is placed in a renal artery and the therapeutic ultrasound is configured for renal denervation). In one embodiment, the metal solder material sealing the ends of the chamber is ring-shaped, and its side opposite the chamber does not contact other parts of the transducer body, i.e., defines the outer surface of the transducer body. This ensures that the metal solder material can be added and sealed during manufacturing, with the transducer body and the tubular backing support already assembled, and that the location of the metal solder material remains accessible. The ring-shaped metal component is not made of a metal solder material, i.e., the ring-shaped metal component does not melt at a temperature of 450°C, and at least at temperatures of 300°C or 350°C. The metal of the ring-shaped metal component and the solder metal material are different from each other. In a specific embodiment, the ring-shaped metal component includes a tin-lead alloy, such as a 63 / 37 tin-lead alloy. Alternatively or additionally, the ring-shaped metal component includes a lead-free alloy, such as tin-silver-copper or tin-copper. The (metallic) solder material and the (metallic) material of the conductive part that are adjacent to each other (for example in the form of two adjacent rings) are different from each other, which can be easily determined by standard analytical methods.

[0275] The metal solder material preferably hermetically connects the radially inner surface of the piezoelectric transducer body to the radially outer surface of the tubular backing support member. In another embodiment, the metal solder material only provides a hermetic seal between the standoff members of the tubular backing support member and the radially inner surface of the piezoelectric transducer body. This means that the standoff members need to be integrally formed with the tubular backing support member or attached in some other way such that the metal solder material does not need to provide a hermetic seal between the standoff members and the tubular backing support member.

[0276] Additionally or alternatively, sufficient solder metal material may be present within the chamber to provide an electrical connection between the transducer and the backing support member.

[0277] [Example / Embodiment 2] 1. An ultrasound transducer configured to emit ultrasound waves (preferably therapeutic ultrasound waves), comprising: an ultrasound transducer having a hollow piezoelectric transducer body comprising a tube (cylindrical tube) of piezoelectric material, the tube having a radially inner surface and a radially outer surface; an inner electrode disposed on at least a portion of the inner surface of the tube of piezoelectric material (the inner electrode optionally having a coating on a side opposite the piezoelectric material); an outer electrode disposed on at least a portion of the outer surface of the tube of piezoelectric material (the outer electrode optionally having a coating / protection on a side opposite the piezoelectric material); a tubular backing support member extending longitudinally through the piezoelectric transducer body and having a radially outer surface; and a tubular backing support member extending longitudinally through the piezoelectric transducer body and having a radially outer surface. a chamber defined between a first axial end and an opposite second axial end, each end being formed by a conductive element (e.g., a ring-shaped conductive (metal) element, such as a standoff element of the tubular backing support member) and a hermetic sealing layer of metal solder material contacting a surface of the conductive element (the ring-shaped conductive (metal) element) opposite the chamber (the metal solder material thus connects the radially inner surface of the piezoelectric transducer body to the ring-shaped conductive (metal) element and optionally also to the radially outer surface of the tubular backing support member) (preferably the device is disposed in a renal artery and the therapeutic ultrasound is configured for renal denervation) (optionally a device satisfying the requirements of embodiment 1). The piezoelectric transducer body is configured to generate ultrasound waves in response to application of a voltage between an inner electrode and an outer electrode. The device may also be referred to as an "airbag device" and includes an airtight chamber that is evacuated or filled with gas but not liquid. In one embodiment, the backing support member does not include a tubular backing support member, in which the chamber is defined by a radially inner surface of the piezoelectric transducer body, and the chamber has a first axial end and an opposite second axial end configured such that a guidewire can pass therethrough and extend longitudinally through the chamber while the chamber is still airtight.

[0278] [Example / Embodiment 3] 10. The device of any preceding embodiment or any combination thereof, wherein a central portion of the piezoelectric transducer body is configured to vibrate in response to application of a voltage between the inner electrode and the outer electrode to generate the ultrasonic waves, and proximal and distal portions of the piezoelectric transducer body are configured not to vibrate in response to application of a voltage between the inner electrode and the outer electrode, the central portion of the piezoelectric transducer body being located between the proximal and distal portions of the piezoelectric transducer body, and first and second standoff members are attached to the proximal and distal portions of the piezoelectric transducer body, respectively, that are configured not to vibrate in response to application of a voltage between the inner electrode and the outer electrode.

[0279] [Example / Embodiment 4] Optionally, the ultrasonic transducer is free of any (organic) adhesive.

[0280] [Example / Embodiment 5] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the ring-shaped conductive (metallic) part is a standoff member.

[0281] [Example / Embodiment 6] The apparatus of any preceding embodiment or any combination thereof, wherein at one or both ends of the chamber, the tubular backing support member, the ring-shaped conductive (metal) part, and the transducer body form a recess to accommodate the metal solder material.

[0282] [Example / Embodiment 7] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the metallic solder material does not extend beyond the recess / pocket.

[0283] [Example / Embodiment 8] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the metallic solder material is or is in the form of a molten solder washer, optionally provided by placing a metallic solder ball or a ring of metallic solder material (e.g., a solder washer having an inner diameter of 0.02-0.03 inches and an outer diameter of 0.028-0.038 inches before soldering and / or a thickness of 0.005-0.015 inches after soldering) into the recess and then heating the metallic solder material until it melts.

[0284] [Example / Embodiment 9] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the metallic solder material is not present within the chamber.

[0285] [Example / Embodiment 10] The apparatus of any preceding embodiment or any combination thereof, wherein the ring-shaped conductive (metallic) component has a width (in the longitudinal direction of the tubular backing support member) of between 0.003 inches and 0.007 inches.

[0286] [Example / Embodiment 11] The apparatus of any preceding embodiment or any combination thereof, wherein the ring-shaped conductive (metal) piece has an outer diameter of 0.028 inches to 0.038 inches and an inner diameter of 0.02 inches to 0.03 inches.

[0287] [Example / Embodiment 12] The apparatus of any preceding embodiment or any combination thereof, wherein the tubular backing support member has an outer diameter of 0.019 inches to 0.033 inches and an inner diameter of 0.015 inches to 0.029 inches.

[0288] [Example / Embodiment 13] The apparatus of any preceding embodiment or any combination thereof, wherein the tube of piezoelectric material has an outer diameter of between 0.04 inches and 0.061 inches and an inner diameter of between 0.02 inches and 0.045 inches.

[0289] [Example / Embodiment 14] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the longitudinal length of the chamber (i.e., the empty space of the chamber) is 90%-95% of the transducer length.

[0290] Example / Embodiment 15a 10. The apparatus of any preceding embodiment or any combination thereof, wherein the metal solder material is a tin-lead alloy, such as a 63 / 37 tin-lead alloy.

[0291] Example / Embodiment 15b 10. The apparatus of any preceding embodiment or any combination thereof, wherein the metal solder material is a lead-free alloy, such as tin-silver-copper or tin-copper.

[0292] [Example / Embodiment 16] The apparatus of any preceding embodiment or any combination thereof, wherein the radially outer surface of the tubular backing support member is made of gold.

[0293] [Example / Embodiment 17] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the thickness of the tube of piezoelectric material is uniform along the entire length of the piezoelectric transducer body, and the thickness at any two different locations differs by no more than 0.1 mm, no more than 0.05 mm, or no more than 0.025 mm.

[0294] [Example / Embodiment 18] The apparatus of any preceding embodiment or any combination thereof, wherein the tubular backing support member does not delaminate when the apparatus is operated for 30 sonication cycles at an ultrasonic power of 20 W to 42 W for 10 seconds while cooling the apparatus with water.

[0295] [Example / Embodiment 19] The apparatus of any preceding embodiment or any combination thereof, wherein the tubular backing support member does not delaminate when the apparatus is operated for 30 sonication cycles at an ultrasonic power of 30 W to 42 W for 10 seconds while cooling the apparatus with water.

[0296] [Example / Embodiment 20] The device of any preceding embodiment or any combination of those embodiments, wherein the device does not exhibit delamination of the tubular backing support member after use.

[0297] [Example / Embodiment 21] The apparatus of any preceding embodiment or any combination thereof, wherein the piezoelectric transducer with external electrodes and optional insulators has a maximum diameter of 1.5 mm, 1.4 mm, or 1.3 mm.

[0298] [Example / Embodiment 22] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the piezoelectric transducer body has a chamfered end.

[0299] [Example / Embodiment 23] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the piezoelectric transducer body does not have chamfered edges or steps.

[0300] Example / Embodiment 24A 10. The device of any preceding embodiment or any combination of embodiments, wherein the device achieves renal denervation when positioned within a renal artery by ablating the renal nerve at a distance of 1.6 mm to 5.5 mm from the radially outer surface of the transducer body.

[0301] Example / Embodiment 24B 10. The device of any preceding embodiment, or any combination thereof, wherein the device achieves renal denervation when positioned within the renal artery by ablating the renal nerve at a distance of 0.3 mm to 10 mm, e.g., 0.5 mm to 7 mm, or 1 mm to 6 mm, from the radially outer surface of the renal artery vessel.

[0302] [Example / Embodiment 25] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the chamber remains airtight when operated at 15 W of ultrasonic power for 10 seconds for 30 sonication cycles while the apparatus is water-cooled.

[0303] [Example / Embodiment 26] The apparatus of any preceding embodiment or any combination thereof, wherein the chamber remains airtight after being operated at 70 W of ultrasonic power for 10 seconds in air at 20° C. without further cooling. The apparatus may also be referred to as an "airbag apparatus," which may also be referred to as a gas-bag apparatus or an apparatus with a vacuum chamber, depending on whether or not gas is present in the chamber and the type of gas.

[0304] [Example / Embodiment 27] 10. The device of any preceding embodiment or any combination thereof, wherein the backing support member does not include a hollow tube, and only a ring-shaped conductive (metal) part and a metal solder material form the chamber with the inner surface of the hollow piezoelectric transducer body. To ensure that the chamber is airtight, the ring-shaped conductive (metal) part may have a means (such as a membrane) that allows a guidewire or other means to pass longitudinally through the ring-shaped conductive (metal) part and the chamber while providing an airtight seal.

[0305] [Example / Embodiment 28] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the standoff members are sealed to the backing support member using soldering without the use of adhesive.

[0306] [Example / Embodiment 29] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the first and second standoff members are attached by at least one of solder or adhesive to the proximal and distal portions of the piezoelectric transducer body configured not to vibrate, respectively, and the at least one of solder or adhesive provides a hermetic seal that prevents fluid located within the piezoelectric transducer body from leaking into the chamber; and wherein the first and second standoff members are attached to the proximal and distal portions of the piezoelectric transducer body configured not to vibrate in response to application of a voltage between the inner electrode and the outer electrode, respectively, reducing the likelihood of the hermetic seal provided by the at least one of the solder or adhesive failing and causing fluid to leak into the chamber compared to if the at least one of the first and second standoff members were instead attached to the central portion of the piezoelectric transducer body configured to vibrate in response to application of a voltage between the inner electrode and the outer electrode.

[0307] [Example / Embodiment 30] 10. The apparatus of any preceding embodiment or any combination thereof, wherein a wall thickness of the piezoelectric material between the inner and outer surfaces of the piezoelectric transducer body is uniform along at least the central portion of the piezoelectric transducer body configured to vibrate.

[0308] [Example / Embodiment 31] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the inner and outer surfaces of the piezoelectric transducer body correspond to inner and outer diameters of the piezoelectric transducer body, each having a corresponding center, and wherein a concentricity of the wall thickness of the piezoelectric transducer body corresponding to the difference between the centers of the inner and outer diameters of the piezoelectric transducer body is less than or equal to 0.025 mm along the entire length of the piezoelectric transducer body.

[0309] [Example / Embodiment 32] 10. The apparatus of any preceding embodiment or any combination thereof, wherein a wall thickness of the piezoelectric material between the inner surface and the outer surface of the piezoelectric transducer body varies along at least a portion of the central portion of the piezoelectric transducer body configured to vibrate.

[0310] [Example / Embodiment 33] The device of any preceding embodiment or any combination thereof, wherein the piezoelectric transducer body / piezoelectric material is fabricated from Navy Type III (PZT-8) high density lead zirconate titanate (PZT) piezoelectric material, preferably fabricated by hot isostatic pressing (HIP) Navy Type III high density lead zirconate titanate (PZT) piezoelectric material, preferably wherein the HIP reduces the porosity of the Navy Type III high density lead zirconate titanate (PZT) piezoelectric material and increases its density by 7-10%.

[0311] [Example / Embodiment 34] 1. A device comprising an ultrasound transducer configured to emit ultrasound waves (optionally therapeutic ultrasound), optionally the device is positioned within a renal artery and the therapeutic ultrasound is configured for renal denervation, optionally the device is configured for radial access, optionally the device is 4F-5F, the ultrasound transducer is airbag-type, and the piezoelectric transducer body / piezoelectric material is fabricated from Navy Type III (PZT-8) high density lead zirconate titanate (PZT) piezoelectric material, preferably fabricated by hot isostatic pressing (HIP) Navy Type III high density lead zirconate titanate (PZT) piezoelectric material, preferably wherein the HIP reduces porosity of the Navy Type III high density lead zirconate titanate (PZT) piezoelectric material and increases its density by 7-10%.

[0312] [Example / Embodiment 36] 10. The device of any preceding embodiment or any combination thereof, wherein the piezoelectric transducer body / piezoelectric material is fabricated from Navy Type III high density lead zirconate titanate (PZT) piezoelectric material, which has a dissipation factor DF (tan δ) at 1 kHz of less than 0.006 as measured by ASTM D150.

[0313] [Example / Embodiment 37] The device of any preceding embodiment or any combination thereof, wherein the piezoelectric transducer body has an active area length of 0.216 inches to 0.230 inches and / or an overall length (including active and inactive areas) of 0.227 inches to 0.255 inches. Navy Type III (PZT-8) material may be classified using standard MIL-STD-1376B (e.g., February 1995 or later).

[0314] [Example / Embodiment 38] 170W / cm 2 ~327W / cm 2 an airbag ultrasonic transducer configured to generate ultrasonic waves having a power density in the range of

[0315] [Example / Embodiment 39] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the first standoff member, the second standoff member and the backing support member are integrally formed and therefore one piece.

[0316] [Example / Embodiment 40] The apparatus of any preceding embodiment or any combination thereof, wherein at least one of the first standoff member and the second standoff member and the backing support member are formed separately and thus are at least two separate components.

[0317] [Example / Embodiment 41] 10. The apparatus of any preceding embodiment or any combination thereof, wherein at least one of the first standoff member and the second standoff member includes a collar formed separately from the backing support member and having an angled portion configured to provide an interference fit between the outer surface of the backing support member and the inner surface of the piezoelectric transducer body.

[0318] [Example / Embodiment 42] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the (airbag) ultrasonic transducer is configured to withstand at least four separate sonication cycles without failure.

[0319] [Example / Embodiment 43] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the backing support member and the first standoff member are electrically conductive, and the apparatus further comprises a non-conductive tube disposed along the inner surface of the backing support member, thereby electrically isolating the backing support member from fluids or wires entering the hollow tube of the backing support member.

[0320] [Example / Embodiment 44] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the chamber is occupied by a low acoustic impedance medium comprising at least one of air, helium, argon, carbon dioxide, or nitrogen, or the chamber is evacuated.

[0321] [Example / Embodiment 45] 10. The device of any preceding embodiment or any combination thereof, further comprising: a first electrical conductor soldered to a proximal portion of the backing support member; and a second electrical conductor soldered to a proximal portion of the outer electrode; wherein the first standoff member is attached to the inner electrode; each of the backing support member and the first standoff member is electrically conductive; the first electrical conductor soldered to the proximal portion of the backing support member is electrically coupled to the inner electrode; and the proximal portion of the backing support member to which the first electrical conductor is soldered is covered with a dielectric to prevent a short circuit between the inner electrode and the outer electrode when the (airbag type) ultrasound transducer is placed in a conductive fluid and a voltage is applied between the inner electrode and the outer electrode.

[0322]

[0323] [Example / Embodiment 46] An apparatus according to embodiment 45, characterized in that the dielectric covering the proximal portion of the backing support member to which the first electrical conductor is soldered comprises a conformal coating comprising at least one of parylene or polyimide.

[0324]

[0325] [Example / Embodiment 47] 47. The device of embodiment 45 or 46, wherein the dielectric covering the proximal portion of the backing support member to which the first electrical conductor is soldered comprises a dielectric tube.

[0326] [Example / Embodiment 48] 48. The device of any one of embodiments 45 to 47, further comprising a dielectric adhesive on at least a portion of the interior of the dielectric tube.

[0327] [Example / Embodiment 49] 10. The device of any preceding embodiment or any combination thereof, further comprising a catheter including a catheter shaft having a distal portion configured to be inserted into a body cavity of a patient, wherein the (airbag) ultrasound transducer is disposed on the distal portion of the catheter shaft.

[0328] [Example / Embodiment 50] The device of embodiment 49 further comprises a balloon disposed in the distal portion of the catheter shaft and configured to receive a cooling fluid, and the (airbag type) ultrasound transducer is disposed within the balloon.

[0329] [Example / Embodiment 51] 10. The device of any preceding embodiment or any combination thereof, further comprising: a first electrical conductor soldered to a proximal portion of the backing support member; and a second electrical conductor soldered to a proximal portion of the outer electrode; wherein the cooling fluid is a conductive fluid; the first standoff member is attached to the inner electrode; each of the backing support member and the first standoff member is conductive; the first electrical conductor soldered to the proximal portion of the backing support member is electrically coupled to the inner electrode; and the proximal portion of the backing support member to which the first electrical conductor is soldered is covered by a dielectric to prevent a short circuit between the inner electrode and the outer electrode when the (airbag-type) ultrasound transducer is placed in the conductive fluid received by the balloon and a voltage is applied between the inner electrode and the outer electrode.

[0330] [Example / Embodiment 52] 10. The apparatus of any preceding embodiment or any combination thereof, further comprising an excitation source configured to selectively apply a voltage between the inner electrode and the outer electrode of the (airbag) ultrasound transducer.

[0331] [Example / Embodiment 53] An apparatus according to embodiment 49, further comprising a controller configured to control the excitation source so that the (airbag type) ultrasonic transducer is energized at a frequency between 1 MHz and 30 MHz for a time between 3 seconds and 9 seconds.

[0332] [Example / Embodiment 54] An apparatus according to embodiment 50, characterized in that the controller is configured to control the excitation source so that the ultrasonic transducer is energized at a frequency between 8 MHz and 13 MHz for a period of approximately 7 seconds.

[0333] [Example / Embodiment 55] An apparatus according to embodiment 54, characterized in that the controller is configured to control the excitation source so that the (airbag type) ultrasonic transducer is energized at a frequency between 8.5 MHz and 9.5 MHz for a period of approximately 7 seconds.

[0334] [Example / Embodiment 56] 10. The apparatus of any preceding embodiment or any combination thereof, further comprising a controller configured to control the excitation source to cause the (airbag) ultrasonic transducer to emit ultrasonic waves having a first power density during a first time period and to emit ultrasonic waves having a second power density during a second time period occurring after the first time period, the second power density being different from the first power density.

[0335] [Example / Embodiment 57] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the first period of time has a duration within a first range of 2 seconds to 4 seconds, and the second period of time has a duration within a second range of 2 seconds to 4 seconds.

[0336] [Example / Embodiment 58] An apparatus according to any one of embodiments 54 to 57, wherein the controller is further configured to control the excitation source to cause the (airbag-type) ultrasonic transducer not to emit ultrasonic waves during a third period between the first period and the second period, and the third period has a duration within a third range of 2 seconds to 4 seconds.

[0337] [Example / Embodiment 59] 10. The apparatus of any preceding embodiment or any combination thereof, wherein one of the first power density and the second power density is 170 W / cm 2 ~327W / cm 2 and the other of the first power density and the second power density is in the range of 50 W / cm 2~169W / cm 2 The device is characterized in that the range of

[0338] [Example / Embodiment 60] 10. The device of any preceding embodiment or any combination thereof, wherein the catheter is balloon-less and the (airbag) ultrasound transducer is configured to be exposed to conductive blood when the distal portion of the catheter is inserted into a body cavity of a patient.

[0339] [Example / Embodiment 61] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the piezoelectric material is fabricated by hot isostatic pressing a Navy Type III high density lead zirconate titanate (PZT) piezoelectric material.

[0340] [Example / Embodiment 62] The apparatus of any preceding embodiment or any combination thereof, wherein the (airbag) ultrasonic transducer is 2 ~327W / cm 2 10. An apparatus configured to generate ultrasound waves having a power density in the range of

[0341] [Example / Embodiment 63] The apparatus of any preceding embodiment or any combination thereof, wherein the (airbag) ultrasonic transducer is 2 ~327W / cm 2 10. An apparatus configured to generate ultrasound waves having a power density in the range of

[0342] [Example / Embodiment 64] 1. A method of using a catheter having an airbag ultrasound transducer in a distal portion, the method comprising: inserting the distal portion of the catheter into a body cavity of a patient so that the airbag ultrasound transducer is positioned adjacent to a nerve surrounding the body cavity to be ablated; causing the airbag ultrasound transducer to emit ultrasound waves having a first power density for a first period of time while the airbag ultrasound transducer is positioned adjacent to the nerve surrounding the body cavity to be ablated; and causing the airbag ultrasound transducer to emit ultrasound waves having a second power density for a second period of time occurring after the first period of time while the airbag ultrasound transducer is positioned adjacent to the nerve surrounding the body cavity to be ablated, the second power density being different from the first power density.

[0343] [Example / Embodiment 65] 65. The method of embodiment 64, wherein the first period has a duration within a first range of 2 seconds to 4 seconds, and the second period has a duration within a second range of 2 seconds to 4 seconds.

[0344] [Example / Embodiment 66] A method according to embodiment 64 or 65, further comprising a step of causing the ultrasonic transducer not to emit ultrasonic waves during a third period between the first period and the second period, the third period having a duration within a third range of 2 seconds to 4 seconds.

[0345] [Example / Embodiment 67] 67. The method of any of embodiments 64 to 66, wherein one of the first power density and the second power density is 170 W / cm 2 ~327W / cm 2 and the other of the first power density and the second power density is in the range of 50 W / cm 2 ~169W / cm 2 The method according to claim 1, wherein the range is

[0346] [Example / Embodiment 68] 1. An ultrasound transducer configured to emit ultrasound waves (preferably therapeutic ultrasound waves), the ultrasound transducer comprising: a hollow piezoelectric transducer body comprising a tube (cylindrical tube) of piezoelectric material, the tube having a radially inner surface and a radially outer surface; an inner electrode disposed on at least a portion of the inner surface of the tube of piezoelectric material, the inner electrode optionally having a coating on a side opposite the piezoelectric material; an outer electrode disposed on at least a portion of the outer surface of the tube of piezoelectric material, the outer electrode optionally having a coating / protection on a side opposite the piezoelectric material; a tubular backing support member extending longitudinally through the piezoelectric transducer body and having a radially outer surface; and an airtight chamber defined between the radially inner surface of the piezoelectric transducer body and the radially outer surface of the tubular backing support member, the airtight chamber having a first end and an axially opposite second end, the piezoelectric material being fabricated from Navy Type III (PZT-8) high density lead zirconate titanate (PZT) piezoelectric material, preferably Navy Type III (PZT-8). a device (preferably the device is placed in a renal artery and the therapeutic ultrasound is configured for renal denervation) (preferably a device that satisfies the requirements of embodiment 1) fabricated by hot isostatic pressing (HIP) Navy Type III high density lead zirconate titanate (PZT) piezoelectric material, preferably wherein the HIP reduces the porosity of the Navy Type III high density lead zirconate titanate (PZT) piezoelectric material and increases its density by 5-20% or 7-10%.

[0347] [Example / Embodiment 69] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the ring-shaped conductive (metallic) part is a standoff member.

[0348] [Example / Embodiment 70] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the metallic solder material does not extend beyond the recess.

[0349] [Example / Embodiment 71] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the metallic solder material is not present within the chamber.

[0350] [Example / Embodiment 72] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the metal solder material is a tin-lead alloy, such as a 63 / 37 tin-lead alloy, or a lead-free alloy, such as tin-silver-copper or tin-copper.

[0351] [Example / Embodiment 73] The apparatus of any preceding embodiment or any combination thereof, wherein the radially outer surface of the tubular backing support member is made of gold.

[0352] [Example / Embodiment 74] The device of any preceding embodiment or any combination of those embodiments, wherein the device does not exhibit delamination of the tubular backing support member after use.

[0353] [Example / Embodiment 75] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the piezoelectric transducer body has a chamfered end.

[0354] [Example / Embodiment 76] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the piezoelectric material is fabricated by hot isostatic pressing (HIP) a Navy Type III high density lead zirconate titanate (PZT) piezoelectric material, preferably wherein the HIP reduces the porosity of the Navy Type III high density lead zirconate titanate (PZT) piezoelectric material and increases its density by 5-20%.

[0355] [Example / Embodiment 77] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the inner and outer surfaces of the piezoelectric transducer body correspond to inner and outer diameters of the piezoelectric transducer body, each having a corresponding center, and wherein a concentricity of the wall thickness of the piezoelectric transducer body corresponding to the difference between the centers of the inner and outer diameters of the piezoelectric transducer body is less than or equal to 0.025 mm along the entire length of the piezoelectric transducer body.

[0356] [Example / Embodiment 78] The apparatus of any preceding embodiment or any combination thereof, wherein the (airbag) ultrasonic transducer is 2 ~327W / cm 2 10. An apparatus configured to generate ultrasound waves having a power density in the range of

[0357] [Example / Embodiment 79] 10. The apparatus of any preceding embodiment or any combination thereof, wherein the first standoff member, the second standoff member and the backing support member are integrally formed and therefore one piece.

[0358] [Example / Embodiment 80] The apparatus of any preceding embodiment or any combination thereof, wherein at least one of the first standoff member and the second standoff member and the backing support member are formed separately and thus are at least two separate components.

[0359] [Example / Embodiment 81] The apparatus of any preceding embodiment or any combination thereof, wherein the (airbag) ultrasonic transducer is 2 ~327W / cm 2 10. An apparatus configured to generate ultrasound waves having a power density in the range of

[0360] [Example / Embodiment 82] The apparatus of any preceding embodiment or any combination thereof, wherein the (airbag) ultrasonic transducer is 2 ~327W / cm 2 10. An apparatus configured to generate ultrasound waves having a power density in the range of

[0361] [Example / Embodiment 83] 1. A catheter comprising an airbag or gasbag transducer, the transducer having different thicknesses at different locations on the transducer, the catheter configured to selectively steer acoustic signals generated by the transducer.

[0362] [Example / Embodiment 84] 1. A device for denervating a renal artery, comprising an airbag or gasbag transducer having different thicknesses at different locations on the transducer, the device configured to selectively steer an acoustic signal generated by the transducer toward the renal nerve while avoiding non-target tissue.

[0363] [Example / Embodiment 85] 10. The device of any preceding embodiment or any combination thereof, comprising an airbag or gasbag transducer, the transducer having different thicknesses at different locations on the transducer, and the catheter configured to selectively steer acoustic signals generated by the transducer.

[0364] [Example / Embodiment 86] 10. The device of any preceding embodiment or any combination thereof, comprising an airbag or gasbag transducer having different thicknesses at different locations on the transducer, the device configured to selectively steer acoustic signals generated by the transducer toward a renal nerve while avoiding non-target tissue.

[0365] [Example / Embodiment 87] The device of embodiment 86, wherein the non-target tissue includes a lymph node.

[0366] [Example / Embodiment 88] The device of embodiment 88, wherein the non-target tissue comprises one or more of lymph nodes, hypoaxial skeletal muscle with fibrous sheath, calcification, peritoneum, periaqueductal vessels, ureters, intestines, liver, pancreas, urethra, renal pelvis, bladder, liver, pancreas, spleen, or kidneys.

[0367] [Example / Embodiment 89] 10. The device of any preceding embodiment or any combination thereof, comprising a catheter for ablation of tumor and / or cancer cells, the catheter having an airbag or gasbag transducer, the transducer having different thicknesses at different locations on the transducer, the catheter configured to selectively steer acoustic signals generated by the transducer toward the tumor and / or cancer cells while avoiding non-target tissue.

[0368] [Example / Embodiment 90] 10. The device of any preceding embodiment or any combination thereof, comprising a transducer having different thicknesses at different locations on the transducer, and wherein the catheter is configured to selectively steer acoustic signals generated by the transducer toward cardiac target tissue while avoiding non-target cardiac tissue and / or other non-target tissue.

[0369] [Example / Embodiment 91] 1. A method of treating a patient, comprising: imaging a blood vessel and / or surrounding anatomical structures; and selectively activating multiple regions of an airbag or gasbag transducer based on the imaging step to direct acoustic signals toward and / or away from non-targeted areas.

[0370] [Example / Embodiment 92] 1. A method of treating a patient, comprising: imaging a blood vessel and / or surrounding anatomical structures; and selecting, with a processor, an ablation output based on said imaging step, wherein said ablation output comprises an alternating current frequency that selectively activates one or more regions of an airbag-style transducer to direct acoustic signals toward and / or away from non-targets.

[0371] [Example / Embodiment 93] 1. A method of treating a patient using an ablation catheter, comprising: imaging a blood vessel and / or surrounding anatomical structures; and selecting, with a processor, an ablation output of the ablation catheter based on said imaging step, wherein the ablation output comprises a combination of electrodes of the catheter to which an alternating current is applied to selectively activate one or more regions of a gas-bag or air-bag transducer to direct acoustic signals toward and / or away from non-targets.

[0372] [Example / Embodiment 94] The method of embodiment 93, further comprising performing an ablation procedure using a selected ablation output, thereby selectively ablating target structures while avoiding non-target structures.

[0373] [Example / Embodiment 95] A method according to embodiment 94, characterized in that the step of selecting the ablation output of the ablation catheter using a processor based on the imaging step further comprises the step of selecting the vector, amplitude, power, duration, frequency and / or duty cycle of the ultrasonic energy using the processor.

[0374] [Example / Embodiment 96] A method of embodiment 95, characterized in that the step of selecting the ablation output of the ablation catheter using a processor based on the imaging step further includes a step of selecting a flow rate and / or temperature associated with the coolant of the catheter using the processor.

[0375] [Example / Embodiment 97] The method of embodiment 93, wherein the blood vessel is a renal artery and the target is one or more nerves.

[0376] [Example / Embodiment 98] A method of embodiment 93, further comprising the steps of sensing activity of one or more nerves using sensing electrodes of the catheter and determining characteristics of the sensed activity of the one or more nerves, wherein the characteristics indicate one or more of the size, type, function, or health of the one or more nerves, indicate the proximity of the one or more nerves to the sensing electrodes of the catheter, and / or indicate the distribution / location of the nerves around the renal artery.

[0377] [Example / Embodiment 99] A method of embodiment 98, further comprising a step of selecting the frequency of the alternating current to be applied to the gas-bag or air-bag transducer of the catheter, and / or a step of selecting nerve denervation electrodes of the transducer based on the characteristics of the sensed activity of the one or more nerves to selectively target nerves according to their nerve distribution around the body cavity, wherein the nerve denervation parameters are used when performing a nerve denervation procedure intended to denervate at least a portion of the one or more nerves.

[0378] [Example / Embodiment 100] A method according to embodiment 99, characterized in that in the step of selecting the frequency of the alternating current to be applied to the gas-bag or air-bag transducer and / or in the step of selecting the nerve-densifying electrodes of the gas-bag or air-bag transducer, the processor takes into account both (all) of the nerve distribution and the location of structures such as lymph nodes, hypoaxial skeletal muscles with fibrous sheaths, peritoneum, periatrial vessels, ureters, intestines, liver, pancreas, urethra, renal pelvis, bladder, liver, pancreas, spleen, kidneys, etc., and / or calcifications and / or plaques.

[0379] [Example / Embodiment 101] 1. A method of ablating a renal nerve to treat a diagnosed condition in a patient, comprising: stimulating the renal nerve; detecting an evoked response; determining a delay between delivery of the stimulus and detection of the evoked nerve response; determining a depth of the nerve surrounding a renal artery using the delay; and using a processor to select an ablation output of an ablation catheter based on the delay, the ablation output comprising a combination of electrodes of the catheter to which an alternating current is applied to selectively activate one or more regions of a gas-bag or air-bag transducer to direct acoustic signals to the depth of the nerve.

[0380] [Example / Embodiment 102] 1. A method of ablating a renal nerve to treat a diagnosed condition in a patient, comprising: stimulating the renal nerve; detecting an evoked response; determining a delay between delivery of the stimulus and detection of the evoked nerve response; determining a depth of the nerve surrounding a renal artery using the delay; and using a processor to select an ablation output of an ablation catheter based on the delay, wherein the ablation output comprises an alternating current frequency that selectively activates one or more regions of a gas-bag or air-bag transducer to direct acoustic signals to the depth of the nerve.

[0381] [Example / Embodiment 103] 1. A tissue treatment device comprising: a catheter having a distal end; an ultrasound transducer positioned at the distal end of the catheter; and a backing support member, wherein the ultrasound transducer has an inner surface and an outer surface, each of the inner surface and the outer surface having an electrode; the ultrasound transducer attached to the backing support member and defining an air chamber adjacent the inner surface, the air chamber being insulated to prevent fluid from entering the air chamber during use; the backing support member having a distal end and a proximal end; and the ultrasound transducer configured to deliver sufficient acoustic energy during sonication, such as to thermally induce modulation of nerve fibers surrounding a blood vessel to improve a measurable physiological parameter corresponding to a diagnosed patient condition.

[0382] [Example / Embodiment 104] A tissue treatment device of embodiment 103, characterized in that the backing support member has at least one first standoff post at a distal end of the backing support member and at least one second standoff post at a proximal end of the backing support member, each of the at least one first standoff post and the at least one second standoff post having an inner surface and an outer surface, the inner surface being inside the air chamber and the outer surface being outside the air chamber, and the at least one first standoff post and the at least one second standoff post being soldered to the ultrasonic transducer only at the outer surfaces of the at least one first standoff post and the at least one second standoff post.

[0383] [Example / Embodiment 105] 104. The tissue treatment device of embodiment 103, wherein at least the first standoff post and the second standoff post are soldered using a solder preform.

[0384] [Example / Embodiment 106] 104. The tissue treatment device of embodiment 103, wherein the backing support member is a single piece.

[0385] [Example / Embodiment 106] 104. The tissue treatment device of embodiment 103, wherein the backing support member is at least two separate pieces.

[0386] [Example / Embodiment 107] 10. An apparatus, preferably of any preceding embodiment or any combination thereof, comprising: an ultrasonic transducer configured to emit ultrasonic waves, the ultrasonic transducer having a hollow piezoelectric transducer body having a longitudinal axis and a radially inner surface; a tubular backing support member extending longitudinally through the piezoelectric transducer body and having a radially outer surface; a chamber defined between the radially inner surface of the piezoelectric transducer body and the radially outer surface of the tubular backing support member, the chamber being defined between a first axial end and an opposite second axial end; and wherein the ultrasonic transducer is configured to emit an ultrasonic wave having an ultrasonic power of 170 W / cm for a time period between 2 seconds and 4 seconds. 2 ~327W / cm 2 and a controller configured to cause the ends to emit ultrasonic waves having a power density between 0.01 and 0.15, wherein each of the ends is formed by a conductive component and a hermetic sealing layer of metal solder material in contact with a surface of the conductive component opposite the chamber.

[0387] In certain exemplary embodiments described herein, a tissue treatment device is provided comprising: a catheter having a distal end; an ultrasound transducer positioned at the distal end of the catheter; and a backing support member, wherein the ultrasound transducer has an inner (posterior) surface and an outer (anterior) surface, each of the inner and outer surfaces having an electrode; the ultrasound transducer is attached to the backing support member to define an air chamber adjacent the inner surface, the air chamber being insulated to prevent fluid from entering the air chamber during use; the backing support member having a distal end and a proximal end; and the ultrasound transducer is configured to deliver sufficient acoustic energy during sonication, such as to thermally induce modulation of nerve fibers surrounding a blood vessel to improve a measurable physiological parameter corresponding to a diagnosed patient condition.

[0388] In certain exemplary embodiments described herein, there is provided a method of ablating target tissue, the method comprising advancing a catheter including an ablation element through at least one body vessel to a location at or near the target tissue, the ablation element including a piezoelectric component, a backing support member, and an air chamber therebetween, the method further comprising energizing the piezoelectric component of the ablation element to deliver energy to the target tissue, thereby ablating the target tissue, the target tissue including one or more sympathetic nerves or nerve branches.

[0389] In certain exemplary embodiments described herein, a system for ablating target tissue is provided, the system comprising: an ultrasonic energy generator; and a catheter coupled to the ultrasonic energy generator, the catheter configured to be advanceable through at least one body vessel to a location at or near the target tissue, the catheter comprising a catheter shaft and an ablation element at a distal end of the catheter, the ablation element including a piezoelectric element, a backing support member, and an air chamber therebetween, the ultrasonic energy generator operably coupled to the ablation element and supplying energy to the piezoelectric element to deliver energy to the target tissue, thereby ablating the target tissue, the target tissue including one or more sympathetic nerves or nerve branches.

[0390] In certain exemplary embodiments described herein, an ultrasound tissue treatment catheter is provided having a cylindrical ultrasound transducer having an outer diameter of approximately 1.3 mm and an operating frequency of 11-15 MHz, the ultrasound transducer configured to deliver sufficient acoustic energy during sonication, such as to thermally induce modulation of nerve fibers surrounding blood vessels to improve measurable physiological parameters corresponding to a diagnosed patient condition.

[0391] In certain exemplary embodiments described herein, a tissue treatment device is provided comprising a catheter configured to be advanceable through at least one body vessel to a location at or near a target tissue, the catheter including a catheter shaft and an ablation element at a distal end of the catheter shaft, the ablation element including a piezoelectric component having a first edge and a second edge, a backing support member having a cap at a distal end, and an air chamber between the piezoelectric component and the backing support member, the air chamber being insulated to prevent fluids from entering the air chamber during use, and the piezoelectric component configured to deliver energy to the target tissue to ablate the target tissue.

[0392] While several embodiments and examples are disclosed herein, the present application extends beyond the specifically disclosed embodiments to other alternative embodiments and / or uses of the invention, as well as modifications and equivalents thereof. Furthermore, various combinations or subcombinations of specific features and aspects of the embodiments may be made and are within the scope of the invention. Accordingly, it should be understood that various features and aspects of the disclosed embodiments may be combined with or substituted for one another to form varying modes of the disclosed invention. Accordingly, the scope of the invention disclosed herein should not be limited by the specifically disclosed embodiments described above, but should be determined solely by a fair reading of the following claims.

[0393] While the invention is susceptible to various modifications and alternative forms, specific examples thereof have been shown in the drawings and are herein described in detail. It should be understood, however, that the invention is not limited to the particular forms or methods disclosed, but rather is intended to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the various embodiments described and the appended claims. Any methods disclosed herein need not be performed in the order described.

[0394] In the foregoing specification, the invention has been described with reference to specific exemplary embodiments thereof. It will be apparent that various changes may be made therein without departing from the broader spirit and scope of the invention as set forth in the following claims. The specification and drawings are, therefore, to be regarded in an illustrative rather than a restrictive sense.

Claims

1. an ultrasonic transducer configured to emit ultrasonic waves, the ultrasonic transducer having a hollow piezoelectric transducer body having a longitudinal axis and a radially inner surface; a tubular backing support member extending longitudinally through the piezoelectric transducer body and having a radially outer surface; a chamber defined between the radially inner surface of the piezoelectric transducer body and the radially outer surface of the tubular backing support member, the chamber being defined between a first axial end and an opposite second axial end; Equipped with The ends are each formed by a conductive component and a hermetic sealing layer of a metal solder material in contact with a surface of the conductive component opposite the chamber. An apparatus characterized in that

2. the hollow piezoelectric transducer body comprises a tube of piezoelectric material; the tube having a radially inner surface and a radially outer surface; an inner electrode disposed on at least a portion of the interior surface of the tube of piezoelectric material; an outer electrode disposed on at least a portion of the outer surface of the tube of piezoelectric material; Each conductive part is a ring-shaped conductive part.

2. The device of claim 1 .

3. a central portion of the piezoelectric transducer body configured to vibrate and generate the ultrasonic waves in response to application of a voltage between the inner electrode and the outer electrode; the proximal and distal portions of the piezoelectric transducer body are configured not to vibrate in response to application of a voltage between the inner electrode and the outer electrode; the central portion of the piezoelectric transducer body is located between the proximal and distal portions of the piezoelectric transducer body; The ring-shaped conductive portions are attached to the proximal and distal portions, respectively, of the piezoelectric transducer body, the proximal and distal portions being configured not to vibrate in response to application of a voltage between the inner electrode and the outer electrode.

3. The device according to claim 2.

4. The ring-shaped conductive component includes a first standoff member and a second standoff member integrally formed with the tubular backing support member or attached to the tubular backing support member by soldering.

4. The device according to claim 2 or 3.

5. At one or both ends of the chamber, the tubular backing support member, the ring-shaped conductive piece, and the transducer body form a pocket that contains the metal solder material.

4. The device according to claim 2 or 3.

6. The metal solder material is a molten solder washer or is in the form of a molten solder washer.

6. Apparatus according to any one of claims 1 to 5.

7. The ring-shaped conductive piece has a width of 0.003 inches to 0.007 inches.

7. Apparatus according to any one of claims 2 to 6.

8. The ring-shaped conductive piece has an outer diameter of 0.028 inches to 0.038 inches; and an inner diameter of 0.02 inches to 0.03 inches.

8. Apparatus according to any one of claims 2 to 7.

9. the tubular backing support member having an outer diameter of between 0.019 inches and 0.033 inches; and an inner diameter of 0.015 inches to 0.029 inches.

9. Apparatus according to any one of claims 1 to 8.

10. the tube of piezoelectric material has an outer diameter of between 0.04 inches and 0.061 inches; and an inner diameter of 0.02 inches to 0.045 inches.

10. Apparatus according to any one of claims 1 to 9.

11. the chamber is unconstrained; The longitudinal length of the chamber is 90% to 95% of the length of the transducer.

11. Apparatus according to any one of claims 1 to 10.

12. the thickness of the tube of piezoelectric material is uniform along the entire length of the piezoelectric transducer body; The thickness at any two different locations differs by no more than 0.1 mm, no more than 0.05 mm, or no more than 0.025 mm.

12. Apparatus according to any one of claims 1 to 11.

13. The tubular backing support member does not delaminate when the device is water cooled and operated for 30 sonication cycles at an ultrasonic power of 20 W to 42 W for 10 seconds.

13. Apparatus according to any one of claims 1 to 12.

14. The tubular backing support member does not delaminate when the device is water cooled and operated for 30 sonication cycles at an ultrasonic power of 30 W to 42 W for 10 seconds.

14. Apparatus according to any one of claims 1 to 13.

15. The tubular backing support member is not concentrically disposed within the hollow tubular piezoelectric transducer body.

15. Apparatus according to any one of claims 1 to 14.

16. The piezoelectric transducer with its external electrodes and optional insulator has a maximum diameter of 1.5 mm, 1.4 mm, or 1.3 mm.

16. Apparatus according to any one of claims 1 to 15.

17. The piezoelectric transducer body does not have chamfered edges or steps 17. The device of claim 16.

18. The device achieves renal denervation when positioned within the renal artery by ablating the renal nerve at a distance of 1.6 mm to 5.5 mm from the radially outer surface of the transducer body.

18. Apparatus according to any one of claims 1 to 17.

19. The chamber remains airtight when the device is cooled with water and subjected to 30 sonication cycles at 15 W ultrasonic power for 10 seconds.

19. Apparatus according to any one of claims 1 to 18.

20. The chamber remains airtight after being operated at 70 W ultrasonic power for 10 seconds in air at 20° C. without further cooling.

20. Apparatus according to any one of claims 1 to 19.

21. the first standoff member and the second standoff member are attached to the proximal and distal portions of the piezoelectric transducer body, respectively, by at least one of solder or adhesive, the at least one of solder or adhesive providing an airtight seal that prevents fluid located within the piezoelectric transducer body from leaking into the chamber; Because the first and second standoff members are attached to the proximal and distal portions, respectively, of the piezoelectric transducer body that are configured not to vibrate in response to application of a voltage between the inner and outer electrodes, the likelihood that the hermetic seal provided by the at least one of the solder and adhesive will fail and cause fluid to leak into the chamber is reduced compared to if at least one of the first and second standoff members were instead attached to the central portion of the piezoelectric transducer body that is configured to vibrate in response to application of a voltage between the inner and outer electrodes.

5. The device according to claim 4.

22. a wall thickness of the piezoelectric material between the inner and outer surfaces of the piezoelectric transducer body is uniform along at least the central portion of the piezoelectric transducer body configured to vibrate; 22. Apparatus according to any one of claims 1 to 21.

23. the inner and outer surfaces of the piezoelectric transducer body correspond to inner and outer diameters of the piezoelectric transducer body, each having a corresponding center; a concentricity of the wall thickness of the piezoelectric transducer body corresponding to the difference between the centers of the inner and outer diameters of the piezoelectric transducer body is less than or equal to 0.025 mm along the entire length of the piezoelectric transducer body; 23. Apparatus according to any one of claims 1 to 22.

24. A wall thickness of the piezoelectric material between the inner and outer surfaces of the piezoelectric transducer body varies along at least a portion of the central portion of the piezoelectric transducer body that is configured to vibrate.

24. Apparatus according to any one of claims 1 to 23.

25. The piezoelectric transducer body / piezoelectric material is fabricated from Navy Type III (PZT-8) high density lead zirconate titanate (PZT) piezoelectric material by hot isostatic pressing (HIP) of Navy Type III high density lead zirconate titanate (PZT) piezoelectric material.

25. Apparatus according to any one of claims 1 to 24.

26. the piezoelectric transducer body / piezoelectric material is fabricated from Navy Type III high density lead zirconate titanate (PZT) piezoelectric material; The Navy Type III high density lead zirconate titanate (PZT) piezoelectric material has a dissipation factor DF (tan δ) of less than 0.006 at 1 kHz as measured by ASTM D150.

26. Apparatus according to any one of claims 1 to 25.

27. The piezoelectric transducer body has an active area length of 0.216 inches to 0.230 inches and / or an overall length (including active and non-active areas) of 0.227 inches to 0.255 inches.

27. Apparatus according to any one of claims 1 to 26.

28. The piezoelectric transducer body has an active area length of 0.098 inches to 0.118 inches and / or an overall length (including active and inactive areas) of 0.10 inches to 0.13 inches.

28. Apparatus according to any one of claims 1 to 27.

29. The ultrasonic transducer has a power of 90 W / cm 2 ~327 W / cm 2 is configured to generate ultrasound waves having a power density in the range of 29. Apparatus according to any one of claims 1 to 28.

30. The ultrasonic transducer has a power of at least 108 W / cm 2 and configured to generate ultrasonic waves having a power density of 30. Apparatus according to any one of claims 1 to 29.

31. At least one of the first standoff member and the second standoff member is formed separately from the backing support member and includes a collar having an angled portion configured to provide an interference fit between the outer surface of the backing support member and the inner surface of the piezoelectric transducer body.

22. Apparatus according to claim 4 or 21.

32. The ultrasonic transducer is configured to withstand at least four separate sonication cycles without failure.

32. Apparatus according to any one of claims 1 to 31.

33. the backing support member and the first standoff member are electrically conductive; The device comprises: a non-conductive tube disposed along the inner surface of the backing support member; Further provided with This electrically insulates the backing support member from fluids or wires entering the hollow tube of the backing support member.

32. Apparatus according to claim 4, 21 or 31.

34. the chamber is occupied by a low acoustic impedance medium including at least one of air, helium, argon, carbon dioxide, or nitrogen; or The chamber is evacuated 34. Apparatus according to any one of claims 1 to 33.

35. a first electrical conductor soldered to a proximal portion of the backing support member; a second electrical conductor soldered to a proximal portion of the outer electrode; Further provided with the first standoff member is attached to the inner electrode; the backing support member and the first standoff member are each electrically conductive, and the first electrical conductor soldered to the proximal portion of the backing support member is electrically coupled to the inner electrode; The proximal portion of the backing support member to which the first electrical conductor is soldered is covered with a dielectric to prevent a short circuit from occurring between the inner electrode and the outer electrode when the ultrasonic transducer is placed in a conductive fluid and a voltage is applied between the inner electrode and the outer electrode.

34. Apparatus according to claim 4, 21, 31 or 33.

36. The dielectric covering the proximal portion of the backing support member to which the first electrical conductor is soldered includes a conformal coating including at least one of parylene or polyimide.

36. The apparatus of claim 35.

37. The dielectric covering the proximal portion of the backing support member to which the first electrical conductor is soldered includes a dielectric tube.

36. The apparatus of claim 35.

38. Further, a dielectric adhesive is provided on at least a portion of the interior of the dielectric tube.

38. The apparatus of claim 37.

39. a catheter having a distal portion configured to be inserted into a body cavity of a patient; a balloon disposed in the distal portion of the catheter and configured to receive a cooling fluid; Further provided with the ultrasound transducer is disposed in the distal portion of the catheter; The ultrasonic transducer is disposed within the balloon.

39. Apparatus according to any one of claims 4, 21, 31, 33, 35 to 38.

40. the cooling fluid is an electrically conductive fluid; the first standoff member is attached to the inner electrode; the backing support member and the first standoff member are each electrically conductive, and the first electrical conductor soldered to the proximal portion of the backing support member is electrically coupled to the inner electrode; The proximal portion of the backing support member to which the first electrical conductor is soldered is covered with a dielectric to prevent a short circuit from occurring between the inner electrode and the outer electrode when the ultrasound transducer is placed in the conductive fluid received by the balloon and a voltage is applied between the inner electrode and the outer electrode.

40. The apparatus of claim 39.

41. an excitation source configured to selectively apply a voltage between the inner electrode and the outer electrode of the ultrasound transducer; 41. The apparatus of claim 40, further comprising:

42. a controller configured to control the excitation source such that the ultrasonic transducer is energized at a frequency between 1 MHz and 30 MHz for a time between 3 seconds and 9 seconds.

42. The apparatus of claim 41 further comprising:

43. The controller is configured to control the excitation source so that the ultrasonic transducer is energized at a frequency between 8 MHz and 13 MHz for a duration of approximately 7 seconds.

43. The apparatus of claim 42.

44. The controller is configured to control the excitation source so that the ultrasonic transducer is energized at a frequency between 8.5 MHz and 9.5 MHz for a duration of approximately 7 seconds.

43. The apparatus of claim 42.

45. The excitation source is controlled to cause the ultrasonic transducer to emitting ultrasonic waves having a first power density for a first period of time; emitting ultrasonic waves having a second power density during a second period occurring after the first period; Controller configured as Further provided with The second power density is different from the first power density.

45. Apparatus according to any one of claims 1 to 44.

46. the first period of time has a duration within a first range of 2 seconds to 4 seconds; The second period has a duration within a second range of 2 seconds to 4 seconds.

46. ​​The apparatus of claim 45.

47. The controller controls the excitation source to cause the ultrasonic transducer to No ultrasonic waves are emitted during a third period between the first period and the second period. It is further structured as follows: The third period of time has a duration within a third range of 2 seconds to 4 seconds.

43. The apparatus of claim 42.

48. One of the first power density and the second power density is 170 W / cm 2 ~327 W / cm 2 is within the range of The other of the first power density and the second power density is 50 W / cm 2 ~169 W / cm 2 is within the range 46. ​​The apparatus of claim 45.

49. CATHETER HAVING A DISTAL PORTION CONFIGURED FOR INSERTION INTO A BODY CAVITY OF A PATIENT - Patent application Further provided with the ultrasound transducer is disposed in the distal portion of the catheter; The catheter is balloon-free, The ultrasound transducer is configured to be exposed to conductive blood when the distal portion of the catheter is inserted into a body cavity of a patient.

45. Apparatus according to any one of claims 4, 21, 31, 33, 35 to 44.

50. The piezoelectric material is fabricated by hot isostatic pressing Navy Type III high density lead zirconate titanate (PZT) piezoelectric material.

50. The apparatus of claim 49.

51. The metal solder material seal is provided by placing a metal solder ball or ring of metal solder material (e.g., a solder washer having an inner diameter of 0.02-0.03 inches and an outer diameter of 0.028-0.038 inches before soldering and / or a thickness of 0.005-0.015 inches after soldering) into the pocket and then heating the metal solder material until it melts.

50. Apparatus according to any one of claims 1 to 49.

52. 1. An apparatus including an ultrasonic transducer configured to emit ultrasonic waves, The ultrasonic transducer includes: a hollow piezoelectric transducer body comprising a tube of piezoelectric material, the tube having a radially inner surface and a radially outer surface; an inner electrode disposed on at least a portion of the interior surface of the tube of piezoelectric material; an outer electrode disposed on at least a portion of the outer surface of the tube of piezoelectric material; a tubular backing support member extending longitudinally through the piezoelectric transducer body and having a radially outer surface; an airtight chamber defined between the radially inner surface of the piezoelectric transducer body and the radially outer surface of the tubular backing support member, the airtight chamber having a first end and a second end axially opposite the first end; Equipped with The piezoelectric transducer body / piezoelectric material is fabricated from Navy Type III (PZT-8) high density lead zirconate titanate (PZT) piezoelectric material. An apparatus characterized in that

53. 1. A method of using a catheter with an airbag ultrasound transducer in a distal portion, comprising: inserting the distal portion of the catheter into a body cavity of a patient so that the airbag ultrasound transducer is positioned adjacent to a nerve surrounding the body cavity that is to be ablated; causing the airbag ultrasound transducer to emit ultrasound waves having a first power density for a first time period while the airbag ultrasound transducer is positioned proximate to a nerve surrounding the body cavity to be ablated; causing the airbag ultrasound transducer to emit ultrasound waves having a second power density for a second time period occurring after the first time period while the airbag ultrasound transducer is positioned proximate to a nerve surrounding the body cavity to be ablated; The second power density is different from the first power density. A method characterized by:

54. the first period of time has a duration within a first range of 2 seconds to 4 seconds; The second period has a duration within a second range of 2 seconds to 4 seconds.

54. The method of claim 53.

55. causing the ultrasonic transducer not to emit ultrasonic waves during a third period between the first period and the second period; Further provided with The third period of time has a duration within a third range of 2 seconds to 4 seconds.

55. The method of claim 53 or 54.

56. One of the first power density and the second power density is 170 W / cm 2 ~327 W / cm 2 is within the range of The other of the first power density and the second power density is 50 W / cm 2 ~169 W / cm 2 is within the range 56. A method according to any one of claims 52 to 55.

57. a catheter having a distal end; an ultrasound transducer positioned at the distal end of the catheter; a backing support member; Equipped with the ultrasonic transducer has an inner surface and an outer surface; each of the inner surface and the outer surface has an electrode; the ultrasonic transducer is attached to the backing support member and defines an air chamber adjacent the inner surface; the air chamber is insulated to prevent fluid from entering the air chamber during use; the backing support member has a distal end and a proximal end; the backing support member has at least one first standoff post at a distal end thereof and at least one second standoff post at a proximal end thereof; each of the at least one first standoff post and the at least one second standoff post having an inner surface and an outer surface; the inner surface is within the air chamber; the outer surface is external to the air chamber; the at least one first standoff post and the at least one second standoff post are soldered to the ultrasonic transducer only at outer surfaces of the at least one first standoff post and the at least one second standoff post; The ultrasound transducer is configured to deliver sufficient acoustic energy during ultrasound treatment, such as to thermally induce modulation of nerve fibers surrounding blood vessels to improve a measurable physiological parameter corresponding to a diagnosed patient condition. A tissue treatment device characterized by:

58. The at least first and second standoff posts are soldered using a solder preform.

58. The tissue treatment device of claim 57.

59. The backing support member is one piece 59. The tissue treatment device of claim 57 or 58.

60. The backing support member is made up of at least two separate pieces.

59. The tissue treatment device of claim 57 or 58.

61. an ultrasonic transducer configured to emit ultrasonic waves, the ultrasonic transducer having a hollow piezoelectric transducer body having a longitudinal axis and a radially inner surface; a tubular backing support member extending longitudinally through the piezoelectric transducer body and having a radially outer surface; a chamber defined between the radially inner surface of the piezoelectric transducer body and the radially outer surface of the tubular backing support member, the chamber being defined between a first axial end and an opposite second axial end; The ultrasonic transducer was set to 170 W / cm for a time period between 2 and 4 seconds. 2 ~327 W / cm 2 a controller configured to emit ultrasound waves having a power density between Equipped with The ends are each formed by a conductive component and a hermetic sealing layer of a metal solder material in contact with a surface of the conductive component opposite the chamber. An apparatus characterized in that

Images