POMD04490SEC_WO01 CATHETER-BASED HIGH INTENSITY THERAPEUTIC ULTRASOUND (HITU) TRANSDUCER WITH FLEX CIRCUIT CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Application Nos. 63/552,018, filed February 9, 2024, and 63/554,061, filed February 15, 2024, the contents of each are incorporated by reference herein. TECHNICAL FIELD [0002] This description generally relates to minimally invasive apparatuses, systems, and methods that provide energy delivery to a targeted anatomical location of a subject, and more specifically, to catheter-based, intraluminal devices and systems configured to deliver ultrasonic energy to treat tissue, such as nerve tissue. BACKGROUND [0003] High blood pressure, also known as hypertension, commonly affects adults. Left untreated, hypertension can result in renal disease, arrhythmias, and heart failure. Treatment of hypertension has focused on interventional approaches to inactivate the renal nerves surrounding a renal artery. Autonomic nerves tend to follow blood vessels to the organs that they innervate. Intraluminal devices, such as catheters, may reach specific structures, such as the renal nerves, that are proximate to the lumens in which the catheters travel. Accordingly, catheter-based systems can deliver energy from within the lumens to inactivate the renal nerves in and/or surrounding the vessel walls. [0004] One approach to renal nerve deactivation uses radio frequency (RF) energy. The RF energy is delivered to a catheter having multiple electrodes placed against the intima of the renal artery to create an electrical field in the vessel wall and surrounding tissue. The electrical field results in resistive (ohmic) heating of the tissue to ablate the tissue and the renal nerve passing through that tissue. To treat the renal nerves surrounding the renal arteries, the RF electrodes are repositioned several times around the inside of the renal artery. [0005] A system having an ultrasound transducer that emits one or more therapeutic doses of unfocused ultrasound energy has advantages over RF systems. The ultrasound transducer can be mounted at a distal end of the catheter, and the unfocused ultrasound energy can heat tissue adjacent to a body lumen within which the catheter (and the transducer) is disposed. The
POMD04490SEC_WO01 unfocused ultrasound energy system may also include a balloon mounted at the distal end of the catheter around the ultrasound transducer. A cooling fluid can be circulated through the balloon to cool the transducer and body lumen during ultrasound energy delivery. Such an unfocused ultrasound energy system may, for example, ablate target nerves surrounding the body lumen, without damaging non-target tissue such as the inner lining of the body lumen or unintended organs outside of the body lumen. Such a design enables creation of one or more ablation zones sufficient to achieve long-term nerve inactivation at different locations around the circumference of the blood vessel. [0006] Catheters that output ultrasound energy advantageously allow ablative energy to be distributed around a vessel wall at greater depths than permissible with a radiofrequency ablative catheter. Ultrasound energy can be applied to nerves arranged around the vessel. For instance, ultrasound energy can be applied to the renal nerves surrounding the renal artery in order to deactivate these nerves. However, the arrangement of the nerves can change from patient to patient and can be at different locations around the vessel. Additionally, the vessel can be located near tissues and/or organs. As a result, it would be desirable to be able to limit the application of ultrasound energy to the targeted nerves while eliminating or reducing the application of ultrasound energy to the tissues and/or organs in order to optimize procedural efficacy and safety. Further, the vessels can include features such as calcification or plaque. Depending on the conditions, it may be desirable to apply ultrasound energy to the feature or to avoid the feature. As a result, it is desirable to be able to control the application of ultrasound energy within the vessel. SUMMARY [0007] In some aspects, implementations provide a catheter assembly comprising: a high intensity therapeutic ultrasound (HITU) transducer shaped as a cylindrical shell that includes an inner surface defining a chamber, an outer shell for launching ultrasound waves outward, a proximal rim and a distal rim ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ and a flex circuit comprising at least one signal pad electrically connected the outer shell of the HITU transducer and at least one ground pad electrically connected to the post structure. [0008] In some aspects, implementations provide a method to manufacture a catheter assembly, the method comprising: providing a high intensity therapeutic ultrasound (HITU) transducer shaped as a cylindrical shell that includes an inner surface defining a chamber, an
POMD04490SEC_WO01 outer shell for launching ultrasound waves outward, a proximal rim and a distal rim between ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^positioning a post structure in the chamber, wherein the ^^^^^ ^^^^^^^^^^ ^^^ ^^^^^^^^^^^^^ ^^^^^^^^^^ ^^^ ^^^^ ^^^^^^ ^^^^^^^^ ^^^ ^^^^ ^^^^^^^^^^^^ ^^^^^^^ ^^^ electrically connecting at least one signal pad of a flex circuit to the outer shell of the HITU transducer and at least one ground pad of the flex circuit to the post structure. [0009] In certain implementations, a catheter assembly is provided herein comprising: a high intensity therapeutic ultrasound (HITU) transducer shaped as a cylindrical shell that includes an inner surface defining a chamber, an outer shell for launching ultrasound waves outward, a proximal rim and a distal rim between the inner surface and the outer shell; and an electrically-conductive ring adapter, comprising a retaining clip, and a mounting surface extending proximally from the retaining clip; wherein an inner surface of the retaining clip contacts the outer shell of the HITU transducer. [0010] The details of one or more implementations of the subject matter of this specification are set forth in the description, the claims, and the accompanying drawings. Other features, aspects, and advantages of the subject matter will become apparent from the description, the claims, and the accompanying drawings. DESCRIPTION OF DRAWINGS [0011] The novel features of the present disclosure are set forth with particularity in the claims that follow. 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 examples of implementations, in which the principles of the innovative subject matter are utilized, and the accompanying drawings. [0012] FIG. 1 illustrates a side view of a catheter system, in accordance with some implementations. [0013] FIG.2 illustrates a side view of a hub of a catheter system, in accordance with some implementations. [0014] FIG. 3 illustrates a section view along line 1C of the catheter shaft in FIG. 2, in accordance with many implementations. [0015] FIG.4 illustrates an example transducer, in accordance with many implementations. [0016] FIG. 5 illustrates an example post structure, in accordance with many implementations. [0017] FIG.6 illustrates a longitudinal cross-sectional view of a distal portion of a water-
POMD04490SEC_WO01 backed transducer tissue treatment catheter, in accordance with some implementations. [0018] FIG.7 illustrates a longitudinal cross-sectional view of a transducer, wherein both the inner and the outer electrodes of the transducer are selectively insulated, in accordance with some implementations. [0019] FIG.8 illustrates a radial cross-sectional view of the transducer of FIG.7, wherein both the inner and the outer electrodes of the transducer are selectively insulated, in accordance with some implementations. [0020] FIG. 9 illustrates an example of connecting flex circuit pads to the transducer of FIG.4, in accordance with some implementations. [0021] FIG. 10 illustrates an example interconnecting the transducer of FIG. 16 and a micro-coaxial cable using a flex circuit, in accordance with some implementations. [0022] FIG.11 illustrates an example of a micro-coaxial cable terminated on flex pads on a flex circuit, in accordance with some implementations. [0023] FIG. 12 illustrates an example of signal pad and ground pad on a flex circuit, in accordance with some implementations. [0024] FIG. 13 illustrates an example of providing signal pads and ground pads on a flex circuit, in accordance with some implementations. [0025] FIG.14 illustrates an example of mounting a flex circuit using an embodiment of a ring adapter, in accordance with some implementations. [0026] FIG. 15 illustrates an example of mounting a flex circuit using a second embodiment of a ring adapter, in accordance with some implementations [0027] FIG.16 illustrates an example of mounting a flex circuit using a third embodiment of a ring adapter, in accordance with some implementations. [0028] FIG.17 illustrates an example of mounting a flex circuit using a fourth embodiment of a ring adapter, in accordance with some implementations [0029] FIG. 18 illustrates a saline compatible transducer, in accordance with many implementations. [0030] FIG. 19 is a flow chart illustrating a process for manufacturing a high-power transducer using the ring adapter configuration, according to many implementations. [0031] Like reference numbers and designations in the various drawings indicate like elements.
POMD04490SEC_WO01 DETAILED DESCRIPTION [0032] The disclosed technology is directed to systems and methods for providing a catheter assembly that includes a HITU transducer and a flex circuit directly connected to the HITU transducer (e.g., on the proximal side). The HITU transducer is generally shaped as a cylindrical shell with a central void and an outer shell. The implementations incorporate a flex circuit, which can be an interposer that interconnects the HITU transducer and a micro- coaxial cable so that a driving circuit can provide sufficient electrical current to power the operation of the HITU transducer. The flex circuit can also connect the HITU transducer directly to the driving circuit without the micro-coaxial cable. Significantly, the flex circuit can include a matching and tuning network including, for example, series and shunt passive energy storage components (such as capacitors and inductors) based on surface mount technology (SMT). The matching and tuning network refers to a collection of circuit components (such as capacitors and inductors) designed to tune a resonant frequency of HITU transducer and perform impedance matching to allow for efficient coupling between the driving circuit and the HITU transducer so that acoustic output power can be improved while reducing dissipative heating. Moreover, the flex circuit may include a thermocouple layer incorporation, a junction of two or more metals so that the temperature at the junction can be sensed based on, for example, a voltage signal between the metals. Further, the flex circuit can improve the compact form factor by further reducing the footprint of the HITU transducer assembly. For example, in some implementations the post structure of the HITU transducer assembly does not need to protrude substantially outward from the central void. In some cases, the post structure can be substantially flush with respect to the proximal rim of the cylindrical shell of the HITU transducer. In some implementations the compact form factor, along with the flexibility of the flex circuit (e.g., bend ratio), can improve the surgeon’s ability to maneuver the catheter assembly when navigating the tortuosity of human vasculature so that the catheter assembly can easily reach the target vessel (e.g., renal artery) after the catheter assembly is inserted into the human body through a vascular entry point on the human body (e.g., femoral artery). In some implementations, the flex circuit can be disposed on a flexible surface of a ring adapter mounted on the proximal rim of the HITU transducer. Such features can significantly improve the form factor, the flexibility, and the utility of the catheter assembly for intra-operative applications, as discussed in more detail below. [0033] FIGS.1-3 show an exemplary catheter system according to some implementations. The catheter system may include a catheter 10 having a proximal end and a distal end. The
POMD04490SEC_WO01 catheter 10 may include a catheter shaft 12, a balloon 14, and a tip member 15. The balloon 14 can be positioned between the catheter shaft 12 and the tip member 15. The balloon 14 can 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 films, thermoplastic elastomers such as those marked under the trademark PEBAX™, medical-grade thermoplastic polyurethane elastomers such as those marketed under the trademark PELLETHANE™, pellethane, isothane, and other suitable polymers or any combination thereof. [0034] In some implementations, the catheter system for ablating target tissue may comprise an ultrasound energy generator (electronics) 22 and a catheter 10 coupled to the ultrasound energy generator 22. The ultrasound energy generator 22 may also be referred to as the generator 22, the driving circuit and/or the controller. The catheter 10 may be configured to be advanceable through at least one bodily vessel to a position at or near the target tissue. The catheter 10 may comprise a catheter shaft 12 and an ablation element on a distal portion of the catheter 10. The ablation element may comprise a piezoelectric component, e.g., a HITU transducer 200, a post structure 210, and a chamber 231 therebetween, where the chamber 231 can include air or a liquid, such as water. The ultrasound energy generator 22 may be operatively coupled to the ablation element to energize the HITU transducer 200 (e.g., a high intensity therapeutic ultrasound transducer) to deliver energy to the target tissue, ablating the target tissue. The target tissue may comprise one or more nerves or nerve branches. In an example, the target tissue may include nerves or nerve branches starting within the adventitia (i.e., beyond the intima-media thickness) and ending at or less than about 10 mm from the lumen of the blood vessel, e.g., at or less than 6 mm from the lumen. In certain implementations, an imaging transducer is used to find the media-adventitia border and ablation is initiated a set distance, e.g., .1 mm, from the media-adventitia border. In certain implementations, the target tissue may comprise nerves or nerve branches starting within more than 0.3 mm to 10 mm from the lumen of the blood vessel, e.g., 0.5 mm to 6 mm, or 1 mm to 6 mm of the lumen of one or more blood vessels, e.g., a renal artery, hepatic artery, and/or pulmonary artery. In some examples, the target tissue may include cardiac tissue, e.g., electrically conductive cardiac tissue. [0035] In some implementations, the generator 22 may be configured to energize the piezoelectric component, e.g., the HITU transducer 200, for a time period of between 5 to 20 seconds, at a frequency of 11 to 15 MHz, or using both the timing and frequency parameters.
POMD04490SEC_WO01 In some implementations, the generator 22 may be configured to energize the piezoelectric component for a time period of between 6 to 10 seconds, at a frequency of 12 to 14 MHz, or using both the timing and frequency parameters. In various implementations, the generator 22 may be configured to energize the piezoelectric component for a time period of about 7 seconds, at a frequency of about 13 MHz, or using both the timing and frequency parameters. Energizing the piezoelectric component by the generator 22 may increase a temperature of the piezoelectric component by, e.g., no more than 50° C. Energizing the piezoelectric component by the generator 22 delivers energy at an average surface acoustic intensity of between 20 and 150 W/cm2. [0036] The catheter 10 can have a handle 16 at the proximal end of the catheter shaft 12. The handle 16 can include one or more electrical couplings 18 for connecting the catheter 10 to one or more external electrical conductors 20 that are each in electrical communication with the generator 22 and/or other electronics. Suitable external electrical conductors 20 include, but are not limited to, wires, cables, and Flexible Printed Circuits (FPC). [0037] The generator 22 can control the catheter 10 to sweep the operating frequency and can control the durations of the individual pulses and total time of series of pulses to control the temperature in the ablation zones and shape the lesion. [0038] The catheter shaft 12 can include one or more electrical lumens 121. Each of the electrical lumens 121 may extend from one or more of the electrical couplings 18 along a longitudinal length of the catheter shaft 12 toward a distal end of the catheter shaft 12. The electrical lumen can each hold one or more electrical conductor carriers that each carry one or more electrical conductors. The electrical conductors can be in electrical communication with the generator 22 through the electrical coupling 18 and one or more of the external electrical conductors 20. Suitable electrical conductors include, but are not limited to, wires, insulated wires, cables, and Flexible Printed Circuits (FPC). When an electrical conductor carrier carries multiple electrical conductors 20, a suitable electrical conductor carrier can be an electrically insulating jacket. When an electrical conductor carrier carries a single electrical conductor 20, an electrical insulator on the electrical conductor can serve as the electrical conductor carrier. [0039] The handle 16 can include one or more fluid ports 24 for connecting the catheter to a conduit 26. Suitable conduits 26 include, but are not limited to, tubes and hoses. A conduit 26 can provide fluid communication between the fluid port 24 and a fluid source 28. Suitable fluid sources 28 include, but are not limited to, pumps, tanks, reservoirs, and vessels. The catheter shaft 12 can include one or more fluid lumens 239. Each of the fluid lumens 239 can
POMD04490SEC_WO01 be in fluid communication with one of the fluid ports 24 along a longitudinal length of the catheter shaft 12 toward a distal end of the catheter shaft 12. Each fluid lumen 239 may be in fluid communication with a different fluid port, or at least one fluid lumen 239 may be in fluid communication with the same fluid port 24 as at least one other fluid lumen 239. [0040] The handle 16 can include one or more guidewire ports 30 for receiving a guidewire 31. The catheter shaft 12 can include a guidewire lumen 301. The guidewire lumen 301 can extend along a longitudinal length of the catheter shaft 12 toward a distal end of the catheter shaft 12. The guidewire lumen 301 can be in fluid communication with the guidewire port 30 such that a guidewire 31 inserted into the guidewire port 30 can be received within the guidewire lumen 301. [0041] In some implementations, the catheter 10 can include an ultrasonic imaging transducer 17, e.g., a transducer of a single element or an array, at the distal end of catheter 10. The imaging transducer 17 may have a center frequency of 15 – 50 MHz, e.g., 20 – 30 MHz, which can be used to identify target and nontarget structures. The imaging transducer 17 can be positioned proximal to or distal to the balloon 14. The imaging transducer 17 can comprise of a ring array having a single ring or multiple rings. The imaging depth can be up to approximately 12 mm and can be used to size the vessel, image anatomy, pathology, lesion formation, temperature changes, heat sinks such as lymph nodes, vessel walls, plaques, calcification, tissue layers and nerves. The imaging frequency can be approximately 20 MHz – 35 MHz, the bandwidth can be equal or greater to 10 MHz, and/or the array size can comprise 16 to 256 elements, however, these characteristics are descriptive, not restrictive. The array element dimension can be 0.5 mm – 1.5 mm in length and 0.5 – 2 wavelengths in width. Multiple-row cylindrical array can help reduce the image slice thickness to achieve better contrast resolution. The elements may be individually controlled to transmit and receive, for example, by an ASIC circuit, to reduce the number of cables needed. In other embodiments, the HITU transducer 200 is utilized for imaging as well as for treatment, and a separate ultrasonic imaging transducer 17 thus may be omitted. In still other embodiments, imaging is not performed utilizing the catheter 10. [0042] In some implementations, the catheter 10 may additionally or alternatively include electrodes on the balloon 14, configured to sense nerve activity and/or confirm the effectiveness of the treatment, as disclosed in U.S. Patent Publication No. 20230021354, to Zhai et al., which is incorporated herein by reference in its entirety. [0043] In some implementations, the catheter system may additionally or alternatively
POMD04490SEC_WO01 include the nerve sensing and/or treatment confirmation components disclosed in U.S. Patent Application No.63/320,103 to Barman et al. filed March 15, 2022, which is incorporated herein by reference in its entirety. As disclosed in further detail in U.S. Patent Application No. 63/320,103, treatment confirmation components may be used to determine a latency of sensed electrical impulses to determine the type, size, function and/or health of the fibers whose neural response is being sensed. The delay (aka latency) may be indicative of a depth of nerves surrounding a biological lumen (e.g., a renal artery) within which a catheter used to measure the delay is located. In accordance with some implementations of the present technology, the above-described delay can be used to select the frequency used for the ablations. The generator 22 controls the catheter 10 to sweep the operating frequency and control the durations of the individual and total treatment time to control the temperature in the ablation zones, and shape the tissue lesion caused by the application of ultrasound to tissue. Application of lower frequency ultrasound by the HITU transducer 200 may be used to aim at deeper regions, when it is determined that nerves are located in the deeper regions. Application of higher frequency ultrasound by the HITU transducer 200 may be used to target shallower regions, when it is determined that nerves are located in the shallower regions. Additional details are disclosed in US Application No.: 18/451,044 filed on August 16, 2023, which is incorporated herein by reference in its entirety. [0044] Some implementations provide a tissue treatment catheter 10 that includes a therapy intravascular ultrasound transducer assembly 211. The therapy intravascular ultrasound transducer assembly includes an HITU transducer 200 positioned at the distal end of the catheter 10, as illustrated in FIG. 4. The HITU transducer 200 is arranged as a hollow cylindrical tube of piezoelectric material having an outer shell, an inner surface defining a void, and a rim connecting the outer shell with the inner surface. The post structure 210 is arranged inside the inner shell of the cylindrical tube and is electrically coupled to the inner surface of the cylindrical tube. As further depicted in FIGS.5 to 13, the implementations can incorporate various configurations in which the HITU transducer 200 is directly and proximally connected to a flex circuit 240. [0045] As illustrated in FIG.4, the implementations may provide an HITU transducer 200. In some cases, the back of the HITU transducer 200 is coupled to a chamber that includes a gas or liquid. The HITU transducer 200 can be constructed as an air-backed or water-backed transducer, e.g., that includes a chamber inside an inner shell of a cylindrical tube. The chamber 231 may be filled with a gas, such as air, to form an air-backed transducer. The phrase
POMD04490SEC_WO01 “air-backed” is not limited to the use of air alone, and is expressly defined to include other suitable gases, such as helium, argon, and/or nitrogen. An inner electrode 502 may be formed on an inner surface of the cylindrical tube of the HITU transducer 200 and an outer electrode may be formed on an outer surface of the cylindrical tube of the HITU transducer 200, in any suitable manner. [0046] The interface between the medium within the chamber 231, e.g., air or a liquid, and the body of the HITU transducer 200 can be highly reflective. For example, the interface can be highly reflective because, e.g., gas or liquid may have an acoustic impedance far lower than that of the ceramic of the piezoelectric material. This interface can serve as a backing interface and can help to direct acoustic vibrations through the outer surface of the cylindrical tube, which serves as the front or emitting surface of the transducer. Backed transducers, such as air-backed or water-backed transducers, can provide good efficiency and can be compact. In some implementations, the HITU transducer 200 may withstand the levels of power required to ablate target tissue, e.g., renal nerves, for example, up to about 150 W/cm2 or more across the outer surface area of the HITU transducer 200, such that the HITU transducer 200 is configured to deliver sufficient acoustic energy during sonication such as to thermally induce modulation of neural fibers surrounding the blood vessel, the thermally induced modulation being sufficient to improve a measurable physiological parameter corresponding to a diagnosed condition of the patient, while being sufficiently small to fit in a renal artery and/or permit radial access using a 5F or smaller catheter. Implementations of the present disclosure incorporate various ring adapter configurations for connecting, for example, a proximal end of the HITU transducer 200, to a micro-coaxial cable 270. The implementations are not limited to air-backed or water-backed transducers. [0047] In some embodiments, the catheter shaft 12 has an outer diameter of 5 French or less. The catheter shaft 12 may include a water-backed HITU transducer 200 that may emit ultrasound energy at a frequency of about 9 MHz. In certain embodiments, the HITU transducer 200 is configured to emit ultrasound energy in a frequency range of 8.5 to 9.5 MHz. The HITU transducer 200 may be configured to produce an acoustic output power within a range of 20 to 45 Watts, in response to an input electrical power from the generator 22 within a range of 25 to 50 Watts. In some embodiments, the generator 22 is configured to output to the HITU transducer 200, via the external electrical conductors 20, a power of about 50 W into 63 ohms at 7 seconds on, having an output frequency of about 8.5-9.5 MHz. In some embodiments, the generator 22 is configured to output to the HITU transducer 200, via the
POMD04490SEC_WO01 external electrical conductors 20, a power of about 25 W to 50 W at 7 to 10 seconds on, resulting in an output frequency from the HITU transducer 200 of about 8.5-9.5 MHz. [0048] In some embodiments, the catheter shaft 12 has an outer diameter of 4 French or less. In some embodiments, the catheter shaft 12 may include a water-backed HITU transducer 200 that may emit ultrasound energy at a frequency of about 12-16 MHz. In other embodiments, the HITU transducer 200 may emit ultrasound energy at a frequency between 16 MHz and 20 MHz, e.g., 8.5 MHz to 9.5 MHz, 10 MHz, 12 MHz, or 15 MHz, or at a frequency of between 6 MHz and 20 MHz, e.g., 8.5 MHz to 9.5 MHz, 10 MHz, 12 MHz, or 15 MHz. In some embodiments, the catheter shaft 12 may have a working length of at least 155 cm or at least 145 cm. In some embodiments, the generator 22 is configured to output to the HITU transducer 200, via the external electrical conductors 20, a power of about 15 W to 35 W at 7 to 12 seconds on, having an output frequency of about 12-16 MHz. In some embodiments, the catheter is a 4 F catheter and the generator 22 is configured to output to the HITU transducer 200, via the external electrical conductors 20, a power of about 15 W to 35 W at 7 to 12 seconds on, resulting in an output frequency from the HITU transducer 200 of about 12-16 MHz. In some embodiments, the HITU transducer 200 is configured to produce an acoustic output power within a range of 25 to 50 Watts, in response to an input electrical power within a range of 10 to 80 Watts received from the generator 22 via the external electrical conductors 20. [0049] FIG.6 illustrates a longitudinal cross-sectional view of a distal portion of a water- backed transducer catheter of an ultrasound-based tissue treatment system, in accordance with an embodiment. The HITU transducer 200 can be generally supported via a backing member or post 507. In certain embodiments, the backing member 507 comprises stainless steel coated with nickel and gold. Nickel can be used as a bonding material between the stainless steel and gold plating. In certain embodiments suitable, e.g., for renal denervation, an outer diameter of the HITU transducer 200 may be about 1.5 mm, an inner diameter of the HITU transducer 200 may be about 1 mm, and the HITU transducer 200 may have a length of about 6 mm. Ultrasound transducers 200 having other inner diameters, outer diameters, and lengths, and more generally dimensions and shapes, are also within the scope of the embodiments described herein. Further, it is noted that the drawings in the figures are not necessarily drawn to scale and often are not drawn to scale. [0050] In order to permit liquid cooling along both the inner and outer electrodes 502, 504, the backing member 507 may include one or more stand-off posts 212. The stand-off
POMD04490SEC_WO01 assemblies 512 may define one or more annular openings through which cooling fluid 403 may enter the space of the HITU transducer 200 (which may be selectively insulated as described with respect to FIGS. 7-8) between the backing member 507 and the inner electrode 502. Accordingly, the backing member 507 may serve as a fluid barrier between the cooling fluid 403 circulated within an interior 506 of the balloon 112 and the lumen of the backing member 507 that receives the guidewire 31. [0051] In accordance with certain embodiments, the stand-off posts 212 are electrically conductive, so as to electrically couple the inner electrode 502 of the HITU transducer 200 to the backing member 507. One or more conductors of the electrical cabling 230 may be electrically coupled to the backing member 507. Thus, as the controller 120 is activated, current may be delivered from the electrical cabling 230 to the inner electrode 502 of the HITU transducer 200 via the backing member 507 and the stand-off posts 212, which advantageously eliminates the need to couple the cabling 230 directly to the inner electrode 502 of the HITU transducer 200. In other embodiments, the backing member 507 and the stand-off assemblies 512 are made of one or more electrical insulator material(s), or if made of an electrically conductive material(s), are coated with one or more electrical insulator material(s). In certain embodiments, one or more electrical conductors of the cabling 230 are directly coupled (e.g., soldered) to the inner electrode 502 of the HITU transducer 200. [0052] Referring again to FIG. 6, for both the water-backed and air-backed HITU transducer 200, the backing member 507 may have an isolation tube 520 disposed along its interior surface so as to prevent or reduce the likelihood of electrical conduction between the guidewire 31 and the backing member 507, for use in embodiments where such an electrical conduction is not desired. The isolation tube 520 can be formed of a non-electrically conductive material (e.g., a polymer, such as polyimide), which can also be referred to as an electrical insulator. As illustrated in FIGS. 5A and 5B, the isolation tube 520 may extend through the lumen of the backing member 507 within the HITU transducer 200 toward the catheter tip 404. [0053] FIGS. 7-8 illustrate, respectively, a longitudinal cross-sectional view and a radial- cross sectional view, of an embodiment of a water-backed HITU transducer 200 where both an inner electrode 502 and an outer electrode 504 (which are located on inner and outer surfaces, respectively, of a tubular HITU transducer 200) are covered by electrical insulators. More specifically, the inner electrode 502 is covered by the inner electrical insulator 1302, and the outer electrode 504 is covered by the outer electrical insulator 1304. Both the inner and outer
POMD04490SEC_WO01 electrodes 502, 504 may be insulated with insulators 1302, 1304. In other embodiments, only one of the inner electrode 502 and the outer electrode 504, is insulated with the corresponding insulator 1302, 1304. In some embodiments, only the inner electrode 502 is insulated with the inner electrical insulator 1302, and the outer electrode 504 is uninsulated. In some embodiments, only the outer electrode 504 is insulated with the outer electrical insulator 1304, and the inner electrode 502 is uninsulated. [0054] FIG. 5 illustrates the post structure 210 for the HITU transducer 200 of FIG. 16. The post structure 210 may include at least a first conductive part 212, e.g., a first stand-off post 212, at the distal end of the post structure 210 and at least a second conductive part 212, e.g., a second stand-off post 212, at the proximal end of the post structure 210. Some implementations, e.g., instead of the stand-off post 212, may include a chamfered portion. The HITU transducer 200 may optionally be mounted to at least the first and second stand-off posts 212 of the post structure 210 to define the chamber 231 adjacent the inner surface 207, the chamber 231 being insulated to prevent entry of a substance, such as an outside fluid, into the chamber 231 during use, such as to prevent entry of electrically conductive fluid. The device can be saline compatible, that is, the HITU transducer 200 can operate when immersed in electrically conductive fluid to deliver sufficient acoustic energy during sonication such as to thermally induce modulation of neural fibers surrounding the blood vessel sufficient to improve a measurable physiological parameter corresponding to a diagnosed condition of the patient, e.g., to create an ablation zone 3 mm to 6 mm wide, e.g., 5 mm wide, and 0.5 mm to 10 mm, e.g., 1 mm to 6 mm, in depth from the lumen of the blood vessel. [0055] FIGS.9 to 13 illustrate various configurations for directly connecting, for example, the proximal end of the HITU transducer 200, to the flex circuit 240. In FIG. 9, flex pad 241 on flex circuit 240 is soldered to a signal electrode 200A of the HITU transducer 200. Here, the signal electrode 200A is located towards the proximal rim where the outer shell may be chamfered or depressed inward so that, after soldering, the HITU transducer 200 may generally retain the original dimension or form factor. For example, the outer diameter of the HITU transducer 200 after soldering may remain between about 0.015” (0.381 mm) and about 0.118” (3 mm), as before soldering. Connecting the flex circuit 240 to the electrode is not limited to soldering. Other approaches such as epoxying and welding can also be used. Example configurations of signal pad 241 can be found in FIG.12. [0056] FIG. 10 shows the flex circuit 240 connected to the HITU transducer 200 with micro-coaxial cable 270. At the distal end, the flex circuit 240 is electrically connected to
POMD04490SEC_WO01 signal electrodes 200A on the HITU transducer 200. One or more signal conductors on the flex circuit 240 can be interconnected to the outer shell of the HITU transducer 200. In some cases, more than one signal electrode 200A can be arranged on the outer shell of the HITU transducer 200. Because each signal electrode 200A in this arrangement has a smaller gauge conductor when compared to a single larger gauge conductor used for a single electrode, this arrangement can improve flexibility of the transducer assembly while providing sufficient electrical power to the transducer. The flex circuit 240 is also electrically connected to post structure 210, which serves as the ground electrode for the HITU transducer 200. At the proximal side, the flex circuit 240 is electrically connected to the signal lines and grounding lines of micro-coaxial cable 270. The body of the flex circuit 240 may take various forms including, for example, multi-pronged configurations with a central stem where the prongs are branches extending distally (e.g., to connect with the HITU transducer 200) and proximally (to connect with micro-coaxial cable 270). Such configurations may improve the flexibility of the catheter assembly when navigating the tortuosity of human vessels. [0057] The flex circuit 240 can include one or more layers of conductor traces (e.g., signal trace and ground trace). Significantly, the flex circuit 240 can include series (within the signal trace) and/or shunt (between the signal and ground trace) surface mount components such as capacitors and inductors. As passive components that may not require, for example, battery power, capacitors and inductors can be either in series or in parallel with the HITU transducer 200 to form a tuning and matching network 244. By judiciously selecting the capacitance and inductance parameters as well as the serial/parallel arrangements, the HITU transducer 200 can resonate at a frequency substantially tuned to, for example, the driving frequency provided by the generator 22 of FIG. 1. At the resonant frequency, the HITU transducer 200 may exhibit an impedance substantially matched to that of the driving circuit so that acoustic output generated by the HITU transducer 200 can be significantly increased and potentially maximized without dissipating significant power over the micro-coaxial cable 270 and the flex circuit 240. The tuning and matching network may include additional control traces to operate digitally tunable capacitors--the capacitance of which can be varied according to a control voltage--so that the HITU transducer 200 can be dynamically tuned to operate a multitude of resonating frequencies. [0058] The flex circuit 240 can also include a thermocouple layer 243 configured for temperature sensing. Thermocouple layer 243 may include a junction formed by at least two metal traces. By monitoring a voltage generated at the junction in response to varying
POMD04490SEC_WO01 temperature, the thermocouple layer can sense the temperature at the junction. Thermocouple layer 243 can be more distally located than the tuning and matching network 244. For example, thermocouple layer 243 can be disposed in a vicinity of the HITU transducer 200. In this example, thermocouple layer 243 can be routed more distally so that the junction is placed in the immediate vicinity of the HITU transducer 200 (e.g., the proximal end of the HITU transducer 200). In some cases, the junction of the thermocouple layer 243 can be routed through the inner space of post structure 210 to reach the distal side of the HITU transducer 200. For example, the thermocouple layer can be routed more distally than the proximal connection of the flex circuit 240 to reach the transducer’s distal side either through the chamber space between the HITU transducer 200 and the post structure 210, or inside the lumen of post structure 210. In either case, the arrangement does not interfere with the guidewire for the catheter assembly. As an additional example, the thermocouple layer can be routed to reach the balloon surface or inside the balloon volume. [0059] FIG. 11 illustrates an example in which micro-coaxial cable 270 is terminated at pads on the flex circuit 240. In this example, the micro-coaxial cable 270 is distally terminated to the flex circuit 240 at the proximal end of the flex circuit 240 to facilitate packaging the catheter 10. The proximal end of the micro-coaxial cable 270 can then be terminated directly to the proximal connector or the integrated cable printed wire board (both not shown) for connecting to the generator 22 of FIG.1. In this example, the flex circuit 240 is short enough to improve the flexibility of the catheter 10. When the flex circuit 240 is terminated to the HITU transducer 200, the remaining pads on the flex circuit 240 can allow for transducer performance testing without having to terminate the micro-coaxial cable 270. In this scenario, additional cable pads may then allow termination of the micro-coaxial cable 270 to the flex circuit 240. Additionally, or alternatively, the micro-coaxial cable 270 can be terminated to the flex circuit 240 at the proximal end of the micro-coaxial cable 270 so that there would be no need to reprepare the proximal end of the micro-coaxial cable 270 in order to install it in the catheter lumen. In this scenario, the proximal end of the flex circuit 240 can then be terminated directly to the proximal connector or the integrated cable printed wire board. [0060] While the examples shown in FIGS.9 to 11 represent direct termination to the HITU transducer 200 with a sample flex circuit 240, the examples demonstrate functionalities of the implementations. To deliver the +/- 100 peak rms (root mean square) voltage and 0.8 peak rms amps for 80 W peak electrical power for transducer excitation, the flex circuit 240 trace cross sectional area can be increased using thicker copper layers and/or wider traces. Either or both
POMD04490SEC_WO01 of these approaches may be employed to achieve the desired electrical performance. For example, when incorporating a flex circuit 240 in the electrical pathway between the transducer and the proximal connector, the flex circuit 240 copper layer can be characterized by at least one ounce copper (Cu) and the trace widths can be 200 microns or more to support the excitation voltages and currents of the transducer. Meanwhile, the flex circuit 240 is flexible enough to provide a bend ratio of at least 10:1. In this way, the flexibility of the catheter 10 is enhanced to allow for denervation of nerve tissue, or treatment of other tissue, accessible through other, more tortuous blood vessels. Thus, nerves such as the splanchnic nerve, the hepatic nerve, the celiac ganglion, and/or other nerves may be more effectively treated with the catheter 10. [0061] FIGS.12 and 13 illustrate example arrangements of pads on flex circuit 240 (shown in FIGS. 9 to 11) to achieve the desired form factor. As illustrated in FIG. 12, signal pad 241 and ground pad 242 are disposed on a flexible substrate. Ground pad 242 can be 0.030” (0.762 mm) in height and 0.008” (0.203 mm) in width. Signal pad 241 (smaller than ground pad 242) can be offset from ground 242 by 0.01475” (0.37465 mm) laterally and 0.05675” (1.44145 mm) vertically. For the interposer configuration illustrated in FIG. 10, the signal pad 241 and the ground pad 242 on the flex circuit 240 can be soldered to the transducer signal electrode 200A and the post structure 210 respectively. Additionally, or alternatively, the signal pad 241 and the ground pad 242 can be bonded, using conductive adhesive, to the transducer signal electrode 200A and the post structure 210 respectively. In the example depicted in FIG. 12, the ground pad 242 is disposed on a flex circuit wing, which can wrap around the post structure 210. [0062] FIG.13 includes an upper panel showing area 250 encircling a signal pad 241 and a ground pad 242. As illustrated, the signal pad 241 is shaped as square of 0.0065” (0.1651 mm) by 0.0065” (0.1651 mm), and the ground pad 242 is measured in 0.04” (1.016 mm) in height and 0.02275” (0.57785 mm) in width. [0063] FIG. 13 also includes a lower panel showing an interposer arrangement 251 with two (2) signal pads 241 and two ground pads 242. In addition to using one signal pad 241 and one ground pad 242 for connecting to the HITU transducer 200 and post structure 210, FIG. 13 allows for the other signal pad 241 and the other ground pad 242 for connecting to the conductor and shield of micro-coaxial cable 270. The two signal pads 241 are disposed on a layer of conducting metal or connected by a conducting trace. The two ground pads 242 are likewise electrically connected by an underlying layer of conducting metal or an underlying
POMD04490SEC_WO01 trace of conducting metal. As illustrated, the two signal pads 241 and the two ground pads 242 are sized at 0.030” (0.762 mm) in height and 0.008” (0.203 mm) in width. [0064] The implementations may also incorporate a ring adapter 260 for connecting the flex circuit 240 to the HITU transducer 200. Referring to FIG. 14, one embodiment of a ring adapter 260 is shown. While direct connection of the micro-coaxial cable 270, which may include two wires 271, 272, to the electrodes 502, 504 is an effective way to couple the micro- coaxial cable 270 to the electrodes 502, 504, such a connection may be difficult to manufacture. Soldering an end of each of the wires 271, 272 to the corresponding electrode 502, 504, such as by tack soldering, may be challenging to perform. Further, soldering an end of one of the wires 271, 272 to the outer electrode 504 increases the outer diameter of the HITU transducer 200, which may be undesirable where the HITU transducer 200 is used to treat one or more blood vessels where the diameter of the blood vessel lumen is small. As an alternative, the micro-coaxial cable 270 may be connected to the electrodes 502, 504 via a ring adapter 260. [0065] An exemplary ring adapter 260 may include a retaining clip 263 configured to fit around the proximal end of the HITU transducer 200. In some embodiments, the retaining clip 263 may be shaped as an interrupted ring, allowing for the retaining clip 263 to flex at least slightly. In this way, the retaining clip 263 may be flexed to a more-open configuration, placed over the HITU transducer 200, then released to engage the outer surface of the HITU transducer 200. In such a configuration, the retaining clip 263 may be configured to have an inner circumference, prior to placement on the HITU transducer 200, slightly less than the outer circumference of the HITU transducer 200. In this way, when the retaining clip 263 is released, the retaining clip 263 may apply a compressive force to the HITU transducer 200, assisting in holding the retaining clip 263 in place. In other embodiments, the retaining clip 263 may be substantially rigid, and/or may be shaped as an uninterrupted ring. In such embodiments, the retaining clip 263 may be slid onto an end of the HITU transducer 200 without substantially flexing. [0066] In some embodiments, the HITU transducer 200 may be stepped, meaning that it includes a step defined at a proximal end thereof, where the outer diameter of the HITU transducer 200 at the step is less than the outer diameter of the remainder of the HITU transducer 200. In such embodiments, the retaining clip 263 may be sized to have a thickness such that the inner diameter of the retaining clip 263 contacts the outer diameter of the step, and the outer diameter of the retaining clip 263 is substantially flush with the remainder of the HITU transducer 200.
POMD04490SEC_WO01 [0067] In some embodiments, the ring adapter 260 may have one or more tabs 264 arranged, for example, in two instances on the distal edge of retaining clip 263, oriented toward the center of the retaining clip 263. The tab(s) 264 contact a proximal end of the HITU transducer 200 in order to place the retaining clip 263 at the proximal end of the HITU transducer 200. In this way, the ring adapter 260 may be placed at a consistent location relative to the HITU transducer 200, facilitating the manufacturing process. A mounting surface 262 extends outward from the retaining clip 263. Where the tabs 264 are utilized, the mounting surface 262 extends from the opposite end of the retaining clip 263 from which the tabs 264 extend. The mounting surface 262 extends along part of the circumference of the retaining clip 263 and may have the same inner radius of curvature as the inner surface of the retaining clip 263 and the same outer radius of curvature as the outer surface of the retaining clip 263. As seen in FIG. 14, at least one wire 271 of the micro-coaxial cable 270 extends along the mounting surface 262, and the mounting surface 262 extends proximally from the HITU transducer 200. During the manufacturing process, solder may be applied to the at least one wire 271 and the mounting surface 262 to secure the at least one wire 271 to the mounting surface 262. The ring adapter 260 is electrically conductive. Thus, the solder connection between the at least one wire 271 and the mounting surface 262 electrically connects the at least one wire 271 to the retaining clip 263 and the surface of the HITU transducer 200 as well. Further, the use of the mounting surface 262 provides for a relatively large contact surface for the at least one wire 271 and provides for a solder location radially inward from the outer circumference of the HITU transducer 200. In this way, manufacturing may be simplified and the overall diameter of the HITU transducer 200 and the connected at least one wire 271 may be reduced compared to existing manufacturing methods. Other and/or additional methods of electrical connection than solder may be utilized. [0068] In some embodiments, the end of the at least one wire 271 extends along the mounting surface 262 to the retaining clip 263, where that end of the at least one wire 271 is held between the mounting surface 262 and the outer surface of the HITU transducer 200. In some such embodiments, the portion of the at least one wire 271 in contact with the mounting surface 262 may be soldered and/or otherwise electrically connected to the mounting surface 262 as described above. In other such embodiments, the retaining clip 263 may be crimped or otherwise compressed to hold the end of the least one wire 271 securely between the retaining clip 263 and the outer surface of the HITU transducer 200, without the need for a soldered or similar connection between the at least one wire 271 and the mounting surface 262.
POMD04490SEC_WO01 [0069] In some embodiments, two or more apertures 265 may be defined through the mounting surface 262, and the at least one wire 271 may be threaded through longitudinally- adjacent apertures 265 in order to hold the at least one wire 271 in place during manufacturing and provide additional security for the at least one wire 271 after manufacturing. [0070] In some embodiments, one or more notches 266 may be defined in one or more lateral edges of the mounting surface 262 to break an otherwise continuous surface so that mounting surface 262 is more flexible and bendable. In this way, the flexibility of the distal end of the catheter 10 is enhanced, thereby enhancing steerability of the catheter 10 within a patient’s vasculature. [0071] Referring to FIG. 15, another embodiment of a ring adapter 260 is shown. This embodiment omits the apertures 265 and the notches 266 in the mounting surface 262 described above with regard to the embodiment of FIG. 14. In this way, manufacturability of the ring adapter 260 may be simplified. [0072] Referring to FIG. 16, another embodiment of a ring adapter 260 is shown. This embodiment omits the apertures 265 and the notches 266 in the mounting surface 262 described above with regard to the embodiment of FIG. 14. The mounting surface 262 is substantially solid. A pocket 268 is defined in the mounting surface 262 along at least a portion of its length. In some embodiments, the pocket 268 extends from the proximal end 269 of the mounting surface 262 to a location at or near the junction between the mounting surface 262 and the retaining clip 263. The pocket 268 is a depression in the outer surface of the mounting surface 262 toward the longitudinal centerline of the retaining clip 263. In this way, the pocket 268 is configured to hold the end of at least one wire 271, and solder that is applied to the at least one wire 271. The orientation of the pocket 268 allows for soldering to be performed, during manufacturing, on an outer surface of the ring adapter 260, providing for better clearance and accessibility for the soldering process. [0073] Referring to FIG. 17, another embodiment of a ring adapter 260 is shown. This embodiment omits the apertures 265 and the notches 266 in the mounting surface 262 described above with regard to the embodiment of FIG. 14. The mounting surface 262 is substantially solid, and is flexible. A flex lead 273 is defined in or attached to the mounting surface 262, and that flex lead 273 may extend onto and/or across the retaining clip 263 to a distal end of the retaining clip 263. As with the embodiments described above, an end of at least one wire 271 may extend onto the mounting surface 262, where that at least one wire 271 may be soldered thereon in order to provide an electrical connection to the HITU transducer 200. In
POMD04490SEC_WO01 this embodiment, at least the mounting surface 262 is flexible, to improve steerability of the catheter 10. [0074] As explained above with reference to FIG. 10, the flex circuit 240 can include a tuning and matching network and a thermocouple layer. The flex circuit 240 can include pads such as one or more signal pads 241 for connecting to a micro-coaxial cable 270, which in turn may include two or more separate wires 271, 272. This configuration can likewise improve the flexibility of the assembly (e.g., mounting surface 262 and flex circuit 240 are bendable), and allow for a symmetric configuration of the (e.g., distally and proximally symmetric) post structure 210 and the HITU transducer 200. As seen in FIGS. 14-17, the micro-coaxial cable 170 may connect to the ring adapter 260, and the mounting surface 262 of the ring adapter 260 can hold at least one wire 271 of the flex circuit 240. [0075] Additional and alternative arrangements are available because the physical and/or electrical constraints on the connecting cable dictated by direct termination to the transducer are no longer relevant with implementations of the present disclosure. More efficient transducer performance can be achieved because the flex circuit can allow for surface mount tuning elements (such as a series capacitor with a parallel inductor, a series inductor with a parallel capacitor, or a Pi- or T-network that are composed of capacitors and inductors) to match the electrical parameters of the generator 22, the micro-coaxial cable 270, and the HITU transducer 200. [0076] The flex circuit 240 of the present disclosure may not require preparation to terminate the flex circuit 240 distally to the transducer or to at least one electrical coupling 18. The proximal end of the flex circuit 240 can include a feature for pulling the flex circuit 240 into the catheter cable lumen. When the flex circuit 240 is terminated directly to the HITU transducer 200, the assembly of the transducer and the flex circuit 240 can be sized to meet mechanical constraints (both size and flexibility) of the catheter assembly and generate more consistent catheter processing. Use of the flex circuit 240 of the present disclosure may reduce costs by parting with at least some of the procedures for stripping, breakout, preparation of the micro-coaxial cable 270 for soldering, thereby simplifying installation of the HITU transducer 200 inside the catheter cable lumen. [0077] FIG. 18 illustrates a side view of a transducer assembly that is saline compatible. As illustrated, the inner shell of the HITU transducer 200 includes a backing design. The HITU transducer 200 can be isolated from fluid (i.e., fluid within a balloon 14 or body fluid, e.g., blood, in a balloon-less implementation) to render the catheter saline compatible. The adhesive
POMD04490SEC_WO01 303 and 304 that can be used to keep the seal intact may include a bond that adheres to and seals flex circuit 240 that connects to micro-coaxial cable 270 to the HITU transducer 200 and post structure 210, as illustrated above. The adhesive is generally durable because vibrations can cause the adhesive to delaminate. An example of an applicable adhesive is epoxy. [0078] FIG. 19 is a flow chart illustrating a process 400 for manufacturing a catheter assembly. In step 401, the process 400 may include providing a HITU transducer 200, for example, a high-power air-backed or water-backed transducer shaped as a cylindrical shell with a central void and an outer shell. As described above in association with FIGS. 1 to 4, the ultrasonic transducer 200 is capable of generating an average acoustic that exceeds 30 watts/cm2, exceeds 50 W/cm2, or exceeds 150 W/cm2. The cylindrical shell can have a length less than about 10 mm, or less than about 6 mm, and has a diameter between about 1 and about 3 mm, or in some implementations about 1.5 mm. [0079] In step 402, process 400 may include positioning a post structure 210 inside the central void of the cylindrical shell with the post 212 extending axially outside the cylindrical shell. As described above in association with FIGS.1 to 4, the post structure 210 can be shaped as a cylinder positioned inside the central void of the cylindrical shell, and, in some implementations, coaxial with respective to the cylindrical shell of the ultrasonic transducer 200. The post structure 210 may be positioned such that an outer surface of the post structure 210 is within 200 µm of an inner surface of the central void of the cylindrical shell. The outer surface of the post structure 210 and the inner surface of the central void of the cylindrical shell may be separated by a gas or liquid, e.g., water, air, or other gas. The substance of the cylindrical shell can help ensure the therapy transducer remains backed by the substance, e.g., air-backed or water-backed. The post structure 210 may be electrically coupled to an inner surface of the cylindrical shell. [0080] In step 403, process 400 may include connecting the flex circuit 240 to a signal electrode 200A on the HITU transducer 200 (e.g., the HITU transducer 200 in FIGS. 9 to 13) and the post structure 210 (e.g., post structure 210 in FIGS.9 to 13). The implementations can use soldering for making the electrical connection. Additionally, or alternatively, the implementations may use epoxy or adhesive to, for example, connect the signal pad to the transducer, and connect the ground pad to the post structure 210. The implementations may also apply laser welding to connect the signal pad to the HITU transducer 200 and connect the ground pad to the post structure 210. The flex circuit 240 may include multiple signal pads disposed over an underlying signal trance. Similarly, the flex circuit 240 may include multiple
POMD04490SEC_WO01 ground pads disposed over an underlying ground trance that is separate and distinct from the signal trace. As discussed above with reference to FIGS. 9 to 12, the flex circuit 240 may include series (within the signal trace) and/or shunt (between the signal and ground trace) surface mount components to form a tuning and matching network so that the HITU transducer 200 is tuned to a frequency of the driving circuit and the impedance of the HITU transducer 200 is matched to that of the driving circuit for efficient coupling of electrical power. The flex circuit 240 may also include a thermocouple layer that includes a junction of two or more metals so that a temperature of the junction can be sensed based on, at least in part, a measured voltage at the junction. The flex circuit 240 can include multiple layers of conducting metal. The flex circuit 240 has a bend ratio of at least 10:1. [0081] In step 404, process 400 may include attaching a micro-coaxial cable 270 to the pads of the flex circuit 240. In various implementations, the conductor wirings of the micro- coaxial cable 270 can be soldered, laser welded, crimped or crimped with adhesive to, e.g., signal pad and ground pad of flex circuit 240 as depicted in FIG.13. The implementations can operate in the absence of the micro-coaxial cable 270. For example, the flex circuit 240 can be lengthened up to 2.5 meters long, or longer, so that the flex circuit 240 can directly couple to the proximal connector and receive the driving signal from the driving circuit regardless of whether the catheter 10 is introduced into the patient’s vasculature by femoral access or radial access, or other access locations. [0082] While various embodiments and implementations of the present disclosure have been shown and described herein, it will be obvious to those skilled in the art that such embodiments and implementations are provided by way of example only. Numerous variations, changes, and substitutions may occur to those skilled in the art without departing from the present disclosure. It should be understood that various alternatives to the embodiments and implementations of the present disclosure described herein may be employed. [0083] While this disclosure has described the use of a flex circuit 240 in conjunction with a HITU transducer 200, the flex circuit 240 described herein may be utilized with a lower- power ultrasound transducer as well. [0084] The terms rear surface, inner surface, and inner diameter of the active element refer to the same region of the active element of the transducer. [0085] Whenever the term “at least,” “greater than,” or “greater than or equal to” precedes the first numerical value in a series of two or more numerical values, the term "at least," "greater than" or "greater than or equal to" applies to each of the numerical values in that series of
POMD04490SEC_WO01 numerical values. For example, greater than or equal to 1, 2, or 3 is equivalent to greater than or equal to 1, greater than or equal to 2, or greater than or equal to 3. [0086] Whenever the term "no more than," "less than," or "less than or equal to" precedes the first numerical value in a series of two or more numerical values, the term "no more than," "less than," or "less than or equal to" applies to each of the numerical values in that series of numerical values. For example, less than or equal to 3, 2, or 1 is equivalent to less than or equal to 3, less than or equal to 2, or less than or equal to 1. [0087] Certain implementations herein contemplate numerical ranges. When ranges are present, the ranges include the range endpoints. Additionally, every sub range and value within the range is present as if explicitly written out. The term "about" or "approximately" may mean within an acceptable error range for the particular value, which will depend in part on how the value is measured or determined, e.g., the limitations of the measurement system. For example, "about" may mean within 1 or more than 1 standard deviation, per the practice in the art. Alternatively, "about" may mean a range of up to 20%, up to 10%, up to 5%, or up to 1% of a given value. Where particular values are described in the application and claims, unless otherwise stated the term "about" meaning within an acceptable error range for the particular value may be assumed. [0088] The disclosure generally incorporates by reference the entire contents of the following patents and applications: U.S. Patent Application No. 18/451,044, to Thirumalai, et ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ ^^!^^"^^^^^^^^!^^^^^^^^^^^^^^^^^^#^^^^^$^%^^^^&^^^^^^d August 16, 2022, U.S. Patent Publication No. 20230021354, to Zhai et al., U.S. Publication No. 20230293229, to Barman et al., U.S. Provisional Application No. 63/552,018 to Vuich et al., filed February 9, 2024, U.S. Patent No.10,230,041, and U.S. Patent No.10,456,605.