Monitoring vessel wall stiffness

Abstract

An intravascular ultrasound transducer assembly for monitoring stiffness of a vessel wall. The assembly comprises a catheter shaft sized and shaped for insertion inside a vessel having a vessel wall and one or more intravascular devices integrated on the catheter shaft. The one or more intravascular devices are configured to monitor at least one of i) at least one anatomic structure of the vessel wall in response to a pulse wave being launched on the vessel wall so that a pulse wave velocity is determined, by operating in a pulse echo mode to track the at least one anatomic structure, and ii) signals indicative of an ambient pressure of the ultrasound transducer assembly, wherein the ambient is defined by a balloon encapsulating one of the one or more intravascular devices. The pulse wave velocity and the ambient pressure are related to, i.e., proportional to, the stiffness of the vessel wall.

Description

MONITORING VESSEL WALL STIFFNESSPRIORITY

[0001] This application claims the benefit of priority of U.S. Provisional Patent Applications Nos. 63 / 677,873, titled PULSE WAVE VELOCITY MONITORING DURING RENAL DENERVATION, filed July 31, 2024, and 63 / 677,364 titled MONITORING PRESSURE AND VESSEL WALL STIFFNESS, filed July 30, 2024, each of which is incorporated herein by reference in their entirety to provide continuity of disclosure.TECHNICAL FIELD

[0002] This description generally relates generally 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 catheter, and the unfocused ultrasound energy can heat tissueadjacent to a body lumen within which the catheter (and the transducer) is disposed. The 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 method that includes placing one or more sensor ultrasound transducers inside a vessel of a subject receiving an intravascular therapy procedure; in response to an event launching a pulse wave on the vessel wall, driving the one or more sensor ultrasound transducers in a pulse-echo imaging mode to receive, at the one or more sensor ultrasound transducers, ultrasound signals backscattered from anatomical structures of the vessel wall; tracking, based on the ultrasound signals backscattered from anatomical structures of the vessel wall, a displacement of the anatomical structures of the vessel wall as the pulse wave travels along the vessel wall; based on the displacement of the anatomical structures with respect to time elapsed between the event and the tracking,determining a velocity of the pulse wave travelling along the vessel wall; and estimating a wall stiffness of the vessel wall based on the velocity of the pulse wave.

[0008] In some aspects, implementations provide a intravascular ultrasound transducer assembly that includes a catheter shaft sized and shaped for insertion inside a vessel having a vessel wall; and one or more sensor ultrasound transducers integrated on the catheter shaft and configured to operate in a pulse-echo imaging mode to track at least one anatomic structure of the vessel wall in response to a pulse wave being launched on the vessel wall so that a pulse wave velocity is determined.

[0009] In some aspects, implementations of a method to monitor stiffness of a vessel wall include deploying a balloon inside a vessel of a subject receiving an intravascular procedure, wherein the balloon encapsulates an intravascular device and comprises an inlet and an outlet; inflating the balloon to a first pre-determined pressure, wherein the balloon is expanded radially to press against the vessel wall from inside the vessel; injecting a first bolus of fluid into the balloon through the inlet and with the outlet closed; and measuring, using the intravascular device, a first pressure change resulting from injecting the first bolus of fluid.

[0010] In other aspects, implementations of a system include a catheter assembly comprising a balloon encapsulating an intravascular device, wherein the balloon comprises an inlet and an outlet; a fluid pump coupled to an inlet of the balloon and programmed to inject a controllable amount of fluid into the balloon; and a receiving circuit coupled to the intravascular device and configured to measure signals from the intravascular device.

[0011] In some aspects, a method for monitoring stiffness of a vessel wall is provided. The method comprises inserting a distal end of a catheter of an intravascular ultrasound transducer assembly into a vessel having a vessel wall, monitoring, with one or more intravascular devices integrated on the distal end of the catheter , at least one of i) at least one anatomic structure of the vessel wall in response to a pulse wave being launched on the vessel wall so that a pulse wave velocity is determined, by operating in a pulse echo mode to track the at least one anatomic structure, and ii) signals indicative of an ambient pressure of the ultrasound transducer assembly. The ambient is defined by a balloon encapsulating at least one of the one or more intravascular devices. The pulse wave velocity and the ambient pressure are (e.g., directly) related to the stiffness of the vessel wall.

[0012] In some aspects, an intravascular ultrasound transducer assembly for monitoring stiffness of a vessel wall is provided. The assembly comprises a catheter shaft sized and shaped for insertion inside a vessel having a vessel wall and one or more intravascular devicesintegrated on the catheter shaft. The intravascular devices are configured to monitor at least one of i) at least one anatomic structure of the vessel wall in response to a pulse wave being launched on the vessel wall so that a pulse wave velocity is determined by operating in a pulse echo mode to track the at least one anatomic structure, and ii) signals indicative of an ambient pressure of the ultrasound transducer assembly. The ambient is defined by a balloon encapsulating at least one of the one or more sensor ultrasound transducers. The pulse wave velocity and the ambient pressure are (e.g., directly) related to the stiffness of the vessel wall.

[0013] In some variants of any of the methods described herein, the method may comprise determining whether the monitored wall stiffness fulfills a predefined wall stiffness criterium, wherein, optionally, the wall stiffness criterium defines at least one of a wall stiffness threshold and a wall stiffness range.

[0014] In some variants of any of the methods described herein, the method may comprise determining whether the monitored wall stiffness is within a predefined range and outputting an instruction to reposition the catheter shaft, when the wall stiffness criterium is not fulfilled or outputting a confirmation of a treatment site, when the wall stiffness criterium is fulfilled.

[0015] In some variants of any of the methods described herein, the method may comprise, after monitoring of the stiffness of the vessel wall, outputting an instruction to ablate material of the vessel wall, monitoring the stiffness of the vessel wall after ablation, comparing the monitored stiffnesses before and after ablation to determine a stiffness change, determining whether the stiffness change fulfills a predetermined stiffness change criterium, and determining that further ablation is needed at the present location of the catheter shaft, when the stiffness change criterium is not fulfilled.

[0016] In some variants of any of the methods described herein, the method may comprise, triggering display of a current catheter state via a graphical user interface. The current catheter state may be indicative of at least one of a method step that is currently performed, one or more options for proceeding with a subsequent method step, and an indicator representative of a wall stiffness criterium or a wall stiffness change criterium being currently fulfilled or not fulfilled.

[0017] In some aspects, a computer program product is provided. The computer program product comprises instructions which, when the program is executed by a computer, cause the computer to carry out any steps of the methods described herein. The computer program product may be stored on a computer-readable storage medium.

[0018] 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

[0019] 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.

[0020] FIG. 1A illustrates a side view of a catheter system, in accordance with some implementations .

[0021] FIG. IB illustrates a side view of a hub of a catheter system, in accordance with some implementations.

[0022] FIG. 1C illustrates a section view along line 1C of the catheter shaft in FIG. IB, in accordance with many implementations.

[0023] FIG. 2A illustrates an example of launching a pulse wave on a vessel wall and monitoring the pulse wave propagating on the vessel wall according to many implementations.

[0024] FIG. 2B illustrates another example of launching a shear wave on a vessel wall and monitoring the shear wave propagating on the vessel wall according to some implementations .

[0025] FIG. 2C illustrates yet another example of launching a shear wave on a vessel wall and monitoring the shear wave propagating on the vessel wall according to some implementations .

[0026] FIG. 3 is a flow chart illustrating a process for pulse wave velocity monitoring according to many implementations.

[0027] FIG. 4A illustrates an example of monitoring pressure and vessel wall stiffness during an intravascular procedure according to many implementations.

[0028] FIG. 4B demonstrates an example of measured voltages as a function of pressures according to many implementations.

[0029] FIG. 4C illustrates another example of monitoring pressure and vessel wall stiffness during an intravascular procedure according to many implementations.

[0030] FIG. 5 is a flow chart illustrating a process for measuring a pressure change inside a balloon according to many implementations.

[0031] FIGS. 6A and 6B are flow charts illustrating a process for treatment site selection based on a determined vessel wall stiffness.

[0032] FIG. 7 is a flow chart illustrating a process for treatment confirmation.

[0033] FIG. 8 is a schematic representation of exemplary graphical user interfaces, GUIs, during an intravascular therapy procedure, e.g., a renal denervation (RDN) procedure.

[0034] Like reference numbers and designations in the various drawings indicate like elements.DETAILED DESCRIPTION

[0035] The disclosed technology is directed to systems and methods for monitoring wall stiffness of a vessel wall in the context of intravascular interventions, e.g., denervation procedures, e.g., RDN procedures. Some systems and methods are configured for monitoring a pulse wave before, during, and / or after an intravascular therapy procedure, e.g., a RDN procedure. One or more ultrasound sensors (also known as sensor ultrasound transducers) are integrated into the ablation catheter assembly at the proximal and / or the distal side of therapy transducer. Each sensor ultrasound transducer has both transmit and receive capabilities and operates in pulse-echo imaging mode.

[0036] In some cases, the therapy transducer of the ablation catheter assembly may be used to “push” the vessel wall and generate a disturbance that propagates longitudinally along the vessel wall. The one or more sensor ultrasound transducers can monitor the pulse wave passing through a corresponding location on the vessel wall that is covered by the line-of-sight of the sensor transducer. In some cases, the pulse wave may be generated actively, for example, using the therapy ultrasound transducer to generate sufficient acoustic radiation force (ARF) to “push” the vessel wall radially outward. The pulse wave may also be generated actively using a sensor ultrasound transducer operating at high-intensity mode to generate a burst of ultrasound waves to create the acoustic radiation force. In other cases, the pulse wave may be generated by a physiologic event of the human body, for example, when the left ventricle contracts and injects a bolus of oxygenated blood supply into the descending aorta to reach the renal artery. In these cases, the operation of the sensor ultrasound transducers may be synchronized with an electrocardiogram (ECG) so that precise timing information is maintained for calculating pulse wave velocity. Significantly, the pulse wave velocity is determined by wall stiffness (or wall compliance). By monitoring pulse wave velocity beforeand after the RDN procedure, estimates of wall stiffness can be performed and compared, thereby allowing for quantitative and objective assessment of the therapeutic effect.

[0037] In some cases, a catheter assembly may be inserted into a subject’s vasculature, such as via a vascular access point (e.g., in a femoral artery or radial artery), for a RDN procedure. The catheter assembly may include a balloon encapsulating an intravascular device such as a therapy ultrasound transducer and / or a separate micro-electro-mechanical system (MEMS) device. While the therapy ultrasound transducer is turned on for delivering denervation, e.g., RDN, treatment, the therapy ultrasound transducer, or the separate MEMS device, can be configured to record signals, such as voltage signals, caused by ambient pressure of the therapy ultrasound transducer (or the separate MEMS device). For example, the balloon may be fully expanded to overcome the physiological peak pressure and balloon elastic stress to contact the inside of the vessel wall. Once this condition is established, a fixed volume of fluid can be injected into the balloon with its outlet closed so that the balloon undergoes a constant volume expansion. The voltage signals from the intravascular device can be recorded to determine a pressure change resulting from the constant volume expansion. This pressure change is proportional to wall stiffness, which can then be monitored before, during, and / or after the intravascular procedure. According to other embodiments, the signals may be related to other characteristics of electric power, mechanical or thermal energy, and / or other kinds of energy. Additional details of the system and method are provided below in FIGS. 1A to 8.

[0038] Some systems and methods may be a combination of the previously described systems and methods. For example, some systems may be configured to be able to monitor at least one of a pulse wave velocity and an ambient pressure. Consequently, such systems may be configured for monitoring a wall vessel stiffness based on at least one of a pulse wave velocity and an ambient pressure. Examples of some diseases that may be treated using an embodiment of the technology described in this specification include pulmonary hypertension, diabetes, metabolic disorder, insulin resistance, obesity, nonalcoholic fatty liver disease, chronic kidney disease (CKD), heart failure, myocardial infarction, contrast nephropathy, atrial fibrillation, end-stage renal disease, digestive disease, pancreatic cancer, other cancers, tumors, pain, polycystic kidney disease, asthma, sepsis, rheumatoid arthritis, Crohn’s disease, ulcerative colitis, gastrointestinal motility disorders, chronic obstructive pulmonary disease (COPD), sleep apnea, anxiety, and depression.

[0039] FIGS. 1A-1C show an exemplary catheter system 101 according to many implementations. The catheter system 101 may include a catheter 10 having a proximal endand a distal end. The 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 marketed under the trademark PEBAX™, medical-grade thermoplastic polyurethane elastomers such as those marketed under the trademarks PELLETHANE® or ISOTHANE®, and other suitable polymers or any combination thereof. In some implementations, the catheter system 101 for ablating target tissue may comprise an ultrasound energy generator 22 coupled to the catheter 10. Significantly, 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., ultrasound transducer 200. The ultrasound energy generator 22 may be operatively coupled to the ablation element to energize the ultrasound transducer 200 to deliver energy to the target tissue, ablating the target tissue. The target tissue may include one or more nerves or nerve branches. In an example, the target tissue may include nerves or nerve branches starting at about 1 mm from the lumen of the blood vessel, e.g., within the adventitia (z.e., beyond the intima-media thickness) and ending at or less than about 10 mm from the lumen of the blood vessel, e.g., less than 6mm from the lumen. In certain implementations, an imaging transducer is used to find the media-adventitia border and ablation is initiated at a set distance, e.g., 0.1 mm, from the media- adventitia border. In certain implementations, the target tissue may include nerves or nerve branches within about 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, superior mesenteric artery, inferior mesenteric artery, femoral artery, pelvic artery, portal vein, hepatic artery, gastroduodenal artery, splenic artery, gastric artery, celiac trunk, pulmonary artery, pulmonary vein, aorta, vena cava, etc. In some examples, the target tissue may include cardiac tissue, e.g., electrically conductive cardiac tissue.

[0040] In some implementations, the generator 22 may be configured to energize the piezoelectric component, e.g., ultrasound transducer 200, for a time period of between 5 to 20 seconds and at a frequency of 1 to 30 MHz , which is optionally within the range of 7 MHz to 15 MHz, is optionally within the range of 8 MHz to 13 MHz, and optionally within the range of 8.5 MHz to 9.5 MHz, or 8.7 MHz to 9.3 MHz. In one implementation, the generator 22 maybe configured to energize the piezoelectric component for a time period of between 6 to 10 seconds at a frequency of 12 to 14 MHz. In one implementation, the generator 22 may be configured to energize the piezoelectric component for a time period of about 7 seconds at a frequency of about 9 to 13 MHz. Energizing the piezoelectric component by the generator 22 may increase a temperature of the piezoelectric component by no more than 50° C. In certain embodiments, the piezoelectric component is an ultrasound transducer 200 that is water or liquid-backed transducers. In certain embodiments, the piezoelectric component is an ultrasound transducer 200 that is water or liquid-backed transducers. The water or liquid- backed transducer is configured to generate ultrasonic waves having an average surface power intensity within a range of 1 and 300 Watts per centimeter square (W / cm2), optionally 1 to 50 W / cm2.

[0041] In certain embodiments, the ultrasound transducer 200 is an air-backed ultrasound transducer configured to generate ultrasonic waves having an average surface power intensity within a range of 1 W / cm2to 300 W / cm2. The air-backed transducer may comprise an inner (back) and outer (front) surfaces, each of the inner and outer surfaces comprising an electrode; and a backing support member, wherein the ultrasound transducer 200 is mounted to the backing support member to define an air chamber adjacent the inner surface, the air chamber being insulated to prevent entry of fluid into the air chamber during use, the backing support member having a distal end and a proximal end, wherein the ultrasound transducer 200 is configured to deliver sufficient acoustic energy during sonication such as to thermally induce modulation of neural fibers surrounding a blood vessel sufficient to improve a measurable physiological parameter corresponding to a diagnosed condition of the patient.

[0042] 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 system to one or more external electrical conductors 20 that are each in electrical communication with the generator 22. Suitable external electrical conductors 20 include, but are not limited to, wires, cables, and Flexible Printed Circuits (FPCs).

[0043] The generator 22 may be configured to control the catheter 10 to sweep the operating frequency, and / or may be configured to 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.

[0044] 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 alongitudinal length of the catheter shaft 12 toward a distal end of the catheter shaft 12. Each of the electrical lumens 121 can each hold one or more electrical conductor carriers that each carry one or more internal electrical conductors. The internal 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 internal electrical conductors include, but are not limited to, wires, insulated wires, cables, and FPCs. 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 internal electrical conductor 20, an electrical insulator e.g., a wiring sheath) on the internal electrical conductor 20 can serve as the electrical conductor carrier.

[0045] The handle 16 can include one or more fluid ports 24 for connecting the catheter 10 to a corresponding 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, a fluid source 28 A, and a fluid sink 28B. Suitable fluid source 28A and fluid sink 28B include, but are not limited to, pumps, tanks, reservoirs, and vessels. The catheter shaft 12 can include one or more fluid lumens 241. Although one fluid source 28A and one fluid sink 28B are depicted in FIG. 1A, the implementations can have more than one fluid source or more than one fluid sink. Each of the fluid lumens 241 can 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 241 may be in fluid communication with a different fluid port 16, or at least one fluid lumen 241 may be in fluid communication with the same fluid port 16 as at least one other fluid lumen 241.

[0046] The handle 16 can include one or more guidewire ports 30 for receiving a guide wire 31. The catheter shaft 12 can include a guide wire lumen 301. The guide wire 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 guide wire lumen 301.

[0047] 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. , 20-35 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 aring 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, and / or image anatomy, pathology, lesion formation, temperature changes, and / or 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 5 MHz, optionally greater than 10 MHz and / or the array size can comprise 16 to 256 elements, however, these characteristics are descriptive and not restrictive. The array element dimension can be 0.5 mm - 1.5 mm in length and 0.5 - 2 wavelengths in width. A 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 ultrasound 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.

[0048] In some implementations, the catheter system 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. US20230021354A1, to Zhai et al. , which is incorporated herein by reference in its entirety.

[0049] In some implementations, the catheter system may additionally or alternatively include the nerve sensing and / or treatment confirmation components disclosed in U.S. Patent Application Publication No. US20230293229A1 of Barman et al., having a priority date of March 15, 2022, which is incorporated herein by reference in its entirety. As disclosed in further detail in U.S. Patent Application Publication No. US20230293229A1, 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 10 used to measure the delay is located. In accordance with some implementations of the present technology, the above-described delay (aka latency) 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 times 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 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 frequencyultrasound by the 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 Patent Application Publication No. US 20240058028A1, filed on August 16, 2023, which is incorporated herein by reference in its entirety.

[0050] The implementations described here provide a tissue treatment catheter 10 that includes an ultrasound transducer assembly 211. The ultrasound transducer assembly 211 illustrated in FIGS. 2A-2C, in turn, includes a therapy ultrasound transducer 205 for sonifying the vessel wall, for example, the adventitia of renal artery during a renal denervation (RDN) procedure. The ultrasound transducer assembly 211 may also include impedance matching circuitry (not shown), one or more electrical cables connecting to driving circuitry (not shown), and mechanical packaging (not shown). As illustrated in FIGS. 2A-2C, the ultrasound transducer assembly 211 also includes one or more sensor ultrasound transducers 201 that are integrated, for example, on the catheter shaft 204, and configured to operate in pulse-echo imaging mode so that the pulse wave launched on the wall of a blood vessel 210 can be tracked as the pulse wave propagates along the vessel wall. For context, in pulse-echo imaging mode, each sensor ultrasound transducer may transmit an ultrasound pulse to sonify a region of interest inside a line-of-sight of the sensor ultrasound transducer. Microscopic tissue structures and blood cells are demonstrated as echo-genetic, the degree of which is related to the frequency of the ultrasound pulse. The returned echo signals are also known as back-scattered ultrasound signals. These back-scattered ultrasound signals carry information of the scatterers, the location and density of which give rise to the return echoes. The sensor ultrasound transducer receives these back-scattered ultrasound signals, which can reveal the information of the underlying scatterers.

[0051] FIG. 2A illustrates a cross-sectional view of a vessel wall 202 including an outer coat 202A (also known as the tunica adventitia or the adventitia), a muscle coat 202B (also known as the tunica media or the media) adjacent to and inside the outer coat 202 A, a lining 202D (also known as the tunica intima or the intima), and elastic and white fibrous tissue 202C adjacent to and between the lining 202D and the muscle coat 202B. The ultrasound transducer assembly 211 is shown inside the blood vessel 210 and mounted on the catheter shaft 204. As illustrated, two sensor ultrasound transducers 201 are facing outward radially, and are configured to operate in pulse-echo imaging mode. More than two sensor ultrasound transducers 201 may be utilized in some implementations; in others, a single sensor ultrasound transducer 201 may be utilized. In some cases, each sensor ultrasound transducer 201 caninclude a ring-annular transducer having a ring annulus of piezoelectric transducer shell vibrating radially with respect to the vessel wall 202. In these situations, each sensor transducer201 may have an axial spatial resolution determined by, for example, the pulse width of the imaging pulse, which is sufficient to track the motion of anatomic structures of the blood vessel 210 such as the intima 202D, media 202B, and / or adventitia 202A. The ring-annular transducer can be an array of transducer elements evenly distributed on the annulus and facing outward radially. In other cases, each sensor ultrasound transducer 201 may be shaped as an arc of the ring-annulus, or a pad-sized transducer, facing outward radially. In these cases, each sensor ultrasound transducer 201 can generate a line of sight that covers a portion of the vessel wall202 being monitored. Specifically, the longitudinal and angular sizes of the sensor transducer can be optimized based on its spatial resolution requirement. For example, the size for a single element transducer on the annulus can range from 0.1 mm to 0.6 mm in each dimension, rather than the full (or substantially the full) annulus.

[0052] Wall motions can manifest as a natural physiological event associated with each cardiac cycle. This natural physiological event can visually dilate vessel wall 202 radially outward with displacement magnitudes on the order of hundreds of microns or more, followed by a contracting phase during which the vessel wall 202 relaxes inward. During operation, the physiological event of a pulse wave 203 originating from the heart (e.g., the left ventricle) and propagating from an artery e.g., the descending aortic artery) is monitored by one or more sensor ultrasound transducers 201. Each of the sensor ultrasound transducers 201 has a line of sight and covers a particular segment of the vessel wall 202. In one example, two or more sensor ultrasound transducers can operate in pulse-echo imaging mode to simultaneously monitor the displacement at each corresponding segment. In this example, the sensor ultrasound transducers can monitor wall motion at locations longitudinally separated by known distances as the pulse wave propagates along the wall. Additionally or alternatively, the sensor ultrasound transducers 201 can operate sequentially. In an example of the sequential operation, two sensor ultrasound transducers can be activated one after the other to take a snapshot of wall motions. The known delay in activating each sensor ultrasound transducer is taken into account when determining the propagation delay of a pulse wave traveling on vessel wall 202. In both situations, the sensor ultrasound transducers 201 can use an electrocardiogram (ECG) as a timing reference e.g., revealing temporal relationship to a cardiac cycle) to track the pulse wave as it propagates longitudinally along the long axis of vessel 210 with radial displacements on vessel wall 202. The estimated pulse wave velocity can be calculated from the relativedelay between motion (e.g., displacement) on vessel wall 202 monitored at different segments of vessel 210. For example, the motion being monitored can be characterized as the maximum radial displacement at each corresponding segment of the vessel 210. To improve accuracy of motion tracking, numerous techniques may be applied at each tracking location to compensate artifacts caused by non-pulse-wave motions (e.g., general displacement, respiratory motion). For example, these techniques may model background motion as a linear component or a quadratic component that can be subtracted.

[0053] The arrival time of the pulse wave at each corresponding segment of vessel 210 can thus be determined using the ECG as the timing reference so that the timing basis is relative to an underlying cardiac cycle. Because the distance between two corresponding segments is known, the pulse wave velocity can be determined accordingly. As the pulse wave refers to a transverse wave or shear wave travelling longitudinally along vessel 210 with displacements radially on the vessel wall 202, the terms of “pulse wave” and “shear wave” are used interchangeably within the confines of this disclosure. In addition to a natural physiological event associated with each cardiac cycle, the wall motions can also be artificially created using an ultrasound “push” pulse to assert acoustic radiation force (ARF) on vessel wall 202. When using the ARF to create wall motion, the resulting displacement can have a magnitude smaller than those seen during the natural physiological event. For example, the resulting displacement can have a microscopic magnitude not visible to the naked eye.

[0054] FIG. 2B illustrates an example of active monitoring where the sensor ultrasound transducer 201 or therapy ultrasound transducers 205 generate a shear wave on the vessel wall 202. For example, the therapy ultrasound transducer 205 can be turned on to create a jolting force, known as acoustic radiation force (ARF), at the interface between fluid inside the blood vessel 210 and the vessel wall 202 as a result of the transfer of momentum from the ultrasound wave to the vessel wall 202. Specifically, the therapy ultrasound transducer 205 can apply a high-intensity ultrasound pulse for a very short duration (e.g., on the order of tens to hundreds of microseconds) to create a localized radiation force that pushes the vessel wall 202 radially outward to generate a displacement and a transient mechanical disturbance, thereby launching pulse wave 203S that propagates longitudinally along a long axis of vessel 210 with displacements radially on the vessel wall 202, as illustrated in FIG. 2B. This pulse wave (or shear wave) is a type of elastic wave where the displacement at each location in the path of the pulse wave is perpendicular to the propagating direction of the pulse wave. The speed of the pulse wave is slower than the longitudinal wave. Significantly, the speed of the pulse wave ishighly correlated with stiffness of the vessel wall 202. The sensor ultrasound transducer 201 can operate in pulse-echo imaging mode to track pulse wave 203 S as it propagates along the long axis of vessel 210 with local displacement radially on the vessel wall 202. The tracking can be performed by synchronizing the pulse-echo operation of the sensor transducer 201 with the activation of therapy ultrasound transducer 205. One or more sensor transducers 201 can image the vessel wall from various segments to track pulse wave 203S.

[0055] FIG. 2C illustrates another example of active monitoring where a selected sensor ultrasound transducer 201 is used to generate a shear wave 203SS on the vessel wall. The selected sensor ultrasound transducer 201 may be turned on to generate high-intensity ultrasound (e.g., using a continuous wave mode of transmission for a duration on the order of milliseconds). In comparison, during pulse-echo imaging, each sensor ultrasound transducer201 is turned on for transmission that lasts a maximum of a few tenths of a millisecond. The propagating pulse wave 203 SS can be tracked by the other sensor ultrasound transducers 201 e.g., mounted on the catheter shaft 204).

[0056] FIG. 3 is a flow-chart illustrating a process 300 for monitoring pulse wave velocity (PWV) on a vessel wall 202. First, at box 301, one or more sensor ultrasound transducers 201 are placed inside a blood vessel 210. As described above with reference to FIGS. 1A to 2C, the sensor ultrasound transducers 201 may be mounted on a catheter shaft inserted into the vessel of the subject receiving an intravascular therapy such as a renal denervation (RDN) procedure. The sensor ultrasound transducers 201 can have an outer diameter between about 1 and about 3 mm, or in some implementations about 1.5mm. The sensor ultrasound transducers 201 can be shaped as a ring annulus with an inner void for the guide wire to pass through during the RDN procedure. The sensor ultrasound transducers 201 may emit ultrasound pulses radially outward to monitor a respective segment of the vessel wall202 facing the corresponding sensor ultrasound transducer. The sensor ultrasound transducers 201 may operate at a center frequency from about 15 MHz to about 30 MHz.

[0057] Next, at box 302, the one or more sensor ultrasound transducers 201 operate in pulse-echo imaging mode to track motion of the vessel wall 202 responsive to a pulse wave being launched on the vessel wall. The pulse wave may be launched as a physiologic event as the left ventricle contracts and pushes a bolus of fluid into the descending aorta that flows into the abdominal aorta and into the renal artery, causing initial dilation and then subsequent contraction of the vessel wall. The sensor ultrasound transducers can be synchronized with the electrocardiogram (ECG) by, for example, triggering the sensor ultrasound transducers at thestart of a cardiac cycle (or a precise moment into a cardiac cycle), to record wall motions that indicate the arrival time of the pulse wave at a corresponding section of the renal artery. For example, as described above with reference to FIGS. 1A to 3C, the sensor ultrasound transducers 201 each have a line of sight covering a corresponding section of the vessel wall 202. The pulse wave may also be launched using a therapy ultrasound transducer 205 to “push” the vessel wall with a burst of ultrasound waves (e.g., tens to hundreds of cycles). In some cases, the “push” generates sufficient acoustic radiation force (ARF) around the vessel wall 202 to launch a pulse wave. Additionally or alternatively, a sensor ultrasound transducer 201 may be used to generate a “push” on the vessel wall 202 in similar manner by virtue of acoustic radiation force (ARF). In pulse-echo imaging mode, each sensor ultrasound transducer 201 can then record the location of anatomical structures of the vessel wall 202 (such as the intima202D, media 202B, and adventitia 202A). For example, the sensor ultrasound transducers 201 may emit ultrasound waves at a pulse repetition frequency of about 10 kHz to about 20 kHz to repeatedly visualize the relative locations of the intima 202D, media 202B, and adventitia 202A. The location information over time at each corresponding section of vessel 210 can be analyzed to determine the arrival time of the pulse wave.

[0058] Next, at box 303, pulse wave velocity may be determined based on tracking of the pulse wave. For example, the pulse wave velocity may be determined based on the arrival times of the pulse wave (e.g., as indicated by peak displacement) at the corresponding sections of vessel 210, and the separation distance between the corresponding sections of vessel 210.

[0059] Next, at box 304, the wall stiffness can be estimated based on the determined pulse wave velocity. Here, the pulse wave velocity is directly related to vessel wall stiffness. In a cylindrical elastic tube filled with an incompressible fluid, the pulse wave velocity (PWV) is related to the elastic Young’s modulus by the following equation:where E and v respectively corresponds to the Young’s modulus of the Poisson ration of the wall, R is the lumen radius, and h is wall thickness, and p is density of the wall.

[0060] Significantly, the implementations may determine pulse wave velocity before and after the RDN therapy and compare the determined pulse wave velocity or estimated wall stiffness before and after RDN therapy to determine an objective and quantitative metric of the therapeutic effect.

[0061] FIGS. 4A-4C depict examples for monitoring pressure and vessel wall stiffness in the context of intravascular procedures such as denervation procedures, e.g., RDN procedures. Referring to FIG. 4A, FIG. 4A illustrates a cross-sectional view of a vessel wall 202 including an outer coat 202 A (also known as the tunica adventitia or the adventitia), a muscle coat 202B (also known as the tunica media or the media) adjacent to and inside the outer coat 202A, a lining 202D (also known as the tunica intima or the intima), and elastic and white fibrous tissue 202C adjacent to and between the lining 202D and the muscle coat 202B. An ultrasound transducer assembly 211 is shown inside the vessel 210. As illustrated, the ultrasound transducer assembly 211 includes balloon 14 encapsulating pressure sensor 201 and therapy transducer 205. The ultrasound transducer assembly 211 may also include impedance matching circuitry (not shown), one or more electrical cables connecting to driving circuitry (not shown), and mechanical packaging (not shown). Balloon 14 may have an inlet for receiving incoming fluid from fluid pump 404, and an outlet (not shown) for circulating the fluid outside the balloon 14. The inlet and the outlet each can be sealed. In certain embodiments, therapy transducer 205 can include ultrasound transducer 200, as illustrated in FIGS. 1A-1C. In certain embodiments, pressure sensor 201 can be a therapy transducer, thus obviating the need for a separate therapy transducer 205. Pressure sensor 201 can also be a micro-electro-mechanical systems (MEMS) transducer. In some cases, pressure sensor 201 can have two input terminals and a surface area that is pressure sensitive.

[0062] Referring to FIG. 4B, FIG. 4B shows an example of measured electrical voltages as a function of fluidic pressure on a 9 MHz ultrasound transducer configured as an example of pressure sensor 201. Here, the pressure sensor 201 is placed inside a catheter device (e.g., catheter 10) with an inflatable balloon embedded therein. As a proof of concept, the balloon 14 is inflated under a series of inflation pressures while the corresponding voltage recordings are taken from the ultrasound transducer configured as pressure sensor 201. The voltage recordings correspond to direct current voltages recorded by pressure sensor 201. The example curve in FIG. 4B thus demonstrates the direct current voltage measured by pressure sensor 201 as a function of the inflation pressure experienced by pressure sensor 201. As can be seen, the voltage recordings are strongly correlated with the inflation pressure.

[0063] Referring to FIG. 4C, FIG. 4C shows another example of a system for monitoring pressure and wall stiffness. In this example, a catheter assembly 420C is inserted into the vascular space of a subject receiving an intravascular therapy (such as RDN therapy). As illustrated, the catheter assembly 420C includes balloon 14 that encapsulates therapytransducer 205. Pump 404 is coupled to an inlet of balloon 14 so that fluid can be injected into balloon 14. In some cases, pump 404 is a programmable pump controlled by fluid control 414, which can be a logic interface for driving, for example, a peristaltic pump, dual peristaltic pump, or syringe pump. The fluid control logic, in turn, may be driven by central control unit 415, which can include one or more computer processors.

[0064] In operation, the catheter assembly 420C is prepared before the intravascular procedure to have air flushed out of the catheter tip. During the intravascular procedure, the balloon 14 is inflated to a first pre-determined pressure so that the balloon 14 is expanded radially around the vessel wall from inside to fully engage the inside of the vessel. Specifically, the first pre-determined pressure overcomes the physiological pressure and the balloon’s elastic stress, for example, by 3.5 to 4 psi. The outlet of the balloon 14 may then be sealed so that pressure increments can be applied accordingly. In some cases, the pressure increments are applied by injecting, using pump 404, a fixed volume of fluid into the balloon 14, which causes a concomitant pressure change, as indicated by increments in the example curve of FIG. 4B. In these cases, the induced pressure change is proportional to the fixed volume of fluid being injected into the balloon 14.

[0065] As illustrated in FIG. 4C, the pressure measurements, as direct current voltages coming off transducer 205, can be coupled to receiving circuit 420R, and those measurements may be recorded. The recorded direct current voltages can be subject to amplification 418 and then filtering 419 so that the recordings can be digitized using an analog-to-digital converter, ADC, 420 for additional processing by central control unit 415. In some cases, the injection can be repeated, each time with the same fixed volume. The pressure recordings over consecutive injections can be analyzed using a regression analysis to improve the precision of the pressure read-outs. The regression analysis can be performed by central control unit 415. In other cases, varied sizes of injection volume can be applied, and the regression analysis can be adjusted accordingly. An upper limit may be imposed to protect the vessel from mechanical damage. In some cases, the upper limit can be about 15 psi of pressure above the physiological peak pressure.

[0066] The central control unit 415 may additionally drive a radio frequency (RF) generator / control circuit 416, which can adjust, for example, the RF waveform for delivering to RF amplifier 417 that drives therapy transducer 205 for intravascular treatment (e.g., nerve modulation). To protect the pressure sensing signal path, switch 421 may be open when the RF amplifier 417 is on for driving transducer 205.

[0067] FIG. 5 is a flow chart illustrating a process 500 according to many implementations. At box 510, catheter assembly 420C is deployed inside a subject receiving an intravascular procedure, for example, a RDN procedure. The catheter assembly 420C includes a balloon 14 that encapsulates an intravascular device (e.g., pressure sensor 201). As explained with reference to FIGS. 4 A to 4C, the balloon 14 can include an inlet (receiving fluid injection) and an outlet (releasing fluid). The balloon 14 can be prepared to have air flushed out prior to the intravascular procedure.

[0068] At box 520, the balloon 14 is inflated inside the catheter assembly 420C to a first pre-determined pressure. The inflation may be performed using a programmable pump (e.g., pump 404). The first pre-determined pressure is where the balloon is expanded radially to press against the vessel wall from inside the vessel for full contact. To reach this stage, the first pre-determined pressure may overcome the physiological peak pressure inside the vessel as well as the balloon’s elastic stress. The elastic balloon stress can depend on the balloon’s size. In some cases, the elastic balloon stress can be pre-determined or modeled based on the size. The elastic balloon stress can be zero when the inflated vessel size is smaller than the balloon’s size. In other words, the balloon is inflated sufficiently, at the first pre-determined pressure, to prop open the lumen opening above the balloon’s natural size.

[0069] At box 530, a fixed volume of fluid is injected into the balloon, for example, using pump 404 as explained with reference to FIG. 4C. The fluid pump can be programmed to inject the fixed volume of fluid with the outlet of the balloon closed. The injection can be performed within a predetermined time to cause a temporal pressure response inside the balloon.

[0070] At box 540, the pressure change resulting from the injection of the fixed volume is recorded, for example, by an intravascular device, such as therapy transducer 205 (configured as an example of pressure sensor 201). As explained with reference to FIG. 4C, therapy transducer 205 may record a direct current (DC) voltage, which, as demonstrated in FIG. 4B, can manifest as a linear function of the underlying pressure change experienced by the therapy transducer. Wall stiffness can be estimated based on the pressure change, in response to a fixed volume expansion.

[0071] In some cases, the injection in box 530 can be repeated, each time with the same fixed volume of fluid. Subsequently in box 540, the pressure change in response to each injection can be measured. In some cases, the series of measured pressure changes in response to series of injections can be analyzed using a regression module to improve the precision ofestimating wall stiffness. In other cases, the injection at box 530 can be repeated, each time with varied volume of fluid so that the pressure change becomes modulated. The recordings of pressure change can be likewise analyzed using regression analysis to improve the estimation precision. These estimates of wall stiffness can be performed before, during, and after the RDN procedure to gauge treatment efficacy.

[0072] When using a simple cylindrical balloon geometry, the volume (V) of a cylinder can be expressed as:V = nr2L (1) where r is the radius of the cylindrical base and L is the cylindrical length.

[0073] For a small balloon expansion due to an increment of pressure Ap , the incremental volume expansion can be expressed as:AF = 2nrL ■ Ar (2)

[0074] The radius change Ar due to Ap can then be described asAr = ^ Et(V3)7

[0075] Accordingly, the volume expansion (AF) and Young’s modulus (E) can be expressed as:where t is the thickness of the artery. When measured values of t are not available, a value of 0.5 mm can be used for t in the above calculation. E is the Young’s modulus characterizing stiffness of the vessel wall.

[0076] As revealed by Equation (5) above, the control variable can be Ap (pressure increment) or AF(volume increment). In one example, the pressure increment can be Ipsi and the inflow volume can be recorded so that the Young’s modulus can be analyzed. In another example, the volume increment ( F) can be provided by injecting a constant volume, e.g., 1ml, into the balloon and the pressure change can be observed so that the Young’s modulus can be analyzed accordingly. In the above calculation, r and L can be measured or assumed to be constant when the introduced change AF is small.

[0077] Equation (5) can be further simplified as follows:E = K(r, t) - ^ (6) where K is a function of r and t for a given balloon design. K (r, t) can be pre-determinedduring the calibration process. Since K (r, t) can be any function, either r or t (or both) can be treated as constant in some implementations.

[0078] FIGS. 6A and 6B are flow charts illustrating a process 600, 700 for treatment site selection based on a determined vessel wall stiffness. In a first step 610, 710, a catheter 10 according to any implementation described herein may be positioned inside a vessel 210 having a vessel wall 202. In a second step 620, 720, a stiffness of the vessel wall is measured as described herein, e.g. with reference to FIGS. 3 and 5. In a third step 630,730 it is determined whether the measured stiffness of the vessel wall fulfills a stiffness criterium, e.g., whether the stiffness is smaller than a predetermined wall stiffness threshold, i.e., a threshold for the Young’s modulus, for example E being smaller or equal to 100 kPa, or whether the stiffness is within a predefined range, e.g., between 10 and 80 kPa. In case the stiffness criterium is not fulfilled, the process may return to the first step 610, 710 for repositioning of the catheter 10. In case the stiffness criterium is fulfilled, in a fourth step 640, 740 the treatment site is confirmed and / or ablation via the catheter 10 is triggered. Confirming a treatment site may reduce a risk of unnecessary treatment of an area and a risk of treating a wrong area. A confirmation of the treatment site may trigger an output of a confirmation signal to a user, e.g., a message may be displayed via a GUI and / or an acoustic and / or haptic signal may be output. Such outputs may result in at least one of a reduced cognitive load of a surgeon, reduced health risks for a patient, an indicator for assisting medical personnel.

[0079] FIG. 7 is a flow chart illustrating a process 800 for treatment confirmation. In a first step 810 a catheter 10 according to any implementation described herein may be positioned at a first location inside a vessel 210 having a vessel wall 202. In a second step 820, a stiffness of the vessel wall is measured as described herein, for example with reference to FIGS. 3 and 5. Further in a third step 830, an ablation is triggered. Optionally, before triggering ablation, it may be determined whether a stiffness criterium is fulfilled, as described with reference to FIGS. 6A and 6B. In this case, the first three steps 810, 820, 830 of the process 800 shown in Fig. 8 may correspond to variants of the processes 600, 700 shown in FIGS. 6 A and 6B. In a fourth step 840 the stiffness of the vessel wall is measured again after the ablation. In a fifth step 850, a stiffness change is determined by comparing the wall stiffnesses measured before and after the ablation, and it is determined whether the stiffness change fulfills a stiffness change criterium. For example, the stiffness change may be compared to a stiffness change threshold. In some variants, the stiffness change and the stiffness change threshold may be indicative of a relative change compared to the stiffness before the ablation, i.e., in % of thestiffness before the ablation as shown in the fifth step 850 of the process 800 shown in FIG. 7. For example, the change threshold may be a change of at least 10% of the previous stiffness, at least 5% of the previous stiffness, or at least 1% of the previous stiffness. In other variants, the stiffness change and the change threshold may be total values of the Youngs’s modulus, i.e., in kPA. For example, the change threshold may be a change of at least 10 kPA, at least 1 kPA, or at least 0.1 kPA. In case the stiffness change criterium is not fulfilled, the process 800 may return to the third step 830 and a subsequent ablation may be performed. In case the stiffness change criterium is fulfilled, it is determined in a sixth step 860 whether the treatment is completed or has to be continued at another location, e.g., based on a treatment plan. In case the treatment has to be continued at the another location, the method may continue with performing steps 810 to 860 at the another location. Confirming a treatment may improve the surgical results since real-time feedback to a surgeon can be provided. Also, the cognitive load of a surgeon may be further reduced.

[0080] FIG. 8 is a schematic representation of a GUI that may be shown to a user during the process 800 shown in FIG. 7. The GUI may indicate a current state of a catheter 10. For example, after ablation has started in step 930, the GUI may indicate that the catheter 10 is in a “sonicate” state, e.g., by highlighting a section of the GUI as shown in FIG. 8. Highlighting a section may comprise displaying the highlighted section in a predefined color, e.g., green, yellow, or red. The indicatable catheter 10 states may further comprise at least one of a “precool” state, a “post-cool” state and a deflate state. After ablation, the stiffness change criterium is checked in step 950 as described with reference to step 850 of FIG. 7. In case the stiffness change criterium is not fulfilled, the GUI may indicate that another ablation should be started 930, which may be triggered or aborted by a user interaction. In case the stiffness change criterium is fulfilled, the GUI may indicate a successful treatment, optionally together with further options, e.g., to end the treatment, proceed at another location 960, or to exchange the catheter 10 before continuing at the another location. Outputting information via a GUI as described herein provides an easy and intuitive way to check a present state of a method and to decide between different options on how to proceed. As a result, cognitive load on a surgeon and health risks for a patient may be reduced. While a particular GUI is shown in FIG. 8, any methods or method steps described herein may be visualized via the GUI, e.g., to provide realtime feedback to a surgeon.

[0081] 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 suchembodiments 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. For example, some of the method steps described herein with reference to a particular embodiment may be readily combined with other embodiments in isolation from at least some of the other method steps of the particular embodiment, e.g. a recorded pulse velocity, pressure or a determined wall stiffness may be displayed via the GUI.

[0082] 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 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.

[0083] 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.

[0084] 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” or “substantially” mean within an acceptable error range, measurement tolerance, and / or manufacturing tolerance 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.

[0085] The following numbered clauses define further embodiments of the present disclosure.

[0086] 1. A method comprising: placing one or more sensor ultrasound transducers inside a vessel of a subject receiving an intravascular therapy procedure; in response to an event launching a pulse wave on the vessel wall, driving the one or more sensor ultrasound transducers in a pulse-echo imaging mode to receive, at the one or more sensor ultrasound transducers, ultrasound signals backscattered from anatomical structures of the vessel wall;tracking, based on the ultrasound signals backscattered from anatomical structures of the vessel wall, a displacement of the anatomical structures of the vessel wall as the pulse wave travels along the vessel wall; and based on the displacement of the anatomical structures with respect to time elapsed between the event and the tracking, determining a velocity of the pulse wave travelling along the vessel wall.

[0087] 2. The method of clause 1 , further comprising estimating a wall stiffness of the vessel wall based on the velocity of the pulse wave.

[0088] 3. The method of clauses 1 or 2, wherein the tracking comprises: detecting the displacement of the anatomical structures by cross-correlating successively received ultrasound signals when the pulse wave is launched on the vessel wall and the one or more sensor ultrasound transducers are driven in the pulse-echo imaging mode.

[0089] 4. The method of any one of clauses 1-3, further comprising: estimating the wall stiffness of the vessel wall more than once before, during, and after the intravascular therapy procedure, wherein the vessel comprises a renal artery, and wherein the intravascular therapy procedure comprises a renal denervation procedure.

[0090] 5. The method of any one of clauses 1-4, further comprising: comparing the estimated wall stiffness from at least two instances of estimating; and determining an effect of the renal denervation procedure based on results of the comparing.

[0091] 6. The method of any one of clauses 1-5, wherein the one or more sensor ultrasound transducers comprise a ring-annular ultrasound transducer configured to emit ultrasound pulses radially outward and receive the ultrasound signals backscattered from anatomical structures of the vessel wall.

[0092] 7. The method of any one of clauses 1-6, wherein the one or more sensor ultrasound transducers include a plurality of sensor ultrasound transducers in which a sensor ultrasound transducer is axially spaced apart from a neighboring sensor ultrasound transducer by a pre-determined distance.

[0093] 8. The method of clause 7, wherein the velocity of the pulse wave is determined based on, at least in part, an arrival time for the pulse wave to travel the predetermined distance from the sensor ultrasound transducer to the neighboring sensor ultrasoundtransducer.

[0094] 9. The method of any one of clauses 1-8, wherein the one or more sensor ultrasound transducers are characterized by a center frequency from about 15 MHz to about 60 MHz.

[0095] 10. The method of any one of clauses 1-9, wherein the driving and tracking are performed at a repetition rate of about 10 kHz to about 200 kHz.

[0096] 11. The method of any one of clauses 1-10, wherein the event corresponds to a cardiac event detectable on an electrocardiogram (ECG) for the subject.

[0097] 12. The method of any one of clauses 1-11, wherein the event corresponds to a pushing event in which an ultrasound transducer is activated to generate sufficient acoustic radiation force around the vessel wall such that the pulse wave is launched to propagate along the vessel wall.

[0098] 13. The method of any one of clauses 1-12, wherein the ultrasound transducer is a therapy ultrasound transducer characterized by a center frequency from about 7 MHz to about 12 MHz.

[0099] 14. The method of clause 13, wherein the therapy ultrasound transducer is activated for a duration from about 100 ps to about 500 ps.

[0100] 15. The method of any one of clauses 1-12, wherein the ultrasound transducer comprises a sensor ultrasound transducer.

[0101] 16. An intravascular ultrasound transducer assembly comprising:

[0102] a catheter shaft sized and shaped for insertion inside a vessel having a vessel wall; and one or more sensor ultrasound transducers integrated on the catheter shaft and configured to operate in a pulse-echo imaging mode to track at least one anatomic structure of the vessel wall in response to a pulse wave being launched on the vessel wall so that a pulse wave velocity is determined.

[0103] 17. The intravascular ultrasound transducer assembly of clause 16, wherein the one or more sensor ultrasound transducers are synchronized with an electrocardiogram (ECG).

[0104] 18. The intravascular ultrasound transducer assembly of clauses 16 or 17, further comprising a therapy ultrasound transducer configured to launch the pulse wave on the vessel wall, wherein the therapy ultrasound transducer operates at a center frequency from about 7 MHz to about 12 MHz.

[0105] 19. The intravascular ultrasound transducer assembly of any one of clauses16-18, wherein one of the one or more sensor ultrasound transducers is configured to launch the pulse wave on the vessel wall, and wherein the one or more sensor ultrasound transducers operate at a center frequency from about 15 MHz to about 30 MHz.

[0106] 20. The intravascular ultrasound transducer assembly of any one of clauses16-19, further comprising: control logic in communication with the one or more sensor ultrasound transducers and configured to drive the one or more sensor ultrasound transducers to track a displacement of the at least one anatomic structure of the vessel wall as the pulse wave travels along the vessel wall.

[0107] 21. The intravascular ultrasound transducer assembly of any one of clauses16-20, wherein the at least one anatomic structure comprises: an intima of the vessel wall, a media of the vessel wall, and an adventitia of the vessel wall.

[0108] I. A method to monitor stiffness of a vessel wall, the method comprising: deploying a balloon inside a vessel of a subject receiving an intravascular procedure, wherein the balloon encapsulates an intravascular device and comprises an inlet and an outlet; inflating the balloon to a first pre-determined pressure, wherein the balloon is expanded radially to press against the vessel wall from inside the vessel; injecting a first bolus of fluid into the balloon through the inlet and with the outlet closed; and measuring, using the intravascular device, a first pressure change resulting from injecting the first bolus of fluid.

[0109] II. The method of clause I, further comprising: measuring a size of the vessel wall before the balloon is inflated, or before the first bolus of fluid is injected, or when the pressure change is measured.

[0110] III. The method of clauses I or II, further comprising: estimating a wall stiffness for the vessel wall based on the first pressure change and the size of the vessel.

[0111] IV. The method of any one of clauses I-III, further comprising: injecting a second bolus of fluid into the balloon with the outlet closed; and measuring, using the intravascular device, a second pressure change induced by injecting the second bolus of fluid.

[0112] V. The method of clause IV, further comprising: estimating the wall stiffness based on, at least in part, the first and second pressure changes.

[0113] VI. The method of clauses IV or V, further comprising: injecting a third bolus of fluid into the balloon with the outlet closed; measuring, using the intravascular device, a third pressure change induced by injecting the second bolus of fluid; and applying a regression model to the first, the second, and the third pressure changes.

[0114] VII. The method of clause VI, wherein the first bolus, the second bolus, and the third bolus have a pre-determined volume.

[0115] VIII. The method of clauses VI or VII, wherein the first pressure change, the second pressure change, and the third pressure change are cumulatively within an upper limit.

[0116] IX. The method of any one of clauses I- VIII, wherein the first predetermined pressure causes a net pressure of the balloon to be higher than a physiological peak blood pressure, wherein the net pressure of the balloon is determined by subtracting an elastic balloon stress from the first pre-determined pressure, and wherein the elastic balloon stress depends on a size of the balloon.

[0117] X. The method of any one of clauses I-IX, wherein the intravascular device comprises a therapy ultrasound transducer, or a micro-electromechanical systems (MEMS) device.

[0118] XI. The method of any one of clauses I-X, wherein measuring the first pressure change comprises: measuring an amplitude of voltage between input terminals of the intravascular device before and after injecting the first bolus of fluid.

[0119] XII. The method of any one of clauses III-XI, wherein said estimating the wall stiffness of the vessel wall is performed before, during, and after a renal denervation procedure.

[0120] XIII. The method of clause XII, further comprising: comparing the estimated wall stiffness before, during, and after the renal denervation procedure; and determining an effect of the renal denervation procedure based on results of saidcomparing.

[0121] XIV. A system comprising: a catheter assembly comprising a balloon encapsulating an intravascular device, wherein the balloon comprises an inlet and an outlet; a fluid pump coupled to an inlet of the balloon and programmed to inject a controllable amount of fluid of into the balloon; and a receiving circuit coupled to the intravascular device and configured to measure voltage signals from the intravascular device.

[0122] XV. The system of clause XIV, wherein the signals are voltage signals.

[0123] XVI. The system of clauses XIV or XV, further comprising a computer processor in communication with the receiving circuit and the fluid pump, wherein the computer processor is configured to: control the fluid pump to inflate the balloon to a first pre-determined pressure, wherein the balloon is expanded radially to press against the vessel wall from inside the vessel; and inject a first bolus of fluid into the balloon through the inlet and with the outlet closed, wherein the at least one of the controllable amount of fluid comprises the first bolus.

[0124] XVII. The system of clause XVI, wherein the computer processor is further configured to: obtain, using the receiving circuit, signals from the intravascular device resulting from injecting the first bolus of fluid; determine, based on, at least in part, the signals, a first pressure change resulting from injecting the first bolus of fluid; and estimating a wall stiffness based on, at least in part, the first pressure change.

[0125] XVIII. The system of clauses XVI or XVII, wherein the computer processor is further configured to: inject a second bolus of fluid into the balloon through the inlet and with the outlet closed.

[0126] XIX. The system of clauses XVII or XVIII, wherein said estimating comprises a performing a regression analysis.

[0127] XX. The system of any one of clauses XIV-XIX, wherein the intravascular device comprises one of: a therapy ultrasound transducer, or a micro-electromechanical systems (MEMS) device.

[0128] XXI. The system of any one of clauses XIV-XX, wherein the voltage signals are measured between input terminals of the intravascular device before and after injecting the first bolus of fluid.

[0129] XXII. A method comprising: receiving records indicative of ultrasound signals backscattered from anatomical structures of the vessel wall, the ultrasound signals being backscattered in response to an event launching a pulse wave on the vessel wall; determining, based on the records, a displacement of the anatomical structures of the vessel wall as the pulse wave travels along the vessel wall; and based on the displacement of the anatomical structures with respect to time elapsed between the event and the determined displacement, determining a velocity of the pulse wave travelling along the vessel wall.

[0130] XXIII. A method to monitor stiffness of a vessel wall, the method comprising: receiving a record of at least one pressure measurement indicative of a first pressure change resulting from injecting the first bolus of fluid in a balloon deployed inside a vessel of a subject receiving an intravascular procedure, wherein the balloon encapsulates an intravascular device and comprises an inlet and an outlet, is inflated to a first pre-determined pressure, and is expanded radially to press against the vessel wall from inside the vessel; determining, based on the first pressure change, the stiffness of the vessel wall.

[0131] Any step described herein comprising receiving a record may not comprise a step of generating the record.

[0132] Any of the methods described herein or at least parts thereof may be implemented as computer implemented methods. In other words, any of the method steps described herein that may be performed by a processor may form a computer implemented method according to the present disclosure.

Claims

CLAIMSWhat is claimed is:

1. A method for monitoring stiffness of a vessel wall, the method comprising: obtaining records indicative of at least one of vessel wall motions and pressure measurements, wherein the at least one of vessel wall motions and pressure measurements have been recorded with one or more intravascular devices; monitoring, based on the records, at least one of: i) at least one anatomic structure of the vessel wall in response to a pulse wave being launched on the vessel wall so that a pulse wave velocity is determined; and ii) signals indicative of an ambient pressure of the ultrasound transducer assembly, wherein the ambient is defined by a balloon encapsulating at least one of the one or more intravascular devices wherein the pulse wave velocity and the ambient pressure are related to the stiffness of the vessel wall.

2. The method of claim 1, further comprising estimating a wall stiffness of the vessel wall based on the velocity of the pulse wave.

3. The method of claim 1 or 2, wherein one or more intravascular devices comprise one or more sensor ultrasound transducers.

4. The method of claim 3, wherein monitoring at least one anatomic structure of the vessel wall in response to a pulse wave being launched on the vessel wall comprises: receiving records from one or more ultrasound transducers indicative of ultrasound signals backscattered from anatomical structures of the vessel wall, the ultrasound signals being backscattered in response to an event launching a pulse wave on the vessel wall; determining, based on the records, a displacement of the anatomical structures of the vessel wall as the pulse wave travels along the vessel wall; and based on the displacement of the anatomical structures with respect to time elapsed between the event and the determined displacement, determining a velocity of the pulse wave travelling along the vessel wall.

5. The method of claims 3 or 4, wherein determining the displacement comprises: detecting the displacement of the anatomical structures by cross-correlating successively received ultrasound signals when the pulse wave is launched on the vessel wall and the one or more sensor ultrasound transducers are driven in the pulse-echo imaging mode.

6. The method of any one of claims 3 to 5, further comprising: estimating the wall stiffness of the vessel wall more than once before, during, and after a or the intravascular therapy procedure, wherein the vessel comprises a renal artery, and wherein the intravascular therapy procedure comprises a renal denervation procedure.

7. The method of any one of claims 3 to 6, further comprising: comparing the estimated wall stiffness from at least two instances of estimating; and determining an effect of the renal denervation procedure based on results of the comparing.

8. The method of any one of claims 3 to 7, wherein the one or more sensor ultrasound transducers comprise a ring-annular ultrasound transducer configured to emit ultrasound pulses radially outward and receive the ultrasound signals backscattered from anatomical structures of the vessel wall.

9. The method of any one of claims 3 to 8, wherein the one or more sensor ultrasound transducers include a plurality of sensor ultrasound transducers in which a sensor ultrasound transducer is axially spaced apart from a neighboring sensor ultrasound transducer by a pre-determined distance.

10. The method of claim 9, wherein the velocity of the pulse wave is determined based on, at least in part, an arrival time for the pulse wave to travel the pre-determined distance from the sensor ultrasound transducer to the neighboring sensor ultrasound transducer.

11. The method of any one of claims 3 to 10, wherein the one or more sensor ultrasound transducers are characterized by a center frequency from about 15 MHz to about 60 MHz.

12. The method of any one of claims 3 to 11, wherein the driving and tracking are performed at a repetition rate of about 10 kHz to about 200 kHz.

13. The method of claim 4 or any claim depending thereon, wherein the event corresponds to a cardiac event detectable on an electrocardiogram (ECG) for the subject.

14. The method of claim 4 or any claim depending thereon, wherein the event corresponds to a pushing event in which an ultrasound transducer is activated to generate sufficient acoustic radiation force around the vessel wall such that the pulse wave is launched to propagate along the vessel wall.

15. The method of claim 14, wherein the ultrasound transducer that is activated to generate sufficient acoustic radiation force around the vessel wall such that the pulse wave is launched to propagate along the vessel wall is a therapy ultrasound transducer characterized by a center frequency from about 7 MHz to about 12 MHz.

16. The method of claim 15, wherein the therapy ultrasound transducer is activated for a duration from about 100 ps to about 500 ps.

17. The method of claim 14, wherein the ultrasound transducer that is activated to generate sufficient acoustic radiation force around the vessel wall such that the pulse wave is launched to propagate along the vessel wall comprises a sensor ultrasound transducer.

18. The method of any one of claims 1 to 17, wherein monitoring signals indicative of an ambient pressure of the ultrasound transducer assembly comprises: receiving a record of at least one pressure measurement indicative of a first pressure change resulting from injecting the first bolus of fluid in a balloon with a closed outlet of the ballon deployed inside a vessel of a subject receiving an intravascular procedure, wherein theballoon comprises an inlet and the outlet, is inflated to a first pre-determined pressure, and is expanded radially to press against the vessel wall from inside the vessel; determining, based on the first pressure change, the stiffness of the vessel wall.

19. The method of claim 18, further comprising: receiving a record indicative of a size of the vessel wall before the balloon is inflated, or before the first bolus of fluid is injected, or when the pressure change is measured.

20. The method of claims 18 or 19, further comprising: estimating a wall stiffness for the vessel wall based on the first pressure change and the size of the vessel.

21. The method of any one of claims 18 to 20, further comprising: receiving a record indicative of a second pressure change induced by injecting the second bolus of fluid into the balloon with the outlet closed.

22. The method of claim 21, further comprising: estimating the wall stiffness based on, at least in part, the first and second pressure changes.

23. The method of claims 21 or 22, further comprising: receiving a record indicative of a third pressure change induced by injecting the second bolus of fluid into the balloon with the outlet closed; and applying a regression model to the first, the second, and the third pressure changes.

24. The method of claim 23, wherein the first bolus, the second bolus, and the third bolus have a pre-determined volume.

25. The method of claims 23 or 24, wherein the first pressure change, the second pressure change, and the third pressure change are cumulatively within an upper limit.

26. The method of any one of claims 18 to 25, wherein the first pre-determined pressure causes a net pressure of the balloon to be higher than a physiological peak blood pressure, wherein the net pressure of the balloon is determined by subtracting an elastic balloon stress from the first pre-determined pressure, and wherein the elastic balloon stress depends on a size of the balloon.

27. The method of any one of claims 18 to 26, wherein the intravascular device comprises a therapy ultrasound transducer, or a micro-electromechanical systems (MEMS) device.

28. The method of any one of claims 18 to 27, wherein the first pressure change is indicated by an amplitude of voltage between input terminals of the intravascular device before and after injecting the first bolus of fluid.

29. The method of any one of claims 18 to 28, wherein said estimating the wall stiffness of the vessel wall is performed before, during, and after a renal denervation procedure.

30. The method of claim 29, further comprising: comparing the estimated wall stiffness before, during, and after the renal denervation procedure; and determining an effect of the renal denervation procedure based on results of said comparing.

31. The method of any preceding claim, further comprising: determining whether the monitored wall stiffness fulfills a predefined wall stiffness criterium, wherein, optionally, the wall stiffness criterium defines at least one of a wall stiffness threshold and a wall stiffness range.

32. The method of claim 31 , further comprising: determining whether the monitored wall stiffness is within a predefined range; andoutputting an instruction to reposition the catheter shaft, when the wall stiffness criterium is not fulfilled; or outputting a confirmation of a treatment site, when the wall stiffness criterium is fulfilled.

33. The method of any preceding claim, further comprising: after monitoring of the stiffness of the vessel wall, outputting an instruction to ablate material of the vessel wall; monitoring the stiffness of the vessel wall after ablation; comparing the monitored stiffnesses before and after ablation to determine a stiffness change; determining whether the stiffness change fulfills a predetermined stiffness change criterium; determine that further ablation is needed at the present location of the catheter shaft, when the stiffness change criterium is not fulfilled.

34. The method of any preceding claim, further comprising: triggering display of a current catheter state via a graphical user interface.

35. The method of claim 26, wherein the current catheter state is indicative of at least one of: a method step that is currently performed, one or more options for proceeding with a subsequent method step, and an indicator representative of a wall stiffness criterium or a wall stiffness change criterium being currently fulfilled or not fulfilled.

36. A computer program product comprising instructions which, when the program is executed by a computer, cause the computer to carry out the steps of any one of claims 1 to 32, wherein optionally, the computer program product is stored on a computer-readable storage medium.

37. A method comprising: placing one or more sensor ultrasound transducers inside a vessel wall of a subject receiving an intravascular therapy procedure;in response to an event launching a pulse wave on the vessel wall, driving the one or more sensor ultrasound transducers in a pulse-echo imaging mode to receive, at the one or more sensor ultrasound transducers, ultrasound signals backscattered from anatomical structures of the vessel wall; tracking, based on the ultrasound signals backscattered from anatomical structures of the vessel wall, a displacement of the anatomical structures of the vessel wall as the pulse wave travels along the vessel wall; and based on the displacement of the anatomical structures with respect to time elapsed between the event and the tracking, determining a velocity of the pulse wave travelling along the vessel wall.

38. A method to monitor stiffness of a vessel wall, the method comprising: deploying a balloon inside a vessel of a subject receiving an intravascular procedure, wherein the balloon encapsulates an intravascular device and comprises an inlet and an outlet; inflating the balloon to a first pre-determined pressure, wherein the balloon is expanded radially to press against the vessel wall from inside the vessel; injecting a first bolus of fluid into the balloon through the inlet and with the outlet closed; and measuring, using the intravascular device, a first pressure change resulting from injecting the first bolus of fluid.

39. An intravascular ultrasound transducer assembly for monitoring stiffness of a vessel wall comprising: a catheter shaft sized and shaped for insertion inside a vessel having a vessel wall; and one or more intravascular devices integrated on the catheter shaft and configured to monitor at least one of: i) at least one anatomic structure of the vessel wall in response to a pulse wave being launched on the vessel wall so that a pulse wave velocity is determined by operating in a pulse echo mode to track the at least one anatomic structure; and ii) signals indicative of an ambient pressure of the ultrasound transducer assembly, wherein the ambient is defined by a balloon encapsulating at least one of the one or more sensor ultrasound transducers; whereinthe pulse wave velocity and the ambient pressure are related to the stiffness of the vessel wall.

40. The intravascular ultrasound transducer assembly of claim 31 , wherein the one or more intravascular devices comprise one or more sensor ultrasound transducers.

41. An intravascular ultrasound transducer assembly comprising: a catheter shaft sized and shaped for insertion inside a vessel having a vessel wall; and one or more sensor ultrasound transducers integrated on the catheter shaft and configured to operate in a pulse-echo imaging mode to track at least one anatomic structure of the vessel wall in response to a pulse wave being launched on the vessel wall so that a pulse wave velocity is determined.

42. The intravascular ultrasound transducer assembly of claim 40 or 41, wherein the one or more sensor ultrasound transducers are synchronized with an electrocardiogram (ECG).

43. The intravascular ultrasound transducer assembly of any one of claims 40 to 42, further comprising a therapy ultrasound transducer configured to launch the pulse wave on the vessel wall, wherein the therapy ultrasound transducer operates at a center frequency from about 7 MHz to about 12 MHz.

44. The intravascular ultrasound transducer assembly of any one of claims 40 to 42, wherein one of the one or more sensor ultrasound transducers is configured to launch the pulse wave on the vessel wall, and wherein the one or more sensor ultrasound transducers operate at a center frequency from about 15 MHz to about 30 MHz.

45. The intravascular ultrasound transducer assembly of any one of claims 40 to 44, further comprising: control logic in communication with the one or more sensor ultrasound transducers and configured to drive the one or more sensor ultrasound transducers to track a displacement of the at least one anatomic structure of the vessel wall as the pulse wave travels along the vessel wall.

46. The intravascular ultrasound transducer assembly of any one of claims 40 to45, wherein the at least one anatomic structure comprises: an intima of the vessel wall, a media of the vessel wall, and an adventitia of the vessel wall.

47. The intravascular ultrasound transducer assembly of any one of claims 40 to46, further comprising the balloon.

48. A system comprising: a catheter assembly comprising a balloon encapsulating an intravascular device, wherein the balloon comprises an inlet and an outlet; a fluid pump coupled to an inlet of the balloon and programmed to inject at least one controllable amount of fluid of into the balloon; and a receiving circuit coupled to the intravascular device and configured to measure signals from the intravascular device.

49. The system of claim 48, wherein the signals are voltage signals.

50. The system of claims 48 or 49, further comprising a computer processor in communication with the receiving circuit and the fluid pump, wherein the computer processor is configured to: control the fluid pump to inflate the balloon to a first pre-determined pressure, wherein the balloon is expanded radially to press against the vessel wall from inside the vessel; and inject a first bolus of fluid into the balloon through the inlet and with the outlet closed, wherein the at least one of the controllable amount of fluid comprises the first bolus.

51. The system of claim 50, wherein the computer processor is further configured to: obtain, using the receiving circuit, signals from the intravascular device resulting from injecting the first bolus of fluid; determine, based on, at least in part, the signals, a first pressure change resulting from injecting the first bolus of fluid; andestimating a wall stiffness based on, at least in part, the first pressure change.

52. The system of claims 50 or 51, wherein the computer processor is further configured to: inject a second bolus of fluid into the balloon through the inlet and with the outlet closed.

53. The system of claims 51 or 52, wherein said estimating comprises performing a regression analysis.

54. The system of any one of claims 48 to 53, wherein the intravascular device comprises at least one of: a therapy ultrasound transducer, and a micro-electromechanical systems (MEMS) device.

55. The system of any one of claims 48 to 54, wherein the voltage signals are measured between input terminals of the intravascular device before and after injecting the first bolus of fluid.

56. The system of any one of claims 48 to 55, wherein the catheter assembly comprises a catheter shaft and the catheter shaft, the balloon and the intravascular device form the intravascular ultrasound transducer assembly of claim 47.

57. The system of any one of claims 48 to 56, further comprising a display for displaying a graphical user interface indicative of a current catheter state.

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